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1.
Am J Transplant ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39098448

RESUMO

Currently, lung transplantation outcome remains inferior compared to other solid organ transplantations. A major cause for limited survival after lung transplantation is chronic lung allograft dysfunction. Numerous animal models have been developed to investigate chronic lung allograft dysfunction to discover adequate treatments. The murine orthotopic lung transplant model has been further optimized over the last years. However, different degrees of genetic mismatch between donor and recipient mice have been used, applying a single, minor, moderate, and major genetic mismatch. This review aims to reassess the existing murine mismatch models and provide a comprehensive overview, with a specific focus on their eventual histopathological presentation. This will be crucial to leverage this model and tailor it according to specific research needs.

2.
Curr Opin Pulm Med ; 30(4): 377-381, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38305383

RESUMO

PURPOSE OF REVIEW: Chronic lung allograft dysfunction (CLAD) remains a life-threatening complication following lung transplantation. Different CLAD phenotypes have recently been defined, based on the combination of pulmonary function testing and chest computed tomography (CT) scanning and spurred renewed interests in differential diagnosis, risk factors and management of CLAD. RECENT FINDINGS: Given their crucial importance in the differential diagnosis, we will discuss the latest development in assessing the pulmonary function and chest CT scan, but also their limitations in proper CLAD phenotyping, especially with regards to patients with baseline allograft dysfunction. Since no definitive treatment exists, it remains important to timely identify clinical risk factors, but also to assess the presence of specific patterns or biomarkers in tissue or in broncho alveolar lavage in relation to CLAD (phenotypes). We will provide a comprehensive overview of the latest advances in risk factors and biomarker research in CLAD. Lastly, we will also review novel preventive and curative treatment strategies for CLAD. SUMMARY: Although this knowledge has significantly advanced the field of lung transplantation, more research is warranted because CLAD remains a life-threatening complication for all lung transplant recipients.


Assuntos
Transplante de Pulmão , Testes de Função Respiratória , Tomografia Computadorizada por Raios X , Humanos , Transplante de Pulmão/efeitos adversos , Fatores de Risco , Rejeição de Enxerto/diagnóstico , Aloenxertos , Biomarcadores/metabolismo , Biomarcadores/análise , Doença Crônica , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/terapia , Disfunção Primária do Enxerto/etiologia , Disfunção Primária do Enxerto/fisiopatologia , Diagnóstico Diferencial , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem
3.
Clin Transplant ; 38(1): e15171, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37897208

RESUMO

BACKGROUND & AIMS: Concomitant respiratory disease is a common finding in patients with hepatopulmonary syndrome (HPS). Among patients who underwent liver transplantation (LT) for HPS, we compared characteristics and outcome of patients with versus without concomitant respiratory disease. METHODS: This single center retrospective observational study included patients with HPS who underwent LT between 1999 and 2020. RESULTS: During the study period, 32 patients with HPS received a LT; nine (28%) with concomitant respiratory disease of whom one required a combined lung-liver transplantation. Patients with concomitant respiratory disease had higher PaCO2 (38 vs. 33 mm Hg, p = .031). The 30-day postoperative mortality was comparable, but the estimated cumulative probability of resolution of oxygen therapy after LT in HPS patients with versus those without concomitant respiratory disease was lower: 63% versus 91% at 12 months and 63% versus 100% at 18 months (HR 95% CI .140-.995, p = .040). In addition to the presence of concomitant respiratory disease (p = .040), history of smoking (p = .012), and high baseline 99mTcMAA shunt fraction (≥20%) (p = .050) were significantly associated with persistent need of oxygen therapy. The 5-year estimated cumulative probability of mortality in patients with concomitant respiratory disease was worse: 50% versus 23% (HR 95% CI .416-6.867, p = .463). CONCLUSIONS: The presence of a concomitant respiratory disease did not increase the short-term postoperative mortality after LT in patients with HPS. However, it resulted in a longer need for oxygen therapy.


