Noninvasive Marker Of Airway Inflammation Research Articles

Correlation of Atopy and FeNO in Allergic Rhinitis: An Indian Study

Fractional exhaled nitric oxide (FeNO) is a non-invasive marker of airway inflammation. Limited published data are available on the effect of atopy on FeNO in allergic rhinitis. To investigate the relationship between atopy and FeNO in patients with allergic rhinitis. Patients with allergic rhinitis were assessed for atopy and exhaled breath analysis of nitric oxide. Atopy was assessed by skin prick testing (SPT) against 58 common aero-allergens; a wheal size of 3mm or more as compared to buffer saline was considered positive. Patients were labelled to be atopic if they had at least one positive SPT result. The measurement of FeNO level was done by using NIOX chemiluminescence analyser. Forty-nine participants (26 males) aged between 8-50 years were studied and 31 of them were found to be atopic. The average value of FeNO in the subjects studied (n = 49) was 26.0 +/- 22.7 parts per billion (ppb) with significantly higher values being observed in atopic group as compared to non-atopic group (34.2 +/- 24.3 versus 11.9 +/- 9.0 ppb; p < 0.05). As FeNO is a marker of lower airway inflammation, significantly higher FeNO levels in atopic allergic rhinitis patients suggest that it may be a predictor for onset of asthma in these patients.

Offline exhaled nitric oxide in children: chemiluminescence vs. electrochemical devices.

Exhaled nitric oxide (eNO) is a noninvasive marker of airway inflammation that has been used in children, using the "offline" technique. To the extent of our knowledge, no article reported in literature compares the concordance and correlation between the two different technologies used to measure eNO at tidal volume offline. This study aimed to report the concordance and correlation of the eNO measured "offline" at tidal volume, using chemioluminiscence (cl) vs electrochemical devices (eq). A cross-sectional, observational, and prospective study was conducted in the National Institute of Respiratory Diseases (Instituto Nacional de Enfermedades Respiratorias), Mexico City. Healthy children and those with a lung disease between 1 and 11 years of age were included. The exhaled air sample at tidal volume was obtained by attaching a mask connected to a Mylar® bag. We studied 36 children. The mean ± standard deviation (SD) age of the study population was 6 ± 2.6 years; 25% of the subjects included were healthy, and the rest had a lung disease. The concordance correlation coefficient between the two measuring devices was 0.98 (p < 0.001), with a mean difference of 1.46 ± 3.5 ppb and 95% limits of agreement from -5.3 ppb to 8.3 ppb. The linear regression model equation for the estimation of eNO was eNOcl = (eNOeq·1.0718) - 0.1343 (r2 = 0.97). The measurement of eNO at tidal volume by the offline method can be analyzed by electrochemical devices, and the results are interchangeable with those analyzed by chemiluminescence technology.

A comparative study of the RuiBreath and NIOX VERO analyzers for detecting fractional exhaled nitric oxide.

BackgroundFractional exhaled nitric oxide (FeNO) measurement is a reliable, noninvasive marker of airway inflammation. Portable FeNO analyzers facilitate the assessment of airway inflammation in primary care. Differences between analyzers from different manufacturers are not comparable. Here, we aimed to compare the FeNO values obtained by a new portable device (RuiBreath, Guangzhou Ruipu Medical Technology Co., Ltd, Guangzhou, China) to those obtained by the widely used NIOX VERO portable analyzer (Aerocrine AB, Solna, Sweden) in patients with asthma.MethodsThis prospective validation study enrolled patients (≥14 years old) with asthma over a 2-month period (July and August 2019) at the Beijing Chao-Yang Hospital. At least one valid FeNO measurement was obtained using each analyzer for all the participants.ResultsThere were 197 participants in this study. The FeNONIOX and FeNORuiBreath values significantly differed (P=0.016). After log-transformation, a difference was found only when the FeNONIOX was <25 ppb (P<0.001). The FeNONIOX and FeNORuiBreath values had a significant correlation (r=0.938, P<0.001), which was confirmed by the Altman-Bland plot. Using a receiver-operating characteristic curve analysis, when using 49 ppb as the cut-off point for the two devices in identifying patients with symptomatic asthma symptoms, the sensitivity and specificity were 0.42 and 0.88, respectively, by NIOX, and 0.40 and 0.89, respectively, by RuiBreath.ConclusionsThis is the first report of FeNO values obtained by the new portable RuiBreath FeNO analyzer. The FeNORuiBreath values are reliable and directly comparable with the FeNONIOX values.

Repeatability and variation of the flow independent nitric oxide parameters

Introduction: Fractional exhaled nitric oxide (FENO) is a non-invasive marker of airway inflammation. Measuring FENO at several flow rates enables the calculation of flow independent NO-parameters (alveolar NO concentration (CANO), bronchial flux of NO (JawNO), bronchial mucosal NO concentration (CawNO) and bronchial wall NO diffusion capacity (DawNO)) that are capable of partitioning the source and release mechanism of NO from the lower respiratory tract. However, the current literature on repeatability and normal variation of the NO-parameters is deficient, and this information is needed to develop the method towards clinical use. Methods: We calculated NO-parameters in 28 healthy subjects using two different mathematical methods and used three different study protocols to investigate: (i) repeatability of two consecutive measurements of NO-parameters, (ii) within-day variation of the NO-parameters over one working day and (iii) day-to-day variation of the NO-parameters between consecutive days during course of a working week. Results: JawNO was the most repeatable among the NO-parameters, whereas DawNO and CawNO were notably least repeatable. CANO was higher during the second consecutive measurement (1.22 versus 1.57 ppb, p = 0.017). Both investigated mathematical methods yielded equally repeatable results. JawNO was slightly higher in the afternoon compared to morning (716 versus 881 pl/s, p = 0.01), but other parameters showed no diurnal variation. Upper 95% limit for the day-to-day difference in the parameters in healthy subjects was about 1.2 ppb in CANO, 400 pl/s in JawNO, 92 ppb in CawNO and 16 pl/s/ppb in DawNO. Conclusions: This is the first study assessing short-time repeatability of the NO-parameters. Repeatability of the NO-parameters was good and day-to-day variation in NO-parameters was quite low. We recommend scheduling FENO-measurements at the same time of day, if possible, and in clinical use variation in NO-parameters above the normal limits found in this study suggest changes in the disease’s activity.

Exhaled nitric oxide as a marker of chlorine exposure in young asthmatic swimmers

BackgroundSwimming is recommended for people with asthma. However, the inevitable exposure to chlorine and its disinfectant byproducts in indoor swimming pools could be responsible for bronchial inflammation and asthma development. Fractional exhaled nitric oxide (FeNO) is a noninvasive marker of airway inflammation that predicts asthma exacerbations. ObjectivesTo evaluate pretraining and posttraining FeNO levels in young swimmers with asthma attending an indoor chlorinated pool compared with a set of healthy swimmers and to examine the potential risk of exposure to chlorine as a factor associated with bronchial inflammation. MethodsA total of 146 children (8-18 years old) constantly attending an indoor chlorinated swimming pool were enrolled. Spirometry and FeNO measurements were performed 30 minutes after their arrival at the pool and immediately after exercise. Pre-exercise and postexercise spirometric and FeNO levels were assessed in a random subgroup of 14 swimmers (10 with asthma and 4 without) who performed cardiopulmonary exercise testing. ResultsAsthma was detected in 23 swimmers. In swimmers with asthma, preswimming FeNO values were significantly elevated compared with swimmers without asthma and their FeNO values measured before cardiopulmonary exercise testing. Postexercise FeNO values were significantly decreased by approximately one-third in healthy children and children with asthma in all sporting backgrounds. However, postswimming FeNO values remained significantly higher in swimmers with asthma compared with those without asthma. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio values showed no significant difference before and after 2 types of activity. ConclusionElevated FeNO levels before and after swimming were recorded in swimmers with asthma not observed in a different exercise field. The presence of chlorine in the indoor swimming pool seems to explain this finding.

