Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Phys Med Rehabil Clin N Am ; 30(4): xvii, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31563179
2.
Europace ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31408153

RESUMO

AIMS: To evaluate population-based electronic health record (EHR) definitions of atrial fibrillation (AF) and valvular heart disease (VHD) subtypes, time trends in prevalence and prognosis. METHODS AND RESULTS: A total of 76 019 individuals with AF were identified in England in 1998-2010 in the CALIBER resource, linking primary and secondary care EHR. An algorithm was created, implemented, and refined to identify 18 VHD subtypes using 406 diagnosis, procedure, and prescription codes. Cox models were used to investigate associations with a composite endpoint of incident stroke (ischaemic, haemorrhagic, and unspecified), systemic embolism (SSE), and all-cause mortality. Among individuals with AF, the prevalence of AF with concomitant VHD increased from 11.4% (527/4613) in 1998 to 17.6% (7014/39 868) in 2010 and also in individuals aged over 65 years. Those with mechanical valves, mitral stenosis (MS), or aortic stenosis had highest risk of clinical events compared to AF patients with no VHD, in relative [hazard ratio (95% confidence interval): 1.13 (1.02-1.24), 1.20 (1.05-1.36), and 1.27 (1.19-1.37), respectively] and absolute (excess risk: 2.04, 4.20, and 6.37 per 100 person-years, respectively) terms. Of the 95.2% of individuals with indication for warfarin (men and women with CHA2DS2-VASc ≥1 and ≥2, respectively), only 21.8% had a prescription 90 days prior to the study. CONCLUSION: Prevalence of VHD among individuals with AF increased from 1998 to 2010. Atrial fibrillation associated with aortic stenosis, MS, or mechanical valves (compared to AF without VHD) was associated with an excess absolute risk of stroke, SSE, and mortality, but anticoagulation was underused in the pre-direct oral anticoagulant (DOAC) era, highlighting need for urgent clarity regarding DOACs in AF and concomitant VHD.

3.
Curr Opin Pulm Med ; 25(5): 426-433, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31365376

RESUMO

PURPOSE OF REVIEW: Computer algorithms possess an intrinsic speed, objectivity, reproducibility and scalability unmatched by visual quantitation methods performed by trained readers. The question of how well quantitative CT (QCT) analysis methods compare with visual CT analysis to predict functional status in fibrosing lung diseases (FLDs) is of increasing relevance to understand the future role QCT may have in prognostication of FLD. RECENT FINDINGS: The latest computer algorithms demonstrate improved performance over visual CT analysis in predicting baseline disease severity as measured by correlations with functional indices of lung damage. QCT analysis may, therefore, have a role in aiding clinical decision-making as well as in the enrichment of drug trial populations. Quantitative analysis on longitudinal CTs has also shown better correlations with changes in functional indices whenever compared with visual scores of change suggesting the potential of QCT analysis as an imaging biomarker of disease progression in FLD. Importantly, computer algorithms are now able to identify prognostic imaging biomarkers that cannot be quantified visually (e.g. vessel-related structures). SUMMARY: QCT holds great promise for the evaluation of damage in FLD. Challenges for QCT include accommodating measurement noise from variation in CT acquisition techniques and developing patient-friendly visualizations of quantitative outputs.

4.
Chest ; 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31351047

RESUMO

BACKGROUND: Patients with interstitial lung disease (ILD) may develop pulmonary hypertension (PH), often disproportionate to the severity of the ILD. The right ventricular to left ventricular diameter (RV:LV) ratio measured at CT pulmonary angiogram (CTPA) has been shown to provide valuable information in patients with pulmonary arterial hypertension and to predict death or deterioration in acute pulmonary embolism. METHODS: Demographic characteristics, ILD subtype, echocardiography, and detailed CTPA measurements were collected in consecutive patients undergoing both CTPA and right heart catheterization at the Royal Brompton Hospital between 2005 and 2015. Fibrosis severity was formally scored according to CT criteria. The RV:LV ratio at CTPA was evaluated by using three different methods. Cox proportional hazards analysis was used to assess the relation of CTPA-derived parameters to predict death or lung transplantation. RESULTS: A total of 92 patients were included (64% male; mean age 65 ± 11 years) with an FVC 57 ± 20% predicted, corrected transfer factor of the lung for carbon monoxide 22 ± 8% predicted, and corrected transfer coefficient of the lung for carbon monoxide 51 ± 17% predicted. PH was confirmed at right heart catheterization in 78%. Of all the CTPA-derived measures, an RV:LV ratio ≥ 1.0 strongly predicted mortality or transplantation at univariate analysis (hazard ratio, 3.26; 95% CI, 1.49-7.13; P = .003), whereas invasive hemodynamic data did not. The RV:LV ratio remained an independent predictor at multivariate analysis (hazard ratio, 3.19; 95% CI, 1.44-7.10; P = .004), adjusting for an ILD diagnosis of idiopathic pulmonary fibrosis and CT imaging-derived ILD severity. CONCLUSIONS: An increased RV:LV ratio measured at CTPA provides a simple, noninvasive method of risk stratification in patients with suspected ILD-PH. This should prompt closer follow-up, more aggressive treatment, and consideration of lung transplantation.

