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Article ; Online: Hypertrophic Osteoarthropathy in Cystic Fibrosis.

Clarke, Elizabeth / Bright-Thomas, Rowland

Arthritis & rheumatology (Hoboken, N.J.)

2019 Volume 71, Issue 10, Page(s) 1633

MeSH term(s)	Arthralgia/diagnostic imaging ; Arthralgia/etiology ; Cystic Fibrosis/complications ; Edema/diagnostic imaging ; Edema/etiology ; Humans ; Male ; Osteoarthropathy, Secondary Hypertrophic/diagnostic imaging ; Osteoarthropathy, Secondary Hypertrophic/etiology ; Radius/diagnostic imaging ; Ulna/diagnostic imaging ; Wrist ; Young Adult
Language	English
Publishing date	2019-08-27
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.41014
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Article ; Online: Longitudinal effects of elexacaftor/tezacaftor/ivacaftor on liver tests at a large single adult cystic fibrosis centre.

Tewkesbury, Daniel H / Athwal, Varinder / Bright-Thomas, Rowland J / Jones, Andrew M / Barry, Peter J

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

2023 Volume 22, Issue 2, Page(s) 256–262

Abstract: Background: Elexacaftor/tezacaftor/ivacaftor (E/T/I) therapy has resulted in substantial improvements in health status for many with cystic fibrosis. Monitoring of liver tests is recommended due to observed rises in transaminases in trials and cases of ... ...

Abstract	Background: Elexacaftor/tezacaftor/ivacaftor (E/T/I) therapy has resulted in substantial improvements in health status for many with cystic fibrosis. Monitoring of liver tests is recommended due to observed rises in transaminases in trials and cases of hepatotoxicity. Comprehensive data in large populations of unselected individuals and those with established CF related liver disease (CFLD) is lacking. Methods: Patients prescribed E/T/I at a large, adult centre had liver tests monitored at least 3 monthly for 12 months. Changes in individual liver tests were analysed and abnormalities were compared in those with and without CFLD. Results: 255 of 267 eligible patients were included. Mild rises in median ALT, AST and bilirubin from baseline to 3 months (all p < 0.001) within normal limits were noted which were sustained. There were no differences in changes in liver tests between those with or without CFLD. There was a significant difference in alkaline phosphatase for those with raised levels at baseline versus those with normal baseline level (-18.5 vs +2.0 IU/L, p = 0.002). Clinically significant rises in ALT and AST occurred in 8 (3.1%) and 6 (2.4%) cases respectively, with derangements in 2 individuals attributed to therapy. Conclusions: E/T/I leads to a mild, likely clinically insignificant increase in ALT, AST and bilirubin after 3 months which is sustained but does not appear to increase further in the vast majority. Underlying CFLD should not be a barrier to treatment. Although there was a reduction in ALP when elevated at baseline, this was not unique to those with pre-existing CFLD.
MeSH term(s)	Humans ; Adult ; Cystic Fibrosis/diagnosis ; Cystic Fibrosis/drug therapy ; Cystic Fibrosis/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Aminophenols/adverse effects ; Benzodioxoles/adverse effects ; Bilirubin ; Liver ; Mutation
Chemical Substances	elexacaftor (RRN67GMB0V) ; ivacaftor (1Y740ILL1Z) ; tezacaftor ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Aminophenols ; Benzodioxoles ; Bilirubin (RFM9X3LJ49)
Language	English
Publishing date	2023-01-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2084724-5
ISSN	1873-5010 ; 1569-1993
ISSN (online)	1873-5010
ISSN	1569-1993
DOI	10.1016/j.jcf.2023.01.007
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Article ; Online: Lessons of the month 1: Salbutamol induced lactic acidosis: clinically recognised but often forgotten.

Pearmain, Laurence / Gupta, Ravi / Bright-Thomas, Rowland J

Clinical medicine (London, England)

2020 Volume 20, Issue 1, Page(s) 101–104

Abstract: We present the case of an 83-year-old woman, with known asthma, admitted with increasing dyspnoea, wheeze and a productive cough. In addition to maintenance inhaled therapy, the patient was also on long-term mirtazapine and furosemide. Following acute ... ...

