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.

Fig 1. Classification of patients with COPD and antibody deficiency.

42 patients were identified initially and 1 excluded. Twenty-nine patients were confirmed to have a concomitant diagnosis of COPD with frequent exacerbations, and an antibody deficiency syndrome (CVID, SAD, SIgAD). Seven of 8 patients with CVID were treated with IG replacement, 1 patient declined and was treated with prophylactic antibiotics. Eleven of 20 patients with SAD were treated with prophylactic antibiotics. Those who failed treatment with prophylactic antibiotics (n = 2) were treated with IG replacement. Seven patients had not received treatment by the time of writing. 1 patient with SIgAD was treated with prophylactic antibiotics.