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3.
Med Mycol Case Rep ; 21: 30-33, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30023164

RESUMO

Invasive fungal infections in immunosuppressed transplant patients are associated with significant morbidity and mortality. We present a case of splenic mucormycosis post-double lung transplant, presenting as uncontrolled near-fatal upper gastrointestinal haemorrhage, to remind clinicians of the need to consider pre-transplant invasive fungal infection risk factors if an unexpected fungal infection arises in the post-transplant period. This case also highlights the valuable contribution of molecular technology for fungal identification but also the need for clinical correlation.

4.
Exp Lung Res ; 44(8-9): 405-416, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30675820

RESUMO

AIM OF THE STUDY: Nucleic acid-based therapies have the potential to provide clinically meaningful benefit across a wide spectrum of lung disease. However, in vivo delivery remains a challenge. Here we examined the feasibility of using electrospray to deliver nucleic acids to both porcine tracheal tissue sections and whole lung ex vivo. MATERIALS AND METHODS: The effect of electrospray solution, emitter gauge, flow rate and voltage on plasmid DNA integrity was examined by analyzing supercoiled:open circle structure ratio by gel electrophoresis. Optimal parameters were used to deliver luciferase DNA and mRNA and siRNA-FITC to tracheal tissue sections. Luciferase mRNA was delivered to whole porcine lungs ex vivo using a catheter and bronchoscope system. Luciferase activity and fluorescence were analyzed by luminometry and microscopy respectively. RESULTS: The incidence of DNA plasmid nicking was greatest in a low salt solution without ethanol compared with 1% and 20% ethanol with salt. From a range of emitters tested, a 32 gauge emitter produced the best supercoiled:open circle structure ratio, likely because less voltage was required to produce a stable electrospray with this emitter. Lower flow rates also showed a trend towards reduced DNA nicking. GFP DNA electrosprayed at 5 kV and 6 kV resulted in lower levels of GFP expression in A549 lung cells following lipofection compared with 3 kV and 4 kV. Optimised parameters of 20% ethanol solution, 32 gauge emitter, low flow rates and voltages of 3-5 kV, nucleic acid molecules were successful for delivery of luciferase DNA and mRNA as well as siRNA-FITC to porcine tracheal tissue sections and for delivery of luciferase mRNA to whole porcine lungs via bronchoscope. CONCLUSIONS: We report ex vivo delivery of nucleic acids to porcine lung tissue via electrospray and bronchoscopic electrospray delivery of nucleic acid to an ex vivo porcine lung model.


Assuntos
Aerossóis/uso terapêutico , Técnicas de Transferência de Genes/instrumentação , Pulmão/metabolismo , Traqueia/metabolismo , Células A549 , Animais , DNA/administração & dosagem , Humanos , Luciferases/genética , RNA Mensageiro/administração & dosagem , Suínos
7.
BMJ Case Rep ; 20152015 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-26531732

RESUMO

We present the first reported case of successful surgical management of esophageal cancer post-lung transplantation for cystic fibrosis. This case of a 42-year-old man highlights the risk factors for esophageal adenocarcinoma associated with cystic fibrosis and lung transplantation, the management options for early esophageal cancer and the surgical option chosen to minimise respiratory risks. Individualised patient care may allow for curative surgical approaches, even where complex surgery is required.


Assuntos
Adenocarcinoma/cirurgia , Fibrose Cística/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Imunossupressores/administração & dosagem , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Fibrose Cística/tratamento farmacológico , Fibrose Cística/patologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Humanos , Transplante de Pulmão , Masculino , Fatores de Risco , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Perda de Peso
8.
Am J Respir Cell Mol Biol ; 51(3): 334-43, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24828366