Assuntos
Síndrome Hepatopulmonar , Transplante de Fígado , Humanos , Síndrome Hepatopulmonar/cirurgia , Síndrome Hepatopulmonar/complicações , Transplante de Fígado/efeitos adversos , Pulmão , Oxigênio , Oxigenoterapia , Estudos Retrospectivos
4.
Transpl Int ; 37: 12061, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38328617

RESUMO

Lung transplant (LTx) recipients are at high risk for COVID-19 related morbidity and mortality. Data regarding pre-exposure prophylaxis (PrEP) with tixagevimab-cilgavimab in this population are scarce. We therefore evaluated COVID-19 breakthrough infections and COVID-19 related complications after PrEP in a retrospective single-center study, including 264 LTx recipients who received PrEP between June 2022 and December 2022, when Omicron BA.5 was the dominant circulating SARS-CoV-2 variant. PrEP was indicated for fully vaccinated patients with poor seroconversion (anti-S <260 BAU/mL). COVID-19 breakthrough infection after PrEP occurred in 11.0% within the first 3 months, increasing to 17.4% within 6 months. Hospitalization rate rose from 27.6% to 52.9% (p = 0.046), while ICU admissions and COVID-19 mortality remained low, respectively occurring in 6.5% and 4.3% of patients with breakthrough infection within 6 months. COVID-19 breakthrough infection and associated hospitalization remained an important problem during the Omicron BA.5 surge in fully vaccinated LTx recipients with deficient seroconversion, despite PrEP with tixagevimab-cilgavimab. However, ICU admissions and COVID-19 mortality were low. Waning of neutralizing effects of PrEP and changing circulating SARS-CoV-2 variants may explain increases in COVID-19 infections and hospitalizations over time after PrEP, highlighting the need for novel, long-term effective PrEP strategies in these high-risk patients.


Assuntos
Anticorpos Monoclonais , Infecções Irruptivas , COVID-19 , Profilaxia Pré-Exposição , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Estudos Retrospectivos , Transplantados , Pulmão
5.
Transpl Infect Dis ; 26(3): e14251, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38351512

RESUMO

PURPOSE: Antimicrobial misuse contributes to antimicrobial resistance in thoracic transplant (TTx) and mechanical circulatory support (MCS) recipients. This study uses a modified Delphi method to define the expected appropriate antimicrobial prescribing for the common clinical scenarios encountered in TTx and MCS recipients. METHODS: An online questionnaire on managing 10 common infectious disease syndromes was submitted to a multidisciplinary Delphi panel of 25 experts from various disciplines. Consensus was predefined as 80% agreement for each question. Questions where consensus was not achieved were discussed during live virtual live sessions adapted by an independent process expert. RESULTS: An online survey of 62 questions related to 10 infectious disease syndromes was submitted to the Delphi panel. In the first round of the online questionnaire, consensus on antimicrobial management was reached by 6.5% (4/62). In Round 2 online live discussion, the remaining 58 questions were discussed among the Delphi Panel members using a virtual meeting platform. Consensus was reached among 62% (36/58) of questions. Agreement was not reached regarding the antimicrobial management of the following six clinical syndromes: (1) Burkholderia cepacia pneumonia (duration of therapy); (2) Mycobacterium abscessus (intra-operative antimicrobials); (3) invasive aspergillosis (treatment of culture-negative but positive BAL galactomannan) (duration of therapy); (4) respiratory syncytial virus (duration of antiviral therapy); (5) left ventricular assist device deep infection (initial empirical antimicrobial coverage) and (6) CMV (duration of secondary prophylaxis). CONCLUSION: This Delphi panel developed consensus-based recommendations for 10 infectious clinical syndromes seen in TTx and MCS recipients.


