Imperial College London

ProfessorJaneDavies

Faculty of MedicineNational Heart & Lung Institute

Professor of Paediatric Respirology & Experimental Medicine
 
 
 
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Contact

 

+44 (0)20 7594 7973j.c.davies

 
 
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Assistant

 

Mrs Gina Rivellini +44 (0)20 7594 7986

 
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Location

 

171Emmanuel Kaye BuildingRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

358 results found

Bayfield KJ, Douglas TA, Rosenow T, Davies JC, Elborn SJ, Mall M, Paproki A, Ratjen F, Sly PD, Smyth AR, Stick S, Wainwright CE, Robinson PDet al., 2021, Time to get serious about the detection and monitoring of early lung disease in cystic fibrosis., Thorax

Structural and functional defects within the lungs of children with cystic fibrosis (CF) are detectable soon after birth and progress throughout preschool years often without overt clinical signs or symptoms. By school age, most children have structural changes such as bronchiectasis or gas trapping/hypoperfusion and lung function abnormalities that persist into later life. Despite improved survival, gains in forced expiratory volume in one second (FEV1) achieved across successive birth cohorts during childhood have plateaued, and rates of FEV1 decline in adolescence and adulthood have not slowed. This suggests that interventions aimed at preventing lung disease should be targeted to mild disease and commence in early life. Spirometry-based classifications of 'normal' (FEV1≥90% predicted) and 'mild lung disease' (FEV1 70%-89% predicted) are inappropriate, given the failure of spirometry to detect significant structural or functional abnormalities shown by more sensitive imaging and lung function techniques. The state and readiness of two imaging (CT and MRI) and two functional (multiple breath washout and oscillometry) tools for the detection and monitoring of early lung disease in children and adults with CF are discussed in this article.Prospective research programmes and technological advances in these techniques mean that well-designed interventional trials in early lung disease, particularly in young children and infants, are possible. Age appropriate, randomised controlled trials are critical to determine the safety, efficacy and best use of new therapies in young children. Regulatory bodies continue to approve medications in young children based on safety data alone and extrapolation of efficacy results from older age groups. Harnessing the complementary information from structural and functional tools, with measures of inflammation and infection, will significantly advance our understanding of early CF lung disease pathophysiology and responses to therapy

Journal article

Davies J, Kos R, Brinkman P, Neerincx A, Paff T, Gerritsen M, Lammers A, Kraneveld A, Heijerman H, Janssens H, Majoor C, Weersink E, Sterk P, Haarman E, Bos L, Maitland-van der Zee Aet al., 2021, Targeted exhaled breath analysis for detection of Pseudomonas aeruginosa in cystic fibrosis patients, Journal of Cystic Fibrosis, ISSN: 1569-1993

Journal article

Davies J, MacSweeney R, Reddy K, Parker M, Kelly B, Elborn JS, Conlon J, Verghis RM, Calfee CS, Matthay MA, Alton EWFW, McAuley Det al., 2021, Trans-epithelial nasal potential difference in patients with, and at risk of acute respiratory distress syndrome, Thorax, ISSN: 0040-6376

Journal article

Dobra R, Elborn JS, Madge S, Allen L, Boeri M, Kee F, Goundry S, Purcell T, Saunders C, Davies JCet al., 2021, Guiding the rational design of patient-centred drug trials in Cystic Fibrosis: A Delphi study., J Cyst Fibros

BACKGROUND: Making trials more patient-centred improves recruitment and retention, patient satisfaction and makes research accessible to a more representative population. We aimed to understand the factors that influence participation and engagement in clinical trials in cystic fibrosis (CF) trials to guide the rational design and delivery of patient-centred trials. METHODS: We used a Delphi process, supported by extensive literature review and 3 workshops, to determine which factors stakeholders think exert significant influence in participation and engagement in CF trials. Panellists were recruited from across the UK and the study was administered online. RESULTS: We had representation from 19 CF centres; 28 people with CF (pwCF), 26 parents and 30 healthcare professionals (HCPs). Panels were presented with a shortlist of 104 factors and asked which they thought influence participation and engagement in CF trials. After 3 iterations, 43 statements met consensus for pwCF, 48 for the parents and 69 for the HCPs. CONCLUSIONS: We identified many targets to make trials more patient-centred. Whilst some require an overhaul of trial delivery, many are relatively easy to implement. We outline a list of 'dos and don'ts' for sponsors and research teams including: focus on good communication; recognise that lack of time is the greatest barrier to trial participation so minimise the frequency and length of visits; help participants fit trials around busy lives; remember trial participation can be a major life-event and support participants accordingly; and don't underestimate the impact of simple strategies e.g. on-site access to Wifi and cups of tea.

