Fractional Concentration Of Exhaled Nitric Oxide Levels Research Articles

The Effects of High Intensity Interval Training (HIIT) on Asthmatic Adult Males

Background – This study explored the effects of High-Intensity Interval Training (HIIT) on pulmonary function, exercise tolerance, and fractional concentration of exhaled nitric oxide (FeNO) in asthmatic and healthy adults. FeNO levels, associated with lung inflammation, are a diagnostic tool for asthma treatment, making this study significant for understanding HIIT's impact on asthma management. Materials and Methods: Fourteen male subjects (7 asthmatic, 7 healthy) participated in a two-week HIIT protocol. Pulmonary function was assessed using peak expiratory flow (PEF), forced vital capacity (FVC), and the FEV1/FVC ratio. FeNO was measured with a NIOX portable device. Subjects underwent a progressive exercise test on a cycle ergometer to determine peak oxygen uptake (VO2 peak), CO2 output (VCO2 peak), ventilation (VE), and time to exhaustion (TTE). HIIT sessions included warm-ups, 10 x 60-second high-intensity bouts with 60-second recovery intervals, and cool-downs. Intensity targeted 75% peak work rate (WR) for asthmatics and 80% for controls. Results: Significant differences were observed between groups in FeNO, VO2 peak, TTE, and peak WR, with no significant changes in pulmonary function measures. Pre-HIIT, asthmatics showed a mean FeNO of 28 ± 2 ppb compared to controls at 18 ± 1 ppb, with post-HIIT levels remaining stable. TTE and peak WR improved in both groups post-HIIT, indicating enhanced exercise tolerance and performance capacity. Specifically, asthmatics showed an increase in TTE from 691 ± 40 s to 781 ± 41 s and in peak WR from 175 ± 13 W to 203 ± 14 W. Conclusion: HIIT was well-tolerated by asthmatic subjects, leading to improved exercise tolerance, higher ventilation, CO2 output, and work rate performance, without significant changes in pulmonary function or FeNO levels. These findings suggest that HIIT can be a safe and effective exercise intervention for asthmatic individuals to enhance exercise performance.

Identification and treatment of persistent small airway dysfunction in paediatric patients with asthma: a retrospective cohort study

BackgroundAsthma is a common respiratory disease. In asthma, the small airways have more intensive inflammation and prominent airway remodelling, compared to the central airways. We aimed to investigate the predictive value of risk factors and the fractional concentration of exhaled nitric oxide (FeNO) for persistent small airway dysfunction (p-SAD), and compare the effects of different treatment modalities.MethodsThis retrospective cohort study included 248 children with asthma (aged 4–11 years). Binary logistic regression was used to analyse the risk factors for p-SAD. Correlations among FEV1/FVC, small airway function parameters, and FeNO levels in patients with asthma were analysed using Spearman’s rank correlation. The receiver operating characteristic curve and the Delong test were used to analyse the predictive value of FeNO for p-SAD. Differences in the treatment effects of inhaled corticosteroids (ICS) and ICS with a long-acting beta-agonist (ICS/LABA) on p-SAD were analysed using Fisher’s exact test.ResultsAsthmatic children with older age of receiving the regular treatment (OR 1.782, 95% CI 1.082–2.935), with younger age at the time of onset of suspected asthma symptoms (OR 0.602, 95% CI 0.365–0.993), with longer duration of using ICS or ICS/LABA (OR 1.642, 95% CI 1.170–2.305) and with worse asthma control (OR 3.893, 95% CI 1.699–8.922) had increased risk for p-SAD. Significant negative correlations of small airway function parameters with FeNO at a 200 mL/s flow rate (FeNO200), and the concentration of nitric oxide in the alveolar or acinar region (CaNO) were observed. The areas under the curve of FeNO200 (cut-off:10.5ppb), CaNO (cut-off:5.1ppb), and FeNO200 combined with CaNO were 0.743, 0.697, and 0.750, respectively, for asthma with p-SAD. After using ICS or ICS/LABA, switching to ICS/LABA was easier than continuing with ICS to improve small airway dysfunction (SAD) in the 8th month.ConclusionsPaediatric asthma with p-SAD is associated with older age at receiving regular treatment, younger age at the time of onset of suspected asthma symptoms, longer duration of using ICS or ICS/LABA, worse asthma control, and higher FeNO200 and CaNO levels, all of which can be combined with small airway function indicators to distinguish p-SAD from asthma. ICS/LABA improves SAD better than ICS alone.

