TY - JOUR T1 - Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.00453-2019 VL - 53 IS - 6 SP - 1900453 AU - Jeanne-Marie Perotin AU - James P.R. Schofield AU - Susan J. Wilson AU - Jonathan Ward AU - Joost Brandsma AU - Fabio Strazzeri AU - Aruna Bansal AU - Xian Yang AU - Anthony Rowe AU - Julie Corfield AU - Rene Lutter AU - Dominick E. Shaw AU - Per S. Bakke AU - Massimo Caruso AU - Barbro Dahlén AU - Stephen J. Fowler AU - Ildikó Horváth AU - Peter Howarth AU - Norbert Krug AU - Paolo Montuschi AU - Marek Sanak AU - Thomas Sandström AU - Kai Sun AU - Ioannis Pandis AU - Charles Auffray AU - Bertrand De Meulder AU - Diane Lefaudeux AU - John H. Riley AU - Ana R. Sousa AU - Sven-Erik Dahlen AU - Ian M. Adcock AU - Kian Fan Chung AU - Peter J. Sterk AU - Paul J. Skipp AU - Jane E. Collins AU - Donna E. Davies AU - Ratko Djukanović A2 - , Y1 - 2019/06/01 UR - http://erj.ersjournals.com/content/53/6/1900453.abstract N2 - Gastro-oesophageal reflux disease (GORD) and obesity are associated with frequent exacerbations and poor quality of life in people living with asthma. Multiple mechanisms have been proposed for the effect of obesity, including modification of inflammation affecting epithelial cell proliferation and wound repair, while the role of GORD is poorly understood and proton pump inhibitors (PPIs) are of variable efficacy. GORD might exert a deleterious effect by inducing vagal reflex, neuroinflammation and directly triggering airway inflammation (via microaspiration). Studies of reflux in animal models and human bronchial epithelial cell culture show varying impact on inflammation and airway remodelling. We have recently demonstrated changes in the sputum proteome in severe asthmatics with GORD, providing supportive evidence for gastric secretions exerting a direct effect on the airways [1]. The epithelium plays a key role in asthma, so in this study, we speculated that severe asthma in obese patients with GORD would be associated with epithelial dysfunction. Because GORD is treated with PPIs, drugs associated with risk of pneumonia and exacerbations of chronic obstructive pulmonary disease (COPD) and cystic fibrosis, the impact of PPIs was also assessed.Stratification of severe asthma on the basis of bronchial epithelial gene expression identified a subset whose endotype is defined by marked epithelial dysregulation associated with obesity, gastro-oesophageal reflux and proton pump inhibitors http://bit.ly/2EeKv23J-M. Perotin is the recipient of a European Respiratory Society Long-Term Fellowship (LTRF 2017) and received additional funding to support her research in Southampton, UK, from the Association Régionale pour l'Aide aux Insuffisants Respiratoires de Champagne-Ardenne, Association Nationale de Formation Continue en Allergologie, Association des Allergologues de Champagne-Ardenne and Association des Pneumologues de Champagne-Ardenne. This funding is gratefully acknowledged. ER -