High-resolution computed tomographic evaluation of airway distensibility and the effects of lung inflation on airway caliber in healthy subjects and individuals with asthma.

The effects of a deep inspiration (DI) in individuals with asthma differ from those observed in healthy subjects. It has been postulated that the beneficial effect of lung inflation is mediated by airway stretch. One hypothesis to explain the defects in the function of lung inflation in asthma is that a DI may be unable to stretch the airways. This may result from attenuation of the tethering forces between the airways and the surrounding parenchyma. In the current study, we used high-resolution computed tomography (HRCT) to examine the ability of a DI to distend the airways of subjects with asthma (n = 10) compared with healthy subjects (n = 9) at baseline and after increasing airway tone with methacholine (MCh). We found that both at baseline and after the induction of smooth muscle tone with MCh, a DI distended the airways of healthy and asthmatic subjects to a similar extent, indicating that abnormal interdependence between the lung parenchyma and the airways is unlikely to play a major role in the loss or attenuation of the beneficial effect of lung inflation that characterizes asthma. Furthermore, we observed that after constriction had already been induced by MCh, following a DI, bronchodilation occurred in the healthy subjects but further bronchoconstriction occurred in the subjects with asthma. Our findings suggest that an abnormal excitation contraction mechanism in the airway smooth muscle of subjects with mild asthma counteracts the bronchodilatory effect of a DI. Therefore, the mechanism for reduced bronchodilation after DIs in subjects with mild asthma could be intrinsic to the airway smooth muscle.

Endogenous glucocorticoids and antigen-induced acute and late phase pulmonary responses.

BACKGROUND: Several studies suggest that endogenous glucocorticoids can dampen the severity of experimental allergic reactions in animals. OBJECTIVE: To investigate the influence that endogenous glucocorticoids have on the course of IgE-mediated pulmonary early and late phase reactions. METHODS: Twenty-one allergic asthmatic and six healthy control subjects underwent inhaled antigen challenge with measurements of plasma cortisol and cortisone by gas chromatography-mass spectrometry. RESULTS: There were no differences between the asthmatic and control groups in the baseline levels of cortisol or cortisone. However, the asthmatic subjects had significantly higher cortisol levels (67.2 +/- 8.6 vs 35.1 +/- 4.5 ng/mL; P = 0.04) and had higher cortisol/cortisone ratios (4.8 +/- 0. 6 vs 3.0 +/- 0.2; P = 0.01) 8 h after challenge compared to the control subjects. Among the asthmatic subjects, those whose FEV1 recovered rapidly had higher baseline levels of cortisol and those who displayed a late phase reaction had lower levels of cortisol during the late phase period. CONCLUSION: The results suggest that endogenous glucocorticoids may play a significant role in the modulation of airway responses to antigen challenge, and that antigen challenge may induce cortisol production in allergic subjects.

Airway narrowing in healthy humans inhaling methacholine without deep inspirations demonstrated by HRCT.

Normal subjects prevented from taking a deep breath show changes in airflow similar to those of asthmatics when challenged with methacholine (MCh). To confirm airway narrowing by MCh in this setting and to determine its location, we concurrently measured changes in airway lumenal area using high resolution computed tomography (HRCT) and airflow using partial spirometry in five normal subjects challenged with increasing doses of MCh under prohibition of deep breaths. In an attempt to improve imaging accuracy, we corrected for the changes in lung volume during bronchoprovocation. At every step of the provocation, scanning was performed at approximately the same lung volume. On the HRCT images, airway area decreased in response to the increasing doses of MCh to 91 +/- 2%, 88 +/- 2%, and 80 +/- 2% of baseline at the doses of MCh 0.25, 0.75, and 2.5 mg/ml, respectively (p < 0.001). Airway narrowing showed no predilection for particular airway sizes and occurred in a heterogeneous pattern. The changes in the mean airway lumenal area as measured by HRCT and the mean partial spirometric outcomes were highly correlated: FEV(1)p (r(2) = 0.46, p = 0.001), FVCp (r(2) = 0.20, p = 0.05), FEV(1)/FVCp (r(2) = 0.55, p = 0.002), MMEFp (r(2) = 0.31, p = 0.01), and taup (r(2) = 0.51, p = 0.0004). We conclude that in normal subjects who are prevented from taking a deep breath, the spirometric changes occurring with aerosol MCh challenge are associated with conducting airway narrowing.