Legionnaires Disease in Solid Organ Transplant Recipients: A Decade-Long Nationwide Study in France.

BACKGROUND: Legionnaires disease (LD) is a rare, life-threatening opportunistic bacterial infection that poses a significant risk to patients with impaired cell-mediated immunity such as solid organ transplant recipients. However, the epidemiologic features, clinical presentation, and outcomes of LD in this population are poorly described. RESEARCH QUESTION: What are the clinical manifestations, radiologic presentation, risk factors for severity, treatment, and outcome of LD in solid organ transplant recipients? STUDY DESIGN AND METHODS: In this 10-year multicenter retrospective cohort study in France, where LD notification is mandatory, patients were identified by hospital discharge databases. Diagnosis of LD relied on positive culture findings from any respiratory sample, positive urinary antigen test (UAT) results, positive specific serologic findings, or a combination thereof. Severe LD was defined as admission to the ICU. RESULTS: One hundred one patients from 51 transplantation centers were eligible; 64 patients (63.4%) were kidney transplant recipients. Median time between transplantation and LD was 5.6 years (interquartile range, 1.5-12 years). UAT results were positive in 92% of patients (89/97). Among 31 patients with positive culture findings in respiratory samples, Legionella pneumophila serogroup 1 was identified in 90%. Chest CT imaging showed alveolar consolidation in 98% of patients (54 of 57), ground-glass opacity in 63% of patients (36 of 57), macronodules in 21% of patients (12 of 57), and cavitation in 8.8% of patients (5 of 57). Fifty-seven patients (56%) were hospitalized in the ICU. In multivariate analysis, severe LD was associated with negative UAT findings at presentation (P = .047), lymphopenia (P = .014), respiratory symptoms (P = .010), and pleural effusion (P = .039). The 30-day and 12-month mortality rates were 8% (8 of 101) and 20% (19 of 97), respectively. In multivariate analysis, diabetes mellitus was the only factor associated with 12-month mortality (hazard ratio, 3.2; 95% OR, 1.19-8.64; P = .022). INTERPRETATION: LD is a late and severe complication occurring in solid organ transplant recipients that may present as pulmonary nodules on which diabetes impacts its long-term prognosis.

Improvement in severe asthma patients receiving biologics and factors associated with persistent insufficient control: a real-life national study.

BACKGROUND: Biological therapies have revolutionized the treatment of severe asthma with type 2 inflammation. Although such treatments are very effective in reducing exacerbation and the dose of oral steroids, little is known about the persistence of symptoms in severe asthma patients treated with biologics. PURPOSE: We aim to describe asthma control and healthcare consumption of severe asthma patients treated with biologics. DESIGN: The Second Souffle study is a real-life prospective observational study endorsed by the Clinical Research Initiative in Severe Asthma: a Lever for Innovation & Science Network. METHODS: Adults with a confirmed diagnosis of severe asthma for at least 12 months' duration were enrolled in the study. A self-administered questionnaire including the Asthma Control Questionnaire (ACQ), Asthma Quality of Life Questionnaire (AQLQ) and a compliance evaluation test was given to the patients. Healthcare consumption within 12 months prior to enrolment was documented. In patients receiving biologics, doctors indicated whether the patients were biologic responders or non-responders. RESULTS: The characteristics of 431 patients with severe asthma were analysed. Among them, 409 patients (94.9%) presented asthma with type 2 inflammation (T2 high) profile, and 297 (72.6%) patients with a T2 high phenotype were treated with a biologic. Physicians estimated that 88.2% of patients receiving biologics were responders. However, asthma control was only achieved in 25.3% of those patients (ACQ > 0.75). A high proportion of patients (77.8%) identified as responders to biologics were not controlled according to the ACQ score. About 50% of patients continue to use oral corticosteroids either daily (25.2%) or more than three times a year for at least three consecutive days (25.6%). Gastro-oesophageal Reflux Disease (GERD) and Obstructive Sleep Apnoea syndrome (OSA) were identified as independent factors associated with uncontrolled asthma. CONCLUSION: Although a high proportion of severe asthma patients respond to biologics, only 25.3% have controlled asthma. GERD and OSA are independent factors of uncontrolled asthma.

