Publications
318 results found
Carr SB, Leadbetter J, Caine N, et al., 2018, FIVE-YEAR POST-AUTHORISATION SAFETY STUDY OF INHALED MANNITOL IN THE UK, Publisher: WILEY, Pages: 332-332, ISSN: 8755-6863
Bessonova L, Volkova N, Higgins M, et al., 2018, Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor, Thorax, Vol: 73, Pages: 731-740, ISSN: 0040-6376
Background Ivacaftor is the first cystic fibrosis transmembrane conductance regulator (CFTR) modulator demonstrating clinical benefit in patients with cystic fibrosis (CF). As ivacaftor is intended for chronic, lifelong use, understanding long-term effects is important for patients and healthcare providers.Objective This ongoing, observational, postapproval safety study evaluates clinical outcomes and disease progression in ivacaftor-treated patients using data from the US and the UK CF registries following commercial availability.Methods Annual analyses compare ivacaftor-treated and untreated matched comparator patients for: risks of death, transplantation, hospitalisation, pulmonary exacerbation; prevalence of CF-related complications and microorganisms and lung function changes in a subset of patients who initiated ivacaftor in the first year of commercial availability. Results from the 2014 analyses (2 and 3 years following commercial availability in the UK and USA, respectively) are presented here.Results Analyses included 1256 ivacaftor-treated and 6200 comparator patients from the USA and 411 ivacaftor-treated and 2069 comparator patients from the UK. No new safety concerns were identified based on the evaluation of clinical outcomes included in the analyses. As part of safety evaluations, ivacaftor-treated US patients were observed to have significantly lower risks of death (0.6% vs 1.6%, p=0.0110), transplantation (0.2% vs 1.1%, p=0.0017), hospitalisation (27.5% vs 43.1%, p<0.0001) and pulmonary exacerbation (27.8% vs 43.3%, p<0.0001) relative to comparators; trends were similar in the UK. In both registries, ivacaftor-treated patients had a lower prevalence of CF-related complications and select microorganisms and had better preserved lung function.Conclusions While general limitations of observational research apply, analyses revealed favourable results for clinically important outcomes among ivacaftor-treated patients, adding to the growing body of
Boyle M, Moore JE, Whitehouse JL, et al., 2018, Laboratory Diagnosis and Characterization of Fungal Disease in Patients with Cystic Fibrosis (CF): A Survey of Current UK Practice in a Cohort of Clinical Microbiology Laboratories, MYCOPATHOLOGIA, Vol: 183, Pages: 723-729, ISSN: 0301-486X
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- Citations: 7
Bilton D, Caine N, Cunningham S, et al., 2018, Use of a rare disease patient registry in long-term post-authorisation drug studies: a model for collaboration with industry, LANCET RESPIRATORY MEDICINE, Vol: 6, Pages: 495-496, ISSN: 2213-2600
Stephenson AL, Bilton D, 2018, The impact of National Cystic Fibrosis Registries: A review series, JOURNAL OF CYSTIC FIBROSIS, Vol: 17, Pages: 287-288, ISSN: 1569-1993
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- Citations: 4
Keogh RH, Szczesniak R, Taylor-Robinson D, et al., 2018, Up-to-date and projected estimates of survival for people with cystic fibrosis using baseline characteristics: A longitudinal study using UK patient registry data, JOURNAL OF CYSTIC FIBROSIS, Vol: 17, Pages: 218-227, ISSN: 1569-1993
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- Citations: 120
Hippolyte SS, Simmonds NJ, Bilton D, et al., 2017, DIABETES AND PSEUDOMONAS, A TERRIBLE COMBINATION? EXAMINING THE UK CYSTIC FIBROSIS REGISTRY FOR A SEX DIFFERENCE IN OUTCOMES (2008-2013), Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A2-A3, ISSN: 0040-6376
Hippolyte SS, Simmonds NJ, Bilton D, et al., 2017, ARE GIRLS ALWAYS THINNER THAN BOYS? USING UK CYSTIC FIBROSIS (CF) REGISTRY DATA (2008-2013) TO EXAMINE WEIGHT CHANGES BETWEEN THE SEXES FROM CHILDHOOD AND BEYOND, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A76-A77, ISSN: 0040-6376
Macdougall A, Archangelidi O, Cullinan P, et al., 2017, EARLY GROWTH TRAJECTORIES IN CYSTIC FIBROSIS, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A55-A56, ISSN: 0040-6376
Bilton D, 2017, News, JOURNAL OF CYSTIC FIBROSIS, Vol: 16, Pages: 651-652, ISSN: 1569-1993
Plant BJ, Downey DG, Eustace JA, et al., 2017, A treatment evaluator tool to monitor the real-world effectiveness of inhaled aztreonam lysine in cystic fibrosis, JOURNAL OF CYSTIC FIBROSIS, Vol: 16, Pages: 695-701, ISSN: 1569-1993
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- Citations: 3
Taylor-Robinson D, Archangelidi O, Carr SB, et al., 2017, Data resource profile: the UK Cystic Fibrosis Registry, International Journal of Epidemiology, Vol: 47, Pages: 9-10e, ISSN: 1464-3685
Volkova N, Bessonova L, Higgins M, et al., 2017, REAL-WORLD OUTCOMES IN PATIENTS WITH CF TREATED WITH IVACAFTOR: 2015 US AND UK CF REGISTRY ANALYSES, Publisher: WILEY, Pages: S407-S407, ISSN: 8755-6863
Volkova N, Bessonova L, Higgins M, et al., 2017, DISEASE PROGRESSION IN PATIENTS WITH CF TREATED WITH IVACAFTOR: ANALYSES OF REAL-WORLD DATA FROM THE US AND UK CF REGISTRIES, Publisher: WILEY, Pages: S407-S407, ISSN: 8755-6863
Bosch B, Bilton D, Sosnay P, et al., 2017, Ethnicity impacts the cystic fibrosis diagnosis: A note of caution, JOURNAL OF CYSTIC FIBROSIS, Vol: 16, Pages: 488-491, ISSN: 1569-1993
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- Citations: 25
Hilliam Y, Moore MP, Lamont IL, et al., 2017, Pseudomonas aeruginosa adaptation and diversification in the non-cystic fibrosis bronchiectasis lung, European Respiratory Journal, Vol: 49, Pages: 1-8, ISSN: 0903-1936
To characterise Pseudomonas aeruginosa populations during chronic lung infections of non-cystic fibrosis bronchiectasis patients, we used whole-genome sequencing to 1) assess the diversity of P. aeruginosa and the prevalence of multilineage infections; 2) seek evidence for cross-infection or common source acquisition; and 3) characterise P. aeruginosa adaptations.189 isolates, obtained from the sputa of 91 patients attending 16 adult bronchiectasis centres in the UK, were whole-genome sequenced.Bronchiectasis isolates were representative of the wider P. aeruginosa population. Of 24 patients from whom multiple isolates were examined, there were seven examples of multilineage infections, probably arising from multiple infection events. The number of nucleotide variants between genomes of isolates from different patients was in some cases similar to the variations observed between isolates from individual patients, implying the possible occurrence of cross-infection or common source acquisition.Our data indicate that during infections of bronchiectasis patients, P. aeruginosa populations adapt by accumulating loss-of-function mutations, leading to changes in phenotypes including different modes of iron acquisition and variations in biofilm-associated polysaccharides. The within-population diversification suggests that larger scale longitudinal surveillance studies will be required to capture cross-infection or common source acquisition events at an early stage.
Cox MJ, Turek EM, Hennessy C, et al., 2017, Longitudinal assessment of sputum microbiome by sequencing of the 16S rRNA gene in non-cystic fibrosis bronchiectasis patients, PLOS ONE, Vol: 12, ISSN: 1932-6203
Background:Bronchiectasis is accompanied by chronic bronchial infection that may drive disease progression. However, the evidence base for antibiotic therapy is limited. DNA based methods offer better identification and quantification of microbial constituents of sputum than standard clinical culture and may help inform patient management strategies. Our study objective was to determine the longitudinal variability of the non-cystic fibrosis (CF) bronchiectasis microbiome in sputum with respect to clinical variables. Eighty-five patients with non-CF bronchiectasis and daily sputum production were recruited from outpatient clinics and followed for six months. Monthly sputum samples and clinical measurements were taken, together with additional samples during exacerbations. 16S rRNA gene sequencing of the sputum microbiota was successful for 381 samples from 76 patients and analysed in conjunction with clinical data.Results:Microbial communities were highly individual in composition and stability, usually with limited diversity and often containing multiple pathogens. When compared to DNA sequencing, microbial culture had restricted sensitivity in identifying common pathogens such as Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis. With some exceptions, community characteristics showed poor correlations with clinical features including underlying disease, antibiotic use and exacerbations, with the subject showing the strongest association with community structure. When present, the pathogens mucoid Pseudomonas aeruginosa and Haemophilus influenzae may also shape the structure of the rest of the microbial community.Conclusions:The use of microbial community analysis of sputum added to information from microbial culture. A simple model of exacerbations driven by bacterial overgrowth was not supported, suggesting a need for revision of principles for antibiotic therapy. In individual patients, the management of chronic bronchial infection may be imp
Bryant JM, Grogono DM, Rodriguez-Rincon D, et al., 2016, Emergence and spread of a human-transmissible multidrug-resistant nontuberculous mycobacterium, Science, Vol: 354, Pages: 751-757, ISSN: 0036-8075
Lung infections with Mycobacterium abscessus, a species of multidrug-resistantnontuberculous mycobacteria, are emerging as an important global threat to individuals withcystic fibrosis (CF), in whom M. abscessus accelerates inflammatory lung damage, leading toincreased morbidity and mortality. Previously, M. abscessus was thought to be independentlyacquired by susceptible individuals from the environment. However, using whole-genomeanalysis of a global collection of clinical isolates, we show that the majority of M. abscessusinfections are acquired through transmission, potentially via fomites and aerosols, of recentlyemerged dominant circulating clones that have spread globally. We demonstrate that theseclones are associated with worse clinical outcomes, show increased virulence in cell-based andmouse infection models, and thus represent an urgent international infection challenge.
Elborn JS, Horsley A, MacGregor G, et al., 2016, Phase I studies of acebilustat: biomarker response and safety in patients with cystic fibrosis, Clinical and Translational Science, Vol: 10, Pages: 28-34, ISSN: 1752-8054
There is a significant unmet need for safe and effective anti-inflammatory treatment for cystic fibrosis. The aim of this study was to evaluate the safety of acebilustat, a leukotriene A4 hydrolase inhibitor, and its effect on inflammation biomarkers in patients with cystic fibrosis. Seventeen patients with mild to moderate cystic fibrosis were enrolled and randomized into groups receiving placebo or doses of 50 mg or 100 mg acebilustat administered orally, once daily for 15 days. Sputum neutrophil counts were reduced by 65% over baseline values in patients treated with 100 mg acebilustat. A modestly significant 58% reduction vs. placebo in sputum elastase was observed with acebilustat treatment. Favorable trends were observed for reduction of serum C-reactive protein and sputum neutrophil DNA in acebilustat-treated patients. No changes in pulmonary function were observed. Acebilustat was safe and well tolerated. The results of this study support further clinical development of acebilustat for treatment of cystic fibrosis.
Volkova N, Bessonova L, Higgins M, et al., 2016, ANALYSIS OF DISEASE PROGRESSION IN PATIENTS WITH CF TREATED WITH IVACAFTOR IN THE REAL WORLD USING DATA FROM THE UK CF REGISTRY, Publisher: WILEY-BLACKWELL, Pages: 382-382, ISSN: 8755-6863
Bessonova L, Higgins M, Volkova N, et al., 2016, ANALYSIS OF REAL-WORLD OUTCOMES IN PATIENTS WITH CF TREATED WITH IVACAFTOR FROM THE 2014 US AND UK CF REGISTRIES, Publisher: WILEY-BLACKWELL, Pages: 381-382, ISSN: 8755-6863
Ostrenga J, Elbert A, Petren KM, et al., 2016, COMBINING INTERNATIONAL REGISTRIES: A MATCHING ALGORITHM USING LONGITUDINAL DATA, Publisher: WILEY-BLACKWELL, Pages: 380-381, ISSN: 8755-6863
Bilton D, Caine N, Cosgriff R, et al., 2016, Use of national disease registries in the conduct of long-term post-authorisation drug safety studies (LTSSs), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Winstanley C, Hilliam Y, Moore M, et al., 2016, LATE-BREAKING ABSTRACT: Pseudomonas aeruginosa strain prevalence, adaptation and diversification, during chronic lung infections of UK non-cystic fibrosis bronchiectasis patients, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Thompson V, Mayer-Hamblett N, Kloster M, et al., 2016, Corrigendum to "Risk of hemoptysis in cystic fibrosis clinical trials: A retrospective cohort study" [J Cyst Fibros (2015) 632-638]., J Cyst Fibros, Vol: 15, Pages: e54-e55
Shah A, Shoemark A, MacNeill SJ, et al., 2016, A longitudinal study characterising a large adult primary ciliary dyskinesia population, European Respiratory Journal, Vol: 48, Pages: 441-450, ISSN: 1399-3003
Primary ciliary dyskinesia (PCD) in adults has not been well described. In this retrospective observational study we aimed to characterise a large adult population and identify features associated with disease progression.We retrospectively analysed 151 adult patients at a single tertiary centre at baseline and longitudinally for a median of 7 years.We found significant variation in age at diagnosis (median 23.5 years; range <1-72 years). Older age at diagnosis was associated with impaired baseline forced expiratory volume in 1 s (FEV1) (r= -0.30, p=0.01) and increased Pseudomonas aeruginosa colonisation (difference in medians 17 years (95% CI 4.5-20 years); p=0.002). Lung function decline was estimated at FEV1 decline of 0.49% predicted per year. Lung function decline was associated with ciliary ultrastructure, with microtubular defect patients having the greatest decline (p=0.04). High-resolution computed tomography (HRCT) scores of severity of bronchial wall dilatation (p<0.001) and extent of bronchiectasis (p=0.03) additionally showed evidence of modifying FEV1 decline with age.Our study reveals that a large proportion of adult PCD patients are diagnosed late, with impaired FEV1 and increased P. aeruginosa colonisation. Increased disease burden on HRCT and ciliary ultrastructure may predict progressive lung function decline. This study characterises a large adult PCD population, identifies features associated with disease progression and highlights the need for prospective trials to determine whether early diagnosis of high-risk subgroups alongside optimal management can modify disease progression.
Cox MJ, Turek EM, Hennessy C, et al., 2016, Longitudinal assessment of sputum microbiome by sequencing of the 16S rRNA gene in non-CF bronchiectasis patients
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Bronchiectasis is accompanied by chronic bronchial infection that may drive disease progression. However, the evidence base for antibiotic therapy is limited. DNA based methods offer better identification and quantification of microbial constituents of sputum than standard clinical culture and may help inform patient management strategies. Our study objective was to determine the longitudinal variability of the non-CF bronchiectasis microbiome in sputum with respect to clinical variables.</jats:p><jats:p>Eighty-five patients with non-cystic fibrosis (CF) bronchiectasis and daily sputum production were recruited from outpatient clinics and followed for six months. Monthly sputum samples and clinical measurements were taken, together with additional samples during exacerbations. 16S rRNA gene sequencing of the sputum microbiota was successful for 381 samples from 76 patients and analysed in conjunction with clinical data.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Microbial communities were highly individual in composition and stability, usually with limited diversity and often containing multiple pathogens. When compared to DNA sequencing, microbial culture had restricted sensitivity in identifying common pathogens. With some exceptions, community characteristics showed poor correlations with clinical features including underlying disease, antibiotic use and exacerbations, with the subject showing the strongest association with community structure. When present, certain pathogens may also shape the structure of the rest of the microbial community.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The use of microbial community analysis of sputum added to information from microbial culture. A simple model of exacerbat
Vermeulen F, Le Camus C, Davies JC, et al., 2016, Variability of sweat chloride concentration in subjects with cystic fibrosis and G551D mutations, Journal of Cystic Fibrosis, Vol: 16, Pages: 36-40, ISSN: 1569-1993
Introduction:Sweat chloride concentration, a biomarker of CFTR function, is an appropriate outcome parameter in clinical trials aimed at correcting the basic CF defect. Although there is consensus on a cut-off value to diagnose CF, we have only limited information on the within subject variability of sweat chloride over time. Such information would be useful for sample size calculations in clinical trials. Therefore, we retrospectively analyzed repeated sweat chloride values obtained in patients with G551D mutation(s) assigned to placebo in an ivacaftor interventional trial.Methods:In subjects with G551D at least 12 years of age, a pilocarpine sweat test using Macroduct collector was taken on both arms at 8 time points over 48 weeks. We explored 1062 pilocarpine sweat test values obtained in 78 placebo patients of the VX08-770-102 trial.Results:Mean overall sweat chloride value (all patients, all tests, n = 1062) was 100.8 mmol/L (SD 12.7 mmol/L). Using a multilevel mixed model, the between-subject standard deviation (SD) for sweat chloride was 8.9 mmol/L (95% CI 7.4–10.6) and within-subject SD was 8.1 mmol/L (95% CI 7.5–8.7). Limits of repeatability for repeat measurements were − 19.7 to + 21.6 mmol/L using values from one arm, and − 13.3 to 11.8 mmol/L using mean of values obtained at 4 test occasions. Sample size calculations showed that the minimal treatment effect on sweat chloride concentration that can be demonstrated for a group of 5 patients is around 15 mmol/L, using a cross-over design and combinations of 4 tests for each phase of the trial. Conclusion:Although the sweat test is considered a robust measure, sweat chloride measurements in patients with CF and a G551D mutation had an inherent biological variability that is higher than commonly considered. Further analyses of placebo group data are crucial to learn more about the natural variability of this outcome parameter.
Burgess JC, Bridges N, Winston B, et al., 2016, HbA1c as a screening tool for cystic fibrosis related diabetes Response, JOURNAL OF CYSTIC FIBROSIS, Vol: 15, Pages: 265-266, ISSN: 1569-1993
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- Citations: 2
Burgess JC, Bridges N, Banya W, et al., 2016, HbA1c as a screening tool for cystic fibrosis related diabetes, JOURNAL OF CYSTIC FIBROSIS, Vol: 15, Pages: 251-257, ISSN: 1569-1993
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- Citations: 45
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