Predictors of Low and High Exhaled Nitric Oxide Values in Asthma: A Real-World Study

Background: In asthma, exhaled nitric oxide (FENO) is a clinically established biomarker of airway T2 inflammation and an indicator for anti-inflammatory therapy. Objectives: The aim of the study was to identify, in an observational real-world cross-sectional study, the main characteristics of patients with asthma as classified by their FENO level. Method: We stratified 398 patients with stable mild-to-severe asthma according to FENO level as low (<= 25 ppb) versus elevated (>25 ppb), subdividing the latter into two subgroups: moderately elevated (26-50 ppb) versus very high FENO (>50 ppb). Clinical, functional, and blood parameters were extrapolated from patients' chart data and compared with the FENO stratification. Predictors of low and elevated FENO asthma were detected by logistic regression model. Results: Low BMI, higher blood eosinophilia, allergen poly-sensitization, the severest airflow obstruction (FEV1/FVC), and anti-leukotriene use are predictors of elevated FENO values in asthma, as well as persistent rhinitis and chronic rhinosinusitis with or without nasal polyps. Beyond these, younger age, more than 2 asthma exacerbations/year, higher airflow reversibility (post-bronchodilator increment FEV1), and oral corticosteroid dependence are predictors of very high FENO values. In contrast, obesity, obstructive sleep apnoea syndrome, gastroesophageal reflux disease, arterial hypertension, and myocardial infarction are predictors of low FENO asthma. In our population, FENO correlated with blood eosinophils, airflow obstruction, and reversibility and negatively correlated with age and BMI. Conclusions: Stratifying patients by FENO level can identify specific asthma phenotypes with distinct clinical features and predictors useful in clinical practice to tailor treatment and improve asthmatic patients' outcomes.