Reproducibility and comparison of responses to inhaled histamine and methacholine.

Abstract

. Thorax, 33,. Reproducibility and comparison of responses to inhaled histamine and methacholine. The efficiency of a standardised inhalation test procedure was studied by examining the reproducibility of responses to histamine and methacholine. In addition, the responses to the two agents were compared. Each set of duplicate tests was carried out on a separate day within one week, and all factors known or presumed to influence responses were carefully controlled. The results were expressed as the provocative concentration of the agent causing a 20% fall in forced expired volume in one second (PC20). Responses to histamine and methacholine were highly reproducible (coefficients of determination [r2] = 0 994 and 0 990 respectively).Responsiveness to histamine correlated closely with responsiveness to methacholine (r2 = 0 85).There was a small but significant cumulative dose effect with methacholine (P<0 01) but not with histamine. Side effects of throat irritation, flushing, and headache were more frequent with histamine than methacholine, and were dose-related. The high level of reproducibility indicates the efficiency of the test procedure. The similar severity of effects by agents with different mnechanisms of action suggests that the primary cause of non-specific bronchial hyperreactivity lies at the level of bronchial smooth muscle.Non-specific bronchial reactivity is the term used to indicate the responsiveness of the airways to chemical mediators, such as histamine, acetylcholine, and prostaglandin F2a, or to the synthetic analogues of acetylcholine, such as methacholine and carbachol. Its measurement is becoming increasingly important in clinical practice, epidemiology, and research.Non-specific bronchial reactivity is measured by inhalation tests, usually with histamine or methacholine. In the past different methods have been used, making critical analysis of results difficult. Recently Chai et al (1975) and Orehek and Gayrard (1976) have emphasised the importance of the standardisation of tests. Standardisation requires consideration of the many different factors that will influence the results.In this study we have standardised a simple inhalation test using histamine and methacholine. We have investigated the efficiency of the method by examining the reproducibility of responses over a short period. In addition we have compared the responsiveness to each agent and investigated the possibility of cumulative dose-effects and recorded side effects. Subjects and methods SUBJECTSThe patients were adults with asthma attending the regional chest and allergy unit. All had episodic dyspnoea or wheezing and documented variation in forced expired volume in one second (FEV1) of more than 20%, either spontaneously or after medication. None had features of any other respiratory disorder.Normal adults were volunteers from hospital staff. They had no present or past symptoms of rhinitis, asthma, or other respiratory disorder. They were non-smokers, non-atopic, and had normal spirometry. Non-atopic implied that they...

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