Publications
396 results found
Keir GJ, John Wort S, Kokosi M, et al., 2018, Pulmonary hypertension in interstitial lung disease: limitations of echocardiography compared to cardiac catheterization, Respirology, Vol: 23, Pages: 687-694, ISSN: 1323-7799
BACKGROUND AND OBJECTIVE: In interstitial lung disease (ILD), pulmonary hypertension (PH) is a major adverse prognostic determinant. Transthoracic echocardiography (TTE) is the most widely used tool when screening for PH, although discordance between TTE and right heart catheter (RHC) measured pulmonary haemodynamics is increasingly recognized. We evaluated the predictive utility of the updated European Society of Cardiology/European Respiratory Society (ESC/ERS) TTE screening recommendations against RHC testing in a large, well-characterized ILD cohort. METHODS: Two hundred and sixty-five consecutive patients with ILD and suspected PH underwent comprehensive assessment, including RHC, between 2006 and 2012. ESC/ERS recommended tricuspid regurgitation (TR) velocity thresholds for assigning high (>3.4 m/s), intermediate (2.9-3.4 m/s) and low (<2.8 m/s) probabilities of PH were evaluated against RHC testing. RESULTS: RHC testing confirmed PH in 86% of subjects with a peak TR velocity >3.4 m/s, and excluded PH in 60% of ILD subjects with a TR velocity <2.8 m/s. Thus, the ESC/ERS guidelines misclassified 40% of subjects as 'low probability' of PH, when PH was confirmed on subsequent RHC. Evaluating alternative TR velocity thresholds for assigning a low probability of PH did not significantly improve the ability of TR velocity to exclude a diagnosis of PH. CONCLUSION: In patients with ILD and suspected PH, currently recommended ESC/ERS TR velocity screening thresholds were associated with a high positive predictive value (86%) for confirming PH, but were of limited value in excluding PH, with 40% of patients misclassified as low probability when PH was confirmed at subsequent RHC.
Cowman SA, Jacob J, Hansell DM, et al., 2018, Whole blood gene expression in pulmonary non-tuberculous mycobacterial infection, American Journal of Respiratory Cell and Molecular Biology, Vol: 58, Pages: 510-518, ISSN: 1044-1549
RATIONALE: The factors predisposing towards the development of pulmonary non-tuberculous mycobacterial disease (pNTM) and influencing disease progression remain unclear. Impaired immune responses have been reported in individuals with pNTM but data are limited and inconsistent. OBJECTIVES: To use gene expression profiling to examine the host response to pNTM. METHODS: Microarray analysis of whole blood gene expression was performed on 25 subjects with pNTM and 27 uninfected controls with respiratory disease. Gene expression results were compared to phenotypic variables and survival data. MEASUREMENTS AND MAIN RESULTS: Compared with uninfected controls, pNTM was associated with down-regulation of 213 transcripts enriched for terms related to T cell signalling including IFNG. Reduced IFNG expression was associated with more severe CT changes and impaired lung function. Mortality was associated with the expression of transcripts related to the innate immune response and inflammation, whereas transcripts related to T and B cell function were associated with improved survival. CONCLUSIONS: These findings suggest that pNTM is associated with an aberrant immune response which may reflect an underlying propensity to infection, or result from NTM infection itself. There were important differences in the immune response associated with survival and mortality in pNTM.
Castillo D, Walsh S, Hansell DM, et al., 2018, Validation of multidisciplinary diagnosis in IPF, LANCET RESPIRATORY MEDICINE, Vol: 6, Pages: 88-89, ISSN: 2213-2600
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- Citations: 10
Nair A, Screaton NJ, Holemans JA, et al., 2018, The impact of trained radiographers as concurrent readers on performance and reading time of experienced radiologists in the UK Lung Cancer Screening (UKLS) trial, EUROPEAN RADIOLOGY, Vol: 28, Pages: 226-234, ISSN: 0938-7994
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- Citations: 15
Lynch DA, Sverzellati N, Travis WD, et al., 2017, Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper., Lancet Respiratory Medicine, Vol: 6, Pages: 138-153, ISSN: 2213-2600
This Review provides an updated approach to the diagnosis of idiopathic pulmonary fibrosis (IPF), based on a systematic search of the medical literature and the expert opinion of members of the Fleischner Society. A checklist is provided for the clinical evaluation of patients with suspected usual interstitial pneumonia (UIP). The role of CT is expanded to permit diagnosis of IPF without surgical lung biopsy in select cases when CT shows a probable UIP pattern. Additional investigations, including surgical lung biopsy, should be considered in patients with either clinical or CT findings that are indeterminate for IPF. A multidisciplinary approach is particularly important when deciding to perform additional diagnostic assessments, integrating biopsy results with clinical and CT features, and establishing a working diagnosis of IPF if lung tissue is not available. A working diagnosis of IPF should be reviewed at regular intervals since the diagnosis might change. Criteria are presented to establish confident and working diagnoses of IPF.
Cottin V, Hansell DM, Sverzellati N, et al., 2017, Effect of Emphysema Extent on Serial Lung Function in Patients with Idiopathic Pulmonary Fibrosis, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 196, Pages: 1162-1171, ISSN: 1073-449X
Jacob J, Bartholmai BJ, Brun AL, et al., 2017, Evaluation of visual and computer-based CT analysis for the identification of functional patterns of obstruction and restriction in hypersensitivity pneumonitis, RESPIROLOGY, Vol: 22, Pages: 1585-1591, ISSN: 1323-7799
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- Citations: 20
Jacob J, Bartholmai BJ, Rajagopalan S, et al., 2017, Automated computer-based CT stratification as a predictor of outcome in hypersensitivity pneumonitis, EUROPEAN RADIOLOGY, Vol: 27, Pages: 3635-3646, ISSN: 0938-7994
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- Citations: 28
Walsh SLF, Maher TM, Kolb M, et al., 2017, Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: an international case-cohort study., European Respiratory Journal, Vol: 50, ISSN: 0903-1936
We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts.A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (κw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the C-index.A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (κw=0.65, IQR 0.53-0.72, p<0.0001) than academic physicians (κw=0.56, IQR 0.45-0.65, p<0.0001) or physicians with access to multidisciplinary team (MDT) meetings (κw=0.54, IQR 0.45-0.64, p<0.0001). The prognostic accuracy of academic physicians with >20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75).Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts.
Jacob J, Bartholmai BJ, Rajagopalan S, et al., 2017, Unclassifiable-interstitial lung disease: Outcome prediction using CT and functional indices, RESPIRATORY MEDICINE, Vol: 130, Pages: 43-51, ISSN: 0954-6111
BackgroundUnclassifiable-interstitial lung disease (uILD) represents a heterogeneous collection of pathologies encompassing those fibrosing lung diseases which do not fulfill current diagnostic criteria. We evaluated baseline and longitudinal functional and CT (visual and quantitative computer [CALIPER] analysis) variables to identify outcome predictors in uILD.MethodsConsecutive patients with uILD on multidisciplinary review (n = 95) had baseline functional (FVC, DLco, CPI [composite physiologic index]) and CT features (visual evaluation: CT pattern, fibrosis extent, honeycombing presence, traction bronchiectasis severity, pulmonary artery (PA) diameter; CALIPER evaluation: fibrosis extent, pulmonary vessel volume (PVV)) examined in univariate and multivariate Cox regression models. Change in functional and CT variables were examined in a patient subset (n = 37), to identify indicators of outcome.ResultsOn univariate analysis, CPI was the most powerful functional predictor of mortality (p < 0.0001). Visual traction bronchiectasis (p < 0.0001), PA diameter (p < 0.0001) and honeycombing presence (p = 0.0001) and CALIPER PVV (p = 