Study objectives: The interpretation of nonspecific bronchial provocation dose-response curves in COPD is still a matter of debate. Bronchial hyperresponsiveness (BHR) in patients with COPD could be influenced by the destruction of the parenchyma and the augmented mechanical behavior of the lung. Therefore, we studied the interrelationships between indexes of BHR, on the one hand, and markers of lung parenchymal destruction, on the other. Patients and methods: COPD patients were selected by clinical symptoms, evidence of chronic, nonreversible airways obstruction, and BHR, which was defined as a provocative dose of a substance (histamine) causing a 20% fall in FEV 1 (PC 20 ) of < 8 mg/mL. BHR was subsequently studied by methacholine dose-response curves to which a sigmoid model was fitted for the estimation of plateau values and reactivity. Model fits of quasi-static lung pressure-volume (PV) curves yielded static lung compliance (Cstat), the exponential factor (KE) and elastic recoil at 90% of total lung capacity (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 data could be obtained from 19. The following mean values ( ؎ SD) were taken: FEV 1 , 65 ؎ 12% of predicted; reversibility, 5.6 ؎ 3.1% of predicted; the PC 20 for methacholine, 4.3 ؎ 5.2 mg/mL; reactivity, 11.0 ؎ 5.6% FEV 1 /doubling dose; plateau, 48.8 ؎ 17.4% FEV 1 ; transfer factor, 76.7 ؎ 17.9% 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 relationships between Cstat, on the one hand, and KE (p < 0.0001), P90TLC (p ؍ 0.0012), and KCO percent predicted (p ؍ 0.006), on the other hand. The indexes of the methacholine provocation test were not related to any parameter of lung elasticity and CO transfer. Conclusion: BHR in COPD patients who smoke most probably is determined by airways pathology rather than by the augmented mechanical behavior caused by lung parenchymal destruction.(CHEST 2000; 117:984 -990)Key words: bronchial provocation tests; COPD; dose-response relationship; forced expiratory flow rates; human; lung compliance; lung volume measurements; methacholine bromide/diagnostic use; pulmonary diffusing capacity Abbreviations: BHR ϭ bronchial hyperresponsiveness; CO ϭ carbon monoxide; Cstat ϭ static lung compliance; FRC ϭ functional residual capacity; IVC ϭ inspiratory vital capacity; KCO ϭ transfer coefficient for carbon monoxide; KE ϭ shape factor; LE ϭ linear-exponential; PC 20 ϭ provocative concentration of a substance causing a 20% fall in FEV 1 ; P90TLC ϭ elastic recoil pressure at 90% of total lung capacity; PV ϭ pressure-volume; TLC ϭ total lung capacity; Tlco ϭ transfer factor for carbon monoxide.
Bronchial hyperresponsiveness (BHR) is present in patients with asthma and COPD. 1 Approximately half of the subjects with COPD in a general population have BHR. 2 In t...