Emphysema and interstitial lung disease in systemic sclerosis-related pulmonary hypertension

Abstract

Pulmonary hypertension (PH) is a major cause of morbidity and mortality among patients with systemic sclerosis (SSc) [ [1] Steen V.D. Medsger T.A. Changes in causes of death in systemic sclerosis, 1972-2002. Ann. Rheum. Dis. 2007 Feb 2; 66 (PMCID: PMC1955114): 940-944 Crossref PubMed Scopus (1174) Google Scholar ]. Patients with SSc-PH and concomitant interstitial lung disease (ILD) have worse clinical outcomes compared to those with SSc-PH, alone [ 2 Chauvelot L. Gamondes D. Berthiller J. Nieves A. Renard S. Catella-Chatron J. Ahmad K. Bertoletti L. Camara B. Gomez E. Launay D. Montani D. Mornex J.F. Prévot G. Sanchez O. Schott A.M. Subtil F. Traclet J. Turquier S. Zeghmar S. Habib G. Reynaud-Gaubert M. Humbert M. Cottin V. Hemodynamic response to treatment and outcomes in pulmonary hypertension associated with interstitial lung disease versus pulmonary arterial hypertension in systemic sclerosis: data from a study identifying prognostic factors in pulmonary hypertension associated with interstitial lung disease. Arthritis Rheumatol Hoboken NJ. 2021 Feb; 73 (PMID: 32892515): 295-304 Google Scholar , 3 Le Pavec J. Girgis R.E. Lechtzin N. Mathai S.C. Launay D. Hummers L.K. Zaiman A. Sitbon O. Simonneau G. Humbert M. Hassoun P.M. Systemic sclerosis-related pulmonary hypertension associated with interstitial lung disease: impact of pulmonary arterial hypertension therapies. Arthritis Rheum. 2011 Aug; 63 (PMID: 21538327): 2456-2464 Crossref PubMed Scopus (102) Google Scholar , 4 Mathai S.C. Hummers L.K. Champion H.C. Wigley F.M. Zaiman A. Hassoun P.M. Girgis R.E. Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease. Arthritis Rheum. 2009 Feb; 60 (PMID: 19180517): 569-577 Crossref PubMed Scopus (208) Google Scholar ]. In patients with increasing ILD severity, as assessed by forced vital capacity (FVC), there is a trend toward increased all-cause mortality [ [5] Sangani R.A. Lui J.K. Gillmeyer K.R. Trojanowski M.A. Bujor A.M. LaValley M.P. Klings E.S. Clinical Characteristics and outcomes in pulmonary manifestations of systemic sclerosis: contribution from pulmonary hypertension and interstitial lung disease severity. Pulm. Circ. 2022 Jul 16; (pul2.12117) Crossref Scopus (0) Google Scholar ]. Common in restrictive lung diseases including ILD [ [5] Sangani R.A. Lui J.K. Gillmeyer K.R. Trojanowski M.A. Bujor A.M. LaValley M.P. Klings E.S. Clinical Characteristics and outcomes in pulmonary manifestations of systemic sclerosis: contribution from pulmonary hypertension and interstitial lung disease severity. Pulm. Circ. 2022 Jul 16; (pul2.12117) Crossref Scopus (0) Google Scholar ], reduced FVC also occur in obstructive lung diseases, including chronic obstructive pulmonary disease (COPD), which can also affect SSc patients. To date, little is known about the impact of concurrent obstructive lung disease in SSc-PH which may both confound FVC on pulmonary function testing (PFT) used as a marker for ILD severity [ [5] Sangani R.A. Lui J.K. Gillmeyer K.R. Trojanowski M.A. Bujor A.M. LaValley M.P. Klings E.S. Clinical Characteristics and outcomes in pulmonary manifestations of systemic sclerosis: contribution from pulmonary hypertension and interstitial lung disease severity. Pulm. Circ. 2022 Jul 16; (pul2.12117) Crossref Scopus (0) Google Scholar ], and its contribution to overall mortality [ [6] Koo B.S. Park K.Y. Lee H.J. Kim H.J. Ahn H.S. Yim S.Y. Jun J.B. Effect of combined pulmonary fibrosis and emphysema on patients with connective tissue diseases and systemic sclerosis: a systematic review and meta-analysis. Arthritis Res. Ther. 2021 Apr 6; 23 (PMCID: PMC8022385): 100 Crossref Scopus (4) Google Scholar , [7] Ariani A. Silva M. Bravi E. Parisi S. Saracco M. De Gennaro F. Caimmi C. Girelli F. De Santis M. Volpe A. Lumetti F. Hax V. Bredemeier M. Alfieri V. Santilli D. Bodini F.C. Lucchini G. Mozzani F. Seletti V. Bacchini E. Arrigoni E. Giuggioli D. Chakr R. Idolazzi L. Bertorelli G. Imberti D. Michieletti E. Paolazzi G. Fusaro E. Chetta A.A. Scirè C.A. Sverzellati N. Overall mortality in combined pulmonary fibrosis and emphysema related to systemic sclerosis. RMD Open. 2019; 5 (PMCID: PMC6397433)e000820 Crossref Scopus (14) Google Scholar ]. Our goal in this study was to characterize the impact of FVC on clinical outcomes in SSc-PH when adjusted for radiologic ILD/emphysema. We hypothesized that FVC decline in any hypoxic lung disease, regardless of etiology, was associated with increased transplant-free, all-cause mortality in SSc-PH.