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1.
Eur Respir J ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609097

RESUMO

BACKGROUND: International guidelines recommend airway clearance management as one of the important pillars of bronchiectasis treatment. However, the extent to which airway clearance is used for people with bronchiectasis in Europe is unclear. The aim of the study was to identify the use of airway clearance management in patients with bronchiectasis across different countries and factors influencing airway clearance use. METHODS: Prospective observational study using data from the EMBARC Registry between January 2015 and April 2022. Pre-specified options for airway clearance management were recorded, including airway clearance techniques, devices and use of mucoactive drugs. RESULTS: 16 723 people with bronchiectasis from 28 countries were included in the study. Mean age was 67 years (interquartile range 57-74 years, range 18-100 years) and 61% were females. Seventy-two percent of the participants reported daily sputum expectoration and 52% (95% CI 51-53%) of all participants reported using regular airway clearance management. Active cycle of breathing technique was used by 28% of the patients and airway clearance devices by 16% of participants. The frequency of airway clearance management and techniques used varied significantly between different countries. Patients who used airway clearance management had greater disease severity and worse symptoms, including a higher daily sputum volume compared to those who did not use it regularly. Mucoactive drugs were also more likely to be used in patients with more severe disease. Access to specialist respiratory physiotherapy was low throughout Europe, but particularly low in Eastern Europe. CONCLUSIONS: Only half of the people with bronchiectasis in Europe use airway clearance management. Use and access to devices, mucoactive drugs and specialist chest physiotherapy appears to be limited in many European countries.

2.
Eur Respir J ; 63(4)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38609095

RESUMO

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 (FEV1), 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<0.0001), while the rates were even higher for patients with purulent (IRR 1.55, 95% CI 1.44-1.67; p<0.0001) and severely purulent sputum (IRR 1.91, 95% CI 1.52-2.39; p<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<0.0001), 1.98 (95% CI 1.77-2.21; p<0.0001) and 3.05 (95% CI 2.25-4.14; p<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.


Assuntos
Bronquiectasia , Fosfatos de Cálcio , Escarro , Adulto , Humanos , Estudos Prospectivos , Escarro/microbiologia , Cor , Qualidade de Vida , Bronquiectasia/diagnóstico , Bronquiectasia/microbiologia , Sistema de Registros
3.
Artigo em Inglês | MEDLINE | ID: mdl-38635862

RESUMO

RATIONALE: Chest computed tomography -scans (CTs) are essential to diagnose and monitor bronchiectasis (BE). To date, little quantitative data is available about the nature and extent of structural lung abnormalities (SLA) on CTs of BE patients. OBJECTIVES: to investigate SLA on CTs of patients with bronchiectasis and the relationship of SLAs to clinical features using the European Bronchiectasis Registry (EMBARC) Methods: CTs from BE patients included in the EMBARC registry were analyzed using the validated Bronchiectasis Scoring Technique for CT (BEST-CT). BEST-CT subscores are expressed as % of total lung volume. Scored items are: atelectasis/consolidation (%ATCON), bronchiectasis with and without mucus plugging (%BEMP, %BEwMP), airway wall thickening (%AWT), mucus plugging (%MP), ground-glass opacities (%GGO), bullae (%BUL), airways and parenchyma (%A,%P). Four composite scores were calculated: Total BE (%TBE=%BEMP+%BEwMP), total MP (%TMP=%BEMP+%MP), total inflammatory changes (%TinF=%ATCON+%BEMP+%MP+%GGO) and total disease (%DIS= all but %A & %P).¬ Measurments and Main Results: CTs of 524 BE patients were analyzed. Mean (range) of subscores were: %TBE 4.6 (2.3-7.7), %TMP 4.2 (1.2-8.1), %TinF 8.3 (3.5-16.7) and %DIS 14.9 (9.1-25.9). BE associated with primary ciliary dyskinesia was associated with more SLA, while COPD was associated with less SLA. Lower FEV1, longer disease duration, Pseudomonas aeruginosa and NTM infection, and severe exacerbations were all independently associated with worse SLA. CONCLUSION: Patients with bronchiectasis have highly heterogeneous type and extent of structural lung abnormalities. Strong relationships between radiological disease and clinical features suggest CT analysis may be a useful tool for clinical phenotyping.

