Comparison of anti-interleukin-5 therapies in patients with severe asthma: global and indirect meta-analyses of randomized placebo-controlled trials.

Inconsistent results have been reported regarding IL-5 blockade treatment in asthma. There were no direct between-treatment comparisons. Only differences between each drug and placebo were studied. We identified all RCTs with anti-IL5 treatments for patients with asthma over the 1990-September 2015 period. RCTs were searched on Medline, Cochrane and Embase. At least 50 patients were enrolled in each study. Outcomes considered were exacerbation rate reduction, FEV1 changes, ACQ-5 improvement, adverse events and serious adverse events. A global meta-analysis was first conducted followed by an indirect comparison of each IL-5-targeting drug: benralizumab, reslizumab and mepolizumab. Further eosinophilic subgroup analysis and sensitivity analysis were also conducted in case of heterogeneity. Ten trials involving 3421 patients were eligible for meta-analysis. IL-5 blockade significantly reduced annual exacerbation rates vs. placebo by 40% [29-50] (P < 0.01, I2 = 0.61). ACQ-5 was significantly improved vs. placebo but below the recognized MCID level (-0.31 [-0.41, -0.21], P < 0.01, I2 = 0.11). FEV1 changes from baseline were improved vs. placebo by 0.09 L [0.05-0.12] (P < 0.01, I2 = 0.28). The subgroup analysis identified a slight additional improvement in mean treatment effects in eosinophilic (> 300 mm3 /L) patients with severe asthma. Similar patterns and rates of adverse events and severe adverse events were reported with the three drugs. The data interpretations were not affected by the sensitivity analysis. IL-5 blockade appears to be a relevant treatment strategy to improve severe asthma management, particularly for eosinophilic patients. No clear superiority appeared between the drugs when appropriate doses were compared.

Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment.

BACKGROUND: We performed post hoc analyses to evaluate the effect of humanized monoclonal antibody mepolizumab in patients with severe eosinophilic asthma previously treated with omalizumab. METHODS: Data were collected from two randomized double-blind, placebo-controlled studies: MENSA (NCT01691521: 32-week treatment phase) and SIRIUS (NCT01691508: 24-week treatment phase). Active treatment was 75 mg intravenous mepolizumab (MENSA) or 100 mg subcutaneous mepolizumab (MENSA, SIRIUS). Patients had evidence of eosinophilic inflammation ≥150 cells/µl (at screening) or ≥300 cells/µl (during the previous year). Primary outcomes were the rate of exacerbations (MENSA) and the percentage reduction in oral corticosteroid (OCS) dose (SIRIUS). Other outcomes included lung function (forced expiratory volume in 1 s and morning peak expiratory flow), Asthma Control Questionnaire (ACQ-5), St George's Respiratory Questionnaire (SGRQ) scores, and safety. RESULTS: Overall, 576 patients were included from MENSA and 135 from SIRIUS, with 13% and 33% previously receiving omalizumab, respectively. In MENSA, mepolizumab reduced the rate of exacerbations by 57% (prior omalizumab) and 47% (no prior omalizumab) vs placebo. In SIRIUS, reductions in OCS use were comparable regardless of prior omalizumab use. Despite reducing chronic OCS use, mepolizumab also resulted in similar reductions in exacerbation rate relative to placebo in both subgroups. Asthma control and quality of life improved with mepolizumab vs placebo in both studies independent of prior omalizumab use, as shown by ACQ-5 and SGRQ scores. Adverse events were also comparable irrespective of prior omalizumab use. CONCLUSIONS: These post hoc analyses indicate that patients with severe eosinophilic asthma respond positively to mepolizumab regardless of prior use of omalizumab.

[Subcutaneous immunoglobulin and support program: what level of interest of patients?]. / Immunogtobulines sous-cutanées et programme d'accompagnement: quel est l'intérêt des patients?

Two different routes of administration exist for the immunoglobulin therapy: intravenous (Ig IV - monthly administration in medical setting) and subcutaneous (Ig SC - weekly self-administration at home). According to the literature, efficacy and safety are similar,. but Ig SC could improve quality of life and treatment satisfaction. The Policlinique Médicale Universitaire of Lausanne has developed an interdisciplinary program for the long-term support of Ig SC patients. Moreover, it conducted an exploratory survey interviewing Ig IV patients about their interest for Ig SC: patients interested judged less favourably efficacy and/or tolerance of Ig IV and considered that Ig SC would improve their motivation for treatment and its impact on their private and professional life.

Integrated care pathways for airway diseases (AIRWAYS-ICPs).

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

[Modeling T2 high severe asthma using human induced pluripotent stem cells (hiPSC)]. / Modélisation de l'asthme sévère par la technologie des cellules humaines souches pluripotentes induites (hiPSC).

Severe asthma patients with persistent airflow obstruction are characterized by functional obstruction due to mucus plugs containing mucins, fibrin, and eosinophil derived Charcot- Leyden crystals. The molecular mechanisms underlying this endotype are not clearly understood. Developing new models is crucial to respiratory research insofar as critical differences exist between human and rodent airway epithelium. We (and other teams) have shown that it is possible to reconstitute in vitro a complex and functional airway epithelium displaying all the features described in vivo from human-induced pluripotent stem cells (hiPSC). Our aim is to establish a human in vitro model of severe asthma that will recapitulate airway epithelium remodeling and mucus plugs.

Role of comorbid conditions in asthma hospitalizations in the south of France.

BACKGROUND: Reasons for asthma hospitalizations are dynamic and complex. Comorbid conditions are important contributors to most chronic diseases today. We aim to characterize and describe risk factors associated with hospitalizations due to asthma in the Languedoc-Roussillon region (France) in 2009. METHODS: Programme de Médicalisation des Systèmes d'Information (PMSI) data records from 2009 were sorted using selected International Classification of Diseases (ICD10) codes eliciting three groups of asthma hospitalizations according to acute severity. All available data including demographics, comorbid conditions, past hospitalizations either related or unrelated to asthma, seasonality and distance to medical facilities were used to compare the subjects within the three groups. RESULTS: One thousand two hundred and eighty-nine hospitalizations due to asthma exacerbation were found, concerning 1122 patients. We observed significant differences within the groups, using univariate analysis, concerning duration of hospitalizations (mean ± SD, 4.9 ± 5.9 days vs 6.4 ± 6.8 vs 15.8 ± 16.8, P < 0.001), deaths (percentage, 0.03% vs 1.50% vs 9.20%, P < 0.001) and numbers of comorbid conditions (0.80 ± 0.95 vs 0.75 ± 0.97 vs 1.74 ± 1.36, P < 0.001). Recurrent admissions for asthma during the period 2006-2008 were significantly more frequent in the more severe group (1.93 ± 3.91 vs 2.56 ± 4.47 vs 2.81 ± 3.97, P = 0.006). In the multivariate model, age and number of comorbid conditions were independently associated with severe hospitalizations and deaths. CONCLUSIONS: Asthma hospitalizations can be appropriately assessed using PMSI coding databases. In this study, age and the presence of comorbid conditions are the major risk factors for asthma hospitalizations and deaths.

Change in cardiorespiratory parameters following surgical correction of pectus excavatum: protocol for the historical-prospective HeartSoar cohort.

