Bronchial hyperresponsiveness and anti-asthmatic therapy

Many asthmatic patients experience shortness of breath or wheezing, when exposed to cold air, or irritants like baking fumes, exhaust gases or cigarette smoke. This clinical phenomenon has been called bronchial hypemsponsiveness (BHR), which is defined as an exaggerated broncho-obstructive response following exposure to a small quantity of a non-allergic stimulus that does not provoke such a response in normal subjects. BHR has been observed in patients with asthma, emphysema, and bronchitis, and it is therefore regarded as a characteristic phenomenon in chronic obstructive lung diseases. The underlying mechanism of BHR, although extensively studied, is only partly understood. Possible mechanisms include an imbalance in autonomic nervous control, intrinsic hyperresponsiveness of airway smooth muscle or mediator releasing cells, and airway inflammation (e.g. caused by viral infection, exposure to chemical irritants and allergic reactions). The degree of BHR has been shown to be related to the severity of the disease and to the amount of drugs required to control symptoms. Furthermore, it has been suggested that the degree of BHR is correlated to the rate of annual decline in lung function in chronic airflow obstruction. For these reasons, reduction of BHR can be considered as an important aim in the treatment of patients with obstructive lung diseases, and the effectiveness of anti-asthmatic drugs in this respect might be an important criterion of their usefulness. This thesis deals with the effect of anti-asthmatic drugs on bronchial hyperresponsiveness. The pharrnacokinetic behaviour of some of these drugs has been studied. These studies will be summarized first, followed by a summary of the studies on the effect of drugs on BHR