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BackgroundSurvivors of severe-to-critical coronavirus disease 2019 (COVID-19) may have functional impairment, radiological sequelae and persistent symptoms requiring prolonged follow-up. This pragmatic study aimed to describe their clinical follow-up and determine their respiratory recovery trajectories, and the factors that could influence them and their health-related quality of life.MethodsAdults hospitalised for severe-to-critical COVID-19 were evaluated at 3 months and up to 12 months post-hospital discharge in this prospective, multicentre, cohort study.ResultsAmong 485 enrolled participants, 293 (60%) were reassessed at 6 months and 163 (35%) at 12 months; 89 (51%) and 47 (27%) of the 173 participants initially managed with standard oxygen were reassessed at 6 and 12 months, respectively. At 3 months, 34%, 70% and 56% of the participants had a restrictive lung defect, impaired diffusing capacity of the lung for carbon monoxide (DLCO) and significant radiological sequelae, respectively. During extended follow-up, bothDLCOand forced vital capacity percentage predicted increased by means of +4 points at 6 months and +6 points at 12 months. Sex, body mass index, chronic respiratory disease, immunosuppression, pneumonia extent or corticosteroid use during acute COVID-19 and prolonged invasive mechanical ventilation (IMV) were associated withDLCOat 3 months, but not its trajectory thereafter. Among 475 (98%) patients with at least one chest computed tomography scan during follow-up, 196 (41%) had significant sequelae on their last images.ConclusionsAlthough pulmonary function and radiological abnormalities improved up to 1 year post-acute COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up.

Introduction Sleep troubles have been associated with respiratory and allergic health problems in children, however the time line of their association is overlooked. The current study examined the associations between: (1) sleep patterns at age 1 year and respiratory and allergic multi-trajectories between 1 and 5.5 years; (2) respiratory and allergic multi-trajectories between 1 and 5.5 years and sleep patterns at age 5.5 years in a French birth cohort. Methods Clusters of sleep characteristics at age 1 year (nocturnal sleep duration (NSD), day sleep duration (DSD), sleep onset difficulties (SOD), night awakenings (NA)) and at age 5.5 years (NSD, SOD, NA) and respiratory and allergic symptoms multi-trajectory groups between 1 and 5.5 years (wheezing, asthma medication, eczema, allergic conjunctivitis) were identified using unsupervised methods. Associations between sleep clusters at each age and multi-trajectory groups were assessed using multinomial regressions adjusted for potential confounding factors among 9,577 children. Results Two sleep clusters were identified at both age 1 and 5.5 years: C1a (79.9%, age 1 year) and C1b (83.1%, age 5.5 years) characterized by adequate sleep duration and good sleep quality; C2a (20.1%, age 1 year) and C2b (16.9%, age 5.5 years) characterized by shorter sleep duration and poorer sleep quality. Four multi-trajectory groups were also identified: G1 (no/few symptoms, 44.4%), G2 (persistent non-respiratory allergic symptoms, 23.1%), G3 (transient early respiratory symptoms, 25.2%), G4 (persistent respiratory and allergic symptoms, 7.3%). Belonging to cluster C2a was associated with an increased odds of belonging to G3 (adjusted odds ratio [95% interval confidence]; 1.14 [0.99-1.31]) and G4 (1.29 [1.05-1.59]). After accounting for sleep clusters at age 1 year, belonging to G4 was associated with an increased odds of belonging to cluster C2b (1.21 [0.98-1.5]). Conclusion Sleep disturbances at 1 year were associated with poorer respiratory and allergic health between 1 and 5.5 years and respiratory and allergic problems between age 1 and 5.5 years were associated with sleep troubles at 5.5 years suggesting bidirectionality. Further research is needed to explore potential coevolution of sleep and allergic and respiratory troubles during early childhood. Support (if any) ANR-21-CE36-0001-01

Resume Introduction L’objectif de cette etude est d’evaluer l’observance aux traitements et ses determinants dans une population d’asthmatiques severes. Methodes Le college des pneumologues des hopitaux generaux a realise une vaste etude observationnelle, prospective, transversale et multicentrique sur 1502 patients adultes asthmatiques severes. Resultats Le nombre moyen de traitements de fond etait de 2,5 ± 1,1. L’observance evaluee par auto-questionnaire chez 1289 patients etait de 64,8 %, concordant avec l’impression du pneumologue traitant (p Conclusion Dans cette large etude, 64,8 % des patients asthmatiques severes etaient observants et semblaient etre associes a un meilleur controle selon les criteres definis dans notre etude. L’observance est meilleure chez les patients plus âges, de longue duree d’evolution de l’asthme ou recevant une biotherapie par anti-IgE.

IntroductionObesity is a known risk factor for asthma. Although some evidence showed asthma causing obesity in children, the link between asthma and obesity has not been investigated in adults.MethodsWe used data from the European Community Respiratory Health Survey (ECRHS), a cohort study in 11 European countries and Australia in 3 waves between 1990 and 2014, at intervals of approximately 10 years. We considered two study periods: from ECRHS I (t) to ECRHS II (t+1), and from ECRHS II (t) to ECRHS III (t+1). We excluded obese (body mass index≥30 kg/m2) individuals at visitt. The relative risk (RR) of obesity att+1associated with asthma attwas estimated by multivariable modified Poisson regression (lag) with repeated measurements. Additionally, we examined the association of atopy and asthma medication on the development of obesity.ResultsWe included 7576 participants in the period ECRHS I-II (51.5% female, mean (SD) age of 34 (7) years) and 4976 in ECRHS II-III (51.3% female, 42 (8) years). 9% of participants became obese in ECRHS I-II and 15% in ECRHS II—III. The risk of developing obesity was higher among asthmatics than non-asthmatics (RR 1.22, 95% CI 1.07 to 1.38), and particularly higher among non-atopic than atopic (1.47; 1.17 to 1.86 vs 1.04; 0.86 to 1.27), those with longer disease duration (1.32; 1.10 to 1.59 in >20 years vs 1.12; 0.87 to 1.43 in ≤20 years) and those on oral corticosteroids (1.99; 1.26 to 3.15 vs 1.15; 1.03 to 1.28). Physical activity was not a mediator of this association.ConclusionThis is the first study showing that adult asthmatics have a higher risk of developing obesity than non-asthmatics, particularly those non-atopic, of longer disease duration or on oral corticosteroids.

