Relationship between loss in parenchymal elastic recoil pressure and maximal airway narrowing in subjects with alpha1-antitrypsin deficiency.
Airway hyperresponsiveness is characterized by an increase in sensitivity and excessive airway narrowing to inhaled bronchoconstrictor stimuli. There is experimental evidence that maximal airway narrowing is related to lung elasticity in normal and asthmatic subjects. We hypothesized that reduced lung elasticity by parenchymal destruction increases the level of maximal airway narrowing in subjects with alpha1-antitrypsin deficiency. To that end, we measured complete dose-response curves to methacholine, quasistatic pressure-volume (P-V) curves, diffusion capacity for carbon monoxide per unit lung volume (DLCO/VA), and mean lung density by spirometrically controlled computed tomography (CT) scan in eight non- or ex-smoking subjects with alpha1-antitrypsin deficiency. Methacholine dose-response curves were expressed as the provocative concentration causing 20% fall in FEV1 (PC20). A maximal response plateau was considered if > or = 3 highest doses fell within a 5% response range, the maximal response (MFEV1) being the average value on the plateau. The P-V curves were characterized by an index of compliance (exponent K), and elastic recoil pressures at 90, and 100% of TLC (PL90 and PLmax). In all subjects a complete dose-response curve to methacholine could be recorded. MFEV1 was significantly correlated with logPC20 (r = -0.94, p < 0.001), but not with baseline FEV1 (r = -0.53, p > 0.15). There was a significant relationship between MFEV1 and PL90 (r = -0.79, p < 0.02), PLmax (r = -0.87, p < 0.005), and K (r = 0.79, p < 0.02). Furthermore MFEV1 was significantly correlated with DLCO/VA (r = -0.76, p < 0.03) and with lung density (r = 0.78, p < 0.04). We conclude that in subjects with alpha1-antitrypsin deficiency the level of maximal airway narrowing increases with loss in lung elasticity, with reduction in diffusing capacity, and with lowered mean lung density. This suggests that loss in elastic recoil pressure secondary to parenchymal destruction contributes to excessive airway narrowing in humans in vivo.
Cheung
D
D
Department of Pulmonology, Leiden University Hospital, and Department of Medical Statistics, State University Leiden, the Netherlands.
Schot
R
R
Zwinderman
A H
AH
Zagers
H
H
Dijkman
J H
JH
Sterk
P J
PJ
D000328:Adult; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000000981:diagnostic imaging; D008170:Lung Compliance; D008176:Lung Volume Measurements; D008297:Male; D008449:Maximal Expiratory Flow-Volume Curves; D016210:Methacholine Chloride; D008875:Middle Aged; D011653:Pulmonary Diffusing Capacity; D014057:Tomography, X-Ray Computed; D019896:alpha 1-Antitrypsin Deficiency
D016210:Methacholine Chloride