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Les contes traditionnels sont étroitement associés à une variété de langue qu’on qualifie de populaire, c’est-à-dire à une façon de parler qui n’est pas freinée par les normes sociales dictées par les groupes dominants. Le français québécois, issu des idiomes provinciaux des premiers colons, possède un registre populaire qui convenait bien aux conteurs par son ton dégagé, son exubérance et ses rapports décontractés avec la norme. Les conteurs en ont exploité les ressources pour créer des mondes imaginaires, hors norme. On dégage ici quelques traits de cette langue à partir de l’examen des paronymes clapoter, flacoter et placoter qui servent à parler du mouvement de l’eau agitée et que la verve populaire a enrichis de divers emplois analogiques., Traditional folktales have close ties to what we could call folk speech, meaning a form of expression that is not dictated by the norms imposed by dominant groups. Québécois French, a way of speaking that evolved from the provincial dialects of the early settlers, possesses a folk vernacular that suited storytelling very well, being light-hearted, exuberant and free from social constraints. Traditional storytellers took advantage of the language possibilities that were available to them, in order to create imaginary, extraordinary worlds. This article highlights some of the traits of folk speech through an examination of three paronyms, “clapoter”, “flacoter” and “placoter”, all words that refer to the movement of water that is stirred up, but that have acquired various parallel meanings in folk speech.

Objective Health literacy (HL) is a person’s ability to practically apply a wide range of cognitive and non-cognitive skills, to make health-related decisions. Currently, no tool applies all HL core domains to capture necessary data to measures HL in adult asthma and COPD patients. We endeavored to develop a comprehensive, function-based tool that adequately and accurately measures HL skills of this patient population. We explored the perspectives of patients related to each core HL domain, with an emphasis on self-management practices. Methods Sixteen focus groups were conducted (n = 93; 40 asthma and 53 COPD) across Canada. Data was analyzed using NVivo12. Results Thirteen subthemes were identified within five HL domains: (a) access: active access; passive access; lack of access; (b) understanding: how to improve understanding; (c) trustworthiness; relevancy and validity of information: pre- and post- application of information; (d) communication: barriers to proper communication; (e) application of information: making health decisions. Conclusions Participants provided valuable insight in terms of disease management topics and corresponding items to include in our HL tool. Practice implications Involvement of patients from initial stage allowed us to develop a tool that will serve as a first ever developed HL tool for asthma and COPD patient group.

International audience; The seminal plasma is a very complex fluid, which surrounds sperm in semen. It contains numerous proteins including proteases and protease inhibitors that regulate proteolytic processes associated with protein activation and degradation. We previously identified a seminal protein, chicken liver trypsin inhibitor 1 (ClTI‐1) over expressed in semen of roosters with high fertility, suggesting a role in male fertility. In the present study, we showed that ClTI‐1 gene is actually SPINK2. Using normal healthy adult roosters, we showed that SPINK2 amount in seminal plasma was positively correlated with male fertility in chicken lines with highly contrasted genetic backgrounds (broiler and layer lines). Using affinity chromatography combined to mass spectrometry analysis and kinetic assays, we demonstrated for the first time that two chicken acrosin isoforms (acrosin and acrosin‐like proteins) are the physiological serine protease targets of SPINK2 inhibitor. SPINK2 transcript was overexpressed all along the male tract, and the protein was present in the lumen as expected for secreted proteins. Altogether, these data emphasize the role of seminal SPINK2 Kazal‐type inhibitor as an important actor of fertility in birds through its inhibitory action on acrosin isoforms proteins.

Although mainly described in patients with chronic obstructive pulmonary disease, pursed lip breathing (PLB) could prove useful in patients with interstitial lung disease (ILD) by improving exertional tachypnea and respiratory control. This prospective, randomized, crossover trial aimed at evaluating the impact of PLB on dyspnea and walking distance in ILD patients.ILD patients with total lung capacity of80% predicted were randomized to 6-min walk tests using either PLB or usual breathing. Patients were crossed over for the second 6-min walk tests and served as their own controls. Ventilatory and metabolic variables were recorded using a portable metabolic cart and were compared at 1-min intervals.Thirty-five patients were included (mean forced vital capacity of 64 ± 10% predicted). Use of PLB resulted in lower mean respiratory rates and larger tidal volumes (both P.001), worsened dyspnea ratings (post-6-min walk test Borg score: 5.2 ± 2.6 vs 4.2 ± 2.3, P.001), and walking distance (403 ± 102 m vs 429 ± 93 m, P.001). Twenty-nine patients (83%) described PLB as less comfortable than usual breathing. Both groups had similar total ventilation and oxygen saturation (all P.05), but PLB resulted in higher mean oxygen uptake (13.9 ± 3.6 vs 12.9 ± 3.2 mL/kg/min, P = .02), even when corrected for walking distance (P.001).In ILD patients, acute exposure to PLB did not improve exertional dyspnea, walking distance, or gas exchange, and was associated with higher metabolic demands than usual breathing. These results cast doubt on the usefulness of this technique in ILD patients and should be taken into account when tailoring pulmonary rehabilitation programs to this population.

