Review Series: Palliation of dyspnea

Nonpharmacological interventions for managing respiratory symptoms in lung cancer

Janelle Yorke1, Alison Brettle1 and Alex Molassiotis2

Chronic Respiratory Disease 9(2) 117129 The Author(s) 2012 Reprints and permission: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1479972312441632 crd.sagepub.com

Abstract Patients with lung cancer experience significant symptom burden, particularly symptoms of a respiratory nature. Such symptom burden can be distressing for patients and negatively impact their functional status and quality of life. The aim of this review is to evaluate studies of nonpharmacological and noninvasive interventions for the management of respiratory symptoms experienced by patients with lung cancer. In total, 13 studies met the inclusion criteria for this review and included 1383 participants of which 1296 were lung cancer patients. The most frequently assessed and reported symptom was breathlessness (n 9 studies). Cough and haemoptysis were reported in one study. A variety of outcome measurement tools were used and a broad range of intervention strategies evaluated. Lack of consistency between studies impinged on the ability to combine studies. It is not possible to draw any firm conclusion as to the effectiveness of nonpharmacological interventions for the management of respiratory symptoms in lung cancer. Nonpharmacological interventions may well have an important role to play in the management of some of the respiratory symptoms (or combinations of respiratory symptoms), but more work of higher quality is necessary in the future. Keywords Lung cancer, complementary therapies, breathlessness, cough, nonpharmacological interventions

Introduction
Patients with lung cancer experience significant symptom burden, particularly symptoms of a respiratory nature. The symptom experience can vary widely among patients and generally is the result of the disease and its progression or its treatments.1 Respiratory symptoms, such as breathlessness, cough, wheeze, haemoptysis and hoarseness are reported by patients with lung cancer, occurring in 20% to 90% of patients.2 Such symptom burden can be distressing for patients and negatively impact their functional status and quality of life (QOL).35 There is limited work in the development and testing of nonpharmacological interventions for the management of respiratory symptoms. Much of this work concerns breathlessness, but little or no work exists in relation to other respiratory symptoms. Breathlessness is a complex subjective experience defined as an uncomfortable awareness or sensation of breathing.6

Breathlessness represents one of the most common and distressing symptoms in lung cancer.7 Patients with all stages of lung cancer, who report breathlessness, also experience a significantly lower QOL,8 and those with the most severe breathlessness experience more pain and anxiety.4,8,9 A longitudinal study of 105 patients with advanced lung cancer demonstrated that breathlessness increased overtime, most dramatically during the first 3 months, while QOL declined over the same

1 School of Nursing, Midwifery and Social Work, University of Salford, Manchester, UK 2 School of Nursing, Midwifery and Social Work, University of Manchester, Manchester, UK

Corresponding author: Alex Molassiotis, School of Nursing, Midwifery and Social Work, Jean McFarlane Building, University of Manchester, Oxford Road, Manchester M13 9LP Email: alex.molassiotis@manchester.ac.uk

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period.4 Optimal management of breathlessness requires a combination of pharmacological and nonpharmacological interventions.10 The evidence base for pharmacological interventions has been reported in several systematic reviews.10,11 These reviews indicate a limited evidence base for the use of opioids for symptom relief; benzodiazepines to relieve anxiety; and the use of oxygen. Pharmacological interventions alone often do not relieve breathlessness adequately and the use of drugs to treat breathlessness is sometimes limited as they can cause adverse effects and require careful titrating.10,12 As breathlessness is a subjective experience, nonpharmacological interventions as an adjunct to drug treatments offer promise for the management of this distressing symptom. Cough presents a significant burden for people with lung cancer and is reported to be present in 40% to 70% of patients with lung cancer at initial presentation and as the disease progresses.2 Cough may exacerbate breathlessness13,14 and has a profound effect on QOL, particularly its psychosocial aspects.5,15 In lung cancer, the aetiology for cough is multifactorial and can be the result of direct anatomic effects of the cancer (obstruction), indirect effects of cancer (pleural effusion or pneumonitis secondary to radiation or chemotherapy), or underlying chronic conditions (asthma, COPD and postnasal drip).16,17 There are few management options for cough in lung cancer that are evidence based.18,19 One of the oldest medications for the control of cough is codeine that suppresses the central nervous symptoms responsible for triggering cough.20 Other pharmacological treatments are largely based on the use of antitussive drugs (cough suppressants) opioids or nonopioids for which the evidence base is minimal or conflicting. A Cochrane review of interventions (pharmacological and nonpharmacological) for cough in cancer concluded that research in this area was limited with poor quality and significant methodological problems.18 The Cochrane review reported that a range of pharmacological treatments (e.g. codeine, morphine, dihydrocodeine, sodiumcromoglycate and butamirate citrate linctus cough syrup) showed some improvements in cough, although all studies had significant risk of bias. Molassiotis et al.18 also included studies that evaluated the efficacy of invasive treatments, such as brachytherapy and photodynamic therapy, and reported encouraging results. No studies that evaluated the effectiveness of nonpharmacological and noninvasive interventions for the management of cough in cancer were included in the review as no studies were identified.18 Interventions that encompass a

