Breathlessness is common in advanced disease and can have a devastating impact on patients and carers. Research on the management of breathlessness is challenging. There are relatively few studies, and many studies are limited by inadequate power or design. This paper represents a consensus statement of the National Cancer Research Institute Palliative Care Breathlessness Subgroup. The aims of this paper are to facilitate the design of adequately powered multi-centre interventional studies in breathlessness, to suggest a standardised, rational approach to breathlessness research and to aid future ‘between study’ comparisons. Discussion of the physiology of breathlessness is included.
1 Dudgeon DJ Kristjanson L Sloan JA Lertzman M Clement K . Dyspnea in cancer patients: prevalence and associated factors. J Pain Symptom Manage2001; 21(2): 95–102.
2.
2 Heyse-Moore LH Ross V Mullee MA . How much of a problem is dyspnoea in advanced cancer? Palliat Med1991; 5: 20–26.
3.
3 Nordgren L Sorensen S . Symptoms experienced in the last six months of life in patients with end-stage heart failure. Eur J Cardiovasc Nurs2003; 2: 213–217.
4.
4 Rennard S Decramer M Calverley PM Pride NB Soriano JB Vermeire PA . Impact of COPD in North America and Europe in 2000: subjects' perspective of Confronting COPD International Survey. Eur Respir J2002; 20: 799–805.
5.
5 De Vries J Kessels BL Drent M . Quality of life of idiopathic pulmonary fibrosis patients. Eur Respir J2001; 17: 954–961.
6.
6 Murtagh FEM Addington-Hall J Higginson IJ . The prevalence of symptoms in end-stage renal disease: a systematic review. Adv Chronic Kidney Dis2007; 14: 82–99.
7.
7 American Thoracic Society. Dyspnea: mechanisms, assessment, and management: a consensus statement. Am J Respir Crit Care Med1999; 159: 321–340.
8.
8 Booth S Silvester S Todd C . Breathlessness in cancer and chronic obstructive pulmonary disease: Using a qualitative approach to describe the experience of patients and carers. Palliat Support Care2003; 1: 337–344.
9.
9 Booth S Moosavi S Higginson I . The etiology and management of intractable breathlessness in patients with advanced cancer: a systematic review of pharmacological therapy. Nat Clin Pract Oncol2008; 5: 90–100.
10.
10 Roberts DK Thorne SE Pearson C . The experience of dyspnea in late-stage cancer. Patients' and nurses' perspectives. Cancer Nurs1993; 16: 310–320.
11.
11 Stroemgren AS Groenvold M Pedersen L Olsen AK Spile M Sjogren P . Does the medical record cover the symptoms experienced by cancer patients receiving palliative care? A comparison of the record and patient self-rating. J Pain Symptom Manage2002; 21: 189–196.
12.
12 Booth S . Improving research methodology in breathlessness: a meeting convened by the MRC. Palliat Med2006; 20: 219–220.
13.
13 Jennings AL Davies AN Higgins JPT Broadley K . Opioids for the palliation of breathlessness in terminal illness. Cochrane Database of Systematic Reviews 2001, issue 3, Art. No. CD002066. DOI: 10.1002/14651858.CD002066.
14.
14 Guz A . Brain, breathing and breathlessness. Respir Physiol1997; 109: 197–204.
15.
15 O’Donnell D Banzett R Carrieri-Kohlman V Casaburi R Davenport P Gandevia S . Pathophysiology of dyspnea in chronic obstructive pulmonary disease: a roundtable. Proc Am Thorac Soc2007; 4: 145–168.
16.
16 Killian K Campbell M . Dyspnea. In: C Roussos , (ed). The Thorax.New York: Marcel Dekker, 1995. p. 1709–1747.
17.
17 Manning HL Schwartzstein RM . Pathophysiology of dyspnea. N Engl J Med1995; 333: 1547–1553.
18.
18 Killian K Gandevia S Summers E Campbell E . Effect of increased lung volume on perception of breathlessness, effort, and tension. J Appl Physiol1984; 57: 686–691.
