A Retrospective Longitudinal Within-Subject Risk Interval Analysis of Immunoglobulin Treatment for Recurrent Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Abstract

BackgroundRecurrent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, debilitating, costly and often difficult to prevent.MethodsWe reviewed records of patients who had COPD and immunoglobulin (Ig) treatment as adjunctive preventative treatment for AECOPD, and documented all AECOPD episodes for one year before and after initiation of Ig treatment. We graded AECOPD episodes as moderate for prescription of antibiotics and/or corticosteroids or for visit to the Emergency Department, and as severe for hospital admission. We conducted a retrospective within-subject self-controlled risk interval analysis to compare the outcome of annual AECOPD rate before and after treatment.ResultsWe identified 22 cases of certain COPD, of which three had early discontinuation of Ig treatment due to rash and local swelling to subcutaneous Ig, and five had incomplete records leaving 14 cases for analyses. The median baseline IgG level was 5.9 g/L (interquartile range 4.1–7.4). Eight had CT radiographic bronchiectasis. Overall, the incidence of AECOPD was consistently and significantly reduced in frequency from mean 4.7 (± 3.1) per patient-year before, to 0.6 (± 1.0) after the Ig treatment (p = 0.0001). There were twelve episodes of severe AECOPD (in seven cases) in the year prior, and one in the year after Ig treatment initiation (p = 0.016).ConclusionsIg treatment appears to decrease the frequency of moderate and severe recurrent AECOPD. A prospective, controlled evaluation of adjunctive Ig treatment to standard therapy of recurrent AECOPD is warranted.

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“…This is associated with an increased incidence of exacerbations and hospitalizations (usually because of respiratory tract infections), and this is mainly in patients with deficiencies in IgG1 and/or IgG2 subclasses . This is consistent with reports that intra‐venous Ig (IVIG) replacement therapy reduces respiratory infections and exacerbations in COPD . Administration of IVIG is also beneficial in a range of autoimmune diseases, and substantial evidence exists for the occurrence of autoimmunity in COPD—particularly the production of autoantibodies; thus, IVIG may help to reduce inflammation as well as infection in COPD.…”

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“…The patient was started on IVIG replacement therapy and shortly thereafter his exacerbation rate decreased, consistent with case series reported in the literature 24 and he was no longer hospital-dependent for his care. Unfortunately, despite the IVIG therapy and "triple" inhaler therapy regimen, his lung function continued to decline and he has become more symptomatic with increased breathlessness over the ensuing 3 years.…”

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“…Deficiencies in airway IgG1 may therefore predispose to infection of the COPD lung by this bacterium. Indeed, these observations may provide a rationale for the recent observation of the efficacy of intravenous immunoglobulin therapy in reducing the frequency of COPD exacerbations[27]. …”