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BackgroundLife expectancy for people with cystic fibrosis (CF) varies considerably both within and between countries. The objective of this study was to compare survival among countries with single-payer healthcare systems while accounting for markers of disease severity.MethodsThis cohort study used data from established national CF registries in Australia, Canada, France and New Zealand from 2015 to 2019. Median age of survival for each of the four countries was estimated using the Kaplan-Meier method. A Cox proportional hazards model was used to compare risk of death between Canada, France and Australia after adjusting for prognostic factors. Due to low number of deaths, New Zealand was not included in final adjusted models.ResultsBetween 2015 and 2019, a total of 14 842 people (3537 Australia, 4434 Canada, 6411 France and 460 New Zealand) were included. The median age of survival was highest in France 65.9 years (95% CI: 59.8 to 76.0) versus 53.3 years (95% CI: 48.9 to 59.8) for Australia, 55.4 years (95% CI: 51.3 to 59.2) for Canada and 54.8 years (95% CI: 40.7 to not available) for New Zealand. After adjusting for individual-level factors, the risk of death was significantly higher in Canada (HR 1.85, 95% CI: 1.48 to 2.32; pInterpretationWe observed significantly higher survival in France compared with countries with single-payer healthcare systems. The median age of survival in France exceeded 60 years of age despite having the highest proportion of underweight patients which may be due to differences in availability of transplant.

Neutrophils are key players in the hyperinflammatory response upon SARS-CoV-2 infection. We have previously described that cytosolic proliferating cell nuclear antigen (PCNA) controls neutrophil survival and NADPH oxidase-dependent ROS production. We here show that both PCNA and S100A8 expression and interaction were elevated in neutrophils from patients with COVID-19 compared to healthy donors and this was correlated with disease severity. Increased PCNA expression was accompanied by a decreased apoptosis and increased NADPH-oxidase activity in neutrophils from COVID-19 patients compared to healthy donors. These effects, as well as the interaction between PCNA and S100A8, were potently counteracted by T2 amino alcohol (T2AA), a PCNA inhibitor, demonstrating that the PCNA scaffold orchestrated neutrophil activation. Notably, the interaction between PCNA-S100A8 was more intense in the CD16high-CD62Llowactivated neutrophil subset. We propose that PCNA-S100A8 complex acts as potential driver for neutrophil dysregulation in COVID-19 and show for the first time that the PCNA scaffold is a decisive component of both neutrophil activation and heterogeneity.

International audience; Lung transplantation (LTx) is a steadily expanding field. The considerable developments have been driven over the years by indefatigable work conducted at LTx centers to improve donor and recipient selection, combined with multifaceted efforts to overcome challenges raised by the surgical procedure, perioperative care, and long-term medical complications. One consequence has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. The Francophone Pulmonology Society (Société de Pneumology de Langue Française, SPLF) set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force examined the most recent literature and evaluated the risk factors that limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while also improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.

Introduction: Clinical guidelines recommend airway clearance techniques (ACTs) in adults with bronchiectasis. There is a paucity of evidence about their clinical implementation, particularly in different healthcare systems. Multicentre registries can facilitate studying patterns and differences across countries. Methods: Outpatients with bronchiectasis were prospectively recruited to the multicentre European Bronchiectasis Registry EMBARC. Patient-reported ACTs were registered in 31 countries. Demographic, baseline health status, exacerbations, radiology, and treatments were recorded. Results: Data were collected between 2015 and 2018. 13,512 patients participated, mean (SD) age 64.2 (14.6) years old, 8,121 females (60.1%). Only 48.3% of the participants reported performing airway clearance regularly. The most commonly used techniques were active cycle of breathing techniques (ACBT) (26.8%) and postural drainage (6.0%). 21.2% of patients used one or more airway clearance devices. Flutter (8.9%), fixed positive expiratory pressure (PEP) (6.5%) and Acapella (4.4%) were the most commonly used ones. The vast majority of patients perform regular ACTs in Denmark (91.7%) and Finland (88.7%), compared to less than 10% of participants in Bulgaria, North Macedonia, Moldova, Romania, and Sweden. The primary reason for not doing airway clearance was that it was not required in the opinion of the clinicians (67.9%). Conclusions: Most patients with bronchiectasis do not routinely perform ACTs. Clinicians’ opinion is often that bronchiectasis patients do not require ACTs. Acknowledgments: EMBARC has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking iABC grant agreement no 115721.

Background: Randomized Trials in bronchiectasis may have been underpowered due to unexpectedly large “placebo effects”. We used a combination of meta-analysis and analysis of the European Bronchiectasis Registry (EMBARC) to quantify “placebo effects” in randomized trials in bronchiectasis Method: We searched electronic databases from 1990-2019, to identify double blind, randomized, placebo-controlled trials of drug treatment in bronchiectasis. We defined the “placebo effects” by comparing the outcomes at the end of placebo treatment and at baseline prior to treatment. EMBARC registry data were employed to model changes in exacerbation rate and quality of life (QoL) Result: 27 trials were included for meta-analysis (N=1739 placebo-treated patients). Placebo treatment was associated with significantly reduced exacerbation rate (mean difference [MD] -1.79, -2.03 to -1.56; p Conclusion: Placebo treatment was associated with improved QoL and reduced exacerbation in bronchiectasis. Enrolling patients with 1 or more exacerbation may be an optimal inclusion criteria

Pseudomonas aeruginosa is a common respiratory pathogen found in patients with cystic fibrosis (CF), contributing to increased hospitalization, more rapid progression of CF lung disease, and increased risk of death. Guidelines recommend early therapy using tobramycin inhaled solution (TIS) or inhaled powder (TIP). Both TIS and TIP treatment regimens have demonstrated positive clinical outcomes in efficacy and safety, including improvements in FEV

Background: Alveolar macrophages (AMs) play key roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to characterise the mechanisms of defective phagocytosis in AMs from COPD patients. We hypothesised that respiratory viruses could impair the ability of AMs to phagocytose lung bacteria. Materials and methods: AMs were isolated from bronchoalveolar lavage (BAL) and phenotyped using flow cytometry. AMs were pre-challenged with major or minor group rhinoviruses (RVs) and then phagocytosis of Moraxella catarrhalis or non-typeable Haemophilus influenzae (NTHi) examined. We repeated experiments using monocyte-derived macrophages (MDMs). Results: AMs consisted of separate populations. AMs from COPD patients had reduced cell surface marker expression, were immature and defective in phagocytosis and bacterial clearance. AMs pre-infected with major group RVs showed reduced phagocytosis, not seen in AMs pre-infected with a minor group RV. This inhibition was likely viral mediated because it was not observed in AMs treated with UV inactivated virus. Using MDMs we observed the same. We are currently investigating how viral infection or viral products affect the capacities of macrophages to engulf bacteria, generate phagolysosomes and eliminate them, and produce cytokines. Conclusion: Our results suggest AMs from COPD patients are phenotypically different to AMs from healthy patients and defective in phagocytosis. We show major group RVs impair AM and MDM phagocytic functions. These results could explain why COPD patients show exacerbations with bacterial pathogens found in the lung and why they show infections with major group RVs first.