{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:37:16Z","timestamp":1787020636665,"version":"build-2736575974"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T00:00:00Z","timestamp":1595462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Systemic sclerosis (SSc) is a multi-organ autoimmune disease with complex interactions between immune-mediated inflammatory processes and vascular pathology leading to small vessel obliteration, promoting uncontrolled fibrosis of skin and internal organs. Interstitial lung disease (ILD) is a common but highly variable manifestation of SSc and is associated with high morbidity and mortality. Treatment approaches have focused on immunosuppressive therapies, which have shown some efficacy on lung function. Recently, a large phase 3 trial showed that treatment with nintedanib was associated with a reduction in lung function decline. None of the conducted randomized clinical trials have so far shown convincing efficacy on other outcome measures including quality of life determined by patient reported outcomes. Little evidence is available for non-pharmacological treatment and supportive care specifically for SSc-ILD patients, including pulmonary rehabilitation, supplemental oxygen, symptom relief and adequate information. Improved management of SSc-ILD patients based on a holistic approach is necessary to support patients in maintaining as much quality of life as possible throughout the disease course and to improve long-term outcomes.<\/jats:p>","DOI":"10.1186\/s12931-020-01459-0","type":"journal-article","created":{"date-parts":[[2020,7,23]],"date-time":"2020-07-23T08:03:26Z","timestamp":1595491406000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["The need for a holistic approach for SSc-ILD \u2013 achievements and ambiguity in a devastating disease"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6467-7422","authenticated-orcid":false,"given":"Anna-Maria","family":"Hoffmann-Vold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Allanore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Bendstrup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosimo","family":"Bruni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Distler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toby M.","family":"Maher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies","family":"Wijsenbeek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kreuter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,23]]},"reference":[{"key":"1459_CR1","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1016\/S0140-6736(17)30933-9","volume":"390","author":"CP Denton","year":"2017","unstructured":"Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017;390:1685\u201399.","journal-title":"Lancet"},{"key":"1459_CR2","doi-asserted-by":"crossref","unstructured":"Hoffmann-Vold AM, Fretheim H, Halse AK, Seip M, Bitter H, Wallenius M, Garen T, Salberg A, Brunborg C, Midtvedt \u00d8, et al. Tracking impact of interstitial lung disease in systemic sclerosis in a complete Nationwide cohort. Am J Respir Crit Care Med. 2019;200(10):1258\u201366.","DOI":"10.1164\/rccm.201903-0486OC"},{"key":"1459_CR3","doi-asserted-by":"publisher","first-page":"1427","DOI":"10.1513\/AnnalsATS.201806-362OC","volume":"15","author":"SA Guler","year":"2018","unstructured":"Guler SA, Winstone TA, Murphy D, Hague C, Soon J, Sulaiman N, Li KH, Dunne J, Wilcox PG, Ryerson CJ. Does systemic sclerosis-associated interstitial lung disease burn out? Specific phenotypes of disease progression. Ann Am Thorac Soc. 2018;15:1427\u201333.","journal-title":"Ann Am Thorac Soc"},{"key":"1459_CR4","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1136\/annrheumdis-2017-211448","volume":"76","author":"M Elhai","year":"2017","unstructured":"Elhai M, Meune C, Boubaya M, Avouac J, Hachulla E, Balbir-Gurman A, Riemekasten G, Airo P, Joven B, Vettori S, et al. Mapping and predicting mortality from systemic sclerosis. Ann Rheum Dis. 2017;76:1897\u2013905.","journal-title":"Ann Rheum Dis"},{"key":"1459_CR5","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1136\/ard.2006.066068","volume":"66","author":"VD Steen","year":"2007","unstructured":"Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis. 2007;66:940\u20134.","journal-title":"Ann Rheum Dis"},{"key":"1459_CR6","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1002\/art.39166","volume":"67","author":"AM Hoffmann-Vold","year":"2015","unstructured":"Hoffmann-Vold AM, Aalokken TM, Lund MB, Garen T, Midtvedt O, Brunborg C, Gran JT, Molberg O. Predictive value of serial high-resolution computed tomography analyses and concurrent lung function tests in systemic sclerosis. Arthritis Rheumatol. 