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Severe alpha-1 antitrypsin deficiency (AATD) is associated with an increased risk of emphysema. However, the clinical manifestations are very heterogeneous, and an individual prognosis is very difficult to establish. Intravenous augmentation therapy with alpha-1 antitrypsin (AAT) from pooled blood donors is the only specific treatment available, but it requires weekly or biweekly administration for life. Several guidelines provide the indication criteria for the initiation of AAT augmentation therapy. However, in clinical practice, there are situations in which the decision as to when to start treatment becomes uncertain and some studies have shown great variability in the indication of this treatment even among specialists. The usual dilemma is between initiating augmentation therapy in individuals who may not develop significant lung disease or in whom disease will not progress or delaying it in patients who may otherwise rapidly and irreversibly progress. We illustrate this dilemma with five clinical cases: from the case of a patient with normal lung function who requests initiation of therapy to a moderately stable patient without augmentation or a mild patient who, after several years of remaining stable without treatment, deterioration in lung function initiated and, consequently, augmentation therapy was begun. All the nuances associated with the indication of augmentation justify a personalised approach and the decision about initiating augmentation therapy must be made after careful consideration of the pros and cons with the patient in reference centres with experience in treatment. These reference centres can work in collaboration with local hospitals where patients can be closely followed and augmentation therapy can be administered to avoid unnecessary travelling, making periodical administrations more comfortable for the patient.
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Enfisema Pulmonar , Deficiencia de alfa 1-Antitripsina , alfa 1-Antitripsina , Humanos , Deficiencia de alfa 1-Antitripsina/complicaciones , Deficiencia de alfa 1-Antitripsina/diagnóstico , Deficiencia de alfa 1-Antitripsina/tratamiento farmacológico , Deficiencia de alfa 1-Antitripsina/fisiopatología , alfa 1-Antitripsina/administración & dosificación , Enfisema Pulmonar/fisiopatología , Enfisema Pulmonar/etiología , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/terapia , Masculino , Persona de Mediana Edad , Femenino , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Medicina de Precisión , Adulto , Progresión de la Enfermedad , AncianoRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent and preventable condition. Mesenchymal stem cell (MSC) therapy is being explored to aid in the regeneration of lung cells and airway structure, aiming to restore lung function. AIM: To examine varied responses of MSCs when cultured with peripheral blood mononuclear cells (PBMCs) from different COPD phenotypes, patients were grouped into ACOS, emphysema, and chronic bronchitis categories. METHODS: PBMCs from these groups and controls were co-cultured with MSCs derived from dental follicles, revealing differing rates of apoptosis among COPD phenotypes compared to controls. RESULTS: While the chronic bronchitis group exhibited the least lymphocyte viability (p<0.01), introducing MSCs notably enhanced viability across all phenotypes except emphysema, with the chronic bronchitis group showing the most improvement (p<0.05). CONCLUSION: Stem cell therapy might reduce peripheral lymphocyte apoptosis in COPD, with varying responses based on phenotype, necessitating further research to understand mechanisms and optimize tailored therapies for each COPD subtype.
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Apoptosis , Bronquitis Crónica , Enfermedad Pulmonar Obstructiva Crónica , Linfocitos T , Humanos , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfermedad Pulmonar Obstructiva Crónica/patología , Masculino , Bronquitis Crónica/terapia , Bronquitis Crónica/patología , Femenino , Persona de Mediana Edad , Linfocitos T/inmunología , Anciano , Células Madre Mesenquimatosas/citología , Trasplante de Células Madre Mesenquimatosas , Enfisema Pulmonar/terapia , Enfisema Pulmonar/patología , Enfisema/terapia , Enfisema/patologíaRESUMEN
Impaired and limited alveolar regeneration upon injury advances pulmonary disorders and irreversibly affects millions of people worldwide. Adult mammals do not have a strong potential to regenerate functional lung tissues, while neonatal lungs robustly proliferate and regenerate the functional tissue within a week of birth upon injury. The differential composition of the extracellular matrix (ECM) of neonatal tissues favors cellular proliferation and migration, fostering lung regeneration. Regardless, conventional ECM therapies employ adult-derived tissues. Therefore, the potential differences in regenerative properties of adult and neonatal lung ECM were investigated using in vitro and in vivo lung emphysema model. Decellularization of the neonatal and adult lungs was performed using freeze-thaw cycle method. Decellularization process was structurally characterized using SEM and immunostaining. In vitro treatment of neonatal lung-derived ECM (NECM) significantly enhanced the cellular migration and proliferation compared to adult-lung derived ECM (AECM) treated cigarette smoke-extract (CSE)-stimulated A549 cells. Following the administration of AECM and NECM, we observed a significant decline in emphysematous features and an improvement in lung functions in NECM group. NECM treatment increased the ratio of HOPX+/SpC+ cells with an active proliferation in SpC+ cells shown by colocalization of SpC+/Ki67+ and SpC+/Brdu+ cells. Moreover, NECM treatment activated the Neureguline-1/Erbb2 signaling and fostered a regenerative environment by upregulating the expression of regenerative genes including FGF, WNTs and AXIN-2 as compared to AECM treatment. Our findings suggested the potential utilization of NECM as novel therapeutics in regenerative medicine, deviating from the conventional application of adult-derived ECM treatments in pre-clinical and clinical research.
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Animales Recién Nacidos , Proliferación Celular , Matriz Extracelular Descelularizada , Pulmón , Enfisema Pulmonar , Regeneración , Animales , Humanos , Pulmón/metabolismo , Enfisema Pulmonar/terapia , Matriz Extracelular Descelularizada/química , Células A549 , Movimiento Celular , Modelos Animales de Enfermedad , Matriz Extracelular/metabolismo , MasculinoRESUMEN
There has been an increased recognition of a subset of congenital lobar emphysema (CLE), termed congenital sublobar hyperinflation (CSLH), which may affect only a segment of lung as opposed to an entire lobe. This is an uncommon variant for which there is a paucity of information in published literature. The majority of CLE are managed surgically. Current literature suggests non-operative management for CSLH. However, there has been slow adoption of non-operative management and there is not a well-established observation pathway. A retrospective review of all pediatric patients diagnosed with CSLH at a single institution was performed from 2017 to 2023 to determine if this variant may be safely managed with observation. A total of 10 patients were identified. Of these, three patients had consolidation on cross-sectional imaging; therefore, operative intervention was undertaken given diagnostic uncertainty. All patients managed observationally remained asymptomatic. This case series validates non-operative management for patients with asymptomatic CSLH.
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Enfisema Pulmonar , Humanos , Estudios Retrospectivos , Enfisema Pulmonar/congénito , Enfisema Pulmonar/terapia , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/cirugía , Femenino , Masculino , Lactante , Preescolar , Espera Vigilante , Niño , Recién Nacido , Tomografía Computarizada por Rayos XRESUMEN
INTRODUCTION: Since early in the HIV epidemic, emphysema has been identified among people with HIV (PWH) and has been associated with increased mortality. Smoking cessation is key to risk reduction. Health maintenance for PWH and emphysema should ensure appropriate vaccination and lung cancer screening. Treatment should adhere to inhaler guidelines for the general population, but inhaled corticosteroid (ICS) should be used with caution. Frontiers in treatment include targeted therapeutics. Major knowledge gaps exist in the epidemiology of and optimal care for PWH and emphysema, particularly in low and middle-income countries (LMIC). AREAS COVERED: Topics addressed include risk factors, pathogenesis, current treatment and prevention strategies, and frontiers in research. EXPERT OPINION: There are limited data on the epidemiology of emphysema in LMIC, where more than 90% of deaths from COPD occur and where the morbidity of HIV is most heavily concentrated. The population of PWH is aging, and age-related co-morbidities such as emphysema will only increase in salience. Over the next 5 years, the authors anticipate novel trials of targeted therapy for emphysema specific to PWH, and we anticipate a growing body of evidence to inform optimal clinical care for lung health among PWH in LMIC.
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Enfisema , Infecciones por VIH , Neoplasias Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Detección Precoz del Cáncer , Neoplasias Pulmonares/complicaciones , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/epidemiología , Enfisema Pulmonar/terapia , Enfisema/complicaciones , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiologíaAsunto(s)
Enfisema , Enfisema Pulmonar , Humanos , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/terapiaRESUMEN
OBJECTIVES: Pulmonary emphysema is characterized by the destruction of alveolar units and reduced gas exchange capacity. In the present study, we aimed to deliver induced pluripotent stem cell-derived endothelial cells and pneumocytes to repair and regenerate distal lung tissue in an elastase-induced emphysema model. METHODS: We induced emphysema in athymic rats via intratracheal injection of elastase as previously reported. At 21 and 35 days after elastase treatment, we suspended 80 million induced pluripotent stem cell-derived endothelial cells and 20 million induced pluripotent stem cell-derived pneumocytes in hydrogel and injected the mixture intratracheally. On day 49 after elastase treatment, we performed imaging, functional analysis, and collected lungs for histology. RESULTS: Using immunofluorescence detection of human-specific human leukocyte antigen 1, human-specific CD31, and anti--green fluorescent protein for the reporter labeled pneumocytes, we found that transplanted cells engrafted in 14.69% ± 0.95% of the host alveoli and fully integrated to form vascularized alveoli together with host cells. Transmission electron microscopy confirmed the incorporation of the transplanted human cells and the formation of a blood-air barrier. Human endothelial cells formed perfused vasculature. Computed tomography scans revealed improved vascular density and decelerated emphysema progression in cell-treated lungs. Proliferation of both human and rat cell was higher in cell-treated versus nontreated controls. Cell treatment reduced alveolar enlargement, improved dynamic compliance and residual volume, and improved diffusion capacity. CONCLUSIONS: Our findings suggest that human induced pluripotent stem cell-derived distal lung cells can engraft in emphysematous lungs and participate in the formation of functional distal lung units to ameliorate the progression of emphysema.
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Enfisema , Células Madre Pluripotentes Inducidas , Enfisema Pulmonar , Ratas , Humanos , Animales , Enfisema Pulmonar/inducido químicamente , Enfisema Pulmonar/terapia , Enfisema Pulmonar/patología , Células Epiteliales Alveolares/metabolismo , Células Epiteliales Alveolares/patología , Células Madre Pluripotentes Inducidas/metabolismo , Células Endoteliales/metabolismo , Pulmón , Enfisema/inducido químicamente , Enfisema/metabolismo , Enfisema/patología , Elastasa Pancreática/efectos adversos , Elastasa Pancreática/metabolismoRESUMEN
COPD is a chronic lung disease that affects millions of people, declining their lung function and impairing their life quality. Despite years of research and drug approvals, we are still not capable of halting progression or restoring normal lung function. Mesenchymal stem cells (MSC) are cells with extraordinary repair capacity, and MSC-based therapy brings future hope for COPD treatment, although the best source and route of administration are unclear. MSC from adipose tissue (AD-MSC) represents an option for autologous treatment; however, they could be less effective than donor MSC. We compared in vitro behavior of AD-MSC from COPD and non-COPD individuals by migration/proliferation assay, and tested their therapeutic potential in an elastase mouse model. In addition, we tested intravenous versus intratracheal routes, inoculating umbilical cord (UC) MSC and analyzed molecular changes by protein array. Although COPD AD-MSC have impaired migratory response to VEGF and cigarette smoke, they were as efficient as non-COPD in reducing elastase-induced lung emphysema. UC-MSC reduced lung emphysema regardless of the administration route and modified the inflammatory profile in elastase-treated mice. Our data demonstrate equal therapeutic potential of AD-MSC from COPD and non-COPD subjects in the pre-clinical model, thus supporting their autologous use in disease.
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Enfisema , Células Madre Mesenquimatosas , Enfisema Pulmonar , Animales , Ratones , Elastasa Pancreática , Enfisema Pulmonar/inducido químicamente , Enfisema Pulmonar/terapia , Células Madre Mesenquimatosas/fisiología , Fenómenos Fisiológicos RespiratoriosRESUMEN
Endoscopic lung volume reduction procedure with valves is a well-studied treatment option for advanced lung emphysema to target lung hyperinflation in carefully selected patients with COPD. Before valve implantation, collateral ventilation (CV) of the target lobe needs to be assessed to obtain an optimal treatment effect. The analysis of CV according to current standards occurs via an in vivo assessment with the Chartis®system (PulmonX Inc., Redwood City, CA, USA) and a computed tomography (CT) scan of the thorax with interlobar fissure analysis. The focus of this review is to provide detailed information about the Chartis®procedure and interpretation of Chartis® phenotypes. As a main tool in the assessment of CV and being a safe procedure, the Chartis® assessment should be performed by default to confirm interlobar fissure analysis in most emphysema patients. Based on the obtained results, lung volume reduction therapy options should be discussed in an interdisciplinary emphysema conference.
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Enfisema , Enfisema Pulmonar , Humanos , Pulmón , Broncoscopía/métodos , Ventilación Pulmonar , Enfisema Pulmonar/terapiaRESUMEN
We describe three patients with chronic obstructive pulmonary disease (COPD) and emphysema who developed a pneumothorax while receiving chronic home non-invasive ventilation (NIV). These cases raise the question whether the high alveolar pressures given by NIV may have contributed to the development of their pneumothorax by barotrauma. Pneumothorax in patients with COPD receiving NIV is uncommon, the pressures in our patients with COPD who developed pneumothorax were not extremely high and time to development of pneumothorax was relatively long after the initiation of NIV. Further, in our patients, the CT scan showed paraseptal emphysema, a known risk factor for pneumothorax. This suggests that COPD/emphysema phenotype is probably a more important factor for indicating pneumothorax risk than ventilator settings. Better phenotyping of patients with COPD in whom benefits of NIV can be expected at minimal risk of serious side-effects is needed to inform our patients properly and bring the field of chronic NIV in COPD forward.
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Enfisema , Ventilación no Invasiva , Neumotórax , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Insuficiencia Respiratoria , Humanos , Ventilación no Invasiva/efectos adversos , Neumotórax/diagnóstico por imagen , Neumotórax/etiología , Neumotórax/terapia , Insuficiencia Respiratoria/etiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfisema Pulmonar/complicaciones , Enfisema Pulmonar/diagnóstico por imagen , Enfisema Pulmonar/terapia , Enfisema/complicaciones , Ventiladores Mecánicos/efectos adversos , FenotipoRESUMEN
El síndrome de Swyer-James-Mac Leod es una entidad poco frecuente adquirida en la infancia, generalmente tras una infección pulmonar moderada a grave de tipo bronquiolitis o neumonía, generalmente virales. Ocasionalmente se tiene el antecedente de infecciones repetidas de este tipo. Consiste en el desarrollo de enfisema hipoplásico pulmonar unilateral, que puede a veces relacionarse con bronquiectasias ipsilaterales o bilaterales, obstrucción fija al flujo aéreo y puede también asociarse a reducción del flujo sanguíneo del pulmón hipoplásico, de manera focal o difusa, con o sin tortuosidad de la vascularización proximal y a veces con una compensación del pulmón contralateral, en forma de sobredistensión e hiperflujo vascular relativo. Presentamos el caso de un varón de 79 años de edad con antecedentes de infecciones tipo bronquiolitis virales repetidas en la infancia, obstrucción fija grave al flujo aéreo y hemoptisis masiva secundaria a una infección por Pseudomonas aeruginosa sensible a la terapia antibiótica habitual.
Swyer-James-Mac Leod syndrome is a rare condition acquired in childhood, usually after a moderate to severe lung infection such as bronchiolitis or pneumonia, usually viral. Occasionally there is a history of repeated infections of this type. It consists of the development of unilateral pulmonary hypoplastic emphysema, which can sometimes be related to ipsilateral or bilateral bronchiectasis, fixed airflow obstruction, and may also be associated with reduced blood flow in the hypoplastic lung, with or without tortuosity of the proximal vascular supply and sometimes with compensation from the contralateral lung, in the form of overdistension and relative vascular hyperflow. We present the case of a 79-year-old man with a history of recurrent viral bronchiolitis-type infections in childhood, severe fixed airflow obstruction, and massive hemoptysis secondary to a Pseudomonas aeruginosa infection sensitive to usual antibiotic therapy.
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Humanos , Masculino , Anciano , Enfisema Pulmonar/complicaciones , Pulmón Hiperluminoso/complicaciones , Hemoptisis/etiología , Enfisema Pulmonar/terapia , Enfisema Pulmonar/diagnóstico por imagen , Radiografía Torácica , Pulmón Hiperluminoso/terapia , Pulmón Hiperluminoso/diagnóstico por imagen , Angiografía por Tomografía ComputarizadaRESUMEN
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in chronic lung disease patients throughout the world. Mesenchymal stem cells (MSCs) have been shown to regulate immunomodulatory, anti-inflammatory, and regenerative responses. However, the effects of human-umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) on the lung pathophysiology of COPD remain unclear. We aimed to investigate the role of hUC-MSCs in emphysema severity and Yes-associated protein (Yap) phosphorylation (p-Yap) in a porcine-pancreatic-elastase (PPE)-induced emphysema model. We observed that the emphysema percentages (normalized to the total lung volume) measured by chest computed tomography (CT) and exercise oxygen desaturation were significantly reduced by hUC-MSCs at 107 cells/kg body weight (BW) via intravenous administration in emphysematous mice (p < 0.05). Consistently, the emphysema index, as assessed by the mean linear intercept (MLI), significantly decreased with hUC-MSC administration at 3 × 106 and 107 cells/kg BW (p < 0.05). Changes in the lymphocytes, monocytes, and splenic cluster of differentiation 4-positive (CD4+) lymphocytes by PPE were significantly reversed by hUC-MSC administration in emphysematous mice (p < 0.05). An increasing neutrophil/lymphocyte ratio was reduced by hUC-MSCs at 3 × 106 and 107 cells/kg BW (p < 0.05). The higher levels of tumor necrosis factor (TNF)-α, keratinocyte chemoattractant (KC), and lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF) were significantly decreased by hUC-MSC administration (p < 0.05). A decreasing p-Yap/Yap ratio in type II alveolar epithelial cells (AECII) of mice with PPE-induced emphysema was significantly increased by hUC-MSCs (p < 0.05). In conclusion, the administration of hUC-MSCs improved multiple pathophysiological features of mice with PPE-induced emphysema. The effectiveness of the treatment of pulmonary emphysema with hUC-MSCs provides an essential and significant foundation for future clinical studies of MSCs in COPD patients.
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Enfisema , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Animales , Enfisema/metabolismo , Humanos , Células Madre Mesenquimatosas/metabolismo , Ratones , Elastasa Pancreática/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/terapia , Porcinos , Cordón UmbilicalAsunto(s)
Enfisema Pulmonar , Fibrosis Pulmonar , Humanos , Enfisema Pulmonar/complicaciones , Enfisema Pulmonar/diagnóstico por imagen , Enfisema Pulmonar/terapia , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/diagnóstico , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/terapiaRESUMEN
In addition to recommendations for pharmacological treatment stratified for risk and phenotype, the new 2021 edition of the Spanish COPD Guidelines (GesEPOC 2021) proposes a personalized approach to treatable traits, defined as a characteristic (clinical, physiological, or biological) that can be identified by diagnostic tests or biomarkers, for which a specific treatment is available. Some treatable traits, such as malnutrition, sedentarism, emphysema or respiratory failure, can be treated with non-pharmacological therapies, and this was not covered in detail in the guidelines. This section of GesEPOC 2021 includes a narrative update with recommendations on dietary treatment, physical activity, respiratory rehabilitation, oxygen therapy, non-invasive ventilation, volume reduction, and lung transplantation. A PICO question with recommendations on the use of supplemental oxygen during exercise in COPD patients without severe hypoxemia is also included.
