title: Predictors of lung function decline in scleroderma-related interstitial lung disease based on high-resolution computed tomography: implications for cohort enrichment in systemic sclerosis-associated interstitial lung disease trials.
abstract: BACKGROUND
  The extent of lung involvement visualized by high-resolution computed tomography (HRCT) is a predictor of decline in forced vital capacity (FVC) in scleroderma-interstitial lung disease. Our objective was to evaluate the performance of three different HRCT-defined staging systems in the Scleroderma Lung Study I (SLS I) over a 1-year period.
  
  
  METHODS
  We assessed two visual semiquantitative scores: the maximum fibrosis score (MaxFib, the fibrosis score in the zone of maximal lung involvement) and visual assessment of total lung involvement (TLI) as proposed by Goh and Wells. In addition, we evaluated the computer-aided diagnosis and calculated the quantitative percentage with fibrosis (QLF) and TLI.
  
  
  RESULTS
  The mean duration of the disease was 3.2 years, and the mean FVC was 67.7 %. Regardless of the staging system used, a greater degree of fibrosis/TLI on HRCT scans was associated with a greater decline in FVC in the placebo group. Using the MaxFib and QLF, the mean absolute changes in FVC from baseline were 0.1% and -1.4%, respectively, in <25% lung involvement vs. a change of -6.2% and -6.9%, respectively, with >25% involvement (negative score denotes worsening in FVC). Conversely, cyclophosphamide was able to stabilize decline in FVC in subjects with greater degree of involvement detected by HRCT. Using the visual MaxFib and QLF, the mean absolute improvements in FVC were 1.2 and 1.1, respectively, with >25% involvement.
  
  
  CONCLUSIONS
  HRCT-defined lung involvement was a predictor of decline in FVC in SLS I. The choice of staging system for cohort enrichment in a clinical trial depends on feasibility.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT00004563 (Scleroderma Lung Study I) ISRCTN15982171. Registered 19 Aug 2015.
authors.affiliation: University of Michigan Scleroderma Program, Division of Rheumatology, Department of Internal Medicine, University of Michigan, Suite 7C27, 300 North Ingalls Street, SPC 5422, Ann Arbor, MI, 48109, USA. khannad@med.umich.edu.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
authors.affiliation: Division of Rheumatology, University of Toledo, Toledo, OH, USA. vivek.nagaraja@utoledo.edu.
authors.forename: Vivek
authors.initials: V
authors.lastname: Nagaraja
authors.affiliation: Department of Biostatistics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. ctseng@mednet.ucla.edu.
authors.forename: Chi-Hong
authors.initials: CH
authors.lastname: Tseng
authors.affiliation: Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. fabtin@mednet.ucla.net.
authors.forename: Fereidoun
authors.initials: F
authors.lastname: Abtin
authors.affiliation: Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. rsuh@mednet.ucla.net.
authors.forename: Robert
authors.initials: R
authors.lastname: Suh
authors.affiliation: Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. gracekim@mednet.ucla.net.
authors.forename: Grace
authors.initials: G
authors.lastname: Kim
authors.affiliation: Division of Pulmonary and Critical Care, Royal Brompton Hospital, London, UK. athol.wells@rbht.nhs.uk.
authors.forename: Athol
authors.initials: A
authors.lastname: Wells
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. defurst@mednet.ucla.net.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. pclements@mednet.ucla.net.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Clements
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. mroth@mednet.ucla.net.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Roth
authors.affiliation: Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. dtashkin@mednet.ucla.net.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.affiliation: Department of Radiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. jgoldin@mednet.ucla.net.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Goldin
mesh_terms: D000328:Adult; D003520:Cyclophosphamide / Q000627:therapeutic use; D003936:Diagnosis, Computer-Assisted; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D017563:Lung Diseases, Interstitial / Q000000981:diagnostic imaging* / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000150:complications* / Q000188:drug therapy; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide