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 sensitiv ity and excessive airway narrowing to inhaled bronchoconstrictor stimu li. There is experimental evidence that maximal airway narrowing is re lated to lung elasticity in normal and asthmatic subjects. We hypothes ized 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 cap acity for carbon monoxide per unit lung volume (DL(CO)/VA), and mean l ung density by spirometrically controlled computed tomography (CT) sca n in eight non- or ex-smoking subjects with al-antitrypsin deficiency. Methacholine dose-response curves were expressed as the provocative c oncentration causing 20% fall in FEV(1) (PC20). A maximal response pla teau was considered if greater than or equal to 3 highest doses fell w ithin a 5% response range, the maximal response (MFEV(1)) being the av erage value on the plateau. The P-V curves were characterized by an in dex of compliance (exponent K), and elastic recoil pressures at 90, an d 100% of TLC (PL(90) and PLmax). In all subjects a complete dose-resp onse curve to methacholine could be recorded. MFEV(1) was significantl y correlated with logPC(20) (r = -0.94, p < 0.001), but not with basel ine 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 signifi cantly correlated with DL(CO)/VA (r = -0.76, p < 0.03) and with lung d ensity (r = 0.78, p < 0.04). We conclude that in subjects with al-anti trypsin deficiency the level of maximal airway narrowing increases wit h loss in lung elasticity with reduction in diffusing capacity, and wi th lowered mean lung density. This suggests that loss in elastic recoi l pressure secondary to parenchymal destruction contributes to excessi ve airway narrowing in humans in vivo.