broad range of psychosocial, behavioural, educational and environmental strategies may provide a more comprehensive approach to ameliorating the effects of this distressing symptom. Other respiratory symptoms such as haemoptysis, hoarseness and wheeze are much less common than breathlessness and cough. At presentation, up to 20% of patients report mild haemoptysis,21 and approximately 9% of patients have reported haemoptysis in the last 8 weeks of life.22 While much less prevalent than breathlessness and cough, haemoptysis can be alarming for both patients and their families. Intrusive interventions target bronchial vessels since these vessels supply the airways and are under higher pressure than pulmonary arteries. At present, there are no clinical trials specifically evaluating the efficacy of these invasive interventions to treat haemoptysis in patients with lung cancer. Other, less common symptoms are also likely to cause distress, such as hoarseness and wheeze, and may also occur as a result of the cancer or underlying comorbidity such as asthma and COPD. In the context of lung cancer, it is not known whether nonpharmacological interventions have a role to play in ameliorating the distressing effects of these symptoms. Given the multitude of respiratory symptoms patients can experience, alleviating discomfort and symptom distress often requires several treatment modalities to reach an acceptable outcome. In addition, symptom incidence and distress levels may vary over time and lung cancer treatment, making their management challenging. Usually managed as isolated symptoms, they often occur simultaneously. It may be that interventions that include behavioural, psychosocial and/or educational strategies assist patients to better cope with distressing symptomology. The aim of this review is to evaluate studies of nonpharmacological and noninvasive interventions for the management of respiratory symptoms experienced by patients with lung cancer. We aimed to include studies that incorporated a broad range of interventions including psychosocial, behavioural, educational, complementary therapies and environmental/service delivery strategies.

Methods
Searches were conducted on a range of electronic databases, covering a range of perspectives. These included Medline (Ovid interface; biomedical), Psychinfo (Ovid interface; psychological), Amed (Ovid

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interface; complementary and allied health, Cinahl (EBSCO interface; nursing and allied health), Cochrane Library (Wiley; systematic reviews and randomised controlled trials (RCTs) in health care). A combination of thesaurus and free text terms were combined to maximise sensitivity for the following keywords including lung cancer, symptoms, psychological therapies and complementary therapies. No date or research methodology restrictions were applied. Studies were included in the review if they were a report of a RCT or quasi-experimental designs. Patients of either gender and any age with lung cancer at any stage, including primary and secondary malignancy, were included. If an article included a heterogeneous group, then the study was only included if greater than 70% of participants had a diagnosis of lung cancer. We included articles that reported one or more respiratory outcomes (including breathlessness, cough, haemoptysis, wheeze, or hoarseness) as a primary or secondary outcome. Such outcomes were required to be reported as a separate outcome, either on a symptom-specific questionnaire for example, a Visual Analogue Scale (VAS)23 or Numerical Rating Scale (NRS)24 or extracted from a questionnaire that contains symptom-specific items (e.g. Symptom Distress Scale (SDS)).25 Due to the low number of studies that reported single symptoms, except breathlessness, we extended our inclusion criteria to include studies that reported combined/overall symptom scores this included studies that only reported, for example, a total score for the SDS and Rotterdam Symptom Checklist.26

Description of included studies

In total, 13 studies2739 met the inclusion criteria for this review and included 1383 participants of which 1296 were lung cancer patients. Please see Table 1 for detailed information on the included studies. The most frequently assessed and reported symptom was breathlessness (n 9).2734,39 Cough was included as a single outcome measure in one study35 and haemoptysis was reported separately in the same study. No other respiratory symptoms related to lung cancer were reported as a single outcome measure in any included studies. Studies included in the review were categorised and reported in terms of respiratory symptomatology: (a) studies reporting breathlessness as a single outcome measure; (b) studies reporting cough as a single outcome measure; (c) studies reporting haemoptysis as a single outcome measure; and (d) studies that reported combined/overall symptom scores.