Journal article

Hughes DA, Price H, Rosenthal M, Davies JCet al., 2021, Pseudomonas aeruginosa in the cystic fibrosis airway: does it deserve its reputation as a predatory 'Bully'?, American Journal of Respiratory and Critical Care Medicine, Vol: 203, Pages: 1027-1030, ISSN: 1073-449X

Journal article

Davies J, Sepahzad A, Morris-Rosendahl D, 2021, Cystic fibrosis lung disease modifiers and their relevance in the new era of precision medicine, Genes

Journal article

Sabnis A, Haggard K, Kloeckner A, Becce M, Evans L, Furniss R, Mavridou D, Stevens M, Murphy R, Davies J, Clarke T, Edwards Aet al., 2021, Colistin kills bacteria by targeting lipopolysaccharide in the cytoplasmic membrane, eLife, ISSN: 2050-084X

Journal article

Davies J, Dobra R, Pike K, Allen L, Brendell R, Carr S, Simmonds N, Davies Get al., 2021, Optimising equity of access: how should we allocate slots to the most competitive trials in Cystic Fibrosis (CF)?, Journal of Cystic Fibrosis, ISSN: 1569-1993

Journal article

Davies J, Martin I, Kenna D, Morales S, Alton EWFWet al., 2021, Variability in bacteriophage and antibiotic sensitivity in serial Pseudomonas aeruginosa isolates from cystic fi-brosis airway cultures over 12 months, Mircoorganisms

Journal article

Zemanick ET, Taylor-Cousar JL, Davies J, Gibson RL, Mall MA, McKone EF, McNally P, Ramsey BW, Rayment JH, Rowe SM, Tullis E, Ahluwalia N, Chu C, Ho T, Moskowitz SM, Noel S, Tian S, Waltz D, Weinstock TG, Xuan F, Wainwright CE, McColley SA, VX18-445-106 Study Groupet al., 2021, A Phase 3 open-label study of ELX/TEZ/IVA in children 6 through 11 years of age with CF and at least one F508del allele., American Journal of Respiratory and Critical Care Medicine, ISSN: 1073-449X

RATIONALE: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and safe in patients aged 12 years and older with cystic fibrosis and at least one F508del-CFTR allele, but has not been evaluated in children <12 years of age. OBJECTIVES: To assess the safety, pharmacokinetics, and efficacy of ELX/TEZ/IVA in children 6 through 11 years of age with F508del-minimal function or F508del-F508del genotypes. METHODS: In this 24-week open-label Phase 3 study, children (N=66) weighing <30 kg received 50% of the ELX/TEZ/IVA adult daily dose (ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 hours) while children weighing ≥30 kg received the full adult daily dose (ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 hours). MEASUREMENTS AND MAIN RESULTS: The primary endpoint was safety and tolerability. The safety and pharmacokinetic profiles of ELX/TEZ/IVA were generally consistent with those observed in older patients. The most common reported adverse events (AEs) included cough, headache, and pyrexia; in most of the children who had AEs, these were mild or moderate in severity. Through Week 24, ELX/TEZ/IVA treatment improved the ppFEV1 (10.2 percentage points; 95% confidence interval [CI], 7.9 to 12.6), Cystic Fibrosis Questionnaire-Revised respiratory domain score (7.0 points; 95% CI, 4.7 to 9.2), lung clearance index2.5 (-1.71 units; 95% CI, -2.11 to -1.30), and sweat chloride (-60.9 mmol/L; 95% CI, -63.7 to -58.2); body mass index-for-age z-score increased over the 24-week treatment period compared to the pre-treatment baseline. CONCLUSIONS: Our results show ELX/TEZ/IVA is safe and efficacious in children 6 through 11 years of age with at least one F508del-CFTR allele, supporting its use in this patient population. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT03691779 This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No D

Journal article

Davies J, Dobra R, Boeri M, Elborn S, Kee F, Madge Set al., 2021, Protocol: A discrete choice experiment (DCE) to quantify the influence of trial features on the decision to participate in Cystic Fibrosis (CF) clinical trials, British medical journal, Vol: 11, Pages: 1-7, ISSN: 0007-1447

Introduction Engaging people with cystic fibrosis (CF) in clinical trials is critical to improving outcomes for this fatal disease. Following extensive exploration of engagement in CF trials we believe six key concepts require a quantitative understanding of their influence in the current CF trials landscape including how controversial issues like placebos, washouts, stipend provision and location of trial visits are viewed by the CF community and how these might be modified depending on the type of medicine being investigated and the mechanism of access to the drug on trial completion.Methods and analysis We have designed and will administer an online discrete choice experiment to elicit and quantify preferences of people with CF for these trials’ attributes and estimate the relative importance of an attribute when choosing to participate in a trial. The cross-sectional data generated will be explored using conditional multinomial logit model. Mixed logit models such as the random-parameters logit and a latent class models will be used to explore preference heterogeneity. To determine the relative importance of an attribute, the difference between the attribute level with the highest preference weight and the level with the lowest preference weight will be calculated.Ethics and dissemination Imperial College London Joint Research Compliance Office has granted ethical approval for this study. Patient consent will be sought following full explanation. No identifying information will be collected. Dissemination will be via international conferences, peer-review publication and patient accessible forums. Major CF trials networks have agreed to incorporate our findings into their review process, meaning our results can realistically influence and optimise CF trial delivery.PROSPERO registration number CRD42020184886.

Journal article

Davies JC, Wainwright CE, Sawicki GS, Higgins MN, Campbell D, Harris C, Panorchan P, Haseltine E, Tian S, Rosenfeld Met al., 2021, Ivacaftor in Infants Aged 4 to < 12 Months with Cystic Fibrosis and a Gating Mutation Results of a Two-Part Phase 3 Clinical Trial, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 203, Pages: 585-593, ISSN: 1073-449X

Journal article

Davies J, Dobra R, Huband K, Matthews J, Scott S, Simmonds Net al., 2021, Strengthening clinical trial pharmacovigilance: simple interventions improve communication over serious adverse events, Journal of Clinical Trials

Journal article

Coates M, Alton E, Rapeport W, Davies J, Ito Ket al., 2021, Pseudomonas aeruginosa induces p38MAP kinase-dependent IL-6 and CXCL8 release from bronchial epithelial cells via a Syk kinase pathway, PLoS One, Vol: 16, ISSN: 1932-6203

Pseudomonas aeruginosa (Pa) infection is a major cause of airway inflammation in immunocompromised and cystic fibrosis (CF) patients. Mitogen-activated protein (MAP) and tyrosine kinases are integral to inflammatory responses and are therefore potential targets for novel anti-inflammatory therapies. We have determined the involvement of specific kinases in Pa-induced inflammation. The effects of kinase inhibitors against p38MAPK, MEK 1/2, JNK 1/2, Syk or c-Src, a combination of a p38MAPK with Syk inhibitor, or a novel narrow spectrum kinase inhibitor (NSKI), were evaluated against the release of the proinflammatory cytokine/chemokine, IL-6 and CXCL8 from BEAS-2B and CFBE41o- epithelial cells by Pa. Effects of a Syk inhibitor against phosphorylation of the MAPKs were also evaluated. IL-6 and CXCL8 release by Pa were significantly inhibited by p38MAPK and Syk inhibitors (p<0.05). Phosphorylation of HSP27, but not ERK or JNK, was significantly inhibited by Syk kinase inhibition. A combination of p38MAPK and Syk inhibitors showed synergy against IL-6 and CXCL8 induction and an NSKI completely inhibited IL-6 and CXCL8 at low concentrations. Pa-induced inflammation is dependent on p38MAPK primarily, and Syk partially, which is upstream of p38MAPK. The NSKI suggests that inhibiting specific combinations of kinases is a potent potential therapy for Pa-induced inflammation.

Journal article

Dave K, Dobra R, Scott S, Saunders C, Matthews J, Simmonds NJ, Davies JCet al., 2021, Entering the era of highly effective modulator therapies, PEDIATRIC PULMONOLOGY, Vol: 56, Pages: S79-S89, ISSN: 8755-6863

Journal article

Farrant KV, Spiga L, Davies JC, Williams Het al., 2021, Response of Pseudomonas aeruginosa to the innate immune system-derived oxidants hypochlorous acid and hypothiocyanous acid, Journal of Bacteriology, Vol: 203, ISSN: 0021-9193

Pseudomonas aeruginosa is a significant nosocomial pathogen and associated with lung infections in cystic fibrosis (CF). Once established, P. aeruginosa infections persist and are rarely eradicated despite host immune cells producing antimicrobial oxidants, including hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN). There is limited knowledge as to how P. aeruginosa senses, responds to, and protects itself against HOCl and HOSCN, and the contribution of such responses to its success as a CF pathogen. To investigate the P. aeruginosa response to these oxidants we screened 707 transposon mutants, with mutations in regulatory genes, for altered growth following HOCl exposure. We identified regulators of antibiotic resistance, methionine biosynthesis and catabolite repression, and PA14_07340, the homologue of the Escherichia coli HOCl-sensor RclR (30% identical), that are required for protection against HOCl. We have shown that RclR (PA14_07340) protects specifically against HOCl and HOSCN stress, and responds to both oxidants by upregulating expression of a putative peroxiredoxin, rclX (PA14_07355). Transcriptional analysis revealed that while there was specificity in the response to HOCl (231 genes upregulated) and HOSCN (105 genes upregulated) there was considerable overlap, with 74 genes upregulated by both oxidants. These included genes encoding the type III secretion system, sulphur and taurine transport, and the MexEF-OprN efflux pump. RclR coordinates part of the response to both oxidants, including upregulation of pyocyanin biosynthesis genes, and in the presence of HOSCN, downregulation of chaperone genes. These data indicate that the P. aeruginosa response to HOCl and HOSCN is multifaceted, with RclR playing an essential role.

Journal article

Davies JC, Sermet-Gaudelus I, Naehrlich L, Harris RS, Campbell D, Ahluwalia N, Short C, Haseltine E, Panorchan P, Saunders C, Owen CA, Wainwright CEet al., 2021, A phase 3, double-blind, parallel-group study to evaluate the efficacy and safety of tezacaftor in combination with ivacaftor in participants 6 through 11 years of age with cystic fibrosis homozygous for F508del or heterozygous for the F508del-CFTR mutation and a residual function mutation, JOURNAL OF CYSTIC FIBROSIS, Vol: 20, Pages: 68-77, ISSN: 1569-1993

Journal article

Barben J, Castellani C, Munck A, Davies JC, de Winter-de Groot KM, Gartner S, Kashirskaya N, Linnane B, Mayell SJ, McColley S, Ooi CY, Proesmans M, Ren CL, Salinas D, Sands D, Sermet-Gaudelus I, Sommerburg O, Southern KW, European CF Society Neonatal Screening Working Group ECFS NSWGet al., 2020, Updated guidance on the management of children with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen positive, inconclusive diagnosis (CRMS/CFSPID)., J Cyst Fibros

Over the past two decades there has been considerable progress with the evaluation and management of infants with an inconclusive diagnosis following Newborn Screening (NBS) for cystic Fibrosis (CF). In addition, we have an increasing amount of evidence on which to base guidance on the management of these infants and, importantly, we have a consistent designation being used across the globe of CRMS/CFSPID. There is still work to be undertaken and research questions to answer, but these infants now receive more consistent and appropriate care pathways than previously. It is clear that the majority of these infants remain healthy, do not convert to a diagnosis of CF in childhood, and advice on management should reflect this. However, it is also clear that some will convert to a CF diagnosis and monitoring of these infants should facilitate their early recognition. Those infants that do not convert to a CF diagnosis have some potential of developing a CFTR-RD later in life. At present, it is not possible to quantify this risk, but families need to be provided with clear information of what to look out for. This paper contains a number of changes from previous guidance in light of developing evidence, but the major change is the recommendation of a detailed assessment of the child with CRMS/CFSPID in the sixth year of age, including respiratory function assessment and imaging. With these data, the CF team can discuss future care arrangements with the family and come to a shared decision on the best way forward, which may include discharge to primary care with appropriate information. Information is key for these families, and we recommend consideration of a further appointment when the individual is a young adult to directly communicate the implications of the CRMS/CFSPID designation.