Abstract	We present the case of an 83-year-old woman, with known asthma, admitted with increasing dyspnoea, wheeze and a productive cough. In addition to maintenance inhaled therapy, the patient was also on long-term mirtazapine and furosemide. Following acute treatment with nebulised salbutamol she became increasingly dyspnoeic and developed a metabolic acidosis with a significantly raised blood lactate level. After cessation of ß
MeSH term(s)	Acidosis, Lactic/chemically induced ; Acidosis, Lactic/drug therapy ; Administration, Inhalation ; Aged, 80 and over ; Albuterol/adverse effects ; Asthma/drug therapy ; Female ; Humans
Chemical Substances	Albuterol (QF8SVZ843E)
Language	English
Publishing date	2020-01-14
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2048646-7
ISSN	1473-4893 ; 1470-2118
ISSN (online)	1473-4893
ISSN	1470-2118
DOI	10.7861/clinmed.2019-0271
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Article: Renal transplantation in a patient with cystic fibrosis: a changing disease landscape.

Tewkesbury, Daniel H / Dhanda, Raman / Looi, Evelyn / Bright-Thomas, Rowland J

British journal of hospital medicine (London, England : 2005)

2021 Volume 82, Issue 10, Page(s) 1–3

MeSH term(s)	Cystic Fibrosis/therapy ; Humans ; Kidney Transplantation ; Lung Transplantation
Language	English
Publishing date	2021-10-14
Publishing country	England
Document type	Journal Article
ISSN	1750-8460
ISSN	1750-8460
DOI	10.12968/hmed.2020.0744
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Article ; Online: Aetiology of Significant Liver Test Abnormalities in a Single-Centre Cohort of People with Cystic Fibrosis Exposed to Elexacaftor/Tezacaftor/Ivacaftor, Utilizing the Updated RUCAM.

Tewkesbury, Daniel / Jones, Andrew M / Bright-Thomas, Rowland / Cratchley, Alyn / Hanley, Karen Piper / Wyatt, Judith / Athwal, Varinder / Barry, Peter J

Drugs

2023 Volume 83, Issue 18, Page(s) 1699–1707

Abstract: Background: The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (E/T/I) has been associated with substantial multisystem benefits for people with CF eligible for therapy. In a minority, ... ...

Abstract	Background: The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (E/T/I) has been associated with substantial multisystem benefits for people with CF eligible for therapy. In a minority, tolerance has been limited by hepatic toxicity. It is unknown whether there may be particular risk factors for significant drug-induced elevation in transaminases. Objective: We aimed to determine the cause of raised transaminases following the introduction of E/T/I, and whether E/T/I can safely be continued in some individuals with elevated transaminases. Methods: At a large, single, adult CF centre, individuals with transaminases >3 × the upper limit of normal (ULN) since commencing E/T/I underwent clinical assessment to exclude known causes of raised transaminases. Where an alternative cause could not be identified, individuals were discussed with hepatology to advise on further investigations to establish aetiology in addition to calculation of the updated Roussel Uclaf Causality Assessment Method (RUCAM) score to assess causality grading of drug-induced liver injury (DILI) due to E/T/I, and to guide management of ongoing CFTR modulator therapy. Results: Of 337 adults taking E/T/I for a median of 27 months, 19 (5.6%) had transaminases >3 × ULN. In 12 individuals, there was clear evidence of an aetiology unrelated to E/T/I (RUCAM scores -2 to 1 [excluded-unlikely]). Of the remaining cases, two had RUCAM scores in the 'possible' range and one had a RUCAM score in the 'probable' range. Liver biopsy was performed in four individuals, showing hepatic steatosis in one individual, normal histology in one individual, and hepatocyte necrosis suggestive of DILI in two individuals. E/T/I was suspended in those with hepatocyte necrosis, with one permanent discontinuation due to synthetic dysfunction. One individual with hepatocyte necrosis on histology was successfully re-established on E/T/I therapy. Conclusions: Alternative causes were identified in the majority of patients with clinically significant increases in transaminases following E/T/I, highlighting the importance of thorough investigation. Multidisciplinary assessment involving an experienced hepatologist is crucial in cases of diagnostic uncertainty or suggestion of significant DILI, as discontinuation of therapy can have significant consequences for individuals.
MeSH term(s)	Adult ; Humans ; Cystic Fibrosis/drug therapy ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Aminophenols/adverse effects ; Benzodioxoles/adverse effects ; Liver Diseases ; Chemical and Drug Induced Liver Injury/etiology ; Transaminases/therapeutic use ; Necrosis/chemically induced ; Mutation
Chemical Substances	Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; elexacaftor (RRN67GMB0V) ; ivacaftor (1Y740ILL1Z) ; tezacaftor ; Aminophenols ; Benzodioxoles ; Transaminases (EC 2.6.1.-)
Language	English
Publishing date	2023-11-15
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	120316-2
ISSN	1179-1950 ; 0012-6667
ISSN (online)	1179-1950
ISSN	0012-6667
DOI	10.1007/s40265-023-01969-3
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Article ; Online: Effects of elexacaftor/tezacaftor/ivacaftor on liver fibrosis markers in adults with cystic fibrosis.