Cyanobacteria growth in Missisquoi Bay of Lake Champlain is triggered by the P load carried by tributaries in surrounding watersheds where agriculture is a dominant land use. The objective of this study was to apportion the total P (TP) load in streamflow from an agricultural subwatershed into distinct hydrologic pathways: groundwater resurgence, surface runoff, and tile drainage components (matrix flow and preferential flow). Stream discharge during peak flow was separated into these four components using electrical conductivity (EC)-discharge relationships developed from the stream water EC at the subwatershed outlet and from EC values of surface runoff and tile drain water in 10 fields within the subwatershed. The four-component hydrograph model revealed that 46 to 67% of the TP load at the outlet originated from surface runoff during peak flow. Preferential flow was responsible for most of the particulate P and dissolved reactive P loads lost through tile drainage. Groundwater resurgence was a minor source of TP, whereas other sources such as streambank erosion and resuspended sediments contributed up to 21% of the TP load and from 36 to 41% of the particulate P load at the subwatershed outlet. This work confirms that tile drainage contributes to the TP load in agricultural subwatersheds in the Missisquoi Bay region.

Malcolm Begg,1 J Nicole Hamblin,1 Emily Jarvis,2 Glyn Bradley,3 Stephen Mark,4 David Michalovich,5 Mark Lennon,6 Hannah E Wajdner,5 Augustin Amour,5 Robert Wilson,1 Ken Saunders,5 Rikako Tanaka,7 Saki Arai,7 Teresa Tang,8 Cedric Van Holsbeke,9 Jan De Backer,9 Wim Vos,9 Ingrid L Titlestad,10 J Mark FitzGerald,11 Kieran Killian,12 Jean Bourbeau,13 Claude Poirier,14 François Maltais,15 Anthony Cahn,1 Edith M Hessel1 1Refractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, UK; 2Biostatistics, GlaxoSmithKline R&D, Stevenage, UK; 3Computational Biology, Medicinal Science and Technology, GlaxoSmithKline, Stevenage, UK; 4Study Management, Clinical Development, GlaxoSmithKline, Mississauga, ON, Canada; 5Adaptive Immunity Research Unit, GlaxoSmithKline, Stevenage, UK; 6Nonclinical and Translational Statistics, GlaxoSmithKline, Stevenage, UK; 7Data Management & Strategy, Clinical Development, GlaxoSmithKline, Tokyo, Japan; 8Pharma Safety, Clinical Development, GlaxoSmithKline, Brentford, Middlesex, UK; 9FLUIDDA nv, Kontich, 2550, Belgium; 10Department of Respiratory Medicine, Odense University Hospital and University of Southern Denmark, Odense, Denmark; 11Centre for Heart and Lung Health, University of British Columbia, Vancouver, BC, Canada; 12Cardiorespiratory Research Laboratory, Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada; 13Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, QC, Canada; 14Department of Medicine, Respiratory Medicine Division, University of Montreal, Montreal, QC, Canada; 15Institut Universitaire de Cardiologie et de Pneumologie de Québe, Université Laval, Quebec City, QC, CanadaCorrespondence: Malcolm BeggRefractory Respiratory Inflammation Discovery Performance Unit, GlaxoSmithKline, Stevenage, Herts, UKEmail malcolm.5.begg@gsk.comBackground: Inhibition of phosphoinositide 3-kinase δ (PI3Kδ) exerts corrective effects on the dysregulated migration characteristics of neutrophils isolated from patients with chronic obstructive pulmonary disease (COPD).Objective: To develop novel, induced sputum endpoints to demonstrate changes in neutrophil phenotype in the lung by administering nemiralisib, a potent and selective inhaled PI3Kδ inhibitor, to patients with stable COPD or patients with acute exacerbation (AE) of COPD.Methods: In two randomized, double-blind, placebo-controlled clinical trials patients with A) stable COPD (N=28, randomized 3:1) or B) AECOPD (N=44, randomized 1:1) received treatment with inhaled nemiralisib (1mg). Endpoints included induced sputum at various time points before and during treatment for the measurement of transcriptomics (primary endpoint), inflammatory mediators, functional respiratory imaging (FRI), and spirometry.Results: In stable COPD patients, the use of nemiralisib was associated with alterations in sputum neutrophil transcriptomics suggestive of an improvement in migration phenotype; however, the same nemiralisib-evoked effects were not observed in AECOPD. Inhibition of sputum inflammatory mediators was also observed in stable but not AECOPD patients. In contrast, a placebo-corrected improvement in forced expiratory volume in 1 sec of 136 mL (95% Credible Intervals − 46, 315mL) with a probability that the true treatment ratio was > 0% (Pr(θ> 0)) of 93% was observed in AECOPD. However, FRI endpoints remained unchanged.Conclusion: We provide evidence for nemiralisib-evoked changes in neutrophil migration phenotype in stable COPD but not AECOPD, despite improving lung function in the latter group. We conclude that induced sputum can be used for measuring evidence of alteration of neutrophil phenotype in stable patients, and our study provides a data set of the sputum transcriptomic changes during recovery from AECOPD.Keywords: nemiralisib, sputum, transcriptomics, COPD exacerbations, PI3Kdelta

