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

Abstract

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.

Figure 1. Number of subjects in each FE_NO quartile (FE_NO Q₁–Q₄) for non-smoking non-atopics, non-smoking atopics, smoking non-atopics and smoking atopics, respectively.

Figure 2. Methacholine challenge dose-response slope for all subjects divided upon their FE_NO quartiles values and smoking status.

Data is presented as mean values ± standard error of the mean and a regression line (p-value in the brackets) is drawn for non- and current smokers, respectively.

Figure 3. Effect size* (95%CI) for the association between slope and FE_NO (log-transformed) in non-, light (<10 cigarettes/day) and heavy smokers (≥10 cigarettes/day).

* The effect size is the regression coefficient obtained by linear regression models with slope as outcome and log-transformed FE_NO as dependent variable where the estimates of the three centres were combined by meta-analysis.

Figure 4. Methacholine challenge dose-response slope for all subjects divided upon their FE_NO quartiles values and atopy status.

Data is presented as mean values ± standard error of the mean and a regression line (p-value in the brackets) is drawn for non-atopics and atopics, respectively.