Published ahead of print on March 23, 2006, doi:10.1164/rccm.200512-1861OC Am. J. Respir. Crit. Care Med., Volume 173, Number 11, June 2006, 1194-1200 A more recent version of this article appeared on June 1, 2006
Submitted on December 6, 2005 Dissociation of Lung Function Changes with Humoral Immunity During Inhaled Human Insulin TherapyJohn G Teeter1* and Richard J Riese11 Global Research and Development, Pfizer, New London, Connecticut, USA * To whom correspondence should be addressed. E-mail: john.g.teeter{at}pfizer.com.
Rationale: Inhaled human insulin (INH; Exubera® (insulin human [rDNA origin] inhalation powder)) causes small, consistent, changes in pulmonary function tests and increases in insulin antibodies compared with subcutaneous (SC) insulin. Objectives: To investigate the relationship between changes in pulmonary function and insulin antibodies, and acute effects of INH on lung function. Methods: In a 24-week multicenter study, 226 patients with type 1 diabetes were randomized to receive daily premeal INH or SC insulin for 12 weeks (comparative phase), followed by SC insulin for 12 weeks (washout phase). Measurements: Spirometry tests were conducted and insulin antibody levels measured, throughout the study. Acute insulin-induced changes in lung function were calculated as the difference between forced expiratory volume in 1 second (FEV1) before, and 10 and 60 minutes after insulin. Main Results: There was a temporal dissociation between pulmonary function changes and insulin antibody generation. Small treatment group differences in changes from baseline in FEV1 favoring SC insulin were fully manifest by 2 weeks of INH therapy, did not increase during the remainder of the comparative phase, and resolved within 2 weeks of INH discontinuation. By contrast, insulin antibody levels remained low for the first 2 weeks 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-minutes postinhalation. Conclusion: 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 following insulin inhalation. Key words: Exubera, inhaled human insulin, acute lung function, insulin antibodies
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