Delineating associations of progressive pleuroparenchymal fibroelastosis in patients with pulmonary fibrosis

BACKGROUND: Computer quantification of baseline computed tomography (CT) radiological pleuroparenchymal fibroelastosis (PPFE) associates with mortality in idiopathic pulmonary fibrosis (IPF). We examined mortality associations of longitudinal change in computer-quantified PPFE-like lesions in IPF and fibrotic hypersensitivity pneumonitis (FHP). METHODS: Two CT scans 6-36 months apart were retrospectively examined in one IPF (n=414) and one FHP population (n=98). Annualised change in computerised upper-zone pleural surface area comprising radiological PPFE-like lesions (Δ-PPFE) was calculated. Δ-PPFE >1.25% defined progressive PPFE above scan noise. Mixed-effects models evaluated Δ-PPFE against change in visual CT interstitial lung disease (ILD) extent and annualised forced vital capacity (FVC) decline. Multivariable models were adjusted for age, sex, smoking history, baseline emphysema presence, antifibrotic use and diffusion capacity of the lung for carbon monoxide. Mortality analyses further adjusted for baseline presence of clinically important PPFE-like lesions and ILD change. RESULTS: Δ-PPFE associated weakly with ILD and FVC change. 22-26% of IPF and FHP cohorts demonstrated progressive PPFE-like lesions which independently associated with mortality in the IPF cohort (hazard ratio 1.25, 95% CI 1.16-1.34, p<0.0001) and the FHP cohort (hazard ratio 1.16, 95% CI 1.00-1.35, p=0.045). INTERPRETATION: Progression of PPFE-like lesions independently associates with mortality in IPF and FHP but does not associate strongly with measures of fibrosis progression

Production of He-4 and (4) in Pb-Pb collisions at root(NN)-N-S=2.76 TeV at the LHC

Results on the production of He-4 and (4) nuclei in Pb-Pb collisions at root(NN)-N-S = 2.76 TeV in the rapidity range vertical bar y vertical bar <1, using the ALICE detector, are presented in this paper. The rapidity densities corresponding to 0-10% central events are found to be dN/dy4(He) = (0.8 +/- 0.4 (stat) +/- 0.3 (syst)) x 10(-6) and dN/dy4 = (1.1 +/- 0.4 (stat) +/- 0.2 (syst)) x 10(-6), respectively. This is in agreement with the statistical thermal model expectation assuming the same chemical freeze-out temperature (T-chem = 156 MeV) as for light hadrons. The measured ratio of (4)/He-4 is 1.4 +/- 0.8 (stat) +/- 0.5 (syst). (C) 2018 Published by Elsevier B.V.Peer reviewe

What proportion of patients with Idiopathic pulmonary fibrosis fall outside UK prescribing criteria for anti-fibrotic treatment? A UK specialist centre review

Background: anti-fibrotic therapies have transformed the care of patients with Idiopathic Pulmonary Fibrosis (IPF). Within the United Kingdom, prescribing criteria set by NICE (National Institute for Health and Care Excellence) restrict anti-fibrotic prescription to patients with an FVC of 50-80% predicted, potentially excluding a significant proportion of patients with IPF from receiving anti-fibrotic treatment.Aims and objectives: to investigate the proportion of patients with IPF that do not meet UK NICE prescribing criteria for anti-fibrotic treatment.Methods: this is a retrospective specialist centre cohort study. Consecutive patients with an MDT diagnosis of IPF and a minimum of 12 months follow up were included in the analysis.Results: 194 patients with IPF were identified. 150 (77%) were male and 120 (62%) were ex-smokers. Mean age at diagnosis was 73 years (SD=8 years). The most common comorbidity was GORD (n=73, 38%) while 36 (19%) had a background of ischaemic heart disease. At diagnosis mean FVC was 75% predicted (SD=20%) and mean TLCO was 47% predicted (SD=16%). 150 patients (77%) were eligible for anti-fibrotic treatment on diagnosis. 29 (15%) patients were not eligible for anti-fibrotics when assessed by NICE criteria, with 20 having an FVC&gt;80% predicted while 9 had an FVC80% have subsequently received anti-fibrotic treatment following FVC decline.Conclusions: 15% of patients with IPF referred for specialist centre care were ineligible for anti-fibrotic treatment as a consequence of the NICE FVC prescribing criteria

