Predictors of Mortality in Progressive Fibrosing Interstitial Lung Diseases

Abstract

Background: Progressive fibrosing interstitial lung disease (PF-ILD) and idiopathic pulmonary fibrosis (IPF) share similar progression phenotype but with different pathophysiological mechanism. The purpose of this study was to assess clinical characteristics and outcomes of patients with PF-ILD in a single-center cohort. Methods: Patients with PF-ILD treated in Shanghai Pulmonary Hospital from Jan. 2013 to Dec. 2014 were retrospectively analyzed. Baseline characteristics and clinical outcomes were collected for survival analysis to identifying clinical predictors of mortality. Results: Among 608 patients with ILD, 132 patients met the diagnostic criteria for PF-ILD. In this single-center cohort, there were 51 (38.6%) cases with connective tissue disease-associated interstitial lung disease (CTD-ILD) and 45 (34.1%) with unclassifiable ILDs. During follow-up, 83 patients (62.9%) either died (N = 79, 59.8%) or underwent lung transplantations (N = 4, 3.0%) with a median duration follow-up time of 53.7 months. Kaplan-Meier survival curves revealed that the 1, 3 and 5-years survival of PF-ILD were 90.9, 58.8 and 48.1%, respectively. In addition, the prognosis of patients with PF-ILD was similar to those with IPF, while it was worse than non-PF-ILD ones. Multivariate Cox regression analysis demonstrated that high-resolution computed tomography (HRCT) scores (HR 1.684, 95% CI 1.017-2.788, p = 0.043) and systolic pulmonary artery pressure (SPAP) > 36.5 mmHg (HR 3.619, 95%CI 1.170-11.194, p = 0.026) were independent risk factors for the mortality of PF-ILD. Conclusion: Extent of fibrotic changes on HRCT and pulmonary hypertension were predictors of mortality in patients with PF-ILD.

Keywords: fibrotic changes; high-resolution computed tomography; predictor of mortality; progressive fibrosing interstitial lung disease; pulmonary arterial hypertension.

FIGURE 1

Flow chart of enrollment; Abbreviation: PF-ILD, progressive fibrosing interstitial lung disease; IPF, idiopathic pulmonary fibrosis.

FIGURE 2

Classifications of PF-ILD in this study; Abbreviations: PF-ILD, progressive fibrosing interstitial lung disease; CTD-ILD, connective tissue disease-associated interstitial lung disease; CPFE, combined pulmonary fibrosis and emphysema; IPAF, interstitial pneumonia with autoimmune features; PAP, pulmonary alveolar proteinosis; RBILD, respiratory bronchiolitis-associated interstitial lung disease; NSIP, nonspecific interstitial pneumonia; HP, Hypersensitivity pneumonitis. Number of cases: CTD-ILD = 51, Unclassifiable ILD = 45, IPAF = 11, NSIP = 10, CPFE = 7, PAP = 2, RBILD = 2, Pneumoconiosis = 2, HP = 2.

FIGURE 3

Survival curves of PF-ILD (A) Survival curves of PF-ILD, non PF-ILD and IPF. Kaplan-Meier survival analysis showed no difference between PF-ILD and IPF group (p = 0.305). But significant difference was seen in PF-ILD group and non PF-ILD group (p < 0.001). The median survival times were 54 (95%CI: 39-69) and 58 (95%CI: 37-79) months in IPF and PF-ILD group respectively, NA in non PF-ILD group (B) Survival curves of subgroups of PF-ILD. Kaplan-Meier survival analysis showing a significant difference between groups (p = 0 001), a higher mortality in NSIP subgroup and a lower mortality in CTD-ILD + IPAF subgroup. The median survival times were 108 (95%CI: 64-152), 39 (95%CI: 4-74), 25 (95%CI: 19-31), 48 (95%CI: 33-63) months in CTD-ILD + IPAF, Unclassifiable ILD, NSIP and other ILDs groups respectively.; Abbreviations: PF-ILD, progressive fibrosing interstitial lung disease; IPF, idiopathic pulmonary fibrosis; CTD-ILD, connective tissue disease-associated interstitial lung disease; IPAF, interstitial pneumonia with autoimmune features; NSIP, nonspecific interstitial pneumonia.

FIGURE 4

Multivariate regression analysis of mortality; Abbreviations: SPAP, systolic pulmonary artery pressure; HRCT: high-resolution computed tomography; HR, hazard ratio. Cox regression analysis suggested that SPAP >36.5 mmHg and HRCT scores were independent risk factors for mortality in patients with PF-ILD (p = 0.026, 0.043 respectively).

FIGURE 5

Survival curves according to risk factors for mortality (A) Survival curves according to SPAP with a 36.5 mmHg threshold. Log-rank p = 0.001. The median survival times were 43 (95%CI: 23-63) months in SPAP >36.5 mmHg group and NA in SPAP ≤36.5 mmHg group (B) Survival curves according to HRCT scores. Log-rank p < 0.001. The median survival times were 108 (95%CI: 68-148) months in 2-point group, 39 (95%CI: 20-58) months in 3-point group, 21 (95%CI:17-25) months in 4-point group, and NA in 1-point group.; Abbreviations: SPAP, systolic pulmonary artery pressure; HRCT: high-resolution computed tomography.