Associations of Mucus Plugging, Small Airway Dysfunction, and Airway Wall Thickening in Cough-Variant Versus Classic Asthma

Background Mucus plugs have been implicated in airflow obstruction in asthma and chronic obstructive pulmonary disease (COPD). However, the role of mucus plugs in cough-variant asthma (CVA) remains understudied, and their associations with classic asthma (CA), CVA, and small airway dysfunction (SAD) are poorly defined. This retrospective cohort study aimed to evaluate the relationship between mucus plugs and lung function in CA and CVA patients, and to investigate their correlations with quantitative CT-derived airway wall thickness parameters. Methods A total of 109 CVA patients and 65 CA patients were enrolled. Clinical characteristics, laboratory parameters, quantitative CT data, and pulmonary function metrics were systematically collected. Airway structural measurements, including airway wall thickness (WT), wall area percentage (WA%), and wall thickness-to-outer diameter ratio (T/OR), were derived from chest CT scans. Multivariable regression models were employed to assess the associations of mucus plugs with airway structural features, lung function, and clinical profiles. Results Although the prevalence of mucus plugs in CVA was lower than in CA (20% [22/109] vs. CA), CVA patients with mucus plugs exhibited significantly worse WA%, spirometric indices (FEV1/FVC, PEF%pred, MMEF%pred, MEF75%pred, MEF50%pred), and impulse oscillometry (IOS) parameters (X5) compared to CA patients. In CVA, mucus plug scores demonstrated significant positive correlations with WA%, spirometric metrics (FEV1/FVC, PEF%pred, MMEF%pred, MEF75%pred, MEF50%pred), and X5. Multivariable logistic regression identified disease duration, peripheral blood eosinophil count (Eos), WA%, and SAD parameters as independent risk factors for mucus plug formation in CVA. Conclusions Mucus plugs are present in CVA patients, albeit at a lower prevalence than in classic asthma. Their severity correlates positively with WA% and small airway dysfunction, underscoring their potential role in CVA pathophysiology.