Exhaled Nitric Oxide and its role in Asthma Management

Exhaled Nitric Oxide in Asthma

2010-03-24T02:13:00.000-07:00

by Bruno Battistini, PhD

Exhaled nitric oxide may allow clinicians to improve diagnosis, determine proper initial treatment, and monitor the progression of various pulmonary diseases including asthma.

Nitric oxide, an atmospheric gas and free radical, was found in the 1970s to activate guanylate cyclase and increase guanosine 3':5'-cyclic monophosphate (cGMP) levels in various tissue preparations.1 Soon after (in 1981), a relationship between cGMP formation and the relaxation of coronary arterial smooth muscle in response to glyceryl trinitrate, nitroprusside, nitrite, and nitric oxide was established.2 It is reported that activation of endothelial cells by acetylcholine and other agents lead to arterial vasodilatation, from which emerged the new concept of endothelium-derived relaxing factor (EDRF) and the subsequent endothelium-related increase in smooth muscle cGMP.3 Nitric oxide emerged as the molecule responsible for the biological activity of EDRF.4 Of the more than 40,000 publications that can be found on nitric oxide today, about 5,000 (13%) focus on the biochemistry, pharmacology, and molecular biology of this molecule in the lung and pulmonary system. The first description of the presence and measurement of endogenous nitric oxide in the exhaled air of various species, including humans, was reported by Gustafsson et al.5 As of March 2001, 502 publications can be found on exhaled nitric oxide, but close to 2,000 can be found on the the inhalation of nitric oxide as a mean of therapeutic intervention, such as reversing pulmonary vasoconstriction.6

Biotransformation function
Nitric oxide is endogenously produced in the lung and many other organs, tissues, and cells by three subtypes of nitric oxide synthase (NOS I, II, and III).7 Once released, nitric oxide (having a half-life of 0.05 to <1 second) is almost immediately transformed into nitrite and nitrate. It may also react with superoxide to form peroxynitrite, as well as reacting with many bioreactants in circulating blood.8 Nitric oxide, as a vasodilator released by the normal endothelium, counterbalances, with atrial natriuretic peptide and bradykinin, the effects of vasoconstrictors (angiotensin II and endothelins) on blood flow and pressure.9 Thus, nitric oxide, under normal pulmonary-circulation and respiratory conditions, dilates human pulmonary arteries.10 Under hypoxic conditions, the release and action of nitric oxide are reduced.10 In hypoxia and other disease states such as acute lung injury and pneumonia, the loss or attenuation of endogenous nitric oxide inevitably leads to pulmonary hypertension.

Nitric oxide is produced not only by endothelial cells, but also by many other types of cells, such as epithelial cells, macrophages, eosinophils, neutrophils, and neurons11 that contribute to the roles of nitric oxide in respiration and as a bronchodilator.12-14 Nitric oxide is also involved as a neurotransmitter for the nonadrenergic noncholinergic nerves,15 and it shows antimicrobial activity.16 Conversely, nitric oxide, reacting with superoxide and forming peroxynitrite, can induce membrane lipid peroxidation that leads to cell-membrane damage, thus revealing the cytotoxic potential of superoxide and nitric oxide.17 Nitric oxide can also cause DNA breaks, apoptosis, and cytostasis, and it can be involved in angiogenesis and tumor progression.18 In short, nitric oxide is not merely a marker; it plays significant vascular and nonvascular regulatory and host-defense roles in pulmonary physiology and pathophysiology.

Measuring exhaled nitric oxide
Considering the close anatomical proximity of blood capillaries to membranous airways (alveolar space), pulmonary endothelial nitric oxide was expected to enter the airspace and, therefore, to be measured in the exhaled air. The first measurement of exhaled nitric oxide in normal human subjects5 used chemiluminescence (based on a photochemical reaction between nitric oxide and ozone), diazotization, and mass spectrometry, and was later confirmed using gas chromatography/mass spectrometry.19 Several other groups20-22 have since measured basal levels of exhaled nitric oxide in normal human subjects. Some noticeable variations in exhaled–nitric-oxide values were reported. A number of recommendations have been made to help ensure the reproducibility of the technique.23 At first, the exact origin of nitric oxide in exhaled air was not known. Most variations in exhaled nitric oxide can be explained by contamination from the upper respiratory tract.24 Such contamination was not fully eliminated by the use of nasal blockage (encouraging only oral airflow). Rather, the problem was solved by the selection of an online single constant expiratory flow-controlled rate.25 This later observation suggested that exhaled nitric oxide is released within the conducting airways, whereas alveolar nitric oxide levels are negligible. Thus, under normal conditions, levels of exhaled nitric oxide are less than 10 parts per billion (109), reflecting the minor contribution of alveolar nitric oxide and the total absence of nasal nitric oxide.

About 125 publications have presented data on the levels of exhaled nitric oxide in children. The first of these was by Lundberg et al.24 Further relationships between exhaled nitric oxide and childhood asthma have also been reported.26-28 Compared to induced sputum, exhaled nitric oxide presents undeniable advantages29 as a novel, noninvasive way to assess the degree of airway inflammation in this particular population.

Exhaled Nitric Oxide in Children
In mildly atopic asthma patients, the levels of exhaled nitric oxide seen during oral breathing were two to three times those seen in normal human subjects.30 In many other groups of asthma patients, the level of nitric oxide was also shown to be elevated.10-22,25,31 Thus, since increased production of nitric oxide in the lower airways may involve activated macrophages or neutrophils, exhaled nitric oxide was proposed for use to monitor underlying bronchial inflammation. Exhaled nitric oxide was not shown to be increased in patients with stable chronic obstructive pulmonary disease (COPD), but it was higher in unstable COPD,32 in bronchiectasis,33 following lung transplantation, and in association with obliterative bronchiolitis.34 Patients with cystic fibrosis had lower levels of exhaled nitric oxide35 as did patients with primary ciliary dyskinesia.36

The lungs of patients with primary pulmonary hypertension produced low levels of exhaled nitric oxide that may reflect the reduced blood capillary volume in these patients, rather than a decreased basal production of nitric oxide.37 The levels of exhaled nitric oxide are also reduced in patients with hypertension.38 The decrease is more pronounced in males than in females. Other patients with renal failure presented no differences, but sepsis was associated with a significant increase.38 Upon major surgery, the levels of exhaled nitric oxide dropped 79% , rising toward normal postoperatively (but still remaining 30% below baseline values).38 Furthermore, the absence of nasal nitric oxide in children with Kartagener syndrome was proposed as a simple noninvasive test supporting the diagnosis.

Stimulation and Inhibition
In addition to the elevation of exhaled nitric oxide associated with various pulmonary and other disorders, upregulation of the endogenous basal levels of exhaled nitric oxide can be induced by other factors. Nitric oxide concentrations in exhaled air have been reported to increase during physical exercise.39,40 Exercise on a stationary bicycle also produces rapid and reversible increases in pulmonary nitric oxide excretion rates that are well correlated with observed changes in heart rate.41 Conversely, graded dynamic (treadmill) exercise does not affect exhaled nitric oxide, which is maintained at the same level as work rates increase.42

The generation of nitric oxide in the human lung is endogenous, and it has been shown to be inhibited by L-NAME and NG-monomethyl-L-arginine (L-NMMA), inhibitors of cNOS.5 In human study subjects, exhaled–nitric oxide levels were significantly reduced by the inhalation of the specific nitric oxide synthase inhibitor NG-monomethyl-L-arginine31,43 or intravenous administration of L-NMMA.44 Voluntary twofold hyperventilation for 1 minute decreased expired nitric oxide by 50% (from 9.5±2.5 parts per billion) in six subjects.42 Smoking attenuated the levels of exhaled nitric oxide by 21% in men and by 41% in women.38 This effect is also supported by other studies.45 Ethanol (given at 0.25 g/kg and 1 g/kg in four times its volume of orange juice) produced dose-dependent reductions of exhaled nitric oxide in humans.46 Thus, drinking prior to analysis may affect the levels of exhaled nitric oxide in human subjects. Prednisolone, a glucocorticosteroid, did not inhibit exhaled nitric oxide in normal subjects, suggesting that the increased exhaled nitric oxide seen in asthma patients is likely to be caused by the induction of inducible NOS.43

Pharmacological inhibition of exhaled nitric oxide by inhaled L-NMMA was also reported43 in asthma patients and those with other pulmonary diseases, just like in normal subjects. Existing drugs such as inhaled or oral corticosteroids were also shown to attenuate the increased levels of exhaled nitric oxide found in asthma significantly.31,43,47 Anti-leukotrienes also inhibit the rise in exhaled nitric oxide moderately.48 Conversely, bronchodilators, such as albuterol or salmeterol, did not influence exhaled nitric oxide.49,50

Conclusion
The levels of exhaled nitric oxide in normal and ill subjects have been established for different age categories, and significant relationships with more direct measurements of inflammation in the airways (induced sputum, bronchoalveolar lavage, bronchial biopsy, and clinical signs and symptoms of asthma, especially during acute exacerbations) have been described. While exhaled nitric oxide has attracted much interest, the inhalation of nitric oxide as a therapy in patients with pulmonary hypertension and other conditions has attracted even more interest.51

Combining rapid, noninvasive, standardized analysis of exhaled nitric oxide with traditional techniques for assessing pulmonary function, airway reactivity, and inflammation may allow the clinician to assess airway inflammation and oxidative stress more accurately in patients with pulmonary diseases that include asthma, COPD, and interstitial lung disease. It may also allow the clinician to improve diagnosis, determine the proper initial treatment, monitor the progression of disease, and assess the efficacy of treatment and subsequent adjustments over time.52 Knowing the level of nitric oxide (and, by association, airway inflammation) may help clinicians keep the patient’s medication to a minimum while maintaining therapeutic efficacy. Thus, more longitudinal studies are needed to confirm that the analysis of exhaled nitric oxide may be used for the short-term and long-term management and treatment of diseases. Then, nitric oxide analysis may take the place that it deserves in pulmonology. Technological advances will make it possible to miniaturize nitric oxide analyzers (and will make them less expensive) so they will become portable and may even be used, in the not-so-distant future, at home in conjunction with peak flow meters.

Bruno Battistini, PhD, is assistant professor of medicine and research scientist, Department of Medicine, Laval University, Laval Hospital Research Center, Institut de Cardiologie et de Pneumologie, Ste-Foy, Quebec, Canada.

Source: http://www.rtmagazine.com/issues/articles/2001-04_05.asp

The Use of Exhaled Nitric Oxide to Guide Asthma Management

2010-03-14T23:07:00.001-07:00

Rationale: Current asthma guidelines recommend adjusting antiinflammatory treatment on the basis of the results of lung function tests and symptom assessment, neither of which are closely associated with airway inflammation.

Objectives: We tested the hypothesis that titrating corticosteroid dose using the concentration of exhaled nitric oxide in exhaled breath (FENO) results in fewer asthma exacerbations and more efficient use of corticosteroids, when compared with traditional management.

Methods: One hundred eighteen participants with a primary care diagnosis of asthma were randomized to a single-blind trial of corticosteroid therapy based on either FENO measurements (n = 58) or British Thoracic Society guidelines (n = 60). Participants were assessed monthly for 4 months and then every 2 months for a further 8 months. The primary outcome was the number of severe asthma exacerbations. Analyses were by intention to treat.

Measurements and Main Results: The estimated mean (SD) exacerbation frequency was 0.33 per patient per year (0.69) in the FENO group and 0.42 (0.79) in the control group (mean difference, –21%; 95% confidence interval [CI], –57 to 43%; p = 0.43). Overall the FENO group used 11% more inhaled corticosteroid (95% CI, –17 to 42%; p = 0.40), although the final daily dose of inhaled corticosteroid was lower in the FENO group (557 vs. 895 µg; mean difference, 338 µg; 95% CI, –640 to –37; p = 0.028).

Conclusions: An asthma treatment strategy based on the measurement of exhaled nitric oxide did not result in a large reduction in asthma exacerbations or in the total amount of inhaled corticosteroid therapy used over 12 mo, when compared with current asthma guidelines.

Source: http://ajrccm.atsjournals.org/cgi/content/short/176/3/231

Exhaled nitric oxide and asthma control: a longitudinal study in unselected patients

2010-03-10T21:12:00.001-08:00

Controlled studies have shown that monitoring of the exhaled nitric oxide fraction (FeNO) improves asthma management. However, the studies seldom consider the full range of patients seen in clinical practise. In the present study, the ability of FeNO to reflect asthma control over time is investigated in a regular clinical setting, and meaningful FeNO cut-off points and changes are identified.

Answers to the Asthma Control Questionnaire and FeNO were recorded at least once in 341 unselected asthma patients. The whole population and subgroups were considered, i.e. both inhaled corticosteroid (ICS)-naïve and low or high-to-medium (≤ or >500 µg beclomethasone dipropionate equivalents·day–1) ICS-dose groups.

An FeNO decrease <40% or increase <30% precludes asthma control optimisation or deterioration, respectively (negative predictive value 79 and 82%, respectively). In the present study’s low-dose group, a decrease >40% indicated asthma control optimisation (positive predictive value (PPV) 83%). In ICS-naïve patients, FeNO >35 ppb predicted asthma control improvement in response to ICS (PPV 68%). In most cases, forced expiratory volume in one second assessments were not useful.

In conclusion, in a given patient, exhaled nitric oxide fraction was found to be significantly related to asthma control over time. The overall ability of exhaled nitric oxide fraction to reflect asthma control was reduced in patients using high doses of inhaled corticosteroids. Forced expiratory volume in one second had little additional value in assessing asthma control.

Source: http://erj.ersjournals.com/cgi/content/abstract/31/3/539

Exhaled Nitric Oxide and its role in the treatment of Asthma Part I

2010-03-07T23:44:00.000-08:00

In medicine, exhaled nitric oxide (eNO) can be measured in a breath test for asthma which is characterized by airway inflammation. Nitric oxide (NO) is a gaseous molecule produced by certain cell types in an inflammatory response. Exhaled NO (also referred to as FENO) is a promising biomarker as a guide to therapy in adults and children with asthma. The breath test has recently become available in many well-equipped hospitals in developed countries. Clinical trials have looked at whether tailoring asthma therapy based on eNO values is better than conventional care, in which therapy is gauged by symptoms and the results of lung function tests.
An excerpt from the New England Journal of Medicine in a study by Andrew D. Smith, M.B., Ch.B., Jan O. Cowan, Karen P. Brassett, G. Peter Herbison, M.Sc., and D. Robin Taylor, M.D. details the trial to establish the use of eNO in the measurements to guide treatment in chronic asthma.

The findings of the study are detailed below.

Background

International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FeNO) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment.

Methods

In a single-blind, placebo-controlled trial, the investigators randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FeNO measurements or an algorithm based on conventional guidelines. After the optimal dose was determined (phase 1), patients were followed up for 12 months (phase 2). The primary outcome was the frequency of exacerbations of asthma; the secondary outcome was the mean daily dose of inhaled corticosteroid.

Results

Forty-six patients in the FeNO group and 48 in the group whose asthma was treated according to conventional guidelines (the control group) completed the study. The final mean daily doses of fluticasone, the inhaled corticosteroid that was used, were 370 μg per day for the FeNO group (95 percent confidence interval, 263 to 477) and 641 μg per day for the control group (95 percent confidence interval, 526 to 756; P=0.003), a difference of 270 μg per day (95 percent confidence interval, 112 to 430). The rates of exacerbation were 0.49 episode per patient per year in the FeNO group (95 percent confidence interval, 0.20 to 0.78) and 0.90 in the control group (95 percent confidence interval, 0.31 to 1.49), representing a non-significant reduction of 45.6 percent (95 percent confidence interval for mean difference, ¡78.6 percent to 54.5 percent) in the FeNO group. There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils).

Conclusions

With the use of FeNO measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control.

Source: http://www.healthcentral.com/asthma/c/907259/97668/exhaled-treatment

Exhaled Nitric Oxide Measurements Can Be Used to Both Diagnose and Rule Out Asthma: Presented at AAAAI

2010-03-03T22:49:00.000-08:00

Doctors have been using fractional exhaled nitric oxide (FeNO) measurements to indicate airway inflammation and aid in asthma diagnosis for some time, leading many to believe that these measurements could play a role in actually diagnosing the problem. As it turns out, this noninvasive, inflammatory marker may not only send up a red flag for a positive diagnosis but also aid in confirming a negative one, according to a study presented here at the 2010 American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

In the study, a group of 115 patients who were reporting asthma symptoms were assembled. The patients had "perennial symptoms consistent with asthma," with normal spirometry and a negative bronchodilator test. They also met medication withdrawal requirements before testing and completed an Asthma Control Test and Asthma Control Questionnaire before the research protocol began. After undergoing a methacholine challenge test following the standard 5-breath dosimeter protocol, FeNO measurements were taken with a portable device at a 50-mL/s exhalation flow rate.

Thirty-five of the 115 patients had a positive methacholine test and were diagnosed with asthma, making the prevalence of asthma in the test population 30.43%. FeNO levels in asthmatic patients averaged 58 parts per billion (ppb) (interquartile range [IQR] 36.00-112.00), whereas they averaged 29.5 ppb in patients not diagnosed with asthma (IQR 21.00-42.75; P = .0001). Maria Pedrosa, MD, University Hospital La Paz, Madrid, Spain, stated in a presentation on February 27 that these results showed that "FeNO levels are significantly higher for asthmatics…than non-asthmatics."

Source: http://www.docguide.com/news/content.nsf/news/852576140048867C852576DB00726E6F

Relationship of exhaled nitric oxide to clinical and inflammatory markers of persistent asthma in children

2010-03-02T23:12:00.000-08:00

Exhaled nitric oxide (eNO) is a noninvasive test that measures airway inflammation.eNO provides information about the asthmatic state consistent with information from other markers of inflammation. It is a noninvasive technique that could be used in decisional management of children with asthma.

Asthma control is monitored by means of symptoms using pulmonary function tests, particularly FEV1 and FEV1/forced vital capacity (FVC), to supplement the clinical information. There is growing interest in determining the role of biomarkers in asthma care. Most of these studies have been conducted in adults. Peripheral blood eosinophils1,and sputum eosinophils correlate with response to oral corticosteroids. Studies in adults have shown that improved asthma control can be attained by use of airway responsiveness to methacholine and sputum eosinophils to modulate asthma therapy rather than waiting for clinical symptoms to appear or pulmonary functions to deteriorate. Because the application of biomarkers to assessment of asthma management has become more widespread, exhaled nitric oxide (eNO) has been studied to predict the clinical course with reductions in or response to medications. eNO levels correlate with response to inhaled corticosteroids (ICSs), in that patients with higher levels have better responses.Jones et al demonstrated that increases of eNO have a positive predictive value for loss of control of asthma as ICSs are withdrawn, providing information about control of asthma equal to induced sputum eosinophils and methacholine responsiveness. eNO is a particularly attractive biomarker, because the test requires little effort from the patient, can be measured even in young children,and the results of the test can be immediately available.

Source: http://www.asthma-carenet.org/Publication%20pdfs/CLIC%20Baseline%2017.pdf

Comparisons between Exhaled Nitric Oxide Measurements and Conventional Tests

2010-02-25T23:08:00.001-08:00

International guidelines recommend a range of clinical tests to confirm the diagnosis of asthma. These focus largely on identifying variable airflow obstruction and responses to bronchodilator or corticosteroid. More recently, exhaled nitric oxide (FENO) measurements and induced sputum analysis to assess airway inflammation have been highlighted. However, to date, no systematic comparisons to confirm the diagnostic utility of each of these methods have been performed. To do so, we investigated 47 consecutive patients with symptoms suggestive of asthma, using a comprehensive fixed-sequence series of diagnostic tests. Sensitivities and specificities were obtained for peak flow measurements, spirometry, and changes in these parameters after a trial of steroid. Comparisons were made against FENO and sputum cell counts. Sensitivities for each of the conventional tests (0–47%) were lower than for FENO (88%) and sputum eosinophils (86%). Overall, the diagnostic accuracy when using FENO and sputum eosinophils was significantly greater. Results for conventional tests were not improved, using a trial of steroid. We conclude that FENO measurements and induced sputum analysis are superior to conventional approaches, with exhaled nitric oxide being most advantageous because the test is quick and easy to perform.c asthma, do not display elevated FENO.

Source: http://171.66.122.149/cgi/content/abstract/169/4/473

Comparison of Exhaled Nitric Oxide Measurement With Conventional Tests in Steroid-Naive Asthma Patients

2010-02-23T00:56:00.000-08:00

Background: Nitric oxide (NO) is a molecule with potent biological activity that plays an important role in the physiology of the respiratory system. Increased expression of inducible nitric oxide synthase (iNOS) and elevated fractional concentration of exhaled nitric oxide (FENO) are seen in asthmatic patients. Measurement of FENO has become increasingly recognized for use in the evaluation of bronchial inflammation during monitoring of antiinflammatory treatment.

Objectives: The aim of this study was to evaluate FENO in a group of steroid-naive asthmatics and assess the relationship of this parameter with the results of other tests used in the diagnosis of asthma and monitoring of antiinflammatory treatment in asthmatic patients.

Methods: The study was conducted in a group of 101 steroid-naive asthmatics (56 allergic and 45 nonallergic) and 39 healthy volunteers. All patients underwent measurement of FENO, skin prick tests with common inhaled allergens,analysis of serum eosinophil cationic protein (ECP) and blood eosinophilia, and flow-volume spirometry. When the forced expiratory volume in the first second (FEV1) was less than 80% of predicted, reversibility of airway obstruction with a ß2-agonist was assessed. A nonspecific bronchial provocation test with histamine was carried out in asthmatic patients with a baseline FEV1 of more than 70% of predicted.

Results: Compared to the healthy volunteers, FENO was elevated in both groups of asthmatics. FENO in the allergic asthma group was higher than in the group of nonallergic asthmatics. In allergic and nonallergic asthmatics, FENO was significantly correlated with bronchial hyperresponsiveness to histamine, reversibility of airway obstruction,serum ECP levels, and blood eosinophilia. FENO did not correlate with baseline FEV1 in either group of asthmatics. In 31% of nonallergic and 9% of allergic patients, FENO was less than 20 parts per billion.

Conclusions: We suggest that measurement of FENO could be clinically useful in steroid-naive asthmatics and should be more widely used in clinical practice. Measurement of FENO is a noninvasive, simple, and reproducible procedure, the results of which correlate with other routinely used methods in the diagnosis of asthma. However, it is worth noting that some patients, especially those with nonallergic asthma, do not display elevated FENO.

Source:http://www.jiaci.org/issues/vol16issue04/4.pdf

Exhaled Nitric Oxide Shows Promise For COPD

2010-02-18T23:07:00.000-08:00

With the use of exhaled nitric oxide blossoming as a diagnostic and management tool on the asthma front, researchers now are exploring applications in other pulmonary diseases. Some respiratory specialists believe it has all the star-quality characteristics they look for in a lung-assessment tool - a noninvasive device that offers convenience, ease of use, and reliability at an affordable cost.

"It's still early and it's difficult at this point to say how it's going to end up, but I think the whole field of exhaled breath analysis is growing, and it's going to become more and more important," said Philip O'Reilly, MD, assistant professor of medicine at the University of Alabama, Birmingham.

As the field has gained momentum, the race to find new applications has too. A handful of small European trials have investigated a range of potential uses for eNO in chronic obstructive pulmonary disease - from predicted corticosteroid response to identification of exacerbations. They have not produced any winning results yet; however, investigators suggest eNO could be a useful clinical tool in COPD for certain patient populations.

Clinicians would need a special machine to measure eNO at different points in exhalation instantaneously, but Dr. O'Reilly noted the standard devices on the market can provide an average eNO measure across the range of expiration.

Source:http://respiratory-care-sleep-medicine.advanceweb.com/Features/Article-2/Exhaled-Nitric-Oxide-Shows-Promise-For-COPD.aspx

Outcomes Using Exhaled Nitric Oxide Measurements

2010-02-17T04:04:00.001-08:00

Background: Exhaled nitric oxide (FENO) measurements may help to highlight when inhaled corticosteroid (ICS) therapy should or should not be adjusted in asthma. This is often difficult to judge. Our aim was to evaluate a decision-support algorithm incorporating FENO measurements in a nurse-led asthma clinic.

Methods: Asthma management was guided by an algorithm based on high (>45ppb), intermediate (30-45ppb), or low (<30ppb) FENO levels and asthma control status. This provided for one of eight possible treatment options, including diagnosis review and ICS dose adjustment.

Study measurements at each visit: FENO was measured according to current guidelines19 using a NIOX MINO electrochemical analyser20-22 or a NIOX chemiluminescence analyser (both Aerocrine, Solna, Sweden). The latter was available at the Research Unit, 5km. from the Health Centre, but was used only when there was technical failure of the NIOX MINO. To validate FENO results, the sensors from the NIOX MINO device were tested against a calibrated standard, and where appropriate, a correction factor was applied to take account of signal drift. Spirometry was performed according to accepted standards using a Spiro USB spirometer (Micro Medical, Kent, England). The study received ethical approval from the Lower South Island Ethics Committee, and each participant gave written informed consent. Each GP participated in a start-up meeting, but thereafter further directions regarding the conduct of the study were not given.

Results: Well controlled asthma increased from 41% at visit 1 to 68% at visit 5 (p=0.001). The mean fluticasone dose decreased from 312 mcg/day at visit 2 to 211mcg/day at visit 5 (p=0.022). There was a high level of protocol deviations (25%), often related to concerns about reducing the ICS dose. The % fall in FENO associated with a change in asthma status from poor control to good control was 35%.

Conclusion: An FENO-based algorithm provided for a reduction in ICS doses without compromising asthma control. However, the results may have been influenced by the education and support which patients received. Reluctance to reduce ICS dose was an issue which may have influenced the overall results.

Source: http://www.scribd.com/doc/25420058/Outcomes-Using-Exhaled-Nitric-Oxide-Measurements

Regular monitoring of eNO provides a more complete picture of your asthma

2010-02-15T01:19:00.000-08:00

When airways get inflamed, the inner walls of the airway swell,so there is less space for smooth flow of air. Inflammation of the airways leads to symptoms such as shortness of breath,wheezing and coughing. The primary focus of asthma treatment is to reduce inflammation. Unfortunately, current methods of testing lung function do not measure inflammation. Therefore, your physician has to correlate symptoms to disease severity when prescribing or adjusting your medication.

Inflamed airways produce nitric oxide which becomes part of your breath. Exhaled nitric oxide has been studied well over the last 10 years. These studies have shown a strong relation between eNO and airway inflammation. Exhaled nitric oxide (eNO) increases as inflammation increases, and it decreases as inflammation decreases. Simple breath tests are now available to measure your eNO level. You simply breathe out steadily into a breath tube that is connected to the test device. The test itself takes just about 10 seconds. The results are available within one minute.

Adding eNO tests to other standard clinical measures gives your physician a better picture of your airway inflammation. This can help improve asthma control. By regularly monitoring your eNO levels, your physician can treat your asthma more precisely.

Source: http://www.scribd.com/doc/21625994/Regular-monitoring-of-eNO-provides-a-more-complete-picture-of-your-asthma

Noninvasive Monitoring of Airway Inflammation in Childhood Asthma

2010-02-11T03:32:00.000-08:00

Airway inflammation plays a central role in the pathogenesis of asthma. Accurate assessment of the degree of airway inflammation may allow us to fine-tune the anti-inflammatory treatment. There are many methods of assessing the degree of airway inflammation such as bronchial biopsy and broncho-alveolar lavage.

These methods, however, are invasive and can be very difficult to perform in children. Monitoring of induced sputum eosinophils and measurement of bronchial hyperresponsiveness has been found to be useful in adjusting asthma treatment. However, these measurements are not easily performed in the primary care setting. A simple noninvasive measurement of inflammation would be extremely useful to guide individual asthma therapy in the childhood population. Exhaled nitric oxide (eNO) has been found to be measurable in exhaled air and its level has been found to be increased in asthmatic. Use of inhaled corticosteroid can reduce asthma symptoms and eNO. Accurate and reliable tools in measuring eNO are now commercially available. Many research studies in the past few years have confirmed that eNO can be used for the diagnosis, monitoring of control, and guiding treatment of anti-inflammatory therapy.

Recent prospective studies have suggested that the addition of eNO monitoring would allow clinicians to use lower dose of inhaled steroid without compromising asthma control. Analyses of exhaled breath condensate (EBC) have been extensively investigated as another possible way to monitor airway inflammation. A variety of makers of inflammation can be measured in the EBC such as cytokines, chemokines,leukotrienes, and hydrogen peroxide. Further research is necessary to standardise the methodology of collection of EBC. Prospective trials are needed to confirm that the additional monitoring of these markers in the EBC may result in better control of asthma and optimal dosing of anti-inflammatory therapy in asthmatics.

Source:http://www.fmshk.org/database/articles/6_2.pdf

Exhaled nitric oxide: relation to sensitization and respiratory symptoms

2010-02-08T22:53:00.000-08:00

BACKGROUND: Conflicting data have been presented as to whether nitric oxide (NO) in exhaled air is merely reflecting atopy rather than airway inflammation. OBJECTIVE: To investigate the relationship between exhaled NO (eNO) and nasal NO (nNO), respiratory symptoms, and atopy, in the context of a cross-sectional study of the respiratory health of bleachery workers.

METHODS: Two hundred and forty-six non-smoking bleachery and paper-mill workers answered a questionnaire and were examined by measurements of eNO and nNO and spirometry, outside the pollen season. Blood samples were collected and analysed for specific IgE against common aeroallergens (birch, timothy, cat and house dust mite). Atopy was defined as a positive Phadiatop trade mark test.

RESULTS: The atopic and the non-atopic subjects without asthma or rhinitis had similar levels of eNO. Subjects reporting asthma or rhinitis who were also sensitized to perennial allergens had higher levels of eNO, whereas those sensitized to only seasonal allergens had similar eNO levels as non-atopic subjects with asthma or rhinitis. In multiple linear regression models adjusted for nNO, eNO was associated with asthma and sensitization to perennial allergens.

CONCLUSION: The results indicate that only atopic subjects who have recently been exposed to the relevant allergen have elevated levels of eNO. Atopic subjects who are not being exposed to a relevant allergen or have never experienced symptoms of asthma or rhinitis show normal eNO. These data indicate that eNO relates to airway inflammation in atopic subjects.

Source:http://www.ncbi.nlm.nih.gov/pubmed/14987301

Use of Exhaled Nitric Oxide Measurements to Guide Treatment in Chronic Asthma

2010-02-04T22:25:00.000-08:00

Background: International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FENO) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment.

Methods: In a single-blind, placebo-controlled trial, we randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FENO measurements or an algorithm based on conventional guidelines. After the optimal dose was determined (phase 1), patients were followed up for 12 months (phase 2). The primary outcome was the frequency of exacerbations of asthma; the secondary outcome was the mean daily dose of inhaled corticosteroid.

Results: Forty-six patients in the FENO group and 48 in the group whose asthma was treated according to conventional guidelines (the control group) completed the study. The final mean daily doses of fluticasone, the inhaled corticosteroid that was used, were 370 µg per day for the FENO group (95 percent confidence interval, 263 to 477) and 641 µg per day for the control group (95 percent confidence interval, 526 to 756; P=0.003), a difference of 270 µg per day (95 percent confidence interval, 112 to 430). The rates of exacerbation were 0.49 episode per patient per year in the FENO group (95 percent confidence interval, 0.20 to 0.78) and 0.90 in the control group (95 percent confidence interval, 0.31 to 1.49), representing a nonsignificant reduction of 45.6 percent (95 percent confidence interval for mean difference, –78.6 percent to 54.5 percent) in the FENO group. There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils).

Conclusions: With the use of FENO measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control.

Source:http://content.nejm.org/cgi/content/short/352/21/2163

Long Term Implications of Asthma

2010-02-03T01:03:00.000-08:00

One of the leading experts in asthma management devices discusses asthma and its implications. An excerpt from an article by Apieron:

Asthma Overview

Asthma is a chronic disease characterized by inflammation of the airways caused by allergens and other triggers. When airways are inflamed, the inner walls of the airways swell making them irregular. This causes the flow of air to become turbulent. The events that lead to obstruction of airflow and thus to asthma symptoms are complex and usually involve the following events:
Bronchoconstriction, where the smooth muscle surrounding the airways tightens in response to a trigger and narrows the airway.
Inflammation, where inner walls of airways swell.
Mucus formation within the airways that obstructs airflow.
Typical asthma symptoms include wheezing, coughing, chest tightness (dyspnea) and shortness of breath.

The Role of Inflammation in Asthma

Asthma signs and symptoms evolve from three basic characteristics that underlie the disease and its exacerbations: airway obstruction, airway hyper responsiveness and airway inflammation. Airway obstruction and hyperresponsiveness represent the classic physiology of asthma, and their contribution to the disease process and symptomatology have been well recognized for some time. Appreciation of the role of airway inflammation in asthma has evolved more recently.

Today asthma experts consider airway inflammation a central feature of asthma pathogenesis and its clinical manifestations. In fact, airway inflammation likely plays a critical role in airway obstruction and hyper responsiveness. In recent years, clinical and scientific knowledge of asthma has evolved from a model of episodic constriction of bronchial smooth muscle to a model which involves chronic airway inflammation.

Source:http://myasthma.net/blog/Long-Term-Implications-Of-Asthma

Non-invasive asthma marker helps minimize the need for steroids

2010-02-03T01:01:00.000-08:00

Known for its negative environmental impact, nitric oxide (NO) causes acid rain and photochemical smog. As a molecule produced in the respiratory system, however, it's vital for the dilation of airways and blood vessels, and the beating of cilia to clear secretions from the lung. Nitric oxide is produced by the enzyme nitric oxide synthase. This enzyme is up-regulated under inflammatory conditions and down-regulated when an anti-inflammatory (i.e. corticosteroids) is taken. When nitric oxide is produced, it spreads readily into the airways, where it can be collected and measured upon exhalation. Screening individuals with an exhaled nitric oxide test is an effective means to diagnose asthma and can help tailor treatment and dosing, particularly in patients with chronic disease.

What's the current inflammatory model of asthma?

It's now known that asthma isn't just an occasional narrowing of the air tubes causing shortness of breath, wheeze and cough. It's a complex relationship between airflow obstruction, hyper-responsiveness, inflammation and airway remodelling over a period of time. This interaction, along with exposure to triggers, determines the severity of asthma and the frequency of exacerbations. While a person with asthma may feel well between flare-ups, biopsy studies show that the destructive eosinophilic airway inflammation process continues even when the patient is asymptomatic. As a result, daily control of inflammation with anti-inflammatory inhaled corticosteroids (ICs) is the cornerstone of medical treatment for asthma.

Are there drawbacks to using spirometry alone?

Spirometry is vital as a readily available tool for the screening and initial diagnosis of asthma, and is useful for long-term follow-up. An improvement in forced expiratory volume in one second (FEV1) can prove to the clinician whether a new medication is helping the patient. There are pitfalls, though, when relying on spirometry alone. Airway inflammation continues even when spirometry is normal; this can lead to under-treatment of asthma, with poor quality of life and frequent visits to the emergency department.

Asthma has been described as a "nocturnal" disease. The main problem that many people with asthma have is that they wake up at night due to cough and shortness of breath, despite feeling fine during the day. Of course, when they visit their physician about these nighttime complaints, their spirometry will be normal if it's measured in the day-time. This can be confusing for the doctor who may not suspect asthma if the FEV1 is normal.

There's also a well-described "learning effect" where patients who take spirometry tests repeatedly discover how to improve their results by performing the test better. But in reality, their asthma isn't better. This can lead to a false sense of reassurance for clinicians if they rely on spirometry values to gauge if an individual with asthma is properly controlled.

Physicians who treat young children are at a particular disadvantage — spirometry is rarely done until at least the age of six. Under this age, spirometric testing doesn't consistently produce accurate results.

Good studies show that asthma control isn't necessarily reflected well by self-reported symptoms and spirometry. Clearly, there's a need for objective tests that correlate with asthma control and airway inflammation, remain constant at different times of the day and night, and don't show a learning effect.

So, how does eNO work?

When nitric oxide is exhaled into an exhaled nitric oxide (eNO) analyzer, it reacts with ozone and is measured by the process of chemiluminescence, accurate to one part per billion (ppb). Since NO is produced continuously in the airways, the concentration of NO depends on the flow rate. Consequently, a standard flow rate (50 mL/second) is mandated by international guidelines.

Source:http://www.parkhurstexchange.com/clinical-reviews/ud_02_vol14

Measurement of Exhaled Nitric Oxide and Exhaled Breath Condensate in the Diagnosis and Management of Asthma and Other Respiratory Disorders

2010-01-28T00:46:00.000-08:00

Description

Clinical Background

The National Heart, Lung, and Blood Institute, in its clinical guidelines regarding the management of asthma, offers the following definition of asthma: (2)

"Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular: mast cells, eosinophils, T lymphocytes, macrophages, neutrophils and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyper responsiveness to a variety of stimuli."

Guidelines for the management of persistent asthma stress the importance of long-term suppression of inflammation using steroids, leukotriene inhibitors, or other anti-inflammatory drugs. Existing techniques for monitoring the status of underlying inflammation have focused on bronchoscopy, with lavage and biopsy, or analysis by induced sputum. Given the cumbersome nature of these techniques, the ongoing assessment of asthma focuses not on the status of the underlying chronic inflammation, but rather on regular assessments of respiratory parameters such as FEV-1 and peak flow. Therefore, there has been interest in noninvasive techniques to assess the underlying pathogenic chronic inflammation as reflected by measurements of inflammatory mediators. Two new strategies have been investigated, the measurement of exhaled nitric oxide and the evaluation of exhaled breath condensate. Nitric oxide (NO) is an important endogenous messenger that is widespread in the human body, functioning for example, to regulate peripheral blood flow, platelet function, immune reactions, and neurotransmission, and also to mediate inflammation. In biologic tissues, nitric oxide is unstable, limiting measurement. However, in the gas phase nitric oxide is fairly stable, permitting its measurement in exhaled air. While nitric oxide is a volatile mediator that can be measured in exhaled air, most inflammatory mediators are not volatile and thus cannot be detected in the gas phase. Exhaled breath condensate (EBC) consists of exhaled air passed through a condensing or cooling apparatus, resulting in an accumulation of fluid. Although EBC is primarily derived from water vapor, it also contains aerosol particles or respiratory fluid droplets, which in turn contain various nonvolatile inflammatory mediators, such as cytokines, leukotrienes, oxidants, antioxidants, and various other markers of oxidative stress. The pH of EBC can also be measured. Various studies have focused on different components of EBC as inflammatory markers in respiratory disease. The following clinical roles for measurement of NO and EBC have been investigataed in the diagnosis and management of asthma:

* Diagnosis of asthma

The current method of asthma diagnosis focuses on the clinical history and the demonstration of reversible airflow limitation. For example, spirometry measurements may be performed before and after the administration of a short-acting bronchodilator to demonstrate the presence of reversible airflow limitation. Measurement of exhaled nitric oxide levels has been suggested as either an alternative or adjunct to spirometry.
* Response to anti-inflammatory treatment

Declining levels of exhaled nitric oxide suggest declining inflammation.
* Monitoring compliance of anti-inflammatory treatment

Persistent elevation of exhaled nitric oxide may suggest poor compliance with long-term therapy.
* Detection of steroid resistance

Steroid resistance may be reflected by persistently high nitric oxide levels despite corticosteroid treatment. Steroid resistance may be related to poor inhalation technique, inadequate dosage, overwhelming anti-inflammatory technique, or poor compliance.
* Prediction of exacerbation of asthma

Currently, prediction of exacerbation of asthma is based on self-assessment of peak flow meter measurements. Increasing levels of exhaled nitric oxide may be able to predict exacerbations before the onset of clinical symptoms or changes in peak flow values.
* Dose Optimization

There has been interest in using measurements of exhaled nitric oxide to guide dosing of anti-inflammatory medications.

In addition to asthma, the following clinical applications of NO measurement have been proposed:

* Assessment of chronic cough

Chronic cough may be related to smoking, postnasal drip, gastroesophageal reflux, COPD, or asthma. Elevation of exhaled nitric oxide may point to asthma as the etiology.
* Assessment of cystic fibrosis

Exhaled nitric oxide appears to be decreased in patients with cystic fibrosis
* Rhinitis

Nasal nitric oxide (as opposed to exhaled nitric oxide) may be increased in patients with allergic rhinitis.
* Primary ciliary dyskinesia

Nasal nitric oxide may be decreased in patients with primary ciliary dyskinesia.

Source:http://www.everydayhealth.com/blogs/asthma-management/measurement-of-exhaled-nitric-oxide-and-exhaled-breath-condensate-in-the-diagnosis-and-management-of-asthma-and-other-respiratory-disorders

Tailored interventions based on exhaled nitric oxide versus clinical symptoms for asthma in children and adults

2010-01-28T00:44:00.000-08:00

Background
The measurement of severity and control of asthma in both children and adults can be based on subjective or objective measures. It has been advocated that fractional exhaled nitric oxide (FeNO) can be used to monitor airway inflammation as it correlates with some markers of asthma. Interventions for asthma therapies have been traditionally based on symptoms and/or spirometry.

Objectives
To evaluate the efficacy of tailoring asthma interventions based on exhaled nitric oxide in comparison to clinical symptoms (with or without spirometry/peak flow) for asthma related outcomes in children and adults.

Search strategy
We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last search was completed in February 2009.

Selection criteria
All randomised controlled comparisons of adjustment of asthma therapy based on exhaled nitric oxide compared to traditional methods (primarily clinical symptoms and spirometry/peak flow).

Data collection and analysis
Results of searches were reviewed against pre-determined criteria for inclusion. Relevant studies were independently selected in duplicate. Two authors independently assessed trial quality and extracted data. Authors were contacted for further information with response from one.

Main results
Two studies have been added for this update, which now includes six (2 adults and 4 children/adolescent) studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut off levels, the way in which FeNO was used to adjust therapy and duration of study. Of 1053 participants randomised, 1010 completed the trials. In the meta-analysis, there was no significant difference between groups for the primary outcome of asthma exacerbations or for other outcomes (clinical symptoms, FeNO level and spirometry). In post-hoc analysis, a significant reduction in mean final daily dose inhaled corticosteroid per adult was found in the group where treatment was based on FeNO in comparison to clinical symptoms, (mean difference -450 mcg; 95% CI -677 to -223 mcg budesonide equivalent/day). However, the total amount of inhaled corticosteroid used in one of the adult studies was 11% greater in the FeNO arm. In contrast, in the paediatric studies, there was a significant increase in inhaled corticosteroid dose in the FeNO strategy arm (mean difference of 140 mcg; 95% CI 29 to 251, mcg budesonide equivalent/day).

Source:http://mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD006340/frame.html

Exhaled Nitric Oxide in Children With Asthma Receiving Xolair (Omalizumab), a Monoclonal Anti-Immunoglobulin E Antibody

2010-01-20T01:48:00.000-08:00

Objective. To evaluate the effect of a humanized monoclonal antibody to immunoglobulin E, omalizumab (Xolair, Novartis Pharmaceuticals, East Hanover, NJ; Genentech Inc, South San Francisco, CA), on airway inflammation in asthma, as indicated by the fractional concentration of exhaled nitric oxide (FENO), a noninvasive marker of airway inflammation. Xolair was approved recently by the US Food and Drug Administration for moderate-to-severe allergic asthma in adolescents and adults.

Study Design. As an addendum at 2 sites to a randomized, multicenter double-blind, placebo-controlled trial, FENO was assessed in children with allergic asthma over 1 year. There were 3 consecutive study periods: 1) stable dosing of inhaled beclomethasone dipropionate (BDP) when the dose was optimized (period of 16 weeks); 2) inhaled steroid-reduction phase (period of 12 weeks), during which BDP was tapered if subjects remained stable; and 3) open-label extension phase, during which subjects receiving placebo were switched to active omalizumab (period of 24 weeks). The primary outcome was area under the FENO versus time curve (AUC) for adjusted FENO, defined as the ratio of FENO at each time point compared with the value at baseline.

Results. Twenty-nine subjects participated and were randomized to omalizumab (n = 18) and placebo (n = 11) treatment groups in a 2:1 ratio dictated by the main study. There was a significant difference for age, resulting in a difference in absolute forced expiratory volume in 1 second but no difference in asthma severity based on the forced expiratory volume in 1 second percentage predicted. Baseline BDP dose was comparable between groups, as were baseline values of mean FENO (active: 38.6 ± 25.6 ppb; placebo: 52.7 ± 52.9 ppb). The degree of BDP dose reduction during the steroid-reduction and open-label phases was equivalent between the omalizumab and placebo-treated groups; subjects in the omalizumab- and placebo-treated groups had reduced their BDP dose by an average of 51% and 60%, respectively, at the end of the steroid-reduction phase and by 68% and 94%, respectively, by the end of the open-label period. In the active and placebo groups, 44% and 27% and 75% and 73% of subjects had stopped use of inhaled corticosteroids at the end of the steroid-reduction and open-label phases, respectively. There was no significant difference between the active and placebo groups during the steroid-stable phase for AUC of adjusted nitric oxide (1.31 ± 1.511 vs 1.45 ± 0.736). However, during the steroid-reduction phase, the variability of adjusted FENO in the placebo-treated group was greater than that of the omalizumab-treated group at most visits, with a significant difference between groups for AUC of adjusted nitric oxide (0.88 ± 0.69 vs 1.65 ± 1.06). FENO fell from 82.1 ± 55.6 ppm at the end of the steroid-reduction phase to 33.3 ± 21.6 ppb at the end of the open-label period in the placebo group who were placed on active omalizumab. This decrease occurred while the mean dose of BDP remained very low. Analysis of FENO over 52 weeks of omalizumab treatment in the active group demonstrated that there was a significant reduction from baseline to the end of the open-label period (41.9 ± 29.0 to 18.0 ± 21.8 ppb) despite a high degree of steroid reduction.

Conclusion. In this preliminary study based on FENO, a noninvasive marker of airway inflammation, treatment with omalizumab may inhibit airway inflammation during steroid reduction in children with allergic asthma. The degree of inhibition of FENO was similar to that seen for inhaled corticosteroids alone, suggesting an antiinflammatory action for this novel therapeutic agent in asthma. This is in keeping with recent evidence that omalizumab inhibits eosinophilic inflammation in induced sputum and endobronchial tissue.

