Background Chronic inflammation and immunity play an important role in the pathophysiology and progression of bronchiectasis. However, the role of sputum immunoglobulins (Igs) and their association with disease progression is still unknown. Research question What is the relationship between airway immunoglobulins and disease progression in bronchiectasis? Study design and methods Patients from the prospective European Bronchiectasis Registry (EMBARC-BRIDGE; NCT03791086 ) were included. We defined three severity groups (mild, moderate, and severe) according to the Bronchiectasis Severity Index, which ranges from 0 to 26. The levels of sputum IgG, IgM, and IgA were quantified in sputum supernatants using commercial ELISA kits (R&D Systems), and correlations of local Igs with severity were estimated using Spearmańs coefficients. p - trend values were obtained to evaluate the trend of the correlation across the spectrum of severity. Results 227 patients were analyzed (49% were female, and 64% were older than 65 years). IgA accounted for 90% of the total sputum Igs in the mild risk group, 89% in the moderate risk group, and 86% in the severe risk group (p - trend value=0.007). IgG accounted for 6% of the total sputum Igs in the mild risk group, 9% in the moderate risk group, and 11% in the severe risk group (p-trend value=0.008). IgA/IgG ratio varied between 23 (IQR 11–53) in the mild risk group, 21 (IQR 8–40) in the moderate risk group and 14 (IQR7–27) in the severe risk group (p-trend value=0.02). We found moderate positive correlations between IgG levels and severity among patients with COPD (rho: 0.41, pairwise comparison p-value=0.04) and post-infective as the underlying etiology (rho: 0.40, pairwise comparison p-value=0.05). Interpretation In this bronchiectasis cohort, we have provided evidence of imbalanced immunoglobulin isotypes in severe bronchiectasis. This could indicate less functional antimicrobial defenses, contributing to persistent airway inflammation and airway remodeling in disease progression.
González-Jaramillo et al. (Thu,) studied this question.