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Background While sleep disruption is a common complaint among children with cystic fibrosis (CF), only a few studies have investigated insomnia in adults. The aim of this study was to identify factors associated with insomnia in clinically stable adult CF patients. Methods Twenty-eight CF patients (18M/10F), with a median age of 27 (22–34) (median (interquartile range) years and a median of forced expiratory volume in one second of 72 (39–93) % predicted completed questionnaires on insomnia (Insomnia Severity Index, ISI), sleep quality (PSQI), daytime sleepiness (Epworth), restless legs syndrome (IRLS), pain (NRS), anxiety/depression (HAD) and quality of life (CFQ-R 14+). Respiratory assessment data, including symptoms, sputum analysis, arterial blood gases, 6-min walking test, pulmonary function tests and polysomnographic variables, were also analyzed. Results Forty-three percent of patients were insomniac (ISI > 7). Compared with non-insomniac patients (ISI ≤ 7), insomniac patients had more severely impaired quality of life and a higher HAD score: median anxiety score of 9 (8–11) vs 4 (3–6) (p p p 2 during sleep. Conclusions The strong association between insomnia, impaired quality of life and increased HAD score should prompt physicians to be particularly attentive to the management of anxiety and depression in adult CF patients with insomnia. Trial registration: On clinicaltrials.gov (NCT02924818, date of registration: October 5, 2016).

Background In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP). In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be modulated by EP in COPD patients. Methods CD4+ and CD8+ T-cells, sorted from peripheral blood mononuclear cells (PBMC) collected from COPD patients (n = 29) and controls (n = 13) were cultured with or without EP. Cytokine expression in T-cell phenotypes was analyzed by multicolor flow cytometry, whereas desmosine concentration, a specific marker of elastin degradation, was measured in sera. Results Compared with control, the percentage of IL-4 (Th2) producing CD4+ T-cells was decreased in COPD patients (35.3 ± 3.4% and 26.3 ± 2.4%, respectively, p + T-cells, of which only one expressed high IL-4 levels in association with high levels of desmosine and strong smoking exposure (n = 7). Upon stimulation with VGVAPG, a bioactive EP motif, the percentage of CD4+ T cells expressing IL-4 significantly increased in COPD patients (p Conclusions The present study demonstrates that the VGVAPG elastin peptide modulates CD4+ T-cells IL-4 production in COPD. Monitoring IL-4 in circulating CD4+ T-cells may help to better characterize COPD phenotypes and could open a new pharmacologic opportunity through CD4+ T-cells stimulation via the VGVAPG/S-gal receptor in order to favor an anti-inflammatory response in those COPD patients.

Despite its efficacy in solid tumours, in particular HER2+ breast cancer, HER2-targeted therapy has given rise to disappointing results in non-small cell lung cancer (NSCLC). With the aim of refining the target population for anti-HER2 therapies in NSCLC, we investigated the relationships between HER2 and the tumour suppressor fragile histidine triad (FHIT) in lung tumour cells. First, we observed a negative correlation between FHIT expression and the activated form of HER2 (pHER2) in NSCLC samples and in lung tumour cell lines. Moreover, the silencing or overexpression of FHIT in lung cell lines led to an increase or decrease of HER2 activity, respectively. We also demonstrated that two anti-HER2 drugs, irbinitinib and trastuzumab, restore a more epithelial phenotype and counteract cell invasiveness and growth of FHIT-silenced tumour cell lines. Finally, we showed that the FHITlow /pHER2high phenotype predicts sensitivity to an anti-HER2 therapy in primary tumour cells from NSCLC patients. Our results show that FHIT regulates the activity of HER2 in lung tumour cells and that FHIT-inactivated tumour cells are sensitive to HER2 inhibitors. A new subclass of patients with NSCLC may be eligible for an anti-HER2 therapy. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

International audience; 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.

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels responsible for the rapid neural and neuromuscular signal transmission. Although it is well documented that 16 subunits are encoded by the human genome, their presence in airway epithelial cells (AEC) remains poorly understood, and contribution to pathology is mainly discussed in the context of cancer. We analysed nAChR subunit expression in the human lung of smokers and non-smokers using transcriptomic data for whole lung tissues, isolated large AEC, and isolated small AEC. We identified differential expressions of nAChRs in terms of detection and repartition in the three modalities. Smoking-associated alterations were also unveiled. Then, we identified a nAChR transcriptomic print at a single cell level. Finally, we reported the localizations of detectable nAChRs in bronchi and large bronchioles. Thus, we compiled the first complete atlas of pulmonary nAChRs to open new avenues to further unravel the involvement of these receptors in lung homeostasis and respiratory diseases.

Resume Introduction Les hemangiomes sont des malformations vasculaires de localisation frequentes cutanees, hepatiques et spleniques. L’atteinte respiratoire reste rare et peu decrite. Observation Une femme de 35 ans se presente pour hemoptysie recidivante. L’iconographie met en evidence une masse lobaire inferieure gauche associee a des adenomegalies sus et sous-diaphragmatiques, ainsi qu’une splenomegalie heterogene et une lesion rachidienne isolee sans hyper metabolisme au TEP-scanner. La fibroscopie bronchique simple ainsi que l’echo-endoscopie bronchique seront non contributives. Une preuve histologique sera obtenue par une splenectomie avec curage lombo-aortique, puis une lobectomie d’hemostase. Sera retenu le diagnostic d’hemangiomatose multi-viscerale bronchique, ganglionnaire, splenique et osseuse. Conclusions Les hemangiomes caverneux broncho-pulmonaires associes a des hemangiomes extra-thoraciques sont exceptionnels. La presentation faisant suspecter une pathologie maligne doit conduire a une analyse histologique. Nous rapportons ici une premiere observation combinant des atteintes pulmonaires, spleniques, ganglionnaires et osseuses.

Background: An alteration of primary cilia is observed in remodelled airways in the context of COPD. Since this organelle is required to activate Hedgehog (HH) signalling pathway orchestrating cell fate during lung development, we explored HH activation during human airway epithelial cell differentiation and in adult lungs from COPD and non-COPD patients. Methods: Human airway epithelial cells were cultured from nasal polyps and bronchial brushing in air-liquid interface conditions to reconstitute an epithelium representative of the adult airways. ELISA and immunostaining analysis of the principal ligand Sonic Hedgehog (SHH) were performed at different steps of differentiation on airway epithelial cell cultures, bronchial aspirations and formalin-fixed paraffin embedded lung tissues of non-COPD and COPD patients. Results: Non-differentiated airway epithelial cells produced SHH in vitro during the course of differentiation (from 6pg/ml at ALI-0 to 238pg/ml at ALI-35). Depriving culture medium of SHH with a specific antibody induced epithelial remodelling particularly impacting ciliogenesis (2 fold decrease of ciliated cells). SHH was observed on bronchial tissue sections and detected by ELISA with a 2 fold decrease expression for COPD patients. Conclusion: These findings suggest a crucial involvement of HH pathway in airway basal cells to guide differentiation and indicate an alteration of its activation in COPD patients. Measuring HH elements in biological samples may help categorize COPD patients and propose novel diagnostic and therapeutic strategies.

In non-metastatic non-small-cell lung cancer (NSCLC), outcomes remain poor. Adjuvant chemotherapies provide a limited improvement in disease-free survival. Recent exploratory studies on early-stage NSCLC show that immunotherapy given according to Programmed Death&ndash, Ligand 1 expression generates variable results, emphasizing a need to improve tumor characterization. We aimed to conjointly assess NSCLC, the expression of PD&ndash, L1, and epithelial&ndash, mesenchymal transition, frequently involved in tumor aggressiveness. 188 resected NSCLCs were analyzed. Among 188 patients with curatively resected NSCLC, 127 adenocarcinomas and 61 squamous cell carcinomas were stained for PD&ndash, L1 and vimentin expression. Overall survival has been compared regarding PD&ndash, L1 and vimentin statuses both separately and conjointly in Tumor Cancer Genome Atlas databases. PD&ndash, L1 and vimentin higher expressions were strongly associated (OR = 4.682, p &lt, 0.0001). This co-expression occurred preferentially in tumors with lymph node invasion (p = 0.033). PD&ndash, L1 was significantly associated with high EMT features. NSCLC harboring both PD&ndash, L1high/vimentinhigh expressions were significantly associated with poor overall survival (p = 0.019). A higher co-expression of vimentin and PD&ndash, L1 was able to identify patients with worse outcomes. Similar to an important prognostic marker in NSCLC, this tandem marker needs to be further presented to anti-PD&ndash, L1 immunotherapies to improve outcome.