Severe asthma care trajectories: the French RAMSES cohort.

Background: The French RAMSES study is an observational prospective multicentre real-life cohort including severe asthmatic subjects. The objective of the study was to compare the characteristics of patients, in terms of phenotype and asthma care trajectories, between those managed by tertiary referral centres (TRCs) or secondary care centres (SCCs). Methods: Patients were prospectively recruited and enrolled for a 5-year follow-up. Patients' characteristics were analysed at inclusion and compared between TRCs and SCCs. Results: 52 centres (24 TRCs and 28 SCCs) included 2046 patients: 1502 (73.4%) were included by a TRC and 544 (26.6%) by a SCC. Patients were mainly women (62%), 53±15 years old, 67% with Asthma Control Test <20; at inclusion, 14% received oral corticosteroids (OCS) and 66% biologics. Compared with the SCC group, the TRC group had more frequent comorbidities and lower blood eosinophil counts (262 versus 340 mm-3; p=0.0036). OCS and biologics use did not differ between groups, but patients in the TRC group benefited more frequently from an educational programme (26% versus 18%; p=0.0008) and received more frequently two or more sequential lines of biologics (33% versus 24%; p=0.0105). In-depth investigations were more frequently performed in the TRC group (allergy tests: 74% versus 62%; p<0.0001; exhaled nitric oxide fraction: 56% versus 21%; p<0.0001; induced sputum: 6% versus 3%; p=0.0390). Conclusions: Phenotypes and care trajectories differed in the RAMSES cohort between SCCs and TRCs, probably related to different levels of asthma severity and differences in medical resources and practices among centres. This highlights the need for standardisation of severe asthma care.

Airway replacement using stented aortic matrices: Long-term follow-up and results of the TRITON-01 study in 35 adult patients.

Over the past 25 years, we have demonstrated the feasibility of airway bioengineering using stented aortic matrices experimentally then in a first-in-human trial (n = 13). The present TRITON-01 study analyzed all the patients who had airway replacement at our center to confirm that this innovative approach can be now used as usual care. For each patient, the following data were prospectively collected: postoperative mortality and morbidity, late airway complications, stent removal and status at last follow-up on November 2, 2021. From October 2009 to October 2021, 35 patients had airway replacement for malignant (n = 29) or benign (n = 6) lesions. The 30-day postoperative mortality and morbidity rates were 2.9% (n = 1/35) and 22.9% (n = 8/35) respectively. At a median follow-up of 29.5 months (range 1-133 months), 27 patients were alive. There have been no deaths directly related to the implanted bioprosthesis. Eighteen patients (52.9%) had stent-related granulomas requiring a bronchoscopic treatment. Ten among 35 patients (28.6%) achieved a stent free survival. The actuarial 2- and 5-year survival rates (Kaplan-Meier estimates) were respectively 88% and 75%. The TRITON-01 study confirmed that airway replacement using stented aortic matrices can be proposed as usual care at our center. Clinicaltrials.gov Identifier: NCT04263129.

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.

Observational study on off-label use of tocilizumab in patients with severe COVID-19.

BACKGROUND: In December 2019 a novel coronavirus designated SARS-CoV-2 was identified, and the disease COVID-19 has caused many deaths. SARS-CoV-2 infection has been associated with the development of cytokine storm (including interleukin 6 (IL-6)), which can cause lung damage and lack of oxygen. Tocilizumab (TCZ) inhibits ligand binding to the IL-6 receptor and may be a potential treatment for the hyperinflammation symptoms of COVID-19. However, data regarding the efficacy of TCZ in COVID-19 are lacking. The rapid spread of the pandemic in France, especially in the Paris region, constrained us to the off-label use of TCZ in patients with severe clinical conditions. METHODS: A single-centre observational cohort study of 44 patients infected with COVID-19 was carried out between 6 April and 21 April 2020 in Groupe Hospitalier Intercommunal Le Raincy-Montfermeil (GHILRM). Twenty-two patients diagnosed with COVID-19 were treated with TCZ and were compared with 22 patients not treated with TCZ matched for age, gender and length of hospital stay for COVID-19. Respiratory rate and oxygen supplementation as well as laboratory parameters (such as C-reactive protein (CRP), aspartate aminotransferase and alanine aminotransferase) were collected at baseline and during 14 days of follow-up. Our primary objective was to assess the efficacy of TCZ on respiratory clinical conditions. FINDINGS: The average respiratory rate was lower in the TCZ group than in the control group (21.5 vs 25.5 breaths/min at day 14, 95% CI -7.5 to -0.4; p=0.03). Treated patients tended to be intubated less during the course of the disease (2/22 vs 6/22, 95% CI -0.4 to 0.1; p=0.12). In each group, 10 patients no longer required oxygen therapy. We found a significant decrease in CRP in treated patients on day 7 (p=0.04). TCZ caused cytolysis in more than half (14/22) of the patients but without clinical impact. INTERPRETATION: There was a significant difference in the respiratory rate on day 14 of follow-up, with a greater decrease observed in the treated group. Fewer patients required mechanical ventilation in the TCZ group, especially among patients with more extensive CT lung damage, than in the control group. The same number of patients were weaned off oxygen on day 14 in the two groups, while the patients in the TCZ group had more severe impairment at inclusion. We consider that TCZ showed significant control of the biological inflammatory syndrome, suggesting that it may limit the effect of the cytokine storm. Our study seems to indicate the efficacy of TCZ, particularly in patients with severe initial pulmonary impairment. Selecting the best candidates and the best timing for TCZ therapy needs to be determined in randomised clinical trials.

