Search

PEGylation is a promising approach to increase the residence time of antibody fragments in the lungs and sustain their therapeutic effects. However, concerns arise as to the potential pulmonary toxicity of antibody fragments conjugated to high molecular weight (HMW)polyethylene glycol (PEG), notably after repeated administrations, and the possibility of PEG accumulation in the lungs. The purpose of this proof-of-concept study is to give insights about the safety of lung administration of a Fab’ anti-IL17A antibody fragment conjugated to two-armed 40kDa PEG (PEG40). The presence of the PEG40 moiety inside alveolar macrophages remained stable for at least 24 hours after intratracheal administration of PEG40-Fab’ to mice. PEG40 was then progressively cleared from alveolar macrophages. Incubation of PEG40 alone with macrophages in vitro did not significantly harm macrophages and did not affect phagocytosis or the production of inflammatory markers. After acute or chronic administration of PEG40-Fab’ to mice, no signs of significant pulmonary toxicity or inflammatory cell accumulation were observed. A vacuolization of alveolar macrophages not associated with any inflammation was noticed when PEG40, PEG40-Fab’, or unPEGylated Fab’ were administered. To conclude this preliminary proof of concept study, acute or repeated pulmonary administrations of PEGylated Fab’ appear safe in rodents.

Oestrogen signalling pathways are emerging targets for lung cancer therapy. Unravelling the contribution of oestrogens in lung cancer development is a pre-requisite to support the development of sex-based treatments and identify patients who could potentially benefit from anti-oestrogen treatments. In this study, we highlight the contribution of lymphatic and blood endothelia in the sex-dependent modulation of lung cancer. The orthotopic graft of syngeneic lung cancer cells into immunocompetent mice showed that lung tumours grow faster in female mice than in males. Moreover, oestradiol (E2) promoted tumour development, increased lymph/angiogenesis and VEGFA and bFGF levels in lung tumours of females through an oestrogen receptor (ER) alpha-dependent pathway. Furthermore, while treatment with ERb antagonist was inefficient, ERa antagonist (MPP) and tamoxifen decreased lung tumour volumes, altered blood and lymphatic vasculature and reduced VEGFA and bFGF levels in females, but not in males. Finally, the quantification of lymphatic and blood vasculature of lung adenocarcinoma biopsies from patients aged between 35 and 55 years revealed more extensive lymphangiogenesis and angiogenesis in tumour samples issued from women than from men. In conclusion, our findings highlight an E2/ERa-dependent modulation of lymphatic and blood vascular components of lung tumour microenvironment. Our study has potential clinical implication in a personalised medicine perspective by pointing to the importance of oestrogen status or supplementation on lung cancer development that should be considered to adapt therapeutic strategies., info:eu-repo/semantics/published

Evidence and guidelines are becoming increasingly clear about imbalance between the risks and benefits of inhaled corticosteroids (ICSs) in patients with COPD. While selected patients may benefit from ICS-containing regimens, ICSs are often inappropriately prescribed with – according to Belgian market research data – up to 70% of patients in current practice receiving ICSs, usually as a fixed combination with a long-acting β2-adrenoreceptor agonist. Studies and recommendations support withdrawal of ICSs in a large group of patients with COPD. However, historical habits appear difficult to change even in the light of recent scientific evidence. We have built a collaborative educational platform with chest physicians and primary care physicians to increase awareness and provide guidance and support in this matter., SCOPUS: re.j, info:eu-repo/semantics/published

Didier Cataldo,1 Eric Derom,2 Giuseppe Liistro,3 Eric Marchand,4,5 Vincent Ninane,6 Rudi Peché7 Hans Slabbynck,8 Walter Vincken,9 Wim Janssens10 1Department of Respiratory Medicine, Centre Hospitalier Universitaire de Liège (CHU) and University of Liège, Liège, Belgium; 2Department of Respiratory Medicine, Ghent University Hospital, Gent, Belgium; 3Department of Respiratory Medicine, University Hospitals Saint-Luc, Brussels, Belgium; 4Department of Respiratory Medicine, University Hospital UCL Namur, Yvoir, Belgium; 5URPhyM, University of Namur, Namur, Belgium; 6Department of Respiratory Medicine, University Hospital Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium; 7Department of Respiratory Medicine, University Hospital Vésale, Montigny-le-Tilleul, Belgium; 8Department of Respiratory Medicine, ZNA Middelheim, Antwerpen, Belgium; 9Respiratory Division, University Hospital Brussels (UZ Brussel), Vrije Universiteit Brussel, Brussels, Belgium; 10Department of Respiratory Medicine, University Hospitals Leuven, Leuven, Belgium Abstract: Evidence and guidelines are becoming increasingly clear about imbalance between the risks and benefits of inhaled corticosteroids (ICSs) in patients with COPD. While selected patients may benefit from ICS-containing regimens, ICSs are often inappropriately prescribed with – according to Belgian market research data – up to 70% of patients in current practice receiving ICSs, usually as a fixed combination with a long-acting β2-adrenoreceptor agonist. Studies and recommendations support withdrawal of ICSs in a large group of patients with COPD. However, historical habits appear difficult to change even in the light of recent scientific evidence. We have built a collaborative educational platform with chest physicians and primary care physicians to increase awareness and provide guidance and support in this matter. Keywords: COPD, ex

Le cancer du col de l’utérus était le 4ème cancer féminin le plus fréquent pour l’année 2012 avec la majorité des cas se manifestant dans les pays en voie de développement. Bien que ce cancer soit induit par les infections, très courantes, de papillomavirus humains (HPV), seul un très faible pourcentage des femmes infectées développera un jour la maladie. Les défenses immunitaires de l’hôte sont essentielles pour éradiquer l’infection et éliminer les cellules infectées qui se sont transformées. En effet, la majorité des femmes infectées éliminent le virus dans les deux années qui suivent l’infection tandis que les patientes immunodéprimées sont plus susceptibles de développer des lésions précancéreuses et cancéreuses du col de l’utérus. Dans différents modèles, les lymphocytes T γδ protègent contre la formation de carcinomes épidermoïdes (SCC). À ce jour, la contribution des lymphocytes T γδ dans les SCC du col utérin associés à HPV reste inconnue. Dans cette étude, nous avons cherché à identifier l’impact des lymphocytes T γδ dans un modèle murin transgénique de carcinogenèse induite par les oncoprotéines d’HPV16. Contre toute attente, les lymphocytes T γδ favorisaient le développement des lésions induites par les oncoprotéines d’HPV16. Ces oncoprotéines induisaient une diminution de l’expression de Skint-1 au niveau de l’épiderme et des modifications des lymphocytes T Vγ5+ anti-tumoraux (ou DETC), qui ont été rejoints par d’autres sous-types de lymphocytes T γδ producteurs d’IL-17. Ces derniers promouvaient la formation de vaisseaux sanguins dans le derme sous-jacent des lésions induites par HPV, en accord avec les effets pro-angiogéniques de l’IL-17. Dans les biopsies humaines de col utérin, seules les lésions SCC, où les oncoprotéines sont hautement exprimées, présentaient des lymphocytes T γδ IL-17+. Ce résultat soutient la pertinence clinique de nos observations obtenues grâce à notre modèle murin. Ensemble, nos résultats suggèrent que les oncoprotéines d’HPV1, Doctorat en Sciences biomédicales et pharmaceutiques (Pharmacie), info:eu-repo/semantics/nonPublished

Didier Cataldo,1 Jean-Louis Corhay,1 Eric Derom,2 Renaud Louis,1 Eric Marchand,3,4 Alain Michils,5 Vincent Ninane,6 Rudi Peché,7 Charles Pilette,8 Walter Vincken,9 Wim Janssens10 1Department of Respiratory Diseases, CHU Liège, University of Liège, Liège, 2Department of Respiratory Medicine, Ghent University Hospital, Ghent, 3Department of Respiratory Medicine, CHU – UCL – Namur, Université catholique de Louvain, Yvoir, 4Molecular Physiology Research Unit (URPhyM)-NARILIS, Laboratory of General Physiology, University of Namur, Namur, 5Chest Department, Erasme University Hospital, Université Libre de Bruxelles, Brussels, 6Department of Respiratory Medicine, University Hospital Saint-Pierre, Université Libre de Bruxelles, Brussels, 7Department of Respiratory Medicine, University Hospital Vésale, Montigny-le-Tilleul, 8Department of Respiratory Medicine, Cliniques universitaires St Luc, Université Catholique de Louvain, Brussels, 9Respiratory Division, University Hospital Brussels (UZ Brussel), Vrije Universiteit Brussel, Brussels, 10Department of Respiratory Diseases, University Hospitals Leuven, Leuven, Belgium Introduction: Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma–COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse and inconsistent. This survey aimed to identify consensus on criteria for diagnosing ACOS.Methods: A Belgian expert panel developed a survey on ACOS diagnosis, which was completed by 87 pulmonologists. Answers chosen by ≥70% of survey respondents were considered as useful criteria for ACOS diagnosis. The two most frequently selected answers were considered as major criteria, others as minor criteria. The expert panel proposed a minimal requirement of two major criteria and one minor criterion for ACOS diagnosis. Respondents wer

Introduction: Patients with chronic airway disease may present features of both asthma and COPD, commonly referred to as asthma–COPD overlap syndrome (ACOS). Recommendations on their diagnosis are diffuse and inconsistent. This survey aimed to identify consensus on criteria for diagnosing ACOS. Methods: A Belgian expert panel developed a survey on ACOS diagnosis, which was completed by 87 pulmonologists. Answers chosen by ≥70% of survey respondents were considered as useful criteria for ACOS diagnosis. The two most frequently selected answers were considered as major criteria, others as minor criteria. The expert panel proposed a minimal requirement of two major criteria and one minor criterion for ACOS diagnosis. Respondents were also asked which criteria are important for considering inhaled corticosteroids prescription in a COPD patient. Results: To diagnose ACOS in COPD patients, major criteria were “high degree of variability in airway obstruction over time (change in forced expiratory volume in 1 second ≥400 mL)” and “high degree of response to bronchodilators (>200 mL and ≥12% predicted above baseline)”. Minor criteria were “personal/family history of atopy and/or IgE sensitivity to ≥1 airborne allergen”, “elevated blood/sputum eosinophil levels and/or increased fractional exhaled nitric oxide”, “diagnosis of asthma <40 years of age”; “symptom variability”, and “age (in favor of asthma)”. To diagnose ACOS in asthma patients, major criteria were “persistence of airflow obstruction over time (forced expiratory volume in 1 second/forced vital capacity ratio <0.7)” and “exposure to noxious particles/gases, with ≥10 pack-years for (ex-)smokers”; minor criteria were “lack of response on acute bronchodilator test”; “reduced diffusion capacity”; “limited variability in airway obstruction”; “age >40 years”; “emphysema on chest computed tomography scan”. Conclusion: Specific criteria were identified that may guide physicians to a more uniform diagnostic approach for AC, SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Pharmaceutical companies offer an increasing number of inhaler devices, whether or not together with new substances, for maintenance treatment of patients with COPD or asthma. However, well-designed studies to support these developments are scarce. Objectives: The aim of this research was to evaluate how far new developments of inhaler devices are scientifically supported and translate into improvements of patient preferences and/or clinical outcomes. Methods: A systematic literature review was performed to retrieve randomised controlled trials in patients with COPD or asthma that studied the in-company evolution of inhaler devices. Results were tabulated and discussed. Results: A total of 30 studies were found comparing Respimat® vs. HandiHaler®, Diskus®(Accuhaler®) vs. Diskhaler®(Rotadisk®) or pMDI, Ellipta® vs. Diskus®(Accuhaler®), Nexthaler® vs. pMDI, or Breezhaler® vs. Aerolizer®. These studies show that developments of inhaler devices may improve patient satisfaction but do not lead to demonstrable improvements in clinical efficacy. Current changes of devices are most commonly parallelled by changes in administration frequency towards once daily treatment. The only well-documented effect was found for the Respimat® Soft Mist™ Inhaler, which realises a more than 3-fold lowering of the once-daily tiotropium dose through increased performance of the inhaler device. There are however, no data on clinical efficacy or safety comparing the two devices at the same dosage. Conclusions: Future developments of inhaler devices should all require well-designed studies to demonstrate patient benefit.