Molassiotis et al. Cough 2010, 6:9 http://www.coughjournal.com/content/6/1/9 Cough REVIEW Open Access Clinical expert guidelines for the management of cough in lung cancer: report of a UK task group on cough Alex Molassiotis1*, Jaclyn A Smith2, Mike I Bennett3, Fiona Blackhall4, David Taylor5, Burhan Zavery6, Amelie Harle4, Richard Booton7, Elaine M Rankin8, Mari Lloyd-Williams9, Alyn H Morice10 Abstract Background: Cough is a common and distressing symptom in lung cancer patients. The clinical management of cough in lung cancer patients is suboptimal with limited high quality research evidence available. The aim of the present paper is to present a clinical guideline developed in the UK through scrutiny of the literature and expert opinion, in order to aid decision making in clinicians and highlight good practice. Methods: Two systematic reviews, one focusing on the management of cough in respiratory illness and one Cochrane review specifically on cancer, were conducted. Also, data from reviews, phase II trials and case studies were synthesized. A panel of experts in the field was also convened in an expert consensus meeting to make sense of the data and make clinical propositions. Results: A pyramid of cough management was developed, starting with the treatment of reversible causes of cough/specific pathology. Initial cough management should focus on peripherally acting and intermittent treatment; more resistant symptoms require the addition of (or replacement by) centrally acting and continuous treatment. The pyramid for the symptomatic management starts from the simpler and most practical regimens (demulcents, simple linctus) to weak opioids to morphine and methadone before considering less well-researched and experimental approaches. Conclusion: The clinical guidelines presented aim to provide a sensible clinical approach to the management of cough in lung cancer. High quality research in this field is urgently required to provide more evidence-based recommendations. 1. Introduction little high quality evidence to guide practice. Much of Cough is a common symptom in about 23-37% of gen- the current practice on the symptomatic management of eral cancer patients and 47-86% of lung cancer patients cough in lung cancer is experiential and primarily is [1]. The first author’s data on 100 cancer patients geared around the use of oral opioids. Current guide- assessed using the Memorial Symptom Assessment lines on the management of cough are often broad and Scale from the beginning of cancer treatment to 3, 6 non-specific (suggesting difficulty in making any specific and 12 months showed a prevalence of 42.9%, 39.2%, recommendations) and either focus on non-cancer 35.1% and 36.1% respectively, similarly to the experience respiratory illnesses with different pathophysiology from of breathlessness, although less distressing than breath- cancer-related cough, or provide broad reviews of gener- lessness [2]; these numbers almost doubled in the lung ally poor quality studies [3-7]. Professional societies that cancer subgroup analysis. Despite such high prevalence, have developed guidelines (non-cancer) include the the management of cough remains suboptimal, with American College of Chest Physicians (ACCP) [3,8], the European Respiratory Society (ERS) [9] and the British Thoracic Society (BTS) [7]. * Correspondence: [email protected] 1School of Nursing, University of Manchester, UK Full list of author information is available at the end of the article © 2010 Molassiotis et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Molassiotis et al. Cough 2010, 6:9 Page 2 of 8 http://www.coughjournal.com/content/6/1/9 Rationale for the guidelines trials that were not part of the systematic reviews were With currently available information, clinicians have dif- also retrieved and summarized. The group members ficulty in making appropriate treatment choices, often reviewed the evidence and made recommendations that treating patients on a trial-and-error basis. This has reflected the evidence found combined with clinical been highlighted through discussions with many clini- experience in an attempt to provide a sensible approach cians. Our own work with lung cancer patient interviews to the clinician and guide practice in a field with mini- over time [10] has shown the distressing nature of mal evidence. cough and its significant impact on patients’ quality of life as well as the difficulty in obtaining relief from 2.3. Clinical consultation of the guidelines offered treatments. Our consultation with patient An assessment of the appropriateness, usability and research forums has also highlighted the