Genetic factors controlling airway responsiveness

Summary

The airways have a repertoire of defense mechanisms against stimuli entering the tracheobronchial tree. Bronchial asthma can be regarded as an exaggerated airway response to different exogenous stimuli. There is indirect evidence that asthmatics form a heterogeneous population characterized by an increased responsiveness in one or more of these airway defense mechanisms. Furthermore, human investigations and animal experiments suggest that both environmental and genetic factors operate at these different levels. The aim of the present paper is to review the evidence that genetic factors control the airway response to exogenous stimuli and correlate these observations with the evidence that genetic factors are involved in the pathogenesis of human bronchial asthma.

The airways are controlled by a complex network of defense mechanisms that aim at guarding the normal physiological function of the airways, i.e., the conduction and conditioning of air (1,2). The airway defense mechanisms can be divided roughly in the following more or less interwoven aspects

• 1. Reflex bronchoconstriction either by local axon reflexes, or vagal reflexes via the central nervous system;

• 2. Increase in mucus production and mucociliary clearance;

• 3. Cough;

• 4. Inflammation involving different cell types, such as the airway epithelial cells, macrophages, mast cells, and the influx of secondary cells such as neutrophils, eosinophils, and platelets; and

• 5. Immunological response resulting in a more rapid and a more intense inflammatory and possibly also reflex response.