Dataset Information

Mediators of systemic sclerosis-associated interstitial lung disease (SSc-ILD): systematic review and meta-analyses.

ABSTRACT: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is rare, poorly understood, with heterogeneous characteristics resulting in difficult diagnosis. We aimed to systematically review evidence of soluble markers in peripheral blood or bronchoalveolar lavage fluid (BALF) as biomarkers in SSc-ILD.

Method

Five databases were screened for observational or interventional, peer-reviewed studies in adults published between January 2000 and September 2021 that assessed levels of biomarkers in peripheral blood or BALF of SSc-ILD patients compared with healthy controls. Qualitative assessment was performed using Critical Appraisal Skills Programme (CASP) checklists. Standardised mean difference (SMD) in biomarkers were combined in random-effects meta-analyses where multiple independent studies reported quantitative data.

Results

768 published studies were identified; 38 articles were included in the qualitative synthesis. Thirteen studies were included in the meta-analyses representing three biomarkers: KL6, SP-D and IL-8. Greater IL-8 levels were associated with SSc-ILD in both peripheral blood and BALF, overall SMD 0.88 (95% CI 0.61 to 1.15; I²=1%). Greater levels of SP-D and KL-6 were both estimated in SSc-ILD peripheral blood compared with healthy controls, at an SMD of 1.78 (95% CI 1.50 to 2.17; I²=8%) and 1.66 (95% CI 1.17 to 2.14; I²=76%), respectively.

Conclusion

We provide robust evidence that KL-6, SP-D and IL-8 have the potential to serve as reliable biomarkers in blood/BALF for supporting the diagnosis of SSc-ILD. However, while several other biomarkers have been proposed, the evidence of their independent value in diagnosis and prognosis is currently lacking and needs further investigation.

Prospero registration number

CRD42021282452.

SUBMITTER: Fields A

PROVIDER: S-EPMC10359532 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Mediators of systemic sclerosis-associated interstitial lung disease (SSc-ILD): systematic review and meta-analyses.

Fields Aislin A Potel Koray N KN Cabuhal Rhandel R Aziri Buena B Stewart Iain D ID Schock Bettina C BC

Thorax 20221019 8

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is rare, poorly understood, with heterogeneous characteristics resulting in difficult diagnosis. We aimed to systematically review evidence of soluble markers in peripheral blood or bronchoalveolar lavage fluid (BALF) as biomarkers in SSc-ILD.<h4>Method</h4>Five databases were screened for observational or interventional, peer-reviewed studies in adults published between January 2000 and September 2021 that assessed levels of biom ...[more]

PMID: 36261273

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Project description:BackgroundInterstitial lung disease (ILD) is a common organ manifestation in systemic sclerosis (SSc) and is the leading cause of death in patients with SSc. A decline in forced vital capacity (FVC) is an indicator of ILD progression and is associated with mortality in patients with SSc-associated ILD (SSc-ILD). However, the relationship between FVC decline and hospitalisation events in patients with SSc-ILD is largely unknown. The objective of this post hoc analysis was to investigate the relationship between FVC decline and clinically important hospitalisation endpoints.MethodsWe used data from SENSCIS®, a phase III trial investigating the efficacy and safety of nintedanib in patients with SSc-ILD. Joint models for longitudinal and time-to-event data were used to assess the association between rate of decline in FVC% predicted and hospitalisation-related endpoints (including time to first all-cause hospitalisation or death; time to first SSc-related hospitalisation or death; and time to first admission to an emergency room [ER] or admission to hospital followed by admission to intensive care unit [ICU] or death) during the treatment period, over 52 weeks in patients with SSc-ILD.ResultsThere was a statistically significant association between FVC decline and the risk of all-cause (n = 78) and SSc-related (n = 42) hospitalisations or death (both P < 0.0001). A decrease of 3% in FVC corresponded to a 1.43-fold increase in risk of all-cause hospitalisation or death (95% confidence interval [CI] 1.24, 1.65) and a 1.48-fold increase in risk of SSc-related hospitalisation or death (95% CI 1.23, 1.77). No statistically significant association was observed between FVC decline and admission to ER or to hospital followed by admission to ICU or death (n = 75; P = 0.15). The estimated slope difference for nintedanib versus placebo in the longitudinal sub-model was consistent with the primary analysis in SENSCIS®.ConclusionsThe association of lung function decline with an increased risk of hospitalisation suggests that slowing FVC decline in patients with SSc-ILD may prevent hospitalisations. Our findings also provide evidence that FVC decline may serve as a surrogate endpoint for clinically relevant hospitalisation-associated endpoints.Trial registrationClinicalTrials.gov NCT02597933 . Registered on 8 October 2015.