19.
19 Polkey M . Muscle metabolism and exercise tolerance in COPD. Chest2002; 121(5 Suppl): 131S–135S.
20.
20 Adams L Lane R Shea S Cockcroft A Guz A . Breathlessness during different forms of ventilatory stimulation: a study of mechanisms in normal subjects and respiratory patients. Clin Sci (Lond)1985; 69: 663–672.
21.
21 Campbell EJ Howell JB . The sensation of breathlessness. Br Med Bull1963; 19: 36–40.
22.
22 Shea S Banzett R . Respiratory sensations and their role in the control of breathing. In: L Adams A Guz , (eds). Respiratory sensation.New York: Dekker; 1995. p. 923–957.
23.
23 Evans KC Banzett RB Adams L McKay L Frackowiak RSJ Corfield DR . BOLD fMRI identifies limbic, paralimbic, and cerebellar activation during air hunger. J Neurophysiol2002; 88: 1500–1511.
24.
24 Parsons LM Egan G Liotti M Brannan S Denton D Shade R . Neuroimaging evidence implicating cerebellum in the experience of hypercapnia and hunger for air. Proc Natl Acad Sci U S A2001; 98: 2041–2046.
25.
25 von Leupoldt A Dahme B . Cortical substrates for the perception of dyspnea. Chest2005; 128: 345–354.
26.
26 von Leupoldt A Sommer T Kegat S Baumann HJ Klose H Dahme B . The unpleasantness of perceived dyspnea is processed in the anterior insula and amygdala. Am J Respir Crit Care Med2008; 177: 1026–1032.
27.
27 Kendall M Harris F Boyd K Sheikh A Murray S Brown D . Key challenges and ways forward in researching the “good death”: qualitative in-depth interview and focus group study. BMJ2007; 334: 521–526.
28.
28 Riley J Ross J . Research into care at the end of life. Lancet2005; 365: 735–737.
29.
29 Addington-Hall J . Research sensitivities to palliative care patients. Eur J Cancer Care2002; 11: 220–224.
30.
30 Ewing G Rogers M Barclay S McCabe J Martin A Todd C . Recruiting patients into a primary care based study of palliative care: why is it so difficult?Palliat Med2004; 18: 452–459.
31.
31 Bakitas M Lyons K Dixon J Ahles T . Palliative care program effectiveness research: developing rigor in sampling design, conduct, and reporting. J Pain Symptom Manage2006; 31: 270–284.
32.
32 Jordhoy M Kaasa S Fayers P Ovreness T Underland G Ahlner-Elmqvist M . Challenges in palliative care research; recruitment, attrition and compliance: experience from a randomized controlled trial. Palliat Med1999; 13: 299–310.
33.
33 Steinhauser K Clipp E Hays J Olsen M Arnold R Christakis N . Identifying, recruiting, and retaining seriously-ill patients and their caregivers in longitudinal research. Palliat Med2006; 20: 745–754.
34.
34 Cook A Finlay A Butler-Keating R . Recruiting into palliative care trials: lessons learnt from a feasibility study. Palliat Med2002; 16: 163–165.
35.
35 Henderson M Addington-Hall JM Hotopf M . The willingness of palliative care patients to participate in research. J Pain Symptom Manage2005; 29: 116–118.
36.
36 Emanuel E Fairclough D Wolfe P Emanuel L . Talking with terminally ill patients and their caregivers about death, dying, and bereavement: is it stressful? Is it helpful?Arch Intern Med2004; 164: 1999–2004.
37.
37 Takesaka J Crowley R Casarett D . What is the risk of distress in palliative care survey research?J Pain Symptom Manage2004; 28: 593–598.
38.
38 Ross C Cornbleet M . Attitudes of patients and staff to research in a specialist palliative care unit. Palliat Med2003; 17: 491–497.
39.
39 Seamark D Gilbert J Lawrence C Williams S . Are post-bereavement research interviews distressing to carers? Lessons learned from palliative care research. Palliat Med2000; 14: 55–56.
40.
40 Davies E Hall S Clarke C Bannon M Hopkins A . Do research interviews cause distress or interfere in management? Experience from a study of cancer patients. J R Coll Physicians Lond1998; 32: 406–411.
41.
41 Terry W Olson L Ravenscroft P Wilss L Boulton-Lewis G . Hospice patients' views on research in palliative care. Int Med J2006; 36: 406–413.
42.
42 Perkins P Barclay S Booth S . What are patients' priorities for palliative care research? Focus group study. Palliat Med2007; 21: 219–225.
43.
43 Stroemgren AS Sjogren P Goldschmidt D Peterson MA Pedersen L Hoermann L . Longitudinal study of palliative care: patient-evaluated outcome and impact of attrition. Cancer2005; 103: 1745–1755.
44.
44 Tang ST McCorkle R . Appropriate time frames for data collection in quality of life research among cancer patients at the end of life. Qual Life Res2002; 11: 145–155.
45.
45 Rinck GC van den Bos GA Kleijnen J de Haes HJ Schade E Veenhof CH . Methodologic issues in effectiveness research on palliative cancer care: a systematic review. J Clin Oncol1997; 15: 1697–1707.
46.
46 Kirkham S Abel J . Placebo-controlled trials in palliative care: the argument against. Palliat Med1997; 11: 489–492.
47.
47 Abernethy A Currow D Frith P Fazekas B McHugh A Bui C . Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea. BMJ2003; 327: 523–528.
48.
49.
49 Craig P Dieppe P Macintyre S Michie S Nazareth I Petticrew M . Developing and evaluating complex interventions: the new Medical Research Council guidance. BMJ2008; 337: a1655.
50.
50 Richardson W Wilson M Nishikawa J Hayward R . The well-built clinical question: a key to evidence-based decisions [editorial]. ACP Journal Club1995; 123: A12–A13.
51.
51 Brown P Brunnhuber K Chalkidou K Chalmers I Clarke M Fenton M . Suggested format for research recommendations on the effects of treatments. BMJ2006; 333: 804–806.
52.
52 Altman DG Schulz KF Moher D Egger M Davidoff F Elbourne D . The revised CONSORT statement for reporting randomized trials: explanation and elaboration. Ann Intern Med2001; 134: 663–694.
53.
53 Zwarenstein M Treweek S Gagnier JJ Altman DG Tunis S Haynes B . Improving the reporting of pragmatic trials: an extension of the CONSORT statement. BMJ2008; 337: a2390.
54.
54 Williams SJ Bury MR . Impairment, disability and handicap in chronic respiratory illness. Soc Sci Med1989; 29: 609–616.
55.
56.
56 Hardie GE Janson S Gold WM Carrieri-Kohlman V Boushey HA . Ethnic differences: word descriptors used by African-American and white asthma patients during induced bronchoconstriction. Chest2000; 117: 935–943.
57.
57 Charlson M Szatrowski TP Peterson J Gold J . Validation of a Combined Comorbidity Index. J Clin Epidemiol1994; 47: 1245–1251.
58.
58 Heyse-Moore LH . On dyspnoea in advanced cancer [DM]. Southampton University; 1993.
59.
59 Bestall JC Paul EA Garrod R Garnham R Jones PW Wedzicha JA . Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax1999; 54: 581–586.
60.
60 Medical Research Council. Questionnaire on Respiratory Symptoms.London: Publications Group, Medical Research Council; 1986.
61.
61 Fairburn AJ Wood CH Fletcher CM . Variability in answers to a questionnaire on respiratory symptoms. Br J Prev Soc Med1959; 13: 175–193.
62.
62 Fletcher CM Elmes PC Fairbairn AS Wood CH . The significance of respiratory symptoms and the diagnosis of chronic bronchitis in a working population. Br Med J1959; 2: 257–266.
63.
63 Karnofsky D Abelmann W Craver L Burchenal J . The use of nitrogen mustard in the palliative treatment of cancer. Cancer1948; 1: 634–656.
64.
64 Abernethy A Shelby-James T Fazekas B Woods D Currow D . The Australia-modified Karnofsky Performance Status (AKPS) Scale: a revised scale for contemporary palliative care clinical practice.BMC Palliat Care2005; 4: 7.
65.
65 Simon PM Schwartzstein RM . Distinguishable sensations of breathlessness induced in normal volunteers. Am Rev Respir Dis1989; 140: 1021–1027.
66.
66 Simon PM Schwartzstein RM Weiss JW Fencl V Teghtsoonian M Weinberger SE . Distinguishable types of dyspnea in patients with shortness of breath. Am Rev Respir Dis1990; 142: 1009–1014.
67.
67 Tanaka K Akechi T Okuyama T Nishiwaki Y Uchitomi Y . Development and validation of the Cancer Dyspnoea Scale: A multidimensional, brief, self-rating scale. Br J Cancer2000; 82: 800–805.
68.
68 Parshall MB . Psychometric characteristics of dyspnea descriptor ratings in emergency department patients with exacerbated chronic obstructive pulmonary disease. Res Nurs Health2002; 25: 331–344.
69.
69 Parshall MB Welsh JD Brockopp DY Heiser RM Schooler MP Cassidy KB . Reliability and validity of dyspnea sensory quality descriptors in heart failure patients treated in an emergency department. Heart Lung2001; 30: 57–65.
70.
70 Gift AG Narsavage G . Validity of the numeric rating scale as a measure of dyspnea. Am J Crit Care1998; 7: 200–204.
71.
71 Wilcock A Crosby V Clarke D Tattersfield A . Repeatability of breathlessness measurements in cancer patients. Thorax1999; 54: 375.
72.
72 Borg G . A category scale with ratio properties for intermodal and intervindividual comparisons. In: HG Geissler T Petzoldt , (eds). Psychophysical judgements and the process of perception.Berlin: Deutscher Verlag; 1982.
73.
73 Eakin EG Sassi-Dambron EE Ries AL Kaplan RL . Reliability and validity of dyspnoea measures in patients with obstructive lung disease. Int J Behav Med1995; 2: 118–134.
74.
74 Powers J Bennett SJ . Measurement of dyspnea in patients treated with mechanical ventilation. Am J Crit Care1999; 8: 254–261.
75.
75 Guyatt GH Berman LB Townsend M Pugsley SO Chambers LW . A measure of quality of life for clinical trials in chronic lung disease. Thorax1987; 42: 773–778.
76.
76 The EuroQol Group. EuroQol: A new facility for the measurement of health related quality of life. Health Policy1990; 16: 199–208.
77.
77 Cella DF Bonomi AE Lloyd SR Tulsky DS Kaplan E Bonomi P . Reliability and validity of the Functional Assessment of Cancer Therapy - Lung (FACT-L) quality of life instrument. Lung Cancer1995; 12: 199–220.
78.
78 Groenvold M Petersen MA Aaronson NK Arraras JI Blazeby JM Bottomley A . The development of the EORTC QLQ-C15-PAL: a shortened questionnaire for cancer patients in palliative care. Eur J Cancer2006; 42: 55–64.
79.
79 Bergman B Aaronson NK Ahmedzai S Kaasa S Sullivan M . The EORTC QLQ-LC13: a modular supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC Study Group on Quality of Life. Eur J Cancer1994; 30A: 635–642.
80.
80 Booth S Farquhar M Gysels M Bausewein C Higginson I . The impact of a breathlessness intervention service (BIS) on the lives of patients with intractable dyspnea: A qualitative phase 1 study. Palliat Support Care2006; 4: 287–293.
81.
81 Booth S Adams L . The shuttle walking test: a reproducible method for evaluating the impact of shortness of breath on functional capacity in patients with advanced cancer. Thorax2001; 56: 146–150.
82.
82 Wilcock A Crosby V Clarke D Corcoran R Tattersfield A . Reading numbers aloud: a measure of the limiting effect of breathlessness in patients with cancer. Thorax1999; 54: 1099–1103.
83.
83 Congleton J Muers MF . The incidence of airflow obstruction in bronchial carcinoma, its relation to breathlessness, and response to bronchodilator therapy. Respir Med1995; 89: 291–296.
84.
84 Dudgeon DJ Lertzman M . Dyspnea in the advanced cancer patient. J Pain Symptom Manage1998; 16: 212–219.
85.
85 Oken MM Creech RH Tormey DC Horton J Davis TE McFadden ET . Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol1982; 5: 649–655.
86.
86 Skevington SM Pilaar M Routh D Macleod RD . On the language of breathlessness. Psychol Health1997; 12: 677–689.
87.
87 Wilcock A Crosby V Hughes A Fielding K Corcoran R Tattersfield AE . Descriptors of breathlessness in patients with cancer and other cardiorespiratory diseases. J Pain Symptom Manage2002; 23: 182–189.
88.
88 Henoch I Bergman B Gaston-Johansson F . Validation of a Swedish version of the Cancer Dyspnea Scale. J Pain Symptom Manage2006; 31: 353–361.
89.
89 Campbell M Fitzpatrick R Haines A Kinmonth A Sandercock P Spiegelhalter D . Framework for design and evaluation of complex interventions to improve health. BMJ2000; 321: 694–696.
90.
90 Booth S Kelly MJ Cox NP Adams L Guz A . Does oxygen help dyspnea in patients with cancer? Am J Respir Crit Care Med1996; 153: 1515–1518.
91.
91 Uronis H Currow D McCrory D Samsa G Abernethy A . Oxygen for relief of dyspnoea in mildly- or non-hypoxaemic patients with cancer: a systematic review and meta-analysis. Br J Cancer2008; 98: 294–299.
92.
92 Bredin M Corner J Krishnasamy M Plant H Bailey C A’Hern R . Multicentre randomised controlled trial of nursing intervention for breathlessness in patients with lung cancer. BMJ1999; 318: 901–904.
93.
93 Hately J Laurence V Scott A Baker R Thomas P . Breathlessness clinics within specialist palliative care settings can improve the quality of life and functional capacity of patients with lung cancer. Palliat Med2003; 17: 410–417.
94.
94 Streiner DL Norman GR . Health measurement scales.3rd ed.New York: Oxford University Press; 2003.
95.
95 Borg G . Perceived exertion as an indicator of somatic stress. Scand J Rehabil Med1970; 2: 92–98.
96.
96 Martinez JA Straccia L Sobrani E Silva GA Vianna EO Filho JT . Dyspnea scales in the assessment of illiterate patients with chronic obstructive pulmonary disease. Am J Med Sci2000; 320: 240–243.
97.
97 Lacasse Y Wong E Guyatt GH . A systematic overview of the measurement properties of the chronic respiratory questionnaire. Can Respir J1997; 4: 131–139.
98.
98 Williams JE Singh SJ Sewell L Guyatt GH Morgan MD . Development of a self-reported Chronic Respiratory Questionnaire (CRQ-SR). Thorax2001; 56: 954–959.
99.
99 Williams JE Singh SJ Sewell L Morgan MD . Health status measurement: sensitivity of the self-reported Chronic Respiratory Questionnaire (CRQ-SR) in pulmonary rehabilitation. Thorax2003; 58: 515–518.
100.
100 Puhan MA Behnke M Laschke M Lichtenschopf A Brandli O Guyatt GH . Self-administration and standardisation of the chronic respiratory questionnaire: a randomised trial in three German-speaking countries. Respir Med2004; 98: 342–350.
101.
101 Schunemann HJ Griffith L Jaeschke R Goldstein R Stubbing D Austin P . A comparison of the original chronic respiratory questionnaire with a standardized version. Chest2003; 124: 1421–1429.
102.
102 Dougan CF Connell CO Thornton E Young CA . Development of a patient-specific dyspnoea questionnaire in motor neurone disease (MND): the MND dyspnoea rating scale (MDRS). J Neurol Sci2000; 180: 86–93.
103.
103 Fitzpatrick R Davey C Buxton M Jones DR . Evaluating patient-based outcome measures for use in clinical trials. Health Technol Assess1998; 2: 1–74.
104.
104 Bruera E Schmitz B Pither J Neumann CM Hanson J . The frequency and correlates of dyspnea in patients with advanced cancer. J Pain Symptom Manage2000; 19: 357–362.
105.
105 Dudgeon DJ Lertzman M Askew GR . Physiological changes and clinical correlations of dyspnea in cancer outpatients. J Pain Symptom Manage2001; 21: 373–379.
106.
106 Wilcock A Maddocks M Lewis M England R Manderson C . Symptoms limiting activity in cancer patients with breathlessness on exertion: ask about muscle fatigue. Thorax2008; 63: 91–92.
107.
107 Guyatt GH Townsend M Berman LB Pugsley SO . Quality of life in patients with chronic airflow limitation. Br J Dis Chest1987; 81: 45–54.
108.
108 von Leupoldt A Dahme B . Psychological aspects in the perception of dyspnea in obstructive pulmonary disease. Respir Med2007; 101: 411–422.
109.
109 Magnusson S Gislason T . Chronic bronchitis in Icelandic males: prevalence, sleep disturbances and quality of life. Scand J Prim Health Care1999; 17: 100–104.
110.
110 Dorman S Byrne A Edwards A . Which measurement scales should we use to measure breathlessness in palliative care? A systematic review. Palliat Med2007; 21: 177–191.
111.
111 Bausewein C Farquhar M Booth S Gysels M Higginson IJ . Measurement of breathlessness in advanced disease: A systematic review. Respirat Med2007; 101: 399–410.
112.
112 Scientific Advisory Committee of the Medical Outcomes Trust. Assessing health status and quality of life instruments: attributes and review criteria. Qual Life Res2002; 11: 193–205.
113.
113 Ries AL . Minimally Clinically Important Difference for the UCSD Shortness of Breath Questionnaire, Borg Scale, and Visual Analog Scale. COPD: J Chron Obstruct Pulmon Dis2005; 2: 105–110.
114.
114 Harper R Brazier JE Waterhouse JC Walters SJ Jones NMB Howard P . Comparison of outcome measures for patients with chronic obstructive pulmonary disease (COPD) in an outpatient setting. Thorax1997; 52: 879–887.
115.
115 Guyatt GH Townsend M Keller J Singer J Nogradi S . Measuring functional status in chronic lung disease: conclusions from a randomized control trial. Respirat Med1989; 83: 293–297.
116.
116 Hajiro T Nishimura K Tsukino M Ikeda A Koyama H Izumi T . Comparison of discriminative properties among disease-specific questionnaires for measuring health-related quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med1998; 157(3Pt 1): 785–790.
117.
117 Wijkstra PJ TenVergert EM Van Altena R Otten V Postma DS Kraan J . Reliability and validity of the chronic respiratory questionnaire (CRQ). Thorax1994; 49: 465–467.
118.
118 Chang JA Curtis JR Patrick DL Raghu G . Assessment of health-related quality of life in patients with interstitial lung disease. Chest1999; 116: 1175–1182.
119.
119 Bradley J Dempster M Wallace E Elborn S . The adaptations of a quality of life questionnaire for routine use in clinical practice: the Chronic Respiratory Disease Questionnaire in cystic fibrosis. Qual Life Res1999; 8: 65–71.
120.
120 Knebel AR Leidy NK Sherman S . Health related quality of life and disease severity in patients with alpha-1 antitrypsin deficiency. Qual Life Res1999; 8: 385–391.
121.
121 Guyatt GH Nogradi S Halcrow S Singer J Sullivan MJ Fallen EL . Development and testing of a new measure of health status for clinical trials in heart failure. J Gen Intern Med1989; 4: 101–107.
122.
122 Schünemann HJ Puhan M Goldstein R Jaeschke R Guyatt GH . Measurement Properties and Interpretability of the Chronic Respiratory Disease Questionnaire (CRQ). COPD2005; 2: 81–89.
123.
123 Joyce C McGee H O’Boyle C . Individual quality of life: approaches to conceptualisation and assessment.Amsterdam: Harwood Academic Publishers; 1999.
124.
124 Bowling A . Measuring Disease. A review of disease-specific quality of life measurement scales.2nd ed.Buckingham, UK: Open University Press; 2001.
125.
125 Aaronson NK Ahmedzai S Bergman B Bullinger M Cull A Duez NJ . The Euorpean Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst1993; 85: 365–376.
126.
126 Farquhar M Higginson IJ Booth S . Repeated measurement of quality of life in palliative care research: the experience of using the SEIQoL-DW in a pilot Phase II RCT of a complex intervention for breathlessness. Palliat Med2008; 22: 589–603.
127.
127 Bernhard J . Timing of quality of life assessment in cancer clinical trials: fine tuning remains a challenge. Ann Oncol2005; 16: 523–524.
128.
128 Wolkove N Dajczman E Colacone A Kreisman H . The relationship between pulmonary function and dyspnea in obstructive lung disease. Chest1989; 96: 1247–1251.
129.
129 Eakin EG Kaplan RM Ries AL Sassi-Dambron DE . Patients' self-reports of dyspnea: An important and independent outcome in chronic obstructive pulmonary disease. Ann Behav Med1996; 18: 87–90.
130.
130 Executive Summary. Global Strategy for the Diagnosis, Management, and Prevention of COPD Revised 2006. Am J Respir Crit Care Med2007; 176: 532–555.
131.
131 Eakin EG Kaplan RM Ries AL . Measurement of dyspnoea in chronic obstructive pulmonary disease. Qual Life Res1993; 2: 181–191.
132.
132 O’Donnell D Webb K . Exertional breathlessness in patients with chronic airflow limitation. The role of lung hyperinflation. Am Rev Respir Dis1993; 148: 1351–1357.
133.
133 O’Donnell D Laveneziana P . Dyspnea and activity limitation in COPD: mechanical factors. COPD2007; 4: 225–236.
134.
134 O’Donnell D Revill S Webb K . Dynamic hyperinflation and exercise intolerance in chronic obstructive pulmonary disease. Am J Respir Crit Care Med2001; 164: 770–777.
135.
135 O’Donnell D Fluge T Gerken F . Effects of tiotropium on lung hyperinflation, dyspnoea and exercise tolerance in COPD. Eur Respir J2004; 23: 832–840.
136.
136 O’Donnell D Hamilton A Webb K . Sensory-mechanical relationships during high-intensity, constant-work-rate exercise in COPD. J Appl Physiol2006; 101: 1025–1035.
137.
137 American Thoracic Society, European Respiratory Society. ATS/ERS Statement on respiratory muscle testing. Am J Respir Crit Care Med2002; 166: 518–624.
138.
138 Steier J Kaul S Seymour J Jolley C Rafferty G Man W . The value of multiple tests of respiratory muscle strength. Thorax2007; 62: 975–980.
139.
139 Hughes P Polkey M Kyroussis D Hamnegard C Moxham J Green M . Measurement of sniff nasal and diaphragm twitch mouth pressure in patients. Thorax1998; 53: 96–100.
140.
140 Edgecombe J Wilcock A Carr D Clarke D Corcoran R Tattersfield A . Re: Dyspnea in the advanced cancer patient. J Pain Symptom Manage1999; 18: 313–315.
141.
141 Feathers L Wilcock A Manderson C Weller R Tattersfield AE . Measuring inspiratory muscle weakness in patients with cancer and breathlessness. J Pain Symptom Manage2003; 25: 305–306.
