Original articleAsthma, lower airway diseasePassive and active smoking and exhaled nitric oxide levels according to asthma and atopy in adults
Introduction
The noninvasive measure of fractional concentration of endogenous exhaled nitric oxide (FeNO) has great potential in the clinical setting and in epidemiologic study as a biomarker of pulmonary inflammation. However, methodological aspects and insufficient knowledge regarding its determinants currently limit its applicability as a good “inflammometer” to guide the management of asthma.1, 2 In a recent review,3 differences in design and methodological issues and the lack of consideration of environmental and host factors have been proposed to explain that FeNO-based algorithms are less successful at guiding asthma therapy than are sputum eosinophils. As underlined by the author, no data are available regarding the utility of FeNO to guide therapy in smoking asthmatic patients, and identification of the effect of smoking in large samples is needed.
Epidemiologic studies led to conflicting results regarding the complex associations of FeNO with smoking, asthma, and atopy. FeNO was negatively associated with current smoking in atopic individuals only4 and was positively associated with asthma symptoms in the last month in never-smokers only.5 Whereas recent observations by Malinovschi et al6 suggest that increased FeNO levels in asthma (allergic or not) may be restricted to never smokers, those by Michils et al7 show an association of FeNO level with asthma control, even in smokers. The debate regarding the clinical relevance of monitoring FeNO levels in asthma remains open. Further studies are needed to disentangle the complex relationships of atopy, smoking, and asthma, particularly in adults.
Although the decrease in FeNO levels in relation to active smoking is established, few studies7, 8 have been conducted on the effect of smoking in asthmatic patients. Studies9, 10 in infants and children suggest that in utero exposure to tobacco and environmental tobacco smoke (ETS) decrease FeNO levels, but it is unknown whether usual exposure to ETS modifies FeNO levels in adults. Understanding the effect of ETS in asthmatic individuals across the lifespan is of particular relevance.
The overall hypothesis of this study is that the association between asthma and FeNO level varies according to active and passive smoking. Using data from the EGEA (Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy), the aim of the present study was to investigate the effects of active and passive smoking on FeNO levels in adults according to current asthma and atopy status, simultaneously taking into account host factors (age, sex, and height).
Section snippets
Study Design
The EGEA combines a case-control and family study of asthma (http://ifr69.vjf.inserm.fr/∼egeanet/). Participants were recruited between 1991 and 1995, and the protocol and descriptive characteristics have been described elsewhere.11, 12 The present cross-sectional analysis is based on FeNO measurements recorded during follow-up conducted between 2003 and 2007.13 The studied population included 654 adults (325 men and 329 women; 299 in Paris, 63 in Montpellier [France], and 292 in Grenoble) with
Results
The overall characteristics of the 654 adults according to current asthma status are summarized in Table 1. As expected, compared with nonasthmatic participants, asthmatic participants had a significantly lower mean forced expiratory volume in 1 second (107.3% vs 96.4% of predicted, P < .001); had more frequent bronchial hyperresponsiveness (odds ratio [OR], 6.5; 95% confidence interval [CI], 4.1–10.1), atopy (OR, 5.5; 95% CI, 3.7–8.0), and eosinophilia (OR, 3.5; 95% CI, 2.0–5.9); and more
Discussion
The present epidemiologic study shows for the first time, to our knowledge, that not only active but also passive smoking affect FeNO levels in adults. Level of FeNO decreased with active smoking, with ex-smokers having intermediate values. The association was observed in nonasthmatic and asthmatic participants, and especially in atopic asthmatic participants. Furthermore, lower FeNO levels were found in participants exposed to ETS at least 2 h/d, an association observed in nonasthmatic and
Acknowledgments
We thank all those who participated in the various aspects of this study: interviewers, technicians for lung function testing and skin prick tests, blood samplers, IgE determinators, and coders and those involved in quality control, data and sample management, and study supervision at all the centers. We are also grateful to the CIC-Inserm of Necker and Grenoble, which supported the study and in which participants were examined. We are indebted to all the individuals who participated, without
References (32)
- et al.
Exhaled nitric oxide in guideline-based asthma management
Lancet
(2008) - et al.
Measuring exhaled nitric oxide levels in adults: the importance of atopy and airway responsiveness
Chest
(2004) - et al.
Height, age, and atopy are associated with fraction of exhaled nitric oxide in a large adult general population sample
Chest
(2006) - et al.
Noninvasive evaluation of airway inflammation in asthmatic patients who smoke: implications for application in clinical practice
Ann Allergy Asthma Immunol
(2008) - et al.
A comparison of exhaled nitric oxide measurements performed using three different analysers
Respir Med
(2006) - et al.
Fraction of exhaled nitric oxide at 50 mL/s: reference values for adult lifelong never-smokers
Chest
(2007) - et al.
Exhaled nitric oxide: independent effects of atopy, smoking, respiratory tract infection, gender and height
Respir Med
(2008) - et al.
Reactive nitrogen species in the respiratory tract
Eur J Pharmacol
(2006) - et al.
Oxidative and nitrosative events in asthma
Free Radic Biol Med
(2003) - et al.
Daily telemonitoring of exhaled nitric oxide and symptoms in the treatment of childhood asthma
Am J Respir Crit Care Med
(2009)
Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm studies
Clin Exp Allergy
Both allergic and nonallergic asthma are associated with increased FE(NO) levels, but only in never-smokers
Allergy
Exhaled nitric oxide as a marker of asthma control in smoking patients
Eur Respir J
Smoke exposure, airway symptoms and exhaled nitric oxide in infants: the Generation R study
Eur Respir J
Passive smoking is a major determinant of exhaled nitric oxide levels in allergic asthmatic children
Allergy
EGEA (Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy): descriptive characteristics
Clin Exp Allergy
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2018, Annals of Allergy, Asthma and ImmunologyCitation Excerpt :A recent review showed FeNO testing can be routinely performed in basic clinical settings, and it is inexpensive and clinically useful.3 Like all other established clinical laboratory tests, FeNO concentration levels can be influenced by current or recent anti-inflammatory medication usage, current or recent respiratory infection, smoking,4–6 and a diet rich in NO in addition to demographic factors (ethnicity, race, age, sex, weight, and height). FeNO concentration levels also can be influenced by laboratory factors (ie, analyzer used, measurement technique, exhalation flow rate, etc).
Disclosures: Authors have nothing to disclose.
Funding Sources: This research was funded in part by PHRC-Paris, ANR 05-SEST-020-02/05-9-97, ANR-06-CEBS, Merck Sharp & Dohme, and the GA2LEN project (Global Allergy and Asthma European Network).