PURPOSE: Small, stable and reversible declines in lung function have been observed in clinical trials of inhaled human insulin (EXU; Exubera® (insulin human [rDNA origin]) Inhalation Powder). This study assessed cellular and soluble constituents in the airway lining fluid in order to exclude pulmonary inflammation as a possible cause.
METHODS: Open-label study of 24 nonsmoking, nonasthmatic adults with type 2 diabetes: 4-week run-in, subcutaneous insulin (SC) for 12 weeks, followed (after 1 additional week) by 12 weeks of EXU. Bronchoalveolar lavage (BAL) was performed using a standardized protocol with measurements of cell counts and protein constituents (total protein, albumin, and fibrinogen) after run-in (baseline, Week 0), SC (Week 12), and EXU (Week 25).
RESULTS: Baseline demographics were mean age of 45.1 years, body mass index of 30.2 kg/m2, and disease duration of 9.7 years. Baseline BAL fluid (BALF) cellular and protein constituents were similar to those reported for nondiabetic healthy adults (BAL Cooperative Group Steering Committee. Am Rev Respir Dis 1990;141:S169-S202). An analysis of variance model with time and subject as fixed effects and an unstructured within-subject covariance matrix revealed statistically significant increases in % neutrophils and % macrophages in SC and EXU, respectively, but the increases were small, and clinically not meaningful (Table).
CONCLUSION: Twelve weeks of EXU therapy does not give rise to a cellular or protein change within the lung that is indicative of inflammation.
CLINICAL IMPLICATIONS: The treatment effects on lung function observed in EXU clinical trials are not caused by lung inflammation.
DISCLOSURE: Karl van Gundy, No Product/Research Disclosure Information; Employee Employee of Pfizer Inc. who funded this study