Athol U Wells

Royal Brompton and Harefield NHS Foundation Trust, Harefield, England, United Kingdom

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Publications (305)1604.38 Total impact

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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.
  • Athol U Wells, Katerina M Antoniou
    Chest 04/2014; 145(4):672-4. · 5.85 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: 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
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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. · 5.85 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. · 5.85 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; · 3.55 Impact Factor
  • The lancet. Respiratory medicine. 01/2014; 2(1):e1.
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    ABSTRACT: Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology-a non-profit international organisation dedicated to consensus methodology in identification of outcome measures-conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field.
    Thorax 12/2013; · 8.38 Impact Factor
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    ABSTRACT: Pulmonary hypertension (PH), a common complication of left heart diseases (LHD), negatively impacts symptoms, exercise capacity, and outcome. Although the true prevalence of PH-LHD is unknown, a subset of patients might present significant PH that cannot be explained by a passive increase in left-sided filling pressures. The term "out-of-proportion" PH has been used to identify that population without a clear definition, which has been found less than ideal and created confusion. We propose a change in terminology and a new definition of PH due to LHD. We suggest to abandon "out-of-proportion" PH and to distinguish "isolated post-capillary PH" from "post-capillary PH with a pre-capillary component" on the basis of the pressure difference between diastolic pulmonary artery pressure and pulmonary artery wedge pressure. Although there is no validated treatment for PH-LHD, we provide insights into management and discuss completed and randomized trials in this condition. Finally, we provide recommendations for future clinical trials to establish safety and efficacy of novel compounds to target this area of unmet medical need.
    Journal of the American College of Cardiology 12/2013; 62(25 Suppl):D100-8. · 14.09 Impact Factor
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    ABSTRACT: Chronic obstructive lung disease (COPD) and diffuse parenchymal lung diseases (DPLD), including idiopathic pulmonary fibrosis (IPF) and sarcoidosis, are associated with a high incidence of pulmonary hypertension (PH), which is linked with exercise limitation and a worse prognosis. Patients with combined pulmonary fibrosis and emphysema (CPFE) are particularly prone to the development of PH. Echocardiography and right heart catheterization are the principal modalities for the diagnosis of COPD and DPLD. For discrimination between group 1 PH patients with concomitant respiratory abnormalities and group 3 PH patients (PH caused by lung disease), patients should be transferred to a center with expertise in both PH and lung diseases for comprehensive evaluation. The task force encompassing the authors of this article provided criteria for this discrimination and suggested using the following definitions for group 3 patients, as exemplified for COPD, IPF, and CPFE: COPD/IPF/CPFE without PH (mean pulmonary artery pressure [mPAP] <25 mm Hg); COPD/IPF/CPFE with PH (mPAP ≥25 mm Hg); PH-COPD, PH-IPF, and PH-CPFE); COPD/IPF/CPFE with severe PH (mPAP ≥35 mm Hg or mPAP ≥25 mm Hg with low cardiac index [CI <2.0 l/min/m(2)]; severe PH-COPD, severe PH-IPF, and severe PH-CPFE). The "severe PH group" includes only a minority of chronic lung disease patients who are suspected of having strong general vascular abnormalities (remodeling) accompanying the parenchymal disease and with evidence of an exhausted circulatory reserve rather than an exhausted ventilatory reserve underlying the limitation of exercise capacity. Exertional dyspnea disproportionate to pulmonary function tests, low carbon monoxide diffusion capacity, and rapid decline of arterial oxygenation upon exercise are typical clinical features of this subgroup with poor prognosis. Studies evaluating the effect of pulmonary arterial hypertension drugs currently not approved for group 3 PH patients should focus on this severe PH group, and for the time being, these patients should be transferred to expert centers for individualized patient care.
    Journal of the American College of Cardiology 12/2013; 62(25 Suppl):D109-16. · 14.09 Impact Factor
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    ABSTRACT: In patients with severe interstitial lung disease (ILD) progressing despite conventional immunosuppression, rituximab, a B-lymphocyte depleting monoclonal antibody, may offer an effective rescue therapy. Retrospective assessment of 50 patients with severe, progressive ILD (of varying aetiologies, excluding idiopathic pulmonary fibrosis (IPF)) treated with rituximab between 2010 and 2012. Change in pulmonary function tests compared with pre-rituximab levels was assessed at 6-12 months post-treatment. ILD was associated with connective tissue disease in 33 patients, hypersensitivity pneumonitis in 6 patients and miscellaneous conditions in 11 patients. At the time of rituximab administration, patients had severe physiologic impairment with a median forced vital capacity (FVC) of 44.0% (24.0-99.0%) and diffusing capacity of carbon monoxide (DLCO ) of 24.5% (11.4-67.0%). In contrast with a median decline in FVC of 14.3% and DLCO of 18.8% in the 6-12 months prior to rituximab, analysis of paired pulmonary function data revealed a median improvement in FVC of 6.7% (P < 0.01) and stability of DLCO (0% change; P < 0.01) in the 6-12 months following rituximab treatment. Two patients developed serious infections (pneumonia) requiring hospitalization following rituximab, and 10 patients died from progression of underlying ILD, a median of 5.1 (1.2-24.5) months after treatment. In patients with severe, progressive non-IPF ILD unresponsive to conventional immunosuppression, rituximab may offer an effective therapeutic intervention. Future prospective, controlled trials are warranted to validate these findings, and to assess safety outcomes.
    Respirology 11/2013; · 2.78 Impact Factor
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    ABSTRACT: Pulmonary hypertension is frequently observed in advanced idiopathic pulmonary fibrosis (IPF) and is associated with poor prognosis. Cardiopulmonary exercise testing (CPET) can be used to detect less advanced pulmonary vascular impairment, and therefore may be of prognostic use. We studied the predictive value of non-invasive exercise parameters that were associated with elevated systolic pulmonary artery pressure (sPAP) for survival in IPF patients. From our interstitial lung disease database, we reviewed records of consecutive patients with IPF in whom CPET and echocardiography were performed within 2 weeks (n = 38). Eleven patients (29%) had increased sPAP (≥40 mm Hg). From all non-invasive CPET parameters, only the ventilatory equivalent for CO2 (V'E /V'CO2 ) at anaerobic threshold differed significantly between patients with and without sPAP ≥ 40 mm Hg. The receiver-operator characteristic curve for V'E /V'CO2 resulted in areas under the curve of 0.77 (95% CI: 0.569-0.970; P = 0.026), with a cut-off value for predicting sPAP ≥ 40 mm Hg of >45.0. Patients with V'E /V'CO2 > 45.0 had significantly worse survival compared with patients with V'E /V'CO2 ≤ 45.0 (P = 0.001). In contrast, sPAP did not predict survival. V'E /V'CO2 , the only CPET parameter associated with elevated sPAP, appears a potentially useful non-invasive marker for early detection of pulmonary vascular impairment, and therefore may be of use for a more accurate prognostic assessment in IPF patients.
    Respirology 11/2013; · 2.78 Impact Factor
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    ABSTRACT: The clinical course of IPF is characterized by progressive decline in lung function and eventual mortality. We sought to determine if future declines in pulmonary function and/or mortality can be predicted from prior trends in pulmonary function tests (PFT). 4431 PFTs and mortality were analyzed from 734 IPF subjects collected from 1981 to 2008. Kaplan-Meier method was used for mortality analyses. Mixed models were used to describe longitudinal pulmonary function dynamics since PFTs were observed at varying time points from baseline. During the first year of follow up 135 subjects (73%) had stable FVC while 50 subjects (37%) showed a decline in FVC. During months 12-24 (1-2 years after diagnosis) a stable FVC occurred with the same frequency among both subjects whose FVC had declined during year one and whose FVC had remained stable 84.0% and 80.7% respectively, p=0.59. Among subjects alive at the end of year 1, those with a stable FVC were more likely to be alive at the end of year 2 than those whose FVC declined: HR 0.91 [95%CI 0.87-0.94] and 0.71 [0.62-0.78] respectively. PFT decline predicts early mortality, but not future declines in physiology, regardless of time since diagnosis.
    Chest 11/2013; · 5.85 Impact Factor
  • Katerina M Antoniou, Athol U Wells
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    ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and ultimately fatal disease, with a highly variable course in individual patients. Episodes of rapid deterioration are not uncommon, often following a period of stability. In cases of uncertain etiology, with typical clinical and high-resolution computed tomography (HRCT) features, the term 'acute exacerbation of IPF' (AE-IPF) has been coined to describe a combination of diffuse alveolar damage and preexisting usual interstitial pneumonia. In 2007, a consensus definition and diagnostic criteria were proposed. Although the presence of overt infection is currently an exclusion criterion, it appears likely that occult infection, reflux and thoracic surgical procedures are all trigger factors for AE-IPF. The development of new, usually bilateral infiltrates (ground-glass attenuation with variable admixed consolidation) is a defining HRCT feature. The outcome is poor with a short-term mortality in excess of 50% despite therapy. A number of pathophysiologic pathways are activated, with immunologic dysregulation, epithelial damage and circulating fibrocytes all believed to play a pathogenetic role. Acute exacerbations are less prevalent in other fibrotic lung diseases than in IPF and may have a better outcome, with the exception of acute exacerbations of rheumatoid lung. In AE-IPF, the exclusion of alternative causes of rapid deterioration, including heart failure and infection, is the main goal of investigation. Empirical high-dose corticosteroid steroid therapy is generally used in AE-IPF, without proven benefit. © 2013 S. Karger AG, Basel.
    Respiration 10/2013; · 2.62 Impact Factor

Publication Stats

7k Citations
1,604.38 Total Impact Points

Institutions

  • 2006–2014
    • Royal Brompton and Harefield NHS Foundation Trust
      Harefield, England, United Kingdom
  • 2013
    • University of Crete
      • Department of Thoracic Medicine
      Retimo, Crete, Greece
    • Claude Bernard University Lyon 1
      • Service de neurologie
      Villeurbanne, Rhone-Alpes, France
    • The Princess Alexandra Hospital NHS Trust
      Harlow, England, United Kingdom
  • 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
    • University of Auckland
      • Department of Medicine
      Auckland, Auckland, New Zealand
  • 2011
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 2010–2011
    • University Hospital of Parma
      Parma, Emilia-Romagna, Italy
  • 2008
    • University of Michigan
      Ann Arbor, Michigan, United States
    • Memorial Sloan-Kettering Cancer Center
      • Department of Pathology
      New York City, NY, United States
    • Vancouver General Hospital
      • Department of Radiology
      Vancouver, British Columbia, Canada
  • 2007
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
    • Hôpital Avicenne – Hôpitaux Universitaires Paris-Seine-Saint-Denis
      Bobigny, Île-de-France, France
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, CA, United States
  • 2005
    • Auckland City Hospital
      • Department of Radiology
      Окленд, Auckland, New Zealand
  • 1992–2005
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 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
    • University of Nottingham
      • Division of Respiratory Medicine
      Nottingham, ENG, United Kingdom
  • 1999
    • University of British Columbia - Vancouver
      • Department of Radiology
      Vancouver, British Columbia, Canada