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.

Assessment of the progression of emphysema by quantitative analysis of spirometrically gated computed tomography images.

RATIONALE AND OBJECTIVES: The authors assessed the progression of pulmonary emphysema by means of quantitative analysis of computed tomography images. METHODS: Twenty-three patients suffering from emphysema due to an alpha 1-antitrypsin deficiency, aged 45 +/- 7 years and exsmokers, were scanned twice with a 1-year time interval. At 90% of the vital lung capacity, slices with a thickness of 1.5 mm were acquired at the level of the carina and 5 cm above the carina; slices with a thickness of 1 cm were acquired 5 cm below the carina. The entire lung was scanned spirally at a respiratory status, corresponding with 75% of the total lung capacity at baseline. The mean lung densities (MLD) were calculated in an objective manner with new analytic software featuring automated detection of the lung contours. RESULTS: Mean lung densities decreased by 14.2 +/- 12.0 Hounsfield units (HU; P < 0.001) above the carina, by 18.1 +/- 14.4 HU (P < 0.001) at the carina level, by 23.6 +/- 15.0 HU (P < 0.001) below the carina, and by 12.8 +/- 22.2 HU (P < 0.01) for the entire lung. The decrease in MLD was most obvious in the lower lung lobes. For the same patient group, the annual decrease in the forced expiratory volume (FEV1) and the carbon monoxide-diffusion were 120 +/- 190 mL (P < 0.01) and 10 +/- 70 mmol/kg/minute ( P < 0.2), respectively. No significant correlation was found between the decrease in MLD and the decrease in FEV1. CONCLUSIONS: Progression of emphysema can be assessed in an objective manner based on the mean lung density (MLD), measured from computed tomography volume scans as well as from single-slice scans. Mean lung density has proved to be more sensitive than FEV1 and carbon monoxide-diffusion.