Temporal progression of mediastinal lymphadenopathy in idiopathic pulmonary fibrosis

[No Abstract Available]NIHR Southampton Biomedical Research Centre; Wellcome Trust [209553/Z/17/Z]; NIHR UCLH Biomedical Research Centre, UKJ.M. Wallis receives a research fellowship from the NIHR Southampton Biomedical Research Centre. This research was funded in whole or in part by the Wellcome Trust (209553/Z/17/Z). For this project, J. Jacob and E. Gudmundsson were also supported by the NIHR UCLH Biomedical Research Centre, UK. Funding information for this article has been deposited with the Crossref Funder Registry

Temporal changes in mediastinal lymphadenopathy in patients with idiopathic pulmonary fibrosis

Background: mediastinal lymph node enlargement (LNE) is commonly identified in patients with idiopathic pulmonary fibrosis (IPF), however its clinical significance and temporal progression is poorly understood.Aim: to investigate the incidence of mediastinal LNE in IPF, its progression over time, and relationship to patient demographics and outcomes in a single centre UK cohort.Methods: patients with a multi-disciplinary diagnosis of IPF and 2 sequential chest computed tomographs (CTs) were retrospectively identified from the Southampton Interstitial Lung Disease Database. Patients with an alternative cause for LNE were excluded. Two radiologists independently reviewed CTs for mediastinal LNE (short-axis diameter ≥10mm). Findings were related to patient demographics and outcomes.Results: 37 patients were identified. 29 (78%) were male, mean age at baseline CT was 73 years and 21 (57%) were ex-smokers. Median time between CTs was 16 months (7-74), and median follow-up time was 42 months (9-94).At baseline CT, 23 patients (62%) had mediastinal LNE, most commonly in station 4. Patients with LNE were typically male (87% vs. 64%), with reduced FVC (74% vs. 86%) and DLCO (45% vs. 59%). Mean size of the largest node was 14mm (10-17mm), with progression on interval CT in 20 patients (87%) to a mean size of 15mm (11-20mm). 4 patients (29%) with no LNE at baseline developed LNE on interval CT. At 3 years follow up, 5 (22%) in the LNE group were deceased and 0 (0%) in the no LNE group. LNE progression was not associated with increased mortality.Conclusions: in this cohort intrathoracic LNE was common, more prevalent in patients with greater physiological impairment, and progressed over time

A review of patients following a diagnosis of unclassified interstitial lung disease (ILD) at a tertiary centre

Introduction: a proportion of patients with ILD remain unclassified after multidisciplinary discussion (MDD). Without a definitive diagnosis there is currently a lack of licensed treatment options for this group. We aimed to review outcomes in this cohort of patients.Method: UK single centre retrospective review of all patients with unclassified ILD diagnosis following ILD MDD between 12/11/2012 and 19/6/2017 with a minimum 2 year follow up. Data extracted from electronic records. Ethical approval obtained.Results: 145 patients included with a mean (SD) follow-up period of 3.9 years (1.2). Baseline demographics were as follows: males 62.1% with mean (SD); age 70.7 years (9.2), FVC% 81.4 (21.4) and DLCO% 55.4 (17.1).At censor, 40.7% of patients had been reclassified to an alternative diagnosis. The median time taken to re-classify patients was 90 days with a wide range (16-2052 days). Common review diagnosis were (n); idiopathic pulmonary fibrosis (29), hypersensitivity pneumonitis (10) and connective tissue disease related ILD (3). Repeat CT and MDD re-discussion led to re-classification in 23% of patients. 15% of patients had a surgical lung biopsy and this led to subsequent re-classification of ILD in 82% of people biopsied.In patients with serial FVC% (n=101), 25% had a &gt;10% decline over a mean interval of 2.5 years. 40% of patients with &gt;10% FVC decline remained unclassified. No baseline characteristics were found to predict progression.Conclusion: these results highlight the importance of MDD follow up of patients with unclassified ILD over time to both review diagnosis and monitor for disease progression to enable appropriate disease targeted therapy

