Publications by authors named "D Testelmans"

66 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-24360-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257697PMC
July 2021

High adherence to continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) in Belgium: a narrative review.

Acta Clin Belg 2021 Jul 1:1-11. Epub 2021 Jul 1.

Clinical Department of Respiratory Diseases, UZ Leuven, Leuven, Belgium.

Objectives: : Continuous positive airway pressure (CPAP) is the 'gold standard' treatment for moderate-to-severe obstructive sleep apnea (OSA); adherence is an important issue. The aim of this paper is to review Belgian data on CPAP users and their adherence over a period of 11 years.

Methods: : Data delivered annually by the CPAP centers to the Belgian National Institute for Health Insurance (RIZIV/INAMI) were studied. Comments on these results were embedded in a narrative review.

Results: : On 1 January 2008 27.266 Belgian patients were treated with CPAP, at the end of 2018 this number increased to 121.605. In 2018, the short-term adherence (≤3 months) to CPAP was at least twice as high compared to the United States: the CPAP termination rate in Belgium (mainly due to stop of reimbursement because adherence <4 h/night) was estimated to be 12.4%, considerably lower than the 31.1% of patients on CPAP in the United States using the device <4 h.

Conclusion: : We speculate that this good adherence might be attributed to a stringent Belgian diagnostic and treatment convention model. This model uses 'gold standard' techniques (including in-hospital polysomnography), imposes a minimum capacity of medical doctors and paramedical collaborators, a strict follow-up of the patients, multidisciplinary care and proof of competency. Taking into account the increasing number of patients, a change in the Belgian care strategy is under consideration focusing on more out-of-centre patient's management; we propose a step-by step approach with careful monitoring of the impact of changing policy on adherence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/17843286.2021.1943954DOI Listing
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.resmer.2021.100832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177497PMC
June 2021

Comorbidity clusters in patients with moderate-to-severe OSA.

Sleep Breath 2021 May 3. Epub 2021 May 3.

Department of Pulmonology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.

Purpose: Obstructive sleep apnea (OSA) is a prevalent and multifaceted disease. To date, the presence and severity of objectively identified comorbidities and their association with specific OSA phenotypes, CPAP adherence, and survival remain to be elucidated. The aim of this study is to cluster patients with OSA based on 10 clinically important objectively identified comorbidities, and to characterize the comorbidity clusters in terms of clinical and polysomnographic characteristics, CPAP adherence, and survival.

Study Design And Methods: Seven hundred ten consecutive patients starting CPAP for moderate-to-severe OSA were included. Comorbidities were based on generally accepted cutoffs identified in the peer-reviewed literature. Self-organizing maps were used to order patients based on presence and severity of their comorbidities and to generate clusters.

Results: The majority of patients were men (80%). They were generally middle-aged (52 years) and obese (BMI: 31.5 kg/m). Mean apnea-hypopnea index (AHI) was 41 ± 20 per h of sleep. More than 94% of the patients had one or more comorbidities with arterial hypertension, dyslipidemia, and obesity being the most prevalent. Nine comorbidity clusters were identified. The clinical relevance of these comorbidity clusters was highlighted by the difference in symptoms, PSG parameters, and cardiovascular risk. Also, differences in CPAP adherence, improvements in ESS, and long-term survival were present between the clusters.

Conclusion: Comorbidity prevalence in patients with OSA is high, and different comorbidity clusters, demonstrating differences in cardiovascular risk, CPAP adherence, and survival, can be identified. These results further substantiate the need for a comprehensive assessment of patients with OSA beyond the AHI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11325-021-02390-4DOI Listing
May 2021

Neuropathy of the phrenic nerve associated with antiganglioside antibodies.

Eur J Neurol 2021 Jun;28(6):2138-2141

Department of Neurology, University Hospitals Leuven, Leuven, Belgium.

Background And Purpose: Antiganglioside antibodies have been implicated in several autoimmune-mediated neuropathies, and binding of these antibodies can result in inflammatory changes of the nerves. Diaphragmatic paralysis is a rare condition, mostly arising from diseases affecting the phrenic nerve, neuromuscular junction, or skeletal muscle.

Objectives: In this case series, we identified five patients with diaphragmatic paralysis due to unilateral or bilateral neuropathy of the phrenic nerve associated with the presence of antiganglioside antibodies (immunoglobulin G anti-GT1a antibodies and immunoglobulin M anti-GM1 antibodies).

Discussion: The combination of an isolated phrenic nerve palsy with anti-GM1 antibodies has only once been described. On the other hand, the association of anti-GT1a antibodies with phrenic nerve palsy has never been reported before.

Conclusions: We report an association between phrenic nerve palsy and the presence of antiganglioside antibodies, but it remains unclear if there is a causal relationship. Further studies are needed to explore this matter.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ene.14814DOI Listing
June 2021
-->