Six-minute walk test in systemic sclerosis: A systematic review and meta-analysis.

BACKGROUND Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are the leading causes of death in systemic sclerosis (SSc). Although the six-minute walk test (6MWT) is generally used for evaluating PAH and ILD, utility in SSc is undetermined. This study evaluates the role of 6MWT in SSc by systematic review and meta-analysis. METHODS A systematic literature search on PubMed, Web of Science and Cochrane Library Online was performed using the medical subject heading search terms for "systemic sclerosis", "CREST" and "six minute walk test", "six minute walk distance (6MWD)", "(cardiopulmonary) exercise test", "treadmill test" or "step test". RESULTS Meta-analysis of 43 included studies (3185 SSc-all patients) revealed that the mean 6MWD was comparable between the SSc-PAH and SSc-ILD-PH subgroups (288m [95% CI: 259-317m] vs 286m [95% CI: 259-314m], p=0.93). The pooled mean of 725 SSc-PAH patients was significantly lower than the pooled mean of 413 SSc-noPAH patients (430m [95% CI: 402-458m], p<0.001). 95 SSc-ILD-PH patients walked significantly less than 328 SSc-ILD patients (388m [95% CI: 362-415m], p<0.001) and significantly less than 86 SSc-noILD patients (420m [95% CI: 325-515m], p=0.008). 81-98% of the SSc-PAH/ILD/ILD-PH patients performed a 6MWT. CONCLUSIONS During a 6MWT, SSc-PAH patients walk less than SSc-noPAH patients and SSc-ILD-PH patients walk less than SSc-ILD and SSc-noILD patients.

[1]  W. Gross,et al.  Bosentan for severe pulmonary arterial hypertension related to systemic sclerosis with interstitial lung disease , 2006, European journal of clinical investigation.

[2]  M. Humbert,et al.  Systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease: impact of pulmonary arterial hypertension therapies. , 2011, Arthritis and rheumatism.

[3]  T. Huizinga,et al.  Randomized comparison of a multidisciplinary team care program with usual care in patients with systemic sclerosis , 2011, Arthritis care & research.

[4]  D. Huscher,et al.  Six-minute walk distance as a marker for disability and complaints in patients with systemic sclerosis. , 2011, Clinical and experimental rheumatology.

[5]  A. Banerjee,et al.  A study on pulmonary complications of systemic sclerosis in eastern India. , 2014, The Indian journal of chest diseases & allied sciences.

[6]  Simon Gibbs,et al.  2015 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension. , 2016, Revista espanola de cardiologia.

[7]  Oliver Distler,et al.  Defining appropriate outcome measures in pulmonary arterial hypertension related to systemic sclerosis: a Delphi consensus study with cluster analysis. , 2008, Arthritis and rheumatism.

[8]  E. Feierl,et al.  Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database , 2010, Annals of the rheumatic diseases.

[9]  G. Giannakoulas,et al.  Significance of serum uric acid in pulmonary hypertension due to systemic sclerosis: a pilot study , 2011, Rheumatology International.

[10]  J. Krishnan,et al.  Clinical differences between idiopathic and scleroderma-related pulmonary hypertension. , 2006, Arthritis and rheumatism.

[11]  G. Mercuro,et al.  Contractile reserve in systemic sclerosis patients as a major predictor of global cardiac impairment and exercise tolerance , 2015, The International Journal of Cardiovascular Imaging.

[12]  B. Kuźnar-Kamińska,et al.  Circulating adipokines and organ involvement in patients with systemic sclerosis. , 2015, Acta reumatologica portuguesa.

[13]  A. Paladini,et al.  Functional assessment of patients with systemic sclerosis by the use of 'Six-minutes-walking-test'. , 2009, La Clinica terapeutica.

[14]  Qiu-Ning Sun,et al.  Telangiectasia as a potential clinical marker of microvascular lesions in systemic sclerosis patients from EUSTAR data in China. , 2015, Clinical and experimental rheumatology.

[15]  P. Sarzi-Puttini,et al.  Performance capacity evaluated using the 6-minute walk test: 5-year results in patients with diffuse systemic sclerosis and initial interstitial lung disease. , 2015, Clinical and experimental rheumatology.

[16]  M. Kurzyna,et al.  Assessment of left and right ventricular diastolic function in patients with systemic sclerosis. , 2008, Kardiologia polska.

[17]  G. Guyatt,et al.  The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure. , 1985, Canadian Medical Association journal.

[18]  D. Furst,et al.  Expert consensus for performing right heart catheterisation for suspected pulmonary arterial hypertension in systemic sclerosis: a Delphi consensus study with cluster analysis , 2013, Annals of the rheumatic diseases.

[19]  F. Maltais,et al.  Assessment of Daily Life Physical Activities in Pulmonary Arterial Hypertension , 2011, PloS one.

[20]  L. Marino Claverie,et al.  Organ involvement in Argentinian systemic sclerosis patients with “late” pattern as compared to patients with “early/active” pattern by nailfold capillaroscopy , 2013, Clinical Rheumatology.

[21]  C. Denton,et al.  Systemic sclerosis associated pulmonary hypertension: improved survival in the current era , 2005, Heart.

[22]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[23]  C. Denton,et al.  Role of N-terminal brain natriuretic peptide (N-TproBNP) in scleroderma-associated pulmonary arterial hypertension. , 2006, European heart journal.

[24]  R. Scorza,et al.  Validity of the Saint George's Respiratory Questionnaire in the evaluation of the health-related quality of life in patients with interstitial lung disease secondary to systemic sclerosis. , 2006, Rheumatology.

[25]  M. Humbert,et al.  Long-term outcome of systemic sclerosis-associated pulmonary arterial hypertension treated with bosentan as first-line monotherapy followed or not by the addition of prostanoids or sildenafil. , 2010, Rheumatology.

[26]  M. Humbert,et al.  Validation of the 6 min walk test according to the OMERACT filter: a systematic literature review by the EPOSS-OMERACT group , 2010, Annals of the rheumatic diseases.

[27]  A. Zaiman,et al.  Disproportionate elevation of N-terminal pro-brain natriuretic peptide in scleroderma-related pulmonary hypertension , 2009, European Respiratory Journal.

[28]  P. Emery,et al.  Randomized, prospective, placebo-controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis. , 2010, Arthritis and rheumatism.

[29]  P. Airó,et al.  An individualized rehabilitation program in patients with systemic sclerosis may improve quality of life and hand mobility , 2009, Clinical Rheumatology.

[30]  T. Medsger,et al.  Changes in causes of death in systemic sclerosis, 1972–2002 , 2007, Annals of the rheumatic diseases.

[31]  A. Masi Preliminary criteria for the classification of systemic sclerosis (scleroderma). , 1980, Bulletin on the rheumatic diseases.

[32]  M. Mayes,et al.  Development of pulmonary hypertension in a high-risk population with systemic sclerosis in the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) cohort study. , 2014, Seminars in arthritis and rheumatism.

[33]  Thierry Troosters,et al.  An official systematic review of the European Respiratory Society/American Thoracic Society: measurement properties of field walking tests in chronic respiratory disease , 2014, European Respiratory Journal.

[34]  S. Kaur,et al.  Prospective, open-label, uncontrolled pilot study to study safety and efficacy of sildenafil in systemic sclerosis–related pulmonary artery hypertension and cutaneous vascular complications , 2013, Rheumatology International.

[35]  M. Humbert,et al.  Survival in systemic sclerosis-associated pulmonary arterial hypertension in the modern management era , 2012, Annals of the rheumatic diseases.

[36]  Y. Allanore,et al.  Effects of oral treatments on exercise capacity in systemic sclerosis related pulmonary arterial hypertension: a meta-analysis of randomised controlled trials , 2007, Annals of the rheumatic diseases.

[37]  C. Strange,et al.  Limitations to the 6-Minute Walk Test in Interstitial Lung Disease and Pulmonary Hypertension in Scleroderma , 2009, The Journal of Rheumatology.

[38]  M. Humbert,et al.  Immunosuppressive therapy in connective tissue diseases-associated pulmonary arterial hypertension. , 2006, Chest.

[39]  G. Giannakoulas,et al.  Asymmetrical dimethylarginine in systemic sclerosis-related pulmonary arterial hypertension. , 2008, Rheumatology.

[40]  Stefano Diciotti,et al.  Lung CT densitometry in systemic sclerosis: correlation with lung function, exercise testing, and quality of life. , 2007, Chest.

[41]  D. Playford,et al.  Prevalence of pulmonary arterial hypertension in an Australian scleroderma population: screening allows for earlier diagnosis , 2009, Internal medicine journal.

[42]  M. Humbert,et al.  Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. , 2005, Arthritis and rheumatism.

[43]  M. Mayes,et al.  Baseline characteristics and follow-up in patients with normal haemodynamics versus borderline mean pulmonary arterial pressure in systemic sclerosis: results from the PHAROS registry , 2012, Annals of the rheumatic diseases.

[44]  A. Holland,et al.  The six‐minute walk test: a useful metric for the cardiopulmonary patient , 2009, Internal medicine journal.

[45]  J. Wharton,et al.  Iron deficiency in systemic sclerosis patients with and without pulmonary hypertension. , 2014, Rheumatology.

[46]  J. E. Hansen,et al.  Developing Pulmonary Vasculopathy in Systemic Sclerosis, Detected with Non-Invasive Cardiopulmonary Exercise Testing , 2010, PloS one.

[47]  Oliver Distler,et al.  2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. , 2013, Arthritis and rheumatism.

[48]  D. Furst,et al.  Submaximal exercise testing in the assessment of interstitial lung disease secondary to systemic sclerosis: reproducibility and correlations of the 6-min walk test , 2006, Annals of the rheumatic diseases.

[49]  H. Heinzl,et al.  Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study , 2013, Annals of the rheumatic diseases.

[50]  Thierry Troosters,et al.  An official European Respiratory Society/American Thoracic Society technical standard: field walking tests in chronic respiratory disease , 2014, European Respiratory Journal.

[51]  A. Lopes,et al.  Lower limb muscle strength is associated with functional performance and quality of life in patients with systemic sclerosis , 2015, Brazilian journal of physical therapy.

[52]  N. Laird,et al.  Meta-analysis in clinical trials. , 1986, Controlled clinical trials.

[53]  G. Karabıyıkoğlu,et al.  Evaluation of the functional parameters in scleroderma cases with pulmonary involvement. , 2010, Tuberkuloz ve toraks.

[54]  D L Sherrill,et al.  Reference equations for the six-minute walk in healthy adults. , 1998, American journal of respiratory and critical care medicine.

[55]  F. Saulnier,et al.  Aerosolized iloprost in CREST syndrome related pulmonary hypertension. , 2001, The Journal of rheumatology.

[56]  P. Sampaio-Barros,et al.  Six-minute walk test for the evaluation of pulmonary disease severity in scleroderma patients. , 2007, Chest.

[57]  A. Lopes,et al.  Relationship between functional capacity, joint mobility and pulmonary function in patients with systemic sclerosis. , 2015, Journal of bodywork and movement therapies.

[58]  S. Iliceto,et al.  Bosentan therapy of pulmonary arterial hypertension in connective tissue diseases , 2006, European journal of clinical investigation.

[59]  M. Gaga,et al.  ERS guidelines, statements and technical standards published in the ERJ in 2014: a year in review , 2015, European Respiratory Journal.

[60]  G. Giannakoulas,et al.  Neurohormonal activation in patients with systemic sclerosis-related pulmonary arterial hypertension. , 2007, International Journal of Cardiology.

[61]  R. Damico,et al.  Severity of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension in African Americans , 2014, Medicine.

[62]  M. Humbert,et al.  Clinical characteristics and survival in systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease. , 2011, Chest.

[63]  J. Pope,et al.  Lack of correlation of the health assessment questionnaire disability index with lung parameters in systemic sclerosis associated pulmonary arterial hypertension. , 2008, Clinical and experimental rheumatology.

[64]  R. Doughty,et al.  The six‐minute walk test using forehead oximetry is reliable in the assessment of scleroderma lung disease , 2012, Respirology.

[65]  A. Zaiman,et al.  Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension , 2007, European Respiratory Journal.

[66]  O. Sitbon,et al.  Treatment goals of pulmonary hypertension. , 2013, Journal of the American College of Cardiology.

[67]  Y. Allanore,et al.  Lack of Specificity of the 6-Minute Walk Test as an Outcome Measure for Patients with Systemic Sclerosis , 2009, The Journal of Rheumatology.

[68]  T. Medsger,et al.  Criteria for the classification of early systemic sclerosis. , 2001, The Journal of rheumatology.

[69]  M. Kurzyna,et al.  Non-invasive diagnostic and functional evaluation of cardiac involvement in patients with systemic sclerosis , 2006, Clinical Rheumatology.

[70]  M. Humbert,et al.  Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension: a systematic review and meta-analysis. , 2013, Arthritis and rheumatism.

[71]  A. Holmes,et al.  Significance of plasma N-terminal pro-brain natriuretic peptide in patients with systemic sclerosis-related pulmonary arterial hypertension. , 2003, Respiratory medicine.

[72]  M. Humbert,et al.  Is pulmonary arterial hypertension really a late complication of systemic sclerosis? , 2009, Chest.

[73]  Stuart Rich,et al.  Continuous Intravenous Epoprostenol for Pulmonary Hypertension Due to the Scleroderma Spectrum of Disease , 2000, Annals of Internal Medicine.

[74]  James F. Fries,et al.  Preliminary criteria for the classification of systemic sclerosis (scleroderma). Subcommittee for scleroderma criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. , 1980, Arthritis and rheumatism.

[75]  R. Goeree,et al.  The excess burden of rheumatoid arthritis in Ontario, Canada. , 2013, Clinical and experimental rheumatology.

[76]  M. Humbert,et al.  Screening for pulmonary arterial hypertension in patients with systemic sclerosis: clinical characteristics at diagnosis and long-term survival. , 2011, Arthritis and rheumatism.