INTRODUCTION: How cardiorespiratory function changes following the surgical correction of pectus excavatum (PE) often gives mixed results, with meta-analyses demonstrating no benefit in terms of pulmonary function but improvement in cardiac function. Functional responses may depend on type of surgery, follow-up time and/or the patient's presurgical functional status, and debate persists on the purely aesthetic nature of such surgery. The aim of this protocol is to analyse data describing lung function and incremental exercise testing before vs after the surgical correction of PE. METHODS AND ANALYSIS: A historical-prospective before-after surgical correction of PE cohort will be constituted. Historical inclusions are recruited during follow-up visits at approximately 12, 24, 36 or 48 months following a prior surgery (with presurgical data mined from patient records). Prospective inclusions are recruited during presurgical work-ups and followed for 1 year following surgery. The data collected include spirometry, incremental exercise testing, body mass index, body composition, questionnaires targeting general health status, self-esteem and body image. Any complications due to surgery are also described.The primary outcome is oxygen pulse during incremental exercise testing, and 44 data points are required to demonstrate a moderate postsurgical change (ie, a Cohen's effect of d=0.5). Wilcoxon signed-rank tests or t-tests for paired data will be used for before-after comparisons (with false discovery rate corrections for secondary analyses). ETHICS AND DISSEMINATION: This study will be conducted according to the principles of the Declaration of Helsinki (as revised in 2013) and was approved by a randomly assigned, independent, ethics committee (Comité de Protection des Personnes Sud-Méditerranée II, reference number: 218 B21) as per French law on 6 July 2018. Informed, written consent for study participation is required of all study candidates prior to enrolment. Results will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03770390; Clinicaltrials.gov.

[Production of innervated bronchial epithelium from a blood sample]. / Fabrication d'un épithélium bronchique innervé à partir d'une prise de sang.

Asthma is a frequent respiratory disease, with severe asthma occurring in 3 to 5% of cases. Chronic inflammation of the bronchial epithelium is essential to its pathophysiology. When activated by the bronchial environment, the peripheral sensory nervous system contributes to inflammation of the airways. However, due to a lack of reliable models, the mechanisms of action remain largely unknown. Using induced pluripotent stem cells reprogrammed from blood cells, we have set up a model of bronchial epithelium innervated by sensory neurons. This model will ensure better understanding of the mechanisms of action underlying neurogenic inflammation.

Feasibility of a nasal breathing training during pulmonary rehabilitation. A pilot randomized controlled study.

Hyperventilation syndrome (HVS) is a common source of dyspnea and disability. While pulmonary rehabilitation (PR) including breathing exercises is indicated, randomized controlled trial are warranted to recommend one type of breathing exercise than another. We aimed to compare during PR, the effect of 5 sessions of nasal ventilation exercise (NV+PR) versus voluntary hypoventilation (vHV+PR) on exercise dyspnea (primary outcome) and capacity and health-related quality of life in patients. In this open label randomized controlled trial, 19 HVS patients (age=48.3 ± 15.2 y.o, female/male=18/1, Nijmegen score=33 ± 7.7) were randomized in a NV+PR (n = 9) or vHV+PR (n = 10) group. Modified Medical Research Council (mMRC) dyspnea, 6-minute walking distance (6MWD) with nasal/oral ventilation were assessed before and after 3 months of PR, and questionnaires (Nijmegen, VQ-11). There was a significant effect of PR of but no significant difference between groups in the improvements of dyspnea@max exercise (time effect (T): p < 0.01; group (G): p = 0.63; group*time interaction (G*T): p = 0.49), mMRC dyspnea (T: p < 0.01; G: p = 0.45; G*T: p = 0.62), 6MWD (T: p < 0.05; G: p = 0.36; G*T: p = 0.31), VQ-11 (T: p < 0.001; G: p = 0.16; G*T: p = 0.09) and plasma HCO3- (T: p < 0.05; G: p = 0.93; G*T; p = 0.36), Yet, Nijmegen score (T: p < 0.01; G: p = 0.32; G*T: p < 0.05) improvement was larger in NV+PR group. The exercise oronasal breathing shift during the 6MWT was significantly delayed in all patients (T: p < 0.05; G: p = 0.30; G*T: p = 0.32) and positively correlated with plasma HCO3-(r = 0.42; p < 0.05). Nasal exercise was not superior versus voluntary hypoventilation during PR in HVS patients. Yet, nasal exercise appeared feasible, leading to acquisition of a nasal breathing pattern during walking, improvement of PR outcomes and ventilatory alkalosis. The link between nasal breathing and hyperventilation is discussed in the light of the nasal ventilation rhythm in the limbic system and its role on the limbic emotional and ventilatory functions.

