206 results found
Hull RC, Huang JT, Barton AK, et al., 2021, Sputum Proteomics in non-Tuberculous Mycobacterial Lung Disease., Chest
BACKGROUND: Non-tuberculous mycobacterial (NTM) infections are difficult to diagnose and treat. Biomarkers to identify patients with active infection or at risk of disease progression would have clinical utility. Sputum is the most frequently used matrix for diagnosis of NTM lung disease. RESEARCH QUESTION: Can sputum proteomics be used to identify NTM associated inflammatory profiles in sputum? STUDY DESIGN AND METHODS: Patients with NTM lung disease and a matched cohort of patients with chronic obstructive pulmonary disease (COPD), bronchiectasis (BE) and cystic fibrosis (CF) without NTM lung disease were enrolled from two hospitals in the UK. Liquid chromatography-tandem mass spectrometry was used to identify proteomic biomarkers associated with underlying diagnosis (COPD, BE, CF), the presence of NTM lung disease defined by ATS/IDSA criteria and severity of NTM. A subset of patients receiving guideline concordant NTM treatment were studied to identify protein changes associated with treatment response. RESULTS: We analysed 95 sputum samples from 55 subjects (21 BE, 19 COPD, 15 CF). Underlying disease and infection with Pseudomonas aeruginosa were the strongest drivers of sputum protein profiles. Comparing protein abundance in COPD, BE and CF showed 12 proteins were upregulated in CF including MPO, AZU1, CTSG, CAT and RNASE3 with 21 proteins downregulated including SCGB1A1, IGFBP2, SFTPB, GC and CFD. Across CF, BE and COPD, NTM infection (n=15) was not associated with statistically significant differences in sputum protein profiles compared to those without NTM. 2 proteins associated with iron chelation were significantly downregulated in severe NTM disease. NTM treatment was associated with heterogeneous changes in sputum protein profile. NTM patients with a decrease in immune response proteins had a subjective symptomatic improvement. INTERPRETATION: Sputum proteomics identified candidate biomarkers of NTM severity and treatment response, however underlying lun
Mosgrove F, Haworth C, Loebinger M, et al., 2021, THE MICROBIOLOGY OF BRONCHIECTASIS EXACERBATIONS IN THE UK EMBARC REGISTRY AND IMPLICATIONS FOR PRESCRIBING IN PRIMARY CARE: A COHORT STUDY, Publisher: BMJ PUBLISHING GROUP, Pages: A41-A41, ISSN: 0040-6376
Housley GM, Peake S, Loebinger M, 2021, BREATHING PATTERN DYSFUNCTION IN PRIMARY CILIARY DYSKINESIA: MYTH OR REALITY?, Publisher: BMJ PUBLISHING GROUP, Pages: A130-A131, ISSN: 0040-6376
McLeese RH, Spinou A, Alfahl Z, et al., 2021, Psychometrics of health-related quality of life questionnaires in bronchiectasis: a systematic review and meta-analysis., Eur Respir J, Vol: 58
INTRODUCTION: Understanding the psychometric properties of health-related quality of life (HRQoL) questionnaires can help inform selection in clinical trials. Our objective was to assess the psychometric properties of HRQoL questionnaires in bronchiectasis using a systematic review and meta-analysis of the literature. METHODS: A literature search was conducted. HRQoL questionnaires were assessed for psychometric properties (reliability, validity, minimal clinically important difference (MCID) and floor/ceiling effects). Meta-analyses assessed the associations of HRQoL with clinical measures and responsiveness of HRQoL in clinical trials. RESULTS: 166 studies and 12 HRQoL questionnaires were included. The Bronchiectasis Health Questionnaire (BHQ), Leicester Cough Questionnaire (LCQ), Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) and Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) had good internal consistency in all domains reported (Cronbach's α≥0.7) across all studies, and the Quality of Life-Bronchiectasis (QOL-B), St George's Respiratory Questionnaire (SGRQ), Chronic Respiratory Disease Questionnaire (CRDQ) and Seattle Obstructive Lung Disease Questionnaire (SOLQ) had good internal consistency in all domains in the majority of (but not all) studies. BHQ, SGRQ, LCQ and CAT had good test-retest reliability in all domains reported (intraclass correlation coefficient ≥0.7) across all studies, and QOL-B, CRDQ and SOLQ had good test-retest reliability in all domains in the majority of (but not all) studies. HRQoL questionnaires were able to discriminate between demographics, important markers of clinical status, disease severity, exacerbations and bacteriology. For HRQoL responsiveness, there was a difference between the treatment and placebo effect. CONCLUSIONS: SGRQ was the most widely used HRQoL questionnaire in bronchiectasis studies and it had good psychometric properties; however, good psychometric data are emergin
Kumar K, Loebinger MR, 2021, Nontuberculous Mycobacterial Pulmonary Disease: Clinical Epidemiologic Features, Risk Factors, and Diagnosis., Chest
Nontuberculous mycobacterial pulmonary disease (NTM-PD) continues to impose a significant clinical burden of disease on susceptible patients. The incidence of NTM-PD is rising globally, but it remains a condition that is challenging to diagnose and treat effectively. This review provides an update on the global epidemiologic features, risk factors, and diagnostic considerations associated with the management of NTM-PD.
