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Marina Gueçamburu,1– 3 Guillaume Verdy,4 Julie Cuadros,1 Cécilia Nocent-Ejnaini,2 Julie Macey,1 Laurent Portel,3 Amandine Rapin,5,6 Maéva Zysman1,7 1Service des Maladies Respiratoires, CHU Bordeaux, Pessac, 33604, France; 2Service de pneumologie, Centre Hospitalier de la Côte Basque, Bayonne, France; 3Service de pneumologie, Centre Hospitalier Robert Boulin, Libourne, France; 4Unité d’Informatique et d’Archivistique Médicales, Service d’Information Médicale, CHU Bordeaux, Pessac, 33604, France; 5Université de Reims Champagne-Ardenne, VieFra, Reims, F-51100, France; 6CHU de Reims, Unité de Médecine Physique et de Réadaptation, Reims, F-51100, France; 7Univ-Bordeaux, Centre de Recherche cardio-thoracique de Bordeaux, U1045, CIC 1401, Pessac, F-33604, FranceCorrespondence: Marina Gueçamburu, Service des Maladies Respiratoires, CHU Bordeaux, Pessac, 33604, France, Email marina.guecamburu@live.frPurpose: Pulmonary rehabilitation (PR) is a type of multidisciplinary care strongly recommended after severe exacerbation of chronic obstructive pulmonary disease (COPD). Recently, a national French study reported a very low rate of PR uptake (8.6%); however, important clinical data were missing. Here, we aimed to identify the main factors associated with insufficient PR uptake after hospitalisation for COPD exacerbation.Patients and Methods: This multicentre retrospective study included patients hospitalised with COPD exacerbation between 1 January 2017 and 31 December 2018, as identified by both coding and a detailed review of medical records. PR was defined as inpatient care in a specialised centre or unit within 90 days of discharge. Multivariate logistic regression was used to identify associations between PR uptake and patient characteristics, such as comorbidities, non-invasive ventilation (NIV), inhaled treatment, and forced expiratory volume in 1 second (FEV1).Results: Among the 325 patients admitted for severe COPD exacerbation, 92 (28.3%) underwent PR within 90 days of discharge. In univariate analysis, relative to those who underwent PR, patients without PR had significantly more comorbidities, were less often treated with triple bronchodilator therapy or NIV, and had a higher FEV1. In multivariate analysis, variables independently associated with the lack of PR uptake were the presence of comorbidities (adjusted odds ratio (aOR) = 1.28 [1.10– 1.53], p = 0.003) and a higher FEV1 (aOR = 1.04 [1.02– 1.06], p < 0.001). There was no significant correlation between PR uptake and departmental PR centre capacity (notably, some departments had no PR facilities).Conclusion: These data highlight the lack of PR in the early stages of COPD. Collaboration among all healthcare providers involved in patient management is crucial for improved PR uptake.Plain Language Summary: Pulmonary rehabilitation (PR) is multidisciplinary care strongly recommended after severe exacerbation of chronic obstructive pulmonary disease (COPD); however, referral remains very low in France. We have shown, in three French centres, that early-stage COPD and associated comorbidities are the main factors contributing to insufficient PR after hospitalisation for exacerbation. Collaboration among all healthcare providers involved in patient management is crucial to improve PR uptake in the years ahead because physical medicine and rehabilitation professionals play key roles in the promotion and early initiation of PR programs.Keywords: COPD, comorbidities, healthcare resources, pulmonary rehabilitation

Chronic obstructive pulmonary disease (COPD) is a frequently occurring disease entailing high morbidity and mortality, and relevant therapeutic resources are limited. As is the case with asthma, the current trend consists in the phenotyping of COPD patients so as to develop personalized medicine tailored to a given individual's inflammatory profile. The aim of this review is to summarize the role of biologic agents in the management of COPD, taking into consideration not only COPD pathophysiology, but also the previously published studies and the relatively encouraging prospects for the future., (Copyright © 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

MEDICATION MANAGEMENT OF COPD. The management of chronic obstructive pulmonary disease (COPD) is based on drug and non-drug measures. Inhaled therapies are the major issues including the use of short-acting bronchodilators for respiratory symptoms. If symptoms are daily, such as disabling dyspnea or frequent exacerbations, daily treatment with a long-acting bronchodilator is proposed: anti-muscarinic (LAMA) or β2-agonist (LABA). If there is no improvement, escalation to dual and then triple therapy is proposed. Another major issue in the management of COPD is de-escalation in the event of ineffectiveness or side effects of inhaled corticosteroids (ICS). Finally, the role of blood eosinophils and other biomarkers is even more important that biotherapies could expand the therapeutic options for some subtypes of COPD patients., Competing Interests: M. Gueçamburu déclare n’avoir aucun lien d’intérêts. M. Zysman déclare des interventions ponctuelles pour Boehringer Ingelheim, GSK, AstraZeneca, Chiesi, CSL Behring, AVAD et avoir été prise en charge, à l’occasion de déplacement pour congrès, par Boehringer Ingelheim, GSK, AstraZeneca, Chiesi.

Introduction: Sequential anti-programmed cell death protein 1 (PD-1) or anti-programmed death-ligand 1 (PD-L1) followed by small targeted therapy use is associated with increased prevalence of adverse events (AEs) in NSCLC. KRASG12C inhibitor sotorasib may trigger severe immune-mediated hepatotoxicity when used in sequence or in combination with anti-PD-(L)1. This study was designed to address whether sequential anti-PD-(L)1 and sotorasib therapy increases the risk of hepatotoxicity and other AEs., Methods: This is a multicenter, retrospective study of consecutive advanced KRAS G12C -mutant NSCLC treated with sotorasib outside clinical trials in 16 French medical centers. Patient records were reviewed to identify sotorasib-related AEs (National Cancer Institute Common Classification Criteria for Adverse Events-Version 5.0). Grade 3 and higher AE was considered as severe. Sequence group was defined as patients who received an anti-PD-(L)1 as last line of treatment before sotorasib initiation and control group as patients who did not receive an anti-PD-(L)1 as last line of treatment before sotorasib initiation., Results: We identified 102 patients who received sotorasib, including 48 (47%) in the sequence group and 54 (53%) in the control group. Patients in the control group received an anti-PD-(L)1 followed by at least one treatment regimen before sotorasib in 87% of the cases or did not receive an anti-PD-(L)1 at any time before sotorasib in 13% of the cases. Severe sotorasib-related AEs were significantly more frequent in the sequence group compared with those in the control group (50% versus 13%, p < 0.001). Severe sotorasib-related AEs occurred in 24 patients (24 of 48, 50%) in the sequence group, and among them 16 (67%) experienced a severe sotorasib-related hepatotoxicity. Severe sotorasib-related hepatotoxicity was threefold more frequent in the sequence group compared with that in the control group (33% versus 11%, p = 0.006). No fatal sotorasib-related hepatotoxicity was reported. Non-liver severe sotorasib-related AEs were significantly more frequent in the sequence group (27% versus 4%, p < 0.001). Severe sotorasib-related AEs typically occurred in patients who received last anti-PD-(L)1 infusion within 30 days before sotorasib initiation., Conclusions: Sequential anti-PD-(L)1 and sotorasib therapy are associated with a significantly increased risk of severe sotorasib-related hepatotoxicity and severe non-liver AEs. We suggest avoiding starting sotorasib within 30 days from the last anti-PD-(L)1 infusion., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

COPD is a major cause of morbidity and mortality worldwide. As research progresses, new patient phenotypes are being defined, providing hope for more personalized management of the disease. A significant proportion of patients present with an increased level of blood eosinophils, which may reflect bronchial eosinophilic inflammation. The aims of this article are to characterize the role of eosinophils in COPD in terms of pathophysiology, associated respiratory symptoms, impact on treatment and, finally, to consider different future treatment options., (Copyright © 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.)