ArticleBMJ open2015
Can variability in the effect of opioids on refractory breathlessness be explained by genetic factors?
Article in BMJ open, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Systematic review of the literature on the occurrence and characteristics of dyspnea in oncology patients.Critical reviews in oncology/hematology · 2023Pooled it
- Fentanyl or morphine for persistent dyspnoea in COPD: a multicentre randomised crossover trial.The European respiratory journal · 2026Trial
- Trial
- Associations Between Preoperative Shortness of Breath and Potassium Channels Gene Variations in Women With Breast Cancer.Biological research for nursing · 2025Article
- Perturbations in inflammatory pathways are associated with shortness of breath profiles in oncology patients receiving chemotherapy.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Article
- Opioids in Treatment of Refractory Dyspnea in Chronic Obstructive Pulmonary Disease: Yes, No or Maybe.Journal of personalized medicine · 2024Review
- Common and distinct risk factors that influence more severe and distressing shortness of breath profiles in oncology outpatients.Cancer medicine · 2024Article
- Higher Lifetime Stress and Symptom Burden Contribute to the Occurrence of Shortness of Breath.Seminars in oncology nursing · 2023Article
- Relationship of Postoperative Pain and PONV after Minimally Invasive Surgery with the Serotonin Concentrations and Receptors' Gene Polymorphisms.Journal of personalized medicine · 2021Article
- Unanswered questions and future direction in the management of terminal breathlessness in patients with cancer.ESMO open · 2020Review
- Lack of Efficacy: When Opioids Do Not Achieve Analgesia from the Beginning of Treatment in Cancer Patients.Cancer management and research · 2019Article
- Cardiac arrhythmia and neuroexcitability gene variants in resected brain tissue from patients with sudden unexpected death in epilepsy (SUDEP).NPJ genomic medicine · 2018Article
- Patient-Controlled Therapy with Intravenous Oxycodone in Breathlessness due to Advanced Cancer: A Case Report.Indian journal of palliative careArticle
- A Preliminary Prospective Study on the Association of Polymorphisms inCancer control : journal of the Moffitt Cancer CenterArticle
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesOpioids modulate the perception of breathlessness with a considerable variation in response, with poor correlation between the required opioid dose and symptom severity. The objective of this hypothesis-generating, secondary analysis was to identify candidate single nucleotide polymorphisms (SNP) from those associated with opioid receptors, signalling or pain modulation to identify any related to intensity of breathlessness while on opioids. This can help to inform prospective studies and potentially lead to better tailoring of opioid therapy for refractory breathlessness.
setting17 hospice/palliative care services (tertiary services) in 11 European countries.
participants2294 people over 18 years of age on regular opioids for pain related to cancer or its treatment. PRIMARY OUTCOME MEASURES: The relationship between morphine dose, breathlessness intensity (European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire; EORTCQLQC30 question 8) and 112 candidate SNPs from 25 genes (n=588). SECONDARY OUTCOME MEASURES: The same measures for people on oxycodone (n=402) or fentanyl (n=429).
resultsSNPs not in Hardy-Weinberg equilibrium or with allele frequencies (<5%) were removed. Univariate associations between each SNP and breathlessness intensity were determined with Benjamini-Hochberg false discovery rate set at 20%. Multivariable ordinal logistic regression, clustering over country and adjusting for available confounders, was conducted with remaining SNPs. For univariate morphine associations, 1 variant on the 5-hydroxytryptamine type 3B (HTR3B) gene, and 4 on the β-2-arrestin gene (ARRB2) were associated with more intense breathlessness. 1 SNP remained significant in the multivariable model: people with rs7103572 SNP (HTR3B gene; present in 8.4% of the population) were three times more likely to have more intense breathlessness (OR 2.86; 95% CIs 1.46 to 5.62; p=0.002). No associations were seen with fentanyl nor with oxycodone.
conclusionsThis large, exploratory study identified 1 biologically plausible SNP that warrants further study in the response of breathlessness to morphine therapy.
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