Source: http://pediatrics.aappublications.org/cgi/content/abstract/113/4/e308

Exhaled Nitric Oxide Shows Promise For COPD

2010-01-20T01:47:00.000-08:00

With the use of exhaled nitric oxide blossoming as a diagnostic and management tool on the asthma front, researchers now are exploring applications in other pulmonary diseases. Some respiratory specialists believe it has all the star-quality characteristics they look for in a lung-assessment tool - a noninvasive device that offers convenience, ease of use, and reliability at an affordable cost.

"It's still early and it's difficult at this point to say how it's going to end up, but I think the whole field of exhaled breath analysis is growing, and it's going to become more and more important," said Philip O'Reilly, MD, assistant professor of medicine at the University of Alabama, Birmingham.

As the field has gained momentum, the race to find new applications has too. A handful of small European trials have investigated a range of potential uses for eNO in chronic obstructive pulmonary disease - from predicted corticosteroid response to identification of exacerbations. They have not produced any winning results yet; however, investigators suggest eNO could be a useful clinical tool in COPD for certain patient populations.

"eNO measurement is not perfect, but it's useful if you're looking at it in the right context and asking the right question," said D. Robin Taylor, MD, PhD, FRCP, professor of respiratory medicine at the University of Otago in Dunedin, New Zealand.

Source: http://respiratory-care-sleep-medicine.advanceweb.com/Editorial/Content/Editorial.aspx?CC=213380

Exhaled Nitric Oxide Analysis

2010-01-18T21:21:00.000-08:00

Nitric oxide (NO) is a molecular gas previously considered to have a health-related role only in the context of its formation from the combustion of fossil fuels and its contribution to air pollution. However, this view has been greatly modified since the discovery in 1987 that the free radical NO was the previously uncharacterized endothelial-derived relaxing factor. It has now become clear that NO plays an important role in most human organ systems.

Within the respiratory system, NO regulates vascular and bronchial tone (promoting dilation of both vessels and airway), helps to facilitate the coordinated beating of ciliated epithelial cells, and is an important neurotransmitter for non-adrenergic, non-cholinergic neurons that run in the bronchial wall [1-8]. This molecule can be detected in exhaled gas in concentrations, which vary in health and disease.

The biology of NO, techniques available for measuring this gas in exhaled breath, and potential uses of these measurements in clinical practice will be reviewed here.

Source: http://www.uptodate.com/patients/content/topic.do?topicKey=~P33aJ4TN8/xTf

Exhaled nitric oxide and airway hyperresponsiveness in workers: a preliminary study in lifeguards

2010-01-15T01:56:00.000-08:00

Background

Airway inflammation and airway hyperresponsiveness (AHR) are two characteristic features of asthma. Fractional exhaled nitric oxide (FENO) has shown good correlation with AHR in asthmatics. Less information is available about FENO as a marker of inflammation from work exposures. We thus examined the relation between FENO and AHR in lifeguards undergoing exposure to chloramines in indoor pools.

Methods

39 lifeguards at six indoor pools were given a respiratory health questionnaire, FENO measurements, spirometry, and a methacholine bronchial challenge (MBC) test. Subjects were labeled MBC+ if the forced expiratory volume (FEV1) fell by 20% or more. The normalized linear dose-response slope (NDRS) was calculated as the percentage fall in FEV1 at the last dose divided by the total dose given. The relation between MBC and FENO was assessed using logistic regression adjusting on confounding factors. The association between NDRS and log-transformed values of FENO was tested in a multiple linear regression model.

Results

The prevalence of lifeguards MBC+ was 37.5%. In reactors, the median FENO was 18.9 ppb (90% of the predicted value) vs. 12.5 ppb (73% predicted) in non-reactors. FENO values ≥ 60% of predicted values were 80% sensitive and 42% specific to identify subjects MBC+. In the logistic regression model no other factor had an effect on MBC after adjusting for FENO. In the linear regression model, NDRS was significantly predicted by log FENO.

Conclusions

In lifeguards working in indoor swimming pools, elevated FENO levels are associated with increased airway responsiveness.

Source: http://www.biomedcentral.com/1471-2466/9/53

Exhaled nitric oxide in the diagnosis of childhood asthma

2010-01-15T01:53:00.000-08:00

Although asthma is the most common chronic disease of childhood,1 it remains a clinical diagnosis.Common symptoms include recurrent wheezing, cough, difficulty in breathing, and chest tightness, but no agreed "gold standard" definition exists. Improvements in symptoms and lung function seen after adequate treatment often provide retrospective confirmation of the diagnosis.

Accurate diagnosis of asthma in children may be difficult but is vital for two reasons. Firstly, a correct diagnosis is essential for the institution of guideline based treatment, which may involve specialist referral; this is needed to avoid the morbidity and rarely mortality associated with poorly controlled disease. Secondly, the exclusion of asthma prevents potential harm from inappropriate anti-asthma treatment and may highlight other crucial diagnoses such as cystic fibrosis.

Asthma is a heterogeneous disease, and data from large population based studies have informed the concept of different patterns or "phenotypes" in children who wheeze.

Source:http://www.bmj.com/cgi/content/extract/339/dec29_1/b5418

Exhaled nitric oxide in diagnosis and management of respiratory diseases

2010-01-11T02:48:00.000-08:00

The analysis of biomarkers in exhaled breath constituents has recently become of great interest in the diagnosis, treatment and monitoring of many respiratory conditions. Of particular interest is the measurement of fractional exhaled nitric oxide (FENO) in breath. Its measurement is noninvasive, easy and reproducible. The technique has recently been standardized by both American Thoracic Society and European Respiratory Society. The availability of cheap, portable and reliable equipment has made the assay possible in clinics by general physicians and, in the near future, at home by patients. The concentration of exhaled nitric oxide is markedly elevated in bronchial asthma and is positively related to the degree of esinophilic inflammation. Its measurement can be used in the diagnosis of bronchial asthma and titration of dose of steroids as well as to identify steroid responsive patients in chronic obstructive pulmonary disease. In primary ciliary dyskinesia, nasal NO is diagnostically low and of considerable value in diagnosis. Among lung transplant recipients, FENO can be of great value in the early detection of infection, bronchioloitis obliterans syndrome and rejection. This review discusses the biology, factors affecting measurement, and clinical application of FENO in the diagnosis and management of respiratory diseases.

Source: http://www.thoracicmedicine.org/article.asp?issn=1817-1737;year=2009;volume=4;issue=4;spage=173;epage=181;aulast=Abba

CareFirst BlueCross BlueShield has Developed a New Medical Policy for Exhaled Nitric Oxide (eNO) Monitoring

2010-01-07T22:42:00.000-08:00

CareFirst Blue Cross Blue Shield is now the 1st major plan to cover exhaled nitric oxide (eNO) measurement in the diagnosis and treatment of asthma under CPT® code 95012.

Based on strong physician demand for eNO (exhaled nitric oxide), the medical directors of the CareFirst BlueCross BlueShield determined that the published, peer-reviewed evidence is sufficient to support benefit coverage of exhaled nitric oxide measurement for the diagnosis and treatment of asthma. A new Medical Policy has been developed and is being implemented for claims for CPT code 95012 filed after June 1, 2009.

CareFirst is the largest health care insurer in the Mid-Atlantic region, serving nearly 3.4 million members in Maryland, District of Columbia and portions of Virginia. This is an important milestone that demonstrates the recognition of exhaled nitric oxide in asthma care and management.

At Apieron, we are leading efforts to drive favorable coverage policies for exhaled nitric oxide on both national and regional levels. We look forward to bringing similar successes to your area and to ensuring that you and your patients can continue to benefit from the newest advancements in asthma care.

Source: www.apieron.com

Exhaled nitric oxide measurements: clinical application and interpretation

2010-01-05T03:14:00.001-08:00

The use of exhaled nitric oxide measurements (FEno) in clinical practice is now coming of age. There are a number of theoretical and practical factors which have brought this about. Firstly, FEno is a good surrogate marker for eosinophilic airway inflammation. High FEno levels may be used to distinguish eosinophilic from non-eosinophilic pathologies. This information complements conventional pulmonary function testing in the assessment of patients with non-specific respiratory symptoms. Secondly, eosinophilic airway inflammation is steroid responsive. There are now sufficient data to justify the claim that FEno measurements may be used successfully to identify and monitor steroid response as well as steroid requirements in the diagnosis and management of airways disease. FEno measurements are also helpful in identifying patients who do/do not require ongoing treatment with inhaled steroids. Thirdly, portable nitric oxide analysers are now available, making routine testing a practical possibility. However, a number of issues still need to be resolved, including the diagnostic role of FEno in preschool children and the use of reference values versus individual FEno profiles in managing patients with difficult or severe asthma.

Source: http://thorax.bmj.com/content/61/9/817.abstract

Outcomes using Exhaled Nitric Oxide Measurements

2009-12-30T22:24:00.000-08:00

Background: Exhaled nitric oxide (FENO) measurements may help to highlight when inhaled corticosteroid (ICS) therapy should or should not be adjusted in asthma. This is often difficult to judge. Our aim was to evaluate a decision-support algorithm incorporating FENO measurements in a nurse-led asthma clinic.

Methods: Asthma management was guided by an algorithm based on high (>45ppb), intermediate (30-45ppb), or low (<30ppb) FENO levels and asthma control status. This provided for one of eight possible treatment options, including diagnosis review and ICS dose adjustment.

Study measurements at each visit: FENO was measured according to current guidelines19 using a NIOX MINO electrochemical analyser20-22 or a NIOX chemiluminescence analyser (both Aerocrine, Solna, Sweden). The latter was available at the Research Unit, 5km. from the Health Centre, but was used only when there was technical failure of the NIOX MINO. To validate FENO results, the sensors from the NIOX MINO device were tested against a calibrated standard, and where appropriate, a correction factor was applied to take account of signal drift. Spirometry was performed according to accepted standards using a Spiro USB spirometer (Micro Medical, Kent, England). The study received ethical approval from the Lower South Island Ethics Committee, and each participant gave written informed consent. Each GP participated in a start-up meeting, but thereafter further directions regarding the conduct of the study were not given.

Source: http://bx.businessweek.com/health-20/outcomes-using-exhaled-nitric-oxide-measurements-as-an-adjunct-to-primary-care-asthma-management/10191006889617114657-51e7208d9510751bc632218ad12db87f/

Asthma is a chronic illness characterized by airway inflammation

2009-12-28T03:56:00.001-08:00

Asthma is a chronic illness characterized by symptoms such as shortness of breath, wheezing and cough, which vary in intensity over time. The primary pathogenic process driving the manifestations of asthma is airway inflammation which leads to two pathophysiological features of asthma: hyper-responsiveness or twitchiness of the airways in response to stimuli such as exercise or allergen exposure, and airway obstruction.5

Airway obstruction in asthma is due to three main factors:

1. Bronchoconstriction, where the smooth muscle surrounding the airways tightens in response to a trigger (e.g. exercise) and narrows the airway
2. Swelling of the airway wall due to inflammation
3. Mucus formation within the airways that obstructs the airflow

Narrower airways obstruct the normal flow of air, making it difficult to breathe and leading to typical signs and symptoms of asthma (like wheezing, coughing, chest tightness and shortness of breath). Worsening symptoms can result in an episode of “asthma attack,” or exacerbation.

Source: http://www.apieron.com/

Asthma Monitoring Devices - NIOX MINO

2009-12-23T23:04:00.000-08:00

I came to know about my asthma one year back. My asthma gets worse when I feel stressed. I start wheezing heavily and my breathing starts to get labored.I have been using peak flow meter for monitoring asthma. Recently I came across medical journals and articles which states that exhaled nitric oxide can be measured in a breath test for asthma or other conditions characterized by airway inflammation. Also we have certain devices like NIOX MINO to measure exhaled nitric oxide in asthmatic patients.

An excerpt from Primary Care Respiratory Journal (2009), states that FENO was measured according to current guidelines using a NIOX MINO electrochemical analyzer or a NIOX chemiluminescence analyzer (both Aerocrine, Solna, Sweden). The latter was available at the Research Unit, 5km. from the Health Centre, but was used only when there was technical failure of the NIOX MINO. It seems that the NIOX MINO Analyzer had frequent technical failures and significant sensor inaccuracy issues causing the researcher to apply a manual correction factor and/or rely on the expensive NIOX lab instrument as a backup.

Doesn't these devices sounds cumbersome to use it? Any information about it.

Source:http://www.healthcentral.com/asthma/c/52325/97595/comments/

The Insight eNO System does NOT require inhalation of NO free air

2009-12-21T00:36:00.000-08:00

Ambient Nitric Oxide

Nitric oxide in air constitutes what is called ‘ambient NO’. Most of the inhaled ambient NO enters the pulmonary blood by diffusion and binds to hemoglobin. The residual NO becomes part of the exhaled breath that only appears in the initial wash-out phase of a typical 11-second exhaled breath. Ambient NO is a function of the location, time of day etc. and can vary between 0 ppb and upwards of 200 ppb.

Exhaled NO (eNO) Profile

The exhaled nitric oxide (eNO) measurement profile of the Insight eNO System is characterized by an initial rise followed by a plateau. The Insight System analyzes nitric oxide sampled when the profile has reached the plateau which occurs during the last 4 sec of the exhalation breath maneuver. Nitric oxide (NO) is washed out in the initial phase and therefore does not affect the eNO readings obtained from the Insight System.

Studies Confirm Theory

A study was conducted where 12 subjects each performed 5 eNO tests preceded by inhalation of NO free air alternating with 5 eNO tests preceded by inhalation of air
containing a 200 ppb concentration of nitric oxide (NO). Testing based on these 120 measurements shows that the overall impact of high ambient NO on the results from
the Insight System is statistically insignificant (0.8 ppb). This result is consistent with a landmark publication2 confirming that the eNO results when sampled properly do not get affected by ambient NO.

Source: http://www.scribd.com/doc/23659899/Ambient-Nitric-Oxide

Outcomes using exhaled nitric oxide measurements as an adjunct to primary care asthma management

2009-12-16T23:21:00.001-08:00

BACKGROUND: Exhaled nitric oxide (FENO) measurements may help to highlight when inhaled corticosteroid (ICS) therapy should or should not be adjusted in asthma. This is often difficult to judge. Our aim was to evaluate a decision-support algorithm incorporating FENO measurements in a nurse-led asthma clinic.

METHODS: Asthma management was guided by an algorithm based on high (>45ppb), intermediate (30-45ppb), or low (<30ppb) FENO levels and asthma control status. This provided for one of eight possible treatment options, including diagnosis review and ICS dose adjustment.

RESULTS: Well controlled asthma increased from 41% at visit 1 to 68% at visit 5 (p=0.001). The mean fluticasone dose decreased from 312 mcg/day at visit 2 to 211mcg/day at visit 5 (p=0.022). There was a high level of protocol deviations (25%), often related to concerns about reducing the ICS dose. The % fall in FENO associated with a change in asthma status from poor control to good control was 35%.

CONCLUSION: An FENO-based algorithm provided for a reduction in ICS doses without compromising asthma control. However, the results may have been influenced by the education and support which patients received. Reluctance to reduce ICS dose was an issue which may have influenced the overall results. Trial registration: Australian Clinical Trials Registry # 012605000354684

Source: http://www.thepcrj.org/journ/view_article.php?article_id=667

Exhaled Nitric Oxide and its role in the treatment of Asthma - Part IV

2009-12-14T22:22:00.000-08:00

In the fourth part of the ongoing series, we discuss the findings from the reputed American Journal of Respiratory and Critical Care Medicine

An excerpt from American Journal of Respiratory and Critical Care Medicine in a study by Marie¨lle W. Pijnenburg, E. Marije Bakker, Wim C. Hop, and Johan C. De Jongste details the Titrating Steroids on Exhaled Nitric Oxide in Children with Asthma.

Rationale

Corticosteroids are the anti-inflammatory treatment of choice in asthma. Treatment guidelines are mainly symptom-driven but symptoms are not closely related to airway inflammation. The fraction of nitric oxide in exhaled air (FeNO) is a marker of airway inflammation in asthma.

Objective

We evaluated whether titrating steroids on FeNO improved asthma management in children.

Methods

Eighty-five children with atopic asthma, using inhaled steroids, were allocated to a FeNO group (n _ 39) in which treatment decisions were made on both FeNO and symptoms or to a symptom group (n _ 46) treated on symptoms only. Children were seen every 3 months over a 1-year period.

Measurements

Symptoms were scored during 2 weeks before visits and 4 weeks before the final visit. FeNO was measured at all visits, and airway hyper responsiveness and FEV1 were measured at the start and end of the study. Primary endpoint was cumulative steroid dose.

Results

Changes in steroid dose from baseline did not differ between groups. In the FeNO group, hyper responsiveness improved more than in the symptom group (2.5 vs. 1.1 doubling dose, p _0.04). FEV1 in the FeNO group improved, and the change in FEV1 was not significantly different between groups. The FeNO group had 8 severe exacerbations versus 18 in the symptom group. The change in symptom scores did not differ between groups. FeNO increased in the symptom group; the change in FeNO from baseline differed between groups (p _ 0.02).

Conclusion

In children with asthma, 1 year of steroid titration on FeNO did not result in higher steroid doses and did improve airway hyper responsiveness and inflammation.

Source:http://www.articlesbase.com/medicine-articles/exhaled-nitric-oxide-and-its-role-in-the-treatment-of-asthma-part-iv-1476602.html

Outcomes using exhaled nitric oxide measurements as an adjunct to primary care asthma management

2009-12-09T01:18:00.000-08:00

In a recent study, the feasibility of obtaining FENO measurements in primary care has been confirmed.13 Here, we evaluated the utility of using FENO levels in an unselected population of patients with a diagnosis of asthma in a primary care setting. The aims were two-fold: firstly, to assess whether an open FENO-based protocol – similar to, but less resourceintensive than those used in previous randomised controlled trials – could be applied in the primary care setting, and what the impact on asthma outcomes would be; and secondly, to evaluate the practical issues associated with using and interpreting FENO levels in a nurse-led asthma clinic.

FENO was measured according to current guidelines using a NIOX MINO electrochemical analyser or a NIOX chemiluminescence analyser (both Aerocrine, Solna, Sweden).The latter was available at the Research Unit, 5km. from the Health Centre, but was used only when there was technical failure of the NIOX MINO. To validate FENO results, the sensors from the NIOX MINO device were tested against a calibrated standard, and where appropriate, a correction factor was applied to take account of signal drift.

Source: http://www.scienceagogo.com/forum/ubbthreads.php?ubb=showflat&Number=32743

Insight eNO System

2009-12-06T22:52:00.000-08:00

The Insight eNO System measures exhaled nitric oxide (eNO), also known as FeNO, which is a well established indicator of airway inflammation in asthma. The Insight system is a highly accurate device, expressly designed for the physician’s office. It is non-invasive, safe, easy to use, and provides eNO results in less than a minute for better asthma management and care. Apieron's medical solution is a unique biosensor that, helps in asthma care by detecting trace amounts of nitric oxide molecules in a single human breath utilizing a proprietary technology.

Source: http://www.apieron.com/

Ambient Nitric Oxide: The Real Insight

2009-12-02T23:10:00.000-08:00

Nitric oxide in air constitutes what is called ‘ambient NO’. Most of the inhaled ambient NO enters the pulmonary blood by diffusion and binds to hemoglobin.The residual NO becomes part of the exhaled breath that only appears in the initial wash-out phase of a typical 11-second exhaled breath. Ambient NO is a function of the location, time of day etc. and can vary between 0 ppb and upwards of 200 ppb.

The exhaled nitric oxide (eNO) measurement profile of the Insight eNO System is characterized by an initial rise followed by a plateau. The Insight System analyzes nitric oxide sampled when the profile has reached the plateau which occurs during the last 4 sec of the exhalation breath maneuver. Nitric oxide (NO) is washed out in the initial phase and therefore does not affect the eNO readings obtained from the Insight System.

A study was conducted where 12 subjects each performed 5 eNO tests preceded by inhalation of NO free air alternating with 5 eNO tests preceded by inhalation of air containing a 200 ppb concentration of nitric oxide (NO). Testing based on these 120 measurements shows that the overall impact of high ambient NO on the resultsfrom the Insight System is statistically insignificant (0.8 ppb).This result is consistent with a landmark publication confirming that the eNO results when sampled properly do not get affected by ambient NO.

Source: http://www.apieron.com/asthma-information-downloads/Ambient-Nitric-Oxide-The-Real-Insight.pdf

Exhaled Nitric Oxide Levels Indicate Treatment Efficacy in Children

2009-12-01T22:42:00.000-08:00

MIAMI BEACH -- Children younger than 7 can successfully use devices that measure exhaled nitric oxide and monitor how well some treatments are controlling their asthma, a researcher reported here.

The measurement of nitric oxide gives doctors the opportunity to determine how well certain medications are handling asthma-caused inflammation in the airways.

"Similar to inhaled and systemic steroids, the anti-inflammatory effects of nebulized budesonide inhalation suspension can be monitored by measuring exhaled nitric oxide," Miguel Lanz, MD, of the AAADRS Clinical Research Center in Coral Gables, Fla., noted at a poster presentation during the annual meeting of the American College of Allergy, Asthma & Immunology.

Lanz said that in a small pilot study of 15 children with a mean age of 5 years, he determined the following:

* The effect of nebulized budesonide starts to occur within three days after initiation of treatment, as evidenced by the significant improvement in exhaled nitric oxide.
* Cessation of budesonide therapy revealed a return to baseline exhaled nitric oxide levels.
* The exhaled nitric oxide test is a quick, easy-to-perform, reproducible, and noninvasive marker of airway inflammation in young people with asthma.
* Children younger than 7 years can perform the respiratory maneuvers necessary for nitric oxide measurements in research mode, but only with a large, nonportable NIOX device.

"These children are capable of working with the larger NIOX device -- which is about the size of a mini-refrigerator -- better than the newer football-sized instrument," Lanz added.

He said the portable device -- although potentially handheld -- requires too many operations for youngsters to perform easily. The larger testing machine, which would require children to come to the clinic, requires only that the child exhale in a tube, and the machine does the rest of the work.

To conduct the the study, researchers obtained parental consent for children 4 to 6 years old who had been diagnosed with asthma for more than a year, were on stable medication, and were able to operate the nitric oxide measuring device.

At baseline, the mean exhaled nitric oxide level for the children was 25 parts per billion, Lanz said.

After three days of treatment with nebulized budesonide at a dose of 0.5 mg/2cc once daily in the open label study, the exhaled nitric oxide had decreased to 18 ppb (P<0.01) from baseline. By the end of the two-week trial, the exhaled nitric oxide level had fallen to 15 ppb (P<0.001) from baseline.

After a washout period, the exhaled nitric oxide levels rose to 26 ppb, he said.

Mean forced expiratory volume in one second (FEV1) improved from 85 to 96 (P<0.05). Mean peak expiratory flow improved from 143 L/min to 162 (P<0.05). After the washout period, the FEV1 and peak expiratory volume did not worsen, Lanz said.

Lanz said the study showed that the impact of nebulized budesonide on exhaled nitric oxide is similar to that of inhaled corticosteroids.

"This study is interesting in that we see we can make these measurements with young children," said Talal Nsouli, MD, director of the Watergate and Burke Allergy and Asthma Centers in Washington, D.C. He said that determining levels of exhaled nitric oxide "is one of the best ways of measuring inflammation."

Source:http://www.medpagetoday.com/MeetingCoverage/ACAAI/16939

Exhaled Nitric Oxide Monitoring For Asthma

2009-11-26T22:16:00.000-08:00

A couple of people have recently asked about the use of exhaled nitric oxide markers as part of your asthma care plan. Exhaled nitric oxide is a marker of airway inflammation, one of the key components of the pathophysiology of asthma. While exhaled nitric oxide testing has been available for some time at specialized asthma centers, the development of home monitoring devices for exhaled nitric oxide has recently had researchers asking the question if home monitoring could improve asthma control.

