Imperial College London

Professor Nicholas Simmonds

Faculty of MedicineNational Heart & Lung Institute

Professor of Practice (Respiratory Medicine)
 
 
 
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Contact

 

+44 (0)20 7351 8997n.simmonds

 
 
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Location

 

Dept of Cystic FibrosisRoyal BromptonRoyal Brompton Campus

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Summary

 

Publications

Publication Type
Year
to

130 results found

Archangelidi O, Cullinan P, Simmonds NJ, Mentzakis E, Peckham D, Bilton D, Carr SBet al., 2022, Incidence and risk factors of cancer in individuals with cystic fibrosis in the UK; a case-control study., Journal of Cystic Fibrosis, Vol: 21, Pages: 302-308, ISSN: 1569-1993

To assess cancer incidence in the UK cystic fibrosis (CF) population and determine the associated risk factors, we undertook a nested case-control study of patients with CF, registered with the UK CF Registry. Each case with a first reported cancer between 1999 and 2017 was matched with up to 4 controls: by age (±2-years) and year of cancer diagnosis. Conditional logistic regressions were adjusted for sex, lung function (FEV1%), CF related diabetes (CFRD), F508del status, transplant status, DIOS, gastro-oesophageal reflux disease, meconium ileus, Pseudomonas aeruginosa infection, pancreatic insufficiency, proton pump inhibitor (PPI) use, IV antibiotic days and BMI. Results: From 12,886 registered patients, 146 (1.1%) cases of malignancy were identified with 14.3% of cases occurring post solid organ transplant. Site of primary cancer was available for 98 patients: 22% were gastro-intestinal in origin (77% lower, 23% upper GI), 13% skin, 13% breast and 11% lymphomas/leukaemia. In univariable analysis, transplantation increased the odds of reporting any cancer by 2.46 times (95%CI: 1.3-4.6). CFRD also increased the odds of reporting any cancer (OR 2.35; CI: 1.37-4.0) and PPI use (OR 2.0; CI 1.28-3.19). In the multivariable models significant associations with CFRD and transplant remained, while PA infection, PPI use and being overweight showed increased, but statistically insignificant risks. The incidence of GI cancer was strongly associated with CFRD (OR=4.04; 1.47-11.1). Conclusions: We observed a high incidence of lower GI cancers in our cohort which was significantly affected by the presence of CFRD. Screening for gastrointestinal cancers could benefit patients at higher risk.

Journal article

Cirilli N, Southern KW, Barben J, Vermeulen F, Munck A, Wilschanski M, Nguyen-Khoa T, Aralica M, Simmonds NJ, De Wachter E, ECFS Diagnostic Network Working Groupet al., 2022, Standards of care guidance for sweat testing; phase two of the ECFS quality improvement programme., J Cyst Fibros

More than five decades after the introduction of the quantitative pilocarpine iontophoresis technique, surveys still highlight inconsistencies in the performance and reporting of sweat tests in Europe. The sweat test remains key for the Cystic Fibrosis (CF) diagnostic pathway for all age groups, as it reflects the basic pathophysiological defect in the sweat gland. It is also critical following newborn screening as a confirmatory diagnostic step. Despite its importance, sweat test quality is variable whether performed in the laboratory or as a point of care test. The ECFS DNWG aims to improve sweat test performance, taking into account the barriers and issues identified in the European survey; the previous step in the ECFS sweat test project. This manuscript proposes a grading of sweat test guidance from "acceptable" to "optimal", aiming to pragmatically improve quality while taking into account local situations, especially in resource-limited settings.

Journal article

Balfour-Lynn IM, Puckey M, Simmonds NJ, Davies JCet al., 2021, Revisiting a diagnosis of cystic fibrosis - Uncertainties and considerations., Paediatr Respir Rev

There is now increased knowledge and experience of newborn screening around the world. There is also a better understanding of CF gene analysis, informed by international databases. This has resulted in a small number of children and adults having their diagnosis of CF reversed. This article illustrates this issue with three cases. It considers how best to tell children and adults with their families, and the reactions that may be encountered. It also discusses practical issues of removing the diagnosis.

Journal article

Simmonds NJ, van der Ent K, Colombo C, Kinnman N, DeSouza C, Thorat T, Chandarana K, Castellani Cet al., 2021, OBSERVATIONAL STUDY OF IVACAFTOR IN PEOPLE WITH CYSTIC FIBROSIS AND SELECTED NON-G551D GATING MUTATIONS: FINAL RESULTS FROM VOCAL, Publisher: BMJ PUBLISHING GROUP, Pages: A40-A41, ISSN: 0040-6376

Conference paper

Castellani C, Simmonds NJ, Colombo C, Kinnman N, DeSouza C, Thorat T, Chew M, Chandarana K, van der Ent Ket al., 2021, RESPIRATORY MICROBIOLOGY OUTCOMES FROM AN OBSERVATIONAL STUDY OF IVACAFTOR IN PEOPLE WITH CYSTIC FIBROSIS AND NON-G551D GATING MUTATIONS (VOCAL), Publisher: BMJ PUBLISHING GROUP, Pages: A41-A41, ISSN: 0040-6376

Conference paper

Dobra R, Davies G, Pike K, Strassle C, Allen L, Brendell R, Brownlee K, Carr S, Simmonds N, Davies Jet al., 2021, Optimising equity of access: how should we allocate slots to the most competitive trials in Cystic Fibrosis (CF)?, Journal of Cystic Fibrosis, Vol: 20, Pages: 978-985, ISSN: 1569-1993

Background:Trial participation can allow people with CF early access to CFTR modulator therapies, with high potential for clinical benefit. Therefore, the number of people wishing to participate can substantially exceed the number of slots available. We aimed to understand how the CF community thinks slots to competitive trials should be allocated across the UK and whether this should be driven by clinical need, patients’ engagement/adherence or be random. For the latter, we explored site-level versus registry-based, national randomisation processes.Methods:We developed an online survey, recruiting UK-based stakeholders through social media, newsletters and personal contacts. Closed questions were analysed for frequencies and percentages of responses. Free-text questions were analysed using thematic analysis.Results:We received 203 eligible responses. Overall, 75% of stakeholders favoured allocation of slots to individual sites based on patient population size, although pharma favoured allocation based on previous metrics. Currently, few centres have defined strategies for allocating slots locally. At face-value, stakeholders believe all eligible participants should have an equal chance of getting a slot. However, further questioning reveals preference for prioritisation strategies, primarily perceived treatment adherence, although healthcare professionals were less likely to favour this strategy than other stakeholder groups. The majority of stakeholders would prefer to allocate slots and participate in trials locally but 80% said if necessary, they would engage in a system of national allocation.Conclusions:Fair allocation to highly competitive trials does not appear to have a universally acceptable solution. Therefore, transparency and empathy remain critical to negotiate this uncertain territory.

Journal article

Castellani C, Simmonds NJ, Colombo C, Kinnman N, Desouza C, Thorat T, Chew M, Chandarana K, Van Der Ent Ket al., 2021, Respiratory microbiology outcomes from an observational study of ivacaftor in people with cystic fibrosis and non-G551D gating mutations (VOCAL), European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Dave K, Dunk R, Madge S, Gerovasili V, Reed A, Simmonds NJet al., 2021, Could a 2-year mortality prediction model have prevented deaths from respiratory failure: a single UK centre experience, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Simmonds N, Van Der Ent K, Colombo C, Kinnman N, Desouza C, Thorat T, Chandarana K, Castellani Cet al., 2021, Observational study of ivacaftor in people with cystic fibrosis and selected non-G551D gating mutations: final results from VOCAL, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Van Koningsbruggen-Rietschel S, Dunlevy F, Bulteel V, Hayes K, Verbrugge A, Janssens HM, Dufeu N, Simmonds NJ, Dupont LJ, Downey DGet al., 2021, Protecting clinical trials in cystic fibrosis during the SARS-CoV-2 pandemic: risks and mitigation measures, TRIALS, Vol: 22

Journal article

Dave K, Gerovasili V, Simmonds NJ, Carby M, Reed Aet al., 2021, The Changing Face of Lung Transplant Waiting Lists in the Era of CFTR Modulators, Publisher: ELSEVIER SCIENCE INC, Pages: S368-S368, ISSN: 1053-2498

Conference paper

Kazani S, Rowlands DJ, Bottoli I, Milojevic J, Alcantara J, Jones I, Kulmatycki K, Machineni S, Mostovy L, Nicholls I, Nick JA, Rowe SM, Simmonds NJ, Vegesna R, Verheijen J, Danahay H, Gosling M, Ayalavajjala PS, Salman M, Strieter Ret al., 2021, Safety and efficacy of the cystic fibrosis transmembrane conductance regulator potentiator icenticaftor (QBW251), JOURNAL OF CYSTIC FIBROSIS, Vol: 20, Pages: 250-256, ISSN: 1569-1993

Journal article

Cuthbertson L, Felton I, James P, Cox MJ, Bilton D, Schelenz S, Loebinger MR, Cookson WOC, Simmonds NJ, Moffatt MFet 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.

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

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

Hughes DA, Cuthbertson L, Price H, Felton I, Coates M, Simmonds NJ, Loebinger MR, Armstrong-James D, Elborn JS, Cookson WO, Moffatt MF, Davies JCet al., 2021, PSEUDOMONAS AERUGINOSA IMPAIRS GROWTH OF ASPERGILLUS FROM CF AIRWAY SAMPLES, Publisher: BMJ PUBLISHING GROUP, Pages: A159-A159, ISSN: 0040-6376

Conference paper

Simmonds NJ, 2021, Introducing the Adult Cystic Fibrosis Series An Exciting Time of Change, But New Challenges Lie Ahead, CHEST, Vol: 159, Pages: 3-4, ISSN: 0012-3692

Journal article

Stanford GE, Dave K, Simmonds NJ, 2021, Pulmonary Exacerbations in Adults With Cystic Fibrosis A Grown-up Issue in a Changing Cystic Fibrosis Landscape, CHEST, Vol: 159, Pages: 93-102, ISSN: 0012-3692

Journal article

Savi D, Graziano L, Giordani B, Schiavetto S, De Vito C, Migliara G, Simmonds NJ, Palange P, Elborn JSet al., 2020, New strategies of physical activity assessment in cystic fibrosis: a pilot study, BMC PULMONARY MEDICINE, Vol: 20, ISSN: 1471-2466

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

van der Ent K, Simmonds NJ, Colombo C, DeSouza C, Kinnman N, Thorat T, Chandarana K, Castellani Cet al., 2020, AN OBSERVATIONAL STUDY OF IVACAFTOR IN PEOPLE WITH CYSTIC FIBROSIS AND SELECTED NON-G551D GATING MUTATIONS: OUTCOMES FROM THE THIRD INTERIM ANALYSIS OF THE VOCAL STUDY, Publisher: WILEY, Pages: S220-S220, ISSN: 8755-6863

Conference paper

Hughes D, Cuthbertson L, Price H, Felton I, Coates M, Simmonds NJ, Loebinger M, Armstrong-James D, Elborn J, Cookson W, Moffatt M, Davies JCet al., 2020, PSEUDOMONAS AERUGINOSA IMPAIRS GROWTH OF ASPERGILLUS FROM CF AIRWAY SAMPLES, Publisher: WILEY, Pages: S153-S153, ISSN: 8755-6863

Conference paper

Silva GF, Simmonds NJ, Roth Dalcin PDT, 2020, Clinical characteristics and outcomes in adult cystic fibrosis patients with severe lung disease in Porto Alegre, southern Brazil, BMC Pulmonary Medicine, Vol: 20, Pages: 1-8, ISSN: 1471-2466

