Sabina A Guler1,2,3, Tiffany A Winstone1,2, Darra Murphy4, Cameron Hague4, Jeanette Soon4, Nada Sulaiman4, Kathy H Li5,6, James Dunne1, Pearce G Wilcox1, Christopher J Ryerson1,2. 1. 1 Department of Medicine. 2. 2 Centre for Heart Lung Innovation. 3. 3 Department of Pulmonary Medicine, University Hospital and University of Bern, Bern, Switzerland; and. 4. 4 Department of Radiology. 5. 6 Collaboration for Outcomes Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada. 6. 5 Centre for Health Evaluation and Outcome Sciences, Providence Healthcare, St. Paul's Hospital, Vancouver, British Columbia, Canada.
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 (DlCO) 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 DlCO (-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.
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 (DlCO) 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 DlCO (-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.
Entities:
Keywords:
phenotype; pulmonary fibrosis; respiratory function tests; systemic scleroderma
Authors: G S R S N K Naidu; Shefali Khanna Sharma; M B Adarsh; Varun Dhir; Anindita Sinha; Sahajal Dhooria; Sanjay Jain Journal: Rheumatol Int Date: 2019-12-07 Impact factor: 2.631
Authors: David Roofeh; Shaney L Barratt; Athol U Wells; Leticia Kawano-Dourado; Donald Tashkin; Vibeke Strand; James Seibold; Susanna Proudman; Kevin K Brown; Paul F Dellaripa; Tracy Doyle; Thomas Leonard; Eric L Matteson; Chester V Oddis; Joshua J Solomon; Jeffrey A Sparks; Robert Vassallo; Lara Maxwell; Dorcas Beaton; Robin Christensen; Whitney Townsend; Dinesh Khanna Journal: Semin Arthritis Rheum Date: 2021-08-20 Impact factor: 5.431
Authors: Christian Stock; Oliver Distler; Toby M Maher; Arnaud Bourdin; Elizabeth R Volkmann; Serena Vettori; Jörg H W Distler; Margarida Alves Journal: Respir Res Date: 2022-07-05
Authors: Anna-Maria Hoffmann-Vold; Yannick Allanore; Elisabeth Bendstrup; Cosimo Bruni; Oliver Distler; Toby M Maher; Marlies Wijsenbeek; Michael Kreuter Journal: Respir Res Date: 2020-07-23
Authors: Adelle S Jee; Robert Sheehy; Peter Hopkins; Tamera J Corte; Christopher Grainge; Lauren K Troy; Karen Symons; Lissa M Spencer; Paul N Reynolds; Sally Chapman; Sally de Boer; Taryn Reddy; Anne E Holland; Daniel C Chambers; Ian N Glaspole; Helen E Jo; Jane F Bleasel; Jeremy P Wrobel; Leona Dowman; Matthew J S Parker; Margaret L Wilsher; Nicole S L Goh; Yuben Moodley; Gregory J Keir Journal: Respirology Date: 2020-11-24 Impact factor: 6.424
Authors: Kevin K Brown; Fernando J Martinez; Simon L F Walsh; Victor J Thannickal; Antje Prasse; Rozsa Schlenker-Herceg; Rainer-Georg Goeldner; Emmanuelle Clerisme-Beaty; Kay Tetzlaff; Vincent Cottin; Athol U Wells Journal: Eur Respir J Date: 2020-06-25 Impact factor: 16.671
Authors: Toby M Maher; Maureen D Mayes; Michael Kreuter; Elizabeth R Volkmann; Martin Aringer; Ivan Castellvi; Maurizio Cutolo; Christian Stock; Nils Schoof; Margarida Alves; Ganesh Raghu Journal: Arthritis Rheumatol Date: 2021-03-08 Impact factor: 10.995