RESUMO

The porcine model has contributed significantly to biomedical research over many decades. The similar size and anatomy of pig and human organs make this model particularly beneficial for translational research in areas such as medical device development, therapeutics and xenotransplantation. In recent years, a major limitation with the porcine model was overcome with the successful generation of gene-targeted pigs and the publication of the pig genome. As a result, the role of this model is likely to become even more important. For the respiratory medicine field, the similarities between pig and human lungs give the porcine model particular potential for advancing translational medicine. An increasing number of lung conditions are being studied and modeled in the pig. Genetically modified porcine models of cystic fibrosis have been generated that, unlike mouse models, develop lung disease similar to human cystic fibrosis. However, the scientific literature relating specifically to porcine lung anatomy and airway histology is limited and is largely restricted to veterinary literature and textbooks. Furthermore, methods for in vivo lung procedures in the pig are rarely described. The aims of this review are to collate the disparate literature on porcine lung anatomy, histology, and microbiology; to provide a comparison with the human lung; and to describe appropriate bronchoscopy procedures for the pig lungs to aid clinical researchers working in the area of translational respiratory medicine using the porcine model.


Assuntos
Pulmão/anatomia & histologia , Pulmão/fisiologia , Animais , Pesquisa Biomédica , Biópsia , Brônquios/fisiologia , Broncoscopia , Cartilagem/fisiologia , Modelos Animais de Doenças , Genoma , Humanos , Inflamação , Respiração , Suínos , Pesquisa Médica Translacional , Transplante Heterólogo
10.
Adv Ther ; 31(4): 375-91, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24639005

RESUMO

Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Fibrose Pulmonar Idiopática , Piridonas , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Gerenciamento Clínico , Intervalo Livre de Doença , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Testes de Função Respiratória/métodos
12.
Ann Intern Med ; 158(9): 641-9, 2013 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-23648946

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is characterized by formation and proliferation of fibroblast foci. Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A (ETA) receptor. OBJECTIVE: To determine whether ambrisentan, an ETA receptor-selective antagonist, reduces the rate of IPF progression. DESIGN: Randomized, double-blind, placebo-controlled, event-driven trial. (ClinicalTrials.gov: NCT00768300). SETTING: Academic and private hospitals. PARTICIPANTS: Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans. INTERVENTION: Ambrisentan, 10 mg/d, or placebo. MEASUREMENTS: Time to disease progression, defined as death, respiratory hospitalization, or a categorical decrease in lung function. RESULTS: The study was terminated after enrollment of 492 patients (75% of intended enrollment; mean duration of exposure to study medication, 34.7 weeks) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study. Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression (90 [27.4%] vs. 28 [17.2%] patients; P = 0.010; hazard ratio, 1.74 [95% CI, 1.14 to 2.66]). Lung function decline was seen in 55 (16.7%) ambrisentan-treated patients and 19 (11.7%) placebo-treated patients (P = 0.109). Respiratory hospitalizations were seen in 44 (13.4%) and 9 (5.5%) patients in the ambrisentan and placebo groups, respectively (P = 0.007). Twenty-six (7.9%) patients who received ambrisentan and 6 (3.7%) who received placebo died (P = 0.100). Thirty-two (10%) ambrisentan-treated patients and 16 (10%) placebo-treated patients had pulmonary hypertension at baseline, and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point. LIMITATION: The study was terminated early. CONCLUSION: Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations. PRIMARY FUNDING SOURCE: Gilead Sciences.


Assuntos
Antagonistas do Receptor de Endotelina A , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fenilpropionatos/uso terapêutico , Piridazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Fibrose Pulmonar Idiopática/fisiopatologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenilpropionatos/efeitos adversos , Estudos Prospectivos , Piridazinas/efeitos adversos , Resultado do Tratamento
13.
Eur Respir J ; 41(5): 1207-18, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23100500

RESUMO

Pulmonary fibrosis is the end stage of many diffuse parenchymal lung diseases. It is characterised by excessive matrix formation leading to destruction of the normal lung architecture and finally death. Despite an exponential increase in our understanding of potentially important mediators and mechanisms, the delineation of primary pathways has proven to be elusive. In this review susceptibility and injurious agents, such as viruses and gastro-oesophageal reflux, and their probable role in initiating disease will be discussed. Further topics that are elaborated are candidate ancillary pathways, including immune mechanisms, oxidative and endoplasmic reticulum stress, activation of the coagulation cascade and the potential role of stem cells. This review will try to provide the reader with an integrated view on the current knowledge and attempts to provide a road map for future research. It is important to explore robust models of overall pathogenesis, reconciling a large number of clinical and scientific observations. We believe that the integration of current data into a "big picture" overview of fibrogenesis is essential for the development of effective antifibrotic strategies. The latter will probably consist of a combination of agents targeting a number of key pathways.


Assuntos
Fibrose Pulmonar/fisiopatologia , Animais , Coagulação Sanguínea , Progressão da Doença , Estresse do Retículo Endoplasmático , Células Epiteliais/citologia , Refluxo Gastroesofágico/fisiopatologia , Predisposição Genética para Doença , Humanos , Camundongos , Mutação , Estresse Oxidativo , Alvéolos Pulmonares/metabolismo , Fibrose Pulmonar/diagnóstico , Fibrose Pulmonar/genética , Células-Tronco/citologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-22927751

RESUMO

INTRODUCTION: Endoscopic lung volume reduction has been developed as a therapeutic option for advanced emphysema. Six-month results following treatment with endoscopic thermal vapor ablation (InterVapor; Uptake Medical, Tustin, CA) were described previously, and here we report observations from the 12-month assessment. METHODS: Two multicenter, international, single-arm trials of InterVapor (unilateral upper lobe treatment) in patients with upper lobe predominant emphysema were conducted. INCLUSION CRITERIA: forced expiratory volume in 1 second (FEV(1)) 15%-45% predicted, residual volume > 150%, total lung capacity > 100%, 6-minute walk distance (6MWD) > 140 m, and diffusing capacity for carbon monoxide > 20% predicted. Efficacy endpoints: spirometry, body plethysmography, lung volumes by high-resolution computed tomography, St George's Respiratory Questionnaire, modified Medical Research Council dyspnea scale, and 6MWD. All adverse events were collected and independently adjudicated. RESULTS: Forty four patients were treated at a mean (standard deviation) age of 63 (5.6) years, FEV(1) 0.86 mL (0.25 mL) (n = 22 men and 22 women). Mean (standard deviation) changes from baseline at 12 months were: FEV(1) 86.2 mL (173.8 mL), St George's Respiratory Questionnaire -11.0 (14.0) units, treated lobar volume from high-resolution computed tomography -751.8 mL (653.9 mL), residual volume -302.8 mL (775.6 mL), 6MWD 18.5 m (63.7 m), and modified Medical Research Council dyspnea scale score -0.83 (0.97) (P < 0.05 for all except 6MWD). Improvements were numerically larger at 6 versus 12 months. GOLD stage III and IV patients had similar outcomes at 6 months; however, improvements relative to baseline were numerically higher in GOLD stage IV patients. Larger improvements were observed in patients with higher heterogeneity. In total, 39 serious adverse events were reported in 23 patients with 10 events in 8 patients between 6 and 12 months. CONCLUSION: Unilateral lobar InterVapor treatment of heterogeneous emphysema improved lung function and health outcomes 1 year following treatment. The magnitude of improvement was larger at 6 months compared to 12 months. Improvements relative to baseline continue to be exhibited at 12 months despite the expected disease related decline over time.


Assuntos
Técnicas de Ablação , Broncoscopia , Pulmão/cirurgia , Pneumonectomia/métodos , Enfisema Pulmonar/terapia , Técnicas de Ablação/efeitos adversos , Idoso , Austrália , Broncoscopia/efeitos adversos , Europa (Continente) , Teste de Esforço , Tolerância ao Exercício , Feminino , Volume Expiratório Forçado , Humanos , Pulmão/fisiopatologia , Medidas de Volume Pulmonar , Masculino , Pessoa de Meia-Idade , Pletismografia Total , Pneumonectomia/efeitos adversos , Capacidade de Difusão Pulmonar , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/fisiopatologia , Recuperação de Função Fisiológica , Volume Residual , Índice de Gravidade de Doença , Espirometria , Inquéritos e Questionários , Fatores de Tempo , Tomografia Computadorizada por Raios X , Capacidade Pulmonar Total , Resultado do Tratamento , Estados Unidos , Caminhada
16.
BMJ Open ; 2(2): e000605, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22457478

RESUMO

OBJECTIVE: Prior to 2005, Irish citizens had exclusively availed of lung transplantation services in the UK. Since 2005, lung transplantation has been available to these patients in both the UK and Ireland. We aimed to evaluate the outcomes of Irish patients undergoing lung transplantation in both the UK and Ireland. DESIGN: We retrospectively examined the outcome of Irish patients transplanted in the UK and Ireland. Lung allocation score (LAS) was used as a marker of disease severity. RESULTS: A total of 134 patients have undergone transplantation. 102 patients underwent transplantation in the UK and 32 patients in Ireland. In total, 52% were patients with cystic fibrosis, 19% had emphysema and 15% had idiopathic pulmonary fibrosis. In Ireland, 44% of the patients suffered from idiopathic pulmonary fibrosis, 31% had emphysema and 16% had cystic fibrosis. A total of 96 double sequential transplants and 38 single transplants have been performed. LAS of all patients undergoing lung transplantation was 37.8 (±1.02). The mean LAS for patients undergoing lung transplantation in Ireland was 44.7 (±3.1), and 35 (±0.4) for patients undergoing lung transplantation in the UK (p<0.05). The 5-year survival of all Irish citizens who had undergone lung transplantation was 73%. The 5-year survival of Irish patients transplanted in the UK was 69% and in Ireland was 91% and 73% at 5.01 years. CONCLUSIONS: International collaboration can be achieved, as evidenced by the favourable outcomes seen in Irish citizens who undergo lung transplantation in both the UK and Ireland. Irish citizens undergoing lung transplantation in Ireland have a higher LAS score. Despite excellent outcomes, an intention-to-treat analysis of the treatment utility (transplant) indicates the limited effectiveness of lung transplantation in Ireland and emphasises the need for increased rates of lung transplantation.

17.
Eur Respir J ; 39(6): 1334-42, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22282552

RESUMO

The Endobronchial Valve for Emphysema Palliation Trial (VENT) was a multi-centre, prospective, randomised, controlled trial conducted to evaluate the safety and effectiveness of unilateral endobronchial valve (EBV) treatment. The purpose of this analysis was to assess outcomes in the previously unreported European VENT study cohort. Patients with advanced emphysema were randomly assigned (2:1) to receive Zephyr® (Pulmonx Inc., Redwood City, CA, USA) EBV treatment (n = 111) or medical management (n = 60). At 6 months, EBV patients demonstrated a significant improvement compared with the controls for mean ± SD change in forced expiratory volume in 1 s (7 ± 20% versus 0.5 ± 19%; p = 0.067), cycle ergometry (2 ± 14 W versus -3 ± 10 W; p = 0.04) and St George's Respiratory Questionnaire (-5 ± 14 points versus 0.3 ± 13 points; p = 0.047). At 12 months, the magnitude of the difference between groups for change from baseline was of similar magnitude to the differences seen at 6 months. Rates for complications did not differ significantly. EBV patients with computed tomography (CT) scans suggestive of complete fissure and lobar occlusion had a mean ± SD lobar volume reduction of -80 ± 30% and >50% met minimal clinical difference thresholds. The degree of emphysema heterogeneity did not preclude excellent outcomes. Unilateral lobar volume reduction using EBV treatment is safe and superior clinical results correlated with CT suggestive of complete fissures and successful lobar occlusion. Emphysema heterogeneity was not critical for determining positive outcomes.


Assuntos
Pneumonectomia/métodos , Enfisema Pulmonar/cirurgia , Idoso , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Enfisema Pulmonar/diagnóstico por imagem , Qualidade de Vida , Testes de Função Respiratória , Índice de Gravidade de Doença , Inquéritos e Questionários , Tomografia Computadorizada por Raios X , Resultado do Tratamento
18.
Eur Respir J ; 40(1): 93-100, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22135282

RESUMO

The aim of this study was to evaluate the risk factors for and outcomes of acute exacerbations in patients with advanced idiopathic pulmonary fibrosis (IPF), and to examine the relationship between disease severity and neovascularisation in explanted IPF lung tissue. 55 IPF patients assessed for lung transplantation were divided into acute (n=27) and non-acute exacerbation (n=28) groups. Haemodynamic data was collected at baseline, at the time of acute exacerbation and at lung transplantation. Histological analysis and CD31 immunostaining to quantify microvessel density (MVD) was performed on the explanted lung tissue of 13 transplanted patients. Acute exacerbations were associated with increased mortality (p=0.0015). Pulmonary hypertension (PH) at baseline and acute exacerbations were associated with poor survival (p<0.01). PH at baseline was associated with a significant risk of acute exacerbations (HR 2.217, p=0.041). Neovascularisation (MVD) was significantly increased in areas of cellular fibrosis and significantly decreased in areas of honeycombing. There was a significant inverse correlation between mean pulmonary artery pressure and MVD in areas of honeycombing. Acute exacerbations were associated with significantly increased mortality in patients with advanced IPF. PH was associated with the subsequent development of an acute exacerbation and with poor survival. Neovascularisation was significantly decreased in areas of honeycombing, and was significantly inversely correlated with mean pulmonary arterial pressure in areas of honeycombing.


Assuntos
Hipertensão Pulmonar/complicações , Fibrose Pulmonar Idiopática/complicações , Pulmão/fisiopatologia , Doença Aguda , Feminino , Hemodinâmica , Humanos , Hipertensão Pulmonar/mortalidade , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/cirurgia , Transplante de Pulmão , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Prognóstico , Fatores de Risco , Análise de Sobrevida
19.
Eur Respir J ; 39(6): 1326-33, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22075481

RESUMO

The need for a less invasive procedure than surgical lung volume reduction that can produce consistent improvements with reduced morbidity remains a medical goal in patients with emphysema. We sought to determine the effect of bronchoscopic thermal vapour ablation (BTVA) on lung volumes and outcomes in patients with emphysema. 44 patients with upper lobe-predominant emphysema were treated unilaterally with BTVA. Entry criteria included: age 40-75 yrs, forced expiratory volume in 1 s (FEV(1)) 15-45% predicted, previous pulmonary rehabilitation and a heterogeneity index (tissue/air ratio of lower lobe/upper lobe) from high-resolution computed tomography (HRCT) ≥ 1.2. Changes in FEV(1), St George's Respiratory Questionnaire (SGRQ), 6-min walk distance (6 MWD), modified Medical Research Council (mMRC) dyspnoea score, and hyperinflation were measured at baseline, and 3 and 6 months post-BTVA. At 6 months, mean ± SE FEV(1) improved by 141 ± 26 mL (p<0.001) and residual volume was reduced by 406 ± 113 mL (p<0.0001). SGRQ total score improved by 14.0 ± 2.4 points (p<0.001), with 73% improving by ≥ 4 points. Improvements were observed in 6 MWD (46.5 ± 10.6 m) and mMRC dyspnoea score (0.9 ± 0.2) (p<0.001 for both). Lower respiratory events (n=11) were the most common adverse event and occurred most often during the initial 30 days. BTVA therapy results in clinically relevant improvements in lung function, quality of life and exercise tolerance in upper lobe predominant emphysema.


Assuntos
Técnicas de Ablação/métodos , Broncoscopia/métodos , Pneumonectomia/métodos , Enfisema Pulmonar/cirurgia , Adulto , Idoso , Broncoscopia/efeitos adversos , Dispneia/cirurgia , Tolerância ao Exercício/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Qualidade de Vida , Testes de Função Respiratória , Inquéritos e Questionários , Resultado do Tratamento
20.
Interact Cardiovasc Thorac Surg ; 13(2): 198-200, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21543364

RESUMO

We report the use of the Novalung pumpless device in self-ventilating patients awaiting a lung transplantation. Two patients developed carbon dioxide retention with respiratory acidosis that did not respond to maximum medical therapy. The Novalung interventional lung assist was established as a bridge to lung transplantation. The first patient was successfully transplanted after 140 days, and this is the longest support that has been reported so far. The second patient was weaned off the Novalung after a short period. The Novalung is a valuable device for self-ventilating patients with carbon dioxide retention being bridged to lung transplantation.


Assuntos
Oxigenação por Membrana Extracorpórea/instrumentação , Transplante de Pulmão/métodos , Respiração , Insuficiência Respiratória/cirurgia , Desenho de Equipamento , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/fisiopatologia
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