<p>Hypogammaglobulinemia and Risk of Exacerbation and Mortality in Patients with COPD</p>

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.

Prediction of Acute COPD Exacerbation in the Swiss Multicenter COPD Cohort Study (TOPDOCS) by Clinical Parameters, Medication Use, and Immunological Biomarkers

“…Further, IgG2 levels were associated with AECOPD independent of patient's FEV 1 % predicted or GOLD stage. A recent study showed that hypogammaglobulinemia (IgG-levels below 6 g/L) is more common in patients with higher GOLD or MMRC score [29]. Moreover -in line with our findings -hypogammaglobulinemia remained an independent risk factor for AECOPD after correction for FEV 1 % predicted and was associated with reduced survival.…”

“…Moreover – in line with our findings – hypogammaglobulinemia remained an independent risk factor for AECOPD after correction for FEV 1 % predicted and was associated with reduced survival. Specifically, low IgG2 levels were associated with severe AECOPD in the year before measurement [29].…”

Association of mannose-binding lectin, ficolin-2 and immunoglobulin concentrations with future exacerbations in patients with chronic obstructive pulmonary disease: secondary analysis of the randomized controlled REDUCE trial

“…Second, different assays for the measurement of IgG subclass concentrations were used with different cut-offs suggested by the manufacturer (e.g. IgG1 < 4.9 g/L vs. < 2.8 g/L[ 12 ]) and the definition of hypogammaglobulinemia varied (from < 6.1 g/L to < 7.5 g/L [ 15 , 40 ]). Third, adjustment may have been limited in the present study due to the rather small sample size.…”

Polyvalent Immunoglobulin as a Potential Treatment Option for Patients with Recurrent COPD Exacerbations

“… 18 An additional study of 262 stable COPD patients followed prospectively for five years in Norway also showed that hypogammaglobulinemia was associated with higher risk for AECOPD. 19 The cause of hypogammaglobulinemia in these cases is not well known. However, it should be recognized that corticosteroids have been the mainstay treatment for AECOPD, and hence frequent or prolonged use of corticosteroids is inevitable in individuals at high-risk of exacerbations.…”