Exhaled nitric oxide: A biomarker for chronic obstructive pulmonary disease.

The fractional concentration of exhaled nitric oxide (FeNO) is recognized as a biomarker of type 2 inflammation in asthma, which is related to airway eosinophilia. We conducted a prospective observational study in a cohort of Japanese patients with chronic obstructive pulmonary disease (COPD) to evaluate the relationship between FeNO and clinical features and patient outcomes over a 3-year period. Participants were categorized into two groups based on FeNO levels (high and low), and the clinical features and outcomes were compared between the groups. Patients with high FeNO levels showed features of asthma and eosinophilic inflammation compared to those with low levels. However, high FeNO levels were not associated with worse outcomes (exacerbations, hospital admissions, all-cause and disease-specific mortality) compared to low levels. These results provide evidence that baseline FeNO is related to eosinophilic inflammation; however, is not a predictor of future exacerbations or prognosis in patients with stable COPD.

Study of the role of exhaled nitric oxide (NO) in predicting controlled or uncontrolled asthma in asthmatic children.

BackgroundExhaled nitric oxide (NO), especially fractional concentration of exhaled NO (FENO) has been used to predict the responsiveness to inhaled corticosteroid (ICS) in children with asthma. However, the use of exhaled NO for predicting asthma control in children is still controversial.MethodsThis was a perspective observational study. Asthmatic children who were naïve to inhaled corticosteroid (ICS) were included in the present study. The measurements of FENO and CANO (concentration of NO in the gas phase of the alveolar), spirometry, blood eosinophil counts (BEC), and total IgE levels were done for each asthmatic child. All study subjects started proper asthma treatment after the enrollment.ResultsNinety three asthmatic children (9±3 years) with moderate (63.4%) to severe (36.6%) asthma were included and finished the 3-month study. The levels of FENO and CANO at inclusion were 37±11 ppb and 5.8±1.4 ppb, respectively; the mean of BEC was 617±258 cells/μL; the level of total IgE was 1563±576 UI/mL; 89% of subjects were positive for at least one respiratory allergen. The percentage of severe asthma was reduced significantly after 3 months (P<0.001). Well controlled asthma subjects at 3 months had higher levels of FENO and lower levels of CANO at inclusion (P<0.05 and P<0.05). FENO<20 ppb or CANO>5ppb had a risk of uncontrolled asthma at 3 months (OR: 1.7, CI 95% [(0.8) - (3.3)], P<0.05; OR: 1.9, CI 95% [(0.9) - (2.7)], P<0.05; respectively). FENO>35 ppb at inclusion had a positive predictive value for asthma control at 3 months (OR: 3.5, CI 95% [2.2-5.9], P<0.01).ConclusionsExhaled NO is a biomarker of asthma which may have a potential role to predict the control of asthma in short-term follow up in asthmatic children.

