Bronchial responsiveness is related to increased exhaled NO (FE(NO)) in non-smokers and decreased FE(NO) in smokers

PLoS One. 2012;7(4):e35725. doi: 10.1371/journal.pone.0035725. Epub 2012 Apr 26.


Rationale: Both atopy and smoking are known to be associated with increased bronchial responsiveness. Fraction of nitric oxide (NO) in the exhaled air (FE(NO)), a marker of airways inflammation, is decreased by smoking and increased by atopy. NO has also a physiological bronchodilating and bronchoprotective role.

Objectives: To investigate how the relation between FE(NO) and bronchial responsiveness is modulated by atopy and smoking habits.

Methods: Exhaled NO measurements and methacholine challenge were performed in 468 subjects from the random sample of three European Community Respiratory Health Survey II centers: Turin (Italy), Gothenburg and Uppsala (both Sweden). Atopy status was defined by using specific IgE measurements while smoking status was questionnaire-assessed.

Main results: Increased bronchial responsiveness was associated with increased FE(NO) levels in non-smokers (p = 0.02) and decreased FE(NO) levels in current smokers (p = 0.03). The negative association between bronchial responsiveness and FE(NO) was seen only in the group smoking less <10 cigarettes/day (p = 0.008). Increased bronchial responsiveness was associated with increased FE(NO) in atopic subjects (p = 0.04) while no significant association was found in non-atopic participants. The reported interaction between FE(NO) and smoking and atopy, respectively were maintained after adjusting for possible confounders (p-values<0.05).

Conclusions: The present study highlights the interactions of the relationship between FE(NO) and bronchial responsiveness with smoking and atopy, suggesting different mechanisms behind atopy- and smoking-related increases of bronchial responsiveness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bronchial Hyperreactivity / diagnosis*
  • Bronchial Provocation Tests
  • Exhalation
  • Female
  • Humans
  • Male
  • Methacholine Chloride
  • Middle Aged
  • Nitric Oxide / analysis*
  • Smoking*
  • Surveys and Questionnaires


  • Methacholine Chloride
  • Nitric Oxide