2015;67:2205\u201312.","journal-title":"Arthritis Rheumatol"},{"key":"1459_CR7","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s13075-018-1517-z","volume":"20","author":"S Adler","year":"2018","unstructured":"Adler S, Huscher D, Siegert E, Allanore Y, Czirjak L, DelGaldo F, Denton CP, Distler O, Frerix M, Matucci-Cerinic M, et al. Systemic sclerosis associated interstitial lung disease - individualized immunosuppressive therapy and course of lung function: results of the EUSTAR group. Arthritis Res Ther. 2018;20:17.","journal-title":"Arthritis Res Ther"},{"key":"1459_CR8","doi-asserted-by":"crossref","unstructured":"Wijsenbeek M, Kreuter M, Olson A, Fischer A, Bendstrup E, Wells CD, Denton CP, Mounir B, Zouad-Lejour L, Quaresma M, Cottin V. Progressive fibrosing interstitial lung diseases: current practice in diagnosis and management. Curr Med Res Opin. 2019;35(11):2015\u201324.","DOI":"10.1080\/03007995.2019.1647040"},{"key":"1459_CR9","doi-asserted-by":"publisher","first-page":"249","DOI":"10.3899\/jrheum.181173","volume":"47","author":"JK De Vries-Bouwstra","year":"2020","unstructured":"De Vries-Bouwstra JK, Allanore Y, Matucci-Cerinic M, Balbir-Gurman A. Worldwide expert agreement on updated recommendations for the treatment of systemic sclerosis. J Rheumatol. 2020;47:249\u201354.","journal-title":"J Rheumatol"},{"key":"1459_CR10","doi-asserted-by":"publisher","first-page":"e71","DOI":"10.1016\/S2665-9913(19)30144-4","volume":"2","author":"A-M Hoffmann-Vold","year":"2020","unstructured":"Hoffmann-Vold A-M, Maher TM, Philpot EE, Ashrafzadeh A, Barake R, Barsotti S, Bruni C, Carducci P, Carreira PE, Castellv\u00ed I, et al. The identification and management of interstitial lung disease in systemic sclerosis: evidence-based European consensus statements. Lancet Rheumatol. 2020;2:e71\u201383.","journal-title":"Lancet Rheumatol"},{"key":"1459_CR11","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1016\/S2213-2600(17)30383-1","volume":"5","author":"M Kreuter","year":"2017","unstructured":"Kreuter M, Bendstrup E, Russell A-M, Bajwah S, Lindell K, Adir Y, Brown CE, Calligaro G, Cassidy N, Corte TJ, et al. Palliative care in interstitial lung disease: living well. Lancet Respir Med. 2017;5:968\u201380.","journal-title":"Lancet Respir Med"},{"key":"1459_CR12","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/nrrheum.2014.149","volume":"10","author":"AU Wells","year":"2014","unstructured":"Wells AU, Denton CP. Interstitial lung disease in connective tissue disease\u2014mechanisms and management. Nat Rev Rheumatol. 2014;10:728\u201339.","journal-title":"Nat Rev Rheumatol"},{"key":"1459_CR13","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1136\/annrheumdis-2016-209909","volume":"76","author":"O Kowal-Bielecka","year":"2017","unstructured":"Kowal-Bielecka O, Fransen J, Avouac J, Becker M, Kulak A, Allanore Y, Distler O, Clements P, Cutolo M, Czirjak L, et al. Update of EULAR recommendations for the treatment of systemic sclerosis. Ann Rheum Dis. 2017;76:1327\u201339.","journal-title":"Ann Rheum Dis"},{"key":"1459_CR14","doi-asserted-by":"publisher","first-page":"2655","DOI":"10.1056\/NEJMoa055120","volume":"354","author":"DP Tashkin","year":"2006","unstructured":"Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354:2655\u201366.","journal-title":"N Engl J Med"},{"key":"1459_CR15","doi-asserted-by":"publisher","first-page":"3962","DOI":"10.1002\/art.22204","volume":"54","author":"RK Hoyles","year":"2006","unstructured":"Hoyles RK, Ellis RW, Wellsbury J, Lees B, Newlands P, Goh NSL, Roberts C, Desai S, Herrick AL, McHugh NJ, et al. A multicenter, prospective, randomized, double-blind, placebo-controlled trial of corticosteroids and intravenous cyclophosphamide followed by oral azathioprine for the treatment of pulmonary fibrosis in scleroderma. Arthritis Rheumatism. 2006;54:3962\u201370.","journal-title":"Arthritis Rheumatism"},{"key":"1459_CR16","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1016\/S2213-2600(16)30152-7","volume":"4","author":"DP Tashkin","year":"2016","unstructured":"Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, Goldin J, Arriola E, Volkmann ER, Kafaja S, et al. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016;4:708\u201319.","journal-title":"Lancet Respir Med"},{"key":"1459_CR17","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1093\/rheumatology\/kep093","volume":"49","author":"D Daoussis","year":"2010","unstructured":"Daoussis D, Liossis S-NC, Tsamandas AC, Kalogeropoulou C, Kazantzi A, Sirinian C, Karampetsou M, Yiannopoulos G, Andonopoulos AP. Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology. 2010;49:271\u201380.","journal-title":"Rheumatology"},{"key":"1459_CR18","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/j.semarthrit.2016.10.003","volume":"46","author":"D Daoussis","year":"2017","unstructured":"Daoussis D, Melissaropoulos K, Sakellaropoulos G, Antonopoulos I, Markatseli TE, Simopoulou T, Georgiou P, Andonopoulos AP, Drosos AA, Sakkas L, Liossis S-N. A multicenter, open-label, comparative study of B-cell depletion therapy with rituximab for systemic sclerosis-associated interstitial lung disease. Semin Arthritis Rheum. 2017;46:625\u201331.","journal-title":"Semin Arthritis Rheum"},{"key":"1459_CR19","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1136\/annrheumdis-2013-204522","volume":"74","author":"S Jordan","year":"2015","unstructured":"Jordan S, Distler JHW, Maurer B, Huscher D, Van Laar JM, Allanore Y, Distler O. Effects and safety of rituximab in systemic sclerosis: an analysis from the European scleroderma trial and research (EUSTAR) group. Ann Rheum Dis. 2015;74:1188\u201394.","journal-title":"Ann Rheum Dis"},{"key":"1459_CR20","doi-asserted-by":"publisher","first-page":"2106","DOI":"10.1093\/rheumatology\/key213","volume":"57","author":"G Sircar","year":"2018","unstructured":"Sircar G, Goswami RP, Sircar D, Ghosh A, Ghosh P. Intravenous cyclophosphamidevsrituximab for the treatment of early diffuse scleroderma lung disease: open label, randomized, controlled trial. Rheumatology. 2018;57:2106\u201313.","journal-title":"Rheumatology"},{"key":"1459_CR21","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1136\/annrheumdis-2018-214816","volume":"78","author":"M Elhai","year":"2019","unstructured":"Elhai M, Boubaya M, Distler O, Smith V, Matucci-Cerinic M, Alegre Sancho JJ, Truchetet M-E, Braun-Moscovici Y, Iannone F, Novikov PI, et al. Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study. Ann Rheum Dis. 2019;78:979\u201387.","journal-title":"Ann Rheum Dis"},{"key":"1459_CR22","doi-asserted-by":"publisher","first-page":"2630","DOI":"10.1016\/S0140-6736(16)00232-4","volume":"387","author":"D Khanna","year":"2016","unstructured":"Khanna D, Denton CP, Jahreis A, van Laar JM, Frech TM, Anderson ME, Baron M, Chung L, Fierlbeck G, Lakshminarayanan S, et al. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate): a phase 2, randomised, controlled trial. Lancet. 2016;387:2630\u201340.","journal-title":"Lancet"},{"key":"1459_CR23","unstructured":"Khanna D, Lin CJF, Kuwana M, Allanore Y, Batalov A, Butrimiene I, Carreira PE, Matucci Cerinic M, Distler O, Kaliterna DM, et al. Efficacy and Safety of Tocilizumab for the Treatment of Systemic Sclerosis: Results from a Phase 3 Randomized Controlled Trial. Arthritis Rheumatol. 2018;70(suppl 10)."},{"key":"1459_CR24","doi-asserted-by":"crossref","unstructured":"Wu W, Jordan S, Graf N, De Oliveira PJ, Curram J, Allanore Y, Matucci-Cerinic M, Pope JE, Denton CP, Khanna D, Distler O. Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort. Ann Rheum Dis. 2019;78(5):648\u201356.","DOI":"10.1136\/annrheumdis-2018-213455"},{"key":"1459_CR25","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1136\/annrheumdis-2018-214477","volume":"78","author":"D Khanna","year":"2019","unstructured":"Khanna D, Lin CJF, Goldin J, Kim G, Kuwana M, Allanore Y, Batalov A, Butrimiene I, Carreira PE, Matucci-Cerinic M, et al. OP0245 PRESERVATION OF LUNG FUNCTION OBSERVED IN A PHASE 3 RANDOMIZED CONTROLLED TRIAL OF TOCILIZUMAB FOR THE TREATMENT OF EARLY SSC 2019;78:202\u2013203. Ann Rheumatic Dis. 2019;78:202\u20133.","journal-title":"Ann Rheumatic Dis"},{"key":"1459_CR26","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1097\/MCP.0000000000000408","volume":"23","author":"M Kreuter","year":"2017","unstructured":"Kreuter M, Walscher J, Behr J. Antifibrotic drugs as treatment of nonidiopathic pulmonary fibrosis interstitial pneumonias: the time is now (?). Curr Opin Pulm Med. 2017;23:418\u201325.","journal-title":"Curr Opin Pulm Med"},{"key":"1459_CR27","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.3899\/jrheum.151322","volume":"43","author":"D Khanna","year":"2016","unstructured":"Khanna D, Albera C, Fischer A, Khalidi N, Raghu G, Chung L, Chen D, Schiopu E, Tagliaferri M, Seibold JR, Gorina E. An open-label, phase II study of the safety and tolerability of Pirfenidone in patients with scleroderma-associated interstitial lung disease: the LOTUSS trial. J Rheumatol. 