Bronchiectasis in Europe:data on disease characteristics from the European Bronchiectasis registry (EMBARC)

Background: Bronchiectasis is a heterogeneous, neglected disease with few multicentre studies exploring the causes, severity, microbiology, and treatment of the disease across Europe. This aim of this study was to describe the clinical characteristics of bronchiectasis and compare between different European countries.Methods: EMBARC is an international clinical research network for bronchiectasis. We report on a multicentre, prospective, observational, non-interventional, cohort study (the EMBARC registry) conducted across 27 European countries and Israel. Comprehensive clinical data were collected from adult patients (aged ≥18 years) at baseline and annual follow-up visits using electronic case report form. Data from individual countries were grouped into four regions (the UK, northern and western Europe, southern Europe, and central and eastern Europe according to modified EU EuroVoc classification). Follow-up data were used to explore differences in exacerbation frequency between regions using a negative binomial regression model.Findings: Between Jan 12, 2015, and April 12, 2022, 16 963 individuals were enrolled. Median age was 67 years (IQR 57-74), 10 335 (60·9%) participants were female and 6628 (39·1%) were male. The most common cause of bronchiectasis in all 16 963 participants was post-infective disease in 3600 (21·2%); 6466 individuals (38·1%) were classified as idiopathic. Individuals with bronchiectasis experienced a median of two exacerbations (IQR 1-4) per year and 4483 (26·4%) patients had a hospitalisation for exacerbation in the previous year. When examining the percentage of all isolated bacteria, marked differences in microbiology were seen between countries, with a higher frequency of Pseudomonas aeruginosa and lower Haemophilus influenzae frequency in southern Europe, compared with higher H influenzae in the UK and northern and western Europe. Compared with other regions, patients in central and eastern Europe had more severe bronchiectasis measured by the Bronchiectasis Severity Index (51·3% vs 35·1% in the overall cohort) and more exacerbations leading to hospitalisations (57·9% vs 26·4% in the overall cohort). Overall, patients in central and eastern Europe had an increased frequency of exacerbations (adjusted rate ratio [RR] 1·12, 95% CI 1·01-1·25) and a higher frequency of exacerbations leading to hospitalisations (adjusted RR 1·71, 1·44-2·02) compared with patients in other regions. Treatment of bronchiectasis was highly heterogeneous between regions.Interpretation: Bronchiectasis shows important geographical variation in causes, microbiology, severity, and outcomes across Europe.</p

European Respiratory Society guidelines for the management of adult bronchiectasis

Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines.The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature.A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy.These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes

The EMBARC European Bronchiectasis Registry:protocol for an international observational study

Bronchiectasis is one of the most neglected diseases in respiratory medicine. There are no approved therapies and few large-scale, representative epidemiological studies. The EMBARC (European Multicentre Bronchiectasis Audit and Research Collaboration) registry is a prospective, pan-European observational study of patients with bronchiectasis. The inclusion criterion is a primary clinical diagnosis of bronchiectasis consisting of: 1) a clinical history consistent with bronchiectasis; and 2) computed tomography demonstrating bronchiectasis. Core exclusion criteria are: 1) bronchiectasis due to known cystic fibrosis; 2) age <18 years; and 3) patients who are unable or unwilling to provide informed consent. The study aims to enrol 1000 patients by April 2016 across at least 20 European countries, and 10 000 patients by March 2020. Patients will undergo a comprehensive baseline assessment and will be followed up annually for up to 5 years with the goal of providing high-quality longitudinal data on outcomes, treatment patterns and quality of life. Data from the registry will be available in the form of annual reports. and will be disseminated in conference presentations and peer-reviewed publications. The European Bronchiectasis Registry aims to make a major contribution to understanding the natural history of the disease, as well as guiding evidence-based decision making and facilitating large randomised controlled trials.info:eu-repo/semantics/publishedVersio

Objective sputum colour assessment and clinical outcomes in bronchiectasis: data from the European Bronchiectasis Registry (EMBARC)

Background A validated 4-point sputum colour chart can be used to objectively evaluate the levels of airway inflammation in bronchiectasis patients. In the European Bronchiectasis Registry (EMBARC), we tested whether sputum colour would be associated with disease severity and clinical outcomes. Methods We used a prospective, observational registry of adults with bronchiectasis conducted in 31 countries. Patients who did not produce spontaneous sputum were excluded from the analysis. The Murray sputum colour chart was used at baseline and at follow-up visits. Key outcomes were frequency of exacerbations, hospitalisations for severe exacerbations and mortality during up to 5-year follow-up. Results 13 484 patients were included in the analysis. More purulent sputum was associated with lower forced expiratory volume in 1 s (FEV 1), worse quality of life, greater bacterial infection and a higher bronchiectasis severity index. Sputum colour was strongly associated with the risk of future exacerbations during follow-up. Compared to patients with mucoid sputum (reference group), patients with mucopurulent sputum experienced significantly more exacerbations (incident rate ratio (IRR) 1.29, 95% CI 1.22–1.38; p&lt;0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44–1.67; p&lt;0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52–2.39; p&lt;0.0001). Hospitalisations for severe exacerbations were also associated with increasing sputum colour with rate ratios, compared to patients with mucoid sputum, of 1.41 (95% CI 1.29–1.56; p&lt;0.0001), 1.98 (95% CI 1.77–2.21; p&lt;0.0001) and 3.05 (95% CI 2.25–4.14; p&lt;0.0001) for mucopurulent, purulent and severely purulent sputum, respectively. Mortality was significantly increased with increasing sputum purulence, hazard ratio 1.12 (95% CI 1.01–1.24; p=0.027), for each increment in sputum purulence. Conclusion Sputum colour is a simple marker of disease severity and future risk of exacerbations, severe exacerbations and mortality in patients with bronchiectasis.</p

