ABNORMALITIES IN AIRWAY SMOOTH-MUSCLE IN FATAL ASTHMA

The characteristics of asthmatic airway smooth muscle are poorly described. Using standard organ bath techniques, the in vitro isometric contractile and relaxant responses of tracheal strips obtained from seven asthmatics (A) (mean age, 48 ± 6 SEM yr) dying during severe asthma attacks outside hospital were studied 7.6 ± 1.3 h after death. Drug therapy had varied, but it had always included inhaled β2-agonists. Control data (C) were obtained from 31 subjects (54 ± 2 yr) studied 9.5 ± 0.4 h after sudden nonrespiratory death. Cholinergic contractile and nonadrenergic noncholinergic inhibitory (NANC(I)) neural responses were studied with electrical field stimulation (EFS); histamine, isoproterenol (ISO), and theophylline (THEO) responses were studied using cumulative techniques. The maximal response (Tmax, g/g tissue) to histamine, cholinergic EFS (A = 61.3 ± 13.2, C = 33.6 ± 3.6, p < 0.0001), (A = 70.3 ± 11.8, C = 47.3 ± 4.5, p = 0.041), and acetylcholine (ACh) (A = 101.9 ± 17.4, C = 62.7 ± 7.5, p = 0.012) was greater in the asthmatics but NANC(I) responses were similar. Cholinergic Tmax (EFS) as a percentage of Tmax (ACh), EC50 (histamine), and EFc50 (EFS) were similar in the two groups. With tissues contracted to 60% of maximum with histamine, the concentrations of ISO (A = 60.3 nM, C = 12.7, p = 0.01) and THEO (A = 31.9 μM, C = 5.7, p = 0.041) to reduce tension by 50% (IC50) were greater in asthmatics. It is concluded that after a fatal attack isolated asthmatic airway smooth muscle has a greater maximal response to contractile agonists and impaired relaxation to β-agonists and theophylline.