Periselneris J, Schelenz S, Loebinger M, et al., 2021, Bronchiectasis severity correlates with outcome in patients with primary antibody deficiency, THORAX, Vol: 76, Pages: 1036-1039, ISSN: 0040-6376
Aliberti S, Goeminne PC, O'Donnell AE, et al., 2021, Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials: international consensus recommendations., Lancet Respir Med
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.
Nwankwo L, McLaren K, Donovan J, et al., 2021, Utilisation of remote capillary blood testing in an outpatient clinic setting to improve shared decision making and patient and clinician experience: a validation and pilot study, BMJ Open Quality, Vol: 10, Pages: 1-11, ISSN: 2399-6641
Background In a tertiary respiratory centre, large cohorts of patients are managed in an outpatient setting and require blood tests to monitor disease activity and organ toxicity. This requires either visits to tertiary centres for phlebotomy and physician review or utilisation of primary care services.Objectives This study aims to validate remote capillary blood testing in an outpatient setting and analyse impact on clinical pathways.Methods A single-centre prospective cross-sectional validation and parallel observational study was performed. Remote finger prick capillary blood testing was validated compared with local standard venesection using comparative statistical analysis: paired t-test, correlation and Bland-Altman. Capillary was considered interchangeable with venous samples if all three criteria were met: non-significant paired t-test (ie, p>0.05), Pearson’s correlation coefficient (r)>0.8% and 95% of tests within 10% difference through Bland-Altman (limits of agreement). In parallel, current clinical pathways including phlebotomy practice were analysed over 4 weeks to review test predictability. A subsequent pilot cohort study analysed potential impact of remote capillary blood sampling on shared decision making. A final implementation phase ensued to embed the service into clinical pathways within the institution.Results 117 paired capillary and venous blood samples were prospectively analysed. Interchangeability with venous blood was seen with glycated haemoglobin (%), total protein and C reactive protein. Further tests, although not interchangeable, are likely useful to enable longitudinal remote monitoring (eg, liver function and total IgE). 65% of outpatient clinic blood tests were predictable with 16% of patients requiring further follow-up. Patient and clinician-reported improvement in shared decision making given contemporaneous blood test results was observed.Conclusions Remote capillary blood sampling can be used accurately fo
Adeloye D, Elneima O, Daines L, et al., 2021, The long-term sequelae of COVID-19: an international consensus on research priorities for patients with pre-existing and new-onset airways disease., Lancet Respir Med
Persistent ill health after acute COVID-19-referred to as long COVID, the post-acute COVID-19 syndrome, or the post-COVID-19 condition-has emerged as a major concern. We undertook an international consensus exercise to identify research priorities with the aim of understanding the long-term effects of acute COVID-19, with a focus on people with pre-existing airways disease and the occurrence of new-onset airways disease and associated symptoms. 202 international experts were invited to submit a minimum of three research ideas. After a two-phase internal review process, a final list of 98 research topics was scored by 48 experts. Patients with pre-existing or post-COVID-19 airways disease contributed to the exercise by weighting selected criteria. The highest-ranked research idea focused on investigation of the relationship between prognostic scores at hospital admission and morbidity at 3 months and 12 months after hospital discharge in patients with and without pre-existing airways disease. High priority was also assigned to comparisons of the prevalence and severity of post-COVID-19 fatigue, sarcopenia, anxiety, depression, and risk of future cardiovascular complications in patients with and without pre-existing airways disease. Our approach has enabled development of a set of priorities that could inform future research studies and funding decisions. This prioritisation process could also be adapted to other, non-respiratory aspects of long COVID.
