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Excessive daytime sleepiness (EDS) is frequent among patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and can persist despite the optimal correction of respiratory events (apnea, hypopnea and respiratory efforts), using continuous positive airway pressure (CPAP) or mandibular advancement device. Symptoms like apathy and fatigue may be mistaken for EDS. In addition, EDS has multi-factorial origin, which makes its evaluation complex. The marketing authorization [Autorisation de Mise sur le Marché (AMM)] for two wake-promoting agents (solriamfetol and pitolisant) raises several practical issues for clinicians. This consensus paper presents recommendations of good clinical practice to identify and evaluate EDS in this context, and to manage and follow-up the patients. It was conducted under the mandate of the French Societies for sleep medicine and for pneumology [Société Française de Recherche et de Médecine du Sommeil (SFRMS) and Société de Pneumologie de Langue Française (SPLF)]. A management algorithm is suggested, as well as a list of conditions during which the patient should be referred to a sleep center or a sleep specialist. The benefit/risk balance of a wake-promoting drug in residual EDS in OSAHS patients must be regularly reevaluated, especially in elderly patients with increased cardiovascular and psychiatric disorders risks. This consensus is based on the scientific knowledge at the time of the publication and may be revised according to their evolution., Competing Interests: Declaration of competing interest Pr Andrejak has been a speaker at symposiums for Moderna, Chiesi, AstraZeneca et Insmed, unrelated to this subject. Pr Arnulf was a paid consultant for Idorsia Pharma in 2020 and unpaid for Takeda Pharma in 2022, unrelated to this subject. Dr Baillieul has been paid for work for Jazz Pharmaceuticals; clinical study investigator for Bioprojet; received support from Agiradom, Vitalaire and Bioprojet for participation in a congress. Dr Barateau was a consultant for Bioprojet, Takeda, Idorsia, and Jazz Pharmaceuticals between 2020 and 2022, and a speaker for Bioprojet, Jazz Pharmaceuticals and Idorsia. Dr Bequignon has been a consultant for Air Liquide Santé, GSK, Sanofi, paid talks for Bioprojet, Inspire, GSK, Sanofi, Amplifon. Pr Boutouyrie was a consultant for Bioprojet and Jazz-pharmaceutics in 2021 and 2022, related to this subject. Pr Dauvilliers has been consultant and speaker and has been invited to conferences by UCB Pharma, Jazz, Theranexus, Idorsia, Takeda, Avadel and Bioprojet. Pr Gagnadoux has worked as consultant for Air Liquide Santé, Asten santé, Bioprojet, Inspire, Sefam, Resmed; and as a paid speaker for Bioprojet, Cidelec, Inspire, Jazz Pharmaceuticals, Philips Respironics. Pr Geoffroy has been paid speaker for Biocodex, Bioprojet, Idorsia, Janssen-Cilag, Jazz pharmaceuticals, Lundbeck, MySom- meil, Withings; received fees as expert for Apneal, Biocodex, Dayvia, Idorsia, Janssen-Cilag, Jazz pharmaceuti- cals, Myndblue, Posos, ResilEyes, Withings; and is a member of the advisory boards of: Apneal, Idorsia, Mindblue, Mysommeil. Dr Jaffuel has been involved in clinical trials, scientific work, consulting, conferences, symposiums and other activities over the past 5 years for the following companies and organizations: ALK, AstraZeneca, Bohringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi; en rapport avec l'article, Adene, Bastide, Bioprojet, Jazz, Löwenstein, LVL, Nomics, Philips Respironics, Resmed, Sefam, Tali. Pr Micoulaud-Franchi has been a consultant for Gilead, Eisai et Bioprojet. Pr Monaca has been speaker for UCB Pharma, Jazz; consultant for Resmed, investigator for Jazz, Bioprojet, Theranexus. Pr Montani and Dr report no conflicts of interest. Dr Patout: research project funding: Fisher & Paykel, Resmed, Asten Santé - Consultant: Resmed, Philips Respironics, Asten Santé, GSK - Paid talks: Philips Respironics, Resmed, Elivie, SOS O2, Chiesi, Asten Santé, Air Liquide Medical Système, Antadir, Jazz Pharmaceutical, Lowenstein - Actions: Kernel Biomedical - Conference support: Asten Santé. Pr Pépin has received research funding from: Air Liquide Foundation, Agiradom, AstraZeneca, Fisher and Paykel, Mutualia, Philips, Resmed and Vitalaire; et a été consultant pour Agiradom, AstraZeneca, Boehringer Ingelheim, Jazz pharmaceutical, Night Balance, Philips, Resmed et Sefam. Pr Philip reports that he has been a consultant for Jazz Phar maceuticals and Bioprojet. Pr Tamisier has received payment for scientific communication from Resmed, Philips, Elivie and Agiradom, support for participating in a congress for Laboratoires Agiradom. RT received financing for research from Fondations Resmed APMC, Resmed, Philips, and Vitalaire, took part in scientific committees for Respicardia, Sorin et Jazz Pharmaceutical, Inspire and Resmed. Pr Trzepizur was invited to scientific congress by Asten and gave a paid talk for AstraZeneca., (Copyright © 2024 SPLF and Elsevier Masson SAS. All rights reserved.)

Background: The airway epithelium (AE) fulfils multiple functions to maintain pulmonary homeostasis, among which ensuring adequate barrier function, cell differentiation and polarization, and actively transporting immunoglobulin A (IgA), the predominant mucosal immunoglobulin in the airway lumen, via the polymeric immunoglobulin receptor (pIgR). Morphological changes of the airways have been reported in ARDS, while their detailed features, impact for mucosal immunity, and causative mechanisms remain unclear. Therefore, this study aimed to assess epithelial alterations in the distal airways of patients with ARDS., Methods: We retrospectively analyzed lung tissue samples from ARDS patients and controls to investigate and quantify structural and functional changes in the small airways, using multiplex fluorescence immunostaining and computer-assisted quantification on whole tissue sections. Additionally, we measured markers of mucosal immunity, IgA and pIgR, alongside with other epithelial markers, in the serum and the broncho-alveolar lavage fluid (BALF) prospectively collected from ARDS patients and controls., Results: Compared to controls, airways of ARDS were characterized by increased epithelial denudation (p = 0.0003) and diffuse epithelial infiltration by neutrophils (p = 0.0005). Quantitative evaluation of multiplex fluorescence immunostaining revealed a loss of ciliated cells (p = 0.0317) a trend towards decreased goblet cells (p = 0.056), and no change regarding cell progenitors (basal and club cells), indicating altered mucociliary differentiation. Increased epithelial permeability was also shown in ARDS with a significant decrease of tight (p < 0.0001) and adherens (p = 0.025) junctional proteins. Additionally, we observed a significant decrease of the expression of pIgR, (p < 0.0001), indicating impaired mucosal IgA immunity. Serum concentrations of secretory component (SC) and S-IgA were increased in ARDS (both p < 0.0001), along other lung-derived proteins (CC16, SP-D, sRAGE). However, their BALF concentrations remained unchanged, suggesting a spillover of airway and alveolar proteins through a damaged AE., Conclusion: The airway epithelium from patients with ARDS exhibits multifaceted alterations leading to altered mucociliary differentiation, compromised defense functions and increased permeability with pneumoproteinemia., (© 2024. The Author(s).)

In this observational study, we show that switching biologics in severe asthma results in a high proportion of controlled patients., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: Nasal polyposis (NP) is a comorbidity of type 2 severe asthma (SA) which could influence response to SA biologics., Methods: We evaluated (super-) response in SA patients with (NP +) and without NP (NP-) enrolled in the Belgian Severe Asthma Registry (BSAR)., Results: 914 patients, of whom 31% NP + , were included. At enrollment, NP + patients had higher annual exacerbation rates, higher number of emergency room visits and more elevated type 2 biomarkers. In the longitudinal subanalysis of 104 patients, both groups had significant and similar asthma responses to asthma biologics, except for a greater increase in FEV 1 in the NP + group. Super-response was achieved in 33 patients (32%), irrespective of NP status or type of biologic., Conclusion: In conclusion, both NP + and NP - patients had positive treatment responses, with some able to achieve super-response. In SA patients with NP, a greater FEV 1 improvement as compared to SA patients without NP was observed., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Chronic rhinosinusitis (CRS) is a highly prevalent airway disease worldwide. Whereas eosinophilic CRS with nasal polyps (eCRSwNP) represents its most severe phenotype, pathogenic mechanisms remain poorly understood despite a wide spectrum of in vitro and in vivo experimental models. A mouse model of experimental ovalbumin (OVA)-induced airway allergy with coadministration of Staphylococcus aureus enterotoxin B (SEB) has been widely used to study eosinophilic eCRSwNP. This study revisits the features of this model and its suitability for studying eCRS., Methodology: We implemented the most used eCRSwNP mouse model based on OVA+SEB intranasal challenges. Readouts including inflammatory features by (immuno)histology of the sinonasal epithelium (NP formation, eosinophils, epithelial and basement membrane thickness, fibrosis, goblet cells, Charcot-Leyden crystals (CLC)-like, tight junctions) and IgE production by enzyme-linked immunosorbent assay (ELISA), were compared to features of the corresponding human disease., Results: The OVA+SEB model induced eosinophilic inflammation of upper and lower airways, with epithelial and basement membrane thickening, goblet cell hyperplasia and subepithelial fibrosis in the sinuses, along increased IgE production. Except local IgE in nasal lavage (NL), which was only increased in OVA+SEB group, all other features did not differ between OVA and OVA+SEB groups. Macro- or microscopic NP were not detected., Conclusions: With the notable exception of local IgE production, the addition of SEB did not induce additional inflammatory or structural change in the sinuses from mice exposed to and challenged with OVA. This model might represent a model for severe upper airway allergy rather than a specific model of human eCRSwNP.