RESUMEN
SUMMARY: The purpose of this study is to evaluate changes in the trachea and bronchi using 3-dimensional reconstruction images obtained from the initial and follow-up computed tomography (CT) scans of COVID-19 patients. A hundred COVID-19 patients over the age of 18 were included in our study. CT images were transferred to Mimics software, and a 3-dimensional reconstruction of the trachea and bronchi was performed. The initial and follow-up CT images of COVID-19 patients were graded as none (grade 0), mild (grade 1), moderate (grade 2), and severe (grade 3) according to the total lung severity score. The patients were divided into progression and regression groups according to the grade increase/decrease between the initial and follow-up CTs. Moreover, the patients were divided into groups as 0-2 weeks, 2-4 weeks, 4-12 weeks, and over 12 weeks according to the duration between the initial and follow-up CTs. The mean cross-sectional area, circumference, and diameter measurements of the right upper lobar bronchus, intermediate bronchus, middle lobar bronchus, and left lower lobar bronchus decreased in the follow-up CTs of the progression group. This decrease was not found to be statistically significant. In the follow-up CTs of the regression group, the left upper lobar bronchus and left lower lobar bronchus measurements increased but not statistically significant. Upon comparing the onset of the disease and the follow-up period, statistically significant changes did not occur in the trachea, main bronchus, and lobar bronchus of COVID-19 patients.
El propósito de este estudio fue evaluar los cambios en la tráquea y los bronquios utilizando imágenes de reconstrucción tridimensionales obtenidas de las tomografías computarizadas (TC) iniciales y de seguimiento de pacientes con COVID-19. En nuestro estudio se incluyeron 100 pacientes con COVID-19 mayores de 18 años. Las imágenes de TC se transfirieron al software Mimics y se realizó una reconstrucción tridimensional de la tráquea y los bronquios. Las imágenes de TC iniciales y de seguimiento de los pacientes con COVID-19 se calificaron como ninguna (grado 0), leve (grado 1), moderada (grado 2) y grave (grado 3) según la puntuación total de gravedad pulmonar. Los pacientes se dividieron en grupos de progresión y regresión según el aumento/disminución del grado entre las TC iniciales y de seguimiento. Además, los pacientes se dividieron en grupos de 0 a 2 semanas, de 2 a 4 semanas, de 4 a 12 semanas y de más de 12 semanas según la duración entre la TC inicial y la de seguimiento. Las mediciones medias del área transversal, la circunferencia y el diámetro del bronquio lobar superior derecho, el bronquio intermedio, el bronquio lobar medio y el bronquio lobar inferior izquierdo disminuyeron en las TC de seguimiento del grupo de progresión. No se encontró que esta disminución fuera estadísticamente significativa. En las TC de seguimiento del grupo de regresión, las mediciones del bronquio lobar superior izquierdo y del bronquio lobar inferior izquierdo aumentaron pero no fueron estadísticamente significativas. Al comparar el inicio de la enfermedad y el período de seguimiento, no ocurrieron cambios estadísticamente significativos en la tráquea, el bronquio principal y el bronquio lobar de los pacientes con COVID-19.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Tráquea/diagnóstico por imagen , Bronquios/diagnóstico por imagen , COVID-19/patología , Tráquea/patología , Bronquios/patología , Tomografía Computarizada por Rayos X , Estudios de Seguimiento , Impresión TridimensionalRESUMEN
Central airway obstruction refers to the occlusion of more than 50% of the trachea, main stem bronchi, or lobar bronchus. It can potentially become a life-threatening condition. Pulmonary hamartomas (PH) are rare tumors with an incidence of 0.25%, constituting about 8% of all benign lung neoplasms. Only 10% of PH occur endobronchially, while the remaining appear peripherally. We present the case of a women with an endobronchial hamartoma that required emergent resection by bronchoscopy. This is 44-year-old woman, with a history of an endobronchial mass on the right main stem bronchus (RMSB) without histopathological diagnosis or surgical management. She presented with a history of chronic cough and expectoration. Upon admission, a chest X-ray was performed, showing opacities of the right lung and amputations of the RMSB. Bronchoscopy was performed and a tumor-like mass that occludes the RMSB was found, with valve effect causing intermittent occlusion. In anesthetic induction, she presents severe airway obstruction and cardiorespiratory arrest. During resuscitation maneuvers, the lesion that was obstructing the light is seen and resection was performed with electrocautery and cryotherapy probes. Histopathological report described an endobronchial chondromesenchymal hamartoma, with no signs of malignancy. The control X-ray showed adequate re-expansion of the right lung. In conclusion, although endobronchial hamartoma has a low incidence and has a slow growth rate, it can manifest as severe airway obstruction. To achieve a complete resection of an endobronchial lesion, both rigid and/or flexible bronchoscopy plus multimodal interventions are recommended.
Asunto(s)
Enfermedades Bronquiales , Hamartoma , Neoplasias Pulmonares , Humanos , Femenino , Adulto , Enfermedades Bronquiales/diagnóstico , Enfermedades Bronquiales/etiología , Enfermedades Bronquiales/cirugía , Broncoscopía , Bronquios/patología , Neoplasias Pulmonares/complicaciones , Hamartoma/complicaciones , Hamartoma/diagnóstico , Hamartoma/cirugíaRESUMEN
INTRODUCCIÓN. La enfermedad relacionada con IgG4 es una patología fibroinflamatoria multiorgánica, de origen desconocido, que simula trastornos malignos, infecciosos e inflamatorios. Los criterios del American College of Rheumatology y la European League against Rheumatism 2019, son útiles para el diagnóstico diferencial de ésta enfermedad cuando se no se cuenta con evidencia de inmunoglobulina G4 en sangre. CASO CLÍNICO. Paciente hombre de 45 años de edad, nacido en Ambato-Ecuador, con ingreso en noviembre del 2017, en emergencias del Hospital de Especialidades Carlos Andrade Marín, con presencia de tos con hemoptisis leve, febrícula, astenia, pérdida de peso e hiporexia de dos semanas de evolución. Se realizó múltiples exámenes, tras observar infiltrados pulmonares intersticiales, con elevación de inmunoglobulina G en suero, negativas para malignidad; se sospechó de enfermedad relacionada a inmunoglobulina G4. Se ampliaron los estudios para descartar otras patologías más prevalentes y cuyo diferencial es primordial. Se inició tratamiento con prednisona y micofenolato con buena respuesta clínica; durante dos años. DISCUSIÓN. La evidencia científica registró que el hallazgo más importante en la enfermedad relacionada con inmunoglobulina G4 fue un aumento de sus niveles séricos. La recurrencia de la enfermedad en un órgano afectado o la aparición de un nuevo órgano involucrado pudo conducir al diagnóstico en el caso presentado. CONCLUSIÓN. La enfermedad relacionada con inmunoglobulina G4 al ser una patología heterogénea, inmunomediada, al simular otras afecciones puede retrasar el diagnóstico; se debe tener una alta sospecha clínica, si al excluir otros procesos infecciosos, autoinmunes y/o eoplásicos, hay evidencia de patología fibroesclerosante multiorgánica sin causa establecida.
INTRODUCTION. IgG4-related disease is a multiorgan fibroinflammatory pathology of unknown origin that mimics malignant, infectious, and inflammatory disorders. The criteria of the American College of Rheumatology and the European League against Rheumatism 2019 are useful for the differential diagnosis of this disease when there is no evidence of immunoglobulin G4 in blood. CLINICAL CASE. 45-year-old male patient, born in Ambato-Ecuador, with admission in November 2017, in the emergency room of the Hospital de Especialidades Carlos Andrade Marín, with the presence of cough with mild hemoptysis, fever, asthenia, weight loss and hyporexia of two weeks of evolution. Multiple tests were performed, after observing interstitial pulmonary infiltrates, with elevated serum immunoglobulin G, negative for malignancy; immunoglobulin G4-related disease was suspected. Studies were extended to rule out other more prevalent pathologies whose differential is paramount. Treatment with prednisone and mycophenolate was started with good clinical response; for two years. DISCUSSION. The scientific evidence recorded that the most important finding in immunoglobulin G4-related disease was an increase in its serum levels. Recurrence of the disease in an affected organ or the appearance of a new involved organ could have led to the diagnosis in the presented case. CONCLUSION. Immunoglobulin G4-related disease, being a heterogeneous, immune-mediated pathology, by simulating other conditions may delay diagnosis; a high clinical suspicion should be maintained if, when other infectious, autoimmune and/or neoplastic processes are excluded, there is evidence of multiorgan fibrosclerosing pathology without established cause.
Asunto(s)
Humanos , Masculino , Adulto , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/sangre , Órbita/patología , Glándula Parótida/patología , Bronquios/patología , Biomarcadores/sangre , Diagnóstico Diferencial , Edema , Enfermedad Relacionada con Inmunoglobulina G4/patología , Hipertrofia , Pulmón/patologíaRESUMEN
INTRODUCTION: Acquired pulmonary bullous emphysema is an infrequent complication of assisted ventilation in the premature infant that is difficult to manage. OBJECTIVE: The goal of this report is to present the case of a premature infant who required selective bronchial intubation as well as to provide a review of the current literature on the subject. CLINICAL CASE: The patient is a 27-week gestational age neonatal female patient whose clinical course was complicated by left unilateral bullous emphysema during assisted ventilation for respiratory distress syndrome. Lower peak inspiratory pressures, higher res piratory frequencies, patient positioning, and lower inspiration time failed to improve the patient's condition. The left lung became critically overinflated and compressed the right lung to the point of atelectasis. The patient was selectively mono intubated through the right main bronchus, which resulted in a collapse of the left emphysematous lung. Single right lung ventilation was continued for 48 hours before restarting conventional ventilation of both lungs. Our patient improved significantly, was extubated 6 days after the procedure and later discharged home with normal chest x-ray images. CONCLUSION: Selective bronchial intubation is a safe and effective procedure in cases of acquired bu llous emphysema when usual ventilatory management fails.
Asunto(s)
Bronquios/anomalías , Enfermedades del Prematuro , Intubación Intratraqueal/métodos , Enfisema Pulmonar/terapia , Bronquios/patología , Enfisema , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Intubación Intratraqueal/efectos adversosRESUMEN
BACKGROUND: The interaction of Cryptococcus neoformans with airway epithelial cells is crucial for the establishment of cryptococcosis. Aspirin-triggered-resolvin D1 (AT-RvD1) is a lipid mediator produced during the resolution of inflammation and demonstrates anti-inflammatory and pro-resolution effects in several inflammatory experimental models including in the airways. METHOD: Here, we evaluated the effects of AT-RvD1 (1, 10 or 100 nM) on human bronchial epithelial cells (BEAS-2B) stimulated with C. neoformans (1, 10 or 100 multiplicities of infection; MOI). RESULTS: After 24 h, C. neoformans (all MOI) demonstrated no cytotoxic effects and increased IL-8 production on BEAS-2B cells when compared to controls. In addition, C. neoformans (MOI 100) increased the concentration of IL-6, but not of IL-10. AT-RvD1 (100 nM) significantly reduced the concentration of IL-8 and IL-6 and increased IL-10 production in C. neoformans-stimulated BEAS-2B cells. C. neoformans increased the phosphorylation of NF-κB and ERK1/2, and ALX/FPR2 expression. AT-RvD1 reduced the activation of NF-kB without altering the ERK1/2 and ALX/FPR2 expression. The anti-inflammatory effects of AT-RvD1 were dependent on the ALX/FPR2, once its antagonist (BOC2) reversed its anti-inflammatory effects. No alteration on the fungal burden as well as interactions with BEAS-2B cells was observed by AT-RvD1. CONCLUSION: AT-RvD1 demonstrated significant anti-inflammatory effects in bronchial epithelial cells infected with C. neoformans without affecting the development of C. neoformans infection in the airways. TRIAL REGISTRATION: Not applicable.
Asunto(s)
Antiinflamatorios/farmacología , Criptococosis/tratamiento farmacológico , Ácidos Docosahexaenoicos/farmacología , Inflamación/tratamiento farmacológico , Antiinflamatorios/administración & dosificación , Bronquios/citología , Bronquios/microbiología , Bronquios/patología , Línea Celular , Criptococosis/patología , Cryptococcus neoformans/aislamiento & purificación , Ácidos Docosahexaenoicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Células Epiteliales/efectos de los fármacos , Células Epiteliales/microbiología , Células Epiteliales/patología , Humanos , Inflamación/microbiologíaRESUMEN
Tuberculosis (TB) is the leading cause of death by a single infectious agent, Mycobacterium tuberculosis (Mtb). Alveolar macrophages and respiratory epithelial cells are the first cells exposed to Mtb during the primary infection, once these cells are activated, secrete cytokines and antimicrobial peptides that are associated with the Mtb contention and elimination. Vitamins are micronutrients that function as boosters on the innate immune system, however, is unclear whether they have any protective activity during Mtb infection. Thus, we investigated the role of vitamin A (retinoic acid), vitamin C (ascorbic acid), vitamin D (calcitriol), and vitamin E (alfa-tocopherol) as inductors of molecules related to mycobacterial infection in macrophages and epithelial cells. Our results showed that retinoic acid promotes the expression of pro- and anti-inflammatory molecules such as Thymic stromal lymphopoietin (TSLP), ß-defensin-2, IL-1ß, CCL20, ß-defensin-3, Cathelicidin LL-37, TGF-ß, and RNase 7, whereas calcitriol, ascorbic acid, and α-tocopherol lead to an anti-inflammatory response. Treatment of Mtb-infected epithelial cells and macrophage-like cells with the vitamins showed a differential response, where calcitriol reduced Mtb in macrophages, while retinoic acid reduced infection in epithelial cells. Thereby, we propose that a combination of calcitriol and retinoic acid supplementation can drive the immune response, and promotes the Mtb elimination by increasing the expression of antimicrobial peptides and cytokines, while simultaneously modulating inflammation.
Asunto(s)
Péptidos Antimicrobianos/farmacología , Bronquios/efectos de los fármacos , Citocinas/metabolismo , Células Epiteliales/efectos de los fármacos , Mycobacterium tuberculosis/efectos de los fármacos , Tretinoina/farmacología , Tuberculosis/tratamiento farmacológico , Antineoplásicos/farmacología , Autofagia , Bronquios/metabolismo , Bronquios/microbiología , Bronquios/patología , Células Cultivadas , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Células Epiteliales/patología , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/microbiología , Macrófagos/patología , Tuberculosis/metabolismo , Tuberculosis/microbiología , Tuberculosis/patologíaRESUMEN
SUMMARY: Diabetes mellitus increases the risk of developing chronic obstructive pulmonary disease (COPD). The small bronchiole is a prominent site of airflow obstruction that causes increased airway resistance in patients with the COPD. Therefore, the histological and ultrastructural changes in small bronchioles in streptozotocin (STZ)-induced chronic diabetes were determined. Twenty-four weeks after STZ induction, rats were sacrificed, and the right and left lungs were collected for examination by light and electron microscopy. The alterations to the small bronchioles were the same in both lungs of these diabetic rats. The bronchiolar epithelial cells, both ciliated and secretory club cells, showed pyknotic nuclei and damaged cytoplasmic organelles. Increased thickening of the bronchiolar wall occurred in diabetic rats due to smooth muscle layer thickening, inflammatory cell infiltration, and increased numbers of myofibroblasts with collagen deposition.These results indicated that chronic diabetes caused extreme damage to small bronchioles, which may lead to chronic small airway obstruction and ultimately increase the likelihood of COPD progression. This basic knowledge provides a better understanding of the progression of pathogenesis in the small airways of patients with prolonged diabetes.
RESUMEN: La diabetes mellitus aumenta el riesgo de desarrollar enfermedad pulmonar obstructiva crónica (EPOC). El bronquiolo es un sitio prominente de obstrucción del flujo de aire que causa una mayor resistencia de las vías respiratorias en pacientes con EPOC. Por lo tanto, se determinaron los cambios histológicos y ultraestructurales en los bronquiolos en la diabetes crónica inducida por estreptozotocina (STZ). 24 semanas después de la inducción de STZ, se sacrificaron las ratas y se analizaron los pulmones derecho e izquierdo por microscopía óptica y electrónica. Las alteraciones de los pequeños bronquiolos fueron las mismas en ambos pulmones de estas ratas diabéticas. Las células epiteliales bronquiolares, tanto ciliadas como secretoras, mostraban núcleos picnóticos y orgánelos citoplasmáticos dañados. Se produjo un aumento del engrosamiento de la pared bronquiolar en ratas diabéticas debido al engrosamiento de la capa de músculo liso, infiltración de células inflamatorias y un mayor número de miofibroblastos con colágeno. Estos resultados indicaron que la diabetes crónica causaba daño extremo a los pequeños bronquiolos, lo que puede conducir a una obstrucción crónica de las vías respiratorias pequeñas y además aumentar la probabilidad de progresión de la EPOC. Esta información proporcionará un mejor conocimiento de la patogénesis en las vías respiratorias pequeñas de los pacientes con diabetes prolongada.
Asunto(s)
Animales , Masculino , Ratas , Bronquios/patología , Diabetes Mellitus Experimental/patología , Bronquios/ultraestructura , Enfermedad Crónica , Ratas Sprague-Dawley , Microscopía Electrónica de TransmisiónRESUMEN
We present results from clinical, radiologic, gas exchange, lung mechanics, and fibre-optic bronchoscopy-guided transbronchial biopsies in a case of acute respiratory failure due to SARS-CoV-2 (Covid-19). This report highlights the pulmonary, immunological, and inflammatory changes found during acute diffuse alveolar damage and the later organizing phase. An early diffuse alveolar damage pattern with predominant epithelial involvement with active recruitment of T cells and monocytes was observed followed by a late organizing pattern with pneumocyte hyperplasia, inflammatory infiltration, prominent endotheliitis, and secondary germinal centers. The patient's deterioration paralleling the late immuno-pathological findings based the decision to administer intravenous corticosteroids, resulting in clinical, gasometric, and radiologic improvement. We believe that real-time clinicopathological correlation, along with the description of the immunological processes at play, will contribute to the full clinical picture of Covid-19 and might lead to a more rational approach in the precise timing of anti-inflammatory, anti-cytokine, or steroid therapies.
Asunto(s)
Bronquios/patología , Tratamiento Farmacológico de COVID-19 , Esteroides/uso terapéutico , Anciano , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/virología , Biopsia/métodos , Bronquios/virología , COVID-19/patología , COVID-19/virología , Humanos , Pulmón/patología , Masculino , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/virología , Insuficiencia Respiratoria/tratamiento farmacológico , Insuficiencia Respiratoria/patología , Insuficiencia Respiratoria/virología , SARS-CoV-2/aislamiento & purificaciónRESUMEN
IL-4 coordinates the Th2-type immune response in inflammatory diseases such as asthma. IL-27 can inhibit the development of both Th2 and Th1 cells. However, IL-27 can also drive naïve T cells to differentiate toward the Th1 phenotype. In this study, we investigated the effects of IL-27 on the activation of IL-4-induced human bronchial epithelial cells (BEAS-2B). Compared to controls, both IL-4 and IL-27 (25-100â¯ng/mL) increased the concentrations of CCL2 and IL-8 in a dose-dependent manner. However, compared to cells stimulated individually with IL-4 or IL-27, treatment with a combination of both cytokines reduced CCL2 and IL-8 concentrations in a dose- and time-dependent manner. IL-4 increased the activation of p38 MAPK, ERK1/2, STAT6 and NF-κB, while IL-27 increased the activation of p38 MAPK and ERK1/2 but not STAT6 and NF-κB. Compared to IL-4-stimulated cells, cells treated with both IL-27 and IL-4 displayed decreased activation of STAT6 and NF-κB but not ERK1/2 and p38 MAPK. Taken together, these results suggest that IL-27 plays a pro-inflammatory role when administered alone but downregulates bronchial epithelial cell activation when combined with IL-4. Therefore, IL-27 may be an interesting target for the treatment of Th2 inflammatory diseases.
Asunto(s)
Bronquios/patología , Células Epiteliales/fisiología , Enfermedades del Sistema Inmune/inmunología , Inflamación/inmunología , Interleucina-27/metabolismo , Células TH1/inmunología , Células Th2/inmunología , Movimiento Celular , Quimiocinas/metabolismo , Regulación de la Expresión Génica , Humanos , Interleucina-27/genética , Interleucina-4/metabolismo , Terapia Molecular Dirigida , FN-kappa B/metabolismo , Factor de Transcripción STAT6/metabolismoRESUMEN
Mounier-Kuhn syndrome (MKS) is a rare congenital disease with an autosomal recessive inheritance pattern, characterized by an enlargement of the trachea and bronchi. MKS is secondary to a thinning of the muscular mucosa and atrophy of the longitudinal muscle and elastic fibers of the tracheobronchial tree. As a consequence, tracheal diverticulosis and dilatations in the posterior membranous wall appear, along with bronchiectasis that tend to be cystic in appearance. Overall, there is an impairment of mucocilliary clearance, with an ineffective cough, which predisposes the patient to recurrent lower respiratory tract infections. Clinical manifestations vary from asymptomatic to respiratory failure and death, most patients being diagnosed between the third and fourth decades of life. It is an often undiagnosed disease, with a diagnostic algorithm that includes the use of radiological techniques, alone or in combination with bronchoscopy. Specific diagnostic criteria have been developed, based on patients' tracheal and main bronchi diameter on chest X-ray and thoracic computed tomography scan. We present the case of a 45-year-old African American man who presented with a history of multiples episodes of pneumonia that required management in the intensive care unit, on whom MKS was diagnosed.
Asunto(s)
Bronquios/patología , Bronquiectasia/etiología , Divertículo/etiología , Tráquea/patología , Traqueobroncomegalia/complicaciones , Negro o Afroamericano , Bronquios/fisiopatología , Bronquiectasia/diagnóstico , Bronquiectasia/fisiopatología , Broncoscopía , Dilatación Patológica , Divertículo/diagnóstico , Divertículo/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Tráquea/diagnóstico por imagen , Traqueobroncomegalia/fisiopatologíaRESUMEN
BACKGROUND: More than 300 million people carry a diagnosis of asthma, with data to suggest that they are at a higher risk for infection or adverse outcomes from severe acute respiratory syndrome coronavirus 2. Asthma is remarkably heterogeneous, and it is currently unclear how patient-intrinsic factors may relate to coronavirus disease 2019. OBJECTIVE: We sought to identify and characterize subsets of patients with asthma at increased risk for severe acute respiratory syndrome coronavirus 2 infection. METHODS: Participants from 2 large asthma cohorts were stratified using clinically relevant parameters to identify factors related to angiotensin-converting enzyme-2 (ACE2) expression within bronchial epithelium. ACE-2-correlated gene signatures were used to interrogate publicly available databases to identify upstream signaling events and novel therapeutic targets. RESULTS: Stratifying by type 2 inflammatory biomarkers, we identified subjects who demonstrated low peripheral blood eosinophils accompanied by increased expression of the severe acute respiratory syndrome coronavirus 2 receptor ACE2 in bronchial epithelium. Genes highly correlated with ACE2 overlapped with type 1 and 2 IFN signatures, normally induced by viral infections. T-cell recruitment and activation within bronchoalveolar lavage cells of ACE2-high subjects was reciprocally increased. These patients demonstrated characteristics corresponding to risk factors for severe coronavirus disease 2019, including male sex, history of hypertension, low peripheral blood, and elevated bronchoalveolar lavage lymphocytes. CONCLUSIONS: ACE2 expression is linked to upregulation of viral response genes in a subset of type 2-low patients with asthma with characteristics resembling known risk factors for severe coronavirus disease 2019. Therapies targeting the IFN family and T-cell-activating factors may therefore be of benefit in a subset of patients.
Asunto(s)
Asma/epidemiología , Asma/genética , Infecciones por Coronavirus/epidemiología , Pandemias , Peptidil-Dipeptidasa A/genética , Neumonía Viral/epidemiología , Receptores Virales/genética , Adolescente , Adulto , Enzima Convertidora de Angiotensina 2 , Asma/clasificación , Asma/inmunología , Betacoronavirus/genética , Betacoronavirus/inmunología , Biomarcadores/metabolismo , Bronquios/inmunología , Bronquios/patología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , COVID-19 , Estudios de Cohortes , Infecciones por Coronavirus/virología , Eosinófilos/inmunología , Eosinófilos/patología , Femenino , Perfilación de la Expresión Génica , Humanos , Interferón Tipo I/genética , Interferón Tipo I/inmunología , Interferón gamma/genética , Interferón gamma/inmunología , Masculino , Persona de Mediana Edad , Peptidil-Dipeptidasa A/inmunología , Neumonía Viral/virología , Mapeo de Interacción de Proteínas , Receptores Virales/inmunología , Factores de Riesgo , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Linfocitos T/clasificación , Linfocitos T/inmunología , Linfocitos T/patología , Transcriptoma , Estados Unidos/epidemiologíaRESUMEN
Tracheobronchopathia osteochondroplastica (TO) is a rare idiopathic and benign disease that is often underdiagnosed. TO is characterized by multiple submucosal cartilaginous and osseous tracheobronchial nodules that spare the posterior wall. It usually affects the elderly, developing when the person is around 60 years old without gender preference and has a reported incidence of 0.11%. TO can be symptomatic and should be considered in patients with chronic cough, dyspnea, and recurrent pulmonary infections. Diagnosis is usually incidental by computed tomography or bronchoscopy, the latter being the gold standard diagnostic test for TO. Many thoracic imagers are not well acquainted with TO; thus, these patients are often underdiagnosed or misdiagnosed. We came across 5 patients in our institution who were incidentally diagnosed with TO, inspiring us to review the available literature on this disease. A total of 33 patients diagnosed with TO between 2009 and 2019 were identified by our retrospective review. Clinical and imaging data were collected on these patients. We also included the clinical, radiological, and endoscopic data of our 5 cases. TO should be considered in patients with chronic cough, dyspnea, and recurrent pulmonary infections. Our experience is that both computed tomography and bronchoscopy can be used to make a reliable diagnosis. It is crucial for physicians, especially radiologists and pulmonologists, to be aware of the existence of TO in order to ensure proper diagnosis.
Asunto(s)
Bronquios/patología , Osteocondrodisplasias/diagnóstico , Tráquea/diagnóstico por imagen , Tráquea/patología , Enfermedades de la Tráquea/diagnóstico , Anciano , Broncoscopía , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteocondrodisplasias/diagnóstico por imagen , Osteocondrodisplasias/patología , Tomografía Computarizada por Rayos X , Enfermedades de la Tráquea/diagnóstico por imagen , Enfermedades de la Tráquea/patologíaRESUMEN
OBJECTIVE: To determine the diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in non-neoplastic patients with isolated intrathoracic lymphadenopathy (IL). METHODS: This was a retrospective study of patients with isolated IL referred for EBUS-TBNA. We calculated the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of EBUS-TBNA in the diagnosis of granulomatous, reactive, and neoplastic lymphadenopathy. In cases of nonspecific granulomas, reactive lymphadenopathy, or inconclusive results, a definitive diagnosis was established by other diagnostic procedures or during a follow-up period of at least 18 months. RESULTS: Among the 58 patients included in the study, EBUS-TBNA established a diagnosis of granulomatous disease in 22 (38%), reactive lymphadenopathy in 15 (26%), cancer in 8 (14%), and other diseases in 3 (5%). Results were inconclusive in 10 (17%), the diagnosis being established by other bronchoscopic procedures in 2 (20%) and by surgical procedures in 8 (80%). A final diagnosis of reactive lymphadenopathy was established in 12. Of those, 11 (92%) had their diagnosis confirmed during follow-up and 1 (8%) had their diagnosis confirmed by mediastinoscopy. In another 3, a final diagnosis of sarcoidosis or neoplasm was established. For the diagnosis of granulomatous disease, neoplasms, and reactive lymphadenopathy, EBUS-TBNA was found to have a sensitivity of 73%, 68%, and 92%, respectively; a specificity of 100%, 100%, and 93%, respectively; an accuracy of 86%, 93%, and 93%, respectively; a PPV of 100%, 100%, and 80%, respectively; and an NPV of 78%, 92%, and 98%, respectively. CONCLUSIONS: In non-neoplastic patients, granulomatous disease and reactive lymphadenopathy appear to be common causes of isolated IL. EBUS-TBNA shows promising results as a first-line minimally invasive diagnostic procedure. The results obtained by EBUS-TBNA can be optimized by examining clinical and radiological findings during follow-up or by comparison with the results obtained with other bronchoscopic methods.
Asunto(s)
Bronquios/diagnóstico por imagen , Broncoscopía , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Ganglios Linfáticos/diagnóstico por imagen , Linfadenopatía/diagnóstico por imagen , Mediastino/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Biopsia con Aguja Fina , Biopsia con Aguja/métodos , Bronquios/patología , Humanos , Ganglios Linfáticos/patología , Linfadenopatía/patología , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Diesel exhaust particles (DEP) are known to generate reactive oxygen species in the respiratory system, triggering cells to activate antioxidant defence mechanisms, such as Keap1-Nrf2 signalling and autophagy. The aim of this study was to investigate the relationship between the Keap1-Nrf2 signalling and autophagy pathways after DEP exposure. BEAS-2B cells were transfected with silencing RNA (siRNA) specific to Nrf2 and exposed to DEP. The relative levels of mRNA for Nrf2, NQO1, HO-1, LC3B, p62 and Atg5 were determined using RT-PCR, while the levels of LCB3, Nrf2, and p62 protein were determined using Western blotting. The autophagy inhibitor bafilomycin caused a significant decrease in the production of Nrf2, HO-1 and NQO1 compared to DEPs treatment, whereas the Nrf2 activator sulforaphane increased the LC3B (p = 0.020) levels. BEAS-2B cells exposed to DEP at a concentration of 50 µg/mL for 2 h showed a significant increase in the expression of LC3B (p = 0.001), p62 (p = 0.008), Nrf2 (p = 0.003), HO-1 (p = 0.001) and NQO1 (p = 0.015) genes compared to control. In siRNA-transfected cells, the LC3B (p < 0.001), p62 (p = 0.001) and Atg5 (p = 0.024) mRNA levels and the p62 and LC3II protein levels were decreased, indicating that Nrf2 modulated the expression of autophagy markers (R < 1). These results imply that, in bronchial cells exposed to DEP, the Nrf2 system positively regulates autophagy to maintain cellular homeostasis.
Asunto(s)
Antioxidantes/metabolismo , Autofagia , Bronquios/metabolismo , Células Epiteliales/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Emisiones de Vehículos/toxicidad , Bronquios/patología , Línea Celular , Células Epiteliales/patología , Regulación de la Expresión Génica , HumanosRESUMEN
BACKGROUND: Compromised microvasculature resulting from disrupted bronchial arterial circulation appears to trigger chronic lung allograft dysfunction. Maintaining the microvasculature throughout the transplant process could improve the long-term health of transplanted lungs. We recently developed a bronchial-arterial-circulation-sparing (BACS) lung preservation approach and tested whether this approach would decrease microvascular damage and improve allograft function. METHODS: The lungs of Lewis rats were procured using either the BACS approach, where the bronchial and pulmonary arteries were synchronously perfused; a conventional approach, where only the pulmonary artery was perfused; or a conventional approach with a prostaglandin flush. After 4 hours of cold ischemia, physiologic function and vascular tone of the grafts were evaluated during ex vivo lung perfusion (EVLP), and microvasculature damage was assessed using 2-photon microscopy analysis. Lung function was compared after transplant among the groups. RESULTS: After 4 hours of cold ischemia, the BACS group exhibited significantly higher adenosine triphosphate levels and lower expression of phosphorylated myosin light chain, which is essential for vascular smooth muscle contraction. On EVLP, the BACS and prostaglandin groups showed lower pulmonary vascular resistance and less arterial stiffness. BACS attenuated microvasculature damage in the lung grafts when compared with conventional preservation. After transplantation, the lungs preserved with the BACS approach exhibited significantly better graft function and lower expression of phosphorylated myosin light chain. CONCLUSIONS: Our data suggest that BACS lung preservation protects the dual circulation inherent to the lungs, facilitating robust microvasculature in lung grafts after transplantation, leading to better posttransplant outcomes.
Asunto(s)
Rechazo de Injerto/prevención & control , Trasplante de Pulmón/efectos adversos , Perfusión/métodos , Aloinjertos/irrigación sanguínea , Aloinjertos/patología , Animales , Bronquios/irrigación sanguínea , Bronquios/patología , Arterias Bronquiales/patología , Arterias Bronquiales/trasplante , Modelos Animales de Enfermedad , Circulación Extracorporea/instrumentación , Circulación Extracorporea/métodos , Rechazo de Injerto/patología , Humanos , Trasplante de Pulmón/métodos , Masculino , Microvasos/patología , Preservación de Órganos , Soluciones Preservantes de Órganos , Perfusión/instrumentación , Neumonectomía/métodos , Arteria Pulmonar/patología , Arteria Pulmonar/trasplante , Ratas , Ratas Endogámicas Lew , Obtención de Tejidos y Órganos/métodos , Isquemia Tibia/efectos adversosRESUMEN
ABSTRACT Objective: To determine the diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in non-neoplastic patients with isolated intrathoracic lymphadenopathy (IL). Methods: This was a retrospective study of patients with isolated IL referred for EBUS-TBNA. We calculated the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of EBUS-TBNA in the diagnosis of granulomatous, reactive, and neoplastic lymphadenopathy. In cases of nonspecific granulomas, reactive lymphadenopathy, or inconclusive results, a definitive diagnosis was established by other diagnostic procedures or during a follow-up period of at least 18 months. Results: Among the 58 patients included in the study, EBUS-TBNA established a diagnosis of granulomatous disease in 22 (38%), reactive lymphadenopathy in 15 (26%), cancer in 8 (14%), and other diseases in 3 (5%). Results were inconclusive in 10 (17%), the diagnosis being established by other bronchoscopic procedures in 2 (20%) and by surgical procedures in 8 (80%). A final diagnosis of reactive lymphadenopathy was established in 12. Of those, 11 (92%) had their diagnosis confirmed during follow-up and 1 (8%) had their diagnosis confirmed by mediastinoscopy. In another 3, a final diagnosis of sarcoidosis or neoplasm was established. For the diagnosis of granulomatous disease, neoplasms, and reactive lymphadenopathy, EBUS-TBNA was found to have a sensitivity of 73%, 68%, and 92%, respectively; a specificity of 100%, 100%, and 93%, respectively; an accuracy of 86%, 93%, and 93%, respectively; a PPV of 100%, 100%, and 80%, respectively; and an NPV of 78%, 92%, and 98%, respectively. Conclusions: In non-neoplastic patients, granulomatous disease and reactive lymphadenopathy appear to be common causes of isolated IL. EBUS-TBNA shows promising results as a first-line minimally invasive diagnostic procedure. The results obtained by EBUS-TBNA can be optimized by examining clinical and radiological findings during follow-up or by comparison with the results obtained with other bronchoscopic methods.
RESUMO Objetivo: Determinar o rendimento diagnóstico da endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA, aspiração transbrônquica com agulha guiada por ultrassonografia endobrônquica) em pacientes não neoplásicos com linfonodomegalia intratorácica (LI) isolada. Métodos: Estudo retrospectivo com pacientes com LI isolada encaminhados para EBUS-TBNA. Foram calculados a sensibilidade, especificidade, precisão, valor preditivo positivo (VPP) e valor preditivo negativo (VPN) da EBUS-TBNA no diagnóstico de linfadenopatia granulomatosa, reacional e neoplásica. Em casos de granulomas inespecíficos, linfadenopatia reacional ou resultados inconclusivos, o diagnóstico definitivo foi estabelecido por meio de outros procedimentos diagnósticos ou ao longo de pelo menos 18 meses de acompanhamento. Resultados: Nos 58 pacientes incluídos, a EBUS-TBNA permitiu que se estabelecesse o diagnóstico de doença granulomatosa em 22 (38%), linfadenopatia reacional em 15 (26%), câncer em 8 (14%) e outras doenças em 3 (5%). Os resultados foram inconclusivos em 10 (17%), nos quais o diagnóstico foi feito por meio de outros procedimentos broncoscópicos, em 2 (20%), ou de procedimentos cirúrgicos, em 8 (80%). O diagnóstico final de linfadenopatia reacional foi feito em 12. Destes, 11 (92%) receberam confirmação diagnóstica durante o acompanhamento e 1 (8%), por meio de mediastinoscopia. Em outros 3, o diagnóstico final foi sarcoidose ou neoplasia. Para o diagnóstico de doença granulomatosa, câncer e linfadenopatia reacional, a EBUS-TBNA apresentou sensibilidade de 73%, 68% e 92%, respectivamente; especificidade de 100%, 100% e 93%, respectivamente; precisão de 86%, 93% e 93%, respectivamente; VPP de 100%, 100% e 80%, respectivamente; VPN de 78%, 92% e 98%, respectivamente. Conclusões: Em pacientes não neoplásicos, doenças granulomatosas e linfadenopatia reacional parecem ser causas comuns de LI isolada. A EBUS-TBNA apresenta resultados promissores como procedimento diagnóstico minimamente invasivo de primeira linha. Os resultados obtidos pela EBUS-TBNA podem ser otimizados pelos achados clínicos e radiológicos durante o acompanhamento ou pela comparação com os resultados de outros métodos broncoscópicos.
Asunto(s)
Humanos , Bronquios/diagnóstico por imagen , Broncoscopía , Ultrasonografía Intervencional/métodos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Linfadenopatía/diagnóstico por imagen , Ganglios Linfáticos/diagnóstico por imagen , Mediastino/diagnóstico por imagen , Biopsia con Aguja/métodos , Bronquios/patología , Estudios Retrospectivos , Sensibilidad y Especificidad , Biopsia con Aguja Fina , Linfadenopatía/patología , Ganglios Linfáticos/patologíaRESUMEN
The landscape of infant bronchiolitis and viral pneumonia may be altered by preventive interventions against respiratory syncytial virus under evaluation today. Pediatric wards in 2018 in developing countries may differ from those attended by future generation pediatricians who may not witness the packed emergency rooms, lack of available beds, or emergency situations that all physicians caring for children with RSV experience every year. In this review, we describe and discuss different prevention strategies under evaluation to protect pediatric patients. Then, we outline a number of potential challenges, benefits, and concerns that may result from successful interventions after licensure.
Asunto(s)
Bronquios/inmunología , Bronquiolitis Viral/inmunología , Neumonía Viral/inmunología , Infecciones por Virus Sincitial Respiratorio/inmunología , Virus Sincitial Respiratorio Humano/inmunología , Bronquios/patología , Bronquios/virología , Bronquiolitis Viral/prevención & control , Niño , Predicción , Humanos , Lactante , Neumonía Viral/prevención & control , Neumonía Viral/virología , Medicina Preventiva/métodos , Medicina Preventiva/tendencias , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/fisiologíaRESUMEN
Long-term survivors of bronchopulmonary dysplasia develop chronic obstructive lung disease. Herein we report in vivo histopathology from bronchial biopsies of 3 adolescent survivors of severe bronchopulmonary dysplasia. Thickened basement membranes with lymphocytic infiltrates and signs of immature neoangiogenesis in the absence of T-helper lymphocytes or eosinophils suggest the presence of an ongoing active airway process.
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Bronquios/patología , Displasia Broncopulmonar/patología , Sobrevivientes , Adolescente , Biopsia , Bronquios/metabolismo , Broncoscopía , Linfocitos T CD8-positivos/metabolismo , Niño , Femenino , Fibrosis , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Pruebas de Función Respiratoria , Mucosa Respiratoria/patología , Ruidos RespiratoriosAsunto(s)
Bronquios/diagnóstico por imagen , Neoplasias de los Bronquios/secundario , Melanoma/diagnóstico por imagen , Anciano , Bronquios/patología , Neoplasias de los Bronquios/diagnóstico por imagen , Neoplasias de los Bronquios/genética , Disnea/etiología , Femenino , Humanos , Melanoma/genética , Melanoma/patología , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Tomografía Computarizada por Rayos XRESUMEN
Recombinant adeno-associated virus (rAAV) vector platforms have shown considerable therapeutic success in gene therapy for inherited disorders. In cystic fibrosis (CF), administration of first-generation rAAV2 was safe, but clinical benefits were not clearly demonstrated. Therefore, next-generation vectors that overcome rate-limiting steps in rAAV transduction are needed to obtain successful gene therapy for this devastating disease. In this study, we evaluated the effects of single-strand or self-complementary (sc) rAAV vectors containing single or multiple tyrosine-to-phenylalanine (Y-F) mutations in capsid surface-exposed residues on serotypes 2, 8 or 9. For this purpose, CF bronchial epithelial (CFBE) cells were transduced with rAAV vectors, and the transgene expression of enhanced green fluorescence protein (eGFP) was analyzed at different time points. The effects of vectors on the cell viability, host cell cycle and in association with co-adjuvant drugs that modulate intracellular vector trafficking were also investigated. Six rAAV vectors demonstrated greater percentage of eGFP+ cells compared to their counterparts at days 4, 7 and 10 post-transduction: rAAV2 Y(272,444,500,730)F, with 1.95-, 3.5- and 3.06-fold increases; rAAV2 Y(252,272,444,500,704,730)F, with 1.65-, 2.12-, and 2-fold increases; scrAAV2 WT, with 1.69-, 2.68-, and 2.32-fold increases; scrAAV8 Y773F, with 57-, 6.06-, and 7-fold increases; scrAAV9 WT, with 7.47-, 4.64-, and 3.66-fold increases; and scrAAV9 Y446F, with 8.39-, 4.62-, and 4.4-fold increases. At days 15, 20, and 30 post-transduction, these vectors still demonstrated higher transgene expression than transfected cells. Although the percentage of eGFP+ cells reduced during the time-course analysis, the delta mean fluorescence intensity increased. These vectors also led to increased percentage of cells in G1-phase without eliciting any cytotoxicity. Prior administration of bortezomib or genistein did not increase eGFP expression in cells transduced with either rAAV2 Y(272,444,500,730)F or rAAV2 Y(252,272,444,500,704,730)F. In conclusion, self-complementary and tyrosine capsid mutations on rAAV serotypes 2, 8, and 9 led to more efficient transduction than their counterparts in CFBE cells by overcoming the intracellular trafficking and second-strand DNA synthesis limitations.