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

TitleLower serum IgA is associated with COPD exacerbation risk in SPIROMICS.
Publication TypePublication
AuthorsPutcha N, Paul GG, Azar A, Wise RA, O'Neal WK, Dransfield MT, Woodruff PG, Curtis JL, Comellas AP, M Drummond B, Lambert AA, Paulin LM, Fawzy A, Kanner RE, Paine R, Han MK, Martinez FJ, Bowler RP, R Barr G, Hansel NN
Corporate AuthorsSPIROMICS Investigators
JournalPLoS One
Date Published2018
KeywordsAdult, Aged, Aged, 80 and over, biomarkers, Cohort Studies, Disease Progression, Female, Humans, Immunoglobulin A, Incidence, Male, Middle Aged, Pulmonary Disease, Chronic Obstructive, Regression Analysis, Risk, Treatment Outcome

BACKGROUND: Decreased 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.METHODS: Data 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.RESULTS: Mean 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).CONCLUSIONS: Subnormal 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.

Alternate JournalPLoS ONE
PubMed ID29649230
PubMed Central IDPMC5896903
Grant ListK23 ES025781 / ES / NIEHS NIH HHS / United States
P30 ES005605 / ES / NIEHS NIH HHS / United States
K23HL123594 / NH / NIH HHS / United States
K23 HL123594 / HL / NHLBI NIH HHS / United States
I01 CX000911 / CX / CSRD VA / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
P30 DK054759 / DK / NIDDK NIH HHS / United States
UL1 TR002319 / TR / NCATS NIH HHS / United States
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: Baltimore (Johns Hopkins University)
Manuscript Status: