Marching to the beat of different drummers: individual airway response diversity.

The complicated structures of the lungs can be viewed in the most simplistic form as airways, vessels, and nerves. These structures work together to perform the marvellous feat of respiration and gas exchange. During disease states, one of these structures is impaired, either temporarily or permanently , and respiration and gas exchange are hindered. Asthma is a disease that primarily affects the airways. In asthma, while the aetiology may be varied, and remains a source of scientific controversy, the final common process is constriction of the airway smooth muscle, airway narrowing, and decreased ventilation that, in the severest form, can lead to death. The causes for this pathological constriction of the airways in asthmatics compared to healthy subjects are elusive and remain an area of intense research. It is well recognised that the airway tree structure throughout the lungs is not uniform in structure or composition [1]. On the simplest level, the airways change in size from the trachea to the alveoli [2]. In addition, the cellular composition of the airways changes along the airway tree. For example, the amount of airway smooth muscle, cartilage, and nerves progressively decreases along the airway tree. Therefore , it is logical to suggest that the airways along the tree would not respond in a homogeneous manner in health or disease. However, the next step in the understanding of the heterogeneous response of the airways is not so intuitive. Most investigators accept the idea of heterogeneity along the airway tree [3–5]. However, the idea of heterogeneous responses at the same level of the airway tree has not been clearly established. Recently, computer modelling has been used to simulate the process of bronchoconstriction, including airway heterogeneity. The amount and location of the constriction may be selectively adjusted and the resulting level of calculated lung resistance and elastance observed. LUTCHEN and GILLIS [6] found that both lung resistance and elastance were extremely sensitive to inhomogeneous constriction. A few highly constricted or nearly closed airways, randomly dispersed throughout the periphery of the lung, had a significant impact on the calculated breathing capacity. Of interest, their model was quite tolerant of very inhomoge-neous changes in airway diameters, as long as there were no airways nearly or fully closed. THORPE and BATES [7] also evaluated inhomogeneous constriction in another computational model. They found similar results. The increases in lung resistance and elastance were largely due to the development of …