How Airway Caliber Affects FeNO Thresholds Used to Identify Type 2 Inflammation in Asthma

Fractional exhaled nitric oxide (FeNO) has emerged as a biomarker of type 2 (T2) airway inflammation (AI), primarily reflecting IL-13 activity. Reducing airway caliber reduces FeNO levels, suggesting an impact of airway obstruction.

This study compared the relative contributions of airway IL-13 and airway caliber to FeNO values in patients with asthma. We also investigated how airway caliber reduction affects FeNO thresholds for detecting active T2 AI.

FeNO and forced expiratory volume in 1 second (FEV₁) measurements as well as sputum induction were performed in 120 patients with asthma and 13 controls. Elevated sputum IL-13, IL-5, or eosinophils identified 100 patients with active T2 AI. The contributions of IL-13 and FEV₁ to FeNO were assessed in asthmatics with clear evidence of T2 AI by multivariable linear models. Receiver operating characteristic (ROC) curve analysis was used to identify FeNO thresholds marking the presence of active T2 AI according to FEV₁.

In T2 patients, IL-13 and FEV₁ contribute significantly (P = .005 and P = .008, respectively) to FeNO based on multivariable analysis. From the ROC curve analysis, the FeNO threshold corresponding to a specificity >85% was 45 parts per billion (ppb) in the whole population and dropped to 22 ppb in patients with FEV₁ <70%.

Airway caliber is a major determinant of FeNO values in asthma, as crucial as concomitant T2 AI. As a result, the optimal thresholds for FeNO to signal the presence of active T2 AI in asthmatics decrease significantly as FEV₁ decreases. New thresholds considering the impact of lung function should be established in larger cohorts.