In a 2008 study sponsored by the National Institute of Allergy and Infectious Disease Inner City Asthma Consortium, compared standard asthma guideline treatment to treatment based on exhaled nitric oxide levels. While there was no difference in asthma symptoms, admissions to the hospital, or asthma exacerbations, it appeared that obese and highly allergic patients might benefit from using exhaled nitric oxide testing.

A 2005 study published in the New England Journal Of Medicine demonstrated that while inhaled nitric oxide did not decrease symptoms compared to standard care, patients utilizing inhaled nitric oxide could lower the doses of their inhaled steroids compared to standard care potentially decreasing risk of side effects.

A 2008 Cochrave Collaboration, an international not-for-profit and independent organization providing non-biased reviews of the evidence of healthcare treatments, review concluded"Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the four studies that were found, and the results show only modest differences. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids is currently uncertain."

Currently, many insurers consider exhaled nitric oxide testing investigational which means they will not pay for it. In reviewing the clinical policy guidelines of a national insurer, the insurer cites numerous studies which failed to show a clinical benefit. However, in reviewing clinical trials websites, there are several ongoing studies of inhaled nitric oxide in asthma patients. Thus, exhaled nitric oxide testing has not yet been definitively proven to improve asthma care although it may improve asthma outcomes in some groups.

Until more results are made available, you might want to discuss your particular case with your doctor, but expect to bear the costs if you decide to move forward. Alternatively, you could consider looking into a clinical trial using exhaled nitric oxide monitoring.

What do you think? Have you ever used exhaled nitric oxide monitoring?

Source: http://stanford.wellsphere.com/asthma-article/exhaled-nitric-oxide-monitoring-for-asthma/884205

Patent suite against Aerocrine for exhaled nitric oxide by Apieron, Inc.

2009-11-23T23:09:00.000-08:00

Apieron, Inc. the medical device company filed a patent suite relating to exhaled nitric oxide against Aerocrine. Read more on the patent suite filed by Apieron. Apieron is ventured backed medical device company that has challenged Aerocrine patent.

MENLO PARK, CALIF., Nov 18, 2009 – Apieron, Inc. has asked the court presiding over its patent suit against Aerocrine, Inc. to allow it to raise additional grounds for invalidating Aerocrine’s broadest patent relating to exhaled nitric oxide, U.S. Patent No. 5,922,610.

In its motion, Apieron alleges that recently obtained deposition testimony and interrogatory responses indicate that Drs. Kjell Alving, JanLundberg, and Edward Weitzberg, inventors named on the ’610 patent, were in possession of information material to the patentability of their invention—namely, the prior invention in the United States of the claimed subject matter by Dr. Benjamin M. Gaston—yet intentionally failed to disclose this information to the United States Patent and Trademark Office.

For its part, Aerocrine has asked the court to procedurally block Apieron from raising the new allegations, which it claims are not stated with the requisite specificity. Redacted versions of the parties' pleadings and exhibits are publicly available via the website of the U.S. District Court for the District of Delaware.

About Apieron Inc.

Apieron Inc. is a private, venture-backed medical device company based in Menlo Park, CA that was formed in early 2001 to develop a simple-to-use, non-invasive monitor for the measurement of exhaled nitric oxide (eNO) for the management of asthma. The Apieron biosensor technology platform utilizes a patented technology that allows for the highly sensitive detection of selected analytes like eNO. Apieron is committed to collaborating with physicians and patients to develop innovative medical solutions to improve quality of life and standards of care.

Source: http://www.pr-inside.com/patent-suite-against-aerocrine-for-exhaled-r1596787.htm

Asthma and Exhaled Nitric Oxide (eNO) - A Simple, New Breath Test to Help Manage Asthma

2009-11-20T04:46:00.000-08:00

Inflamed airways produce nitric oxide which becomes part of your breath.Exhaled nitric oxide has been studied well over the last 10 years. These studies have shown a strong relation between eNO and airway inflammation.Exhaled nitric oxide (eNO) increases as inflammation increases, and it decreases as inflammation decreases.

Simple breath tests are now available to measure eNO levels. Your patients simply breathe out steadily into a breath tube that is connected to the test device. The test itself takes just about 10 seconds. The results are available within one minute.

Source:http://www.slideshare.net/exhalednitricoxide/asthma-and-exhaled-nitric-oxide-eno-a-simple-new-breath-test-to-help-manage-asthma

Exhaled nitric oxide in the diagnosis and management of asthma

2009-11-16T22:43:00.000-08:00

Exhaled nitric oxide (eNO) used as an aid to the diagnosis and management of lung disease is receiving attention from pulmonary researchers and clinicians alike because it offers a noninvasive means to directly monitor airway inflammation. Research evidence suggests that eNO levels significantly increase in individuals with asthma before diagnosis, decrease with inhaled corticosteroid administration, and correlate with the number of eosinophils in induced sputum. These observations have been used to support an association between eNO levels and airway inflammation. This review presents an update on current opportunities regarding use of eNO in patient care, and more specifically on its potential usage for asthma diagnosis and monitoring. The review will also discuss factors that may complicate use of eNO as a diagnostic tool, including changes in disease severity, symptom response, and technical measurement issues. Regardless of the rapid, convenient, and noninvasive nature of this test, additional well-designed, long-term longitudinal studies are necessary to fully evaluate the clinical utility of eNO in asthma management.

Source: http://crd.sagepub.com/cgi/content/abstract/6/1/19

Asthma and Exhaled Nitric Oxide (eNO) - A Simple, New Breath Test to Help Manage Asthma

2009-11-13T02:05:00.000-08:00

When airways get inflamed, the inner walls of the airway swell, so there is less space for a smooth flow of air. Inflammation of the airways leads symptoms such as shortness of breath, wheezing and coughing. The primary focus of asthma treatment is to reduce inflammation. Unfortunately, current methods of testing lung function do not measure inflammation. Therefore, you have to correlate symptoms to disease severity when prescribing or adjusting medication.

Source: http://www.scribd.com/doc/22048625/Asthma-and-Exhaled-Nitric-Oxide-eNO-A-Simple-New-Breath-Test-to-Help-Manage-Asthma

Measurement of Exhaled Nitric Oxide and Exhaled Breath Condensate in the Diagnosis and Management of Asthma and Other Respiratory Disorders

2009-11-09T00:52:00.000-08:00

Description

Clinical Background

The National Heart, Lung, and Blood Institute, in its clinical guidelines regarding the management of asthma, offers the following definition of asthma: (2)

"Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular: mast cells, eosinophils, T lymphocytes, macrophages, neutrophils and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyper responsiveness to a variety of stimuli."

Guidelines for the management of persistent asthma stress the importance of long-term suppression of inflammation using steroids, leukotriene inhibitors, or other anti-inflammatory drugs. Existing techniques for monitoring the status of underlying inflammation have focused on bronchoscopy, with lavage and biopsy, or analysis by induced sputum. Given the cumbersome nature of these techniques, the ongoing assessment of asthma focuses not on the status of the underlying chronic inflammation, but rather on regular assessments of respiratory parameters such as FEV-1 and peak flow. Therefore, there has been interest in noninvasive techniques to assess the underlying pathogenic chronic inflammation as reflected by measurements of inflammatory mediators. Two new strategies have been investigated, the measurement of exhaled nitric oxide and the evaluation of exhaled breath condensate. Nitric oxide (NO) is an important endogenous messenger that is widespread in the human body, functioning for example, to regulate peripheral blood flow, platelet function, immune reactions, and neurotransmission, and also to mediate inflammation. In biologic tissues, nitric oxide is unstable, limiting measurement. However, in the gas phase nitric oxide is fairly stable, permitting its measurement in exhaled air. While nitric oxide is a volatile mediator that can be measured in exhaled air, most inflammatory mediators are not volatile and thus cannot be detected in the gas phase. Exhaled breath condensate (EBC) consists of exhaled air passed through a condensing or cooling apparatus, resulting in an accumulation of fluid. Although EBC is primarily derived from water vapor, it also contains aerosol particles or respiratory fluid droplets, which in turn contain various nonvolatile inflammatory mediators, such as cytokines, leukotrienes, oxidants, antioxidants, and various other markers of oxidative stress. The pH of EBC can also be measured. Various studies have focused on different components of EBC as inflammatory markers in respiratory disease. The following clinical roles for measurement of NO and EBC have been investigataed in the diagnosis and management of asthma:

* Diagnosis of asthma

The current method of asthma diagnosis focuses on the clinical history and the demonstration of reversible airflow limitation. For example, spirometry measurements may be performed before and after the administration of a short-acting bronchodilator to demonstrate the presence of reversible airflow limitation. Measurement of exhaled nitric oxide levels has been suggested as either an alternative or adjunct to spirometry.
* Response to anti-inflammatory treatment

Declining levels of exhaled nitric oxide suggest declining inflammation.
* Monitoring compliance of anti-inflammatory treatment

Persistent elevation of exhaled nitric oxide may suggest poor compliance with long-term therapy.
* Detection of steroid resistance

Steroid resistance may be reflected by persistently high nitric oxide levels despite corticosteroid treatment. Steroid resistance may be related to poor inhalation technique, inadequate dosage, overwhelming anti-inflammatory technique, or poor compliance.
* Prediction of exacerbation of asthma

Currently, prediction of exacerbation of asthma is based on self-assessment of peak flow meter measurements. Increasing levels of exhaled nitric oxide may be able to predict exacerbations before the onset of clinical symptoms or changes in peak flow values.
* Dose Optimization

There has been interest in using measurements of exhaled nitric oxide to guide dosing of anti-inflammatory medications.

In addition to asthma, the following clinical applications of NO measurement have been proposed:

* Assessment of chronic cough

Chronic cough may be related to smoking, postnasal drip, gastroesophageal reflux, COPD, or asthma. Elevation of exhaled nitric oxide may point to asthma as the etiology.
* Assessment of cystic fibrosis

Exhaled nitric oxide appears to be decreased in patients with cystic fibrosis
* Rhinitis

Nasal nitric oxide (as opposed to exhaled nitric oxide) may be increased in patients with allergic rhinitis.
* Primary ciliary dyskinesia

Nasal nitric oxide may be decreased in patients with primary ciliary dyskinesia.

Measurement of Nitric Oxide

The most commonly used technique for measurement of exhaled nitric oxide is chemiluminescence after reaction with ozone. Exhaled nitric oxide is typically measured during single breath exhalations. First, the subject inspires nitric oxide-free air via a mouthpiece until total lung capacity is achieved, followed immediately by exhalation through the mouthpiece into the measuring device. The early studies of exhaled nitric oxide showed various levels of nitric oxide in health and disease, attributed to the lack of a standardized technique of measurement. In 2005, the American Thoracic Society published updated recommendations for the standardized measurement of exhaled nitric oxide. (3)

In 2003, the U.S. Food and Drug Administration (FDA) approved for marketing the NIOX® Breath Nitric Oxide Test System for the following indication (4):

"[Measurements of the fractional nitric oxide (NO) concentration in expired breath (FE-NO)] provide the physician with means of evaluating an asthma patient’s response to anti-inflammatory therapy, as an adjunct to established clinical and laboratory assessments in asthma. NIOX should only be used by trained physicians, nurses and laboratory technicians. NIOX cannot be used with infants or by children approximately under the ages of 4, as measurement requires patient cooperation. NIOX should not be used in critical care, emergency care or in anesthesiology."

The Breathmeter is another device used to measure exhaled nitric oxide using laser spectroscopy. The Breathmeter has not yet received FDA approval for marketing.

Collection and Measurement of Exhaled Breath Condensate (EBC)

The basic technique of collecting EBC consists of a technique to cool exhaled air and collect EBC droplets. One commercially available system, the RTube consists of a disposable polypropylene condensation chamber that is cooled by an overlying aluminum cooling sleeve. There are a variety of laboratory techniques to measure the components of EBC, including such simple techniques as pH measurement, to the more sophisticated gas chromatography/mass spectrometry or high performance liquid chromatography, depending on the component of interest.

Source: http://bx.businessweek.com/medical-devices/view?url=http%3A%2F%2Fblue.regence.com%2Ftrgmedpol%2Fmedicine%2Fmed108.html

Assessment of Utility of Exhaled Nitric Oxide Measurement for Treatment Monitoring in Children With Asthma

2009-11-09T00:50:00.000-08:00

Purpose

The aim of this study is to assess the utility of exhaled nitric oxide measurement (FeNO) in treatment monitoring in children with asthma.

According to the aim of the study following assumptions are formulated:

1. Comparison of annual cumulative steroid dose, number of bronchodilator doses taken, number of asthma exacerbation, number of hospitalisation due to asthma, between group of children with asthma with FeNO monitored treatment (study group), and group of children with treatment monitored by GINA's grade of disease clinical control (control group)

2. Assessment of corelation of FeNO (ppb) with symptom score (points)and lung function (FEV1)

3. Comparison of values of non-specific bronchial hyperresponsiveness with methacholine (PC20M)between both study groups after 12. months of treatment.

Source: http://clinicaltrials.gov/ct2/show/NCT00500253

Exhaled Nitric Oxide as a Noninvasive Assessment of Chronic Cough

2009-10-23T03:33:00.000-07:00

Exhaled Nitric Oxide Measurement for Treatment of Asthma

2009-10-22T00:21:00.000-07:00

Description

Asthma is characterized by inflammation of the respiratory tract, with periodic airway obstruction and symptoms of wheezing, coughing, and dyspnea. The chronic inflammatory process can lead to degenerative changes in the respiratory tissues and impaired pulmonary function. Exhaled gaseous nitric oxide (NO), which is normally produced in the airway mucosa, is known to be elevated in asthmatic patients, and is even higher during acute exacerbations than during remissions. The measurement of exhaled NO has therefore been proposed as a surrogate marker of airway inflammation for purposes of evaluating a patient's response to medications and perhaps reduce dosages of inhaled corticosteroids.

Policy

Measurement of exhaled nitric oxide is considered medically necessary in the management of asthma patients.

Measurement of exhaled nitric oxide is considered experimental / investigational for all other conditions as it does not meet TEC criteria # 2-5.

Source: http://notesnet.carefirst.com/ecommerce/medicalpolicy.nsf/vwwebtablex/a11ca33d60150817852575f9004710ab?OpenDocument

Exhaled Nitric Oxide and Breath Condensate pH in Asthmatic Reactions Induced by Isocyanates

2009-10-19T23:18:00.000-07:00

Background: We investigated the usefulness of measurements of fractional exhaled nitric oxide (FeNO) and pH of exhaled breath condensate (EBC) for monitoring airway response after specific inhalation challenges with isocyanates in sensitized subjects.

Methods: Lung function (FEV1), FeNO, and pH in argon-deaerated EBC were measured before and at intervals up to 30 days after a specific inhalation challenge in 15 subjects with isocyanate asthma, in 24 not sensitized control subjects exposed to isocyanates, and in 3 nonasthmatic subjects with rhinitis induced by isocyanate. Induced sputum was collected before and 24 h after isocyanate exposure.

Results: Isocyanate-induced asthmatic reactions were associated with a rise in sputum eosinophil levels at 24 h (p < 0.01), and an increase in FeNO at 24 h (p < 0.05) and 48 h (p < 0.005), whereas FeNO level did not vary with isocyanate exposure in subjects with rhinitis and in control subjects. FeNO changes at 24 h positively correlated with corresponding sputum eosinophil changes (ρ = 0.66, p < 0.001). A rise in pH was observed in the afternoon samples of EBC, irrespective of the occurrence of isocyanate-induced asthmatic reactions.

Conclusions: We demonstrated that isocyanate-induced asthmatic reactions are associated with a consistent delayed increase in FeNO but not with the acidification of EBC.

Source: http://chestjournal.chestpubs.org/content/136/1/155.abstract

Exhaled Nitric Oxide: A Predictor of Steroid Response

2009-10-15T02:25:00.000-07:00

In the second part of the ongoing series, we discuss the findings from the reputed American Journal of Respiratory and Critical Care Medicine

An excerpt from American Journal of Respiratory and Critical Care Medicine in a study by Andrew D. Smith, Jan O. Cowan, Karen P. Brassett, Sue Filsell, Chris McLachlan, Gabrielle Monti-Sheehan, G. Peter Herbison, and D. Robin Taylor details the trial to establish the use of eNO in the measurements to guide treatment in chronic asthma.

The findings of the study are detailed below.

Rationale

The initial management of patients who present with persistent respiratory symptoms
includes recognizing those with the potential to benefit from inhaled steroid therapy. To date, this has required undertaking a “trial of steroid” to identify responders. There is increasing evidence that steroid response is more likely in patients with eosinophilic airway inflammation, and this can be assessed indirectly using exhaled nitric oxide (FENO) measurements.

Objectives

The aim was to assess the predictive accuracy of FENO to identify steroid response in 52 patients presenting with undiagnosed respiratory symptoms in a single-blind, fixed-sequence, Placebo controlled trial of inhaled fluticasone for 4 weeks.

Methods

Comparisons of predictive accuracy were made between FENO and other conventional predictors: peak flows, spirometry, bronchodilator response, and airway hyperresponsiveness measured at baseline. “Steroid response” was defined as change in symptoms, peak flows, spirometry, or airway hyperresponsiveness to adenosine based on established guidelines and recommendations.

Results

Steroid response was significantly greater in the highest FENO tertile (_ 47 ppb) for each endpoint. This outcome was independent of the diagnostic label. The predictive values for FENO were significantly greater than for almost all other baseline predictors, with an optimum cut point of 47 ppb.

Conclusions

FENO measurements greater than 47 ppb provide a means of predicting steroid response in patients with undiagnosed respiratory symptoms. Assessing airway inflammation is of more practical value than diagnostic labeling when considering the potential usefulness of inhaled anti-inflammatory therapy.

Source: http://www.zimbio.com/Bodybuilding/articles/n0uY6bS4m2C/Exhaled+Nitric+Oxide+Predictor+Steroid+Response

Advancing Asthma Management with Exhaled Nitric Oxide

2009-10-13T21:59:00.000-07:00

Exhaled nitric oxide (eNO) is an established marker of airway inflammation that can be safely and accurately measured in people with asthma. Asthma is a chronic disease characterized by inflammation of the airways caused by allergens and other triggers. Airway inflammation precedes symptoms. Evidence of inflammation is present at the onset of symptoms in newly diagnosed patients with asthma. Nitric oxide (NO), a free radical, is produced by the body as part of the inflammatory response and can be detected as exhaled nitric oxide in expired human breath. An elevated eNO level is suggestive of an inadequate anti-inflammatory regimen, which may be due to poor compliance or under-medication. The eNO test is simple to administer compared to some of the conventional lung function testing methods or breath analyses. The patient has to be seated and is required to exhale steadily for 11 seconds after taking in a deep breath. The Insight eNO System was developed to provide a practical and accurate means for measuring eNO levels via a simple breath test. Designed for routine use in physician offices and clinics, the Insight system enables physicians to monitor and manage asthma on a regular basis. The system includes a small desktop monitor with a large color display. It employs an eNO sensor to measure nitric oxide from the breath sample.

Source: http://www.apieron.com/asthma-information-downloads/Exhaled-Nitric-Oxide-Resource-Kit.pdf

Exhaled Nitric Oxide - Non-Invasive marker of Airway Inflammation

2009-10-12T21:39:00.000-07:00

• Exhaled nitric oxide (eNO) is a ubiquitous molecule in the body and is a non-invasive marker of airway inflammation
• eNO is known to be elevated in individuals with asthma, is increased when a subject is having an asthma attack, and is decreased in those individuals using corticosteroid medication
• eNO has been compared with other techniques for measuring inflammation (ex. breath condensate, induced sputum)

Source: http://depts.washington.edu/pmcenter/koenighealth05symp.pdf

Exhaled Nitric Oxide as a Noninvasive Assessment of Chronic Cough

2009-10-08T22:06:00.000-07:00

Exhaled nitric oxide (ENO) has been suggested as a marker of airway inflammation. This study aimed to evaluate the role of ENO in the investigation of chronic cough. We measured ENO in 38 adult patients reporting chronic cough, in 23 healthy control subjects, and in 44 asthmatics. In addition to the regular investigation, ENO was measured by a chemiluminescent analyzer using the restricted breath technique. In the chronic cough group, 30 were considered as nonasthmatic, whereas asthma was diagnosed in eight by a positive methacholine challenge. ENO values were significantly higher in patients with chronic cough attributable to asthma as compared with those with chronic cough not attributable to asthma and to healthy volunteers (75.0 ppb; 16.7 ppb; and 28.3 ppb, respectively). The sensitivity and specificity of ENO for detecting asthma, using 30 ppb as the ENO cutoff point, were 75 and 87%, respectively. The positive and negative predictive values were 60 and 93%, and the positive and negative likelihood ratios were 5.8 and 0.3, respectively. We conclude that ENO may have a role in the evaluation of chronic cough. In this group of patients, low ENO suggested little likelihood of asthma. The patients with chronic cough not attributable to asthma showed a low ENO value as compared with healthy volunteers and asthmatics.

Source: http://171.66.122.149/cgi/content/abstract/159/6/1810

Portable Exhaled Nitric Oxide as a Screening Tool for Asthma in Young Adults During Pollen Season

2009-10-07T02:06:00.000-07:00

Background: The fraction of exhaled NO (FeNO) is valuable for the follow-up of asthmatic patients. However, its usefulness as a screening tool for asthma is not established.

Methods: We screened a population of 961 university students with a modified European Community Respiratory Health Survey questionnaire that has been previously used for the screening of respiratory symptoms related to asthma. All subjects with a positive answer to at least one question (n = 149) were submitted to FeNO measurement with a portable nitric oxide analyzer. Subsequently, they were submitted to spirometry and evaluated by a physician blinded to FeNO measurements. Seventy students with no respiratory symptoms served as control subjects.

Results: Asthma was diagnosed in 63 subjects, and allergic rhinitis was diagnosed in 57 subjects. Asthmatics presented higher FeNO values than control subjects (median, 20 parts per billion [ppb]; interquartile range, 14 to 31 ppb; vs median, 11 ppb; interquartile range, 7 to 13 ppb, respectively; p < 0.0001), whereas they did not differ from patients with allergic rhinitis (median, 17 ppb; interquartile range, 12 to 23 ppb; p = 0.28). FeNO values > 19 ppb presented 85.2% specificity and 52.4% sensitivity for the diagnosis of asthma (area under the curve [AUC], 0.723). The diagnostic performance of FeNO was better in nonsmokers (AUC, 0.805), yet FeNO values > 25 ppb were characterized by specificity > 90% for the diagnosis of asthma both in smokers and in nonsmokers. However, FeNO was not a good marker for the differentiation between asthma and allergic rhinitis.

Conclusions: FeNO measurement with a portable analyzer is useful for the screening for asthma in young adults. Significant confounding factors are allergic rhinitis and current smoking.

Source: http://chestjournal.chestpubs.org/content/133/4/906.abstract

Clinical Utility of Exhaled Nitric Oxide Highlighted By American Thoracic Society Panel

2009-10-06T02:32:00.000-07:00

09.14.2009 – MENLO PARK, CALIF., June 2, 2009 – Apieron, Inc. highlighted recent clinical panel presentations underscoring the positive impact of measuring exhaled nitric oxide (eNO) for treating asthma in adults and children. The company also cited recognition that design and methodology issues led to mixed results in some randomized trials of eNO-guided therapy. Apieron develops and markets non-invasive monitors that measure exhaled nitric oxide (eNO) for better asthma management.

