[A multicenter, prospective, observational study of cough variant asthma in China: clinical features, airway...

Objective: To investigate the changes in cough severity, lung function, and airway inflammation after anti-asthma treatment in patients with cough variant asthma (CVA), as well as the factors related to treatment response. Methods: This nationwide, multicenter, prospective observational cohort study enrolled newly diagnosed cough-variant asthma (CVA) patients from 17 hospitals across China between December 2017 and January 2020. Patients received anti-asthma treatment and were followed for 6 months. Changes in cough severity, lung function, induced sputum and fractional exhaled nitric oxide (FeNO) were assessed. Type 2 inflammation was defined as sputum eosinophils ≥3%, and/or FeNO ≥50 ppb, and/or blood eosinophils ≥0.3×10⁹ cells/L. Continuous variables were presented as mean±standard deviation or median (Q₁, Q₃), and intergroup comparisons were conducted using t-tests, analysis of variance (ANOVA), or rank-sum tests. Categorical variables were analyzed using chi-squared or Fisher's exact tests. Repeated measures were analyzed using a mixed-effects model, and Cox regression was used to identify factors associated with complete cough resolution. Results: A total of 342 CVA patients (114 males and 228 females) were included, with a mean (±SD) age of (41.2±12.9) years (range 18-70 years). After 2 months of treatment, the median values for lung function parameters, FeNO levels, and sputum eosinophil counts of included CVA patients returned to near-normal levels, while the greatest improvement in cough severity was observed after 4 months of treatment. In 125 (36.5%) CVA patients, cough persisted despite 6 months of treatment. Compared with patients who achieved complete cough resolution, those with persistent cough were older, had a longer disease duration, higher baseline sputum neutrophil counts, lower sputum eosinophil counts, lower FeNO levels, and a lower proportion of type 2 inflammation [42.4% (53/125) vs. 65.3% (141/216)], P=0.001). Type 2 inflammation (HR=1.733, 95%CI: 1.188-2.528, P=0.004) was a predictive factor for complete cough resolution. Conclusions: CVA patients achieved the greatest improvement in cough after 4 months of anti-asthma treatment, suggesting that the treatment course may need to extend beyond 4 months. In some CVA patients, cough remained incompletely resolved despite treatment, which may be related to non-type 2 inflammation.