Background The long-term efficacy and safety of mepolizumab for treatment of severe eosinophilic asthma are well established. Here, we examine the clinical impact of stopping mepolizumab after long-term use. Methods COMET (NCT02555371) was a randomised, double-blind, placebo-controlled, parallel-group, multicentre study. Patients who had completed COLUMBA (NCT01691859) or COSMEX (NCT02135692) and received continuous mepolizumab treatment for ≥3 years were randomised 1:1 to stop (switch to placebo) or continue subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks. Primary end-point: time to first clinically significant exacerbation; secondary end-points: time to first exacerbation requiring hospitalisation/emergency department visit, time to decrease in asthma control (≥0.5-point increase in Asthma Control Questionnaire-5 score from COMET baseline) and blood eosinophil count ratio to COMET baseline. Safety was assessed. Results Patients stopping (n=151) versus continuing (n=144) mepolizumab had significantly shorter times to first clinically significant exacerbation (hazard ratio 1.61, 95% CI 1.17–2.22; p=0.004) and decrease in asthma control (hazard ratio 1.52, 95% CI 1.13–2.02; p=0.005), and higher blood eosinophil counts at week 52 (270 versus 40 cells·µL−1; ratio (stopping versus continuing) 6.19, 95% CI 4.89–7.83; p, This randomised study demonstrates increased exacerbation risk and a decrease in asthma control in patients with severe eosinophilic asthma who stop mepolizumab treatment after long-term use, when compared with those who continue treatment. https://bit.ly/3fsxGV2

Background: The long-term efficacy and safety of mepolizumab in severe eosinophilic asthma (SEA) have been shown. Aims: To assess the impact of stopping versus continuing long-term mepolizumab on asthma worsening. Methods: COMET (NCT02555371) was a randomised, double-blind, placebo-controlled study. Patients had completed COLUMBA (NCT01691859) or COSMEX (NCT02135692), had continuous mepolizumab for ≥3 years (mean 46.6 months), and stayed on asthma controller therapy. Randomisation was 1:1 to stop (switch to placebo) or continue subcutaneous mepolizumab 100 mg for 52 weeks. Composite endpoint: time to first asthma worsening (defined in Table). Daily eDiary data were analysed using Kaplan–Meier estimates and a Cox proportional hazards model adjusted for covariates. Results: Treatment differences for those who stopped versus continued mepolizumab emerged by Week 4 (8 weeks post last open-label mepolizumab dose). For those who stopped mepolizumab, 51.7% reported asthma worsening by Week 52 versus 35.0% who continued mepolizumab (Table), leading to a significantly shorter time to first asthma worsening in those who stopped mepolizumab. Conclusion: Stopping mepolizumab in patients with SEA led to an increased risk of asthma worsening with a significantly shorter time to first asthma worsening versus those continuing long-term mepolizumab. Funding: GSK [201810/NCT02555371].

La pièce d’artisanat appelée catalogne a suscité la curiosité des lettrés depuis le xixe siècle. Les définitions que les dictionnaires anciens donnent du mot concordent difficilement avec la réalité d’aujourd’hui. Couverture de laine au départ, la catalogne désigne de nos jours une sorte de tapis ou une couverture de lit qu’on fabrique avec des retailles de tissus. Les auteurs qui ont étudié la question se sont demandé quel rôle avait pu jouer la région appelée Catalogne, dans la péninsule ibérique, quant à la genèse de cette étoffe aux motifs multicolores confectionnée chez nous au métier dans les campagnes. On se propose ici de revisiter la question avec les méthodes de la philologie et de la lexicologie dans une monographie linguistique élaborée dans le cadre de la préparation de la deuxième édition du Dictionnaire historique du français québécois., The handicraft work commonly called a quilt, or catalogne in French, began to attract the curiosity of erudite individuals in the xixe century. The definitions found in period dictionaries are hardly consistent with today’s reality. Initially defined as simply a woolen blanquet, the quilt has become a type of rug or bedspread made with scraps of fabric. Authors who have studied the question have wondered what role the region called Catalonia, in the Iberian Peninsula, could possibly have played by in the development of this multicoloured textile work made by rural artisans using looms. We propose to revisit the topic, borrowing methods taken from philology and lexicology, in a linguistic study elaborated as part of the preparation of the second edition of the Dictionnaire historique du français québécois.

Introduction Chronic obstructive pulmonary disease (COPD) is a respiratory condition that causes a significant deterioration of the quality of life. However, exercise can improve the quality of life for COPD patients and it is for this reason previous study observed the effects of active video games to increase exercise. Using motion capture devices with short bursts of exercise never been tried with COPD patients. Objectives The objective was to observe the feasibility of using this device safely and easily with COPD patients. Methods A total of 14 participants (8 men, 69 ± 6 years, 6 women, 74 ± 6 years), with a moderate to severe COPD diagnosis performed exercise games (Shape-Up, Ubisoft, Mtl) adapted under supervision. Gaming sessions of 10-15 min duration were composed of four games of about 1.5 min separated by rest. Results Average and peak minute ventilation, and METs peak were, respectively: Stunt Run game (lifting knees on spot) 25.3 ± 6.8, 33.5 ± 8.2 L/min and 4.2 ± 1.5 METs; Arctic Punch game (punching targets): 23.1 ± 5.6, 31.8 ± 9.8 L/min and 3.7 ± 1.2 METs; To the Core game (core twist), 22.2 ± 7.3, 29.2 ± 9.9 L/min and 3.3 ± 1.1 METs; and Squat me to the Moon game (sitting to standing), 27.8 ± 6.7, 36.8 ± 11.1 L/min and 4.4 ± 1.1 METs. Conclusion Knowing the pleasure reported by the participants, the safety, and the ability to use it with assistance, it seems that the games could be a good tool in order for COPD patients to exercise at home. However, further investigation needs to be completed in order to observe the benefits in comparison to a traditional training program.

