Serum IgG Levels and Risk of COPD Hospitalization: A Pooled Meta-analysis

Fernando Sergio Leitao Filho; Andre Mattman; Robert Schellenberg; Gerard J Criner; Prescott Woodruff; Stephen C Lazarus; Richard K Albert; John Connett; Meilan K Han; Steven E Gay; Fernando J Martinez; Anne L Fuhlbrigge; James K Stoller; Neil R MacIntyre; Richard Casaburi; Philip Diaz; Ralph J Panos; J Allen Cooper Jr; William C Bailey; David C LaFon; Frank C Sciurba; Richard E Kanner; Roger D Yusen; David H Au; Kenneth C Pike; Vincent S Fan; Janice M Leung; Shu-Fan Paul Man; Shawn D Aaron; Robert M Reed; Don D Sin

doi:10.1016/j.chest.2020.04.058

Serum IgG Levels and Risk of COPD Hospitalization: A Pooled Meta-analysis

Chest. 2020 Oct;158(4):1420-1430. doi: 10.1016/j.chest.2020.04.058. Epub 2020 May 19.

Authors

Fernando Sergio Leitao Filho¹, Andre Mattman², Robert Schellenberg¹, Gerard J Criner³, Prescott Woodruff⁴, Stephen C Lazarus⁴, Richard K Albert⁵, John Connett⁶, Meilan K Han⁷, Steven E Gay⁷, Fernando J Martinez⁸, Anne L Fuhlbrigge⁹, James K Stoller¹⁰, Neil R MacIntyre¹¹, Richard Casaburi¹², Philip Diaz¹³, Ralph J Panos¹⁴, J Allen Cooper Jr¹⁵, William C Bailey¹⁶, David C LaFon¹⁶, Frank C Sciurba¹⁷, Richard E Kanner¹⁸, Roger D Yusen¹⁹, David H Au²⁰, Kenneth C Pike²⁰, Vincent S Fan²¹, Janice M Leung¹, Shu-Fan Paul Man¹, Shawn D Aaron²², Robert M Reed²³, Don D Sin²⁴

Affiliations

¹ Centre for Heart Lung Innovation, St. Paul's Hospital & Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
² Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
³ Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA.
⁴ Department of Medicine, University of California, San Francisco, San Francisco, CA.
⁵ Department of Medicine, University of Colorado, Aurora, CO.
⁶ Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN.
⁷ Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI.
⁸ Division of Pulmonary and Critical Care Medicine, Weill Cornell Medical College, New York, NY.
⁹ Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado School of Medicine, Aurora, CO.
¹⁰ Education Institute, Cleveland Clinic, Cleveland, OH.
¹¹ Department of Medicine, Duke University Medical Center, Durham, NC.
¹² Division of Respiratory and Critical Care Physiology and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA.
¹³ Department of Internal Medicine, Ohio State University, Columbus, OH.
¹⁴ Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH.
¹⁵ Birmingham VA Medical Center, Birmingham, AL; Department of Medicine, University of Alabama Medical School, Birmingham, AL.
¹⁶ Department of Medicine, University of Alabama Medical School, Birmingham, AL.
¹⁷ Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA.
¹⁸ Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT.
¹⁹ Divisions of Pulmonary and Critical Care Medicine and General Medical Sciences, Washington University School of Medicine in Saint Louis, Saint Louis, MO.
²⁰ Division of Pulmonary, Critical Care and Sleep Medicine and School of Nursing, University of Washington, Seattle, WA.
²¹ Division of Pulmonary, Critical Care and Sleep Medicine and School of Nursing, University of Washington, Seattle, WA; VA Puget Sound Health Care System, Seattle, WA.
²² Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
²³ Department of Medicine, University of Maryland, Baltimore, MD.
²⁴ Centre for Heart Lung Innovation, St. Paul's Hospital & Department of Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address: don.sin@hli.ubc.ca.

PMID: 32439504
DOI: 10.1016/j.chest.2020.04.058

Abstract

Background: Hypogammaglobulinemia (serum IgG levels < 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations.

Research question: To determine the relationship between hypogammaglobulinemia and the risk of hospitalization in patients with COPD.

Study design and methods: Serum IgG levels were measured on baseline samples from four COPD cohorts (n = 2,259): Azithromycin for Prevention of AECOPD (MACRO, n = 976); Simvastatin in the Prevention of AECOPD (STATCOPE, n = 653), Long-Term Oxygen Treatment Trial (LOTT, n = 354), and COPD Activity: Serotonin Transporter, Cytokines and Depression (CASCADE, n = 276). IgG levels were determined by immunonephelometry (MACRO; STATCOPE) or mass spectrometry (LOTT; CASCADE). The effect of hypogammaglobulinemia on COPD hospitalization risk was evaluated using cumulative incidence functions for this outcome and deaths (competing risk). Fine-Gray models were performed to obtain adjusted subdistribution hazard ratios (SHR) related to IgG levels for each study and then combined using a meta-analysis. Rates of COPD hospitalizations per person-year were compared according to IgG status.

Results: The overall frequency of hypogammaglobulinemia was 28.4%. Higher incidence estimates of COPD hospitalizations were observed among participants with low IgG levels compared with those with normal levels (Gray's test, P < .001); pooled SHR (meta-analysis) was 1.29 (95% CI, 1.06-1.56, P = .01). Among patients with prior COPD admissions (n = 757), the pooled SHR increased to 1.58 (95% CI, 1.20-2.07, P < .01). The risk of COPD admissions, however, was similar between IgG groups in patients with no prior hospitalizations: pooled SHR = 1.15 (95% CI, 0.86-1.52, P =.34). The hypogammaglobulinemia group also showed significantly higher rates of COPD hospitalizations per person-year: 0.48 ± 2.01 vs 0.29 ± 0.83, P < .001.

Interpretation: Hypogammaglobulinemia is associated with a higher risk of COPD hospital admissions.

Keywords: COPD; hospitalizations; hypogammaglobulinemia; immunoglobulin G; meta-analysis.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Agammaglobulinemia / blood*
Agammaglobulinemia / complications
Aged
Female
Hospitalization / statistics & numerical data*
Humans
Immunoglobulin G / blood*
Incidence
Male
Middle Aged
Pulmonary Disease, Chronic Obstructive / blood*
Pulmonary Disease, Chronic Obstructive / complications
Pulmonary Disease, Chronic Obstructive / epidemiology
Risk Assessment

Substances

Immunoglobulin G

Grants and funding

CIHR/Canada