Modulation of airway sensitivity to inhaled irritants: Role of inflammatory mediators

Lu Yuan Lee, John G. Widdicombe

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Bronchopulmonary C-fiber endings and rapidly adapting pulmonary receptors (RARs) are primarily responsible for eliciting the defense reflexes in protecting the lungs against inhaled irritants. In anesthetized animals, inhalation of cigarette smoke, one of the common inhaled irritants, into the lungs elicits pulmonary chemoreflexes that are mediated through the stimulation of pulmonary C fibers. When the C-fiber conduction is selectively blocked in the vagus nerves, the same smoke inhalation triggered only augmented breaths, a reflex effect of activating RARs, in the same animals. Indeed, electrophysiologic study shows that inhaled smoke exerts a direct stimulatory effect on both types of afferents. Increasing evidence indicates that the excitability of these afferents and therefore their reflex actions are enhanced by airway mucosal inflammation; one such example is the airway hyperresponsiveness induced by acute exposure to ozone. Although the mechanism underlying the inflammation-induced hypersensitivity of C-fiber endings is not fully understood, the possible involvement of local release of certain inflammatory mediators, such as histamine and prostaglandin E2 (PGE2), should be considered. It is believed that changes in the membrane properties mediated by the activation of certain specific receptor proteins located on the membrane of these nerve terminals are involved, as the sensitizing effects of PGE2 can be also demonstrated in cultured pulmonary C neurons.

Original languageEnglish
Pages (from-to)585-589
Number of pages5
JournalEnvironmental Health Perspectives
Issue numberSUPPL. 4
StatePublished - 2001


  • Airway inflammation
  • Airway receptors
  • Airway reflexes
  • Bronchial hyperreactivity
  • Cigarette smoke
  • Inhaled irritants
  • Ozone

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis


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