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

Canadian Respiratory Research Network (CRRN)

doi:10.1186/s12931-018-0733-z

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

Canadian Respiratory Research Network (CRRN)

Biostatistics

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29 Scopus citations

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.

Original language	English (US)
Article number	30
Journal	Respiratory research
Volume	19
Issue number	1
DOIs	https://doi.org/10.1186/s12931-018-0733-z
State	Published - Feb 14 2018

Bibliographical note

Funding Information:
This work was supported by the BC Lung Association and the Canadian Respiratory Research Network (CRRN). The MACRO and STATCOPE trials were funded by the US National Heart Blood and Lung Institute (NHLBI).

Funding Information:
We thank the COPD Clinical Research Network for conducting both the MACRO and STATCOPE trials and for providing us access to all available samples in both cohorts. Dr. Leitao Filho FS gratefully acknowledges postdoctoral support from CNPq-Brazil and the Canadian Institutes of Health Research (CIHR) Integrated and Mentored Pulmonary and Cardiovascular Training program (IMPACT).

Publisher Copyright:
© 2018 The Author(s).

Keywords

COPD
Exacerbation
Hospitalization
IgG
IgG subclass deficiency

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5813358

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title = "Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD",

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.",

keywords = "COPD, Exacerbation, Hospitalization, IgG, IgG subclass deficiency",

author = "{Canadian Respiratory Research Network (CRRN)} and {Leitao Filho}, {Fernando Sergio} and Ra, {Seung Won} and Andre Mattman and Schellenberg, {Robert S.} and Criner, {Gerard J.} and Woodruff, {Prescott G.} and Lazarus, {Stephen C.} and Richard Albert and Connett, {John E.} and Han, {Meilan K.} and Martinez, {Fernando J.} and Leung, {Janice M.} and {Paul Man}, {S. F.} and Aaron, {Shawn D.} and Reed, {Robert M.} and Sin, {Don D.}",

note = "Funding Information: This work was supported by the BC Lung Association and the Canadian Respiratory Research Network (CRRN). The MACRO and STATCOPE trials were funded by the US National Heart Blood and Lung Institute (NHLBI). Funding Information: We thank the COPD Clinical Research Network for conducting both the MACRO and STATCOPE trials and for providing us access to all available samples in both cohorts. Dr. Leitao Filho FS gratefully acknowledges postdoctoral support from CNPq-Brazil and the Canadian Institutes of Health Research (CIHR) Integrated and Mentored Pulmonary and Cardiovascular Training program (IMPACT). Publisher Copyright: {\textcopyright} 2018 The Author(s).",

year = "2018",

month = feb,

day = "14",

doi = "10.1186/s12931-018-0733-z",

language = "English (US)",

volume = "19",

journal = "Respiratory research",

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TY - JOUR

T1 - Serum IgG subclass levels and risk of exacerbations and hospitalizations in patients with COPD

AU - Canadian Respiratory Research Network (CRRN)

AU - Leitao Filho, Fernando Sergio

AU - Ra, Seung Won

AU - Mattman, Andre

AU - Schellenberg, Robert S.

AU - Criner, Gerard J.

AU - Woodruff, Prescott G.

AU - Lazarus, Stephen C.

AU - Albert, Richard

AU - Connett, John E.

AU - Han, Meilan K.

AU - Martinez, Fernando J.

AU - Leung, Janice M.

AU - Paul Man, S. F.

AU - Aaron, Shawn D.

AU - Reed, Robert M.

AU - Sin, Don D.

N1 - Funding Information: This work was supported by the BC Lung Association and the Canadian Respiratory Research Network (CRRN). The MACRO and STATCOPE trials were funded by the US National Heart Blood and Lung Institute (NHLBI). Funding Information: We thank the COPD Clinical Research Network for conducting both the MACRO and STATCOPE trials and for providing us access to all available samples in both cohorts. Dr. Leitao Filho FS gratefully acknowledges postdoctoral support from CNPq-Brazil and the Canadian Institutes of Health Research (CIHR) Integrated and Mentored Pulmonary and Cardiovascular Training program (IMPACT). Publisher Copyright: © 2018 The Author(s).

PY - 2018/2/14

Y1 - 2018/2/14

N2 - 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.

AB - 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.

KW - COPD

KW - Exacerbation

KW - Hospitalization

KW - IgG

KW - IgG subclass deficiency

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

Abstract

Bibliographical note

Keywords

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