Evolving Concepts in Chronic Obstructive Pulmonary Disease Blood-Based Biomarkers

Cazzola, Mario; Puxeddu, Ermanno; Ora, Josuel; Rogliani, Paola

doi:10.1007/s40291-019-00413-1

Cited by 18 publications

(13 citation statements)

References 77 publications

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“…They are crucial in monitoring and predicting disease progression and predicting responders to treatment [8,79]. COPD and IPF are highly complex and heterogeneous, and no single biomarker has been identified for clinical applications in either disease [80][81][82]. Dividing COPD and IPF into endotypes is critical for breaking the diseases down into molecular pathways and disease mechanisms, and for linking molecular mechanisms to clinical features.…”

Section: Biomarkersmentioning

confidence: 99%

Chronic lung diseases: prospects for regeneration and repair

et al. 2021

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COPD and idiopathic pulmonary fibrosis (IPF) together represent a considerable unmet medical need, and advances in their treatment lag well behind those of other chronic conditions. Both diseases involve maladaptive repair mechanisms leading to progressive and irreversible damage. However, our understanding of the complex underlying disease mechanisms is incomplete; with current diagnostic approaches, COPD and IPF are often discovered at an advanced stage and existing definitions of COPD and IPF can be misleading. To halt or reverse disease progression and achieve lung regeneration, there is a need for earlier identification and treatment of these diseases. A precision medicine approach to treatment is also important, involving the recognition of disease subtypes, or endotypes, according to underlying disease mechanisms, rather than the current “one-size-fits-all” approach. This review is based on discussions at a meeting involving 38 leading global experts in chronic lung disease mechanisms, and describes advances in the understanding of the pathology and molecular mechanisms of COPD and IPF to identify potential targets for reversing disease degeneration and promoting tissue repair and lung regeneration. We also discuss limitations of existing disease measures, technical advances in understanding disease pathology, and novel methods for targeted drug delivery.

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Section: Biomarkersmentioning

confidence: 99%

Chronic lung diseases: prospects for regeneration and repair

et al. 2021

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“…Recently the role of combinations of multiple biomarkers has been reported (14,16,49). The ECLIPSE and COPDGene studies both indicated that combinations of multiple biomarkers were much more strongly predictive of AO [CC16, soluble receptor for advanced glycation end products (sRAGE), fibrinogen, CRP and SP-D], emphysema (SP-D, CRP, sRAGE and fibrinogen), and mortality (SP-D, CRP and fibrinogen) than any single biomarker, although the amount of variance explained by the multiple biomarkers was lower than that of clinical variables (44,49).…”

Section: Multiple Biomarkers (Combination Of Inflammatory Biomarkers and Pneumoproteins)mentioning

confidence: 99%

“…The potential roles of different biomarkers in association with COPD progression, exacerbation and mortality have already been studied, including cellular biomarkers [i.e., circulating white blood cells (WBCs)] and blood protein biomarkers [i.e., C-reactive protein (CRP), fibrinogen, interleukins, Clara cell secretory protein 16 (CC16), surfactant protein D (SP-D], and blood protease enzymes [i.e., matrix metallopeptidase 9 (MMP9)] (14-17). As COPD is a complex disorder no single biomarker can be used to assess it (16) but rather a model has been proposed using multiple classes of proteins such as acute phase proteins and signaling proteins playing a role in systemic inflammation, pneumoproteins involved in impaired lung homeostasis, and protease enzymes involved in oxidant injury (18).…”

Section: Introductionmentioning

confidence: 99%

Inflammatory parameters and pulmonary biomarkers in smokers with and without chronic obstructive pulmonary disease (COPD)

