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1.
Clin Rheumatol ; 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31916109

RESUMO

Although several genetic associations with scleroderma (SSc) are defined, very little is known on genetic susceptibility to SSc-associated interstitial lung disease (SSc-ILD). A number of common polymorphisms have been associated with SSc-ILD, but most have not been replicated in separate populations. Four SNPs in IRF5, and one in each of STAT4, CD226 and IRAK1, selected as having been previously the most consistently associated with SSc-ILD, were genotyped in 612 SSc patients, of European descent, of whom 394 had ILD. The control population (n = 503) comprised individuals of European descent from the 1000 Genomes Project. After Bonferroni correction, two of the IRF5 SNPs, rs2004640 (OR (95% CI)1.30 (1.10-1.54), pcorr = 0.015) and rs10488631 (OR 1.48 (1.14-1.92), pcorr = 0.022), and the STAT4 SNP rs7574865 (OR 1.43 (1.18-1.73), pcorr = 0.0015) were significantly associated with SSc compared with controls. However, none of the SNPs were significantly different between patients with SSc-ILD and controls. Two SNPs in IRF5, rs10488631 (OR 1.72 (1.24-2.39), pcorr = 0.0098), and rs2004640 (OR 1.39 (1.11-1.75), pcorr = 0.03), showed a significant difference in allele frequency between controls and patients without ILD, as did STAT4 rs7574865 (OR 1.86 (1.45-2.38), pcorr = 6.6 × 10-6). A significant difference between SSc with and without ILD was only observed for STAT4 rs7574865, being less frequent in patients with ILD (OR 0.66 (0.51-0.85), pcorr = 0.0084). In conclusion, IRF5 rs2004640 and rs10488631, and STAT4 rs7574865 were significantly associated with SSc as a whole. Only STAT4 rs7574865 showed a significant difference in allele frequency in SSc-ILD, with the T allele being protective against ILD.Key points• We confirm the associations of the IRF5 SNPs rs2004640 and rs10488631, and the STAT4 SNP rs7574865, with SSc as a whole.• None of the tested SNPs were risk factors for SSc-ILD specifically.• The STAT4 rs7574865 T allele was protective against the development of lung fibrosis in SSc patients.• Further work is required to understand the genetic basis of lung fibrosis in association with scleroderma.

2.
Chest ; 157(1): 89-98, 2020 Jan.
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.

4.
BMC Pulm Med ; 19(1): 185, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651292

RESUMO

BACKGROUND: Diffuse alveolar haemorrhage (DAH) is characterized by the diffuse accumulation of red blood cells within the alveoli, presence of ground glass opacities and/or consolidation on computed tomography (CT). Aside from identifiable non-immune causes, DAH is classically subdivided into idiopathic (idiopathic pulmonary haemosiderosis, IPH) and autoimmune DAH. Here we describe three cases presenting with recurrent pulmonary haemorrhage, initially classified as IPH, who, several years after first presentation, develop anti myeloperoxidase antibodies (MPO) positivity, emphysema on CT and, in one case, renal involvement. CASE PRESENTATION: Patient 1 was diagnosed with IPH aged 14. Her disease remained poorly controlled despite immunosuppression, although ANCA remained negative over the years. Nineteen years from initial presentation, she developed MPO-ANCA positive antibodies and mild renal impairment. She was treated with Rituximab with good response. From first presentation, the chest CT was consistently characterized by diffuse ground-glass opacities and interlobular septal thickening. Ten years later, cystic opacities consistent with emphysema, with a striking peribronchovascular distribution, developed. Patient 2 was diagnosed with IPH aged 32. He was treated with corticosteroids and methotrexate, with fluctuating response. At 11 years from initial presentation, MPO-ANCA positivity was identified, and emphysema with a peribronchovascular distribution was observed on CT, with subsequent significant increase in extent. Patient 3 was diagnosed with IPH at the age of seven, and had recurrent episodes of haemoptysis of varying degree of severity, treated with intermittent courses of corticosteroids until age 11, when he was intubated due to severe DAH. Eight years after the diagnosis emphysematous changes were noted on CT and MPO-ANCA positivity developed for the first time 11 years after initial diagnosis. CONCLUSIONS: We believe these three cases highlight: 1) the possibility of development of ANCA positivity several years down the line from first DAH presentation 2) the possibility that DAH may lead to cystic/emphysematous changes with peribronchovascular distribution on CT. Moreover, the need for ongoing immunosuppressive treatment and the development of emphysema, emphasize a possible role played by autoimmune phenomena, even when DAH is initially diagnosed as "idiopathic". Further studies are required to better understand the relationship between DAH, ANCA positivity and development of emphysema.

