Influence of lung parenchymal destruction on the different indexes of the methacholine dose-response curve in COPD patients

Study objectives: The interpretation of nonspecific bronchial provocation d ose-response curves in COPD is still a matter of debate. Bronchial hyperres ponsiveness (BHR) in patients with COPD could be influenced by the destruct ion of the parenchyma and the augmented mechanical behavior of the lung. Th erefore, we studied the interrelationships between indexes of BHR, on the o ne hand, and markers of lung parenchymal destruction, on the other. Patients and methods: COPD patients were selected by clinical symptoms, evi dence of chronic, nonreversible airways obstruction, and BHR, which was def ined as a provocative dose of a substance (histamine) causing a 20% fall in FEV1 (PC20) of less than or equal to 8 mg/mL. BHR was subsequently studied by methacholine dose-response curves to which a sigmoid model was fitted f or the estimation of plateau values and reactivity. Model fits of quasi-sta tic lung pressure-volume (PV) curves yielded static lung compliance (Cstat) , the exponential factor (KE) and elastic recoil at 90% of total lung capac ity (P90TLC). Carbon monoxide (CO) transfer was measured with the standard single-breath method. Results: Twenty-four patients were included in the study, and reliable PV d ata could be obtained from 19. The following mean values (+/- SD) were take n: FEV1, 65 +/- 12% of predicted; reversibility, 5.6 +/- 3.1% of predicted; the PC20 for methacholine, 4.3 +/- 5.2 mg/mL; reactivity; 11.0 +/- 5.6% FE V1/doubling dose; plateau, 48.8 +/- 17.4% FEV1; transfer factor, 76.7 +/- 1 7.9% of predicted; transfer coefficient for carbon monoxide (KCO), 85.9 +/- 22.6% of predicted; Cstat, 4.28 +/- 2.8 kPa; shape factor (KE), 1.9 +/- 1. 5 kPa; and P90TLC, 1.1 +/- 0.8 kPa, We confirmed earlier reported relations hips between Cstat, on the one hand, and KE (p < 0.0001), P90TLC (p = 0.001 2), and KCO percent predicted (p = 0.006), on the other hand. The indexes o f the methacholine provocation test were not related to any parameter of lu ng elasticity and CO transfer. Conclusion: BHR in COPD patients who smoke most probably is determined by a irways pathology rather than by the augmented mechanical behavior caused by lung parenchymal destruction.