5.
Chest ; 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38309462

RESUMO

BACKGROUND: Inhaled antibiotics are recommended conditionally by international bronchiectasis guidelines for the treatment of patients with bronchiectasis, but results of individual studies are inconsistent. A previous meta-analysis demonstrated promising results regarding the efficacy and safety of inhaled antibiotics in bronchiectasis. Subsequent publications have supplemented the existing body of evidence further in this area. RESEARCH QUESTION: To what extent do inhaled antibiotics demonstrate both efficacy and safety as a treatment option for adults with bronchiectasis?. STUDY DESIGN AND METHODS: Systematic review and meta-analysis of randomized controlled trials of inhaled antibiotics in adult patients with bronchiectasis. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for eligible studies. Studies were included if they enrolled adults with bronchiectasis diagnosed by CT imaging and had a treatment duration of at least 4 weeks. The primary end point was exacerbation frequency, with additional key efficacy end points including severe exacerbations, bacterial load, symptoms, quality of life, and FEV1. Data were pooled through random-effects meta-analysis. RESULTS: Twenty studies involving 3,468 patients were included. Inhaled antibiotics were associated with reduced number of patients with exacerbations (risk ratio, 0.85; 95% CI, 0.75-0.96), a slight reduction in exacerbation frequency (rate ratio [RR], 0.78; 95% CI, 0.68-0.91), a probable reduction in the frequency of severe exacerbations (RR, 0.48; 95% CI, 0.31-0.74), and a likely slight increase in time to first exacerbation (hazard ratio, 0.80; 95% CI, 0.68-0.94). Inhaled antibiotics likely lead to a slight increase in the Quality of Life-Bronchiectasis respiratory symptom score (2.51; 95% CI, 0.44-4.31) and may reduce scores on the St. George's Respiratory Questionnaire (-3.13; 95% CI, -5.93 to -0.32). Bacterial load consistently was reduced, but FEV1 was not changed with treatment. Evidence suggests little to no difference in adverse effects between groups (OR, 0.99; 95% CI, 0.75-1.30). Antibiotic-resistant organisms likely were increased by treatment. INTERPRETATION: Inhaled antibiotics result in a slight reduction in exacerbations, a probable reduction in severe exacerbations, and a likely slight improvement in symptoms and quality of life in adults with bronchiectasis. TRIAL REGISTRY: International Prospective Register of Systematic Reviews; No.: CRD42023384694; URL: https://www.crd.york.ac.uk/prospero/.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38401857

RESUMO

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.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38271696

RESUMO

RATIONALE AND OBJECTIVE: Bronchiectasis and COPD are associated conditions but misdiagnosis is believed to be common. A recently published international consensus definition of bronchiectasis (BE) and COPD association: The ROSE criteria (radiological bronchiectasis(R), obstruction: FEV1/FVC ratio<0.7 (O), symptoms (S) and exposure:≥10 pack year smoking (E) allows objective diagnosis of the BE-COPD association. METHODS: Analysis of the EMBARC registry, a prospective observational study of patients with CT confirmed bronchiectasis from 28 countries. The ROSE criteria were used to objectively defined BE-COPD association. Key outcomes during up to 5-years follow-up were exacerbations, hospitalization and mortality. MEASUREMENT AND MAIN RESULTS: 16730 patients with bronchiectasis were included. 4336 had a co-diagnosis of COPD and these patients had more exacerbations, worse quality of life and higher severity scores. We observed marked overdiagnosis of COPD using the ROSE criteria: 22.2% of patients with a diagnosis of COPD did not have airflow obstruction and 31.9% did not have a history of ≥10 pack years smoking. Therefore the proportion meeting the ROSE criteria for COPD was 2157 (55.4%). Compared to patients without COPD, patients meeting ROSE criteria had increased risk of exacerbations and exacerbations resulting in hospitalisation during follow-up (IRR 1.25 95%CI 1.15-1.35 and 1.69 95%CI 1.51-1.90 respectively) but patients with a diagnosis of COPD who did not meet ROSE criteria also had increased risk of exacerbations. CONCLUSIONS: The label of COPD is often applied to bronchiectasis patients without objective evidence of airflow obstruction and smoking history. Patients with a clinical label of COPD have worse clinical outcomes.

