Does Systemic Sclerosis-associated Interstitial Lung Disease Burn Out? Specific Phenotypes of Disease Progression

Abstract

Rationale: Previous studies have suggested that interstitial lung disease (ILD) progresses most rapidly early in the course of systemic sclerosis-associated (SSc)-ILD, and that SSc-ILD is often more stable or even "burned out" after the first 4 years following diagnosis.

Objectives: Our objectives were to determine whether an apparent plateau in pulmonary function decline is due to survival bias and to identify distinct prognostic phenotypes of ILD progression.

Methods: Consecutive patients with SSc-ILD from a single center were included. Pulmonary function measurements were typically performed every 6 months. Study participants were categorized into long-term survivors (>8 yr survival from diagnosis), and those with medium-term and short-term mortality (4-8 and <4 yr survival, respectively). We excluded those censored with less than 8 years of follow-up. Subject-specific slopes for change in forced vital capacity (FVC) and diffusing capacity of the lung for carbon monoxide (Dl_CO) were calculated using generalized linear models with mixed effects. The rate of decline in FVC was compared across prognostic groups.

Results: The cohort included 171 study participants with SSc-ILD. A plateau in the progression of FVC was apparent in the full cohort analysis but disappeared with stratification into prognostic subgroups to account for survival bias. Those with short-term mortality had a higher annual rate of decline in FVC (-4.10 [95% confidence interval (CI), -7.92 to -0.28] vs. -2.14 [95% CI, -3.31 to -0.97] and -0.94 [-1.46 to -0.42]; P = 0.003) and Dl_CO (-5.28 [95% CI, -9.58 to -0.99] vs. -3.13 [95% CI, -4.35 to -1.92] and -1.32 [95% CI, -2.01 to -0.63]; P < 0.001) than those with medium-term mortality and long-term survival with adjustment for age, sex, and pack-years. Change in FVC in the previous year did not predict FVC change in the subsequent year.

Conclusions: Adults with SSc-ILD have distinct patterns of physiological progression that remain relatively consistent during long-term follow-up; however, recent change in FVC cannot be used to predict future change in FVC within shorter follow-up intervals. The findings of this study provide important information on the course of disease in SSc-ILD and identify specific phenotypes of progression that may improve clinical decision-making and design of future therapeutic trials.

Keywords: phenotype; pulmonary fibrosis; respiratory function tests; systemic scleroderma.