Jose RJ, Loebinger MR, 2021, Clinical and Radiological Phenotypes and Endotypes, SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 42, Pages: 549-555, ISSN: 1069-3424
Shoemark A, Rubbo B, Legendre M, et al., 2021, Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia, EUROPEAN RESPIRATORY JOURNAL, Vol: 58, ISSN: 0903-1936
van Ingen J, Aliberti S, Andrejak C, et al., 2021, Management of Drug Toxicity in Mycobacterium avium Complex Pulmonary Disease: An Expert Panel Survey, CLINICAL INFECTIOUS DISEASES, Vol: 73, Pages: E256-E259, ISSN: 1058-4838
Rademacher J, Dettmer S, Fuge J, et al., 2021, The Primary Ciliary Dyskinesia Computed Tomography Score in Adults with Bronchiectasis: A Derivation und Validation Study, RESPIRATION, Vol: 100, Pages: 499-509, ISSN: 0025-7931
De Soyza A, Mawson P, Hill AT, et al., 2021, BronchUK: protocol for an observational cohort study and biobank in bronchiectasis, ERJ OPEN RESEARCH, Vol: 7
Lipman M, Kunst H, Loebinger MR, et al., 2021, Non tuberculous mycobacteria pulmonary disease: patients and clinicians working together to improve the evidence base for care., Int J Infect Dis
Non-tuberculous mycobacterial pulmonary disease is on the rise globally. It is often missed, and causes significant morbidity and even mortality. Here, members of a clinical research network and a patient support group discuss some of the current key issues in NTM management. In addition to the need for research into epidemiology, immunology and treatment, we recommend greater use of patient and clinician networks to: (i) educate primary and secondary care clinicians to develop a high index of suspicion when investigating and treating at risk populations. (ii) promote a multidisciplinary team. (iii) promote shared patient-clinician decision making throughout care. (iv) incorporate use of patient self-report measures to assess progress and outcomes. (v) increase education of patients on their illness and its management. (vi) recruit patients into research projects and registries to improve the clinical evidence base. (vii) increase co-production of research with key stakeholders such as patients and their families, using expert patients and patient groups. (viii) understand more about the psychological, social and economic consequences of the disease.
Cuthbertson L, Felton I, James P, et al., 2021, The fungal airway microbiome in cystic fibrosis and non-cystic fibrosis bronchiectasis, Journal of Cystic Fibrosis, Vol: 20, Pages: 295-302, ISSN: 1569-1993
BackgroundThe prevalence of fungal disease in cystic fibrosis (CF) and non-CF bronchiectasis is increasing and the clinical spectrum is widening. Poor sensitivity and a lack of standard diagnostic criteria renders interpretation of culture results challenging. In order to develop effective management strategies, a more accurate and comprehensive understanding of the airways fungal microbiome is required. The study aimed to use DNA sequences from sputum to assess the load and diversity of fungi in adults with CF and non-CF bronchiectasis.MethodsNext generation sequencing of the ITS2 region was used to examine fungal community composition (n = 176) by disease and underlying clinical subgroups including allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, non-tuberculous mycobacteria, and fungal bronchitis. Patients with no known active fungal disease were included as disease controls.ResultsITS2 sequencing greatly increased the detection of fungi from sputum. In patients with CF fungal diversity was lower, while burden was higher than those with non-CF bronchiectasis. The most common operational taxonomic unit (OTU) in patients with CF was Candida parapsilosis (20.4%), whereas in non-CF bronchiectasis sputum Candida albicans (21.8%) was most common. CF patients with overt fungal bronchitis were dominated by Aspergillus spp., Exophiala spp., Candida parapsilosis or Scedosporium spp.ConclusionThis study provides a framework to more accurately characterize the extended spectrum of fungal airways diseases in adult suppurative lung diseases.
Loebinger MR, Polverino E, Chalmers JD, et al., 2021, Efficacy and safety of TOBI Podhaler in Pseudomonas aeruginosa-infected bronchiectasis patients: iBEST study, EUROPEAN RESPIRATORY JOURNAL, Vol: 57, ISSN: 0903-1936
Chalmers JD, Haworth CS, Metersky ML, et al., 2020, Phase 2 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 383, Pages: 2127-2137, ISSN: 0028-4793
O'Neill K, Ferguson K, Cosgrove D, et al., 2020, Multiple Breath Washout (MBW) in bronchiectasis clinical trials – Is it feasible?, European Respiratory Journal, Vol: 6, Pages: 1-10, ISSN: 0903-1936
Background: Evaluation of Multiple Breath Washout (MBW) set-up including staff training, certification and central “over-reading” for data quality control is essential to determine the feasibility of MBW in future bronchiectasis studies. Aims: To assess the outcomes of a MBW training, certification and central over-reading programme. Methods: MBW training and certification was conducted in European sites collecting LCI data in the BronchUK clinimetrics and/or i-BEST-1 studies. The blended training programme included the use of an eLearning tool and a 1-day face-to-face session. Sites submitted MBW data to trained central over-readers who determined validity and quality. Results: Thirteen training days were delivered to 56 participants from 22 sites. 18/22 (82%) were MBW naïve. Participant knowledge and confidence increased significantly (p<0.001). By the end of the study recruitment, 15/22 sites (68%) had completed certification with a mean (range) time since training of 6.2 (3-14) months. In the BronchUK clinimetrics study, 468/589 (79%) tests met45 the quality criteria following central over-reading, compared with 137/236 (58%) tests in the i-BEST-1 study. Conclusions: LCI is feasible in a bronchiectasis multicentre clinical trial setting however, consideration of site experience in terms of training as well as assessment of skill drift and the need for re-training may be important to reduce time to certification and optimise data quality. Longer times to certification, a higher percentage of naive sites and patients with worse lung function may have contributed to the lower success rate in the i-BEST-1 study.
Doyle OM, van der Laan R, Obradovic M, et al., 2020, Identification of potentially undiagnosed patients with nontuberculous mycobacteria lung disease using machine learning applied to primary care data in the UK, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, Pages: S879-S879, ISSN: 0903-1936
Hughes D, Cuthbertson L, Price H, et al., 2020, PSEUDOMONAS AERUGINOSA IMPAIRS GROWTH OF ASPERGILLUS FROM CF AIRWAY SAMPLES, Publisher: WILEY, Pages: S153-S153, ISSN: 8755-6863
Loebinger M, Aliberti S, Menendez R, et al., 2020, Alpha-1 antitrypsin deficiency in patients with bronchiectasis: data from the European Bronchiectasis Registry EMBARC, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Mitchelmore P, Polverino E, Rademacher J, et al., 2020, Immunodeficiency associated bronchiectasis in the European Bronchiectasis Registry (EMBARC), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Chalmers JD, Haworth C, Metersky M, et al., 2020, Late Breaking Abstract - Efficacy of DPP1 inhibition with brensocatib in subgroups of patients with bronchiectasis-the WILLOW study, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Wheway G, Legebeke J, Carr SB, et al., 2020, Primary ciliary dyskinesia and non-CF bronchiectasis Project, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Spinou A, Aliberti S, Menendez R, et al., 2020, Airway clearance techniques in patients with bronchiectasis. Data from the EMBARC Registry, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Loebinger M, Polverino E, Blasi F, et al., 2020, Efficacy of inhaled dry powder tobramycin (TOBI Podhaler) in P. aeruginosa infected patients with bronchiectasis - iBEST study, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Shoemark A, Finch S, Torres A, et al., 2020, Sex related differences in aetiology, severity and quality of life in bronchiectasis: data from the EMBARC, EMBARC-India and Australian bronchiectasis registries, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Gao Y, Lonergan M, Abo-Leyah H, et al., 2020, Placebo effects in pharmaceutical clinical trials in bronchiectasis: an EMBARC study, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Carreto L, Morrison M, Donovan J, et al., 2020, Utility of routine screening for alpha-1 antitrypsin deficiency in patients with bronchiectasis, THORAX, Vol: 75, Pages: 592-593, ISSN: 0040-6376
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.