Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Eur Radiol ; 32(12): 8182-8190, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35708839

RESUMO

The importance of lung cancer as a complication of lung transplantation is increasingly recognised. It may become an important survival-limiting factor in lung transplant patients as management of other complications continues to improve and utilisation of extended criteria donors grows. Radiology can play a key role in tackling this issue at multiple stages in the transplantation pathway and follow-up process. Routine chest CT as part of pre-transplant recipient assessment (and donor assessment if available) can identify suspicious lung lesions with high sensitivity and detect chronic structural lung diseases such as pulmonary fibrosis associated with an increased risk of malignancy post-transplant. Pre-transplant CT also provides a comparison for later CT studies in the assessment of nodules or masses. The potential role of regular chest CT for lung cancer screening after transplantation is less certain due to limited available evidence on its efficacy. Radiologists should be cognisant of how the causes of pulmonary nodules in lung transplant patients may differ from the general population, vary with time since transplantation and require specific recommendations for further investigation/follow-up as general guidelines are not applicable. As part of the multidisciplinary team, radiology is involved in an aggressive diagnostic and therapeutic management approach for nodular lung lesions after transplant both through follow-up imaging and image-guided tissue sampling. This review provides a comprehensive overview of available clinical data and evidence on lung cancer in lung transplant recipients, and in particular an assessment of the current and potential roles of pre- and post-transplant imaging. KEY POINTS: • Lung cancer after lung transplantation may become an increasingly important survival-limiting factor as mortality from other complications declines. • There are a number of important roles for radiology in tackling the issue which include pre-transplant CT and supporting an aggressive multidisciplinary management strategy where lung nodules are detected in transplant patients. • The introduction of routine surveillance chest CT after transplant in addition to standard clinical follow-up as a means of lung cancer screening should be considered.


Assuntos
Neoplasias Pulmonares , Transplante de Pulmão , Nódulos Pulmonares Múltiplos , Radiologia , Humanos , Neoplasias Pulmonares/diagnóstico , Detecção Precoce de Câncer , Nódulos Pulmonares Múltiplos/patologia , Transplante de Pulmão/efeitos adversos , Pulmão/patologia
2.
Lung ; 196(5): 543-552, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30066212

RESUMO

BACKGROUND: Pirfenidone is a novel anti-fibrotic agent in idiopathic pulmonary fibrosis with proven clinical benefit. Better human tissue models to demonstrate the immunomodulatory and anti-fibrotic effect of pirfenidone are required. OBJECTIVES: The purpose of the study was to use transbronchial lung cryobiopsy (TBLC), a novel technique which provides substantial tissue samples, and a large panel of biomarkers to temporally assess disease activity and response to pirfenidone therapy. METHODS: Thirteen patients with confirmed idiopathic pulmonary fibrosis (IPF) underwent full physiological and radiological assessment at diagnosis and after 6-month pirfenidone therapy. They underwent assessment for a wide range of potential serum and bronchoalveolar lavage biomarkers of disease activity. Finally, they underwent TBLC before and after treatment. Tissue samples were assessed for numbers of fibroblast foci, for Ki-67, a marker of tissue proliferation and caspase-3, a marker of tissue apoptosis. RESULTS: All patients completed treatment and investigations without significant incident. There was no significant fall in number of fibroblast foci per unit tissue volume after treatment (pre-treatment: 0.14/mm2 vs. post-treatment 0.08/mm2, p = 0.1). Likewise, there was no significant change in other markers of tissue proliferation, Ki-67 or Caspase-3 with pirfenidone treatment. We found an increase in three bronchoalveolar lavage angiogenesis cytokines, Placental Growth Factor, Vascular Endothelial Growth Factor-A, and basic Fibroblast Growth Factor, two anti-inflammatory cytokines Interleukin-10 and Interleukin-4 and Surfactant Protein-D. CONCLUSIONS: TBLC offers a unique opportunity to potentially assess the course of disease activity and response to novel anti-fibrotic activity in IPF.


