The Dual Role of Chemerin in Lung Diseases

Chemerin is an atypical chemokine first described as a chemoattractant agent for monocytes, natural killer cells, plasmacytoid and myeloid dendritic cells, through interaction with its main receptor, the G protein-coupled receptor chemokine-like receptor 1 (CMKLR1). Chemerin has been studied in various lung disease models, showing both pro- and anti-inflammatory properties. Given the incidence and burden of inflammatory lung diseases from diverse origins (infectious, autoimmune, age-related, etc.), chemerin has emerged as an interesting therapeutical target due to its immunomodulatory role. However, as highlighted by this review, further research efforts to elucidate the mechanisms governing chemerin’s dual pro- and anti-inflammatory characteristics are urgently needed. Moreover, although a growing body of evidence suggests chemerin as a potential biomarker for the diagnosis and/or prognosis of inflammatory lung diseases, this review underscores the necessity for standardizing both sampling types and measurement techniques before drawing definitive conclusions.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Comparison of antemortem clinical diagnosis and post-mortem findings in intensive care unit patients.

Autopsy is an important quality assurance indicator and a tool to advance medical knowledge. This study aims to compare the premortem clinical and postmortem pathology findings in patients who died in the Intensive Care Unit (ICU), to analyze if there are any discrepancies between them, and to compare the results to two similar studies performed in our institution in 2004 and 2007. Between January 1, 2016, and December 31, 2018, 888 patients died in the ICU and 473 underwent post-mortem examination (PME) of whom 437 were included in the present study. Autopsies revealed discrepancies between clinical diagnosis and pathologic findings according to in 101 cases (23.1%) according to Goldman classification. Forty-eight major discrepancies (class I and class II) were identified in 44 cases and the most frequent identified discrepancies were pulmonary embolism (3/12) as class I and malignancies (13/35) as class II. They were more frequent in patients hospitalized for less than 10 days then in the group with more than 10 days of hospitalization (13.8% vs 4.5%; p = 0.002). No statistical difference has been noticed concerning age, gender, and ICU stay. We observed an increase of performed autopsies and a total discrepancy rate similar to the studies performed in the same institution in 2004 (22.5%) and 2007 (21%). In conclusion, discrepancies between clinical and PME diagnoses persist despite the medical progress. Secondly, the autopsy after a short hospital stay may reveal unexpected findings whose diagnosis is challenging even if it may be suspected by the intensivist.info:eu-repo/semantics/publishe

Fibroblast Activation Protein Inhibitor, a Promising Radiotracer inFibrogenesis

Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible interstitial lung diseasefor which biomarker of the fibrotic activity of the disease are lacking. Fibroblast activation protein-α(FAP) is a marker of activated fibroblasts. The development of quinoline-based PET tracers that actas FAP inhibitors (FAPIs) demonstrated promising results in oncology with a high and selectivetumor uptake. In the present study, we evaluated the potential role of FAPI as a biomarker of lungfibrogenesis. Methods: The lung uptake of FAPI and its kinetic was assessed in a mouse model ofpulmonary fibrosis. Thus, intratracheal instillation of bleomycin (0.02U/mouse) was performed onC56BL/6 mice. Control mice received an intratracheal instillation of NaCl 0.9%. FAPI was providedby SOFIE (Totowa, USA) and the radiotracer 18F-FAPI was produced in the department of NuclearMedicine of Erasme Hospital. PET/CT imaging were determined at different timepoints (days 3, 10,16 and 28) after the instillation of bleomycin. A time course of uptake of the radiotracer wasevaluated. The results are presented as the mean standardized uptake value (SUV mean) in thelungs and the calculation of a lung-to-muscle ratio (LMR). To correlate with the PET scan results, theextent of fibrosis was assessed by measuring lung content of hydroxyproline and by evaluating theAshcroft modified scale. Results: The optimal imaging window was determined between 40 and 90minutes after radiotracer injection. Bleomycin-treated mice presented a significantly higher uptakeof 18F-FAPI (both SUV mean and LMR) at days 10 and 16 after instillation as compared to controlmice (p < 0.01). No significant statistical difference was observed at day 3 and day 28 afterinstillation. At day 10 and day 16, a strong correlation between 18F-FAPI uptake and hydroxyprolinelung content was observed, as well as a moderate correlation with the Ashcroft modified score.Conclusions: Our results suggest that FAPI constitutes a promising marker of fibrogenesis whoseexpression can be assessed by PET/CT imaging in a mouse model of lung fibrosis. Interestingly, nosignificant increase of lung FAPI uptake was observed during the initial inflammatory phase afterbleomycin instillation as well as at the later stage when fibrotic changes are established and nolonger grow. 18F-FAPi PET/CT could be a useful tool for preclinical evaluation of antifibrotic drugsand further studies should assess its value in patients with IPF.info:eu-repo/semantics/publishe

Usefulness of FAPα assessment in bronchoalveolar lavage as a marker of fibrogenesis: results of a preclinical study and first report in patients with idiopathic pulmonary fibrosis.

Fibroblast activation protein-α (FAPα) is a marker of activated fibroblasts that can be selectively targeted by an inhibitor (FAPI) and visualised by PET/CT imaging. We evaluated whether the measurement of FAPα in bronchoalveolar lavage fluids (BALF) and the uptake of FAPI by PET/CT could be used as biomarkers of fibrogenesis.info:eu-repo/semantics/publishe

Usefulness of FAPα assessment in bronchoalveolar lavage as a marker of fibrogenesis: results of a preclinical study and first report in patients with idiopathic pulmonary fibrosis

Background: Fibroblast activation protein-α (FAPα) is a marker of activated fibroblasts that can be selectively targeted by an inhibitor (FAPI) and visualised by PET/CT imaging. We evaluated whether the measurement of FAPα in bronchoalveolar lavage fluids (BALF) and the uptake of FAPI by PET/CT could be used as biomarkers of fibrogenesis. Methods: The dynamics of lung uptake of 18F-labeled FAPI ([18F]FAPI-74) was assessed in the bleomycin mouse model at various time points and using different concentrations of bleomycin by PET/CT. FAPα was measured in BALFs from these bleomycin-treated and control mice. FAPα levels were also assessed in BALFs from controls and patients with idiopathic pulmonary fibrosis (IPF). Results: Bleomycin-treated mice presented a significantly higher uptake of [18F]FAPI-74 during lung fibrinogenesis (days 10 and 16 after instillation) compared to control mice. No significant difference was observed at initial inflammatory phase (3 days) and when fibrosis was already established (28 days). [18F]FAPI-74 tracer was unable to show a dose-response to bleomycin treatment. On the other hand, BALF FAPα levels were steeply higher in bleomycin-treated mice at day 10 and a significant dose-response effect was observed. Moreover, FAPα levels were strongly correlated with lung fibrosis as measured by the modified Aschroft histological analysis, hydroxyproline and the percentage of weight loss. Importantly, higher levels of FAPα were observed in IPF patients where the disease was progressing as compared to stable patients and controls. Moreover, patients with FAPα BALF levels higher than 192.5 pg/mL presented a higher risk of progression, transplantation or death compared to patients with lower levels. Conclusions: Our preclinical data highlight a specific increase of [18F]FAPI-74 lung uptake during the fibrotic phase of the bleomycin murine model. The measurement of FAPα in BALF appears to be a promising marker of the fibrotic activity in preclinical models of lung fibrosis and in IPF patients. Further studies are required to confirm the role of FAPα in BALF as biomarker of IPF activity and assess the relationship between FAPα levels in BALF and [18F]FAPI-74 uptake on PET/CT in patients with fibrotic lung disease

Chemerin plasma levels are increased in COVID-19 patients and are an independent risk factor of mortality.

Chemerin is an extracellular protein with chemotactic activities and its expression is increased in various diseases such as metabolic syndrome and inflammatory conditions. Its role in lung pathology has not yet been extensively studied but both known pro- and anti-inflammatory properties have been observed. The aim of our study was to evaluate the involvement of the chemerin/ChemR23 system in the physiopathology of COVID-19 with a particular focus on its prognostic value.info:eu-repo/semantics/publishe

SP-D and CC-16 Pneumoproteins' Kinetics and Their Predictive Role During SARS-CoV-2 Infection.

Surfactant protein D (SP-D) and pulmonary club cell protein 16 (CC-16) are called "pneumoproteins" and are involved in host defense against oxidative stress, inflammation, and viral outbreak. This study aimed to determine the predictive value of these pneumoproteins on the incidence of acute respiratory distress syndrome (ARDS) or death in patients with coronavirus disease-2019 (COVID-19).info:eu-repo/semantics/publishe

Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients.

Post-mortem studies can provide important information for understanding new diseases and small autopsy case series have already reported different findings in COVID-19 patients.info:eu-repo/semantics/publishe