Assuntos
Técnica Delphi , Humanos , Inquéritos e Questionários , Coração Auxiliar/efeitos adversos , Consenso , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas , Transplantados , Transplante de Pulmão/efeitos adversos , Antibacterianos/uso terapêutico , Doenças Transmissíveis
6.
Respiration ; 103(5): 251-256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38447551

RESUMO

INTRODUCTION: Lung transplant recipients are often physically inactive and are at risk of developing comorbidities. We investigated whether objectively measured physical activity was associated with the prevalence of comorbidities. METHODS: Physical activity (accelerometry) and the presence of cardiovascular disease, symptoms of depression and anxiety, diabetes, dyslipidaemia, hypertension, lower extremity artery disease, muscle weakness, obesity, and osteoporosis were assessed in 108 lung transplant recipients. Patients were divided into four groups based on daily step count. RESULTS: A cohort of 108 patients (60 ± 7 years, 51% male, 20 ± 14 months since transplantation) was included. Active patients (>7,500 steps/day) had significantly fewer comorbidities (4 comorbidities) compared to severely inactive patients (<2,500 steps/day, 6 comorbidities), and muscle weakness and high symptoms of depression were less prevalent. Severely inactive patients had significantly more cardiovascular comorbidities compared to all other groups. No other significant differences were observed. CONCLUSION: Physically active lung transplant recipients have fewer comorbidities, lower prevalence of muscle weakness, and fewer symptoms of depression compared to very inactive patients.


Assuntos
Comorbidade , Depressão , Exercício Físico , Transplante de Pulmão , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Prevalência , Idoso , Depressão/epidemiologia , Doenças Cardiovasculares/epidemiologia , Debilidade Muscular/epidemiologia , Debilidade Muscular/etiologia , Hipertensão/epidemiologia , Diabetes Mellitus/epidemiologia , Osteoporose/epidemiologia , Acelerometria , Ansiedade/epidemiologia , Dislipidemias/epidemiologia , Obesidade/epidemiologia , Obesidade/complicações , Transplantados/estatística & dados numéricos
7.
Am J Physiol Lung Cell Mol Physiol ; 325(5): L675-L688, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37724349

RESUMO

Lung transplantation (LTx) is a challenging procedure. Following the process of ischemia-reperfusion injury, the transplanted pulmonary graft might become severely damaged, resulting in primary graft dysfunction. In addition, during the intraoperative window, the right ventricle (RV) is at risk of acute failure. The interaction of right ventricular function with lung injury is, however, poorly understood. We aimed to address this interaction in a translational porcine model of pulmonary ischemia-reperfusion injury. Advanced pulmonary and hemodynamic assessment was used, including right ventricular pressure-volume loop analysis. The acute model was based on clamping and unclamping of the left lung hilus, respecting the different hemodynamic phases of a clinical lung transplantation. We found that forcing entire right ventricular cardiac output through a lung suffering from ischemia-reperfusion injury increased afterload (pulmonary vascular resistance from baseline to end experiment P < 0.0001) and induced right ventricular failure (RVF) in 5/9 animals. Notably, we identified different compensation patterns in failing versus nonfailing ventricles (arterial elastance P = 0.0008; stroke volume P < 0.0001). Furthermore, increased vascular pressure and flow produced by the right ventricle resulted in higher pulmonary injury, as measured by ex vivo CT density (correlation: pressure r = 0.8; flow r = 0.85). Finally, RV ischemia as measured by troponin-T was negatively correlated with pulmonary injury (r = -0.76); however, troponin-T values did not determine RVF in all animals. In conclusion, we demonstrate a delicate balance between development of pulmonary ischemia-reperfusion injury and right ventricular function during lung transplantation. Furthermore, we provide a physiological basis for potential benefit of extracorporeal life support technology.NEW & NOTEWORTHY In contrast to the abundant literature of mechanical pulmonary artery clamping to increase right ventricular afterload, we developed a model adding a biological factor of pulmonary ischemia-reperfusion injury. We did not only focus on the right ventricular behavior, but also on the interaction with the injured lung. We are the first to describe this interaction while addressing the hemodynamic intraoperative phases of clinical lung transplantation.