Project description:OBJECTIVES:This study was designed (a) to evaluate an improved quantitative lung fibrosis score based on a computer-aided diagnosis (CaM) system in patients with systemic sclerosis (SSc),-related interstitial lung disease (SSc-ILD), (b) to investigate the relationship between physiologic parameters (forced vital capacity [FVC] and single-breath diffusing capacity for carbon monoxide [DLCO]), patient-centred measures of dyspnea and functional disability and CaM and visual reader-based (CoVR) methods, and (c) to identify potential surrogate measures from quantitative and visual HRCT measurement. METHODS:126 patients with SSc underwent chest radiography, HRCT and PFTs. The following patient-centred measures were obtained: modified Borg Dyspnea Index (Borg score), VAS for breathing, and Health Assessment Questionnaire-Disability Index (HAQ-DI). HRCT abnormalities were scored according to the conventional visual reader-based score (CoVR) and by a CaM. The relationships among the HRCT scores, physiologic parameters (FVC and DLCO, % predicted) results and patient-centred measures, were calculated using linear regression analysis and Pearson's correlation. Multivariate regression models were performed to identify the predictor variables on severity of pulmonary fibrosis. RESULTS:Subjects with limited cutaneous SSc had lower HAQ-DI scores than subjects with diffuse cutaneous SSc (p <0.001). CaM and CoVR scores were similar in the 2 groups. In univariate analysis, a strong correlation between CaM and CoVR was observed (p <0.0001). In multivariate analysis the CaM and CoVR scores were predicted by DLco, FVC, Borg score and HAQ-DI. Age, sex, disease duration, anti-topoisomerase antibodies and mRSS were not significantly associated with severity of pulmonary fibrosis on CaM- and CoVR methods. CONCLUSIONS:Although a close correlation between CaM score results and CoVR total score was found, CaM analysis showed a more significant correlation with DLco (more so than the FVC), patient-centred measures of perceived dyspnea and functional disability. Computer-aided tomographic analysis is computationally efficient, and in combination with physiologic and patient-centred measures, it could allow a means for accurately assessing and monitoring the disease progression or response to therapy.

Project description:BackgroundThe aim of the current systematic review was to summarize and evaluate the overall advantages of lung ultrasonography (LUS) examination using high-resolution computed tomography (HRCT) as a reference standard in assessing the presence of interstitial lung disease (ILD) in systemic sclerosis (SSc) patients.MethodsDatabases PubMed, Scopus, and Web of Science were searched for studies evaluating LUSs in ILD assessments including SSc patients on 1 February 2023. In assessing risk of bias and applicability, the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used. A meta-analysis was performed and the mean specificity, sensitivity, and diagnostic odds ratio (DOR) with a 95% confidence interval (CI) were obtained. In addition, in a bivariate meta-analysis, the summary receiver operating characteristic (SROC) curve area was additionally calculated.ResultsNine studies with a total of 888 participants entered the meta-analysis. A meta-analysis was also performed without one study that used pleural irregularity to assess the diagnostic accuracy of LUSs using B-lines (with a total of 868 participants). Overall sensitivity and specificity did not differ significantly, with only the analysis of the B-lines having a specificity of 0.61 (95% CI 0.44-0.85) and a sensitivity of 0.93 (95% CI 0.89-0.98). The diagnostic odds ratio of univariate analysis of the eight studies using the B-lines as a criterion for ILD diagnosis was 45.32 (95% CI 17.88-114.89). The AUC value of the SROC curve was 0.912 (and 0.917 in consideration of all nine studies), which indicates high sensitivity and a low false-positive rate for the majority of the included studies.ConclusionsLUS examination proved to be a valuable tool in discerning which SSc patients should receive additional HRCT scans to detect ILD and therefore reduces the doses of ionizing radiation exposure in SSc patients. However, further studies are needed to achieve consensus in scoring and the evaluation methodology of LUS examination.

Dataset Information

Mediators of systemic sclerosis-associated interstitial lung disease (SSc-ILD): systematic review and meta-analyses.

Method

Results

Conclusion

Prospero registration number

Publications

Mediators of systemic sclerosis-associated interstitial lung disease (SSc-ILD): systematic review and meta-analyses.

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