Tewkesbury, Daniel H / Scott, Jennifer / Barry, Peter J / Bright-Thomas, Rowland J / Hanley, Karen Piper / Athwal, Varinder / Jones, Andrew M

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

2023

Abstract: Background: There are limited studies to date on the effects of elexacaftor/tezacaftor/ivacaftor (E/T/I) on markers of liver fibrosis in adults with cystic fibrosis (CF). This study aims to analyse changes in makers of liver fibrosis before and after ... ...

Abstract	Background: There are limited studies to date on the effects of elexacaftor/tezacaftor/ivacaftor (E/T/I) on markers of liver fibrosis in adults with cystic fibrosis (CF). This study aims to analyse changes in makers of liver fibrosis before and after initiation of E/T/I in CF adults. Methods: Outcome measures of liver fibrosis, including liver stiffness measurement (LSM) using FibroScan, AST-to-platelet-ratio index (APRI) and gamma-GT-to-platelet-ratio (GPR) were available in 74 CF adults following initiation of E/T/I. This was compared to historical data collected in 2018 prior to UK availability of E/T/I. Results: The median duration of E/T/I therapy at the time liver fibrosis markers were repeated was 21 (IQR: 17-25) months. There was an increase in APRI from historical measurement to follow-up but no change in LSM or GPR. There were no differences in change in fibrosis markers according to CF liver disease (CFLD) status, although those with a raised LSM at baseline (>6.8 kPa) (n = 14) had a significant reduction in LSM from historical measurement to follow-up versus those with a normal historical value (-3.3 kPa vs 0.25 kPa, p < 0.01). Conclusions: Apart from APRI, we found no changes in liver fibrosis outcomes after initiation of E/T/I in adults with CF. Those with a historical diagnosis of CFLD had no significant worsening or improvement of liver fibrosis markers. We did observe a reduction in LSM in those with liver nodularity, with an initial highest result suggesting a potential positive treatment effect of E/T/I in this category of those with severe CFLD.
Language	English
Publishing date	2023-09-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2084724-5
ISSN	1873-5010 ; 1569-1993
ISSN (online)	1873-5010
ISSN	1569-1993
DOI	10.1016/j.jcf.2023.09.006
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Article ; Online: Thoracic movement screening in adults with cystic fibrosis: reliability of the Manchester musculoskeletal screening tool.

Hodgson, Nicola / Taylor, Julia / Ashbrook, Jane / Goodwin, Peter / Bright-Thomas, Rowland / Caunt, Jenny

Physiotherapy theory and practice

2021 Volume 38, Issue 12, Page(s) 2195–2201

Abstract: Objectives: The Manchester Musculoskeletal Screening Tool (MMST) is used internationally to screen for pain, postural changes, and urinary incontinence in adults with cystic fibrosis (CF). The tool has been validated for the outcome measures of pain and ...

Abstract	Objectives: The Manchester Musculoskeletal Screening Tool (MMST) is used internationally to screen for pain, postural changes, and urinary incontinence in adults with cystic fibrosis (CF). The tool has been validated for the outcome measures of pain and incontinence but not for the thoracic movement section. The aim of this study was to assess intra (single rater) and inter-rater (between rater) reliability of the thoracic movement screen section of the MMST. Methods: This is a prospective reliability study. Digital videos of thoracic movement were taken of adults with CF during their annual musculoskeletal screening at a large UK Adult CF Center. Twelve physiotherapists independently watched the videos and scored the movements on two occasions, 2 weeks apart, using MMST. Cohen's kappa and Krippendorff alpha were used to establish intra- and inter-rater reliability. Results: Intra-rater reliability using Cohen's kappa calculation ranged between 0.35 and 0.93. Eleven out of 12 physiotherapists had a moderate-substantial reliability score as assessed by the Landis Koch criteria. Percentage agreement for each physiotherapist ranged from 67%-97%. The inter-rater reliability was poor (Krippendorff alpha score = 0.422 (CI: 0.24-0.60)). Conclusion: The thoracic section of the MMST is reliable in adults with CF to highlight changes in posture and thoracic mobility that may go undetected or under-reported by the patient when repeated by the same clinician. However, the inter-rater variability is high, and it should not be considered reliable when carried out by different clinicians over time.
MeSH term(s)	Adult ; Humans ; Reproducibility of Results ; Observer Variation ; Cystic Fibrosis/diagnosis ; Prospective Studies ; Pain
Language	English
Publishing date	2021-04-06
Publishing country	England
Document type	Journal Article
ZDB-ID	1045333-7
ISSN	1532-5040 ; 0959-3985
ISSN (online)	1532-5040
ISSN	0959-3985
DOI	10.1080/09593985.2021.1904470
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Article ; Online: Meteorological Factors Influence the Presence of Fungi in the Air; A 14-Month Surveillance Study at an Adult Cystic Fibrosis Center.

van Rhijn, Norman / Coleman, James / Collier, Lisa / Moore, Caroline / Richardson, Malcolm D / Bright-Thomas, Rowland J / Jones, Andrew M

Frontiers in cellular and infection microbiology

2021 Volume 11, Page(s) 759944

Abstract: Background: Cystic fibrosis is an inherited disease that predisposes to progressive lung damage. Cystic fibrosis patients are particularly prone to developing pulmonary infections. Fungal species are commonly isolated in lower airway samples from ... ...

Abstract	Background: Cystic fibrosis is an inherited disease that predisposes to progressive lung damage. Cystic fibrosis patients are particularly prone to developing pulmonary infections. Fungal species are commonly isolated in lower airway samples from patients with cystic fibrosis. Fungal spores are prevalent in the air. Methods: We performed environmental air sampling surveillance at the Manchester Adult Cystic Fibrosis Centre, UK (MACFC) over a 14-month period to assess fungal growth inside and outside the CF center. Results: Airborne counts of fungal spores peaked from May to October, both in outdoor and indoor samples. Collection of meteorological data allowed us to correlate fungal presence in the air with elevated temperatures and low wind speeds. Additionally, we demonstrated patient rooms containing windows had elevated fungal counts compared to rooms not directly connected to the outdoors. Conclusions: This study suggests that airborne
MeSH term(s)	Adult ; Air Microbiology ; Cystic Fibrosis/complications ; Cystic Fibrosis/epidemiology ; Fungi ; Humans ; Meteorological Concepts ; Spores, Fungal
Language	English
Publishing date	2021-11-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2021.759944
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Article ; Online: Cardiac involvement in cystic fibrosis evaluated using cardiopulmonary magnetic resonance.

