Chest
Volume 146, Issue 2, August 2014, Pages 422-436
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Original Research
Diffuse Lung Disease
Predictors of Mortality and Progression in Scleroderma-Associated Interstitial Lung Disease: A Systematic Review

https://doi.org/10.1378/chest.13-2626Get rights and content

BACKGROUND

Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in patients with systemic sclerosis (SSc); however, prognostication of SSc-associated ILD (SSc-ILD) remains challenging. We conducted a systematic review to identify variables that predict mortality and ILD progression in SSc-ILD.

METHODS

Three databases were searched to identify all studies relating to predictors of mortality or ILD progression in SSc-ILD. Studies were eligible if they were published in English and included ≥ 10 adults with SSc-ILD. Two authors independently reviewed and extracted data from acceptable studies.

RESULTS

The initial search identified 3,145 unique citations. Twenty-seven studies, including six abstracts, met the inclusion criteria. A total of 1,616 patients with SSc-ILD were included. Patient-specific, ILD-specific, and SSc-specific variables predicted mortality and progression; however, most predictors were identified in only one study. Most studies did not fully account for potential confounders, and none of the studies included a validation cohort. Older age, lower FVC, and lower diffusing capacity of carbon monoxide predicted mortality in more than one study. Male sex, extent of disease on high-resolution CT (HRCT) scan, presence of honeycombing, elevated KL-6 values, and increased alveolar epithelial permeability were identified as predictors of both mortality and ILD progression on unadjusted analysis. The extent of disease on HRCT scan was the only variable that independently predicted both mortality and ILD progression.

CONCLUSIONS

Mortality and ILD progression were predicted by several patient-specific, ILD-specific, and SSc-specific factors. Additional prospective studies are required to validate these preliminary findings and to identify combinations of variables that accurately predict the prognosis of SSc-ILD.

Section snippets

Data Sources and Search

We performed a systematic search of the literature using the MEDLINE, Embase, and Evidence-Based Medicine Reviews databases. The search was designed to capture all studies related to predictors of mortality and ILD progression in SSc-ILD. Two authors (T. A. W. and C. J. R.) reviewed citations independently using predefined criteria. Searches covered the period from the onset of the database to April 2013. Bibliographies from selected articles and major reviews were screened for additional

Search Results and Study Characteristics

The initial search identified 3,145 unique citations, and 167 were reviewed in full text. Twenty-seven descriptive studies met the eligibility criteria,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 including six abstracts (Fig 1, Table 1).7, 9, 21, 24, 30, 31 A total of 1,616 patients with SSc-ILD were included (range, 18-215 patients per study). The duration of follow-up was reported in 21 studies and ranged from 1 to 14 years. There was

Discussion

We conducted a rigorous systematic review of the literature to identify variables that predict mortality or ILD progression in patients with SSc-ILD. Several patient-specific, ILD-specific, and SSc-specific variables predicted mortality and ILD progression in SSc-ILD; however, included studies were of variable methodologic quality, and the predictors identified in this review should be considered within the context of these limited data. A minority of studies performed a multivariate analysis,

Conclusions

In summary, we found that several patient-specific, ILD-specific, and SSc-specific features predict worse prognosis in SSc-ILD. Dlco was the most consistent predictor of mortality and may help identify patients with a poor prognosis; however, more rigorous studies are needed to confirm and expand on these preliminary findings. A clearer understanding of how to determine prognosis with variables such as Dlco is required prior to incorporation of these findings into clinical practice. Additional

Acknowledgments

Author contributions: C. J. R. takes responsibility as the guarantor of the manuscript, including the data and analysis. T. A. W. and C. J. R. contributed to the design of the study, primary analysis and interpretation of the data, production of the initial draft of the manuscript, and approval of the final version and D. A., P. G. W., J. V. D., C. J. H., J. L., and H. R. C. contributed to the analysis and interpretation of the data, drafting of the manuscript, and approval of the final version.

References (38)

  • D Bouros et al.

    Histopathologic subsets of fibrosing alveolitis in patients with systemic sclerosis and their relationship to outcome

    Am J Respir Crit Care Med

    (2002)
  • A de Lauretis et al.

    Serum markers of disease progression in idiopathic pulmonary fibrosis and in interstitial lung disease associated with systemic sclerosis

    Am J Respir Crit Care Med

    (2010)
  • M De Santis et al.

    β-Thymosins and interstitial lung disease: study of a scleroderma cohort with a one-year follow-up

    Respir Res

    (2011)
  • M De Santis et al.

    Bronchoalveolar lavage fluid and progression of scleroderma interstitial lung disease

    Clin Respir J

    (2012)
  • N Fertig et al.

    Anti-U11/U12 RNP antibodies in systemic sclerosis: a new serologic marker associated with pulmonary fibrosis

    Arthritis Rheum

    (2009)
  • NS Goh et al.

    Bronchoalveolar lavage cellular profiles in patients with systemic sclerosis-associated interstitial lung disease are not predictive of disease progression

    Arthritis Rheum

    (2007)
  • NS Goh et al.

    Interstitial lung disease in systemic sclerosis: a simple staging system

    Am J Respir Crit Care Med

    (2008)
  • NS Goh et al.

    Increased epithelial permeability in pulmonary fibrosis in relation to disease progression

    Eur Respir J

    (2011)
  • D Khanna et al.

    Clinical course of lung physiology in patients with scleroderma and interstitial lung disease: analysis of the Scleroderma Lung Study Placebo Group

    Arthritis Rheum

    (2011)
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    FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

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