Effects of inhaled human insulin on airway lining fluid composition in adults with diabetes

Inhaled human insulin (Exubera (human insulin of rDNA origin) Inhalation Powder) causes small, early and reversible changes in pulmonary function in subjects with diabetes mellitus. The present study assessed whether changes occur in cellular and soluble constituents of airway lining fluid consistent with inflammation as a possible cause for Exubera-associated lung function alterations. Two 31-week, open-label, sequential design phase 2 studies were conducted, one with 20 subjects with type 1 and one with 24 subjects with type 2 diabetes. After run-in, all subjects received subcutaneous insulin for 12 weeks, followed after 1 week by 12 weeks of Exubera. Bronchoalveolar lavage fluid cell counts and protein constituents were determined at baseline, after 12 weeks of subcutaneous insulin and after 12 weeks of Exubera. Baseline cellular and soluble constituents of lavage fluid were similar to those reported for nondiabetic adults. Exubera produced no consistent clinically or statistically significant changes in total or differential lavage fluid cell counts or protein concentrations, even though Exubera-associated changes in pulmonary function are known to be fully manifest within 12 weeks. Therefore, 12 weeks of Exubera treatment is not associated with evidence of pulmonary inflammation. The treatment effects on lung function observed in Exubera trials are not caused by lung inflammation.