Exhaled Nitric Oxide is Not a Biomarker for Pulmonary Tuberculosis

.To reduce transmission of tuberculosis (TB) in resource-limited countries where TB remains a major cause of mortality, novel diagnostic tools are urgently needed. We evaluated the fractional concentration of exhaled nitric oxide (FeNO) as an easily measured, noninvasive potential biomarker for diagnosis and monitoring of treatment response in participants with pulmonary TB including multidrug resistant–TB in Lima, Peru. In a longitudinal study however, we found no differences in baseline median FeNO levels between 38 TB participants and 93 age-matched controls (13 parts per billion [ppb] [interquartile range (IQR) = 8–26] versus 15 ppb [IQR = 12–24]), and there was no change over 60 days of treatment (15 ppb [IQR = 10–19] at day 60). Taking this and previous evidence together, we conclude FeNO is not of value in either the diagnosis of pulmonary TB or as a marker of treatment response.

Relationship between upper airway diseases, exhaled nitric oxide, and bronchial hyperresponsiveness to methacholine

ABSTRACTObjective: The “united airway disease” concept is based on the bidirectional interaction between asthma and rhinitis. The aim of this study was to determine the relationship between upper airway diseases and bronchial hyperresponsiveness (BHR), as well as their association with the fractional concentration of exhaled nitric oxide (FeNO) and atopy in patients with persistent symptoms suggestive of asthma requiring methacholine challenge testing (MCT) to confirm asthma diagnosis. Methods: A cross-sectional prospective study was carried out in adult patients with persistent asthma-like symptoms and negative bronchodilator testing. FeNO and MCT were performed in all patients. Asthma was confirmed based on the presence of suggestive symptoms and MCT results. Associated upper airway diseases included allergic rhinitis, nonallergic rhinitis, chronic rhinosinusitis with nasal polyps (CRSwNP), and aspirin-exacerbated respiratory disease (AERD). Results: The study included 575 patients; asthma was confirmed in 32.3%, and FeNO values ≥ 50 ppb were found in 27% of the patients. Elevated FeNO was significantly associated to AERD. The prevalence of atopy in asthma patients was 86.6%. Atopy was present in 90.4% of patients with asthma and FeNO levels ≥ 50 ppb. A significant association was found between AERD, asthma, and FeNO ≥ 50 ppb. Conclusions: Patients with symptoms suggestive of asthma but negative bronchodilator testing are commonly seen in usual practice. In this population, the association of high FeNO levels and BHR to atopy, as well as to AERD, suggests the presence eosinophilic inflammation in both the upper and lower airways and supports the “one airway” hypothesis.

Decreased expression of indolamine 2,3-dioxygenase in childhood allergic asthma and its inverse correlation with fractional concentration of exhaled nitric oxide

BackgroundThe tryptophan metabolic pathway mediated by indolamine 2,3-dioxygenase (IDO), a tryptophan-degrading enzyme, plays an important role in controlling the development of allergic inflammation. The fractional concentration of exhaled nitric oxide (FeNO) is closely associated with the allergic state and is extensively used for the clinical evaluation of airway allergic inflammation. Clinical trials have rarely assessed the expression of IDO in childhood allergic asthma and its correlation with FeNO. ObjectiveTo evaluate the IDO level in children with childhood allergic asthma and the relation between IDO levels and FeNO. MethodsThirty children older than 5 years who were diagnosed the first time with allergic asthma were selected from the pediatric outpatient department. Another 30 healthy children were selected as controls. The subjects were evaluated by complete medical history, pulmonary function test results, skin prick test reaction, FeNO concentration test result, eosinophil count, and a disease severity score. Peripheral venous blood and induced sputum were obtained to measure the concentrations of IDO metabolites (ie, tryptophan and kynurenine). ResultsThe IDO levels in the peripheral blood and induced sputum were significantly lower in patients with childhood allergic asthma than in children in the control group. The IDO level was negatively correlated with FeNO but was not significantly correlated with age, sex, blood eosinophil count, or disease severity scale. ConclusionThe expression of IDO was significantly lower in childhood allergic asthma, particularly in children with high FeNO levels. There was no significant relation between IDO levels and asthma severity. Trial RegistrationChinese Clinical Trial Register (www.chictr.org.cn) Identifier: ChiCTR-COC-15006080.