Adherence in severe asthma.

Adherence in asthma is an important cause for concern. Although nearly 50% of asthma patients are considered poorly adherent to therapeutic advices, adherence is still difficult to assess, understand and improve despite major medical consequences. In this review, we revisited the literature of the last 10 years related to adherence in severe asthma. The concepts have changed and "compliance" is usually replaced by "adherence". Assessment of adherence is addressing ethical issues, but provides important insight into difficult-to-treat asthma. Different tools have been used but none is routinely recommended. Health-related outcomes (poor control, exacerbations, hospitalizations, lung function decline), which are clearly associated with severe asthma, are often worsened by non-adherence with consequences also on patient related outcomes (quality of life). The potential behaviour associated with non-adherence and all other related factors including easy-to-recognize psychological traits can help for patient's future management. Therapeutic educational interventions have been recognized with a scientifically proven efficiency even though evolution and improvements are needed. A multidisciplinary approach is required in severe asthma. Therapeutic adherence for a given patient is always a prerequisite to any other aspects when addressing severe asthma phenotypes. Severe asthma should be considered only in those who still experienced poor asthma outcomes despite optimal adherence. At a glance, poor adherence and severe asthma should be considered antinomic. Better understanding of the causes and customised management are potential future directions.

Voriconazole for chronic pulmonary aspergillosis: a prospective multicenter trial.

Early evidence suggests the efficacy of voriconazole for chronic pulmonary aspergillosis (CPA). We conducted a prospective, open, multicenter trial to evaluate the efficacy and safety of voriconazole for proven CPA in minimally or non-immunocompromised patients. Patients had CPA confirmed by chest computed tomography (CT) and/or endoscopy, positive Aspergillus culture from a respiratory sample, and positive serologic test for Aspergillus precipitins. Patients received voriconazole (200 mg twice daily) for a period of 6-12 months and were followed for 6 months after the end of therapy (EOT). The primary endpoint was global success at 6 months, defined as complete or partial (≥50 % improvement) radiological response and mycological eradication. Forty-one patients with confirmed CPA were enrolled. All patients had A. fumigatus as the etiologic agent. By EOT, five patients had died from comorbidities and seven had discontinued voriconazole due to toxicity. The global success rate at 6 months was 13/41 (32 %): 10/19 (53 %) for chronic necrotizing aspergillosis and 3/22 (14 %) for chronic cavitary aspergillosis (p = 0.01). The respective success rates at EOT were 58 and 32 %. Clinical symptoms and quality of life also improved during treatment. Voriconazole is effective for CPA, with acceptable toxicity. The response rate is higher and obtained more rapidly in necrotizing than cavitary forms.

Hedgehog pathway and its inhibitors in chronic obstructive pulmonary disease (COPD).

COPD affects millions of people and is now ranked as the third leading cause of death worldwide. This largely untreatable chronic airway disease results in irreversible destruction of lung architecture. The small lung hypothesis is now supported by epidemiological, physiological and clinical studies. Accordingly, the early and severe COPD phenotype carries the most dreadful prognosis and finds its roots during lung growth. Pathophysiological mechanisms remain poorly understood and implicate individual susceptibility (genetics), a large part of environmental factors (viral infections, tobacco consumption, air pollution) and the combined effects of those triggers on gene expression. Genetic susceptibility is most likely involved as the disease is severe and starts early in life. The latter observation led to the identification of Mendelian inheritance via disease-causing variants of SERPINA1 - known as the basis for alpha-1 anti-trypsin deficiency, and TERT. In the last two decades multiple genome wide association studies (GWAS) identified many single nucleotide polymorphisms (SNPs) associated with COPD. High significance SNPs are located in 4q31 near HHIP which encodes an evolutionarily highly conserved physiological inhibitor of the Hedgehog signaling pathway (HH). HHIP is critical to several in utero developmental lung processes. It is also implicated in homeostasis, injury response, epithelial-mesenchymal transition and tumor resistance to apoptosis. A few studies have reported decreased HHIP RNA and protein levels in human adult COPD lungs. HHIP+/- murine models led to emphysema. HH pathway inhibitors, such as vismodegib and sonidegib, are already validated in oncology, whereas other drugs have evidenced in vitro effects. Targeting the Hedgehog pathway could lead to a new therapeutic avenue in COPD. In this review, we focused on the early and severe COPD phenotype and the small lung hypothesis by exploring genetic susceptibility traits that are potentially treatable, thus summarizing promising therapeutics for the future.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, full version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version intégrale.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

[French practical guidelines for the diagnosis and management of IPF - 2021 update, short version]. / Recommandations pratiques pour le diagnostic et la prise en charge de la fibrose pulmonaire idiopathique ­ Actualisation 2021. Version courte.

BACKGROUND: Since the previous French guidelines were published in 2017, substantial additional knowledge about idiopathic pulmonary fibrosis has accumulated. METHODS: Under the auspices of the French-speaking Learned Society of Pulmonology and at the initiative of the coordinating reference center, practical guidelines for treatment of rare pulmonary diseases have been established. They were elaborated by groups of writers, reviewers and coordinators with the help of the OrphaLung network, as well as pulmonologists with varying practice modalities, radiologists, pathologists, a general practitioner, a head nurse, and a patients' association. The method was developed according to rules entitled "Good clinical practice" in the overall framework of the "Guidelines for clinical practice" of the official French health authority (HAS), taking into account the results of an online vote using a Likert scale. RESULTS: After analysis of the literature, 54 recommendations were formulated, improved, and validated by the working groups. The recommendations covered a wide-ranging aspects of the disease and its treatment: epidemiology, diagnostic modalities, quality criteria and interpretation of chest CT, indication and modalities of lung biopsy, etiologic workup, approach to familial disease entailing indications and modalities of genetic testing, evaluation of possible functional impairments and prognosis, indications for and use of antifibrotic therapy, lung transplantation, symptom management, comorbidities and complications, treatment of chronic respiratory failure, diagnosis and management of acute exacerbations of fibrosis. CONCLUSION: These evidence-based guidelines are aimed at guiding the diagnosis and the management in clinical practice of idiopathic pulmonary fibrosis.

Expectations about treatment of idiopathic pulmonary fibrosis: Comparative survey of patients, carers and physicians (the RESPIR French survey).

CONTEXT: Idiopathic pulmonary fibrosis (IPF) is a severe chronic disease during which anxiety and depression are frequent comorbidities. Better knowledge of patients' expectations is needed to inform an action plan to improve medical care. AIM: To describe feelings and expectations of patients suffering from IPF and of their carers about antifibrotic therapy and compare them to what is perceived by their pulmonologist. METHODS: National prospective study on practices and perceptions. Specific questionnaires were e-mailed to all 3276 pulmonologists in France who, in turn, invited patients and carers to participate in a survey. RESULTS: 147 pulmonologists, 161 patients and 144 carers participated in the survey. The role of the carer was evaluated as "important" or "very important" by more than 90% of participants, i.e. pulmonologists, patients or carers. Inconsistencies between how patients felt and how pulmonologists perceived them were identified: 88% of patients responded that they understood quite well what IPF is (vs. 75% of patients according to pulmonologists); 85.5% of patients said they were determined to fight the disease (vs. 68.0%); 61.7% of patients wanted to be kept informed of potential complications before they occurred (vs. 69.6%) and 81.2% wanted to be involved in therapeutic decisions (vs. 43.1%). Globally, patients had a more positive view of antifibrotic therapies than expected by pulmonologists: 41.5% evaluated their advantages superior to what they had expected (vs. 29.1% of patients according to pulmonologists) and 76.5% had a positive image of the benefits/disadvantages ratio (vs. 62.4%). Although pulmonologists had the impression that they were keeping their patients well-informed about exacerbations, hospital stays and the possible negative evolution of the disease despite antifibrotic therapies, 34.0%, 42.0% and 22.0% of patients respectively declared not being aware of these aspects. CONCLUSION: The feelings of patients suffering from IPF regarding their disease and treatment globally proved more positive compared with how pulmonologists perceived them. Taking into account the expectations and needs of patients may allow healthcare professionals to better address their needs and priorities.

