Publications by authors named "J Yserbyt"

67 Publications

Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity.

Nat Commun 2021 07 5;12(1):4117. Epub 2021 Jul 5.

KU Leuven Flow & Mass Cytometry Facility, KU Leuven, Leuven, Belgium.

Epidemiological and clinical reports indicate that SARS-CoV-2 virulence hinges upon the triggering of an aberrant host immune response, more so than on direct virus-induced cellular damage. To elucidate the immunopathology underlying COVID-19 severity, we perform cytokine and multiplex immune profiling in COVID-19 patients. We show that hypercytokinemia in COVID-19 differs from the interferon-gamma-driven cytokine storm in macrophage activation syndrome, and is more pronounced in critical versus mild-moderate COVID-19. Systems modelling of cytokine levels paired with deep-immune profiling shows that classical monocytes drive this hyper-inflammatory phenotype and that a reduction in T-lymphocytes correlates with disease severity, with CD8+ cells being disproportionately affected. Antigen presenting machinery expression is also reduced in critical disease. Furthermore, we report that neutrophils contribute to disease severity and local tissue damage by amplification of hypercytokinemia and the formation of neutrophil extracellular traps. Together our findings suggest a myeloid-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.
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http://dx.doi.org/10.1038/s41467-021-24360-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257697PMC
July 2021

Early lung ultrasound assessment for the prognosis of patients hospitalized for COVID-19 pneumonia. A pilot study.

Respir Med Res 2021 Jun 4;80:100832. Epub 2021 Jun 4.

Department of Respiratory Diseases, University Hospitals KU Leuven, Herestraat 49, 3000 Leuven, Belgium.

Objective: SARS CoV-2 is an epidemic viral infection that can cause mild to severe lung involvement. Newly apprehended knowledge on thoracic imaging abnormalities and the growing clinical experience on the evolution of this disease make the radiographic follow-up of hospitalized patients relevant. The value of consecutive bedside lung ultrasonography in the follow-up of hospitalized patients with SARS CoV-2 pneumonia and its correlation with other clinical and laboratory markers needs to be evaluated.

Methods: We assessed 39 patients [age: 64 y(60.1-68.7)] with confirmed SARS CoV-2 pneumonia. A total of 24 patients were hospitalized until the follow-up test, 9 were discharged early and 6 required a transfer to critical care unit. Two ultrasound scans of the lung were performed on day 1 and 4 of patients' hospitalization. Primary endpoint was the magnitude of association between a global lung ultrasound score (LUS) and clinical and laboratory markers. Secondary endpoint was the association between the evolution of LUS with the corresponded changes in clinical and laboratory outcomes during hospitalization period.

Results: LUS score on admission was higher among the deteriorating patients and significantly (P=0.038-0.0001) correlated (Spearman's rho) with the levels of C-reactive protein (0.58), lymphocytes (-0.33), SpO (-0.48) and oxygen supplementation (0.48) upon admission. The increase in LUS score between the two scans was significantly correlated (0.544, P=0.006) with longer hospital stay.

Conclusion: Lung ultrasound assessment can be a useful as an imaging modality for SARS CoV-2 patients. Larger studies are needed to further investigate the predictive role of LUS in the duration and the outcome of the hospitalization of these patients.
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http://dx.doi.org/10.1016/j.resmer.2021.100832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177497PMC
June 2021

Clinical characteristics of sarcoidosis patients in Belgium.

Acta Clin Belg 2020 Sep 16:1-8. Epub 2020 Sep 16.

Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium.

Background: Sarcoidosis is a non-caseating granulomatous disease, mostly affecting previously healthy persons in their fourth and fifth decade. In Belgium, there is a paucity of epidemiological data concerning sarcoidosis and it is unknown to what respect national data on sarcoidosis relates to the global epidemiology of the disease.

Objectives: In this cohort study we describe the patient population in an academic center of reference, serving both as a regional care center and a center for a tertiary referral.

Methods: We collected epidemiological data among 234 consecutive patients consulting the outpatient sarcoidosis clinic during a two-year time period. We manually explored the electronic patient file for data retrieval.

