Publications
283 results found
Williams P, Buttery S, Mweseli R, et al., 2022, Immediate smoking cessation support vs usual care in smokers attending a targeted lung health check; the QuLIT trial, BMJ Open Respiratory Research, Vol: 9, ISSN: 2052-4439
Objectives: Lung cancer screening programmes offer an opportunity to address tobacco dependence in current smokers. The effectiveness of different approaches to smoking cessation in this context has not yet been established. We investigated if immediate smoking cessation support, including pharmacotherapy, offered as part of a lung cancer screening programme, increases quit rates compared to usual care (Very Brief Advice to quit and signposting to smoking cessation services).Materials and Methods: We conducted a single-blind randomised controlled trial of current smokers aged 55-75 years attending a Targeted Lung Health Check (TLHC). On randomly allocated days smokers received either (1) immediate support from a trained smoking cessation counsellor with appropriate pharmacotherapy or (2) usual care. The primary outcome was self-reported quit rate at three months. We performed thematic analysis of participant interview responses.Results: Of 412 people attending between January and March 2020, 115(27.9%) were current smokers; 46% female, mean(SD) 62.4(5.3) years. Follow up data were available for 84 smokers. At 3 months quit rates in the intervention group were higher 14/48(29.2%) versus 4/36(11%) (2 3.98, p=0.04). Participant interviews revealed four smoking-cessation related themes; 1) Stress and anxiety, 2) Impact of the COVID-19 pandemic, 3) Computerised tomography scans influencing desire to quit, 4) Individual beliefs about stopping smoking. Conclusion: The provision of immediate smoking cessation support is associated with a substantial increase in quit rates at three months. Further research is needed to investigate longer term outcomes and to refine future service delivery.
Maher TM, Brown KK, Kreuter M, et al., 2022, Effects of nintedanib by inclusion criteria for progression of interstitial lung disease, European Respiratory Journal, Vol: 59, Pages: 1-10, ISSN: 0903-1936
The INBUILD trial investigated nintedanib versus placebo in patients with progressive fibrosing interstitial lung diseases (ILDs). We investigated decline in forced vital capacity (FVC) in subgroups based on the inclusion criteria for ILD progression.Subjects had a fibrosing ILD other than idiopathic pulmonary fibrosis and met these criteria for ILD progression within the 24 months before screening despite management deemed appropriate in clinical practice: Group A, relative decline in FVC ≥10% predicted; Group B, relative decline in FVC ≥5-<10% predicted with worsened respiratory symptoms and/or increased extent of fibrosis on HRCT; Group C, worsened respiratory symptoms and increased extent of fibrosis on HRCT only.In the placebo group, the rates of FVC decline over 52 weeks in Groups A, B and C, respectively, were -241.9, -133.1 and -115.3 mL·year-1 in the overall population (p=0.0002 for subgroup-by-time interaction) and -288.9, -156.2 and -100.1 mL·year-1 among subjects with a usual interstitial pneumonia [UIP]-like fibrotic pattern on HRCT (p=0.0005 for subgroup-by-time interaction). Nintedanib had a greater absolute effect on reducing the rate of FVC decline in Group A than Group B or C. However, the relative effect of nintedanib versus placebo was consistent across the subgroups (p>0.05 for heterogeneity).In conclusion, the inclusion criteria used in the INBUILD trial, based on FVC decline or worsening of symptoms and extent of fibrosis on HRCT, were effective at identifying patients with progressive fibrosing ILDs. Nintedanib reduced the rate of decline in FVC across the subgroups based on the inclusion criteria related to ILD progression.
