Relationship between loss in parenchymal elastic recoil pressure and maximal airway narrowing in subjects with alpha(1)-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 ar-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 (DL(CO)/VA), and mean lung density by spirometrically controlled computed tomography (CT) scan in eight non- or ex-smoking subjects with al-antitrypsin deficiency. Methacholine dose-response curves were expressed as the provocative concentration causing 20% fall in FEV(1) (PC20). A maximal response plateau was considered if greater than or equal to 3 highest doses fell within a 5% response range, the maximal response (MFEV(1)) 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 (PL(90) and PLmax). In all subjects a complete dose-response curve to methacholine could be recorded. MFEV(1) was significantly correlated with logPC(20) (r = -0.94, p < 0.001), but not with baseline FEV(1) (r = -0.53, p > 0.15). There was a significant relationship between MFEV(1) and PL(90) (r = -0.79, p < 0.02), PLmax (r = -0.87, p < 0.005), and K (r = 0.79, p < 0.02). Furthermore MFEV(1) was significantly correlated with DL(CO)/VA (r = -0.76, p < 0.03) and with lung density (r = 0.78, p < 0.04). We conclude that in subjects with al-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.