Acute effects of long acting bronchodilators on small airways detected in COPD patients by single breath N2 test and lung P-V curve

Small airways represent the key factor of chronic obstructive pulmonary disease (COPD) pathophysiology. The effect of different classes of bronchodilators on small airways is still poorly understood and difficult to assess. Hence, the acute effects of tiotropium (18 µg) and indacaterol (150 µg) on closing volume (CV) and ventilation inhomogeneity were investigated and compared in 51 stable patients (mean age (SD): 70±7 years; 82% males) with moderate to very severe COPD. Patients underwent body-plethysmography, arterial blood gas-analysis, tidal expiratory flow limitation (EFL), dyspnea assessment, and simultaneous recording of single breath nitrogen test (SBN) and transpulmonary pressure-volume curve (PL-V), before and one hour after drug administration. The effects produced by indacaterol on each variable did not differ from those caused by tiotropium, independent of the severity of disease, assessed according to the GOLD scale, and the presence of EFL. Bronchodilators significantly decreased the slope of phase III and CV (-5±4% and -2.5±2.1%, both P<0.001), with an increase in both slope and height of phase IV, and of the anatomical dead space. Arterial oxygen pressure and saturation significantly improved (3±3 mmHg and 2±2%, both P<0.001); their changes negatively correlated with those of phase III slope (r=-0.659 and r=-0.454, both P<0.01). The vital capacity (VC) increased substantially but the PL-V/VC curve above CV was unaffected. In conclusion, bronchodilators reduce the heterogeneity of peripheral airway mechanical properties and the extent of their closure, with minor effects on critical closing pressure. This should lessen the risk of small airways damage and positively affect gas exchange.