Fractional Exhaled Nitric Oxide: A Potential Biomarker in Allergic Rhinitis?

Background: The fractional concentration of exhaled nitric oxide (FeNO) is a surrogate biomarker for Th2-dependent bronchial inflammation. The present study investigated whether FeNO may characterize allergic rhinitis (AR) patients. Methods: A total of 553 AR patients (497 males, mean age 28.8 years) were evaluated. Those patients with a high FeNO underwent a 2-year follow-up. Results: Increased FeNO was associated with a significantly longer AR duration, impaired lung function, more severe symptoms, and more frequent bronchial hyperresponsiveness (BHR). At follow-up, 22 out of 82 patients (26.8%) with high FeNO levels (>50 ppb) developed asthma. Conclusions: AR patients may frequently have high FeNO values, exceeding 50 ppb. This might be associated with an initial impaired lung function, BHR, a perceived worsening of respiratory symptoms, and potential progression to asthma.

A population-based study of smoking, serum cotinine and exhaled nitric oxide among asthmatics and a healthy population in the USA

Background: Fractional concentration of exhaled nitric oxide (FeNO) is recommended by the American Thoracic Society (ATS) as a noninvasive biomarker of airway inflammation. In addition to inflammation, many factors may be associated with FeNO, particularly tobacco exposure; however, only age has been included as an influential factor for children below 12 years. Numerous studies have demonstrated negative associations between tobacco exposure and FeNO levels with self-reported data, but few with an objective assessment of smoking.Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2007–2012 were analyzed to examine the association between FeNO and active/passive tobacco. Exposure was assessed by both self-report and serum cotinine levels among 11,160 subjects aged 6–79 years old with asthma, or without any respiratory disease.Results: Study results indicated 28.8% lower FeNO, 95% CI [25.2%, 32.3%] and 38.1% lower FeNO, 95% CI: [28.1, 46.2] was observed among healthy and asthmatic participants with serum cotinine in the highest quartile compared to those in the lowest quartile, respectively. Self-reported smoking status and recent tobacco use were also associated with decreased FeNO. Self-reported passive smoking was significantly associated with a 1.0% decrease in FeNO 95% CI [0.0, 2.0] among asthmatic subjects but not among healthy subjects.Conclusions: Active smoking, whether measured by self-report or serum cotinine, was associated with decreased FeNO levels. In addition to age, increased attention should be given to tobacco exposure when using FeNO as a biomarker in clinical practice. Additional research is needed to establish reference value of FeNO considering the impact of tobacco exposure.

Exhaled nitric oxide as a better diagnostic indicator for evaluating wheeze and airway hyperresponsiveness in preschool children

Objective: Fractional concentration of exhaled nitric oxide (FeNO) is a known marker of airway inflammation. The aims of this study were to evaluate FeNO, impulse oscillometry (IOS), and spirometry in preschool children and to investigate their relationship with wheeze and airway hyperresponsiveness (AHR). Methods: We performed a population-based, cross-sectional study with 561 children aged 5–6 years. A total of 544 children completed a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and eligible for the study. We measured FeNO, spirometry, methacholine bronchial provocation, and IOS. AHR was defined as the induction of a 20% decrease in FEV1(PC20) by a methacholine concentration ≤8.0 mg/dL. Results: Children who had wheeze or AHR had higher FeNO levels than children without these symptoms. However, neither IOS nor spirometry parameters showed significant differences between children with wheeze or AHR and those without. FeNO was associated with AHR, whereas IOS or spirometry parameters showed no association. Mean FeNO levels were positively correlated with a dose–response slope for methacholine, but neither IOS nor spirometry parameters showed significant correlations. Conclusions: FeNO is a more sensitive measurement of AHR and wheeze than spirometry or IOS in preschool children.

Low alveolar and bronchial nitric oxide in severe uncomplicated obesity

Fractional concentration of exhaled nitric oxide (FeNO) is a recognized biomarker of the lower respiratory tract, where it is produced by the proximal conducting airways and the expansible peripheral bronchoalveolar compartment. We have previously shown that large increase in body mass decreases FeNO. Here we evaluated bronchial and alveolar components of the NO output of the lower respiratory tract in subjects with severe uncomplicated obesity (OB). Fifteen OB subjects (BMI 45.3 ± 5.6 kg/m(2)), 15 healthy controls (HC) (BMI 22.4 ± 2.4 kg/m(2)) and 10 obese subjects who experienced weight loss after bariatric surgery (OBS) (BMI 31.2 ± 3.4 kg/m(2)), were examined. Anthropometry and respiratory lung tests were performed. Exhaled NO was assessed using multiple single-breath NO analysis at different constant expiratory flow rates. From the fractional NO concentration measured at each flow-rate, the total NO flux between tissue and gas phase in the bronchial lumen (J'awNO), and the alveolar NO concentration (CANO) were extrapolated. Measured FeNO levels at 50 mL/s were lower in OB compared with HC and OBS (11.6 ± 2.8 ppb, 18.0 ± 4.1 ppb and 17.6 ± 2.9 ppb, respectively, p < 0.05). In OB, both J'awNO and CANO resulted significantly lower than OBS and HC values. Respiratory NO output is decreased in severe uncomplicated obesity for the reduction of both large/central airway maximal NO flux and alveolar NO concentration. The pathophysiological relevance of airway NO abnormalities in severe obese phenotype remains to be investigated.

Dose-dependent anti-inflammatory effect of inhaled mometasone furoate/formoterol in subjects with asthma

A well-controlled study in patients with allergic asthma was warranted to assess dose-dependency between fractional concentration of exhaled nitric oxide (FeNO) and sputum eosinophils to a combination of an inhaled corticosteroid plus a long-acting β2-agonist. We sought to characterize the dose-dependency of mometasone furoate/formoterol (MF/F) using FeNO and sputum eosinophil percentage as surrogates of airway inflammation in subjects with allergic asthma. Following a 2-week, open-label run-in, 93 subjects (≥12y) using only short-acting beta agonist reliever medication as needed, were randomized to twice daily (BID) placebo; MF/F 100/10μg, 200/10μg, or 400/10μg (via pressurized metered-dose inhaler [MDI]); MF-MDI 200μg; or MF 200μg via dry powder inhaler (DPI) during a 2-week, double-blind treatment period. All active treatments demonstrated significant percentage reductions from baseline in FeNO compared with placebo at all time points (P≤0.034). At endpoint, mean MF/F treatment group FeNO reductions ranged from -35.3% to -61.4%. Sputum eosinophil percentage reductions from baseline were significant compared with placebo for the MF/F 200/10μg, MF/F 400/10μg, and MF-DPI 200μg groups at endpoint (P≤0.023). Escalating MF/F doses significantly reduced both FeNO (P≤0.001) and sputum eosinophil (P≤0.022) levels in a dose-dependent manner at all time points. All treatments were well tolerated; no serious adverse events were observed. All 3MF/F doses demonstrated pronounced, clinically meaningful, dose-dependent reductions in FeNO, with reduced sputum eosinophil levels for MF/F 200/10μg and MF/F 400/10μg. These findings suggest both inflammatory markers may be useful in assessing corticosteroid responsiveness in asthma patients, and perhaps identifying the same asthma subphenotype. Clinical Trials.gov: NCT00635882.

Relationships Between Exhaled Nitric Oxide and Atopy Profiles (Mono-sensitization/Poly-sensitization) in Children with Asthma

In the atopic population, some individuals are sensitized only to 1 class of aeroallergens (mono-sensitized), whereas others are sensitized to more than 1 class of allergens (poly-sensitized). Fractional concentration of exhaled nitric oxide (FeNO) is one of the useful markers of eosinophilic airway inflammation in asthmatic patients. The aim of this study was to examine whether FeNO levels are associated with atopy profiles in terms of mono-sensitization and poly-sensitization in children with asthma.