Extracorporeal Artificial Lungs: Co-Creating Future Technology - A Qualitative Analysis.

Background: Terminal lung diseases such as chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) in progression cause a large reduction in quality of life and may lead to bilateral lung transplantation (bLTx). An artificial portable lung could provide a bridge to lung transplantation, allowing patients to remain at home and mobile for longer. To advance the development of such an artificial lung, patient feedback is essential. The aim of this study is to analyze patient acceptance about an extracorporeal artificial lung and to implement these findings into the development. Methods: In collaboration with a medical device developer, we presented a portable dummy oxygenator to patients with advanced lung disease, as potential end users. Data collection in Germany and France was based on two different methods: an online questionnaire and face-to-face interviews (F2F). Results: A total of 604 participants answered the online questionnaire and 17 participants were included in the F2F interviews. The majority of participants (COPD n=140, PH n=17) were able to walk more than 1 km with a mean suffering pressure of 2.87 and 3, respectively. Six of the 17 F2F participants who could walk <1 km were interested in an assistive device. The statistical value of Fisher's exact test for suffering pressure and desire for a portable oxygenator was 0.45. Conclusion: In patients with advanced lung disease, there is no statistically significant association between subjectively increased suffering pressure and desire for a portable oxygenator, so market introduction may be difficult. Potential end users should be implemented early in device development. Data collection via an online questionnaire combined with personal interviews has proven to be a successful approach here.

Systems prediction of chronic lung allograft dysfunction: Results and perspectives from the Cohort of Lung Transplantation and Systems prediction of Chronic Lung Allograft Dysfunction cohorts.

Background: Chronic lung allograft dysfunction (CLAD) is the leading cause of poor long-term survival after lung transplantation (LT). Systems prediction of Chronic Lung Allograft Dysfunction (SysCLAD) aimed to predict CLAD. Methods: To predict CLAD, we investigated the clinicome of patients with LT; the exposome through assessment of airway microbiota in bronchoalveolar lavage cells and air pollution studies; the immunome with works on activation of dendritic cells, the role of T cells to promote the secretion of matrix metalloproteinase-9, and subpopulations of T and B cells; genome polymorphisms; blood transcriptome; plasma proteome studies and assessment of MSK1 expression. Results: Clinicome: the best multivariate logistic regression analysis model for early-onset CLAD in 422 LT eligible patients generated a ROC curve with an area under the curve of 0.77. Exposome: chronic exposure to air pollutants appears deleterious on lung function levels in LT recipients (LTRs), might be modified by macrolides, and increases mortality. Our findings established a link between the lung microbial ecosystem, human lung function, and clinical stability post-transplant. Immunome: a decreased expression of CLEC1A in human lung transplants is predictive of the development of chronic rejection and associated with a higher level of interleukin 17A; Immune cells support airway remodeling through the production of plasma MMP-9 levels, a potential predictive biomarker of CLAD. Blood CD9-expressing B cells appear to favor the maintenance of long-term stable graft function and are a potential new predictive biomarker of BOS-free survival. An early increase of blood CD4 + CD57 + ILT2+ T cells after LT may be associated with CLAD onset. Genome: Donor Club cell secretory protein G38A polymorphism is associated with a decreased risk of severe primary graft dysfunction after LT. Transcriptome: blood POU class 2 associating factor 1, T-cell leukemia/lymphoma domain, and B cell lymphocytes, were validated as predictive biomarkers of CLAD phenotypes more than 6 months before diagnosis. Proteome: blood A2MG is an independent predictor of CLAD, and MSK1 kinase overexpression is either a marker or a potential therapeutic target in CLAD. Conclusion: Systems prediction of Chronic Lung Allograft Dysfunction generated multiple fingerprints that enabled the development of predictors of CLAD. These results open the way to the integration of these fingerprints into a predictive handprint.

Routine Rehabilitation as a Treatment Component for Patients With Pulmonary Arterial or Chronic Thromboembolic Pulmonary Hypertensions.