6.
Eur Urol Focus ; 5(5): 748-755, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31147264

RESUMO

BACKGROUND: Metastatic testicular sex cord stromal tumors of the testis (MSCSTs) comprise an extremely uncommon form of genitourinary malignancy. OBJECTIVE: To perform comprehensive genomic profiling (CGP) to enable the search for potential therapy targets. DESIGN, SETTING, AND PARTICIPANTS: Ten patients with testicular Leydig cell tumors (LCTs), six with Sertoli cell tumors (SCTs), and three with undifferentiated sex cord stromal tumors (USCSTs) and a comparison group of 366 patients with ovarian sex cord stromal tumors (SCSTs) underwent hybrid-capture-based CGP to evaluate all classes of genomic alterations (GAs). The tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA, and microsatellite instability (MSI) was determined on 114 loci. INTERVENTION: CGP on tumor samples. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive analyses and differences between histological subgroups were reported. RESULTS AND LIMITATIONS: In these patients, all of whom had metastatic disease at the time of sequencing, the primary testis tumor was sequenced in six (32%) patients and a metastatic site in 13 (68%) patients. The overall frequencies of GAs were similar in LCTs, SCTs, and USCSTs, ranging from 3.0 to 3.5 GAs/tumor. The most frequent untargetable GAs included CTNNB1 and CDKN2A/B, both ranging from 20% to 33% of cases. Targetable GAs were uncommon in all MSCST subgroups, but several tumors showed potential for cell-cycle inhibitors (CDK4 in LCTs), mTOR inhibitors (RICTOR, NF2, and PTEN in all three tumor types), hedgehog inhibitors (PTCH1 in LCTs), and poly(ADP-ribose) polymerase inhibitors (BAP1 in SCTs). No MSI-high status was identified. The TMB was also low in all MSCST groups, and tumors featuring a TMB of ≥10 mutations/Mb were not identified. GA findings from ovarian SCSTs largely recapitulated those from MSCSTs. A lack of clinical outcome correlation is a limitation of the present analyses. CONCLUSIONS: Rare cases of testicular MSCSTs have GAs linked to potential targeted therapy benefits on CGP. In contrast, the lack of MSI-high status and an overall low TMB indicate a likely lack of benefit for immunotherapies. PATIENT SUMMARY: Genomic profiling can guide clinical research and disclose therapeutic opportunities for patients with rare testicular cancers for which standard therapies are lacking.

