Treatment of chronic cough: P2X3 receptor antagonists and beyond

Sykes, Dominic L.; Zhang, Mengru; Morice, Alyn H.

doi:10.1016/j.pharmthera.2022.108166

Cited by 14 publications

(53 citation statements)

References 128 publications

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“…Gefapixant has been confirmed for its antitussive efficacy and has been approved for clinical use in some countries. 7 , 28 , 29 Hopefully, it will be the first licenced agent for CC. However, its higher selectivity for P2X2/3 heterotrimers over P2X3 homotrimers leaves taste disturbance as a common adverse effect.…”

Section: Discussionmentioning

confidence: 99%

Antitussive efficacy of the current treatment protocol for refractory chronic cough: our real-world experience in a retrospective cohort study

Zhang

Morice

et al. 2023

Ther Adv Respir Dis

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Background: The management of refractory chronic cough (RCC) is a great challenge. Neuromodulators have long been used for RCC with imperfect efficacy. Objectives: We summarized the outcomes of the current treatments used at our specialist cough clinic, which provides a guideline-led service and real-world experience for the future management of RCC. Design: This is a single-centre retrospective observational cohort study. Methods: Consecutive RCC patients (the first clinic visit between January 2016 and May 2021) were included into this observational cohort study. Medical records in the Chronic Cough Clinical Research Database were fully reviewed using uniform criteria. The included subjects were followed-up for at least 6 months after the final clinic visit via instant messages with the link to self-scaled cough-associated questionnaires. Results: Overall, 369 RCC patients were analysed with a median age of 46.6 years and a cough duration of 24.0 months. A total of 10 different treatments were offered. However, 96.2% of patients had been prescribed at least one neuromodulator. One-third of patients had alternative treatments prescribed given the poor response to the initial therapy and 71.3% favourably responded to at least one of the treatments. Gabapentin, deanxit, and baclofen had comparable therapeutic efficacy (56.0%, 56.0%, and 62.5% respectively; p = 0.88) and overall incidences of adverse effects (28.3%, 22.0%, and 32.3% respectively; p = 0.76). However, 19.1 (7.7–41.8) months after the last clinic visit, 65.0% reported improvement (24.9%) or control of their cough (40.1%); 3.8% reported a spontaneous remission and 31.2% still had a severe cough. Both HARQ ( n = 97; p < 0.001) and LCQ ( n = 58; p < 0.001) demonstrated marked improvement. Conclusion: Trying different neuromodulators is a pragmatic strategy for RCC, which helped around two-thirds of patients. Relapse is common on withdrawal or reduction of dosage. Novel medication for RCC is an urgent clinical need. Plain language summary This is the first report that fully represented a guideline-led treatment protocol for refractory chronic cough (RCC) based on a large series of patients, which evaluated the short- and long-term effects of the currently available treatments for RCC. We found that the therapeutic trial of different neuromodulators is a pragmatic strategy, which helped around two-thirds of patients. Gabapentin, deanxit (flupentixol/melitracen), and baclofen had similar therapeutic outcomes. This study may offer real-world experience for the future management of RCC.

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Section: Discussionmentioning

confidence: 99%

Antitussive efficacy of the current treatment protocol for refractory chronic cough: our real-world experience in a retrospective cohort study

Zhang

Morice

et al. 2023

Ther Adv Respir Dis

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“…Similarly, why cough presents as an early symptom in many CANVAS patients is equally perplexing. In RCC, epithelial-derived and other inflammatory mediators, notably including adenosine triphosphate (ATP), may be important for the development of vagal hypersensitivity [68,69]. However, there is no evidence that pulmonary inflammation exists in CANVAS.…”

Section: Why Do Canvas Patients Have Chronic Cough?mentioning

confidence: 99%

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome: a neurogenic cough prototype

Guilleminault,

Mazzone,

Chazelas

et al. 2024

ERJ Open Res

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Chronic cough is a frequent disorder that is defined by a cough of more than 8 weeks duration. Despite extensive investigation, some patients exhibit no aetiology and others do not respond to specific treatments directed against apparent causes of cough. Such patients are identified as having unexplained or refractory chronic cough. Recently, a high proportion of patients with chronic cough in the context of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) was highlighted. CANVAS is a rare neurological disorder with a biallelic variation in the replication factor C subunit 1 (RFC1) gene corresponding mostly to an intronic AAGGG repeat expansion. Chronic cough in patients with CANVAS shares similar characteristics with cough hypersensitivity syndrome. The high prevalence of chronic cough in CANVAS gives the opportunity to better understand the neurogenic mechanism of chronic cough. In this review, we will describe the characteristics and mechanisms of CANVAS. We will also address the potential mechanisms responsible for chronic cough in CANVAS. Finally, we will address chronic cough management in the context of CANVAS.

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“…Capsaicin and histamine are notable cough inducers with transient receptor potential vanilloid (TRPV) receptor involvement [25], but they are not regarded as cough hypersensitivity inducers. ATP receptor antagonists have emerged as novel treatments of CC [30]. Targeting inflammatory mediators through medicines, such as the non-steroidal anti-inflammatory drug (NSAID) indomethacin, may offer therapeutic relief for cough hypersensitivity through anti-prostanoid effects.…”

Section: Pathophysiology Of Coughmentioning

confidence: 99%

Chronic Bronchitis in Children and Adults: Definitions, Pathophysiology, Prevalence, Risk Factors, and Consequences

Zhang,

Wurzel,

Perret

et al. 2024

JCM

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The complex nature of chronic bronchitis (CB) and changing definitions have contributed to challenges in understanding its aetiology and burden. In children, CB is characterised by persistent airway inflammation often linked to bacterial infections and is therefore termed “protracted bacterial bronchitis” (PBB). Longitudinal studies suggest that CB in childhood persists into adulthood in a subgroup. It can also be associated with future chronic respiratory diseases including asthma, bronchiectasis, and chronic obstructive pulmonary disease (COPD). Adult CB is traditionally associated with smoking, occupational exposures, and lower socioeconomic status. The interplay between risk factors, childhood CB, adult CB, and other chronic respiratory diseases is intricate, requiring comprehensive longitudinal studies for a clearer understanding of the natural history of CB across the lifespan. Such longitudinal studies have been scarce to date given the logistic challenges of maintaining them over time. In this review, we summarise current evidence on the evolution of the definitions, pathophysiology, risk factors, and consequences of childhood and adulthood chronic bronchitis.

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Treatment of chronic cough: P2X3 receptor antagonists and beyond

Cited by 14 publications

References 128 publications

Antitussive efficacy of the current treatment protocol for refractory chronic cough: our real-world experience in a retrospective cohort study

Antitussive efficacy of the current treatment protocol for refractory chronic cough: our real-world experience in a retrospective cohort study

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome: a neurogenic cough prototype

Chronic Bronchitis in Children and Adults: Definitions, Pathophysiology, Prevalence, Risk Factors, and Consequences

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