0.0003) were the strongest CT outcome predictors.On multivariate analysis of baseline indices, traction bronchiectasis (p = 0.003), PA diameter (p = 0.003) and CPI (p = 0.0001) independently predicted mortality. Colinearity with functional indices precluded the evaluation of CALIPER PVV in multivariate models.On evaluation of longitudinal variables, increasing CALIPER fibrosis extent was the strongest outcome predictor, and remained so following adjustment for baseline disease severity, and when FVC declines were marginal.ConclusionsIn uILD patients, CPI, traction bronchiectasis severity and PA diameter independently predicted outcome at baseline. Increasing fibrosis extent measured by CALIPER was the most powerful index of outcome regardless of baseline disease severity and strongly predicted outcome in patients with marginal FVC de
Jacob J, Bartholmai BJ, Rajagopalan S, et al., 2017, Functional and prognostic effects when emphysema complicates idiopathic pulmonary fibrosis, European Respiratory Journal, Vol: 50, ISSN: 0903-1936
This study aimed to investigate whether the combination of fibrosis and emphysema has a greater effect than the sum of its parts on functional indices and outcome in idiopathic pulmonary fibrosis (IPF), using visual and computer-based (CALIPER) computed tomography (CT) analysis.Consecutive patients (n=272) with a multidisciplinary IPF diagnosis had the extent of interstitial lung disease (ILD) scored visually and by CALIPER. Visually scored emphysema was subcategorised as isolated or mixed with fibrotic lung. The CT scores were evaluated against functional indices forced vital capacity (FVC), diffusing capacity of the lungs for carbon monoxide (DLCO), transfer coefficient of the lung for carbon monoxide (KCO), composite physiologic index (CPI)) and mortality.The presence and extent of emphysema had no impact on survival. Results were maintained following correction for age, gender, smoking status and baseline severity using DLCO, and combined visual emphysema and ILD extent. Visual emphysema quantitation indicated that relative preservation of lung volumes (FVC) resulted from tractionally dilated airways within fibrotic lung, ventilating areas of admixed emphysema (p<0.0001), with no independent effect on FVC from isolated emphysema. Conversely, only isolated emphysema (p<0.0001) reduced gas transfer (DLCO).There is no prognostic impact of emphysema in IPF, beyond that explained by the additive extents of both fibrosis and emphysema. With respect to the location of pulmonary fibrosis, emphysema distribution determines the functional effects of emphysema.
Egashira R, Jacob J, Kokosi MA, et al., 2017, Diffuse Pulmonary Ossification in Fibrosing Interstitial Lung Diseases: Prevalence and Associations, Radiology, Vol: 284, Pages: 255-263, ISSN: 0033-8419
PurposeTo investigate the prevalence of diffuse pulmonary ossification (DPO) in patients with fibrosing interstitial lung disease (ILD) and determine whether there are differences among the types of ILDs.Materials and MethodsInstitutional review board approval was given and patient consent was not required for this study. The study population comprised 892 consecutive patients with fibrosing ILD, including 456 patients with idiopathic pulmonary fibrosis (IPF) (men, 366; women, 90; median age, 72 years [range, 38–93 years]), 244 with nonspecific interstitial pneumonia (men, 79; women, 165; median age, 60.5 years [range, 23–86 years]), and 192 with chronic hypersensitivity pneumonitis (men, 76; women, 116; median age, 66 years [range, 35–88 years]). Pulmonary ossifications were recorded when nodules (<4 mm diameter) were identified on bone window images (width, 2500 HU; level, 500 HU). DPO was defined as 10 or more bilateral nodular ossifications (definition 1) or as one or more lobes with five or more bilateral nodular ossifications (definition 2). Relationships among pulmonary ossification and parenchymal patterns, clinical parameters, and multidisciplinary team diagnoses were examined. The prevalence of DPO was compared with the χ2 statistic or Fisher exact test, and multivariate analysis was performed with logistic regression.ResultsIn the whole population, the prevalence of DPO was 166 (18.6%) and 106 (11.9%) of 892 patients according to definitions 1 and 2, respectively. The prevalence of DPO (definition 1) was significantly higher in patients with IPF (28.5%) than in those without IPF (8.3%, P < .001). Nine of 192 (4.7%) had chronic hypersensitivity pneumonitis (P < .001), and 27 of 244 (11.1%) had nonspecific interstitial pneumonia (P < .001). At multivariate analysis, DPO according to definition 1 was an independent predictor of IPF diagnosis (P < .001) and male sex (P = .003). Coarseness of fibrosing ILD (P = .011) and IP
Johannson KA, Strambu I, Ravaglia C, et al., 2017, Antacid therapy in idiopathic pulmonary fibrosis: more questions than answers?, LANCET RESPIRATORY MEDICINE, Vol: 5, Pages: 591-598, ISSN: 2213-2600
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- Citations: 63
Jacob J, Bartholmai BJ, Egashira R, et al., 2017, Chronic hypersensitivity pneumonitis: identification of key prognostic determinants using automated CT analysis, BMC PULMONARY MEDICINE, Vol: 17, ISSN: 1471-2466
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- Citations: 41
Hind M, Jordan S, Hansell DM, et al., 2017, A man with progressive type II respiratory failure, Lancet Respiratory Medicine, Vol: 5, Pages: 456-456, ISSN: 2213-2600
Goh NS, Hoyles RK, Denton CP, et al., 2017, Short term pulmonary function trends are predictive of mortality in interstitial lung disease associated with systemic sclerosis., Arthritis & Rheumatology, Vol: 69, Pages: 1670-1678, ISSN: 2326-5191
OBJECTIVE: To determine the prognostic value of pulmonary function test (PFT) trends at one and two years in interstitial lung disease associated with systemic sclerosis (SSc-ILD). METHODS: The prognostic significance of PFT trends at one year (n=162), and two years (n=140) was examined against 15 year survival. PFT trends, expressed as continuous and categorical change in separate analyses, were examined against mortality in univariate and multivariate models. SSc-ILD was defined at presentation as limited lung fibrosis or extensive lung fibrosis using the UKRSA staging system. RESULTS: One year PFT trends were predictive of mortality only in patients with extensive lung fibrosis: categorical FVC change, alone or in combination with categorical change in DLco, had greater prognostic significance than continuous FVC change or trends in other PFT variables. Taking into account both prognostic value and sensitivity to change, the optimal definition of progression for trial purposes was an FVC and DLco composite, consisting of either an FVC decline from baseline ≥10% or an FVC decline of 5-9% in association with a DLco decline of ≥15%. At two years, gas transfer trends had the greatest prognostic significance, in the whole cohort and in limited lung fibrosis. However, in extensive lung fibrosis, the composite end-point defined above was the strongest prognostic determinant. Larger changes were required in the FVC/DLco ratio than in Kco to achieve prognostic significance. CONCLUSION: Our findings provide support for routine spirometric and gas transfer monitoring in SSc-ILD, based on linkages to long-term outcome, with further evaluation of a composite FVC and DLco end-point warranted for trial purposes. This article is protected by copyright. All rights reserved.
Jacob J, Nicholson AG, Wells AU, et al., 2017, Impact of pulmonary vascular volume on mortality in IPF: is it time to reconsider the role of vasculature in disease pathogenesis and progression?, EUROPEAN RESPIRATORY JOURNAL, Vol: 49, ISSN: 0903-1936
Jacob J, Nicholson AG, Wells AU, et al., 2017, Impact of pulmonary vascular volume on mortality in IPF: is it time to reconsider the role of vasculature in disease pathogenesis and progression?, EUROPEAN RESPIRATORY JOURNAL, Vol: 49, ISSN: 0903-1936
Jacob J, Bartholmai BJ, Rajagopalan S, et al., 2017, Mortality prediction in idiopathic pulmonary fibrosis: evaluation of computer-based CT analysis with conventional severity measures, EUROPEAN RESPIRATORY JOURNAL, Vol: 49, ISSN: 0903-1936
Jacob J, Bartholmai BJ, Rajagopalan S, et al., 2016, Evaluation of computer-based computer tomography stratification against outcome models in connective tissue disease-related interstitial lung disease: a patient outcome study, BMC MEDICINE, Vol: 14, ISSN: 1741-7015
Woodfield G, Nisbet M, Jacob J, et al., 2016, Bronchiectasis in yellow nail syndrome, Respirology, Vol: 22, Pages: 101-107, ISSN: 1440-1843
BACKGROUND AND OBJECTIVE: Yellow nail syndrome (YNS) is a rare and poorly described disease process. In this case-control study, clinical features and findings on HRCT were compared with idiopathic bronchiectasis (IBx). METHODS: A review of all patients attending an adult bronchiectasis clinic between 2007 and 2013 identified 25 YNS patients. IBx patients were matched in a 2:1 ratio for age, duration of symptoms and gender. RESULTS: Median age of onset was 53 years. There were 12 male and 23 Caucasian YNS patients. Respiratory manifestations included chronic productive cough (100%), chronic rhinosinusitis (88%), pleural effusions (20%) and lymphoedema (12%). Chest symptoms preceded yellow nails in the majority (68%). Abnormal nails persisted at follow-up in 23 of 25 patients but improved in 14. In both disorders, there was symmetrical, predominantly lower lobe bronchiectasis on HRCT. Extent (P = 0.04), severity (P = 0.03) and bronchial wall thickness (P = 0.05) scores were lower in YNS, with less upper and middle lobe disease. Multivariate analysis showed an independent association with increased mucus plugging in YNS. There was a similar prevalence of Pseudomonas aeruginosa infection and mild lung function abnormalities. CONCLUSION: Bronchiectasis in YNS is less severe than IBx but is associated with increased mucus plugging, onset is in middle age and there is no female predominance. Treatment targeted at improved secretion clearance may improve both chest and nail symptoms, with consideration of long-term macrolide antibiotics.