Assuntos
Insuficiência Cardíaca , Lesão Pulmonar , Transplante de Pulmão , Traumatismo por Reperfusão , Disfunção Ventricular Direita , Suínos , Animais , Função Ventricular Direita , Troponina T , Pulmão , Hemodinâmica/fisiologia
8.
Am J Transplant ; 23(1): 111-114, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36695613

RESUMO

Pulmonary vein stenosis (PVS) and pulmonary vein occlusion (PVO) represent rare complications after lung transplantation (LTx), with limited therapeutic options and a high risk of graft loss. We present 2 cases of successful endovascular transatrial stenting following double LTx. A 60-year-old woman with chronic obstructive pulmonary disease who underwent double lobar LTx was diagnosed at postoperative day 72 with a high-grade PVS on the left side. A 22-year-old woman with idiopathic pulmonary arterial hypertension who underwent double LTx was diagnosed 9 days later with PVO of the left upper lobe vein. To avoid surgical reintervention, endovascular transatrial dilatation and stenting were performed successfully in both cases. Transatrial endovascular stenting of PVS or PVO after LTx seems an effective and safe treatment option that should be considered for these life-threatening complications and executed with care.


Assuntos
Pneumopatias , Transplante de Pulmão , Veias Pulmonares , Pneumopatia Veno-Oclusiva , Estenose de Veia Pulmonar , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Adulto , Estenose de Veia Pulmonar/cirurgia , Estenose de Veia Pulmonar/complicações , Veias Pulmonares/cirurgia , Pneumopatia Veno-Oclusiva/etiologia , Pneumopatia Veno-Oclusiva/cirurgia , Pulmão , Pneumopatias/complicações , Transplante de Pulmão/efeitos adversos , Resultado do Tratamento , Estudos Retrospectivos
9.
Ann Surg ; 278(3): e641-e649, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-36735450

RESUMO

OBJECTIVE: To describe our experience with lung transplantation (LTx) from donors ≥70 years and compare short and long-term outcomes to a propensity-matched cohort of donors <70 years. BACKGROUND: Although extended-criteria donors have been widely used to enlarge the donor pool, the experience with LTx from older donors (≥70 years) remains limited. METHODS: All single-center bilateral LTx between 2010 and 2020 were retrospectively analyzed. Matching (1:1) was performed for the donor (type, sex, smoking history, x-ray abnormalities, partial pressure of oxygen/fraction of inspired oxygen ratio, and time on ventilator) and recipient characteristics (age, sex, LTx indication, perioperative extracorporeal life support, and cytomegalovirus mismatch). Primary graft dysfunction grade-3, 5-year patient, and chronic lung allograft dysfunction-free survival were analyzed. RESULTS: Out of 647 bilateral LTx, 69 were performed from donors ≥70 years. The mean age in the older donor cohort was 74 years (range: 70-84 years) versus 49 years (range: 12-69 years) in the matched younger group. No significant differences were observed in the length of ventilatory support, intensive care unit, or hospital stay. Primary graft dysfunction-3 was 26% in the older group versus 29% in younger donor recipients ( P = 0.85). Reintervention rate was comparable (29% vs 16%; P = 0.10). Follow-up bronchoscopy revealed no difference in bronchial anastomotic complications ( P = 1.00). Five-year patient and chronic lung allograft dysfunction-free survivals were 73.6% versus 73.1% ( P = 0.72) and 51.5% versus 59.2% ( P = 0.41), respectively. CONCLUSIONS: LTx from selected donors ≥70 years is feasible and safe, yielding comparable short and long-term outcomes in a propensity-matched analysis with younger donors (<70 years).


Assuntos
Transplante de Pulmão , Disfunção Primária do Enxerto , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Resultado do Tratamento , Doadores de Tecidos , Oxigênio
10.
Radiology ; 307(1): e221145, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36537894

RESUMO

Background Interstitial lung abnormalities (ILAs) reflect imaging features on lung CT scans that are compatible with (early) interstitial lung disease. Despite accumulating evidence regarding the incidence, risk factors, and prognosis of ILAs, the histopathologic correlates of ILAs remain elusive. Purpose To determine the correlation between radiologic and histopathologic findings in CT-defined ILAs in human lung explants. Materials and Methods Explanted lungs or lobes from participants with radiologically documented ILAs were prospectively collected from 2010 to 2021. These specimens were air-inflated, frozen, and scanned with CT and micro-CT (spatial resolution of 0.7 mm and 90 µm, respectively). Subsequently, the lungs were cut and sampled with core biopsies. At least five samples per lung underwent micro-CT and subsequent histopathologic assessment with semiquantitative remodeling scorings. Based on area-specific radiologic scoring, the association between radiologic and histopathologic findings was assessed. Results Eight lung explants from six donors (median age at explantation, 71 years [range, 60-83 years]; four men) were included (unused donor lungs, n = 4; pre-emptive lobectomy for oncologic indications, n = 2). Ex vivo CT demonstrated ground-glass opacification, reticulation, and bronchiectasis. Micro-CT and histopathologic examination demonstrated that lung abnormalities were frequently paraseptal and associated with fibrosis and lymphocytic inflammation. The histopathologic results showed varying degrees of fibrosis in areas that appeared normal on CT scans. Regions of reticulation on CT scans generally had greater fibrosis at histopathologic analysis. Vasculopathy and bronchiectasis were also often present at histopathologic examination of lungs with ILAs. Fully developed fibroblastic foci were rarely observed. Conclusion This study demonstrated direct histologic correlates of CT-defined interstitial lung abnormalities. © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Jeudy in this issue.


Assuntos
Bronquiectasia , Doenças Pulmonares Intersticiais , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Pulmão/diagnóstico por imagem , Pulmão/patologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Fibrose , Microtomografia por Raio-X
11.
Transpl Int ; 36: 10768, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873745

RESUMO

Fungal exposure and sensitization negatively affect outcomes in various respiratory diseases, however, the effect of fungal sensitization in lung transplant (LTx) recipients is still unknown. We performed a retrospective cohort study of prospectively collected data on circulating fungal specific IgG/IgE antibodies, and their correlation with fungal isolation, chronic lung allograft dysfunction (CLAD) and overall survival after LTx. 311 patients transplanted between 2014 and 2019 were included. Patients with elevated Aspergillus fumigatus or Aspergillus flavus IgG (10%) had more mold and Aspergillus species isolation (p = 0.0068 and p = 0.0047). Aspergillus fumigatus IgG was specifically associated with Aspergillus fumigatus isolation in the previous or consecutive year (AUC 0.60, p = 0.004 and AUC 0.63, p = 0.022, respectively). Elevated Aspergillus fumigatus or Aspergillus flavus IgG was associated with CLAD (p = 0.0355), but not with death. Aspergillus fumigatus, Aspergillus flavus or Aspergillus niger IgE was elevated in 19.3% of patients, but not associated with fungal isolation, CLAD or death. Mold isolation and Aspergillus species isolation from respiratory cultures were associated with CLAD occurrence (p = 0.0011 and p = 0.0005, respectively), and Aspergillus species isolation was also associated with impaired survival (p = 0.0424). Fungus-specific IgG could be useful in long-term follow-up post-LTx, as a non-invasive marker for fungal exposure, and thus a diagnostic tool for identifying patients at risk for fungal-related complications and CLAD.


Assuntos
Transplante de Pulmão , Humanos , Estudos Retrospectivos , Imunoglobulina G , Imunoglobulina E , Pulmão , Aloenxertos
12.
Am J Transplant ; 22(5): 1418-1429, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35029023

RESUMO

Primary graft dysfunction (PGD) is a major obstacle after lung transplantation (LTx), associated with increased early morbidity and mortality. Studies in liver and kidney transplantation revealed prolonged anastomosis time (AT) as an independent risk factor for impaired short- and long-term outcomes. We investigated if AT during LTx is a risk factor for PGD. In this retrospective single-center cohort study, we included all first double lung transplantations between 2008 and 2016. The association of AT with any PGD grade 3 (PGD3) within the first 72 h post-transplant was analyzed by univariable and multivariable logistic regression analysis. Data on AT and PGD was available for 427 patients of which 130 (30.2%) developed PGD3. AT was independently associated with the development of any PGD3 ≤72 h in uni- (odds ratio [OR] per 10 min 1.293, 95% confidence interval [CI 1.136-1.471], p < .0001) and multivariable (OR 1.205, 95% CI [1.022-1.421], p = .03) logistic regression analysis. There was no evidence that the relation between AT and PGD3 differed between lung recipients from donation after brain death versus donation after circulatory death donors. This study identified AT as an independent risk factor for the development of PGD3 post-LTx. We suggest that the implantation time should be kept short and the lung cooled to decrease PGD-related morbidity and mortality post-LTx.


Assuntos
Transplante de Pulmão , Disfunção Primária do Enxerto , Anastomose Cirúrgica/efeitos adversos , Estudos de Coortes , Humanos , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/etiologia , Estudos Retrospectivos , Fatores de Risco
13.
Transpl Int ; 35: 10159, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35651878

RESUMO

The MUC5B promoter polymorphism (rs35705950) has been associated with interstitial lung disease (ILD) and with prolonged pre-transplant survival in idiopathic pulmonary fibrosis (IPF), but no information is available regarding its prevalence in other respiratory diseases and its influence on post-transplant outcome. We included the Leuven lung transplantation cohort between 1991 and 2015 (n = 801). We assessed the minor allele frequency (MAF) of the MUC5B variant in the entire study cohort and investigated the influence of recipient MUC5B promoter polymorphism on post-transplant outcome in patients who were transplanted after 2004. MUC5B was successfully genotyped in 746 patients. The MAF was significantly higher in ILD (17.6%) compared to chronic obstructive pulmonary disease (COPD)/emphysema (9.3%), cystic fibrosis (CF)/bronchiectasis (BRECT) (7.5%) and pulmonary hypertension (PHT) (7.4%) (p < 0.001). No association was observed between rs35705950 and chronic lung allograft dysfunction (CLAD)/graft loss in the ILD population [CLAD: HR 1.37 95% CI (0.70-2.68); graft loss: HR 1.02 95% CI (0.55-1.89)], nor the entire study cohort [CLAD: HR 0.96 95% CI (0.69-1.34); graft loss: HR 0.97 95% CI (0.70-1.35)]. The MUC5B promoter polymorphism is a very specific predictive factor for the presence of pulmonary fibrosis as it is only associated with pulmonary fibrosis and not with other chronic respiratory diseases. While the MUC5B promoter variant is associated with better pre-transplant survival among IPF patients, recipient MUC5B promoter variant does not play a role in post-transplant outcome.


Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Predisposição Genética para Doença , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/cirurgia , Doenças Pulmonares Intersticiais/genética , Doenças Pulmonares Intersticiais/cirurgia , Mucina-5B/genética , Polimorfismo Genético , Regiões Promotoras Genéticas
14.
BMC Pulm Med ; 22(1): 110, 2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35346142

RESUMO

BACKGROUND: Variability in triazole plasma concentrations by drug interactions is well known. An interaction between voriconazole and flucloxacillin has already been described. In our case we observed a similar interaction between posaconazole and flucloxacillin, which in our knowledge has not ever been reported in literature. CASE PRESENTATION: A 60-year-old male who had a double lung transplantation for end-stage chronic obstructive pulmonary disease was being treated with voriconazole for invasive pulmonary aspergillosis (IPA). During this treatment he presented at the emergency room and was diagnosed with endocarditis for which a combination of amoxicillin, flucloxacillin and gentamicin was initiated. A known interaction between voriconazole and flucloxacillin was observed, with a drop of the voriconazole levels, and treatment for IPA was switched to posaconazole. After ending the treatment for endocarditis, the patient had a catheter infection for which flucloxacillin was reinitiated. Unexpectedly we saw a similar immediate drop in posaconazole levels, recovering after ending treatment with flucloxacillin. CONCLUSIONS: We describe a new interaction between posaconazole and flucloxacillin. Presumably the underlying mechanism is activation of the pregnane X receptor by flucloxacillin, which can induce cytochrome P450, uridine glucuronosyl transferase (UGT1A4) and P-glycoprotein. We advise caution when combining flucloxacillin and triazoles, because interactions may lead to undertreatment of invasive aspergillosis.


Assuntos
Aspergilose , Transplante de Pulmão , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Aspergilose/tratamento farmacológico , Floxacilina/uso terapêutico , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Triazóis/farmacologia , Triazóis/uso terapêutico
15.
Curr Opin Organ Transplant ; 27(1): 1-6, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34939958

RESUMO

PURPOSE OF REVIEW: Chronic lung allograft dysfunction (CLAD) remains a major barrier preventing long-term survival following lung transplantation. As our clinical knowledge regarding its definition and presentation has significantly improved over the last years, adequate biomarkers to predict development of CLAD, phenotype of CLAD or prognosis post-CLAD diagnosis are definitely needed. RECENT FINDINGS: Radiological and physiological markers are gradually entering routine clinical practice. In-depth investigation of biological samples including broncho-alveolar lavage, biopsy and serum has generated potential biomarkers involved in fibrogenesis, airway injury and inflammation but none of these are universally accepted or implemented although progress has been made, specifically regarding donor-derived cell-free DNA and donor-specific antibodies. SUMMARY: Although a lot of promising biomarkers have been put forward, a very limited number has made it to routine clinical practice. Nevertheless, a biomarker that leads to earlier detection or more adequate disease phenotyping would advance the field enormously.


Assuntos
Transplante de Pulmão , Pulmão , Aloenxertos , Biomarcadores , Doença Crônica , Humanos , Transplante de Pulmão/efeitos adversos , Transplante Homólogo
16.
Curr Opin Organ Transplant ; 27(3): 211-216, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35649111

RESUMO

PURPOSE OF REVIEW: New chronic lung allograft dysfunction (CLAD) consensus documents were published in 2019, defining four phenotypes; bronchiolitis obliterans syndrome, restrictive allograft syndrome, mixed and undefined. Clearly, validation of these guidelines in a real life cohort is critical. RECENT FINDINGS: Indeed, validation has been performed recently, both after bilateral lung transplantation (LTx) and after single LTx illustrating that precise phenotyping based on pulmonary function alone can be difficult. Undertaking regular chest computed tomography scanning does appear very helpful in establishing the prognosis of the patients with CLAD. SUMMARY: Pulmonary function changes may not always identify the exact phenotype of CLAD and we provide further evidence for the important role of chest imaging at diagnosis and during the follow-up of patients with CLAD.


Assuntos
Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Transplante de Pulmão , Aloenxertos , Bronquiolite Obliterante/diagnóstico por imagem , Bronquiolite Obliterante/etiologia , Humanos , Pulmão/diagnóstico por imagem , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/métodos , Fenótipo
17.
Am J Transplant ; 21(1): 281-290, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32519458

RESUMO

Data concerning sleep-disordered breathing (SDB) after lung transplantation (LTX) are scarce. This study aims to analyze prevalence, associated factors, and impact on survival of moderate to severe SDB in a large cohort of consecutive LTX patients (n = 219). Patients underwent a diagnostic polysomnography 1 year after LTX. Moderate to severe SDB was present in 57.5% of patients, with the highest prevalence in chronic obstructive pulmonary disease/emphysema (71.1%) and pulmonary fibrosis (65.1%). SDB patients were older, mostly male, and had higher body mass index and neck circumference. Nocturnal diastolic and 24-hour blood pressures were higher in SDB patients. In 45 patients, polysomnography was also performed pre-LTX. Compared to pre-LTX, mean apnea/hypopnea index (AHI) increased significantly after LTX. A significant correlation was seen between lung function parameters and AHI, suggesting a role of decreased caudal traction on the pharynx. Presence of SDB had no impact on mortality or prevalence of chronic lung allograft dysfunction. However, survival was better in continuous positive airway pressure (CPAP) compliant SDB patients compared to SDB patients without CPAP treatment. These findings may be pertinent for systematic screening of SDB after LTX.


Assuntos
Transplante de Pulmão , Síndromes da Apneia do Sono , Estudos de Coortes , Pressão Positiva Contínua nas Vias Aéreas , Feminino , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , Polissonografia , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/etiologia
18.
J Viral Hepat ; 28(1): 105-111, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32989861

RESUMO

BACKGROUND: Hepatitis B virus (HBV) immunity is recommended to optimize outcomes after solid organ transplantation (SOT). This study assessed the prevalence and predictors of HBV immunity at the time patients were placed on transplant waiting list over a period from 1997 to 2019 in a low HBV endemic region. METHODS: Data were obtained from the University Hospitals Leuven transplant database. Minors and patients with past/current HBV infection were excluded. From 1986, Belgian patients are covered by the universal infant vaccination; therefore, birth cohort was stratified in those born ≥1986 vs <1986. RESULTS: The study population consisted of 3297 SOT candidates. HBV immunity rate was superior in renal transplant candidates (55.3%), and this number was 21.5%, 15.4% and 16.8% for liver, cardiac and pulmonary transplant candidates, respectively, P < .001. Among liver transplant candidates, HBV immunity rate was 14.8% in decompensated cirrhotic patients and 27.9% in those without advanced cirrhosis (P < .001). The overall immunity rate increased from 19.3% in period 1997-2008 to 32.8% in 2009-2019, P < .001. In multivariable analyses, younger age (odds ratio (OR) 95% confidence interval (CI): 0.97-0.98, P < .001) and birth cohort ≥ 1986 (OR 95% CI: 1.18-2.66, P = .006) were associated with increased HBV immunity. CONCLUSION: An increase in HBV immunity was observed over a 20-year period related to the introduction of universal infant HBV vaccination. Nevertheless, this study highlights the low overall HBV immunity at the time of listing for organ transplantation and points out the need of an increased awareness and vaccination strategy at an early disease stage.


Assuntos
Hepatite B , Transplante de Órgãos , Adulto , Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Vacinas contra Hepatite B , Vírus da Hepatite B , Humanos , Lactente , Prevalência , Vacinação
19.
J Vasc Interv Radiol ; 32(1): 56-60, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33132025

RESUMO

This report discusses 3 bilateral lung transplant recipients (2 female, 1 male) who presented with late hemoptysis (10 y, 18 y, and 19 y after transplantation). All patients had a history of pulmonary infections, bronchiectasis, and/or Aspergillus infection. Arteriography, through catherization of the common femoral artery, demonstrated spontaneous bronchial and systemic neovascularization arising from the thyrocervical trunk, internal thoracic artery, intercostal arteries, and dorsal scapular artery. Embolization was performed with microspheres, polyvinyl alcohol microparticles, and/or glue and effectively terminated hemoptysis. One patient died 10 d later as a result of fungal infection, and the 2 others remained in stable condition (18- and 26-mo postembolization follow-up available).


Assuntos
Artérias Brônquicas/patologia , Embolização Terapêutica , Hemoptise/terapia , Transplante de Pulmão/efeitos adversos , Neovascularização Patológica , Adulto , Artérias Brônquicas/diagnóstico por imagem , Feminino , Hemoptise/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
20.
Transpl Infect Dis ; 23(1): e13398, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32609944

RESUMO

Cutibacterium (C) acnes, a Gram-positive bacterium that is part of the commensal flora, is increasingly noticed as an opportunistic pathogen in serious infections in both immunocompromised and immunocompetent patients. The indolent character and often difficult identification because of its slow growth contribute to delayed diagnosis or underdiagnosis. This report highlights a unique case of a lung transplant recipient with a C acnes intracerebral abscess, and we recommend including this organism in such differential diagnosis. A 66-year-old woman, 2 years after bilateral lung transplantation for chronic obstructive pulmonary disease, presented with frontal headache, without other complaints, and with normal neurological examination. Magnetic resonance imaging showed an extensive lesion in the right frontal lobe with extensive perilesional edema. Given the broad differential diagnosis, stereotactic brain biopsy was performed and culture became positive for C acnes. She was treated with intravenous ceftriaxone for 8 weeks and per oral clindamycin for 6 months, as well as corticosteroids in tapered dose. There was a rapid favorable clinical and radiographic evolution.


Assuntos
Infecções por Bactérias Gram-Positivas , Transplante de Pulmão , Idoso , Abscesso Encefálico , Ceftriaxona , Feminino , Humanos , Propionibacterium acnes
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