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Background: Data describing patients hospitalized in medical rehabilitation wards after the acute phase of COVID-19 could help to better understand the rehabilitation needs in the current pandemic situation. Methods: Cohort including all patients with COVID-19 hospitalized in a single, large university hospital in Northeast France from 25 February to 30 April 2020. Results: 479 patients were admitted with COVID-19 during the study period, of whom 128 died (26.7%). Among the 351 survivors, 111 were referred to rehabilitation units, including 63 (17.9%) referred to physical and rehabilitation medicine (PRM) units. The median age of patients referred to rehabilitation units was 72 years. Patients who had been in intensive care, or who had had a long hospital stay, required referral to PRM units. Two biomarkers were associated with referral to rehabilitation units, namely, elevated troponin (p = 0.03) and impaired renal function (p = 0.03). Age was associated with referral to PRM units (p = 0.001). Conclusions: Almost one-third of COVID-19 patients required post-acute care, but only one-fifth had access to PRM units. The optimal strategy for post-acute management of COVID-19 patients remains to be determined. The need for rehabilitation wards during a pandemic is a primary concern in enabling the long-term functioning of infected patients.

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.

Background: Dysregulated inflammation as seen in chronic obstructive pulmonary disease (COPD) is associated with impaired wound healing. IL-20 cytokines are known to be involved in wound healing processes. The purpose of this study was to use ex vivo and in vitro approaches mimicking COPD to evaluate the potential modulatory role of interleukin-20 (IL-20) on the inflammatory and healing responses to epithelial wounding. Methods: The expression of IL-20 cytokines and their receptors was investigated in lung-derived samples collected from non-COPD and COPD patients, from mice chronically exposed to cigarette smoke and from airway epithelial cells from humans and mice exposed in vitro to cigarette smoke. To investigate the role of IL-20 cytokines in wound healing, experiments were performed using a blocking anti-IL-20Rb antibody. Results: Of interest, IL-20 cytokines and their receptors were expressed in bronchial mucosa, especially on airway epithelial cells. Their expression correlated with the disease severity. Blocking these cytokines in a COPD context improved the repair processes after a lesion induced by scratching the epithelial layer. Conclusions: Collectively, this study highlights the implication of IL-20 cytokines in the repair of the airway epithelium and in the pathology of COPD. IL-20 subfamily cytokines might provide therapeutic benefit for patients with COPD to improve epithelial healing.

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.

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.

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.