Lung function in A/J mice following sub-chronic cigarette smoke exposure Patterns of emphysematous and fibrotic changes

J.L. Pype, E. Van Miert, K.T. Meurrens, M.J. Peck1 and P.M. Vanscheeuwijck

Philip Morris Research Laboratories bvba, 3001 Leuven, Belgium, Philip Morris Research Laboratories GmbH, Cologne, Germany1

Airflow limitation due to small airway diseases and emphysema is a defining feature of COPD. We investigated lung function in female A/J mice exposed to fresh air or MS from the Reference Cigarette 2R4F for 2, 3, or 4 x 1 hour/day, 5 days/week at 750 µg total particulate matter (TPM)/l for 3 and 5 months. Respiratory mechanics were determined in anesthetized mice (10/group) using a computer-controlled small animal ventilator (Flexivent).

At 3 months, no significant increase in tissue elastance (Htis) was found, while at 5 months Htis was significantly increased at all smoke doses (14.6±1.2, 19.1±5.9, 18.9±2.0 and 19.4±1.8 for 0, 1500, 2250, and 3000 µg TPM/(l x day), respectively). For all MS-exposed mice at 3 and 5 months, maximal lung volume (at 30 cm H2O) was significantly increased (30.3±3.2 vs 58.5±4.2 ml/kg, sham vs 3000 µg TPM/(l x day) group at 5 months) and the maximal airway pressure at total lung capacity was significantly decreased (40.4.±4.4 vs 24.9±4.1 cm H2O, sham vs 3000 µg TPM/(l x day) group at 5 months).

Sub-chronic MS exposure in A/J mice resulted in time- and dose-dependent changes in lung function parameters, similar to changes observed in bleomycin (fibrosis)- and elastase (emphysema)-treated mice.

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