Feasibility of a cardiopulmonary exercise test (CPET) derived high-intensity interval training programme (HIIT) in idiopathic pulmonary fibrosis (IPF)

Introduction: exercise training is recommended for IPF patients but the optimum program and the mechanisms underlying improvements in exercise capacity are unknown. We tested feasibility of a HIIT in IPF.Methods: a single-centre study of IPF patients. An 8-week twice-weekly cycle-ergometer based HIIT was personalised using participants volume of oxygen consumption at anaerobic threshold (VO2AT) and peak (VO2peak) assessed by incremental CPET. Primary outcome was endurance time on constant load test at 75% VO2peak. Ethical approval obtained (REC 17/SC/0342).Results: interim analysis of 11 patients. Baseline demographics as follows; males 82% with mean (SD) age 73.5years (6.8), FVC% 76.5 (13.4) and DLCO% 50.1 (15.8). Participants had significantly impaired exercise capacity at baseline with mean (SD) VO2peak of 12.3ml/kg/min (3.3) and VO2AT 8.3ml/kg/min (1.3).Participants had good adherence to HITT with mean of 15/16 sessions attended with no serious adverse events. HITT led to clinically meaningful improvement in mean endurance time [pre 8.3min vs post 16.8min difference 8.5min (95%CI 4.2-12.8) p&lt;0.01] and 6min walk [pre 374m vs post 409m difference 35m (95%CI 0.6-69.4) p&lt;0.05]. Significant increase was also observed in mean peak minute ventilation (peakVE) [pre 60.2L/min vs post 69.3L/min p=0.02]. However no change was observed in either VO2peak or VO2AT following HITT.Conclusion: a CPET derived HIIT was feasible in this cohort of IPF patients and led to significant improvement in endurance time and 6min walk. Increased peakVE following HITT suggests improved ventilatory mechanics may in part account for increased exercise test performance

New Perspectives on Difficult Asthma; Sex and Age of Asthma-Onset Based Phenotypes

International audienceBackground: Asthma is a diverse condition that differs with age and sex. However, it remains unclear how sex, age of asthma-onset, and/or their interaction, influence clinical expression of more problematic adult “difficult” asthma.Objectives: To better understand the clinical features of difficult asthma within a real-world clinical setting using novel phenotypic classification, stratifying subjects by sex and age of asthma-onset.Methods: Participants in a longitudinal difficult asthma clinical cohort study (Wessex AsThma CoHort of difficult asthma; WATCH), United Kingdom, (n=501) were stratified into 4 difficult asthma phenotypes based on sex and age of asthma-onset (early<18-years or adult≥18-years) and characterised in relation to clinical and pathophysiological features.Results: The cohort had more female participants (65%) but had similar proportions of participants with early or adult-onset disease. Early-onset female disease was commonest (35%), highly atopic, with good spirometry and strong associations to some physical comorbidities but highest psychophysiologic comorbidities. Adult-onset females also had considerable psychophysiologic comorbidities, highest obesity, and were least atopic. Amongst male subjects, proportionately more had adult-onset disease. Early-onset male disease was rarest (14%) but associated with worst lung function, high smoking, atopy and fungal sensitisation. Despite shortest disease duration, adult-onset males had highest use of maintenance oral corticosteroid, poor lung function and highest FeNO in spite of highest smoking prevalence.Conclusion: This study shows that sex, age of asthma-onset, and their interactions influence different clinical manifestations of difficult asthma and identifies a greater risk for lung function loss and oral corticosteroid dependency associated with smoking in adult-onset male subject