Fraction of exhaled nitric oxide and wheezing phenotypes in preschool children

Asthma is a chronic lower airway inflammatory disease. Nitric oxide is an inflammatory mediator produced endogenously in the airway. Previous studies have demonstrated that the fractional concentration of exhaled nitric oxide (FeNO) is increased in asthma. To investigate if FeNO concentrations were correlated with wheezing phenotypes in preschool children and to compare the FeNO results with airway hyperresponsiveness (AHR) and pulmonary function test (PFT) results. We performed skin prick tests, methacholine provocation tests, PFT, impulse oscillometry bronchodilator response (IOS BDR) tests, and FeNO measurements in 372 preschool children between the ages of 4 and 6 years. Wheezing phenotypes were defined according to the age of onset and persistency. Persistent wheezers had higher FeNO levels than transient wheezers and non-wheezers. Among persistent wheezers, those with atopy and AHR had significantly higher FeNO levels than those without atopy or AHR. FeNO levels were significantly higher in late-onset wheezers than early-onset wheezers and non-wheezers. Among late-onset wheezers, those with atopy and AHR had a significantly higher FeNO concentration than those without atopy or AHR as well as those with either atopy or AHR. However, there were no significant differences in AHR, PFT, or IOS BDR between persistent and transient wheezers or between late-onset wheezers and early-onset wheezers. FeNO may be a better marker for asthma phenotypes in preschool children than AHR and PFT results.

Exhaled Nitric Oxide May Predict Bronchial Hyperreactivity in Patients with Allergic Rhinitis

Background: Nowadays it is possible to assess airway inflammation by measuring the fractional concentration of exhaled nitric oxide (FeNO) during an office visit and there is international consensus on the testing methodology. The aim of this study was to evaluate whether FeNO measurement may be a predictor of bronchial hyperreactivity (BHR) in patients with allergic rhinitis (AR). Methods: Two hundred eleven patients (196 males, median age 28.5 years) suffering from persistent AR were evaluated. Values for bronchial function (FVC, FEV₁, and FEF_25–75), bronchial provocation tests (methacholine), exhaled nitric oxide (FeNO), a visual analogue scale for nasal and bronchial symptoms, and sensitization were assessed. Results: A strong and inverse correlation between FeNO levels and BHR severity was found (r = –0.58). FeNO was a predictive factor for BHR, and 37 ppb was found to be the best cutoff (area under the curve 0.90) to define the presence of BHR in patients with AR. Conclusions: This study highlights the relevance of FeNO as a possible predictive marker for BHR in AR patients and underlines the close link between upper and lower airways. Thus, FeNO measurement could be a useful screening tool in identifying subjects with rhinitis at risk of developing asthma.

Incidence of Bronchial Hyperresponsiveness among Apprentices Exposed to Flour Dust and Hairdressing Chemicals and Changes in Exhaled Nitric Oxide

ISEE-0063 Background and Objective: The fractional concentration of exhaled nitric oxide (FENO), a simple, non-invasive and reproducible test, has been used as a surrogate marker of airways inflammation in several studies on asthma. It is still unclear, however, how useful FENO is to investigate occupational asthma (OA) or detect bronchial hyperresponsiveness (BHR). Methods: The association between changes in FENO levels since inception of exposure among bakery, pastry-cooking and hairdressing apprentices and the incidence of BHR was studied along their two-year training programme. At months 3, 9, 15 and 18, on average, after start of the programme, a metacholine challenge and measurement of FENO were performed during a medical visit, with completion of a standardized questionnaire and skin prick tests with common and specific occupational allergens. Results: Among 441 apprentices initially included, 351 completed the study. FENO values are influenced by gender (males>females), atopy (atopics>non atopics), smoking (non smokers>smokers). Increase in FENO values since inception of exposure was associated with the incidence of BHR (OR = 2.00 [95%CI = 1.21-3.32] per unit increase in log ppb), both among atopic and non-atopic volunteers, and was unrelated to past or current smoking habits, gender or training track. Incidence of BHR was also associated with atopy among bakers and pastry cooks (OR = 2.37 [1.2-4.7]) and skin sensitization to alkaline persulfaltes among hairdressers ([OR = 4.3 [0.9-21.4]). Conclusion: We conclude that measurement of FENO is a convenient means for early detection of BHR in occupations at risk of asthma. Studies should be undertaken to assess its usefulness as an early marker of non-occupational asthma.