8.
ERJ Open Res ; 10(1)2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38226061

RESUMO

Specialists caring for people with bronchiectasis recommend specialised nebulisers for inhaled antibiotics, but are often limited by availability and cost of nebulisation devices https://bit.ly/40FvFdZ.

9.
BMJ Open ; 13(8): e071906, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37562935

RESUMO

INTRODUCTION: Bronchiectasis is a long-term lung condition, with dilated bronchi, chronic inflammation, chronic infection and acute exacerbations. Recurrent exacerbations are associated with poorer clinical outcomes such as increased severity of lung disease, further exacerbations, hospitalisations, reduced quality of life and increased risk of death. Despite an increasing prevalence of bronchiectasis, there is a critical lack of high-quality studies into the disease and no treatments specifically approved for its treatment. This trial aims to establish whether inhaled dual bronchodilators (long acting beta agonist (LABA) and long acting muscarinic antagonist (LAMA)) taken as either a stand-alone therapy or in combination with inhaled corticosteroid (ICS) reduce the number of exacerbations of bronchiectasis requiring treatment with antibiotics during a 12 month treatment period. METHODS: This is a multicentre, pragmatic, double-blind, randomised controlled trial, incorporating an internal pilot and embedded economic evaluation. 600 adult patients (≥18 years) with CT confirmed bronchiectasis will be recruited and randomised to either inhaled dual therapy (LABA+LAMA), triple therapy (LABA+LAMA+ICS) or matched placebo, in a 2:2:1 ratio (respectively). The primary outcome is the number of protocol defined exacerbations requiring treatment with antibiotics during the 12 month treatment period. ETHICS AND DISSEMINATION: Favourable ethical opinion was received from the North East-Newcastle and North Tyneside 2 Research Ethics Committee (reference: 21/NE/0020). Results will be disseminated in peer-reviewed publications, at national and international conferences, in the NIHR Health Technology Assessments journal and to participants and the public (using lay language). TRIAL REGISTRATION NUMBER: ISRCTN15988757.


Assuntos
Bronquiectasia , Doença Pulmonar Obstrutiva Crônica , Adulto , Humanos , Broncodilatadores/uso terapêutico , Qualidade de Vida , Agonistas de Receptores Adrenérgicos beta 2 , Antagonistas Muscarínicos , Bronquiectasia/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Quimioterapia Combinada , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
11.
Lancet Respir Med ; 11(7): 637-649, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37105206

RESUMO

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. FUNDING: European Union-European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative. TRANSLATIONS: For the Arabic, French, German, Greek, Hebrew, Irish, Russian and Spanish translations of the abstract see Supplementary Materials section.


Assuntos
Bronquiectasia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Bronquiectasia/tratamento farmacológico , Estudos de Coortes , Progressão da Doença , Europa (Continente)/epidemiologia , Estudos Prospectivos , Sistema de Registros
13.
Nat Commun ; 14(1): 693, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36755044

RESUMO

We are currently witnessing transformative change for people with cystic fibrosis with the introduction of small molecule, mutation-specific drugs capable of restoring function of the defective protein, cystic fibrosis transmembrane conductance regulator (CFTR). However, despite being a single gene disorder, there are multiple cystic fibrosis-causing genetic variants; mutation-specific drugs are not suitable for all genetic variants and also do not correct all the multisystem clinical manifestations of the disease. For many, there will remain a need for improved treatments. Those patients with gene variants responsive to CFTR modulators may have found these therapies to be transformational; research is now focusing on safely reducing the burden of symptom-directed treatment. However, modulators are not available in all parts of the globe, an issue which is further widening existing health inequalities. For patients who are not suitable for- or do not have access to- modulator drugs, alternative approaches are progressing through the trials pipeline. There will be challenges encountered in design and implementation of these trials, for which the established global CF infrastructure is a major advantage. Here, the Cystic Fibrosis National Research Strategy Group of the UK NIHR Respiratory Translational Research Collaboration looks to the future of cystic fibrosis therapies and consider priorities for future research and development.