Nair A, Gartland N, Barton B, et al., 2016, Comparing the performance of trained radiographers against experienced radiologists in the UK lung cancer screening (UKLS) trial., British Journal of Radiology, Vol: 89, ISSN: 1748-880X
OBJECTIVE: To compare the performance of radiographers against that of radiologists for CT lung nodule detection in the UK Lung Cancer Screening (UKLS) pilot trial. METHODS: Four radiographers, trained in CT nodule detection, and three radiologists were prospectively evaluated. 290 CTs performed for the UKLS were independently read by 2 radiologists and 2 radiographers. The reference standard comprised all radiologist-identified positive nodules after arbitration of discrepancies. For each radiographer and radiologist, relative sensitivity and average false positives (FPs) per case were compared for all cases read, as well as for subsets of cases read by each radiographer-radiologist combination (10 combinations). RESULTS: 599 nodules in 209/290 (72.1%) CT studies comprised the reference standard. The relative mean (±standard deviation) sensitivity of the four radiographers was 71.6 ± 8.5% compared with 83.3 ± 8.1% for the three radiologists. Radiographers were less sensitive and detected more FPs per case than radiologists in 7/10 and 8/10 radiographer-radiologist combinations, respectively (ranges of difference 11.2-33.8% and 0.4-2.6; p < 0.05). In 3/10 and 2/10 combinations, there was no difference in sensitivity and FPs per case between radiographers and radiologists. For nodules ≥100 mm(3) in volume or ≥5 mm in maximum diameter, radiographers were relatively less sensitive than radiologists in only 5/10 radiographer-radiologist combinations (range of difference 16.1-30.6%; p < 0.05) and not significantly different in the remaining 5/10 combinations. CONCLUSION: Although overall radiographer performance was lower than that of experienced radiologists in this study, some radiographer performances were comparable with that of radiologists. ADVANCES IN KNOWLEDGE: Overall, radiographers were less sensitive than radiologists reading the same CTs and also displayed h
Garner J, Kemp SV, Toma TP, et al., 2016, Survival after endobronchial valve placement for emphysema: a 10-Year follow-up study, American Journal of Respiratory and Critical Care Medicine, Vol: 194, Pages: 519-521, ISSN: 1535-4970
Shah A, Shoemark A, MacNeill SJ, et al., 2016, A longitudinal study characterising a large adult primary ciliary dyskinesia population, European Respiratory Journal, Vol: 48, Pages: 441-450, ISSN: 1399-3003
Primary ciliary dyskinesia (PCD) in adults has not been well described. In this retrospective observational study we aimed to characterise a large adult population and identify features associated with disease progression.We retrospectively analysed 151 adult patients at a single tertiary centre at baseline and longitudinally for a median of 7 years.We found significant variation in age at diagnosis (median 23.5 years; range <1-72 years). Older age at diagnosis was associated with impaired baseline forced expiratory volume in 1 s (FEV1) (r= -0.30, p=0.01) and increased Pseudomonas aeruginosa colonisation (difference in medians 17 years (95% CI 4.5-20 years); p=0.002). Lung function decline was estimated at FEV1 decline of 0.49% predicted per year. Lung function decline was associated with ciliary ultrastructure, with microtubular defect patients having the greatest decline (p=0.04). High-resolution computed tomography (HRCT) scores of severity of bronchial wall dilatation (p<0.001) and extent of bronchiectasis (p=0.03) additionally showed evidence of modifying FEV1 decline with age.Our study reveals that a large proportion of adult PCD patients are diagnosed late, with impaired FEV1 and increased P. aeruginosa colonisation. Increased disease burden on HRCT and ciliary ultrastructure may predict progressive lung function decline. This study characterises a large adult PCD population, identifies features associated with disease progression and highlights the need for prospective trials to determine whether early diagnosis of high-risk subgroups alongside optimal management can modify disease progression.
