RESUMEN
Recent studies have demonstrated the feasibility of islet implantation into the alveoli. However, until today, there are no data on islet behavior and morphology at their transplant site. This study is the first to investigate islet distribution as well insulin production at the implant site. Using an ex vivo postmortem swine model, porcine pancreatic islets were isolated and aerosolized into the lung using an endoscopic spray-catheter. Lung tissue was explanted and bronchial airways were surgically isolated and connected to a perfusor. Correct implantation was confirmed via histology. The purpose of using this new lung perfusion model was to measure static as well as dynamic insulin excretions following glucose stimulation. Alveolar islet implantation was confirmed after aerosolization. Over 82% of islets were correctly implanted into the intra-alveolar space. The medium contact area to the alveolar surface was estimated at 60 +/- 3% of the total islet surface. The new constructed lung perfusion model was technically feasible. Following static glucose stimulation, insulin secretion was detected, and dynamic glucose stimulation revealed a biphasic insulin secretion capacity during perfusion. Our data indicate that islets secrete insulin following implantation into the alveoli and display an adapted response to dynamic changes in glucose. These preliminary results are encouraging and mark a first step toward endoscopically assisted islet implantation in the lung.
Asunto(s)
Secreción de Insulina/fisiología , Insulina/biosíntesis , Trasplante de Islotes Pancreáticos/métodos , Islotes Pancreáticos/metabolismo , Alveolos Pulmonares/cirugía , Administración por Inhalación , Aerosoles/administración & dosificación , Animales , Glucemia/análisis , Diabetes Mellitus Tipo 1/terapia , Glucosa/administración & dosificación , Glucosa/metabolismo , PorcinosRESUMEN
Paracrine erythropoietin (EPO) signaling in the lung recruits endothelial progenitor cells, promotes cell maturation and angiogenesis, and is upregulated during canine postpneumonectomy (PNX) compensatory lung growth. To determine whether inhalational delivery of exogenous EPO augments endogenous post-PNX lung growth, adult canines underwent right PNX and received, via a permanent tracheal stoma, weekly nebulization of recombinant human EPO-containing nanoparticles or empty nanoparticles (control) for 16 wk. Lung function was assessed under anesthesia pre- and post-PNX. The remaining lobes were fixed for detailed morphometric analysis. Compared with control treatment, EPO delivery significantly increased serum EPO concentration without altering systemic hematocrit or hemoglobin concentration and abrogated post-PNX lipid oxidative stress damage. EPO delivery modestly increased post-PNX volume densities of the alveolar septum per unit of lung volume and type II epithelium and endothelium per unit of septal tissue volume in selected lobes. EPO delivery also augmented the post-PNX increase in alveolar double-capillary profiles, a marker of intussusceptive capillary formation, in all remaining lobes. EPO treatment did not significantly alter absolute resting lung volumes, lung and membrane diffusing capacities, alveolar-capillary blood volume, pulmonary blood flow, lung compliance, or extravascular alveolar tissue volumes or surface areas. Results established the feasibility of chronic inhalational delivery of growth-modifying biologics in a large animal model. Exogenous EPO selectively enhanced cytoprotection and alveolar angiogenesis in remaining lobes but not whole-lung extravascular tissue growth or resting function; the nonuniform response contributes to structure-function discrepancy, a major challenge for interventions aimed at amplifying the innate potential for compensatory lung growth.
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Capilares/crecimiento & desarrollo , Eritropoyetina/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Neumonectomía , Alveolos Pulmonares , Administración por Inhalación , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Perros , Rendimiento Pulmonar/efectos de los fármacos , Masculino , Alveolos Pulmonares/metabolismo , Alveolos Pulmonares/patología , Alveolos Pulmonares/cirugíaRESUMEN
A clinical case of successful procurement and transplantation of bilateral lungs from 6-week-old infant with sepsis secondary to bacterial meningitis is reported. Forty-one-day-old male infant (height 60 cm, weight 4 kg) died of cerebral edema secondary to Escherichia coli meningitis and bacteremia. Preretrieval assessment included the following: arterial gases; pO2 50.4 kPa (378 mm Hg), pCO2 4.9 kPa (37 mm Hg), on FiO2 100%, PEEP 5 cm H2 O. Fiberoptic bronchoscopy showed no secretions nor mucosal inflammation; CXR revealed clear lung fields and pleural spaces. Inspection revealed dense adhesions in pericardial cavity and purulent left hemithorax effusion (urgent Gram-stain came back as negative) but there was no consolidation in the lung. Good compliance of the lungs on inflation/deflation test was observed. The lungs were retrieved using the technique described. The recipient was a 4-month-old infant with alveolar capillary dysplasia and malaligned pulmonary veins. Implantation of the lungs was performed via bilateral thoracosternotomy on cardiopulmonary bypass, cooling to 30°C. Elective support with nitric oxide was used postoperatively. Two years after the transplantation, the recipient doing well with normal lung function. Lung procurement from a 6-week donor with infectious complications and prolonged ventilation is a challenging undertaking but can be successful and should be attempted whenever possible given the paucity of organs available for pediatric recipients.
Asunto(s)
Trasplante de Pulmón , Pulmón/cirugía , Síndrome de Circulación Fetal Persistente/cirugía , Alveolos Pulmonares/anomalías , Broncoscopía , Escherichia coli , Femenino , Humanos , Lactante , Enfermedades Pulmonares/cirugía , Masculino , Meningitis Bacterianas , Alveolos Pulmonares/cirugía , Venas Pulmonares/cirugía , Sepsis , Donantes de Tejidos , Obtención de Tejidos y ÓrganosRESUMEN
OBJECTIVE: To describe disease course, histopathology, and outcomes for infants with atypical presentations of alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) who underwent bilateral lung transplantation. STUDY DESIGN: We reviewed clinical history, diagnostic studies, explant histology, genetic sequence results, and post-transplant course for 6 infants with atypical ACDMPV who underwent bilateral lung transplantation at St. Louis Children's Hospital. We compared their histology with infants with classic ACDMPV and compared their outcomes with infants transplanted for other indications. RESULTS: In contrast with neonates with classic ACDPMV who present with severe hypoxemia and refractory pulmonary hypertension within hours of birth, none of the infants with atypical ACDMPV presented with progressive neonatal respiratory failure. Three infants had mild neonatal respiratory distress and received nasal cannula oxygen. Three other infants had no respiratory symptoms at birth and presented with hypoxemia and pulmonary hypertension at 2-3 months of age. Bilateral lung transplantation was performed at 4-20 months of age. Unlike in classic ACDMPV, histopathologic findings were not distributed uniformly and were not diffuse. Three subjects had apparent nonmosaic genetic defects involving FOXF1. Two infants had extrapulmonary anomalies (posterior urethral valves, inguinal hernia). Three transplanted children are alive at 5-16 years of age, similar to outcomes for infants transplanted for other indications. Lung explants from infants with atypical ACDMPV demonstrated diagnostic but nonuniform histopathologic findings. CONCLUSIONS: The 1- and 5-year survival rates for infants with atypical ACDMPV are similar to infants transplanted for other indications. Given the clinical and histopathologic spectra, ACDMPV should be considered in infants with hypoxemia and pulmonary hypertension, even beyond the newborn period.
Asunto(s)
Trasplante de Pulmón/métodos , Síndrome de Circulación Fetal Persistente/diagnóstico , Alveolos Pulmonares/anomalías , Femenino , Factores de Transcripción Forkhead/genética , Humanos , Lactante , Recién Nacido , Pulmón/patología , Masculino , Mutación , Síndrome de Circulación Fetal Persistente/complicaciones , Síndrome de Circulación Fetal Persistente/cirugía , Alveolos Pulmonares/cirugía , Venas Pulmonares/anomalías , Tasa de SupervivenciaRESUMEN
PURPOSE OF REVIEW: The method for identification of alveolopleural fistulae (APF) by visual inspection of air bubbles in the chest drainage system has several limitations and suffers from poor accuracy. Here we discuss the use of a novel technique of pleural gas analysis in the identification and management of APF. RECENT FINDINGS: We found that pleural gas analysis has higher sensitivity and specificity than visual inspection in identifying APF. Additionally, we demonstrated that intrapleural gas milieu impacts lung healing and reduction of intrapleural carbon dioxide can promote resolution of APF. SUMMARY: Pleural gas analysis is a novel technique to identify and manage APF. Integration of gas analysis in chest drainage systems would provide a more objective method for managing chest tubes and providing a favorable pleural gas environment for lung healing.