Assuntos
Fibrose Cística , Humanos , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Mutação , Terapia Genética
14.
Clin Infect Dis ; 76(10): 1854-1859, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-36763042

RESUMO

This is an account that should be heard of an important struggle: the struggle of a large group of experts who came together at the beginning of the COVID-19 pandemic to warn the world about the risk of airborne transmission and the consequences of ignoring it. We alerted the World Health Organization about the potential significance of the airborne transmission of SARS-CoV-2 and the urgent need to control it, but our concerns were dismissed. Here we describe how this happened and the consequences. We hope that by reporting this story we can raise awareness of the importance of interdisciplinary collaboration and the need to be open to new evidence, and to prevent it from happening again. Acknowledgement of an issue, and the emergence of new evidence related to it, is the first necessary step towards finding effective mitigation solutions.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Pandemias/prevenção & controle , Organização Mundial da Saúde , Sociedades
15.
Thorax ; 78(3): 309-312, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36627190

RESUMO

The diagnosis of non-tuberculous mycobacteria (NTM) is a particular challenge in people with cystic fibrosis. Current standard diagnostic approaches rely on serial sputum culture, which is resource demanding, dependent on patient expectoration and may be compromised by excessive decontamination, conventional bacterial overgrowth and masking by concomitant oral and nebulised antibiotics. An alternative rapid, reliable and inexpensive diagnostic method is therefore urgently needed. Serum of patients with Mycobacterium abscessus infection and chronic suppurative lung disease without NTM infection was tested against an array of novel synthetic mycolic acids, identical or similar to natural components of mycobacterial cell walls, and glycopeptidolipid (GPL)-core antigen, which has previously been investigated in Mycobacterium avium pulmonary infection. Diagnostic accuracy of individual antigens and combination of various antigens were calculated. An ELISA using individual trehalose dimycolates and GPL-core antigen was able to effectively distinguish serum from infected and non-infected individuals with a specificity of 88% and a sensitivity of up to 88%, which increased to 88% sensitivity and 93% specificity by combining several antigens in the test. These results suggest synthetic mycolic acid antigens, used individually or in combination with GPL-core antigen could be successfully used to distinguish patients with M. abscessus infection from disease controls.


Assuntos
Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Infecção por Mycobacterium avium-intracellulare , Humanos , Micobactérias não Tuberculosas , Ácidos Micólicos , Complexo Mycobacterium avium , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/complicações , Infecção por Mycobacterium avium-intracellulare/complicações , Infecção por Mycobacterium avium-intracellulare/diagnóstico , Fibrose Cística/complicações , Ensaio de Imunoadsorção Enzimática , Testes Sorológicos
16.
Clin Chest Med ; 43(1): 165-177, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35236556

RESUMO

Antibiotics are an essential component of the management of patients with bronchiectasis. This article reviews the role of antibiotics in the treatment of exacerbations, for maintenance therapy to reduce exacerbation frequency, and for eradicating potentially harmful organisms such as Pseudomonas aeruginosa.


Assuntos
Bronquiectasia , Antibacterianos/uso terapêutico , Bronquiectasia/tratamento farmacológico , Humanos
17.
Respir Med ; 192: 106728, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34998112

RESUMO

BACKGROUND: Inhaled antibiotics have been incorporated into contemporary European and British guidelines for bronchiectasis, yet no inhaled antibiotics have been approved in the United States or Europe for the treatment of bronchiectasis not related to cystic fibrosis. Pseudomonas aeruginosa infection is common in patients with bronchiectasis, contributing to a cycle of progressive inflammation, exacerbations, and airway remodelling. OBJECTIVE: The aim of the current study was to identify and evaluate published studies of inhaled tobramycin solution or powder in patients with bronchiectasis and P. aeruginosa infection not associated with cystic fibrosis. METHODS: A literature review was conducted utilising the PubMed and Cochrane databases. Studies published in the English language that reported safety and/or efficacy outcomes of inhaled tobramycin either alone or in combination with other antibiotics were included. RESULTS: Seven clinical trials published between 1999 and 2021 were identified that met inclusion criteria. Inhaled tobramycin therapy was effective in reducing P. aeruginosa microbial density in the sputum of patients with bronchiectasis. Several studies demonstrated favourable impacts on hospitalisations, number and severity of exacerbations, and symptoms. Other studies were underpowered for these clinical outcomes or were exploratory in nature. Although tobramycin was generally well tolerated, some evidence of treatment-associated wheezing was reported. CONCLUSIONS: In patients with bronchiectasis and chronic P. aeruginosa infection, inhaled tobramycin was effective in reducing the density of bacteria in sputum, which may be associated with additional clinical benefits. Definitive phase 3 trials of inhaled tobramycin in patients with bronchiectasis are indicated to determine clinical efficacy and long-term safety.