Exhaled breath temperature as a tool for monitoring asthma control after an attack in children.

Exhaled breath temperature (EBT) has been suggested as a non-invasive marker of airway inflammation in asthma. There have been no studies examining longitudinal changes in EBT following asthma attacks. To investigate changes in EBT during and after an asthma attack and to relate these changes to changes in respiratory physiological measurements. We evaluated 38 hospitalized children aged 5-18 years diagnosed with an asthma attack. Spirometry was performed upon hospitalization. During hospitalization, EBT, peak expiratory flow rate (PEFR), and asthma score were measured daily. These tests were repeated 1 week and 1 month after discharge. The overall PEFR change, temporal changes in plateau values at the end of expiration, and time-dynamic associations were evaluated using linear mixed models. FEV1 was lower at admission than at discharge (63.3 ± 24 vs 99.5 ± 14 percent of predicted, P < 0.001). The EBT was higher at admission than at 1 week after discharge (34.1°C [range: 33.9-34.8°C] vs 33.6°C [range: 33.0-34.2°C], P = 0.007); overall, EBTs decreased over time (P = 0.007). Among individual subjects, decreased EBT was correlated with increased PEFR over time. Furthermore, plateau values at the end of expiration had a time-dependent, dynamic association with the PEFR during hospitalization (P = 0.005) and between asthma attack onset and asthma status stabilization (P = 0.032). The EBT was elevated during asthma attacks and gradually decreased until asthma was well controlled. The EBT may be a useful, non-invasive tool for monitoring asthma control in children.

Measurement of fractional exhaled nitric oxide and nasal nitric oxide in male patients with obstructive sleep apnea

ObjectiveAirway inflammation plays an important role in obstructive sleep apnea (OSA); exhaled nitric oxide is regarded as a noninvasive marker of airway inflammation. The aim of this study was to evaluate fractional exhaled nitric oxide (FeNO) and nasal nitric oxide (nNO) in patients with OSA.MethodsSeventy-five patients with OSA and 30 health controls were enrolled in this study. FeNO and nNO were measured before and after sleep. Nasal lavage was performed in 31 non-smoking individuals immediately after NO measurement in the morning. The sample of nasal lavage was taken for cell classification and analyzing interleukin 6 (IL-6) and interleukin 8 (IL-8).ResultsBoth FeNO and nNO were significantly higher in OSA (before sleep FeNO 21.08 ± 8.79 ppb vs.16.90 ± 6.86 ppb, p = 0.022; after sleep FeNO 25.57 ± 15.58 ppb vs.18.07 ± 6.25 ppb, p = 0.003; before sleep nNO 487.03 ± 115.83 ppb vs. 413.37 ± 73.10 ppb, p = 0.001; after sleep nNO 550.07 ± 130.24 ppb vs. 460.43 ± 109.77 ppb, p < 0.001). Furthermore, in non-smoking OSA, nNO levels were positively correlated with apnea hypopnea index (AHI) and average decrease of pulse arterial oxygen saturation (SpO2); after sleep, nNO was also positively associated to recording time with SpO2 < 90% and negatively associated to minimum SpO2. Both before and after sleep nNO levels were positively correlated with the percentage of neutrophils in nasal lavage (r = 0.528, p = 0.014; r = 0.702, p < 0.001, respectively). Additionally, before sleep nNO was also positively associated with IL-6 (r = 0.586, p = 0.005) and IL-8 (r = 0.520, p = 0.016) concentration.ConclusionThis study sustains the presence of airway inflammation in OSA patients with the increase of FeNO and nNO. The data suggests nNO might have greater value than FeNO since it positively correlated with OSA severity, and nNO is a potential bio-marker of nasal inflammation in non-smoking OSA patients.

