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Background Data on the diagnostic accuracy of ultralow-dose (ULD) CT protocols for periodic surveillance in recipients of lung transplant are lacking. Purpose To assess the potential for radiation dose reduction using ULD photon-counting CT (PCT) to detect lung abnormalities in recipients of lung transplant during repeat CT follow-up. Materials and Methods Consecutive adult recipients of lung transplant undergoing same-day standard-of-care low-dose (LD) and ULD PCT from March 2023 to May 2023 were prospectively included. The ULD protocols were performed with two target effective doses comprising 20% (hereafter, ULD1) and 10% (hereafter, ULD2) of the standard LD protocol. The 1-mm reconstructions were reviewed by three readers. Subjective image quality, the visibility of certain anatomic structures (using a five-point Likert scale), and the presence of lung abnormalities were independently assessed. The χ2 or t tests were used to evaluate differences between the ULD1 and ULD2 protocols. Results A total of 82 participants (median age, 64 years [IQR, 54-69 years]; 47 male) were included (41 participants for each ULD protocol). The mean effective doses per protocol were 1.41 mSv ± 0.44 (SD) for LD, 0.26 mSv ± 0.08 for ULD1, and 0.17 mSv ± 0.04 for ULD2. According to three readers, the subjective image quality of the ULD images was deemed diagnostic (Likert score ≥3) in 39-40 (ULD1) and 40-41 (ULD2) participants, and anatomic structures could be adequately visualized (Likert score ≥3) in 33-41 (ULD1) and 34-41 (ULD2) participants. The detection accuracy for individual lung anomalies exceeded 70% for both ULD protocols, except for readers 1 and 3 detecting proximal bronchiectasis and reader 3 detecting bronchial wall thickening and air trapping. No evidence of a statistically significant difference in noise (P = .96), signal-to-noise ratio (P = .77), or reader accuracy (all P ≥ .05) was noted between the ULD protocols. Conclusion ULD PCT was feasible for detecting lung abnormalities following lung transplant, with a tenfold radiation dose reduction. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ciet in this issue.
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Trasplante de Pulmón , Pulmón , Dosis de Radiación , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Anciano , Estudios Prospectivos , Pulmón/diagnóstico por imagen , Fotones , Enfermedades Pulmonares/diagnóstico por imagenRESUMEN
OBJECTIVES: Inspiratory muscle training is used in rehabilitation to exercise respiratory muscles in various conditions associated with limited ventilatory reserve. In this review, we investigated inspiratory muscle training in lung transplant candidates and recipients. MATERIALS AND METHODS: We searched 5 primary databases from inception through April 2024. Two key word entries, "lung transplantation" and "inspiratory muscle training," were matched using the Boolean operator AND. No filters were applied for document type, age, sex, publication date, language, and subject. RESULTS AND CONCLUSIONS: The searched databases returned 119 citations. Seven articles that considered 64 patients (47% female) were included in the final analysis, with 1 study involving a pediatric patient. Lung transplant recipients used a threshold trainer at 15% to 60% of maximal inspiratory pressure and mostly exercised twice daily for 10 to 15 minutes per session. Lung transplant candidates exercised at 30% to >50% of maximal inspiratory pressure twice daily, performing 30 to 60 inspirations or for 15 minutes. The highest inspiratory muscle strength was observed in a series of adult lung transplant recipients whose mean value improved by 31.8 ± 14.6 cmH2O versus baseline after treatment. To the same extent, the highest value of maximal inspiratory pressure was detected in a pediatric patient who scored 180 cmH2O after training. Overall, participants obtained improvements in lung function (forced expiratory volume in 1 second, forced vital capacity), functional performance, dyspnea intensity, and exercise tolerance. Inspiratory muscle training is easy to perform and can be done at home without specific supervision (in adults) before or after a lung transplant. Nevertheless, additional rigorous investigations should aim to replicate the positive effects reported in the present review.
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Ejercicios Respiratorios , Trasplante de Pulmón , Pulmón , Fuerza Muscular , Recuperación de la Función , Músculos Respiratorios , Humanos , Músculos Respiratorios/fisiopatología , Femenino , Resultado del Tratamiento , Masculino , Pulmón/fisiopatología , Adulto , Niño , Persona de Mediana Edad , Adolescente , Adulto Joven , Inhalación , Factores de Tiempo , Tolerancia al Ejercicio , AncianoRESUMEN
Perioperative antibiotic prophylaxis (PAP) in lung transplant recipients (LuTRs) has high heterogeneity between centers. Our aim was to investigate retrospectively the approach to PAP in our center over a 20-year period (2002-2023), and its impact on early post-operative infections (EPOIs) after lung transplantation (LuT). Primary endpoint was diagnosis of EPOI, defined as any bacterial infection including donor-derived events diagnosed within 30 days from LuT. Main exposure variables were type of PAP (combination vs. monotherapy) and PAP duration. We enrolled 111 LuTRs. PAP consisted of single-agent or combination regimens in 26 (25.2%) and 85 (74.8%) LuTR. Median PAP duration was 10 days (IQR 6-13) days. Piperacillin/tazobactam was the most common agent used either as monotherapy (n = 21, 80.7%) or as combination with levofloxacin (n = 79, 92.9%). EPOIs were diagnosed in 30 (27%) patients. At multivariable analysis no advantages were found for combination regimens compared to single-agent PAP in preventing EPOI (OR: 1.57, 95% CI: 0.488-5.068, p:0.448). The impact of PAP duration on EPOIs development was investigated including duration of PAP ≤6 days as main exposure variables, without finding a significantly impact (OR:2.165, 95% CI: 0.596-7.863, p: 0.240). Our results suggest no advantages for combination regimens PAP in preventing EPOI in LuTR.
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Antibacterianos , Profilaxis Antibiótica , Trasplante de Pulmón , Humanos , Trasplante de Pulmón/efectos adversos , Profilaxis Antibiótica/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Adulto , Levofloxacino/uso terapéutico , Levofloxacino/administración & dosificación , Anciano , Combinación Piperacilina y Tazobactam/uso terapéutico , Combinación Piperacilina y Tazobactam/administración & dosificación , Infecciones Bacterianas/prevención & control , Infecciones Bacterianas/etiología , Complicaciones Posoperatorias/prevención & control , Quimioterapia CombinadaRESUMEN
BACKGROUND: Post-lung transplantation (LTx) fluid accumulation can lead to dilution of serum creatinine (SCr). We hypothesized that fluid accumulation might impact the diagnosis, staging, and outcome of posttransplant acute kidney injury (AKI). METHODS: In this retrospective study, we analyzed data from 131 adult LTx patients at a single German lung center between 2005 and 2018. We assessed the occurrence of AKI within 7 days posttransplant, both before and after SCr-adjustment for fluid balance (FB), and investigated its impact on all-cause mortality. Transient and persistent AKIs were defined as return to baseline kidney function or continuation of AKI beyond 72 h of onset, respectively. RESULTS: AKI was diagnosed in 58.8% of patients according to crude SCr values. When considering FB-adjusted SCr values, AKI severity was underestimated in 20.6% of patients, that is, AKI was detected in an additional 6.9% of patients and led to AKI upstaging in 23.4% of cases. Patients initially underestimated but detected with AKI only after FB adjustment had higher mortality compared to those who did not meet AKI criteria (hazard ratio [HR] 2.98; 95% confidence interval [CI] 1.06, 8.36; p = 0.038). Persistent AKI was associated with higher mortality than transient AKI, regardless of using crude or adjusted SCr values (p < 0.05). Persistent AKI emerged as an independent risk factor for mortality (HR 2.35; 95% CI 1.29, 4.30; p = 0.005). CONCLUSION: Adjusting for FB and evaluating renal recovery patterns post-AKI may enhance the sensitivity of AKI detection. This approach could help identify patients with poor prognosis and potentially improve outcomes in lung transplant recipients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03039959, NCT03046277.
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Lesión Renal Aguda , Trasplante de Pulmón , Complicaciones Posoperatorias , Humanos , Masculino , Femenino , Trasplante de Pulmón/efectos adversos , Estudios Retrospectivos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Persona de Mediana Edad , Pronóstico , Complicaciones Posoperatorias/diagnóstico , Estudios de Seguimiento , Factores de Riesgo , Tasa de Supervivencia , Tasa de Filtración Glomerular , Adulto , Receptores de Trasplantes , Índice de Severidad de la Enfermedad , Supervivencia de Injerto , Creatinina/sangreRESUMEN
Lung transplantation offers a lifesaving option for patients with end-stage lung disease, but it is marred by a high risk of post-transplant infections, particularly involving multidrug-resistant bacteria, Cytomegalovirus, and fungal pathogens. This elevated infection rate, the highest among solid organ transplants, poses a significant challenge for clinicians, particularly within the first year post-transplantation, where infections are the leading cause of mortality. The direct exposure of lung allografts to the external environment exacerbates this vulnerability leading to constant immune stimulation and consequently to an elevated risk of triggering alloimmune responses to the lung allograft. The necessity of prolonged immunosuppression to prevent allograft rejection further complicates patient management by increasing susceptibility to infections and neoplasms, and complicating the differentiation between rejection and infection, which require diametrically opposed management strategies. This review explores the intricate balance between preventing allograft rejection and managing the heightened infection risk in lung transplant recipients.
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Rechazo de Injerto , Trasplante de Pulmón , Humanos , Trasplante de Pulmón/efectos adversos , Rechazo de Injerto/inmunología , Animales , Terapia de InmunosupresiónRESUMEN
Lung transplant recipients (LTRs) are particularly at risk of developing severe coronavirus disease-2019 (COVID-19), but are also difficult to protect by vaccination due to their immunocompromised state. Here, we investigated the immunogenicity of mRNA-based COVID-19 vaccines in LTRs who had a prior natural SARS-CoV-2 infection. At a median of 184 days after SARS-CoV-2 infection, LTRs were vaccinated twice with the mRNA-1273 COVID-19 vaccine, with a 28-day interval. Blood samples were obtained pre-vaccination, 28 days after the first dose, and 28 days and 6 months after the second dose. Spike (S-) and nucleocapsid (N-) specific antibodies were measured, as well as neutralization of the ancestral and Omicron BA.5 variant. S-specific T cell responses were evaluated using IFN-γ ELISpotï¼IGRA, and activation markers by flow cytometry. Phenotyping of T cells was performed by using high-resolution spectral flow cytometry. Most LTRs with prior infection had detectable S-specific antibodies and T cells at baseline. After the first vaccination, S-specific antibody levels increased significantly; an additional increase was observed after the second vaccination. N-specific antibodies decreased during the study period, indicative of the fact that no further breakthrough infections occurred. An increase in IFN-γ producing T cells was observed after the first vaccination, but no additional boost could be detected after the second vaccination. Antibody levels and virus-specific T cell responses remained significantly higher compared to pre-vaccination levels at 6 months post-vaccination, indicating an additive and durable effect of vaccination after infection in LTRs. Neutralizing antibodies were detected against the ancestral strain and retained cross-reactivity with Omicron BA.5, albeit at lower levels. Moreover, the quantity and phenotype of SARS-CoV-2 spike-specific T cells were similar in LTRs compared to controls with hybrid immunity. In conclusion, mRNA-based COVID-19 vaccines are immunogenic in LTRs with prior immunity, and antibody and T cell responses are durable up to 6 months post-vaccination.
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Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Trasplante de Pulmón , SARS-CoV-2 , Linfocitos T , Receptores de Trasplantes , Humanos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Linfocitos T/inmunología , SARS-CoV-2/inmunología , Persona de Mediana Edad , Masculino , Femenino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacuna nCoV-2019 mRNA-1273/inmunología , Adulto , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Glicoproteína de la Espiga del Coronavirus/inmunología , Anciano , Vacunación , Inmunogenicidad VacunalRESUMEN
BACKGROUND: There is a lack of information on the waitlist performance and post-transplant outcomes of lung transplants in elderly recipients in Korea. METHODS: We retrospectively reviewed and analyzed data from the Korean Network for Organ Sharing database between March 2010 and August 2023. RESULTS: In total, 2574 patients were listed for lung transplantation during the study period, with 511 (19.9%) of them being over 65 years of age. Among these, 188 patients (36.8%) underwent transplantation, while 184 patients (36%) passed away without undergoing transplantation at the time of data extraction. The most prevalent underlying disease on the waitlist was idiopathic pulmonary fibrosis, accounting for 68.1%. The 1-year survival rate was significantly lower in the elderly compared to that in the nonelderly (65.4 vs. 75.4%; p = .004). In the multivariate Cox analysis, elderly (hazard ratio [HR], 1.49; 95% CI, 1.14-1.97; p = .004) and a high urgent status at registration (HR, 1.83; 95% CI, 1.40-2.40; p < .001) were significantly associated with post-transplant 1-year mortality. Kaplan-Meier curves demonstrated a significant difference in post-transplant mortality based on the urgency status at enrollment (χ2 = 8.302, p = .016). Even with the same highly urgent condition at the time of transplantation, different prognoses were observed depending on the condition at listing (χ2 = 9.056, p = .029). CONCLUSION: The elderly exhibited worse transplant outcomes than nonelderly adults, with a highly urgent status at registration identified as a significant risk factor. Unprepared, highly urgent transplantation was associated with poor outcomes.
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Trasplante de Pulmón , Listas de Espera , Humanos , Trasplante de Pulmón/mortalidad , Masculino , Femenino , Listas de Espera/mortalidad , República de Corea/epidemiología , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Tasa de Supervivencia , Estudios de Seguimiento , Pronóstico , Factores de Riesgo , Adulto , Supervivencia de Injerto , Obtención de Tejidos y Órganos/estadística & datos numéricos , Complicaciones Posoperatorias/mortalidad , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Rechazo de Injerto/epidemiología , Enfermedades Pulmonares/cirugía , Enfermedades Pulmonares/mortalidadRESUMEN
Idiopathic pulmonary fibrosis (IPF) is a severe and currently incurable disease that is associated with irreversible fibrotic remodeling of the lung parenchyma. Pathological remodeling of the lung leads to damage of the alveolo-capillary barrier. There is a reduction in the diffusing capacity of the lungs for respiratory gases. Later, changes in the mechanical properties of lung tissue occur - their compliance decreases and respiratory work increases. Impaired respiratory gases exchange with restrictive ventilatory failure lead to tissue hypoxia and muscle weakness. Progressive respiratory insufficiency develops. The triggers of fibrotic remodeling of the lung are currently unknown, as are the pathomechanisms that keep this process active. IPF can only be slowed pharmacologically, not reversed. It is therefore very important to start its treatment as soon as possible. Early detection of IPF patients requires a multidisciplinary approach. Diagnosis, treatment initiation, and monitoring in specialized centers offer the best chance of slowing disease progression, enhancing quality of life, and extending patient survival. In addition to antifibrotic therapy, good lifestyle management, maintenance of physical fitness and treatment of associated chronic diseases such as diabetes and cardiac comorbidities are important. Lung transplantation is an option for some patients with IPF. This is a challenging treatment modality, requiring close collaboration with transplant centers and expert selection of suitable candidates, influenced, among other things, by the availability of suitable donor lungs. Our article aims to provide current information about IPF, focusing on its functional consequences and clinical manifestation. We discuss the molecular and cellular mechanisms potentially involved in IPF development, as well as the morphological changes observed in lung biopsies and high-resolution computed tomography (HRCT) images. Finally, we summarize the existing treatment options. Key words: Idiopathic pulmonary fibrosis, Lung biopsy, HRCT, Antifibrotic therapy, Lung transplantation.
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Fibrosis Pulmonar Idiopática , Humanos , Fibrosis Pulmonar Idiopática/terapia , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/fisiopatología , Fibrosis Pulmonar Idiopática/patología , Animales , Trasplante de Pulmón , Pulmón/patología , Pulmón/fisiopatologíaRESUMEN
PURPOSE OF REVIEW: Blastocyst complementation represents a promising frontier in next-generation lung replacement therapies. This review aims to elucidate the future prospects of lung blastocyst complementation within clinical settings, summarizing the latest studies on generating functional lungs through this technique. It also explores and discusses host animal selection relevant to interspecific chimera formation, a challenge integral to creating functional human lungs via blastocyst complementation. RECENT FINDINGS: Various gene mutations have been utilized to create vacant lung niches, enhancing the efficacy of donor cell contribution to the complemented lungs in rodent models. By controlling the lineage to induce gene mutations, chimerism in both the lung epithelium and mesenchyme has been improved. Interspecific blastocyst complementation underscores the complexity of developmental programs across species, with several genes identified that enhance chimera formation between humans and other mammals. SUMMARY: While functional lungs have been generated via intraspecies blastocyst complementation, the generation of functional interspecific lungs remains unrealized. Addressing the challenges of controlling the host lung niche and selecting host animals relevant to interspecific barriers between donor human and host cells is critical to enabling the generation of functional humanized or entire human lungs in large animals.
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Blastocisto , Trasplante de Pulmón , Pulmón , Humanos , Animales , Pulmón/cirugía , Blastocisto/metabolismo , Quimera por Trasplante , Enfermedades Pulmonares/cirugía , Enfermedades Pulmonares/genéticaRESUMEN
PURPOSE OF REVIEW: This review delves into the intricate landscape of airway complications post lung transplantation. With the rising prevalence of end-stage lung disease and the increasing number of lung transplantation worldwide, understanding and effectively managing airway complications are crucial. Given the nuanced nature of these complications and the array of treatment options available, this review aims to provide a comprehensive overview of how to identify, classify, mitigate risk factors for, and manage these complications. RECENT FINDINGS: Several donor, recipient, and surgical risk factors are associated with the increased risk of airway complications. In managing these complications, bronchoscopic interventions, notably balloon dilation and stenting, are pivotal. Although self-expanding metallic stents offer versatility, silicone stents are preferred in certain scenarios for their durability. Emerging techniques such as biodegradable stents and advancing imaging modalities show promise in mitigating complications and improving outcomes. SUMMARY: These findings underscore the significance of a multidisciplinary approach and personalized treatment algorithms in managing airway complications post lung transplantation. By elucidating specific indications and complications of treatment modalities, this review serves as a valuable resource for optimally managing airway complications. Ongoing research into novel interventions holds promise for further enhancing outcomes in this challenging clinical setting.
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Broncoscopía , Trasplante de Pulmón , Stents , Trasplante de Pulmón/efectos adversos , Humanos , Factores de Riesgo , Resultado del Tratamiento , DilataciónRESUMEN
BACKGROUND End-stage renal disease is a major issue in the management of patients undergoing lung transplantation. Combined kidney-lung transplantation (CKLT) and kidney after lung transplantation (KALT) are the 2 preferred solutions to manage this situation. To evaluate these strategies, we describe kidney and lung graft outcomes and patient survival in patients managed with CKLT and KALT. MATERIAL AND METHODS We conducted a retrospective single-center cohort study. Patients who underwent a CKLT or a KALT were included in this study. Retrospective extraction of data from medical records was performed. RESULTS Seventeen patients underwent CKLT and 9 underwent KALT. Most of the patients had cystic fibrosis and presented renal failure related to anti-calcineurin toxicity. The 30-day and 1-year survival of CKLT recipients were both 75.6%. No patients with KALT died during the follow-up. Kidney graft prognosis was almost exclusively influenced by patient survival in relation to postoperative lung transplant complications. The rate of severe surgical complications was close to 60% for CKLT compared with 30% for KALT. The kidney graft function (estimated kidney graft function) did not differ according to the transplantation strategy. CONCLUSIONS KALT is a safe option, with postoperative morbidity and renal graft function identical to those of kidney transplantation in non-lung-transplanted patients. The results of CKLT depend mainly on the morbidity associated with lung transplantation but remain an attractive option for patients with respiratory failure associated with end-stage renal disease. The choice of transplant strategy must also take into account the most ethical and efficient allocation of kidney grafts.
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Supervivencia de Injerto , Fallo Renal Crónico , Trasplante de Riñón , Trasplante de Pulmón , Humanos , Trasplante de Pulmón/efectos adversos , Trasplante de Pulmón/mortalidad , Trasplante de Pulmón/métodos , Estudios Retrospectivos , Trasplante de Riñón/mortalidad , Trasplante de Riñón/efectos adversos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Fallo Renal Crónico/cirugía , Complicaciones Posoperatorias/etiología , Adulto Joven , Resultado del TratamientoRESUMEN
BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension with a low incidence. Despite pulmonary endarterectomy(PEA) being the preferred treatment for CTEPH, for patients who failed medical therapy and who are not suitable candidates for PEA, lung transplantation (LT) is still the only effective treatment for end-stage CTEPH; however, there are currently very few reports on the efficacy of LT for CTEPH. METHODS: We retrospectively analyzed the clinical data of seven patients diagnosed with CTEPH between July 2019 and July 2021. The follow-up deadline was March, 2022. RESULTS: The mean age at admission was 54 ± 12 years. The average value of mean pulmonary artery pressure (mPAP) was 40 ± 5 mmHg. The mean preoperative oxygenation index(PaO2/FiO2) was 203 ± 56 mm Hg. After evaluation, one patient underwent left LT and the rest underwent bilateral LT. Three patients received intraoperative veno-venous extracorporeal membrane oxygenation (ECMO) support, and four patients received intraoperative veno-arterial ECMO support. The average postoperative mPAP was 19 ± 4 mmHg. The mean postoperative oxygenation index(PaO2/FiO2) was 388 ± 83 mmHg. There was a significant difference between the preoperative and postoperative mPAP and oxygenation index(PaO2/FiO2). All patients recovered well and were discharged 37 ± 19 days postoperatively. The mean follow-up duration was 19 ± 8 months. There was no recurrence of CTEPH. CONCLUSIONS: LT is an effective treatment for end-stage CTEPH, which can improve cardiopulmonary function and quality of life and prolong survival. Patients who are unable to tolerate PEA should be considered for LT as early as possible when internal medicine failed.
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Hipertensión Pulmonar , Trasplante de Pulmón , Embolia Pulmonar , Humanos , Persona de Mediana Edad , Femenino , Masculino , Estudios Retrospectivos , Hipertensión Pulmonar/cirugía , Embolia Pulmonar/cirugía , Embolia Pulmonar/complicaciones , Adulto , Enfermedad Crónica , Resultado del Tratamiento , Oxigenación por Membrana Extracorpórea/métodos , Anciano , Endarterectomía/métodosRESUMEN
Tissue fibrosis remains unamenable to meaningful therapeutic interventions and is the primary cause of chronic graft failure after organ transplantation. Eukaryotic translation initiation factor (eIF4E), a key translational regulator, serves as convergent target of multiple upstream profibrotic signaling pathways that contribute to mesenchymal cell (MC) activation. Here, we investigate the role of MAP kinase-interacting serine/threonine kinase-induced (MNK-induced) direct phosphorylation of eIF4E at serine 209 (Ser209) in maintaining fibrotic transformation of MCs and determine the contribution of the MNK/eIF4E pathway to the pathogenesis of chronic lung allograft dysfunction (CLAD). MCs from patients with CLAD demonstrated constitutively higher eIF4E phosphorylation at Ser209, and eIF4E phospho-Ser209 was found to be critical in regulating key fibrogenic protein autotaxin, leading to sustained ß-catenin activation and profibrotic functions of CLAD MCs. MNK1 signaling was upregulated in CLAD MCs, and genetic or pharmacologic targeting of MNK1 activity inhibited eIF4E phospho-Ser209 and profibrotic functions of CLAD MCs in vitro. Treatment with an MNK1/2 inhibitor (eFT-508) abrogated allograft fibrosis in an orthotopic murine lung-transplant model. Together these studies identify what we believe is a previously unrecognized MNK/eIF4E/ATX/ß-catenin signaling pathway of fibrotic transformation of MCs and present the first evidence, to our knowledge, for the utility of MNK inhibitors in fibrosis.
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Aloinjertos , Factor 4E Eucariótico de Iniciación , Trasplante de Pulmón , Proteínas Serina-Treonina Quinasas , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Animales , Ratones , Fosforilación , Humanos , Factor 4E Eucariótico de Iniciación/metabolismo , Factor 4E Eucariótico de Iniciación/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Masculino , Fibrosis , Femenino , Transducción de SeñalRESUMEN
Idiopathic pulmonary fibrosis is a major cause of death with few treatment options. Here, we demonstrate the therapeutic efficacy for lung fibrosis of adult lung cell transplantation using a single-cell suspension of the entire lung in two distinct mouse systems: bleomycin treatment and mice lacking telomeric repeat-binding factor 1 expression in alveolar type 2 (AT2) cells (SPC-Cre TRF1fl/fl), spontaneously developing fibrosis. In both models, the progression of fibrosis was associated with reduced levels of host lung progenitors, enabling engraftment of donor progenitors without any additional conditioning, in contrast to our previous studies. Two months after transplantation, engrafted progenitors expanded to form numerous donor-derived patches comprising AT1 and AT2 alveolar cells, as well as donor-derived mesenchymal and endothelial cells. This lung chimerism was associated with attenuation of fibrosis, as demonstrated histologically, biochemically, by computed tomography imaging, and by lung function measurements. Our study provides a strong rationale for the treatment of lung fibrosis using lung cell transplantation.
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Modelos Animales de Enfermedad , Animales , Ratones , Bleomicina , Fibrosis Pulmonar/terapia , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/metabolismo , Pulmón/patología , Pulmón/metabolismo , Fibrosis Pulmonar Idiopática/terapia , Fibrosis Pulmonar Idiopática/patología , Trasplante de Pulmón/efectos adversosRESUMEN
Chromoblastomycosis (CBM), also known as chromomycosis is a chronic, granulomatous fungal infection of the skin and subcutaneous tissue. It usually occurs by the traumatic inoculation of various dematiaceous fungi and is more common in the developing world. This condition is rare in North America and the developed world. Herein, we present a case of a 75-year-old man who received a bilateral lung transplant 4 months prior and presented for evaluation of a painful, erythematous papule on the elbow which was diagnosed as CBM. This case highlights that immunosuppression used in patients who undergo solid organ transplantation not only increases the risk of opportunistic infections like CBM but can also be confused for cutaneous squamous cell carcinoma as both these entities share many overlapping clinical and histopathologic features and may be a potential source of misdiagnosis.
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Carcinoma de Células Escamosas , Cromoblastomicosis , Neoplasias Cutáneas , Humanos , Masculino , Anciano , Carcinoma de Células Escamosas/diagnóstico , Cromoblastomicosis/diagnóstico , Neoplasias Cutáneas/diagnóstico , Diagnóstico Diferencial , Trasplante de Pulmón/efectos adversos , Antifúngicos/uso terapéutico , Huésped Inmunocomprometido , Receptores de Trasplantes , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéuticoRESUMEN
During the last few years, cell-free DNA (cfDNA) has emerged as a possible non-invasive biomarker for prediction of complications after lung transplantation. We previously published a proof-of-concept study using a digital droplet polymerase chain reaction (ddPCR)-based method for detection of cfDNA. In the current study, we aimed to further evaluate the potential clinical usefulness of detecting chronic lung allograft dysfunction (CLAD) using three different ddPCR applications measuring and calculating the donor fraction (DF) of cfDNA as well as one method using the absolute amount of donor-derived cfDNA. We analyzed 246 serum samples collected from 26 lung transplant recipients. Nine of the patients had ongoing CLAD at some point during follow-up. All four methods showed statistically significant elevation of the measured variable in the CLAD samples compared to the non-CLAD samples. The results support the use of ddPCR-detected cfDNA as a potential biomarker for prediction of CLAD. These findings need to be validated in a subsequent prospective study.
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Biomarcadores , Ácidos Nucleicos Libres de Células , Trasplante de Pulmón , Humanos , Trasplante de Pulmón/efectos adversos , Ácidos Nucleicos Libres de Células/sangre , Masculino , Femenino , Persona de Mediana Edad , Adulto , Biomarcadores/sangre , Donantes de Tejidos , Anciano , Reacción en Cadena de la Polimerasa/métodos , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Disfunción Primaria del Injerto/sangre , Disfunción Primaria del Injerto/diagnóstico , Disfunción Primaria del Injerto/etiología , Aloinjertos , Rechazo de Injerto/sangre , Rechazo de Injerto/diagnósticoRESUMEN
BACKGROUND: To assess changes in bone density and vertebral body height of patients undergoing lung transplant surgery using computed tomography (CT). METHODS: This institutional review board (IRB) approved retrospective observational study enrolled patients with a history of lung transplant who had at least two chest CT scans. Vertebral body bone density (superior, middle, and inferior sections) and height (anterior, middle, and posterior sections) were measured at T1-T12 at baseline and follow up CT scans. Changes in the mean bone density, mean vertebral height, vertebral compression ratio (VBCR), percentage of anterior height compression (PAHC), and percentage of middle height compression (PMHC) were calculated and analyzed. RESULTS: A total of 93 participants with mean age of 58 ± 12.3 years were enrolled. The most common underlying disease that led to lung transplants was interstitial lung diseases (57 %). The inter-scan interval was 34.06 ± 24.8 months. There were significant changes (p-value < 0.05) in bone density at all levels from T3 to T12, with the greatest decline at the T10 level from 163.06 HU to 141.84 HU (p-value < 0.05). The average VBCR decreased from 96.91 to 96.15 (p-value < 0.05). CONCLUSION: Routine chest CT scans demonstrate a gradual decrease in vertebral body bone density over time in lung transplant recipients, along with evident anatomic changes such as vertebral body bone compression. This study shows that utilizing routine chest CT for lung transplant recipients can be regarded as a cost-free tool for assessing the vertebral body bone changes in these patients and potentially aiding in the prevention of complications related to osteoporosis.