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

Guler, Sabina; Winstone, Tiffany A; Murphy, Darra; Hague, Cameron; Soon, Jeanette; Sulaiman, Nada; Li, Kathy H; Dunne, James; Wilcox, Pearce G; Ryerson, Christopher J (2018). Does Systemic Sclerosis-associated Interstitial Lung Disease Burn Out? Specific Phenotypes of Disease Progression. Annals of the American Thoracic Society, 15(12), pp. 1427-1433. American Thoracic Society 10.1513/AnnalsATS.201806-362OC

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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) 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 (-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.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Guler, Sabina


600 Technology > 610 Medicine & health




American Thoracic Society




Rahel Holderegger

Date Deposited:

31 Jan 2019 11:30

Last Modified:

31 Jan 2019 11:30

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

phenotype pulmonary fibrosis respiratory function tests systemic scleroderma


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