Asunto(s)
Fuga Anastomótica/diagnóstico , Dióxido de Carbono/análisis , Oxígeno/análisis , Cavidad Pleural/química , Fístula del Sistema Respiratorio/diagnóstico , Tubos Torácicos , Drenaje , Humanos , Cavidad Pleural/cirugía , Neumonectomía/efectos adversos , Alveolos Pulmonares/cirugía , Pruebas de Función Respiratoria , Fístula del Sistema Respiratorio/etiologíaRESUMEN
BACKGROUND: Bronchopulmonary dysplasia and emphysema are life-threatening diseases resulting from impaired alveolar development or alveolar destruction. Both conditions lack effective therapies. Angiogenic growth factors promote alveolar growth and contribute to alveolar maintenance. Endothelial colony-forming cells (ECFCs) represent a subset of circulating and resident endothelial cells capable of self-renewal and de novo vessel formation. We hypothesized that resident ECFCs exist in the developing lung, that they are impaired during arrested alveolar growth in experimental bronchopulmonary dysplasia, and that exogenous ECFCs restore disrupted alveolar growth. METHODS AND RESULTS: Human fetal and neonatal rat lungs contain ECFCs with robust proliferative potential, secondary colony formation on replating, and de novo blood vessel formation in vivo when transplanted into immunodeficient mice. In contrast, human fetal lung ECFCs exposed to hyperoxia in vitro and neonatal rat ECFCs isolated from hyperoxic alveolar growth-arrested rat lungs mimicking bronchopulmonary dysplasia proliferated less, showed decreased clonogenic capacity, and formed fewer capillary-like networks. Intrajugular administration of human cord blood-derived ECFCs after established arrested alveolar growth restored lung function, alveolar and lung vascular growth, and attenuated pulmonary hypertension. Lung ECFC colony- and capillary-like network-forming capabilities were also restored. Low ECFC engraftment and the protective effect of cell-free ECFC-derived conditioned media suggest a paracrine effect. Long-term (10 months) assessment of ECFC therapy showed no adverse effects with persistent improvement in lung structure, exercise capacity, and pulmonary hypertension. CONCLUSIONS: Impaired ECFC function may contribute to arrested alveolar growth. Cord blood-derived ECFC therapy may offer new therapeutic options for lung diseases characterized by alveolar damage.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Células Endoteliales/fisiología , Oxígeno/toxicidad , Alveolos Pulmonares/efectos de los fármacos , Alveolos Pulmonares/cirugía , Trasplante de Células Madre/métodos , Animales , Animales Recién Nacidos , Células Cultivadas , Células Endoteliales/trasplante , Feto , Células Endoteliales de la Vena Umbilical Humana/fisiología , Células Endoteliales de la Vena Umbilical Humana/trasplante , Humanos , Ratones , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Alveolos Pulmonares/lesiones , Ratas , Ratas Desnudas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Controversies surrounding the efficacy of sealants against alveolar air leak (AAL) are abundant in the literature. We sought to test the widely used sealants, TachoSil (Takeda Pharmaceutical Company Limited, Osaka, Japan) and BioGlue (CryoLife Europa Ltd., Surrey, United Kingdom) in an in vitro model. Materials and METHODS: After creation of a focal superficial defect (40 × 25 mm) in swine lungs (n=40), AAL was assessed with increasing inspired tidal volume (TVi). Upon sealant application in a randomized order, AAL was assessed in the same way until sealant burst. RESULTS: At TVi =400, 500, 600, and 700 mL, BioGlue achieved sealing in 19, 19, 16, and 14 tests, while TachoSil sealed in 19, 14, 4, and no test, respectively. The maximally tolerated pressure of BioGlue was higher than TachoSil (40.3 ± 3.0 vs. 36.0 ± 4.9 cm H2O, p=0.003). Cohesive and adhesive failures were found in 10 and 1 tests of BioGlue, respectively, while all burst failures of TachoSil were adhesive. Concerning elasticity, TachoSil allowed more expansion of the covered defect than BioGlue (6.3 ± 3.9 vs. 1.4 ± 1.0 mm, p<0.001). CONCLUSION: The tested sealants demonstrated high sealing efficacy. While BioGlue was superior in resisting higher ventilation pressure, TachoSil possessed better elasticity.
Asunto(s)
Fibrinógeno/farmacología , Neumotórax/terapia , Proteínas/farmacología , Alveolos Pulmonares/cirugía , Trombina/farmacología , Adhesivos Tisulares/farmacología , Animales , Combinación de Medicamentos , Elasticidad , Femenino , Fibrinógeno/química , Técnicas In Vitro , Masculino , Presión , Proteínas/química , Alveolos Pulmonares/patología , Respiración Artificial , Porcinos , Trombina/química , Adhesivos Tisulares/químicaRESUMEN
In rodents and some other mammals, partial pneumonectomy (PNX) of adult lungs results in rapid compensatory lung growth. In the past, quantification of compensatory lung growth and realveolarization could only be accomplished after killing the animal, removal of lungs, and histologic analysis of lungs at single time points. Hyperpolarized (3)He diffusion magnetic resonance imaging (MRI) allows in vivo morphometry of human lungs; our group has adapted this technique for application to mouse lungs. Through imaging, we can obtain maps of lung microstructural parameters that allow quantification of morphometric and physiologic measurements. In this study, we employed our (3)He MRI technique to image in vivo morphometry at baseline and to serially assess compensatory growth after left PNX of mice. (1)H and hyperpolarized (3)He diffusion MRI were performed at baseline (pre-PNX), 3-days, and 30-days after PNX. Compared with the individual mouse's own baseline, MRI was able to detect and serially quantify changes in lung volume, alveolar surface area, alveolar number, and regional changes in alveolar size that occurred during the course of post-PNX lung growth. These results are consistent with morphometry measurements reported in the literature for mouse post-PNX compensatory lung growth. In addition, we were also able to serially assess and quantify changes in the physiologic parameter of lung compliance during the course of compensatory lung growth; this was consistent with flexiVent data. With these techniques, we now have a noninvasive, in vivo method to serially assess the effectiveness of therapeutic interventions on post-PNX lung growth in the same mouse.
Asunto(s)
Imagen de Difusión por Resonancia Magnética/métodos , Helio , Hidrógeno , Pulmón/cirugía , Neumonectomía , Regeneración , Animales , Pulmón/irrigación sanguínea , Pulmón/crecimiento & desarrollo , Pulmón/patología , Rendimiento Pulmonar , Mediciones del Volumen Pulmonar , Ratones , Ratones Endogámicos C57BL , Modelos Animales , Neovascularización Fisiológica , Alveolos Pulmonares/irrigación sanguínea , Alveolos Pulmonares/crecimiento & desarrollo , Alveolos Pulmonares/patología , Alveolos Pulmonares/cirugía , Intercambio Gaseoso Pulmonar , Recuperación de la Función , Factores de TiempoRESUMEN
An alveolar-pleural fistula is a communication between the pulmonary parenchyma distal to a segmental bronchus and the pleural space. A postoperative pulmonary expiratory air leak after an anatomic pulmonary resection is usually managed conservatively. The use of endobronchial valves is a minimal invasive method that may be effective for the treatment of a persistent postoperative pulmonary air leak. We present and discuss the advantages of a digital thoracic drainage system for the accurate, objective and reproducible air leak assessment during endobronchial valve placement. Our case also illustrates that, even after lobectomy, lobar exclusion with valves allows air leak resolution without atelectasis and with moderate functional alteration. We discuss the anatomic and physiologic changes induced by valves placed for air leak closure.
Asunto(s)
Cavidad Pleural/cirugía , Complicaciones Posoperatorias/cirugía , Alveolos Pulmonares/cirugía , Fístula del Sistema Respiratorio/cirugía , Anciano , Drenaje/instrumentación , Humanos , Masculino , Neumonectomía , Instrumentos QuirúrgicosRESUMEN
Multipotent mesenchymal progenitor cells, termed "mesenchymal stem cells" (MSCs), have been demonstrated to reside in human adult lungs. However, there is little information regarding the associations of these local mesenchymal progenitors with other resident somatic cells and their potential for therapeutic use. Here we provide in vivo and in vitro evidence for the ability of human adult lung-resident MSCs (LR-MSCs) to interact with the local epithelial cells. The in vivo retention and localization of human LR-MSCs in an alveolar microenvironment was investigated by placing PKH-26 or DsRed lentivirus-labeled human LR-MSCs in the lungs of immunodeficient (SCID) mice. At 3 weeks after intratracheal administration, 19.3 ± 3.21% of LR-MSCs were recovered, compared with 3.47 ± 0.51% of control fibroblasts, as determined by flow cytometry. LR-MSCs were found to persist in murine lungs for up to 6 months and demonstrated preferential localization to the corners of the alveoli in close proximity to type II alveolar epithelial cells, the progenitor cells of the alveolar epithelium. In vitro, LR-MSCs established gap junction communications with lung alveolar and bronchial epithelial cells and demonstrated an ability to secrete keratinocyte growth factor, an important modulator of epithelial cell proliferation and differentiation. Gap junction communications were also demonstrable between LR-MSCs and resident murine cells in vivo. This study demonstrates, for the first time, an ability of tissue-specific MSCs to engraft in their organ of origin and establishes a pathway of bidirectional interaction between these mesenchymal progenitors and adult somatic epithelial cells in the lung.
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Células Epiteliales Alveolares/metabolismo , Comunicación Celular , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/metabolismo , Alveolos Pulmonares/cirugía , Animales , Separación Celular/métodos , Rastreo Celular , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Factor 7 de Crecimiento de Fibroblastos/metabolismo , Citometría de Flujo , Colorantes Fluorescentes/metabolismo , Uniones Comunicantes/metabolismo , Vectores Genéticos , Supervivencia de Injerto , Humanos , Lentivirus/genética , Proteínas Luminiscentes/biosíntesis , Proteínas Luminiscentes/genética , Ratones , Ratones SCID , Compuestos Orgánicos/metabolismo , Alveolos Pulmonares/metabolismo , Factores de Tiempo , Transfección , Proteína Fluorescente RojaRESUMEN
Bronchopleural (BPF) and alveolar-pleural (APF) fistulas are frequently encountered in clinical practice with persistent air leaks that can lead to significant morbidity, prolonged hospital stay, and potentially increased mortality. BPF and APF are commonly related to pulmonary resections. Other etiologies include minimally invasive procedures (thoracentesis and image-guided biopsies), and spontaneous fistulas related to an underlying structural lung disease (e.g., emphysema) or a necrotizing pulmonary process (e.g., infection or malignancy). Radiofrequency ablation for pulmonary malignancies is an effective modality that can rarely lead to APF with persistent air leak. Surgical intervention remains the standard treatment option for BPF and APF. A variety of minimally invasive bronchoscopic approaches can be considered for selected nonsurgical candidates. The use of one-way endobronchial valves to manage severe and persistent air leaks can be considered a minimally invasive option in selected patients. The valves selectively block inspiratory airflow to a specific segmental or subsegmental airway but allow expiratory flow with drainage of air and secretions from the corresponding distal airways and lung parenchyma.
Asunto(s)
Fístula Bronquial/cirugía , Ablación por Catéter/efectos adversos , Tratamiento de Urgencia/instrumentación , Fístula/cirugía , Enfermedades Pleurales/cirugía , Neumotórax/cirugía , Enfisema Subcutáneo/cirugía , Enfermedades de la Tráquea/cirugía , Fístula Bronquial/diagnóstico por imagen , Fístula Bronquial/etiología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Urgencias Médicas , Resultado Fatal , Femenino , Fístula/diagnóstico por imagen , Fístula/etiología , Humanos , Neoplasias Pulmonares/cirugía , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Proyectos Piloto , Enfermedades Pleurales/diagnóstico por imagen , Enfermedades Pleurales/etiología , Neumotórax/diagnóstico por imagen , Neumotórax/patología , Alveolos Pulmonares/cirugía , Radiografía , Enfisema Subcutáneo/diagnóstico por imagen , Enfisema Subcutáneo/patología , Enfermedades de la Tráquea/diagnóstico por imagen , Enfermedades de la Tráquea/etiologíaRESUMEN
BACKGROUND: The treatment of persistent air leak is a challenge. Herein, we reported the combined intrabronchial and intrapleural injection of fibrin glue using fiber bronchoscopy to seal off an alveolar pleura fistula developed following necrotizing pneumonia in high-risk patient. CASE PRESENTATION: A 74-year-old man was intubated in emergency for acute ischemic stroke. Percutaneous dilatational tracheostomy was then performed, and 15 days later patient returned to spontaneous breathing. However, he developed alveolar pleural fistula following necrotizing pneumonia with persistent air leaks. The intrabronchial and intrapleural injection of fibrin glue using fiber bronchoscopy sealed off the alveolar pleura fistula after that other endoscopic treatments as bronchial valve and intrabronchial fibrin glue application had failed. CONCLUSIONS: Our strategy is safe and easy to reproduce. It represents an additional method in the armamentarium of the physicians for the management of PAL when all standard strategies are unfeasible or fail.
Asunto(s)
Fístula Bronquial/cirugía , Adhesivo de Tejido de Fibrina/uso terapéutico , Enfermedades Pleurales/tratamiento farmacológico , Alveolos Pulmonares/cirugía , Anciano , Isquemia Encefálica/complicaciones , Bronquios , Fístula Bronquial/tratamiento farmacológico , Broncoscopía , Endoscopía , Fístula/complicaciones , Humanos , Inyecciones , Masculino , Enfermedades Pleurales/etiología , Accidente Cerebrovascular/complicaciones , Traqueostomía/efectos adversosRESUMEN
Although lung diffusing capacity for carbon monoxide (DL(CO)) is a widely used test of diffusive O2 transfer, few studies have directly related DL(CO) to O2-diffusing capacity (DL(O2)); none has used the components of Dl(CO), i.e., conductance of alveolar membrane and capillary blood, to predict DL(O2) from rest to exercise. To understand the relationship between DL(CO) and DL(O2) at matched levels of cardiac output, we analyzed cumulative data from rest to heavy exercise in 43 adult dogs, with normal lungs or reduced lung capacity following lung resection, that were studied by two techniques. 1) A rebreathing (RB) technique was used to measure Dl(CO) and pulmonary blood flow at two O2 tensions, independent of O2 exchange. DL(CO) was partitioned into CO-diffusing capacity of alveolar membrane and pulmonary capillary blood volume using the Roughton-Forster equation and converted into an equivalent DL(O2), [DL(O2)(RB)]. 2) A multiple inert-gas elimination technique (MIGET) was used to measure ventilation-perfusion distributions, O2 and CO2 exchange under hypoxia, to derive DL(O2) [DL(O2)(MIGET)] by the Lilienthal-Riley technique and Bohr integration. For direct comparisons, DL(O2)(RB) was interpolated to the cardiac output measured by the Fick principle corresponding to DL(O2)(MIGET). The DL(O2)-to-DL(CO) ratio averaged 1.61. Correlation between DL(O2)(RB) and DL(O2)(MIGET) was similar in normal and post-resection groups. Overall, DL(O2)(MIGET) = 0.975 DL(O2)(RB); mean difference between the two techniques was under 5% for both animal groups. We conclude that, despite various uncertainties inherent in these two disparate methods, the Roughton-Forster equation adequately predicts diffusive O2 transfer from rest to heavy exercise in canines with normal, as well as reduced, lung capacities.
Asunto(s)
Oxígeno/metabolismo , Esfuerzo Físico , Alveolos Pulmonares/metabolismo , Capacidad de Difusión Pulmonar , Animales , Dióxido de Carbono/sangre , Dióxido de Carbono/metabolismo , Gasto Cardíaco , Perros , Hipoxia/metabolismo , Hipoxia/fisiopatología , Mediciones del Volumen Pulmonar , Masculino , Microcirculación , Modelos Biológicos , Oxígeno/sangre , Neumonectomía , Alveolos Pulmonares/irrigación sanguínea , Alveolos Pulmonares/cirugía , Circulación Pulmonar , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Diffuse alveolar damage (DAD) is a relatively common histopathologic finding at autopsy, particularly in patients dying with ARDS, and can result from a variety of causes. The spectrum of causes and associated prognostic implications for DAD diagnosed by surgical lung biopsy are unclear. METHODS: We identified 58 consecutive patients with DAD diagnosed by surgical lung biopsy over a 7-year period, January 1996 through December 2002. The presenting clinicoradiologic features, causes, and clinical course of these patients were studied. RESULTS: The median age was 61 years, 48% were women, and 60% were immunocompromised. Ninety percent of patients fulfilled the criteria for ARDS at the time of surgical lung biopsy. Chest radiography demonstrated bilateral parenchymal infiltrates, while CT revealed predominantly ground-glass and consolidative opacities. Infections were the most common cause of DAD (22%). Other causes were noninfectious pulmonary complications of hematopoietic stem-cell or solid-organ transplantation (17%), connective tissue diseases (16%), acute exacerbation of idiopathic pulmonary fibrosis (12%), drugs (10%), and radiation therapy (2%). Twelve patients (21%) had acute interstitial pneumonia (ie, no identifiable cause or predisposing condition for DAD). Overall hospital mortality was 53%, with the highest mortality (86%) occurring among patients for whom DAD represented acute exacerbation of idiopathic pulmonary fibrosis. CONCLUSION: Our study showed that infections and acute interstitial pneumonia are the most common causes of DAD diagnosed by surgical lung biopsy. Hospital mortality rate associated with DAD may vary depending on the underlying cause.
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Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Alveolos Pulmonares/patología , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/diagnóstico , Adulto , Anciano , Biopsia , Femenino , Mortalidad Hospitalaria , Humanos , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Alveolos Pulmonares/cirugía , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/diagnóstico , Radiografía Torácica , Estudios RetrospectivosRESUMEN
Catamenial pneumothorax (CP) is generally caused by intraperitoneal air leaking from the uterus into the thoracic cavity via a defect in the endometrial tissue of the diaphragm and is usually detected in the right thorax. We report a case of left-sided CP caused by endometriosis in the visceral pleura and with no abnormal findings in the diaphragm. A 33-year-old female patient presented at the end of a course of low-dose contraceptive pills for pelvic endometriosis, with spontaneous pneumothorax in the left chest. Chest CT revealed a bulla in the left upper lung lobe. The patient underwent partial resection of the lung. Immunohistochemistry confirmed the presence of endometrial stromal tissue in the visceral pleura and confirmed this as the cause of pneumothorax since there were no observable abnormalities in the diaphragm. This case suggests that immunohistochemical examination of patients with spontaneous pneumothorax can detect alternative endometrial lesions.
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Vesícula/complicaciones , Endometriosis/complicaciones , Neumotórax/complicaciones , Neumotórax/etiología , Alveolos Pulmonares , Enfermedades Torácicas/complicaciones , Adulto , Biopsia , Vesícula/diagnóstico por imagen , Vesícula/cirugía , Endometriosis/diagnóstico por imagen , Endometriosis/cirugía , Femenino , Humanos , Inmunohistoquímica , Neumonectomía , Neumotórax/diagnóstico por imagen , Neumotórax/cirugía , Alveolos Pulmonares/diagnóstico por imagen , Alveolos Pulmonares/cirugía , Enfermedades Torácicas/diagnóstico por imagen , Enfermedades Torácicas/cirugía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: Pulmonary emphysema is the pathological prototype of chronic obstructive pulmonary disease and is also associated with other lung diseases. We considered that observation with different approaches may provide new insights for the pathogenesis of emphysema. PATIENTS AND METHODS: We reviewed tissue blocks of the lungs of 25 cases with/without emphysema and applied a three-dimensional observation method to the blocks. Based on the three-dimensional characteristics of the alveolar structure, we considered one face of the alveolar polyhedron as a structural unit of alveoli and called it a framework unit (FU). We categorized FUs based on their morphological characteristics and counted their number to evaluate the destructive changes in alveoli. We also evaluated the number and the area of pores of Kohn in FUs. We performed linear regression analysis to estimate the effect of these data on pulmonary function tests. RESULTS: In multivariable regression analysis, a decrease in the number of FUs without an alveolar wall led to a significant decrease in the diffusing capacity of the lung for carbon monoxide (DLCO) and DLCO per unit alveolar volume, and an increase in the area of pores of Kohn had a significant effect on an increase in residual capacity. CONCLUSION: A breakdown in the lung framework and an increase in pores of Kohn are associated with a decrease in DLCO and DLCO per unit alveolar volume with/without emphysema.
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Alveolos Pulmonares/patología , Alveolos Pulmonares/fisiopatología , Capacidad de Difusión Pulmonar , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfisema Pulmonar/patología , Enfisema Pulmonar/fisiopatología , Anciano , Femenino , Volumen Espiratorio Forzado , Humanos , Imagenología Tridimensional , Modelos Lineales , Masculino , Microscopía , Persona de Mediana Edad , Análisis Multivariante , Porosidad , Alveolos Pulmonares/cirugía , Enfisema Pulmonar/cirugía , Pruebas de Función Respiratoria , Capacidad VitalRESUMEN
The pulmonary alveolar epithelium undergoes extensive regeneration in response to lung injuries, including lung resection. In recent years, our understanding of cell lineage relationships in the pulmonary alveolar epithelium has improved significantly. However, the molecular and cellular mechanisms that regulate pneumonectomy (PNX)-induced alveolar regeneration remain largely unknown. In this study, we demonstrate that mechanical-tension-induced YAP activation in alveolar stem cells plays a major role in promoting post-PNX alveolar regeneration. Our results indicate that JNK and p38 MAPK signaling is critical for mediating actin-cytoskeleton-remodeling-induced nuclear YAP expression in alveolar stem cells. Moreover, we show that Cdc42-controlled actin remodeling is required for the activation of JNK, p38, and YAP in post-PNX lungs. Our findings together establish that the Cdc42/F-actin/MAPK/YAP signaling cascade is essential for promoting alveolar regeneration in response to mechanical tension in the lung.
