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Maéva Zysman,1 Gaëtan Deslee,2 Thierry Perez,3 Pierre-Régis Burgel,4 Olivier Le Rouzic,3 Graziella Brinchault-Rabin,5 Pascale Nesme-Meyer,6 Isabelle Court-Fortune,7 Gilles Jebrak,8 Pascal Chanez,9 Denis Caillaud,10 Jean-Louis Paillasseur,11 Nicolas Roche4 1Pulmonary Department, Pôle Cardio-thoracique, CHU Haut-Lévèque, INSERM U1045, Bordeaux, France; 2Pulmonary Department, Maison Blanche University Hospital, INSERM U01250, Reims, France; 3University Lille, CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 – UMR 9017 – CIIL - Center for Infection and Immunity of Lille, Lille, France; 4Respiratory Medicine, Cochin Hospital, AP-HP and Université de Paris, Institut Cochin, INSERM U1016, Paris, France; 5Service de Pneumologie, Hôpital Pontchaillou, Rennes, France; 6Service de Pneumologie, Hôpital de la Croix-Rousse, Lyon, France; 7Service de Pneumologie, CHU Saint Etienne, Saint Etienne, France; 8Service de Pneumologie, Hôpital Bichat, AP-HP, Paris, France; 9Département des Maladies Respiratoires, AP-HM, Université de la Méditerranée, Marseille, France; 10Service de Pneumologie, Hôpital Gabriel Montpied, CHU, Clermont-Ferrand, France; 11EFFI-STAT, Paris, FranceCorrespondence: Maéva ZysmanAvenue de Magellan, Service des Maladies Respiratoires, CHU Haut Lévèque, Pessac, 33600, FranceTel +33 5 56 79 56 79Email maeva.zysman@chu-bordeaux.frBackground: Chronic respiratory failure may occur as a consequence of chronic obstructive pulmonary disease (COPD) and is associated with significant morbidity and mortality. Hypoxemia is determined by underlying disease characteristics and comorbidities. Severe hypoxemia is typically only found in subjects with severe airflow obstruction (FEV1< 50% predicted). However, how hypoxemia relates to disease characteristics is not fully understood.Methods: In the French Initiatives BPCO real-life cohort, arterial blood gases were routinely collected in most patients. Relationships between severe hypoxemia, defined by a Pa02< 60 mmHg (8 kPa) and clinical/lung function features, comorbidities and mortality were assessed. In subjects with severe hypoxemia, clinical characteristics and comorbidities were compared between those with non-severe versus severe airflow limitation. Classification and regression trees (CART) were used to define clinically relevant subgroups (phenotypes).Results: Arterial blood gases were available from 887 subjects, of which 146 (16%) exhibited severe hypoxemia. Compared to subjects with a PaO2≥ 60 mmHg, the severe hypoxemia group exhibited higher mMRC dyspnea score, lower FEV1, higher RV and RV/TLC, more impaired quality of life, lower 6-minute walking distance, less frequent history of asthma, more frequent diabetes and higher 3-year mortality rate (14% versus 8%, p=0.026). Compared to subjects with Pa02< 60 mmHg and FEV1< 50% (n=115, 13%), those with severe hypoxemia but FEV1≥ 50% predicted (n=31) were older, had higher BMI, less hyperinflation, better quality of life and a higher rate of diabetes (29% versus 13%, p=0.02). Severe hypoxemia was better related to CART-defined phenotypes than to GOLD ABCD classification.Conclusion: In this cohort of stable COPD subjects, severe hypoxemia was associated with worse prognosis and more severe symptoms, airflow limitation and hyperinflation. Compared to subjects with severe hypoxemia and severe airflow limitation, subjects with severe hypoxemia despite non-severe airflow limitation were older, had higher BMI and more diagnosed diabetes.Trial Registration: 04– 479.Keywords: chronic obstructive pulmonary disease, severe hypoxemia, airflow limitation

