227 results found
Kumar K, Loebinger MR, 2022, Response., Chest, Vol: 162
Davies J, Hughes D, Rosenthal M, et al., 2022, An invisible threat? Aspergillus positive cultures and co-infecting bacteria in airway sample, Journal of Cystic Fibrosis, ISSN: 1569-1993
BackgroundAspergillus fumigatus (Af) infection is associated with poor lung health in chronic suppurative lung diseases but often goes undetected. We hypothesised that inhibition of Af growth by Pseudomonas aeruginosa (Pa) increases the frequency of false-negative Af culture in co-infected people. Using a substantial group of cystic fibrosis (CF) airway samples, we assessed the relationship between Af and bacterial pathogens, additionally comparing fungal culture with next-generation sequencing.MethodsFrequency of co-culture was assessed for 44,554 sputum/BAL cultures, from 1,367 CF patients between the years 2010–2020. In a subgroup, Internal Transcribed Spacer-2 (ITS2) fungal sequencing was used to determine sequencing-positive, culture-negative (S+/C-) rates.ResultsPa+ samples were nearly 40% less likely (P<0.0001) than Pa- samples to culture Af, an effect that was also seen with some other Gram-negative isolates. This impact varied with Pa density and appeared to be moderated by Staphylococcus aureus co-infection. Sequencing identified Af-S+/C- for 40.1% of tested sputa. Samples with Pa had higher rates of Af-S+/C- (49.3%) than those without (35.7%; RR 1.38 [1.02–1.93], P<0.05). Af-S+/C- rate was not changed by other common bacterial infections. Pa did not affect the S+/C- rates of Candida, Exophiala or Scedosporium.ConclusionsPa/ Af co-positive cultures are less common than expected in CF. Our findings suggest an Af-positive culture is less likely in the presence of Pa. Interpretation of negative cultures should be cautious, particularly in Pa-positive samples, and a companion molecular diagnostic could be useful. Further work investigating mechanisms, alternative detection techniques and other chronic suppurative lung diseases is needed.
Kumar K, Loebinger MR, Ghafur S, 2022, The role of wirelessly observed therapy in improving treatment adherence., Future Healthc J, Vol: 9, Pages: 179-182, ISSN: 2514-6645
Wirelessly observed therapy (WOT) offers a novel way of monitoring treatment adherence. In this article, we provide an overview of how this technology works and discuss the evidence for its clinical effectiveness in tuberculosis, hepatitis C virus infection, mental health and cardiovascular disease. We consider the acceptability of WOT to patients as well as potential issues relating to patient autonomy and data protection. We highlight the current limited data on its economic impact and reflect on its future role in patient care.
Shoemark A, Griffin H, Wheway G, et al., 2022, Genome sequencing reveals underdiagnosis of primary ciliary dyskinesia in bronchiectasis., Eur Respir J
BACKGROUND: Bronchiectasis can result from infectious, genetic, immunological and allergic causes. 60-80% cases are idiopathic, but a well-recognised genetic cause is the motile ciliopathy, primary ciliary dyskinesia (PCD). Diagnosis of PCD has management implications including addressing co-morbidities, implementing genetic and fertility counselling and future access to PCD-specific treatments. Diagnostic testing can be complex, however PCD genetic testing is rapidly moving from research into clinical diagnostics and would confirm the cause of bronchiectasis. METHODS: This observational study used genetic data from severe bronchiectasis patients recruited to the UK 100,000 Genomes Project and patients referred for gene panel testing within a tertiary respiratory hospital, Patients referred for genetic testing due to clinical suspicion of PCD were excluded from both analyses. Data was accessed from the British Thoracic Society audit, to investigate whether motile ciliopathies are underdiagnosed in people with bronchiectasis in the UK. RESULTS: Pathogenic or likely pathogenic variants were identified in motile ciliopathy genes in 17/142 (12%) individuals by whole genome sequencing. Similarly in a single centre with access to pathological diagnostic facilities, 5-10% patients received a PCD diagnosis by gene panel, often linked to normal/inconclusive nasal nitric oxide and cilia functional test results. In 4,898 audited patients with bronchiectasis, <2% were tested for PCD and <1% received genetic testing. CONCLUSIONS: PCD is underdiagnosed as a cause of bronchiectasis. Increased uptake of genetic testing may help to identify bronchiectasis due to motile ciliopathies and ensure appropriate management.
Bottier M, Delgado L, Shuttleworth MK, et al., 2022, Characterization of Ciliary Function in Bronchiectasis (EMBARC-BRIDGE Study), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Hull RC, Huang JTJ, Barton AK, et al., 2022, Sputum Proteomics in Nontuberculous Mycobacterial Lung Disease., Chest, Vol: 161, Pages: 1180-1191
BACKGROUND: Nontuberculous 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 the 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 COPD, bronchiectasis (BE), and cystic fibrosis (CF) without NTM lung disease were enrolled from two hospitals in the United Kingdom. Liquid chromatography-tandem mass spectrometry was used to identify proteomic biomarkers associated with underlying diagnosis (COPD, BE, and CF), the presence of NTM lung disease defined according to American Thoracic Society/Infectious Diseases Society of America 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: This study analyzed 95 sputum samples from 55 subjects (BE, n = 21; COPD, n = 19; CF, n = 15). Underlying disease and infection with Pseudomonas aeruginosa were the strongest drivers of sputum protein profiles. Comparing protein abundance in COPD, BE, and CF found that 12 proteins were upregulated in CF compared with COPD, 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 with those without NTM. Two proteins associated with iron chelation were significantly downregulated in severe NTM disease. NTM treatment was associated with heterogeneous changes in the sputum protein profile. Patients with NTM and a decrease in immune response proteins had a subjective symptomatic improve
O'Neill K, Lakshmipathy GR, Neely C, et al., 2022, Multiple Breath Washout Outcome Measures in Adults with Bronchiectasis., Ann Am Thorac Soc
RATIONALE: Lung Clearance index (LCI) has good intra-visit repeatability with better sensitivity in detecting lung disease on CT scan compared to Forced Expiratory Volume in 1 second (FEV1) in adults with bronchiectasis. Alternative multiple breath washout (MBW) parameters have not been systematically studied in bronchiectasis. OBJECTIVES: To determine the validity, repeatability, sensitivity, specificity and feasibility of standard LCI (LCI2.5), shortened LCI (LCI5.0), ScondVT and SacinVT in a cross-sectional observational cohort of adults with bronchiectasis. METHODS: Cross-sectional MBN2W data (Exhalyzer® D) from 132 patients with bronchiectasis across 5 UK centres (Bronch-UK Clinimetrics study) and 88 healthy controls were analysed. RESULTS: Within test repeatability (mean CV%) was <5% for both LCI2.5 and LCI5.0 in patients with bronchiectasis and there was no difference in mean CV% in LCI2.5 and LCI5.0 in patients with bronchiectasis compared to healthy volunteers. Moderate strength correlations were seen between FEV1 and LCI2.5 (r=-0.54), LCI5.0 (r=-0.53), ScondVT (r=-0.35) and SacinVT z-scores (r=-0.38). The proportion of subjects with abnormal MBW (>2 z-score) but normal FEV1 (<-2 z-score) was 42% (LCI2.5) and 36% (LCI5.0). Overall results from the receiver operator characteristic curve (AUCROC) indicated that LCI2.5 had greatest combined sensitivity and specificity to discriminate between bronchiectasis and control subjects, followed by LCI5.0, FEV1 and ScondVT z-scores. There was a 57% time saving with LCI5.0. CONCLUSIONS: LCI2.5 and LCI5.0 had good within test repeatability and superior sensitivity compared with spirometry measures, in differentiating between health and bronchiectasis disease. LCI5.0 is shorter and more feasible than LCI2.5. Clinical trial registered with ClinicalTrials.gov (NCT02468271).
Shoemark A, Shteinberg M, De Soyza A, et al., 2022, Characterization of Eosinophilic Bronchiectasis A European Multicohort Study, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 205, Pages: 894-902, ISSN: 1073-449X
Meldrum OW, Belchamber KBR, Chichirelo-Konstantynovych KD, et al., 2022, ERS International Congress 2021: highlights from the Respiratory Infections Assembly, ERJ OPEN RESEARCH, Vol: 8
Kumar K, Daley CL, Griffith DE, et al., 2022, Management of Mycobacterium avium complex and Mycobacterium abscessus pulmonary disease: therapeutic advances and emerging treatments, EUROPEAN RESPIRATORY REVIEW, Vol: 31, ISSN: 0905-9180
Halbeisen FS, Pedersen ESL, Goutaki M, et al., 2022, Lung function from school age to adulthood in primary ciliary dyskinesia., Eur Respir J
Primary ciliary dyskinesia (PCD) presents with symptoms early in life and the disease course may be progressive, but longitudinal data on lung function are scarce. This multinational cohort study describes lung function trajectories in children, adolescents, and young adults with PCD. We analysed data from 486 patients with repeated lung function measurements obtained between the age of 6 and 24 years from the international PCD Cohort (iPCD) and calculated z-scores for forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC ratio using the Global Lung Function Initiative 2012 references. We described baseline lung function and change of lung function over time and described their associations with possible determinants in mixed-effects linear regression models. Overall, FEV1, FVC, and FEV1/FVC z-scores declined over time (average crude annual FEV1 decline was -0.07 z-scores) but not at the same rate for all patients. FEV1 z-scores improved over time in 21% of patients, remained stable in 40% and declined in 39%. Low BMI was associated with poor baseline lung function and with further decline. Results differed by country and ultrastructural defect, but we found no evidence of differences by sex, calendar year of diagnosis, age at diagnosis, diagnostic certainty, or laterality defect. Our study shows that on average lung function in PCD declines throughout the entire period of lung growth, from childhood to young adult age, even among patients treated in specialised centres. It is essential to develop strategies to reverse this tendency and improve prognosis.
Kumar K, Loebinger MR, 2022, Nontuberculous Mycobacterial Pulmonary Disease: Clinical Epidemiologic Features, Risk Factors, and Diagnosis The Nontuberculous Mycobacterial Series, CHEST, Vol: 161, Pages: 637-646, ISSN: 0012-3692
Aliberti S, Goeminne PC, O'Donnell AE, et al., 2022, Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials: international consensus recommendations, LANCET RESPIRATORY MEDICINE, Vol: 10, Pages: 298-306, ISSN: 2213-2600
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, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 113, Pages: S73-S77, ISSN: 1201-9712
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 RESPIRATORY MEDICINE, Vol: 9, Pages: 1467-1478, ISSN: 2213-2600
Macfarlane L, Kumar K, Scoones T, et al., 2021, Diagnosis and management of non-cystic fibrosis bronchiectasis, CLINICAL MEDICINE, Vol: 21, Pages: E571-E577, ISSN: 1470-2118
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
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
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, EUROPEAN RESPIRATORY JOURNAL, Vol: 58, ISSN: 0903-1936
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
Hull R, Huang JT-J, Dicker A, et al., 2021, Sputum proteomics of CF, BE and COPD with or without NTM infections, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Aliberti S, Manendez R, Blasi F, et al., 2021, Deteriorating heath status in bronchiectasis : longitudinal data from the EMBARC registry, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Thomson RM, Waterer G, Loebinger MR, et al., 2021, Use of inhaled GM-CSF in treatment-refractory NTM infection. An open-label, exploratory clinical trial, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Polverino E, Chalmers JD, Aliberti S, et al., 2021, Inhaled corticosteroids use in patients with bronchiectasis: Data from the EMBARC registry, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Goeminne P, Burgel P-R, Shteinberg M, et al., 2021, Quality of care in bronchiectasis using the European Respiratory Society Guidelines as a reference standard- data from the EMBARC registry, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Shoemark A, Shteinberg M, De Soyza A, et al., 2021, Characterisation of eosinophilic bronchiectasis: A European multicohort study, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Shteinberg M, Polverino E, Burgel P-R, et al., 2021, The prevalence and impact of autoantibodies among people with bronchiectasis: a data analysis of the EMBARC registry, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Shteinberg M, Polverino E, Burgel P-R, et al., 2021, The microbiology of stable bronchiectasis: data from the EMBARC bronchiectasis registry, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Alfahl Z, Einarsson GG, O'Neill K, et al., 2021, Changes in sputum bacterial density in people with bronchiectasis: BRONCH UK Study data, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
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
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