At the American Thoracic Society’s recent annual meeting, panelists in a session titled “Understanding Exhaled Nitric Oxide Gas Exchange” reported that adopters of eNO measurement have seen a significantly positive impact in treatment of adults and children, and that numerous academic studies support these clinical observations. The panelists also concurred with a paper by Prof. P.G. Gibson, University of Newcastle in Australia, outlining the limitations present in the design and methodology of ASthma TReatment ALgorithm (ASTRAL) studies and suggested design features for future studies. These design features, Dr. Gibson concludes in his paper, “should improve study performance and aid in obtaining a better estimate of eNO-guided asthma therapy.” Clinical & Experimental Allergy published the paper, “Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm studies,” in its April 2009 issue. An abstract is available here.

“eNO measurement needs to be an integral part of asthma treatment, and we look forward to stronger studies and practice guidelines for eNO to bring this important marker into mainstream practice,” said Bhairavi Parikh, PhD, Apieron Founder and Chief Technology Officer. “In clinical practice, adopters of eNO monitoring have reported that eNO is predictive of asthma in patients with normal lung function, predictive of lack of compliance with proscribed therapy, and predictive of response to steroids.”

The American Thoracic Society is presently developing guidelines for eNO monitoring.

The panel was held at the American Thoracic Society’s 2009 Annual Meeting in San Diego, on Wednesday, May 20, 2009. Details on the panel are available here.

About the Insight eNO System

The Insight eNO System has been available for use in the physician’s office since March 2008. The system uses a proprietary biosensor technology to measure exhaled nitric oxide, a well established indicator of asthma severity and steroid responsive airway inflammation. Measuring eNO and determining the level of airway inflammation can help clinicians more closely manage their patients’ inflammatory condition and therefore more precisely titrate medications, which can lead to fewer exacerbations.

About Apieron Inc.

Apieron Inc. is a private, venture-backed medical device company based in Menlo Park, CA that was formed in early 2001 to develop a simple-to-use, non-invasive monitor for the measurement of exhaled nitric oxide (eNO) for the management of asthma. The Apieron biosensor technology platform utilizes a patented technology that allows for the highly sensitive detection of selected analytes like eNO. Apieron is committed to collaborating with physicians and patients to develop innovative medical solutions to improve quality of life and standards of care.

Source: http://www.pitchengine.com/apieroninc/clinical-utility-of-exhaled-nitric-oxide-highlighted-by-american-thoracic-society-panel/25605/

Exhaled nitric oxide analysis

2009-10-04T21:54:00.000-07:00

INTRODUCTION — Nitric oxide (NO) is a molecular gas previously considered to have a health-related role only in the context of its formation from the combustion of fossil fuels and its contribution to air pollution. However, this view has been greatly modified since the discovery in 1987 that the free radical NO was the previously uncharacterized endothelial-derived relaxing factor. It has now become clear that NO plays an important role in most human organ systems.

Within the respiratory system, NO regulates vascular and bronchial tone (promoting dilation of both vessels and airway), helps to facilitate the coordinated beating of ciliated epithelial cells, and is an important neurotransmitter for non-adrenergic, non-cholinergic neurons which run in the bronchial wall [1-7]. This molecule can be detected in exhaled gas in concentrations, which vary in health and disease.

The biology of NO, techniques available for measuring this gas in exhaled breath, and potential uses of these measurements in clinical practice will be reviewed here. The therapeutic use of inhaled NO is discussed separately. (See "Inhaled nitric oxide in adults with pulmonary hypertension" and see "Novel therapies for the acute respiratory distress syndrome").

FORMATION OF NO — In biological systems, NO is formed by the action of one of the isoforms of the enzyme nitric oxide synthase (NOS). Three such isoforms have been identified and are termed type I or neuronal NOS (nNOS), type II or inducible NOS (iNOS), and type III or endothelial NOS (eNOS) (show table 1) [8,9]. Although these enzymes are distinct proteins encoded by genes on disparate chromosomes, all three catalyze the adduction of the guanidino nitrogen of the amino acid arginine to molecular oxygen, yielding NO and water (show figure 1).

Regulation of NOS — While the three isoforms of NOS catalyze the same reaction, regulation of the activity of these isozymes occurs through distinct processes. Both nNOS and eNOS are usually constitutively active and produce low amounts of NO, with output varying with changes in the intracellular calcium concentration. In contrast, iNOS binds calcium so avidly that its function is not influenced by calcium fluxes within the physiologic range. While not constitutively active in most settings, it has the capacity to generate large quantities of NO when transcriptionally upregulated by the inflammatory cytokines tumor necrosis factor-alpha (TNFa), interleukin 1-beta (IL-1B), and interferon-gamma (IFN-gamma) [8,9]. In vitro evidence suggests that this upregulation can be abolished by glucocorticoids [10].

Source: http://utdol.com/patients/content/topic.do?topicKey=~P33aJ4TN8/xTf&selectedTitle=37~66&source=search_result

Exhaled Nitric Oxide: A Predictor of Steroid Response Part – II

2009-09-30T23:50:00.000-07:00

In the second part of the ongoing series, we discuss the findings from the reputed American Journal of Respiratory and Critical Care Medicine

An excerpt from American Journal of Respiratory and Critical Care Medicine in a study by Andrew D. Smith, Jan O. Cowan, Karen P. Brassett, Sue Filsell, Chris McLachlan, Gabrielle Monti-Sheehan, G. Peter Herbison, and D. Robin Taylor details the trial to establish the use of eNO in the measurements to guide treatment in chronic asthma.

The findings of the study are detailed below.

Rationale

The initial management of patients who present with persistent respiratory symptoms
includes recognizing those with the potential to benefit from inhaled steroid therapy. To date, this has required undertaking a “trial of steroid” to identify responders. There is increasing evidence that steroid response is more likely in patients with eosinophilic airway inflammation, and this can be assessed indirectly using exhaled nitric oxide (FENO) measurements.

Objectives

The aim was to assess the predictive accuracy of FENO to identify steroid response in 52 patients presenting with undiagnosed respiratory symptoms in a single-blind, fixed-sequence, Placebo controlled trial of inhaled fluticasone for 4 weeks.

Methods

Comparisons of predictive accuracy were made between FENO and other conventional predictors: peak flows, spirometry, bronchodilator response, and airway hyperresponsiveness measured at baseline. “Steroid response” was defined as change in symptoms, peak flows, spirometry, or airway hyperresponsiveness to adenosine based on established guidelines and recommendations.

Results

Steroid response was significantly greater in the highest FENO tertile (_ 47 ppb) for each endpoint. This outcome was independent of the diagnostic label. The predictive values for FENO

were significantly greater than for almost all other baseline predictors, with an optimum cut point of 47 ppb.

Conclusions

FENO measurements greater than 47 ppb provide a means of predicting steroid response in patients with undiagnosed respiratory symptoms. Assessing airway inflammation is of more practical value than diagnostic labeling when considering the potential usefulness of inhaled anti-inflammatory therapy.

Source: http://www.articlesbase.com/medicine-articles/exhaled-nitric-oxide-a-predictor-of-steroid-response-part-ii-1233731.html

Exhaled nitric oxide in diagnosis and management of respiratory diseases

2009-09-29T00:40:00.000-07:00

Abba Abdullah AAnnals of Thoracic Medicine 2009 4(4):173-181The analysis of biomarkers in exhaled breath constituents has recently become of great interest in the diagnosis, treatment and monitoring of many respiratory conditions. Of particular interest is the measurement of fractional exhaled nitric oxide (FENO) in breath. Its measurement is noninvasive, easy and reproducible. The technique has recently been standardized by both American Thoracic Society and European Respiratory Society. The availability of cheap, portable and reliable equipment has made the assay possible in clinics by general physicians and, in the near future, at home by patients. The concentration of exhaled nitric oxide is markedly elevated in bronchial asthma and is positively related to the degree of esinophilic in…

Source: http://asthma.jbnewsblog.com/?p=3098

Exhaled Nitric Oxide in Evaluation of Young Adults with Chronic Cough

2009-09-23T01:41:00.000-07:00

Background. Bronchial asthma (A) is frequently diagnosed in patients with chronic cough. The study was conducted to determine whether an evaluation of fractional exhaled nitric oxide (FeNO) concentration can be used as a screening test for asthma in young adults with chronic cough (CCP). Methods. The study was performed on 540 (mean age 26.5; range 18-45 years), nonsmoking young CCP. All patients had resting spirometry within normal limits and no abnormalities on chest radiographs. Skin prick tests with common aeroallergens, bronchial provocation challenge with histamine, and evaluation of FeNO concentration were performed in all patients. One hundred healthy, nonsmoking, nonatopic subjects were used as control subjects (HC). Results. Asthma (A) was diagnosed in 178 CCP (32.96%). Other frequent diagnoses included rhinitis/sinusitis (R) and gastroesophageal reflux (GERD). The median FeNO concentration in A (86 ppb; 95% CI 72 to 94,5 ppb) was significantly greater than in R (37 ppb; 95% CI 35,6 to 42,9 ppb; p < 0.0001), GERD (14,8 ppb; 95%CI 13.3 to 16.2 ppb; p < 0.0001), or in HC (13 ppb; 95%CI 11 to 15 ppb; p < 0.0001). Significant correlation was found between logFeNO and bronchial reactivity expressed as logPC20 (r = -0.529; 95%CI -0.616 to -0.429; p < 0.0001), but even stronger correlation was demonstrated between logFeNO and peripheral blood eosinophilia (r = 0.757; 95%CI 0.717 to 0.792). Receiver Operator Characteristic (ROC) curve analysis revealed that CCP can be screened for A by measuring FeNO concentration. Using 40 ppb as a cut-off value for the FeNO concentration, the specificity 82.6% and sensitivity 88.3% can be achieved. Conclusion. In clinical practice, assessment of FeNO concentration can be used as a screening test for asthma in young adults who have chronic cough.

Source: http://www.informaworld.com/smpp/content~content=a914291690~db=all~jumptype=rss

Exhaled Nitric Oxide: A Predictor of Steroid Response Part – II

2009-09-21T00:15:00.000-07:00

In the second part of the ongoing series, we discuss the findings from the reputed American Journal of Respiratory and Critical Care Medicine

An excerpt from American Journal of Respiratory and Critical Care Medicine in a study by Andrew D. Smith, Jan O. Cowan, Karen P. Brassett, Sue Filsell, Chris McLachlan, Gabrielle Monti-Sheehan, G. Peter Herbison, and D. Robin Taylor details the trial to establish the use of eNO in the measurements to guide treatment in chronic asthma.

The findings of the study are detailed below.

Rationale

The initial management of patients who present with persistent respiratory symptoms includes recognizing those with the potential to benefit from inhaled steroid therapy. To date, this has required undertaking a “trial of steroid” to identify responders. There is increasing evidence that steroid response is more likely in patients with eosinophilic airway inflammation, and this can be assessed indirectly using exhaled nitric oxide (FENO) measurements.

Objectives

The aim was to assess the predictive accuracy of FENO to identify steroid response in 52 patients presenting with undiagnosed respiratory symptoms in a single-blind, fixed-sequence, Placebo controlled trial of inhaled fluticasone for 4 weeks.

Methods

Comparisons of predictive accuracy were made between FENO and other conventional predictors: peak flows, spirometry, bronchodilator response, and airway hyperresponsiveness measured at baseline. “Steroid response” was defined as change in symptoms, peak flows, spirometry, or airway hyperresponsiveness to adenosine based on established guidelines and recommendations.

Results

Steroid response was significantly greater in the highest FENO tertile (_ 47 ppb) for each endpoint. This outcome was independent of the diagnostic label. The predictive values for FENO

were significantly greater than for almost all other baseline predictors, with an optimum cut point of 47 ppb.

Conclusions

FENO measurements greater than 47 ppb provide a means of predicting steroid response in patients with undiagnosed respiratory symptoms. Assessing airway inflammation is of more practical value than diagnostic labeling when considering the potential usefulness of inhaled anti-inflammatory therapy.

Source: http://asthmaeno.livejournal.com/9484.html

Exhaled Nitric Oxide: A Predictor of Steroid Response Part – II

2009-09-17T00:24:00.000-07:00

In the second part of the ongoing series, we discuss the findings from the reputed American Journal of Respiratory and Critical Care Medicine

An excerpt from American Journal of Respiratory and Critical Care Medicine in a study by Andrew D. Smith, Jan O. Cowan, Karen P. Brassett, Sue Filsell, Chris McLachlan, Gabrielle Monti-Sheehan, G. Peter Herbison, and D. Robin Taylor details the trial to establish the use of eNO in the measurements to guide treatment in chronic asthma.

The findings of the study are detailed below.

Rationale

The initial management of patients who present with persistent respiratory symptoms includes recognizing those with the potential to benefit from inhaled steroid therapy. To date, this has required undertaking a “trial of steroid” to identify responders. There is increasing evidence that steroid response is more likely in patients with eosinophilic airway inflammation, and this can be assessed indirectly using exhaled nitric oxide (FENO) measurements.

Objectives

The aim was to assess the predictive accuracy of FENO to identify steroid response in 52 patients presenting with undiagnosed respiratory symptoms in a single-blind, fixed-sequence, Placebo controlled trial of inhaled fluticasone for 4 weeks.

Methods

Comparisons of predictive accuracy were made between FENO and other conventional predictors: peak flows, spirometry, bronchodilator response, and airway hyperresponsiveness measured at baseline. “Steroid response” was defined as change in symptoms, peak flows, spirometry, or airway hyperresponsiveness to adenosine based on established guidelines and recommendations.

Results

Steroid response was significantly greater in the highest FENO tertile (_ 47 ppb) for each endpoint. This outcome was independent of the diagnostic label. The predictive values for FENO

were significantly greater than for almost all other baseline predictors, with an optimum cut point of 47 ppb.

Conclusions

FENO measurements greater than 47 ppb provide a means of predicting steroid response in patients with undiagnosed respiratory symptoms. Assessing airway inflammation is of more practical value than diagnostic labeling when considering the potential usefulness of inhaled anti-inflammatory therapy.

Source: http://healthyweightlossprograms.net/?p=1604

Clinical Utility of Exhaled Nitric Oxide Highlighted By American Thoracic Society Panel

2009-09-13T23:53:00.000-07:00

PRLog (Press Release) – Sep 11, 2009 – MENLO PARK, CALIF., June 2, 2009 – Apieron, Inc. highlighted recent clinical panel presentations underscoring the positive impact of measuring exhaled nitric oxide (eNO) for treating asthma in adults and children. The company also cited recognition that design and methodology issues led to mixed results in some randomized trials of eNO-guided therapy. Apieron develops and markets non-invasive monitors that measure exhaled nitric oxide (eNO) for better asthma management.

At the American Thoracic Society’s recent annual meeting, panelists in a session titled “Understanding Exhaled Nitric Oxide Gas Exchange” reported that adopters of eNO measurement have seen a significantly positive impact in treatment of adults and children, and that numerous academic studies support these clinical observations. The panelists also concurred with a paper by Prof. P.G. Gibson, University of Newcastle in Australia, outlining the limitations present in the design and methodology of ASthma TReatment ALgorithm (ASTRAL) studies and suggested design features for future studies. These design features, Dr. Gibson concludes in his paper, “should improve study performance and aid in obtaining a better estimate of eNO-guided asthma therapy.” Clinical & Experimental Allergy published the paper, “Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm studies,” in its April 2009 issue. An abstract is available here.

“eNO measurement needs to be an integral part of asthma treatment, and we look forward to stronger studies and practice guidelines for eNO to bring this important marker into mainstream practice,” said Bhairavi Parikh, PhD, Apieron Founder and Chief Technology Officer. “In clinical practice, adopters of eNO monitoring have reported that eNO is predictive of asthma in patients with normal lung function, predictive of lack of compliance with proscribed therapy, and predictive of response to steroids.”

The American Thoracic Society is presently developing guidelines for eNO monitoring.
The panel was held at the American Thoracic Society’s 2009 Annual Meeting in San Diego, on Wednesday, May 20, 2009. Details on the panel are available here.

About the Insight eNO System

The Insight eNO System has been available for use in the physician’s office since March 2008. The system uses a proprietary biosensor technology to measure exhaled nitric oxide, a well established indicator of asthma severity and steroid responsive airway inflammation. Measuring eNO and determining the level of airway inflammation can help clinicians more closely manage their patients’ inflammatory condition and therefore more precisely titrate medications, which can lead to fewer exacerbations.

About Apieron Inc.

Apieron Inc. is a private, venture-backed medical device company based in Menlo Park, CA that was formed in early 2001 to develop a simple-to-use, non-invasive monitor for the measurement of exhaled nitric oxide (eNO) for the management of asthma. The Apieron biosensor technology platform utilizes a patented technology that allows for the highly sensitive detection of selected analytes like eNO. Apieron is committed to collaborating with physicians and patients to develop innovative medical solutions to improve quality of life and standards of care.

Source: http://hel-healthblog.blogspot.com/2009/09/clinical-utility-of-exhaled-nitric.html

Exhaled Nitric Oxide and its role in the treatment of Asthma

2009-09-10T01:33:00.000-07:00

In a series of discussions substantiated by findings and excerpts from reputed medical journals and scientists, we strive to understand the importance of exhaled nitric oxide and its role in the treatment of asthma.
In the first part of the series, we discuss the findings from the reputed New England Journal of Medicine on Use of Exhaled Nitric Oxide Measurements to Guide Treatment in Chronic Asthma.

In medicine, exhaled nitric oxide (eNO) can be measured in a breath test for asthma which is characterized by airway inflammation. Nitric oxide (NO) is a gaseous molecule produced by certain cell types in an inflammatory response. Exhaled NO (also referred to as FENO) is a promising biomarker as a guide to therapy in adults and children with asthma. The breath test has recently become available in many well-equipped hospitals in developed countries. Clinical trials have looked at whether tailoring asthma therapy based on eNO values is better than conventional care, in which therapy is gauged by symptoms and the results of lung function tests.
An excerpt from the New England Journal of Medicine in a study by Andrew D. Smith, M.B., Ch.B., Jan O. Cowan, Karen P. Brassett, G. Peter Herbison, M.Sc., and D. Robin Taylor, M.D. details the trial to establish the use of eNO in the measurements to guide treatment in chronic asthma.

The findings of the study are detailed below.

Background

International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FeNO) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment.

Methods

In a single-blind, placebo-controlled trial, the investigators randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FeNO measurements or an algorithm based on conventional guidelines. After the optimal dose was determined (phase 1), patients were followed up for 12 months (phase 2). The primary outcome was the frequency of exacerbations of asthma; the secondary outcome was the mean daily dose of inhaled corticosteroid.

Results

Forty-six patients in the FeNO group and 48 in the group whose asthma was treated according to conventional guidelines (the control group) completed the study. The final mean daily doses of fluticasone, the inhaled corticosteroid that was used, were 370 μg per day for the FeNO group (95 percent confidence interval, 263 to 477) and 641 μg per day for the control group (95 percent confidence interval, 526 to 756; P=0.003), a difference of 270 μg per day (95 percent confidence interval, 112 to 430). The rates of exacerbation were 0.49 episode per patient per year in the FeNO group (95 percent confidence interval, 0.20 to 0.78) and 0.90 in the control group (95 percent confidence interval, 0.31 to 1.49), representing a non-significant reduction of 45.6 percent (95 percent confidence interval for mean difference, ¡78.6 percent to 54.5 percent) in the FeNO group. There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils).

Conclusions

With the use of FeNO measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control.

Source: http://www.inspire.com/groups/us-news-health/journal/exhaled-nitric-oxide-and-its-role-in-the-treatment-of-asthma/

Exhaled NO helps diagnose suspected pediatric asthma

2009-09-07T21:58:00.000-07:00

NEW YORK (Reuters Health) - Measuring fractional exhaled nitric oxide (FeNO), a marker of airway inflammation, is useful in the early confirmation or exclusion of asthma in children, especially in cases where the diagnosis is not clear at presentation, researchers from Israel have found.

FeNO levels are elevated in at least 90% of children with asthma, Dr. Yakov Sivan from Dana Children's Hospital, Tel Aviv Sourasky Medical Center, noted in an email to Reuters Health.

In 150 consecutive school-aged children referred for evaluation of possible asthma, Dr. Sivan and his colleagues recorded FeNO, eosinophil counts in coughed sputum specimens, and spirometry results. After 18 months, asthma was diagnosed or ruled out using conventional criteria.

According to a report in the August issue of the Journal of Pediatrics, FeNO and eosinophil counts were significantly higher in the 69 children with steroid-naïve asthma, compared to the 44 children without asthma and the 37 children with asthma who were receiving controller medication.

At a cutoff point of 19 parts per billion (ppb), FeNO had high sensitivity, specificity, and positive and negative predictive values, at 80%, 92%, 89%, and 86%, respectively.

The sensitivity, specificity, and positive and negative predictive values of eosinophil count at a cutoff point of 2.7% were similar to that of FeNO (81%, 92%, 89%, and 85%, respectively).

"The results of this study demonstrate that FeNO in children with asthma is significantly increased when compared to children with similar symptoms in the absence of asthma," Dr. Sivan said.

The measurement of FeNO in children with clinical suspicion of asthma, the investigator continued, "provides very similar results to eosinophil count in induced sputum and offers a significantly higher diagnostic yield than the standard approach based on spirometry."

According to Dr. Sivan, "Children with FeNO levels greater than 23 ppb are very likely to have asthma, with a false-positive rate of less than 5%. In these patients, omitting further diagnostic workup, such as challenge testing, is justified."

"On the other hand, symptomatic children with FeNO levels not exceeding 15 ppb exhibit a very low chance of having asthma, with a false-negative rate not exceeding 5%, suggesting that other diseases than asthma should be considered to explain the patient's reported symptoms," the researcher added.

For assessing the status of airway inflammation, Dr. Sivan concluded, "measurement of the FeNO may be easier, more practical and less expensive" than measuring the percentage of eosinophils in induced sputum.

Source: http://www.rtmagazine.com/reuters_article.asp?id=20090828clin008.html

CareFirst BlueCross BlueShield: Exhaled Nitric Oxide Medically Necessary

2009-09-03T22:58:00.000-07:00

The largest health care insurer CareFirst BlueCross BlueShield in the Mid-Atlantic has adopted a policy stating that measurement of exhaled nitric oxide is considered medically necessary in the management of asthma patients.

In its policy update, CareFirst refers to research demonstrating that exhaled nitric oxide measurement can be used to both predict and avoid relapsing of your asthma. Additionally, exhaled nitric oxide can be used to monitor medication compliance and may help in identifying possible environmental trigger.

The policy change will now allow measurement of exhaled nitric oxide as part of your doctor's plan for your asthma.

Source: http://asthma.about.com/b/2009/08/22/carefirst-bluecross-blueshield-exhaled-nitric-oxide-medically-necessary.htm

Exhaled Nitric Oxide and its role in the treatment of Asthma

2009-09-01T23:21:00.000-07:00

In a series of discussions substantiated by findings and excerpts from reputed medical journals and scientists, we strive to understand the importance of exhaled nitric oxide and its role in the treatment of asthma.
In the first part of the series, we discuss the findings from the reputed New England Journal of Medicine on Use of Exhaled Nitric Oxide Measurements to Guide Treatment in Chronic Asthma.

