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Alexis Dupuis,1 Aurore Thierry,2 Jeanne-Marie Perotin,1,3 Julien Ancel,1,3 Valérian Dormoy,3 Sandra Dury,1 Gaëtan Deslée,1,3 Claire Launois1,3 1Department of Respiratory Diseases, University Hospital of Reims, Reims, France; 2Université de Reims Champagne-Ardenne, VieFra, CHU Reims, Unité d’Aide Méthodologique, Reims, F-51100, France; 3University of Reims Champagne-Ardenne (URCA), Inserm UMR-S 1250, SFR Cap-Santé, Reims, FranceCorrespondence: Claire Launois, Service des Maladies Respiratoires, 45, Rue Cognacq Jay, Reims Cedex, Reims, 51092, France, Tel +33 3 26 78 76 14, Fax +33 3 26 06 03 19, Email claunois@chu-reims.frBackground: The role of obesity on dyspnea in chronic obstructive pulmonary disease (COPD) patients remains unclear. We aimed to provide an assessment of dyspnea in COPD patients according to their Body Mass Index (BMI) and to investigate the impact of obesity on dyspnea according to COPD severity.Methods: One hundred and twenty seven COPD patients with BMI ≥ 18.5 kg/m² (63% male, median (interquartile range) post bronchodilator forced expiratory volume of 1 second (post BD FEV1) at 51 (34– 66) % pred) were consecutively included. Dyspnea was assessed by mMRC (Modified medical research council) scale. Lung function tests were recorded, and emphysema was quantified on CT-scan (computed tomography-scan).Results: Twenty-five percent of the patients were obese (BMI ≥ 30kg/m²), 66% of patients experienced disabling dyspnea (mMRC ≥ 2). mMRC scores did not differ depending on BMI categories (2 (1– 3) for normal weight, 2 (1– 3) 1 for overweight and 2 (1– 3) for obese patients; p = 0.71). Increased mMRC scores (0– 1 versus 2– 3 versus 4) were associated with decreased post BD-FEV1 (p < 0.01), higher static lung hyperinflation (inspiratory capacity/total lung capacity (IC/TLC), p < 0.01), reduced DLCO (p < 0.01) and higher emphysema scores (p < 0.01). Obese patients had reduced static lung hyperinflation (IC/TLC p < 0.01) and lower emphysema scores (p < 0.01) than non-obese patients. mMRC score increased with GOLD grades (1– 2 versus 3– 4) in non-obese patients but not in obese patients, in association with a trend towards reduced static lung hyperinflation and lower emphysema scores.Conclusion: By contrast with non-obese patients, dyspnea did not increase with spirometric GOLD grades in obese patients. This might be explained by a reduced lung hyperinflation related to the mechanical effects of obesity and a less severe emphysema in severe COPD patients with obesity.Keywords: chronic obstructive pulmonary disease, obesity, dyspnea, lung function, pulmonary emphysema

Jeanne-Marie Perotin,1,2 Anaëlle Muggeo,3 Quentin Lecomte-Thenot,3 Audrey Brisebarre,1 Sandra Dury,2 Claire Launois,1,2 Julien Ancel,1,2 Valérian Dormoy,1 Thomas Guillard,3 Gaëtan Deslee1,2 1Université de Reims Champagne-Ardenne, INSERM UMR-S 1250, P3Cell, Reims, France; 2CHU de Reims, Service des Maladies Respiratoires, Reims, France; 3Université de Reims Champagne-Ardenne, INSERM UMR-S 1250, P3Cell, CHU de Reims, Laboratoire de bactériologie-Virologie-Hygiène hospitalière-Parasitologie-Mycologie, Reims, FranceCorrespondence: Jeanne-Marie Perotin, Service des Maladies Respiratoires, CHU Maison Blanche, Inserm UMR-S 1250, 45 Rue Cognacq-Jay, Reims cedex, 51092, France, Email jmperotin-collard@chu-reims.frPurpose: The heterogeneity of clinical features in COPD at stable state has been associated with airway microbiota. Blood eosinophil count (BEC) represents a biomarker for a pejorative evolution of COPD, including exacerbations and accelerated FEV1 decline. We aimed to analyse the associations between BEC and airway microbiota in COPD at stable state.Patients and Methods: Adult COPD patients at stable state (RINNOPARI cohort) were included and characterised for clinical, functional, biological and morphological features. BEC at inclusion defined 2 groups of patients with low BEC < 300/mm3 and high BEC ≥ 300/mm3. Sputa were collected and an extended microbiological culture was performed for the identification of viable airway microbiota.Results: Fifty-nine subjects were included. When compared with the low BEC (n=40, 67.8%), the high BEC group (n=19, 32.2%) had more frequent exacerbations (p< 0.001) and more pronounced cough and sputum (p< 0.05). The global composition, the number of bacteria per sample and the α-diversity of the microbiota did not differ between groups, as well as the predominant phyla (Firmicutes), or the gender repartition.Conclusion: In our study, high BEC in COPD at stable state was associated with a clinical phenotype including frequent exacerbation, but no distinct profile of viable airway microbiota compared with low BEC.Keywords: COPD, eosinophil, sputum, microbiota

Jeanne-Marie Perotin,1,2 Claire Launois,1 Maxime Dewolf,1 Antoine Dumazet,1 Sandra Dury,1 François Lebargy,1 Valérian Dormoy,2 Gaëtan Deslee1,2 1Department of Respiratory Diseases, University Hospital of Reims, Reims, France; 2INSERM UMRS 1250, University Hospital of Reims, Reims, France Abstract: Chronic cough is a common complaint and a frequent cause of medical consultation. Its management can be difficult. We present here an overview of the current guidelines for the management of chronic cough. Different steps are detailed, including the initial research of an obvious etiology and alert signs that should lead to further investigation of underlying condition. The diagnosis of the most frequent causes: asthma, non-asthmatic eosinophilic bronchitis, gastroesophageal reflux disease and upper airway cough syndrome should be considered, assessed and treated accordingly. Recent advances have been made in the comprehension of refractory chronic cough pathophysiology as well as its pharmacologic and non-pharmacologic treatment, especially speech pathology therapy. Keywords: asthma, gastroesophageal reflux, upper airway cough syndrome, chronic hypersensitivity syndrome, refractory chronic cough, speech pathology therapy

Background and Aims: The recurrence of obstructive sleep apnoea (OSA) after positive airway pressure (PAP) therapy termination has physiological consequences that may increase cardiovascular (CV) risk. We aimed to determine whether PAP termination is associated with an increased incidence of major adverse CV events (MACE) compared with adherent PAP continuation., Methods: Data from the Pays de la Loire Sleep Cohort were linked to the French national health insurance database to identify incident MACE (composite outcome of mortality, stroke and cardiac diseases), and CV active drug (lipid-lowering, antihypertensive and antiplatelet drugs, beta-blockers) adherence (medication possession ratio ≥80%). The association of PAP termination with MACE was evaluated using a time-dependent survival Cox model, with adjustment for confounders including CV active drug status., Results: After a median follow-up of 8 years, 969 of 4188 included patients (median age 58 years, 69.6% men) experienced MACE, 1485 had terminated PAP while 2703 continued PAP with at least 4 hours/night use. 38% of patients were adherent to all CV drugs in the PAP continuation group versus 28% in the PAP termination group (p<0.0001). After adjustment for confounders, PAP termination was associated with an increased risk of MACE (HR (95% CI): 1.39 (1.20 to 1.62); p<0.0001). PAP termination was not associated with incident heart failure and coronary artery disease., Conclusions: In this multicentre clinical-based cohort involving 4188 patients with OSA, PAP termination compared with adherent PAP continuation was associated with an increased risk of MACE. More research is needed to determine whether support programmes on PAP adherence could improve CV outcomes., Competing Interests: Competing interests: FGag declares receipt of personal fees from AIR LIQUIDE SANTE, INSPIRE, BIOPROJET, RESMED and SEFAM outside the submitted work; payment for presentations from PHILIPS RESPIRONICS, JAZZ PHARMACEUTICAL, BIOPROJET, CIDELEC and RESMED, non-financial support from ASTEN SANTE outside the submitted work. WT received support from ASTEN for attending scientific meetings and payment from AstraZeneca for lectures. SL has declared links of interest with Bioprojet, Idorsia, Vifor Pharma France (consultant), Resmed, Philips, Bioprojet, Jazz Pharmaceuticals, Cidelec, SOS Oxygène, Vitalaire, Zambon (speaker’s fees), ISIS Médical, Bioprojet, Resmed, SOS Oxygène (invitation to scientific meetings) and Bioserenity France (paid employee from 2019 to 2021). CL reports payment or presentations from RESMED, outside the submitted work. AS has recently been hired by SEFAM and has had links with interest with SOS Oxygène, Philips Respironics, Nukute, Nyxah and Cidelec. The other authors have no interests to disclose., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Obstructive sleep apnea (OSA) is associated with the impairment of a range of cognitive functions. Whether treatment with continuous positive airway pressure (CPAP) improves these cognitive functions is still a matter of