BackgroundAdvanced lung disease in adult cystic fibrosis (CF) drives most clinical care requirements. The aim was to evaluate outcome (time to death while in the study) in a cohort of adult CF patients with severe lung disease, and to determine the association among baseline patient characteristics and outcome.MethodsA retrospective cohort study was performed and clinical records between 2000 and 2015 were reviewed. Severe lung disease was defined as forced expiratory volume in the first second (FEV1) < 30% of predicted. Outcomes of all patients, including their date of death or transplantation, were determined till January 1st, 2016. Clinical data were recorded at the entry date.ResultsAmong 39 subjects included in the study, 20 (51.3%) died, 16 (41.0%) underwent bilateral lung transplantation, and 3 were alive at the end of the study period. Two variables were independently associated with death: body mass index (BMI ≥ 18.5 kg/m2) (HR = 0.78, 95% CI = 0.64–0.96 and p = 0.017) and use of tobramycin inhalation therapy (HR = 3.82, 95% CI = 1.38–10.6 and p = 0.010). Median survival was 37 (95% CI = 16.4–57.6) months. The best cut-off point for BMI was 18.5 kg/m2. Median survival in patients with BMI < 18.5 kg/m2 was 36 months (95% CI = 18.7–53.3).ConclusionMedian survival of CF subjects with FEV1 < 30% was 37 months. BMI and tobramycin inhalation therapy were independently associated with death. Median survival in patients with BMI < 18.5 kg/m2 was significantly lower than in patients with BMI ≥ 18.5 kg/m2. The association of tobramycin inhalation with death was interpreted as confounding by severity (use was reserved for advanced lung disease).

Journal article

Vijayasingam A, Frost E, Wilkins J, Gillen L, Premachandra P, Mclaren K, Gilmartin D, Picinali L, Vidal-Diez A, Borsci S, Ni MZ, Tang WY, Morris-Rosendahl D, Harcourt J, Elston C, Simmonds NJ, Shah Aet al., 2020, Tablet and web-based audiometry to screen for hearing loss in adults with cystic fibrosis, Thorax, Vol: 75, Pages: 632-639, ISSN: 0040-6376

INTRODUCTION: Individuals with chronic lung disease (eg, cystic fibrosis (CF)) often receive antimicrobial therapy including aminoglycosides resulting in ototoxicity. Extended high-frequency audiometry has increased sensitivity for ototoxicity detection, but diagnostic audiometry in a sound-booth is costly, time-consuming and requires a trained audiologist. This cross-sectional study analysed tablet-based audiometry (Shoebox MD) performed by non-audiologists in an outpatient setting, alongside home web-based audiometry (3D Tune-In) to screen for hearing loss in adults with CF. METHODS: Hearing was analysed in 126 CF adults using validated questionnaires, a web self-hearing test (0.5 to 4 kHz), tablet (0.25 to 12 kHz) and sound-booth audiometry (0.25 to 12 kHz). A threshold of ≥25 dB hearing loss at ≥1 audiometric frequency was considered abnormal. Demographics and mitochondrial DNA sequencing were used to analyse risk factors, and accuracy and usability of hearing tests determined. RESULTS: Prevalence of hearing loss within any frequency band tested was 48%. Multivariate analysis showed age (OR 1.127; (95% CI: 1.07 to 1.18; p value<0.0001) per year older) and total intravenous antibiotic days over 10 years (OR 1.006; (95% CI: 1.002 to 1.010; p value=0.004) per further intravenous day) were significantly associated with increased risk of hearing loss. Tablet audiometry had good usability, was 93% sensitive, 88% specific with 94% negative predictive value to screen for hearing loss compared with web self-test audiometry and questionnaires which had poor sensitivity (17% and 13%, respectively). Intraclass correlation (ICC) of tablet versus sound-booth audiometry showed high correlation (ICC >0.9) at all frequencies ≥4 kHz. CONCLUSIONS: Adults with CF have a high prevalence of drug-related hearing loss and tablet-based audiometry can be a practical, accurate screening tool within integrated ototoxicity monitoring programmes for early detection.