7.
AJR Am J Roentgenol ; 213(2): 318-324, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31063425

RESUMO

OBJECTIVE. The purpose of this study is to establish the relationship between CT markers of lung volume and pulmonary function test (PFT) parameters of lung volume in idiopathic pulmonary fibrosis (IPF). MATERIALS AND METHODS. The relationships between PFT-derived parameters of lung volume (forced vital capacity [FVC] and total lung capacity [TLC]) and both CT-derived automated lung volume and manually derived surrogate measurements of lung volume on CT were evaluated in 273 patients (212 men and 61 women; median age, 67 years) with a multidisciplinary diagnosis of IPF. All patients underwent unenhanced volumetric high-resolution CT of the thorax. Automated lung volume was extracted using commercially available software. Three manual CT surrogate measurements of lung volume previously tested in the setting of radiation-induced lung fibrosis were evaluated by two raters. These measurements were lung height, aortosternal distance, and oblique fissure retraction distance. Fibrosis extent on CT was scored by two observers. Correlation coefficients and multivariable regression analyses were performed to assess the relationship between CT measurements and percentage of predicted FVC (hereafter referred to as "percentage FVC") and TLC. Interobserver agreement for CT markers was evaluated on the basis of the intraclass correlation coefficient. RESULTS. There was a strong correlation between CT-derived automated lung volume and TLC (rP = 0.92; p < 0.0005). There was excellent interobserver agreement for all manual CT measurements (intraclass correlation coefficient, 0.82-0.96). There were significant correlations between manual CT measurements and percentage FVC. Lung height had the strongest relationship with percentage FVC (rP = 0.44; p < 0.0005). In multivariable analysis, the CT measurements were independent determinants of lung volumes, after adjustment for fibrosis and emphysema (R2 = 0.48; p < 0.0005 and p < 0.003, respectively). Lung height had the most significant impact on the fit against lung volumes. CONCLUSION. Automated and manual CT measurements of lung volume are significantly related to PFT-derived parameters of lung volume, independent of fibrosis and emphysema.

8.
Curr Opin Pulm Med ; 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31033636

RESUMO

PURPOSE OF REVIEW: Computer algorithms possess an intrinsic speed, objectivity, reproducibility and scalability unmatched by visual quantitation methods performed by trained readers. The question of how well quantitative CT (QCT) analysis methods compare with visual CT analysis to predict functional status in fibrosing lung diseases (FLDs) is of increasing relevance to understand the future role QCT may have in prognostication of FLD. RECENT FINDINGS: The latest computer algorithms demonstrate improved performance over visual CT analysis in predicting baseline disease severity as measured by correlations with functional indices of lung damage. QCT analysis may, therefore, have a role in aiding clinical decision-making as well as in the enrichment of drug trial populations. Quantitative analysis on longitudinal CTs has also shown better correlations with changes in functional indices whenever compared with visual scores of change suggesting the potential of QCT analysis as an imaging biomarker of disease progression in FLD. Importantly, computer algorithms are now able to identify prognostic imaging biomarkers that cannot be quantified visually (e.g. vessel-related structures). SUMMARY: QCT holds great promise for the evaluation of damage in FLD. Challenges for QCT include accommodating measurement noise from variation in CT acquisition techniques and developing patient-friendly visualizations of quantitative outputs.

9.
Respirology ; 24(5): 445-452, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30786325

RESUMO

BACKGROUND AND OBJECTIVE: This study aimed to investigate whether quantitative lung vessel morphology determined by a new fully automated algorithm is associated with functional indices in idiopathic pulmonary fibrosis (IPF). METHODS: A total of 152 IPF patients had vessel volume, density, tortuosity and heterogeneity quantified from computed tomography (CT) images by a fully automated algorithm. Separate quantitation of vessel metrics in pulmonary arteries and veins was performed in 106 patients. Results were evaluated against readouts from lung function tests. RESULTS: Normalized vessel volume expressed as a percentage of total lung volume was moderately correlated with functional indices on univariable linear regression analysis: forced vital capacity (R2 = 0.27, P < 1 × 10-6 ), diffusion capacity for carbon monoxide (DLCO ; R2 = 0.12, P = 3 × 10-5 ), total lung capacity (TLC; R2 = 0.45, P < 1 × 10-6 ) and composite physiologic index (CPI; R2 = 0.28, P < 1 × 10-6 ). Normalized vessel volume was correlated with vessel density but not with vessel heterogeneity. Quantitatively derived vessel metrics (and artery and vein subdivision scores) were not significantly linked with the transfer factor for carbon monoxide (KCO ), and only weakly with DLCO . On multivariable linear regression analysis, normalized vessel volume and vessel heterogeneity were independently linked with DLCO , TLC and CPI indicating that they capture different aspects of lung damage. Artery-vein separation provided no additional information beyond that captured in the whole vasculature. CONCLUSION: Our study confirms previous observations of links between vessel volume and functional measures of disease severity in IPF using a new vessel quantitation tool. Additionally, the new tool shows independent linkages of normalized vessel volume and vessel heterogeneity with functional indices. Quantitative vessel metrics do not appear to reflect vasculopathic damage in IPF.

