Sex: U
Vaccine: PPV
Symptoms: Unevaluable event
Clinical narrative: This literature market report has been received from the author of a article. 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. The authors identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal lgG titers was performed. The 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, specific antibody deficiency (20), and selective lgA deficiency. 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. Materials and methods: The authors identified patients with COPD seen in the authors' Pulmonary Clinic between January of 2012 and December of 2014 with 2 or more exacerbations per year and were referred to the Allergy/Immunology Clinic for immune evaluation. All acute exacerbations of COPD (AECOPD) were classified as either moderate or severe requiring the use of prednisone and/or antibiotics as an outpatient (moderate) or inpatient (severe). All patients had blood tests done to check Complete Blood Count (CBC) with differential, serum Immunoglobulins (IgG, IgA, IgM, IgE), as well as antibody IgG response to the pneumococcal vaccine (PPV23). Additional immune evaluation was performed as directed by their clinical history. Patients on oral corticosteroids had their serum IGs repeated when off steroids; for patients where oral corticosteroid use could not be discontinued, serum IGs were repeated on the lowest tolerated dose of oral corticosteroids. Serum immunoglobulin measurement Serum samples were assayed for total IgG, IgA, IgM, and IgE by nephelometry on Roche Diagnostics cobas c701 analyzers in the core clinical chemistry laboratory at the Hospital and Clinics. Pneumococcal IgG titers measurement IgG titers to Streptococcus pneumoniae serotypes were sent to laboratories and processed by quantitative multiplex bead assay. Pre and post vaccination samples were used to determine humoral immune response to the vaccine. Subjects who had received the pneumococcal vaccine with the past 12 months had random titers checked. In our institution the 14 serotype vaccine was changed to the 23 serotype vaccine during the course of our analysis. Diagnosis of immunodeficiency Patients were diagnosed with a primary antibody deficiency syndrome per published guidelines, as evidenced by a reduction in serum IG levels below standardized reference ranges and/or inadequate response to pneumococcal vaccination. The diagnosis of common variable immunodeficiency (CVID) was based on a serum IgG level that is more than 2 standard deviations (SD) below the mean, with a low serum IgA and/or IgM, and a deficient antibody response to vaccines. The diagnosis of specific antibody deficiency was made based on a deficient IgG antibody response to PPV23, with normal serum IG levels. Antibody response to PPV23 was interpreted based on the most recent published consensus parameters. The diagnosis of selective IgA deficiency was defined as a serum IgA level that is less than 7 mg/dL (lowest detectable laboratory limit), with normal serum IgG and IgM. Results: The authors described a total of 29 patients with poorly controlled COPD as evidenced by moderate to severe AECOPD per year and with documented evidence of an antibody deficiency syndrome. Among this group 8 had common variable immunodeficiency (CVID), 20 had specific antibody deficiency and 1 had selective IgA deficiency. Of 8 patients with CVID, 7 were treated with IG replacement while 1 declined IG replacement and received prophylactic antibiotics. Of 20 patients with antibody deficiency, 11 were treated with prophylactic antibiotics, 2 with IG replacement because of recurrent infections and COPD exacerbations despite prophylactic antibiotics, and the remaining 7 were diagnosed with specific antibody deficiency but had yet to be commenced on treatment. The one patient with selective IgA deficiency was treated with prophylactic antibiotics. This report refers to 20 patients (age and gender unknown) who categorized as specific antibody deficiency. On unknown dates, the patients were diagnosed as specific antibody deficiency which was made based on a deficient IgG antibody response to PNEUMOVAX 23, with normal serum IG levels. Antibody response to PPV23 was interpreted based on the most recent published consensus parameters. The outcome of the event was unspecified. The reporter considered the event to be related to PNEUMOVAX 23. Additional information has been requested.