Breathlessness
Breathlessness was the primary outcome for six studies27,28,3032,39 and was a secondary outcome in three studies.29,33,35 This section presents details relating to the method of breathlessness assessment used in the review studies and types of interventions evaluated, where breathlessness was measured as a single symptom. Methods of breathlessness assessment. A variety of methods were used to assess breathlessness (see Table 2 for a description of the instruments used). Six studies used VAS23 and two studies used NRS.24 The scaling range used for the VAS and NRS measures was 010, except for Chan et al.29 who used 0100 and Connors et al. who did not specify a scaling range. The majority of studies measured breathlessness intensity on a VAS or NRS at best or worst breathlessness over the preceding 24-h period. In a feasibility RCT, Barton et al.27 used area under the curve analysis and concluded that the NRS measures of worst and average breathlessness over the past 24 h were the most useful assessments. The majority of studies that applied the VAS and NRS to assess the intensity of breathlessness also used the same scaling method to assess distress associated with breathlessness.27,28,3033 The European Organisation for Research and Treatment of Cancerlung cancer quality of life questionnaire (EORTC-LC13)41 is a multidimensional QOL instrument that contains three items relating to breathlessness. Moore et al. used the EORTC-LC13

Results
Searches resulted in 1289 records that were uploaded onto endnote, de-duplicated and filtered for relevance to the review question. A additional three studies were located by checking reference lists of relevant systematic reviews. This process resulted in 54 articles that were further scrutinised for relevance to this review. Studies were further excluded because they were reviews or opinion articles (n 15), case studies or descriptive studies (n 11). Other studies were excluded because the sample was heterogenous or respiratory symptoms were not grouped. Noncancer participants or cancer patients with mixed aetiology or respiratory symptoms were not included as an outcome measure (n 10). Further five studies were excluded because the intervention was not classified as nonpharmacological.

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Intervention Lung cancer (n 22) Breathlessness NRS; brief COPE; breathlessness distress; HADS Breathlessness VAS best and worse, and related distress Rotterdam Symptom Checklist Diagnostic groups Symptoms/outcomes assessed relevant to this review Results Lung cancer (n 119) High (3 sessions) vs. low (1 session) intensity training in breathing Nurse intervention breathlessness focus, muscle relaxation, psychosocial support vs. standard care Psychoeducational vs. usual care Lung cancer (n Lung cancer (n 169), only 15 completed protocol Lung cancer (n 20) 140) Physiotherapy teaching breathing control, relaxation, energy conservation Nurse intervention counselling, breathing retraining, relaxation, coping strategies vs. control (speak freely about breathlessness but no training or counselling) Sternal and L14 acupuncture points Primary or secondary lung cancer (n 20) Lung cancer (n 30) Breathlessness, anxiety, and relaxation on VAS Symptom cluster and separate breathlessness scores on VAS Breathlessness scores on VAS at worst and best; and associated distress Breathlessness and associated distress on VAS Specialist physiotherapy sessions Lung cancer (n Advanced lung cancer (n 203) Lung cancer (n 239) 166) Breathlessness and associated distress Rotterdam Symptom Checklist Symptom Distress Scale Specialist home nursing care vs. standard home care vs. clinic care Nurse-led follow-up vs. conventional medical follow-up Caregiver-assisted coping skills training vs. education/support including caregiver Structured nursing assessment EORTC QOL score and lung cancer module breathlessness, cough, haemoptysis FACT-L with breathlessness and cough subscales Lung cancer (n 48), newly diagnosed, need paper Symptom Distress Scale Pivot nurse in oncology Acupuncture vs. placebo Lung cancer (n 113) and breast cancer (n 77) Lung cancer 80%; breast 20% (n 47) Symptom Distress Scale no specific symptoms Breathlessness NRS

Table 1. Characteristics of included studies

Reference and country

Type of study

Barton et al.27 UK

Feasibility RCT

No effectiveness data: worst and average past 24 h most useful assessment Significant improvement in breathlessness best; b/ness distress; depression; physical symptoms

Bredin et al.28 UK

Multicentre RCT

Chan et al.29 Hong Kong Connors et al.30 UK

RCT

Cohort study

Significant improvement in symptom cluster and specific symptoms breathlessness High attrition, breathlessness improved but not statistically Significant improvements compared with the control in breathlessness at best (p < 0.02) and worst (p < 0.05), distress caused by breathlessness (p < 0.01)

Corner et al.31 UK

RCT

Filshie et al.32 UK

Open pilot pretestposttest

Hately et al.33 UK

Pretestposttest

Within group significant improvement in all symptoms at least up to 6 h post tx; maximal at 90 min Significant improvement (within sample) in all VAS scores, Rotterdam scores

McCorkle et al.34 USA

RCT

Moore et al.35 UK

RCT

Porter et al.36 USA

RCT

Sarna37 USA

RCT

RCT

Skrutkowski et al.38 Canada Vickers et al.39 USA

RCT

Significant difference in Symptom Distress Score Significantly improved breathlessness but not cough and haemoptysis at 3 months, none at 6 months Patient: significant improvements in functional well-being, symptoms; Caregiver: significant improvements in anxiety and self-efficacy Fatigue was the most severely distressing symptom; multivariate model chemotherapy and systematic nursing assessment were associated with less symptom distress over time SDS no significant difference between groups No effect 95% CI excludes the prespecified MCD of a 20% greater improvement in acupuncture group

EORTC: The European Organisation for Research and Treatment of Cancer; FACT-L: Functional Assessment of Cancer Treatment Lung cancer; MCD: Minimal clinical difference; NRS: Numerical Rating Scale; QOL: quality of life; RCT: randomised controlled trial; SDS: Symptom Distress Scale; VAS: Visual Analogue Scale.