Journal article

Short C, Saunders C, Davies JC, 2020, Utility of lung clearance index in CF: What we know, what we don't know and musings on how to bridge the gap, JOURNAL OF CYSTIC FIBROSIS, Vol: 19, Pages: 852-855, ISSN: 1569-1993

Journal article

Nissenbaum C, Davies G, Horsley A, Davies JCet al., 2020, Monitoring early stage lung disease in cystic fibrosis., Current Opinion in Pulmonary Medicine, Vol: 26, Pages: 671-678, ISSN: 1070-5287

PURPOSE OF REVIEW: Early stage lung disease has long been synonymous with infancy and childhood. As diagnosis happens earlier and conventional management improves, we are seeing larger proportions of people with cystic fibrosis (CF) in adolescence and even adulthood with well preserved lung health. The availability of highly effective cystic fibrosis transmembrane conductance regulator modulator drugs for a large proportion of the CF population will impact even further. Transitioning into adult care with 'normal' lung function will become more common. However, it is crucial that we are not blasé about this phase, which sets the scene for future lung health. It is well recognized that lung function assessed by spirometry is insensitive to 'early' changes occurring in the distal, small airways. Much of our learning has come from studies in infants and young children, which have allowed assessment and optimization of alternative forms of monitoring. RECENT FINDINGS: Here, as a group of paediatric and adult CF specialists, we review the evidence base for sensitive physiological testing based on multibreath washout, lung imaging, exercise and activity monitoring, assessment of infection and quality of life measures. SUMMARY: We seek to emphasise the importance of further work in these areas, as outcome measures become widely applicable to a growing CF population.

Journal article

Davies J, Chilvers MA, Milla C, Tian S, Han Z, Cornell AG, Owen CA, Ratjen Fet al., 2020, Long-term safety and efficacy of lumacaftor/ivacaftor therapy in children aged 6–11 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a phase 3, open-label extension study, The Lancet Respiratory Medicine, ISSN: 2213-2600

Background: The safety and efficacy of 24 weeks of lumacaftor/ivacaftor combination therapy in children aged 6–11 years with cystic fibrosis homozygous for the F508del-CFTR mutation was previously demonstrated in two phase 3 studies. Here, we report long-term safety and efficacy data in children who rolled over from these two parent studies into a 96-week lumacaftor/ivacaftor open-label extension study (NCT02544451).Methods: The primary endpoint was safety. Secondary endpoints included change from baseline in lung clearance index 2∙5% (LCI2·5), sweat chloride concentration, body mass index, and Cystic Fibrosis Questionnaire–Revised respiratory domain score.Findings: Of 239 children who enrolled in the study and received at least one dose of lumacaftor/ivacaftor, 215 completed 96 weeks of treatment. Most children had adverse events (AEs) that were mild or moderate in severity, and there was a low rate of AEs leading to treatment discontinuation. The most frequently reported AEs were common manifestations or complications of cystic fibrosis or were consistent with the known safety profile of lumacaftor/ivacaftor in older children and adults. No new safety concerns were identified with extended lumacaftor/ivacaftor treatment. Children treated with placebo in the parent study and who began lumacaftor/ivacaftor in this extension study had improvements in efficacy endpoints consistent with those observed in the parent studies. Improvements observed in lumacaftor/ivacaftor-treated children in the parent studies were generally maintained in the extension study. Interpretation: Lumacaftor/ivacaftor therapy in children homozygous for F508del-CFTR who initiated treatment at ages 6–11 years was generally safe and well tolerated, and efficacy was sustained for up to 120 weeks in this open-label extension study. These data support the long-term use of lumacaftor/ivacaftor to treat children aged ≥6 years homozygous for the F508del-CFTR mutation.

Journal article

Kerem E, Cohen-Cymberknoh M, Tsabari R, Wilschanski M, Reiter J, Shoseyov D, Gileles-Hillel A, Pugatsch T, Davies JC, Short C, Saunders C, DeSouza C, Sullivan JC, Doyle JR, Chandarana K, Kinnman Net al., 2020, Ivacaftor in people with cystic fibrosis and a 3849+10kb C →T or D1152H residual function mutation., Annals of the American Thoracic Society, Vol: 18, Pages: 433-441, ISSN: 1546-3222

Rationale: Ivacaftor's clinical effects in the residual function mutations 3849+10kb C →T and D1152H warrant further characterization. Objectives: Evaluate ivacaftor's effect in people with cystic fibrosis aged ≥6 years with 3849+10kb C→T or D1152H residual function mutations; explore the correlation between ivacaftor-induced organoid-based cystic fibrosis transmembrane conductance regulator function measurements and clinical response to ivacaftor. Methods: Participants were randomized (1:1) in this placebo-controlled crossover study; each treatment sequence included two 8-week treatments with an 8-week washout period. The primary endpoint was absolute change in lung clearance index2.5 from baseline through Week 8. Additional endpoints included lung function, patient-reported outcomes, and in vitro intestinal organoid-based measurements of ivacaftor-induced cystic fibrosis transmembrane conductance regulator function. Results: Of 38 participants, 37 completed the study. The primary endpoint was met; the Bayesian posterior probability of improvement in lung clearance index2.5 with ivacaftor vs placebo was >99%. Additional endpoints improved with ivacaftor. Safety findings were consistent with ivacaftor's known safety profile. Dose-dependent swelling was observed in 23/25 viable organoid cultures with ivacaftor treatment. Correlations between ivacaftor-induced organoid swelling and clinical endpoints were negligible to low. Conclusions: In people with cystic fibrosis aged ≥6 years with a 3849+10kb C →T or D1152H mutation, ivacaftor treatment improved clinical endpoints vs placebo; however, there was no correlation between organoid swelling and change in clinical endpoints. The organoid assay may assist in identification of ivacaftor-responsive mutations but in this study did not predict magnitude of clinical benefit for individual people with cystic fibrosis with these two mutations. Clinical trial registered with ClinicalTrials.gov (NCT0306831

Journal article

O'Neill K, Ferguson K, Cosgrove D, Tunney MM, De Soyza A, Carroll M, Chalmers JD, Gatheral T, Hill AT, Hurst JR, Johnson C, Loebinger MR, Angyalosi G, Haworth CS, Jensen R, Ratjen F, Saunders C, Short C, Davies J, Elborn JS, Bradley JMet 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.

Journal article

Stanford G, Davies JC, Usmani O, Banya W, Charman S, Jones M, Simmonds NJ, Bilton Det al., 2020, Investigating outcome measures for assessing airway clearance techniques in adults with cystic fibrosis: protocol of a single-centre randomised controlled crossover trial, BMJ Open Respiratory Research, Vol: 7, ISSN: 2052-4439

INTRODUCTION: Airway clearance techniques (ACTs) are a gold standard of cystic fibrosis management; however, the majority of research evidence for their efficacy is of low standard; often attributed to the lack of sensitivity from outcome measures (OMs) used historically. This randomised controlled trial (RCT) investigates these standard OMs (sputum weight, forced expiratory volume in 1 s) and new OMs (electrical impedance tomography (EIT), multiple breath washout (MBW) and impulse oscillometry (IOS)) to determine the most useful measures of ACT. METHODS AND ANALYSIS: This is a single-centre RCT with crossover design. Participants perform MBW, IOS and spirometry, and then are randomised to either rest or supervised ACT lasting 30-60 min. MBW, IOS and spirometry are repeated immediately afterwards. EIT and sputum are collected during rest/ACT. On a separate day, the OMs are performed with the other intervention. Primary endpoint is difference in change in OMs before and after ACT/rest. Sample size was calculated with 80% power and significance of 5% for each OM (target n=64). ETHICS AND DISSEMINATION: Ethics approval was gained from the London-Chelsea Research Ethics Committee (reference 16/LO/0995, project ID 154635). Dissemination will involve scientific conference presentation and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBERS: ISRCTN11220163 and NCT02721498.

Journal article

Gardner L, Pinto LA, Davies JC, Semple Tet al., 2020, THE USE OF THORACIC CT TO DETERMINE BONE MINERAL DENSITY IN ADULTS AND CHILDREN WITH CYSTIC FIBROSIS, Publisher: WILEY, Pages: S87-S87, ISSN: 8755-6863

Conference paper

Rosenfeld M, Wainwright C, Sawicki GS, Higgins M, Campbell D, Harris C, Panorchan P, Tian S, Davies JCet al., 2020, IVACAFTOR IN 4-TO < 6-MONTH-OLD INFANTS WITH CYSTIC FIBROSIS AND A GATING MUTATION: RESULTS OF A 2-PART, SINGLE-ARM, PHASE 3 STUDY, Publisher: WILEY, Pages: S200-S200, ISSN: 8755-6863

Conference paper

Murphy RA, Thrane S, Schelenz S, Harrison J, Vorup-Jensen T, Davies JCet al., 2020, SYNERGY WITH GLATIRAMER ACETATE REDUCES TOBRAMYCIN MINIMUM INHIBITORY CONCENTRATIONS AGAINST PSEUDOMONAS AERUGINOSA FROM CYSTIC FIBROSIS AIRWAYS, Publisher: WILEY, Pages: S154-S155, ISSN: 8755-6863

Conference paper

van Koningsbruggen-Rietschel S, Davies J, Pressler T, Fischer R, MacGregor G, Donaldson SH, Smerud K, Meland N, Mortensen J, Fosbøl MØ, Downey DG, Myrset AH, Flaten H, Rye PDet al., 2020, Inhaled dry powder alginate oligosaccharide (OligoG) in cystic fibrosis: A randomized, double-blind, placebo-controlled cross-over Phase 2b study, European Respiratory Journal, Vol: 6, ISSN: 0903-1936

Background: OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of CF mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG was evaluated in adult patients with cystic fibrosis (CF). Methods: A randomized, double-blind, placebo-controlled multi-centre cross-over study was used to demonstrate safety and efficacy of inhaled dry powder OligoG. Subjects were randomly allocated to receive OligoG 1050mg per day (10 capsules TID) or matching placebo for 28-days, with 28-day washout periods following each treatment period. The primary endpoint was absolute change in percent predicted FEV1 at the end of 28-day treatment. The ITT population (N=65) was defined as randomised to treatment with at least one administration of study medication and post-dosing evaluation.Results:Ninety adult subjects were screened and 65 randomized. Statistically significant improvement in FEV1 was not observed in the ITT population. Adverse events (AEs) included nasopharyngitis, cough and pulmonary exacerbation. The number and proportions of patients with AEs and SAEs were similar between OligoG and placebo group.Conclusions: Inhalation of OligoG-DPI over 28-days was safe in adult CF subjects. Statistically significant improvement of FEV1 was not reached. The planned analyses did not indicate a significant treatment benefit with OligoG compared to placebo. Post-hoc exploratory analyses showed subgroup results which indicate that further studies of OligoG in this patient population are justified.

Journal article

Edmondson C, Westrupp N, Wallenburg J, Brownlee K, Alton EW, Bush A, Davies JCet al., 2020, WHAT IS FEASIBLE WHEN IT COMES TO MONITORING YOUNG PEOPLE WITH CYSTIC FIBROSIS AT HOME? THE RESULTS OF THE CLIMB-CF STUDY, Publisher: WILEY, Pages: S297-S297, ISSN: 8755-6863

Conference paper

Kos R, Brinkman P, Neerincx AH, Paff T, Gerritsen MG, Lammers A, Kraneveld AD, Heijerman HGM, Davies JC, Janssens HM, Majoor CJ, Weersink EJ, Sterk PJ, Haarman EG, Bos L, Maitland-Van der Zee AHet al., 2020, Targeted exhaled breath analysis for detection of Pseudomonas aeruginosa in cystic fibrosis patients, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

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