Purpose Lung transplantation is the only therapeutic option for patients with a terminal lung condition. Unfortunately, survival rates after transplantation remains too low. Primary graft dysfunction (PGD) is the first cause of death in the perioperative period and is associated with acute respiratory distress syndrome (ARDS), higher risk of lung infections, chronic rejection, and lower survival rates. We hypothesized that the alveolar epithelial dysfunction in donor grafts and then in the recipient, is a critical component of PGD pathophysiology. Our goal was to identify markers of alveolar damage and dysfunction in the donor grafts associated with PGD development within recipients. Methods We collected human samples and the clinical data from 174 donors and their recipients at different time points (before, during and after lung transplantation, in the ICU and follow-ups at the transplantation clinic). We also isolated alveolar epithelial cells from donor lung biopsies to assess the expression of integrity (ZO-1) and functionality biomarkers (such as ENaC and CFTR channels, which play a key role in the resorption of lung edema, a key feature of ARDS/PGD). Results Among our cohort of 174 lung transplants, suffering from various lung diseases (i.e. CF, PF/IPF, COPD, PAH), 26% developed a PGD. Several phenotypic factors from donors and intervention/procedures during transplantations were analysed. Among them, we found that although below the defined acceptable limit (6h), the mean duration of cold ischemia of the donor grafts among recipients subsequently developing a PGD was significantly longer (266 min) than the one from non-PGD recipients (233 min). We also demonstrated that alveolar cells, isolated from donor grafts within recipients developing a PGD, featured a severe decrease in ZO-1, ENaC and CFTR expression. Moreover, longer cold ischemia duration was associated with the observed ENaC and CFTR downregulation. Conclusion This study provides novel insights on epithelial alteration within donor graft, associated with subsequent PGD development. Moreover, our data pave the way for the identification of novel biomarkers and therapeutic targets for the restoration of alveolar integrity and functionality, with the ultimate goal to prevent PGD in lung transplants.

Sitting-to-supine fall in vital capacity (ΔVC) can be used to help identify diaphragm dysfunction (DD), but its optimal predictive threshold value is uncertain. Our aim was to evaluate the diagnostic performance of ΔVC in identifying the presence of unilateral or bilateral DD.Patients referred to the diaphragm dysfunction clinic of our center (2017-2018) were included. All subjects had lung function testing (including measurement of ΔVC) and an ultrasound assessment of diaphragm thickening fraction (TFdi). Unilateral DD was defined as a single hemidiaphragm with TFdi ≤30 % and bilateral DD as a mean TFdi value of both hemidiaphragms ≤30 %. Clinical and physiological characteristics were compared across groups, and sensitivity/specificity analyses of ΔVC to identify DD were performed.84 patients were included (31 unilateral DD, 17 bilateral DD and 36 without significant DD). DD groups had similar age, gender and BMI (all p0.05), but patients with bilateral DD had lower FVC, FEV1, MIP, TLC, ΔVC and more frequent orthopnea than patients with unilateral DD (all p0.05). There was a significant correlation between TFdi and ΔVC (rho=-0.56, p0.001). The optimal ΔVC value to identify bilateral DD was ≤-15 % [AUC 0.97 (95 %CI 0.89-1.00), p0.001, with sensitivity and specificity of 100 % and 89 %, respectively]. No single threshold of ΔVC could accurately predict unilateral DD [AUC 0.58 (95 %CI 0.45-0.72), p = 0.24].ΔVC performs poorly in identifying patients with unilateral DD. However, a ΔVC value ≤-15 % is strongly associated with the presence of bilateral DD. These findings should be taken into account when using ΔVC in the evaluation of patients with suspected DD.

Purpose Home-based exercise programs offer an alternative way to provide exercise pre-transplant; it gives access to rehabilitation to a larger number of patients and it may be associated with lower healthcare cost. We described the changes in functional exercise capacity (6-minute walk distance (6MWD)) in lung transplant candidates who participated in a home-based exercise program and evaluated relationships between changes in functional exercise capacity pre-transplant and post-transplant variables. Methods Retrospective cohort study of 159 individuals who received a lung transplant between 2011-2015, who participated in a home-based exercise program while waiting for transplantation and had available pre-transplant data. Our primary outcome was 6MWD at 3 time points: time of assessment for transplant, last test prior to transplant and one-month post-transplant. Other variables included: age, sex, primary diagnosis, date of transplantation, body mass index (BMI), total hospital length of stay (LOS), intensive care unit (ICU) LOS and time on mechanical ventilation. Results The median LOS on the waiting list was 1.9 yrs. There was a mean decrease of 28±93.9m between the 6MWD at the time of assessment and the last 6MWD prior to transplantation (p Conclusion The majority of the patients (54.7%) were able to either increase or maintain their 6MWD by participating in a home-based pre-habilitation program while on the waiting list. These results are similar to what has been found for hospital-based programs in lung transplant candidates. *Financial support: Funded by the Canadian Society of Transplantation-Allied Health Group Research Grant (2017). Dr Massierer holds the Quebec Respiratory Health Network (RHN) Scholarship Supplement Program Award. Dr Janaudis-Ferreira holds FRQS Junior 1 career award.

