Introduction La dyspnée chronique est un symptôme fréquent, associé à une consommation importante de soins et, de façon indépendante, à une augmentation de la mortalité. Ce symptôme complexe et multifactoriel demeure insuffisamment caractérisé dans les grandes études épidémiologiques. L’objectif de ce travail était d’estimer la prévalence de la dyspnée et d’en identifier les facteurs associés au sein de CONSTANCES, la plus grande cohorte en population générale française. Méthodes Les données de spirométrie, le score de dyspnée Modified Medical Research Council (mMRC) et le statut tabagique étaient disponibles pour 114 346 des 205 116 adultes inclus entre 2012 et 2021. La dyspnée a été catégorisée en trois classes : mMRC 0, 1, ≥2. Les différentes associations ont été évaluées grâce à des régressions log-binomiales bivariées (référence : mMRC=0) stratifiées selon le sexe. Résultats La prévalence pondérée de la dyspnée mMRC ≥1 était de 23,8 %, celle de la dyspnée mMRC ≥2 de 11,9 %. La prévalence était plus élevée chez les femmes : RR=2,68 [2,59–2,81]. Les analyses bivariées stratifiées sur le sexe ont identifié plusieurs variables associées avec la dyspnée, avec des RR plus élevés chez les hommes dans tous les cas sauf pour l’asthme au cours de la vie. Les RR ci-dessous sont relatifs aux hommes et à mMRC ≥2. La dyspnée chronique était fortement associée à la bronchite chronique (RR=4,50 [4,05–4,98]), la bronchopneumopathie chronique obstructive (RR=7,84 [6,85–8,97]), l’asthme au cours de la vie (RR=1,61 [1,48–1,71]), un âge plus élevé, le tabagisme, les maladies cardiovasculaires (RR=2,57 [2,38–2,77]), la dépression (RR=3,82 [3,55–4,11]), l’état nutritionnel (relation en U avec l’IMC : RR=2,06 [1,44–2,93] pour un IMC <18,5kg/m2, RR=6,64 [6,05–7,28] pour un IMC ≥30kg/m2 ; p quadratique de tendance <10−4, réf.=IMC entre 18,5 et 25kg/m2). Les facteurs socioéconomiques étaient également fortement et positivement associés à la dyspnée chronique : faible revenu, faible niveau d’éducation et indice élevé de défavorisation sociale (FDep : quintile des plus défavorisés vs. quintile des moins défavorisés : RR 2,05 [1,82–2,31]). Bien que le grade mMRC ≥2 soit le seuil généralement utilisé pour qualifier la dyspnée d’invalidante, les participants de grade mMRC1 déclaraient également d’importantes limitations liées à leur santé (RR=2,84 [2,49–3,25]). Conclusion La dyspnée chronique est fréquente dans la population générale, et plus d’un participant sur dix rapportait une dyspnée invalidante. Les facteurs associés étant multiples et fortement corrélés entre eux, une méthode de classification non supervisée est actuellement appliquée afin d’identifier des profils de patients dyspnéiques.

Abstract Rationale Cardiopulmonary risk refers to the elevated likelihood of serious cardiovascular or respiratory events among patients with COPD, compared with the general population, beyond what would be attributable to shared risk factors (eg, smoking, older age). This study evaluated healthcare resource utilization and associated costs in patients with COPD who have experienced cardiopulmonary events. Methods This retrospective study utilized data from 100% Medicare Fee-for-Service and Inovalon MORE2 Registry® of closed claims from 1/1/2020-3/31/2024. Patients 40+ years old with ≥2 COPD diagnosis codes in 2021 were categorized based on the presence or absence of a cardiopulmonary event (hospitalization for COPD, acute heart failure, cardiac arrest, myocardial infarction or revascularisation procedure) any time after COPD diagnosis. For those with an event, index date was the earliest event date. Patients without an event were matched according to age, sex, payer type, region of residence, and the Elixhauser Comorbidity Index, and assigned a proxy index date based on the time between the COPD diagnosis and the cardiopulmonary event of their matched counterpart. All patients were required to present 12 months of continuous health plan enrolment preceding and following the index date. All-cause, COPD-related, and cardiovascular disease (CVD)-related healthcare resource utilization, associated costs, and other select clinical outcomes/therapies of interest were assessed during the 12-month follow-up period. Differences were assessed using paired t-tests. Results After matching, 138,584 pairs of patients with COPD with and without a cardiopulmonary event (representing 13.5% of the full ABACOS OUTCOMES cohort) were included in the analysis (Table). Patients experiencing a cardiopulmonary event were significantly more likely to have subsequent all-cause, COPD-related, and CVD-related hospital admissions, and all-cause, COPD-related, and CVD-related emergency department visits compared with patients without a cardiopulmonary event during the follow-up period. Similar trends were observed for outpatient utilization. All-cause hospital costs were 433% greater and total direct healthcare costs were 126% greater among patients with a cardiopulmonary event compared with patients without an event. Patients with cardiopulmonary events also experienced significantly more moderate COPD exacerbations, utilization of oxygen therapy, mechanical ventilation, and ICU stays. Conclusions Patients with COPD experiencing a cardiopulmonary event exhibit significantly increased CVD- and COPD-related healthcare resource utilization and costs during 1 year of follow-up, as well as higher need for critical care, compared with patients without such an event in a real-world setting. Results highlight the importance of proactive management of COPD to help reduce cardiopulmonary risk and economic burden. This abstract is funded by: AstraZeneca

Abstract Background Chronic dyspnoea is a common condition, characterised by complex interactions between determinants. Therefore, we applied unsupervised methods among dyspnoeic adults to identify distinct profiles based on clinical, functional, and sociodemographic factors. Methods Data from the largest French population-based cohort CONSTANCES were used. A factorial analysis of mixed data (25 variables covering: demographic, socioeconomic, and clinical/functional characteristics, behavioural/environmental exposures, blood biomarkers) was followed by k-means clustering. Logistic models assessed associations between clusters and mMRC scale, health-related limitation and physical activity Results Among 114,346 participants with spirometry, mMRC dyspnoea grade, and smoking data, 24,165 (21.2%) reported chronic dyspnoea (mMRC ≥1). Among the 15,282 without missing data, three profiles were identified: C1 (n = 6,951, 45.5%) characterised by middle-aged healthier women from higher socioeconomic backgrounds; C2 (n = 4,207, 27.5%) characterised by younger socially disadvantaged women with multiple lifestyle-related risks, including smoking, at risk alcohol consumption, and obesity; and C3 (n = 4,124, 27.0%) characterised by older men with multiple cardiovascular comorbidities, impaired lung function, and high environmental and occupational exposures.Compared with C1, perceived dyspnoea severity (mMRC≥2) was more associated with C2 (OR 1.55 [1.43-1.67]) than with C3 (OR 1.20 [1.11-1.30]). Conversely, health-related limitation, was more associated with C3 (OR 2.07 [1.92-2.24]) than with C2 (OR 1.48 [1.37-1.60]). C2 had lower odds of achieving sufficient physical activity (defined as ≥ 4/6 on a composite scale of weekly manual tasks, sports, and active transportation) (OR 0.73 [0.68-0.80]), whereas C3 did not differ from C1. Conclusion Three distinct multifactorial profiles were identified, with characteristics highlighting the mismatch between perceived dyspnoea and functional limitation. Younger disadvantaged participants showed lower physical activity, suggesting that sedentary behaviour may contribute to chronic dyspnoea. This abstract is funded by: INSERM- French national health and medical research body

Abstract Rationale Chronic obstructive pulmonary disease (COPD) activity includes exacerbations, which drive disease progression, characterized by worsening symptoms and deteriorating lung function. Disease stability, defined as a sustained state of low disease activity following optimization of management, is an emerging, ambitious and achievable treatment goal in COPD. Mepolizumab is an approved add-on maintenance treatment for adults with COPD and an eosinophilic phenotype, with proven efficacy in several Phase III randomized, controlled trials (RCTs). This pooled analysis assessed the effect of mepolizumab on disease stability in COPD. Methods METREX (GSK ID: 117106/ClinicalTrials.gov identifier: NCT02105948), METREO (117113/NCT02105961), and MATINEE (208657/NCT04133909) were Phase III RCTs assessing the efficacy of mepolizumab 100 mg versus placebo in patients with COPD, a history of exacerbations, and receiving triple therapy. This pooled post hoc analysis in patients with blood eosinophil count (BEC) ≥300 cells/µL at screening, evaluated disease stability in the overall population (N = 1146) and by Global Initiative for Chronic Obstructive Lung Disease (GOLD) status. Disease stability at Week 52 was defined as a three-component composite endpoint of 1) no moderate/severe exacerbations (‘exacerbations’); 2) ≤0 change from baseline in COPD Assessment Test scores (‘health status’); 3) ≥0mL change from baseline in forced expiratory volume in 1 second (‘lung function’). Results At Week 52, disease stability was achieved by more patients receiving triple therapy treated with mepolizumab versus placebo (18% [102/568] vs 15% [84/578]). Among the individual components, exacerbations were the most prominent driver of the numerical difference in achieving disease stability between groups, with the following rates of achieving disease stability criteria: exacerbations (52% [295/568] vs 42% [242/578]); health status (54% [309/568] vs 53% [306/578]) and lung function (45% [256/568] vs 43% [247/578]). There were more patients achieving disease stability with mepolizumab versus placebo across all GOLD subgroups (GOLD 2: 26% vs 23%, GOLD 3: 11% vs 9%, and GOLD 4: 16% vs 6%) (Figure). Conclusions Patients with COPD and BEC ≥300 cells/µL receiving triple therapy treated with mepolizumab achieved disease stability in greater proportions than those receiving placebo. Disease stability is therefore achievable with mepolizumab in patients otherwise poorly controlled on triple therapy, with a wide spectrum of COPD presentations. Funding GSK (117106/117113/208657). This abstract is funded by: GSK (117106/117113/208657)

Introduction Les disparités entre les sexes en termes de prévalence et de sévérité des pathologies respiratoires chroniques, notamment l’asthme et la BPCO, sont bien établies et ont motivé de nombreuses recherches quant au rôle des hormones sexuelles. Cependant, les résultats demeurent inconsistants. Nous avons exploré les associations entre des indicateurs de l’exposition endogène et exogène aux œstrogènes et la fonction respiratoire et l’asthme, chez les femmes de la cohorte Constances. Une modulation par l’IMC et le tabac a également été recherchée. Méthodes L’analyse a porté sur 61 921 femmes âgées de 18 à 69 ans avec des mesures spirométriques reproductibles à l’inclusion. L’exposition hormonale endogène a été approchée par les caractéristiques de la vie reproductive et l’exposition exogène par la prise de pilule contraceptive ou d’un traitement hormonal de la ménopause (THM). Les associations ont été étudiées par régression linéaire (fonction respiratoire) et logistique (asthme actuel), ajustées sur le centre, les données socio-démographiques, l’IMC, les comportements de santé, et les comorbidités. Résultats Parmi les femmes incluses, 10,3 % déclaraient un asthme actuel, 92 % utilisaient une pilule contraceptive, 38 % étaient ménopausées dont 40 % prenant un THM. Comparées aux femmes nullipares, les femmes ayant eu au moins un enfant avaient une meilleure CVF mais un VEMS/CVF plus bas. Une ménarche tardive (>14 ans), la ménopause, un âge précoce à la ménopause et une durée de vie reproductive plus courte étaient associées à une réduction significative de la CVF. La prise de pilule contraceptive était associée à une meilleure CVF et un VEMS/CVF diminué, en particulier chez les femmes en surpoids ou obèses. La prise de THM était associée à une meilleure CVF, sans interaction avec l’IMC. Concernant l’asthme survenu après la puberté, une augmentation du risque d’asthme actuel était observée avec la ménarche précoce (<12 ans) (OR=1,24 [1,11–1,38]) et la prise actuelle de pilule (OR=1,31 [1,08–1,58]). Parmi les femmes ménopausées, on observait un risque accru d’asthme actuel apparu après la ménopause, associé à un âge précoce à la ménopause (<40 vs. 45–55 ans : OR=2,60 [1,56–4,34]). Par ailleurs, une diminution linéaire du risque d’asthme actuel était associée à une durée de vie reproductive plus longue (p-tendance <0,001). Conclusion Dans ce large échantillon de la population générale, les facteurs reproductifs pouvant refléter une exposition plus importante ou plus longue aux œstrogènes étaient associés à une meilleure CVF, mais à une diminution du VEMS/CVF. Cependant, l’asthme actuel était associé à la fois à la ménarche précoce et la ménopause précoce. Ces résultats suggèrent un effet contrasté des œstrogènes sur la santé respiratoire des femmes.

Abstract Rationale Chronic Obstructive Pulmonary Disease (COPD) is the fourth leading cause of death worldwide and remains a major public-health and economic burden. Frequent exacerbators account for a disproportionate share of hospital admissions and healthcare costs. Conventional follow-up rarely allows early detection of exacerbations, limiting timely interventions. AUSTRAAL (NCT06523140) is a multicenter, randomized, controlled, open-label clinical investigation, sponsored by Biosency. It aims to evaluate the clinical and organizational impact of remote monitoring using Bora care®, which combines the Bora band® wearable device, the Bora connect® telemonitoring platform, and the BVS³ predictive algorithm designed to detect early signs of exacerbation from trends in SpO2, heart rate, and respiratory rate. Methods The study comprises two sequential phases: 1. Pilot phase (non-randomized): 20 patients / 3 months / < 3 centers; objective: operational optimization 2. Main phase: 1:1 Randomized Controlled Trial comparing standard care versus standard care + Bora care® telemonitoring in 360 adults with confirmed COPD (French-Language Society of Pneumology criteria) and ≥ 1 hospitalization for exacerbation within 12 months. In the intervention arm, trained nurse Case Managers review daily data via Bora connect® and respond to BVS3 alerts through patient contact, symptom assessment and coordination with pulmonologists according to a standardized escalation plan. The primary endpoint is the number of hospital days due to respiratory deterioration per patient over 12 months; a ≥ 15% reduction is considered clinically meaningful. Secondary endpoints include frequency and duration of hospitalizations, quality of life (CAT, SF-36), symptom scores (EXACT E-RS), healthcare use, organizational impact, adherence, user satisfaction, validation of a new predictive questionnaire for exacerbation and the predictive accuracy of BVS³. Statistical analyses will follow an intention-to-treat approach on the randomized population. The overall two-sided alpha is set at 5%, with a predefined interim analysis. Results The pilot phase began in December 2024; the main phase continues until September 2027, with follow-up through October 2028. Recruitment is ongoing. Feasibility data indicate high patient adherence, robust data transmission and no safety signals. Efficacy results will be reported after completion of the interim and final analyses. Conclusions AUSTRAAL is expected to provide robust evidence on the clinical, organizational, and predictive value of digital telemonitoring in high-risk COPD patients. By enabling earlier intervention and closer coordination between patients, nurses, and pulmonologists, Bora care® may reduce hospitalizations and enhance quality of life supporting large-scale implementation and reimbursement of digital respiratory care solutions. This abstract is funded by: Biosency

Abstract Rationale In BOREAS and NOTUS, add-on dupilumab vs placebo significantly reduced moderate or severe exacerbations and improved lung function and patient-reported outcomes (PROs) in patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation. Mechanisms underlying PRO improvements, including quality of life and daily symptom burden, are not well understood. We used causal mediation analysis to evaluate the effect of dupilumab on PROs. Methods BOREAS (NCT03930732) and NOTUS (NCT04456673), phase 3, randomized, placebo-controlled trials, enrolled 1,874 patients (aged 40 − 85 years) with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophils ≥300 cells/µL). Endpoints: changes in St. George’s Respiratory Questionnaire (SGRQ) and Evaluating Respiratory Symptoms in COPD (E-RS:COPD) total scores from baseline to Week 52. Mediators considered: change in number of moderate or severe exacerbations, change in pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1), and change in fractional exhaled nitric oxide (FeNO) level; the analysis was controlled for potential confounding factors (age, sex, smoking status, region, number of moderate or severe exacerbations in the year prior to study). Results Dupilumab vs placebo total effect on change in SGRQ total score was estimated as − 3.55, −3.54, −3.52, and −3.60 with change in exacerbation frequency, change in pre- and post-bronchodilator FEV1, and change in FeNO as mediators, respectively. Mediators indirectly affected total effect by estimates of − 0.61, −0.78, −0.75, and −0.64 for change in number of exacerbations, change in pre- and post- bronchodilator FEV1, and change in FeNO, respectively, mediating 17% (95% CI: 5%, 29%; P=0.006), 22% (95% CI: 8%, 37%; P=0.003), 21% (95% CI: 7%, 36%; P=0.004), and 18% (95% CI: 4%, 31%; P=0.010), respectively, of total effect. Dupilumab vs placebo total effect on change in E-RS:COPD total score was estimated as − 1.02, −0.99, −0.97, and −1.06 with change in exacerbation frequency, change in pre- and post-bronchodilator FEV1, and change in FeNO as mediators, respectively. Mediators indirectly affected total effect by estimates of − 0.09, −0.17, −0.15, and −0.13 for change in number of exacerbations, change in pre- and post- bronchodilator FEV1, and change in FeNO, respectively, mediating 9% (95% CI: 0%, 17%; P=0.048), 18% (95% CI: 3%, 32%; P=0.016), 15% (95% CI: 2%, 29%; P=0.022), and 12% (95% CI: −1%, 26%; P=0.066), respectively, of total effect. Conclusions Change in exacerbation frequency, lung function, and FeNO partially mediate improvements in PROs with dupilumab, supporting the interplay between type 2 inflammatory biomarkers, clinical events, and PROs in COPD. This abstract is funded by: Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov Identifiers: NCT03930732 and NCT04456673

Abstract Rationale The efficacy and safety of astegolimab (anti-ST2 monoclonal antibody) in patients with COPD with frequent exacerbations was evaluated in two randomized, double-blind, placebo-controlled trials: Phase IIb ALIENTO (NCT05037929) and Phase III ARNASA (NCT05595642). The results from ALIENTO have been reported previously. Here, we present results from ARNASA. Methods Patients with COPD (aged 40-80 years, current/former smokers, and ≥2 moderate or severe exacerbations within previous 12 months, regardless of baseline blood eosinophil count and chronic bronchitis) were randomized (1:1:1) to receive 476 mg astegolimab subcutaneously Q2W or Q4W or placebo, added to optimized maintenance therapy, for 52 weeks. The primary endpoint was annualized rate of moderate and severe COPD exacerbations during the 52-week treatment period. Key secondary endpoints included time to first moderate/severe COPD exacerbation, SGRQ-C total score (mean change from baseline and proportion of participants achieving clinically meaningful improvement [decrease of ≥ 4 points]), annualized rate of severe COPD exacerbations, mean change from baseline in FEV1, and safety. Results 1375 participants were treated in the modified ITT population (astegolimab Q2W, n = 459; astegolimab Q4W, n = 459; placebo, n = 457). Participant characteristics were generally balanced between arms and 74.4% were receiving ICS/LABA/LAMA at baseline. A non-statistically significant 14.5% reduction in annualized rate of moderate or severe COPD exacerbations (primary endpoint) was observed for astegolimab Q2W versus placebo (Figure A; rate ratio [RR] 0.855 [95% CI 0.722, 1.011]; P=0.0675); see Figure A for Q4W versus placebo. This numerical exacerbation rate reduction for astegolimab Q2W versus placebo was consistent across prespecified subgroups, including current/former smokers and those with chronic bronchitis at baseline (Figure B). Astegolimab Q2W achieved a clinically meaningful reduction in severe exacerbations (33.1% reduction; RR 0.669 [95% CI 0.472, 0.948; P=0.0238] and increase in the proportion of participants with ≥4-point decrease from baseline in SGRQ-C total score (odds ratio 1.49 [95% CI 1.14, 1.96; P=0.0037]). Directionally consistent results, numerically favoring astegolimab Q2W versus placebo, were also observed for time to first moderate/severe exacerbation, and mean change from baseline in SGRQ-C total score. No differences were seen in other secondary endpoints such as FEV1. Astegolimab was well tolerated, with comparable proportions of patients experiencing ≥1 AE across the 3 study arms (Q2W, 83.2%; Q4W, 87.9%; placebo, 85.5%). Conclusions Although the primary endpoint was not met in ARNASA, a clinically meaningful treatment effect of astegolimab Q2W versus placebo was observed for key efficacy endpoints. These results were consistent with those reported previously for ALIENTO. This abstract is funded by: This study was sponsored by F. Hoffman-La Roche Ltd.

Prérequis/Contexte Benralizumab est un anticorps monoclonal, dirigé contre la sous-unité α du récepteur de l’interleukine-5, indiqué dans l’asthme sévère à éosinophiles, commercialisé en France depuis janvier 2019. Objectifs Actualiser les données d’utilisation et de suivi à 12 mois en vie réelle de benralizumab dans l’asthme sévère. Méthodes RAMSES est une cohorte française observationnelle multicentrique ayant inclus 2041 patients atteints d’asthme sévère, selon la définition ATS-ERS 2014, entre 2019 et 2022. Résultats/Discussions Parmi les 291 patients ayant initié benralizumab, 139 (47,8 %) étaient bionaïfs et 152 (52,2 %) avaient reçu un biomédicament auparavant. 208 patients (71,5 %) présentaient une rhinosinusite chronique (RC) dont 149 (71,6 %) avaient une polypose naso-sinusienne (PNS) associée. 56 (19,2 %) patients rapportaient une rhinite allergique et 126 patients (n=126/170) présentaient une atopie. Le taux de maintien du benralizumab était de 79,1 % [74,5 % ; 84,1 %] à 12 mois. Sur les 210 patients toujours suivis et sous traitement à 12 mois (T12), on observe une amélioration du score ACT moyen de 13,9±5,2 à T0 à 18,7±4,7 à T12 et de la proportion de patients ayant un asthme bien contrôlé de 16,8 % (T0) à 50 % (T12). Le nombre moyen d’exacerbations dans les 12 derniers mois a diminué de 3,2 (T0) à 0,7 (T12). Le pourcentage de patients ayant eu une hospitalisation ou une visite aux urgences pour asthme a diminué de 18,6 % à T0 à 3,8 % à T12 et de 28,6 % à T0 à 7,1 % à T12 respectivement. Le VEMS moyen passant de 2078,7 (±852,7) mL à 2302,1 (±900,0) mL, avec une augmentation d’au moins 10 % chez 45,9 % des patients (n=34/74). Le score SNOT-22 a diminué d’au moins 9 points entre T0 et T12 chez 51,2 % des patients (n=42/82) présentant une RC à T0 et chez 49,2 % des patients (n=31/63) présentant une PNS à T0. Aucun nouveau signal de tolérance n’a été observé par rapport au profil connu de benralizumab. Conclusion Cette mise à jour confirme l’efficacité en vie réelle à 12 mois de benralizumab sur le contrôle de l’asthme, la survenue d’exacerbations et la fonction respiratoire chez des patients asthmatiques sévères, sans mettre en évidence de problème de sécurité.

Abstract Rationale The efficacy and safety of astegolimab (anti-ST2 monoclonal antibody) in patients with COPD with frequent exacerbations were evaluated in two randomized, double-blind, placebo-controlled trials: Phase IIb ALIENTO (NCT05037929) and Phase III ARNASA (NCT05595642). Here, we present results from prespecified pooled analyses of both studies. Methods Both trials randomized patients with COPD (ALIENTO: aged 40-90 years, ARNASA: aged 40-80 years) who were current/former smokers and had a history of frequent exacerbations, regardless of chronic bronchitis or blood eosinophil counts [BEC] 1:1:1 to receive 476 mg astegolimab subcutaneously Q2W or Q4W or placebo, added to optimized maintenance therapy, for a 52-week treatment period. The primary endpoint in both trials was the annualized rate of moderate and severe COPD exacerbations. Key secondary endpoints included proportion of participants with a decrease of ≥ 4 points SGRQ-C total score, annualized rate of severe COPD exacerbations, and safety. Results 2676 participants were included in the pooled modified intent-to-treat (ITT) population (astegolimab Q2W, n = 892; astegolimab Q4W, n = 896; placebo, n = 888). Pooled participant characteristics were generally balanced between arms. Compared with placebo, astegolimab Q2W significantly reduced the rate of moderate and severe COPD exacerbations by 14.7% (Figure; RR 0.853 [95% CI 0.759, 0.959]; P=0.0077); Q4W data are also included in the figure. This exacerbation rate reduction for astegolimab Q2W versus placebo was consistent across prespecified subgroups such as current/former smokers, baseline BEC, and chronic bronchitis. A greater reduction in exacerbation rate with astegolimab Q2W versus placebo was observed in those with a history of > 2 (vs 2) exacerbations, or moderate airflow obstruction (GOLD II) (vs very severe). Compared with placebo, astegolimab Q2W nominally reduced severe exacerbations (32% reduction; RR 0.68 [95% CI 0.52, 0.87]; P=0.0028) and increased the proportion of participants with ≥4-point decrease from baseline in SGRQ-C total score (odds ratio 1.35 [95% CI 1.11, 1.64]; P=0.0029). Astegolimab Q2W was well tolerated in the pooled population, with adverse event rates per 100 patient-years of 365, 403, and 408 for the Q2W, Q4W, and placebo arms, respectively. Conclusions In this pooled analysis of data from the ALIENTO and ARNASA trials, astegolimab Q2W versus placebo significantly reduced the rate of moderate and severe exacerbations by 14.7% over 52 weeks. There was also a clinically meaningful reduction in severe exacerbations and increase in proportion of participants with ≥4 improvement in SGRQ-C total score, consistent with results from individual trials. This abstract is funded by: This pooled analysis was sponsored by F. Hoffman-La Roche Ltd.

Abstract Rationale Chronic obstructive pulmonary disease (COPD) is characterized by progressive and irreversible lung and airways damage, which may lead to increased exacerbation risk. In BOREAS and NOTUS, dupilumab significantly reduced exacerbations and improved lung function in patients with COPD and type 2 inflammation. We assessed whether airway damage (reflected by percent predicted forced expiratory volume in 1 second [ppFEV1]) and disease activity (type 2 biomarkers) interact to predict future exacerbation risks and lung function decline. Methods BOREAS (NCT03930732) and NOTUS (NCT04456673), two phase 3, randomized, placebo-controlled trials, enrolled patients (40-85 years) with COPD and type 2 inflammation (screening blood eosinophils ≥300 cells/µL) on inhaled triple therapy. Patients received dupilumab 300 mg every 2 weeks or placebo for 52 weeks. This post hoc analysis of pooled data from BOREAS and NOTUS included patients with available data for baseline fractional exhaled nitric oxide (FeNO) and blood eosinophil count. Continuous spline regression was used to assess adjusted annualized exacerbation rate by baseline eosinophil count and FeNO, and Week 52 change from baseline in post-bronchodilator FEV1 by baseline FeNO, in patients stratified by baseline post-bronchodilator ppFEV1 of ≤ 40%, 40%-60%, and >60%. Results 1726 patients were included (dupilumab: N = 861; placebo: N = 865). Continuous spline regression showed that, in both arms, patients with baseline post-bronchodilator ppFEV1 ≤40% experienced more exacerbations than those with ppFEV1 of 40%-60% or > 60%. Greater reductions in moderate or severe exacerbations occurred across all subgroups for dupilumab compared with corresponding placebo arms, with a greater magnitude observed in patients with higher baseline FeNO (Figure 1A) or eosinophil count (Figure 1B), though the biomarker interaction was not statistically significant. Continuous spline regression also indicated that dupilumab vs placebo improved post-bronchodilator FEV1 at Week 52, with a greater magnitude of change observed in patients with higher baseline FeNO (interaction P = 0.049) (Figure 1C). Patients with baseline post-bronchodilator ppFEV1 ≤40% overall had smaller improvements compared with those with baseline ppFEV1 of 40%-60% or > 60%. Conclusion Dupilumab reduced exacerbations and improved lung function across all subgroups, regardless of baseline post-bronchodilator ppFEV1. Patients with better preserved lung function and higher type 2 biomarkers showed better outcomes. This may suggest that starting dupilumab treatment earlier in the disease, when lung function impairment is smaller and lung damage has a greater reversible component, may result in greater benefits than initiating treatment later, especially in patients with more active disease. This abstract is funded by: Sanofi and Regeneron Pharmaceuticals Inc. ClinicalTrials.gov Identifiers: NCT03930732 and NCT04456673

Rationale: Non-adherence to medication is common in COPD and leads to poor outcomes. Digital interventions have improved inhaler adherence in small short-term studies, but there is minimal evidence of their impact on clinical outcomes. Methods: Our 12-month pragmatic cluster randomised trial (MAGNIFY) evaluated the impact of providing primary care with access to a complex intervention for COPD patients designed to enhance adherence (10.2147/POR.S302809). The intervention included identification of high-risk COPD patients (≥2 moderate/severe exacerbations in last 2 years) using Optimum Patient Care electronic medical record (EMR) driven quality improvement algorithms, a remote COPD review and a digital adherence support package (comprising Ultibro® Breezhaler®, Propeller Health electronic inhaler monitoring device and smartphone app). To minimise contamination, primary care centres were randomised to offer the intervention or continue usual care (control). In practices randomized to the intervention arm, high-risk patients aged ≥40 years and deemed clinically suitable and poorly adherent to inhaled therapy at the review, were offered the digital adherence support package and those that accepted were included in the study. In control practices, we identified high-risk COPD patients aged ≥40 years on the basis of LABA/LAMA prescription date. Primary outcome was time to treatment failure (moderate/severe exacerbation, prescription of ICS or other additional COPD therapy, or death) and secondary outcomes were moderate/severe exacerbation rate and time to exacerbation in 12-month follow-up. Analyses were adjusted for three pre-specified confounders: age, baseline exacerbation rate & baseline adherence. Results: 164 primary care centres (87 intervention, 77 control) were included in the trial. 835 patients were offered the digital adherence support package and 656 (78.6%) accepted. There was a 23% reduced risk of treatment failure over the 12-month trial period (adjusted HR 0.77; 95% CI 0.64, 0.94; p=0.009) in patients provided with the digital intervention compared to controls. The median time to treatment failure was 263 days in the intervention and 361 days in the control arm. Exacerbation rates were 11% lower in the intervention arm (adjusted IRR 0.89; 95% CI 0.79, 0.99; p=0.047). In pre-specified subgroups, the intervention was more effective in patients with FEV1<80% predicted, no previous exacerbations, or a Cambridge Multimorbidity Score ≥3 (Table 1). Conclusions: Offering a digital intervention to optimise adherence reduced risk of treatment failure by almost 25% and reduced exacerbation rate by over 10% in high-risk patients with COPD. This is the first large, year-long trial demonstrating improved clinical outcomes in a real-world primary care setting.

Introduction/Aim: GINA guidelines 2024 currently recommend step-up to either ICS/LABA/LAMA or high dose ICS/LABA for patients whose asthma remains uncontrolled on medium dose ICS/LABA. However there is a lack of real-world evidence on patient characteristics prior to the choice of treatment. This study will generate further understanding on the patient characteristics of both populations in a RW setting. Method: Utilizing UK patients’ electronic medical records extracted from the Optimum Patient Care Research Database (2.9 million patients with asthma; mean follow-up of 11.4 years), this cohort study included adults diagnosed with asthma initiating msBDP/FF/G or hsICS/LABA on/after 1st January 2017 following ≥1 year of msICS/LABA use. Patients’ baseline characteristics were described and stratified by msBDP/FF/G or hsICS/LABA usage. Results: 2.566 patients prescribed msBDP/FF/G and 15.113 patients prescribed hsICS/LABA were included, with similar sex distribution (59,0% vs 63,5% male), ethnicity distribution (white 88,9% vs 84,5, black 2,8% vs 4,9%, asian 0,2% vs 1,4%) and prevalence of allergy diagnosis (52,5% vs 53,6%). Patients prescribed msBDP/FF/G were older than those prescribed hsICS/LABA (mean±standard deviation: 65,7±14,0 vs 53,2±17,3 years), were more active smokers (30,6% vs 17,2%), and had higher prevalence of concomitant COPD diagnosis (44,0% vs 5,4%), and cardiovascular risk factors or diseases – hypertension (48,6% vs 31,6%), diabetes (24,5% vs 13,8%), ischaemic heart disease (24,9% vs 11,3%), heart failure (6,9% vs 2,7%), and chronic kidney disease (14,2% vs 7,3%) -, but less allergic rhinitis (21,7% vs 28,7%). In the year prior, patients prescribed msBDP/FF/G had lower percent predicted PEFR (median 63,1% vs 74,3%) and percent predicted FEV1 (median 65,0% vs 78,7%), two or more exacerbations (32,6% vs 19,0%), three or more SABA prescription (69,7% vs 58,4%) and also had higher cumulative oral corticosteroid doses (684,4±926,8mg vs 533,4±865,8mg). Conclusion: msBDP/FF/G was preferentially prescribed over hsICS/LABA to patients with asthma and concomitant COPD, severe disease, and who were older and active smokers. Exacerbations, SABA, steroid burden and cardiovascular co-morbidities were also important drivers. Confounder-matched/adjusted comparisons of efficacy between msBDP/FF/G and hsICS/LABA are warranted.

Introduction L’individualisation appropriée du traitement de l’asthme nécessite l’identification des déterminants pertinents du contrôle/risque, y compris l’effet du traitement. L’objectif de ce travail était de quantifier les effets des caractéristiques de base et du traitement sur le contrôle des symptômes (questionnaire de contrôle de l’asthme [ACQ-5]) et la réduction du risque d’exac dans l’asthme modéré-sévère. Méthodes Exac et ACQ-5 ont été simulés pendant 1 an à l’aide de modèles temporels et longitudinaux (sur la base de données : 6763 patients [pts], 9 études). Des cartes thermiques ont séparé les caractéristiques de base et les effets du traitement. Pour reproduire la pratique clinique, les données d’une cohorte de 16 000 pts ont été modélisées de manière à ce que le traitement initial soit le propionate de fluticasone, puis qu’il passe au furoate de fluticasone/vilanterol (FF/VI) ou au budésonide/formotérol (BUD/FOR) si les symptômes ne sont pas bien maîtrisés (ACQ-5≥1,5) en 0,25 an. Un test log-rank a permis d’analyser le taux d’exacerbation cumulatif. Résultats L’ACQ-5, l’indice de masse corporelle (IMC), le sexe, le tabagisme et le volume expiratoire forcé en 1 seconde % prédit affectent le risque d’exacerbation indépendamment du Tx (p<0,01). La fréquence cumulée des exacerbations après 1 an était inférieure d’environ 11 % chez les patients dont l’ACQ-5 de base était ≤0,75 vs>1,5 (p<0,01). Le passage à FF/VI a entraîné un taux d’exaction inférieur à celui de BUD/FOR (14,7 % contre 23,9 % ; p<0,01 ; Figure 1). À un an, 81,1 % et 75,7 % des patients sous FF/VI et BUD/FOR avaient un ACQ-5≤1,5 (p<0,01), respectivement. Conclusion Le risque d’ACQ-5/exac est modulé par les caractéristiques des patients (IMC, sexe), le contrôle de l’asthme, la fonction pulmonaire et le traitement, soulignant l’importance d’une prise en charge personnalisée de l’asthme.

BACKGROUND AND OBJECTIVES:The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines classify rhinitis as "intermittent" or "persistent" and "mild" or "moderate-severe". Objectives: To assess ARIA classes in a real-world study in terms of phenotypic differences and their association with asthma. METHODS:We performed a cross-sectional real-world study based on users of the MASK-air® app who reported data for at least 3 different months. We assessed the frequency of users according to the ARIA classes and compared these classes in terms of rhinitis symptoms, use of comedication, frequency of comorbid asthma, and the association between comorbid asthma and rhinitis control. RESULTS:A total of 2273 users (180 796 days) were assessed. Most users had moderate-severe rhinitis (n=2003; 88.1%) and persistent rhinitis (n=1144; 50.3%). The frequency of patients with probable asthma was 35.7% (95%CI, 34.5%-37.0%) for intermittent rhinitis and 48.5% (95%CI, 47.1%-49.9%) for persistent rhinitis. The maximum values on the visual analog scale (VAS) for rhinitis symptoms and the combined symptom-medication score were lower in patients with mild rhinitis than in those with moderate-severe rhinitis (irrespective of whether they had persistent or intermittent rhinitis). In most ARIA classes, VAS nose and VAS eye and rhinitis comedication were more frequent in patients with rhinitis+asthma than in those with rhinitis alone. CONCLUSIONS:This study suggests that the presence of asthma is more closely related to persistence of rhinitis than to severity and that the presence of comorbid asthma may be associated with poorer control of rhinitis across the different ARIA classes.

Introduction L’étude de phase 3 BOREAS (NCT03930732) a démontré que le Dupilumab (DPL) réduit significativement la fréquence des exacerbations chez des patients (pts) atteints de bronchopneumopathie chronique obstructive (BPCO) avec inflammation de type 2. L’essai de phase 3 NOTUS (NCT04456673) était destiné à confirmer l’efficacité et la sécurité du DPL dans la même population de patients. Méthodes NOTUS est un essai de 52 semaines (w), randomisé, en double insu, contrôlé par placebo (PBO), ayant pour objectif d’évaluer l’efficacité et la sécurité de DPL 300mg sous-cutané administré toutes les 2 semaines vs PBO. Les patients recrutés (40 à 85 ans) atteints de BPCO présentaient une obstruction bronchique modérée à sévère, une inflammation de type 2 (éosinophiles sanguins [EOS]≥300 cellules/μL lors du screening) et étaient sous trithérapie avec des corticostéroïdes inhalés (CSI), des β2-agonistes à longue durée d’action (LABA) et des antagonistes muscariniques à longue durée d’action (LAMA) (ou LABA/LAMA si les CSI étaient contre-indiqués). L’analyse primaire a été réalisée à partir de données intermédiaires. Résultats Les patients (n=935) ont été randomisés entre un bras DPL et un bras PBO (n=470/465). DPL vs PBO a réduit le taux annualisé d’exacerbations modérées à sévères (critère d’évaluation principal) de 34 % (risque relatif [IC 95 %] 0,664 [0,535, 0,823] ; p=0,0002). À la 12e semaine, une augmentation du VEMS pré-bronchodilatateur (différence moyenne des moindres carrés : 82mL ; p=0,0001) a été mesurée entre le bras DPL et le bras PBO et maintenue à la semaine 52 (différence moyenne : 62mL ; p=0,0182). À la 52e semaine, l’amélioration du score du questionnaire respiratoire de St. George est supérieure (différence moyenne : −3,37 ; p nominal=0,0068) dans le bras DPL vs le bras PBO. La variation du taux d’EOS médian (cellules/μL) entre la randomisation (baseline, BL) et la semaine 52 était de −45 pour DPL et −40 pour le PBO. L’analyse des sous-groupes en fonction du taux d’EOS sanguin à BL (semaine 0, tous étaient préalablement≥300 au screening), montre une réduction des taux annualisés d’exacerbations modérées à sévères similaire chez les patients ayant un taux EOS<300 (n=372) ou≥300 (n=562) cellules/μL (risque relatif vs PBO : 0,620 et 0,685, respectivement). Les données de sécurité étaient similaires à celles de BOREAS. Conclusion Chez les pts atteints de BPCO avec inflammation de type 2, DPL a permis de réduire le taux d’exacerbations modérées ou sévères, et d’améliorer leur fonction respiratoire et leur qualité de vie liée. Le profil de sécurité de DPL était globalement similaire à celui décrit dans d’autres indications du DPL.

Introduction La bronchopneumopathie chronique obstructive (BPCO) est une maladie bronchique chronique dont l’évolution est marquée par la survenue d’exacerbations aiguës dont la cause est infectieuse dans plus de la moitié des cas. Pseudomonas aeruginosa (PA) est une bactérie impliquée dans 5 à 10 % des exacerbations de BPCO et sa présence est associée à une évolution plus péjorative. Chez les patients atteints de BPCO, l’infection bronchique à PA peut être associée à la présence de dilatations des bronches (DDB), mais on ne dispose que de peu de données sur les caractéristiques scanographiques de ces patients. Objectif L’objectif principal de cette étude est de déterminer si les patients atteints de BPCO et infectés par PA présentent un phénotype scanographique distinct de ceux non infectés par cette bactérie. Méthodes Une étude rétrospective et monocentrique a été menée à l’Hôpital Cochin entre 2015 et 2023. Ont été inclus des patients atteints de BPCO pour lesquels on disposait d’un prélèvement bronchique entre 2015 et 2018, réalisé au maximum à±un an d’une épreuve fonctionnelle respiratoire et d’un scanner thoracique. Les critères d’exclusion incluaient les autres pathologies parenchymateuses significatives. Les scanners ont été analysés à l’aide d’un algorithme développé par Deep Learning afin de quantifier le volume de dilatations des bronches, d’épaississements des parois bronchiques, de micronodules, d’impactions mucoïdes, de condensations, de perfusion mosaïque et d’emphysème. Les patients ont été suivis au moins 5ans après l’inclusion. Les données de quantification ont été comparées entre les patients présentant au moins un prélèvement respiratoire positif à PA (groupe PA) et les autres (groupe Contrôle), à l’inclusion et au cours du suivi. L’évolution de la fonction respiratoire et la survie ont été évaluées. Résultats Au total, 172 patients (59,9 % d’hommes, VEMS médian 43,7 %) ont été inclus dans l’étude. Les patients du groupe PA (n=56, 64,3 % de primo-infection) étaient plus âgés, présentaient plus de comorbidités cardiovasculaires, recevaient plus souvent une trithérapie inhalée et plus de cures d’antibiotiques que les patients du groupe Contrôle (n=116). Les scanners ont été réalisés dans un délai médian de 1,4 mois après l’inclusion. Les patients du groupe PA présentaient significativement plus de condensations (0,30 % contre 0,21 %, p=0,02), mais il n’y avait pas de différence entre les 2 groupes concernant les autres paramètres étudiés. Au terme du suivi, la survie était significativement plus basse dans le groupe PA (33,9 % contre 54,3 %, p=0,04). La fonction respiratoire n’était pas différente entre les 2 groupes. Sur les scanners de suivi (médiane 3,7ans post-inclusion), les patients du groupe PA présentaient significativement plus de DDB, d’épaississement des parois bronchiques, d’impactions mucoïdes, de micronodules et de condensations que ceux du groupe Contrôle. Sur le plan microbiologique, 44,6 % des patients du groupe PA ont eu au moins un autre prélèvement positif à PA dans les 5ans suivant l’inclusion, tandis que peu de patients du groupe Contrôle ont développé une infection à PA (4,3 %). Conclusion Les résultats de notre étude suggèrent que les patients infectés par PA développent un phénotype scanographique de type bronchique.