title: Antibody deficiency in patients with frequent exacerbations of Chronic Obstructive Pulmonary Disease (COPD).
abstract: Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function. A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year. Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors. We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations. We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome. We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency. We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed. Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time. A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year. Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1). Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations. This case series identifies antibody deficiency as a potentially treatable risk factor for frequent COPD exacerbations; testing for antibody deficiency should be considered in difficult to manage frequently exacerbating COPD patients. Further prospective studies are warranted to further test this hypothesis.
authors.affiliation: Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America.
authors.forename: Brian N
authors.initials: BN
authors.lastname: McCullagh
authors.affiliation: Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America.
authors.forename: Alejandro P
authors.initials: AP
authors.lastname: Comellas
authors.affiliation: Division of Immunology, Department of Internal Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States of America.
authors.forename: Zuhair K
authors.initials: ZK
authors.lastname: Ballas
authors.affiliation: Departments of Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Newell
authors.affiliation: Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: M Bridget
authors.initials: MB
authors.lastname: Zimmerman
authors.affiliation: Division of Allergy and Clinical Immunology, Department of Internal Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Antoine E
authors.identifier: http://orcid.org/0000-0003-0782-9084
authors.initials: AE
authors.lastname: Azar
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000627:therapeutic use; D007153:Immunologic Deficiency Syndromes / Q000150:complications* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D014057:Tomography, X-Ray Computed
chemical_list: D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D007132:Immunoglobulin Isotypes