AIMS: We report on investigations exploring the P2X3-receptor antagonist filapixant's effect on taste perception and cough-reflex sensitivity and describe its pharmacokinetics, including its CYP3A4-interaction potential. METHODS: In a randomized, placebo-controlled, double-blind study, 3 × 12 healthy men (18-45 years) were assigned (3:1) to filapixant (20, 80 or 250 mg by mouth) or placebo twice daily over 2 weeks. A single dose of midazolam (1 mg), a CYP3A4 substrate, was administered with and without filapixant. Assessments included a taste-strips test, a taste questionnaire, cough challenge with adenosine triphosphate, adverse event reports and standard safety assessments. RESULTS: Taste disturbances were observed mainly in the 250-mg group: six of nine participants (67%) in this group reported hypo- or dysgeusia in the questionnaire; eight participants (89%) reported taste-related adverse events. Five participants (56%) had a decrease in overall taste-strips-test scores ≥2 points (point estimate -1.1 points, 90% confidence interval [-3.3; 1.1]). Cough counts increased with adenosine triphosphate concentration but without major differences between treatments. Filapixant exposure increased proportionally to dose. Co-administration of filapixant had no clinically relevant effect on midazolam pharmacokinetics. Area under the concentration-time curve ratios and 90% confidence intervals were within 80-125%. No serious or severe adverse events were reported. CONCLUSIONS: Overall, filapixant was safe and well tolerated, apart from mild, transient taste disturbances. Such disturbances occurred more frequently than expected based on (in vitro) receptor-selectivity data, suggesting that other factors than P2X3:P2X2/3 selectivity might also play an important role in this context. The cough-challenge test showed no clear treatment effect. Filapixant has no clinically relevant CYP3A4 interaction potential.
Importance: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Observational studies report that ß-blocker use may be associated with reduced risk of COPD exacerbations. However, a recent trial reported that metoprolol did not reduce COPD exacerbations and increased COPD exacerbations requiring hospital admission. Objective: To test whether bisoprolol decreased COPD exacerbations in people with COPD at high risk of exacerbations. Design, Setting, and Participants: The Bisoprolol in COPD Study (BICS) was a double-blind placebo-controlled randomized clinical trial conducted in 76 UK sites (45 primary care clinics and 31 secondary clinics). Patients with COPD who had at least moderate airflow obstruction on spirometry (ratio of forced expiratory volume in the first second of expiration [FEV1] to forced vital capacity <0.7; FEV1 <80% predicted) and at least 2 COPD exacerbations treated with oral corticosteroids, antibiotics, or both in the prior 12 months were enrolled from October 17, 2018, to May 31, 2022. Follow-up concluded on April 18, 2023. Interventions: Patients were randomly assigned to bisoprolol (n = 261) or placebo (n = 258). Bisoprolol was started at 1.25 mg orally daily and was titrated as tolerated during 4 sessions to a maximum dose of 5 mg/d, using a standardized protocol. Main Outcomes and Measures: The primary clinical outcome was the number of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both during the 1-year treatment period. Safety outcomes included serious adverse events and adverse reactions. Results: Although the trial planned to enroll 1574 patients, recruitment was suspended from March 16, 2020, to July 31, 2021, due to the COVID-19 pandemic. Two patients in each group were excluded postrandomization. Among the 515 patients (mean [SD] age, 68 [7.9] years; 274 men [53%]; mean FEV1, 50.1%), primary outcome data were available for 514 patients (99.8%) and 371 (72.0%) continued taking the study drug. The primary outcome of patient-reported COPD exacerbations treated with oral corticosteroids, antibiotics, or both was 526 in the bisoprolol group, with a mean exacerbation rate of 2.03/y, vs 513 exacerbations in the placebo group, with a mean exacerbation rate of 2.01/y. The adjusted incidence rate ratio was 0.97 (95% CI, 0.84-1.13; P = .72). Serious adverse events occurred in 37 of 255 patients in the bisoprolol group (14.5%) vs 36 of 251 in the placebo group (14.3%; relative risk, 1.01; 95% CI, 0.62-1.66; P = .96). Conclusions and Relevance: Among people with COPD at high risk of exacerbation, treatment with bisoprolol did not reduce the number of self-reported COPD exacerbations requiring treatment with oral corticosteroids, antibiotics, or both. Trial Registration: isrctn.org Identifier: ISRCTN10497306.
PURPOSE: Only limited studies have depicted the unique features and management of refractory chronic cough (RCC) and unexplained chronic cough (UCC). These led to the initiation of this study, which reported the demographic characteristics, manifestations, and long-term outcomes on a large series of consecutive RCC/UCC patients, providing a guideline-led real-world clinical experience. METHODS: Retrospective baseline information was obtained from Clinical Research Database (January 2016 to May 2021). At least 6 months after the last clinic visit, included subjects were prospectively followed up. RESULTS: Three hundred and sixty-nine RCC and UCC patients (199 females, 53.9%) were analyzed. The median cough duration was 24.0 (12.0-72.0) months. Laryngeal symptoms were reported in 95.9% of the patients. The common triggers for coughing were talking (74.9%), pungent odors (47.3%), eating (45.5%), and cold air (42.8%). RCC was considered in 38.2%, and the remainder of 228 patients had UCC, with an equal sex distribution (P = 0.66). Among the 141 RCCs, 90.8% (128) had refractory reflux cough, which was more responsive to current treatments (P < 0.01). Although most features and test results between RCC and UCC were similar, UCC was more commonly inappropriately treated (P < 0.01). Nineteen (7.7-41.1) months after the final clinic visit, 31.2% still coughed persistently, while 68.8% reported cough improvement or remission. RCC reported more favorable treatment outcomes (including cough improvement, control, and spontaneous remission) than UCC (P < 0.01). Coughs with long duration before the initial cough clinic visit (P < 0.01), frequent urinary incontinence (P < 0.01), and being sensitive to "talking" (P < 0.01) or "cold air" (P < 0.01) were less likely to be solved. CONCLUSIONS: The current treatments only improve cough symptoms in two-thirds of patients. Clinical indicators for treatment failure were those coughing for long duration and being sensitive to "talking" or "cold air."
Background: Current guidelines on the management of chronic cough do not provide recommendations for the operation of specialist cough clinics. The objective of the present study was to develop expert consensus on goals and standard procedures for specialist cough clinics. Methods: We undertook a modified Delphi process, whereby initial statements proposed by experts were categorised and presented back to panellists over two ranking rounds using an 11-point Likert scale to identify consensus. Results: An international panel of 57 experts from 19 countries participated, with consensus reached on 15 out of 16 statements, covering the aims, roles and standard procedures of specialist cough clinics. Panellists agreed that specialist cough clinics offer optimal care for patients with chronic cough. They also agreed that history taking should enquire as to cough triggers, cough severity rating scales should be routinely used, and a minimum of chest radiography, spirometry and measurements of type 2 inflammatory markers should be undertaken in newly referred patients. The importance of specialist cough clinics in promoting clinical research and cough specialty training was acknowledged. Variability in healthcare resources and clinical needs between geographical regions was noted. Conclusions: The Delphi exercise provides a platform and guidance for both established cough clinics and those in planning stages.
Background: Over-the-counter therapies, such as Vicks VapoRub, are frequently used in the management of upper respiratory tract infection symptoms. Of these, acute cough is the most bothersome; however, the mechanisms involved have not been fully elucidated. The temperature-sensitive transient receptor potential (TRP) channels, including TRPA1, TRPV1, TRPM8 and TRPV4, are potential candidates. TRPV4 is also thought to be involved in cough through the TRPV4-ATP-P2X3 pathway. Here, we hypothesise that Vicks VapoRub ingredients (VVRIs) modulate the TRP cough channels. Methods: Stably transfected HEK cells expressing TRP channels were challenged with VVRIs, individually or in combination, and the agonist and antagonist effects were measured using calcium signalling responses. In addition, rhinovirus serotype-16 (RV16)-infected A549 airway epithelial cells were pre-incubated with individual or combinations of VVRIs prior to hypotonic challenge and extracellular ATP release analysis. Results: Calcium signalling reconfirmed some previously defined activation of TRP channels by specific VVRIs. The combined VVRIs containing menthol, camphor and eucalyptus oil activated TRPV1, TRPV4, TRPM8 and untransfected wild-type HEK293 cells. However, pre-incubation with VVRIs did not significantly inhibit any of the channels compared with the standard agonist responses. Pre-incubation of RV16-infected A549 cells with individual or combined VVRIs, except menthol, resulted in a 0.45-0.55-fold reduction in total ATP release following hypotonic stimulation, compared with infected cells not treated with VVRIs. Conclusion: These findings suggest that some VVRIs may reduce symptoms associated with upper respiratory tract infection by modulating specific TRP receptors and by reducing RV16-induced ATP release.
Background: Refractory chronic cough (RCC) has a significant impact on patient's health-related quality of life and represents a challenge in clinical management. However, the optimal treatment for RCC remains controversial. This study aimed to investigate and compare the efficacy and safety of the current pharmacological therapeutic options for RCC. Methods: A systematic review was performed by searching PubMed, Web of Science, Embase, and Ovid databases from January 1, 2008 to March 1, 2023. All randomised control trials (RCTs) reporting outcomes of efficacy or/and safety were included in the Bayesian network meta-analysis. Here, we compared the effects on Leicester Cough Questionnaire (LCQ), Visual Analogue Scale (VAS), and objective cough frequency of patients with RCC. Besides, we also compared the incidence of adverse events (AEs) for analysis of safety. PROSPERO registration: CRD42022345940. Findings: 19 eligible RCTs included 3326 patients and 7 medication categories: P2X3 antagonist, GABA modulator, Transient Receptor Potential (TRP) modulator, NK-1 agonist, opioid analgesic, macrolide, and sodium cromoglicate. Compared with placebo, mean difference (MD) of LCQ and 24 h cough frequency for P2X3 antagonist relief were 1.637 (95% CI: 0.887-2.387) and -11.042 (P = 0.035). Compared with placebo, effect sizes (MD for LCQ and cough severity VAS) for GABA modulator were 1.347 (P = 0.003) and -7.843 (P = 0.003). In the network meta-analysis, gefapixant is the most effective treatment for patients with RCC (The Surface Under the Cumulative Ranking Curves (SUCRA) is 0.711 in LCQ, 0.983 in 24 h cough frequency, and 0.786 in cough severity VAS). Lesogaberan had better efficacy than placebo (SUCRA: 0.632 vs. 0.472) in 24 h cough frequency. Eliapixant and lesogaberan had better efficacy than placebo in cough severity VAS. However, TRP modulator had worse efficacy than placebo. In the meta-analysis of AEs, the present study found P2X3 antagonist had a significant correlation to AEs (RR: 1.129, 95% CI: 1.012-1.259), especially taste-related AEs (RR: 6.216, P < 0.05). Interpretation: In this network meta-analysis, P2X3 antagonist showing advantages in terms of efficacy is currently the most promising medication for treatment of RCC. GABA modulator also showed potential efficacy for RCC but with AEs of the central system. Nevertheless, the role of TRP modulator needed to be revisited. Further research is needed to determine the potential beneficiary population for optimizing the pharmacological management of chronic cough. Funding: National Natural Science Foundation of China (81870079), Guangdong Science and Technology Project (2021A050520012), Incubation Program of National Science Foundation for Distinguished Young Scholars (GMU2020-207).
Chronic cough (CC) is a common but poorly understood disease that has a negative impact on quality of life. For years, clinicians have been trying to find the underlying diagnosis and using existing disease models to describe the patients' illness. This presents a confusing picture of CC. Most patients with CC present with hypersensitivity of the cough reflex, which is characterised by laryngeal paraesthesia and an increased response to the tussive stimuli or an innocuous stimulus that would not trigger coughing in healthy people. Recently, it has been proposed that CC is a unique disease characterised by vagal hypersensitivity that projects to the central nervous system altering responsiveness. The evidence supports the hypothesis that CC is primarily a neurological disorder, consisting of different phenotypes.
BACKGROUND: Chronic cough is a burdensome condition characterized by persistent cough lasting longer than 8 weeks. Chronic cough can significantly affect quality of life, physical function and productivity, with many people troubled with a cough that lasts for months or even years. People with chronic cough commonly report a persistent urge to cough with frequent bouts of coughing triggered by innocuous stimuli, which has led to the concept of cough hypersensitivity. MAIN BODY: Both central and peripheral neural pathways regulate cough, and although mechanisms driving development of cough hypersensitivity are not fully known, sensitization of these neural pathways contributes to excessive cough triggering in cough hypersensitivity. Effective therapies that control chronic cough are currently lacking. Recent therapeutic development has focused on several ion channels and receptors involved in peripheral activation of cough (e.g., transient receptor potential channels, P2 × 3 receptors and voltage-gated sodium channels) or central cough processing (e.g., neurokinin-1 [NK-1] receptors and nicotinic acetylcholine receptors). CONCLUSION: These targeted therapies provide novel insights into mechanisms underlying cough hypersensitivity and may offer new treatment options for people with chronic cough. In this review, we explore preclinical and clinical studies that have improved our understanding of the mechanisms responsible for chronic cough and discuss the most promising targeted approaches to date, including trials of P2 × 3-receptor antagonists and NK-1-receptor antagonists.
Cough , Hypersensitivity , Humans , Cough/drug therapy , Quality of Life , Chronic Disease
Background: Chronic cough, defined as daily cough for at least 8â weeks, negatively affects quality of life and work productivity and increases healthcare resource utilisation. We aimed to determine the prevalence and burden of chronic cough in the UK. Methods: Study participants were general population respondents to the 2018 UK National Health and Wellness Survey (NHWS). Respondents completed survey questions relating to health, quality of life, work productivity and activity impairment, and use of healthcare resources. Prevalence estimates were projected to the UK population using post-stratification sampling weights to adjust for sampling bias. The population with chronic cough was matched 1:3 with a group without chronic cough, using propensity score matchingon age, sex and the modified Charlson Comorbidity Index. Results: Of 15 000 NHWS respondents, 715 reported chronic cough in the previous 12â months and 918 during their lifetime. Weighted to the UK adult population, the 12-month prevalence of chronic cough was 4.9% and lifetime prevalence was 6.2%. Prevalence of chronic cough was higher among older respondents and those with smoking histories. Chronic cough respondents experienced higher rates of severe anxiety and depression in the past 2â weeks than matched controls. Poor sleep quality and loss of work productivity were also observed. More chronic cough respondents visited a healthcare provider in the past 6â months than respondents without chronic cough with a mean of 5.8 and 3.7 visits per respondent, respectively. Conclusion: Adults with chronic cough report lower quality of life, reduced work productivity and greater healthcare resource utilisation than matched controls without chronic cough.
INTRODUCTION: The PAGANINI study evaluated the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with refractory chronic cough (RCC). METHODS: PAGANINI was a randomized, double-blind, parallel-group, placebo-controlled, multicenter, dose-finding, phase 2b study. Adults with RCC lasting ≥ 12 months and cough severity ≥ 40 mm on a visual analog scale at screening were enrolled. Participants were randomized 1:1:1:1 to twice-daily 25 mg, 75 mg, or 150 mg oral eliapixant or placebo for 12 weeks. The primary endpoint was change from baseline in 24-h cough count after 12 weeks of intervention. RESULTS: Overall, 310 participants were randomized to twice-daily eliapixant 25 mg (n = 75), 75 mg (n = 78), 150 mg (n = 80), or placebo (n = 77). A statistically significant dose-response signal with eliapixant was detected for the primary endpoint (all dose-response models, adjusted p < 0.1; one-sided). Adverse events (AEs) were reported in 39 (51%) participants with placebo and 43-51 (57-65%) participants receiving eliapixant. The most common AE was dysgeusia, occurring in 1% (n = 1) of the placebo group and 1-16% (n = 1-13) of the eliapixant groups in a dose-related manner. One case of a moderate drug-induced liver injury occurred in a participant receiving 150 mg twice-daily eliapixant. CONCLUSION: Eliapixant demonstrated efficacy and a favorable taste tolerability profile in RCC. However, a drug-induced liver injury contributed to intensified liver monitoring in clinical trials with eliapixant and discontinuation of the entire development program in all indications by Bayer AG. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04562155; registered September 18, 2020.
