FASE-CPHG Study: identification of asthma phenotypes in the French Severe Asthma Study using cluster analysis

BACKGROUND: In France, data regarding epidemiology and management of severe asthma are scarce. The objective of this study was to describe asthma phenotypes using a cluster analysis in severe asthmatics recruited in a real world setting. METHODS: The study design was prospective, observational and multicentric. The patients included were adults with severe asthma (GINA 4-5) followed-up in French Non Academic Hospital between May 2016 and June 2017. One hundred and seven physicians included 1502 patients. Both sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis on a population of 1424 patients. RESULTS: Five clusters were identified: cluster 1 (n = 690, 47%) called early onset allergic asthma (47.5% with asthma before 12 years), cluster 2 (n = 153, 10.5%): obese asthma (63.5% with BMI > 30 kg/m(2)), cluster 3 (n = 299, 20.4%): late-onset asthma with severe obstructive syndrome (89% without atopy), cluster 4 (n = 143, 9.8%): eosinophilic asthma (51.7% had more than 500 eosinophils/mm(3)), and cluster 5 (n = 139, 9.5%): aspirin sensitivity asthma (63% had severe asthma attacks). CONCLUSIONS: In our population of adults with severe asthma followed by pulmonologists, five distinct phenotypes were identified and are quite different from those mentioned in previous studies

ThOracic Ultrasound in Idiopathic Pulmonary Fibrosis Evolution (TOUPIE): research protocol of a multicentric prospective study

Introduction Idiopathic pulmonary fibrosis (IPF) is the most common and severe interstitial lung disease (ILD). It is a progressive disease that requires a regular follow-up: clinical examination, pulmonary function testing (PFT) and CT scan, which is performed yearly in France. These exams have two major disadvantages: patients with severe dyspnoea have difficulties to perform PFT and repeated CT scans expose to high dose of radiations. Considering these limits, it would be relevant to develop new tools to monitor the progression of IPF lesions. Three main signs have been described in ILD with lung ultrasound (LUS): the number of B lines, the irregularity and the thickening of the pleural line. Cross-sectional studies already correlated the intensity of these signs with the severity of fibrosis lesions on CT scan in patients with IPF, but no prospective study described the evolution of the three main LUS signs, nor the correlation between clinical evaluation, PFT and CT scan. Our hypothesis is that LUS is a relevant tool to highlight the evolution of pulmonary lesions in IPF. The main objective of our study is to show an increase in one or more of the three main LUS signs (total number of B lines, pleural line irregularity score and pleural line thickness) during the follow-up.Methods ThOracic Ultrasound in Idiopathic Pulmonary Fibrosis Evolution is a French prospective, multicentric and non-interventional study. Every 3 months, patients with IPF will have a clinical examination, PFT and LUS. CT data will be collected if the CT scan is performed within 3 months before the inclusion; the second CT scan will be performed from 9 to 12 months after the inclusion. The presence, location and severity of LUS signs will be recorded for each patient, and their correlation with clinical, functional and CT scan evolution will be evaluated. 30 patients will be enrolled.Ethics and dissemination The protocol was approved by the French Research Ethics Committee (Comité de Protection des Personnes SUD OUEST ET OUTRE MER II, reference RIPH3-RNI19-TOUPIE) on 11 April 2019. Results will be disseminated via peer-reviewed publication and presentation at international conferences.Trial registration number NCT03944928;Pre-results

Approach to diagnosis and pathological examination in bronchial Dieulafoy disease: a case series-0

<p><b>Copyright information:</b></p><p>Taken from "Approach to diagnosis and pathological examination in bronchial Dieulafoy disease: a case series"</p><p>http://respiratory-research.com/content/9/1/58</p><p>Respiratory Research 2008;9(1):58-58.</p><p>Published online 5 Aug 2008</p><p>PMCID:PMC2529287.</p><p></p

Phenotyping to Target Obstructive Sleep Apnoea Syndrom (OSAS) in adults patients with severe asthma

BACKGROUND: Obstructive sleep apnoea syndrome (OSAS) and severe asthma are frequently associated. This article focuses on the relationship between severe asthma phenotypes and OSAS. METHODS: FASE-CPHG was an observational, cross-sectional, prospective, multicentric study conducted in 104 non-academic hospitals from May-16 to July-17. 1465 patients with severe asthma were analysed and 1424 patients phenotyped. Clusters were compared for OSAS presence; independent factors associated with OSAS were identified by logistic regression. RESULTS: 11% of patients with severe asthma reported OSAS. OSAS incidence differed according to asthma phenotypes. 98% of OSAS patients belonged to the "obese asthma" cluster, and none to the "early onset allergic asthma" cluster. Independent factors associated with OSAS were obesity (OR=5.782 [3.927-8.512]), male gender (OR=3.047 [2.059-4.510]), high blood pressure (OR=2.875 [1.978-4.181]), depression (OR=2.552 [1.607-4.050]), late-onset asthma (OR=1.789 [1.167-2.743]) and atopy (OR=0.622 [0.408-0.948]). Moreover, OSAS patients were more frequently treated with long-term oral corticosteroids (30% vs 15%, p < 0.0001), that may contribute to the high prevalence of obesity in this group of patients. They were more frequently uncontrolled (78% vs 69%, p = 0.03) and they engaged in low level physical activity (vs 80% vs 68% p ≤ 0.001). CONCLUSION: Our study gives an innovative insight into OSAS associated with severe asthma. Most of patients with OSAS belonged to the cluster "obese asthma" and none to the cluster "early onset allergic asthma". In addition to male gender, arterial hypertension and depression, obese asthma, late onset asthma and non-atopic status were identified as specific risk factors. Oral corticosteroids seems to play a deleterious role. Phenotyping asthma can help physicians target severe asthmatic patients with OSAS and may avoid unnecessary examinations

Etiological Work-Up for Adults with Bronchiectasis: A Predictive Diagnostic Score for Primary Ciliary Dyskinesia and Cystic Fibrosis

Background: etiological investigations are not done for all adult patients with bronchiectasis because of the availability and interpretation of tests. The aim of the study was to elaborate a score to identify patients at high risk of having cystic fibrosis or primary ciliary dyskinesia (CF/PCD), which require appropriate management. Methods: diagnostic work-ups were carried out on a French monocenter cohort, and results were subjected to logistic-regression analyses to identify the independent factors associated with CF/PCD diagnosis and, thereby, elaborate a score to validate in a second cohort. Results: among 188 patients, 158 had no obvious diagnosis and were enrolled in the algorithm-construction group. In multivariate analyses, age at symptom onset (8.69 (2.10–35.99); p = 0.003), chronic ENT symptoms or diagnosed sinusitis (10.53 (1.26–87.57); p = 0.03), digestive symptoms or situs inversus (5.10 (1.23–21.14); p = 0.025), and Pseudomonas. aeruginosa and/or Staphylococcus aureus isolated from sputum (11.13 (1.34–92.21); p = 0.02) are associated with CF or PCD. Receiver operating characteristics curve analysis, using a validation group of 167 patients with bronchiectasis, confirmed the score’s performance with AUC 0.92 (95% CI: 0.84–0.98). Conclusions: a clinical score may help identify adult patients with bronchiectasis at higher risk of having CF or PCD

Determinants of a bronchoalveolar lavage of good quality for mineralogical analyses in adults: Experience from the Asbestos Fibers and Particles Laboratory of Paris City

International audienceBackground: Mineralogical analyses of bronchoalveolar lavage (BAL) may help in assessing past exposure to mineral particles. However, their interpretation relies on their quality, meaning their representativeness of the alveolar compartment. The aim of this study was to find predictive factors of BAL samples quality allowing a reliable mineralogical analysis. Methods: All BAL samples analyzed between 2018 and 2020 in the Asbestos Fibers and Particles Laboratory from Paris City were included. They were read by an experienced cyto-pathologist and validated according to their representativeness of the alveolar region compartment. Univariate and stratified analyses were conducted to identify factors associated with the samples’ cytological quality. Results: On the 780 samples included, 64.4% were deemed of good cytological quality and 17.9% were not interpretable. Injected volume and BAL yield (recovery volume on injected volume ratio) were associated with cytological quality. Injecting at least 100mL with a ≥60% yield or injecting at least 150mL with a ≥30% yield allowed having a good proportion of BAL with sufficient cytological quality. Conclusions: Injected volume greater than 100mL with sufficient BAL yield are essential factors to ensure a reliable mineralogical analysis of BAL samples

Digital Action Plan (Web App) for Managing Asthma Exacerbations: Randomized Controlled Trial

International audienceBackground A written action plan (WAP) for managing asthma exacerbations is recommended. Objective We aimed to compare the effect on unscheduled medical contacts (UMCs) of a digital action plan (DAP) accessed via a smartphone web app combined with a WAP on paper versus that of the same WAP alone. Methods This randomized, unblinded, multicenter (offline recruitment in private offices and public hospitals), and parallel-group trial included children (aged 6-12 years) or adults (aged 18-60 years) with asthma who had experienced at least 1 severe exacerbation in the previous year. They were randomized to a WAP or DAP+WAP group in a 1:1 ratio. The DAP (fully automated) provided treatment advice according to the severity and previous pharmacotherapy of the exacerbation. The DAP was an algorithm that recorded 3 to 9 clinical descriptors. In the app, the participant first assessed the severity of their current symptoms on a 10-point scale and then entered the symptom descriptors. Before the trial, the wordings and ordering of these descriptors were validated by 50 parents of children with asthma and 50 adults with asthma; the app was not modified during the trial. Participants were interviewed at 3, 6, 9, and 12 months to record exacerbations, UMCs, and WAP and DAP use, including the subjective evaluation (availability and usefulness) of the action plans, by a research nurse. Results Overall, 280 participants were randomized, of whom 33 (11.8%) were excluded because of the absence of follow-up data after randomization, leaving 247 (88.2%) participants (children: n=93, 37.7%; adults: n=154, 62.3%). The WAP group had 49.8% (123/247) of participants (children: n=45, 36.6%; mean age 8.3, SD 2.0 years; adults: n=78, 63.4%; mean age 36.3, SD 12.7 years), and the DAP+WAP group had 50.2% (124/247) of participants (children: n=48, 38.7%; mean age 9.0, SD 1.9 years; adults: n=76, 61.3%; mean age 34.5, SD 11.3 years). Overall, the annual severe exacerbation rate was 0.53 and not different between the 2 groups of participants. The mean number of UMCs per year was 0.31 (SD 0.62) in the WAP group and 0.37 (SD 0.82) in the DAP+WAP group (mean difference 0.06, 95% CI −0.12 to 0.24; P=.82). Use per patient with at least 1 moderate or severe exacerbation was higher for the WAP (33/65, 51% vs 15/63, 24% for the DAP; P=.002). Thus, participants were more likely to use the WAP than the DAP despite the nonsignificant difference between the action plans in the subjective evaluation. Median symptom severity of the self-evaluated exacerbation was 4 out of 10 and not significantly different from the symptom severity assessed by the app. Conclusions The DAP was used less often than the WAP and did not decrease the number of UMCs compared with the WAP alone. Trial Registration ClinicalTrials.gov NCT02869958; https://clinicaltrials.gov/ct2/show/NCT0286995

c-mip impairs podocyte proximal signaling and induces heavy proteinuria.

International audienceIdiopathic nephrotic syndrome comprises several podocyte diseases of unknown origin that affect the glomerular podocyte, which controls the permeability of the filtration barrier in the kidney to proteins. It is characterized by the daily loss of more than 3 g of protein in urine and the lack of inflammatory lesions or cell infiltration. We found that the abundance of c-mip (c-maf inducing protein) was increased in the podocytes of patients with various acquired idiopathic nephrotic syndromes in which the podocyte is the main target of injury. Mice engineered to have excessive c-mip in podocytes developed proteinuria without morphological alterations, inflammatory lesions, or cell infiltration. Excessive c-mip blocked podocyte signaling by preventing the interaction of the slit diaphragm transmembrane protein nephrin with the tyrosine kinase Fyn, thereby decreasing phosphorylation of nephrin in vitro and in vivo. Moreover, c-mip inhibited interactions between Fyn and the cytoskeletal regulator N-WASP (neural Wiskott-Aldrich syndrome protein) and between the adaptor protein Nck and nephrin, potentially accounting for cytoskeletal disorganization and the effacement of foot processes seen in idiopathic nephrotic syndromes. The intravenous injection of small interfering RNA targeting c-mip prevented lipopolysaccharide-induced proteinuria in mice. Together, these results identify c-mip as a key component in the molecular pathogenesis of acquired podocyte diseases