Background Shortening of smooth muscle around airways is the basis of symptoms and abnormal lung function in asthma. The airway wall is increased in thickness in small and large airways asthma, in relation to the clinical severity of asthma and the airway smooth muscle layer is the main contributor to this thickening. The relative contributions of more airway smooth muscle cells, bigger cells or more extracellular matrix to the increased thickness of the smooth muscle layer in asthma is not clear and has been examined in only a small number of cases, Studies of the natural history of asthma suggest that the clinical severity of asthma is relatively constant over time, deficits in lung function compared with nonasthmatic subjects occur early in the course of the disease and the decline in lung function with age is increased in asthma.

Hypothesis The observations from studies of the quantitative pathology and the natural history of asthma might be combined in the hypothesis that the severity of asthma is determined early (in its natural history) and is related mainly to increased volume density of airways smooth muscle cells (hyperplasia) and that later deposition of extracellular matrix from larger, hypertrophic smooth muscle cells results in fixed and increasing deficits in lung function.

Speculation The relative contribution of more smooth muscle cells, bigger cells and extracellular matrix will be determined by unbiased stereological measurements in many cases of asthma of varying severity. The outcomes of such studies will be methods of monitoring and of treatment that will be tailored to the sort of smooth muscle modelling that is present in individual cases.