Anne-Catherine Maynard-Paquette,1 Claude Poirier,2 Carl Chartrand-Lefebvre,3,4 Bruno-Pierre Dubé2,5 1Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Quebec, Canada; 2Centre Hospitalier de l’Université de Montréal (CHUM), Department of Medicine, Respiratory Medicine Division, Montreal, Quebec, Canada; 3Centre Hospitalier de l’Université de Montréal (CHUM), Department of Radiology, Montréal, Québec, Canada; 4Research Center of the CHUM (CRCHUM) – Imaging and Engineering Axis, Montreal, Quebec, Canada; 5Research Center of the CHUM (CRCHUM) - Health Innovation and Evaluation Hub, Montreal, Quebec, CanadaCorrespondence: Bruno-Pierre DubéCentre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), 850 Rue St-Denis, Montréal, Qc H2X0A9, CanadaTel +1 514 890-8000Email bruno-pierre.dube@umontreal.caRationale: Chronic obstructive pulmonary disease (COPD) is associated with changes in the composition and function of peripheral and respiratory muscles, which can negatively impact quality of life. Ultrasonography can provide a non-invasive evaluation of the integrity of both peripheral muscles and diaphragm, but its use in patients with COPD is still being investigated. We aimed at evaluating the relationship between quadriceps size, using ultrasonography and symptoms, lung function and diaphragm contractility in a cohort of patients with COPD.Methods: COPD patients were prospectively recruited and ultrasonography of the dominant quadriceps and of the diaphragm was performed. Quadriceps size was evaluated using three measurements: 1) cross-sectional area of the rectus femoris (Qcsa), 2) thickness (Qthick) and 3) contractile index (Qci), defined as the ratio of quadriceps thickness/total anterior thigh thickness. Diaphragm contractility was evaluated using thickening fraction (TFdi). Clinical characteristics and number of moderate-to-severe exacerbations in the previous year were retrieved from medical files. Dyspnea (mMRC scale) and disease impact on health status (COPD Assessment Test (CAT)) were measured at inclusion. Fat-free mass index (FFMI) was assessed using bioelectrical impedance.Results: Forty patients were recruited (20 males, mean age and FEV1 66±6 years and 49±17%predicted, respectively). Mean Qcsa, Qthick and Qci were 336±145 mm2, 1.55±0.53 cm and 64±16%, respectively, and mean TFdi was 91±36%. Qci was significantly correlated with FFMI (rho=0.59, p=0.001), TFdi (rho=0.41, p=0.008), FEV1 (rho=0.43, p=0.001) but not with age (rho=0.18, p=0.28). Qci was significantly correlated to CAT score (rho=−0.47, p=0.002), even when controlled for FEV1, and was lower in patients with an mMRC score ≥2 (55±15 vs 70±14%, p=0.002). Qcsa and Qci were significantly lower in patients with frequent exacerbations. In a multiple linear regression analysis that included age, gender, FFMI, FEV1 and TFdi, only FFMI and TFdi were found to be significantly related to lower Qci values.Conclusion: In patients with COPD, ultrasound evaluation of the quadriceps contractile index is feasible and related to disease severity, clinical symptoms, exacerbation history and diaphragm contractility. As such, it may provide a novel tool for the evaluation of the severity and burden of the disease in this population. Further studies are required to better delineate its potential role as a prognostic marker in this population.Keywords: COPD, ultrasound, quadriceps, diaphragm, contractile index

Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody that has been shown to safely reduce exacerbations and improve lung function for patients with asthma. We assessed the long-term safety and efficacy of benralizumab for patients with severe, uncontrolled eosinophilic asthma.We conducted a randomised, double-blind, parallel-group, phase 3 extension study at 447 sites in 24 countries. Eligible patients had to have completed the SIROCCO or CALIMA trials and remained on subcutaneous benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W). Patients who had received placebo in those trials were re-randomised in a 1:1 ratio, using an interactive web-based system, to benralizumab 30 mg either Q4W or Q8W (first three doses 4 weeks apart). Treatment lasted for 56 weeks for adult patients (age ≥18 years) and 108 weeks for adolescent patients (age 12-17 years). The primary endpoint was the safety and tolerability of the two dosing regimens of benralizumab up to 68 weeks for adult patients (including the follow-up visit post-treatment) and up to 56 weeks for adolescent patients. This endpoint was assessed in the full analysis set, which included all patients from the SIROCCO and CALIMA predecessor studies who received at least one dose of study treatment in BORA and did not continue into another trial. This study is registered with ClinicalTrials.gov (NCT02258542).Between Nov 19, 2014, and July 6, 2016, we enrolled 1926 patients, of whom 633 had received benralizumab Q4W and 639 had received benralizumab Q8W in SIROCCO or CALIMA. The remaining 654 patients had received placebo in those trials and were randomly re-assigned in this trial to receive benralizumab Q4W (n=320) or Q8W (n=334). 1576 patients, including 783 who received benralizumab Q4W (265 newly assigned) and 793 who received benralizumab Q8W (281 newly assigned), were included in the full analysis set. The most common adverse events in all groups were viral upper respiratory tract infection (14-16%) and worsening asthma (7-10%). The most common serious adverse events were worsening asthma (3-4%), pneumonia (1% to 1%), and pneumonia caused by bacterial infection (0-1%). The percentages of patients who had any on-treatment adverse event, any serious adverse event, or any adverse event leading to treatment discontinuation during BORA were similar between patients originally assigned benralizumab and those originally assigned placebo and between benralizumab treatment regimens. The percentage of patients who had any adverse event was similar between SIROCCO or CALIMA (71-75%; benralizumab group only) and BORA (65-71%), as was the percentage of patients who had an adverse event that led to treatment discontinuation (2% in SIROCCO and CALIMA vs 2-3% in BORA).The 2 years of safety results validate that observations observed in the first year of benralizumab continued through a second year of treatment. No new consequences of long-term eosinophil depletion occurred, and the incidence of other adverse events, including opportunistic infections, were similar during the second year.AstraZeneca and Kyowa Hakko Kirin.