management of clarity of the guidelines was carried out by international cough as an unmet need in lung cancer. For these rea- experts (N = 15), including 9 consultants in palliative sons, the development of clinical guidelines for the man- medicine, 4 in medical oncology and 2 specialist pallia- agement of cough in lung cancer was deemed necessary tive care nurses (independent prescribers). This was and timely. done through clinicians reading the report and recom- mendations, and completing a feedback form. A number 2. Process of guidelines development of items structured in a Likert-type format of 1 = 2.1. Formation of the Task Group strongly disagree to 5 = strongly agree were included. The Task Group was led by the Cancer Experiences The areas explored were: the rationale and need for the Research Collaborative (CECo) with invited experts guidelines (original score = 4.6); the need for the devel- from the Association for Palliative Medicine (APM). opment of the guidelines (= 4.8); completeness of litera- CECo (see http://www.ceco.org.uk) is a collaborative of ture search (= 4.3); the description of evidence (= 4.6); five UK universities and their clinical partners, funded the methods used to summarise and interpret the evi- in 2005 by the National Cancer Research Institute to dence (= 4.1); interpretation of the evidence presented develop critical mass, capacity and high quality research (= 4); clarity of the recommendations (= 3.7); agreement in supportive and palliative care. Besides its research with the recommendations made (= 4.1), and feeling objectives, the Collaborative also has a remit to have the comfortable having these guidelines applied in their hos- maximum positive impact on policy and practice. The pital (= 4). The likelihood of using these guidelines in APM (see http://www.palliative-medicine.org) is a pro- the reviewers’ own practice was explored with a single- fessional society aiming to provide a national and regio- item scale ranging from 1 = ‘not at all likely to use’ to nal network for palliative medicine doctors with a 10 = ‘very likely to use’, achieving a score of 8.1. After strong focus on developing and implementing educa- the feedback, the guidelines were modified primarily in tional material, and has strong links with the European relation to the dosages in some drugs, and the clarity Association for Palliative Care. and levels of drugs proposed in the cough pyramid (Fig- The Task Group consisted of experts that repre- ure 1). sented palliative medicine, medical/clinical oncology with focus in lung cancer, respiratory medicine, nur- 3. Review of the evidence sing, pharmacy, and supportive care. Experts had clini- 3.1. Pathophysiology and causes of cough cal, academic and research roles and three members of In healthy individuals coughing serves to protect the the group were also running cough clinics in the UK. airway from chemical irritants and foreign bodies. Members of the group have also significant research These stimuli provoke coughing by stimulation of publications in relation to cough, considered key afferent C fibres (chemoreceptors) and Aδ fibres experts in this (limited) field. The group met twice, (mechanoreceptors) in the airways, carried by the once to agree on the methodology to be used and vagus nerve. In disease states, excessive coughing can review the available evidence and once to make sense occur by excessive noxious stimulation of these affer- of this data and develop recommendations. entfibresand/orasaresultof sensitization of neurons involved in the cough reflex. In patients with lung can- 2.2. Evidence searching and selection cer, for example, tumour tissue in the central airways A literature review preceded the meetings over the pre- may cause mechanoreceptor stimulation directly or vious year, with two systematic reviews being underta- indirectly via obstruction and sputum accumulation. ken, one with a focus on cough and respiratory illnesses The inflammatory mediators associated with infection (other than cancer) [11] and a second Cochrane review distal to such an obstruction or mediators released by with a focus specifically in cancer [12]. Other publica- tumour tissue may further induce coughing by sensitiz- tions, including reviews, case study reports and phase II ing peripheral nerves. Molassiotis et al. Cough 2010, 6:9 Page 3 of 8 http://www.coughjournal.com/content/6/1/9 Figure 1 Treatment pyramid for the management of cough in patients with lung cancer.1(e.g. Benylin tickly coughs; Lemsip cough dry). 2 (e.g. Actifed dry coughs; Meltus dry coughs; Benylin cough & congestion; Benylin dry coughs; Day & Night Nurse-also