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

Abstract

BackgroundThe 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.MethodsWe 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.ResultsOne 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.ConclusionsApproximately 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 registrationThis study used serum samples from participants of the MACRO (NCT00325897) and STATCOPE (NCT01061671) trials.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0733-z) contains supplementary material, which is available to authorized users.

Cigarette smoking differentially affects immunoglobulin class levels in serum and saliva: An investigation and review

“…In this context, others have shown that about 25% of COPD patients have total serum IgG levels below the lower limit of normal, consistent with our findings in smokers without COPD. This is associated with an increased incidence of exacerbations and hospitalizations (usually because of respiratory tract infections), and this is mainly in patients with deficiencies in IgG1 and/or IgG2 subclasses . This is consistent with reports that intra‐venous Ig (IVIG) replacement therapy reduces respiratory infections and exacerbations in COPD .…”

“…Thus, there is a strong consensus of evidence that smoking is associated with reduced IgG levels both systemically and in the oral mucosa. It would be of interest to examine the effects of smoking on IgG subclasses, especially as these are known to be affected in COPD …”

Impact of immunoglobulin G2 subclass level on late‐onset bacterial infection after allogeneic hematopoietic stem cell transplantation

“…Its role has been evaluated mostly in children, and IgG2 deficiency has been reported to be an important cause of recurrent sinopulmonary infections and otitis caused by those pathogens . For adults, the Canadian Respiratory Research Network recently reported that low levels of IgG subclasses such as IgG1 and IgG2 were risk factors for exacerbations and/or hospitalizations in patients with chronic obstructive pulmonary disease . Therefore, it is plausible that a low IgG2 level could be associated with susceptibility to bacterial infection not only in children but also in adults, especially those with underlying diseases.…”

Risk factors of chronic obstructive pulmonary disease exacerbations

“…Furthermore, they revealed that approximately 1 in 5 COPD patients had one or more IgG subclass deficiencies and reduced IgG1 or IgG2 levels were associated with increased risk of AECOPD, but only IgG2 remained as an independent predictor of hospitalisations. Lower IgG1 and IgG2 levels were detected in patients who developed two or more exacerbations during follow‐up …”

“…Only a few articles have described the association between the IgG subclass deficiencies and COPD exacerbation risk . Using samples from two large COPD trials, Leitao Filho et al found that reduced total IgG levels are associated with increased risk of AECOPD and hospitalisations, with the greatest risk observed among participants with total IgG levels <7.0 g/L .…”