Thierry Perez,1 Gaëtan Deslée,2 Pierre Régis Burgel,3 Denis Caillaud,4 Olivier Le Rouzic,1 Maeva Zysman,5 Roger Escamilla,6 Gilles Jebrak,7 Pascal Chanez,8 Isabelle Court-Fortune,9 Graziella Brinchault-Rabin,10 Pascale Nesme-Meyer,11 Jean-Louis Paillasseur,12 Nicolas Roche,3 On behalf of the Initiatives BPCO Scientific Committee1CHU Lille, Department of Respiratory Diseases, F-59000 Lille and Univ. Lille, Center for Infection and Immunity of Lille, INSERM U1019 - CNRS UMR 8204, F-59000, Lille, France; 2Department of Respiratory Diseases, Maison Blanche Hospital, CHU de Reims, INSERM UMRS 1250, Reims, France; 3Respiratory and Intensive Care Medicine Department, Cochin Hospital, AP-HP and Paris Descartes University (EA 2511), Sorbonne Paris Cité, Paris, France; 4Department of Respiratory Diseases, Gabriel Montpied Hospital, CHU de Clermont Ferrand, Clermont Ferrand, France; 5Department of Respiratory Diseases, CHU Nancy, Nancy, France; 6Department of Respiratory Diseases, CHU Toulouse, Toulouse, France; 7Department of Respiratory Diseases, Hôpital Bichat, APHP, Paris, France; 8Department of Respiratory Diseases, AP-HM, Université de Méditerranée, Inserm U 1077, Marseille, France; 9Department of Respiratory Diseases, CHU Saint Etienne, Saint Etienne, France; 10Department of Respiratory Diseases, Pontchaillou Hospital, CHU Rennes, Rennes, France; 11Department of Respiratory Diseases, La Croix Rousse Hospital, Lyon, France; 12EFFI-STAT, Paris, FranceBackground: The 6-min walk test (6MWT) allows exercise tolerance to be assessed, and it has a significant prognostic value in COPD. The goal of this study was to analyse the determinants (obtained in routine practice) of a low 6-min walking distance (6MWD) and exercise-induced desaturation (EID) in COPD, including comorbidities.Methods: Patients were recruited from the real-life French COPD cohort “Initiatives BPCO”. A low 6MWD was defined as 30 kg/m2,), low BMI (BMI

Maeva Zysman,1 Gaëtan Deslee,2 Denis Caillaud,3 Pascal Chanez,4 Roger Escamilla,5 Isabelle Court-Fortune,6 Pascale Nesme-Meyer,7 Thierry Perez,8 Jean-Louis Paillasseur,9 Christophe Pinet,10 Gilles Jebrak,11 Nicolas Roche,12,* Pierre-Régis Burgel12,* On behalf of the Initiatives BPCO (broncho-pneumopathie chronique obstructive) Scientific Committee and Investigators 1Pulmonary Dpt, Nancy, Inserm U955, team 04, Créteil, France; 2Pulmonary Dpt, Maison Blanche University Hospital, INSERM U903, Reims, France; 3Pulmonary Dpt, Gabriel Montpied University Hospital, Auvergne University, Clermont-Ferrand, France; 4Pulmonary Dpt, APHM, INSERM U1077, CNRS UMR 7733 Aix Marseille Université, Marseille, France; 5Pulmonary Dpt, Larrey University Hospital, Toulouse, France; 6Pulmonary Dpt, University Hospital, Saint-Etienne, France; 7Pulmonary Dpt, La Croix Rousse University Hospital, Lyon, France; 8Clinique des Maladies Respiratoires, Albert Calmette University Hospital, Lille, France; 9EFFI-STAT, Paris, France; 10Service de pneumologie, polyclinique Les Fleurs, Ollioules, France; 11Pulmonary Dpt, Bichat Hospital, AP-HP, Paris, France; 12Respiratory and Intensive Care Medicine Dpt, Cochin Hospital, AP-HP and Paris Descartes University (EA2511), Sorbonne Paris Cité, Paris, France *These authors contributed equally to this work Abstract: In patients with COPD, there is controversy regarding the association of blood eosinophil (Eos) levels with 1) exacerbation frequency and 2) the effect of inhaled corticosteroids for prevention of exacerbations. To determine whether Eos define subgroups of patients exhibiting attributes of COPD clinical phenotypes, we compared clinical features and mortality rates in COPD patients from the Initiatives BPCO French cohort categorized using different thresholds of blood Eos levels. The following data were collected at inclusion: medical and smoking history, occupational exposures, dyspnea, cough and sputum production, exacerbations in the previous year, history of allergy and asthma, nasal symptoms, body mass index, St George Respiratory Questionnaire (SGRQ) total score, post-bronchodilator spirometry, comorbidities, and medications. Three-year survival between groups was compared using Kaplan–Meier analysis. Three sets of analyses were performed to compare patients with≥2% versus