Lagan, Jakub / Naish, Josephine H / Bradley, Joshua / Fortune, Christien / Palmer, Charlie / Clark, David / Schelbert, Erik B / Schmitt, Matthias / Bright-Thomas, Rowland / Miller, Christopher A

The international journal of cardiovascular imaging

2022

Abstract: Cystic fibrosis (CF) transmembrane conductance regulator is expressed in myocardium, but cardiac involvement in CF remains poorly understood. The recent development of a combined cardiopulmonary magnetic resonance imaging technology allows for a ... ...

Abstract	Cystic fibrosis (CF) transmembrane conductance regulator is expressed in myocardium, but cardiac involvement in CF remains poorly understood. The recent development of a combined cardiopulmonary magnetic resonance imaging technology allows for a simultaneous interrogation of cardiac and pulmonary structure and function. The aim of this study was to investigate myocardial manifestations in adults with CF, both in a stable state and during an acute respiratory exacerbation, and to investigate the relationship between cardiac and pulmonary disease. Healthy adult volunteers (n = 12) and adults with CF (n = 10) were studied using a multiparametric cardiopulmonary magnetic resonance protocol. CF patients were scanned during an acute respiratory exacerbation and re-scanned when stable. Stable CF was associated with left ventricular dilatation and hypertrophy (LVH; left ventricular mass: CF 59 ± 9 g/m
Language	English
Publishing date	2022-01-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2055311-0
ISSN	1875-8312 ; 1573-0743 ; 1569-5794 ; 0167-9899
ISSN (online)	1875-8312 ; 1573-0743
ISSN	1569-5794 ; 0167-9899
DOI	10.1007/s10554-021-02496-6
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Article ; Online: Influenza B outbreak at an adult cystic fibrosis centre - Clinical impact and factors influencing spread.

Dennis, Jordan B / Jones, Andrew M / Davies, Emma A / Welfare, William / Barry, Peter J / Collier, Lisa / Turner, Andrew / Bright-Thomas, Rowland J

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

2020 Volume 19, Issue 5, Page(s) 808–814

Abstract: Introduction: An outbreak of Influenza B occurred at a large United Kingdom (UK) regional adult cystic fibrosis (CF) centre in May 2016. This was late in the UK 2015-2016 influenza season and occurred on a specialist ward with strict infection control ... ...

Abstract	Introduction: An outbreak of Influenza B occurred at a large United Kingdom (UK) regional adult cystic fibrosis (CF) centre in May 2016. This was late in the UK 2015-2016 influenza season and occurred on a specialist ward with strict infection control procedures. This study investigates the spread of influenza, clinical consequences and potential contributing factors. Methods: Patient records, clinical status and pulmonary function data were reviewed for all inpatients during this period. Respiratory viral PCR results, influenza vaccination status of patients and staff, and environmental factors were also recorded. Affected patients were prospectively monitored for the following three months. Results: 10 of 21 inpatients developed influenza B between 5th and 12th May 2016, an attack rate of 48%. All those characterised were confirmed as the same strain of influenza B/Victoria-lineage. Influenza infection resulted in a mean FEV Conclusion: This influenza B outbreak in CF adults had a high attack rate and a significant clinical impact. Room ventilation and a limited protection from the seasonal influenza vaccine were possible contributory factors.
MeSH term(s)	Adult ; Cystic Fibrosis/complications ; Cystic Fibrosis/therapy ; Disease Outbreaks ; Female ; Hospitals, Special ; Humans ; Infection Control ; Influenza B virus ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Influenza, Human/transmission ; Male ; Retrospective Studies ; United Kingdom
Language	English
Publishing date	2020-06-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2084724-5
ISSN	1873-5010 ; 1569-1993
ISSN (online)	1873-5010
ISSN	1569-1993
DOI	10.1016/j.jcf.2020.04.011
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