Dissociation of Lung Function Changes with Humoral Immunity during Inhaled Human Insulin Therapy

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Abstract
Inhaled human insulin (INH; Exubera [human insulin (recombinant DNA origin) Inhalation Powder]) causes small changes in pulmonary function and increases in insulin antibodies compared with subcutaneous (SC) insulin. To investigate the relationship between changes in pulmonary function and insulin antibodies and acute effects of INH on lung function. In a 24-wk multicenter study, 226 patients with type 1 diabetes were randomized to receive daily premeal INH or SC insulin for 12 wk (comparative phase), followed by SC insulin for 12 wk (washout phase). Spirometry tests were conducted and insulin antibody levels were measured throughout the study. Acute insulin-induced changes in lung function were calculated as the difference between FEV1 before, and 10 and 60 min after, insulin. There was a temporal dissociation between pulmonary function changes and insulin antibody generation. Small treatment group differences in changes in FEV1 from baseline, favoring SC insulin, were fully manifest by 2 wk of INH therapy, did not increase during the remainder of the comparative phase, and resolved within 2 wk of INH discontinuation. By contrast, insulin antibody levels remained low for the first 2 wk with INH, increased during Weeks 2 to 12, and gradually declined during washout. There was no evidence of acute insulin-induced alterations in lung function 10 and 60 min postinhalation. The small lung function changes observed with INH therapy are not mediated by the humoral immune response, or associated with acute decrements in lung function immediately after insulin inhalation.