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 Cooper15, 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. 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.
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.
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.
Authors: Samer R Khan; Anna Vanoverschelde; Lies Lahousse; Robin P Peeters; P Martin van Hagen; Guy Brusselle; Layal Chaker; Virgil A S H Dalm Journal: Front Immunol Date: 2022-06-02 Impact factor: 8.786
Authors: Hyun Lee; Cara Kovacs; Andre Mattman; Zsuzsanna Hollander; Virginia Chen; Raymond Ng; Janice M Leung; Don D Sin Journal: Respir Res Date: 2022-05-31
Authors: Joo Hee Kim; Jae Hyuk Jang; So Hee Lee; Eun Mi Yang; Seung Hun Jang; Ki Suck Jung; Hae Sim Park Journal: Allergy Asthma Immunol Res Date: 2021-03 Impact factor: 5.764
Authors: Severin Vogt; Jörg D Leuppi; Jonas Rutishauser; Michael Osthoff; Philipp Schuetz; Beat Mueller; Carmen Volken; Sarah Dräger; Marten Trendelenburg Journal: Respir Res Date: 2021-08-14
Authors: Ana I Hernández Cordero; Chen Xi Yang; Xuan Li; Stephen Milne; Virginia Chen; Zsuzsanna Hollander; Raymond Ng; Gerard J Criner; Prescott G Woodruff; Stephen C Lazarus; John E Connett; MeiLan K Han; Fernando J Martinez; Robert M Reed; S F Paul Man; Janice M Leung; Don D Sin Journal: Respir Res Date: 2021-12-22