Increased vagal airway tone in fatal asthma.
Slow-onset asthma deaths are characterized by eosinophilic airway infiltrates and thickening of the basal membrane, while rapid-onset asthma deaths are associated with fewer airway inflammatory changes, suggesting that bronchospasm may be responsible for the latter events. Airway tone is primarily controlled by the autonomous nervous system and can be pharmacologically modified. Therapies that stimulate the sympathetic beta(2) adrenoreceptor or inhibit the muscarinic receptor signal transduction induce bronchodilation. Parasympathetic (vagal) airway tone is enhanced in some asthmatics due to a number of stimuli, while in others it is constitutively heightened. Mainstream asthma therapy, however, only consists of corticosteroids and beta(2) agonists, not addressing this aspect. In this publication, I propose that increased vagal airway tone resulting in overwhelming bronchoconstriction and mucus plugging could be responsible for the near-fatal or fatal events observed in a number of asthmatics, in spite of their adequate treatment with standard therapies. On the basis of this hypothesis, I recommend that vagal airway tone be assessed in all patients with asthma, particularly in those with a history of near-fatal events. If the airway tone is increased, individuals should be treated with a triple combination of long-acting beta(2) agonists, inhaled steroids, and inhaled anticholinergics to prevent vagally mediated fatal events.
Molfino
Nestor A
NA
MedImmune, LLC, Clinical Development, One MedImmune Way, Office # 45C20, Gaithersburg, MD 20854, USA. molfinon@medimmune.com
D001249:Asthma / Q000209:etiology / Q000401:mortality* / Q000503:physiopathology*; D001980:Bronchi / Q000294:innervation* / Q000503:physiopathology*; D001982:Bronchial Diseases / Q000150:complications / Q000401:mortality* / Q000503:physiopathology*; D015897:Comorbidity; D003251:Constriction, Pathologic / Q000150:complications / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D015994:Incidence; D008954:Models, Biological; D014630:Vagus Nerve / Q000503:physiopathology*