BackgroundThe long-term efficacy and safety of mepolizumab for treatment of severe eosinophilic asthma are well established. Here, we examine the clinical impact of stopping mepolizumab after long-term use.MethodsCOMET (NCT02555371) was a randomised, double-blind, placebo-controlled, parallel-group, multicentre study. Patients who had completed COLUMBA (NCT01691859) or COSMEX (NCT02135692) and received continuous mepolizumab treatment for ≥3 years were randomised 1:1 to stop (switch to placebo) or continue subcutaneous mepolizumab 100 mg every 4 weeks for 52 weeks. Primary end-point: time to first clinically significant exacerbation; secondary end-points: time to first exacerbation requiring hospitalisation/emergency department visit, time to decrease in asthma control (≥0.5-point increase in Asthma Control Questionnaire-5 score from COMET baseline) and blood eosinophil count ratio to COMET baseline. Safety was assessed.ResultsPatients stopping (n=151) versus continuing (n=144) mepolizumab had significantly shorter times to first clinically significant exacerbation (hazard ratio 1.61, 95% CI 1.17–2.22; p=0.004) and decrease in asthma control (hazard ratio 1.52, 95% CI 1.13–2.02; p=0.005), and higher blood eosinophil counts at week 52 (270 versus 40 cells·µL−1; ratio (stopping versus continuing) 6.19, 95% CI 4.89–7.83; pConclusionPatients who stopped mepolizumab had an increase in exacerbations and reduced asthma control versus those who continued.

Introduction L’efficacite et la tolerance du mepolizumab dans ASE etant bien etablies, COMET a examine les resultats apres la poursuite ou l’arret du mepolizumab a long terme. Methodes COMET etait une etude multicentrique, randomisee, en double aveugle, controle par placebo. Les patients eligibles avaient complete COLUMBA/COSMEX, recu un traitement continu par mepolizumab pendant au moins 3 ans. Les patients ont ete randomises 1 :1 pour continuer mepolizumab 100 mg par voie SC toutes les 4 semaines pendant 52 semaines ou pour arreter mepolizumab. Les patients pouvaient revenir au traitement par mepolizumab en ouvert a la suite d’une exacerbation. Le critere primaire etait la duree jusqu’a la premiere exacerbation cliniquement significative. Les criteres secondaires etaient : la duree jusqu’a la diminution du controle de l’asthme ; la reduction de taux d’eosinophiles sanguins. Les criteres ont ete analyses en utilisant le modele des risques proportionnels de Cox et des modeles repetes de modele mixte ajustes pour les covariables. Resultats Cent quarante-quatre patients ont recu mepolizumab et 151 placebo. Quarante-six pour cent (66/144) patients ayant continue mepolizumab versus 59 % (89/151) patients ayant arrete mepolizumab ont eu une exacerbation. Les patients ayant continue versus ceux ayant arrete mepolizumab ont eu une duree plus longue jusqu’a la premiere exacerbation (HR : 0,62 [(IC)95 % : 0,45 ; 0,86] ; p = 0,004) et une duree significativement plus longue jusqu’a la diminution du controle de l’asthme (HR : 0,66 [0,49 ; 0,88] ; p =0,005), sans difference entre les traitements pour la duree jusqu’a la premiere exacerbation necessitant une venue aux urgences ou une consultation (HR : 1,33 [0,50 ; 3,51]). Les patients continuant mepolizumab ont maintenu leur taux d’eosinophiles entre 40 et 60 cellules/μL, les taux d’eosinophiles ont augmente jusqu’a 270 cellules/μL a la semaine 12 pour les patients ayant arrete mepolizumab (ratio : 0,19 [0,15 ; 0,24] ; p Conclusion Les patients ayant arrete mepolizumab ont presente une augmentation du taux d’eosinophiles sanguins, une augmentation des exacerbations, une duree plus courte jusqu’a la premiere exacerbation, et une reduction du controle de l’asthme compare a ceux ayant continue mepolizumab. Ces resultats montrent que le traitement continu par mepolizumab a des benefices cliniques durables chez la plupart des patients avec ASE.

Introduction In methacholine challenge testing (MCT), skipping a methacholine dose is suggested if FEV1 falls by 1 nebulized salbutamol dose (2.5 mg) to reach basal FEV1, palpitations; severe: hypoxemia and/or need for medical attention or intervention] were compared in the skip5–10% group and others. Regression analysis was used to identify predictors of AE. Results 208 MCTs were analysed (135 males, age 52 ± 15 years). Skip5–10% occurred 111 times in 90 tests. Prevalence of AE was 5% and all were mild. Patients who developed AEs had lower FEV1, FVC and FEV1/FVC ratio, and higher lung volume values (all p

The company owner or manager must be the driver of the implementation of a culture on prevention in order to develop sustainable work and a sense of well-being at work among their employees. But, most employers in the construction industry are small or medium size employers (SMEs). They have limited resources, including safety and health expertise. They also typically are the highest risk employers. How can we assist them in improving their safety and health performance? Vision Zero is very practical approach to improving safety, by focusing only on the seven Golden Rules. In France, we have developed an online platform that employers can use to self-assess their safety performance. It is known as DIAGNEO, and is compatible with Vision Zero . DIAGNEO was developed with minimal resources and has been validated by safety and health experts in collaboration with employers in the construction industry and is currently available to over 2 00 000 construction employers in the Paris region, free of charge. It is easy to use, and does not take a lot of time to complete. After answers to several questionnaires, a profile of probable safety and health performance appears immediately in the form of graphics, which allows the employer to easily understand its deficiencies and where its priorities on regulatory, organisational and technical actions need to be placed. The examination of specific risks to the workplace and exposures is a prerequisite for the prevention of occupational risks. DIAGNEO makes it feasible to do so for even very small and resource-poor employers. There is no longer any excuse for employers not to undertake a self-assessment on Safety and Health at Work.

Purpose Ischemia reperfusion (I/R) is a major cause of primary graft dysfunction (PGD) after lung transplantation. I/R and PGD feature endothelial/alveolar epithelial damage, lung edema and inflammation. Edema resorption depends on the restoration of alveolar integrity and its ability to reabsorb Na+ (ENaC) and fluid. We hypothesized that alveolar epithelial damage and repair are critical in PGD pathophysiology and resolution. Our aim is to identify novel markers and therapeutic targets associated with I/R using cellular and animal models as well as human samples from lung transplants. Methods Mimicking I/R protocol was used to evaluate alveolar epithelial barrier integrity and capacity of wound healing in primary cultures of rat's alveolar epithelial cells. These cell cultures were then treated with an activator of K+ channel (KvLQT1). In a porcine model of ischemia/ex-vivo reperfusion, an inflammatory stress was induced by i.v. infusion with LPS. Finally, samples were collected from 38 lung transplant patients. Results In primary cell cultures, we showed altered ENaC and tight junction protein (ZO-1) expression after injury. A decline in transepithelial resistance (TER) and altered alveolar wound repair rates were also observed following the mimicking I/R protocol. Treatment with K+ channel activator (R-L3) showed enhanced repair rates, barrier integrity (higher TER, ZO-1 staining) and ENaC expression. In our porcine model, lung damage and edema was observed as well as exacerbated inflammatory response and decreased ENaC expression. Preliminary data from lung transplant samples indicated an inflammatory response and decreased ENaC and ZO-1 expression in patients with PGD. Conclusion Our data support the hypothesis of alveolar epithelial dysfunction after I/R injury. We will now investigate a potential correlation between levels of inflammatory molecules and epithelial damage markers in bronchoalveolar lavages and blood samples (at different time-points) from lung transplants with various PGD scores.

Background: Pursed lip breathing (PLB) improves exercise capacity and dyspnea in patients with COPD. It has been hypothesized that PLB could be effective in patients with interstitial lung disease (ILD) by improving exertional tachypnea and respiratory control, but this has never been studied. This randomized trial aimed at evaluating the impact of PLB on dyspnea and walking distance in ILD patients. Methods: Patients with ILD and total lung capacity Results: 35 patients were included. Mean forced vital capacity was 64±10%predicted. PLB resulted in lower mean respiratory rate and higher tidal volumes (24±8 vs 31±8 br/min and 1.6±0.6 vs 1.2±0.3 liters, both p 0.05), but PLB resulted in higher oxygen uptake (all p Conclusion: In patients with ILD, PLB did not improve exertional dyspnea, walking distance or gas exchange, and was associated with higher metabolic demands than usual breathing. These findings cast doubt on the usefulness of PLB in patients with ILD.

Introduction: The constant workrate test (CWRT) can be used to estimate improvement after pulmonary rehabilitation (PR) in patients with COPD. The initial endurance time (Tlim) should be within 180 and 480 seconds, but the consequences of a Tlim outside this range on the prognostic value of the CWRT have not been studied. We aimed at evaluating the effect of the initial Tlim on the predictive value of the CWRT. Methods: We studied COPD patients that had completed an 8-week PR program in our centre in 2014. All patients performed a pre- and post-PR CWRT on ergocycle at 80% of the maximal workrate reached on a previous incremental exercise test. Physiological characteristics and changes in COPD Assessment Test scores (ΔCAT) and endurance time (ΔTlim) after PR were compared in patients with an initial Tlim in the recommended range and those that did not. Results: 92 patients were included (52 males). Mean forced expiratory volume in 1 second (FEV1) was 50±16 percent predicted. 28 patients (30%) had initial Tlim outside the recommended range. Age, sex, FEV1, diffusion capacity, ΔCAT, ΔTlim and exacerbation rates pre- and post-RP were similar between the two groups (all p>0.05). However, there was a significant correlation between ΔTlim and ΔCAT in patients that had an initial Tlim in the recommended range (r=-0.44, p=0.01), but not in those that did not (r=0.27, p=0.20). Conclusion: Tlim values outside of the recommended range are frequent, and impair the ability of the CWRT to predict improvement in disease activity / quality of life following PR. This strengthens the recommendation of aiming at an initial Tlim value of 180-480 seconds.

PURPOSE The aim of this study was to explore the potential and safety of a stair-climbing test as a tool to monitor improvement following pulmonary rehabilitation (PR) in patients with chronic obstructive pulmonary disease (COPD). METHODS Stair-climbing capacity was assessed in 139 patients with COPD before and after a comprehensive 8-week PR program, which included stair-climbing training. Stair-climbing capacity was assessed as the total number of flights of stairs climbed without stopping. A constant work rate endurance test (CET) was also performed before and after PR. Change in stair-climbing after PR (Δstairs) was compared and correlated to the change in endurance time (ΔCET) and, for 40 patients, to the change in COPD assessment test (ΔCAT) score. RESULTS Most patients had moderate to severe COPD (mean forced expiratory volume in 1 second = 54% ± 20% predicted). Stair-climbing capacity, endurance time, and CAT score improved after PR (2.8 ± 1.4 vs 8.3 ± 3.3 flights, 408 ± 272 vs 717 ± 415 seconds, and 20.0 ± 6.4 vs 17.6 ± 6.6 units, respectively; P value for all < .001). Δstairs was moderately correlated to ΔCET (r = 0.49; P < .001) and well correlated to ΔCAT (r = -0.71; P < .001). Patients with greater change in Δstairs had better baseline resting lung function and aerobic capacity. No adverse events were reported during stair-climbing. CONCLUSION Stair-climbing is responsive to training in patients with COPD and is correlated to the change in CAT score following PR. Although the test requires further standardization, it could eventually be used as a simple and safe way to assess improvement following interventions in COPD.

Chronic obstructive pulmonary disease (COPD) affects quality of life (QOL). Patients are encouraged to participate in a respiratory rehabilitation program to improve their exercise tolerance and QOL. Stair training is an essential part of the rehabilitation program, mainly because it also represents patient9s daily activities. In 2008, Brunelli & al showed that performance in the maximal stair test in COPD patients was associated with decreased mortality and morbidity in the days following surgery. The goal of this study was to describe the cardio-respiratory adaptation during the stair test (ST) in COPD patients. In this study, we recruted 10 severe COPD patients with a FEV1 less than 50%. Patients were recruited from the rehabilitation program at the Centre hospitalier de l9Universite de Montreal. Breath-by-breath measurements were done using Cosmed K4B2 portable gas analysis system and the climbing was stopped at patient exhaustion. The ST was compared with a traditional incremental cardio-pulmonary exercise test (CPET) done on a bicycle. Patients stopped stair climbing because of leg fatigue (2/10) or dyspnea (8/10). Peak VO2 measured during ST was significantly greater than during CPET done on bicycle (16,7 mL/kg/min versus 12,0 mL/kg/min, p=0,007). Peak ventilation was also higher during ST than during CPET (39,5 Lmin versus 31,1 L/min, P=0,02). No significant differences were observed for peak heart rate or oxygen saturation. No complications were reported. This study showed that ST is a safe test and requires limited equipment. Higher peak VO2, together with higher peak ventilation, suggests that ST is truly a maximal test that could address different muscle groups. The relation between ST and QOL remains to be explored.

Introduction: Pulmonary rehabilitation (PR) plays an important part on the quality of life of chronic obstructive pulmonary disease (COPD) patients. The COPD Assessment Test (CAT) questionnaire is validated to respond positively on quality of life after PR. The goal of the study is to explore on which domain (question) of the CAT questionnaire will PR have an significant impact. Methods: CAT questionnaire has been administered to 72 patients (41 women aged 68 +/- 6 yrs ; 31 men aged 60 yrs +/- 8 yrs) with COPD (FEV1 predicted average 54.93% +/- 16.92%) who completed a 8 week PR program. The components of the CAT questionnaire were analysed pre and post PR. Results: The mean CAT score before PR was 18.65 points, with a clinically significant change of – 3.07 points after PR. Significant changes were found for question 4 (P Conclusion: Results confirmed the hypothesis of a significant improvement on CAT questions 4, 5, 6, and 8 after PR. These domains are partly related to daily activities and exercise tolerance. This study confirms the positive impact of PR on patient9s confidence with physical activity and anxiety. Long term modifications of these scores would be of interest.

Since its creation in 1950, UNHCR has engaged with faith-based organisations, faith communities and faith leaders in carrying out its work. Recently, UNHCR has been more actively exploring the role of faith in humanitarian responses.