Brain K, Lifford KJ, Carter B, et al., 2016, Long-term psychosocial outcomes of low-dose CT screening: results of the UK Lung Cancer Screening randomised controlled trial., Thorax, Vol: 71, Pages: 996-1005, ISSN: 0040-6376
BACKGROUND: The UK Lung Cancer Screening (UKLS) trial is a randomised pilot trial of low-dose CT (LDCT) screening for individuals at high risk of lung cancer. We assessed the long-term psychosocial impact on individuals participating in the UKLS trial. METHODS: A random sample of individuals aged 50-75 years was contacted via primary care. High-risk individuals who completed T0 questionnaires (baseline) were randomised to LDCT screening (intervention) or usual care (no screening control). T1 questionnaires were sent 2 weeks after baseline scan results or control assignment. T2 questionnaires were sent up to 2 years after recruitment. Measures included cancer distress, anxiety, depression and decision satisfaction. RESULTS: A total of 4037 high-risk individuals were randomised and they completed T0 questionnaires (n=2018 intervention, n=2019 control). Cancer distress was higher at T1 in intervention arm participants who received positive screening results (p≤0.001), but not at T2 (p=0.04). T2 anxiety (p≤0.001) and depression (p≤0.01) were higher in the control arm, but the absolute differences were small and not clinically relevant. At both time points, fewer control than screened participants were satisfied with their decision to participate in UKLS (p≤0.001). Regardless of trial allocation, cancer distress was higher in women (p≤0.01), participants aged ≤65 years (p≤0.001), current smokers (p≤0.001), those with lung cancer experience (p≤0.001) and those recruited from the Liverpool area (p≤0.001). CONCLUSION: Lung cancer screening using LDCT appears to have no clinically significant long-term psychosocial impact on high-risk participants. Strategies for engaging and supporting underserved groups are the key to implement routine lung cancer screening in the UK. TRIAL REGISTRATION NUMBER: ISRCTN 78513845; results.
Walsh SLF, Wells AU, Desai SR, et al., 2016, Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study, The Lancet Respiratory Medicine, Vol: 4, Pages: 557-565, ISSN: 2213-2600
BackgroundDiffuse parenchymal lung disease represents a diverse and challenging group of pulmonary disorders. A consistent diagnostic approach to diffuse parenchymal lung disease is crucial if clinical trial data are to be applied to individual patients. We aimed to evaluate inter-multidisciplinary team agreement for the diagnosis of diffuse parenchymal lung disease.MethodsWe did a multicentre evaluation of clinical data of patients who presented to the interstitial lung disease unit of the Royal Brompton and Harefield NHS Foundation Trust (London, UK; host institution) and required multidisciplinary team meeting (MDTM) characterisation between March 1, 2010, and Aug 31, 2010. Only patients whose baseline clinical, radiological, and, if biopsy was taken, pathological data were undertaken at the host institution were included. Seven MDTMs, consisting of at least one clinician, radiologist, and pathologist, from seven countries (Denmark, France, Italy, Japan, Netherlands, Portugal, and the UK) evaluated cases of diffuse parenchymal lung disease in a two-stage process between Jan 1, and Oct 15, 2015. First, the clinician, radiologist, and pathologist (if lung biopsy was completed) independently evaluated each case, selected up to five differential diagnoses from a choice of diffuse lung diseases, and chose likelihoods (censored at 5% and summing to 100% in each case) for each of their differential diagnoses, without inter-disciplinary consultation. Second, these specialists convened at an MDTM and reviewed all data, selected up to five differential diagnoses, and chose diagnosis likelihoods. We compared inter-observer and inter-MDTM agreements on patient first-choice diagnoses using Cohen's kappa coefficient (κ). We then estimated inter-observer and inter-MDTM agreement on the probability of diagnosis using weighted kappa coefficient (κw). We compared inter-observer and inter-MDTM confidence of patient first-choice diagnosis. Finally, we evaluated the progn
Raghu G, Wells AU, Nicholson AG, et al., 2016, Effect of nintedanib in subgroups of idiopathic pulmonary fibrosis by diagnostic criteria, American Journal of Respiratory and Critical Care Medicine, Vol: 195, Pages: 78-85, ISSN: 1535-4970
RATIONALE: In the absence of a surgical lung biopsy, patients diagnosed with idiopathic pulmonary fibrosis (IPF) in clinical practice could participate in the INPULSIS® trials of nintedanib if they had honeycombing and/or traction bronchiectasis plus reticulation, without atypical features of usual interstitial pneumonia (UIP), on high-resolution computed tomography (HRCT). Thus the patients in these trials represented patients with definite UIP and a large subgroup of patients with possible UIP. OBJECTIVE: We investigated the potential impact of diagnostic subgroups on the progression of IPF and effect of nintedanib. METHODS: Post-hoc subgroup analysis of patients with honeycombing on HRCT and/or confirmation of UIP by biopsy versus patients without either, using pooled data from the INPULSIS® trials. MEASUREMENTS AND MAIN RESULTS: 723 (68.1%) patients had honeycombing and/or biopsy and 338 (31.9%) had no honeycombing or biopsy. In these subgroups, respectively, the adjusted annual rate of decline in forced vital capacity (FVC) in patients treated with placebo was -225.7 mL/year and -221.0 mL/year, and the nintedanib versus placebo difference in adjusted annual rate of decline in FVC was 117.0 mL/year (95% CI: 76.3, 157.8) and 98.9 mL/year (95% CI: 36.4, 161.5). There was no significant treatment-by-subgroup interaction (p=0.8139). Adverse events were similar between subgroups. CONCLUSION: Patients with IPF diagnosed in clinical practice who have possible UIP with traction bronchiectasis on HRCT and have not undergone surgical lung biopsy have disease that progresses in a similar way, and responds similarly to nintedanib, as patients with honeycombing on HRCT and/or confirmation of UIP by biopsy. Clinical trial registration available at www.clinicaltrials.gov, IDs NCT01335464 and NCT01335477.
Collard HR, Ryerson CJ, Corte TJ, et al., 2016, Acute Exacerbation of Idiopathic Pulmonary Fibrosis: An International Working Group Report, American Journal of Respiratory and Critical Care Medicine, Vol: 194, Pages: 265-275, ISSN: 1535-4970
Acute exacerbation of idiopathic pulmonary fibrosis has been defined as an acute, clinically significant, respiratory deterioration of unidentifiable cause. The objective of this international working group report on acute exacerbation of idiopathic pulmonary fibrosis was to provide a comprehensive update on the topic. A literature review was conducted to identify all relevant English text publications and abstracts. Evidence-based updates on the epidemiology, etiology, risk factors, prognosis, and management of acute exacerbations of idiopathic pulmonary fibrosis are provided. In addition, to better reflect the current state of knowledge and improve the feasibility of future research into its etiology and treatment, the working group proposes a new conceptual framework for acute respiratory deterioration in idiopathic pulmonary fibrosis and a revised definition and diagnostic criteria for acute exacerbation of idiopathic pulmonary fibrosis.
