Am. J. Respir. Crit. Care Med., Vol 155, No. 1, Jan 1997, 135-140.
Relationship between loss in parenchymal elastic recoil pressure and maximal airway narrowing in subjects with alpha1-antitrypsin deficiency
D Cheung, R Schot, AH Zwinderman, H Zagers, JH Dijkman and PJ Sterk
Department of Pulmonology, Leiden University Hospital, and Department of Medical Statistics, State University Leiden, the Netherlands.
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.
