Activin A/Follistatin Axis in Airway Diseases and its Association With Recurrent Exacerbations

Chronic airway diseases, including chronic obstructive pulmonary disease (COPD), asthma, and asthma COPD overlap (ACO), are characterized by complex inflammatory processes in which Activin A-a key member of the TGF-β superfamily-is implicated. Although its role in the stable state of these diseases has been extensively studied, data regarding its involvement during exacerbations remain limited. Our objective was to investigate the dynamics of Activin A in sputum and serum during acute exacerbations and subsequent convalescence in patients with chronic airway diseases.

In this prospective study, 53 patients with asthma, COPD, and ACO, aged 14 years and older were recruited upon hospitalization for an acute exacerbation. Sputum and peripheral blood samples were collected at admission, hospital discharge, one month, and four months post-exacerbation. Protein levels of Activin A were quantified by ELISA were compared among the patient groups and the kinetics of Activin A expression following exacerbation events were examined.

Baseline Activin A levels were comparable across the patient groups. However, during exacerbations, sputum Activin A levels increased markedly and subsequently declined during convalescence, while serum levels exhibited an inverse pattern-being lower during exacerbations and rising during stable periods. Notably, COPD patients with recurrent exacerbations maintained persistently elevated sputum Activin A levels throughout the study period, suggesting that sustained local inflammation may predispose these patients to frequent exacerbations.

These findings reveal a compartment-specific regulation of Activin A in chronic airway diseases, underscoring its potential as a biomarker for disease activity and exacerbation risk.