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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.

SUBMITTER: Holm AM

PROVIDER: S-EPMC7173948 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Hypogammaglobulinemia and Risk of Exacerbation and Mortality in Patients with COPD.

Holm Are M AM Andreassen Siw L SL Christensen Vivi Lycke VL Kongerud Johny J Almås Øystein Ø Auråen Henrik H Henriksen Anne H AH Aaberge Ingeborg S IS Klingenberg Olav O Rustøen Tone T

International journal of chronic obstructive pulmonary disease 20200416

<h4>Introduction</h4>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.<h4>Methods</h4>Clinical and ...[more]

PMID: 32368026

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Project description:ImportanceRituximab is an anti-CD20 chimeric antibody used in a wide variety of clinical indications. There has not been widespread adoption of consistent immune monitoring before and after rituximab therapy. However, there is a subset of patients who develop prolonged, symptomatic hypogammaglobulinemia following rituximab, and monitoring before and after rituximab therapy could help to identify these patients and initiate measures to prevent excess morbidity and mortality.ObjectiveTo determine the current levels of screening for hypogammaglobulinemia (specifically, low immunoglobulin G), infectious risks associated with hypogammaglobulinemia, and variables associated with an increased risk of mortality.Design, setting, and participantsA cohort study was conducted of 8633 patients receiving rituximab from January 1, 1997, to December 31, 2017, at a large, tertiary referral center (Partners HealthCare System).ExposuresRituximab administration.Main outcomes and measuresThe primary outcome measures were immunoglobulin measurements, infectious complications, and mortality. Cox regression analysis was used to examine the results of infectious complications on survival, adjusted for age, sex, and indication for rituximab use.ResultsOf the 8633 patients who received rituximab in the large, academic, health care system, 4479 satisfied inclusion criteria, with a mean (SD) age of 59.8 (16.2) years; 2280 patients (50.9%) were women. Most patients (3824 [85.4%]) did not have immunoglobulin levels checked before rituximab therapy. Of those who had levels determined, hypogammaglobulinemia was noted in 313 (47.8%) patients before initiation of rituximab. Following rituximab administration, worsening hypogammaglobulinemia was noted. There was an increase in severe infections after rituximab use in the study cohort (from 17.2% to 21.7%; P?<?.001). In the survival analysis, increased mortality was associated with increasing age (hazard ratio [HR], 1.02; 95% CI, 1.01-1.02; P?<?.001), male sex (HR, 1.14; 95% CI, 1.02-1.28; P?=?.02), and severe infectious complications in the 6 months before (HR, 3.14; 95% CI, 2.77-3.55; P?<?.001) and after (HR, 4.97; 95% CI, 4.41-5.60; P?<?.001) the first rituximab infusion. A total of 201 patients (4.5%) received immunoglobulin replacement following rituximab, and among these patients, higher cumulative immunoglobulin replacement dose was associated with a reduced risk of serious infectious complications (HR, 0.98; 95% CI, 0.96-0.99; P?=?.002).Conclusions and relevanceMany patients are not being screened or properly identified as having hypogammaglobulinemia both before and after rituximab administration. Monitoring of immunoglobulin levels both before and after rituximab therapy may allow for earlier identification of risk for developing significant infection and identify patients who may benefit from immunoglobulin replacement, which may in turn help to avoid excess morbidity and mortality.

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Hypogammaglobulinemia and Risk of Exacerbation and Mortality in Patients with COPD.

Publications

Hypogammaglobulinemia and Risk of Exacerbation and Mortality in Patients with COPD.

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