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; 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

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, William C. Bailey, David C. LaFonFrank 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

Biostatistics

Research output: Contribution to journal › Article › peer-review

23 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1420-1430
Number of pages	11
Journal	CHEST
Volume	158
Issue number	4
DOIs	https://doi.org/10.1016/j.chest.2020.04.058
State	Published - Oct 2020

Bibliographical note

Funding Information:
FUNDING/SUPPORT: The MACRO, STATCOPE, LOTT trials and CASCADE cohort were supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, and the Department of Health and Human Services. The current study was funded by the Canadian Institutes of Health Research (CIHR) and BC Lung Association. D. D. S. holds a De Lazzari Family Chair at the UBC Centre for Heart Lung Innovation (HLI) and is a Tier 1 Canada Research Chair in COPD. R. M. R. is supported in part by the Flight Attendant Medical Research Institute (FAMRI).

Funding Information:
FUNDING/SUPPORT: The MACRO, STATCOPE, LOTT trials and CASCADE cohort were supported by the National Heart, Lung, and Blood Institute, National Institutes of Health , and the Department of Health and Human Services. The current study was funded by the Canadian Institutes of Health Research (CIHR) and BC Lung Association. D. D. S. holds a De Lazzari Family Chair at the UBC Centre for Heart Lung Innovation (HLI) and is a Tier 1 Canada Research Chair in COPD. R. M. R. is supported in part by the Flight Attendant Medical Research Institute (FAMRI).

Publisher Copyright:
© 2020 American College of Chest Physicians

Keywords

COPD
hospitalizations
hypogammaglobulinemia
immunoglobulin G
meta-analysis

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10.1016/j.chest.2020.04.058

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Leitao Filho, F. S., Mattman, A., Schellenberg, R., Criner, G. J., Woodruff, P., Lazarus, S. C., Albert, R. K., Connett, J., Han, M. K., Gay, S. E., Martinez, F. J., Fuhlbrigge, A. L., Stoller, J. K., MacIntyre, N. R., Casaburi, R., Diaz, P., Panos, R. J., Cooper, J. A., Bailey, W. C., ... Sin, D. D. (2020). Serum IgG Levels and Risk of COPD Hospitalization: A Pooled Meta-analysis. CHEST, 158(4), 1420-1430. https://doi.org/10.1016/j.chest.2020.04.058

Leitao Filho, FS, Mattman, A, Schellenberg, R, Criner, GJ, Woodruff, P, Lazarus, SC, Albert, RK, Connett, J, Han, MK, Gay, SE, Martinez, FJ, Fuhlbrigge, AL, Stoller, JK, MacIntyre, NR, Casaburi, R, Diaz, P, Panos, RJ, Cooper, JA, Bailey, WC, LaFon, DC, Sciurba, FC, Kanner, RE, Yusen, RD, Au, DH, Pike, KC, Fan, VS, Leung, JM, Man, SFP, Aaron, SD, Reed, RM & Sin, DD 2020, 'Serum IgG Levels and Risk of COPD Hospitalization: A Pooled Meta-analysis', CHEST, vol. 158, no. 4, pp. 1420-1430. https://doi.org/10.1016/j.chest.2020.04.058

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title = "Serum IgG Levels and Risk of COPD Hospitalization: A Pooled Meta-analysis",

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",

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

note = "Funding Information: FUNDING/SUPPORT: The MACRO, STATCOPE, LOTT trials and CASCADE cohort were supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, and the Department of Health and Human Services. The current study was funded by the Canadian Institutes of Health Research (CIHR) and BC Lung Association. D. D. S. holds a De Lazzari Family Chair at the UBC Centre for Heart Lung Innovation (HLI) and is a Tier 1 Canada Research Chair in COPD. R. M. R. is supported in part by the Flight Attendant Medical Research Institute (FAMRI). Funding Information: FUNDING/SUPPORT: The MACRO, STATCOPE, LOTT trials and CASCADE cohort were supported by the National Heart, Lung, and Blood Institute, National Institutes of Health , and the Department of Health and Human Services. The current study was funded by the Canadian Institutes of Health Research (CIHR) and BC Lung Association. D. D. S. holds a De Lazzari Family Chair at the UBC Centre for Heart Lung Innovation (HLI) and is a Tier 1 Canada Research Chair in COPD. R. M. R. is supported in part by the Flight Attendant Medical Research Institute (FAMRI). Publisher Copyright: {\textcopyright} 2020 American College of Chest Physicians",

year = "2020",

month = oct,

doi = "10.1016/j.chest.2020.04.058",

language = "English (US)",

volume = "158",

pages = "1420--1430",

journal = "CHEST",

issn = "0012-3692",

publisher = "Elsevier Inc.",

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TY - JOUR

T1 - Serum IgG Levels and Risk of COPD Hospitalization

T2 - A Pooled Meta-analysis

AU - Leitao Filho, Fernando Sergio

AU - Mattman, Andre

AU - Schellenberg, Robert

AU - Criner, Gerard J.

AU - Woodruff, Prescott

AU - Lazarus, Stephen C.

AU - Albert, Richard K.

AU - Connett, John

AU - Han, Meilan K.

AU - Gay, Steven E.

AU - Martinez, Fernando J.

AU - Fuhlbrigge, Anne L.

AU - Stoller, James K.

AU - MacIntyre, Neil R.

AU - Casaburi, Richard

AU - Diaz, Philip

AU - Panos, Ralph J.

AU - Cooper, J. Allen

AU - Bailey, William C.

AU - LaFon, David C.

AU - Sciurba, Frank C.

AU - Kanner, Richard E.

AU - Yusen, Roger D.

AU - Au, David H.

AU - Pike, Kenneth C.

AU - Fan, Vincent S.

AU - Leung, Janice M.

AU - Man, Shu Fan Paul

AU - Aaron, Shawn D.

AU - Reed, Robert M.

AU - Sin, Don D.

N1 - Funding Information: FUNDING/SUPPORT: The MACRO, STATCOPE, LOTT trials and CASCADE cohort were supported by the National Heart, Lung, and Blood Institute, National Institutes of Health, and the Department of Health and Human Services. The current study was funded by the Canadian Institutes of Health Research (CIHR) and BC Lung Association. D. D. S. holds a De Lazzari Family Chair at the UBC Centre for Heart Lung Innovation (HLI) and is a Tier 1 Canada Research Chair in COPD. R. M. R. is supported in part by the Flight Attendant Medical Research Institute (FAMRI). Funding Information: FUNDING/SUPPORT: The MACRO, STATCOPE, LOTT trials and CASCADE cohort were supported by the National Heart, Lung, and Blood Institute, National Institutes of Health , and the Department of Health and Human Services. The current study was funded by the Canadian Institutes of Health Research (CIHR) and BC Lung Association. D. D. S. holds a De Lazzari Family Chair at the UBC Centre for Heart Lung Innovation (HLI) and is a Tier 1 Canada Research Chair in COPD. R. M. R. is supported in part by the Flight Attendant Medical Research Institute (FAMRI). Publisher Copyright: © 2020 American College of Chest Physicians

PY - 2020/10

Y1 - 2020/10

N2 - 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.

AB - 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.

KW - COPD

KW - hospitalizations

KW - hypogammaglobulinemia

KW - immunoglobulin G

KW - meta-analysis

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ER -

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

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