PURPOSE: Patients with pulmonary hypertension (PH) have long been advised to avoid exercise in fear of deterioration in right-sided heart function. Since the 2009 European Society of Cardiology guidelines, rehabilitation in expert centers is considered to have a specific role in care of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). We report routine rehabilitation effects in patients with PH as a component of real-life multimodal treatment. METHODS: Patients with PAH or CTEPH were recommended for either in- or outpatient rehabilitation in addition to their usual care, unless there were practical problems or the patient declined. Assessment was conducted according to New York Heart Association classes, adverse events, 6 min-walk test, hemodynamics, and risk stratification after rehabilitation. RESULTS: Forty-one patients, 61% female, age 60 ±18 yr were included between March 2010 and May 2019. No major adverse events or deaths related to progression of right-sided heart failure were reported. Nevertheless, 22% of participants suffered adverse events in most cases not linked with physical activity. Rehabilitation as add-on to medical therapy and/or arterial deobstruction improved New York Heart Association class: mean difference, -0.39 (95% CI, -0.68 to -0.10), 6-min walk test: mean difference, 80 m (95% CI, 46-114), and was associated with improved right-sided heart hemodynamics. The risk assessment grade improved by -0.25 points (95% CI, -0.44 to -0.06) after rehabilitation. CONCLUSIONS: For patients with PAH or CTEPH, supervised rehabilitation as add-on to medical therapy and/or arterial deobstruction is safe and effective in improving patient and clinically related outcomes.

2022 Update of indications and contraindications for lung transplantation in France.

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.

Computed tomographic airway morphology after targeted lung denervation treatment in COPD.

This post-hoc analysis of the AIRFLOW-2 trial investigated the changes in airway CT-parameters after targeted lung denervation (TLD) and whether these changes are associated with treatment response. In the treatment group (n = 32), an improvement in air trapping was significantly associated with an improvement in residual volume (RV). Furthermore, improvements in Pi10 and airway lumen were significantly associated with an improvement in both RV and FEV1. Our results could suggest that when improving airway characteristics like decreasing airway wall thickness and increasing the airway lumen, this leads to less air trapping and an improvement in clinical outcomes.

Crossover Patient Outcomes for Targeted Lung Denervation in Moderate to Severe Chronic Obstructive Pulmonary Disease: AIRFLOW-2.

BACKGROUND: Targeted Lung Denervation (TLD) is a potential new therapy for COPD. Radiofrequency energy is bronchoscopically delivered to the airways to disrupt pulmonary parasympathetic nerves, to reduce bronchoconstriction, mucus hypersecretion, and bronchial hyperreactivity. OBJECTIVES: This work assesses the effect of TLD on COPD exacerbations (AECOPD) in crossover subjects in the AIRFLOW-2 trial. METHOD: The AIRFLOW-2 trial is a multicentre, randomized, double-blind, sham-controlled crossover trial of TLD in COPD. Patients with symptomatic COPD on optimal medical therapy with an FEV1 of 30-60% predicted received either TLD or sham bronchoscopy in a 1:1 randomization. Those in the sham arm had the opportunity to cross into the treatment arm after 12 months. The primary end point was rate of respiratory adverse events. Secondary end points included adverse events, changes in lung function and health-related quality of life and symptom scores. RESULTS: Twenty patients were treated with TLD in the crossover phase and were subsequently followed up for 12 months (50% female, mean age 64.1 ± 6.9 years). After TLD, there was a trend towards a reduction in time to first AECOPD (hazard ratio 0.65, p = 0.28, not statistically significant) in comparison to sham follow-up period. There was also a reduction in time to first severe AECOPD in the crossover period (hazard ratio 0.38, p = 0.227, not statistically significant). Symptom scores and lung function showed stability. CONCLUSIONS: AIRFLOW-2 crossover data support that of the randomization phase, showing trends towards reduction in COPD exacerbations with TLD.

