Respiratory sensations evoked by activation of bronchopulmonary C-fibers.

C-fibers represent the majority of vagal afferents innervating the airways and lung, and can be activated by inhaled chemical irritants and certain endogenous substances. Stimulation of bronchopulmonary C-fibers with selective chemical activators by either inhalation or intravenous injection evokes irritation, burning and choking sensations in the throat, neck and upper chest (mid-sternum region) in healthy human subjects. These irritating sensations are often accompanied by bouts of coughs either during inhalation challenge or when a higher dose of the chemical activator is administered by intravenous injection. Dyspnea and breathless sensation are not always evoked when these afferents are activated by different types of chemical stimulants. This variability probably reflects the chemical nature of the stimulants, as well as the possibility that different subtypes of C-fibers encoded by different receptor proteins are activated. These respiratory sensations and reflex responses (e.g., cough) are believed to play an important role in protecting the lung against inhaled irritants and preventing overexertion under unusual physiological stresses (e.g., during strenuous exercise) in healthy individuals. More importantly, recent studies have revealed that the sensitivity of bronchopulmonary C-fibers can be markedly elevated in acute and chronic airway inflammatory diseases, probably caused by a sensitizing effect of certain endogenously released inflammatory mediators (e.g., prostaglandin E(2)) that act directly or indirectly on specific ion channels expressed on the sensory terminals. Normal physiological actions such as an increase in tidal volume (e.g., during mild exercise) can then activate these C-fiber afferents, and consequently may contribute, in part, to the lingering respiratory discomforts and other debilitating symptoms in patients with lung diseases.