debate., Methods: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that included OSA patients (apnea hypopnea index, AHI >10/h), naive to CPAP treatment, with a cognitive assessment before and after CPAP initiation. We compared CPAP versus sham-CPAP or placebo tablet or dietary rules or no treatment. This systematic review and meta-analysis were registered in PROSPERO (ID CRD42021275214)., Results: Eleven RCTs encompassing 923 OSA patients were included. For most of them, CPAP initiation was ≤3 months. A significant post-treatment improvement was found for the Trail Making Test part B (TMT-B; SMD = -0.93, 95 % CI = [-1.60, -0.25], Z = -2.70, p = 0.007), but not for the other neuropsychological assessments. No global effects on other cognitive domains (information processing speed, executive functions, working memory) were found., Conclusion: The significant improvement in the TMT-B supports a short-term enhancement in cognitive flexibility with CPAP treatment. Further studies that take into account OSA comorbidities, cognitive profiles, a more diverse range of cognition assessments and include long-term evaluations are needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The healthy adherer effect has gained increasing attention as potential source of bias in observational studies examining the association of positive airway pressure (PAP) adherence with health outcomes in OSA., Research Question: Is adherence to PAP associated with healthy behaviors and health care resource use prior to device prescription?, Study Design and Methods: Data from the IRSR Pays de la Loire Sleep Cohort were linked to health administrative data to identify proxies of heathy behaviors, including adherence to cardiovascular (CV) drugs (medical possession ratio), cancer screening tests, influenza vaccination, alcohol and smoking consumption, and drowsiness-related road accidents during the 2 years preceding PAP onset in patients with OSA. Multivariable regression analyses were conducted to evaluate the association of heathy behaviors with subsequent PAP adherence. Health care resource use was evaluated according to subsequent PAP adherence., Results: We included 2,836 patients who had started PAP therapy between 2012 and 2018 (65% of whom were PAP adherent with mean daily use ≥ 4 h/night). Being adherent to CV active drugs (medical possession ratio ≥ 80%) and a person who does not smoke were associated with a higher likelihood of PAP adherence (OR, 1.43; 95% CI, 1.15-1.77 and OR, 1.37; 95% CI, 1.10-1.71, respectively). Patients with no history of drowsiness-related road accidents were more likely to continue PAP (OR, 1.39; 95% CI, 1.04-1.87). Patients who were PAP adherent used less health care resources 2 years before PAP initiation than patients who were nonadherent (mean number of outpatient consultations: 19.0 vs 17.2, P = .003; hospitalization days: 5.7 vs 5.0; P = .04; ED visits: 30.7% vs 24.0%, P = .0002, respectively)., Interpretation: Patients who adhere to PAP therapy for OSA were more health-seeking and used less health care resources prior to device initiation than patients who were nonadherent. Until the healthy adherer effect associated with PAP adherence is better understood, caution is warranted when interpreting the association of PAP adherence with CV health outcomes and health care resource use in nonrandomized cohorts., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: C. L. reports lecture honoraria from Resmed. W. T. reports lecture honoraria from Astra Zeneca and travel support from Asten. F. Gagnadoux reports grants from Resmed; consulting fees from Resmed, Sefam, Inspire, and bioprojet; lecture honoraria from Philips Respironics, Inspire, Resmed, Bioprojet, and Asten Sante; and travel support from Asten Sante, MSD, and Bioprojet. None declared (S. B., A. S., T. P., C. H., P. M., A. B.-T., N. M., S. K., F. Goupil)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Bronchiectasis is a chronic airway disease characterized by permanent and irreversible abnormal dilatation of bronchi. Several studies have reported the development of bronchiectasis after renal transplantation (RT), but no prospective study specifically assessed bronchiectasis in this population. This study aimed to compare features of patients with bronchiectasis associated with RT to those with idiopathic bronchiectasis., Methods: Nineteen patients with bronchiectasis associated with RT (RT-B group) and 23 patients with idiopathic bronchiectasis (IB group) were prospectively included in this monocentric cross-sectional study. All patients