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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: Severe asthma is characterized by frequent exacerbations, altered lung function, and impaired quality of life. Tailored patient education allows for the improvement of both asthma management and quality of life. Our study aimed to assess the needs of severe asthma patient in therapeutic education, according to previous therapeutic patient education background and asthma phenotype., Methods: Consecutive patients monitored for severe asthma in a tertiary referral center were considered for inclusion and answered a questionnaire detailing their patient education needs and the topics they would like to discuss. Asthma history, clinical and biological data, and lung function results were recorded., Results: Fifty-three patients were included and 47 (88.7%) expressed at least one need. The most frequently selected topics were "life with asthma" (83%), "treatment use" (68%), and "exacerbation management" (60%), independent of previous participation in a patient education program dedicated to asthma. Patients of older age at inclusion, uncontrolled asthma, and T2-high phenotypes were associated with different profiles of patient education needs., Conclusion: Our study identified frequent and various patient educational needs among severe asthmatics, highlighting the importance of an in-depth assessment of severe asthmatics expectations and the crucial need for the development of dedicated educational tools., (© 2024. The Author(s).)

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).)

Cilia are organelles emanating from the cell surface, consisting of an axoneme of microtubules that extends from a basal body derived from the centrioles. They are either isolated and nonmotile (primary cilia), or grouped and motile (motile cilia). Cilia are at the centre of fundamental sensory processes and are involved in a wide range of human disorders. Pulmonary cilia include motile cilia lining the epithelial cells of the conductive airways to orchestrate mucociliary clearance, and primary cilia found on nondifferentiated epithelial and mesenchymal cells acting as sensors and cell cycle keepers. Whereas cilia are essential along the airways, their regulatory molecular mechanisms remain poorly understood, resulting in a lack of therapeutic strategies targeting their structure or functions. This review summarises the current knowledge on cilia in the context of lung homeostasis and COPD to provide a comprehensive overview of the (patho)biology of cilia in respiratory medicine with a particular emphasis on COPD., Competing Interests: Conflict of interest: J-M. Perotin reports lecture honoraria from AstraZeneca, and travel support from Novartis, AstraZeneca and Chiesi, outside the submitted work. D. Al Alam reports grants from NIH/NHLBI R01HL141856, NIH/NHLBI and Office of the Director R21HL165411, outside the submitted work. G. Deslée reports support for attending meetings from Chiesi, and personal fees from Chiesi, Boehringer, GSK and AstraZeneca, outside the submitted work. V. Dormoy reports personal fees from Chiesi, and personal fees from AstraZeneca, outside the submitted work. All other authors have nothing to disclose., (Copyright ©The authors 2023.)

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).)

Lung cancer remains the first cause of cancer-related death despite many therapeutic innovations, including immune checkpoint inhibitors (ICI). ICI are now well used in daily practice at late metastatic stages and locally advanced stages after a chemo-radiation. ICI are also emerging in the peri-operative context. However, all patients do not benefit from ICI and even suffer from additional immune side effects. A current challenge remains to identify patients eligible for ICI and benefiting from these drugs. Currently, the prediction of ICI response is only supported by Programmed death-ligand 1 (PD-L1) tumor expression with perfectible results and limitations inherent to tumor-biopsy specimen analysis. Here, we reviewed alternative markers based on liquid biopsy and focused on the most promising biomarkers to modify clinical practice, including non-tumoral blood cell count such as absolute neutrophil counts, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, and derived neutrophil to lymphocyte ratio. We also discussed soluble-derived immune checkpoint-related products such as sPD-L1, circulating tumor cells (detection, count, and marker expression), and circulating tumor DNA-related products. Finally, we explored perspectives for liquid biopsies in the immune landscape and discussed how they could be implemented into lung cancer management with a potential biological-driven decision., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ancel, Dormoy, Raby, Dalstein, Durlach, Dewolf, Gilles, Polette and Deslée.)