In medicine, exhaled nitric oxide (eNO) can be measured in a breath test for asthma which is characterized by airway inflammation. Nitric oxide (NO) is a gaseous molecule produced by certain cell types in an inflammatory response. Exhaled NO also referred to as FENO) is a promising biomarker as a guide to therapy in adults and children with asthma. The breath test has recently become available in many well-equipped hospitals in developed countries. Clinical trials have looked at whether tailoring asthma therapy based on eNO values is better than conventional care, in which therapy is gauged by symptoms and the results of lung function tests.

An excerpt from the New England Journal of Medicine in a study by Andrew D. Smith, M.B., Ch.B., Jan O. Cowan, Karen P. Brassett, G. Peter Herbison, M.Sc., and D. Robin Taylor, M.D. details the trial to establish the use of eNO in the measurements to guide treatment in chronic asthma.

The findings of the study are detailed below.

Background

International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FeNO) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment.

Methods

In a single-blind, placebo-controlled trial, the investigators randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FeNO measurements or an algorithm based on conventional guidelines. After the optimal dose was determined (phase 1), patients were followed up for 12 months (phase 2). The primary outcome was the frequency of exacerbations of asthma; the secondary outcome was the mean daily dose of inhaled corticosteroid.

Results

Forty-six patients in the FeNO group and 48 in the group whose asthma was treated according to conventional guidelines (the control group) completed the study. The final mean daily doses of fluticasone, the inhaled corticosteroid that was used, were 370 μg per day for the FeNO group (95 percent confidence interval, 263 to 477) and 641 μg per day for the control group (95 percent confidence interval, 526 to 756; P=0.003), a difference of 270 μg per day (95 percent confidence interval, 112 to 430). The rates of exacerbation were 0.49 episode per patient per year in the FeNO group (95 percent confidence interval, 0.20 to 0.78) and 0.90 in the control group (95 percent confidence interval, 0.31 to 1.49), representing a non-significant reduction of 45.6 percent (95 percent confidence interval for mean difference, ¡78.6 percent to 54.5 percent) in the FeNO group. There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils).

Conclusions

With the use of FeNO measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control.

Source: http://www.medhelp.org/user_journals/show/116970

Clinical Utility of Exhaled Nitric Oxide

2009-08-30T22:26:00.000-07:00

Exhaled nitric oxide has been studied since 1991 and several studies have shown it to be powerful tool in management of asthma. The American Thoracic Society (ATS) and European Respiratory Society (ERS) have jointly published guidelines for the standardized measurement of eNO.1 Recent asthma guidelines (NHLBI) indicate the positive role of inflammation measurements, of which eNO is the most clinically viable.

The clinical utility of measuring eNO include:

1. Selecting and Titrating Medication

Exhaled nitric oxide has been shown to predict the likelihood of a steroid response more consistently than spirometry or bronchodilator response.2 Use of eNO to direct inhaled steroid therapy was shown to reduce dosage while maintaining asthma control.3

2. Monitoring Compliance

An elevated eNO is suggestive of inadequate anti-inflammatory therapy – either from an insufficient dose or due to patient non-compliance.4 Reduction of exhaled NO levels after the start of therapy can reassure a physician that the treatment regime is being followed, and can demonstrate to the patient the physiological change that the therapy could achieve if properly followed.5

3. Predicting Exacerbation and Loss of Control

The ability to predict a worsening of symptoms is the most exciting clinical application of eNO measurement. Exhaled nitric oxide is a better predictor over FEV1 of both asthma control, loss of control and worsening of asthma.6 Elevated eNO measured at a clinic visit indicates increased risk of an exacerbation occurring within the next two weeks.7 Pediatric studies have found that an eNO level above 47 ppb predicts loss of control when inhaled steroids are reduced or withdrawn.8 A rise in eNO among patients who cease steroid therapy is predictive of an upcoming relapse.9 A home monitoring study showed that frequent eNO measurements may have predictive power for impending instability of asthma.10,11

Source: http://www.scienceagogo.com/forum/ubbthreads.php?ubb=showflat&Number=31397

Exhaled Nitric Oxide and its role in the treatment of Asthma - Part I

2009-08-27T00:16:00.000-07:00

In a series of discussions substantiated by findings and excerpts from reputed medical journals and scientists, we strive to understand the importance of exhaled nitric oxide and its role in the treatment of asthma.

In the first part of the series, we discuss the findings from the reputed New England Journal of Medicine on Use of Exhaled Nitric Oxide Measurements to Guide Treatment in Chronic Asthma.

In medicine, exhaled nitric oxide (eNO) can be measured in a breath test for asthma which is characterized by airway inflammation. Nitric oxide (NO) is a gaseous molecule produced by certain cell types in an inflammatory response. Exhaled NO (also referred to as FENO) is a promising biomarker as a guide to therapy in adults and children with asthma. The breath test has recently become available in many well-equipped hospitals in developed countries. Clinical trials have looked at whether tailoring asthma therapy based on eNO values is better than conventional care, in which therapy is gauged by symptoms and the results of lung function tests.
An excerpt from the New England Journal of Medicine in a study by Andrew D. Smith, M.B., Ch.B., Jan O. Cowan, Karen P. Brassett, G. Peter Herbison, M.Sc., and D. Robin Taylor, M.D. details the trial to establish the use of eNO in the measurements to guide treatment in chronic asthma.

The findings of the study are detailed below.

Background

International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FeNO) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment.

Methods

In a single-blind, placebo-controlled trial, the investigators randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FeNO measurements or an algorithm based on conventional guidelines. After the optimal dose was determined (phase 1), patients were followed up for 12 months (phase 2). The primary outcome was the frequency of exacerbations of asthma; the secondary outcome was the mean daily dose of inhaled corticosteroid.

Results

Forty-six patients in the FeNO group and 48 in the group whose asthma was treated according to conventional guidelines (the control group) completed the study. The final mean daily doses of fluticasone, the inhaled corticosteroid that was used, were 370 μg per day for the FeNO group (95 percent confidence interval, 263 to 477) and 641 μg per day for the control group (95 percent confidence interval, 526 to 756; P=0.003), a difference of 270 μg per day (95 percent confidence interval, 112 to 430). The rates of exacerbation were 0.49 episode per patient per year in the FeNO group (95 percent confidence interval, 0.20 to 0.78) and 0.90 in the control group (95 percent confidence interval, 0.31 to 1.49), representing a non-significant reduction of 45.6 percent (95 percent confidence interval for mean difference, ¡78.6 percent to 54.5 percent) in the FeNO group. There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils).

Conclusions

With the use of FeNO measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control.

Source: http://www.slideshare.net/exhalednitricoxide/exhaled-nitric-oxide-and-its-role-in-the-treatment-of-asthma

CareFirst BlueCross BlueShield: Exhaled Nitric Oxide Medically Necessary

2009-08-24T23:23:00.000-07:00

Exhaled Nitric Oxide in the Assessment of Asthma

2009-08-23T23:42:00.000-07:00

Purpose: Asthma is now defined as a TH2-mediated inflammatorydisease involving both large and small airways. However, assessment of airways inflammation is limited by techniques that are time consuming and possibly distressing to the patient. Exhaled nitric oxide, an easily and rapidly obtained noninvasive study, is a potential surrogate for measuring airways inflammation, but its clinical utility remains to be determined. This review examines the role of exhaled nitric oxide in assessing and directing therapy of asthmatic airways inflammation.

Recent Findings: It is well established that exhaled nitric oxide is increased in patients with untreated asthma and decreases with corticosteroid treatment. Exhaled nitric oxide also generally correlates with eosinophilic inflammation in asthmatic patients. Recent studies show that this correlation is especially pronounced in atopic subjects with asthma when compared with nonatopic subgroups. Recent studies also show that exhaled nitric oxide may be useful in identifying subclinical inflammation, assessing the antiinflammatory effects of asthma medications other than inhaled or oral corticosteroids, and heralding an asthma exacerbation. A number of new studies assert the utility of exhaled nitric oxide as a diagnostic tool for asthma.

Summary: Exhaled nitric oxide may be a useful parameter for monitoring asthmatic inflammation, adjusting therapy, and diagnosing asthma, although prospective longitudinal trials investigating the correlation between exhaled nitric oxide and clinical outcomes are necessary to determine its utility.

Source: http://www.mdjunction.com/diary/asthma-awareness/exhaled-nitric-oxide-in-the-assessment-of-asthma-21895

Exhaled Nitric Oxide in Children with Asthma and Short-Term PM2.5 Exposure in Seattle

2009-08-18T23:38:00.000-07:00

The objective of this study was to evaluate associations between short-term (hourly) exposures to particulate matter with aerodynamic diameters < 2.5 µm (PM2.5) and the fractional concentration of nitric oxide in exhaled breath (FeNO) in children with asthma participating in an intensive panel study in Seattle, Washington. The exposure data were collected with tapered element oscillation microbalance (TEOM) PM2.5 monitors operated by the local air agency at three sites in the Seattle area. FeNO is a marker of airway inflammation and is elevated in individuals with asthma. Previously, we reported that offline measurements of FeNO are associated with 24-hr average PM2.5 in a panel of 19 children with asthma in Seattle. In the present study using the same children, we used a polynomial distributed lag model to assess the association between hourly lags in PM2.5 exposure and FeNO levels. Our model controlled for age, ambient NO levels, temperature, relative humidity, and modification by use of inhaled corticosteroids. We found that FeNO was associated with hourly averages of PM2.5 up to 10-12 hr after exposure. The sum of the coefficients for the lag times associated with PM2.5 in the distributed lag model was 7.0 ppm FeNO. The single-lag-model FeNO effect was 6.9 [95% confidence interval (CI) , 3.4 to 10.6 ppb] for a 1-hr lag, 6.3 (95% CI, 2.6 to 9.9 ppb ) for a 4-hr lag, and 0.5 (95% CI, -1.1 to 2.1 ppb) for an 8-hr lag. These data provide new information concerning the lag structure between PM2.5 exposure and a respiratory health outcome in children with asthma.

Source: http://www.ehponline.org/docs/2005/7883/abstract.html

Caffeine decreases exhaled nitric oxide

2009-08-18T23:36:00.000-07:00

Background: Caffeine is known to inhibit phosphodiesterases, to mobilise intracellular calcium, and to act as an antagonist at adenosine receptors, all of which can potentially alter nitric oxide (NO) production. It was therefore hypothesised that caffeine may alter exhaled NO (eNO) levels.

Methods: In a randomised, single blind, crossover manner, 12 normal subjects consumed either (1) coffee and a placebo capsule, (2) decaffeinated coffee and a capsule of 200 mg caffeine, or (3) decaffeinated coffee and a placebo capsule. Serum caffeine levels were measured at baseline and 1 hour later. Exhaled NO levels were also measured at baseline and each hour for 4 hours.

Results: A significant percentage fall in mean (SE) eNO from baseline was seen 1 hour after either caffeinated coffee or a caffeine capsule when compared with placebo (13.5 (4.0)%, p=0.009 and 19.0 (3.8)%, p=0.001, respectively).

Conclusion: Caffeine causes a significant decrease in eNO which will need to be considered when designing trials to measure eNO levels. The mechanism may be via adenosine receptor antagonism or by altering levels of cGMP.

Source: http://thorax.bmj.com/cgi/content/abstract/57/4/361

Daily telemonitoring of exhaled nitric oxide and symptoms in the treatment of childhood asthma

2009-08-17T02:11:00.000-07:00

RATIONALE: Asthma treatment might improve when inhaled steroids are titrated on airway inflammation. Fractional exhaled nitric oxide (FeNO0.05), a marker of eosinophilic airway inflammation, can be measured at home. OBJECTIVES: We assessed daily FeNO0.05 telemonitoring in the management of childhood asthma.

METHODS: Children with atopic asthma (n = 151) were randomly assigned to two groups: FeNO0.05 plus symptom monitoring, or monitoring of symptoms only. All patients scored asthma symptoms in an electronic diary over 30 weeks; 77 received a portable nitric oxide (NO) analyzer. Data were transmitted daily to the coordinating centers. Patients were phoned every 3 weeks and their steroid dose was adapted according to FeNO0.05 and symptoms, or according to symptoms. Children were seen at 3, 12, 21, and 30 weeks for examination and lung function testing. The primary end point was the proportion of symptom-free days in the last 12 study weeks.

MEASUREMENTS AND MAIN RESULTS: Telemonitoring was feasible with reliable FeNO0.05 data for 86% of days, and valid diary entries for 79% of days. Both groups showed an increase in symptom-free days, improvement of FEV1 and quality of life, and a reduction in steroid dose. None of the changes from baseline differed between groups. The difference in symptom-free days over the last 12 weeks was 0.3% (P = 0.95; 95% confidence interval, -10 to 11%). There was a trend for fewer exacerbations in the FeNO0.05 group.

CONCLUSIONS: Thirty weeks of daily FeNO0.05 and symptom telemonitoring was associated with improved asthma control and a lower steroid dose. We found no added value of daily FeNO0.05 monitoring compared with daily symptom monitoring only.

Source: http://www.ncbi.nlm.nih.gov/pubmed/18931330

Exhaled nitric oxide and asthma control

2009-08-17T02:09:00.000-07:00

Exhaled Nitric Oxide Monitoring For Asthma

2009-08-12T23:39:00.001-07:00

A couple of people have recently asked about the use of exhaled nitric oxide markers as part of your asthma care plan. Exhaled nitric oxide is a marker of airway inflammation, one of the key components of the pathophysiology of asthma. While exhaled nitric oxide testing has been available for some time at specialized asthma centers, the development of home monitoring devices for exhaled nitric oxide has recently had researchers asking the question if home monitoring could improve asthma control.

In a 2008 study sponsored by the National Institute of Allergy and Infectious Disease Inner City Asthma Consortium, compared standard asthma guideline treatment to treatment based on exhaled nitric oxide levels. While there was no difference in asthma symptoms, admissions to the hospital, or asthma exacerbations, it appeared that obese and highly allergic patients might benefit from using exhaled nitric oxide testing.

A 2005 study published in the New England Journal Of Medicine demonstrated that while inhaled nitric oxide did not decrease symptoms compared to standard care, patients utilizing inhaled nitric oxide could lower the doses of their inhaled steroids compared to standard care potentially decreasing risk of side effects.

A 2008 Cochrave Collaboration, an international not-for-profit and independent organization providing non-biased reviews of the evidence of healthcare treatments, review concluded "Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the four studies that were found, and the results show only modest differences. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids is currently uncertain."

Currently, many insurers consider exhaled nitric oxide testing investigational which means they will not pay for it. In reviewing the clinical policy guidelines of a national insurer, the insurer cites numerous studies which failed to show a clinical benefit. However, in reviewing clinical trials websites, there are several ongoing studies of inhaled nitric oxide in asthma patients. Thus, exhaled nitric oxide testing has not yet been definitively proven to improve asthma care although it may improve asthma outcomes in some groups.

Until more results are made available, you might want to discuss your particular case with your doctor, but expect to bear the costs if you decide to move forward. Alternatively, you could consider looking into a clinical trial using exhaled nitric oxide monitoring.

What do you think? Have you ever used exhaled nitric oxide monitoring?

Source: http://asthma.about.com/b/2009/07/07/exhaled-nitric-oxide-monitoring-for-asthma.htm

Exhaled Nitric Oxide-1 (NOA-1)

2009-08-12T23:37:00.000-07:00

Research Summary

* Dust particles never settle in microgravity, therefore they are more concentrated in the environment ISS and are inhaled by crewmembers.

* Inhalation of dust particles into the airways leading to the lungs can cause inflammation of the airways.

* Measurements of the amount of Nitric Oxide, an exhaled gas, will be used to determine the amount of airway inflammation experienced by the ISS crewmembers.

* This research will lead to the advancements in treatment for patients that have lung inflammation illnesses, such as asthma, and countermeasures to ensure respiratory health on long duration space missions.

Description

Recent research has demonstrated that an elevation of expired Nitric Oxide is an early and accurate sign of airway inflammation especially in asthma but also after occupational dust inhalation. This experiment will utilize improved techniques for analysis of Nitric Oxide in expired air. This will be used to study physiological reactions in humans in microgravity.

Since dust never settles in microgravity, it is likely that there is an increased exposure of the human airways to inhaled particles in such an environment. The crewmembers will perform a simple inhalation-exhalation procedure on a bi-weekly basis during their stay on the ISS.

Elevated levels of expired Nitric Oxide compared to preflight levels would indicate airway inflammation. Data will be stored on a credit-card size memory unit. This experiment, which started during Expedition 12, is planned to be carried out over multiple Expedition Crews requiring eight subjects.

The Platon device, developed for spaceflight, has a dual use, as it is now also used to improve the treatment of asthma by allowing monitoring of patients at home. (Description provided by ESA: Astrolab Mission)

Source: http://www.nasa.gov/mission_pages/station/science/experiments/NOA-1.html#overview

Exhaled nitric oxide in the diagnosis and management of asthma

2009-08-12T00:01:00.001-07:00

The Predictive Value of Exhaled Nitric Oxide Measurements in Assessing Changes in Asthma Control

2009-08-12T00:00:00.000-07:00

Exhaled nitric oxide (eNO) levels are increased in untreated or unstable asthma and measurements can be made easily. Our aim was to assess the usefulness of eNO for diagnosing and predicting loss of control (LOC) in asthma following steroid withdrawal. Comparisons were made against sputum eosinophils and airway hyperresponsiveness (AHR) to hypertonic saline (4.5%). Seventy-eight patients with mild/moderate asthma had their inhaled steroid therapy withdrawn until LOC occurred or for a maximum of 6 wk. Sixty (77.9%) developed LOC. There were highly significant correlations between the changes in eNO and symptoms (p < 0.0001), FEV1 (p < 0.002), sputum eosinophils (p < 0.0002), and saline PD15 (p < 0.0002), and there were significant differences between LOC and no LOC groups. Both single measurements and changes of eNO (10 ppb, 15 ppb, or an increase of > 60% over baseline) had positive predictive values that ranged from 80 to 90% for predicting and diagnosing LOC. These values were similar to those obtained using sputum eosinophils and saline PD15 measurements. We conclude that eNO measurements are as useful as induced sputum analysis and AHR in assessing airway inflammation, with the advantage that they are easy to perform.

Source: http://ajrccm.atsjournals.org/cgi/content/abstract/164/5/738

Clinical Utility of Exhaled Nitric Oxide Highlighted By American Thoracic Society Panel

2009-08-10T23:52:00.000-07:00

Apieron, Inc. highlighted recent clinical panel presentations underscoring the positive impact of measuring exhaled nitric oxide (eNO) for treating asthma in adults and children. The company also cited recognition that design and methodology issues led to mixed results in some randomized trials of eNO-guided therapy. Apieron develops and markets non-invasive monitors that measure exhaled nitric oxide (eNO) for better asthma management

At the American Thoracic Society’s recent annual meeting, panelists in a session titled “Understanding Exhaled Nitric Oxide Gas Exchange” reported that adopters of eNO measurement have seen a significantly positive impact in treatment of adults and children, and that numerous academic studies support these clinical observations. The panelists also concurred with a paper by Prof. P.G. Gibson, University of Newcastle in Australia, outlining the limitations present in the design and methodology of ASthma TReatment ALgorithm (ASTRAL) studies and suggested design features for future studies. These design features, Dr. Gibson concludes in his paper, “should improve study performance and aid in obtaining a better estimate of eNO-guided asthma therapy.” Clinical & Experimental Allergy published the paper, “Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm studies,” in its April 2009 issue. An abstract is available here.

“eNO measurement needs to be an integral part of asthma treatment, and we look forward to stronger studies and practice guidelines for eNO to bring this important marker into mainstream practice,” said Bhairavi Parikh, PhD, Apieron Founder and Chief Technology Officer. “In clinical practice, adopters of eNO monitoring have reported that eNO is predictive of asthma in patients with normal lung function, predictive of lack of compliance with proscribed therapy, and predictive of response to steroids.”

The American Thoracic Society is presently developing guidelines for eNO monitoring.

The panel was held at the American Thoracic Society’s 2009 Annual Meeting in San Diego, on Wednesday, May 20, 2009. Details on the panel are available here.

About the Insight eNO System

The Insight eNO System has been available for use in the physician’s office since March 2008. The system uses a proprietary biosensor technology to measure exhaled nitric oxide, a well established indicator of asthma severity and steroid responsive airway inflammation. Measuring eNO and determining the level of airway inflammation can help clinicians more closely manage their patients’ inflammatory condition and therefore more precisely titrate medications,which can lead to fewer exacerbations.

About Apieron Inc.

Apieron Inc. is a private, venture-backed medical device company based in Menlo Park, CA that was formed in early 2001 to develop a simple-to-use, non-invasive monitor for the measurement of exhaled nitric oxide (eNO) for the management of asthma. The Apieron biosensor technology platform utilizes a patented technology that allows for the highly sensitive detection of selected analytes like eNO. Apieron is committed to collaborating with physicians and patients to develop innovative medical solutions to improve quality of life and standards of care.

Source: http://www.pr-inside.com/clinical-utility-of-exhaled-nitric-oxide-r1294878.htm

Exhaled Nitric Oxide and its role in the treatment of Asthma

2009-08-10T23:43:00.000-07:00

In a series of discussions substantiated by findings and excerpts from reputed medical journals and scientists, we strive to understand the importance of exhaled nitric oxide and its role in the treatment of asthma.

In the first part of the series, we discuss the findings from the reputed New England Journal of Medicine on Use of Exhaled Nitric Oxide Measurements to Guide Treatment in Chronic Asthma.

In medicine, exhaled nitric oxide (eNO) can be measured in a breath test for asthma which is characterized by airway inflammation. Nitric oxide (NO) is a gaseous molecule produced by certain cell types in an inflammatory response. Exhaled NO (also referred to as FENO) is a promising biomarker as a guide to therapy in adults and children with asthma. The breath test has recently become available in many well-equipped hospitals in developed countries. Clinical trials have looked at whether tailoring asthma therapy based on eNO values is better than conventional care, in which therapy is gauged by symptoms and the results of lung function tests.

An excerpt from the New England Journal of Medicine in a study by Andrew D. Smith, M.B., Ch.B., Jan O. Cowan, Karen P. Brassett, G. Peter Herbison, M.Sc., and D. Robin Taylor, M.D. details the trial to establish the use of eNO in the measurements to guide treatment in chronic asthma.

The findings of the study are detailed below.

Background

International guidelines for the treatment of asthma recommend adjusting the dose of inhaled corticosteroids on the basis of symptoms, bronchodilator requirements, and the results of pulmonary-function tests. Measurements of the fraction of exhaled nitric oxide (FeNO) constitute a noninvasive marker that may be a useful alternative for the adjustment of inhaled-corticosteroid treatment.

Methods

In a single-blind, placebo-controlled trial, the investigators randomly assigned 97 patients with asthma who had been regularly receiving treatment with inhaled corticosteroids to have their corticosteroid dose adjusted, in a stepwise fashion, on the basis of either FeNO measurements or an algorithm based on conventional guidelines. After the optimal dose was determined (phase 1), patients were followed up for 12 months (phase 2). The primary outcome was the frequency of exacerbations of asthma; the secondary outcome was the mean daily dose of inhaled corticosteroid.