Differences in severe exacerbations rates and healthcare utilisation in COPD populations in the UK and France.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality in Europe; however, it is important to understand how clinical practice patterns differ between countries and how this might relate to disease outcomes, to identify ways of improving local disease management. We aimed to describe and compare the management of patients with COPD in the UK and France between 2008 and 2017. METHODS: We used data from the Clinical Practice Research Datalink GOLD and Hospital Episode Statistics in the UK and the Echantillon Généraliste des Bénéficiaire in France to identify patients with COPD each year between 2008 and 2017. We compared patient characteristics, all-cause mortality and COPD exacerbations each year between 2008 and 2017 for patients in the UK and France separately. Health care utilisation and COPD exacerbations in 2017 were compared between France and the UK using t-tests and χ2 tests. RESULTS: Patients with COPD were similar in gender and comorbidities in both countries. Incidence of COPD exacerbations remained stable in the UK and France between 2007 and 2017. In 2017, the proportion of all-cause and COPD-related hospitalisations was greater in the UK than in France (43.9% vs 32.8% and 8.3% vs 4.9%, respectively; p<0.001) as was the proportion of patients visiting accident and emergency (A&E) (39.8% vs 16.2%, respectively; p<0.001). In addition, the mean length of stay in hospital for COPD-related causes was shorter in the UK than in France (6.2 days (SD 8.4) vs 10.5 days (SD 9.1), respectively; p<0.001). DISCUSSION: Overall, UK patients were more likely to go to A&E, be hospitalised for COPD-related causes and stay in hospital for fewer days after being admitted for COPD-related reasons compared with patients in France, illustrating a difference in health-seeking behaviours and access to healthcare.

Information and Communication Technologies in Lung Transplantation: Perception of Patients and Medical Teams.

Optimal therapeutic management is a major determinant of patient prognosis and healthcare costs. Information and communication technologies (ICTs) represent an opportunity to enhance therapeutic management in complex chronic diseases, such as lung transplantation (LT). The objective of this study was to assess the preferences of LT patients and healthcare professionals regarding ICTs in LT therapeutic management. A cross-sectional opinion survey was conducted among lung transplant patients and healthcare professionals from the French lung transplantation centers. Five ICTs were defined (SMS, email, phone, internet, and smartphone application) in addition to face-to-face communication. An unsupervised approach by Principal Component Analysis (PCA) identified lung transplant patient profiles according to their preferences for ICTs. Fifty-three lung transplant patients and 15 healthcare professionals of the French LT centers were included. Both expected ICTs for treatment management and communication. Phone call, face-to-face, and emails were the most preferred communication tools for treatment changes and initiation. PCA identified four ICTs-related profiles ("no ICT", "email", "SMS", and "oral communication"). "Email" and "oral communication" profiles are mainly concerned with treatment changes and transmission of new prescriptions. The "SMS" profile expected reminders for healthcare appointments and optimizing therapeutic management. This study provides practical guidance to enhance LT therapeutic management by ICT intervention. The type of ICT used should take into account patient profiles to improve adherence and thereby the prognosis. A combination of strategies including information, education by a multidisciplinary team, and reminders is a promising approach to ensure an optimal management of our patients.

Assessing Adherence to Healthy Dietary Habits Through the Urinary Food Metabolome: Results From a European Two-Center Study.

Background: Diet is one of the most important modifiable lifestyle factors in human health and in chronic disease prevention. Thus, accurate dietary assessment is essential for reliably evaluating adherence to healthy habits. Objectives: The aim of this study was to identify urinary metabolites that could serve as robust biomarkers of diet quality, as assessed through the Alternative Healthy Eating Index (AHEI-2010). Design: We set up two-center samples of 160 healthy volunteers, aged between 25 and 50, living as a couple or family, with repeated urine sampling and dietary assessment at baseline, and 6 and 12 months over a year. Urine samples were subjected to large-scale metabolomics analysis for comprehensive quantitative characterization of the food-related metabolome. Then, lasso regularized regression analysis and limma univariate analysis were applied to identify those metabolites associated with the AHEI-2010, and to investigate the reproducibility of these associations over time. Results: Several polyphenol microbial metabolites were found to be positively associated with the AHEI-2010 score; urinary enterolactone glucuronide showed a reproducible association at the three study time points [false discovery rate (FDR): 0.016, 0.014, 0.016]. Furthermore, other associations were found between the AHEI-2010 and various metabolites related to the intake of coffee, red meat and fish, whereas other polyphenol phase II metabolites were associated with higher AHEI-2010 scores at one of the three time points investigated (FDR < 0.05 or ß ≠ 0). Conclusion: We have demonstrated that urinary metabolites, and particularly microbiota-derived metabolites, could serve as reliable indicators of adherence to healthy dietary habits. Clinical Trail Registration: www.ClinicalTrials.gov, Identifier: NCT03169088.

Successful Training of Patients to Intervene in Health Education and Clinical Research at Grenoble Patient School.

The primary goal of patient and public involvement (PPI) in healthcare is to improve individual and population health outcomes. This study reports on the successful training of patients to be involved in patient education as peers and clinical research at Grenoble Patients' School (GPS). GPS was founded by patients as an independent association to train patients to the above objectives tasks. The training team was multi-professional and included expert PPI who were part of the professional team. Medical faculty members and 45 patients, 59% females, 52 ± 6.4 years old, trained between 2016 and 2017, showed high satisfaction at the end of the training courses. Almost all the trained patients were involved as peer educators and 4 were involved in clinical research projects at different stages under the guidance of medical teams. Patient involvement at GPS provided strong benefits to trainees and had some impact on education and obtaining research grants. The outcome of this patient training program resulted in the creation of a Patients' Department within the Medical and Pharmacy Schools at the Université Grenoble Alpes in 2020, https://medecine.univ-grenoble-alpes.fr/departements/departement-universitaire-des-patients/.

Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

BACKGROUND: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission. METHODS: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters. RESULTS: Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference -0.6%, 95% CI -16.8- +15.6%; OR 0.98, 95% CI 0.50-1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168-476 days) versus 177 days (64-288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group. CONCLUSIONS: In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.

Determinants of survival after lung transplantation in telomerase-related gene mutation carriers: A retrospective cohort.

Carriers of germline telomerase-related gene (TRG) mutations can show poor prognosis, with an increase in common hematological complications after lung transplantation (LT) for pulmonary fibrosis. The aim of this study was to describe the outcomes after LT in recipients carrying a germline TRG mutation and to identify the predictors of survival. In a multicenter cohort of LT patients, we retrospectively reviewed those carrying pathogenic TRG variations (n = 38; TERT, n = 23, TERC, n = 9, RTEL1, n = 6) between 2009 and 2018. The median age at LT was 54 years (interquartile range [IQR] 46-59); 68% were male and 71% had idiopathic pulmonary fibrosis. During the diagnosis of pulmonary fibrosis, 28 (74%) had a hematological disease, including eight with myelodysplasia. After a median follow-up of 26 months (IQR 15-46), 38 patients received LT. The overall post-LT median survival was 3.75 years (IQR 1.8-NA). The risk of death after LT was increased for patients with myelodysplasia (HR 4.1 [95% CI 1.5-11.5]) or short telomere (HR 2.2 [1.0-5.0]) before LT. After LT, all patients had anemia, 66% had thrombocytopenia, and 39% had neutropenia. Chronic lung allograft dysfunction frequency was 29% at 4 years. The present findings support the use of LT in TRG mutation carriers without myelodysplasia. Hematological evaluation should be systematically performed before LT.

Exercise hyperventilation and pulmonary gas exchange in chronic thromboembolic pulmonary hypertension: Effects of balloon pulmonary angioplasty.

BACKGROUND: Excessive ventilation (V̇E) and abnormal gas exchange during exercise are features of chronic thromboembolic pulmonary hypertension (CTEPH). In selected CTEPH patients, balloon pulmonary angioplasty (BPA) improves symptoms and exercise capacity. How BPA affects exercise hyperventilation and gas exchange is poorly understood. METHODS: In this longitudinal observational study, symptom-limited cardiopulmonary exercise tests and carbon monoxide lung diffusion (DLCO) were performed before and after BPA (interval, mean (SD): 3.1 (2.4) months) in 36 CTEPH patients without significant cardiac and/or pulmonary comorbidities. RESULTS: Peak work rate improved by 20% after BPA whilst V̇E at peak did not change despite improved ventilatory efficiency (lower V̇E with respect to CO2 output [V̇CO2]). At the highest identical work rate pre- and post-BPA (75 (30) watts), V̇E and alveolar-arterial oxygen gradient (P(Ai-a)O2) decreased by 17% and 19% after BPA, respectively. The physiological dead space fraction of tidal volume (VD/VT), calculated from measurements of arterial and mixed expired CO2, decreased by 20%. In the meantime, DLCO did not change. The best correlates of P(Ai-a)O2 measured at peak exercise were physiological VD/VT before BPA and DLCO after BPA. CONCLUSIONS: Ventilatory efficiency, physiological VD/VT, and pulmonary gas exchange improved after BPA. The fact that DLCO did not change suggests that the pulmonary capillary blood volume and probably the true alveolar dead space were unaffected by BPA. The correlation between DLCO measured before BPA and P(Ai-a)O2 measured after BPA suggests that DLCO may provide an easily accessible marker to predict the response to BPA in terms of pulmonary gas exchange.

Peer-driven intervention to help patients resume CPAP therapy following discontinuation: a multicentre, randomised clinical trial with patient involvement.

INTRODUCTION: Obstructive sleep apnoea syndrome (OSAS) is one of the most common chronic diseases. It may be associated with symptoms of excessive daytime sleepiness and neurocognitive and cardiovascular complications. First line therapy for OSAS involves home continuous positive airway pressure (CPAP), however, nearly half of patients do not adhere with this treatment over the long term. Cognitive-behavioural interventions that include health professionals and patient and public involvement are increasingly advocated in the fields of education and research. We hypothesise that a peer-driven intervention could help patients with OSAS to resume CPAP use after discontinuation. METHODS AND ANALYSIS: We have designed a prospective, multicentre randomised, controlled trial that will be coconducted by health professionals, a home provider of CPAP and patients as experts or peers or participants. The primary aim is to evaluate the impact of a 6-month, peer-driven intervention to promote the resumption of CPAP after discontinuation. We anticipate that 20% of patients in the intervention group will reuse CPAP as compared with 6% in control group, thus, 104 patients must be included in each group. The secondary aims are (1) to evaluate the impact of the peer-driven intervention on adherence to CPAP compared with the control group (mean adherence and percentage of nights with at least 4 hours' use/night for 70% of nights); (2) to determine factors associated with resumption of CPAP; (3) to assess patient satisfaction with the peer-driven intervention at 6 months; (4) to evaluate the feasibility and the execution of the peer-driven intervention and peer satisfaction. Adult outpatients with an established diagnosis of severe OSA (Apnoea-Hypopnoea Index >30 events/hour) that have stopped using CPAP within 4-12 months after initiation will be recruited. The peers who will perform the intervention will be patients with OSAS treated with CPAP with good adherence (at least 4 hours/night, 70% of nights) and trained in motivational enhancement and cognitive-behavioural therapies. Trained peers will conduct three interviews within 6 months with participants. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the French Regional Ethics Committee CPP Ouest II-Angers, (IRB 21.02.25.68606 (2021/2025)). All participants will sign written informed consent. The results will be presented at conferences and published in peer-reviewed journals as well as public media. TRIAL REGISTRATION NUMBER: NCT04538274.

Endobronchial Coil System versus Standard-of-Care Medical Management in the Treatment of Subjects with Severe Emphysema.

BACKGROUND: Bronchoscopic lung volume reduction using endobronchial coils is a new treatment for patients with severe emphysema. To date, the benefits have been modest and have been suggested to be much larger in patients with severe hyperinflation and nonmulti-comorbidity. OBJECTIVE: We aimed to evaluate the efficacy and safety of endobronchial coil treatment in a randomized multicenter clinical trial using optimized patient selection. METHOD: Patients with severe emphysema on HRCT scan with severe hyperinflation (residual volume [RV] ≥200% predicted and RV/total lung capacity [TLC] >55%) were randomized to coil treatment or control. Primary outcome measures were differences in the forced expiratory volume in 1 s (FEV1) and St George's Respiratory Questionnaire (SGRQ) total score at 6 months. RESULTS: Due to premature study termination, a total of 120 patients (age 63 ± 7 years, FEV1 29 ± 7% predicted, RV 251 ± 41% predicted, RV/TLC 67 ± 6%, and SGRQ 58 ± 13 points), instead of 210 patients, were randomized. At study termination, 91 patients (57 coil and 34 control) had 6-month results available. Analyses showed significantly greater improvements in favor of the coil group. The increase in FEV1 was greater in the coil group than that in the control group by + 10.3 [+4.7 to +16.0] % and in SGRQ by -10.6 [-15.9 to -5.4] points. At study termination, there were 5 (6.8%) deaths in the coil cohort reported. CONCLUSION: Despite early study termination, coil treatment compared to control results in a significant improvement in the lung function and quality of life benefits for up to 6 months in patients with emphysema and severe hyperinflation. These improvements were of clinical importance but were associated with a higher likelihood of serious adverse events.

The Role of Nutritional Factors in Asthma: Challenges and Opportunities for Epidemiological Research.

The prevalence of asthma has nearly doubled over the last decades. Twentieth century changes in environmental and lifestyle factors, including changes in dietary habits, physical activity and the obesity epidemic, have been suggested to play a role in the increase of asthma prevalence and uncontrolled asthma worldwide. A large body of evidence has suggested that obesity is a likely risk factor for asthma, but mechanisms are still unclear. Regarding diet and physical activity, the literature remains inconclusive. Although the investigation of nutritional factors as a whole (i.e., the "diet, physical activity and body composition" triad) is highly relevant in terms of understanding underlying mechanisms, as well as designing effective public health interventions, their combined effects across the life course has not received a lot of attention. In this review, we discuss the state of the art regarding the role of nutritional factors in asthma, for each window of exposure. We focus on the methodological and conceptual challenges encountered in the investigation of the complex time-dependent interrelations between nutritional factors and asthma and its control, and their interaction with other determinants of asthma. Lastly, we provide guidance on how to address these challenges, as well as suggestions for future research.

Associations between specific IgE sensitization to 26 respiratory allergen molecules and HLA class II alleles in the EGEA cohort.

BACKGROUND: Allergy, the most frequent immune disorder affecting 30% of the world's population, is the consequence of immunoglobin E (IgE) sensitization to allergens. Among the genetic factors suspected to be involved in allergy, the HLA class-II genomic region is a strong candidate. OBJECTIVE: To assess the association between HLA class-II alleles and specific IgE (sIgE) sensitization to a large number of respiratory allergen molecules. METHODS: The analysis relied on 927 participants of the EGEA cohort, including 497 asthmatics. The study focuses on 26 aeroallergens recognized by sIgE in at least 5% of the study population (determined with the MEDALL chip with sIgE ≥ 0.3 ISU) and 23 imputed HLA class-II alleles. For each sIgE sensitization and HLA class-II allele, we fitted a logistic regression model accounting for familial dependence and adjusted for gender, age, and genetic principal components. p-values were corrected for multiple comparisons (False Discovery Rate). RESULTS: Most of the 19 statistically significant associations observed regard pollen allergens (mugwort Art v 1, olive tree Ole e 1, timothy grass Phl p 2, Phl p 5 and plantain Pla l 1), three were mold allergen (Alternaria Alt a 1), and a single one regards house dust mite allergen (Der p 7). No association was observed with pet allergens. The strongest associations were found with mugwort Art v 1 (OR = 5.42 (95%CI, 3.30; 8.88), 4.14 (2.65; 6.47), 3.16 (1.88; 5.31) with DQB1*05:01, DQA1*01:01 and DRB1*01:01, respectively). CONCLUSION: Our results support the important role of HLA class-II alleles as immune response genes predisposing their carriers for sensitization to various major pollen allergens.