Hypogammaglobulinemia and Risk of Exacerbation and Mortality in Patients with COPD

Abstract

Introduction: Chronic obstructive pulmonary disease (COPD) may, in some patients, be characterized by recurring acute exacerbations. Often these exacerbations are associated with airway infections. As immunoglobulins (Ig) are important parts of the immune defence against airway infections, the aim of this study was to relate the levels of circulating immunoglobulins to clinical features in unselected patients with COPD included in a Norwegian multicenter study.

Methods: Clinical and biological data, including circulating levels of immunoglobulins, were assessed in 262 prospectively included patients with COPD GOLD stage II-IV at five hospitals in south-eastern Norway. A revisit was done after one year, and survival was assessed after five years. Clinical features and survival of those with immunoglobulin levels below reference values were compared to those with normal levels.

Results: In total, 11.5% of all COPD patients and 18.5% of those with GOLD stage IV had IgG concentrations below reference values. These patients were more likely to use inhaled or oral steroids, had lower BMI, and lower FEV1%. Moreover, they had significantly more COPD-related hospital admissions (2.8 vs 0.6), number of prednisolone courses (3.9 vs 1.2), and antibiotic treatments (3.7 vs 1.5) in the preceding year. Importantly, hypogammaglobulinemia was significantly associated with reduced survival in a log-rank analysis. In multivariate regression analysis, we found that the higher risk for acute exacerbations in these patients was independent of other risk factors and was associated with impaired survival.

Conclusion: In conclusion, our study suggests that hypogammaglobulinemia may be involved in poor outcome in COPD and may thus be a feasible therapeutic target for interventional studies in COPD.

Keywords: COPD; IGG deficiency; immunodeficiency.

Conflict of interest statement

The authors declare that they have no conflicts of interest or competing interests regarding any of the contents of this document or the work related to it.

© 2020 Holm et al.

Figures

Figure 1

Plasma concentration of immunoglobulins in 262 patients with COPD stage II–IV. Black lines indicate mean and 95% CI, dotted line indicates upper and lower reference values. Numbers in graph indicate percentage of patients with values below reference.

Figure 2

Acute exacerbations of COPD in hypogamma-COPD vs normal-IgG-COPD. Black dots: COPD patients with IgG 

Figure 3

COPD admissions in previous year by serum IgG levels. There was a significant non-parametric correlation between number of COPD admissions in the previous year (the year preceding inclusion) and the serum levels of IgG measured upon inclusion (Spearman's test p

Figure 4

Survival after inclusion in hypogamma-COPD vs normal-IgG-COPD. The Kaplan–Meyer plot shows transplant-free survival of all included patients from time of inclusion to five years after inclusion of the last patient. Black line: normal-IgG-COPD. Dotted line: hypogamma-COPD. Survival compared using Log-rank test (p=0.0003).