Carcinoma, Renal Cell , Kidney Neoplasms , Adult , Humans , Cough/drug therapy , Double-Blind Method , Treatment Outcome
Aim: Short-acting ß2-agonist (SABA) overuse adversely impacts asthma-related outcomes and the environment. The SABA rEductioN Through ImplemeNting Hull asthma guidELines (SENTINEL) programme aims to reduce SABA overuse through supported implementation of an adult asthma guideline, which advocates for a SABA-free maintenance and reliever therapy (MART)-preferred treatment where appropriate, across six primary care networks (PCNs) in the UK. We present findings on patient/disease characteristics, asthma prescribing patterns and exacerbation rates from the pilot PCN. Methods: Patients (aged ≥18â years, prescribed at least one inhaled therapy) and their prescribed asthma treatments were characterised using National Health Service data. Asthma treatments and exacerbations were analysed for three periods: 24â12â months pre-, 12â months pre- and 12â months post-SENTINEL implementation (November 2020âJanuary 2021). Results: Of the 2571 registered asthma patients, 33.6% (n=864) underwent an asthma review, of whom 44.7% (n=386) were transitioned to MART. Fewer patients were prescribed three or more SABA canisters per year post-implementation in the overall asthma population (45.4% and 46.2% during 24â12â months and 12â months pre-implementation, respectively, and 23.9% 12â months post-implementation), and in the two subgroups: 1) those who had an asthma review (74.5% and 83.6% during 24â12â months and 12â months pre-implementation, respectively, and 26.5% post-implementation); and 2) those transitioned to MART following a review (76.4% and 86.5% during 24â12â months and 12â months pre-implementation, respectively, and 16.3% post-implementation). A higher proportion of patients were exacerbation-free post-implementation in the overall asthma population and in the two subgroups. At least 71.5% of patients transitioned to MART were still prescribed MART 12â months post-implementation, of whom ≥86.7% were SABA-free. Conclusion: SENTINEL implementation led to reduced SABA prescribing, increased inhaled corticosteroid uptake and fewer asthma exacerbations. MART was considered appropriate for â¼50% of reviewed patients, with improved prescribing patterns sustained post-implementation.
Aim: The aim of this study was to systematically search and synthesise findings from peer-reviewed qualitative studies describing the experiences of those living with chronic cough. Methods: A systematic search was conducted to identify all studies that used qualitative methodology to report on the experiences of adults living with chronic cough. A thematic synthesis of the first-hand narratives was undertaken. Key themes in relation to personal perspectives and experiences of living with chronic cough were identified and grouped into analytical themes. Results: Six studies met the inclusion criteria. The thematic synthesis generated three analytical themes: 1) "It's just a cough"; 2) "Constant cough and constant worry"; and 3) "No light at the end of the tunnel", highlighting the biopsychosocial nature of chronic cough. The synthesis highlights chronic cough as a heterogeneous experience that may appear idiosyncratic, completely consuming the lives of those living with it. Conclusion: This is to our knowledge the first qualitative synthesis reporting on the perceptions and experiences of adults living with chronic cough. Our review draws attention to the paucity of literature that utilises qualitative methodology to explore the experience of living with chronic cough. We highlight the missing voice of people living with chronic cough in the contemporary literature. There is now a requirement for research exploring the narratives of those living with chronic cough, to gain an understanding of the condition beyond simple quantification.
Therapeutic antitussive effect of octreotide on intractable cough https://bit.ly/3mVMEc6.
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.
