Original article
Asthma, lower airway disease
Passive and active smoking and exhaled nitric oxide levels according to asthma and atopy in adults

https://doi.org/10.1016/j.anai.2010.03.013Get rights and content

Background

No data are available regarding the utility of fractional exhaled nitric oxide (FeNO) level in guiding therapy in smoking asthmatic patients. Identification of the effect of smoking in a large sample is needed.

Objective

To study the association between smoking and FeNO level according to current asthma and atopy status in adults from the French EGEA (Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy).

Methods

Levels of FeNO were measured at 50 mL/s in 654 adults (268 asthmatic participants). Active smoking and environmental tobacco smoke (ETS) exposure at home, at work, and during leisure activities were recorded. Participants were categorized as having no exposure to ETS, mild exposure (ETS <2 h/d), and noticeable exposure (ETS ≥2 h/d). Multivariate analyses were performed, with adjustment for age, sex, height, and center.

Results

Mean adjusted FeNO values increased with asthma (15.1 vs 19.5 ppb), atopy (14.2 vs 18.9 ppb), and eosinophilia (15.8 vs 24.8 ppb) (P < .001 for all). Mean FeNO levels decreased with smoking (18.4, 17.5, and 14.5 ppb in nonsmokers, ex-smokers, and current smokers, respectively; P for trend = .001). The association with smoking was observed in nonasthmatic and asthmatic participants, especially in atopic asthmatic participants. Multivariate analyses showed that ETS exposure of at least 2 h/d and active smoking were negatively and significantly associated with FeNO levels independent of age, sex, height, and center in nonasthmatic participants (mean [SE], −0.13 [0.06], P = .03 and −0.10 [0.03], P < .001) and in asthmatic participants (mean [SE], −0.18 [0.07], P = .01 and −0.14 [0.04], P = .02).

Conclusions

Active and passive smoking decreased FeNO levels in adults. Careful consideration of asthma, atopy, and active and passive smoking are needed to interpret FeNO values.

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

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    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).

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