The natural history of lung growth and senescence in individuals with variable air flow obstruction or clinical asthma has been given less attention than the natural history of chronic airflow obstruction. This article reviews the information available on lung growth during childhood in persons with asthma and on the rate of decline of lung function during adult life in individuals with asthma or bronchial hyperresponsiveness. Lung growth appears to be relatively normal in most children with asthma but is reduced throughout childhood and adolescence in those with severe and persistent symptoms. It is not known if this reflects a failure to reach full growth or reversible bronchoconstriction. During adult life, clinical asthma is associated with a slight increase in the rate of decline in FEV1. In the middle-aged and elderly smoker it is virtually impossible to separate chronic bronchitis and asthma. Bronchial hyperresponsiveness appears to be associated with an increase in the rate of decline of lung function but it is not clear if this is a result of airway disease due to smoking or a true risk factor. Further research needs are identified.

Data from various different types of cross-sectional studies are reviewed in order to examine hypotheses about the etiology of asthma and to more precisely define its relationship with nonspecific bronchial hyperreactivity (NSBH). Although cross-sectional studies have not clarified the precise etiologic links, they have established that NSBH and atopy are linked to the occurrence of asthma and to each other. In children, evidence supports the hypothesis both that atopy is a cause of asthma and that atopic diathesis is the most frequent trigger for NSHB. In adults, the associations are more complex, although in a small subset findings are similar to those in children. It is concluded that further general population-based or clinical epidemiologic cross-sectional studies based on questionnaires will contribute little more to explaining these associations. Criteria are presented for the further application of case-control studies to maximize their use in examining hypotheses of asthma etiology.

The nature of the underlying defect in asthma is still unclear. This article discusses where the primary problem might lie, starting with the assumption that it is likely to be in neurohumoral control, bronchial smooth muscle or cellular dysfunction with increased release of mediators. The weight of the evidence suggests that the latter is most likely. If true, the question of why this occurs still remains.

Mast cells are found beneath the basement membranes, near blood vessels in the submucosa, adjacent to submucous glands, scattered throughout the muscle bundles, in the interalveolar septa and in the bronchial lumen. The evidence that mast cells and mast cell-derived mediators play a role in allergic and non-allergic asthma is discussed. In allergic individuals, inhalation of specific allergens leads to mast cell degranulation and release of mediators. Many of the pathologic features of asthma may be attributed to the effects of mast cell-derived mediators. Their role is clear in allergic asthma and the presence of mast cell derived mediators in the plasma of individuals with exercise-induced and nocturnal asthma suggests involvement in other forms of asthma as well.