Journal article

Aalbers BL, Yaakov Y, Derichs N, Simmonds NJ, De Wachter E, Melotti P, De Boeck K, Leal T, Tuemmler B, Wilschanski M, Bronsveld Iet al., 2020, Nasal potential difference in suspected cystic fibrosis patients with 5T polymorphism, JOURNAL OF CYSTIC FIBROSIS, Vol: 19, Pages: 627-631, ISSN: 1569-1993

Journal article

Keogh RH, Tanner K, Simmonds NJ, Bilton Det al., 2020, The changing demography of the cystic fibrosis population: forecasting future numbers of adults in the UK, SCIENTIFIC REPORTS, Vol: 10, Pages: 1-8, ISSN: 2045-2322

Improvements in management of cystic fibrosis (CF) through specialist centres in the UK have been associated with a step-change in life expectancy. With increasing numbers of adult patients there is a need to review health care provision to ensure it is sufficient to meet future needs. We used UK CF Registry data to project the number of patients aged 16–17 and 18 and older  up to 2030, and numbers therefore requiring specialist adult CF care. Survival modelling was used to estimate age-specific mortality rates. New-diagnosis rates were estimated using diagnoses observed in the Registry and national population figures. Uncertainty in projections was captured through 95% prediction intervals (PI). The number of adults (aged 18 and older) is expected to increase by 28% from 6,225 in 2017 to 7,988 in 2030 (95% PI 7,803–8,169), assuming current mortality rates. If mortality rates improve at the rate seen over recent years, the projected number increases to 8,579 (95% PI 8,386–8,764). The age distribution is also expected to change, with 36% of CF adults being over 40 in 2030, versus 21% in 2017. There is an urgent requirement to review adult CF health care provision, due to both increasing numbers and the changing care needs of an older population.

Journal article

Morris-Rosendahl DJ, Edwards M, McDonnell MJ, John S, Alton EWFW, Davies JC, Simmonds NJet al., 2020, Whole-gene sequencing of CFTR reveals a high prevalence of the intronic variant c.3874-4522A>G in cystic fibrosis., American Journal of Respiratory and Critical Care Medicine, Vol: 201, Pages: 1438-1441, ISSN: 1073-449X

Journal article

Cosgriff R, Ahern S, Bell SC, Brownlee K, Burgel P-R, Byrnes C, Corvol H, Cheng SY, Elbert A, Faro A, Goss CH, Gulmans V, Marshall BC, McKone E, Middleton PG, Ruseckaite R, Stephenson AL, Carr SB, Global Registry Harmonization Groupet al., 2020, A multinational report to characterise SARS-CoV-2 infection in people with cystic fibrosis., J Cyst Fibros, Vol: 19, Pages: 355-358

Information is lacking on the clinical impact of the novel coronavirus, SARS-CoV-2, on people with cystic fibrosis (CF). Our aim was to characterise SARS-CoV-2 infection in people with cystic fibrosis. METHODS: Anonymised data submitted by each participating country to their National CF Registry was reported using a standardised template, then collated and summarised. RESULTS: 40 cases have been reported across 8 countries. Of the 40 cases, 31 (78%) were symptomatic for SARS-CoV-2 at presentation, with 24 (60%) having a fever. 70% have recovered, 30% remain unresolved at time of reporting, and no deaths have been submitted. CONCLUSIONS: This early report shows good recovery from SARS-CoV-2 in this heterogeneous CF cohort. The disease course does not seem to differ from the general population, but the current numbers are too small to draw firm conclusions and people with CF should continue to strictly follow public health advice to protect themselves from infection.

Journal article

Simmonds NJ, Castellani C, Colombo C, van der Ent K, Jha L, DeSouza C, Thorat T, Kinnman Net al., 2019, AN OBSERVATIONAL STUDY OF IVACAFTOR IN PATIENTS WITH CYSTIC FIBROSIS (CF) AND SELECTED NON-G551D GATING MUTATIONS: OUTCOMES FROM THE SECOND INTERIM ANALYSIS OF THE VOCAL STUDY, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A11-A11, ISSN: 0040-6376

Conference paper

Archangelidi O, Abbott J, Bryon M, Cosgriff R, Simmonds N, Duckers J, Bell N, Wildman M, Withers N, Orchard C, Bilton D, Carr SBet al., 2019, QUALITY OF LIFE IN PATIENTS WITH CF USING THREE ONLINE RESEARCH QUESTIONNAIRES: A FEASIBILITY STUDY, Publisher: WILEY, Pages: S419-S419, ISSN: 8755-6863

Conference paper

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