2016;43:1672\u20139.","journal-title":"J Rheumatol"},{"key":"1459_CR28","doi-asserted-by":"crossref","unstructured":"Distler O, Highland KB, Gahlemann M, Azuma A, Fischer A, Mayes MD, Raghu G, Sauter W, Girard M, Alves M, et al. Nintedanib for systemic sclerosis-associated interstitial lung disease. N Engl J Med. 2019;380(26):2518\u201328.","DOI":"10.1056\/NEJMoa1903076"},{"key":"1459_CR29","doi-asserted-by":"publisher","first-page":"2071","DOI":"10.1056\/NEJMoa1402584","volume":"370","author":"L Richeldi","year":"2014","unstructured":"Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, Cottin V, Flaherty KR, Hansell DM, Inoue Y, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2071\u201382.","journal-title":"N Engl J Med"},{"key":"1459_CR30","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.semarthrit.2016.02.005","volume":"46","author":"C Frantz","year":"2016","unstructured":"Frantz C, Avouac J, Distler O, Amrouche F, Godard D, Kennedy AT, Connolly K, Varga J, Matucci-Cerinic M, Allanore Y. Impaired quality of life in systemic sclerosis and patient perception of the disease: a large international survey. Semin Arthritis Rheum. 2016;46:115\u201323.","journal-title":"Semin Arthritis Rheum"},{"key":"1459_CR31","doi-asserted-by":"crossref","unstructured":"Fretheim H, Halse AK, Seip M, Bitter H, Wallenius M, Garen T, Salberg A, Brunborg C, Midtvedt O, Molberg O, Hoffmann-Vold AM. Multidimensional tracking of phenotypes and organ involvement in a complete nationwide systemic sclerosis cohort. Rheumatology (Oxford). 2020. Epub ahead of print.","DOI":"10.1093\/rheumatology\/keaa026"},{"key":"1459_CR32","doi-asserted-by":"crossref","unstructured":"Hoffmann-Vold A-M, Volkmann ER. Gastrointestinal involvement in systemic sclerosis: effects on morbidity and mortality and new therapeutic approaches. Journal of Scleroderma and Related Disorders. 2019. Epub ahead of print.","DOI":"10.1177\/2397198319891282"},{"key":"1459_CR33","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1056\/NEJMoa1908681","volume":"381","author":"KR Flaherty","year":"2019","unstructured":"Flaherty KR, Wells AU, Cottin V, Devaraj A, Walsh SLF, Inoue Y, Richeldi L, Kolb M, Tetzlaff K, Stowasser S, et al. Nintedanib in progressive Fibrosing interstitial lung diseases. N Engl J Med. 2019;381:1718\u201327.","journal-title":"N Engl J Med"},{"key":"1459_CR34","unstructured":"van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, Schuerwegh AJ, Marijt EWA, Vonk MC, Schattenberg AV, et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis. Ann Rheum Dis. 2008;67(1):98\u2013104."},{"key":"1459_CR35","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1056\/NEJMoa1703327","volume":"4","author":"K Sullivan","year":"2018","unstructured":"Sullivan K, Goldmuntz E, Keyes-Elstein L, McSweeney P, Pinckney A, Welch B, Mayes M, Nash R, Crofford L, Eggleston B, et al. Myeloablative autologous stem-cell transplantation for severe scleroderma. N Engl J Med. 2018;4:35\u201347.","journal-title":"N Engl J Med"},{"key":"1459_CR36","doi-asserted-by":"crossref","unstructured":"Spierings J, Van Rhijn-Brouwer FCC, De Bresser CJM, Mosterman PTM, Pieterse AH, Vonk MC, Voskuyl AE, De Vries-Bouwstra JK, Kars MC, Van Laar JM. Treatment decision-making in diffuse cutaneous systemic sclerosis: a patient\u2019s perspective. Rheumatology. 2019. Epub ahead of print.","DOI":"10.1093\/rheumatology\/kez110.068"},{"key":"1459_CR37","doi-asserted-by":"crossref","unstructured":"Cantu E, Appel JZ, Hartwig MG, Woreta H, Green C, Messier R, Palmer SM, Davis RD. Early Fundoplication Prevents Chronic Allograft Dysfunction in Patients with Gastroesophageal Reflux Disease. 2004;78:1142\u201351.","DOI":"10.1016\/j.athoracsur.2004.04.044"},{"key":"1459_CR38","first-page":"1900","volume":"12","author":"MG Patti","year":"2008","unstructured":"Patti MG, Gasper WJ, Fisichella PM, Nipomnick I, Palazzo F. Gastroesophageal Reflux Disease and Connective Tissue Disorders: Pathophysiology and Implications for Treatment. 2008;12:1900\u20136.","journal-title":"Gastroesophageal Reflux Disease and Connective Tissue Disorders: Pathophysiology and Implications for Treatment"},{"key":"1459_CR39","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1001\/jamasurg.2015.4233","volume":"151","author":"MG Patti","year":"2016","unstructured":"Patti MG. An evidence-based approach to the treatment of Gastroesophageal reflux disease. JAMA Surgery. 2016;151:73.","journal-title":"JAMA Surgery"},{"key":"1459_CR40","doi-asserted-by":"crossref","unstructured":"Gasper WJ, Sweet MP, Golden JA, Hoopes C, Leard LE, Kleinhenz ME, Hays SR, Patti MG. Lung transplantation in patients with connective tissue disorders and esophageal dysmotility. 2008;21:650\u20135.","DOI":"10.1111\/j.1442-2050.2008.00828.x"},{"key":"1459_CR41","first-page":"793","volume":"13","author":"CH Miele","year":"2016","unstructured":"Miele CH, Schwab K, Saggar R, Duffy E, Elashoff D, Tseng C-H, Weigt S, Charan D, Abtin F, Johannes J, et al. Lung transplant outcomes in systemic sclerosis with significant esophageal dysfunction. A Comprehensive Single-Center Experience. 2016;13:793\u2013802.","journal-title":"A Comprehensive Single-Center Experience"},{"key":"1459_CR42","doi-asserted-by":"crossref","unstructured":"Brooks P, Boers M, Simon LS, Strand V, Tugwell P. Outcome measures in rheumatoid arthritis: the OMERACT process. Expert Rev Clin Immunol. 2007;3(3):271\u20135.","DOI":"10.1586\/1744666X.3.3.271"},{"key":"1459_CR43","doi-asserted-by":"publisher","first-page":"405","DOI":"10.3899\/jrheum.161040","volume":"45","author":"VM Hsu","year":"2018","unstructured":"Hsu VM, Denton CP, Domsic RT, Furst DE, Rischmueller M, Stanislav M, Steen VD, Distler JHW, Korish S, Cooper A, et al. Pomalidomide in patients with interstitial lung disease due to systemic sclerosis: a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. J Rheumatol. 2018;45:405\u201310.","journal-title":"J Rheumatol"},{"key":"1459_CR44","doi-asserted-by":"crossref","unstructured":"Burt RK, Shah SJ, Dill K, Grant T, Gheorghiade M, Schroeder J, Craig R, Hirano I, Marshall K, Ruderman E, et al. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised phase 2 trial. 2011;378:498\u2013506.","DOI":"10.1016\/S0140-6736(11)60982-3"},{"key":"1459_CR45","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1136\/ard.2010.143974","volume":"70","author":"RF Spiera","year":"2011","unstructured":"Spiera RF, Gordon JK, Mersten JN, Magro CM, Mehta M, Wildman HF, Kloiber S, Kirou KA, Lyman S, Crow MK. Imatinib mesylate (Gleevec) in the treatment of diffuse cutaneous systemic sclerosis: results of a 1-year, phase IIa, single-arm, open-label clinical trial. Ann Rheum Dis. 2011;70:1003\u20139.","journal-title":"Ann Rheum Dis"},{"key":"1459_CR46","doi-asserted-by":"crossref","unstructured":"Seibold JR, Denton CP, Furst DE, Guillevin L, Rubin LJ, Wells A, Matucci-Cerinic M, Riemekasten G, Emery P, Chadha-Boreham H, et al. Randomized, prospective, placebo-controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis. Arthritis Rheumatism. 2010;62(7):2101\u20138.","DOI":"10.1002\/art.27466"},{"key":"1459_CR47","doi-asserted-by":"crossref","unstructured":"Denton CP, Merkel PA, Furst DE, Khanna D, Emery P, Hsu VM, Silliman N, Streisand J, Powell J, \u00c5kesson A, et al. Recombinant human anti\u2013transforming growth factor \u03b21 antibody therapy in systemic sclerosis: A multicenter, randomized, placebo-controlled phase I\/II trial of CAT-192. 2007;56:323\u201333.","DOI":"10.1002\/art.22289"},{"key":"1459_CR48","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/s10067-005-1157-y","volume":"25","author":"O Nadashkevich","year":"2006","unstructured":"Nadashkevich O, Davis P, Fritzler M, Kovalenko W. A randomized unblinded trial of cyclophosphamide versus azathioprine in the treatment of systemic sclerosis. Clin Rheumatol. 2006;25:205\u201312.","journal-title":"Clin Rheumatol"},{"key":"1459_CR49","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1136\/ard.60.6.577","volume":"60","author":"M Binks","year":"2001","unstructured":"Binks M. Phase I\/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease. Ann Rheum Dis. 2001;60:577\u201384..","journal-title":"Ann Rheum Dis"},{"key":"1459_CR50","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/s11926-007-0010-5","volume":"9","author":"D Khanna","year":"2007","unstructured":"Khanna D, Merkel PA. Outcome measures in systemic sclerosis: an update on instruments and current research. Curr Rheumatol Rep. 2007;9:151\u20137.","journal-title":"Curr Rheumatol Rep"},{"key":"1459_CR51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0213444","volume":"14","author":"M Occhipinti","year":"2019","unstructured":"Occhipinti M, Bosello S, Sisti LG, Cicchetti G, De Waure C, Pirronti T, Ferraccioli G, Gremese E, Larici AR. Quantitative and semi-quantitative computed tomography analysis of interstitial lung disease associated with systemic sclerosis: a longitudinal evaluation of pulmonary parenchyma and vessels. PLoS One. 2019;14:e0213444.","journal-title":"PLoS One"},{"key":"1459_CR52","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0177107","volume":"12","author":"M Baqir","year":"2017","unstructured":"Baqir M, Makol A, Osborn TG, Bartholmai BJ, Ryu JH. Mycophenolate mofetil for scleroderma-related interstitial lung disease: a real world experience. PLoS One. 2017;12:e0177107.","journal-title":"PLoS One"},{"key":"1459_CR53","doi-asserted-by":"crossref","unstructured":"Buch MH, Denton CP, Furst DE, Guillevin L, Rubin LJ, Wells AU, Matucci-Cerinic M, Riemekasten G, Emery P, Chadha-Boreham H, 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;66:169\u201373.","DOI":"10.1136\/ard.2006.054866"},{"key":"1459_CR54","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.3899\/jrheum.081221","volume":"36","author":"Y Schoindre","year":"2009","unstructured":"Schoindre Y, Meune C, Dinh-Xuan AT, Avouac J, Kahan A, Allanore Y. Lack of specificity of the 6-minute walk test as an outcome measure for patients with systemic sclerosis. J Rheumatol. 2009;36:1481\u20135.","journal-title":"J Rheumatol"},{"key":"1459_CR55","doi-asserted-by":"crossref","unstructured":"Khanna D, Tashkin DP, Denton CP, Renzoni EA, Desai SR, Varga J. Aetiology, risk factors, and biomarkers in systemic sclerosis with interstitial lung disease. Am J Respir Crit Care Med. 2019. Epub ahead of print.","DOI":"10.1164\/rccm.201903-0563CI"},{"key":"1459_CR56","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1002\/art.40815","volume":"71","author":"M Elhai","year":"2019","unstructured":"Elhai M, Hoffmann-Vold AM, Avouac J, Pezet S, Cauvet A, Leblond A, Fretheim H, Garen T, Kuwana M, Molberg O, Allanore Y. Performance of candidate serum biomarkers for systemic sclerosis-associated interstitial lung disease. Arthritis Rheumatol. 2019;71:972\u201382.","journal-title":"Arthritis Rheumatol"},{"key":"1459_CR57","doi-asserted-by":"publisher","first-page":"792","DOI":"10.3899\/jrheum.131251","volume":"41","author":"LA Saketkoo","year":"2014","unstructured":"Saketkoo LA, Mittoo S, Frankel S, Lesage D, Sarver C, Phillips K, Strand V, Matteson EL. Reconciling healthcare professional and patient perspectives in the development of disease activity and response criteria in connective tissue disease\u2013related interstitial lung diseases. J Rheumatol. 2014;41:792\u20138.","journal-title":"J Rheumatol"},{"key":"1459_CR58","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1136\/thoraxjnl-2013-204202","volume":"69","author":"LA Saketkoo","year":"2014","unstructured":"Saketkoo LA, Mittoo S, Huscher D, Khanna D, Dellaripa PF, Distler O, Flaherty KR, Frankel S, Oddis CV, Denton CP, et al. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials. Thorax. 2014;69:436\u201344.","journal-title":"Thorax"},{"key":"1459_CR59","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.rmed.2009.09.006","volume":"104","author":"JJ Swigris","year":"2010","unstructured":"Swigris JJ, Brown KK, Behr J, Du Bois RM, King TE, Raghu G, Wamboldt FS. The SF-36 and SGRQ: validity and first look at minimum important differences in IPF. Respir Med. 2010;104:296\u2013304.","journal-title":"Respir Med"},{"key":"1459_CR60","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1164\/ajrccm\/145.6.1321","volume":"145","author":"PW Jones","year":"1992","unstructured":"Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A Self-complete Measure of Health Status for Chronic Airflow Limitation: The St. George\u2019s respiratory questionnaire. Am Rev Respir Dis. 1992;145:1321\u20137.","journal-title":"Am Rev Respir Dis"},{"key":"1459_CR61","doi-asserted-by":"crossref","unstructured":"Pauling JD, Caetano J, Campochiaro C, De Luca G, Gheorghiu AM, Lazzaroni MG, Khanna D. Patient-reported outcome instruments in clinical trials of systemic sclerosis. J Scleroderma Related Disord. 2019. Epub ahead of print.","DOI":"10.1177\/2397198319886496"},{"key":"1459_CR62","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1136\/ard.2005.050187","volume":"65","author":"D Khanna","year":"2006","unstructured":"Khanna D, Furst DE, Hays RD, Park GS, Wong WK, Seibold JR, Mayes MD, White B, Wigley FF, Weisman M, et al. Minimally important difference in diffuse systemic sclerosis: results from the D-penicillamine study. Ann Rheum Dis. 2006;65:1325\u20139.","journal-title":"Ann Rheum Dis"},{"key":"1459_CR63","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1002\/art.40114","volume":"69","author":"ER Volkmann","year":"2017","unstructured":"Volkmann ER, Tashkin DP, Li N, Roth MD, Khanna D, Hoffmann-Vold AM, Kim G, Goldin J, Clements PJ, Furst DE, Elashoff RM. Mycophenolate Mofetil versus placebo for systemic sclerosis-related interstitial lung disease: an analysis of scleroderma lung studies I and II. Arthritis Rheumatol. 2017;69:1451\u201360.","journal-title":"Arthritis Rheumatol"},{"key":"1459_CR64","doi-asserted-by":"crossref","unstructured":"Milette K, Thombs BD, Dewez S, K\u00f6rner A, Pel\u00e1ez S. Scleroderma patient perspectives on social support from close social relationships. Disabil Rehabil. 2020;42(11):1588\u201398.","DOI":"10.1080\/09638288.2018.1531151"},{"key":"1459_CR65","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.jad.2018.09.075","volume":"243","author":"NL Bragazzi","year":"2019","unstructured":"Bragazzi NL, Watad A, Gizunterman A, McGonagle D, Mahagna H, Comaneshter D, Amital H, Cohen AD, Amital D. The burden of depression in systemic sclerosis patients: a nationwide population-based study. J Affect Disord. 2019;243:427\u201331.","journal-title":"J Affect Disord"},{"key":"1459_CR66","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1093\/rheumatology\/kex410","volume":"57","author":"S Peytrignet","year":"2018","unstructured":"Peytrignet S, Denton CP, Lunt M, Hesselstrand R, Mouthon L, Silman A, Pan X, Brown E, Czirjak L, Distler JHW, et al. Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European scleroderma observational study. Rheumatology (Oxford). 2018;57:370\u201381.","journal-title":"Rheumatology (Oxford)"},{"key":"1459_CR67","doi-asserted-by":"publisher","first-page":"rkz044","DOI":"10.1093\/rap\/rkz044","volume":"3","author":"SIE Liem","year":"2019","unstructured":"Liem SIE, Vliet Vlieland TPM, Schoones JW, de Vries-Bouwstra JK. The effect and safety of exercise therapy in patients with systemic sclerosis: a systematic review. Rheumatol Adv Pract. 2019;3:rkz044.","journal-title":"Rheumatol Adv Pract"},{"key":"1459_CR68","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1136\/thoraxjnl-2016-208638","volume":"72","author":"LM Dowman","year":"2017","unstructured":"Dowman LM, McDonald CF, Hill CJ, Lee AL, Barker K, Boote C, Glaspole I, Goh NSL, Southcott AM, Burge AT, et al. The evidence of benefits of exercise training in interstitial lung disease: a randomised controlled trial. Thorax. 2017;72:610\u20139.","journal-title":"Thorax"},{"key":"1459_CR69","doi-asserted-by":"crossref","unstructured":"Dowman L, Hill CJ, Holland AE. Pulmonary rehabilitation for interstitial lung disease. Cochrane Database Syst Rev. 2014;10:CD006322.","DOI":"10.1002\/14651858.CD006322.pub3"},{"key":"1459_CR70","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1183\/13993003.01335-2015","volume":"46","author":"KC Wilson","year":"2015","unstructured":"Wilson KC, Raghu G. The 2015 Guidelines for idiopathic pulmonary fibrosis: an important chapter in the evolution of the management of patients with IPF. Eur Respir J. 2015;46:883\u20136.","journal-title":"Eur Respir J"},{"key":"1459_CR71","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1164\/rccm.2009-040GL","volume":"183","author":"G Raghu","year":"2011","unstructured":"Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, et al. An official ATS\/ERS\/JRS\/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788\u2013824.","journal-title":"Am J Respir Crit Care Med"},{"key":"1459_CR72","doi-asserted-by":"crossref","unstructured":"Lim RK, Humphreys C, Morisset J, Holland AE, Johannson KA, the ODC. Oxygen in patients with fibrotic interstitial lung disease: an international Delphi survey. Eur Respir J. 