Results

Forty-six patients in the FeNO group and 48 in the group whose asthma was treated according to conventional guidelines (the control group) completed the study. The final mean daily doses of fluticasone, the inhaled corticosteroid that was used, were 370 μg per day for the FeNO group (95 percent confidence interval, 263 to 477) and 641 μg per day for the control group (95 percent confidence interval, 526 to 756; P=0.003), a difference of 270 μg per day (95 percent confidence interval, 112 to 430). The rates of exacerbation were 0.49 episode per patient per year in the FeNO group (95 percent confidence interval, 0.20 to 0.78) and 0.90 in the control group (95 percent confidence interval, 0.31 to 1.49), representing a non-significant reduction of 45.6 percent (95 percent confidence interval for mean difference, ¡78.6 percent to 54.5 percent) in the FeNO group. There were no significant differences in other markers of asthma control, use of oral prednisone, pulmonary function, or levels of airway inflammation (sputum eosinophils).

Conclusions

With the use of FeNO measurements, maintenance doses of inhaled corticosteroids may be significantly reduced without compromising asthma control.

Source: http://www.articlealley.com/article_963413_17.html%5C

Measurement of Asthma using Exhaled Nitric Oxide

2009-08-10T23:42:00.000-07:00

The Insight eNO System measures exhaled nitric oxide (eNO) which is a well established indicator of airway inflammation in asthma. The Insight system is a highly accurate device, expressly designed for the physician's office. It is non-invasive, safe, easy to use, and provides eNO results in less than a minute. Apieron's unique biosensor detects trace amounts of nitric oxide molecules in a single human breath utilizing a proprietary technology in asthma management.

Source: http://www.mazeer.com/story.php?title=measurement-of-asthma-using-exhaled-nitric-oxide

Clinical utility of Exhaled Nitric Oxide

2009-08-10T01:33:00.001-07:00

Clinical Utility of Exhaled Nitric Oxide Highlighted By American Thoracic Society Panel

2009-08-10T00:36:00.000-07:00

PRLog (Press Release) – Jun 03, 2009 – Apieron, Inc. highlighted recent clinical panel presentations underscoring the positive impact of measuring exhaled nitric oxide (eNO) for treating asthma in adults and children. The company also cited recognition that design and methodology issues led to mixed results in some randomized trials of eNO-guided therapy. Apieron develops and markets non-invasive monitors that measure exhaled nitric oxide (eNO) for better asthma management.

At the American Thoracic Society’s recent annual meeting, panelists in a session titled “Understanding Exhaled Nitric Oxide Gas Exchange” reported that adopters of eNO measurement have seen a significantly positive impact in treatment of adults and children, and that numerous academic studies support these clinical observations. The panelists also concurred with a paper by Prof. P.G. Gibson, University of Newcastle in Australia, outlining the limitations present in the design and methodology of ASthma TReatment ALgorithm (ASTRAL) studies and suggested design features for future studies. These design features, Dr. Gibson concludes in his paper, “should improve study performance and aid in obtaining a better estimate of eNO-guided asthma therapy.” Clinical & Experimental Allergy published the paper, “Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm studies,” in its April 2009 issue. An abstract is available here.

“eNO measurement needs to be an integral part of asthma treatment, and we look forward to stronger studies and practice guidelines for eNO to bring this important marker into mainstream practice,” said Bhairavi Parikh, PhD, Apieron Founder and Chief Technology Officer. “In clinical practice, adopters of eNO monitoring have reported that eNO is predictive of asthma in patients with normal lung function, predictive of lack of compliance with proscribed therapy, and predictive of response to steroids.”

The American Thoracic Society is presently developing guidelines for eNO monitoring.

The panel was held at the American Thoracic Society’s 2009 Annual Meeting in San Diego, on Wednesday, May 20, 2009. Details on the panel are available here.

About the Insight eNO System

The Insight eNO System has been available for use in the physician’s office since March 2008. The system uses a proprietary biosensor technology to measure exhaled nitric oxide, a well established indicator of asthma severity and steroid responsive airway inflammation. Measuring eNO and determining the level of airway inflammation can help clinicians more closely manage their patients’ inflammatory condition and therefore more precisely titrate medications, which can lead to fewer exacerbations.

About Apieron Inc.

Apieron Inc. is a private, venture-backed medical device company based in Menlo Park, CA that was formed in early 2001 to develop a simple-to-use, non-invasive monitor for the measurement of exhaled nitric oxide (eNO) for the management of asthma. The Apieron biosensor technology platform utilizes a patented technology that allows for the highly sensitive detection of selected analytes like eNO. Apieron is committed to collaborating with physicians and patients to develop innovative medical solutions to improve quality of life and standards of care.

Source: http://www.prlog.org/10249401-clinical-utility-of-exhaled-nitric-oxide-highlighted-by-american-thoracic-society-panel.html

Exhaled Nitric Oxide in the Assessment of Asthma

2009-08-07T01:52:00.000-07:00

Purpose: Asthma is now defined as a TH2-mediated inflammatory disease involving both large and small airways. However, assessment of airways inflammation is limited by techniques that are time consuming and possibly distressing to the patient. Exhaled nitric oxide, an easily and rapidly obtained noninvasive study, is a potential surrogate for measuring airways inflammation, but its clinical utility remains to be determined. This review examines the role of exhaled nitric oxide in assessing and directing therapy of asthmatic airways inflammation.

Recent Findings: It is well established that exhaled nitric oxide is increased in patients with untreated asthma and decreases with corticosteroid treatment. Exhaled nitric oxide also generally correlates with eosinophilic inflammation in asthmatic patients. Recent studies show that this correlation is especially pronounced in atopic subjects with asthma when compared with nonatopic subgroups. Recent studies also show that exhaled nitric oxide may be useful in identifying subclinical inflammation, assessing the antiinflammatory effects of asthma medications other than inhaled or oral corticosteroids, and heralding an asthma exacerbation. A number of new studies assert the utility of exhaled nitric oxide as a diagnostic tool for asthma.

Summary: Exhaled nitric oxide may be a useful parameter for monitoring asthmatic inflammation, adjusting therapy, and diagnosing asthma, although prospective longitudinal trials investigating the correlation between exhaled nitric oxide and clinical outcomes are necessary to determine its utility.

Source: http://www.inspire.com/groups/us-news-health/journal/exhaled-nitric-oxide-in-the-assessment-of-asthma/

Clinical Utility of Exhaled Nitric Oxide

2009-08-07T01:51:00.000-07:00

Exhaled Nitric Oxide in Asthma

2009-08-02T23:47:00.000-07:00

PURPOSE OF THE STUDY: To measure and compare exhaled nitric oxide (eNO) levels in patients with asthma and healthy volunteers, to study peripheral blood lymphocyte cytokine expression, and to study the relationship between eNO and intracellular cytokine expression.

STUDY POPULATION: A total of 36 subjects were enrolled onto the study, with 19 asthmatic patients and 17 healthy control subjects.

METHODS: At least once per week for 4 weeks, patients with asthma visited the clinic and underwent a detailed history, physical examination, spirometry, and eNO-level measurement. These patients were maintained on established pharmacologic therapy regimens. A blood sample was taken and analyzed by flow cytometry. eNO was measured by using an NO analyzer. Univariate linear regression analysis was used to determine correlations between continuous variables and eNO concentrations.

RESULTS: eNO levels were significantly elevated in patients with moderate-to-severe asthma compared with those in healthy subjects (18.53 ± 2.00 vs 5.90 ± 0.90 ppb). With treatment, eNO levels in patients with moderate-to-severe asthma decreased to levels near those of the healthy subjects by 4 weeks. Interferon {gamma} expression was decreased in patients with moderate-to-severe asthma. An elevated eNO level was also associated with decreased interleukin 4 and interleukin 13 cytokine expression in CD8 lymphocytes.

CONCLUSIONS: eNO levels were elevated in patients with moderate-to-severe asthma. With 4 weeks of treatment, eNO levels in patients with moderate-to-severe asthma were no different from those in the control subjects. There was decreased interferon {gamma} expression by the CD4- and CD8-positive peripheral blood lymphocytes of patients with moderate-to-severe asthma. Elevated eNO levels were associated with suppression of both T-helper 1 and 2 cytokine expression by the peripheral blood lymphocyte, suggesting a systemic immunomodulatory effect.

REVIEWER COMMENTS: This study adds to the growing information on the utility of eNO levels to monitor asthma-treatment response. It demonstrates how eNO can be used to measure the reduction in airway inflammation as a response to treatment primarily in patients with moderate-to-severe asthma. At this point, it is not clear what the implications are of the association between elevated eNO levels and cytokine suppression.

Source: http://pediatrics.aappublications.org/cgi/content/abstract/120/Supplement_3/S134-a

The use of exhaled nitric oxide to guide asthma management

2009-08-02T23:45:00.000-07:00

RATIONALE: Current asthma guidelines recommend adjusting antiinflammatory treatment on the basis of the results of lung function tests and symptom assessment, neither of which are closely associated with airway inflammation.

OBJECTIVES: We tested the hypothesis that titrating corticosteroid dose using the concentration of exhaled nitric oxide in exhaled breath (Fe(NO)) results in fewer asthma exacerbations and more efficient use of corticosteroids, when compared with traditional management.

METHODS: One hundred eighteen participants with a primary care diagnosis of asthma were randomized to a single-blind trial of corticosteroid therapy based on either Fe(NO) measurements (n = 58) or British Thoracic Society guidelines (n = 60). Participants were assessed monthly for 4 months and then every 2 months for a further 8 months. The primary outcome was the number of severe asthma exacerbations. Analyses were by intention to treat.

MEASUREMENTS AND MAIN RESULTS: The estimated mean (SD) exacerbation frequency was 0.33 per patient per year (0.69) in the Fe(NO) group and 0.42 (0.79) in the control group (mean difference, -21%; 95% confidence interval [CI], -57 to 43%; p = 0.43). Overall the Fe(NO) group used 11% more inhaled corticosteroid (95% CI, -17 to 42%; p = 0.40), although the final daily dose of inhaled corticosteroid was lower in the Fe(NO) group (557 vs. 895 microg; mean difference, 338 microg; 95% CI, -640 to -37; p = 0.028).

CONCLUSIONS: An asthma treatment strategy based on the measurement of exhaled nitric oxide did not result in a large reduction in asthma exacerbations or in the total amount of inhaled corticosteroid therapy used over 12 mo, when compared with current asthma guidelines. Clinical trial registered with www.controlled-trials.com (ISRCTN08067387).

Source: http://www.ncbi.nlm.nih.gov/pubmed/17496226

Exhaled nitric oxide estimation by a simple and efficient noninvasive technique and its utility as a marker of airway inflammation in mice

2009-07-30T23:59:00.000-07:00

Allergic airway inflammation (AI) is commonly associated with enhanced exhaled nitric oxide (ENO) in both humans and mice. Since mouse models are being used to understand various mechanisms of asthma, a noninvasive, simple, and reproducible method to determine ENO in mice is required for serial nonterminal assessment that can be used independent of environmental situations in which the ambient air contains substantial amounts of NO as a contaminant. The aim of this study was to noninvasively measure ENO in individual mice and to test its utility as a marker of AI in different models of allergic AI. We modified the existing ENO measuring methods by incorporating flushing and washout steps that allowed simple but reliable measurements under highly variable ambient NO conditions (1–100 ppb). This method was used to serially follow ENO in acute and chronic models of allergic AI in mice. ENO was reproducibly measured by this modified method and was positively correlated to AI in both acute and chronic models of asthma but was not independently related to airway remodeling. Resolution of AI and other related parameters in dexamethasone-treated mice resulted in reduction of ENO, further confirming this association. Restriction of allergen challenge to pulmonary but not nasal airways was associated with a smaller increase in ENO compared with allergen challenge to both. Hence, ENO can now be reliably measured in mice independent of ambient NO levels and is a valid biomarker for AI. However, nasal and pulmonary airways are likely to be independent sources of ENO, and any results must be interpreted as such.

Source: http://jap.physiology.org/cgi/content/abstract/107/1/295

Effect of natural seasonal pollen exposure and repeated nasal allergen provocations on elevation of exhaled nitric oxide

2009-07-28T01:54:00.001-07:00

Background: Exhaled nitric oxide (FENO) is a marker for allergic airway inflammation. We wondered whether in patients with intermittent allergic rhinitis only (i) natural pollen exposure and (ii) artificial pollen exposure by repeated nasal allergen provocations may lead to an elevation of FENO.Methods: In two prospective studies, we compared the FENO of nonatopic controls with the FENO of nonasthmatic individuals with mild intermittent rhinitis to tree and/or grass pollen. Study I: 13 atopic individuals and seven controls had measurements of FENO, blood eosinophils and eosinophilic cationic protein (ECP) before, during and after pollen season. Study II: 16 atopic individuals and 12 controls had nasal allergen provocations on four following days out of pollen season, with daily measurements of FENO before, 2 and 6 h after provocation, and determination of blood eosinophils, ECP and FEV1 at baseline, on days 5 and 10[ndash]12.Results: Natural pollen exposure (study I) caused a significant elevation of FENO in allergic individuals. Nasal allergen provocations (study II) did not elicit a statistically significant rise neither of FENO nor of blood eosinophils between baseline and day 5. However, a subgroup of four individuals with a rise of blood eosinophils during nasal allergen provocations showed also a rise of FENO.Conclusions: We suppose that in allergic rhinitis a concomitant reaction of the bronchial system is dependent on a strong local inflammation leading to a generalized immune stimulation.

Source: http://idoctor.ro/effect-of-natural-seasonal-pollen-exposure-and-repeated-nasal-allergen-provocations-on-elevation-of-exhaled-nitric-oxide/

CareFirst BCBS Covers eNO Measurement for Diagnosis, Asthma Treatment

2009-07-28T01:51:00.000-07:00

07.23.2009 – MENLO PARK, Calif., July 22, 2009 -- Apieron, Inc. said today that CareFirst BlueCross BlueShield has adopted a positive coverage policy for the measurement of exhaled nitric oxide (eNO). The Medical Directors of CareFirst determined that the published, peer-reviewed evidence is sufficient to support benefit coverage for the treatment of asthma. The policy, effective July 20, 2009, states the measurement of exhaled nitric oxide is considered medically necessary in the management of asthma patients. CareFirst is the largest health care insurer in the Mid-Atlantic region, serving nearly 3.4 million members in Maryland, District of Columbia and portions of Virginia.

"In clinical practice, adopters of eNO monitoring have reported that eNO is predictive of asthma in patients with normal lung function, predictive of lack of compliance with medication regimens, and predictive of response to inhaled corticoid steroids,” said Ms. Holly McGarraugh, Apieron CEO & President. “We are delighted that CareFirst has recognized the valuable impact that eNO measurement can have on asthma treatment. We are working to encourage similar coverage policies among private payers and managed care organizations across the country.”

In a separate development, an official joint statement from the European Respiratory Society and the American Thoracic Society on June 25, 2009 included the recommendation that eNO be used as a biomarker for heightened concentrations of cells associated with asthma and allergy, and in evaluations of response to inhaled corticosteroid (ICS) treatments. The authors stated that eNO is a valuable tool to manage ICS and monitor its effects.

The American Thoracic Society is presently developing guidelines for eNO monitoring.

About the Insight eNO System

The Insight eNO System has been available for use in the physician's office since March 2008. The system uses a proprietary biosensor technology to measure exhaled nitric oxide, a well established indicator of asthma severity and steroid responsive airway inflammation. Measuring eNO and determining the level of airway inflammation can help clinicians more closely manage their patients' inflammatory condition and therefore more precisely titrate medications, which can lead to fewer exacerbations.

About Apieron Inc.

Apieron Inc. is a private, venture-backed medical device company based in Menlo Park, CA that was formed in early 2001 to develop a simple-to-use, non-invasive monitor for the measurement of exhaled nitric oxide (eNO) for the management of asthma. The Apieron biosensor technology platform utilizes a patented technology that allows for the highly sensitive detection of selected analytes like eNO. Apieron is committed to collaborating with physicians and patients to develop innovative medical solutions to improve quality of life and standards of care.

Source: http://www.pitchengine.com/apieroninc/carefirst-bcbs-covers-eno-measurement-for-diagnosis-asthma-treatment/19366/

Apieron Inc – Providing better insight into asthma management with Insight eNO

2009-07-14T00:17:00.000-07:00

Apieron Inc. -- a private, venture-backed company -- was formed in early 2001. Apieron was formed to develop a non-invasive monitor to measure exhaled nitric oxide (eNO) for the management of asthma. It was co-founded by Bhairavi Parikh, a scientist and mother who wanted to develop an innovative approach for measuring eNO in an effort to provide an accurate, reliable and simple-to-use device for her family. The company is collaborating with physicians and patients to develop innovative medical solutions to improve quality of life and standards of care for people living with asthma. The device, called Insight eNO, measures exhaled nitric oxide (NO). NO is a marker for inflammation and offers a means of monitoring a patient's response to anti-inflammatory treatment. Asthmatics are treated primarily by inhaling a type of steroid hormone called corticosteroids to help fight infection and reduce inflammation.

There is strong clinical evidence that suggests that asthma management and control can be significantly improved by regularly monitoring airway inflammation. Until now, the degree of inflammation has not been measurable in a simple and practical way. Measurement of eNO has been shown to optimize medication therapy and improve compliance among patients with asthma. Periodic measurement of eNO, in conjunction with the physician’s usual standard of care, provides a more comprehensive method to manage asthma efficiently and effectively.

The Insight™ eNO System is an accurate, easy-to-use system for measuring exhaled nitric oxide (eNO) levels, suitable for routine use in physician offices. The system uses a proprietary biosensor technology to measure exhaled nitric oxide, a well established indicator of asthma severity and steroid responsive airway inflammation. With eNO measurements, physicians can monitor inflammation on a regular basis. By adding accurate eNO measurements to the current ways in which asthma is monitored, physicians can develop a new level of understanding of their patient’s physiology and disease progression. Measuring eNO and determining the level of airway inflammation can help clinicians more closely manage their patients’ inflammatory condition and therefore more precisely titrate medications, which can lead to fewer asthma exacerbations. Ultimately, physicians can optimize medication and therapy to achieve better asthma control in their patients by incorporating routine eNO measurements into their practices.

The Insight eNO System has been available for use in the physician’s office since March 2008.

Apieron received U.S. Food and Drug Administration approval on March 17 to market the system. The small, desktop monitor, with an easy-to-read display and single-use sensors that measure NO in less than a minute, is designed for the physician's office.

Source: http://www.apieron.com

Exhaled Nitric Oxide Test for Asthma

2009-07-14T00:13:00.000-07:00

Exhaled nitric oxide is a simple test to measure the amount of nitric oxide in your lungs. Nitric oxide is one of the many gases people exhale. It is a marker of airway inflammation. The results from this test make it easier for you and your doctor to monitor your asthma and find the best treatment plan for you.

How do you get ready for the test?

Please follow these directions when getting ready for this test:

1) Do not eat, drink, or do strenuous exercise for 1 hour before the test is scheduled.

2) Do not perform spirometry or peak flow for 1 hour before the test is scheduled.

3) Continue to take all your medicine as you usually do, unless you have been told to withhold medications for other testing you will be doing.

What is done during the test?

You will be seated by the testing equipment and asked to slowly blow out. You will place a mouthpiece in your mouth. Next, you will take a deep breath in filling up your lungs. You will slowly blow the air out of your lungs. This will be repeated several times. You will have small rest times between each effort. The technician will explain the test and coach you to do it correctly.

How long will the test take?

The exhaled nitric oxide test often takes 30 minutes to complete.

How do you get to your test?

This test is performed in the Pediatric or Adult Clinics. If you have questions please call the Pulmonary Physiology Unit at 303-398-1530.

Source: http://www.nationaljewish.org/programs/tests/pulmonary-physiology/pulmonary-function/nitric-oxide.aspx

Monitoring airway inflammation on a regular basis could significantly improve asthma management

2009-07-10T00:00:00.000-07:00

Controlling inflammation of the airways in the lungs has become the central focus for managing asthma.5 Physicians involved in the treatment of asthma see their patients at regular intervals to monitor the severity of their patients' symptoms and measure lung function to assess asthma control and adjust medications to the level of perceived control. A patient who is taking an inadequate dose of anti-inflammatory medication or who is not compliant may have uncontrolled airway inflammation even in the absence of acute symptoms or changes in lung function.

Research has shown that exhaled nitric oxide (eNO) is a strong indicator of eosinophilic airway inflammation in asthma.10,11,12 The level of nitric oxide (NO) in exhaled breath increases as inflammation increases and decreases as inflammation decreases.

The measurement of eNO promises to be an important additional tool for the physician to be used in conjunction with history, physical examination and other standard testing, e.g. lung function. Exhaled nitric oxide (eNO) is elevated in untreated or inadequately treated asthma and falls after treatment with anti-inflammatory medications, and in particular inhaled steroids, thus confirming that airway inflammation is reduced and that the patient has taken the prescribed treatment.

The NHLBI (National Heart, Lung and Blood Institute) asthma guidelines recommend that monitoring patients on a regular basis and adjusting controller medication to the level of asthma control is the most effective way to control and manage asthma in the long-term.5 By better titrating the dosage of medication for each individual patient, physicians can significantly improve management of asthma in their patients. Over-medication exposes patients to potential side-effects of the drugs (steroids are perceived to impact growth in children) and under-medication can make them susceptible to irreversible damage to the airways. Currently, without accurate, routine measurements of airway inflammation at least in more severe asthma, it may be difficult to set the required level of anti-inflammatory therapy which can also vary from time to time due to seasonal changes. The NHLBI and the GINA (Global Initiative for Asthma) asthma guidelines now acknowledge that testing of airway inflammation may play a role in the management of asthma.

The Insight™ eNO System is an accurate, easy-to-use system for measuring exhaled nitric oxide (eNO) levels, suitable for routine use in physician offices. With eNO measurements, physicians can monitor inflammation on a regular basis. By adding accurate eNO measurements to the current ways in which asthma is monitored, physicians can develop a new level of understanding of their patient’s physiology and disease progression. Ultimately, physicians can optimize medication and therapy to achieve better asthma control in their patients by incorporating routine eNO measurements into their practices.

Source: http://www.apieron.com/about-asthma/asthma-management.php

ATS, ERS Jointly Issue Asthma Assessment Guidelines

2009-07-09T23:57:00.000-07:00

Newswise — The American Thoracic Society and the European Respiratory Society have released official standards for clinical trials and practice with respect to the assessment of asthma. The statement appears in the July 1 issue of the American Journal of Respiratory and Critical Care Medicine.

“In the past, there has been no standard way of assessing asthma. This has led to a lot of confusion for doctors who are managing asthma, and in research, it was difficult to compare the results of different studies,” said Helen Reddel, M.D., Ph.D., from the Woolcock Institute of Medical Research in Sydney, Australia, and co-chair of the international task force with D. Robin Taylor, M.D., Ph.D., from the University of Otago in Dunedin, New Zealand.

The American Thoracic Society and European Respiratory Society set up the task force of 24 asthma experts from North America, Europe, South Africa, Australia and New Zealand, to provide standardized definitions and measurement recommendations for three main areas: asthma control, asthma severity and asthma exacerbations.

Asthma Control

Asthma control was defined as the extent to which the features of asthma have been reduced or removed by treatment, with respect to both current clinical control and future risk. The explicit inclusion of future risk is a change from the previous approach that had mainly focused on current clinical control.

“The addition of future risk is important for three reasons: first, because some medications can improve symptoms while not treating the underlying disease; second, because some patients are at increased risk of asthma attacks despite having few symptoms; and third, because medication side-effects should be taken into account when deciding a patient’s need for treatment,” said Dr. Reddel.