10.
Urol Oncol ; 37(3): 182.e9-182.e15, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30528396

RESUMO

INTRODUCTION: Renal cell carcinoma (RCC) brain metastasis is generally viewed as poor prognostic features and often excludes patients from cytoreductive nephrectomy or participation in clinical trials. We aim to evaluate patients presenting with brain metastasis and their outcomes. METHODS: Surveillance Epidemiology and End Results-18 registries database was queried for all patients with metastatic RCC from 2010 to 2014. Patients with renal cancer as their only malignancy were included. Information was available for metastatic disease to bone, liver, lung, and brain. Patients were then further stratified into those with isolated brain metastases and those with additional metastasis to other sites as well. Overall survival was compared between groups using logrank analysis. RESULTS: A total of 6,667 patients were identified with metastatic RCC. Among them, 775 (12.1%) had brain metastasis at time of diagnosis. Of these patients with brain metastasis, 152 (20.4%) had isolated brain metastasis. Only 23.8% of all patients with brain metastasis underwent cytoreductive nephrectomy, compared to 40.8% of patients with isolated brain metastasis. Patients with brain and other metastasis and brain metastasis only treated by cytoreductive nephrectomy exhibited a median survival of 11 and 33 months, respectively. Those patients who did not undergo cytoreductive nephrectomy experienced a median survival of 4 and 5 months, respectively. CONCLUSION: It appears that selected patients with brain metastasis may experience durable long-term survival. This information may be beneficial for patient counseling, surgical planning, and consideration for inclusion in clinical trials.

11.
Eur Respir J ; 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30487199

RESUMO

Aims: To compare radiology-based prediction models in rheumatoid arthritis-related interstitial lung disease (RA-ILD) to identify patients with a progressive fibrosis phenotype.Methods: RAILD patients had CTs scored visually and by CALIPER and forced vital capacity (FVC) measurements. Outcomes were evaluated using three techniques: 1.Scleroderma system evaluating visual ILD extent and FVC values; 2.Fleischer Society IPF diagnostic guidelines applied to RAILD; 3.CALIPER scores of vessel-related structures (VRS). Outcomes were compared to IPF patients.Results: On univariable Cox analysis, all three staging systems strongly predicted outcome: Scleroderma System:HR=3.78, p=9×10-5; Fleischner System:HR=1.98, p=2×10-3; 4.4% VRS threshold:HR=3.10, p=4×10-4 When the Scleroderma and Fleischner Systems were combined, termed the Progressive Fibrotic System (C-statistic=0.71), they identified a patient subset (n=36) with a progressive fibrotic phenotype and similar 4-year survival to IPF.On multivariable analysis, with adjustment for patient age, gender and smoking status, when analysed alongside the Progressive Fibrotic System, the VRS threshold of 4.4% independently predicted outcome (Model C-statistic=0.77).Conclusions: The combination of two visual CT-based staging systems identified 23% of an RAILD cohort with an IPF-like progressive fibrotic phenotype. The addition of a computer-derived VRS threshold further improved outcome prediction and model fit, beyond that encompassed by RAILD measures of disease severity and extent.

12.
J Urol ; 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30218764

RESUMO

PURPOSE: The development of Clostridium difficile infection after cystectomy is associated with significant morbidity and mortality. We implemented a prospective screening program to identify asymptomatic carriers of Clostridium difficile and assessed its impact on clinical Clostridium difficile infection rates compared to historical matched controls. MATERIALS AND METHODS: Prospective Clostridium Difficile screening prior to cystectomy began in March 2015. The 380 consecutive patients undergoing cystectomy prior to initiation of screening (control cohort) were matched based on 5 clinical factors with the 386 patients who underwent cystectomy from March 2015 to December 2017 (trial cohort). Screened positive patients were placed in contact isolation and treated prophylactically with Metronidazole. Multivariable models were built on an intention-to-screen and an effectiveness of screening basis to determine if screening reduced the rates of symptomatic Clostridium Difficile infections postoperatively. RESULTS: With the implementation of the screening protocol, Clostridium difficile infections rates declined from 9.4 to 5.5% (OR 0.52, p=0.0268) on an intention-to-screen protocol and from 9.2 to 4.9% on an effectiveness of screening protocol (OR 0.46, p=0.0174). CONCLUSIONS: Clostridium difficile screening prior to cystectomy is associated with a significant decrease in rates of clinically symptomatic infections postoperatively. These results should be confirmed in a randomized controlled trial.