Andreeva¹,

Pokhasnikova²,

Лебедев³

et al. 2021

J Thorac Dis

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Background: We organized this study in order to investigate differences in serum inflammatory profiles and circulating serum pneumoproteins between smokers with and without chronic obstructive pulmonary disease (COPD). Methods: Patients aged 35-70 years with COPD and a smoking history ≥10 pack-years (cases, n=38) and 38 participants with the same smoking history without COPD (controls) were included in a comparative study conducted as part of a population-based cross-sectional study with 2,388 individuals in northwestern Russia. Cases and controls were matched for age and smoking history. Airflow obstruction (AO) was defined using forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.70 and/or FEV1/FVC < lower limit of the normal cut-off values. Patients at risk for COPD were reassessed using a standardized diagnostic work-up protocol. Several parameters, among which four inflammatory biomarkers [the highsensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) levels] and two pneumoproteins [surfactant protein D (SP-D) and Clara cell secretory protein 16 (CC16)], were measured in the peripheral blood. Systemic inflammation was defined as at least 2 or more elevated biomarker levels. Results: Out of all smokers, 57.9% with normal spirometry and 36.8% with COPD did not have systemic inflammation, whereas 44.7% of the patients with COPD and 5.3% of the patients without AO demonstrated at least two elevated biomarker levels. No difference in age, gender, and smoking history, environmental and occupational exposure was found between the non-inflamed and the inflamed smokers.Of all risk factors studied, only COPD was associated with systemic inflammation [odds ratio (OR) 11.42, 95% confidence interval (CI): 2.13-58.84].Conclusions: Our study describes the systemic inflammatory network pattern associated with COPD and how it differs from the pattern in smokers with normal lung function. Systemic inflammation is not present in all smokers with COPD; in contrast, some non-obstructed smokers are characterized by systemic inflammation. From this perspective, smoking itself could be seen as a disease and studied accordingly.Trial registration: NCT02307799.

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“…2d). Given it was negatively correlated with lung function in COPD [6,7], we evaluated the relation of sRAGE and airway resistance in NA. It showed that there was an opposite trend between sRAGE levels in BALF and airway resistance, however, with no statistical differences ( Fig.…”

Section: Srage Level Decreased In Na Mousementioning

confidence: 99%

“…Soluble advanced glycosylation receptor (sRAGE) as a predictive indicator of airway neutrophil in ammation and a biomarker for COPD, which was decreased in the blood and bronchoalveolar lavage uid (BALF) of patients with COPD [5]. Moreover, it was negatively correlated with COPD grade and lung function [6,7]. We hypothesized that sRAGE may be involved in the pathogenesis of NA and the common pathological process of NA and COPD.…”

Section: Introductionmentioning

confidence: 99%

Soluble advanced glycosylation receptor is a potential target for the treatment of neutrophilic asthma

Zhang¹,

Xie²,

Sun³

et al. 2020

Preprint

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Background Neutrophilic asthma (NA) was a subtype of asthma. Soluble advanced glycosylation receptor (sRAGE) was considered to be associated with the neutrophilic airway. However, the role of sRAGE in NA still limited. Methods A NA mouse model was established and the levels of sRAGE in the bronchoalveolar lavage fluid (BALF) were measured by ELISA. Hematoxylin-eosin (HE) and Masson trichrome staining were used to identifying airway remodeling. Adeno-associated virus 9 (AAV9) overexpressed sRAGE and inhibitors for HMGB1, RAGE, and PI3K were used to intervene NA mouse model via tail-vein injection and intraperitoneally injection. Expressions of airway remodeling, EMT, and signaling markers were detected using qRT-PCR or western blotting. The levels of IL-17 and IL-6 in BALF were measured by ELISA. HMGB1 was applied to induce EMT of human bronchial epithelial cells (16HBE), then E-cadherin and vimentin expressions were examined after sRAGE, RAGE inhibitor, and PI3K inhibitor administration. Results sRAGE levels were significantly reduced in BALF and the airway remodeling was observed in the NA mouse model. AAV9-sRAGE significantly inhibited the neutrophilic airway inflammation, airway remodeling, and the expression of IL-17, IL-6, TGF-β1, RAGE, PI3K, and EMT markers -E-cadherin and vimentin in vivo. HMGB1 inhibitor, RAGE inhibitor, and PI3K inhibitor upregulated E-cadherin level. Moreover, HMGB1 promoted the EMT process via RAGE/PI3K in 16HBE cells and sRAGE reversed HMGB1- induced EMT in vitro. Conclusion sRAGE levels decrease in the mouse model with NA. sRAGE treatment attenuates neutrophilic airway inflammation, airway remodeling, and EMT. This suggests sRAGE may yield benefits in the treatment of NA.

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Evolving Concepts in Chronic Obstructive Pulmonary Disease Blood-Based Biomarkers

Cited by 18 publications

References 77 publications

Chronic lung diseases: prospects for regeneration and repair

Chronic lung diseases: prospects for regeneration and repair

Inflammatory parameters and pulmonary biomarkers in smokers with and without chronic obstructive pulmonary disease (COPD)

Soluble advanced glycosylation receptor is a potential target for the treatment of neutrophilic asthma

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