Effect of Betel (Areca) Nut Chewing on Fractional Exhaled Nitric Oxide: A Pilot Study.

Betel (areca) nuts are extensively chewed in many countries. This has been associated with respiratory symptoms. We aimed to determine whether betel nut chewing is associated with acute changes in fractional exhaled nitric oxide, a non-invasive marker of airway inflammation. Betel nut chewing resulted in an immediate significant decline in fractional exhaled nitric oxide levels that persisted for up to 180 minutes. This effect has to be taken into account in epidemiological studies, reference ranges, and patient preparation.

Exhaled nitric oxide as a guiding tool for bronchial asthma: A randomised controlled trial

BackgroundEvidence regarding the role of non-invasive marker of airway inflammation, fractional exhaled nitric oxide (FeNO) to guide asthma treatment is equivocal. We aimed to evaluate if the use of FeNO to adjust inhaled corticosteroid treatment resulted in reduced daily corticosteroid use and lesser exacerbations. Methods100 patients of bronchial asthma in the age group of 12–70 years were randomised to receive inhaled corticosteroids based on either FeNO measurements (n=50) or as per Global Initiative for Asthma (GINA) guidelines. Follow up was done every 2 months for period of 12 months. Results were compared in terms of mean daily inhaled corticosteroid use and number of exacerbations. ResultsAfter the follow up period of 12 months, mean daily dose of ICS (SD) required in FeNO group was 267.5μg (126.29), as opposed to control group in which mean daily dose of steroid was 320.00μg (138.69). However this observed difference in steroid dose was statistically insignificant (p value=0.061). The estimated mean (SD) rate of asthma exacerbation experienced in follow up period of 12 months in FeNO group was 0.3 episodes (0.54) per patient per year (95% confidence interval, 0.145–455) and 0.4 episodes (0.61) per patient per year in control group (95% confidence interval, 0.228–572). However this difference in rate of exacerbations between the two study groups was not statistically significant (p=0.387). ConclusionFeNO guided management strategy for asthma did not result in statistically significant reduction in dose of inhaled corticosteroids or number of asthma exacerbations.

Validation of a New Portable Exhaled Nitric Oxide Analyzer, NIOX VERO®: Randomized Studies in Asthma

Fractional exhaled nitric oxide (FeNO) is a non-invasive marker of airway inflammation, and a new portable analyzer (NIOX VERO®) is now available. Our studies aimed to assess the agreement of measurements between NIOX VERO® and a reference device (NIOX MINO®) and assess the reproducibility of NIOX VERO®. Paired FeNO readings were obtained from 112 subjects from both devices to assess agreement and reproducibility. FeNO readings were obtained from 122 subjects using NIOX VERO® to assess inter-operator repeatability. All subjects had a diagnosis of asthma and were aged ≥7 years. Agreement was shown with 90.8% of subjects within tolerance limits for the first valid FeNO measurement. Mean observed paired difference for the first valid FeNO measurement on each device was −4.6 ppb [95% confidence interval (CI) −5.825 to −3.377; < 0.0001]. Weighted Deming Regression Analysis showed a slope of 0.842 (95% CI 0.757, 0.927) and a y-intercept of −0.472 (95% CI −1.999, 1.055). Paired differences were centered close to 0. Intra-subject repeatability of NIOX VERO® was significantly better than NIOX MINO® (p = 0.0112). Further, inter-operator repeatability was achieved with NIOX VERO® with a mean intra-subject variance of 6.61 ± 17.954 ppb (upper 95% CI 9.41) and an estimated standard deviation of 2.57 (upper 95% CI 3.07). The coefficient of variance was 0.066 ± 0.054 (upper 95% CI 0.074). Our findings show that the portable instrument NIOX VERO® is clinically equivalent to NIOX MINO® when used in an asthma population. The NIOX VERO® analyzer gives reproducible, consistent measurements that are well within the technical specifications of the device, showing no observable pattern of a training effect or operator-order effect on FeNO results. Thus, our findings validate the NIOX VERO®. Aerocrine AB, Solna, Sweden.

Clinical implication of exhaled breath temperature measurement in pediatric asthma

Purpose: Exhaled breath temperature (EBT) has been suggested as a noninvasive marker of airway inflammation in asthma. The aim of this study was to determine its clinical implication in children with asthma. Methods: A total of 233 children were enrolled in this study. Among them, 116 were asthmatic children and 117 were healthy chil dren. Spirometry, bronchodilator response (BDR) test, methacholine challenge test, and skin prick test were performed. EBT, frac- tional exhaled nitric oxide (FeNO), blood eosinophils, and total IgE levels were measured. EBT was measured by using X-halo. Results: EBT was significantly higher in the asthma group than in the control group (median [interquartile range], 32.1°C [30.0°C- 33.9°C] vs. 29.7°C [29.0°C-31.3°C], P<0.001). EBT was significantly higher in poorly or partly controlled asthmatic children than well-controlled asthmatic children (33.5°C [31.0°C-34.4°C] vs. 30.3°C [29.3°C-32.9°C], P<0.0001). Among total subjects, EBT was signifi cantly higher in the atopic group than in the nonatopic group (32.4°C [30.3°C-34.0°C] vs. 29.8°C [29.0°C-30.3°C], P<0.001). There were neither significant associations between EBT and BDR (r=0.109, P=0.241) nor between EBT and PC20 (provocation concentra -tion causing a 20% fall in FEV1) in total subjects (r=0.127, P=0.316). EBT did not show any association with FeNO (r=0.353, P=0.071). Conclusion: Our study suggests that EBT might play a role as an ancillary marker for allergic airway inflammation and the degree of control in pediatric asthma patients. Additional studies are required to explore the value of EBT in detail. (Allergy Asthma Respir Dis 2017;5:147-152)

Asthma and cystic fibrosis: A tangled web

Successfully diagnosing concomitant asthma in people with cystic fibrosis (CF) is a challenging proposition, and the utility of conventional diagnostic criteria of asthma in CF populations remains uncertain. Nonetheless, the accurate identification of individuals with CF and asthma allows appropriate tailoring of therapy, and should reduce the unnecessary use of asthma medication in broader CF cohorts. In this review, we discuss the diagnostic challenge posed by asthma in CF, both in terms of clinical evaluation, and of interpretation of pulmonary function testing and non-invasive markers of airway inflammation. We also examine how the role of cross-sectional thoracic imaging in CF and asthma can assist in the diagnosis of asthma in these patients. Finally, we critically appraise the evidence base behind the use of asthma medications in CF populations, with a particular focus on the use of inhaled corticosteroids and bronchodilators. As shall be discussed, the gaps in the current literature make further high-quality research in this field imperative.

Correlation of exhaled nitric oxide, nasal nitric oxide and atopic status: A cross-sectional study in bronchial asthma and allergic rhinitis

Objective:Exhaled nitric oxide (FENO) and nasal nitric oxide (n NO) measurement is an area of ongoing research in the study of airway inflammation. The atopic status is known to influence the levels of FENO and n NO. This study was undertaken to study the relationship between nitric oxide measurements in bronchial asthma and allergic rhinitis along with their correlation with atopic profile of Indian population.Materials and Methods:Ninety subjects were recruited for the study comprising of 25 each of bronchial asthma (BA), allergic rhinitis (AR), bronchial asthma with allergic rhinitis (BA-AR) and 15 healthy controls. These were assessed for atopy and exhaled breath analysis of nitric oxide. The measurements of FENO and n NO levels were done using NIOX chemiluminescence analyzer. Atopy was assessed by skin prick testing (SPT) against 58 common aero-allergens and subjects with ≥1 positive SPT were labeled as atopic.Results:The BA-AR and BA groups had higher FENO levels in comparison to the control (P < 0.05) and AR group (P < 0.05). The AR and BA-AR groups had higher n NO levels compared to the control group (P < 0.05) and BA group (P < 0.05). The increasing FENO levels significantly correlated with the increase in the number of allergen sensitization in patients suffering from BA-AR (P < 0.05). However, the BA group showed a weaker positive correlation (P = 0.07).Conclusion:FENO is a non-invasive marker of airway inflammation. Also, FENO levels correlate with presence and degree of atopy in BA and AR. Simultaneously, n NO could be a surrogate marker of rhinitis.

The value of FeNO measurement in childhood asthma: uncertainties and perspectives

Asthma is considered an heterogeneous disease, requiring multiple biomarkers for diagnosis and management. Fractional exhaled nitric oxide in exhaled breath (FeNO) was the first useful non-invasive marker of airway inflammation in asthma and still is the most widely used. The non-invasive nature and the relatively easy use of FeNO technique make it an interesting tool to monitor airway inflammation and rationalize corticosteroid therapy in asthmatic patients, together with the traditional clinical tools (history, physical examination and lung function tests), even if some controversies have been published regarding the use of FeNO to support the management of asthma in children. The problem of multiple confounding factors and overlap between healthy and asthmatic populations preclude the routine application of FeNO reference values in clinical practice and suggest that it would be better to consider an individual “best”, taking into account the context in which the measurement is obtained and the clinical history of the patient. Besides, there is still disagreement about the role of FeNO as a marker of asthma control, due to the complexity of balance among the different items involved in its determination and the lack of homogeneity in the population groups studied in the few studies conducted so far. Heterogeneity of problematic severe asthma greatly limits utility of FeNO alone as a biomarker of inflammation to optimize the disease management on an individual basis. None of the studies conducted so far demonstrated that the use of FeNO was better than current asthma guidelines in controlling asthma exacerbations. In summary, there is a large variation in FeNO levels between individuals, which may reflect the natural heterogeneity in baseline epithelial nitric oxide synthase activity and/or the contribution of other noneosinophilic factors to epithelial nitric oxide synthase activity. FeNO is a promising biomarker, but at present some limits are highlighted. We would recommend that further research can be carried out by organizing studies aimed to obtain reliable reference values of FeNO and in order to better interpret FeNO measurements in clinical settings, taking also into account the influence of genetic and environmental factors.

The Long-Term Variability of FeNO in Pregnant Asthmatic Women with Controlled Asthma

Introduction: Fractional exhaled nitric oxide (FeNO) is considered a useful, noninvasive marker of airway inflammation in asthma and allergic rhinitis. It has also been suggested that anti-inflammatory treatment guided by monitoring of exhaled NO could improve overall asthma control. However, long-term intrasubject variability of this parameter as well as the rate of its change, which can be considered clinically significant, have not been established yet. The aim of our study was to assess the long-term variability of FeNO in pregnant asthmatic women with controlled asthma. Material and methods: Pregnant, non-smoking women with asthma were recruited at between 3 and 6 months of gestation. Exhaled nitric oxide (FeNO) spirometric parameters were measured, and asthma control tests (ACT) were completed at monthly visits up to delivery. The data of 26 subjects with well controlled asthma during pregnancy (ACT values within the range 20–25, normal spirometric parameters, stable treatment) were analysed. The variability of FeNO values was assessed using the variation coefficient CV (standard deviation × 100%/arithmetic mean). Results: The median level of FeNO coefficient of variation (CV) was: 33.8% (range 11.3 to 121.9) in all subjects with well controlled asthma during pregnancy. There were no statistically significant differences in FeNO variability between groups of patients who had at least one measurement of FeNO higher than 50 ppb (39%; 11.8–121.9%) and those with all FeNO values below 50 ppb (29.9%; 11.3–71.8%), as well as between atopic (35.7%; 11.8–121.9%) and nonatopic (24.2%; 11.3–71.8%) pregnant asthmatics (p = 0.95 and 0.11, respectively). Conclusions: High long-term variability of fractional exhaled nitric oxide values revealed in pregnant women with well controlled asthma indicates that changes in this parameter should be interpreted with caution when used for asthma treatment monitoring.

Measurements of fractional exhaled nitric oxide in pediatric asthma

Exhaled nitric oxide (NO) has been extensively investigated as a noninvasive marker of airway inflammation in asthma. The increased NO expression induced by inflammatory mediators in airways can be monitored easily in exhaled air from asthmatic children. Based on the relationship between the increased NO expression and eosinophilic airway inflammation, fractional exhaled nitric oxide (FeNO) measurements become an important adjunct for the evaluation of asthma. In addition, the availability of portable devices makes it possible to measure FeNO more easily and frequently in the routine pediatric practice. Despite various confounding factors affecting its levels, FeNO can be applicable in diagnosing asthma, monitoring treatment response, evaluating asthma control, and predicting asthma exacerbations. Thus, although pulmonary function tests are the standard tools for objective measurements of asthmatic control, FeNO can broaden the way of asthma monitoring and supplement standard clinical asthma care guidelines.

The value of FeNO measurement in childhood asthma: uncertainties and perspectives.

Asthma is considered an heterogeneous disease, requiring multiple biomarkers for diagnosis and management. Fractional exhaled nitric oxide in exhaled breath (FeNO) was the first useful non-invasive marker of airway inflammation in asthma and still is the most widely used. The non-invasive nature and the relatively easy use of FeNO technique make it an interesting tool to monitor airway inflammation and rationalize corticosteroid therapy in asthmatic patients, together with the traditional clinical tools (history, physical examination and lung function tests), even if some controversies have been published regarding the use of FeNO to support the management of asthma in children. The problem of multiple confounding factors and overlap between healthy and asthmatic populations preclude the routine application of FeNO reference values in clinical practice and suggest that it would be better to consider an individual “best”, taking into account the context in which the measurement is obtained and the clinical history of the patient. Besides, there is still disagreement about the role of FeNO as a marker of asthma control, due to the complexity of balance among the different items involved in its determination and the lack of homogeneity in the population groups studied in the few studies conducted so far. Heterogeneity of problematic severe asthma greatly limits utility of FeNO alone as a biomarker of inflammation to optimize the disease management on an individual basis. None of the studies conducted so far demonstrated that the use of FeNO was better than current asthma guidelines in controlling asthma exacerbations. In summary, there is a large variation in FeNO levels between individuals, which may reflect the natural heterogeneity in baseline epithelial nitric oxide synthase activity and/or the contribution of other noneosinophilic factors to epithelial nitric oxide synthase activity. FeNO is a promising biomarker, but at present some limits are highlighted. We would recommend that further research can be carried out by organizing studies aimed to obtain reliable reference values of FeNO and in order to better interpret FeNO measurements in clinical settings, taking also into account the influence of genetic and environmental factors.

Emergency department treatment of adults with acute asthma exacerbations: Effect on exhaled nitric oxide levels

Measurement of exhaled nitric oxide levels (eNO) from asthmatic patients is a noninvasive marker of airway inflammation in both adults and children and has been used as an outpatient measure of asthma control. We examined eNO in acute asthma exacerbations and how it is affected by treatment in the emergency department (ED) setting. Both eNO and peak expiratory flow (PEF) rate were measured at arrival and before discharge for adult asthmatic subjects (n = 28) treated for acute exacerbations in the ED at Kings County Hospital Center during spring and fall pollen seasons. Total serum Immunoglobulin E (IgE), peripheral blood leukocyte numbers, and tobacco smoking history were determined. Routine ED treatment included oral prednisone at 60 mg and inhalation of nebulized albuterol and ipratropium. Both PEF (p = 0.0005) and eNO (p < 0.0001) increased after treatment of subjects. Initial eNO was associated with age (p = 0.0004), absolute eosinophil count (p = 0.003), Asthma Control Test (p = 0.004), and Asthma Quality of Life Questionnaire (p = 0.04). Change in pre- versus posttreatment eNO (ΔeNO) was associated with change in PEF (ΔPEF; p < 0.0001). Initial PEF was associated with oxygen saturation (p < 0.0001). ΔPEF was associated with serum IgE levels. ED visit duration was associated with initial PEF (p = 0.0004), ΔeNO (p = 0.004), and number of albuterol treatments (p = 0.001). These associations remained significant in multivariate models that controlled for demographic factors, asthma control, smoking, and measures of inflammation and ventilation. eNO levels increase after ED treatment of acute asthma exacerbations in adults. Improved ventilation may allow for more accurate measurement of NO produced in inflamed airways.

Exhaled breath condensate pH in patients with cystic fibrosis

Exhaled breath condensate (EBC) pH has been proposed as a useful, non-invasive marker of airway inflammation in pulmonary diseases. In this study we tested whether cystic fibrosis (CF) is associated with acidification of EBC, when pH is assessed by the CO(2) gas standardization method. EBC was collected using two different devices (EcoScreen and R-Tube) in 46 stable CF patients during routine clinical visits and in 28 healthy controls. Mean EBC pH in CF patients and in healthy controls was similar (EcoScreen: CF patients: 6.38±0.03 versus controls: 6.39±0.03, p=0.699; R-tube: CF patients: 5.94±0.04 versus controls: 6.02±0.03, p=0.159). Inflammatory cell counts in spontaneously expectorated sputum obtained in a subset of patients (n=20) showed no correlation with pH values. EBC samples collected with the R-tube were more acidic than those collected with the EcoScreen device (p<0.001). Our data suggest that EBC pH does not discriminate between healthy controls and those with CF disease indicating that the clinical applicability of EBC pH measurements for assessing airway inflammation in CF is limited.

31 Nasal Nitric Oxide and Nasal Polyposis as Determinants of Asthma Control

BackgroundThe relationship between asthma control, its comorbidities and noninvasive markers of airway inflammation has been investigated with controversial results. The aim of this study was to analyze the relationship between level of asthma control (evaluated by ACT and ACQ questionnaires), its main comorbidities (rhinitis, chronic rhinosinusitis - CRS, obesity), exhaled nitric oxide (FENO) and nasal nitric oxide (nNO).MethodsForty-one consecutive asthmatic patients (mean age: 50 years, range: 21–80; 21 females; 2 smokers) were enrolled into the study. All patients were investigated to assess diagnosis of rhinitis, CRS (with or without nasal polyps) and obesity (by measuring the BMI). All patients underwent skin prick tests for a panel of common inhalant allergens, spirometry, FENO and nNO, and completed ACT and ACQ questionnaires. An univariate analysis was performed to identify determinants of asthma control (defined by means of ACT and ACQ values).ResultsTwenty-seven (65.9%) patients had ACQ values indicating asthma control (ACQ ≤1), while, according to ACT, only 14.6% of patients were completely controlled (ACT = 25), 48.8% partially controlled (20≥ ACT <25) and 36.6% uncontrolled (ACT <20). ACT and ACQ values were negatively correlated with nNO levels (R2 = −0.175 and R2 = 0.013 respectively). The univariate analysis showed that the the only significant determinants of lack of asthma control were nNO and the diagnosis of CRS with nasal polyps (P = 0.020 and 0.018 respectively).ConclusionsNasal nitric oxide was the only biomarker, amongst those evaluated, which was correlated to asthma control. This finding suggests that nNO may reflect particular aspects of airway inflammation which may be more strictly correlated with asthma, underlying the importance of CRS with nasal polyps in loosing asthma control.