13.
BMC Pulm Med ; 18(1): 145, 2018 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30170572

RESUMO

BACKGROUND: Nontuberculous mycobacterial (NTM) pulmonary disease has conventionally been classified on the basis of radiology into fibrocavitary and nodular-bronchiectatic disease. Whilst being of great clinical utility, this may not capture the full spectrum of radiological appearances present. The aim of this study was to use latent class analysis (LCA) as an unbiased method of grouping subjects with NTM-pulmonary disease based on their CT features and to compare the clinical characteristics of these groups. METHODS: Individuals with NTM-pulmonary disease were recruited and a contemporaneous CT scan obtained. This was scored using an NTM-specific scoring system. LCA was used to identify groups with common radiological characteristics. The analysis was then repeated in an independent cohort. RESULTS: Three classes were identified in the initial cohort of 85 subjects. Group 1 was characterised by severe bronchiectasis, cavitation and aspergillomas, Group 2 by relatively minor radiological changes, and Group 3 by predominantly bronchiectasis only. These findings were reproduced in an independent cohort of 62 subjects. Subjects in Group 1 had a lower BMI and serum albumin, higher serum CRP, and a higher mortality. CONCLUSIONS: These findings suggest that NTM-pulmonary may be divided into three radiological subgroups, and that important clinical and survival differences exist between these groups.

14.
Respiration ; 96(4): 338-347, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30130749

RESUMO

BACKGROUND: The significance of the nutritional status in idiopathic pulmonary fibrosis (IPF) is largely unknown. Temporal body weight (BW) change, a dynamic index of nutrition status, can detect the malnutrition more accurately than the conventional single-point body mass index evaluation. OBJECTIVE: To investigate how the temporal BW change influences the clinical courses of IPF. METHODS: This multicenter study enrolled IPF patients from four referral hospitals of interstitial lung diseases in Japan (the Japanese cohort, the derivation cohort) and the Royal Brompton Hospital (the UK cohort, the validation cohort). The annual rate of BW change from the initial presentation was evaluated. A > 5% decrease of BW was defined as a significant BW loss. RESULTS: Twenty-seven out of 124 patients in the Japanese cohort and 13 out of 86 patients in the UK cohort showed significant BW loss. Patients with BW loss showed significantly worse survival in both cohorts. Multivariate analyses revealed that BW loss was an independent factor for decreased survival (Japanese cohort: p = 0.047, UK cohort: p = 0.013). A 6.1% loss of BW was chosen as the optimal cutoff value to predict the 2-year mortality from the initial presentation. The stratified analysis revealed that a 6.1% or greater BW loss could predict worse survival specifically in cases without a greater than 10% decline in forced vital capacity (FVC). CONCLUSIONS: BW loss is independently associated with the survival of IPF patients, particularly when a decline in the FVC was not observed. Further studies are needed to understand the mechanisms underlying BW loss in IPF.

15.
Artigo em Inglês | MEDLINE | ID: mdl-29986154

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease with great variability in disease severity and rate of progression. The need for a reliable, sensitive, and objective biomarker to track disease progression and response to therapy remains a great challenge in IPF clinical trials. Over the past decade, quantitative computed tomography (QCT) has emerged as an area of intensive research to address this need. We have gathered a group of pulmonologists, radiologists and scientists with expertise in this area to define the current status and future promise of this imaging technique in the evaluation and management of IPF. In this Pulmonary Perspective, we review the development and validation of six computer-based QCT methods and offer insight into the optimal use of an imaging-based biomarker as a tool for prognostication, prediction of response to therapy, and potential surrogate endpoint in future therapeutic trials.

