Smoking, Urban Housing and Work-Aggravated Asthma are Associated with Asthma Severity in a Cross-Sectional Observational Study.

Purpose: Severe asthma affects 5 to 10% of asthmatics and accounts for a large part of asthma-related morbidity and costs. The determinants of asthma severity are poorly understood. We tested the hypothesis that asthma severity was associated with 1) atopy and allergy and 2) markers associated with environmental exposure. Patients and Methods: Data from the FASE-CPHG study, a cross-sectional, observational, multicenter investigation, were analyzed to identify markers associated with asthma severity. Asthma severity was gauged using the ASSESS score, encompassing symptom control, exacerbations, FEV1 and therapeutic load. Bivariate and multivariate analyses were used to identify patient characteristics associated with the ASSESS score. Results: The analysis involved 948 patients, with 592 women, of which 447 patients (47%) had severe asthma. Among these, 491 patients (52%) had at least one positive aeroallergen skin prick test and 525 (55%) had at least one allergic disease among atopic dermatitis, chronic rhinitis and food allergy. The mean±SD ASSESS score was 11.2±3.4. Characteristics associated with a higher ASSESS score were female sex, secondary or lower education, unemployed occupational status, smoking, work-aggravated asthma and urban housing. There was no association between the ASSESS score and allergic diseases, aeroallergen-specific skin prick tests and IgEs, or blood eosinophil counts. Conclusion: While atopy and allergy were frequent among asthmatics, neither was associated with asthma severity. Modifiable environmental factors such as smoking, urban housing and work-aggravated asthma were independently associated with asthma severity.

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.

Auto-adjusted versus fixed positive airway pressure in patients with severe OSA: A large randomized controlled trial.

BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) in the treatment of severe obstructive sleep apnoea (OSA) can be used in fixed CPAP or auto-adjusted (APAP) mode. The aim of this prospective randomized controlled clinical study was to evaluate the 3 month-efficacy of CPAP used either in fixed CPAP or APAP mode. METHODS: Eight hundred one patients with severe OSA were included in twenty-two French centres. After 7 days during which all patients were treated with APAP to determine the effective pressure level and its variability, 353 and 351 patients were respectively randomized in the fixed CPAP group and APAP group. After 3 months of treatment, 308 patients in each group were analysed. RESULTS: There was no difference between the two groups in terms of efficacy whatever the level of efficient pressure and pressure variability (p = 0.41). Exactly, 219 of 308 patients (71.1%) in the fixed CPAP group and 212 of 308 (68.8%) in the APAP group (p = 0.49) demonstrated residual apnoea hypopnoea index (AHI) <10/h and Epworth Score <11. Tolerance and adherence were also identical with a similar effect on quality of life and blood pressure evaluation. CONCLUSION: The two CPAP modes, fixed CPAP and APAP, were equally effective and tolerated in severe OSA patients.

Characteristics of Severe Non-Eosinophilic Asthma: Analysis of Data from 1075 Patients Included in the FASE-CPHG Study.

Purpose: Data on severe non-eosinophilic asthma are scarce. Moreover, as compared with eosinophilic asthma, non-eosinophilic asthma less frequently benefits from the latest therapeutic advances. This study aimed to highlight differences between non-eosinophilic and eosinophilic asthma as they may help the development of new therapeutic agents. Patients and Methods: Data from 1075 adult patients with severe asthma (GINA treatment: 4/5) collected during the cross-sectional non-interventional FASE-CPHG study were analyzed. Two groups of patients (EOS-/EOS+) were constituted based on blood eosinophil counts (cutoff value: 300 G/l). Characteristics of EOS- (N = 500) and EOS+ (N = 575) patients were described; EOS- patients were also described according to their allergic profile based on skin allergy or allergen-specific immunoglobulin E (IgE) assays (cutoff value: 150 IU/mL). Results: Percentages of patients with obesity (29%), allergen sensitization (57%), or ≥2 annual exacerbations in the last 12 months (68%) were similar in both groups. As compared with EOS+ patients, EOS- patients less frequently reported chronic rhinitis (41.1% vs 50.5%, p < 0.01) or nasal polyposis (13.6% vs 27.5%, p < 0.01), and more frequently reported GERD (45.2% vs 37.1%, p < 0.01), anxiety (45.5% vs 38.1%, p = 0.01), or depression (18.3% vs 13.3%, p = 0.02). EOS- patients had lower serum total IgE levels (median: 158 vs 319 IU/mL, p < 0.01) and were less frequently treated with long-term oral corticosteroid therapy (16.0% vs 23.7%; p < 0.01). Their asthma was more frequently uncontrolled (48% vs 40%, p < 0.01). Similar results were found with a cutoff value for blood eosinophil counts at 150 G/l. EOS- patients with allergic profile less frequently reported high serum IgE levels (35.6% vs 57.9%, p < 0.01). EOS- and EOS+ patients treated with long-term oral corticosteroids had similar profiles. Conclusion: In our patients with severe asthma, EOS- asthma was approximately as frequent as EOS+ asthma; EOS- asthma was frequently poorly controlled or uncontrolled, confirming the need for a better management. Allergy did not appear to worsen clinical profile.

Mid-term pulmonary sequelae after hospitalisation for COVID-19: The French SISCOVID cohort.

BACKGROUND: Even though COVID-19 clinical features, pathogenesis, complications, and therapeutic options have been largely described in the literature, long-term consequences in patients remain poorly known. METHODS: The French, multicentre, non-interventional SISCOVID study evaluated lung impairment three (M3) and six months (M6) after hospital discharge in patients recovered from COVID-19. Evaluation was based on clinical examination, pulmonary function tests, and chest computed tomography (CT-scan). RESULTS: Of the 320 included patients (mean age: 61 years; men: 64.1%), 205 had had a severe form of COVID-19, being hospitalised in an intensive care unit (ICU), and requiring high flow nasal cannula, non-invasive ventilation, or invasive mechanical ventilation. At M6, 54.1% of included patients had persistent dyspnoea (mMRC score ≥1), 20.1% severe impairment in gas diffusing capacity (DLCO <60% pred.), 21.6% restrictive ventilatory pattern (total lung capacity <80% pred.), and 40% a fibrotic-like pattern at CT-scan. Fibrotic-like pattern and restrictive ventilatory pattern were significantly more frequent in patients recovered from severe than non-severe COVID-19. Improved functional and radiological outcomes were observed between M3 and M6. At M6, age was an independent risk factor for severe DLco impairment and fibrotic-like pattern and severe COVID-19 form was independent risk factor for restrictive ventilatory profile and fibrotic-like pattern. CONCLUSION: Six months after discharge, patients hospitalised for COVID-19, especially those recovered from a severe form of COVID-19, frequently presented persistent dyspnoea, lung function impairment, and persistent fibrotic-like pattern, confirming the need for long-term post-discharge follow-up in these patients and for further studies to better understand long-term COVID-19 lung impairment.

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.

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/m2), 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/mm3), 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.

FASE-CPHG study: a panoramic snapshot of difficult-to-treat, severe asthma in French nonacademic hospitals.

BACKGROUND: Real-world data describing management of patients with severe asthma are limited. To address this issue, we conducted FASE-CPHG (France Asthme Sevère - Collège des Pneumologues des Hôpitaux Généraux), a descriptive, multicentric, and observational cross-sectional study. METHODS: French pulmonologists from nonacademic hospitals completed questionnaires on patient characteristics and ongoing asthma treatment for severe asthmatic patients observed during the inclusion period. In addition, we collected data from patients via self-assessment questionnaires. FINDINGS: 104 physicians recruited 1502 patients within 1 year. The mean age of the 1465 patients analysed was 54.4±16.1 years. Severe asthmatic patients were more frequently female (63%), with a history of atopy (65%). Most patients remained poorly controlled or uncontrolled, with an important difference between physicians' opinion and the Global Initiative for Asthma criteria (63% versus 96%). The most common comorbidities included ear, nose and throat diseases (59% of cases); anxiety (40%); and gastro-oesophageal reflux disease (39%). Allergic sensitisation tests and/or blood eosinophil count evaluation, and spirometry were performed in 92% and 98% of patients, respectively. The mean eosinophil count and total serum IgE were 437 cells·mm-3 and 546 UI·L-1, respectively. In addition to high doses of inhaled corticosteroids plus long-acting ß2-agonists, patients were receiving leukotriene receptor antagonists (52%), anticholinergic drugs (34%), anti IgE (27%) and oral corticosteroids (17%); 65% adhered to their treatment. INTERPRETATION: This study provides insight into the characteristics and management of severe asthma in France and may help improve knowledge on this pathology, which represents a high burden to healthcare.