Serum decorin is a potential prognostic biomarker in patients with acute exacerbation of idiopathic pulmonary fibrosis

Nikaido, Takefumi; Tanino, Yoshinori; Wang, Xintao; Sato, Yuki; Togawa, Ryuichi; Kikuchi, Masami; Misa, Kenichi; Saito, Kazue; Fukuhara, Naoko; Kawamata, Takaya; Rikimaru, Mami; Umeda, Takashi; Morimoto, Julia; Koizumi, Tatsuhiko; Suzuki, Yasuhito; Hirai, Kenichiro; Uematsu, Manabu; Minemura, Hiroyuki; Fukuhara, Atsuro; Sato, Suguru; Saito, Junpei; Yokouchi, Hiroshi; Kanazawa, Kenya; Shibata, Yoko

doi:10.21037/jtd.2018.08.60

Cited by 27 publications

(21 citation statements)

References 42 publications

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“…IPF is strongly associated with gastroesophageal reflux disease [137], a condition where acid flow could modulate lung pH and potentially enhance cathepsin activity. CTSS-degraded decorin is also being investigated as a potential biomarker for fibrotic lung disorders including IPF [81] in addition to lung cancer [74]. Interestingly, the endogenous cathepsin inhibitor, cystatin C, is a possible biomarker for IPF [138].…”

Section: Lung Cancermentioning

confidence: 99%

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics

et al. 2020

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Dysregulated expression and activity of cathepsin S (CTSS), a lysosomal protease and a member of the cysteine cathepsin protease family, is linked to the pathogenesis of multiple diseases, including a number of conditions affecting the lungs. Extracellular CTSS has potent elastase activity and by processing cytokines and host defense proteins, it also plays a role in the regulation of inflammation. CTSS has also been linked to G-coupled protein receptor activation and possesses an important intracellular role in major histocompatibility complex class II antigen presentation. Modulated CTSS activity is also associated with pulmonary disease comorbidities, such as cancer, cardiovascular disease, and diabetes. CTSS is expressed in a wide variety of immune cells and is biologically active at neutral pH. Herein, we review the significance of CTSS signaling in pulmonary diseases and associated comorbidities. We also discuss CTSS as a plausible therapeutic target and describe recent and current clinical trials examining CTSS inhibition as a means for treatment. Proteases in pulmonary diseases Research in the last 60 years has demonstrated that proteases are critical contributors to pulmonary disease pathophysiology. Initially known as protein-degrading enzymes with a restricted spectrum of substrates, recent studies have revealed that the diversity of protease substrates and biological effects triggered by their processing is vast [1, 2]. Proteases are primarily known for their matrix degradation capabilities, but also play significant roles in other biological mechanisms such as angiogenesis, growth factor bioavailability, cytokine processing, receptor shedding and activation, as well as cellular processes including migration, proliferation, invasion, and survival [3]. Importantly, protease activity requires tight regulation, and disruption of the close interplay between proteases, substrates and inhibitors may contribute to the pathogenesis and progression of a variety of pulmonary diseases, including muco-inflammatory diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), as well as infection [4]. In pulmonary diseases with a high neutrophil burden such as CF, a protease:antiprotease imbalance is frequently observed. The activity of proteases such as neutrophil elastase (NE) in the respiratory tract is regulated by antiproteases, such as α1-antitrypsin (A1AT) [5], secretory leukoprotease inhibitor (SLPI) [6] and elafin [7]. However, in diseases like CF, the antiproteases are overburdened by their cognate proteases and this imbalance can result in chronic airway inflammation, decreased mucociliary clearance, mucus obstruction, extracellular matrix (ECM) remodeling, increased susceptibility to infection and impaired immune responses [8].

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Section: Lung Cancermentioning

confidence: 99%

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics

et al. 2020

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“…The measure of hQOL was also described in one study. A total of eight research groups conducted multiple studies using the same cohort and published reports (Collard et al, 40 Kim et al, 50 Lee et al, 54 and Song et al 62 ; Kishaba et al 51 52 ; Enomoto et al [41][42][43] ; Furuya et al, 45 Isshiki et al, 46 Koyama et al, 53 and Sakamoto et al 59 ; Nikaido et al 55 and Sand et al 60 ; Kataoka et al, 48 Suzuki et al 64 and Yokoyama et al 71 ; Abe et al 35 and Atsumi et al 38 ; Tomioka et al 66 and Yamazoe et al 70 ; online supplementary e-table 1). Among these multiple research conducted by the same groups, the study with the largest sample size was prioritised and a total of 31 potential prognostic factors, which were investigated for their association with all-cause mortality, were identified and followed by further analysis (online supplementary e-table 2).…”

Section: Confidence In Cumulative Evidencementioning

confidence: 99%

“…Based on the combined result, APACHE II score was significantly associated with all-cause mortality of AE of IPF with an HR of 1.09 (95% CI 1.04 to 1.15;figure 1). The remaining one study excluded from metaanalysis demonstrated a higher APACHE II score for non-survivors although it was not statistically significant (MD 2.80 (95% CI −1.19 to 6.79)55 ; online supplementary e-table 4). A multivariate analysis reported by one study demonstrated a significant result with an HR of 1.10 (95% CI 1.01 to 1.19),49 which was consistent with…”

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confidence: 93%

Systematic review and meta-analysis of prognostic factors of acute exacerbation of idiopathic pulmonary fibrosis

Kamiya

Panlaqui

2020

BMJ Open

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ObjectiveTo clarify prognostic factors of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF).DesignA systematic review and meta-analysis.Data sourcesMedline, Embase and Science Citation Index Expanded were searched from 2002 through 1 March 2019.Eligibility criteria for selecting studiesThe review included primary studies addressing the association between the outcomes such as all-cause mortality of AE of IPF and its potential prognostic factors, which were designated as any clinical information related to the outcomes.Data extraction and synthesisTwo reviewers extracted relevant data independently and assessed risk of bias. Univariate results were pooled using a random-effect model if at least three studies were available. Prognostic factors were determined based on significant and consistent results on both univariate and multivariate analyses in the majority of studies.ResultsOut of a total of 6763 articles retrieved, 37 were eligible and 31 potential prognostic factors for all-cause mortality were selected. Each study was subject to certain methodological shortcomings. The following five factors were statistically significant by a meta-analysis of univariate results, which was confirmed by multivariate analysis, that is, Acute Physiology and Chronic Health Evaluation (APACHE) II score (HR 1.10, 1.01 to 1.19), partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio (ORs 0.99 in two studies and HRs 0.31 and 0.99 in two studies, respectively), lactate dehydrogenase (LDH) (HRs 1.002, 1.003, 1.01 and 1.02), white blood cell (WBC) count (OR 1.38, 1.04 to 1.83) and oxygen therapy before AE (HRs 3.68, 1.05 to 12.9 and 2.34, 1.04 to 5.28) (multivariate analysis, 95% CI).ConclusionsAPACHE II score, PaO2/FiO2 ratio, LDH, WBC count and oxygen therapy before AE were deemed as prognostic factors of AE of IPF. Although there are some methodological limitations in this study, these findings are reliable due to consistent results by both univariate and multivariate analyses.PROSPERO registration numberCRD42018106172.

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“…Furthermore, serum decorin is a small, leucine-rich proteoglycan that has been introduced as a novel marker for AE of IPF. Nikaido et al [23] reported that serum decorin had a significant association with oxygenation. Further multicenter studies will be required for further validation.…”

Section: Biomarkersmentioning

confidence: 99%

Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Kishaba

2019

Medicina

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Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia. Idiopathic pulmonary fibrosis is often seen in elderly men who smoke. A diagnosis of IPF is based on a combination of a detailed clinical history, specific physical examination, laboratory findings, pulmonary function tests, high-resolution computed tomography (HRCT) of the chest, and histopathology. Idiopathic pulmonary fibrosis has a heterogeneous clinical course, from an asymptomatic stable state to progressive respiratory failure or acute exacerbation (AE). Acute exacerbation of IPF has several important differential diagnoses, such as heart failure and volume overload. The International Working Group project proposed new criteria for defining AE of IPF in 2016, which divides it into triggered and idiopathic AE. On the basis of these criteria, physicians can detect AE of IPF more easily. The recent international IPF guidelines emphasized the utility of chest HRCT. In addition, two antifibrotic agents have become available. We should focus on both the management and prevention of AE. The diagnostic process, laboratory findings, typical chest imaging, management, and prognosis of AE are comprehensively reviewed in this article.

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Serum decorin is a potential prognostic biomarker in patients with acute exacerbation of idiopathic pulmonary fibrosis

Cited by 27 publications

References 42 publications

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics

Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics

Systematic review and meta-analysis of prognostic factors of acute exacerbation of idiopathic pulmonary fibrosis

Acute Exacerbation of Idiopathic Pulmonary Fibrosis

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