underwent clinical, functional, laboratory, and CT scan assessments. Sputum was collected from 25 patients (n = 11 with RT-B and n = 14 with IB) and airway microbiota was analyzed using an extended microbiological culture., Results: Dyspnea (≥ 2 on mMRC scale), number of exacerbations, pulmonary function tests, total bronchiectasis score, severity and prognosis scores (FACED and E-FACED), and quality of life scores (SGRQ and MOS SF-36) were similar in the RT-B and IB groups. By contrast, chronic cough was less frequent in the RT-B group than in the IB group (68% vs. 96%, p = 0.03). The prevalence and diversity of the airway microbiota in sputum were similar in the two groups., Conclusion: Clinical, functional, thoracic CT scan, and microbiological characteristics of bronchiectasis are overall similar in patients with IB and RT-B. These results highlight that in RT patients, chronic respiratory symptoms and/or airway infections should lead to consider the diagnosis of bronchiectasis. Further studies are required to better characterize the pathophysiology of RT-B including airway microbiota, its incidence, and impact on therapeutic management., (© 2024. The Author(s).)

Background: Cough and sputum are major symptoms in cystic fibrosis (CF) that contribute to the impairment of quality of life., Methods: This prospective single centre cross-sectional pilot study aimed to evaluate the results of a self-administered questionnaire assessing cough and sputum symptoms (2 domains), and their impact (2 domains) on daily activities in the previous week, named the Cough and Sputum Assessment Questionnaire (CASA-Q) in CF adult patients at stable state, and to analyse associations with clinical, functional, microbiological, radiological data, and two quality of life scales: the Cystic Fibrosis Questionnaire Revised (CFQ-R) and the Saint George Respiratory Questionnaire (SGRQ)., Results: Forty-eight patients were included in this analysis (69% men; median age of 27.8 ± 8.1 years; median body mass index of 21.8 + 3.3 kg/m²; mean FEV 1 of 64 ± 30% of the predicted value). The mean values of the CASA-Q domains were 58 ± 23 for cough symptoms, 77 ± 24 for cough impact, 62 ± 25 for sputum symptoms and 84 ± 21 for sputum impact. Impairment in CASA-Q cough and sputum domains was associated with dyspnea mMRC scale (p < 0.005 for all 4 domains of CASA-Q) and exacerbations in the previous year (p < 0.05 for CASA-Q symptoms domains). We also found correlations between all domains of the CASA-Q and quality of life questionnaires including SGRQ (p < 0.001) and to a lesser extend CFQ-R. We identified a clinical phenotype (female gender, ΔF508 heterozygous mutation, dyspnea mMRC scale) associated with an impairment of CASA-Q score and quality of life using a 2-step cluster analysis., Conclusions: CASA-Q allows the assessment of cough and sputum in CF adult patients and is associated with quality of life impairment. This simple easy-to-use tool could be used in routine clinical practice and in clinical studies to assess cough and sputum in CF patients., Trial Registration: The study was registered on ClinicalTrials.gov (NCT02924818, first posted on 5th October 2016)., (© 2023. The Author(s).)

Background and Objective: Continuous positive airway pressure (CPAP) in the treatment of severe obstructive sleep apnoea (OSA) can be used in fixed CPAP or auto-adjusted (APAP) mode. The aim of this prospective randomized controlled clinical study was to evaluate the 3 month-efficacy of CPAP used either in fixed CPAP or APAP mode., Methods: Eight hundred one patients with severe OSA were included in twenty-two French centres. After 7 days during which all patients were treated with APAP to determine the effective pressure level and its variability, 353 and 351 patients were respectively randomized in the fixed CPAP group and APAP group. After 3 months of treatment, 308 patients in each group were analysed., Results: There was no difference between the two groups in terms of efficacy whatever the level of efficient pressure and pressure variability (p = 0.41). Exactly, 219 of 308 patients (71.1%) in the fixed CPAP group and 212 of 308 (68.8%) in the APAP group (p = 0.49) demonstrated residual apnoea hypopnoea index (AHI) <10/h and Epworth Score <11. Tolerance and adherence were also identical with a similar effect on quality of life and blood pressure evaluation., Conclusion: The two CPAP modes, fixed CPAP and APAP, were equally effective and tolerated in severe OSA patients., (© 2023 Asian Pacific Society of Respirology.)

Recognition and compensation for occupational diseases (OD) is based on the principle of presumption of occupational origin, provided that the disease meets the medical and administrative condition detailed in an OD table appended to the French social security code. A complementary system calling upon a regional committee for recognition of respiratory diseases (CRRMP, in French) attends to cases in which the medical or administrative conditions pertaining to the disease are not fulfilled. Decisions of health insurance funds may be appealed, by employer and employee alike, within the statutory timelines. That said, recent reform of social security litigation and the law of modernization of the justice system have thoroughgoingly modified appeal and redress procedures. Challenge of a decision of non-recognition of the occupational nature of a disease is now addressed to the social pole of the judicial tribunal (JT), which can request the assistance of a CRRMP other than the one that issued the first opinion. As for technical challenges having to do with the date of consolidation (date of the injury) or the degree of partial permanent incapacity (PI), they are put forward in a mandatory preliminary settlement proposal addressed to an amicable settlement board (CRA, in French), whose decisions can be contested face to the social pole of the JT. All judgments regarding medical litigations of social security may be appealed. Information for patients on compensation procedures and available means of remedying decisions by social security is essential to the establishment of the initial medical certificate and to the sequencing of the different phases of expert appraisals, the objectives being to avoid administrative incoherence and inappropriate legal recourse., (Copyright © 2023. Published by Elsevier Masson SAS.)

Rationale: Pomalidomide is an immunomodulatory imide drug used in multiple myeloma and in Kaposi sarcoma., Patient Concerns: A 72-years-old male, treated for multiple myeloma with dexamethasone, pomalidomide and daratumumab, presented dyspnea, hypoxemia, biological inflammatory syndrome, ground glass opacities on computed tomography scan (CT-scan) and lymphocytic and eosinophilic alveolitis, with no specific cytologic or microbiological findings, 2 months after pomalidomide initiation., Intervention and Outcome: Antibiotics were started after bronchoscopy. No improvement was noted in dyspnea and biological inflammatory syndrome after 5 days of treatment. Pomalidomide was then discontinued, with continuation of Daratumumab-Dexamethasone, resulting in a rapid recovery of symptoms and CT-scan anomalies. No recurrence of dyspnea was observed during the 15 months of follow-up., Diagnoses: Pomalidomide-induced lung injury., Lessons: Pomalidomide-induced lung injury is a rare and serious adverse event that can occur early after Pomalidomide introduction. As pomalidomide use is increasing, the identification of drug toxicity as a possible cause of lung injury appears important. We report a rapid recovery of symptoms and CT-scan anomalies after pomalidomide discontinuation., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Survival improvement in cystic fibrosis (CF) is associated with more frequent long-term complications, including CF related bone disease (CFBD). Impact of CFBD on global health outcome remains poorly described. We aimed to assess the relationship between low bone mineral density (BMD) and spinal pain, disability, and quality of life in CF adult patients. This monocentric cross-sectional study with prospective data collection was conducted from November 2016 to December 2019 in the Department of Respiratory Diseases at the University Hospital of Reims (NCT02924818). BMD was assessed by X-ray absorptiometry (DXA). Disability was assessed by the Health Assessment Questionnaire (HAQ). Quality of life was assessed by both the St George's Respiratory Questionnaire and the Cystic Fibrosis Questionnaire for teenagers and adults (CFQ 14+). Forty patients were analyzed, 68% of men, with a median age of 25 years, a median body mass index of 21 kg/m² and a median FEV1% of 54%. Nine patients (23%) had spinal pain. Ten patients (25%) had a low BMD. Compared with patients with normal BMD, patients with low BMD had a significantly lower BMI (22 vs 19 kg/m²; P = .006) and less vitamin D supplementation (33% vs 0%; P = .035). Low BMD was not associated with spinal pain, disability and quality of life. Low BMD is frequent in CF, affecting 1-quarter of adult patients. No significant association was found between low BMD and spinal pain, disability or quality of life., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)