Selected Contribution: Airway caliber in healthy and asthmatic subjects: effects of bronchial challenge and deep inspirations

Abstract

In 9 healthy and 14 asthmatic subjects before and after a standard bronchial challenge and a modified [deep inspiration (DI), inhibited] bronchial challenge and after albuterol, we tracked airway caliber by synthesizing a method to measure airway resistance (Raw; i.e., lung resistance at 8 Hz) in real time. We determined the minimum Raw achievable during a DI to total lung capacity and the subsequent dynamics of Raw after exhalation and resumption of tidal breathing. Results showed that even after a bronchial challenge healthy subjects can dilate airways maximally, and the dilation caused by a single DI takes several breaths to return to baseline. In contrast, at baseline, asthmatic subjects cannot maximally dilate their airways, and this worsens considerably postconstriction. Moreover, after a DI, the dilation that does occur in airway caliber in asthmatic subjects constricts back to baseline much faster (often after a single breath). After albuterol, asthmatic subjects could dilate airways much closer to levels of those of healthy subjects. These data suggest that the asthmatic smooth muscle resides in a stiffer biological state compared with the stimulated healthy smooth muscle, and inhibiting a DI in healthy subjects cannot mimic this.

Force Fluctuation induced Relengthening of Acetylcholine-contracted Airway Smooth Muscle

“…This airway dilation with deep inspiration also was demonstrated directly by looking at computed tomography (CT) scans of normal volunteers (8). Lung tethering forces on the conducting airways probably contributed to this dilation by loading the smooth muscle in the bronchiolar walls (8)(9)(10). However, this reversal of bronchoconstriction with breathing or deep inspiration is absent or minimal in individuals with asthma (9,10); their airways remain constricted to methacholine with breathing and, although CT scans demonstrate increased bronchial diameters with deep inspiration, the airways from individuals with asthma reconstrict almost immediately (8).…”

“…Shen and coworkers demonstrated in ventilated rabbits that breathing reduced methacholine-elicited airway resistance in a tidal volume-dependent manner (5). In normal individuals who demonstrated increased airway resistance to inhaled methacholine, the degree of bronchoconstriction could be reversed again by normal, tidal breathing (6,7) or by taking a single deep inspiration (8)(9)(10). This airway dilation with deep inspiration also was demonstrated directly by looking at computed tomography (CT) scans of normal volunteers (8).…”

“…Lung tethering forces on the conducting airways probably contributed to this dilation by loading the smooth muscle in the bronchiolar walls (8)(9)(10). However, this reversal of bronchoconstriction with breathing or deep inspiration is absent or minimal in individuals with asthma (9,10); their airways remain constricted to methacholine with breathing and, although CT scans demonstrate increased bronchial diameters with deep inspiration, the airways from individuals with asthma reconstrict almost immediately (8). Thus, it becomes apparent that determining the mechanisms relating these differences between normal individuals and individuals with asthma could be of great importance in understanding not only the disease but also in suggesting novel therapies to reverse bronchospasm.…”

Servo-Controlled Pneumatic Pressure Oscillator for Respiratory Impedance Measurements and High-Frequency Ventilation

“…11) makes it ideally suited for protocols involving the tracking effective airway caliber at different lung volumes. 10 Finally, combining an exhalation valve system with our device as described in Ref. (14) would allow it to be used in a variety of different conventional ventilatory modalities, such as assist-control, SIMV, pressure control, or proportional assist ventilation.…”

Deep breaths, methacholine, and airway narrowing in healthy and mild asthmatic subjects

“…This is consistent with in vitro data showing that the tone of airway smooth muscle is fully recovered under static conditions within 8 min after a large stretch (4). The difference in the effect of the deep breaths on FEV 1 and FVC between healthy and asthmatic subjects, but not on the parameters not preceded by a full inflation, may be interpreted as reflecting greater airway stiffness in asthma (7,8). According to the latch-bridge theory (15), unstretched airway smooth muscle goes into a "frozen" state characterized by less hysteresivity and greater stiffness (3).…”