Lower serum IgA is associated with COPD exacerbation risk in SPIROMICS.

Nirupama Putcha,Alejandro P Comellas,Antoine Azar,Prescott G Woodruff,Wanda K O’Neal,Russell P Bowler,Mark T Dransfield,M Bradley Drummond,Meilan K Han,Robert A Wise,Ashraf Fawzy,Robert Paine,Gabriel G Paul,Jeffrey L Curtis,Richard E Kanner,Laura M Paulin,R Graham Barr,Nadia N Hansel,Fernando J Martínez ,Allison Lambert

doi:10.1371/journal.pone.0194924

Abstract

BackgroundDecreased but measurable serum IgA levels (≤70 mg/dL) have been associated with risk for infections in some populations, but are unstudied in COPD. This study tested the hypothesis that subnormal serum IgA levels would be associated with exacerbation risk in COPD.MethodsData were analyzed from 1,049 COPD participants from the observational cohort study SPIROMICS (535 (51%) women; mean age 66.1 (SD 7.8), 338 (32%) current smokers) who had baseline serum IgA measured using the Myriad RBM biomarker discovery platform. Exacerbation data was collected prospectively (mean 944.3 (SD 281.3) days), and adjusted linear, logistic and zero-inflated negative binomial regressions were performed.ResultsMean IgA was 269.1 mg/dL (SD 150.9). One individual had deficient levels of serum IgA (<7 mg/dL) and 25 (2.4%) had IgA level ≤70 mg/dL. Participants with IgA ≤70 mg/dL were younger (62 vs. 66 years, p = 0.01) but otherwise similar to those with higher IgA. In adjusted models, IgA ≤70 mg/dL was associated with higher exacerbation incidence rates (IRR 1.71, 95% CI 1.01–2.87, p = 0.044) and greater risk for any severe exacerbation (OR 2.99, 95% CI 1.30–6.94, p = 0.010). In adjusted models among those in the lowest decile (<120 mg/dL), each 10 mg/dL decrement in IgA (analyzed continuously) was associated with more exacerbations during follow-up (β 0.24, 95% CI 0.017–0.46, p = 0.035).ConclusionsSubnormal serum IgA levels were associated with increased risk for acute exacerbations, supporting mildly impaired IgA levels as a contributing factor in COPD morbidity. Additionally, a dose-response relationship between lower serum IgA and number of exacerbations was found among individuals with serum IgA in the lowest decile, further supporting the link between serum IgA and exacerbation risk. Future COPD studies should more comprehensively characterize immune status to define the clinical relevance of these findings and their potential for therapeutic correction.

Highlights

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the U
Subnormal serum IgA levels were associated with increased risk for acute exacerbations, supporting mildly impaired IgA levels as a contributing factor in COPD morbidity
A dose-response relationship between lower serum IgA and number of exacerbations was found among individuals with serum IgA in the lowest decile, further supporting the link between serum IgA and exacerbation risk

Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the U. S. and is associated with increased risk of respiratory infections. [3,4] the immune function of selective IgA deficiency and subnormal serum IgA levels have been studied in other diseases, such as celiac disease and lymphocytic leukemia,[4] [5] an association with COPD morbidity has not been established. Decreased but measurable serum IgA levels ( 70 mg/dL) have been associated with risk for infections in some populations, but are unstudied in COPD.

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