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Chronic Obstructive Pulmonary disease (COPD) is a chronic and progressive respiratory disorder primarily caused by smoking. It is a leading cause of morbidity, mortality, and hospital admissions world-wide. Acute exacerbation (AECOPD) episodes can be triggered by infection or environmental stressors and are associated with a significant decline in patient pulmonary function as well as low short and long-term survival rates. Current prophylaxis and treatment regimens for AECOPD are of limited benefit. Immunoglobulin therapy is a novel approach to AECOPD patient management but its effectiveness in patient care has not been established and is in need of further study. We will conduct a systematic review and meta-analysis to assess clinical outcomes associated with the administration of intravenous/subcutaneous immunoglobulin (IVIG/SCIG) in the prevention of acute exacerbations of COPD (AECOPD). We will search Embase, Ovid MEDLINE, and Cochrane Central Register of Controlled Trials for randomized and non-randomized studies relevant to this review. As per the PRISMA protocol, retrieved studies will undergo screening and data extraction processes conducted by two independent reviewers. We will report the corresponding relative risk ratios as the primary measure, with 95% confidence intervals (CIs). We will also use a random-effects model to calculate pooled measures for these studies. The risk of bias will be assessed in randomized and nonrandomized trials using the Cochrane Risk of Bias Assessment Tool Version 2 and the ROBINS-I tool, respectively. Our systematic review will provide the current status on the effectiveness of the prophylactic and therapeutic uses of IVIG/SCIG in the management of COPD patients. Results from this review may be applicable to clinical practice and may also lay the foundation for future research in this field.

Dana Unninayar,1 Sara J Abdallah,2 D William Cameron,2– 4 Juthaporn Cowan2– 4 1Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 2Clinical Epidemiology Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada; 3Division of Infectious Diseases, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 4Centre of Infection, Immunity and Inflammation, Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, CanadaCorrespondence: Juthaporn CowanThe Ottawa Hospital, General Campus, 501 Smyth Road, Box 223, Ottawa, Ontario, K1H 8L6, CanadaTel +1 613-737-8899 X 79617Fax +1 613-737-8352Email jcowan@toh.caAbstract: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation and episodes of worsening respiratory symptoms and pulmonary function, termed acute exacerbations of COPD (AECOPD). AECOPD episodes are associated with heightened airway inflammation and are often triggered by infection. A subset of COPD patients develops frequent exacerbations despite maximal existing standard medical therapy. It is therefore clear that a targeted and more effective prevention strategy is needed. Immunoglobulins are glycoprotein molecules that are secreted by B lymphocytes and plasma cells and play a critical role in the adaptive immune response against many pathogens. Altered serum immunoglobulin levels have been observed in patients with immunodeficiencies and inflammatory diseases. Serum immunoglobulin has also been identified as potential biomarkers of AECOPD frequency. Since plasma-derived polyvalent immunoglobulin treatment is effective in preventing recurrent infections in immunodeficient patients and in suppressing inflammation in many inflammatory diseases, it may be conceivable that immunoglobulin treatment may be effective in preventing recurrent AECOPD. In this article, we provide a review of the current knowledge on immunoglobulin treatment in patients with COPD and discuss plausible mechanisms as to how immunoglobulin treatment may work to reduce AECOPD frequency.Keywords: chronic obstructive pulmonary disease, immunoglobulin treatment, exacerbation