Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

Abstract

To assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 ± 5.2 mm vs 19.9 ± 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment.

Clinical characteristics and survival of pulmonary arterial hypertension with or without interstitial lung disease in systemic sclerosis

“…Those with PAH-ILD were more likely to have extensive ILD and a lower FVC than those with ILD-only. This is consistent with recent data demonstrating a higher FVC is associated with better survival in PAH-ILD [10]. Interestingly, whilst univariate analyses indicated worse prognosis with increasing ILD severity, our multivariable model suggested that PAH-ILD with limited ILD conferred a better prognosis than extensive ILD-only.…”

“…Limited data exist in the wider literature to describe individuals with SSc who develop concurrent precapillary PH and ILD. We demonstrated a higher proportion of males in the PAH-ILD group which is consistent with other studies [10,12]. In our cohort, people with both PAH-ILD and PAH-only were older at SSc onset; other data suggest that those with PAH-only may be older than those with ILD-associated PH [12].…”

“…In fact, whilst survival was better in those with SSc-only than limited ILD-only, this did not reach statistical significance. Other studies confirm the dominant importance of PAH in determining survival in PAH-ILD [9,10], finding that the presence of concurrent ILD may not significantly impact survival in SSc-associated precapillary PH. Our study demonstrates that extensive ILD and precapillary PH confers a particularly poor prognosis.…”

“…Up to 75-90% of individuals with SSc may demonstrate some degree of ILD on high-resolution computed tomography (HRCT) [4,5], whilst lifetime prevalence of SSc-PAH is approximately 12% [6,7]. PAH and ILD have been generally viewed as independent manifestations of SSc; however, given the high prevalence of both complications, there is increasing interest in describing individuals who develop both pre-capillary PAH and ILD concurrently [8][9][10]. Existing studies are characterised by modest population size [8,11,12] or are cross-sectional in nature thereby lacking longitudinal data [9].…”

Reproducibility of pulmonary function tests in patients with systemic sclerosis

“…We did not include severe SSc-ILD or patients suffering from severe PAH due to practical issues for the patients. Note that a recent study reports that global survival of PAH-SSc patients was not affected by ILD regardless its severity 22 . Therefore, it is recommended to carry out further research in this line.…”