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Acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality resulting from a direct or indirect injury of the lung. It is characterized by a rapid alveolar injury, lung inflammation with neutrophil accumulation, elevated permeability of the microvascular-barrier leading to an aggregation of protein-rich fluid in the lungs, followed by impaired oxygenation in the arteries and eventual respiratory failure. Very recently, we have shown an involvement of the Gq-coupled P2Y2 purinergic receptor (P2RY2) in allergic airway inflammation (AAI). In the current study, we aimed to elucidate the contribution of the P2RY2 in lipopolysaccharide (LPS)- induced ARDS mouse model. We found that the expression of P2ry2 in neutrophils, macrophages and lung tissue from animals with LPS-induced ARDS was strongly upregulated at mRNA level. In addition, ATPneutralization by apyrase in vivo markedly attenuated inflammation and blocking of P2RY2 by non-selective antagonist suramin partially decreased inflammation. This was indicated by a reduction in the number of neutrophils, concentration of proinflammatory cytokines in the BALF, microvascular plasma leakage and reduced features of inflammation in histological analysis of the lung. P2RY2 blocking has also attenuated polymorphonuclear neutrophil (PMN) migration into the interstitium of the lungs in ARDS mouse model. Consistently, treatment of P2ry2 deficient mice with LPS lead to an amelioration of the inflammatory response showed by reduced number of neutrophils and concentrations of proinflammatory cytokines. In attempts to identify the cell type specific role of P2RY2, a series of experiments with conditional P2ry2 knockout animals were performed. We observed that P2ry2 expression in neutrophils, but not in the airway epithelial cells or CD4+ cells, was associated with the inflammatory features caused by ARDS. Altogether, our findings imply for the first time that increased endogenous ATP concentration via activation of P2RY2 is related to the pathogenesis of LPS-induced lung inflammation and may represent a potential therapeutic target for the treatment of ARDS and predictably assess new treatments in ARDS. [ABSTRACT FROM AUTHOR]

Introduction: Despite many technological advances, the diagnostic yield of bronchoscopic peripheral lung nodule analysis remains limited due to frequent mispositioning. Needle-based confocal laser endomicroscopy (nCLE) enables real-time microscopic feedback on needle positioning, potentially improving the sampling location and diagnostic yield. Previous studies have defined and validated nCLE criteria for malignancy, airway and lung parenchyma. Larger studies demonstrating the effect of nCLE on diagnostic yield are lacking. We aim to investigate if nCLE-imaging integrated with conventional bronchoscopy results in a higher diagnostic yield compared with conventional bronchoscopy without nCLE., Methods and Analysis: This is a parallel-group randomised controlled trial. Recruitment is performed at pulmonology outpatient clinics in universities and general hospitals in six different European countries and one hospital in the USA. Consecutive patients with a for malignancy suspected peripheral lung nodule (10-30 mm) with an indication for diagnostic bronchoscopy will be screened, and 208 patients will be included. Web-based randomisation (1:1) between the two procedures will be performed. The primary outcome is diagnostic yield. Secondary outcomes include diagnostic sensitivity for malignancy, needle repositionings, procedure and fluoroscopy duration, and complications. Pathologists will be blinded to procedure type; patients and endoscopists will not., Ethics and Dissemination: Primary approval by the Ethics Committee of the Amsterdam University Medical Center. Dissemination involves publication in a peer-reviewed journal., Support: Financial and material support from Mauna Kea Technologies., Trial Registration Number: NCT06079970., Competing Interests: Competing interests: JTA declares material and financial support to the sponsor’s institution from Mauna Kea Technologies for this study. All Cellvizio equipment needed for the conduct of the study is provided in-kind to participating centers. All other authors declare no other conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This article summarises the highlights from the European Respiratory Society's "Clinical techniques, imaging and endoscopy" Assembly 14 presented at the virtual 2021 European Respiratory Society International Congress. Cutting-edge innovative developments in both diagnostic approaches and therapeutic strategies in patients with lung cancer, interstitial lung disease, obstructive airway disorders and infectious diseases were presented on this year's interactive congress platform. In this article, the Assembly 14 subgroups summarise the key take home messages given new research outcomes and place them in the context of the current knowledge., Competing Interests: Conflict of interest: C. Bal has nothing to disclose. Conflict of interest: C. Falster reports a fee for a lecture at a professional meeting organised by AstraZeneca outside the submitted work. Conflict of interest: A. Carvalho reports lecture fees from Zambon and Boehringer Ingelheim outside the submitted work. Conflict of interest: N. Hersch has nothing to disclose. Conflict of Interest: J. Brock reports lecture fees and consulting activity from Boehringer Ingelheim, Streamed up! and AstraZeneca outside the submitted work. Conflict of interest: J. Brock reports lecture fees and consulting activity from Boehringer Ingelheim, Streamed up! and AstraZeneca outside the submitted work. C.B. Laursen reports a fee for a lecture at a research symposium organised by AstraZeneca outside the submitted work. Conflict of interest: S. Walsh reports fees for lectures at research symposiums organised by Zambon and Boehringer Ingelheim outside the submitted work. Conflict of interest: J. Annema reports research grants from Boston Scientific and Maunea Kea outside the submitted work. Conflict of interest: D. Gompelmann reports lecture and travel fees from Pulmonx, AstraZeneca, Boehringer Ingelheim, Olympus, Chiesi, Berlin Chemie and Novartis outside the submitted work., (Copyright ©The authors 2022.)