Bronchiectasis and asthma:Data from the European Bronchiectasis Registry (EMBARC)

Background: Asthma is commonly reported in patients with a diagnosis of bronchiectasis. Objective: The aim of this study was to evaluate whether patients with bronchiectasis and asthma (BE+A) had a different clinical phenotype and different outcomes compared with patients with bronchiectasis without concomitant asthma. Methods: A prospective observational pan-European registry (European Multicentre Bronchiectasis Audit and Research Collaboration) enrolled patients across 28 countries. Adult patients with computed tomography–confirmed bronchiectasis were reviewed at baseline and annual follow-up visits using an electronic case report form. Asthma was diagnosed by the local investigator. Follow-up data were used to explore differences in exacerbation frequency between groups using a negative binomial regression model. Survival analysis used Cox proportional hazards regression. Results: Of 16,963 patients with bronchiectasis included for analysis, 5,267 (31.0%) had investigator-reported asthma. Patients with BE+A were younger, were more likely to be female and never smokers, and had a higher body mass index than patients with bronchiectasis without asthma. BE+A was associated with a higher prevalence of rhinosinusitis and nasal polyps as well as eosinophilia and Aspergillus sensitization. BE+A had similar microbiology but significantly lower severity of disease using the bronchiectasis severity index. Patients with BE+A were at increased risk of exacerbation after adjustment for disease severity and multiple confounders. Inhaled corticosteroid (ICS) use was associated with reduced mortality in patients with BE+A (adjusted hazard ratio 0.78, 95% CI 0.63-0.95) and reduced risk of hospitalization (rate ratio 0.67, 95% CI 0.67-0.86) compared with control subjects without asthma and not receiving ICSs. Conclusions: BE+A was common and was associated with an increased risk of exacerbations and improved outcomes with ICS use. Unexpectedly we identified significantly lower mortality in patients with BE+A.</p

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Management of early infection with Pseudomonas aeruginosa in adults with bronchiectasis: A survey of French pulmonologist's practices

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Bronchoalveolar lavage in hypersensitivity pneumonitis: a series of 139 patients.

International audienceHypersensitivity pneumonitis (HP) is characterized by a lymphocytic alveolitis, classically delineated by an increase of CD8+ lymphocytes, with an inversion of the CD4+/CD8+ ratio. The aim of this study is both to describe the yield and cell bronchoalveolar lavage (BAL) profile and to revisit the assumption of low BAL CD4/CD8 ratio in the diagnosis of HP. A multicentric study was conducted on 139 patients who fulfilled the standardized diagnostic criteria of HP, mainly affected by farmer's lung. Mean total cell count in BAL fluid was 594 ± 401.10(3) cells /ml. Prominent absolute lymphocytic alveolitis, moderate neutrophilia, and mild eosinophilia and mastocytosis were found. Mean CD4/CD8 ratio was 3.8 ± 6.1 (median 2.1). Thirty four percent of the patients showed lymphocytic CD8 alveolitis (ratio < 1). The CD4/CD8 ratio was not different between forms, etiologies of HP, and time elapsed since last antigen exposure, but was higher in women (p=0.02). BAL in HP shows high total cell and lymphocyte counts, moderate neutrophilia, and mild eosinophilia and mastocytosis. An absence of low CD4/CD8 ratio should not at all exclude diagnosis

Blood co-expression modules identify potential modifier genes of diabetes and lung function in cystic fibrosis

International audienceCystic fibrosis (CF) is a rare genetic disease that affects the respiratory and digestive systems. Lung disease is variable among CF patients and associated with the development of comorbidities and chronic infections. The rate of lung function deterioration depends not only on the type of mutations in CFTR, the disease-causing gene, but also on modifier genes. In the present study, we aimed to identify genes and pathways that (i) contribute to the pathogenesis of cystic fibrosis and (ii) modulate the associated comorbidities. We profiled blood samples in CF patients and healthy controls and analyzed RNA-seq data with Weighted Gene Correlation Network Analysis (WGCNA). Interestingly, lung function, body mass index, the presence of diabetes, and chronic P. aeruginosa infections correlated with four modules of co-expressed genes. Detailed inspection of networks and hub genes pointed to cell adhesion, leukocyte trafficking and production of reactive oxygen species as central mechanisms in lung function decline and cystic fibrosis-related diabetes. Of note, we showed that blood is an informative surrogate tissue to study the contribution of inflammation to lung disease and diabetes in CF patients. Finally, we provided evidence that WGCNA is useful to analyze-omic datasets in rare genetic diseases as patient cohorts are inevitably small

Hydroxychloroquine in Coronavirus Disease 2019 Patients: What Still Needs to Be Known About the Kinetics

International audienceDifferent dosage regimens of hydroxychloroquine are used to manage coronavirus disease 2019 (COVID-19) patients, without information on the pharmacokinetics in this population. Blood samples (n = 101) were collected from 57 COVID-19 patients for 7 days, and concentrations were compared with simulated kinetic profiles. Hydroxychloroquine exposure is low and cannot be predicted by other populations