TRPV4 antagonist GSK2193874 does not modulate cough response to osmotic stimuli

Buday, Tomáš; Kováčiková, Lea; Ruzinak, Robert; Plevková, Jana

doi:10.1016/j.resp.2016.10.010

Cited by 23 publications

(18 citation statements)

References 27 publications

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“…The speed of the cough response may differ between CPTHAs and TRPV1-involved challenges. In guinea pigs exposed to 10-min inhalations of various cough provoking agents, the coughing started on average 53 s after the start of citric acid inhalation, whereas the coughing in response to hypertonic saline appeared not until 100 s from the start of inhalation [25]. This difference in the speed of the responses can also be detected in humans.…”

Section: Description Of the Cough Response To Cpthasmentioning

confidence: 88%

“…TRPV4 is thought to act as a sensor of osmotic homeostasis [31,32]. However, administration of the TRPV4 antagonist GSK2193874 did not inhibit the cough response to hypertonic saline in guinea pigs suggesting that this receptor is not involved in hypertonicity-induced cough [25].…”

Section: The Possible Mechanisms Of Hypertonic Aerosol-provoked Coughmentioning

confidence: 99%

“…The activation of jugular ganglion sensory fibres started when the concentration of saline exceeded 3% (approximately 900 mosmol•L −1 ) and increased with concentration [23]. However, the exact mechanism through which hypertonicity excites the jugular ganglion fibres is unknown [25]. The excitation may involve an activation of a receptor, which is capable of detecting hyperosmolarity.…”

Section: The Possible Mechanisms Of Hypertonic Aerosol-provoked Coughmentioning

confidence: 99%

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Cough-provocation tests with hypertonic aerosols

2020

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Recent advances in cough research suggest a more widespread use of cough-provocation tests to demonstrate the hypersensitivity of the cough reflex arc. Cough-provocation tests with capsaicin or acidic aerosols have been used for decades in scientific studies. Several factors have hindered their use in everyday clinical work: i.e. lack of standardisation, the need for special equipment and the limited clinical importance of the response. Cough-provocation tests with hypertonic aerosols (CPTHAs) involve provocations with hypertonic saline, hypertonic histamine, mannitol and hyperpnoea. They probably act via different mechanisms than capsaicin and acidic aerosols. They are safe and well tolerated and the response is repeatable. CPTHAs can assess not only the sensitivity of the cough reflex arc but also the tendency of the airway smooth muscles to constrict (airway hyper-responsiveness). They can differentiate between subjects with asthma or chronic cough and healthy subjects. The responsiveness to CPTHAs correlates with the cough-related quality of life among asthmatic subjects. Furthermore, the responsiveness to them decreases during treatment of chronic cough. A severe response to CPTHAs may indicate poor long-term prognosis in chronic cough. The mannitol test has been stringently standardised, is easy to administer with simple equipment, and has regulatory approval for the assessment of airway hyper-responsiveness. Manual counting of coughs during a mannitol challenge would allow the measurement of the function of the cough reflex arc as a part of clinical routine.

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Section: Description Of the Cough Response To Cpthasmentioning

confidence: 88%

Section: The Possible Mechanisms Of Hypertonic Aerosol-provoked Coughmentioning

confidence: 99%

Section: The Possible Mechanisms Of Hypertonic Aerosol-provoked Coughmentioning

confidence: 99%

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Cough-provocation tests with hypertonic aerosols

2020

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“…A previous study showed that a stimulation of TRPA1 was weaker than that of TRPV1 to evoke action potential discharge in tracheal C‐fibres of guinea‐pig . In addition, citric acid can also induce cough in guinea‐pigs not only by activating TRPV1 but also by a TRPV1‐independent pathway that involves TRPV4 …”

Section: Discussionmentioning

confidence: 98%

Traffic‐related air pollution induces non‐allergic eosinophilic airway inflammation and cough hypersensitivity in guinea‐pigs

Zheng

Huang

Zhang

et al. 2019

Clin Experimental Allergy

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Background:The pathogenesis and pathophysiology of eosinophilia-related chronic cough such as non-asthmatic eosinophilic bronchitis and cough variant asthma are still not clear.Objective: This study is to examine the potential role of traffic-related air pollution (TRAP) in eosinophilic inflammation and cough responses.Methods: Non-sensitized guinea-pigs were exposed to TRAP in an urban traffic tunnel or kept in a filtered air environment for 7 or 14 days. Reflexive cough was measured using citric acid and allyl isothiocyanate (AITC) challenges, respectively.Spontaneous cough counting was determined using audio recording and a waveform analysis. Airway inflammation was evaluated using differential cells in bronchoalveolar lavage fluid (BALF) and lung histopathology. To further elucidate the relationship between airway inflammation and cough hypersensitivity, a subgroup of those exposed for 14 days received a dexamethasone treatment.Results: Compared to reflexive cough count (mean (95% confidence interval) in 10 minutes) provoked by the AITC challenge for the unexposed animals (3.1 (1.7-4.5)), those were increased significantly following both the 7-day (12.0 (6.8-17.2), P < 0.01) and the 14-day (12.0 (6.4-17.6), P < 0.01) TRAP exposure. The effect provoked by the citric acid challenge was more profound following the 14-day exposure (26.0 (19.5-32.5) vs 3.8 (1.5-6.0) for the control, P < 0.001). TRAP exposures enhanced spontaneous cough events, caused a significant increase of eosinophils and neutrophils in BALF and resulted in a dramatic eosinophilic infiltration in submucosal layer of trachea and bronchus, which can be inhibited significantly by dexamethasone treatment.Conclusions & Clinical Relevance: TRAP exposures induced cough hypersensitivity and non-allergic eosinophilic inflammation of airways in guinea-pigs. This study highlights the potential mechanisms of eosinophilia-related chronic cough that can be induced by traffic-related air pollution. K E Y W O R D Sairway inflammation, cough hypersensitivity, eosinophil, traffic-related air pollution

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“…The four most common background disorders for chronic coughs are asthma, eosinophilic bronchitis, chronic rhinosinusitis and oesophageal reflux disease (Chung & Pavord, 2008). Some patients cough excessively due to airway nerve hypersensitivity, without any known pathological complications (Buday, Kovacikova, Ruzinak, & Plevkova, 2017). Cough in chronic respiratory tract diseases is an unpleasant experience and may represent an exaggerated reflex.…”

mentioning

confidence: 99%

Cough as an adverse effect on inhalation pharmaceutical products

Chang

Kwok

Ghassabian

et al. 2020

British J Pharmacology

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Cough is an adverse effect that may hinder the delivery of drugs into the lungs. Chemical or mechanical stimulants activate the transient receptor potential in some airway afferent nerves (C-fibres or A-fibres) to trigger cough. Types of inhaler device and drug, dose, excipients and formulation characteristics, including pH, tonicity, aerosol output and particle size may trigger cough by stimulating the cough receptors. Release of inflammatory mediators may increase the sensitivity of the cough receptors to stimulants. The cough-provoking effect of aerosols is enhanced by bronchoconstriction in diseased airways and reduces drug deposition in the target pulmonary regions. In this article, we review the factors by which inhalation products may cause cough.

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TRPV4 antagonist GSK2193874 does not modulate cough response to osmotic stimuli

Cited by 23 publications

References 27 publications

Cough-provocation tests with hypertonic aerosols

Cough-provocation tests with hypertonic aerosols

Traffic‐related air pollution induces non‐allergic eosinophilic airway inflammation and cough hypersensitivity in guinea‐pigs

Cough as an adverse effect on inhalation pharmaceutical products

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