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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:Rationale: There is an association between body mass index (BMI) and mortality in chronic obstructive pulmonary disease (COPD), with underweight individuals having higher mortality risk. Mortality and exacerbation risks among individuals with higher BMI are unclear. Objectives: To examine the relationship between BMI and adverse outcomes in COPD. Methods: This post hoc analysis included data from TIOSPIR (Tiotropium Safety and Performance in Respimat) (N = 17,116) and tiotropium-treated patients in UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) (N = 2,986). BMI classes (underweight [BMI < 20 kg/m2], normal weight [BMI 20 to <25 kg/m2], overweight [BMI 25 to <30 kg/m2], obesity class I [BMI 30 to <35 kg/m2], obesity class II [BMI 35 to <40 kg/m2], and obesity class III [BMI ⩾ 40 kg/m2]) were examined for adjusted associations with mortality, exacerbation, and nonfatal cardiovascular event risk using over 50,000 patient-years of cumulative follow-up data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox regression models. Results: In TIOSPIR, obesity prevalence was 22%, overweight 32%, and underweight 12%. The proportion of females was highest in obesity classes II and III. Overweight and obese participants had better baseline lung function versus other BMI classes; underweight participants were more likely to be current smokers. Underweight participants had a significantly higher risk of death (HR, 1.88; 95% CI, 1.62-2.20; P < 0.0001) and severe exacerbations (HR, 1.31; 95% CI, 1.16-1.47; P < 0.0001) versus normal-weight participants; however, overweight and obese participants were at lower to no additional risk. Results from UPLIFT were similar to TIOSPIR. Conclusions: These results suggest that there is a strong association between body weight, COPD events, and risk of death. A holistic management approach taking into account respiratory and cardiovascular risk factors and nutritional status is needed to improve the general well-being of patients with COPD.

Project description:ObjectiveTo compare the clinical features and outcomes in patients with pre-chronic obstructive pulmonary disease (COPD) and COPD hospitalised for confirmed or suspected acute exacerbation of COPD (AECOPD).DesignA multicentre, longitudinal observational cohort study.SettingData were obtained from the AECOPD Inpatient Registry Study in China.Participants5896 patients hospitalised for AECOPD between 2017 and 2021.OutcomesPatients were divided into the COPD (n=5201) and pre-COPD (n=695) groups according to the lung function test results. The outcomes of interest included all-cause, respiratory disease-related and cardiovascular disease-related deaths as well as readmissions within 30 days and 12 months after discharge. Cumulative incidence functions were used to estimate the risk of cause-specific mortality and readmission. Multivariate hazard function models were used to determine the association between lung function and outcomes.ResultsThere were significant between-group differences in the symptoms at admission and medication use during hospitalisation. However, there was no significant between-group difference in the 30-day all-cause mortality (0.00 vs 2.23/1000 person-month (pm), p=0.6110) and readmission (33.52 vs 30.64/1000 pm, p=0.7175). Likewise, the 30-day and 12-month cause-specific outcomes were not significantly different between groups (30-day readmission with acute exacerbation (AE): 26.07 vs 25.11/1000 pm; 12-month all-cause mortality: 0.20 vs 0.93/1000 pm; all-cause readmission: 11.49 vs 13.75/1000 pm; readmission with AE: 9.15 vs 11.64/1000 pm, p>0.05 for all comparisons). Cumulative incidence curves revealed no significant between-group differences in the 30-day and 12-month prognosis (p>0.05). Multivariate analysis revealed no significant association of lung function categories with 30-day and 12-month mortality or readmission (p>0.05 for all effect estimations).ConclusionsPatients with pre-COPD have mild symptoms and similar risks for mortality and readmission during follow-up as patients with COPD. Patients with pre-COPD should receive optimal therapies before the occurrence of irreversible damage.

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.

Dataset Information

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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