Athol U Wells

The Heart Lung Center, Londinium, England, United Kingdom

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Publications (327)1705.4 Total impact

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  • Athol U Wells, Christopher P Denton
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    ABSTRACT: Pulmonary complications are an important extra-articular feature of autoimmune rheumatic diseases and a major cause of mortality. The underlying pathogenesis probably involves multiple cellular compartments, including the epithelium, lung fibroblasts, and the innate and adaptive immune system. Heterogeneity in the extent and progression of lung fibrosis probably reflects differences in underlying pathogenic mechanisms. Growing understanding of the key pathogenic drivers of lung fibrosis might lead to the development of more effective targeted therapies to replicate the treatment advances in other aspects of these diseases. Interstitial lung disease (ILD) in connective tissue disease (CTD) is characterized using the classification of the idiopathic interstitial pneumonias. Systemic sclerosis is most frequently associated with ILD and, in most of these patients, ILD manifests as a histological pattern of nonspecific interstitial pneumonia. Conversely, in rheumatoid arthritis, the pattern of ILD is most often usual interstitial pneumonia. The key goals of clinical assessment of patients with both ILD and CTD are the detection of ILD and prognostic evaluation to determine which patients should be treated. Data from treatment trials in systemic sclerosis support the use of immunosuppressive therapy, with the treatment benefit largely relating to the prevention of progression of lung disease.
    Nature Reviews Rheumatology 09/2014; · 9.75 Impact Factor
  • Athol U Wells
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    ABSTRACT: Based on international collaborative data, interstitial lung disease is now the most frequent cause of death in systemic sclerosis (SSc), having supplanted renal crisis in that regard. Despite detailed explorations of candidate mediators, no primary pathway in the pathogenesis of interstitial lung disease associated with SSc (SSc-ILD) has been definitively identified and, therefore, treatment with current agents is only partially successful. However, as immunomodulatory agents do, on average, retard progression of lung disease, early identification of SSc-ILD, using thoracic high resolution computed tomography (HRCT), is highly desirable. The decision whether to introduce therapy immediately is often difficult as the balance of risk and benefit favours a strategy of careful observation when lung disease is very limited, especially in long-standing SSc. The threshold for initiating treatment is substantially reduced when lung disease is severe, systemic disease is short in duration or ongoing progression is evident, based on pulmonary function tests and symptoms. This review summarises epidemiology, pathogenesis, difficult clinical problems and management issues in SSc-ILD.
    Presse medicale (Paris, France : 1983). 09/2014;
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    ABSTRACT: Rationale: IPF is a progressive lung disease of unknown cause that leads to respiratory failure and death within 5 years of diagnosis. Overt respiratory infection and immunosuppression carry a high morbidity and mortality, while polymorphisms in genes related to epithelial integrity and host defence predispose to IPF. Objectives: To investigate the role of bacteria in the pathogenesis and progression of IPF. Methods: We prospectively enrolled patients diagnosed with IPF according to international criteria together with healthy smokers, non-smokers and subjects with moderate Chronic Obstructive Pulmonary Disease (COPD) as controls. Subjects underwent bronchoalveolar lavage (BAL) from which genomic DNA was isolated. The V3-V5 region of the bacterial 16S rRNA gene was amplified, allowing quantification of bacterial load and identification of communities by 16S rRNA qPCR and pyrosequencing. Measurements and Main Results: Sixty five IPF patients had double the burden of bacteria in Bronchoalveolar lavage (BAL) fluid compared to 44 controls. Baseline bacterial burden predicted the rate of decline in lung volume, risk of death and associated independently with the rs35705950 polymorphism of the MUC5B mucin gene, a proven host susceptibility factor for IPF. Sequencing yielded 912,883 high quality reads from all subjects. We identified Haemophilus, Streptococcus, Neisseria and Veillonella spp. to be more abundant in cases than controls. Regression analyses indicated that these specific OTUs as well as bacterial burden associated independently with IPF. Conclusions: IPF is characterised by an increased bacterial burden in BAL that predicts decline in lung function and death. Trials of antimicrobial therapy are needed to determine if microbial burden is pathogenic in the disease.
    American Journal of Respiratory and Critical Care Medicine 09/2014; · 11.04 Impact Factor
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    ABSTRACT: Cigarette smoking is a key factor in the development of numerous pulmonary diseases. An international group of clinicians, radiologists and pathologists evaluated patients with previously identified idiopathic interstitial pneumonia (IIP) to determine unique features of cigarette smoking. Phase 1 (derivation group) identified smoking-related features in patients with a history of smoking (n = 41). Phase 2 (validation group) determined if these features correctly predicted the smoking status of IIP patients (n = 100) to participants blinded to smoking history. Finally, the investigators sought to determine if a new smoking-related interstitial lung disease phenotype could be defined. Phase 1 suggested that preserved forced vital capacity with disproportionately reduced diffusing capacity of the lung for carbon monoxide, and various radiographic and histopathological findings were smoking-related features. In phase 2, the kappa coefficient among clinicians was 0.16 (95% CI 0.11-0.21), among the pathologists 0.36 (95% CI 0.32-0.40) and among the radiologists 0.43 (95% CI 0.35-0.52) for smoking-related features. Eight of the 100 cases were felt to represent a potential smoking-related interstitial lung disease. Smoking-related features of interstitial lung disease were identified in a minority of smokers and were not specific for smoking. This study is limited by its retrospective design, the potential for recall bias in smoking history and lack of information on second-hand smoke exposure. Further research is needed to understand the relationship between smoking and interstitial lung disease.
    The European respiratory journal. 07/2014;
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    ABSTRACT: There is wide interindividual variation in response to morphine for cancer-related pain; 30% of patients do not have a good therapeutic outcome. Alternative opioids such as oxycodone are increasingly being used and opioid switching has become common clinical practice.
    Journal of pain and symptom management. 06/2014;
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    ABSTRACT: Rationale: Pulmonary hypertension (PH) associated with fibrotic idiopathic interstitial pneumonia (IIP) confers important additional morbidity and mortality. Objectives: To evaluate the safety and clinical efficacy of the dual endothelin-1 receptor antagonist (ERA) 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 end point was a fall from baseline pulmonary vascular resistance index (PVRi) of 20% or more over 16 weeks. Main Results: Sixty patients (42 men; mean age 66.6±9.2 years), with a mean pulmonary artery pressure of 36.0 (±8.9) mmHg, PVRi 13.0 (±6.7) Wood Units.m2 and reduced cardiac index of 2.21 (±0.5) L/min/m2 were recruited to the study. Accounting for deaths and withdrawals, paired right heart catheter (RHC) 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 ≥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 haemodynamics, functional capacity or symptoms between the bosentan and placebo groups over 16 weeks. Our data does not support therefore the use of the dual ERA, bosentan in patients with PH and fibrotic IIP. Clinical trial registration available at www.clinicaltrials.gov, ID NCT00637065.
    American Journal of Respiratory and Critical Care Medicine 06/2014; · 11.04 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Respirology 04/2014; · 2.78 Impact Factor
  • Athol U Wells, Katerina M Antoniou
    Chest 04/2014; 145(4):672-4. · 7.13 Impact Factor
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    ABSTRACT: Despite many unanswered questions regarding the pathogenesis of interstitial lung disease in systemic sclerosis (SSc-ILD) and the lack of accurate epidemiological risk factors, there have been major advances in the identification and prognostic evaluation of SSc-ILD. The evaluation of disease severity is a multidisciplinary exercise, requiring the integration of pulmonary function tests, high-resolution computed tomography data, and symptomatic severity and these factors all need to be considered in the detection of disease progression. Except in a minority of patients with reversible inflammatory disease, the primary goal of treatment is the prevention of disease progression. Current treatment regimens are centered on immunosuppressive therapy with controlled treatment data largely confined to the use of cyclophosphamide. The results of two controlled trials indicate that cyclophosphamide therapy is appropriate in SSc-ILD patients with extensive fibrotic lung involvement. There is a need to broaden therapeutic approaches with the exploration of rituximab (based on recent pilot data) and antifibrotic agents, shown to have treatment effects in other fibrotic interstitial lung diseases. However, it is also important to avoid the overtreatment of SSc-ILD patients with limited nonprogressive lung involvement. In that setting, an initial policy of nonintervention but meticulous observation ("masterful inactivity with cat-like observation") is often warranted.
