Domiciliary fractional exhaled nitric oxide predicts exacerbation risk and guides ICS tapering in controlled asthma

Fluctuating airway inflammation drives asthma clinical variability, yet current monitoring lacks dynamic assessment. Domiciliary fractional exhaled nitric oxide (FeNO) measurements offer real-time inflammatory tracking. To explore asthma clinical phenotypes and prognosis using FeNO trajectories. In this 24-week prospective cohort study, 89 participants recorded daily FeNO and completed weekly online questionnaires. ICS dose adjustments, including step down decisions, followed GINA stepwise approach based on clinical stability. Spirometry, blood eosinophil counts, exacerbation rates, and corticosteroid requirements were assessed at baseline and during stable-phase control. Patients were classified into three phenotypes based on baseline and stable‑phase FeNO using the 50 ppb threshold (ATS guideline) and a ≥ 20% reduction criterion. Clustering analysis validated the classification. Three phenotypes were identified: (1) Low Group (n = 34): Sustained FeNO < 50 ppb (median: baseline 26.75 (17.33–32.04) ppb, stable-phase 18.05 (13.09–21.93) ppb). (2) Decrease Group (n = 31): Baseline FeNO ≥ 50 ppb (median: baseline 73.70 (62.67–96.00) ppb) with ≥ 20% reduction to stable-phase values < 50 ppb (median: 27.06 (22.77–32.70) ppb). (3) High Group (n = 24): Persistent FeNO ≥ 50 ppb (median: baseline 104.30 (79.00–128.00) ppb, stable-phase 68.48 (59.22–76.98) ppb).The High group had higher late-onset asthma (87.5%) and rhinosinusitis (62.5%) rates, required higher ICS doses (600 vs. 400 µgBDPeq/day, P < 0.05), and showed minimal FEV1 improvement (ΔFEV1 +7.34%, P = 0.32) with FeNO rebound during ICS tapering. The Decrease Group exhibited the greatest FEV1 improvement (P < 0.05) and the lowest exacerbation rate (0.26/person-year). Overall, 95% of patients reached FeNO stability within 41.4 days. Baseline FeNO > 78 ppb combined with FEV₁/FVC > 75% predicted the High phenotype (AUC 0.89, 95% CI 0.79–0.98). Home‑based FeNO monitoring identifies three clinically distinct asthma phenotypes with different treatment responses and ICS tapering safety. The 41‑day stabilization window and prediction model provide an evidence‑based framework for personalized, biomarker‑guided asthma management. 1. What is already known about this topic?​​ Current asthma monitoring relies on cross-sectional assessment, which fails to capture dynamic inflammatory fluctuations or reliably predict long-term outcomes. 2. What does this article add to our knowledge?​​ Longitudinal home FeNO trajectories define three phenotypes (Low, Decrease, High). The High phenotype shows persistent type 2 inflammation despite symptom control, requires higher ICS doses, and risks inflammatory rebound when ICS is tapered. The Decrease phenotype has excellent ICS responsiveness and low exacerbation risk. A 41‑day stabilization window and a baseline prediction model (FeNO >78 ppb + FEV₁/FVC >75%) enable early risk stratification. 3. How does this study impact current management guidelines?​​ This study supports the use of inflammatory trajectory phenotypes monitored by home FeNO to clinical decision‑making, risk of exacerbation, and tapering safety for personalized asthma management.