Assuntos
Bronquiectasia , Infecções por Pseudomonas , Administração por Inalação , Antibacterianos/uso terapêutico , Bronquiectasia/tratamento farmacológico , Bronquiectasia/microbiologia , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Tobramicina
18.
Am J Respir Crit Care Med ; 205(8): 894-902, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35050830

RESUMO

Rationale: Bronchiectasis is classically considered a neutrophilic disorder, but eosinophilic subtypes have recently been described. Objectives: To use multiple datasets available through the European Multicentre Bronchiectasis Audit and Research Collaboration to characterize eosinophilic bronchiectasis as a clinical entity focusing on the impact of eosinophils on bronchiectasis exacerbations. Methods: Patients were included from five countries to examine the relationships between blood eosinophil counts and clinical phenotypes after excluding coexisting asthma. 16S rRNA sequencing was used to examine relationships between eosinophil counts and the sputum microbiome. A post hoc analysis of the PROMIS (Inhaled Promixin in the Treatment of Non-Cystic Fibrosis Bronchiectasis) phase 2 trial was used to examine the impact of blood eosinophil counts on exacerbations in patients with Pseudomonas aeruginosa infection. Measurements and Main Results: A relationship between sputum and blood eosinophil counts was demonstrated in two cohorts. In analysis of 1,007 patients from five countries, 22.6% of patients had blood eosinophil counts of ⩾300 cells/µl. Counts of <100 cells/µl were associated with higher bronchiectasis severity and increased mortality. There was no clear relationship with exacerbations. Blood eosinophil counts of ⩾300 cells/µl were associated with both Streptococcus- and Pseudomonas-dominated microbiome profiles. To investigate the relationship of eosinophil counts with exacerbations after controlling for the confounding effects of infection, 144 patients were studied in a clinical trial after treatment with antipseudomonal antibiotics. Compared with patients with blood eosinophil counts of <100 cells/µl (reference), elevated eosinophil counts of 100-299 cells/µl (hazard ratio, 2.38; 95% confidence interval, 1.33-4.25; P = 0.003) and ⩾300 cells/µl (hazard ratio, 3.99; 95% confidence interval, 2.20-7.85; P < 0.0001) were associated with shorter time to exacerbation. Conclusions: Eosinophilic bronchiectasis affects approximately 20% of patients. After accounting for infection status, raised blood eosinophil counts are associated with shortened time to exacerbation.


Assuntos
Asma , Bronquiectasia , Asma/tratamento farmacológico , Bronquiectasia/tratamento farmacológico , Eosinófilos , Humanos , Contagem de Leucócitos , RNA Ribossômico 16S
19.
Lancet Respir Med ; 10(3): 298-306, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34570994

RESUMO

Bronchiectasis refers to both a clinical disease and a radiological appearance that has multiple causes and can be associated with a range of conditions. Disease heterogeneity and the absence of standardised definitions have hampered clinical trials of treatments for bronchiectasis and are important challenges in clinical practice. In view of the need for new therapies for non-cystic fibrosis bronchiectasis to reduce the disease burden, we established an international taskforce of experts to develop recommendations and definitions for clinically significant bronchiectasis in adults to facilitate the standardisation of terminology for clinical trials. Systematic reviews were used to inform discussions, and Delphi processes were used to achieve expert consensus. We prioritised criteria for the radiological diagnosis of bronchiectasis and suggest recommendations on the use and central reading of chest CT scans to confirm the presence of bronchiectasis for clinical trials. Furthermore, we developed a set of consensus statements concerning the definitions of clinical bronchiectasis and its specific signs and symptoms, as well as definitions for chronic bacterial infection and sustained culture conversion. The diagnosis of clinically significant bronchiectasis requires both clinical and radiological criteria, and these expert recommendations and proposals should help to optimise patient recruitment into clinical trials and allow reliable comparisons of treatment effects among different interventions for bronchiectasis. Our consensus proposals should also provide a framework for future research to further refine definitions and establish definitive guidance on the diagnosis of bronchiectasis.


Assuntos
Bronquiectasia , Adulto , Bronquiectasia/tratamento farmacológico , Consenso , Humanos , Tomografia Computadorizada por Raios X
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