16.
ERJ Open Res ; 4(2)2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29750141

RESUMO

European Respiratory Society (ERS) guidelines recommend the assessment of patients with interstitial lung disease (ILD) and severe pulmonary hypertension (PH), as defined by a mean pulmonary artery pressure (mPAP) ≥35 mmHg at right heart catheterisation (RHC). We developed and validated a stepwise echocardiographic score to detect severe PH using the tricuspid regurgitant velocity and right atrial pressure (right ventricular systolic pressure (RVSP)) and additional echocardiographic signs. Consecutive ILD patients with suspected PH underwent RHC between 2005 and 2015. Receiver operating curve analysis tested the ability of components of the score to predict mPAP ≥35 mmHg, and a score devised using a stepwise approach. The score was tested in a contemporaneous validation cohort. The score used "additional PH signs" where RVSP was unavailable, using a bootstrapping technique. Within the derivation cohort (n=210), a score ≥7 predicted severe PH with 89% sensitivity, 71% specificity, positive predictive value 68% and negative predictive value 90%, with similar performance in the validation cohort (n=61) (area under the curve (AUC) 84.8% versus 83.1%, p=0.8). Although RVSP could be estimated in 92% of studies, reducing this to 60% maintained a fair accuracy (AUC 74.4%). This simple stepwise echocardiographic PH score can predict severe PH in patients with ILD.

17.
Respir Med ; 138: 95-101, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29724400

RESUMO

BACKGROUND: Pleuroparenchymal fibroelastosis (PPFE) has been described in hypersensitivity pneumonitis (HP) yet its functional implications are unclear. Combined pulmonary fibrosis and emphysema (CPFE) has occasionally been described in never-smokers with HP, but epidemiological data regarding its prevalence is sparse. CTs in a large HP cohort were therefore examined to identify the prevalence and effects of PPFE and emphysema. METHODS: 233 HP patients had CT extents of interstitial lung disease (ILD) and emphysema quantified to the nearest 5%. Lobar percentage pleural involvement of PPFE was quantified on a 4-point categorical scale: 0 = absent, 1 = affecting <10%, 2 = affecting 10-33%, 3 = affecting >33%. Marked PPFE reflected a total lung score of ≥3/18. Results were evaluated against FVC, DLco and mortality. RESULTS: Marked PPFE prevalence was 23% whilst 23% of never-smokers had emphysema. Following adjustment for patient age, gender, smoking status, and ILD and emphysema extents, marked PPFE independently linked to reduced baseline FVC (p = 0.0002) and DLco (p = 0.002) and when examined alongside the same covariates, independently linked to worsened survival (p = 0.01). CPFE in HP demonstrated a characteristic functional profile of artificial lung volume preservation and disproportionate DLco reduction. CPFE did not demonstrate a worsened outcome when compared to HP patients without emphysema beyond that explained by CT extents of ILD and emphysema. CONCLUSIONS: PPFE is not uncommon in HP, and is independently associated with impaired lung function and increased mortality. Emphysema was identified in 23% of HP never-smokers. CPFE appears not to link to a malignant microvascular phenotype as outcome is explained by ILD and emphysema extents.

18.
Am J Respir Crit Care Med ; 198(6): 767-776, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-29684284

RESUMO

RATIONALE: Quantitative computed tomographic (CT) measures of baseline disease severity might identify patients with idiopathic pulmonary fibrosis (IPF) with an increased mortality risk. We evaluated whether quantitative CT variables could act as a cohort enrichment tool in future IPF drug trials. OBJECTIVES: To determine whether computer-derived CT measures, specifically measures of pulmonary vessel-related structures (VRSs), can better predict functional decline and survival in IPF and reduce requisite sample sizes in drug trial populations. METHODS: Patients with IPF undergoing volumetric noncontrast CT imaging at the Royal Brompton Hospital, London, and St. Antonius Hospital, Utrecht, were examined to identify pulmonary function measures (including FVC) and visual and computer-derived (CALIPER [Computer-Aided Lung Informatics for Pathology Evaluation and Rating] software) CT features predictive of mortality and FVC decline. The discovery cohort comprised 247 consecutive patients, with validation of results conducted in a separate cohort of 284 patients, all fulfilling drug trial entry criteria. MEASUREMENTS AND MAIN RESULTS: In the discovery and validation cohorts, CALIPER-derived features, particularly VRS scores, were among the strongest predictors of survival and FVC decline. CALIPER results were accentuated in patients with less extensive disease, outperforming pulmonary function measures. When used as a cohort enrichment tool, a CALIPER VRS score greater than 4.4% of the lung was able to reduce the requisite sample size of an IPF drug trial by 26%. CONCLUSIONS: Our study has validated a new quantitative CT measure in patients with IPF fulfilling drug trial entry criteria-the VRS score-that outperformed current gold standard measures of outcome. When used for cohort enrichment in an IPF drug trial setting, VRS threshold scores can reduce a required IPF drug trial population size by 25%, thereby limiting prohibitive trial costs. Importantly, VRS scores identify patients in whom antifibrotic medication prolongs life and reduces FVC decline.

