Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972–2002. Ann Rheum Dis. 2007;66(7):940–4.
Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery JL, Barbera JA, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009;34(6):1219–63.
McGoon MD, Benza RL, Escribano-Subias P, Jiang X, Miller DP, Peacock AJ, et al. Pulmonary arterial hypertension: epidemiology and registries. J Am Coll Cardiol. 2013;62(25 Suppl):D51–9.
Humbert M, Sitbon O, Chaouat A, Bertocchi M, Habib G, Gressin V, et al. Pulmonary arterial hypertension in France: results from a national registry. Am J Respir Crit Care Med. 2006;173(9):1023–30.
Simonneau G, Gatzoulis MA, Adatia I, Celermajer D, Denton C, Ghofrani A, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D34–41.
Hachulla E, Gressin V, Guillevin L, Carpentier P, Diot E, Sibilia J, et al. Early detection of pulmonary arterial hypertension in systemic sclerosis: a French nationwide prospective multicenter study. Arthritis Rheum. 2005;52(12):3792–800.
Avouac J, Airo P, Meune C, Beretta L, Dieude P, Caramaschi P, et al. Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and metaanalysis of 5 studies. J Rheumatol. 2010;37(11):2290–8.
Hachulla E, de Groote P, Gressin V, Sibilia J, Diot E, Carpentier P, et al. The three-year incidence of pulmonary arterial hypertension associated with systemic sclerosis in a multicenter nationwide longitudinal study in France. Arthritis Rheum. 2009;60(6):1831–9.
Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004;351(14):1425–36.
Humbert M, Sitbon O, Yaici A, Montani D, O’Callaghan DS, Jais X, et al. Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur Respir J. 2010;36(3):549–55.
Gutsche M, Rosen GD, Swigris JJ. Connective tissue disease-associated interstitial lung disease: a review. Curr Respir Care Rep. 2012;1:224–32.
Moore OA, Goh N, Corte T, Rouse H, Hennessy O, Thakkar V, et al. Extent of disease on high-resolution computed tomography lung is a predictor of decline and mortality in systemic sclerosis-related interstitial lung disease. Rheumatology (Oxford). 2013;52(1):155–60.
Bauer PR, Schiavo DN, Osborn TG, Levin DL, St Sauver J, Hanson AC, et al. Influence of interstitial lung disease on outcome in systemic sclerosis: a population-based historical cohort study. Chest. 2013;144(2):571–7.
Tyndall AJ, Bannert B, Vonk M, Airo P, Cozzi F, Carreira PE, et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR scleroderma trials and research (EUSTAR) database. Ann Rheum Dis. 2010;69(10):1809–15.
Wells AU, Margaritopoulos GA, Antoniou KM, Denton C. Interstitial lung disease in systemic sclerosis. Semin Respir Crit Care Med. 2014;35(2):213–21.
Gashouta MA, Humbert M, Hassoun PM. Update in systemic sclerosis-associated pulmonary arterial hypertension. Presse Med. 2014;43(10 Pt 2):e293–304.
Humbert M, Yaici A, de Groote P, Montani D, Sitbon O, Launay D, et al. Screening for pulmonary arterial hypertension in patients with systemic sclerosis: clinical characteristics at diagnosis and long-term survival. Arthritis Rheum. 2011;63(11):3522–30. Indirect evidence that early PAH detection might translate into better long-term outcomes in systemic sclerosis.
Khanna D, Gladue H, Channick R, Chung L, Distler O, Furst DE, et al. Recommendations for screening and detection of connective tissue disease-associated pulmonary arterial hypertension. Arthritis Rheum. 2013;65(12):3194–201. Recent recommendations for screening for CTD-associated PAH.
Hoeper MM, Bogaard HJ, Condliffe R, Frantz R, Khanna D, Kurzyna M, et al. Definitions and diagnosis of pulmonary hypertension. J Am Coll Cardiol. 2013;62(25 Suppl):D42–50.
Coghlan JG, Denton CP, Grunig E, Bonderman D, Distler O, Khanna D, et al. Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study. Ann Rheum Dis. 2014;73(7):1340–9. Evidence-based PAH detection score in a subset of systemic sclerosis patients diagnosed for more than 3 years and with a DLCO<60%.
Distler JH, Hoeper MM, Distler O. Diagnosis of pulmonary arterial hypertension in a patient with systemic sclerosis. Nat Clin Pract Rheumatol. 2008;4(3):160–4.
Parks JL, Taylor MH, Parks LP, Silver RM. Systemic sclerosis and the heart. Rheum Dis Clin N Am. 2014;40(1):87–102.
Kahan A, Coghlan G, McLaughlin V. Cardiac complications of systemic sclerosis. Rheumatology (Oxford). 2009;48(3):45–8.
Coghlan G. Does left heart disease cause most systemic sclerosis associated pulmonary hypertension? Eur Respir J. 2013;42(4):888–90.
Fox BD, Shimony A, Langleben D, Hirsch A, Rudski L, Schlesinger R, et al. High prevalence of occult left heart disease in scleroderma-pulmonary hypertension. Eur Respir J. 2013;42(4):1083–91.
Fisher MR, Mathai SC, Champion HC, Girgis RE, Housten-Harris T, Hummers L, et al. Clinical differences between idiopathic and scleroderma-related pulmonary hypertension. Arthritis Rheum. 2006;54(9):3043–50.
Vonk-Noordegraaf A, Westerhof N. Describing right ventricular function. Eur Respir J. 2013;41(6):1419–23.
Overbeek MJ, Lankhaar JW, Westerhof N, Voskuyl AE, Boonstra A, Bronzwaer JG, et al. Right ventricular contractility in systemic sclerosis-associated and idiopathic pulmonary arterial hypertension. Eur Respir J. 2008;31(6):1160–6.
Montani D, Savale L, Natali D, Jais X, Herve P, Garcia G, et al. Long-term response to calcium-channel blockers in non-idiopathic pulmonary arterial hypertension. Eur Heart J. 2010;31(15):1898–907.
Olsson KM, Delcroix M, Ghofrani HA, Tiede H, Huscher D, Speich R, et al. Anticoagulation and survival in pulmonary arterial hypertension: results from the comparative, prospective registry of newly initiated therapies for pulmonary hypertension (COMPERA). Circulation. 2014;129(1):57–65.
Henkens IR, Hazenoot T, Boonstra A, Huisman MV, Vonk-Noordegraaf A. Major bleeding with vitamin K antagonist anticoagulants in pulmonary hypertension. Eur Respir Jrnal. 2013;41(4):872–8.
Humbert MLE, Montani D, Jaïs X, Sitbon O, Simonneau G. Advances in therapeutic interventions for patients with pulmonary arterial hypertension. Circulation 2014;130(24):2189–208.
Badesch DB, Tapson VF, McGoon MD, Brundage BH, Rubin LJ, Wigley FM, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med. 2000;132(6):425–34.
Pulido T, Adzerikho I, Channick RN, Delcroix M, Galie N, Ghofrani HA, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med. 2013;369(9):809–18.
Galie N, Badesch D, Oudiz R, Simonneau G, McGoon MD, Keogh AM, et al. Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2005;46(3):529–35.
Galie N, Ghofrani HA, Torbicki A, Barst RJ, Rubin LJ, Badesch D, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med. 2005;353(20):2148–57.
Galie N, Brundage BH, Ghofrani HA, Oudiz RJ, Simonneau G, Safdar Z, et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation. 2009;119(22):2894–903.
Ghofrani HA, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013;369(4):330–40.
Simonneau G, Rubin LJ, Galie N, Barst RJ, Fleming TR, Frost AE, et al. Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial. Ann Intern Med. 2008;149(8):521–30.
Sitbon O, Jais X, Savale L, Cottin V, Bergot E, Macari EA, et al. Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study. Eur Respir J. 2014;43(6):1691–7.
Hoeper MM, Barst RJ, Bourge RC, Feldman J, Frost AE, Galie N, et al. Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation. 2013;127(10):1128–38.
Schachna L, Medsger Jr TA, Dauber JH, Wigley FM, Braunstein NA, White B, et al. Lung transplantation in scleroderma compared with idiopathic pulmonary fibrosis and idiopathic pulmonary arterial hypertension. Arthritis Rheum. 2006;54(12):3954–61.
Launay D, Savale L, Berezne A, Le Pavec J, Hachulla E, Mouthon L, et al. Lung and heart–lung transplantation for systemic sclerosis patients. A monocentric experience of 13 patients, review of the literature and position paper of a multidisciplinary working group. Presse Med. 2014;43(10):e345–63. A position paper attempting to identify the SSc patients who are best candidates for lung transplantation.
Hassoun PM, Mouthon L, Barbera JA, Eddahibi S, Flores SC, Grimminger F, et al. Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol. 2009;54(1 Suppl):S10–9.
Dorfmuller P, Humbert M, Perros F, Sanchez O, Simonneau G, Muller KM, et al. Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases. Hum Pathol. 2007;38(6):893–902.
O’Callaghan DS, Dorfmuller P, Jais X, Mouthon L, Sitbon O, Simonneau G, et al. Pulmonary veno-occlusive disease: the bete noire of pulmonary hypertension in connective tissue diseases? Presse Med. 2011;40(1 Pt 2):e65–78.
Tamby MC, Humbert M, Guilpain P, Servettaz A, Dupin N, Christner JJ, et al. Antibodies to fibroblasts in idiopathic and scleroderma-associated pulmonary hypertension. Eur Respir J. 2006;28(4):799–807.
Schurawitzki H, Stiglbauer R, Graninger W, Herold C, Polzleitner D, Burghuber OC, et al. Interstitial lung disease in progressive systemic sclerosis: high-resolution CT versus radiography. Radiology. 1990;176(3):755–9.
Launay D, Remy-Jardin M, Michon-Pasturel U, Mastora I, Hachulla E, Lambert M, et al. High resolution computed tomography in fibrosing alveolitis associated with systemic sclerosis. J Rheumatol. 2006;33(9):1789–801.
De Santis M, Bosello S, La Torre G, Capuano A, Tolusso B, Pagliari G, et al. Functional, radiological and biological markers of alveolitis and infections of the lower respiratory tract in patients with systemic sclerosis. Respir Res. 2005;6:96.
Desai SR, Veeraraghavan S, Hansell DM, Nikolakopolou A, Goh NS, Nicholson AG, et al. CT features of lung disease in patients with systemic sclerosis: comparison with idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Radiology. 2004;232(2):560–7.
Douglas WW, Tazelaar HD, Hartman TE, Hartman RP, Decker PA, Schroeder DR, et al. Polymyositis-dermatomyositis-associated interstitial lung disease. Am J Respir Crit Care Med. 2001;164(7):1182–5.
Wells AU, Hansell DM, Corrin B, Harrison NK, Goldstraw P, Black CM, et al. High resolution computed tomography as a predictor of lung histology in systemic sclerosis. Thorax. 1992;47(9):738–42.
Remy-Jardin M, Giraud F, Remy J, Copin MC, Gosselin B, Duhamel A. Importance of ground-glass attenuation in chronic diffuse infiltrative lung disease: pathologic-CT correlation. Radiology. 1993;189(3):693–8.
Shah RM, Jimenez S, Wechsler R. Significance of ground-glass opacity on HRCT in long-term follow-up of patients with systemic sclerosis. J Thorac Imaging. 2007;22(2):120–4.
Wells AU. Pulmonary function tests in connective tissue disease. Semin Respir Crit Care Med. 2007;28(4):379–88.
Steen VD, Conte C, Owens GR, Medsger Jr TA. Severe restrictive lung disease in systemic sclerosis. Arthritis Rheum. 1994;37(9):1283–9.
Peters-Golden M, Wise RA, Hochberg MC, Stevens MB, Wigley FM. Carbon monoxide diffusing capacity as predictor of outcome in systemic sclerosis. Am J Med. 1984;77(6):1027–34.
Morgan C, Knight C, Lunt M, Black CM, Silman AJ. Predictors of end stage lung disease in a cohort of patients with scleroderma. Ann Rheum Dis. 2003;62(2):146–50.
Wells AU, Cullinan P, Hansell DM, Rubens MB, Black CM, Newman-Taylor AJ, et al. Fibrosing alveolitis associated with systemic sclerosis has a better prognosis than lone cryptogenic fibrosing alveolitis. Am J Respir Crit Care Med. 1994;149(6):1583–90.
Wells AU, Hansell DM, Rubens MB, King AD, Cramer D, Black CM, et al. Fibrosing alveolitis in systemic sclerosis: indices of lung function in relation to extent of disease on computed tomography. Arthritis Rheum. 1997;40(7):1229–36.
Wells AU, Denton CP. Interstitial lung disease in connective tissue disease-mechanisms and management. Nature reviews Rheumatology. 2014;10(12):728–39. Comprehensive review on the current knowledge on interstitial lung disease in connective tissue disorders, including a section on SSc ILD.
Steen V. Predictors of end stage lung disease in systemic sclerosis. Ann Rheum Dis. 2003;62(2):97–9.
Goh NS, Desai SR, Veeraraghavan S, Hansell DM, Copley SJ, Maher TM, et al. Interstitial lung disease in systemic sclerosis: a simple staging system. Am J Respir Crit Care Med. 2008;177(11):1248–54.
Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, et al. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006;354(25):2655–66.
Latsi PI, Wells AU. Evaluation and management of alveolitis and interstitial lung disease in scleroderma. Curr Opin Rheumatol. 2003;15(6):748–55.
Hant FN, Ludwicka-Bradley A, Wang HJ, Li N, Elashoff R, Tashkin DP, et al. Surfactant protein D and KL-6 as serum biomarkers of interstitial lung disease in patients with scleroderma. J Rheumatol. 2009;36(4):773–80.
Ohnishi H, Yokoyama A, Kondo K, Hamada H, Abe M, Nishimura K, et al. Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med. 2002;165(3):378–81.
Hasegawa M, Fujimoto M, Hamaguchi Y, Matsushita T, Inoue K, Sato S, et al. Use of serum clara cell 16-kDa (CC16) levels as a potential indicator of active pulmonary fibrosis in systemic sclerosis. J Rheumatol. 2011;38(5):877–84.
Bonella F, Volpe A, Caramaschi P, Nava C, Ferrari P, Schenk K, et al. Surfactant protein D and KL-6 serum levels in systemic sclerosis: correlation with lung and systemic involvement. Sarcoidosis Vasc Diffuse Lung Dis. 2011;28(1):27–33.
De Lauretis A, Sestini P, Pantelidis P, Hoyles R, Hansell DM, Goh NS, et al. Serum interleukin 6 is predictive of early functional decline and mortality in interstitial lung disease associated with systemic sclerosis. J Rheumatol. 2013;40(4):435–46.
Kowal-Bielecka O, Landewe R, Avouac J, Chwiesko S, Miniati I, Czirjak L, et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis. 2009;68(5):620–8.
Hoyles RK, Ellis RW, Wellsbury J, Lees B, Newlands P, Goh NS, 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 Rheum. 2006;54(12):3962–70.
Goldin J, Elashoff R, Kim HJ, Yan X, Lynch D, Strollo D, et al. Treatment of scleroderma-interstitial lung disease with cyclophosphamide is associated with less progressive fibrosis on serial thoracic high-resolution CT scan than placebo: findings from the scleroderma lung study. Chest. 2009;136(5):1333–40.
Khanna D, Yan X, Tashkin DP, Furst DE, Elashoff R, Roth MD, et al. Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: results from the scleroderma lung study. Arthritis Rheum. 2007;56(5):1676–84.
Tashkin DP, Elashoff R, Clements PJ, Roth MD, Furst DE, Silver RM, et al. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am J Respir Crit Care Med. 2007;176(10):1026–34.
Nagaraja V, Denton CP, Khanna D. Old medications and new targeted therapies in systemic sclerosis. Rheumatology (Oxford). 2014.
Berezne A, Valeyre D, Ranque B, Guillevin L, Mouthon L. Interstitial lung disease associated with systemic sclerosis: what is the evidence for efficacy of cyclophosphamide? Ann N Y Acad Sci. 2007;1110:271–84.
Monach PA, Arnold LM, Merkel PA. Incidence and prevention of bladder toxicity from cyclophosphamide in the treatment of rheumatic diseases: a data-driven review. Arthritis Rheum. 2010;62(1):9–21.
Li J, Dai G, Zhang Z. General adverse response to cyclophosphamide in Chinese patients with systemic autoimmune diseases in recent decade—a single-center retrospective study. Clin Rheumatol. 2014. doi:10.1007/s10067-014-2748-2.
Abhishek A, Yazdani R, Pearce F, Regan M, Lim K, Hubbard R, et al. Outcome of systemic sclerosis associated interstitial lung disease treated with intravenous cyclophosphamide. Clin Rheumatol. 2011;30(8):1099–104.
Poormoghim H, Moradi Lakeh M, Mohammadipour M, Sodagari F, Toofaninjed N. Cyclophosphamide for scleroderma lung disease: a systematic review and meta-analysis. Rheumatol Int. 2012;32(8):2431–44.
Roth MD, Tseng CH, Clements PJ, Furst DE, Tashkin DP, Goldin JG, et al. Predicting treatment outcomes and responder subsets in scleroderma-related interstitial lung disease. Arthritis Rheum. 2011;63(9):2797–808.
Koutroumpas A, Ziogas A, Alexiou I, Barouta G, Sakkas LI. Mycophenolate mofetil in systemic sclerosis-associated interstitial lung disease. Clin Rheumatol. 2010;29(10):1167–8.
Zamora AC, Wolters PJ, Collard HR, Connolly MK, Elicker BM, Webb WR, et al. Use of mycophenolate mofetil to treat scleroderma-associated interstitial lung disease. Respir Med. 2008;102(1):150–5.
Gerbino AJ, Goss CH, Molitor JA. Effect of mycophenolate mofetil on pulmonary function in scleroderma-associated interstitial lung disease. Chest. 2008;133(2):455–60.
Panopoulos ST, Bournia VK, Trakada G, Giavri I, Kostopoulos C, Sfikakis PP. Mycophenolate versus cyclophosphamide for progressive interstitial lung disease associated with systemic sclerosis: a 2-year case control study. Lung. 2013;191(5):483–9.
Liossis SN, Bounas A, Andonopoulos AP. Mycophenolate mofetil as first-line treatment improves clinically evident early scleroderma lung disease. Rheumatology (Oxford). 2006;45(8):1005–8.
Mendoza FA, Nagle SJ, Lee JB, Jimenez SA. A prospective observational study of mycophenolate mofetil treatment in progressive diffuse cutaneous systemic sclerosis of recent onset. J Rheumatol. 2012;39(6):1241–7.
Le EN, Wigley FM, Shah AA, Boin F, Hummers LK. Long-term experience of mycophenolate mofetil for treatment of diffuse cutaneous systemic sclerosis. Ann Rheum Dis. 2011;70(6):1104–7.
Nihtyanova SI, Brough GM, Black CM, Denton CP. Mycophenolate mofetil in diffuse cutaneous systemic sclerosis—a retrospective analysis. Rheumatology (Oxford). 2007;46(3):442–5.
Simeon-Aznar CP, Fonollosa-Pla V, Tolosa-Vilella C, Selva-O’Callaghan A, Solans-Laque R, Vilardell-Tarres M. Effect of mycophenolate sodium in scleroderma-related interstitial lung disease. Clin Rheumatol. 2011;30(11):1393–8.
Swigris JJ, Olson AL, Fischer A, Lynch DA, Cosgrove GP, Frankel SK, et al. Mycophenolate mofetil is safe, well tolerated, and preserves lung function in patients with connective tissue disease-related interstitial lung disease. Chest. 2006;130(1):30–6.
Khanna D, Roth M, Furst D, Clements P, Goldin J, Arriola E, et al. FRI0396 Double-blind comparison of mycophenolate mofetil and oral cyclophosphamide for treatment of scleroderma-related interstitial lung disease (scleroderma lung study [SLS] II): rationale, design, methods, baseline characteristics and patient disposition. Ann Rheum Dis. 2013;72 Suppl 3:A507.
Jordan S, Distler JH, Maurer B, Huscher D, van Laar JM, Allanore Y, et al. Effects and safety of rituximab in systemic sclerosis: an analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis. 2014. doi:10.1136/annrheumdis-2013-204522.Observational evidence that Rituximab can reduce the decline in lung function in patients with SSc ILD.
Khanna D DC, van Laar JM, Jahreis A, Cheng S, Spotswood H, Siegel J, Furst DE, on behalf of FaSScinate Clinical Trial in Patients With SS. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis: week 24 data from a phase 2/3 trial. Arthritis and Rheumatology. 2014;66(11 (Supplement)):S386.
van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, et al. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. Jama. 2014;311(24):2490–8. First phase 3 randomized controlled trial showing longer event-free survival and improvement in lung function in scleroderma patients treated with hematopoietic stem cell transplantation.
Herzog EL, Mathur A, Tager AM, Feghali-Bostwick C, Schneider F, Varga J. Review: interstitial lung disease associated with systemic sclerosis and idiopathic pulmonary fibrosis: how similar and distinct? Arthritis Rheumatol. 2014;66(8):1967–78.
Richeldi L, du Bois RM, Raghu G, Azuma A, Brown KK, Costabel U, et al. Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2071–82. Randomized controlled study showing a significant reduction in the annual rate of decline in FVC in patients with idiopathic lung fibrosis treated with nintedanib vs placebo.
King Jr TE, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370(22):2083–92. Randomized controlled trials showing a significantly decreased progression of the decline in lung function in patients with idiopathic lung fibrosis treated with pirfenidone.