Dissociation of lung function changes with humoral immunity during inhaled human insulin therapy.
BACKGROUND
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.


OBJECTIVE
To investigate the relationship between changes in pulmonary function and insulin antibodies and acute effects of INH on lung function.


METHODS
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Pfizer Global Research and Development, New London, CT 06320, USA. john.g.teeter@pfizer.com
John G
JG
Teeter
Richard J
RJ
Riese
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007330:Insulin Antibodies / Q000097:blood*; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D007330:Insulin Antibodies; C473734:Exubera