Elevated Immunoglobulin G as a Predictor of Progression to Severe Lung Disease in Cystic Fibrosis: A Longitudinal Cohort Study.

Background: Elevated immunoglobulin G (IgG) levels are associated with worse lung function and disease severity in people with cystic fibrosis (PwCF). This study evaluated whether elevated IgG levels-defined as values above the 97.5th percentile (Z-score ≥ 1.96 standard deviations above the mean)-can predict progression to severe lung disease. Methods: A retrospective cohort study of children and adults with CF at a single-center clinic was performed. Patients with elevated baseline IgG Z-scores were compared to those with normal or low IgG levels. Progression to severe lung disease was defined as % predicted FEV1 < 40%, referral for lung transplantation, or death. Kaplan-Meier survival curves and Cox models were used to analyze clinical outcomes. A sensitivity analysis was conducted for patients aged 18 years or older. Results: Of 97 patients, 31 (31.9%) had elevated IgG levels. Progression to severe lung disease occurred in 14 (14.4%) patients, 12 (85.7%) of whom had elevated IgG. These patients were significantly older and had a higher prevalence of Pseudomonas aeruginosa colonization. Among adults, those with elevated IgG had lower baseline % predicted FEV1 and greater annual lung function decline. Elevated IgG was independently associated with progression to severe lung disease (adjusted hazard ratio [aHR]: 9.8; 95% CI: 1.9-48.6), even after adjusting for Pseudomonas colonization and annual % predicted FEV1 decline. Conclusions: Elevated IgG was associated with progression to severe lung disease in PwCF and correlated with older age, Pseudomonas colonization, and-in adults-lower baseline lung function and faster decline. These findings highlight elevated serum IgG as a meaningful prognostic biomarker for identifying high-risk PwCF who may benefit from closer monitoring and earlier intervention.