[The relation between morphologic and functional airway changes in bronchial asthma].

Abstract

Asthma is currently defined as a chronic inflammatory disorder of the airways. The exact relationship between this inflammatory process and altered airway behavior in asthma remains to be fully established. More specifically, the question remains as to the exact causal relationship between airway inflammation and bronchial hyperresponsiveness (BHR), which constitutes the predominant lung function abnormality in asthma. The two main determinants of BHR are the hypersensitivity and the hyperreactivity of the airways. Hypersensitivity is reflected in a leftward shift of the dose response curve to the bronchoconstrictor effect of agonists such as histamine. More important from a clinical perspective is the hyperreactivity of the airways, which is characterized by excessive airway narrowing. The airway wall consists of three compartments, namely the inner airway wall area between the airway lumen and the smooth muscle layer, the airway smooth muscle layer and the outer airway wall area between the smooth muscle layer and the lung parenchyma. Mathematical models have calculated that changes within each of these compartments can contribute to airway hyperreactivity. Morphometric analysis of asthmatic airways confirm thickening of each of these three airway wall compartments. The contribution of airway inflammation to the thickening of each of these compartments and their relative functional impact on BHR remains to be further elucidated. Asthmatic airways display signs both of the acute and the chronic phase of an inflammatory reaction. The acute allergic inflammation is characterized by the presence of increased amounts of inflammatory cells including eosinophils, mast cells, macrophages, dendritic cells and T helper 2 (Th2) lymphocytes, and is regulated by a complex network of mutually interacting cytokines. The Th2 lymphocyte plays a crucial role within this network. Based, amongst other observations, on in vivo animal models, the hypothesis can be formulated that through the release of a range of cytokines, Th2 cells affect directly airway responsiveness. It would appear that neither crosslinking of IgE and subsequent mast cell degranulation nor eosinophil influx into the airways play a crucial role in this process. Asthmatic airways also display signs of a chronic inflammatory process, that results in more structural alterations, the so-called airway remodeling. This includes increased deposition of collagen and fibronectin, in addition to airway smooth muscle hypertrophy and hyperplasia. In vivo animal models indicate that these structural alterations have a more profound impact on BHR than the acute inflammation. These models also illustrate that depending on the exact extent and location of structural changes throughout the various airway wall compartments, remodeling can enhance but also protect against excessive airway narrowing, despite the presence of acute inflammation. These results illustrate the necessity to take into account the full extent of histological alterations throughout the airway wall, when evaluating the effect of individual cells and cytokines involved in the acute and chronic inflammatory response in asthma.