Chest
Translating Basic Research Into Clinical PracticeTranslating Cough Mechanisms Into Better Cough Suppressants
Section snippets
Cough Neurobiology in Health and Disease
The act of coughing spans a spectrum from purely voluntary to purely reflexive (Fig 1), the former initiated by the conscious decision-making processes in the cerebral cortex and requiring no input from sensory pathways in the airways and the latter initiated by sensory pathways in the airways and not requiring central neuronal processing above the brain stem level9 (Fig 2). Between these extremes exists coughing that is initiated from the airways but is also under behavioral modulation by the
Novel Antitussive Therapies: Preclinical and Clinical Studies
From a clinical perspective, the treatment of cough that remains refractive to disease-specific therapy would benefit from an efficacious antitussive that blocks cough of multiple causes, which is conceivably achievable by targeting key processes in the neural pathways essential for coughing. However, given the fundamental importance of a defensive cough for maintaining airway patency and preventing pulmonary infection, the “Holy Grail” is to identify targetable mechanisms that do not simply
Conclusions: Translating Preclinical Cough Models
Curiously, compounds that have shown promise in preclinical cough models have largely been disappointing in clinical trials. This naturally brings into question whether the current preclinical animal and cellular models adequately reflect CHS in humans. Alternatively, perhaps such models are simply not being used wisely. For example, the prominent axon reflex in guinea pigs and rodents (which is not present in humans) can seriously confound preclinical antitussive studies if not adequately
Acknowledgments
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: S. B. M. is supported by a grant from the National Health and Medical Research Council of Australia No. 1078943. A. E. M. is a current NHMRC of Australia Research Fellow No. 1121376. None declared (J. A. K.).
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