    Seminars in Respiratory and Critical Care Medicine 04/2014; 35(2):213-21. · 2.75 Impact Factor
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    ABSTRACT: Present guidelines for the diagnosis of idiopathic pulmonary fibrosis require histological confirmation of surgical lung biopsy samples when high-resolution CT images are not definitive for usual interstitial pneumonia. We aimed to assess the predictive value of high-resolution CT in a cohort of patients with suspected idiopathic pulmonary fibrosis from a previous randomised trial. ARTEMIS-IPF was a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial of ambrisentan for adults aged 40-80 years with well-defined idiopathic pulmonary fibrosis and 5% or less honeycombing on high-resolution CT. In December, 2010, an interim analysis showed lack of efficacy and the trial was stopped. In the present follow-on analysis, we assessed patients who were screened for ARTEMIS-IPF who underwent high-resolution CT as part of screening and surgical lung biopsy as part of standard clinical care. A radiologist and a pathologist from a central panel independently assessed anonymised CT scans and biopsy samples. We calculated the positive and negative predictive value of high-resolution CT (classified as usual interstitial pneumonia, possible usual interstitial pneumonia, and inconsistent with usual interstitial pneumonia) for confirmation of histological patterns of usual interstitial pneumonia. This study is registered with ClinicalTrials.gov, number NCT00768300. 315 (29%) of 1087 consecutively screened patients in ARTEMIS-IPF had both high-resolution CT and surgical lung biopsy samples. 108 of 111 patients who met high-resolution CT criteria for usual interstitial pneumonia had histologically confirmed usual interstitial pneumonia (positive predictive value 97·3%, 95% CI 92·3-99·4), as did 79 of 84 patients who met high-resolution CT criteria for possible usual interstitial pneumonia (94·0%, 86·7-98·0). 22 of 120 patients had an inconsistent high-resolution CT pattern for usual interstitial pneumonia that was histologically confirmed as not or possible usual interstitial pneumonia (negative predictive value 18·3%, 95% CI 11·9-26·4). In the appropriate clinical setting, for patients with possible usual interstitial pneumonia pattern on high resolution CT, surgical lung biopsy sampling might not be necessary to reach a diagnosis of idiopathic pulmonary fibrosis if high-resolution CT scans are assessed by experts at regional sites familiar with patterns of usual interstitial pneumonia and management of idiopathic interstitial pneumonia. Gilead Sciences.
    The lancet. Respiratory medicine. 04/2014; 2(4):277-84.
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    ABSTRACT: To test the hypothesis that vascular abnormalities on high-resolution CT (HRCT) would be associated with echocardiographic changes and lung function abnormalities in patients with sickle cell disease (SCD) and the decline in lung function seen in SCD patients. HRCT, echocardiography and lung function assessments were made in 35 adults, 20 of whom had previously been assessed a median of 6.6 years prior to this study. The pulmonary arterial dimensions on HRCT were quantified as the mean segmental pulmonary artery/bronchus (A/B) ratio and the summated cross-sectional area of all pulmonary vessels <5 mm in diameter (cross-sectional area (CSA)<5 mm%). The segmental A/B ratio was negatively correlated with FEV1, vital capacity (VC), forced expiratory flow between 25% and 75% of VC (FEF25/75) and arterial oxygen saturation (SpO2) and positively with the residual volume: total lung capacity ratio (RV:TLC) and respiratory system resistance (Rrs). CSA<5 mm% was negatively correlated with FEV1, FEF25/75 and SpO2 and positively with RV, RV:TLC and respiratory system resistance (Rrs). There were significant correlations between cardiac output assessed by echocardiography and the segmental A/B ratio and CSA<5 mm%. Lung function (FEV1 p=0.0004, VC p=0.0347, FEF25/75 p=0.0033) and the segmental A/B ratio (p=0.0347) and CSA<5 mm% (p<0.0001) significantly deteriorated over the follow-up period. Abnormalities in pulmonary vascular volumes may explain some of the lung function abnormalities and the decline in lung function seen in adults with SCD.
    Thorax 03/2014; · 8.38 Impact Factor
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    ABSTRACT: Objective: We assess survival and incidence of organ-based complications in a large single-centre cohort of unselected systemic sclerosis (SSc) patients. We explore predictors of survival and clinically significant pulmonary fibrosis (csPF) and pulmonary hypertension (PH). Methods: The study cohort consisted of 398 consecutive SSc patients, followed for up to 15 years. Results: Overall survival estimate at the end of follow-up was 57% among limited and 50% among diffuse subset patients (p=0.017). We found that greater age at disease onset, diffuse subset, lower DLCO, lower haemoglobin, higher creatinine and presence of PH or cardiac involvement are independent predictors of worse survival. Over the entire follow-up, 42% of the dcSSc and 22% of the lcSSc patients developed csPF (p<0.001). The variables that predicted csPF development were dcSSc, greater age at onset, lower FVC and DLCO, presence of anti-topoisomerase I antibody (ATA), while presence of anti-centromere antibody was protective. There was no difference in PH cumulative incidence between the two subsets - 24% in lcSSc and 18% in dcSSc (p=0.558). Incidence rates were 1-2%/year. The PH prediction model demonstrated that older age at SSc onset, increase in serum creatinine and presence of anti-RNA polymerase or anti-U3RNP antibodies are associated with increased risk of PH, while ATA positivity reduced the hazard. Conclusion: Our study provides data on long-term outcome of SSc and the timing and frequency of major organ complications. The predictive models we present could be used as clinical tools for patient risk stratification and could facilitate cohort enrichment for event driven studies. © 2014 American College of Rheumatology.
    Arthritis & rheumatology (Hoboken, N.J.). 03/2014;
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    ABSTRACT: Slide PresentationsPRESENTED ON: Saturday, March 22, 2014 at 12:15 PM - 01:15 PMPURPOSE: Although plasma BNP level is considered to be a useful biomarker for identifying cardiac involvement in patients with Sarcoidosis (Sarc) few data exist for its predictive role in mortality. Our aim was to investigate the predictive role of BNP on all-cause mortality. 174 consecutive patients (mean age, 48.95+/- 12. 66 years; male/female, 66/108) with biopsy proven sarcoidosis were prospectively studied. Baseline evaluation included BNP, echocardiography, Holter monitoring with ability to calculate heart rate variability indices and whether was needed cardiac MRI. Also, pulmonary function tests included total lung capacity (TLC) and diffusion lung capacity of oxygen (DLCO) were performed. BNP level of all patients was 24.58±28.2 pg/dl. The baseline BNP was significantly correlated with the age (p=0.0001, r=0.341),left atrium(p=0.0001, r=0.309), interventricular septum(p=0.0001, r=0.280), posterior wall(p=0.001, r=0.240), transmitral A wave(p=0.003, r=0.228), systolic pressure of pulmonary artery(p=0.0001, r=0.382), Forced Expiratory Volume at 1 second(p=0.044, r=-0.153), DLCO(p=0.012, r=-190), the presence of premature ventricular beats(p=0.0001,r=0.281) and the 24hour derived standard deviation of NN, an index of HRV(p=0.001, p=-0.258). During a mean follow-up of 54±20 (range 1-101) months, 15 Sarc patients (36.7%) died. Their baseline BNP was significantly elevated compaired to the alive{ 69.00±48.58 vs 21.45±22,69, p<0.00001). BNP at a cutoff value of 28.35 pg/ml predicted all-cause mortality with a sensitivity of 85,8% and a specificity of 78.1% (area under the ROC curve, 0.857). BNP can be used as an additive predictor of all-cause mortality in patients with sarcoidosis. BNP should be estimated upon admission of every sarcoidosis patients mainly those highly suspicious of cardiac involvement. The following authors have nothing to disclose: Elias Gialafos, Vasileios Kouranos, Aggeliki Rapti, Efrosyni Manali, Theodore Papaioannou, Nikolaos Koulouris, Spuridon Papiris, Athol Wells, George TzelepisNo Product/Research Disclosure Information.
    Chest 03/2014; 145(3 Suppl):253A. · 7.13 Impact Factor
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    ABSTRACT: Cardiovascular Disease PostersSESSION TYPE: Poster PresentationsPRESENTED ON: Saturday, March 22, 2014 at 01:15 PM - 02:15 PMPURPOSE: Spatial QRS T-angle (spQRS T-a) is considered as a novel electrocardiography derived marker of independent predictive value of electrical instability in cardiac disease. Cardiac involvement in sarcoidosis is often underdiagnosed, although a significant contributor to mortality. The present study was conducted to test the hypothesis that patients with sarcoidosis have increased ventricular repolarisation heterogeneity as reflected by spQRS-Ta values. This cross-sectional study included newly diagnosed consecutive patients with biopsy proven sarcoidosis (n=83) and healthy subjects (n=83) who were matched 1:1 for age, gender and BMI. All patients underwent clinical and cardiopulmonary evaluation including cardiac MRI to assess spQRS T-a values and cardiac involvement and identify possible correlations. SpQRS-Ta was significantly increased in sarcoidosis patients compared to healthy controls (18.3 ± 11.4 vs. 11.3 ± 5.1, p<0.01). When known criteria for the clinical diagnosis of cardiac sarcoidosis were applied spQRS-Ta was found significantly increased in patients with presence of criteria compared to totally 'negative' sarcoidosis patients (21.1 ± 11.8 vs. 15.8 ± 10.4, p=0.03). SpQRS-Ta values were significantly greater in those sarcoidosis patients with Lown class >III ventricular arrhythmia than the remaining patients (27.5 ± 15.7 vs. 17.1 ± 10.3, P<0.01), while univariate linear regression analysis showed that Lown classification was independently associated with spQRS-Ta values (p=0.002, b=3.236, 95% CI 1.209-5.263). SpQRS T-a could be used as a noninvasive marker of electrical instability due to cardiac involvement in patients with sarcoidosis The clinical diagnosis of cardiac sarcoidosis is feasible with combination of electrical and structural markers with ranging sensitivity and specificity. This marker seems to be useful in identifying patients with electrical instability and possible cardiac involvement. The following authors have nothing to disclose: Elias Gialafos, Vasileios Kouranos, Aggeliki Rapti, Efrosyni Manali, Konstantina Aggeli, Elias Perros, Theodore Papaioannou, Petros Sfikakis, Christodoulos Stefanadis, George Tzelepis, Athol Wells, Nikolaos KoulourisNo Product/Research Disclosure Information.
    Chest 03/2014; 145(3 Suppl):86A. · 7.13 Impact Factor
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    ABSTRACT: To evaluate the computed tomographic (CT) predictors of a clinically significant yield from microbiological tests in patients with a tree-in-bud pattern. CT examinations in 53 patients (male=34; mean age=52.9±17.3 y) with a tree-in-bud pattern in whom a diagnostic test (sputum analysis, bronchoalveolar lavage or nasopharyngeal aspirates) had been performed within 2 weeks were identified. The following CT patterns were independently quantified by 2 thoracic radiologists: tree-in-bud, bronchiectasis, bronchial wall thickening, consolidation, ground-glass opacification, and nodules. The presence of cavitation (in nodules and/or consolidation) was recorded. Patient charts were reviewed for the presence of a clinically significant positive microbiological result. A clinically significant causal organism was present in 25/53 (47%) patients. The median extent of a tree-in-bud pattern was 5 [range=1 to 16 (maximum range=0 to 18)], and cavitation was present in 14/53 (26%) patients (cavitating nodules=8, cavitation in consolidation=3, and cavitation in consolidation and nodules=3). There was no independent linkage between the extent of a tree-in-bud pattern and the identification of a clinically significant organism. The microbiological yield was significantly higher if there was coexistent cavitation in nodules or consolidation [11/14 (79%) vs. 14/39 (39%); P=0.005]. On stepwise logistic regression, the only CT predictor of a clinically significant microbiological yield was cavitation on CT (odds ratio=9.7; 95% confidence interval=1.9, 49.9; P<0.01); the extent of a tree-in-bud pattern, concurrent use of antibiotics, age, and sex were not independently linked to a significant microbiological yield. A specific clinically significant microbiological diagnosis was obtained in approximately 50% of patients with a tree-in-bud pattern. The microbiological yield rises strikingly when a tree-in-bud pattern coexists with cavitation (in nodules or consolidation) but is not predicted by ancillary CT signs or clinical parameters.
    Journal of thoracic imaging 02/2014; · 1.42 Impact Factor
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    ABSTRACT: Mortality in pulmonary sarcoidosis is highly variable and a reliable prognostic algorithm for disease staging and for guiding management decisions is needed. The objective of this study is to derive and test a staging system for determining prognosis in pulmonary sarcoidosis. We identified the prognostic value of high-resolution computed tomography (HRCT) patterns and pulmonary function tests, including the composite physiological index (CPI) in patients with pulmonary sarcoidosis. We integrated prognostic physiological and HRCT variables to form a clinical staging algorithm predictive of mortality in a test cohort. The staging system was externally validated in a separate cohort by the same methods of discrimination used in the primary analysis and tested for clinical applicability by four test observers. The test cohort included 251 patients with pulmonary sarcoidosis in the study referred to the Sarcoidosis clinic at the Royal Brompton Hospital, UK, between Jan 1, 2000, and June 30, 2010. The CPI was the strongest predictor of mortality (HR 1·04, 95% CI 1·02-1·06, p<0·0001) in the test cohort. An optimal CPI threshold of 40 units was identified (HR 4·24, 2·84-6·33, p<0·0001). The CPI40, main pulmonary artery diameter to ascending aorta diameter ratio (MPAD/AAD), and an extent of fibrosis threshold of 20% were combined to form a staging algorithm. When assessed in the validation cohort (n=252), this staging system was strikingly more predictive of mortality than any individual variable alone (HR 5·89, 2·68-10·08, p<0·0001). The staging system was successfully applied to the test and validation cohorts combined, by two radiologists and two physicians. A clear prognostic separation of patients with pulmonary sarcoidosis is provided by a simple staging system integrating the CPI and two HRCT variables. National Institute of Health Research Respiratory Disease Biomedical Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London.
    The lancet. Respiratory medicine. 02/2014; 2(2):123-30.
  • Thorax 01/2014; · 8.38 Impact Factor
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    ABSTRACT: Sarcoidosis is a systemic granulomatous disorder of unknown aetiology with a wide spectrum of radiological appearances and almost invariably pulmonary involvement. Lung involvement accounts for most of the morbidity and much of the mortality associated with sarcoidosis. Imaging contributes significantly to the diagnosis and management of patients with sarcoidosis. In typical cases, chest radiography may be sufficient to establish the diagnosis with little margin of error and CT is not necessary. However, CT can play a critical role in several clinical settings: atypical clinical and/or radiographic findings; normal or near-normal chest radiograph but clinical suspicion of sarcoidosis; and detection of complications. Moreover, in many patients, CT findings are atypical and unfamiliar to most radiologists (e.g. sarcoidosis mimicking other lung diseases and vice versa), and in these cases histological confirmation of the diagnosis is recommended. CT is also useful in assessing disease extent and may help to discriminate between reversible and irreversible lung disease, thus providing critical prognostic information. This review concentrates on the more difficult imaging aspects of sarcoidosis, in particular differential diagnosis and disease complications. Key points •Sarcoidosis is characterized by a wide spectrum of radiological appearances.•In typical cases, imaging substantially contributes to the diagnosis of sarcoidosis.•CT plays a critical role in atypical and complicated cases.•CT may discriminate between reversible and irreversible lung disease.
    European Radiology 01/2014; · 4.34 Impact Factor
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    ABSTRACT: Background: Pulmonary hypertension (PH), an increasingly recognised complication of pulmonary sarcoidosis, is associated with increased morbidity and mortality Evidence of benefit with targeted therapies in sarcoidosis associated pulmonary hypertension (SAPH) is limited. Methods: We conducted a retrospective review of patients with sarcoidosis and right heart catheter proven PH who received treatment with targeted therapies (phosphodiesterase-5 inhibitors, endothelin receptor antagonists, or combination) at our hospital. Six minute walk test (6MWT), World Health Organisation (WHO) functional class, echocardiography, pulmonary function test (PFT) and serum brain natriuretic peptide (BNP) data were collected at baseline and during follow-up. Results: Thirty-three patients (16 men) with a mean age of 55.5 ± 10.7 years and mean pulmonary artery pressure of 44.0 ± 8.6 mm Hg received treatment with targeted PH therapies (sildenafil=29, bosentan=4). At six months, median six minute walk distance improved from 227 (88-526) meters to 240 (140-380) metres (p=0.04), median serum BNP levels improved from 35 (2-424) pmol/L to 26 (4-255) pmol/L (p<0.01), and at echocardiography, median tricuspid annular plane systolic excursion (TAPSE) improved from 17.5 (8.0-27.0) mm to 20.0 (15.0-27.0) mm (p=0.03). WHO functional class improved in 14 patients. Two patients developed side-effects attributed to sildenafil (n=1) or bosentan (n=1), requiring conversion to alternative PH therapies. Ten patients died, and one patient underwent lung transplantation, a median of 13.5 (3-37) months after commencing targeted therapies. Conclusions: Our results suggest that targeted therapies are safe in patients with SAPH. Controlled trials are warranted before therapeutic recommendations can be made.
    01/2014; 31(2):82-90.

Publication Stats

8k Citations
1,705.40 Total Impact Points

Institutions

  • 2014
    • The Heart Lung Center
      Londinium, England, United Kingdom
  • 2006–2014
    • Royal Brompton and Harefield NHS Foundation Trust
      Harefield, England, United Kingdom
  • 2013
    • The Princess Alexandra Hospital NHS Trust
      Harlow, England, United Kingdom
    • Claude Bernard University Lyon 1
      • Service de neurologie
      Villeurbanne, Rhone-Alpes, France
  • 2008–2013
    • University of Crete
      • Department of Thoracic Medicine
      Retimo, Crete, Greece
    • Memorial Sloan-Kettering Cancer Center
      • Department of Pathology
      New York City, NY, United States
    • University of Michigan
      Ann Arbor, Michigan, United States
    • Vancouver General Hospital
      • Department of Radiology
      Vancouver, British Columbia, Canada
  • 2003–2013
    • King's College London
      • Department of Palliative Care, Policy and Rehabilitation
      Londinium, England, United Kingdom
  • 2001–2013
    • Imperial College London
      • Section of Immunology
      Londinium, England, United Kingdom
    • Mayo Foundation for Medical Education and Research
      Rochester, Michigan, United States
  • 2012
    • University of Cincinnati
      Cincinnati, Ohio, United States
    • The Royal Marsden NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2009–2012
    • Imperial College Healthcare NHS Trust
      • Division of Respiratory Medicine
      Londinium, England, United Kingdom
    • Georg-August-Universität Göttingen
      Göttingen, Lower Saxony, Germany
  • 2000–2012
    • Nottinghamshire Healthcare NHS Trust
      Nottigham, England, United Kingdom
  • 2011
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 2010–2011
    • University Hospital of Parma
      Parma, Emilia-Romagna, Italy
    • Heart Research Institute (UK)
      Norwich, England, United Kingdom
  • 1992–2011
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 2007
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, CA, United States
    • Hôpital Avicenne – Hôpitaux Universitaires Paris-Seine-Saint-Denis
      Bobigny, Île-de-France, France
  • 2005
    • Auckland City Hospital
      • Department of Radiology
      Окленд, Auckland, New Zealand
  • 2004
    • The University of Edinburgh
      • Division of Pathology
      Edinburgh, SCT, United Kingdom
  • 2002–2003
    • Ealing, Hammersmith & West London College
      Londinium, England, United Kingdom
    • St. Antonius Ziekenhuis
      • Department of Pulmonology
      Nieuwegein, Provincie Utrecht, Netherlands
    • Royal Society of Medicine
      Londinium, England, United Kingdom
    • University of Nottingham
      • Division of Respiratory Medicine
      Nottingham, ENG, United Kingdom
  • 1997–2000
    • University of Auckland
      • Department of Medicine
      Auckland, Auckland, New Zealand
  • 1999
    • University of British Columbia - Vancouver
      • Department of Radiology
      Vancouver, British Columbia, Canada