5.
Clin Chest Med ; 40(3): 519-529, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31376888

RESUMO

Systemic lupus erythematosus (SLE) is a systemic inflammatory disease, characterized by an antibody response to nucleic antigens and involvement of any organ system. Pulmonary manifestations are frequent and include pleuritis, acute lupus pneumonitis, chronic interstitial lung disease, alveolar hemorrhage, shrinking lung syndrome, airway disease, pulmonary hypertension (PH), and thromboembolic disease. The antiphospholipid antibody syndrome (APLAS) is a systemic autoimmune disorder where different prothrombotic factors interact to induce arterial and venous thrombosis. The most common pulmonary manifestations are pulmonary thromboembolism and PH. This review will focus on the clinical presentation, diagnosis, and management of the SLE- and APLAS-associated pulmonary conditions.

6.
Curr Opin Pulm Med ; 25(5): 450-458, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31365379

RESUMO

PURPOSE OF REVIEW: Pulmonary alveolar proteinosis (PAP) can be considered the archetype of ultra-rare diseases with a prevalence of under 10 cases per million. We discuss the classification of PAP, the current diagnostic practice and the supplementary role of genetic testing and granulocyte-macrophage colony-stimulating factor (GM-CSF) signalling in the diagnosis of congenital and hereditary PAP. We report on novel therapeutic approaches such as GM-CSF substitution, stem cell transplantation, pioglitazone, statins and immunomodulation. RECENT FINDINGS: The discovery of new genetic mutations underlying this syndrome raises the question whether the classification should be radically revised in the future. Serum GM-CSF autoantibody is the best diagnostic marker for autoimmune PAP, the most common form, but does not correlate with disease severity. Several circulating biomarkers have been investigated to assess disease activity and predict outcome. Imaging techniques have also enormously evolved and offer new tools to quantify disease burden and possibly drive therapeutic decisions. Promising clinical trials are ongoing and will generate new treatment strategies besides or in addition to whole lung lavage in the next future. SUMMARY: Despite impressive advances in understanding pathogenesis, PAP remains a rare syndrome with several unanswered questions impacting diagnosis, management and treatment, and, as a result, patients' quality of life.

8.
Expert Rev Respir Med ; 13(7): 645-658, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31215263

RESUMO

Introduction: Interstitial lung diseases (ILDs) represent a heterogeneous group of rare disorders that include more than 200 entities, mostly associated with high mortality. In recent years, the progress regarding the understanding of the pathogenesis of these diseases led to the approval of specific treatments. In ILDs, the presence of comorbidities has a significant impact on the quality of life and the survival of patients and, therefore, their diagnosis and treatment has a pivotal role in management and could improve overall outcome. Areas covered: We discuss key diagnostic issues with regard to the most frequent comorbidities in ILDs. Treatment options are also discussed as the decision to investigate more definitively in order to identify specific comorbidities (including lung cancer, pulmonary hypertension, GE reflux, and obstructive sleep apnoea) is critically dependent upon whether comorbidity-specific treatments are likely to be helpful in individual patients, judged on a case by case basis. Expert opinion: The extent to which clinicians proactively pursue the identification of comorbidities depends on realistic treatment goals in individual patients.

10.
Respirology ; 24(5): 445-452, 2019 05.
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.

11.
Eur Respir J ; 53(1)2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30487199

RESUMO

The aim of this study was to compare radiology-based prediction models in rheumatoid arthritis-related interstitial lung disease (RAILD) to identify patients with a progressive fibrosis phenotype.RAILD patients had computed tomography (CT) scans scored visually and using CALIPER and forced vital capacity (FVC) measurements. Outcomes were evaluated using three techniques, as follows. 1) Scleroderma system evaluating visual interstitial lung disease extent and FVC values; 2) Fleischner Society idiopathic pulmonary fibrosis (IPF) diagnostic guidelines applied to RAILD; and 3) CALIPER scores of vessel-related structures (VRS). Outcomes were compared to IPF patients.On univariable Cox analysis, all three staging systems strongly predicted outcome (scleroderma system hazard ratio (HR) 3.78, p=9×10-5; Fleischner system HR 1.98, p=2×10-3; and 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, sex and smoking status, when analysed alongside the progressive fibrotic system, the VRS threshold of 4.4% independently predicted outcome (model C-statistic 0.77).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.

