Influence of Lung Parenchymal Destruction on the Different Indexes of the Methacholine Dose-Response Curve in COPD Patients

Abstract

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...

Bronchial hyperresponsiveness in women with chronic obstructive pulmonary disease related to wood smoke

“…In some studies, the correlation between inflammatory markers like exhaled nitric oxide or sputum eosinophils and the PC 20 has been weak, but others have shown that the more severe the airway inflammation, the higher the rate of BHR 36,37. In addition, no functional indexes evaluating the lung parenchyma structure like pressure-volume curves or diffusion capacity (DL, CO ) have been related to BHR, which suggests that BHR is more closely related to airway abnormalities (inflammation and lumen reduction) in COPD patients 38. However, no differences have been observed between BHR in patients with chronic bronchitis and those with emphysema 39…”

Mechanisms of Bronchial Hyperreactivity in Asthma and Chronic Obstructive Pulmonary Disease

“…One recent report in smoking subjects with COPD shows that indices of BHR are not related to measures of impairment of the lung parenchyma structure, as determined by pressure-volume curves and carbon monoxide diffusion (77). This may suggest that BHR in smoking COPD patients is determined by airway pathology rather than parenchymal impairment (77). Another study has demonstrated that the presence of BHR to AMP in subjects with COPD is associated with increased numbers of CD8ϩ T cells in the lamina propria in the large airways and with higher eosinophil counts in induced sputum samples (78).…”

“…One recent report in smoking subjects with COPD shows that indices of BHR are not related to measures of impairment of the lung parenchyma structure, as determined by pressure-volume curves and carbon monoxide diffusion (77). This may suggest that BHR in smoking COPD patients is determined by airway pathology rather than parenchymal impairment (77).…”

Clinical implications of airway hyper-responsiveness in COPD

“…In the context of destroyed lung parenchyma, the load that counteracts the shortening of ASM is depressed and this favors maximal airway narrowing. In this respect, one should focus on the reactivity (the slope of the dose-response curve), which in COPD has been demonstrated to depend on the reduction of FEV 1 (Verhoeven et al 2000) and on airway wall thickness (Corsico et al 2003). The maximal response on the dose-response curve describes a condition of increased risk of severe bronchoconstriction.…”

“…In this study, the authors recruited subjects with α 1 -antitrypsin deficiency and no current history of smoking, and found a close relationship between the degree of parenchymal destruction and the maximal airway narrowing. On the other hand, plateaus in the dose-response curve have been documented in some individuals with COPD (Verhoeven et al 2000). It can, however, be theorized that, given the structural alterations of the lung parenchyma, higher reactivity is likely to occur in COPD subjects.…”