Table 2. Instruments used to assess respiratory symptoms

Construct Unidimensional Unidimensional Unidimensional Unidimensional Unidimensional Unidimensional Unidimensional Past 24 h Not specified Not specified Past 24 h Variable Scaling range Content Recall period General comments

Measure

Review study

Visual Analogue Scale for breathlessness and distress23

Bredin et al.

28

Chan et al.29 Connors et al.30

Corner et al.31

Filshie et al.32 Current Current Past 24 hours

Hately et al.

33

Vickers et al.39

Intensity Distress Intensity Intensity Distress Intensity Distress Intensity Distress Intensity Distress Intensity

010 010 0100 Not specified Not specified 010 010 010 010 010 010 010

Best, worst, average Related to breathlessness Not specified Best, worst Not specified Best, worst, average Related to breathlessness Not clear Related to breathlessness Best, worst Not specified Average for 7 days

Numerical Rating Scale for breathlessness and distress24 Unidimensional 15-Item symptom list, provides a total score Degrees of distress One breathlessness item and one cough item Severity 010 Average, worst distress

Barton et al.27

Current: before and after 1 h treatment; average daily level Past 24 h; not specified Feeling lately

Symptom Distress Scale25

McCorkle et al.34

Feasibility study average and worst scores most sensitive Symptom-specific items not reported separately, only total scores measured

Sarna37 As above As above

15: 1 (breathe normally or seldom cough) to 5 (almost always have severe trouble breathing or persistence severe cough) As above As above

As above

Skrutkowski et al.38 As above As above As above

As above

As above

FACT-L40 Extent of experience

Porter et al.36

04: 0 (not at all) to 4 (very much) 14: 1 (not at all) to 4 (very much)

Past week

Symptom-specific items not reported separately, only total scores measured Symptom-specific items not reported separately, only total scores measured Symptom-specific items not reported separately Past week Symptom-specific items reported separately

EORTC-L41 Extent of experience

Moore et al.35

Multidimensional, quality-of-life measure Multidimensional, quality-of-life measure

Rotterdam Symptom Check List26 As above

Bredin et al.28 Multidimensional symptom distress includes 23 items As above Multiple symptom experience

04: 0 (not very much) to 4 (very much) As above

Two breathlessness items sort of breath and ease of breathing Three breathless items at rest, walking, climbing stairs; one cough item; one haemoptysis item One shortness of breath item As above

Past week

Hately et al.33

As above

Chronic Respiratory Questionnaire42

Connors et al.30 Multidimensional QOL measure

QOL experience

Dyspnoea subscale

Breathlessness item scored but recorded: total scores reported only Breathlessness item scored but recorded: total scores reported only Dyspnoea subscale reported separately

CI: confidence interval; FACT-L: Functional Assessment of Cancer Treatment Lung cancer; HADS: Hospital Anxiety and Depression Scale; MCD: Minimal clinical difference; QOL: quality of life; NRS: Numerical Rating Scale; VAS: Visual Analogue Scale.

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and reported separate scores for breathlessness. Likewise, the Chronic Respiratory Questionnaire,42 a QOL instrument for use in chronic respiratory diseases, was applied in Corner et al.s31 study, and a separate score for the dyspnoea subscale was reported in that study. Multisymptom scales, including the Functional Assessment of Cancer TreatmentLung cancer (FACT-L),40 SDS,25 and the Rotterdam Symptom Checklist,26 were also used in studies included in this review but separate scores for breathlessness were not provided (see Table 2). Breathlessness is a multidimensional experience and consists of different sensations with different intensities,10 yet no study included in this review applied a measure to reflect the entirety of this symptom. Description of interventions with breathlessness as a discrete symptom. A variety of interventions aimed at improving the patients experience of breathlessness were included in this review. Interventions for breathlessness were difficult to categorise as many of the interventions included more than one component, provided by various professionals and in different settings. Therefore, categories were grouped according to the main mode of treatment delivery and included (a) multimodal interventions with a nursing focus; (b) multimodal interventions with a physiotherapy or multiprofessional focus; and (c) acupuncture/acupressure. 1. Multimodal interventions with a nursing focus Three studies were included that evaluated interventions that consisted of a broad range of psychosocial, educational and behavioural strategies, included a specific measure of breathlessness, and were led by nurses.28,31,35 The intervention strategies used across these studies were reasonably similar, with each study including elements of relaxation techniques, counselling and anxiety management. The seminal studies by Corner et al.31 and Bredin et al.28 tested the combination of a nurse-led multimodal intervention that combined breathing and relaxation training, counselling and teaching coping and adaptive strategies. Both studies included the intensity of breathlessness as the primary outcome measured on a VAS, 010 scaling range. In Corners feasibility study, 34 participants with lung cancer were included of which 19 were randomized to the intervention and 15 to the control group.31 The intervention group attended weekly sessions with a nurse practitioner over 36 weeks. Breathlessness at rest,

at worst, and distress caused by breathlessness were reduced over time in the intervention group but not in the control group.31 The feasibility study was stopped early since the intervention group showed a clear benefit. The subsequent adequately powered trial28 included 119 participants of which 103 were included in the final analysis. The intervention was similar between the two studies; however, in Bredins study the intervention strategy was tailored to individual patients needs.28 This included detailed assessment of the meaning of breathlessness and factors that contribute or help to relief it. The intervention strategy also incorporated supportive measures for patients family members. After 8 weeks, the intervention group showed significant improvement in breathlessness at best but there was no significant improvement in breathlessness at worst or distress caused by breathlessness. Moore et al.35 examined the effects of a nurse-led follow-up service compared to conventional medical follow-up. The nurse-led intervention consisted of clinical assessment, access to the nursing clinics and communication with the general practitioner and primary care team. Participants randomized to the intervention were allocated to one of two clinical nurse specialists and were assessed monthly to identify signs of disease progression, symptoms warranting intervention, or serious complications. The nurse specialists provided information and support and coordinated input from other services. Breathlessness was measured41 using EORTC-LC13 and separate breathlessness scores were provided. Three months after study commencement, participants rated their breathlessness severity significantly less severe than participants in the conventional follow-up. There was no difference in breathlessness after 6 months but again there was a significant difference after 12 months. In addition, participants in the intervention group had significantly improved scores for emotional functioning and treatment satisfaction was significantly higher in the intervention group for both patients and carers. A nurse-delivered psychoeducational intervention was tested by Chan et al.29 in Hong Kong. The intervention group received a 40-min education session on symptom management and coaching in the use of progressive muscle relaxation delivered 1 week prior to commencing radiotherapy, and repeated after 3 weeks. The intervention was delivered by registered nurses who had attended a 2-day training session focusing on the educational package and practice of

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progressive muscle relaxation. Symptom data were collected prior to the intervention, 3 weeks, 6 weeks and 12 weeks postintervention. A total of 140 patients consented to participate in the study and the overall attrition rate at week 12 was 27%, with the sole reason being attributed to death. Breathlessness was one of the primary outcomes and was measured on a 100 mm VAS. The study aimed to assess the efficacy of the psychoeducational intervention on symptom clusters in lung disease breathlessness, fatigue and anxiety. We discuss the specific outcomes for breathlessness intensity measured on the VAS here. There was a significant improvement in breathlessness intensity scores between the 2 study groups at week 6 and week 12, although the effect sizes were small (partial Z2 0.04 and 0.043, respectively).43 2. Multimodal interventions with a physiotherapy or multiprofessional focus Two nonrandomised studies30,33 assessed physiotherapy-led multimodal interventions for patients with lung cancer. In a single-centre study, Hately et al.33 evaluated an intervention strategy for patients with lung cancer including physiotherapistled reviews in a specialist outpatient breathlessness clinic. Patients were monitored by the senior physiotherapists at 3 sessions, each lasted a maximum of 90 min, over a period of 46 weeks. The intervention consisted of a range of strategies, including breathing retraining, relaxation techniques, activity pacing and psychosocial support. Compared to other studies included in this review, the inclusion of a specific-activity pacing component was a unique feature of this intervention. Forty-five patients participated in the pretestposttest study, of whom 15 (33%) deteriorated or died before completion results refer to the 30 patients who were able to complete the entire study period. Patient-reported outcomes included a VAS for breathing at worst and at best in the preceding 24 h as well as the distress caused by breathlessness. There was a statistically significant improvement in all VAS breathlessness outcomes from pre- to postintervention. These results should be interpreted with caution due to the small and nonrandomised sample. Over a 4-year period, Connors et al.30 evaluated a physiotherapist-led breathlessness programme for patients with intrathoracic malignancies. The programme consisted of an individual 1-h session on 4 consecutive weeks and a review session 1 month later.

