Diagnostic and Prognostic Biomarkers for Chronic Fibrosing Interstitial Lung Diseases With a Progressive Phenotype

Inoue, Yoshikazu; Kaner, Robert J.; Guiot, Julien; Maher, Toby M.; Tomassetti, Sara; Moiseev, Sergey; Kuwana, Masataka; Brown, Kevin K.

doi:10.1016/j.chest.2020.03.037

Cited by 93 publications

(97 citation statements)

References 143 publications

(216 reference statements)

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“…Different studies highlight the importance of the quest for diagnostic or prognostic biomarkers in pulmonary fibrosing process [ 4 – 6 ]. Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

Could KL-6 levels in COVID-19 help to predict lung disease?

et al. 2020

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Background Coronavirus disease COVID-19 has become a public health emergency of international concern. Together with the quest for an effective treatment, the question of the post-infectious evolution of affected patients in healing process remains uncertain. Krebs von den Lungen 6 (KL-6) is a high molecular weight mucin-like glycoprotein produced by type II pneumocytes and bronchial epithelial cells. Its production is raised during epithelial lesions and cellular regeneration. In COVID-19 infection, KL-6 serum levels could therefore be of interest for diagnosis, prognosis and therapeutic response evaluation. Materials and methods Our study retrospectively compared KL-6 levels between a cohort of 83 COVID-19 infected patients and two other groups: healthy subjects (n = 70) on one hand, and a heterogenous group of patients suffering from interstitial lung diseases (n = 31; composed of 16 IPF, 4 sarcoidosis, 11 others) on the other hand. Demographical, clinical and laboratory indexes were collected. Our study aims to compare KL-6 levels between a COVID-19 population and healthy subjects or patients suffering from interstitial lung diseases (ILDs). Ultimately, we ought to determine whether KL-6 could be a marker of disease severity and bad prognosis. Results Our results showed that serum KL-6 levels in COVID-19 patients were increased compared to healthy subjects, but to a lesser extent than in patients suffering from ILD. Increased levels of KL-6 in COVID-19 patients were associated with a more severe lung disease. Discussion and conclusion Our results suggest that KL-6 could be a good biomarker to assess ILD severity in COVID-19 infection. Concerning the therapeutic response prediction, more studies are necessary.

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Section: Introductionmentioning

confidence: 99%

Could KL-6 levels in COVID-19 help to predict lung disease?

et al. 2020

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“…In this study, we investigated whether there was an association between the level of circulating H3.1 containing nucleosomes and other biomarkers of interest in systemic sclerosis or lung fibrosis such as the serum growth factors IGFBP-1 and the MMP enzyme MMP9, as a suitable approach or the correct identification of SSc-ILD disease [14][15][16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

A new nucleosomic-based model to identify and diagnose SSc-ILD

et al. 2020

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Background: Systemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. Specific biomarkers associated with the evolution of the lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease. Nucleosomes are stable DNA/protein complexes that are shed into the blood stream making them ideal candidates for biomarkers. Methods: We studied circulating cell-free nucleosomes (cf-nucleosomes) in SSc patients, 31 with ILD (SSc-ILD) and 67 without ILD. We analyzed plasma levels for cf-nucleosomes and investigated whether global circulating nucleosome levels in association with or without other biomarkers of interest for systemic sclerosis or lung fibrosis (e.g., serum growth factors: IGFBP-1 and the MMP enzyme: MMP-9), could be suitable potential biomarkers for the correct identification of SSc-ILD disease. Results: We found that H3.1 nucleosome levels were significantly higher in patients with SSc-ILD compared SSc patients without ILD (p < 0.05) and levels of MMP-9 were significantly increased in patients with SSc-ILD compared to SSc patients without ILD (p < 0.05). Conversely, IGFBP-1 was significantly reduced in patients with SSc-ILD compared to SSc without ILD (p < 0.001). The combination of cf-nucleosomes H3.1 coupled to MMP-9 and IGFBP-1 increased the sensitivity for the differential detection of SSc-ILD. High levels of accuracy were reached with this combined model: its performances are strong with 68.4% of positive predictive value and 77.2% of negative predictive value for 90% of specificity. With our model, we identified a significant negative correlation with FVC % pred (r = −0.22) and TLC % pred (r = −0.31). The value of our model at T1 (baseline) has a predictive power over the Rodnan score at T2 (after 6-18 months), showed by a significant linear regression with R 2 = 19% (p = 0.013). We identified in the sole group of SSc-ILD patients a significant linear regression with a R 2 = 54.4% with the variation of DLCO between T1 and T2 (p < 0.05). Conclusion: In our study, we identified a new blood-based model with nucleosomic biomarker in order to diagnose SSc-ILD in a SSc cohort. This model is correlated with TLC and FVC at baseline and predictive of the skin evolution and the DLCO. Further longitudinal exploration studies should be performed in order to evaluate the potential of such diagnostic and predictive model.

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“…However, the percentage of patients without drug treatment in the present study was below 10%. Our findings highlight a lack of specific tests (including biomarkers), standardized diagnostic criteria and treatment for progressive fibrosing ILD [48]. An official international guideline which includes the definition, diagnosis, and management of progressive fibrosing ILD is required.…”

Section: Current Assessment Of Ildmentioning

confidence: 91%

“…[ Figure 4 near here] Differences between regions were seen regarding the types and frequencies of monitoring tests performed for non-autoimmune ILDs. For instance, imaging and blood testing [48] were performed more frequently in Japan than in the United States and European Union, whereas the 6MWT was used more frequently in Western regions than in Japan. Different rates of blood biomarker testing might reflect differences between regions in access and reimbursement.…”

Section: Current Assessment Of Ildmentioning

confidence: 99%