Opiate Therapy in Chronic Cough

Morice, Alyn H.; Menon, M.; Mulrennan, Siobhan A.; Everett, Caroline F.; Wright, Caroline; Jackson, Jennifer; Thompson, Rachel

doi:10.1164/rccm.200607-892oc

Cited by 280 publications

(179 citation statements)

References 28 publications

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“…More than one primary outcome. Baseline imbalance across groups for cough duration-longer for SPT + Placebo group.Morice et al, 2007 [88]Randomized double-blind placebo-controlled crossover trial275 mg twice daily slow-release morphine sulfate or matching placebo for 4 weeks of treatment. An open-label extension of the study was done in a subgroup of patients using 10 mg twice daily for 3 months.Primary efficacy outcome was cough QOL measured by the LCQ.…”

Section: Resultsmentioning

confidence: 99%

“…In a placebo-controlled randomized crossover study, Morice et al [88] investigated the treatment of refractory CC with the opiate morphine sulfate compared to placebo. Cough was reported to be productive in 16 of 27 (59.2%) patients.…”

Section: Resultsmentioning

confidence: 99%

“…The distribution of response seemed to segregate into responders and nonresponders (shown graphically by the author [88]). Response to treatment occurred rapidly, with maximum benefit being achieved by Day 5 in those who responded.…”

Section: Resultsmentioning

confidence: 99%

“…In the gabapentin [89] and morphine [88], RCTs reviewed earlier there was also no change in cough reflex sensitivity assessed with capsaicin suggesting a central mechanism of action. Conversely in a guinea pig study [118], memantine was found to significantly inhibit capsaicin-induced cough suggesting that the memantine site of action was peripheral.…”

Section: Resultsmentioning

confidence: 99%

“…This analysis included the the Jeyakumar et al (Amitriptyline) study [86], the Morice et al (morphine sulfate) study [88], the Ryan et al (Gabapentin) study [89], and the Vertigan et al (Pregabalin + Speech Pathology) study [90]. As the Jeyakumar et al study used a different measure of cough QOL to the other studies, we converted continuous outcome data into Standardized Mean Difference (SMDs) and presented these with 95% CIs.…”

Section: Methodsmentioning

confidence: 99%

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An update and systematic review on drug therapies for the treatment of refractory chronic cough

Ryan

Vertigan

Birring

2018

Expert Opinion on Pharmacotherapy

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Introduction: Chronic Cough (CC) is common and often associated with significant comorbidity and decreased quality of life. In up to 50% of cases, the cough is refractory despite extensive investigation and treatment trials. It is likely that the key abnormality in refractory CC is dysfunctional, hypersensitive sensory nerves, similar to conditions such as laryngeal hypersensitivity and neuropathic pain.Areas covered: The aim of this systematic review is to assess drug therapies for refractory CC. The authors review the current management of CC and provide discussion of the similarities between neuropathic pain and refractory CC. They review repurposed and new pharmacological treatments. Several meta-analyses were performed to compare the efficacy of treatments where possible.Expert opinion: Repurposed pain medications such as gabapentin and pregabalin reduce the frequency of cough and improve quality of life. Along with speech pathology, they are important and alternate treatments for refractory CC. However, more treatments are needed and the P2X3 ion channel receptor antagonists show the most promise. With a better understanding of neuronal activation and sensitisation and their signal processing in the brain, improved animal models of cough, and the use of validated cough measurement tools, more effective treatments will develop.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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An update and systematic review on drug therapies for the treatment of refractory chronic cough

Ryan

Vertigan

Birring

2018

Expert Opinion on Pharmacotherapy

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Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough

Kum,

Patel,

Diab

et al. 2023

JAMA

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ImportanceGefapixant represents an emerging therapy for patients with refractory or unexplained chronic cough.ObjectiveTo evaluate the efficacy and tolerability of gefapixant for the treatment of adults with refractory or unexplained chronic cough.Data SourcesMEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science from November 2014 to July 2023.Study SelectionTwo reviewers independently screened for parallel and crossover randomized clinical trials (RCTs) that compared, in patients with refractory or unexplained chronic cough, either gefapixant with placebo, or 2 or more doses of gefapixant with or without placebo.Data Extraction and SynthesisTwo reviewers independently extracted data. A frequentist random-effects dose-response meta-analysis or pairwise meta-analysis was used for each outcome. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to rate the certainty in whether patients would perceive the effects as important (greater than the minimal important difference [MID]) or small (less than the MID).Main Outcomes and MeasuresCough frequency (measured using the VitaloJAK cough monitor; MID, 20%), cough severity (measured using the 100-mm visual analog scale [VAS]; higher score is worse; MID, 30 mm), cough-specific quality of life (measured using the Leicester Cough Questionnaire [LCQ]; score range, 3 [maximal impairment] to 21 [no impairment]; MID, 1.3 points), treatment-related adverse events, adverse events leading to discontinuation, and taste-related adverse events.ResultsNine RCTs including 2980 patients were included in the primary analysis. Compared with placebo, gefapixant (45 mg twice daily) had small effects on awake cough frequency (17.6% reduction [95% CI, 10.6%-24.0%], moderate certainty), cough severity on the 100-mm VAS (mean difference, −6.2 mm [95% CI, −4.1 to −8.4]; high certainty), and cough-specific quality of life on the LCQ (mean difference, 1.0 points [95% CI, 0.7-1.4]; moderate certainty). Compared with placebo, gefapixant (45 mg twice daily) probably caused an important increase in treatment-related adverse events (32 more per 100 patients [95% CI, 13-64 more], moderate certainty) and taste-related adverse events (32 more per 100 patients [95% CI, 22-46 more], high certainty). High-certainty evidence suggests that gefapixant (15 mg twice daily) had small effects on taste-related adverse events (6 more per 100 patients [95% CI, 5-8 more]).Conclusions and RelevanceCompared with placebo, gefapixant (45 mg orally twice daily) led to modest improvements in cough frequency, cough severity, and cough-specific quality of life but increased taste-related adverse events.

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Interstitial Lung Disease

Maher

2024

JAMA

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ImportanceInterstitial lung disease (ILD) consists of a group of pulmonary disorders characterized by inflammation and/or fibrosis of the lung parenchyma associated with progressive dyspnea that frequently results in end-stage respiratory failure. In the US, ILD affects approximately 650 000 people and causes approximately 25 000 to 30 000 deaths per year.ObservationsThe most common forms of ILD are idiopathic pulmonary fibrosis (IPF), which accounts for approximately one-third of all cases of ILD, hypersensitivity pneumonitis, accounting for 15% of ILD cases, and connective tissue disease (CTD), accounting for 25% of ILD cases. ILD typically presents with dyspnea on exertion. Approximately 30% of patients with ILD report cough. Thoracic computed tomography is approximately 91% sensitive and 71% specific for diagnosing subtypes of ILDs such as IPF. Physiologic assessment provides important prognostic information. A 5% decline in forced vital capacity (FVC) over 12 months is associated with an approximately 2-fold increase in mortality compared with no change in FVC. Antifibrotic therapy with nintedanib or pirfenidone slows annual FVC decline by approximately 44% to 57% in individuals with IPF, scleroderma associated ILD, and in those with progressive pulmonary fibrosis of any cause. For connective tissue disease–associated ILD, immunomodulatory therapy, such as tocilizumab, rituximab, and mycophenolate mofetil, may slow decline or even improve FVC at 12-month follow-up. Structured exercise therapy reduces symptoms and improves 6-minute walk test distance in individuals with dyspnea. Oxygen reduces symptoms and improves quality of life in individuals with ILD who desaturate below 88% on a 6-minute walk test. Lung transplant may improve symptoms and resolve respiratory failure in patients with end-stage ILD. After lung transplant, patients with ILD have a median survival of 5.2 to 6.7 years compared with a median survival of less than 2 years in patients with advanced ILD who do not undergo lung transplant. Up to 85% of individuals with end-stage fibrotic ILD develop pulmonary hypertension. In these patients, treatment with inhaled treprostinil improves walking distance and respiratory symptoms.Conclusions and RelevanceInterstitial lung disease typically presents with dyspnea on exertion and can progress to respiratory failure. First-line therapy includes nintedanib or pirfenidone for IPF and mycophenolate mofetil for ILD due to connective tissue disease. Lung transplant should be considered for patients with advanced ILD. In patients with ILD, exercise training improves 6-minute walk test distance and quality of life.

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Opiate Therapy in Chronic Cough

Abstract: Morphine sulfate is an effective antitussive in intractable chronic cough at the doses of 5 to 10 mg twice daily.

Cited by 280 publications

References 28 publications

An update and systematic review on drug therapies for the treatment of refractory chronic cough

An update and systematic review on drug therapies for the treatment of refractory chronic cough

Efficacy and Tolerability of Gefapixant for Treatment of Refractory or Unexplained Chronic Cough

Interstitial Lung Disease

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