Introduction: In recent decades, the development of immunotherapy and targeted therapies has considerably improved the outcome of non-small cell lung cancer (NSCLC) patients. Despite these impressive clinical benefits, new biomarkers are needed for an accurate stratification of NSCLC patients and a more personalized management. We recently showed that the tumor suppressor fragile histidine triad (FHIT), frequently lost in NSCLC, controls HER2 receptor activity in lung tumor cells and that tumor cells from NSCLC patients harboring a FHIT low /pHER2 high phenotype are sensitive to anti-HER2 drugs. Here, we sought to identify the transcriptomic signature of this phenotype and evaluate its clinical significance., Materials and Methods: We performed RNA sequencing analysis on tumor cells isolated from NSCLC (n=12) according to FHIT/pHER2 status and a functional analysis of differentially regulated genes. We also investigated the FHIT low /pHER2 high signature in The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) (n=489) and lung squamous cell carcinoma (LUSC) (n=493) cohorts and used the tumor immune dysfunction and exclusion (TIDE) model to test the ability of this signature to predict response to immune checkpoint inhibitors (ICI)., Results: We showed that up-regulated genes in FHIT low /pHER2 high tumors were associated with cell proliferation, metabolism and metastasis, whereas down-regulated genes were related to immune response. The FHIT low /pHER2 high signature was associated with the higher size of tumors, lymph node involvement, and late TNM stages in LUAD and LUSC cohorts. It was identified as an independent predictor of overall survival (OS) in LUAD cohort. FHIT low /pHER2 high tumors were also predictive of poor response to ICI in both LUAD and LUSC cohorts., Conclusion: These data suggest that ICI might not be a relevant option for NSCLC patients with FHIT low /pHER2 high tumors and that anti-HER2 targeted therapy could be a good therapeutic alternative for this molecular subclass with poorer prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brisebarre, Ancel, Ponchel, Loeffler, Germain, Dalstein, Dormoy, Durlach, Delepine, Deslée, Polette and Nawrocki-Raby.)

Background: Tracheobronchopathia osteochondroplastica (TO) is a rare condition of unknown etiology. TO is characterized by submucosal nodules, with or without calcifications, protruding in the anterolateral walls of the trachea and proximal bronchi. The objective of this study was to describe TO features and associated comorbidities in a series of patients., Methods: Patients suffering from TO were retrospectively included by investigators from the Groupe d'Endoscopie Thoracique et Interventionnelle Francophone (GETIF). Demographic, clinical, comorbidities, bronchoscopic, functional, and radiological characteristics, and outcomes were recorded and analyzed., Results: Thirty-six patients were included (69% male with a mean of 65 ± 12 years). Chronic symptoms were described by 81% of patients including cough (74%) and dyspnea on exertion (74%). TO was associated with COPD in 19% of the cases and gastroesophageal reflux disease in 6%. A mild to severe airflow obstruction was present in 55% of the cases. CT scan showed tracheal submucosal nodules in 93% of patients and tracheal stenosis in 17%. Bronchoscopy identified TO lesions in the trachea in 65% of the cases, and 66% of them were scattered. A bronchoscopic reevaluation was performed in 7 cases, 9 ± 14 months [1-56] after initial diagnosis, and showed the stability of lesions in all cases. Three patients underwent interventional bronchoscopic treatment., Conclusion: The diagnosis of TO relies on typical bronchoscopic findings and can be evoked on a CT scan. Histologic diagnosis can be useful in atypical cases for differential diagnosis. Given its low consequences in terms of symptoms, lung functions, and evolution, no treatment is usually required., (© 2022. The Author(s).)

Genome-wide association studies unveiled the associations between the single nucleotide polymorphism rs16969968 of CHRNA5, encoding the nicotinic acetylcholine receptor alpha5 subunit (α5SNP), and nicotine addiction, cancer, and COPD independently. Here, we investigated α5SNP-induced epithelial remodeling and inflammatory response in human COPD airways. We included 26 α5SNP COPD patients and 18 wild-type α5 COPD patients in a multi-modal study. A comparative histologic analysis was performed on formalin-fixed paraffin-embedded lung tissues. Isolated airway epithelial cells from bronchial brushings were cultivated in the air-liquid interface. Broncho-alveolar fluids were collected to detect inflammatory mediators. Ciliogenesis was altered in α5SNP COPD bronchial and bronchiolar epithelia. Goblet cell hyperplasia was exacerbated in α5SNP small airways. The broncho-alveolar fluids of α5SNP COPD patients exhibited an increase in inflammatory mediators. The involvement of the rs16969968 polymorphism in airway epithelial remodeling and related inflammatory response in COPD prompts the development of innovative personalized diagnostic and therapeutic strategies.

The remodelling of the airways is a hallmark of chronic obstructive pulmonary disease, but it is highly heterogeneous and erratically distributed in the airways. To assess the genetic print of remodelling in chronic obstructive pulmonary disease (COPD), we performed a comparative whole-exome sequencing analysis on microdissected bronchial epithelia. Lung resections from four non-COPD and three COPD subjects (ex-smokers and current smokers) were formalin-fixed paraffin-embedded (FFPE). Non-remodelled and remodelled bronchial epithelia were isolated by laser microdissection. Genomic DNA was captured and sequenced. The comparative quantitative analysis identified a list of 109 genes as having variants in remodelled epithelia and 160 genes as having copy number alterations in remodelled epithelia, mainly in COPD patients. The functional analysis highlighted cilia-associated processes. Therefore, bronchial-remodelled epithelia appeared genetically more altered than non-remodelled epithelia. Characterizing the unique molecular print of airway remodelling in respiratory diseases may help uncover additional factors contributing to epithelial dysfunctions, ultimately providing additional targetable proteins to correct epithelial remodelling and improve lung function.

The Hedgehog (HH) signaling pathway plays an essential role in mouse lung development. We hypothesize that the HH pathway is necessary for branching during human lung development and is impaired in pulmonary hypoplasia. Single-cell, bulk RNA-sequencing data, and human fetal lung tissues were analyzed to determine the spatiotemporal localization of HH pathway actors. Distal human lung segments were cultured in an air-liquid interface and treated with an SHH inhibitor (5E1) to determine the effect of HH inhibition on human lung branching, epithelial-mesenchymal markers, and associated signaling pathways in vitro. Our results showed an early and regulated expression of HH pathway components during human lung development. Inhibiting HH signaling caused a reduction in branching during development and dysregulated epithelial (SOX2, SOX9) and mesenchymal (ACTA2) progenitor markers. FGF and Wnt pathways were also disrupted upon HH inhibition. Finally, we demonstrated that HH signaling elements were downregulated in lung tissues of patients with a congenital diaphragmatic hernia (CDH). In this study, we show for the first time that HH signaling inhibition alters important genes and proteins required for proper branching of the human developing lung. Understanding the role of the HH pathway on human lung development could lead to the identification of novel therapeutic targets for childhood pulmonary diseases.

Background: Obesity is a risk factor for dyspnea. However, investigations of daily living obesity-related dyspnea are limited and its mechanisms remain unclear. We conducted a cross-sectional study to analyze the relationships between dyspnea in daily living, lung function, and body composition in patients with obesity., Methods: One-hundred and thirty patients (103 women/27 men), candidate for bariatric surgery, with a mean ± SD Body Mass Index (BMI) of 44.8 ± 6.8 kg/m 2 were included. Dyspnea was assessed by the modified Medical Research Council (mMRC) scale. Comorbidities, laboratory parameters, pulmonary function tests, arterial blood gases, six-minute walk test (6MWT), handgrip strength, and DXA body composition were analyzed., Results: Thirty-one percent of patients exhibited disabling dyspnea in daily living (mMRC ≥ 2). Compared with patients without disabling dyspnea (mMRC < 2), significant dyspnea (mMRC ≥ 2) was associated with a lower 6MWT distance (395 ± 103 m vs 457 ± 73 m, p < 0.001), lower lung volumes including Expiratory Reserve Volume (42 ± 28% vs 54 ± 27%, p = 0.024), Vital Capacity (95 ± 14 vs 106 ± 15%, p < 0.001) and Forced expiratory volume in one second (95 ± 13 vs 105 ± 15%, p = 0.002), a higher BMI (48.2 ± 7.7 vs 43.2 ± 5.7 kg/m 2 , p = 0.001) and a higher percentage of fat mass in the trunk (46 ± 5 vs 44 ± 5 p = 0.012) and android region (52 ± 4 vs 51 ± 4%, p = 0.024). There was no difference regarding comorbidities (except hypertension), laboratory parameters, and sarcopenia markers between patients with (mMRC ≥ 2) and without (mMRC < 2) disabling dyspnea., Conclusion: Dyspnea in patients with obesity is associated with a reduction in lung volumes and a higher percentage of fat mass in central body regions. How dyspnea and body composition may change with interventions like physical activity or bariatric surgery remains to be investigated., (© 2022. The Author(s).)

Nicotinic acetylcholine receptors (nAChRs) play an important role in homeostasis and respiratory diseases. Controversies regarding the association between COVID-19 hospitalizations and smoking suggest that nAChRs may contribute to SARS-CoV-2 respiratory syndrome. We recently detailed the expression and localization of all nAChR subunits in the human lung. Since virus association with nAChRs has been shown in the past, we hypothesize that nAChR subunits act as SARS-CoV-2 Spike co-receptors. Based on sequence alignment analysis, we report domains of high molecular similarities in nAChRs with the binding domain of hACE2 for SARS-CoV-2 Spike protein. This hypothesis supported by in silico pilot data provides a rational for the modelling and the in vitro experimental validation of the interaction between SARS-CoV-2 and the nAChRs., Competing Interests: 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., (© 2021 Elsevier Ltd. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease characterized by airflow limitation. This chronic respiratory disease represents the third leading cause of death worldwide. Alteration of the airway microbiota has been reported to be associated with exacerbation frequency in COPD, but its role on the symptoms in patients at stable state is still incompletely described. This study aimed to determine whether bacteria isolated in sputum can be associated with the clinical features of COPD patients within stable state. Our study highlights, for the first time, that altered microbiota with Enterobacterales is associated with pejorative clinical symptoms in stable COPD patients. The airway microbiota of 38 patients was analyzed using an extended culture approach and mass spectrometry identification. Cluster analysis by principal coordinate analysis of the bacterial communities showed that the patients could be classified into three distinct clusters in our cohort. The clusters showed no differences in proportions of the phylum, but one of them was associated with a high prevalence of Enterobacterales (71.4% in cluster 1 vs. 0% in cluster 3), loss of microbiota diversity, and higher bacterial load (10 7 vs. 10 5 CFU/ml, respectively) and characterized by predominant cough and impact on mental health. These novel findings, supported by further studies, could lead to modifying the processing of COPD sputum in the everyday practice of clinical microbiology laboratories., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Muggeo, Perotin, Brisebarre, Dury, Dormoy, Launois, Ancel, Mulette, de Champs, Deslée and Guillard.)

Delocalization of zonula occludens-1 (ZO-1) from tight junctions plays a substantial role in epithelial cell plasticity observed during tumor progression. In vitro , we reported an impact of ZO-1 cyto-nuclear content in modulating the secretion of several pro-inflammatory chemokines. In vivo , we demonstrated that it promotes the recruitment of immune cells in mouse ear sponge assays. Examining lung cancers, we showed that a high density of CD8 cytotoxic T cells and Foxp3 immunosuppressive regulatory T cells in the tumor microenvironment correlated with a cyto-nuclear expression of ZO-1. Taken together, our results support that, by affecting tumor cell secretome, the cyto-nuclear ZO-1 pool may recruit immune cells, which could be permissive for tumor progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Neyrinck-Leglantier, Lesage, Blacher, Bonnomet, Hunziker, Noël, Dormoy, Nawrocki-Raby, Gilles and Polette.)

Respiratory syncytial virus ( RSV ) infection is the principal cause of severe lower respiratory tract disease and accounts for a significant risk for developing asthma later in life. Clinical studies have shown an increase in airway responsiveness and a concomitant Th 2 response in the lungs of RSV-infected patients. These indications suggest that RSV may modulate aspects of the immune response to promote virus replication. Here, we show that CCR3 facilitates RSV infection of airway epithelial cells, an effect that was inhibited by eotaxin-1/CCL11 or upon CCR3 gene silencing. Mechanistically, cellular entry of RSV is mediated by binding of the viral G protein to CCR3 and selective chemotaxis of Th 2 cells and eosinophils. In vivo, mice lacking CCR3 display a significant reduction in RSV infection, airway inflammation, and mucus production. Overall, RSV G protein-CCR3 interaction may participate in pulmonary infection and inflammation by enhancing eosinophils' recruitment and less potent antiviral Th 2 cells., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Chronic Obstructive Pulmonary Disease is a generally smoking-linked major cause of morbidity and mortality. Genome-wide Association Studies identified a locus including a non-synonymous single nucleotide polymorphism in CHRNA5, rs16969968, encoding the nicotinic acetylcholine receptor α5 subunit, predisposing to both smoking and Chronic Obstructive Pulmonary Disease. Here we report that nasal polyps from rs16969968 non-smoking carriers exhibit airway epithelium remodeling and inflammation. These hallmarks of Chronic Obstructive Pulmonary Disease occur spontaneously in mice expressing human rs16969968. They are significantly amplified after exposure to porcine pancreatic elastase, an emphysema model, and to oxidative stress with a polymorphism-dependent alteration of lung function. Targeted rs16969968 expression in epithelial cells leads to airway remodeling in vivo, increased proliferation and production of pro-inflammatory cytokines through decreased calcium entry and increased adenylyl-cyclase activity. We show that rs16969968 directly contributes to Chronic Obstructive Pulmonary Disease-like lesions, sensitizing the lung to the action of oxidative stress and injury, and represents a therapeutic target., (© 2021. The Author(s).)

Rationale: Thoracic endometriosis is a rare disorder that can involve airways, pleura and lung parenchyma. It is the most frequent form of extra-abdominopelvic endometriosis. Multiple lung cavitations are a rare feature of thoracic endometriosis., Patient Concerns: A 46-year-old woman was referred to our hospital after incidental finding of multiple pulmonary cavitations with surrounding areas of ground glass opacity on a thoraco-abdominal computed tomography-scan performed for abdominal pain. Retrospectively, the patient also reported mild hemoptysis occurring 4 months ago., Diagnoses: Positron emission tomography-computed tomography scan revealed moderate and homogeneous [18F] fluoro-2-deoxy-D-glucose (18F-FDG) uptake in pulmonary cavitations (maximum standardized uptake value 5.7). The diagnosis of thoracic endometriosis was confirmed by histological examination of surgical resection of a left lower lobe cavitation., Interventions and Outcome: Gonadotropin-releasing hormone analogues associated with add-back therapy was started. Four months after initiating pharmacological treatment, the chest computed tomography-scan showed a dramatic decrease in lung cavitations size., Lessons: Thoracic endometriosis is a rare disorder requiring a multidisciplinary management including gynaecologist, pulmonologist, radiologist, nuclear physician, pathologist and thoracic surgeon for early diagnosis and treatment. Our case report highlights that an increased 18F-FDG uptake can be found in thoracic endometriosis syndrome presenting as multiple lung cavitations., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Chronic obstructive pulmonary disease (COPD) is a frequent respiratory disease. However, its pathophysiology remains partially elucidated. Epithelial remodeling including alteration of the cilium is a major hallmark of COPD, but specific assessments of the cilium have been rarely investigated as a diagnostic tool in COPD. Here we explore the dysregulation of the ciliary function (ciliary beat frequency (CBF)) and differentiation (multiciliated cells formation in air-liquid interface cultures) of bronchial epithelial cells from COPD ( n = 17) and non-COPD patients ( n = 15). CBF was decreased by 30% in COPD (11.15 +/- 3.37 Hz vs. 7.89 +/- 3.39 Hz, p = 0.037). Ciliary differentiation was altered during airway epithelial cell differentiation from COPD patients. While the number of multiciliated cells decreased ( p < 0.005), the number of primary ciliated cells increased ( p < 0.05) and primary cilia were shorter ( p < 0.05). Altogether, we demonstrate that COPD can be considered as a ciliopathy through both primary non-motile cilia modifications (related to airway epithelial cell repair and remodeling) and motile cilia function impairment (associated with decrease sputum clearance and clinical respiratory symptoms). These observations encourage considering cilia-associated features in the complex COPD physiopathology and highlight the potential of cilia-derived biomarkers for diagnosis.