Serum IgG Levels and Risk of COPD Hospitalization: A Pooled Meta-Analysis.

BACKGROUND: Hypogammaglobulinemia (serum immunoglobulin G (IgG) levels < 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations. RESEARCH QUESTION: To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD. STUDY DESIGN: and methods: Serum IgG levels were measured on baseline samples from four COPD cohorts (n=2,259): Azithromycin for Prevention of AECOPD (MACRO, n=976); Simvastatin in the Prevention of AECOPD (STATCOPE, n=653), Long-Term Oxygen Treatment Trial (LOTT, n=354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n=276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status. RESULTS: The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared to those with normal levels (Gray's test, P < .001); pooled SHR (meta-analysis) was 1.29 (95% CI: 1.06 - 1.56, P = .01). Among patients with prior COPD admissions (n=757), the pooled SHR increased to 1.58 (95% CI: 1.20 - 2.07, P < .01). The risk of COPD admissions, however, was similar between IgG groups in patients with no prior hospitalizations: pooled SHR = 1.15 (95% CI: 0.86 - 1.52, P =.34). The hypogammaglobulinemia group also showed significantly higher rates of COPD hospitalizations per person-year: 0.48 ± 2.01 vs. 0.29 ± 0.83, P < .001. INTERPRETATION: Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions.