Immunosuppression for interstitial lung disease in systemic sclerosis – novel insights and opportunities for translational research
Bibliographic record
Abstract
Systemic sclerosis (SSc) is a chronic inflammatory disorder characterized by a disturbance in fibroblast function culminating in the telltale skin thickening and fibrosis of visceral organs.Interstitial lung disease (ILD) is common (Steele et al. 2011) and is the leading cause of death in this disease (Steen and Medsger 2007).The immunohistopathogenesis of SSc-ILD is characterized by immune dysfunction and inflammation.Thus, immunosuppression has been hypothesized as a useful treatment for SSc-ILD.However, randomized clinical trials (RCTs) have thus far only revealed a modest effect of immunosuppression (Hoyles et al. 2006;Tashkin et al. 2006).We believe that these small observed effects are due, at least in part, to the actual design of the RCTs, in particular subject selection, which did not properly identify patients likely to respond to treatment.SSc is an uncommon disease, with an estimated prevalence ranging from 7-489/million and incidence from 0.6-122/million/year (Chifflot et al. 2008).This rarity has undoubtedly contributed to the paucity of RCTs examining the benefit of immunosuppression in this disease.To date, only cyclophosphamide and azathioprine have been evaluated in RCTs of subjects with SSc-ILD.In the Scleroderma Lung Study (N0158) (Tashkin et al. 2006), SSc-ILD subjects with less than 7 years of disease duration who had not previously received cyclophosphamide were randomized to oral cyclophosphamide or placebo for 1 year.Those treated with cyclophosphamide had a smaller decline than those on placebo in forced vital capacity (FVC) (adjusted difference of 2.5 % [95 % CI 0.3, 4.8 %, p 00.03] favouring cyclophosphamide).In the Fibrosing Alveolitis in Scleroderma Trial (FAST; N045) (Hoyles et al. 2006), SSc-ILD subjects with an average of 5 years of disease who had not been previously treated were randomized to receive 6 monthly infusions of cyclophosphamide followed by 6 months of oral daily azathioprine, or placebo.Although not statistically significant, the adjusted between-group difference in FVC of 4.2 % showed a strong trend in favour of the treated group (95 % CI -0.57, 8.95, p0 0.08).Mycophenolate mofetil (MMF) is a third immunosuppressant that is currently being tested in an ongoing RCT in subjects with SSc-ILD (Scleroderma Lung Study II http://
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.011 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.003 | 0.007 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".