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1. Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study

Author

Paul Michel Mertes, Nadine Petitpain, Charles Tacquard, Marion Delpuech, Cédric Baumann, Jean Marc Malinovsky, Dan Longrois, Aurélie Gouel-Cheron, Diane Le Quang, Pascal Demoly, Jean Louis Guéant, Pierre Gillet, Emmanuelle Aguinet, Pol André Apoil, Jean Eric Autegarden, Faiza Bettayeb, Céline Biermann, Maryline Bordes-demolis, Anca Chiriac, Pierre Antoine Darene, Frédéric Deblay, Sabrina Dessard, Charles Dzviga, Hassan El Hanache, Alain Facon, Yannick Fuhrer, Noémie Gest, Marion Gouitaa, Adela Harpan, Cyrille Hoarau, Lisa Le Guillou, Laurence Lepeltier, Claire Mailhol, Delphine Mariotte, Yannick Meunier, Isabelle Migueres, Martine Morisset, Catherine Neukirch, Dalila Nouar, Yann Ollivier, Isabelle Orsel, Omar Outtas, Minaxi Patel, Christelle Pellerin, Isabelle Petit, Anaïs Pipet, Cécile Rochefort-Morel, Claire Schwartz, Sandrine Seltzer, Alice Seringulian, Angèle Soria, Lilia Soufir, Rodolphe Stenger, Céline Tummino, Marion Verdaguer, Les Hôpitaux Universitaires de Strasbourg (HUS), Biologie et Pharmacologie des Plaquettes sanguines : hémostase, thrombose, transfusion (BPP), Université de Strasbourg (UNISTRA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Nouvel Hôpital Civil de Strasbourg, Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département Méthodologie Promotion Investigation [CHRU Nancy] (MPI), Centre Hospitalier Universitaire de Reims (CHU Reims), Hémostase et Remodelage Vasculaire Post-Ischémie (HERVI - EA 3801), Université de Reims Champagne-Ardenne (URCA), Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre de référence des maladies héréditaires du métabolisme (MaMEA Nancy-Brabois), Service d'Hépato-gastro-entérologie [CHRU Nancy], Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Pharmacologie Clinique et Toxicologie [CHRU Nancy], The ALPHO study NCT02250729 was requested and supported by the European Medicines Agency (EMA). It was funded by a consortium of pharmaceutical companies marketing pholcodine (Zambon, Urgo, Les Laboratoires Pierre Fabre, Boots, Hepatoum, Biocodex, Sanofi, Laboratoires Bouchara Recordati, GlaxoSmithKline, Alliance Pharmaceuticals Ltd, Bells Healthcare, Pinewood, T & R, Ernest Jackson, Vemedia)., and ALPHO Study Group: Emmanuelle Aguinet, Pol André Apoil, Jean Eric Autegarden, Faiza Bettayeb, Céline Biermann, Maryline Bordes-Demolis, Anca Chiriac, Pierre Antoine Darene, Frédéric Deblay, Sabrina Dessard, Charles Dzviga, Hassan El Hanache, Alain Facon, Yannick Fuhrer, Noémie Gest, Marion Gouitaa, Adela Harpan, Cyrille Hoarau, Lisa Le Guillou, Laurence Lepeltier, Claire Mailhol, Delphine Mariotte, Yannick Meunier, Isabelle Migueres, Martine Morisset, Catherine Neukirch, Dalila Nouar, Yann Ollivier, Isabelle Orsel, Omar Outtas, Minaxi Patel, Christelle Pellerin, Isabelle Petit, Anaïs Pipet, Cécile Rochefort-Morel, Claire Schwartz, Sandrine Seltzer, Alice Seringulian, Angèle Soria, Lilia Soufir, Rodolphe Stenger, Céline Tummino, Marion Verdaguer

Subjects
Anesthesiology and Pain Medicine, [SDV]Life Sciences [q-bio], anaphylaxis, anaesthesia, quaternary ammonium compounds, neuromuscular blocking agents, pholcodine
Abstract

International audience; BackgroundNeuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis.MethodsALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated.ResultsOverall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3–7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7–13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (

Published
2023
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2. Circulating Tumor Cells as a Potential Biomarker for Lung Cancer Screening: Results of the AIR Study

Author

Charles-Hugo Marquette, Jacques Boutros, Jonathan Benzaquen, Marion Ferreira, Jean Pastre, Christophe Pison, Bernard Padovani, Faiza Bettayeb, Vincent Fallet, Nicolas Guibert, Damien Basille, Catherine Butori, Marius Ilie, Véronique Hofman, Paul Hofman, and AIR project Study Group

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, Cancer, medicine.disease, Circulating tumor cell, Internal medicine, ISET Test, medicine, Biomarker (medicine), Blood test, business, Lung cancer, Lung cancer screening, Cohort study
Abstract

Background: Lung cancer (LC) screening with low dose chest computed tomography (LDCT) reduces the mortality of eligible individuals. Biological blood signatures act as a screening tool per se and may refine the selection of patients at risk or may help to classify undetermined nodules detected on LDCT.We previously showed that circulating tumor cells (CTC) could be detected by the isolation by size of epithelial tumor cell technique (ISET) long before the cancer was diagnosed radiologically. So, we tested whether CTC could be used as biomarker for screening lung cancer. Methods: We conducted a prospective, multicenter, cohort study in 21 French university centers. Participants had to be eligible for LC screening and to have chronic obstructive pulmonary disease. They underwent 3 screening rounds at 1-year intervals including LDCT and a matched blood test for CTC detection. Participants and investigators were blinded to the results of CTC detection. Cytopathologists were blinded to clinical and radiological findings. Findings: We enrolled 614 participants, predominantly men (71%), aged 65.1 ± 6.5 years, heavy smokers with 52.7 ± 21.5 pack-years. Nodules were detected on 178 (29%) baseline LDCTs. Nineteen subjects (3.1%) were diagnosed with a prevalent LC and nineteen (2.8 %) with an incident LC. Extra-pulmonary cancers (EPC) were diagnosed in 26 (4.2 %) participants. At baseline, the sensitivity of CTC detection for LC detection was 26.3 %. The ISET test was unable to predict LC or EPC development. Interpretation: The CTC detection-based LC screening using ISET failed to confirm our initial promising results. Trial Registration: ClinicalTrials.gov identifier: NCT02500693. Funding Statement: Conseil Departemental 06, Fondation UNICE, Fondation AVENI, Fondation de France, and Ligue Contre le Cancer - Comite des Alpes-Maritimes and private donators. Declaration of Interests: The authors stated: "None declared." Ethics Approval Statement: National ethic committee approval (CPP Sud Mediterranee V; registration # 15.072) and ANSM (Ministry of Health).

Published
2019
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