The sessions involved a broad range of strategies including breathing control, relaxation, anxiety management, energy conservation, goal setting and lifestyle readaption. This programme suffered high attrition 160 patients were recruited at baseline, but only 14 completed the programme. The investigators acknowledged that patient selection was the likely reason for the high dropout, since the sample was selected from the entire lung cancer population which included the frail and patients receiving cancer treatments. In contrast, similar studies included patients who had completed active cancer treatments.28,31 Connors et al.30 reported nonsignificant changes in breathlessness measured on a VAS for breathlessness at best and at worst, distress caused by breathlessness, and the dyspnoea subscale of Chronic Respiratory Questionnaire.42 The feasibility of high- versus low-intensity training in breathing techniques for breathless patients with lung cancer delivered by a specialist physiotherapists or lung cancer specialist nurse was tested by Barton et al.27 This was a single-centre, nonblinded RCT designed to assess recruitment and retention, best end point and variability of breathlessness scores to inform a subsequent powered study. The intervention consisted of training in diaphragmatic breathing, pacing, anxiety management and relaxation during an hour-long clinic session. The control group (low intensity) received the session once and the intervention group (high intensity) received subsequent sessions at weeks 2 and 3. Both groups also received written and DVD reinforcement material and a telephone call from their therapist a week after the last training session. Because this was a feasibility study, no primary or secondary outcome measures were assigned. Breathlessness was recorded on a NRS for worst, average and now, distress caused by breathlessness and coping with breathlessness. Over a 12-month period, 22 patients were randomised with a 40% dropout rate by week 4. From this study, it was concluded that the most useful NRS scores for breathlessness severity were for worst and average over past 24 h. 3. Acupuncture/Acupressure In this category, two studies were included one was an RCT39 and the other was an open pilot study with no randomisation exploring the safety and efficacy of acupuncture.32 Vickers et al.39 used a single session of acupuncture or placebo followed by true or placebo

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acupressure. True treatment points were chosen on the basis of traditionally used points for breathlessness. Placebo points were allocated in body areas away from true acupressure points. Following the single acupuncture session, participants were requested to apply pressure to semipermanent acupressure studs by making small circular movements with fingers the study protocol recommended 2 or 3 cycles per second for 1 or 2 min per point. The subjective sensation of breathlessness was assessed with a NRS (010) immediately before and after acupuncture treatment and daily for a week thereafter. In this study, 47 participants were randomized and 45 provided follow-up data. Participants in the acupuncture/acupressure and control group improved, but there were no differences between the groups at 7 days. In the second acupuncture study, 20 patients whose breathlessness was directly related to primary or secondary malignancy underwent a single acupuncture session using sternal and L14 acupressure points.32 Breathlessness and anxiety were rated by patients using pre and post VADS (- 10) treatment. There was a significant improvement in VAS scores for breathlessness and anxiety at least up to 6-h postacupuncture, which were maximal at 90 min. A reduction in respiratory rate was also reported, which was sustained for 90 min postacupuncture.

There was no study that identified the reported outcome measures for less common respiratory symptoms in lung cancer, such as wheeze and hoarseness.

Trials with combined/overall symptom scores

Four studies applied an instrument that assessed a range of symptoms and associated distress and reported total scores only, that is, no specific symptom either measured by a single item or subscale was provided.34,3638 In this section, we present these studies because each of the instruments used contain at least one item that represents the experience of breathlessness, cough, or haemoptysis. None of these instruments record experience of less common respiratory symptoms of hoarseness and wheeze. The SDS25 was used in an RCT to test the effects of three home care treatment regimens on the psychological well-being of patients with lung cancer.34 The three treatment groups included standard home care; specialised oncology home care; and an office care group who received standard care by the physician. The specialised oncology intervention was delivered by specialised cancer nurses. The SDS measures the patients perceived level of distress in response to 13 symptoms, including breathlessness, cough and haemoptysis.25 A total of 166 patients were randomised and 78 completed 4 interview points and were included in the final analysis at 12 weeks. There was a significant improvement in symptom distress in the two nursing home programmes compared to the office care group. Sarna37 tested the effectiveness of structured nursing assessment of symptom distress in patients with advanced lung cancer compared to usual care. Both groups (N 48) completed the SDS25 every month for a 6-month period. In a multivariate model, chemotherapy and systematic nursing assessment were associated with less symptom distress over time. Skrutkowski et al.38 conducted an RCT to test the impact of a pivot nurse in oncology on symptom distress experienced by patients with lung cancer (n 113) or breast cancer (n 77). The intervention consisted of an experienced palliative care nurse who had received additional training in symptom management. The pivot nurse conducted an in-depth assessment of the patients symptom burden, family and support situation, provided training for symptom management, additional support and initiated follow-up telephone calls. No significant difference in SDS scores between the two groups was found.

Cough
There was no study identified that reported cough as the primary outcome measure. Only one study reported a specific cough outcome. In an RCT, Moore et al.35 applied the EORTC-LC13 which41 includes one item that refers to the frequency of cough in the past week. Responses for this single item were reported 3, 6 and 12 months following either nurseled follow-up or conventional medical follow-up. There was no significant improvement in the single cough item in the nurse-led follow-up group compared to conventional group at any of the three postrandomisation follow-up points.

Haemoptysis
There was no study identified that reported haemoptysis as the primary outcome measure. As with cough, Moore et al.35 provided the only measure of haemoptysis. The EORTC-L13 contains41 one item that assesses how often participants coughed up blood in the past week. In that study, the scores for haemoptysis at each data collection point were zero.