2019;54(2):1900421.","DOI":"10.1183\/13993003.00421-2019"},{"key":"1459_CR73","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/S2213-2600(18)30289-3","volume":"6","author":"D Visca","year":"2018","unstructured":"Visca D, Mori L, Tsipouri V, Fleming S, Firouzi A, Bonini M, Pavitt MJ, Alfieri V, Canu S, Bonifazi M, et al. Effect of ambulatory oxygen on quality of life for patients with fibrotic lung disease (AmbOx): a prospective, open-label, mixed-method, crossover randomised controlled trial. Lancet Respir Med. 2018;6:759\u201370.","journal-title":"Lancet Respir Med"},{"key":"1459_CR74","doi-asserted-by":"crossref","unstructured":"Bajwah S, Davies JM, Tanash H, Currow DC, Oluyase AO, Ekstrom M. Safety of benzodiazepines and opioids in interstitial lung disease: a national prospective study. Eur Respir J. 2018;52.","DOI":"10.1183\/13993003.congress-2018.OA3822"},{"key":"1459_CR75","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/S2213-2600(14)70226-7","volume":"2","author":"IJ Higginson","year":"2014","unstructured":"Higginson IJ, Bausewein C, Reilly CC, Gao W, Gysels M, Dzingina M, McCrone P, Booth S, Jolley CJ, Moxham J. An integrated palliative and respiratory care service for patients with advanced disease and refractory breathlessness: a randomised controlled trial. Lancet Respir Med. 2014;2:979\u201387.","journal-title":"Lancet Respir Med"},{"key":"1459_CR76","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.chest.2016.11.052","volume":"151","author":"DP Tashkin","year":"2017","unstructured":"Tashkin DP, Volkmann ER, Tseng CH, Roth MD, Khanna D, Furst DE, Clements PJ, Theodore A, Kafaja S, Kim GH, et al. Improved cough and cough-specific quality of life in patients treated for scleroderma-related interstitial lung disease: results of scleroderma lung study II. Chest. 2017;151:813\u201320.","journal-title":"Chest"},{"key":"1459_CR77","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1164\/rccm.201903-0614PP","volume":"200","author":"MS Wijsenbeek","year":"2019","unstructured":"Wijsenbeek MS, Holland AE, Swigris JJ, Renzoni EA. Comprehensive supportive Care for Patients with Fibrosing interstitial lung disease. Am J Respir Crit Care Med. 2019;200:152\u20139.","journal-title":"Am J Respir Crit Care Med"},{"key":"1459_CR78","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/j.jpainsymman.2016.12.344","volume":"53","author":"M Kalluri","year":"2017","unstructured":"Kalluri M, Richman-Eisenstat J. Early and integrated palliative care to achieve a home death in idiopathic pulmonary fibrosis. J Pain Symptom Manag. 2017;53:1111\u20135..","journal-title":"J Pain Symptom Manag"},{"key":"1459_CR79","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1136\/thoraxjnl-2014-206583","volume":"70","author":"S Bajwah","year":"2015","unstructured":"Bajwah S, Ross JR, Wells AU, Mohammed K, Oyebode C, Birring SS, Patel AS, Koffman J, Higginson IJ, Riley J. Palliative care for patients with advanced fibrotic lung disease: a randomised controlled phase II and feasibility trial of a community case conference intervention. Thorax. 2015;70:830\u20139.","journal-title":"Thorax"},{"key":"1459_CR80","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1136\/annrheumdis-2019-215145","volume":"78","author":"M Becker","year":"2019","unstructured":"Becker M, Graf N, Sauter R, Allanore Y, Curram J, Denton CP, Khanna D, Matucci-Cerinic M, De Oliveira PJ, Pope JE, Distler O. Predictors of disease worsening defined by progression of organ damage in diffuse systemic sclerosis: a European scleroderma trials and research (EUSTAR) analysis. Ann Rheum Dis. 2019;78:1242\u20138.","journal-title":"Ann Rheum Dis"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-020-01459-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12931-020-01459-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-020-01459-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,17]],"date-time":"2022-04-17T16:36:47Z","timestamp":1650213407000},"score":1,"resource":{"primary":{"URL":"https:\/\/respiratory-research.biomedcentral.com\/articles\/10.1186\/s12931-020-01459-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,23]]},"references-count":80,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1459"],"URL":"https:\/\/doi.org\/10.1186\/s12931-020-01459-0","relation":{},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,23]]},"assertion":[{"value":"20 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}],"article-number":"197"}}