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Actinas/genética , Proteínas Adaptadoras Transductoras de Señales/genética , Fosfoproteínas/genética , Neumonectomía , Alveolos Pulmonares/metabolismo , Regeneración/genética , Proteína de Unión al GTP cdc42/genética , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Citoesqueleto de Actina/genética , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Antracenos/farmacología , Fenómenos Biomecánicos , Proteínas de Ciclo Celular , Proliferación Celular , Células Epiteliales/citología , Células Epiteliales/metabolismo , Regulación de la Expresión Génica , Imidazoles/farmacología , MAP Quinasa Quinasa 4/antagonistas & inhibidores , MAP Quinasa Quinasa 4/genética , MAP Quinasa Quinasa 4/metabolismo , Masculino , Mecanotransducción Celular , Ratones , Fosfoproteínas/metabolismo , Cultivo Primario de Células , Alveolos Pulmonares/citología , Alveolos Pulmonares/cirugía , Piridinas/farmacología , Mucosa Respiratoria/citología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/cirugía , Células Madre/citología , Células Madre/metabolismo , Proteínas Señalizadoras YAP , Proteína de Unión al GTP cdc42/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
PURPOSE: The lack of reliable testing methods limits the evidence-based practice of surgical sealants in treating alveolar air leak (AAL). We developed an in vitro lung model to evaluate sealants' efficacy and tested the widely used human thrombin-fibrinogen sponge, TachoSil as an example. MATERIALS AND METHODS: The caudal lobe of freshly excised swine lung (n = 10) was intubated and ventilated. A focal superficial parenchymal defect (40 × 25 mm) was created in the inflated lung. AAL was assessed with increasing inspired tidal volume (TVi). After sealant application, AAL was assessed in the same way until burst failure, defined as an AAL exceeding 20 mL. To evaluate the elasticity of the sealant, the length of defect was recorded in the inflated lung. RESULTS: Superficial parenchymal defects resulted in AAL increasing with ascending TVi. Multiple linear regression analysis revealed strong correlation between AAL and maximal inspiratory pressure, compliance and resistance. At TVi = 400, 500, and 600 mL, TachoSil achieved sealing in ten, eight, and seven tests, respectively. As TVi increased, superficial defects were still sealed in four, two, and two tests at TVi = 700, 800, and 900 mL, respectively. The burst pressure was 42 ± 5 cmH2O. Adhesive failures were found at the burst pressure in all tests. Concerning elasticity, TachoSil allowed an expansion of the covered lung defect of 7 ± 6 mm. CONCLUSIONS: TachoSil demonstrated a strong sealing efficiency and marked elasticity in treating AAL. These results are consistent to that of the previously published animal experiment, suggesting the reliability of the presented in vitro model.
Asunto(s)
Fibrinógeno/uso terapéutico , Pulmón/cirugía , Alveolos Pulmonares/lesiones , Alveolos Pulmonares/cirugía , Trombina/uso terapéutico , Adhesivos Tisulares/uso terapéutico , Animales , Combinación de Medicamentos , Elasticidad , Femenino , Humanos , Técnicas In Vitro , Pulmón/fisiopatología , Masculino , Modelos Anatómicos , Modelos Animales , Alveolos Pulmonares/fisiopatología , Mecánica Respiratoria , Tapones Quirúrgicos de Gaza , Sus scrofaRESUMEN
Pulmonary alveolar microlithiasis (PAM) is characterized by deposition of calcium phosphate within the alveolar airspaces. There is currently no effective medical therapy and affected individuals may progress to end-stage lung disease requiring transplantation. Two patients with PAM underwent bilateral sequential lung transplantation. This study reviews the clinical manifestations of PAM and discusses the particular difficulties that may be encountered in the use of lung transplantation as treatment for this uncommon disease. Also addressed is the question of recurrence in the allograft.