Drugs and the control of exercise-induced asthma.

Exercise-induced asthma (EIA) is the name used to describe the transitory increase in airways resistance which follows vigorous exercise in most patients with asthma [1). EIA has been recognized since ancient times, but the first modem clinical description was given by JoNES et al. [2] of Liverpool, UK in 1962. Exercise is acknowledged by many paediatricians to be the most common cause for an attack of asttuna in child-ren, and the presence of EIA is diagnostic of asthma. Using standardized protocols for exercise challenge, EIA can be demonstrated in the laboratory in 70-80% of clinically recognized asthmatic adults and children. In the general population, the prevalence of EIA is reported to be 4-12%, and an increase in prevalence from 6.7 to 7.7% was reported in the UK between 1973 and 1988 [1]. A reduction of 10% or more in forced expiratory volume in one second (FEY,) or peak expiratory flow rate (PEFR) in the laboratory is diagnostic of EIA. Like other attacks of asthma, EIA is accompanied by a reduction in arterial oxygen tension and lung hyperinflation. Ftfty percent of subjects are refractory to the effects of exercise, when it is repeated within 30-90 min. There is no increase in bronchial responsiveness to other stimuli following exercise, and the airway response is usually reproducible when the challenge is repeated after an interval of 3-4 h [1]. The stimulus to EIA is the evaporative water loss, which occws in the airways when conditioning large volwnes of air to alveolar temperature and water content in a short time. The mechanism whereby water loss causes the airways to narrow is thought to be due to its thennal and dehydrating effects, which produce a hyperosmolarity of the airways. This is accompanied by the release of mast cell mediators and possibly new-al stimulation, which, in turn, cause the airways to narrow by contraction of bronchial smooth muscle and submucosal oedema [1]. Because exercise initiates the endogeneous release of mediators associated with inflammation that cause the airways of asthmatics to narrow, the severity of EIA is thought to be a reflection of airway inflammation. Exercise challenge was promoted by Godfrey and colleagues in the 1970s, to identify drugs useful in the treatment and prevention of asthma [3-6]. EIA was also used to study the duration of the protective effect of drugs [6, 7]. Many of the early drug studies have been summarized previously [1]. Several studies involved the investigation of the acute effect of a single dose of drug at