Interstitial Lung Disease Unit

United States

Interstitial Lung Disease Unit

United States
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Egashira R.,Saga University | Jacob J.,Saga University | Kokosi M.A.,Interstitial Lung Disease Unit | Brun A.-L.,Saga University | And 4 more authors.
Radiology | Year: 2017

Purpose: To 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 Methods: Institutional 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. Results: In 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 IPF diagnosis (P = .016) were independently associated with pulmonary ossification profusion. Conclusion: DPO is common in patients with fibrosing ILD and is significantly more prevalent in patients with IPF than in those with other fibrosing ILDs, and thus, computed tomographic signs of DPO may be helpful for diagnosis of IPF. © 2017 RSNA.


Zoumot Z.,Imperial College London | Zoumot Z.,Royal Brompton Hospital | Boutou A.K.,Imperial College London | Van Zeller M.,Royal Brompton Hospital | And 7 more authors.
Respirology | Year: 2014

Background and objective Reliable markers of disease progression or stability to assist in management decisions are lacking in patients with non-cystic fibrosis bronchiectasis and Mycobacterium avium complex (MAC) infection. Methods Data from 52 adults with non-cystic fibrosis bronchiectasis and coexisting MAC infection managed at our institution over a 5-year period were retrospectively analysed. High-resolution computed tomography (HRCT) scans were scored using a scoring system that focused on findings associated with MAC infection. Results Chronic pulmonary aspergillosis was independently associated with mortality (hazard ratio (HR) = 8.916, 95% confidence interval (CI) = 1.324-60.027), as were nodules with cavitation (HR = 5.911, 95% CI = 1.095-25.911) and emphysema (HR = 1.027, 95% CI = 1.002-1.053) on HRCT. Anti-MAC chemotherapy was more likely to lead to MAC culture conversion (67% vs 27%, P = 0.005) but did not improve survival as compared with patients managed with observation. Longitudinally, patients who had improvements in HRCT scores were younger (60.2 ± 9.19 years vs 69.83 ± 12.43 years, P = 0.043), while the presence of cavitation within nodules predicted a deterioration in HRCT scores (0.5 (0-3) vs 0 (0-1), P = 0.033). No significant longitudinal differences were found in lung function in the cohort as a whole or within different groups. Conclusions Chronic pulmonary aspergillosis in patients with bronchiectasis and coexisting MAC infection is a strong predictor of mortality. Cavitation within nodules and emphysema on HRCT at presentation were independently associated with mortality. In patients with non-cystic fibrosis bronchiectasis and Mycobacterium avium complex infection, chronic pulmonary aspergillosis is a strong independent predictor of mortality, as are nodules with cavitation and emphysema on high-resolution computerized tomography (HRCT) scans at presentation. Longitudinally, the presence of cavitation within nodules predicted deterioration in HRCT scores. © 2014 Asian Pacific Society of Respirology.


PubMed | University Utrecht, Interstitial Lung Disease Unit, Nagasaki University, University of Paris Pantheon Sorbonne and 16 more.
Type: Journal Article | Journal: The Lancet. Respiratory medicine | Year: 2016

Diffuse 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.We 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 Cohens kappa coefficient (). We then estimated inter-observer and inter-MDTM agreement on the probability of diagnosis using weighted kappa coefficient (w). We compared inter-observer and inter-MDTM confidence of patient first-choice diagnosis. Finally, we evaluated the prognostic significance of a first-choice diagnosis of idiopathic pulmonary fibrosis (IPF) versus not IPF for MDTMs, clinicians, and radiologists, using univariate Cox regression analysis.70 patients were included in the final study cohort. Clinicians, radiologists, pathologists, and the MDTMs assigned their patient diagnoses between Jan 1, and Oct 15, 2015. IPF made up 88 (18%) of all 490 MDTM first-choice diagnoses. Inter-MDTM agreement for first-choice diagnoses overall was moderate (=050). Inter-MDTM agreement on diagnostic likelihoods was good for IPF (w=071 [IQR 064-077]) and connective tissue disease-related interstitial lung disease (w=073 [068-078]); moderate for non-specific interstitial pneumonia (NSIP; w=042 [037-049]); and fair for hypersensitivity pneumonitis (w=029 [024-040]). High-confidence diagnoses (>65% likelihood) of IPF were given in 68 (77%) of 88 cases by MDTMs, 62 (65%) of 96 cases by clinicians, and in 57 (66%) of 86 cases by radiologists. Greater prognostic separation was shown for an MDTM diagnosis of IPF than compared with individual clinicians diagnosis of this disease in five of seven MDTMs, and radiologists diagnosis of IPF in four of seven MDTMs.Agreement between MDTMs for diagnosis in diffuse lung disease is acceptable and good for a diagnosis of IPF, as validated by the non-significant greater prognostic separation of an IPF diagnosis made by MDTMs than the separation of a diagnosis made by individual clinicians or radiologists. Furthermore, MDTMs made the diagnosis of IPF with higher confidence and more frequently than did clinicians or radiologists. This difference is of particular importance, because accurate and consistent diagnoses of IPF are needed if clinical outcomes are to be optimised. Inter-multidisciplinary team agreement for a diagnosis of hypersensitivity pneumonitis is low, highlighting an urgent need for standardised diagnostic guidelines for this disease.National Institute of Health Research, Imperial College London.


PubMed | University of Michigan, University of Houston, Interstitial Lung Disease Unit, Spectrum and 2 more.
Type: Journal Article | Journal: Chest | Year: 2016

Idiopathic pulmonary fibrosis is a progressive lung disease with variable course. The Gender-Age-Physiology (GAP) Index and staging system uses clinical variables to stage mortality risk. It is unknown whether clinical staging predicts future decline in pulmonary function. We assessed whether the GAP stage predicts future pulmonary function decline and whether interval pulmonary function change predicts mortality after accounting for stage.Patients with idiopathic pulmonary fibrosis (N = 657) were identified retrospectively at three tertiary referral centers, and baseline GAP stages were assessed. Mixed models were used to describe average trajectories of FVC and diffusing capacity of the lung for carbon monoxide (Dlco). Multivariable Cox proportional hazards models were used to assess whether declines in pulmonary function 10% in 6 months predict mortality after accounting for GAP stage.Over a 2-year period, GAP stage was not associated with differences in yearly lung function decline. After accounting for stage, a 10% decrease in FVC or Dlco over 6 months independently predicted death or transplantation (FVC hazard ratio, 1.37; Dlco hazard ratio, 1.30; both, P .03). Patients with GAP stage 2 with declining pulmonary function experienced a survival profile similar to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI, 49.4-67.8) vs 56.9% (95% CI, 42.2-69.1).Baseline GAP stage predicted death or lung transplantation but not the rate of future pulmonary function decline. After accounting for GAP stage, a decline of 10% over 6 months independently predicted death or lung transplantation.


Hansell D.M.,Royal Brompton and Harefield National Health Service Foundation Trust | Goldin J.G.,University of California at Los Angeles | King T.E.,University of California at San Francisco | Lynch D.A.,Jewish Medical and Research Center | And 2 more authors.
The Lancet Respiratory Medicine | Year: 2015

CT is increasingly being used to stage and quantify the extent of diffuse lung diseases both in clinical practice and in treatment trials. The role of CT in the assessment of patients entering treatment trials has greatly expanded as clinical researchers and pharmaceutical companies have focused their efforts on developing safe and effective drugs for interstitial lung diseases, particularly for idiopathic pulmonary fibrosis. These efforts have culminated in the simultaneous approval by the US Food and Drug Administration of two new drugs for the treatment of idiopathic pulmonary fibrosis. CT features are a key part of the inclusion criteria in many drug trials and CT is now being used to refine the type of patients enrolled. Interest in the potential use of serial CT as an effectiveness endpoint is increasing. For chronic progressive diseases, mortality may not be a feasible endpoint and many surrogate markers have been explored, ranging from pulmonary function decline to biomarkers. However, these surrogate markers are not entirely reliable and combinations of endpoints, including change in disease extent on CT, are being investigated. Methods to assess disease severity with CT range from simple visual estimates to sophisticated quantification by use of software. In this Position Paper, which cannot be regarded as a comprehensive set of guidelines in view of present knowledge, we examine the uses of serial CT in clinical practice and in drug trials and draw attention to uncertainties and challenges for future research. © 2015 Elsevier Ltd.


Collard H.R.,University of California at San Francisco | Bradford W.Z.,InterMune | Cottin V.,University Claude Bernard Lyon 1 | Flaherty K.R.,University of Michigan | And 10 more authors.
European Respiratory Journal | Year: 2015

The past decade has seen substantial progress in understanding the pathobiology, natural history, and clinical significance of idiopathic pulmonary fibrosis (IPF), culminating in the establishment of two effective medical therapies. Now seems an important time to reconsider the design and conduct of future IPF clinical trials. Building on lessons learned over the past decade, we use this perspective to lay out four key considerations for moving forward effectively and efficiently with the next generation of clinical trials in IPF. These are: development of a coordinated IPF clinical trials network; establishment of expectations for early phase proof of concept studies; adaptation of late-phase efficacy trial designs to the emergence of approved therapies, and; agreement on primary end-points for late phase clinical trials. Continued progress in the field of IPF will require creativity and collaboration on the part of all stakeholders. We believe that addressing these four considerations will encourage and enable investment in this new era of drug development in IPF, and will lead to more rapid development of effective therapies. Copyright © ERS 2015.


