In vivo, breathing movements, including tidal and deep inspirations (DIs), exert a number of beneficial effects on respiratory system responsiveness in healthy humans that are diminished or lost in asthma, possibly as a result of reduced distension (strain) of airway smooth muscle (ASM). We used bronchial segments from pigs to assess airway responsiveness under static conditions and during simulated tidal volume oscillations with and without DI and to determine the roles of airway stiffness and ASM strain on responsiveness. To simulate airway dilations during breathing, we cycled the luminal volume of liquid-filled segments. Volume oscillations (15 cycles/min) were set so that, in relaxed airways, they produced a transmural pressure increase of approximately 5-10 cmH(2)O for tidal maneuvers and approximately 5-30 cmH(2)O for DIs. ACh dose-response curves (10(-7)-3 x 10(-3) M) were constructed under static and dynamic conditions, and maximal response and sensitivity were determined. Airway stiffness was measured from tidal trough-to-peak pressure and volume cycles. ASM strain produced by DI was estimated from luminal volume, airway length, and inner wall area. DIs produced substantial ( approximately 40-50%) dilation, reflected by a decrease in maximal response (P < 0.001) and sensitivity (P < 0.05). However, the magnitude of bronchodilation decreased significantly in proportion to airway stiffening caused by contractile activation and an associated reduction in ASM strain. Tidal oscillations, in comparison, had little effect on responsiveness. We conclude that DI regulates airway responsiveness at the airway level, but this is limited by airway stiffness due to reduced ASM strain.

In healthy individuals, deep inspiration produces bronchodilation and reduced airway responsiveness, which may be a response of the airway wall to mechanical stretch. The aim of this study was to examine the in vitro response of isolated human airways to the dynamic mechanical stretch associated with normal breathing. Human bronchial segments (n = 6) were acquired from patients without airflow obstruction undergoing lung resection for pulmonary neoplasms. The side branches were ligated and the airways were mounted in an organ bath chamber. Airway narrowing to cumulative concentrations of acetylcholine (3 × 10(-6) M to 3 × 10(-3) M) was measured under static conditions and in the presence of "tidal" oscillations with intermittent "deep inspiration." Respiratory maneuvers were simulated by varying transmural pressure using a motor-controlled syringe pump (tidal 5 to 10 cmH(2)O at 0.25 Hz, deep inspiration 5 to 30 cmH(2)O). Airway narrowing was determined from decreases in lumen volume. Tidal oscillation had no effect on airway responses to acetylcholine which was similar to those under static conditions. Deep inspiration in tidally oscillating, acetylcholine-contracted airways produced potent, transient (<1 min) bronchodilation, ranging from full reversal in airway narrowing at low acetylcholine concentrations to ∼50% reversal at the highest concentration. This resulted in a temporary reduction in maximal airway response (P < 0.001), without a change in sensitivity to acetylcholine. Our findings are that the mechanical stretch of human airways produced by physiological transmural pressures generated during deep inspiration produces bronchodilation and a transient reduction in airway responsiveness, which can explain the beneficial effects of deep inspiration in bronchial provocation testing in vivo.

During bronchoconstriction elastic after-loads arise due to distortion of lung parenchyma by the narrowing airway. In the present study, the functional effect of parenchymal elastic after-load on airway narrowing was determined.Airway narrowing was measured in vivo over a range of transpulmonary pressures and compared with in vitro narrowing measured at corresponding transmural pressures. Bronchi were generation 10 with internal diameters of ,4 mm. In vivo luminal narrowing was measured by videobronchoscopy in anaesthetised and ventilated pigs. In vitro luminal narrowing was measured by videoendoscopy in isolated bronchial segments. Airways were activated by maximum vagal nerve stimulation and maximum electrical field stimulation in vivo and in vitro, respectively.At 5 cmH 2 O, stimulation produced a 35.9¡3.2% (n56) and a 36.5¡2.4% (n511) decrease in lumen diameter in vivo and in vitro, respectively. At 30 cmH 2 O, luminal narrowing fell to 23.7¡2.0% in vivo and 23.4¡2.5% in vitro. There was no difference between luminal narrowing in vivo and in vitro at any pressure.In conclusion, these findings suggest that in mid-sized, cartilaginous bronchi, parenchymal elastic after-loads do not restrict airway narrowing.

The present study presents preliminary findings on how structural/functional abnormalities of the airway wall relate to excessive airway narrowing and reduced bronchodilatory response to deep inspiration (DI) in subjects with a history of asthma. Bronchial segments were acquired from subjects undergoing surgery, mostly to remove pulmonary neoplasms. Subjects reported prior doctor-diagnosed asthma (n = 5) or had no history of asthma (n = 8). In vitro airway narrowing in response to acetylcholine was assessed to determine maximal bronchoconstriction and sensitivity, under static conditions and during simulated tidal and DI maneuvers. Fixed airway segments were sectioned for measurement of airway wall dimensions, particularly the airway smooth muscle (ASM) layer. Airways from subjects with a history of asthma had increased ASM (P = 0.014), greater maximal airway narrowing under static conditions (P = 0.003), but no change in sensitivity. Maximal airway narrowing was positively correlated with the area of the ASM layer (r = 0.58, P = 0.039). In tidally oscillating airways, DI produced bronchodilation in airways from the control group (P = 0.0001) and the group with a history of asthma (P = 0.001). While bronchodilation to DI was reduced with increased airway narrowing (P = 0.02; r = -0.64)), when the level of airway narrowing was matched, there was no difference in magnitude of bronchodilation to DI between groups. Results suggest that greater ASM mass in asthma contributes to exaggerated airway narrowing in vivo. In comparison, the airway wall in asthma may have a normal response to mechanical stretch during DI. We propose that increased maximal airway narrowing and the reduced bronchodilatory response to DI in asthma are independent.

Maturational changes in the specific compliance could potentially contribute to the development or clinical presentation of respiratory diseases in infants and children. Changes in the specific compliance during development and its structural basis have been well characterized, but changes in bronchial compliance and the mechanisms involved have received little attention.Semistatic pressure-volume curves were generated for isolated bronchial segments from late-term foetal, immature and adult pigs. A small number of bronchi from human infants were also studied. The amount of cartilage in the bronchial wall of pigs of different ages was measured histologically, and morphometric changes in the wall of inflated bronchi were investigated.The specific compliance of bronchi approximately halved from 1 to 4 weeks of age. No change in specific compliance was observed either between 4 week old and adult pigs, or between late-term foetal and 1 week old pigs. Changes in the total wall and cartilage areas did not correlate with changes in specific compliance. Inflation to 20 cmH 2 O transmural pressure reduced the total wall area of bronchi from 1 week old pigs.Significant changes in bronchial distensibility occur during the early postnatal period. These changes in specific compliance are not caused by an increase in the amount of cartilage. The increase in luminal volume during inflation of bronchial segments occurs, partially, by compression of the airway wall against the cartilage layer.