Increased airway smooth muscle, resulting from either hyperplasia or hypertrophy, has been implicated as a cause of excessive bronchoconstriction in asthma despite the many methodologic limitations of studies to date. Our recent failure to demonstrate increased muscle volume in an asthmatic airway preparation having 3-fold greater shortening than nonasthmatic controls prompted us to reassess the quantity of muscle in asthmatic versus nonasthmatic airways. Smooth muscle was quantified in axially sectioned, 2nd- to 4th-generation bronchi, using standardized stereologic methods on high-magnification images of cross-sectional airway smooth muscle profiles in tissues from five asthmatic subjects and five nonasthmatic smokers. When data were normalized by total cross-sectional tissue area, no differences between the two groups (asthmatic versus nonasthmatic) were detected for the proportion of smooth muscle (3.45 +/- 0.81% versus 2.74 +/- 0.76%), extracellular matrix between muscle cells (1.65 +/- 0.46% versus 1.06 +/- 0.25%), or connective tissue within smooth muscle bundles (1.65 +/- 0.34% versus 1.53 +/- 0.59%). These methodologies for evaluating cross-sectional airway muscle in axial airway sections at high resolution provide no evidence of increased airway smooth muscle in asthmatic large airways, and suggest that differences in mechanical responses of asthmatic airways cannot be explained solely by the amount of smooth muscle.

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The recent demonstration of increased shortening of asthmatic airway smooth muscle could result from increased contractility of the muscle itself or from a decreased load that must be overcome by the smooth muscle to shorten. To evaluate the role of smooth muscle-associated extracellular matrix in limiting smooth muscle responses, we investigated the effect of collagenase on the mechanical responses of human bronchial smooth muscle strips. Contractile responses of second- to fourth-generation bronchi were evoked by electrical field stimulation, and measurements of length and tension were made at preloads between 0 and 2.5 g. The passive tension, active isometric, and isotonic responses were obtained at each preload before and after 90 min of incubation with 20 U/ml collagenase. Shortening to 10(-4) M histamine was also measured. Collagenase treatment caused a significant decrease in passive tension, with the most pronounced change occurring below Lmax (optimal length for force generation). At optimal lengths for shortening, the degree of shortening, expressed as a percentage of starting length, increased significantly from 8.9 +/- 1.4% before to 13.8 +/- 2.9% after collagenase treatment (n = 7) (p < 0.02). Shortening to histamine also increased from 14.3 +/- 2.5% before to 23.5 +/- 5.3% after collagenase treatment (n = 7) (p < 0.02). These results suggest that degradation of the collagenous matrix surrounding muscle in the airway wall reduces the load on the muscle, allowing increased smooth muscle shortening.