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The efficacy of a caregiver-assisted coping skills training was tested in an RCT involving 233 patients with lung cancer and their caregivers.36 Two conditions were tested in this study: caregiver-assisted coping skills training and an education/support condition. The caregiver training condition included training on symptom management where the caregivers role was described as that of a coach, with the goal of helping the patient learn and apply coping skills. The second condition included the provision of information regarding lung cancer and its treatment. Both patients and caregivers were involved in session for both conditions. The FACT-LC13 was used to assess symptoms40 from the patients perspective. The FACT-LC13 consists of items assessing shortness of breath and coughing. Patients in both treatment conditions showed improvements in the FACT-LC13 scores. Exploratory analyses suggested that the caregiving-coping intervention was more beneficial to patients with stage II and III cancers/caregivers, whereas the education/ support intervention was more beneficial to patients with stage I cancer/caregivers.

Discussion
This review of the effectiveness of nonpharmacological interventions for improving the experience of respiratory symptoms in patients with lung cancer found that interventions have largely focused on breathlessness and reflect a broad range of strategies. Given the multitude of respiratory symptoms patients with lung cancer can experience, alleviating symptom burden often requires several treatment modalities. Thirteen studies were included in this review although only one of these assessed cough and haemoptysis as distinct symptoms.

Measurement issues
Breathlessness is the most commonly reported respiratory symptom in patients with lung cancer.7 There is no gold standard measure currently available that has been validated to capture this multifaceted construct.44 In this review, the VAS and NRS were mostly used to measure breathlessness. It has been suggested that, in the absence of a gold standard all-encompassing measure for breathlessness, these unidimensional, single-item scales be used for the assessment of breathlessness in palliative care44 and advanced disease.10 There are limitations to their use. Both VAS and NRS scales have two anchors that are unique to each individual, making comparison

between people difficult.10,45 There are no apparent standard principles to regulate their consistent use: they have been adapted to measure different aspects of breathlessness, such as uncomfortable breathing, severity of breathlessness, intensity of breathlessness, best, worst, average and so on as well as difference in scaling ranges (e.g. 010 or 0100), and different recall period (e.g. now, today, or past 24-hours). This makes comparisons between studies problematic. In our review, it was not possible to combine the results from individual studies in any meaningful way to obtain an overall effect size for studies that evaluated similar interventions and included a VAS or NRS for breathlessness assessment. Because breathlessness is highly correlated with anxiety and distress, some authors applied a VAS to capture distress associated with breathlessness.27,28,3033 Studies that reported breathlessness as a single item extracted from of a list of symptoms (e.g. SDS25) are also limited to the quantification of symptom frequency and intensity only. There is evidence that breathless patients use a variety of descriptors to describe the experience of breathlessness and that these descriptors represent sensory quality and affective dimensions of breathlessness. In this review, no study included a unified measure of breathlessness that reflects its multidimensionality. The Dyspnoea-12 is a recently developed instrument46 that captures the sensory quality physical and emotional dimensions of breathlessness. It consists of 12 items, each ranging from 0 none to 3 severe, 7 items measure the patients physical perceptions of breathlessness and 5 items measure affect. It has been reported as a valid and reliable measure of breathlessness in patients with cardiac46 and respiratory conditions,4749 but it is yet to be validated for use in lung cancer. In this review, no study included a specific instrument to measure cough, haemoptysis and other less common respiratory symptoms. Since cough is frequently reported in the lung cancer population,7 its inclusion as a specific outcome measure in studies designed to assist patients to better cope with distressing symptomology warrants greater attention. Recently, a cough scale has been developed for use with lung cancer patients and could be used as an outcome for such trials, focusing on cough.50 Given the broad range of strategies applied in the interventions included in this review, it is likely that any resilience and coping mechanisms adopted by study participants are likely to influence patients perceptions of the

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burden of multiple symptoms and not just breathlessness. One study35 did report a separate score for cough and haemoptysis extracted40 from the EORTC-LC13. This practice is not ideal because the instrument was not designed to provide individual symptom scores but a combined score for the lung cancer module. Other studies reported total scores that incorporate a variety of symptoms including the SDS25 and Rotterdam Symptom Checklist.26 Such lists are useful for providing overall scores of symptom burden, although it is difficult to discern the full experience and impact of prominent symptomatology, notably breathlessness and cough, with such lists. Studies involving patients with lung cancer suffer from high attrition. Limiting participant research burden plays a key role in successful study recruitment and retention. Introducing a battery of questionnaires for every possible symptom, both respiratory and otherwise, is not a viable option. This presents a challenge for lung cancer researchers to strike a balance between adequately capturing patient-related outcomes and patient burden. The choice of the most appropriate symptoms to include as specific study outcomes and the instruments used to capture these depend on the focus on the intervention and desired outcomes. It would appear that at the least, breathlessness and cough warrant inclusion as specific outcome measures, but it is equally important that the multidimensionality of these symptoms is captured. It is likely that the broad range of strategies used in the interventions included in this review will have greatest impact on affect and ability to cope with distressing symptoms rather than severity only. As noted by Bausewein et al.,10 studies to date have largely focused on the management of symptoms rather their assessment. To gauge the benefits of interventions that require significant health care resources and commitment from patients and their families, measurement tools that reflect the experience of symptoms in lung cancer, and are sensitive enough to detect change in response to interventions need to be applied.