Results: Out of the 234 patients, 140 are male (60%) and 94 are female (40%) patients. Forced vital capacity showed a median decline of 2% during follow-up, whereas median diffusion capacity increased with 4% over the same period of time. Within our study cohort, we observed a preponderance in employment as construction workers (14%), the chemical industry (6%) and in the metal processing industry (6%).

Conclusion: The current study reports on epidemiological findings among the largest cohort of sarcoidosis patients in Belgium published to date.
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http://dx.doi.org/10.1080/17843286.2020.1821493DOI Listing
September 2020

Once daily tacrolimus conversion in lung transplantation: A prospective study on safety and medication adherence.

J Heart Lung Transplant 2021 Jun 27;40(6):467-477. Epub 2021 Feb 27.

Department of Respiratory Diseases, Lung Transplantation Group, UZ Leuven, Campus Gasthuisberg, Leuven, Belgium; Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETA, KU Leuven, Leuven, Belgium.

Background: Lung transplantation (LTx) requires a calcineurin inhibitor-based immunosuppressive regimen. A once daily (QD) tacrolimus regimen was developed to increase medication adherence. However, data concerning its safety and efficacy in LTx are lacking.

Methods: In this prospective study, stable LTx patients were consecutively converted from twice daily (BID) tacrolimus to QD tacrolimus on a 1 mg:1 mg basis. Trough level (C), renal function, cholesterol, fasting glucose, potassium and lung function were monitored six months before and up to one year after conversion. Adherence and its barriers were assessed by self-reported questionnaires (Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) and Identification of Medication Adherence Barriers questionnaire (IMAB)) and blood-based assays (mean C and coefficient of variation (CV)).

Results: We included 372 patients, in whom we observed a decrease in tacrolimus C of 18.5% (p < 0.0001) post-conversion, requiring subsequent daily dose adaptations in both cystic fibrosis (CF) (n = 72) and non-CF patients (n = 300). We observed a small decrease in eGFR one year post-conversion (p = 0.024). No significant changes in blood creatinine, potassium, fasting glucose, cholesterol or rate of lung function decline were observed. In a subgroup of 166 patients, significantly fewer patients missed doses (8.4% vs. 19.3%, p = 0.016) or had irregular intake post-conversion (19.3% vs. 32.5%, p = 0.019). Mean C and CV, as well as the total number of barriers, also decreased significantly post-conversion.

Conclusions: In LTx, conversion from BID to QD tacrolimus (1 mg:1 mg) requires close monitoring of tacrolimus C. QD tacrolimus after transplantation is safe with respect to renal function, metabolic parameters and allograft function and improves LTx recipient adherence.
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http://dx.doi.org/10.1016/j.healun.2021.02.017DOI Listing
June 2021

Progression in the Management of Non-Idiopathic Pulmonary Fibrosis Interstitial Lung Diseases, Where Are We Now and Where We Would Like to Be.

J Clin Med 2021 Mar 23;10(6). Epub 2021 Mar 23.

Laboratory of Respiratory Diseases and Thoracic Surgery (BREATHE), Department CHROMETA, KU Leuven, B-3000 Leuven, Belgium.

A significant proportion of patients with interstitial lung disease (ILD) may develop a progressive fibrosing phenotype characterized by worsening of symptoms and pulmonary function, progressive fibrosis on chest computed tomography and increased mortality. The clinical course in these patients mimics the relentless progressiveness of idiopathic pulmonary fibrosis (IPF). Common pathophysiological mechanisms such as a shared genetic susceptibility and a common downstream pathway-self-sustaining fibroproliferation-support the concept of a progressive fibrosing phenotype, which is applicable to a broad range of non-IPF ILDs. While antifibrotic drugs became the standard of care in IPF, immunosuppressive agents are still the mainstay of treatment in non-IPF fibrosing ILD (F-ILD). However, recently, randomized placebo-controlled trials have demonstrated the efficacy and safety of antifibrotic treatment in systemic sclerosis-associated F-ILD and a broad range of F-ILDs with a progressive phenotype. This review summarizes the current pharmacological management and highlights the unmet needs in patients with non-IPF ILD.
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http://dx.doi.org/10.3390/jcm10061330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004662PMC
March 2021
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