Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD

Respiratory Research

for the Canadian Respiratory Research Network (CRRN)¹  S. F. Paul Man²  Don D. Sin²  Robert S. Schellenberg²  Fernando Sergio Leitao Filho²  Janice M. Leung²  Seung Won Ra²  Meilan K. Han³  Stephen C. Lazarus⁴  Prescott G. Woodruff⁴  Shawn D. Aaron⁵  Andre Mattman⁶  Gerard J. Criner⁷  Robert M. Reed⁸  Fernando J. Martinez⁹  Richard Albert^1,10  John E. Connett^1,11 

[1] ;Centre for Heart Lung Innovation, St. Paul’s Hospital;Department of Internal Medicine, University of Michigan;Department of Medicine, University of California San Francisco;Department of Medicine, University of Ottawa;Department of Pathology and Laboratory Medicine, University of British Columbia;Department of Thoracic Medicine and Surgery, Lewis Katz school of Medicine at Temple University;Division of Pulmonary and Critical Care Medicine, University of Maryland School of Medicine;Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College, Cornell University;Pulmonary Sciences and Critical Care Medicine, University of Colorado;School of Public Health, University of Minnesota;

关键词: IgG;    IgG subclass deficiency;    COPD;    Exacerbation;    Hospitalization;   

DOI  :  10.1186/s12931-018-0733-z

来源: DOAJ

【 摘 要 】

Abstract Background The literature is scarce regarding the prevalence and clinical impact of IgG subclass deficiency in COPD. We investigated the prevalence of IgG subclass deficiencies and their association with exacerbations and hospitalizations using subjects from two COPD cohorts. Methods We measured IgG subclass levels using immunonephelometry in serum samples from participants enrolled in two previous COPD trials: Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO; n = 976) and Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE; n = 653). All samples were collected from clinically stable participants upon entry into both studies. IgG subclass deficiency was diagnosed when IgG subclass levels were below their respective lower limit of normal: IgG1 < 2.8 g/L; IgG2 < 1.15 g/L; IgG3 < 0.24 g/L; and IgG4 < 0.052 g/L. To investigate the impact of IgG subclass levels on time to first exacerbation or hospitalization, we log-transformed IgG levels and performed Cox regression models, with adjustments for confounders. Results One or more IgG subclass deficiencies were found in 173 (17.7%) and 133 (20.4%) participants in MACRO and STATCOPE, respectively. Lower IgG1 or IgG2 levels resulted in increased risk of exacerbations with adjusted hazard ratios (HR) of 1.30 (95% CI, 1.10–1.54, p < 0.01) and 1.19 (95% CI, 1.05–1.35, p < 0.01), respectively in the MACRO study, with STATCOPE yielding similar results. Reduced IgG1 or IgG2 levels were also associated with increased risk of hospitalizations: the adjusted HR for IgG1 and IgG2 was 1.52 (95% CI: 1.15–2.02, p < 0.01) and 1.33 (95% CI, 1.08–1.64, p < 0.01), respectively for the MACRO study; in STATCOPE, only IgG2 was an independent predictor of hospitalization. In our multivariate Cox models, IgG3 and IgG4 levels did not result in significant associations for both outcomes in either MACRO or STATCOPE cohorts. Conclusions Approximately 1 in 5 COPD patients had one or more IgG subclass deficiencies. Reduced IgG subclass levels were independent risk factors for both COPD exacerbations (IgG1 and IgG2) and hospitalizations (IgG2) in two COPD cohorts. Trial registration This study used serum samples from participants of the MACRO (NCT00325897) and STATCOPE (NCT01061671) trials.

【 授权许可】

Unknown