Antitussive Agents , Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Middle Aged , Antitussive Agents/adverse effects , Baclofen/therapeutic use , Chronic Disease , Clinical Protocols , Cohort Studies , Cough/drug therapy , Cough/etiology , Gabapentin/adverse effects , Neoplasm Recurrence, Local/drug therapy , Neurotransmitter Agents/therapeutic use , Retrospective Studies
BACKGROUND: P2X3 receptor antagonists seem to have a promising potential for treating patients with refractory chronic cough. In this double-blind, randomized, placebo-controlled study, we investigated the efficacy, safety, and tolerability of the novel selective P2X3 receptor antagonist filapixant (BAY1902607) in patients with refractory chronic cough. METHODS: Following a crossover design, 23 patients with refractory chronic cough (age: 60.4 ± 9.1 years) received ascending doses of filapixant in one period (20, 80, 150, and 250 mg, twice daily, 4-days-on/3-days-off) and placebo in the other. The primary efficacy endpoint was the 24-h cough frequency on Day 4 of each dosing step. Further, subjective cough severity and health-related quality of life were assessed. RESULTS: Filapixant at doses ≥ 80 mg significantly reduced cough frequency and severity and improved cough health-related quality of life. Reductions in 24-h cough frequency over placebo ranged from 17% (80 mg dose) to 37% (250 mg dose), reductions over baseline from 23% (80 mg) to 41% (250 mg) (placebo: 6%). Reductions in cough severity ratings on a 100-mm visual analog scale ranged from 8 mm (80 mg) to 21 mm (250 mg). No serious or severe adverse events or adverse events leading to discontinuation of treatment were reported. Taste-related adverse events occurred in 4%, 13%, 43%, and 57% of patients treated with filapixant 20, 80, 150, and 250 mg, respectively, and in 12% treated with placebo. CONCLUSIONS: Filapixant proved to be efficacious, safe, and-apart from the occurrence of taste disturbances, especially at higher dosages-well tolerated during the short therapeutic intervention. Clinical trial registration EudraCT, eudract.ema.europa.eu, 2018-000129-29; ClinicalTrials.gov, NCT03535168.
Cough , Purinergic P2X Receptor Antagonists , Humans , Middle Aged , Aged , Cough/chemically induced , Quality of Life , Chronic Disease , Double-Blind Method
BACKGROUND: Upper respiratory tract infections (URTIs) impact all age groups and have a significant economic and social burden on society, worldwide. Most URTIs are mild and self-limiting, but due to the wide range of possible causative agents, including Rhinovirus (hRV), Adenovirus, Respiratory Syncytial Virus (RSV), Coronavirus and Influenza, there is no single and effective treatment. Over-the-counter (OTC) remedies, including traditional medicines and those containing plant derived substances, help to alleviate symptoms including inflammation, pain, fever and cough. PURPOSE: This systematic review focuses on the role of the major plant derived substances in several OTC remedies used to treat cold symptoms, with a particular focus on the transient receptor potential (TRP) channels involved in pain and cough. METHODS: Literature searches were done using Pubmed and Web of Science, with no date limitations, using the principles of the PRISMA statement. The search terms used were 'TRP channel AND plant compound', 'cough AND plant compound', 'cough AND TRP channels AND plant compound', 'cough AND P2X3 AND plant compound' and 'P2X3 AND plant compound' where plant compound represents menthol or camphor or eucalyptus or turpentine or thymol. RESULTS: The literature reviewed showed that menthol activates TRPM8 and may inhibit respiratory reflexes reducing irritation and cough. Menthol has a bimodal action on TRPA1, but inhibition may have an analgesic effect. Eucalyptus also activates TRPM8 and inhibits TRPA1 whilst down regulating P2X3, aiding in the reduction of cough, pain and airway irritation. Camphor inhibits TRPA1 and the activation of TRPM8 may add to the effects of menthol. Activation of TRPV1 by camphor, may also have an analgesic effect. CONCLUSIONS: The literature suggests that these plant derived substances have multifaceted actions and can interact with the TRP 'cough' receptors. The plant derived substances used in cough and cold medicines have the potential to target multiple symptoms experienced during a cold.
TRPM Cation Channels , Transient Receptor Potential Channels , Humans , Menthol/pharmacology , Menthol/therapeutic use , Camphor/pharmacology , TRPA1 Cation Channel , Cough/drug therapy , Cough/etiology , Pain , Analgesics/pharmacology , Analgesics/therapeutic use