Interventions
The interventions evaluated in this review covered a broad range of strategies. The variability and inconsistent use of interventions for respiratory symptoms are also evident in clinical practice, as shown in a UK survey of respiratory management practices.51 Since the focus of this review was to evaluate

nonpharmacological interventions for respiratory symptoms in lung cancer, we categorised studies according to symptoms: breathlessness, cough and haemoptysis. As evidenced in this review, to date breathlessness has been the area of focus for research in the area of nonpharmacological interventions. We elected to further categorise these studies according to the mode of delivery. The majority of these studies included a multimodal intervention that was delivered by nurses.28,29,31,35 Taking account of sample size, dropout rate, outcome measures and repeatability of interventions, feasible interventions emerge from a few nurse-led therapies.28,29,35 The interventions evaluated in these three studies had some common foundations including a focus on breathlessness management, psychological support and an element of patient education. However, key difference also exists in relation to the extent that interventions were tailored to the needs of individual patients, context of comparison groups and functional state of patients at recruitment. Additionally, Bredin et al.28 and Chan et al.29 measured breathlessness on a VAS but used different anchor descriptors and different scaling ranges, and Moore et al. extracted single scores for breathlessness, cough and haemoptysis from items located on the FACT-LC.42 Based on these results, no definitive conclusion for the effect of nurse-led multimodal interventions could be made. Two studies reflected the interventions led by physiotherapist but these were nonrandomised.30,33 Similar to the nurse-led studies, these interventions included a broad range of strategies. It is not possible to draw any firm conclusions from these studies due to the weak methodological approaches used, the small sample size included in Hately et al.33 study, and the remarkably high dropout rate experienced by Connors et al.30 where 160 patients were recruited at baseline yet only 14 completed the programme. Explanations for the high dropout rate are provided by the authors, including broad inclusion criteria and subsequent fragility of participants and many were receiving cancer treatments. This study is important because it highlights important considerations when developing study protocols for interventional studies including patients with lung cancer. The nonstatistical result drawn from these studies is likely to reflect inherent methodological flaws as opposed to the mechanism of intervention delivery by physiotherapists. Complementary and alternative medicine use has become increasingly popular throughout the Western world, as patients seek supplemental strategies to

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medical care.52 We located two small studies that evaluated the effect of acupuncture in a nonrandomised study32 and a single acupuncture session followed by acupressure in an RCT.39 Although Filshie et al.32 describe a significant within-group improvement in breathlessness up to 6 h postintervention, the lack of a control group limits the applicability of the results. Vickers et al.39 found no difference in reported breathlessness between acupuncture and placebo groups. The timing of assessment was also different in the two approaches described, and it may be that acupuncture has only short-lived effects. In the context of management of respiratory symptoms for people with lung cancer, no recommendations for acupuncture can be made. To our surprise, only one study,35 a nurse-led multimodal intervention, assessed cough and haemoptysis. No difference in cough experience was found between the intervention and control groups. Haemoptysis was the single symptom in that study, which no patients reported and the pre- and postintervention scores were zero. It is difficult to gauge the true meaning of these results since the symptoms were assessed as part of the EORTC41 instrument. Due to the lack of studies that included specific respiratory symptoms, we elected to review studies that only included a total score from symptom lists. Three studies measured symptoms on the SDS to evaluate the efficacy of a nurse-led intervention.34,37,38 Although the same outcome measure was used in these studies, the intervention strategies and comparison groups were varied. Positive results were reported in two of these studies,34,37 but it was not possible to combine studies due to the differences between the studies. The FACT-LC41 was used to assess the effect of providing caregivers of people with lung cancer specific training in coping skills. The positive outcomes reported for the caregiver-assisted coping skills training group provide promise for the involvement of caregivers in nonpharmacological interventions. Because these studies did not include any outcome measures for single symptoms, it is not possible to assess the relative effect of these interventions.

nonpharmacological interventions to help address this need has been reviewed in this article. The majority of studies refer to breathlessness or a list of multiple symptoms. The interventions included in this review mostly included a broad range of strategies. Based on these facts, it is not possible to draw any firm conclusion as to the effectiveness of nonpharmacological interventions for the management of respiratory symptoms in lung cancer. Nonpharmacological interventions may well have an important role to play in the management of some of the respiratory symptoms (or combinations of respiratory symptoms), but more work of higher quality is necessary in the future. Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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