Assuntos
Fibrose Pulmonar Idiopática/metabolismo , Pulmão/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/uso terapêutico , Biópsia , Líquido da Lavagem Broncoalveolar/química , Broncoscopia , Caspase 3/metabolismo , Feminino , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/fisiopatologia , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Antígeno Ki-67/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Placentário/metabolismo , Capacidade de Difusão Pulmonar , Proteína D Associada a Surfactante Pulmonar/metabolismo , Piridonas/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Capacidade Vital , Teste de Caminhada
3.
Semin Respir Crit Care Med ; 36(2): 287-98, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25826594

RESUMO

Cystic fibrosis (CF) represents one of the success stories of modern medicine with sustained incremental increases in the survival from one of childhood death to one of adult survival into the middle decades over the past 30 years. Improving survival has focused on multidisciplinary management centered on treating the consequences of this genetic disease. It has been firmly established for more than 20 years that mutations in the CF transmembrane conductance regulator (CFTR) gene result in a defective protein that normally functions as a chloride channel on epithelial cell surfaces. Until recently, modulating CFTR dysfunction was only a research aspiration, however, greater focus placed upon addressing the primary defect of CF has developed several clinical therapeutic strategies in this area. This review highlights the evidence to date on efforts to modulate CFTR and restore robust functional protein to the cell surface. This approach has now led to the licensing of one CFTR potentiator, which has been shown to have significant clinical improvements in a subset of CF patients. This success represents the beginning for CFTR modulation and further research is ongoing which aims to broaden the applicability of these techniques.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/genética , Fibrose Cística/terapia , Terapia Genética , Humanos , Mutação
5.
Clin Chest Med ; 44(1): 121-136, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36774159

RESUMO

Most therapeutic advances in immunosuppression have occurred over the past few decades. Although modern strategies have been effective in reducing acute cellular rejection, excess immunosuppression comes at the price of toxicity, opportunistic infection, and malignancy. As our understanding of the immune system and allograft rejection becomes more nuanced, there is an opportunity to evolve immunosuppression protocols to optimize longer term outcomes while mitigating the deleterious effects of traditional protocols.


Assuntos
Imunossupressores , Transplante de Pulmão , Humanos , Imunossupressores/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Tolerância Imunológica , Transplante Homólogo
6.
J Infect ; 82(3): 363-370, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33444699

RESUMO

PURPOSE: Clostridium difficile has been reported to occur in the gastrointestinal tract of 50% of Cystic Fibrosis (CF) subjects, however, clinical C. difficile infection (CDI) is a rare occurrence in this cohort despite the presence of toxigenic and hypervirulent ribotypes. Here, we present the first longitudinal, multicentre analysis of C. difficile prevalence among adult CF subjects. METHODOLOGY: Faecal samples were collected from adults with CF (selected based on confirmed Pseudomonas aeruginosa pulmonary colonisation) from Ireland, UK and Belgium as part of the CFMATTERS clinical research trial (grant No. 603038) and from non-CF controls. Faecal samples were collected on enrolment, at three monthly intervals, during pulmonary exacerbation and three months post exacerbation. C. difficile was isolated from faecal samples by ethanol shocking followed by culturing on cycloserine cefoxitin egg yolk agar. Isolates were characterised in terms of ribotype, toxin type and antibiotic susceptibility to antibiotics routinely used in the treatment of CDI (metronidazole and vancomycin) and those implicated in induction of CDI (ciprofloxacin and moxifloxacin). RESULTS: Prevalence of C. difficile among CF subjects in the three sites was similar ranging from 47% to 50% at baseline, while the healthy control cohort had a carriage rate of 7.1%. Including subjects who were positive for C. difficile at any time point there was a higher carriage rate of 71.4%, 66.7% and 63.2% in Ireland, UK, and Belgium, respectively. Ribotyping of 80 isolates from 45 CF persons, over multiple time points revealed 23 distinct ribotypes with two ribotypes (046 and 078) shared by all centres. The proportion of toxigenic isolates varied across the sites, ranging from 66.7% in Ireland to 52.9% in Belgium and 100% in the UK. Antibiotic susceptibility rates to vancomycin, metronidazole, ciprofloxacin and moxifloxacin was 100%, 97.5%, 1.3% and 63.8%, respectively. CONCLUSIONS: This study demonstrates the highest carriage rate of C. difficile to date in a CF cohort. Longitudinal data show that C. difficile can be a transient inhabitant of the CF gut, changing both in terms of strain and excretion rates.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Fibrose Cística , Adulto , Antibacterianos/uso terapêutico , Bélgica , Clostridioides difficile/genética , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Fibrose Cística/complicações , Humanos , Irlanda/epidemiologia , Testes de Sensibilidade Microbiana , Ribotipagem
7.
J Cyst Fibros ; 20(5): 747-753, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33549519

RESUMO

BACKGROUND: Treatment with Ivacaftor provides a significant clinical benefit in people with cystic fibrosis (PWCF) with the class III G551D-CFTR mutation. This study determined the effect of CFTR modulation with ivacaftor on the lung microbiota in PWCF. METHODS: Using both extended-culture and culture-independent molecular methods, we analysed the lower airway microbiota of 14 PWCF, prior to commencing ivacaftor treatment and at the last available visit within the following year. We determined total bacterial and Pseudomonas aeruginosa densities by both culture and qPCR, assessed ecological parameters and community structure and compared these with biomarkers of inflammation and clinical outcomes. RESULTS: Significant improvement in FEV1, BMI, sweat chloride and levels of circulating inflammatory biomarkers were observed POST-ivacaftor treatment. Extended-culture demonstrated a higher density of strict anaerobic bacteria (p = 0.024), richness (p = 1.59*10-4) and diversity (p = 0.003) POST-treatment. No significant difference in fold change was observed by qPCR for either total bacterial 16S rRNA copy number or P. aeruginosa density for oprL copy number with treatment. Culture-independent (MiSeq) analysis revealed a significant increase in richness (p = 0.03) and a trend towards increased diversity (p = 0.07). Moreover, improvement in lung function, richness and diversity displayed an inverse correlation with the main markers of inflammation (p < 0.05). CONCLUSIONS: Following treatment with ivacaftor, significant improvements in clinical parameters were seen. Despite modest changes in overall microbial community composition, there was a shift towards a bacterial ecology associated with less severe CF lung disease. Furthermore, a significant correlation was observed between richness and diversity and levels of circulating inflammatory markers.


Assuntos
Aminofenóis/uso terapêutico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/microbiologia , Microbiota/efeitos dos fármacos , Quinolonas/uso terapêutico , Adolescente , Adulto , Agonistas dos Canais de Cloreto/uso terapêutico , Regulador de Condutância Transmembrana em Fibrose Cística , Feminino , Humanos , Masculino , Testes de Função Respiratória , Escarro/microbiologia , Adulto Jovem
8.
BMJ Case Rep ; 12(3)2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30850570

RESUMO

A 26-year-old cachectic man presented with an altered mental status. He was agitated, tremulous, hyperthermic and diaphoretic with largely dilated pupils. Collateral history revealed acute ingestion of 3,4-methylenedioxymethamphetamine on a background of chronic drug abuse. His condition deteriorated requiring sedation and intubation with transfer to the intensive care unit. A diagnosis of serotonin syndrome was made, based on his findings in keeping with the Hunter criteria, and he was treated with supportive management during a resultant and briefly sustained delirium. With gradual resolution of his agitated state, further questioning and blood work a concurrent, and potentially contributory, thyrotoxicosis was revealed. The patient was commenced on treatment for this with urgent outpatient follow-up with both a local otolaryngologist and endocrinologist for consideration of further treatment.


Assuntos
3,4-Metilenodioxianfetamina/análogos & derivados , Síndrome da Serotonina/diagnóstico , Tireotoxicose/diagnóstico , Tremor/diagnóstico , 3,4-Metilenodioxianfetamina/efeitos adversos , 3,4-Metilenodioxianfetamina/toxicidade , Adulto , Assistência ao Convalescente , Antiarrítmicos/uso terapêutico , Antitireóideos/uso terapêutico , Carbimazol/administração & dosagem , Carbimazol/uso terapêutico , Delírio/complicações , Delírio/terapia , Diagnóstico Diferencial , Humanos , Unidades de Terapia Intensiva , Masculino , Propranolol/administração & dosagem , Propranolol/uso terapêutico , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Tireotoxicose/sangue , Tireotoxicose/tratamento farmacológico , Tireotropina/análise , Resultado do Tratamento
9.
J Cyst Fibros ; 18(2): 271-277, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30268371

RESUMO

BACKGROUND: We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy. METHODS: In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1-6 months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI). RESULTS: After 1 month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6 months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r = -0.5376; P < .001 and r = -0.3285; P < .001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (ß = -0.57, P = .019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581-0.863]; P = .029) were used as classifier, especially in the first 2 months of treatment (0.806 [95% CI 0.665-0.947]; P < .001). CONCLUSIONS: This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.


Assuntos
Aminofenóis/uso terapêutico , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística , Volume Expiratório Forçado/efeitos dos fármacos , Quinolonas/uso terapêutico , Proteína 2 do Domínio Central WAP de Quatro Dissulfetos/análise , Adulto , Biomarcadores/análise , Índice de Massa Corporal , Criança , Agonistas dos Canais de Cloreto/uso terapêutico , Fibrose Cística/genética , Fibrose Cística/fisiopatologia , Fibrose Cística/terapia , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Masculino , Mutação , Testes de Função Respiratória/métodos , Estudos Retrospectivos , Suor/química
10.
Chest ; 153(2): 395-403, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29037527

RESUMO

BACKGROUND: Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at the Cork CF Centre is 23%. This study assessed the impact of cystic fibrosis transmembrane conductance regulator modulation on multiple modalities of patient assessment. METHODS: Thirty-three patients with the G551D mutation were assessed at baseline and prospectively every 3 months for 1 year after initiation of ivacaftor. Change in ultra-low-dose chest CT scans, blood inflammatory mediators, and the sputum microbiome were assessed. RESULTS: Significant improvements in FEV1, BMI, and sweat chloride levels were observed post-ivacaftor treatment. Improvement in ultra-low-dose CT imaging scores were observed after treatment, with significant mean reductions in total Bhalla score (P < .01), peribronchial thickening (P = .035), and extent of mucous plugging (P < .001). Reductions in circulating inflammatory markers, including interleukin (IL)-1ß, IL-6, and IL-8 were demonstrated. There was a 30% reduction in the relative abundance of Pseudomonas species and an increase in the relative abundance of bacteria associated with more stable community structures. Posttreatment community richness increased significantly (P = .03). CONCLUSIONS: Early and sustained improvements on ultra-low-dose CT scores suggest it may be a useful method of evaluating treatment response. It paralleled improvement in symptoms, circulating inflammatory markers, and changes in the lung microbiota.


Assuntos
Aminofenóis/uso terapêutico , Agonistas dos Canais de Cloreto/uso terapêutico , Fibrose Cística/tratamento farmacológico , Quinolonas/uso terapêutico , Adolescente , Adulto , Fibrose Cística/diagnóstico por imagem , Fibrose Cística/genética , Fibrose Cística/fisiopatologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Estudos Prospectivos , Radiografia Torácica/métodos , Saliva/microbiologia , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
11.
Presse Med ; 46(6 Pt 2): e125-e138, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28554721

RESUMO

Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed ubiquitously throughout the body. Thus, while respiratory manifestations dominate much of cystic fibrosis (CF) care, there are prominent multi-organ manifestations and comorbidities. In the general population, the number of comorbidities increases with aging. Few illnesses have experienced such a dramatic improvement in survival as CF, which has been transformed from an illness of childhood death to one of adult survival. Hence, as longevity increases in CF, it is paralleled by an increasing number of patients with multicomplex comorbidities availing of care from adult CF multi-disciplinary teams. This review gives an overview of the traditional CF associated comorbidities and those emerging in an aging adult cohort. While historically the treatment of CF focused on the consequences of CFTR dysfunction, the recent advent of CFTR modulators with the potential to enhance CFTR function represents an opportunity to potentially reverse or delay the development of some of the comorbidities associated with CF. Where evidence is available for the impact of CFTR modulatory therapy, namely ivacaftor on comorbidities in CF, this is highlighted.


Assuntos
Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Comorbidade , Estudos Transversais , Fibrose Cística/terapia , Humanos , Lactente , Recém-Nascido , Comunicação Interdisciplinar , Colaboração Intersetorial , Sistema de Registros/estatística & dados numéricos , Adulto Jovem
12.
Chest ; 148(3): e72-e75, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26324139

RESUMO

Cystic fibrosis (CF) conductance transmembrane regulator functions as a chloride (Cl-) channel in multiple organs, including the lungs. More than 1,800 disease-associated mutations have been identified, which can be divided into six classes. In patients with CF due to class III gating mutations, ivacaftor produces significant improvement in lung function, weight, reduction in sweat chloride level, and pulmonary exacerbations by enhancing the probability of chloride channel opening (gating). Although the benefit of ivacaftor in CF due to gating mutations is established, its potential role in patients with CF due to class IV conductance mutations is emerging. We report 6 months' prospective stability of lung function, improved BMI, reduced pulmonary exacerbations, and reduction in sweat chloride level in a patient with severe CF and the class IV R117H mutation. High-resolution CT scan also improved, thus highlighting the potential usefulness of ivacaftor in patients with severe CF due to class IV mutations.


Assuntos
Aminofenóis/uso terapêutico , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Quinolonas/uso terapêutico , Fibrose Cística/diagnóstico por imagem , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Tomografia Computadorizada por Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA