High Blood Eosinophil Count at Stable State is Not Associated with Airway Microbiota Distinct Profile in COPD.

Purpose: 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.

Patient education needs in severe asthma, a pilot study.

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.

Bronchiectasis in renal transplant patients: a cross-sectional study.

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.

Airway ciliated cells in adult lung homeostasis and COPD.

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.

Current cough and sputum assessed by the cough and sputum assessment-questionnaire (CASA-Q) is associated with quality of life impairment in cystic fibrosis.

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 FEV1 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).

Accelerated subsequent lung cancer after post-operative radiotherapy for breast cancer.

BACKGROUND: Post-operative whole breast radiotherapy for breast cancer (BC) may increase the risk of subsequent lung cancer (LC). The impact of radiotherapy intensification (boost) has not been specifically explored in this context. We investigated the role of radiation modalities on the development of subsequent LC among our patients treated by radiotherapy for localized BC. METHODS: All patients with a diagnosis of LC between 2000 and 2020 with a history of prior localized BC treated by surgery and post-operative radiotherapy were retrospectively reviewed. Primary endpoint was time to first diagnosis of LC after BC treatment with radiotherapy (RT). RESULTS: From 98 patients who developed subsequent LC after primary BC treated with post-operative RT, 38% of patients (n = 37) received an additional RT boost, and 46% (n = 45) received hormonal treatment post radiation. A total of 61% (n = 60) were smokers. With regards to LC characteristics, adenocarcinoma was the most frequent histology (68%, n = 66); 36% (n = 35) harbored at least 1 molecular alteration, 57% (n = 20) of them being amenable to targeted therapy. Median time to first diagnosis of LC was 6 years [1.7-28.4 yrs] in the whole cohort. In the subgroup of patients treated with boost this time was reduced to 4 years [1.8-20.8 years] compared to 8 years for patients without boost [1.7-28.4 yrs] (p = 0.007). Boost, smoking usage, endocrine therapy, and age <50 yrs old at BC radiation remained independent factors associated with shorter time to first diagnosis of LC after BC treatment. DISCUSSION: We report for the first time the potential impact of boost -part of BC radiation treatment- for BC on the risk of subsequent LC. The impact of low dose radiation on lung parenchyma could explain this phenomenon, but the underlying physiopathology is still under investigation. This work highlights the need for clinicians to identify patients at risk of developing faster subsequent thoracic malignancy after BC radiation, for implementing personalized surveillance.

Soluble biomarkers to predict clinical outcomes in non-small cell lung cancer treated by immune checkpoints inhibitors.

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.

Assessment of the Association between Entropy in PET/CT and Response to Anti-PD-1/PD-L1 Monotherapy in Stage III or IV NSCLC.

Anti-PD-1/PD-L1 therapy indications are broadened in non-small cell lung cancer (NSCLC) although immune checkpoint inhibitors (ICI) do not provide benefits for the entire population. Texture features based on positron emission tomography/computed tomography (PET/CT), especially entropy (based on a gray-level co-occurrence matrix (GLCM)), could be interesting as predictors in NSCLC. The aim of our retrospective study was to evaluate the association between GLCM-entropy and response to anti-PD-1/PD-L1 monotherapy at the first evaluation in stage III or IV NSCLC, comparing patients with progressive disease (PD) and non-progressive disease (non-PD). In total, 47 patients were included. Response Evaluation Criteria in Solid Tumors (RECIST 1.1) were used to evaluate the response to ICI treatment (nivolumab, pembrolizumab, or atezolizumab). At the first evaluation, 25 patients were PD and 22 were non-PD. GLCM-entropy was not predictive of response at the first evaluation. Furthermore, GLCM-entropy was not associated with progression-free survival (PFS) (p = 0.393) or overall survival (OS) (p = 0.220). Finally, GLCM-entropy measured in PET/CT performed before ICI initiation in stage III or IV NSCLC was not predictive of response at the first evaluation. However, this study demonstrates the feasibility of using texture parameters in routine clinical practice. The interest of measuring PET/CT texture parameters in NSCLC remains to be evaluated in larger prospective studies.

Pomalidomide-induced lung injury: A case report.

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.

Clinical relevance of low bone density in cystic fibrosis adult patients: A pilot study.

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.

HER2 Alterations in Non-Small Cell Lung Cancer: Biologico-Clinical Consequences and Interest in Therapeutic Strategies.

Lung cancer stands as the first cause of death by cancer in the world. Despite the improvement in patients' outcomes in the past decades through the development of personalized medicine approaches, a substantial portion of patients remains ineligible for targeted therapies due to the lack of a "druggable" molecular target. HER2, a receptor tyrosine kinase member of the EGFR/ErbB family, is known to show oncogenic properties. In this review, we focus on the different HER2 dysregulation mechanisms that have been observed in non-small cell lung cancer (NSCLC): gene mutation, gene amplification, protein overexpression and protein hyper-phosphorylation, the latter suggesting that HER2 dysregulation can occur independently of any molecular aberration. These HER2 alterations inevitably have consequences on tumor biology. Here, we discuss how they are not only involved in abnormal proliferation and survival of cancer cells but also potentially in increased angiogenic properties, mesenchymal features and tumor immune escape. Finally, we review the impact of these HER2 alterations in various therapeutic approaches. While standard chemotherapy and groundbreaking immunotherapy seem rather ineffective for HER2-altered NSCLCs, the development of HER2-targeted therapies such as tyrosine kinase inhibitors, anti-HER2 antibodies and especially antibody-drug conjugates could provide new hopes for patients.

Transcriptomic FHITlow/pHER2high signature as a predictive factor of outcome and immunotherapy response in non-small cell lung cancer.

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 FHITlow/pHER2high 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 FHITlow/pHER2high 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 FHITlow/pHER2high tumors were associated with cell proliferation, metabolism and metastasis, whereas down-regulated genes were related to immune response. The FHITlow/pHER2high 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. FHITlow/pHER2high 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 FHITlow/pHER2high tumors and that anti-HER2 targeted therapy could be a good therapeutic alternative for this molecular subclass with poorer prognosis.

The Nicotinic Receptor Polymorphism rs16969968 Is Associated with Airway Remodeling and Inflammatory Dysregulation in COPD Patients.

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.

Health-Related Quality of Life in Adults with Cystic Fibrosis: Familial, Occupational, Social, and Mental Health Predictors.

BACKGROUND: Cystic Fibrosis (CF) adult patients experience daily physical symptoms and disabilities that may impact their quality of life and mental health. METHODS: This prospective study aimed to evaluate the relative contribution of the familial, occupational, and social environment, besides that of the main physical and mental health factors, to the quality of life of CF adult patients using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) in a multivariate model. RESULTS: Fifty patients were analyzed (70% of men; median age of 25 years; median body mass index of 21 kg/m²; median FEV1 of 57%). Anxiety and depression scores were negatively associated with 9 of the 12 CFQ-R domains. When controlling for anxiety and depression, FEV1% and BMI were significant positive predictors of several domains of the CFQ-R. All the familial, occupational, and social components analyzed but one (professional training) were predictors of at least one domain of the CFQ-R. CONCLUSION: Anxiety and depression explained a greater proportion of the variance than physical variables (age, sex, BMI, FEV1%, and exacerbation in the last year) in CF HRQoL. Many familial, occupational, and social components were also specifically and independently predictors of some HRQoL domains. Their screening might help identifying CF patients eligible for specific interventions, focusing on the impaired QoL dimensions.

Clinical Impact of the Epithelial-Mesenchymal Transition in Lung Cancer as a Biomarker Assisting in Therapeutic Decisions.

Lung cancer is one of the most common solid cancers and represents the leading cause of cancer death worldwide. Over the last decade, research on the epithelial-mesenchymal transition (EMT) in lung cancer has gained increasing attention. Here, we review clinical and histological features of non-small-cell lung cancer associated with EMT. We then aimed to establish potential clinical implications of EMT in current therapeutic options, including surgery, radiation, targeted therapy against oncogenic drivers, and immunotherapy.

Extended Bacteria Culture-Based Clustering Identifies a Phenotype Associating Increased Cough and Enterobacterales in Stable Chronic Obstructive Pulmonary Disease.

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 (107 vs. 105 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.

Impaired Ciliary Beat Frequency and Ciliogenesis Alteration during Airway Epithelial Cell Differentiation in COPD.

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.

Identifying specific needs in adult cystic fibrosis patients: a pilot study using a custom questionnaire.

BACKGROUND: Adult patients with cystic fibrosis (CF) experience daily physical symptoms and disabilities that can be challenging to address for health care teams. METHODS: We sought to identify the most frequent topics that CF adults need to discuss with health care teams using a custom questionnaire including 62 items. RESULTS: Fifty patients were included, 70% men, mean age 27.6 years, with a mean body mass index of 21.8 kg/m2. Mean FEV1% was 64% of predicted value. Forty-two percent of patients selected at least one topic. The most frequently selected topics were fatigue (20%), professional or scholar worries (18%), procreation (16%), physical activities (16%) and evolution of CF disease (16%). Women were more frequently concerned about fatigue, procreation and profession/school. CONCLUSIONS: Using a custom questionnaire, we identified that CF adults express various unmet needs that extend beyond usual respiratory and nutritional concerns or treatment adherence. The interest of this questionnaire by health care team for improving therapeutic management of CF patients remains to be validated. TRIAL REGISTRATION: The study was registered on ClinicalTrials.gov (NCT02924818) on 5th October 2016.

Hypoxia in Lung Cancer Management: A Translational Approach.

Lung cancer represents the first cause of death by cancer worldwide and remains a challenging public health issue. Hypoxia, as a relevant biomarker, has raised high expectations for clinical practice. Here, we review clinical and pathological features related to hypoxic lung tumours. Secondly, we expound on the main current techniques to evaluate hypoxic status in NSCLC focusing on positive emission tomography. We present existing alternative experimental approaches such as the examination of circulating markers and highlight the interest in non-invasive markers. Finally, we evaluate the relevance of investigating hypoxia in lung cancer management as a companion biomarker at various lung cancer stages. Hypoxia could support the identification of patients with higher risks of NSCLC. Moreover, the presence of hypoxia in treated tumours could help clinicians predict a worse prognosis for patients with resected NSCLC and may help identify patients who would benefit potentially from adjuvant therapies. Globally, the large quantity of translational data incites experimental and clinical studies to implement the characterisation of hypoxia in clinical NSCLC management.

Chr15q25 Genetic Variant rs16969968 Alters Cell Differentiation in Respiratory Epithelia.

The gene cluster region, CHRNA3/CHRNA5/CHRNB4, encoding for nicotinic acetylcholine receptor (nAChR) subunits, contains several genetic variants linked to nicotine addiction and brain disorders. The CHRNA5 single-nucleotide polymorphism (SNP) rs16969968 is strongly associated with nicotine dependence and lung diseases. Using immunostaining studies on tissue sections and air-liquid interface airway epithelial cell cultures, in situ hybridisation, transcriptomic and cytokines detection, we analysed rs16969968 contribution to respiratory airway epithelial remodelling and modulation of inflammation. We provide cellular and molecular analyses which support the genetic association of this polymorphism with impaired ciliogenesis and the altered production of inflammatory mediators. This suggests its role in lung disease development.