Salisbury M.L.,University of Michigan | Xia M.,University of Michigan | Zhou Y.,University of Michigan | Murray S.,University of Michigan | And 6 more authors.
Chest | Year: 2016

Background: Idiopathic pulmonary fibrosis is a progressive lung disease with variable course. The Gender-Age-Physiology (GAP) Index and staging system uses clinical variables to stage mortality risk. It is unknown whether clinical staging predicts future decline in pulmonary function. We assessed whether the GAP stage predicts future pulmonary function decline and whether interval pulmonary function change predicts mortality after accounting for stage. Methods: Patients with idiopathic pulmonary fibrosis (N = 657) were identified retrospectively at three tertiary referral centers, and baseline GAP stages were assessed. Mixed models were used to describe average trajectories of FVC and diffusing capacity of the lung for carbon monoxide (DLCO). Multivariable Cox proportional hazards models were used to assess whether declines in pulmonary function ≥ 10% in 6 months predict mortality after accounting for GAP stage. Results: Over a 2-year period, GAP stage was not associated with differences in yearly lung function decline. After accounting for stage, a 10% decrease in FVC or DLCO over 6 months independently predicted death or transplantation (FVC hazard ratio, 1.37; DLCO hazard ratio, 1.30; both, P ≤ .03). Patients with GAP stage 2 with declining pulmonary function experienced a survival profile similar to patients with GAP stage 3, with 1-year event-free survival of 59.3% (95% CI, 49.4-67.8) vs 56.9% (95% CI, 42.2-69.1). Conclusions: Baseline GAP stage predicted death or lung transplantation but not the rate of future pulmonary function decline. After accounting for GAP stage, a decline of ≥ 10% over 6 months independently predicted death or lung transplantation. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.


Corte T.J.,Interstitial Lung Disease Unit | Corte T.J.,University of Sydney | Keir G.J.,Interstitial Lung Disease Unit | Keir G.J.,Princess Alexandra Hospital | And 18 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2014

Rationale: Pulmonary hypertension (PH) associated with fibrotic idiopathic interstitial pneumonia (IIP; idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia) confers important additional morbidity and mortality. Objectives: To evaluate the safety and clinical efficacy of the dual endothelin-1 receptor antagonist bosentan in this patient group. Methods: In a randomized, double-blind, placebo-controlled study, 60 patients with fibrotic IIP and right heart catheter confirmed PH were randomized 2:1 to bosentan (n = 40) or placebo (n = 20). The primary study endpoint was a fall from baseline pulmonary vascular resistance index (PVRi) of 20% or more over 16 weeks. Measurements and Main Results: Sixty patients (42 men; mean age, 66.6 6 9.2 yr), with a mean pulmonary artery pressure of 36.0 (68.9)mmHg, PVRi 13.0 (66.7)WoodUnits/m2 and reduced cardiac index of 2.21 (60.5) L/min/m2were recruited to the study.Accounting for deaths and withdrawals, paired right heart catheter data were available for analysis in 39 patients (bosentan = 25, placebo = 14). No difference in the primary outcome was detected, with seven (28.0%) patients receiving bosentan, and four (28.6%) receiving placebo achieving a reduction in PVRi of greater than or equal to 20% (P = 0.97) at 16 weeks. There was no change in functional capacity or symptoms between the two groups at 16 weeks, nor any difference in rates of serious adverse events or deaths (three deaths in each group). Conclusions: This study shows no difference in invasive pulmonary hemodynamics, functional capacity, or symptoms between the bosentan and placebo groups over 16 weeks. Our data do not support the use of the dual endothelin-1 receptor antagonist, bosentan, in patients with PH and fibrotic IIP. Copyright © 2014 by the American Thoracic Society.


Antoniou K.M.,Interstitial Lung Disease Unit | Walsh S.L.,Royal Brompton Hospital | Hansell D.M.,Royal Brompton Hospital | Rubens M.R.,Royal Brompton Hospital | And 7 more authors.
Respirology | Year: 2013

Background and objective A combined pulmonary fibrosis/emphysema syndrome has been proposed, but the basis for this syndrome is currently uncertain. The aim was to evaluate the prevalence of emphysema in idiopathic pulmonary fibrosis (IPF) and rheumatoid lung (rheumatoid arthritis-interstitial lung disease (RA-ILD)), and to compare the morphological features of lung fibrosis between smokers and non-smokers. Methods Using high-resolution computed tomography, the prevalence of emphysema and the pack-year smoking histories associated with emphysema were compared between current/ex-smokers with IPF (n = 186) or RA-ILD (n = 46), and non-chronic obstructive pulmonary disease (COPD) controls (n = 103) and COPD controls (n = 34). The coarseness of fibrosis was compared between smokers and non-smokers. Results Emphysema, present in 66/186 (35%) patients with IPF and 22/46 (48%) smokers with RA-ILD, was associated with lower pack-year smoking histories than in control groups (P < 0.05 for all comparisons). The presence of emphysema in IPF was positively linked to the pack-year smoking history (odds ratio 1.04, 95% confidence interval (CI) 1.02-1.06, P < 0.0005). In IPF, fibrosis was coarser in smokers than in non-smokers on univariate and multivariate analysis (P < 0.01 for all comparisons). In RA-ILD, fibrosis was coarser in patients with emphysema but did not differ significantly between smokers and non-smokers. Conclusions In IPF and RA-ILD, a high prevalence of concurrent emphysema, in association with low pack-year smoking histories, and an association between coarser pulmonary fibrosis and a history of smoking in IPF together provide support for possible pathogenetic linkage to smoking in both diseases. There is a high prevalence of smoking-related emphysema in IPF and rheumatoid lung, often associated with a low pack-year smoking history. Fibrotic abnormalities on HRCT are coarser in smokers with both disorders. These observations raise the possibility of shared mechanisms between fibrogenesis and smoking-related damage. See Editorial, page 1163 © 2013 The Authors. Respirology © 2013 Asian Pacific Society of Respirology.


Loveman E.,University of Southampton | Copley V.R.,University of Southampton | Colquitt J.,University of Southampton | Scott D.A.,Oxford Outcomes | And 6 more authors.
Health Technology Assessment | Year: 2015

Background: Idiopathic pulmonary fibrosis (IPF) is a life-limiting lung disease that generally affects people over 60 years old. The main symptoms are shortness of breath and cough, and as the disease progresses there is a considerable impact on day-to-day life. Few treatments are currently available. Objectives: To conduct a systematic review of clinical effectiveness and an analysis of cost-effectiveness of treatments for IPF based on an economic model informed by systematic reviews of cost-effectiveness and quality of life. Data sources: Eleven electronic bibliographic databases, including MEDLINE, EMBASE, Web of Science, and The Cochrane Library and the Centre for Reviews and Dissemination databases, were searched from database inception to July 2013. Reference lists of relevant publications were also checked and experts consulted. Methods: Two reviewers independently screened references for the systematic reviews, extracted and checked data from the included studies and appraised their risk of bias. An advisory group was consulted about the choice of interventions until consensus was reached about eligibility. A narrative review with meta-analysis was undertaken, and a network meta-analysis (NMA) was performed. A decision-analytic Markov model was developed to estimate cost-effectiveness of pharmacological treatments for IPF. Parameter values were obtained from NMA and systematic reviews. Univariate and probabilistic sensitivity analyses were undertaken. The model perspective is NHS and Personal Social Services, and discount rate is 3.5% for costs and health benefits. Results: Fourteen studies were included in the review of clinical effectiveness, of which one evaluated azathioprine, three N-acetylcysteine (NAC) (alone or in combination), four pirfenidone, one BIBF 1120, one sildenafil, one thalidomide, two pulmonary rehabilitation, and one a disease management programme. Study quality was generally good, with a low risk of bias. The current evidence suggests that some treatments appear to be clinically effective. The model base-case results show increased survival for five pharmacological treatments, compared with best supportive care, at increased cost. General recommendations cannot be made of their cost-effectiveness owing to limitations in the evidence base. Limitations: Few direct comparisons of treatments were identified. An indirect comparison through a NMA was performed; however, caution is recommended in the interpretation of these results. In relation to the economic model, there is an assumption that pharmacological treatments have a constant effect on the relative rate of per cent predicted forced vital capacity decline. Conclusions: Few interventions have any statistically significant effect on IPF and a lack of studies on palliative care approaches was identified. Research is required into the effects of symptom control interventions, in particular pulmonary rehabilitation and thalidomide. Other research priorities include a well-conducted randomised controlled trial on inhaled NAC therapy and an updated evidence synthesis once the results of ongoing studies are reported. © Queen’s Printer and Controller of HMSO 2015.

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