19.
EBioMedicine ; 28: 303-310, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29422289

RESUMO

AIMS: Autoimmune conditions such as rheumatoid arthritis-related interstitial lung disease (RA-ILD) have been linked to the existence of emphysema in never-smokers. We aimed to quantify emphysema prevalence in RA-ILD never-smokers and investigate whether combined pulmonary fibrosis and emphysema (CPFE) results in a worsened prognosis independent of baseline disease extent. METHODS: RA-ILD patients presenting to the Royal Brompton Hospital (n=90) and Asan Medical Center (n=155) had CT's evaluated for a definite usual interstitial pneumonia (UIP) pattern, and visual extents of emphysema and ILD. RESULTS: Emphysema, identified in 31/116 (27%) RA-ILD never-smokers, was associated with obstructive functional indices and conformed to a CPFE phenotype: disproportionate reduction in gas transfer (DLco), relative preservation of lung volumes. Using multivariate logistic regression, adjusted for patient age, gender and ILD extent, emphysema presence independently associated with a CT-UIP pattern in never-smokers (0.009) and smokers (0.02). On multivariate Cox analysis, following adjustment for patient age, gender, DLco, and a CT-UIP pattern, emphysema presence (representing the CPFE phenotype) independently associated with mortality in never-smokers (p=0.04) and smokers (p<0.05). CONCLUSION: 27% of RA-ILD never-smokers demonstrate emphysema on CT. Emphysema presence in never-smokers independently associates with a definite CT-UIP pattern and a worsened outcome following adjustment for baseline disease severity.


Assuntos
Artrite Reumatoide/complicações , Enfisema/complicações , Enfisema/epidemiologia , Doenças Pulmonares Intersticiais/complicações , Fumar , Artrite Reumatoide/diagnóstico por imagem , Demografia , Enfisema/diagnóstico por imagem , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , Modelos de Riscos Proporcionais , Tomografia Computadorizada por Raios X , Resultado do Tratamento
20.
Respirology ; 23(7): 687-694, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29327393

RESUMO

BACKGROUND AND OBJECTIVE: In interstitial lung disease (ILD), pulmonary hypertension (PH) is a major adverse prognostic determinant. Transthoracic echocardiography (TTE) is the most widely used tool when screening for PH, although discordance between TTE and right heart catheter (RHC) measured pulmonary haemodynamics is increasingly recognized. We evaluated the predictive utility of the updated European Society of Cardiology/European Respiratory Society (ESC/ERS) TTE screening recommendations against RHC testing in a large, well-characterized ILD cohort. METHODS: Two hundred and sixty-five consecutive patients with ILD and suspected PH underwent comprehensive assessment, including RHC, between 2006 and 2012. ESC/ERS recommended tricuspid regurgitation (TR) velocity thresholds for assigning high (>3.4 m/s), intermediate (2.9-3.4 m/s) and low (<2.8 m/s) probabilities of PH were evaluated against RHC testing. RESULTS: RHC testing confirmed PH in 86% of subjects with a peak TR velocity >3.4 m/s, and excluded PH in 60% of ILD subjects with a TR velocity <2.8 m/s. Thus, the ESC/ERS guidelines misclassified 40% of subjects as 'low probability' of PH, when PH was confirmed on subsequent RHC. Evaluating alternative TR velocity thresholds for assigning a low probability of PH did not significantly improve the ability of TR velocity to exclude a diagnosis of PH. CONCLUSION: In patients with ILD and suspected PH, currently recommended ESC/ERS TR velocity screening thresholds were associated with a high positive predictive value (86%) for confirming PH, but were of limited value in excluding PH, with 40% of patients misclassified as low probability when PH was confirmed at subsequent RHC.


Assuntos
Cateterismo Cardíaco , Ecocardiografia , Hipertensão Pulmonar/diagnóstico por imagem , Doenças Pulmonares Intersticiais/complicações , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Idoso , Estudos de Coortes , Erros de Diagnóstico , Feminino , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Pressão Propulsora Pulmonar , Insuficiência da Valva Tricúspide/complicações
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA