Pulmonary pharmacology & therapeutics
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Pulm Pharmacol Ther · Jan 2007
Airway irritation and cough evoked by inhaled cigarette smoke: role of neuronal nicotinic acetylcholine receptors.
In a series of studies carried out in different experimental models, we investigated the type(s) of lung afferents and mechanism(s) underlying the cigarette smoke-induced airway irritation and cough. In healthy non-smokers, the intensity of airway irritation and cough evoked by cigarette smoke was markedly reduced after premedication with hexamethonium. A similar pattern of responses was also triggered by inhalation of nicotine aerosol. ⋯ Our results showed that nicotine evoked an abrupt and transient increase in [Ca(2+)](i) in approximately 34% of the 522 neurons tested, and 1,1-dimethyl-4-phenylpiperazinium, a selective agonist of the neuronal nicotinic acetylcholine receptors (NnAChRs), evoked a similar pattern of response as that of nicotine in these neurons. In conclusion, results of these studies show that nicotine exerts a direct stimulatory effect on vagal pulmonary sensory neurons. This stimulatory effect of nicotine is primarily responsible for the airway irritation and cough evoked by inhaled cigarette smoke, and is mediated through an activation of the NnAChRs.
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Pulm Pharmacol Ther · Jan 2007
Controlled Clinical TrialThe effect of montelukast (10mg daily) and loratadine (10mg daily) on wheal, flare and itching reactions in skin prick tests.
Antileukotriene agents are widely used for the treatment of allergic conditions including bronchial asthma and allergic rhinitis. The influence of montelukast on skin reactivity has not been clearly evaluated. The aim of this study was to determine the effect of montelukast on wheal, flare and itching in skin prick tests (SPTs). ⋯ Our data show a tendency to suppressive effect of montelukast on flare and itching but not on wheal which is basic for SPT interpretation. We conclude that found suppression have little impact on clinical effectiveness of SPT as a diagnostic tool.
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The assessment of cough severity solely through consultation with the patient is limited by its subjective nature and variability of physician judgement. The assessment of cough has been hampered by a paucity of objective tools, those available have been poorly validated, non-standardized and are impractical for clinical use. ⋯ These tools can be used to validate the presence of cough and assess response to therapy. They will also have an important role in clinical trials.
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Coughing can be both voluntarily induced and involuntarily initiated by activation of vagal afferent nerves innervating the airways and lungs. Centrally, cough is regulated at the level of the brainstem through integration of vagal afferent nerve input by relay neurones in the nucleus tractus solitarius (nTS). ⋯ Peripherally, both neuronal and non-neuronal elements in the airways regulate the excitability of the vagal afferent nerve terminals regulating cough. These multiple levels of integration and encoding of the cough reflex may render this defensive respiratory response highly susceptible to modulation both by disease processes and through therapeutic intervention.
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Pulm Pharmacol Ther · Jan 2007
Randomized Controlled TrialThe effect of codeine on the Urge-to-Cough response to inhaled capsaicin.
We have shown previously in normal subjects that a sensory measure, the Urge-to-Cough rating, increases at concentrations of inhaled capsaicin that are lower than those necessary to elicit reflex cough. This finding suggests that the Urge-to-Cough may represent an index of the cough response. Research on cough in the human has most often employed challenge with inhaled capsaicin to induce reflex cough. ⋯ These results showed that the initial threshold for responding to capsaicin-induced cough is the perception of an Urge-to-Cough, followed by a motor cough response if the capsaicin is increased above the perceptual threshold. As the capsaicin concentration increases, both the perceptual need to cough and the cough motor response increase. The response of subjects to inhalation of capsaicin consisted of both a sensory component leading to perception of an Urge-to-Cough and motor cough behavior.