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Article: Sputum induction for assessment of biomarkers in early respiratory drug development .

Lins, Robert / Pillu, Haiko / Gheyle, Lien / van Riel, Annick / Lins, Muriel / Vanhoutte, Frederic

International journal of clinical pharmacology and therapeutics

2019 Volume 57, Issue 1, Page(s) 20–23

Abstract: Objective: To study the success rate and reproducibility of sputum induction (SI) in healthy subjects (HS) and asthma patients (AP).: Materials and methods: 130 HSs/APs were recruited for early-phase studies to evaluate sputum biomarkers. SI and ... ...

Abstract	Objective: To study the success rate and reproducibility of sputum induction (SI) in healthy subjects (HS) and asthma patients (AP). Materials and methods: 130 HSs/APs were recruited for early-phase studies to evaluate sputum biomarkers. SI and sample processing were performed according to standard protocols. Results: Adequate samples were obtained from 46% of HSs and 80% of APs. There was no difference between the groups with adequate and nonadequate samples. Differences between HS and AP groups were minor. Reproducibility was 56.0% in HSs and 90.6% in APs. Conclusion: Sputum induction for biomarker assessment in early drug development is feasible in HSs and APs, but only modestly reproducible in HSs. The technique is complex and time consuming. .
MeSH term(s)	Asthma ; Biomarkers/chemistry ; Drug Development ; Humans ; Reproducibility of Results ; Sputum/chemistry
Chemical Substances	Biomarkers
Language	English
Publishing date	2019-01-09
Publishing country	Germany
Document type	Journal Article
ZDB-ID	124384-6
ISSN	0946-1965 ; 0340-0026 ; 0300-9718 ; 0174-4879
ISSN	0946-1965 ; 0340-0026 ; 0300-9718 ; 0174-4879
DOI	10.5414/CP203294
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Article ; Online: CT-derived measurements of pulmonary blood volume in small vessels and the need for supplemental oxygen in COVID-19 patients.

Dierckx, Wendel / De Backer, Wilfried / Lins, Muriel / De Meyer, Yinka / Ides, Kris / Vandevenne, Jan / De Backer, Jan / Franck, Erik / Lavon, Ben R / Lanclus, Maarten / Thillai, Muhunthan

Journal of applied physiology (Bethesda, Md. : 1985)

2022 Volume 133, Issue 6, Page(s) 1295–1299

Abstract: Throughout the COVID-19 pandemic, a portion of those affected have evolved toward acute hypoxic respiratory failure. Initially, this was hypothesized to result from acute lung injury leading to acute respiratory distress syndrome (ARDS). In previous ... ...

Abstract	Throughout the COVID-19 pandemic, a portion of those affected have evolved toward acute hypoxic respiratory failure. Initially, this was hypothesized to result from acute lung injury leading to acute respiratory distress syndrome (ARDS). In previous research, a novel quantitative CT post-processing technique was described to quantify the volume of blood contained within pulmonary blood vessels of a given size. We hypothesized that patients with lower BV5 blood flow would have higher supplemental oxygen needs and less favorable arterial blood gas profiles. From the initial data analysis, 111 hospitalized COVID-19 patients were retrospectively selected based on the availability of CT scans of the lungs with a slice thickness of 1.5 mm or less, as well as PCR-confirmed SARS-CoV2 infection. Three-dimensional (3-D) reconstructions of the lungs and pulmonary vasculature were created. Further analysis was performed on 50 patients. Patients were divided into groups based on their need for oxygen at the time of CT scan acquisition. Eighteen out of 50 patients needed >2 L/min supplemental oxygen and this group demonstrated a significantly lower median percentage of total blood flow in the BV5 vessels compared with the 32 patients who needed <2 L/min supplemental oxygen (41.61% vs. 46.89%,
MeSH term(s)	Humans ; COVID-19 ; Pandemics ; SARS-CoV-2 ; RNA, Viral ; Retrospective Studies ; Lung/diagnostic imaging ; Respiratory Distress Syndrome/therapy ; Tomography, X-Ray Computed/methods ; Oxygen ; Blood Volume
Chemical Substances	RNA, Viral ; Oxygen (S88TT14065)
Language	English
Publishing date	2022-10-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	219139-8
ISSN	1522-1601 ; 0021-8987 ; 0161-7567 ; 8750-7587
ISSN (online)	1522-1601
ISSN	0021-8987 ; 0161-7567 ; 8750-7587
DOI	10.1152/japplphysiol.00458.2022
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Article ; Online: Assessment of Small Pulmonary Blood Vessels in COVID-19 Patients Using HRCT.

Lins, Muriel / Vandevenne, Jan / Thillai, Muhunthan / Lavon, Ben R / Lanclus, Maarten / Bonte, Stijn / Godon, Rik / Kendall, Irvin / De Backer, Jan / De Backer, Wilfried

Academic radiology

2020 Volume 27, Issue 10, Page(s) 1449–1455

Abstract: Rationale and objectives: Mounting evidence supports the role of pulmonary hemodynamic alternations in the pathogenesis of COVID-19. Previous studies have demonstrated that changes in pulmonary blood volumes measured on computed tomography (CT) are ... ...

Abstract	Rationale and objectives: Mounting evidence supports the role of pulmonary hemodynamic alternations in the pathogenesis of COVID-19. Previous studies have demonstrated that changes in pulmonary blood volumes measured on computed tomography (CT) are associated with histopathological markers of pulmonary vascular pruning, suggesting that quantitative CT analysis may eventually be useful in the assessment pulmonary vascular dysfunction more broadly. Materials and methods: Building upon previous work, automated quantitative CT measures of small blood vessel volume and pulmonary vascular density were developed. Scans from 103 COVID-19 patients and 107 healthy volunteers were analyzed and their results compared, with comparisons made both on lobar and global levels. Results: Compared to healthy volunteers, COVID-19 patients showed significant reduction in BV5 (pulmonary blood volume contained in blood vessels of <5 mm Conclusion: COVID-19 patients display striking anomalies in the distribution of blood volume within the pulmonary vascular tree, consistent with increased pulmonary vasculature resistance in the pulmonary vessels below the resolution of CT.
MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Female ; Humans ; Lung ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2 ; Tomography, X-Ray Computed
Keywords	covid19
Language	English
Publishing date	2020-07-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1355509-1
ISSN	1878-4046 ; 1076-6332
ISSN (online)	1878-4046
ISSN	1076-6332
DOI	10.1016/j.acra.2020.07.019
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Article ; Online: Efficacy of oral 20-hydroxyecdysone (BIO101), a MAS receptor activator, in adults with severe COVID-19 (COVA): a randomized, placebo-controlled, phase 2/3 trial.

Lobo, Suzana Margareth / Plantefève, Gaétan / Nair, Girish / Joaquim Cavalcante, Adilson / Franzin de Moraes, Nara / Nunes, Estevao / Barnum, Otis / Berdun Stadnik, Claudio Marcel / Lima, Maria Patelli / Lins, Muriel / Hajjar, Ludhmila Abrahao / Lipinski, Christopher / Islam, Shaheen / Ramos, Fabiano / Simon, Tiago / Martinot, Jean-Benoît / Guimard, Thomas / Desclaux, Arnaud / Lioger, Bertrand /

Neuenschwander, Fernando Carvalho / DeSouza Paolino, Bruno / Amin, Alpesh / Acosta, Samuel Amil / Dilling, Daniel Forde / Cartagena, Edgardo / Snyder, Brian / Devaud, Edouard / Barreto Berselli Marinho, Ana Karolina / Tanni, Suzana / Milhomem Beato, Patricia Medeiros / De Wit, Stephan / Selvan, Vani / Gray, Jeffrey / Fernandez, Ricardo / Pourcher, Valérie / Maddox, Lee / Kay, Richard / Azbekyan, Anait / Chabane, Mounia / Tourette, Cendrine / Esmeraldino, Luis Everton / Dilda, Pierre J / Lafont, René / Mariani, Jean / Camelo, Serge / Rabut, Sandrine / Agus, Samuel / Veillet, Stanislas / Dioh, Waly / van Maanen, Rob / Morelot-Panzini, Capucine

EClinicalMedicine

2024 Volume 68, Page(s) 102383

Abstract: Background: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System ... ...

Abstract	Background: SARS-CoV-2 binding to ACE2 is potentially associated with severe pneumonia due to COVID-19. The aim of the study was to test whether Mas-receptor activation by 20-hydroxyecdysone (BIO101) could restore the Renin-Angiotensin System equilibrium and limit the frequency of respiratory failure and mortality in adults hospitalized with severe COVID-19. Methods: Double-blind, randomized, placebo-controlled phase 2/3 trial. Randomization: 1:1 oral BIO101 (350 mg BID) or placebo, up to 28 days or until an endpoint was reached. Primary endpoint: mortality or respiratory failure requiring high-flow oxygen, mechanical ventilation, or extra-corporeal membrane oxygenation. Key secondary endpoint: hospital discharge following recovery (ClinicalTrials.gov Number, NCT04472728). Findings: Due to low recruitment the planned sample size of 310 was not reached and 238 patients were randomized between August 26, 2020 and March 8, 2022. In the modified ITT population (233 patients; 126 BIO101 and 107 placebo), respiratory failure or early death by day 28 was 11.4% lower in the BIO101 (13.5%) than in the placebo (24.3%) group, (p = 0.0426). At day 28, proportions of patients discharged following recovery were 80.1%, and 70.9% in the BIO101 and placebo group respectively, (adjusted difference 11.0%, 95% CI [-0.4%, 22.4%], p = 0.0586). Hazard Ratio for time to death over 90 days: 0.554 (95% CI [0.285, 1.077]), a 44.6% mortality reduction in the BIO101 group (not statistically significant). Treatment emergent adverse events of respiratory failure were more frequent in the placebo group. Interpretation: BIO101 significantly reduced the risk of death or respiratory failure supporting its use in adults hospitalized with severe respiratory symptoms due to COVID-19. Funding: Biophytis.
Language	English
Publishing date	2024-01-03
Publishing country	England
Document type	Journal Article
ISSN	2589-5370
ISSN (online)	2589-5370
DOI	10.1016/j.eclinm.2023.102383
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Article ; Online: Assessment of Small Pulmonary Blood Vessels in COVID-19 Patients Using HRCT

Lins, Muriel / Vandevenne, Jan / Thillai, Muhunthan / Lavon, Ben R. / Lanclus, Maarten / Bonte, Stijn / Godon, Rik / Kendall, Irvin / De Backer, Jan / De Backer, Wilfried

Academic Radiology

2020 Volume 27, Issue 10, Page(s) 1449–1455

Keywords	Radiology Nuclear Medicine and imaging ; covid19
Language	English
Publisher	Elsevier BV
Publishing country	us
Document type	Article ; Online
ZDB-ID	1355509-1
ISSN	1076-6332
ISSN	1076-6332
DOI	10.1016/j.acra.2020.07.019
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effects of the pyriproxyfen and fenthion on the gonadal morphology of Nile tilapia (Oreochromis niloticus: Perciformes, Cichlidae).

Moises Marques E Silva, Glaucia / Lins Oliveira, Jorge Eduardo / B Silva Farias, Naisandra / Júnior, Raimundo F A / Nascimento, Wallace S

Journal of fish biology

2024 Volume 104, Issue 4, Page(s) 1193–1201

Abstract: Commercially available insecticides present acute toxicity to the health of fish and other aquatic organisms, which may impair the local aquaculture. This study evaluated the gonadal morphology of freshwater fish exposed to pyriproxyfen and fenthion. ... ...

Abstract	Commercially available insecticides present acute toxicity to the health of fish and other aquatic organisms, which may impair the local aquaculture. This study evaluated the gonadal morphology of freshwater fish exposed to pyriproxyfen and fenthion. Forty-five juvenile male Nile tilapias (Oreochromis niloticus) were divided into control, pyriproxyfen-exposed (0.01 g/L), and fenthion-exposed (0.001 g/L) groups. They were evaluated in three moments (30, 60, and 90 days). The variables analyzed were the gonadosomatic index (GSI), weight to length ratio, seminiferous tubules morphometry (diameter and height), tissue damage, and immunohistochemical analysis for caspase-3, tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF). Pyriproxyfen and fenthion injured the seminiferous tubule tissue, and the damage progressed according to the exposure time. In addition, the GSI gradually reduced over time in all groups compared with the first moment (30 days), while caspase-3, TNF-α, and VEGF values increased only in the fenthion-exposed group. Therefore, pyriproxyfen and fenthion changed the gonadal morphology of male Oreochromis niloticus, which may affect their reproduction in the wild or captivity.
MeSH term(s)	Male ; Animals ; Cichlids ; Fenthion/metabolism ; Fenthion/toxicity ; Caspase 3/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Tumor Necrosis Factor-alpha/metabolism ; Pyridines
Chemical Substances	Fenthion (BL0L45OVKT) ; pyriproxyfen (3Q9VOR705O) ; Caspase 3 (EC 3.4.22.-) ; Vascular Endothelial Growth Factor A ; Tumor Necrosis Factor-alpha ; Pyridines
Language	English
Publishing date	2024-01-23
Publishing country	England
Document type	Journal Article
ZDB-ID	410564-3
ISSN	1095-8649 ; 0022-1112
ISSN (online)	1095-8649
ISSN	0022-1112
DOI	10.1111/jfb.15656
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Article ; Online: CT-derived measurements of pulmonary blood volume in small vessels and need for oxygen in COVID-19 patients

De Backer, Wilfried / Lins, Muriel / Dierckx, Wendel / Vandevenne, Jan / De Backer, Jan / Lavon, Benjamin R / Lanclus, Maarten / Rijckaert, Karen / Thillai, Muhunthan

medRxiv

Abstract: In contrast to early reports of conventional acute respiratory distress syndrome (ARDS) as the underlying pathophysiology of hypoxemic respiratory failure observed in patients with severe COVID-19, more recent findings implicate direct involvement of the ...

Abstract	In contrast to early reports of conventional acute respiratory distress syndrome (ARDS) as the underlying pathophysiology of hypoxemic respiratory failure observed in patients with severe COVID-19, more recent findings implicate direct involvement of the pulmonary vasculature in giving rise to these symptoms. In earlier research, we demonstrated that patients with COVID-19 showed markedly reduced pulmonary blood volumes in pulmonary vessels <5 mm<sup>2</sup> in cross-sectional area visible on imaging (termed "BV5"), with attendant dilation of larger, more proximal vessels. Here, we present preliminary results in which reduced BV5 is shown to correlate significantly with increased need for supplemental oxygen and abnormal arterial blood gas measurements in hospitalized COVID-19 patients. We suggest a potential mechanistic link between observed clinical, pathological, and imaging findings, and outline how these may be helpful in clinical assessment as well as the development of novel therapies.
Keywords	covid19
Language	English
Publishing date	2020-06-05
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.06.03.20121483
Database	COVID19

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Article: Assessment of Small Pulmonary Blood Vessels in COVID-19 Patients Using HRCT

Lins, Muriel / Vandevenne, Jan / Thillai, Muhunthan / Lavon, Ben R / Lanclus, Maarten / Bonte, Stijn / Godon, Rik / Kendall, Irvin / De Backer, Jan / De Backer, Wilfried

Acad Radiol

Abstract: RATIONALE AND OBJECTIVES: Mounting evidence supports the role of pulmonary hemodynamic alternations in the pathogenesis of COVID-19. Previous studies have demonstrated that changes in pulmonary blood volumes measured on computed tomography (CT) are ... ...

Abstract	RATIONALE AND OBJECTIVES: Mounting evidence supports the role of pulmonary hemodynamic alternations in the pathogenesis of COVID-19. Previous studies have demonstrated that changes in pulmonary blood volumes measured on computed tomography (CT) are associated with histopathological markers of pulmonary vascular pruning, suggesting that quantitative CT analysis may eventually be useful in the assessment pulmonary vascular dysfunction more broadly. MATERIALS AND METHODS: Building upon previous work, automated quantitative CT measures of small blood vessel volume and pulmonary vascular density were developed. Scans from 103 COVID-19 patients and 107 healthy volunteers were analyzed and their results compared, with comparisons made both on lobar and global levels. RESULTS: Compared to healthy volunteers, COVID-19 patients showed significant reduction in BV5 (pulmonary blood volume contained in blood vessels of <5 mm2) expressed as BV5/(total pulmonary blood volume; p < 0.0001), and significant increases in BV5-10 and BV 10 (pulmonary blood volumes contained in vessels between 5 and 10 mm2 and above 10 mm2, respectively, p < 0.0001). These changes were consistent across lobes. CONCLUSION: COVID-19 patients display striking anomalies in the distribution of blood volume within the pulmonary vascular tree, consistent with increased pulmonary vasculature resistance in the pulmonary vessels below the resolution of CT.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #679392
Database	COVID19

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Article ; Online: Assessment of small pulmonary blood vessels in COVID-19 patients using HRCT

Lins, Muriel / Vandevenne, Jan / Thillai, Muhunthan / Lavon, Ben R. / Lanclus, Maarten / Bonte, Stijn / Godon, Rik / De Backer, Jan / De Backer, Wilfried

medRxiv

Abstract: ... Background ... Mounting evidence supports the role of pulmonary hemodynamic alternations in the pathogenesis of COVID-19. Previous studies have demonstrated that changes in pulmonary blood volumes measured on CT are associated with histopathological ... ...

Abstract	Background Mounting evidence supports the role of pulmonary hemodynamic alternations in the pathogenesis of COVID-19. Previous studies have demonstrated that changes in pulmonary blood volumes measured on CT are associated with histopathological markers of pulmonary vascular pruning, suggesting that quantitative HRCT analysis may eventually be useful in the assessment pulmonary vascular dysfunction more broadly. Methods Building upon previous work, automated HRCT measures of small blood vessel volume and pulmonary vascular density were developed. Scans from 103 COVID-19 patients and 108 healthy volunteers were analyzed and their results compared, with comparisons made both on lobar and global levels. Results Compared to healthy volunteers, COVID-19 patients showed significant reduction in BV5 (pulmonary blood volume contained in blood vessels of <5 mm<sup>2</sup>) expressed as BV5/(Total pulmonary blood volume) (p<0.0001), and significant increases in BV5_10 and BV 10 (pulmonary blood volumes contained in vessels between 5 and 10 mm<sup>2</sup> and above 10 mm<sup>2</sup>, respectively) (p<0.0001). These changes were consistent across lobes. Conclusions COVID-19 patients display striking anomalies in the distribution of blood volume within the pulmonary vascular tree, consistent with increased pulmonary vasculature resistance in the pulmonary vessels below the resolution of HRCT.
Keywords	covid19
Language	English
Publishing date	2020-05-26
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2020.05.22.20108084
Database	COVID19

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Article: Postextubation Obstructive Pseudomembranes: A Case Series and Review of a Rare Complication After Endotracheal Intubation

Lins, Muriel / Dobbeleir, Itte / Germonpré, Paul / Waelput, Wim / Pauwels, Patrick / Jorens, Philippe G

Lung. 2011 Feb., v. 189, no. 1

2011

Abstract: ... stridor due to adherence to the tracheal wall and obstruction of the airway. In most cases, the lesion is ...

Abstract	Endotracheal intubation obviously may be life-saving, but it may also lead to complications, including those related to damage of the airways. Superficial damage of the trachea at the site of the endotracheal cuff may trigger the formation of an obstructive fibrinous tracheal pseudomembrane (OFTP). Shortly after extubation, this clot, consisting of fibrin, leucocytes, and necrotic epithelium, can cause stridor due to adherence to the tracheal wall and obstruction of the airway. In most cases, the lesion is easily removed by rigid or fiberoptic bronchoscopy and virtually never leads to permanent damage. The study consisted of case series and review of the literature. This report describes a series of five adult cases and reviews all 19 other previously described cases. A careful analysis of all reported cases, however, did not highlight a simple predisposing factor or illness. It is important to consider OFTP in the differential diagnosis of stridor and respiratory insufficiency in the postextubation period.
Language	English
Dates of publication	2011-02
Size	p. 81-86.
Publisher	Springer-Verlag
Publishing place	New York
Document type	Article
ZDB-ID	6165-7
ISSN	1432-1750 ; 0341-2040
ISSN (online)	1432-1750
ISSN	0341-2040
DOI	10.1007/s00408-010-9263-2
Database	NAL-Catalogue (AGRICOLA)

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