Allergic inflammation and airway smooth muscle function.

It is widely accepted that airway smooth muscle (ASM) contraction plays a key role in asthmatic attacks. Whether abnormalities of contractility or autonomic regulation exist in the asthmatic ASM is still debated. Studies based on isometric contraction failed to show differences in the force-generation capability between asthmatic and normal ASM. Recent studies in vitro have shown that sensitized ASM: (1) shortens more and more rapidly than normal ASM; and (2) develops a myogenic response to stretching. The increased velocity of shortening may compromise in vivo the ability of tidal cycling to reduce airway tone, which would result in an enhanced response to bronchoconstrictor stimuli. The myogenic response may result in a sustained bronchospasm after a deep inhalation, a maneuver that in normal individuals causes bronchodilatation. Although there is no evidence that neural or humoral abnormalities in the autonomic regulation of ASM tone are central to the pathogenesis of bronchial asthma, recent data suggest that ASM receptor dysfunction may develop secondary to airway allergic response. It has been shown that exposure of passively sensitized human bronchi to allergens in vitro causes M2- and beta2-receptor dysfunction. Impairment of pre-junctional M2-autoreceptors may result in an enhancement of neurally mediated bronchoconstrictor responses, whereas beta2-receptor dysfunction may reduce the sensitivity to bronchodilator treatment. Airway inflammation, which is a characteristic feature of bronchial asthma, may alter both the contractile properties and the autonomic regulation of ASM. These changes may contribute to the severity of asthma, as they may cause an, imbalance between factors favoring and opposing airway narrowing.