Liver function test abnormalities are associated with a poorer prognosis in Covid-19 patients: Results of a French cohort.

AIM: To assess the impact of liver function test (LFT) abnormalities on the prognosis of patients with coronavirus disease 2019 (COVID-19) in a French cohort of hospitalized patients. PATIENTS AND METHOD: From March 13 to April 22, 2020, we collected on a computerized and anonymized database, medical records, laboratory data and clinical outcomes of patients hospitalized for confirmed cases of COVID-19 infection (RT-PCR and/or CT-scan). Patients were followed up until April 22, 2020 or until death or discharge. We have considered for statistical analysis, LFT abnormalities with levels greater than two times the upper limit of normal. Composite endpoint included admission to ICU, mechanical ventilation, severe radiologic injury and death to define disease severity. RESULTS: Among 281 patients (median age 60 years) with COVID-19, 102 (36.3%) had abnormal LFT. Hypertension (45.6%) and diabetes (29.5%) were the main comorbidities. 20.2% were taken liver-toxic drugs at the admission and 27.4% were given drugs known to induce hepatic cytolysis during hospitalization. Patients with elevated levels of ALT or AST were significantly more severe with a higher rate of admission to ICU (40.0% vs 6.0%, p< 0.0001), and global mortality (26.7% vs 12.1%, p= 0.03). In multivariate analysis, obesity and cytolytic profil were associated with the composite endpoint (respectively 2.37 [1.21; 4.64], p= 0.01 and OR 6.20, 95% confidence interval [1.84, 20.95], p-value 0.003) CONCLUSION: Most of liver injuries are mild and transient during COVID-19. LFT abnormalities are associated with a poorer prognosis and could be a relevant biomarker for early detection of severe infection.

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.

A clinical in-hospital prognostic score for acute exacerbations of COPD.

BACKGROUND: The use of a severity score to help orientation decisions could improve the efficiency of care for acute exacerbations of COPD (AECOPD). We previously developed a score ('2008 score', based on age, dyspnea grade at steady state and number of clinical signs of severity) predicting in-hospital mortality in patients with AECOPD visiting emergency departments (EDs). External validity of this score remained to be assessed. OBJECTIVES: To test the predictive properties of the '2008 score' in a population of patients hospitalized in medical respiratory wards for AECOPD, and determine whether a new score specifically derived from this population would differ from the previous score in terms of components or predictive performance. METHODS: Data from a cohort study in 1824 patients hospitalized in a medical ward for an AECOPD were analyzed. Patients were categorized using the 2008 score and its predictive characteristics for in-hospital mortality rates were assessed. A new score was developed using multivariate logistic regression modeling in a randomly selected derivation population sample followed by testing in the remaining population (validation sample). Robustness of results was assessed by case-by-case validation. RESULTS: The 2008 score was characterized by a c-statistic at 0.77, a sensitivity of 69% and a specificity of 76% for prediction of in-hospital mortality. The new score comprised the same variables plus major cardiac comorbidities and was characterized by a c-statistic of 0.78, a sensitivity of 77% and specificity of 66%. CONCLUSIONS: A score using simple clinical variables has robust properties for predicting the risk of in-hospital death in patients hospitalized for AECOPD. Adding cardiac comorbidities to the original score increased its sensitivity while decreasing its specificity.