Jacob J, Bartholmai BJ, Rajagopalan S, et al., 2016, Automated Quantitative Computed Tomography Versus Visual Computed Tomography Scoring in Idiopathic Pulmonary Fibrosis: Validation Against Pulmonary Function, Journal of Thoracic Imaging, ISSN: 1536-0237
PURPOSE: The aim of the study was to determine whether a novel computed tomography (CT) postprocessing software technique (CALIPER) is superior to visual CT scoring as judged by functional correlations in idiopathic pulmonary fibrosis (IPF). MATERIALS AND METHODS: A total of 283 consecutive patients with IPF had CT parenchymal patterns evaluated quantitatively with CALIPER and by visual scoring. These 2 techniques were evaluated against: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLco), carbon monoxide transfer coefficient (Kco), and a composite physiological index (CPI), with regard to extent of interstitial lung disease (ILD), extent of emphysema, and pulmonary vascular abnormalities. RESULTS: CALIPER-derived estimates of ILD extent demonstrated stronger univariate correlations than visual scores for most pulmonary function tests (PFTs): (FEV1: CALIPER R=0.29, visual R=0.18; FVC: CALIPER R=0.41, visual R=0.27; DLco: CALIPER R=0.31, visual R=0.35; CPI: CALIPER R=0.48, visual R=0.44). Correlations between CT measures of emphysema extent and PFTs were weak and did not differ significantly between CALIPER and visual scoring. Intriguingly, the pulmonary vessel volume provided similar correlations to total ILD extent scored by CALIPER for FVC, DLco, and CPI (FVC: R=0.45; DLco: R=0.34; CPI: R=0.53). CONCLUSIONS: CALIPER was superior to visual scoring as validated by functional correlations with PFTs. The pulmonary vessel volume, a novel CALIPER CT parameter with no visual scoring equivalent, has the potential to be a CT feature in the assessment of patients with IPF and requires further exploration.
Field JK, Duffy SW, Baldwin DR, et al., 2016, The UK Lung Cancer Screening Trial: a pilot randomised controlled trial of low-dose computed tomography screening for the early detection of lung cancer., Health Technology Assessment, Vol: 20, Pages: 1-146, ISSN: 1366-5278
BACKGROUND: Lung cancer kills more people than any other cancer in the UK (5-year survival < 13%). Early diagnosis can save lives. The USA-based National Lung Cancer Screening Trial reported a 20% relative reduction in lung cancer mortality and 6.7% all-cause mortality in low-dose computed tomography (LDCT)-screened subjects. OBJECTIVES: To (1) analyse LDCT lung cancer screening in a high-risk UK population, determine optimum recruitment, screening, reading and care pathway strategies; and (2) assess the psychological consequences and the health-economic implications of screening. DESIGN: A pilot randomised controlled trial comparing intervention with usual care. A population-based risk questionnaire identified individuals who were at high risk of developing lung cancer (≥ 5% over 5 years). SETTING: Thoracic centres with expertise in lung cancer imaging, respiratory medicine, pathology and surgery: Liverpool Heart & Chest Hospital, Merseyside, and Papworth Hospital, Cambridgeshire. PARTICIPANTS: Individuals aged 50-75 years, at high risk of lung cancer, in the primary care trusts adjacent to the centres. INTERVENTIONS: A thoracic LDCT scan. Follow-up computed tomography (CT) scans as per protocol. Referral to multidisciplinary team clinics was determined by nodule size criteria. MAIN OUTCOME MEASURES: Population-based recruitment based on risk stratification; management of the trial through web-based database; optimal characteristics of CT scan readers (radiologists vs. radiographers); characterisation of CT-detected nodules utilising volumetric analysis; prevalence of lung cancer at baseline; sociodemographic factors affecting participation; psychosocial measures (cancer distress, anxiety, depression, decision satisfaction); and cost-effectiveness modelling. RESULTS: A total of 247,354 individuals were approached to take part in the trial; 30.7% responded positively to the screening invitation. Recruitment of participants resulted in 2028 in
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