To assess future risk, the report found that the most robust predictors were frequency of asthma exacerbations, repeated measures of lung function, and treatment side-effects. However, Dr. Reddel noted, “if a study is not long enough to measure these directly, the task force provided recommendations about surrogate markers such as sputum analysis or bronchial challenges which can predict the risk of these outcomes.”

The task force found that no single measure of asthma control could be recommended at present for use in clinical trials, but developed a short list of standardized endpoints, which were divided up into essential, desirable and optional. They recommended symptom-free days, reliever use, lung function, quality of life and a validated composite score as robust measurements for current clinical control. Other measurements which may be considered include a daily diary (preferably electronic) and a record of visits to doctors and the emergency room.

Asthma Severity

Asthma severity was defined as the intensity of treatment required to achieve good asthma control. “In the past, asthma severity was usually defined before a patient started asthma treatment, using measures which were almost identical to those used to assess asthma control. This was very confusing, and it meant that asthma severity could not be re-assessed once treatment had started,” explained Dr. Reddel.

Asthma Exacerbations

Asthma exacerbations were defined as events where symptoms worsen enough to require a change in treatment. For clinical trials, the task force standardized the definition of severe asthma exacerbations (also called severe attacks) as events that require urgent treatment such as corticosteroid tablets over three or more days in order to prevent serious consequences.

Recommendations

The task force made the clinical recommendation that doctors routinely ask every asthma patient a few simple questions about their asthma symptoms and management both in the short- and long-term: for the past one to four weeks, how many days a week they have had symptoms, how much quick-relief medication have they used, and whether they have woken at night from asthma; and for the past year, how many times they have had severe attacks, since this can identify patients who are at risk of severe attacks in the future.

“In clinical practice, it is particularly important to measure lung function for the diagnosis of asthma, and also for assessment of patients whose asthma is troublesome either because they have a lot of symptoms despite treatment, or because they have few symptoms but a lot of severe attacks,” said Dr. Reddel. For both research trials and clinical practice, the task force report provided detailed information about how each endpoint should be measured, the range of normal values and how the measurement should be interpreted.

The statement further stressed the need for more research, which will make the assessment of asthma control simpler in the future.

“More research is needed to understand more clearly how asthma control – and risks for asthma exacerbations - can be best assessed for the different types (i.e., phenotypes) of asthma, which have different responses to therapy,” John Heffner, M.D., past president of the ATS confirmed. “The task force identified that studies will need to characterize the clinical features of study patients during enrolment to ‘type’ their asthma and then note patterns of treatment responses for each type. With enough information, accurate type-specific measures to assess asthma control will emerge that will guide physicians in adjusting therapy for each phenotype.”

Future directions of research were suggested at the end of each section, and the statement concludes with an eye toward the possibility of identifying and determining appropriate biomarkers and for some groups of patients relying on those, rather than symptoms, to determine the appropriate medical treatment.

Source: http://www.newswise.com/articles/view/553741/

Asthma Management

2009-07-08T23:54:00.001-07:00

Apieron is a medical device company dedicated to developing technologies to improve the standard of care for people with asthma. Its Insight eNO System measures exhaled nitric oxide which is a well established indicator of airway inflammation for asthma management. Apieron’s Insight eNO System can detect trace amounts of nitric oxide in a patient’s breath, yielding results in less than a minute and can be performed in a doctor’s office, according to the company.

The eNO system was made possible by third-round funding and the Food and Drug Administration, and Apieron began selling the system in 2008, the company reports.

“The ongoing support of our past investors is a significant vote of confidence in our plan to improve the treatment of asthma with the simple, accurate, safe and efficient measurement of exhaled nitric oxide, a well-documented marker for airway inflammation,” said Holly McGarraugh, Apieron president and chief executive officer.

Bhairavi Parikh is Apieron's co-founder.

Source: http://www.indusbusinessjournal.com/ME2/dirmod.asp?sid=&nm=&type=Publishing&mod=Publications%3A%3AArticle&mid=8F3A7027421841978F18BE895F87F791&tier=4&id=96C317D72226473D87AC828859207598

The Use of Exhaled Nitric Oxide in the Diagnosis of Asthma in School Children

2009-07-08T23:52:00.000-07:00

Objectives

To evaluate the yield of the fractional exhaled nitric oxide (FeNO) in the diagnosis of asthma compared with spirometry and induced sputum cytologic study in school-age children.

Study design

Consecutive children referred for evaluation of possible asthma were included. At referral, all children completed FeNO measurement, sputum induction for eosinophil count (eos%) and spirometry. The diagnosis of asthma was performed after 18 months with conventional criteria. Receiver operating curves were used to determine cutoff points for disease status, and accuracy was calculated.

Results

A total of 150 children were included: 69 with steroid-naïve asthma, 44 without asthma, and 37 with asthma treated with controllers. FeNO and eos% levels were significantly higher in those with steroid-naïve asthma (P < .0001). The area under the receiver operating curve for FeNO and eos% were very high compared with forced expiratory volume in 1second (0.906, 0.921, 0.606, respectively). The sensitivity, specificity, and positive and negative predictive values for best cutoff points of FeNO (19 parts per billion) were 80%, 92%, 89%, and 86%, respectively, and were similar to eos% (best cutoff = 2.7%): 81%, 92%, 89%, 85%, respectively.

Conclusions

FeNO measurement is useful in early diagnosis of pediatric asthma. We suggest considering FeNO measurement in the evaluation of children suspected of having asthma, especially in cases where the diagnosis is not clear.

Source: http://www.jpeds.com/article/PIIS0022347609001553/abstract?rss=yes

Clinical Utility of Exhaled Nitric Oxide Highlighted By American Thoracic Society Panel

2009-07-08T01:46:00.000-07:00

Apieron, Inc. highlighted recent clinical panel presentations underscoring the positive impact of measuring exhaled nitric oxide (eNO) for treating asthma in adults and children. The company also cited recognition that design and methodology issues led to mixed results in some randomized trials of eNO-guided therapy. Apieron develops and markets non-invasive monitors that measure exhaled nitric oxide (eNO) for better asthma management.

At the American Thoracic Society’s recent annual meeting, panelists in a session titled “Understanding Exhaled Nitric Oxide Gas Exchange” reported that adopters of eNO measurement have seen a significantly positive impact in treatment of adults and children, and that numerous academic studies support these clinical observations. The panelists also concurred with a paper by Prof. P.G. Gibson, University of Newcastle in Australia, outlining the limitations present in the design and methodology of ASthma TReatment ALgorithm (ASTRAL) studies and suggested design features for future studies. These design features, Dr. Gibson concludes in his paper, “should improve study performance and aid in obtaining a better estimate of eNO-guided asthma therapy.” Clinical & Experimental Allergy published the paper, “Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm studies,” in its April 2009 issue. An abstract is available here.

“eNO measurement needs to be an integral part of asthma treatment, and we look forward to stronger studies and practice guidelines for eNO to bring this important marker into mainstream practice,” said Bhairavi Parikh, PhD, Apieron Founder and Chief Technology Officer. “In clinical practice, adopters of eNO monitoring have reported that eNO is predictive of asthma in patients with normal lung function, predictive of lack of compliance with proscribed therapy, and predictive of response to steroids.”

The American Thoracic Society is presently developing guidelines for eNO monitoring.

The panel was held at the American Thoracic Society’s 2009 Annual Meeting in San Diego, on Wednesday, May 20, 2009. Details on the panel are available here.

About the Insight eNO System

The Insight eNO System has been available for use in the physician’s office since March 2008. The system uses a proprietary biosensor technology to measure exhaled nitric oxide, a well established indicator of asthma severity and steroid responsive airway inflammation. Measuring eNO and determining the level of airway inflammation can help clinicians more closely manage their patients’ inflammatory condition and therefore more precisely titrate medications, which can lead to fewer exacerbations.

About Apieron Inc.

Apieron Inc. is a private, venture-backed medical device company based in Menlo Park, CA that was formed in early 2001 to develop a simple-to-use, non-invasive monitor for the measurement of exhaled nitric oxide (eNO) for the management of asthma. The Apieron biosensor technology platform utilizes a patented technology that allows for the highly sensitive detection of selected analytes like eNO. Apieron is committed to collaborating with physicians and patients to develop innovative medical solutions to improve quality of life and standards of care.

Source: http://www.prlog.org/10249401-clinical-utility-of-exhaled-nitric-oxide-highlighted-by-american-thoracic-society-panel.html

Exhaled Nitric Oxide Monitoring For Asthma

2009-07-08T01:45:00.000-07:00

A couple of people have recently asked about the use of exhaled nitric oxide markers as part of your asthma care plan. Exhaled nitric oxide is a marker of airway inflammation, one of the key components of the pathophysiology of asthma. While exhaled nitric oxide testing has been available for some time at specialized asthma centers, the development of home monitoring devices for exhaled nitric oxide has recently had researchers asking the question if home monitoring could improve asthma control.

In a 2008 study sponsored by the National Institute of Allergy and Infectious Disease Inner City Asthma Consortium, compared standard asthma guideline treatment to treatment based on exhaled nitric oxide levels. While there was no difference in asthma symptoms, admissions to the hospital, or asthma exacerbations, it appeared that obese and highly allergic patients might benefit from using exhaled nitric oxide testing.

A 2005 study published in the New England Journal Of Medicine demonstrated that while inhaled nitric oxide did not decrease symptoms compared to standard care, patients utilizing inhaled nitric oxide could lower the doses of their inhaled steroids compared to standard care potentially decreasing risk of side effects.

A 2008 Cochrave Collaboration, an international not-for-profit and independent organization providing non-biased reviews of the evidence of healthcare treatments, review concluded "Tailoring the dose of inhaled corticosteroids based on exhaled nitric oxide in comparison to clinical symptoms was carried out in different ways in the four studies that were found, and the results show only modest differences. The role of utilising exhaled nitric oxide to tailor the dose of inhaled corticosteroids is currently uncertain."

Currently, many insurers consider exhaled nitric oxide testing investigational which means they will not pay for it. In reviewing the clinical policy guidelines of a national insurer, the insurer cites numerous studies which failed to show a clinical benefit. However, in reviewing clinical trials websites, there are several ongoing studies of inhaled nitric oxide in asthma patients. Thus, exhaled nitric oxide testing has not yet been definitively proven to improve asthma care although it may improve asthma outcomes in some groups.

Until more results are made available, you might want to discuss your particular case with your doctor, but expect to bear the costs if you decide to move forward. Alternatively, you could consider looking into a clinical trial using exhaled nitric oxide monitoring.

What do you think? Have you ever used exhaled nitric oxide monitoring?

Source: http://asthma.about.com/b/2009/07/07/exhaled-nitric-oxide-monitoring-for-asthma.htm

Clinical applications of exhaled nitric oxide for the diagnosis and management of asthma

2009-07-07T00:26:00.000-07:00

BACKGROUND:
Patients with asthma routinely exhibit elevated levels of fractionated exhaled nitric oxide (FE(NO)), and this observation has led to studies investigating FE(NO) as a potential marker of airway inflammation. FE(NO) has been shown to enhance the diagnosis of asthma, detect deterioration in control of patients with asthma, and monitor response to anti-inflammatory therapy.

OBJECTIVES:
The aim of this work was to determine if FE(NO) measurement provides a noninvasive, well-tolerated, and standardized technique to monitor airway inflammation, and if it has the potential to complement standard asthma monitoring tools (eg, symptom diaries, control questionnaires, and pulmonary function testing) and to improve asthma control and patient outcomes.

METHODS:
Thirteen experts in the diagnosis and treatment of asthma met to discuss the use of FE(NO) in the diagnosis and management of patients with asthma. Participants were selected by Aerocrine, a medical, technical company with headquarters in Stockholm, Sweden, in consultation with their medical education partner Cadent Medical Communications located in Irving, Texas, to represent a diversity of specialists, including both clinicians and investigators, in the fields of allergy, immunology, and pulmonology. All participants were nominally compensated for their time to attend this closed scientific roundtable discussion. The meeting was supported by an educational grant from Aerocrine. This report represents the overall consensus reached by the participants on the clinical applicability of this technique.

RESULTS:
Our understanding of asthma has expanded so that investigators are now focusing on inflammation in addition to airway obstruction and hyper-reactivity. Whereas patient history, symptoms, and pulmonary function testing can assist in diagnosing asthma, they are not direct measures of the extent of airway inflammation. Elevated FE(NO) levels have been shown to reflect airway inflammation and to occur together with other conventional markers used to detect inflammation. Studies have confirmed increased levels of FE(NO) in both adults and children with asthma. In most studies, FE(NO) was found to be elevated 2- to 3-fold compared with normal controls. There are many determinants of FE(NO) levels, however, and factors other than inflammation must be considered when FE(NO) measurement is used to diagnose and monitor asthma. FE(NO) measurement alone is not sufficient for diagnosing or monitoring asthma, but it can be a valuable addition to current clinical tools.

CONCLUSIONS:
FE(NO) measurement is a noninvasive and reproducible test that is a surrogate measure of airway inflammation in patients with asthma. The test has demonstrated utility in diagnosing and managing asthma and in predicting response to therapy and, therefore, may be an important tool to incorporate into clinical care.

Source: http://www.find-health-articles.com/rec_pub_16199248-clinical-applications-exhaled-nitric-oxide-diagnosis-management.htm

Insight™ eNO System to Assist Physicians with Patient Asthma Management

2009-07-07T00:22:00.000-07:00

It is estimated that about 26 million people in the U.S. suffer from asthma, making it one of the most common diseases. In fact, over 40,000 American people miss school or work due to asthma and 5,000 people go to the emergency room due to an asthma attack every day. One-quarter of all emergency room visits are asthma related and asthma is the most common chronic childhood disease.

In medicine, exhaled nitric oxide (eNO) can be measured in a breath test for asthma or other conditions characterized by airway inflammation. Exhaled NO is a promising biomarker for the diagnosis, follow-up and as a guide to therapy in adults and children with asthma. The breath test has recently become available in many well-equipped hospitals in developed countries. Medically, eNO is used for people with asthma. Patients with asthma have higher eNO levels than other people. Their levels also rise together with other clinical and laboratory parameters of asthma.

The most widely used technique to measure eNO is with a chemical reaction that produces light. The NO in the breath sample reacts with ozone to form nitrogen dioxide in an excited state. When this returns back to its ground state, it emits light in quantities that are proportional to the amount of exhaled NO. Prior to the availability to measure eNO, assessing and managing airway inflammation was, for all practical purposes, little more than a guess! The ability to measure eNO in the physician’s office is “one giant step” in the care of adults and children with asthma.

The Insight eNO system by Apieron measures exhaled nitric oxide (eNO), which is a well-established indicator of airway inflammation and asthma control. The Insight system is a highly accurate device, expressly designed for the physician’s office. It is non-invasive, safe, easy to use, and provides results in less than a minute. Apieron’s unique biosensor detects trace amounts of nitric oxide molecules in a single human breath utilizing a proprietary technology. Physician office measurement of eNO is a much awaited breakthrough in medical technology that provides physicians with a reliable tool to measure their patients’ respiratory inflammation better than ever before. Measurement of eNO has also been shown to optimize medication therapy and improve adherence among patients with asthma.

Like in the case of 10 year old Maya, who has moderate persistent asthma. Based on her record, her doctor wanted to optimize her therapy, but had no objective way measure of her airway inflammation to monitor her response. Once he had access to exhaled nitric oxide (eNO) measurement with the Insight system, he incorporated exhaled nitric oxide (eNO) testing into her treatment plan. When he first measured Maya’s eNO, he felt it was a little high for her age, but he wanted to establish her usual eNO levels over time before changing her medication. Over the next 8 weeks, he found that her eNO values stayed steady after initially fluctuating. Over the next 8 weeks, Maya’s eNO values decreased. Her doctor was very pleased with the results but the next time he measured her, there was an almost two-fold increase in her eNO bothered him but further investigation with Maya and her father revealed that she had missed taking her medication recently. Her eNO values dropped back down once she resumed her treatment. By continuing to monitor Maya’s eNO levels regularly, her doctor was confident that he could fine-tune her medication. This helps Maya go fishing with her dad every weekend and not worry about her asthma levels.

Apieron Inc received clearance for the Insight eNO system by the U.S. Food and Drug Administration (FDA) in March 2008.

Source: http://www.freebenefittips.com/?p=1647

Apieron Strengthens Senior Leadership With Commercial, Financial Appointments

2009-07-06T00:35:00.000-07:00

Apieron, Inc., a medical device company, significantly strengthened its senior management team with the appointment of Steve Bubrick as Vice President, Sales & Marketing, and Bryan Miller as Vice President, Finance. Both appointments are effective immediately.

Mr. Bubrick has more than 20 years of operational and commercial experience in the consumer medical device industry, mainly in diabetes management. Prior to joining Apieron, Mr. Bubrick was the Vice President of Customer Care & Reimbursement for Bedford, Massachusetts-based Insulet Corp., where he contributed to the company's 170% revenue growth in 2008. Before joining Insulet, Mr. Bubrick was Director, Worldwide Marketing for in-vivo products at Abbott Diabetes Care, which was formed by Abbott's acquisition of TheraSense, at which he was a commercial and R&D director. Prior to TheraSense, Mr. Bubrick held numerous commercial and international roles at LifeScan Inc., a division of Johnson & Johnson. Steve earned his BA at the University of California, Berkeley.

"We see many parallels between the self glucose testing and eNO monitoring markets," said Holly McGarraugh, Apieron CEO. "Steve understands how to grow a start up business like Apieron through great marketing and customer relations. His leadership will play a strategically important role in understanding our markets, serving our customers and driving sales of the Insight eNO System. With Bryan filling a critical financial leadership role, and Steve joining us to focus our commercial efforts, we've significantly increased the depth and experience on the senior management team."

Mr. Miller most recently served as a Principal at Berkshire Financial Management LLC where he handled financial and management consulting and equity management of properties in California, Nevada and Arizona. Prior to that, Mr. Miller was the Senior Director of Finance at eV3, (FoxHollow Technologies, Inc.) the medical device company, where he was responsible for financial planning, forecasting and analysis as well as internal reporting. Mr. Miller has an extensive background in financial leadership roles, having held additional senior positions with Trimble Navigation, Shopping the Globe, Inc. and Sega of America. He earned his MBA at Stanford University Graduate School of Business and his BS at University of California, Los Angeles.

About the Insight eNO System

The Insight eNO System has been available for use in the physicians' office since March 2008 for better management of Asthma. The eNO system uses a proprietary biosensor technology to measure exhaled nitric oxide, a well established indicator of asthma severity and steroid responsive airway inflammation. Measuring eNO and determining the level of airway inflammation can help clinicians more closely manage their patients' asthma and therefore more precisely titrate medications, which can lead to fewer asthma exacerbations.

About Apieron Inc.

Apieron Inc. is a private, venture-backed medical device company based in Menlo Park, CA that was formed in early 2001 to develop a simple-to-use, non-invasive monitor for the measurement of exhaled nitric oxide (eNO) for the management of asthma. The Apieron biosensor technology platform utilizes a patented technology that allows for the highly sensitive detection of selected analytes like eNO. Apieron is committed to collaborating with physicians and patients to develop innovative medical solutions to improve quality of life and standards of care.

Source: http://www.prlog.org/10249358-apieron-strengthens-senior-leadership-with-commercial-financial-appointments.html

Effect of Age on Relationship Between Exhaled Nitric Oxide and Airway Hyperresponsiveness in Asthmatic Children

2009-07-06T00:32:00.000-07:00

Background

Numerous studies have examined the relationship between fractional concentration of exhaled nitric oxide (FeNO) and airway hyperresponsiveness (AHR), but studies regarding the effect of age on the relationship between FeNO and AHR are scarce.

Objective

To determine the effects of age on the relationship between FeNO and AHR in asthmatic children.

Methods

AHR was examined in 267 asthmatic patients (age range, 5 – 20 years). A challenge test was performed using acetylcholine chloride (Ach). We determined the provocation concentration of Ach producing a 20% decrease in FEV1 (PC20). FeNO was examined using the recommended online method before the Ach challenge test.

Results

In children under the age of 12 years (age range, 5 – 11 years), decreasing AHR (PC20) was significantly related to higher FeNO (r=−0.43,β=−0.28, p < 0.001). In adolescents aged 12 years and older (age range, 12 – 20 years), decreasing PC20 was associated with peripheral airway obstruction (FEV1: r = 0.32, β=5.5, p0.002; forced expiratory flow at 50% (FEF50) of the FVC: r = 0.24, β=8.4, p = 0.006; forced expiratory flow at 25% of FVC [FEF25]: r = 0.28, β=11.4, p = 0.002). AHR and FeNO were weakly related (r=−0.18, β=−0.14,p = 0.02).

Conclusions

In children with asthma, AHR is associated with airway inflammation. AHR in children with asthma may consist of variable components reflecting airway inflammation mainly. On the other hand, in adolescents with asthma, AHR is associated with airway structural changes and weakly with airway inflammation. AHR in adolescents with asthma may consist of chronic components reflecting airway remodeling mainly.

Source: http://www.chestjournal.org/content/early/2009/04/20/chest.08-2741.short

New Asthma Test: Will It Help You Breathe Easier?

2009-07-03T02:45:00.000-07:00

For years, physicians have assessed asthma by measuring how much air a patient can exhale. Now, some doctors are beginning to measure what’s in that breathed-out air – specifically, nitric oxide (NO). Scientists have discovered that the amount of nitric oxide in a patient’s breath indicates the degree of inflammation in the airways.

This is important because airway inflammation sets the stage for noisy asthma symptoms such as coughing and wheezing (bronchospasm). Physicians have found that treating the underlying inflammation with anti-inflammatory medications like inhaled corticosteroids reduces the symptoms and prevents the exacerbations associated with asthma.

Asthma treatment guidelines call for use of the lowest possible dose of inhaled corticosteroids to achieve disease control. By measuring NO, physicians will know if there is inflammation present inside the airways and can better tailor anti-inflammatory medications to treat asthma.

Research studies in patients with asthma show:

* Exhaled nitric oxide (eNO) levels may help predict asthma exacerbations before they occur
* eNO levels can help predict which patients will and will not benefit from inhaled corticosteroids
* eNO levels can help physicians determine whether allergen exposure is causing inflammation inside the lungs
* eNO levels can help physicians know if patients are actually taking their anti-inflammatory medications as prescribed

Nitric oxide tests do not replace spirometry and other lung function measurements. However, combined with lung function tests and medical history, nitric oxide measurements can help physicians determine the severity of asthma more accurately, especially among those patients whose asthma symptoms are subtle or inconsistent.

The tests are noninvasive and simple enough for people of all ages, including children, to carry out accurately. In the NIOX MINO® monitoring system, approved by the U.S. Food and Drug Administration, patients first exhale thoroughly to clear their lungs as much as possible, then inhale filtered air through the MINO machine and exhale (breathe out) into the monitor. The resulting exhaled breath is thus clean of nitric oxide that might have been in the environment. Patients control the strength of their exhalation by watching images on a screen and listening for sounds that direct them to blow more or less forcefully. The MINO measures eNO according to guidelines set by the American Thoracic Society.

Some medical researchers look forward to eNO measuring devices that will be so inexpensive that they become available for home use – like a peak flow meter. Then patients and physicians can work together to monitor and manage asthma symptoms with greater precision.

Source: ttp://www.aanma.org/2009/04/new-asthma-test-will-it-help-you-breathe-easier/