Gaëtan Deslee,1 Pierre-Régis Burgel,2 Roger Escamilla,3 Pascal Chanez,4 Isabelle Court-Fortune,5 Pascale Nesme-Meyer,6 Graziella Brinchault-Rabin,7 Thierry Perez,8 Gilles Jebrak,9 Denis Caillaud,10 Jean-Louis Paillasseur,11 Nicolas Roche2On behalf of the Initiatives BPCO Scientific Committee 1Department of Respiratory Diseases, INSERM UMR 903, Maison Blanche Hospital, University Hospital of Reims, Reims, 2Department of Respiratory Diseases, Cochin Hospital, AP-HP and University Paris Descartes, Sorbonne Paris Cité, Paris, 3Department of Respiratory Diseases, Larrey Hospital, Toulouse, 4Department of Respiratory Diseases, APHM, INSERM U1077, CNRS UMR 7733 Aix Marseille Université, Marseille, 5Department of Respiratory Diseases, University Hospital of St Etienne, 6Department of Respiratory Diseases, La Croix Rousse Hospital, Lyon, 7Department of Respiratory Diseases, Pontchaillou Hospital, University Hospital of Rennes, Rennes, 8Department of Respiratory Diseases, Calmette Hospital, University Hospital of Lille, Lille, 9Department of Respiratory Diseases, Bichat Hospital, AP-HP, Paris, 10Department of Respiratory Diseases, Gabriel Montpied Hospital, University Hospital of Clermont-Ferrand, Clermont-Ferrand, 11EFFI-STAT, Paris,FranceBackground: Cough and sputum production are frequent in chronic obstructive pulmonary disease (COPD). The objective of this study was to examine the relationship between cough and sputum production and health-related quality of life in COPD.Methods: A cross-sectional study was conducted in the French Initiatives COPD cohort and assessed cough and sputum production within the past 7 days using the cough and sputum assessment questionnaire (CASA-Q), health-related quality of life, spirometry, smoking status, dyspnea, exacerbations, anxiety and depression, and comorbidities.Results: One hundred and seventy-eight stable COPD patients were included (age, 62 [56–69]years, 128 male, forced expiratory volume in 1 second [FEV1]: 57 [37–72] % predicted) (median [Q1–Q3]). In univariate analyses, health-related quality of life (Saint George’s respiratory questionnaire total score) was associated with each CASA-Q domain and with chronic bronchitis, exacerbations, dyspnea, FEV1, depression, and anxiety. All four domains introduced separately were independently associated with health-related quality of life. When introduced together in multivariate analyses, only the cough impact domain remained independently associated with health-related quality of life (R2=0.60). With chronic bronchitis (standard definition) instead of the CASA-Q, the R2 was lower (R2=0.54).Conclusion: This study provides evidence that current cough in the previous 7 days is an important determinant of health-related quality of life impairment in stable COPD patients.Keywords: signs and symptoms, respiratory, sputum, questionnaires, dyspnea, multivariate analysis

This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses. Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative International Assessment (3CIA) initiative. Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated that the variables relevant for patient grouping differed markedly between patients with isolated respiratory disease (FEV1, dyspnoea grade) and those with multi-morbidity (dyspnoea grade, age, FEV1 and body mass index). Application of this algorithm to the 3CIA cohorts confirmed that it identified subgroups of patients with different clinical characteristics, mortality rates (median, from 4% to 27%) and age at death (median, from 68 to 76 years). A simple algorithm, integrating respiratory characteristics and comorbidities, allowed the identification of clinically relevant COPD phenotypes.