Determinants of FeNO in a population-based cohort: the role of lung volumes and body composition

Introduction: Fractional exhaled nitric oxide (FeNO) is a clinically utilized marker of Type 2 airway inflammation and is used to guide treatment in asthma. Objectives: We aim to resolve the ongoing scientific debate, whether FeNO is affected by obesity-related changes in inflammation and airway architecture. Methods: We assessed the association of FeNO levels with obesity markers and lung function parameters in 1205 respiratory-healthy adult participants (43.1% males) aged 18-82 years from the Austrian LEAD cohort with mean body mass index (BMI) of 26.4±4.7kg/m2. Sensitivity analyses were conducted in the respiratory-healthy obese subpopulation (n=230). Results: Median FeNO levels were 16.0 (interquartile IQR: 12.0 - 23.0; 95th percentile: 34.0) ppb in the respiratory-healthy any-weight population, with higher levels reported in the respiratory-healthy obese (17.5 IQR: 12.0 - 23.0 ppb; 95th percentile: 35.0 ppb) population. Unadjusted multiple regression analyses showed that BMI; indices of fat mass, visceral adipose tissue (VATI), appendicular lean mass; and residual volume (RV) %predicted were associated with higher FeNO levels in respiratory-healthy any-weight individuals. In obese respiratory-healthy individuals, only VATI showed statistically significant association with FeNO. After adjusting for the confounders as age, sex, and smoking status all assessed parameters lost their significance in the assessed populations except for residual volume- and total lung capacity Z-scores, although at low effect size. Conclusion: Our results demonstrate no independent effect of obesity markers on FeNO levels after adjustments for age, sex, and smoking status.