Background: Expert national/global asthma management recommendations raise the issue whether a safe threshold of short-acting beta-2 agonist (SABA) use without concomitant inhaled corticosteroids (ICS) exists.Objective: To examine SABA and maintenance therapy associations with severe asthma exacerbations across North America and Europe.Methods: Observational analyses of 10 SABa use IN Asthma (SABINA) datasets involving 1,033,564 patients (≥12 y) from Canada, France, the Netherlands, Poland, Spain, the United Kingdom, and the United States. Negative binomial models (incidence rate ratio [IRR] [95% CI adjusted for prespecified-covariates]) evaluated associations between SABA and exacerbations.Results: Across severities, 40.2% of patients were prescribed/possessed 3 or more SABA canisters/y. Per the Global Initiative for Asthma (GINA) 2018 definitions, steps 3 to 5–treated patients prescribed/possessing 3 or more versus 1 or 2 SABAs experienced more severe exacerbations (IRR 1.08 [95% CI 1.04‒1.13], U.S. Medicare; IRR 2.11 [95% CI 1.96‒2.27], Poland). This association was not observed in all step 1 or 2–treated patients (the Netherlands, IRR 1.25 [95% CI 0.91‒1.71]; U.S. commercial, IRR 0.92 [95% CI 0.91‒0.93]; U.S. Medicare, IRR 0.74 [95% CI 0.71‒0.76]). We hypothesize that this inverse association between SABA and severe exacerbations in the U.S. datasets was attributable to the large patient population possessing fewer than 3 SABA and no maintenance therapy and receiving oral corticosteroid bursts without face-to-face health care provider encounters. In U.S. SABA monotherapy–treated patients, 3 or more SABAs were associated with more emergency/outpatient visits and hospitalizations (IRR 1.31 [95% CI 1.29‒1.34]). Most GINA 2 to 5–treated study patients (60.6%) did not have maintenance therapy for up to 50% of the time; however, the association of 3 or more SABAs and severe exacerbations persisted (IRR 1.32 [95% CI 1.18‒1.49]) after excluding these patients and the independent effect was further confirmed when U.K. SABA data were analyzed as a continuous variable in patients with up to 100% annual coverage for ICS-containing medications.Conclusions: Increasing SABA exposure is associated with severe exacerbation risk, independent of maintenance therapy. As addressed by GINA, based on studies across asthma severities where as-needed fast-acting bronchodilators with concomitant ICS decrease severe exacerbations compared with SABA, our findings highlight the importance of avoiding a rescue/reliever paradigm utilizing SABA monotherapy.

International audience; An individual's sex (nominally 'male' or 'female', based on biological attributes) and gender (a complex term, referring to socially constructed roles, behaviors, and expressions of identity) influences the clinical course of asthma in several ways. The physiological development of the lungs and effects of sex hormones may explain why more boys have asthma than girls, and post-puberty, more women have asthma than men. Female sex hormones have an impact throughout the lifespan and are associated with poor asthma control. Gender may influence exposure to asthma triggers, and sex and gender can influence the prevalence of comorbidities and interactions with healthcare professionals (HCPs). Despite widely reported sex and gender-based differences in asthma and asthma management, these issues are frequently not considered by HCPs. There is also inconsistency around use of 'sex' and 'gender' in scientific discourse, and research is needed to better define sex and gender-based differences and how they might interact to influence asthma outcomes. This review outlines the impact an individual's sex and gender can have on the pathogenesis, clinical course, diagnosis, treatment, and management of asthma.

In recent years, several researchers have attempted to identify COPD phenotypes using different cluster analysis. This study aimed to determine the most optimal cluster analysis (supervised vs unsupervised) to robustly identify clinical phenotypes. 2,968 COPD patients have been included from January 2014 until February 2020. General information (age, BMI, smoking, comorbidities), lung function, exacerbations and symptoms were collected. After 5 years of follow-up, vital status was recorded. A hierarchical classification on the principal components (HCPC) was performed, followed by two unsupervised classification algorithms: k-means and PAM (Partition Around Medoids). Robustness was defined according to three different indices of validation (Connectivity, Dunn and silhouette). The mean age was 70 years, 63.7% of males, current smokers: 38.7%, mean FEV1: 61.3% predicted, ≥2 exacerbations: 43.6%, mMRC dyspnea grade≥2: 56.3%, chronic cough: 58%. The 5-year mortality rate was 11.3%. Based on our hypothesis, four phenotypes were described, using the PAM method. The phenotype A (24.2%) consisted of elderly patients with severe airflow limitation, low symptoms, cardiovascular comorbidities, diabetes and a higher mortality. The phenotype B (23.9%) contained more female patients, young patients with moderate airflow limitation and a high rate of current smokers. The phenotype C (25.5%) contained patients with very severe airflow limitation, more symptoms and low BMI. The Phenotype D (26.2%) was composed of patients with mild airflow limitation and low dyspnoea. These results showed the superiority of PAM classification compared with two other algorithms (k-means and HCPC) in terms of the robustness.

Smoking remains common, with an exposure that begins early during pregnancy. It induces epigenetic changes, with a trans-generational transmission. Smoking increases the risk of uncontrolled asthma during childhood and adult life. Asthma is also associated with increased risk of a decline of lung function and chronic obstructive pulmonary disease (COPD). Women are more at risk of developing early and severe COPD. The mechanisms are currently poorly known.

International audience; Background: Growing consideration is emerging regarding the burden of persisting sequelae after SARS-CoV-2 infection. Out-patients exhibiting long Covid may benefit from ambulatory rehabilitation which is, to date, poorly documented. Methods: A longitudinal follow-up over a one-year period was conducted in two ambulatory rehabilitation structures in order to describe the characteristics of real-life patients referred with Covid-19 sequelae and their evolution over the course of rehabilitation. Results: 39 consecutive patients were included from April 1st, 2020 to April 1st, 2021. Patients were middle-aged (48 ± 15yr), without comorbidities, and mostly mild to moderate SARS-CoV-2 infection (25(64%) not requiring hospitalisation). Rehabilitation referral was considered with a median delay of 73[34–178] days after disease onset. Most prevalent symptoms were dyspnoea (n = 35(90%)) and fatigue (n = 30(77%)). Hyperventilation syndrome was highly frequent (n = 12(34%)). 29(74%) patients presented with prolonged functional sequelae, which was associated with younger age (43 ± 14 vs. 50 ± 10yr; p = 0.002), greater prevalence of hyperventilation syndrome (n = 12(41%) vs. 0(0%); p = 0.255) and poorer quality of life (VQ-11; 31 ± 10 vs. 23 ± 9; p = 0.030). Over the course of rehabilitation, exertional dyspnoea, 6-min walking distance, 3-min sit-to-stand test, hyperventilation syndrome prevalence and quality of life significantly improved. Conclusion: Hyperventilation is frequent in long Covid and may explain persistent dyspnoea as well as altered quality of life. Our data support screening of hyperventilation syndrome and functional impairment in mild Covid-19 out-patients as both of these components may improve with ambulatory rehabilitation.

Background: Fractional exhaled nitric oxide (FeNO) is a marker of type-2 inflammation used both to support diagnosis of asthma and follow up asthma patients.The associations of FeNO with lung function decline and bronchodilator (BD) response have been studied only scarcely in large populations. Objectives: To study the association between FeNO and a) retrospective lung function decline over 20 years, and b) lung function response to BD among asthmatic subjects compared with non-asthmatic subjects and with regards to current smoking and sex. Methods: Longitudinal analyses of previous lung function decline and FeNO level at follow-up and cross-sectional analyses of BD response and FeNO levels in 4257 participants (651 asthmatics) from the European Community Respiratory Health Survey. Results: Among asthmatic subjects, higher percentage declines of FEV1 and FEV1/FVC were associated with higher FeNO levels (p¼0.001 for both) at follow-up. These correlations were found mainly among non-smoking individuals (p ¼ 0.001) and females (p ¼ 0.001) in stratified analyses. Percentage increase in FEV1 after BD was positively associated with FeNO levels in non-asthmatic subjects. Further, after stratified for sex and smoking separately, a positive association was seen between FEV1 and FeNO levels in non-smokers and women, regardless of asthma status. Conclusions: We found a relationship between elevated FeNO and larger FEV1 decline over 20 years among subjects with asthma who were non-smokers or women. The association between elevated FeNO levels and larger BD response was found in both non-asthmatic and asthmatic subjects, mainly in women and non-smoking subjects. The coordination of ECRHS III was supported by the Medical Research Council (Grant Number 92091).We acknowledge support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.

Chantal Raherison-Semjen,1 Karen Mezzi,2 Konstantinos Kostikas,2 Alexander J Mackay,3 Dave Singh4 1Department of Respiratory Diseases, University of Bordeaux, Bordeaux, France; 2Global Medical Affairs Department, Novartis Pharma AG, Basel, Switzerland; 3Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK; 4Medicines Evaluation Unit, University of Manchester, Manchester University NHS Foundations Trust, Manchester, UKCorrespondence: Chantal Raherison-SemjenCentre INSERM 1219 Equipe Epicene, BPH Bordeaux Population Health Research Center, Université de Bordeaux, ISPED Institut de Santé Publique d’épidémiologie et de Développement, 146 Rue Leo Saignat, Bordeaux, 33076, FranceTel +33 0 557571234Email chantal.raherison-semjen@u-bordeaux.frObjective: To evaluate the perception of physicians on gender-specific differences in the diagnosis of chronic obstructive pulmonary disease (COPD) using a qualitative and anonymous questionnaire-based survey.Methods: The survey was conducted amongst respiratory physicians attending a standalone educational conference (29– 30 September 2017) using the SpotMe® App. The 20-item standardized closed questionnaire had pre-coded responses to questions on physician’s profile, and perception of COPD diagnosis and existing comorbidities between genders. All the responses were recorded anonymously.Results: Of 368 physicians who downloaded the SpotMe® App and had access to the survey, 132 (35.9%) completed the survey. Respondents were predominantly hospital-based (57.3%), aged 30– 49 years (54.2%), male (56.5%), and from large cities (59.5%). 68.7% of physicians perceived the prevalence of COPD to be higher in men; over 50% of physicians perceived that women were more prone to the effects of smoking. More than 60% of physicians agreed that women experience more severe symptoms (anxiety and depression) and have reduced quality of life than men. Over 50% of physicians agreed that misdiagnosis/underdiagnosis of COPD in women was an important factor for gender-differences.Conclusion: Results from this survey indicate that the understanding of COPD burden in women varies among healthcare professionals.Keywords: comorbidity, COPD, gender difference, physician perception, gender bias

International audience; Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.

Background Sexual function is often affected in patients suffering from chronic diseases especially chronic obstructive pulmonary disease (COPD). However, the effect of COPD on sexual satisfaction is underappreciated in clinical practice. The aim of this study is to evaluate the impact of COPD on patient’s sexuality and the explanatory variables of sexual dissatisfaction. Methods Questionnaires were emailed to participants and they submitted their responses on the Santé Respiratoire France website. Data about sexual well-being (Arizona Sexual Experience Scale, ASEX), Quality of life (VQ11), anxiety, depression (Hospitalized anxiety and depression, HAD) and self-declared COPD grade were collected. Results Seven hundred and fifty one subjects were included and were characterized as follows: women—51%, mean age—61 years, in a couple—62% and 70%—retired. Every grade of COPD was represented. Out of 751 participants, 301 participants (40%) had no sexual activity and 450 (60%) had sexual activity. From the 450 participants, 60% needed to change their sexual life because of their disease (rhythm, frequency and position). Subjects often used medications to improve sexual performance (43% used short-acting bronchodilator and 13% -specific erectile dysfunction drugs). ASEX questionnaire confirmed patients’ dissatisfaction (diminution of sexual appetite for 68% and sexual desire for 60%) because of breathlessness and fatigue. Eighty one percent of the responders had an altered quality of life (VQ11 mean score 35) and frequent suspected anxiety or depression (HAD mean score 10.8). Ninety percent declared that sexual dysfunction had never been discussed by their doctors, while 36% of patients would have preferred to undergo a specialized consultation. Conclusion Sexual dysfunction is frequent among COPD patients and leads to an altered well-being, however being a cultural taboo, it remains frequently neglected. Sexual guidance should be a part of patient’s consultations improve quality of sexual life.

Introduction and objective Dyspnoea is a major symptom in COPD patients, but the determinants that could be associated with a higher dyspnoea mMRC score in COPD patients remain unclear. Our research aimed to study the determinants of dyspnoea at the threshold of 1, 2, 3 and 4 mMRC. Patients and methods Diagnosis of COPD was made using spirometry with post-bronchodilator FEV 1 FVC 70 % . An online questionnaire has been employed by pulmonologists to recruit COPD patients. The following variables were collected: age, gender, BMI, FEV1, RV, IC, TLC, FRC, mMRC, frequency of exacerbations and comorbidities. The LASSO was used to select the variables associated with the mMRC dyspnoea scale in a subgroup (who had no missing IC, RV and FRC values) of 421 COPD patients defined by the previously mentioned variables. Results One thousand nine hundred and sevety-three patients (65.3% males, average age = 66 ± 10, 38% current smokers) were included. Dyspnoea was correlated with a low FEV1 and with the number of exacerbations in the past 12 months. Multivariate analysis showed that the determinants of dyspnoea(mMRC ≥ 2) are: FEV1: OR = 3.71[2.86–4.82]; anxiety: OR = 2.52[1.82–3.47]; cough: OR = 1.94[1.57–2.40]; bronchiectasis: OR = 1.84[1.03–3.29]; age: OR = 1.80[1.45–2.24]; hyperinflation (RV/TLC): OR = 1.68[1.34–2.11]; ischemic cardiopathy: OR = 1.63[1.22–2.18]; hypertension: OR = 1.52[1.21–1.91]; exacerbations (≥ 2): OR = 1.41[1.10–1.81]; women: OR = 1.39[1.10–1.74] and overweight: OR = 1.33[1.06–1.67]. The subgroup analysis showed that: FEV1: OR = 3.47[1.96–6.12]; exacerbations (≥ 2) OR = 2.31[1.33–4.17] and hyperinflation (IC/TLC) OR = 0.57[0.35–0.85] were associated with higher dyspnoea (mMRC ≥ 2). Conclusion Our results showed that dyspnoea is related to the severity of airflow limitation, gender, exacerbations, comorbidities and hyperinflation.

Background: Safety concerns around the use of as-needed short-acting β2-agonist (SABA) monotherapy in asthma management warrant evaluation. The SABa use IN Asthma (SABINA) programme captures the current global burden of SABA use. Objective: To examine the extent of SABA use and its association with exacerbations in Western societies. Methods: Data from SABINA (Canada, France, Poland, Spain, Sweden, the Netherlands and the UK) and the US (commercial insurance populations, Medicaid and Medicare) were analysed. SABA prescription data (categorised as ≤2 or ≥3 canisters/year), exacerbations and other covariates from patients with asthma (≥12 years) were obtained from electronic medical records, national patient registries and pharmacy prescriptions. Results: Overall, 1,490,336 patients with asthma were included in the analysis. Across all countries and asthma severities, between 15.7% (The Netherlands) and 46.9% (US Medicaid) of patients filled prescriptions for ≥3 SABA canisters/year. Annual SABA canister fills of ≥3 vs. ≤2 were associated with higher odds of having ≥1 asthma exacerbation/year across countries (odds ratio [confidence interval] ranging from 1.09 [1.02–1.16] for the older US Medicare population to 1.89 [1.70–2.11] for the overall Canada population). Conclusion: SABA use of ≥3 canisters/year was common across a large group of countries with diverse healthcare systems and was associated with increased asthma exacerbations. These results support the GINA recommendations about the need to eliminate SABA monotherapy. These findings also highlight the need for careful monitoring of patients with asthma using ≥3 SABA canisters/year and a detailed understanding of the relationship between SABA use and exacerbations.

Chronic obstructive pulmonary disease (COPD) is a risk factor of lung cancer, even after correcting for smoking. Fibrocytes, which express features of macrophages and fibroblasts (CD45+fsp1+) could be a good candidate to link both diseases. Accumulating evidences suggest that fibrocytes promote lung cancer progression and fibrocytes’ increase is associated with reduced lung function in COPD. During follow-up after surgical resection for localized lung cancer, we tried to determine how COPD could impact prognosis and if bronchial fibrocytes increase was associated with specific outcomes. Methods: We conducted a retrospective study among 35 patients who underwent surgical resection for lung cancer. We collected patients’ characteristics : lung function: forced expiratory volume in one second (FEV1), total lung capacity (TLC), monoxide lung diffusion capacity (DLCO), PDL1 status (TPS score) and emphysema quantification on CT scan. Fibrocytes was quantified by immunohistochemistry in lung biopsies by a co-staining of fsp1+ and CD45+. Judgment criterion was progression-free-survival (PFS). Results: Patients were characterized as follows: male: 40%, mean age: 60.1 years, current smokers: 28%, mean FEV1: 87% predicted, mean TLC 103.5%, median density of fibrocytes: 62/mm3, expressing PD-L1(TPS score ³ 1%): 60%. Median PFS was 1903 days and significantly decreased among patients with airflow obstruction, hyperinflation, altered lung diffusion, expressing PDL1 status. Patients with fibrocytes’ density lower than median tend to have a worsen PFS (1756 days vs 1962 days p=0.06). Conclusion: After surgical resection for lung cancer, prognosis is negatively influenced by COPD and a low level of fibrocytes. Fibrocytes could link COPD and lung cancer.

The main factors that increase the mortality risk of COPD patients are age, comorbidities and the severity of airflow obstruction. This study aimed to validate the clinically relevant COPD phenotypes found by Burgel P-R et al [1] and analyzed their impact on 5-year mortality in the PALOMB cohort. COPD patients (post-BD FEV1/FVC 2,653 patients (66 years old, 64.27% males) were included. Application of the CART-based algorithm to Palomb cohort confirmed that it identified 5 COPD phenotypes with different clinical characteristics. In addition: The high proportion of FEV1 decline (≥100 ml/yr) belongs to phenotype 1 and 4; the majority of patients in these phenotypes were under oxygen therapy and they were associated with higher rates of exacerbation, lung cancer, anxiety and depression. These results confirmed the identification of five clinically relevant COPD phenotypes. A novel finding of this study is that FEV1 decline, frequency of exacerbations and other comorbidities were associated with the more severe phenotypes. Fundings: Bordeaux Univ Foundation, Novartis, Isis Medical, GSK, BI, Chiesi.

Background In France, data regarding epidemiology and management of severe asthma are scarce. The objective of this study was to describe asthma phenotypes using a cluster analysis in severe asthmatics recruited in a real world setting. Methods The study design was prospective, observational and multicentric. The patients included were adults with severe asthma (GINA 4–5) followed-up in French Non Academic Hospital between May 2016 and June 2017. One hundred and seven physicians included 1502 patients. Both sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis on a population of 1424 patients. Results Five clusters were identified: cluster 1 (n = 690, 47%) called early onset allergic asthma (47.5% with asthma before 12 years), cluster 2 (n = 153, 10.5%): obese asthma (63.5% with BMI > 30 kg/m2), cluster 3 (n = 299, 20.4%): late-onset asthma with severe obstructive syndrome (89% without atopy), cluster 4 (n = 143, 9.8%): eosinophilic asthma (51.7% had more than 500 eosinophils/mm3), and cluster 5 (n = 139, 9.5%): aspirin sensitivity asthma (63% had severe asthma attacks). Conclusions In our population of adults with severe asthma followed by pulmonologists, five distinct phenotypes were identified and are quite different from those mentioned in previous studies.

Introduction Exacerbations are key events in the natural history of COPD, but our understanding of their longitudinal determinants remains unclear. We used data from a large observational study to test the hypothesis that vaccination status and comorbidities could be associated with the occurrence of exacerbations profile. Methods Diagnosed COPD patients have been included by their pulmonologists, with up to 3 years of follow-up. Data were analyzed using the KmL method designed to cluster longitudinal data and receiver operating characteristic curve analysis to determine the best threshold to allocate patients to identified clusters. Results 932 COPD patients were included since January 2014, 446 patients (65.68% males, 35.59% current smokers) were followed over a period of 3 years with complete data. 239(28.15%) patients reported two or more exacerbations in the year before enrolment (frequent exacerbations). Among them 142(16.68%) also had frequent exacerbations in the first year of the study, and 69(8.10%) who remained frequent exacerbators in the second year. Based on our hypothesis, we were able to determine four phenotypes: A (infrequent), B (frequent in underweight patients), C (transient), and D (frequent in obese patients). Frequent exacerbators had more airflow limitation and symptoms. Irrespective of cut-offs set to define the optimal number of clusters, a history of exacerbations OR: 3.72[2.53–5.49], presence of anxiety OR: 2.03[1.24–3.31] and absence of the annual influenza vaccination OR: 1.97[1.20–3.24] remained associated with the frequent exacerbator phenotypes. Conclusions The most important determinants of frequent exacerbations are a history of exacerbations, anxiety and unvaccinated against influenza.

BACKGROUND: There is a paucity of epidemiological data on asthma classified by disease severity in France. The ASTHMAPOP cross-sectional study aimed to review the prevalence and current management of asthma in people aged ≥18 years in France. METHODS: A self-administered questionnaire was mailed to 19 676 people representative of the French population in age, gender, region, and socio-economic status. Asthma was classified by treatment steps per the 2017 Global Initiative for Asthma (GINA) report, according to prescribed treatments. Analyses were mostly descriptive. RESULTS: The questionnaire return rate was 81.7% (n = 16 083), and 15 587 questionnaires were analyzed. The prevalence of lifetime asthma was 12.8% (95% confidence interval (CI):12.3-13.3%; n = 1 989) in 2018. The prevalence of current asthma (i.e., 12 months before the survey) was 6.4% (95% CI: 6.0-6.8%; n = 993); most of these respondents (95.3% [n = 946]) were receiving asthma treatment, and 49.4% (n = 491) were treated for mild asthma (GINA step 1 or 2). Of people with current asthma, 47.6% reported ≥1 asthma exacerbation in the past 12 months-defined as episodes (several days) during which symptoms (cough, sputum, and dyspnea) were worse than usual; 14.3% had ≥1 emergency visit, and 3.1% had ≥1 hospitalization due to asthma. Of those taking continuous asthma controller medications who answered all Morisky Medication Adherence Scale questions (n = 501), 46.4% were adherent (score=4) to their treatment regimen. Based on the 6-item Asthma Control Questionnaire scores, asthma was partially controlled or uncontrolled in 47.7% of 969 people. CONCLUSIONS: The prevalence of asthma in France has remained stable since 2006, but levels of asthma control and treatment adherence continue to be relatively poor. Asthma management in France requires improvement.

Introduction L’identification de sous-groupes de patients atteints de BPCO et partageant des caracteristiques cliniques et/ou paracliniques communes est a l’origine du concept de phenotypes dans cette pathologie. De nombreuses etudes de cohortes observationnelles sont en cours, pour tenter d’identifier de nouveaux phenotypes de patients BPCO. L’objectif de cette etude est de determiner l’analyse en cluster la plus optimale (supervise vs non-supervise) pour identifier de facon robuste les phenotypes cliniques dans le cadre de la cohorte PALOMB. Methodes Les patients BPCO (VEMS/CVF Resultats 2968 patients (70 ans, 63,7 % d’hommes, 38,7 % de fumeurs actuels) ont ete inclus ( Tableau 1 ). Parmi eux, 43,6 % ont eu au moins deux exacerbations au cours des 12 derniers mois, 58 % avaient de la toux chronique et 56,3 % avaient une dyspnee plus severe. Selon GOLD 2007, la severite de la BPCO etait representee par le stade I (18,2 %), le stade II (51,7 %), le stade III (24,1 %) et le stade IV (6 %). Le taux de la mortalite a 5 ans est de 11,3 %. Sur la base de notre hypothese, nous avons pu determiner quatre phenotypes, a l’issu de la methode PAM (k-medoides: partition Around Medoids): le phenotype A (24,2 %), B (23,9 %), C (25,5 %), et D (26,2 %). Le phenotype (A) etait constitue de patients âges, comorbides (cardiovasculaire et de diabete), peu symptomatiques, severe sur le VEMS. Le phenotype (B) etait tres severe, plus symptomatique, avec un IMC faible, plus de comorbidite metabolique, osteo-articulaire et neuropsychiatrique. Conclusion Ces Resultats illustrent l’aspect plurifactoriel des differents phenotypes identifies chez les patients BPCO. Parmi toutes les mesures de classification, la methode PAM (Machine Learning) apparait la plus valide.

Introduction Le cancer broncho-pulmonaire est le deuxieme cancer le plus frequent chez l’homme, et la premiere cause de mortalite en France. Le principal facteur de risque identifie est le tabac, associe a 8 cas sur 10. Des facteurs professionnels ont egalement ete identifies, et seraient susceptibles d’expliquer 15 % a 30 % des cas. Un depistage par scanner thoracique annuel a ete propose aux Etats-Unis (National Lung Screnning Trial, NLST) selon trois criteres d’inclusion : l’âge (55-74 ans), et le tabagisme (30 paquets-annee ou PA) non sevre (depuis moins de 15 ans). En France, le depistage n’est pas recommande chez les fumeurs par la Haute Autorite de sante (HAS), mais les recommandations emises en 2015 par les societes savantes et labelisees par la HAS et l’INCA preconisent un depistage chez les agents exposes professionnellement. La faisabilite de ces recommandations doit etre evaluee par l’etude LUCSO (LUng Cancer Screnning with low-dose computed tomography in a smokers population exposed to Occupational lung carcinogens). Objectif Decrire une population repondant aux criteres de LUCSO et du NLST dans une cohorte de patients pris en charge au CHU de Bordeaux pour un cancer broncho-pulmonaire. Materiel et methode Tous les patients suivis pour un cancer broncho-pulmonaire dans les services de pneumologie et chirurgie thoracique beneficient d’une enquete medico-socio-professionnelle au lit du malade, secondairement tele-expertisee, par un specialiste des risques professionnels (preventeur et/ou medecin) suivant une methode formalisee. Ont ete decrits les pourcentages de patients repondant aux criteres du NLST et de LUCSO : exposition au moins 10 ans a un cancerogene et tabac ≥ 30 PA, ou co-exposition a deux cancerogenes et tabac ≥ 20 PA, ou co-exposition a trois cancerogenes et tabac ≥ 10 PA, chez les patients âges de 55 a 74 ans. Resultats Parmi les 318 cas expertises, 38 % auraient ete eligibles aux criteres du NLST, et 23 % selon les criteres de LUCSO. Parmi les patients non eligibles, 26 % sont exclus sur criteres d’âge, 48 % sur criteres d’exposition (non expose ou exposition inferieure a 10 ans), et 46 % sur critere tabagique. Plus d’un tiers des patients exclus a ete co-expose a des agents cancerogenes pulmonaires au moins 10 ans. Conclusion Sur l’ensemble des patients suivis pour cancers broncho-pulmonaires au CHU de Bordeaux, 38 % selon le NLST et 23 % selon LUCSO seraient eligibles au depistage. Ces resultats sont a corroborer a des analyses sur une population plus representative de la population generale.

Introduction Les causes de mortalite chez les patients BPCO sont de reconnaissance recente et incomplete. Le risque de mortalite chez les patients BPCO est influence par l’âge, la severite de l’obstruction bronchique et les comorbidites. Cependant, l’impact des comorbidites semble varier entre les patients BPCO. L’objectif de cette etude est d’evaluer l’impact des symptomes, des fonctions pulmonaires et des comorbidites sur la mortalite chez les patients BPCO dans le cadre de la cohorte PALOMB. Methodes Les patients BPCO (VEMS/CVF 130 %), les traitements inhales et 23 comorbidites. Apres quatre ans de suivi, les donnees sur leur statut vital (au 1er janvier 2018) ont ete obtenues en utilisant le repertoire national d’identification des personnes physiques. Des analyses univariees et multivariees ont ete realisees pour etudier les determinants associes a la mortalite chez les patients BPCO. Resultats Au total, 2653 patients (66 ans, 64,3 % d’hommes) ont ete inclus. Selon GOLD 2019, la severite de la BPCO etait principalement representee par 2 groupes : GOLD A, grade II (21,6 %) et GOLD B, grade II (19 %). En analyse univariee, les patients BPCO etaient plus souvent des hommes, plus âges. Ils avaient plus de toux chronique, de distension thoracique (82,6 % vs 70 %), plus d’exacerbations frequentes, et une dyspnee plus severe que les patients vivants (74 % vs 55,4 %). Un VEMS bas etait egalement associe a un risque eleve de mortalite. Le cancer (toute cause) (32,5 % vs 16,4 %), la cardiopathie ischemique et le trouble de rythme etaient significativement associes a la mortalite. L’analyse multivariee ajustee confirme que le cancer (HR [IC95 %] : 2,64[2,02–3,45]) ; l’âge (HR [IC95 %] : 1,9[1,48–2,45]) ; le VEMS bas (HR [IC95 %] : 1,74[1,31–2,32]) ; l’atherome (HR [IC95 %] : 1,71[1,11–2,62]) ; l’insuffisance cardiaque gauche (HR [IC95 %] : 1,63[1,03–2,59]) ; la dyspnee (HR [IC95 %] : 1,63[1,23–2,16]) ; la distension thoracique (HR [IC95 %] : 1,51[1,13–2]) et la depression (HR [IC95 %] : 1,5[1,07–2,09]) etaient associes a la mortalite chez les patients BPCO. Conclusion Le cancer et les comorbidites cardiovasculaires contribuent a l’augmentation de la mortalite chez les patients BPCO, en plus des criteres connus en rapport avec la severite de la maladie.

COPD is generally considered to be more prevalent in men than women. However, some studies report the existence of differences in the rising trend of COPD severity in women. This study aimed to compare the COPD severity (GOLD III-IV vs I-II) in both women and men in PALOMB cohort. Diagnosed COPD patients were included by their pulmonologists. The following variables were collected: age, sex, BMI, FEV1, dyspnea (mMRC), the frequency of exacerbations, static hyperinflation (RV/TLC ≥130%) and comorbidities. 35.64% of 2,259 COPD patients followed were women (64 average age). Statistically significant (P≤0.001) findings in female COPD patients were as follows: younger, underweight, more likely to be current cigarette smokers, more frequent static hyperinflation (76.1% vs 70.6%) and higher dyspnea. GOLD stage III was lower in women. Exacerbator phenotype was more frequent in women (31.9% vs 23.2%), regardless of their COPD severity. Anxiety (22.7% vs 9.2%) and depression (23.7% vs 9.2%) were more frequent in women. Adjusted multivariate analysis showed that: Hyperinflation: 5.78[3.99-8.36]; higher dyspnea: 2.74[1.96-3.82]; anxiety: 2.04[1.47-2.84]; asthma: 1.55[1.05-2.3] and frequent exacerbations: 1.39[1.04-1.86] were associated with COPD severity in women. Contrastingly in men: Hyperinflation: 7.39[5.81-9.4]; higher dyspnea: 2.8[2.21-3.54]; left heart failure: 1.75[1.13-2.71]; sputum: 1.62[1.32-2]; age: 1.39[1.11-1.74] and hypertension: 1.27[1.03-1.58] were associated with COPD severity. The results are reflective of the commonly found factors of poor prognosis in COPD women: Frequent exacerbations and underweight. Funding: Bordeaux University Foundation, Novartis, Isis Medical, GSK, Boehringer Ingelheim

Resume Introduction Chez les patients atteints de bronchopneumopathie chronique obstructive (BPCO), l’acceptation de la pathologie est probablement un facteur majeur d’amelioration de la qualite de vie. L’objectif de ce travail est d’identifier les criteres associes a une bonne ou une mauvaise acceptation de la pathologie et d’identifier les moyens de l’ameliorer. Methodes Nous avons realise une enquete telephonique au sein de l’ensemble des patients de l’association BPCO a l’aide d’un questionnaire standardise etabli au prealable par differents acteurs de sante. Resultats Sur les 1040 patients de l’association, 356 (34 %) ont repondu au questionnaire. 99 patients ont rapporte ne pas accepter leur pathologie (28 %). Les patients n’acceptant pas leur pathologie sont significativement plus severes et ont plus de difficulte a realiser les actes de la vie quotidienne, notamment une activite physique. Ces patients ont significativement plus de difficulte a comprendre leur pathologie mais rapportent aussi une attitude moralisatrice de leurs proches plus frequente. Conclusion Plus la pathologie est handicapante, plus l’acceptation est difficile pour les patients. Le medecin peut avoir un impact en ameliorant l’education therapeutique et en impliquant plus les proches dans la prise en charge.

Introduction ASTHMAPOP est une enquete conduite en population generale afin d’estimer la prevalence de l’asthme en France en 2018 et de decrire la repartition des asthmatiques en fonction des paliers de traitement GINA. L’un des objectifs secondaires etait de decrire le profil clinique des asthmatiques et notamment leurs comorbidites. Methodes Enquete cross-sectionnelle ayant interroge le panel de foyers Kantar-TNS, representatif de la population francaise. Un questionnaire a ete adresse par voie postale a 19 676 panellistes âges de 18 ans et plus. Les comorbidites ont ete identifiees a partir des reponses a la question suivante : « Etes-vous actuellement suivi(e) pour l’une ou plusieurs des maladies suivantes ? » avec une liste predefinie de comorbidites. Cette question etait posee a l’ensemble des panelistes repondant au questionnaire (asthmatiques et non asthmatiques). Resultats L’analyse a ete conduite sur 15 587 questionnaires. La prevalence de l’asthme actuel a ete estimee a 6,4 %, soit 993 asthmatiques. L’âge moyen des asthmatiques etait de 48,2 ans, 60,5 % etaient des femmes, avec un IMC moyen de 26,7 kg/m2 et un âge median au diagnostic de 19,2 ans. 68,2 % des asthmatiques ont declare au moins une comorbidite, avec une moyenne de 2,4 comorbidites. 40,6 % des asthmatiques ont rapporte au moins une comorbidite atopique. Chez les asthmatiques, le nombre moyen de comorbidites ne differe pas selon le sexe mais il existe d’importantes differences du type de comorbidites entre femmes et hommes. Conclusion En France, en 2018, la prevalence de l’asthme actuel en population generale est estimee a 6,4 %. La frequence des comorbidites est plus elevee chez les asthmatiques que dans la population generale et il existe des differences dans la typologie des comorbidites entre les hommes et les femmes asthmatiques ( Tableau 1 )

Introduction La consommation de 3 flacons ou plus de β2-CDA dans l’annee est associee a une augmentation du risque d’exacerbation severe (GINA 2019). L’objectif principal de l’enquete ASTHMAPOP etait d’estimer, en population generale, la prevalence de l’asthme en France en 2018 et de decrire la repartition des asthmatiques en fonction des paliers de traitement GINA [1] . Dans cette enquete, l’utilisation de flacons de β2-CDA etait egalement recueillie. L’objectif de cette analyse est de decrire le controle de l’asthme (ACQ-6) et la survenue d’evenements lies a l’asthme au cours des 12 derniers mois en fonction du recours aux β2-CDA. Methodes Enquete transversale ayant interroge le panel de foyers Kantar-TNS, representatif de la population francaise. Questionnaire adresse par voie postale a 19 676 panellistes âges de 18 ans et plus. Donnees recueillies entre le 10/01 et le 21/02/2018. L’utilisation de β2-CDA a ete evaluee pour les sujets identifies comme asthmatiques actuels (asthme dans l’annee precedente) a l’aide de la question suivante : « Au cours des 12 derniers mois, combien de flacons de Ventoline®, de salbutamol ou de Bricanyl® Turbuhaler® avez-vous utilises ? Aucun, 1 a 2, 3 a 10, 11 et plus, ne sait pas ». Resultats L’analyse a ete conduite sur 15 587 questionnaires. La prevalence de l’asthme actuel a ete estimee a 6,4 %, soit 993 asthmatiques. 28,3 % des asthmatiques ont rapporte utiliser 3 flacons ou plus de β2-CDA au cours des 12 derniers mois, 20 % aucun. Pour les 969 asthmatiques ayant repondu au questionnaire ACQ-6, 52,3 % etaient bien controles ; pour les asthmatiques ayant utilise ≥ 3 flacons de β2-CDA par an, cette proportion diminue a 25,3 %. Chez ces asthmatiques (≥ 3 flacons de β2-CDA/an), 65,6 % ont reporte au moins une exacerbation dans les 12 derniers mois, cette proportion est superieure pour ceux recevant un traitement GINA 4 et 5 (73,8 % et 69,5 %, respectivement) ( Tableau 1 ). Conclusion En France en 2018, environ la moitie des asthmatiques n’etait pas bien controlee. Pour ceux ayant recours a 3 flacons de β2-CDA ou plus, une majoration de la survenue des evenements lies a l’asthme (exacerbations, visites en urgence et hospitalisations) est observee. Ces resultats sont d’autant plus marques pour les stades plus severes.