Apnoea-hypopnoea indices determined via continuous positive airway pressure (AHI-CPAPflow) versus those determined by polysomnography (AHI-PSGgold): a protocol for a systematic review and meta-analysis.

INTRODUCTION: To date, continuous positive airway pressure (CPAP) remains the cornerstone of obstructive sleep apnoea treatment. CPAP data describing residual sleep-disordered breathing events (ie, the CPAP-measured apnoea-hypopnoea indices (AHI-CPAPflow)) is difficult to interpret because it is an entirely different metric than the polysomnography (PSG) measured AHI gold standard (AHI-PSGgold). Moreover, manufacturer definitions for apnoea and hypopnoea are not only different from those recommended for PSG scoring, but also different between manufacturers. In the context of CPAP initiation and widespread telemedicine at home to facilitate sleep apnoea care, there is a need for concrete evidence that AHI-CPAPflow can be used as a surrogate for AHI-PSGgold. METHODS AND ANALYSIS: No published systematic review and meta-analysis (SRMA) has compared the accuracy of AHI-CPAPflow against AHI-PSGgold and the primary objective of this study is therefore to do so using published data. The secondary objectives are to similarly evaluate other sleep disordered breathing indices and to perform subgroup analyses focusing on the inclusion/exclusion of central apnoea patients, body mass index levels, CPAP device brands, pressure titration modes, use of a predetermined and fixed pressure level or not, and the impact of a 4% PSG desaturation criteria versus 3% PSG on accuracy. The Preferred Reporting Items for SRMA protocols statement guided study design. Randomised controlled trials and observational studies of adult patients (≥18 years old) treated by a CPAP device will be included. The CPAP intervention and PSG comparator must be performed synchronously. PSGs must be scored manually and follow the American Academy of Sleep Medicine guidelines (2007 AASM criteria or more recent). To assess the risk of bias in each study, the Quality Assessment of Diagnostic Accuracy Studies 2 tool will be used. ETHICS AND DISSEMINATION: This protocol received ethics committee approval on 16 July 2020 (IRB_MTP_2020_07_2020000404) and results will be disseminated via peer-reviewed publications. PROSPERO/TRIAL REGISTRATION NUMBERS: CRD42020159914/NCT04526366; Pre-results.

Trends in hospital admissions due to asthma in north-west Spain from 1995 to 2007.

PURPOSE: Asthma is the most common chronic disease in childhood. Hospital admissions in the child population appear to be reducing in different populations. METHODS: We have retrospectively analysed admissions into hospitals in our region due to asthma in a 0 to 14 years population, between the years 1995 and 2007. The age, sex, date of admission, and length of hospital stay of each patient was recorded and analysed. RESULTS: A total of 9106 admissions (64% males) have been included. A gradual trend towards a reduction in admissions is observed during the period analysed. There were more admissions in 1996, with 2.91 per thousand inhabitants, gradually reducing to 1.33 per thousand in 2007. There were more admissions in May and between September and December, being less frequent in July and August. The mean stay in this period was 4.18 days, which was stable during the whole period of the study. Older children tended to have a longer hospital stay. CONCLUSIONS: Our study shows that admissions due to childhood asthma tend to be decreasing, particularly due to younger males, with no change in the length of hospital stay. Asthma exacerbations seemed to be associated with infections and exposure to allergens.

[Modelling the bronchial epithelium in chronic obstructive pulmonary disease using human induced pluripotential stem cells]. / Modélisation de l'épithélium bronchique dans la bronchopneumopathie chronique obstructive par les cellules souches pluripotentes induites humaines.

Chronic obstructive pulmonary disease (COPD) is a chronic lung disease leading to irreversible destruction of the terminal bronchioles. Although the precise patho-physiological mechanisms remain to be elucidated, the bronchial epithelium seems to play a pivotal role in the disease. Recent studies have highlighted a great heterogeneity among COPD patients, with various disease courses including, in about half the cases, an origin in childhood. Modelling of COPD is a major goal but currently available models are imperfect. Our work aims to create a new in vitro cellular model to study the pathology of the disease. The differentiation of human induced pluripotential stem cells (hiPSCs) in bronchial epithelium is a step towards a better understanding of the developmental origin and the identification of new therapeutic targets.

Prioritising outcomes for evaluating eosinophil-guided corticosteroid therapy among patients with acute COPD exacerbations requiring hospitalisation: a Delphi consensus study.

OBJECTIVES: Presently, those outcomes that should be prioritised for chronic obstructive pulmonary disease (COPD) exacerbation studies remain unclear. In order to coordinate multicentre studies on eosinophilia-driven corticosteroid therapy for patients hospitalised for acute exacerbation of COPD (AECOPD), we aimed to find consensus among experts in the domain regarding the prioritisation of outcomes. DESIGN: A modified Delphi study was proposed to recognised COPD experts. Two brainstorming questionnaires were used to collect potential outcomes. Four subsequent rounds of questionnaires were used to rank items according to a six-point Likert scale for their importance in the protocol, as well as for being the primary outcome. Priority outcome criteria were predefined as those for which ≥70% of experts indicated that the outcome was essential for interpreting study results. SETTING: COPD exacerbation management in France. PARTICIPANTS: 34 experts recommended by the French Language Pulmonology Society were invited to participate. Of the latter, 21 experts participated in brainstorming, and 19 participated in all four ranking rounds. RESULTS: 105 outcomes were ranked. Two achieved consensus as candidate primary outcomes: (1) treatment failure defined as death from any cause or the need for intubation and mechanical ventilation, readmission because of COPD or intensification of pharmacologic therapy, and (2) the time required to meet predefined discharge criteria. The 10 secondary priority outcomes included survival, time with no sign of improvement, episodes of hospitalisation, exacerbation, pneumonia, mechanical or non-invasive ventilation and oxygen use, as well as comorbidities during the initial hospitalisation. CONCLUSIONS: This Delphi consensus project generated and prioritised a great many outcomes, documenting current expert views concerning a diversity of COPD endpoints. Among the latter, 12 reached consensus as priority outcomes for evaluating the efficacy of eosinophil-driven corticosteroid therapy in AECOPD inpatients. STUDY REGISTRATION: The eo-Delphi project/protocol was registered on 23 January 2018 at https://osf.io/4ahqw/.

Detection of SARS-CoV-2 antibodies using commercial assays and seroconversion patterns in hospitalized patients.

OBJECTIVES: SARS-CoV-2 antibody assays are needed for serological surveys and as a complement to molecular tests to confirm COVID-19. However, the kinetics of the humoral response against SARS-CoV-2 remains poorly described and relies on the performance of the different serological tests. METHODS: In this study, we evaluated the performance of six CE-marked point-of-care tests (POC) and three ELISA assays for the diagnosis of COVID-19 by exploring seroconversions in hospitalized patients who tested positive for SARS-CoV-2 RNA. RESULTS: Both the ELISA and POC tests were able to detect SARS-CoV-2 antibodies in at least half of the samples collected seven days or more after the onset of symptoms. After 15 days, the rate of detection rose to over 80% but without reaching 100%, irrespective of the test used. More than 90% of the samples collected after 15 days tested positive using the iSIA and Accu-Tell® POC tests and the ID.Vet IgG ELISA assay. Seroconversion was observed 5 to 12 days after the onset of symptoms. Three assays suffer from a specificity below 90% (EUROIMMUN IgG and IgA, UNscience, Zhuhai Livzon). CONCLUSIONS: The second week of COVID-19 seems to be the best period for assessing the sensitivity of commercial serological assays. To achieve an early diagnosis of COVID-19 based on antibody detection, a dual challenge must be met: the immunodiagnostic window period must be shortened and an optimal specificity must be conserved.