142.
142 Wilson R Jones P . Influence of prior ventilatory experience on the estimation of breathlessness during exercise. Clin Sci1980; 78: 149–153.
143.
143 Pino-Garcia J Garcia-Rio F Gomez L Racionero M Diaz-Lobato S Villamor J . Short-term effects of inhaled beta-adrenergic agonist on breathlessness and central inspiratory drive in patients with nonreversible COPD. Chest1996; 110: 637–641.
144.
144 Sinderby C Spahija J Beck J Kaminski D Yan S Comtois N . Diaphragm activation during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med2001; 163: 1637–1641.
145.
145 Duiverman M van Eykern L Vennik P Koeter G Maarsingh E Wijkstra P . Reproducibility and responsiveness of a noninvasive EMG technique of the respiratory muscles in COPD patients and in healthy subjects. J Appl Physiol2004; 96: 1723–1729.
146.
146 Ward M Eidelman D Stubbing D Bellemare F Macklem P . Respiratory sensation and pattern of respiratory muscle activation during diaphragm fatigue. J Appl Physiol1988; 65: 2181–2189.
147.
147 Schellart N Reits D . Voluntary breath holding affects spontaneous brain activity measured by magnetoencephalography. Undersea Hyperb Med1999; 26: 229–234.
148.
148 Palange P Ward S Carlsen K-H Casaburi R Gallagher C Gosselink R . Recommendations on the use of exercise testing in clinical practice. Eur Respir J2007; 29: 185–209.
149.
149 Hamilton AL Killian KJ Summers E Jones NL . Symptom intensity and subjective limitation to exercise in patients with cardiorespiratory disorders. Chest1996; 110: 1255–1263.
150.
150 Wilcock A Walker G Manderson C Carr D Broadhurst D Crosby V . Use of upper limb exercise to assess breathlessness in patients with cancer: tolerability, repeatability, and sensitivity. J Pain Symptom Manage2005; 29: 559–564.
151.
151 Solway S Brooks D Lacasse Y Thomas S . A qualitative systematic overview of the measurement properties of functional walk tests used in the cardiorespiratory domain. Chest2001; 119: 256–270.
152.
152 Brown C Wise R . Field Tests of Exercise in COPD: The Six-Minute Walk Test and the Shuttle Walk Test. COPD2007; 4: 217–223.
153.
153 Revill SM Morgan MDL Singh SJ Williams J Hardman AE . The endurance shuttle walk: a new field test for the assessment of endurance capacity in chronic obstructive pulmonary disease. Thorax1999; 54: 213–222.
154.
154 O’Keeffe ST Lye M Donnellan C Carmichael DN . Reproducibility and responsiveness of quality of life assessment and six minute walk test in elderly heart failure patients. Heart1998; 80: 377–382.
155.
155 Guyatt GH Sullivan MJ Fallen EL Thompson PJ Pugsley SO Taylor DW . The six minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can Med Assoc J1985; 132: 919–923.
156.
156 American Thoracic Society. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med2002; 166: 111–117.
157.
157 Guyatt GH Pugsley SO Sullivan MJ . Effect of encouragement on walking test performance. Thorax1984; 39: 818–822.
158.
158 Maddocks M Wilcock A Mockett S . Re: the effect of a physical exercise program in palliative care: a phase II study. J Pain Symptom Manage2006; 32: 513–515.
159.
159 Gysels M Bausewein C Higginson I . Experiences of breathlessness: a systematic review of the qualitative literature. Palliat Support Care2007; 5: 281–302.
160.
160 Smith J . Qualitative research in psychology.London: Sage; 2003.
161.
161 Ritchie J Lewis J . Qualitative research practice.London, Thousand Oaks, New Delhi: Sage Publications Limited; 2003.
162.
162 Currow D Agar M Tieman J Abernethy A . Multisite research allows adequately powered palliative care trials; web-based data management makes it achievable today. Palliat Med2008; 22: 91–92.