13.
Lancet Respir Med ; 6(10): 759-770, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30170904

RESUMO

BACKGROUND: In fibrotic interstitial lung diseases, exertional breathlessness is strongly linked to health-related quality of life (HRQOL). Breathlessness is often associated with oxygen desaturation, but few data about the use of ambulatory oxygen in patients with fibrotic interstitial lung disease are available. We aimed to assess the effects of ambulatory oxygen on HRQOL in patients with interstitial lung disease with isolated exertional hypoxia. METHODS: AmbOx was a prospective, open-label, mixed-method, crossover randomised controlled clinical trial done at three centres for interstitial lung disease in the UK. Eligible patients were aged 18 years or older, had fibrotic interstitial lung disease, were not hypoxic at rest but had a fall in transcutaneous arterial oxygen saturation to 88% or less on a screening visit 6-min walk test (6MWT), and had self-reported stable respiratory symptoms in the previous 2 weeks. Participants were randomly assigned (1:1) to either oxygen treatment or no oxygen treatment for 2 weeks, followed by crossover for another 2 weeks. Randomisation was by a computer-generated sequence of treatments randomly permuted in blocks of constant size (fixed size of ten). The primary outcome, which was assessed by intention to treat, was the change in total score on the King's Brief Interstitial Lung Disease questionnaire (K-BILD) after 2 weeks on oxygen compared with 2 weeks of no treatment. General linear models with treatment sequence as a fixed effect were used for analysis. Patient views were explored through semi-structured topic-guided interviews in a subgroup of participants. This study was registered with ClinicalTrials.gov, number NCT02286063, and is closed to new participants with all follow-up completed. FINDINGS: Between Sept 10, 2014, and Oct 5, 2016, 84 patients were randomly assigned, 41 randomised to ambulatory oxygen first and 43 to no oxygen. 76 participants completed the trial. Compared with no oxygen, ambulatory oxygen was associated with significant improvements in total K-BILD scores (mean 55·5 [SD 13·8] on oxygen vs 51·8 [13·6] on no oxygen, mean difference adjusted for order of treatment 3·7 [95% CI 1·8 to 5·6]; p<0·0001), and scores in breathlessness and activity (mean difference 8·6 [95% CI 4·7 to 12·5]; p<0·0001) and chest symptoms (7·6 [1·9 to 13·2]; p=0·009) subdomains. However, the effect on the psychological subdomain was not significant (2·4 [-0·6 to 5·5]; p=0·12). The most common adverse events were upper respiratory tract infections (three in the oxygen group and one in the no-treatment group). Five serious adverse events, including two deaths (one in each group) occurred, but none were considered to be related to treatment. INTERPRETATION: Ambulatory oxygen seemed to be associated with improved HRQOL in patients with interstitial lung disease with isolated exertional hypoxia and could be an effective intervention in this patient group, who have few therapeutic options. However, further studies are needed to confirm this finding. FUNDING: UK National Institute for Health Research.


Assuntos
Doenças Pulmonares Intersticiais/terapia , Oxigenoterapia/métodos , Oxigênio/administração & dosagem , Fibrose Pulmonar/terapia , Qualidade de Vida , Idoso , Estudos Cross-Over , Feminino , Humanos , Análise de Intenção de Tratamento , Modelos Lineares , Doenças Pulmonares Intersticiais/psicologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fibrose Pulmonar/psicologia , Resultado do Tratamento
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.


Assuntos
Fibrose Pulmonar Idiopática/fisiopatologia , Estado Nutricional , Perda de Peso , Idoso , Estudos de Coortes , Feminino , Humanos , Fibrose Pulmonar Idiopática/mortalidade , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Capacidade Vital
15.
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.


Assuntos
Alveolite Alérgica Extrínseca/epidemiologia , Pleura/patologia , Enfisema Pulmonar/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alveolite Alérgica Extrínseca/diagnóstico por imagem , Alveolite Alérgica Extrínseca/fisiopatologia , Tecido Elástico/patologia , Feminino , Fibrose/diagnóstico por imagem , Fibrose/epidemiologia , Fibrose/fisiopatologia , Volume Expiratório Forçado/fisiologia , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Pleura/diagnóstico por imagem , Prevalência , Prognóstico , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/fisiopatologia , Testes de Função Respiratória , Fumar/epidemiologia , Tomografia Computadorizada por Raios X , Capacidade Vital/fisiologia
16.
ERJ Open Res ; 4(2)2018 04.
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.
Eur Respir Rev ; 27(148)2018 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-29653950

RESUMO

Interstitial lung diseases in general, and idiopathic pulmonary fibrosis in particular, are complex disorders with multiple pathogenetic pathways, various disease behaviour profiles and different responses to treatment, all facets that make personalised medicine a highly attractive concept. Personalised medicine is aimed at describing distinct disease subsets taking into account individual lifestyle, environmental exposures, genetic profiles and molecular pathways. The cornerstone of personalised medicine is the identification of biomarkers that can be used to inform diagnosis, prognosis and treatment stratification. At present, no data exist validating a personalised approach in individual diseases. However, the importance of the goal amply justifies the characterisation of genotype and pathway signatures with a view to refining prognostic evaluation and trial design, with the ultimate aim of selecting treatments according to profiles in individual patients.


Assuntos
Doenças Pulmonares Intersticiais/terapia , Medicina de Precisão , Animais , Tomada de Decisão Clínica , Interação Gene-Ambiente , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Estilo de Vida , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/genética , Doenças Pulmonares Intersticiais/fisiopatologia , Técnicas de Diagnóstico Molecular , Seleção de Pacientes , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco , Comportamento de Redução do Risco
18.
Am J Respir Crit Care Med ; 198(6): 767-776, 2018 09 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.


Assuntos
Fibrose Pulmonar Idiopática/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Feminino , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Testes de Função Respiratória , Capacidade Vital
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
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