Macaluso C, Boccabella C, Kokosi M, et al., 2022, Short-term lung function changes predict mortality in patients with fibrotic hypersensitivity pneumonitis, Respirology, Vol: 27, Pages: 202-208, ISSN: 1323-7799
Background and objectiveA proportion of patients with fibrotic hypersensitivity pneumonitis (fHP) follow a progressive disease course despite immunosuppressive treatment. Little is known about predictors of mortality in fHP. We aimed to investigate the impact of short-term lung function changes in fHP on mortality.MethodsBaseline demographics for 145 consecutive patients with a multi-disciplinary team diagnosis of fHP, as well as baseline and 1-year follow-up of lung function, baseline echocardiographic findings, bronchoalveolar lavage (BAL) cellularity and all-cause mortality were recorded. Changes in forced vital capacity (FVC) ≥ 5% and ≥10%, and diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 10% and ≥15% at 1 year were calculated. Cox proportional hazards analysis was performed to test for associations with mortality.ResultsBaseline lung function severity, age, presence of honeycombing on computed tomography (CT) and echocardiographic pulmonary arterial systolic pressure (PASP) ≥ 40 mm Hg were associated with early mortality, while BAL lymphocytosis was associated with improved survival. A decline in FVC ≥ 5% (hazard ratio [HR]: 3.10, 95% CI: 2.00–4.81, p < 0.001), FVC ≥ 10% (HR: 3.11, 95% CI: 1.94–4.99, p < 0.001), DLCO ≥ 10% (HR: 2.80, 95% CI: 1.78–4.42, p < 0.001) and DLCO ≥ 15% (HR: 2.92, 95% CI: 1.18–4.72, p < 0.001) at 1 year was associated with markedly reduced survival on univariable and multivariable analyses after correcting for demographic variables, disease severity, honeycombing on CT and treatment, as well as BAL lymphocytosis and PASP ≥ 40 mm Hg on echocardiography, in separate models.ConclusionWorsening in FVC and DLCO at 1 year, including a marginal decline in FVC ≥ 5% and DLCO&th
Sheeka A, Singaravelou A, Bartlett E, et al., 2022, COVID- protected pathways for image- guided lung cancer intervention during the COVID-19 pandemic: A cohort study, BRITISH JOURNAL OF RADIOLOGY, Vol: 96, ISSN: 0007-1285
Folgoc LL, Baltatzis V, Alansary A, et al., 2021, Bayesian analysis of the prevalence bias: learning and predicting from imbalanced data, Publisher: ArXiv
Datasets are rarely a realistic approximation of the target population. Say,prevalence is misrepresented, image quality is above clinical standards, etc.This mismatch is known as sampling bias. Sampling biases are a major hindrancefor machine learning models. They cause significant gaps between modelperformance in the lab and in the real world. Our work is a solution toprevalence bias. Prevalence bias is the discrepancy between the prevalence of apathology and its sampling rate in the training dataset, introduced uponcollecting data or due to the practioner rebalancing the training batches. Thispaper lays the theoretical and computational framework for training models, andfor prediction, in the presence of prevalence bias. Concretely a bias-correctedloss function, as well as bias-corrected predictive rules, are derived underthe principles of Bayesian risk minimization. The loss exhibits a directconnection to the information gain. It offers a principled alternative toheuristic training losses and complements test-time procedures based onselecting an operating point from summary curves. It integrates seamlessly inthe current paradigm of (deep) learning using stochastic backpropagation andnaturally with Bayesian models.
Hewitt RJ, Bartlett EC, Ganatra R, et al., 2021, LUNG CANCER SCREENING PROVIDES A UNIQUE OPPORTUNITY FOR EARLY DIAGNOSIS AND MANAGEMENT OF INTERSTITIAL LUNG DISEASES, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A68-A69, ISSN: 0040-6376
Wells AU, Devaraj A, 2021, Residual Lung Disease at Six-month Follow-up CT after COVID-19: Clinical Significance Is a Key Issue, RADIOLOGY, Vol: 301, Pages: E406-E408, ISSN: 0033-8419
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- Citations: 7
Field JK, Vulkan D, Davies MPA, et al., 2021, Lung cancer mortality reduction by LDCT screening: UKLS randomised trial results and international meta-analysis, LANCET REGIONAL HEALTH-EUROPE, Vol: 10, ISSN: 2666-7762
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- Citations: 54
Macaluso C, Boccabella C, Kokosi M, et al., 2021, MARGINAL SHORT TERM LUNG FUNCTION CHANGES PREDICT MORTALITY IN PATIENTS WITH FIBROTIC HYPERSENSITIVITY PNEUMONITIS, Publisher: BMJ PUBLISHING GROUP, Pages: A146-A147, ISSN: 0040-6376
Nwankwo L, Periselneris J, Gilmartin D, et al., 2021, PREDICTORS OF ADVERSE OUTCOME IN SARCOIDOSIS COMPLICATED BY PULMONARY ASPERGILLOSIS, Publisher: BMJ PUBLISHING GROUP, Pages: A147-A147, ISSN: 0040-6376
Desai S, Devaraj A, Dintakurti S, et al., 2021, INFLUENZA AND COVID-19 PNEUMONIA: THE DIFFERENCE IS PULMONARY HYPERTENSION, Publisher: BMJ PUBLISHING GROUP, Pages: A117-A118, ISSN: 0040-6376
Jacobs C, Setio AAA, Scholten ET, et al., 2021, Deep Learning for Lung Cancer Detection on Screening CT Scans: Results of a Large-Scale Public Competition and an Observer Study with 11 Radiologists, RADIOLOGY-ARTIFICIAL INTELLIGENCE, Vol: 3, ISSN: 2638-6100
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- Citations: 12
Folgoc LL, Baltatzis V, Desai S, et al., 2021, Is MC Dropout Bayesian?
MC Dropout is a mainstream "free lunch" method in medical imaging forapproximate Bayesian computations (ABC). Its appeal is to solve out-of-the-boxthe daunting task of ABC and uncertainty quantification in Neural Networks(NNs); to fall within the variational inference (VI) framework; and to proposea highly multimodal, faithful predictive posterior. We question the propertiesof MC Dropout for approximate inference, as in fact MC Dropout changes theBayesian model; its predictive posterior assigns $0$ probability to the truemodel on closed-form benchmarks; the multimodality of its predictive posterioris not a property of the true predictive posterior but a design artefact. Toaddress the need for VI on arbitrary models, we share a generic VI enginewithin the pytorch framework. The code includes a carefully designedimplementation of structured (diagonal plus low-rank) multivariate normalvariational families, and mixtures thereof. It is intended as a go-tono-free-lunch approach, addressing shortcomings of mean-field VI with anadjustable trade-off between expressivity and computational complexity.
Bartlett E, Kemp S, Rawal B, et al., 2021, Defining growth in small pulmonary nodules using volumetry: results from a "coffee-break" study and implications for current nodule management guidelines, European Radiology, Vol: 32, Pages: 1912-1920, ISSN: 0938-7994
Objectives:An increase in lung nodule volume on serial CT may represent true growth or measurement variation. In nodule guidelines, a 25% increase in nodule volume is frequently used to determine that growth has occurred; this is based on previous same-day, test-retest (coffee-break) studies examining metastatic nodules. Whether results from prior studies apply to small non-metastatic nodules is unknown. This study aimed to establish the interscan variability in the volumetric measurements of small-sized non-metastatic nodules.Methods:Institutional review board approval was obtained for this study. Between March 2019-January 2021, 45 adults (25 males; mean age 65yrs, range 37-84yrs) with previously identified pulmonary nodules (30-150mm3) requiring surveillance, without a known primary tumour, underwent two same-day CT scans. Non-calcified solid nodules were measured using commercial volumetry software, and interscan variability of volume measurements was assessed using a Bland-Altman method and limits of agreement. Results:One hundred nodules (range 28mm3-170mm3; mean 81.1mm3) were analysed. The lower and upper limits of agreement for the absolute volume difference between the two scans were -14.2mm3 and 12.0mm3 respectively (mean difference 1.09mm3, range -33mm3 – 12mm3). The lower and upper limits of agreement for relative volume difference were -16.4% and 14.6% respectively (mean difference 0.90%, range -24.1% - 32.8%). Conclusions:The interscan volume variability in this cohort of small non-metastatic nodules was smaller than in previous studies involving lung metastases of varying sizes. An increase of 15% in nodule volume on sequential CT may represent true growth and closer surveillance of these nodules may be warranted.
Vijayakumar B, Tonkin J, Devaraj A, et al., 2021, Persistent lung abnormalities versus established fibrosis: a prospective study of COVID-19 follow-up, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Creamer A, Dickson J, Horst C, et al., 2021, Delayed interval scanning is not associated with stage-shift at diagnosis: Preliminary results to support guidelines for lung cancer screening during the COVID-19 pandemic, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Bentham R, Litchfield K, Watkins TBK, et al., 2021, Using DNA sequencing data to quantify T cell fraction and therapy response., Nature, Vol: 597, Pages: 555-560
The immune microenvironment influences tumour evolution and can be both prognostic and predict response to immunotherapy1,2. However, measurements of tumour infiltrating lymphocytes (TILs) are limited by a shortage of appropriate data. Whole-exome sequencing (WES) of DNA is frequently performed to calculate tumour mutational burden and identify actionable mutations. Here we develop T cell exome TREC tool (T cell ExTRECT), a method for estimation of T cell fraction from WES samples using a signal from T cell receptor excision circle (TREC) loss during V(D)J recombination of the T cell receptor-α gene (TCRA (also known as TRA)). TCRA T cell fraction correlates with orthogonal TIL estimates and is agnostic to sample type. Blood TCRA T cell fraction is higher in females than in males and correlates with both tumour immune infiltrate and presence of bacterial sequencing reads. Tumour TCRA T cell fraction is prognostic in lung adenocarcinoma. Using a meta-analysis of tumours treated with immunotherapy, we show that tumour TCRA T cell fraction predicts immunotherapy response, providing value beyond measuring tumour mutational burden. Applying T cell ExTRECT to a multi-sample pan-cancer cohort reveals a high diversity of the degree of immune infiltration within tumours. Subclonal loss of 12q24.31-32, encompassing SPPL3, is associated with reduced TCRA T cell fraction. T cell ExTRECT provides a cost-effective technique to characterize immune infiltrate alongside somatic changes.
Devaraj A, Milanese G, Sverzellati N, 2021, Thoracic computed tomography in the progressive fibrotic phenotype, CURRENT OPINION IN PULMONARY MEDICINE, Vol: 27, Pages: 350-354, ISSN: 1070-5287
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- Citations: 3
Vass L, Fisk M, Cheriyan J, et al., 2021, Quantitative F-18-fluorodeoxyglucose positron emission tomography/computed tomography to assess pulmonary inflammation in COPD, ERJ Open Research, Vol: 7, Pages: 1-12, ISSN: 2312-0541
Rationale COPD and smoking are characterised by pulmonary inflammation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging may improve knowledge of pulmonary inflammation in COPD patients and aid early development of novel therapies as an imaging biomarker.Objectives To evaluate pulmonary inflammation, assessed by FDG uptake, in whole and regional lung in “usual” (smoking-related) COPD patients, alpha-1 antitrypsin deficiency (α1ATD) COPD patients, smokers without COPD and never-smokers using FDG PET/CT. Secondly, to explore cross-sectional associations between FDG PET/CT and systemic inflammatory markers in COPD patients and repeatability of the technique in COPD patients.Methods Data from two imaging studies were evaluated. Pulmonary FDG uptake (normalised Ki; nKi) was measured by Patlak graphical analysis in four subject groups: 84 COPD patients, 11 α1ATD-COPD patients, 12 smokers and 10 never-smokers. Within the COPD group, associations between nKi and systemic markers of inflammation were assessed. Repeatability was evaluated in 32 COPD patients comparing nKi values at baseline and at 4-month follow-up.Results COPD patients, α1ATD-COPD patients and smokers had increased whole lung FDG uptake (nKi) compared with never-smokers (0.0037±0.001, 0.0040±0.001, 0.0040±0.001 versus 0.0028±0.001 mL·cm−3·min−1, respectively, p<0.05 for all). Similar results were observed in upper and middle lung regions. In COPD participants, plasma fibrinogen was associated with whole lung nKi (β=0.30, p=0.02) in multivariate analysis adjusted for current smoking, forced expiratory volume in 1 s % predicted, systemic neutrophils and C-reactive protein levels. Mean percentage difference in nKi between the baseline and follow-up was 3.2%, and the within subject coefficient of variability was 7.7%.Conclusions FDG PET/CT has potential as a noninvasive tool to
Bartlett E, Belsey J, Derbyshire J, et al., 2021, Implications of incidental findings from lung screening for primary care: data from a UK pilot, npj Primary Care Respiratory Medicine, Vol: 31, ISSN: 2055-1010
Regional lung cancer screening (LCS) is underway in England, involving a “lung health check” (LHC) and low-dose CT scan for those at high risk of cancer. Incidental findings from LHCs or CTs are usually referred to primary care. We describe the proportion of participants referred from the West London LCS pilot to primary care, the indications for referral, the number of general practitioner (GP) attendances and consequent changes to patient management, and provide an estimated cost-burden analysis for primary care. A small proportion (163/1542, 10.6%) of LHC attendees were referred to primary care, primarily for suspected undiagnosed chronic obstructive pulmonary disease (55/163, 33.7%) or for QRISK® (63/163, 38.7%) assessment. Ninety one of 159 (57.2%) participants consenting to follow-up attended GP appointments; costs incurred by primary care were estimated at £5.69/LHC participant. Patient management changes occurred in only 36/159 (22.6%) referred participants. LHCs result in a small increase to primary care workload provided a strict referral protocol is adhered to. Changes to patient management arising from incidental findings referrals are infrequent.
Bartlett EC, Silva M, Callister ME, et al., 2021, False-Negative Results in Lung Cancer Screening- Evidence and Controversies, JOURNAL OF THORACIC ONCOLOGY, Vol: 16, Pages: 912-921, ISSN: 1556-0864
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- Citations: 8
Kishore AK, Devaraj A, Vail A, et al., 2021, Use of Pulmonary Computed Tomography for Evaluating Suspected Stroke-Associated Pneumonia, JOURNAL OF STROKE & CEREBROVASCULAR DISEASES, Vol: 30, ISSN: 1052-3057
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- Citations: 3
Denton C, Goh N, Humphries SM, et al., 2021, Associations Between Extent of Fibrotic Interstitial Lung Disease (ILD) and Forced Vital Capacity (FVC) at Baseline and Change in FVC in Subjects with Systemic Sclerosis-Associated ILD (SSc-ILD) in the SENSCIS Trial, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Mirsadraee S, Gorog DA, Mahon CF, et al., 2021, Prevalence of Thrombotic Complications in ICU-Treated Patients With Coronavirus Disease 2019 Detected With Systematic CT Scanning, CRITICAL CARE MEDICINE, Vol: 49, Pages: 804-815, ISSN: 0090-3493
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- Citations: 26
Behr J, Brown KK, Walsh SLF, et al., 2021, Does HRCT pattern influence the effect of nintedanib in patients with progressive fibrosing interstitial lung diseases?, Publisher: GEORG THIEME VERLAG KG, Pages: S31-S32, ISSN: 0934-8387
Koschel D, Flaherty KR, Wells AU, et al., 2021, Effects of nintedanib on progression of ILD in patients with fibrosing ILDs and a progressive phenotype: further analyses of the INBUILD trial, Publisher: GEORG THIEME VERLAG KG, Pages: S30-S31, ISSN: 0934-8387
Wells AU, Devaraj A, Desai SR, 2021, Interstitial Lung Disease after COVID-19 Infection: A Catalog of Uncertainties COMMENT, RADIOLOGY, Vol: 299, Pages: E216-E218, ISSN: 0033-8419
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- Citations: 41
Horst C, Dickson J, Tisi S, et al., 2021, The SUMMIT Study: Pulmonary Nodule and Incidental Findings in the First 10,000 Participants of a Population-Based Low-Dose CT Screening Study, Publisher: ELSEVIER SCIENCE INC, Pages: S473-S474, ISSN: 1556-0864
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- Citations: 4
Invernizzi R, Wu BG, Barnett J, et al., 2021, The respiratory microbiome in chronic hypersensitivity pneumonitis is distinct from that of idiopathic pulmonary fibrosis, American Journal of Respiratory and Critical Care Medicine, Vol: 203, Pages: 339-347, ISSN: 1073-449X
RATIONALE: Chronic hypersensitivity pneumonitis (CHP) is a condition that arises following repeated exposure and sensitisation to inhaled antigens. The lung microbiome is increasingly implicated in respiratory disease but to date, no study has investigated the composition of microbial communities in the lower airways in CHP. OBJECTIVE: To characterise and compare the airway microbiome in subjects with CHP, idiopathic pulmonary fibrosis (IPF) and controls. METHODS: We prospectively recruited individuals diagnosed with CHP (n=110), IPF (n=45) and controls (n=28). Subjects underwent bronchoalveolar lavage and bacterial DNA was isolated, quantified by qPCR and the 16S rRNA gene was sequenced to characterise the bacterial communities in the lower airways. MAIN MEASUREMENTS AND RESULTS: Distinct differences in the microbial profiles were evident in the lower airways of subjects with CHP and IPF. At the phylum level, the prevailing microbiota of both IPF and CHP subjects included Firmicutes, Bacteroidetes, Proteobacteria and Actinobacteria. However, in IPF, Firmicutes dominated while the percentage of reads assigned to Proteobacteria in the same group was significantly lower compared to CHP subjects. At the genus level, Staphylococcus was increased in CHP and Actinomyces and Veillonella in IPF. The lower airway bacterial burden in CHP subjects was higher than controls but lower than those with IPF. In contrast to IPF, there was no association between bacterial burden and survival in CHP. CONCLUSIONS: The microbial profile of the lower airways in subjects with CHP is distinct from that of IPF and, notably, bacterial burden in individuals with CHP fails to predict survival.
Chua F, Bartlett E, Barnett J, et al., 2021, PLEUROPARENCHYMAL FIBROELASTOSIS: CLINICAL, FUNCTIONAL AND MORPHOLOGIC DETERMINANTS OF MORTALITY, Publisher: BMJ PUBLISHING GROUP, Pages: A74-A74, ISSN: 0040-6376
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