Supplementary Material for: 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.

引言：呼出气一氧化氮分数（Fractional exhaled nitric oxide, FeNO）是临床常用的2型气道炎症标志物，用于指导哮喘的治疗方案制定。
研究目的：本研究旨在解决当前尚存的科学争议，即呼出气一氧化氮分数是否会受肥胖相关的炎症及气道结构改变的影响。
研究方法：本研究纳入来自奥地利LEAD队列的1205名呼吸健康成人受试者（年龄18~82岁，男性占比43.1%，平均体质量指数（Body Mass Index, BMI）为26.4±4.7kg/m²），评估其呼出气一氧化氮分数水平与肥胖标志物及肺功能参数的相关性。同时针对呼吸健康肥胖亚人群（n=230）开展敏感性分析。
研究结果：在全部呼吸健康受试者中，呼出气一氧化氮分数的中位数为16.0ppb（四分位间距（Interquartile Range, IQR）：12.0~23.0；95百分位数：34.0ppb）；其中呼吸健康肥胖人群的呼出气一氧化氮分数更高，为17.5ppb（四分位间距：12.0~23.0ppb；95百分位数：35.0ppb）。未校正的多元回归分析显示，在所有呼吸健康受试者中，体质量指数、脂肪质量指标、内脏脂肪组织指数（visceral adipose tissue, VATI）、四肢瘦质量以及预测残气量百分比（residual volume %predicted, RV）与更高的呼出气一氧化氮分数水平相关。而在呼吸健康肥胖受试者中，仅内脏脂肪组织指数与呼出气一氧化氮分数存在统计学显著相关性。在校正年龄、性别、吸烟状态等混杂因素后，除残气量及肺总量Z评分（total lung capacity Z-scores）外，所有评估参数在上述人群中均失去统计学意义，不过其效应量较低。
研究结论：本研究结果表明，在校正年龄、性别及吸烟状态后，肥胖相关标志物对呼出气一氧化氮分数水平并无独立影响。