Materials and Methods

Tissues Receptor autoradiographic data were obtained on four of the seven asthmatics in the original two reports (5, 6)(patients 3, 4, 6, and 7) and two further subjects dying in status asthmaticus outside hospital, for whom functional data were obtained: a 37-yr-oldwoman with severe chronic asthma for 20 yr, and a 60-yr-old man with asthma for 32 yr. Comparison was made with airway samples obtained after sudden nonpulmonary deaths from four of the control subjects previously reported (5, 6) matched for age, sex, and postmortem time.

Methods for specimen collection and measurement of isometric relaxant responses to ISO have been previously described (5, 6). In summary, transverse strips of distal tracheal smooth muscle and fourth-generation bronchial spirals were removed during a coroner's autopsy from the lungs of patients dying outside hospital during attacks of asthma. All tissues were removed within 14 h of death. All cadavers had been stored in the coroner's mortuary at 7 C within 3 h of death. The samples were suspended using standard organ bath techniques for the measurement of isometric tension. Cumulative concentration-response relationships to ISO (1nM to 10 j. tM) were obtained on tissues precontracted, with histamine, to 60% of a predetermined maximal response to acetylcholine. The values for concentrations of ISO causing 50% of the maximum relaxant response (ECso) were then calculated for each subject.