Effect of elevated exhaled nitric oxide levels on the risk of respiratory tract illness in preschool-aged children with moderate-to-severe intermittent wheezing

The fractional concentration of exhaled nitric oxide (FeNO) is a noninvasive marker for airway inflammation but requires further study in preschool-aged children to determine its clinical relevance. To determine whether the risk of respiratory tract illnesses (RTIs), disease burden, and atopic features are related to FeNO in preschool-aged children with moderate-to-severe intermittent wheezing. We determined FeNO using the off-line tidal breathing technique in 89 children, aged 12 to 59 months, with moderate-to-severe intermittent wheezing. The risk of RTI was determined by comparing participants with a baseline FeNO of greater than the 75th percentile (24.4 ppb) with those with a baseline FeNO at the 75th percentile or lower using Cox regression analysis. The risk of RTI was significantly higher in children with an FeNO of greater than 24.4 ppb relative to those with lower FeNO values (adjusted relative risk, 3.80; 95% confidence interval, 1.74-8.22; P < .001). FeNO levels of greater than 24.4 ppb were associated with more positive skin test results to aeroallergens (P = .03) but not with other atopic characteristics or historic parameters of illness burden. An elevated FeNO in preschool-aged children with moderate-to-severe intermittent wheezing was associated with an increased risk of RTI during a 1-year follow-up. In addition, a higher FeNO was associated with aeroallergen sensitization.

8-Isoprostane in Exhaled Breath Condensate and Exercise-Induced Bronchoconstriction in Asthmatic Children and Adolescents

Exercise-induced bronchoconstriction (EIB) in the asthmatic child is associated with persistent airway inflammation and poor disease control. EIB could arise partly from airway oxidative stress. Exhaled breath condensate (EBC) levels of 8-isoprostane (IsoP), which is a known marker of oxidative stress, might therefore be helpful for monitoring asthma noninvasively. We recruited 46 asthmatic children and adolescents 6 to 17 years of age (29 boys), all of whom underwent lung function testing, measurement of the fractional concentration of exhaled nitric oxide (FENO), and collection of EBCs for 8-IsoP measurement before and after exercise challenge. FENO was measured before exercise and 5 min and 20 min after exercise. Spirometry was repeated 1, 5, 10, 15, and 20 min after exercise. Baseline 8-IsoP levels (but not baseline FENO levels) correlated with the fall in FEV(1) 5 min after exercise (r = - 0.47; p = 0.002). 8-IsoP levels measured after exercise remained unchanged from baseline levels; conversely, FENO levels decreased in parallel with the decline in FEV(1) at 5 min (r = 0.44; p = 0.002). The mean baseline 8-IsoP concentrations were higher in patients with EIB (n = 12) than in those without EIB (n = 34; 44.9 pg/mL [95% confidence interval (CI), 38.3 to 51.5] vs 32.3 pg/mL [95% CI, 27.6 to 37.0], respectively; p < 0.01). No difference was found in the mean baseline FENO between groups (with EIB group: 38.7 ppb; 95% CI, 24.5 to 61.1; without EIB group: 29.1 ppb; 95% CI, 22.0 to 38.4). Increased 8-IsoP concentrations in EBC samples of asthmatic children and adolescents with EIB suggest a role for oxidative stress in bronchial hyperreactivity.

Variations in Exhaled Nitric Oxide in Children with Asthma During a 1-Week Stay in a Mountain Village Sanatorium

Knowing about spontaneous variations in the fractional concentration of exhaled nitric oxide (FENO) could improve monitoring of airway inflammation in asthmatic children. We aimed to assess FENO variations (expiratory flow 50 mL/sec) in subjects maintained in similar environmental conditions. We tested spirometry and FENO in symptom-free asthmatic children (9 corticosteroid-naive, 8 corticosteroid-treated) during a 1-week stay in a countryside sanatorium and in their healthy relatives (n = 12) staying in the immediate neighborhood on summer holiday (total 29 children, M/F:14/15, 5.8-16.8 yrs). Testing sessions were repeated every 12 hours (8:00 am, 8:00 pm) for 2 days and again on day 7. Measurements were defined as reproducible when they agreed with an intraclass correlation coefficient (ICC) above 0.60; deviation from mean differences was assessed by the coefficient of repeatability (CR = 2 SD). Lung function remained constant throughout the week in all groups. Baseline FENO levels in corticosteroid-naive asthmatic children tended to decrease at the end of the week (from 13.9 ppb, 95% CI 12.2-19.1 to 9.2 ppb, 95% CI 5.8–15.9, p = 0.057). No differences were found between nocturnal and diurnal FENO. Within-session reproducibility for two FENO measurements was high (ICC 0.99 in all groups and CR, 0.9 to 1.3 ppb). Between-session FENO reproducibility at 12 hours and 24 hours was still high for each group but decreased markedly after 6 days in corticosteroid-naive asthmatic children (ICC 0.79 and CR 9.6 ppb at 24 hours vs. ICC 0.13 and CR 20.8 ppb after 6 days), whereas it decreased slightly in corticosteroid-treated asthmatics (from ICC 0.89 and CR 3.1 ppb to ICC 0.88 and CR 3.0 ppb) and healthy children (from ICC 0.79 and CR 4.8 ppb to ICC 0.65 and CR 5.7 ppb). In conclusion, in healthy subjects and in asthmatic children receiving therapy with inhaled corticosteroids (but not in corticosteroid-naïve subjects), FENO measurements are reproducible across a week.

Exhaled nitric oxide identifies the persistent eosinophilic phenotype in severe refractory asthma

The fractional concentration of exhaled nitric oxide (FENO) is increased in asthma, correlates with eosinophilic inflammation, and decreases after steroid therapy. We sought to examine whether persistent eosinophilia would be accompanied by an increased FENO level despite steroid therapy in patients with severe refractory asthma (SRA) as manifestations of steroid resistance. Subjects with SRA, subjects with mild-moderate asthma, and healthy control subjects had FENO measured, followed by endobronchial biopsy and bronchoalveolar lavage. Tissue and bronchoalveolar lavage inflammatory cells were assessed for all subjects, and eosinophil status (EOS+/EOS-) was determined for subjects with SRA. Twenty-four subjects with SRA, 15 subjects with moderate-mild asthma, and 17 healthy control subjects were studied. Subjects with EOS+ SRA had significantly higher median FENO levels compared with levels in subjects with EOS- SRA (P = .0084) and all other groups. In subjects with SRA, FENO levels correlated with tissue eosinophils (r(s) = 0.54, P = .007), lymphocytes (r(s) = 0.40, P = .003), and mast cells (r(s) = 0.44, P = .05). FENO levels of greater than 72.9 ppb were associated with a sensitivity of 0.56 and a specificity of 1.0 for EOS+ status in subjects with SRA. FENO measurement identified the subgroup of subjects with SRA with persistent eosinophilia despite steroid therapy. Further studies are needed on the use of FENO to monitor response to therapy over time in subjects with SRA.