Serum Immunoglobulin G Levels Are Associated with Risk for Exacerbations: An Analysis of SPIROMICS

<b>Rationale:</b> Serum IgG deficiency is associated with morbidity in chronic obstructive pulmonary disease (COPD), but it is unclear whether concentrations in the lower end of the normal range still confer risk. <b>Objectives:</b> To determine if levels above traditional cutoffs for serum IgG deficiency are associated with exacerbations among current and former smokers with or at risk for COPD. <b>Methods:</b> Former and current smokers in SPIROMICS (the Subpopulations and Intermediate Outcome Measures of COPD study) (<i>n</i> = 1,497) were studied: 1,026 with COPD and 471 at risk for COPD. In a subset (<i>n</i> = 1,031), IgG subclasses were measured. Associations between total IgG or subclasses and prospective exacerbations were evaluated with multivariable models adjusting for demographic characteristics, current smoking, smoking history, FEV<sub>1</sub> percent predicted, inhaled corticosteroids, and serum IgA. <b>Measurements and Main Results:</b> The 35th percentile (1,225 mg/dl in this cohort) of IgG was the best cutoff by Akaike information criterion. Below this, there was increased exacerbation risk (incidence rate ratio [IRR], 1.28; 95% confidence interval [CI], 1.08-1.51). Among subclasses, IgG1 and IgG2 below the 35th percentile (354 and 105 mg/dl, respectively) were associated with increased risks of severe exacerbation (IgG1, IRR, 1.39; 95% CI, 1.06-1.84; IgG2, IRR, 1.50; 95% CI, 1.14-1.1.97). These associations remained significant when additionally adjusting for a history of exacerbations. <b>Conclusions:</b> Lower serum IgG is prospectively associated with exacerbations in individuals with or at risk for COPD. Among subclasses, lower IgG1 and IgG2 are prospectively associated with severe exacerbations. The optimal IgG cutoff was substantially higher than traditional cutoffs for deficiency, suggesting that subtle impairment of humoral immunity may be associated with exacerbations.

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Publication Details

Journal
American Journal of Respiratory and Critical Care Medicine
Published
2024-10-23
DOI
https://doi.org/10.1164/rccm.202311-2184oc
Citations
9
Primary Topic
Chronic Obstructive Pulmonary Disease (COPD) Research
Type
article
Field-Weighted Citation Impact
3.77

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article

Serum Immunoglobulin G Levels Are Associated with Risk for Exacerbations: An Analysis of SPIROMICS

Ashraf Fawzy, Nadia N. Hansel, Gerard J. Criner, Russell Paul Bowler et al.
9 citations
American Journal of Respiratory and Critical Care Medicine
Chronic Obstructive Pulmonary Disease (COPD) Research
3.77
article

Serum Immunoglobulin G Levels Are Associated with Risk for Exacerbations: An Analysis of SPIROMICS

Ashraf Fawzy, Nadia N. Hansel, Gerard J. Criner, Russell Paul Bowler, David C. LaFon, MeiLan K. Han, Yvonne J. Huang, Mark T. Dransfield, Stephen P. Peters, Lars Groenke, Jeffrey L. Curtis, Alexander Schaub, Wanda K. O’Neal, Aparna Balasubramanian, Nirupama Putcha, Jerry A. Krishnan, Martin R. Stämpfli, Prescott G. Woodruff, Antoine Azar, Michael Burnim, Alejandro P. Comellas, Neal S. Fedarko, Michael Drummond, Christopher B. Cooper, Robert Paine, David Couper, Fernando J. Martínez, R. Graham Barr, Han Woo
article en
9 citations

Abstract

<b>Rationale:</b> Serum IgG deficiency is associated with morbidity in chronic obstructive pulmonary disease (COPD), but it is unclear whether concentrations in the lower end of the normal range still confer risk. <b>Objectives:</b> To determine if levels above traditional cutoffs for serum IgG deficiency are associated with exacerbations among current and former smokers with or at risk for COPD. <b>Methods:</b> Former and current smokers in SPIROMICS (the Subpopulations and Intermediate Outcome Measures of COPD study) (<i>n</i> = 1,497) were studied: 1,026 with COPD and 471 at risk for COPD. In a subset (<i>n</i> = 1,031), IgG subclasses were measured. Associations between total IgG or subclasses and prospective exacerbations were evaluated with multivariable models adjusting for demographic characteristics, current smoking, smoking history, FEV<sub>1</sub> percent predicted, inhaled corticosteroids, and serum IgA. <b>Measurements and Main Results:</b> The 35th percentile (1,225 mg/dl in this cohort) of IgG was the best cutoff by Akaike information criterion. Below this, there was increased exacerbation risk (incidence rate ratio [IRR], 1.28; 95% confidence interval [CI], 1.08-1.51). Among subclasses, IgG1 and IgG2 below the 35th percentile (354 and 105 mg/dl, respectively) were associated with increased risks of severe exacerbation (IgG1, IRR, 1.39; 95% CI, 1.06-1.84; IgG2, IRR, 1.50; 95% CI, 1.14-1.1.97). These associations remained significant when additionally adjusting for a history of exacerbations. <b>Conclusions:</b> Lower serum IgG is prospectively associated with exacerbations in individuals with or at risk for COPD. Among subclasses, lower IgG1 and IgG2 are prospectively associated with severe exacerbations. The optimal IgG cutoff was substantially higher than traditional cutoffs for deficiency, suggesting that subtle impairment of humoral immunity may be associated with exacerbations.

American Journal of Respiratory and Critical Care MedicineVol. 211(2)
University of North Carolina at Chapel Hill (US), University of Iowa (US), Boston Medical Center (US), Boehringer Ingelheim (Germany) (DE), Johns Hopkins University (US), University of California, Los Angeles (US), University of Pittsburgh (US), University of California, San Francisco (US), Cornell University (US), University of Utah (US), University of Michigan (US), Columbia University Irving Medical Center (US), Johns Hopkins Medicine (US), National Jewish Health (US), University of Alabama at Birmingham (US), University of Illinois Chicago (US), Lung Institute (US), VA Ann Arbor Healthcare System (US), Behringwerke (Germany) (DE), Michigan United (US), Michigan Medicine (US), Birmingham VA Medical Center (US), Temple University Hospital (US), Johns Hopkins Hospital (US), Harbor–UCLA Medical Center (US), Wake Forest University (US), CSL (Switzerland) (CH), Hamilton Health Sciences (CA), Columbia University (US), Temple University (US), University of Colorado Denver (US), McMaster University (CA)
National Heart, Lung, and Blood Institute
Zero hunger
Openalex Percentile: Top 6%
Chronic Obstructive Pulmonary Disease (COPD) Research
3.77
DOIOpen Access PDFOpenAlex
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