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Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Broncodilatadores/uso terapéutico , Humanos , Oxígeno , Terapia por Inhalación de Oxígeno , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfisema Pulmonar/terapiaRESUMEN
Extensive inflammation and apoptosis in structural cells of the lung are responsible for the progression and pathogenesis of chronic obstructive pulmonary disease (COPD). Myotubularin-related protein 14 (MTMR14) has been shown to participate in various biological processes, including apoptosis, inflammation, and autophagy. Nonetheless, the role of MTMR14 in COPD remains elusive. In the present study, we explored the expression of MTMR14 in human lung tissues and investigated the effects of overexpressed MTMR14 on in vitro and in vivo COPD models. Moreover, one of the possible mechanisms of MTMR14 alleviating COPD was explored based on mitochondrial function and mitophagy homeostasis. The results showed that MTMR14 expression was reduced in COPD patients' lungs in comparison to control subjects. MTMR14 overexpression inhibited cigarette smoke extract-induced inflammation and apoptosis and improved mitochondrial function and mitophagy in vitro. Further verification was carried out in COPD model mice. MTMR14 overexpression inhibited lung inflammation and reduced levels of IL-6 and KC in bronchoalveolar lavage fluid, as well as prevented emphysema and a decline in lung function. Furthermore, MTMR14 overexpression improved mitochondrial function and mitophagy to a certain extent. Collectively, our data support the hypothesis that MTMR14 participates in the pathogenesis of COPD. Improving mitochondrial function and mitophagy homeostasis may be one of the mechanisms by which MTMR14 alleviates COPD and may potentially be a novel therapeutic target for COPD.
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Inflamación/metabolismo , Enfermedades Pulmonares/terapia , Monoéster Fosfórico Hidrolasas/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/orina , Enfisema Pulmonar/terapia , Adulto , Anciano , Anciano de 80 o más Años , Animales , Modelos Animales de Enfermedad , Humanos , Enfermedades Pulmonares/genética , Enfermedades Pulmonares/patología , Masculino , Ratones , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfisema Pulmonar/genética , Enfisema Pulmonar/patologíaRESUMEN
BACKGROUND: Endobronchial valve therapy has proven to reduce lung hyperinflation and decrease disease burden in patients with severe lung emphysema. Exclusion of collateral ventilation (CV) of the targeted lobe by using an endobronchial assessment system (Chartis; PulmonX, Drive Redwood City, CA, USA) in combination with software-based fissure integrity analysis (FCS [fissure completeness score]) of computed tomography scans of the lung are established tools to select appropriate patients for endobronchial valve treatment. So far, there is no conclusive evidence if the ventilation mode during bronchoscopy impacts the outcome of Chartis assessments. METHODS: Patients with Chartis assessments and software-based quantification of FCS (StratX; PulmonX, Drive Redwood City, CA, USA) were enrolled in this retrospective study. During bronchoscopy, pulmonary fissure integrity was evaluated with the Chartis assessment system in each patient first under spontaneous breathing and subsequently under high-frequency (HF) jet ventilation. RESULTS: In total, 102 patients were analyzed. Four Chartis phenotypes CV positive (CV+), CV negative (CV-), low flow, and low plateau in spontaneous breathing and HF jet ventilation were identified. The frequency of each Chartis phenotype per lobe was similar in both settings. When comparing Chartis assessments in spontaneous breathing and HF jet ventilation, there was an overall good concordance rate for all analyzed fissures. In agreement, receiver operating characteristic analysis of the FCS showed an almost similar prediction for CV+ and CV- status independent of the ventilation modes. CONCLUSION: Chartis assessment in spontaneous breathing and HF jet ventilation had similar rates in detecting CV in lung emphysema. Our results suggest that both modes are equivalent for the assessment of CV.
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Enfisema Pulmonar , Broncoscopía/métodos , Humanos , Pulmón , Neumonectomía/métodos , Enfisema Pulmonar/terapia , Ventilación Pulmonar , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: Chronic obstructive pulmonary disease (COPD) is a worldwide problem because of its high prevalence and mortality. However, there is no fundamental treatment to ameliorate their pathological change in COPD lung. Recently, adipose-derived mesenchymal stem cells (ADSCs) have attracted attention in the field of regenerative medicine to repair damaged organs. Moreover, their utility in treating respiratory diseases has been reported in some animal models. However, the detailed mechanism by which ADSCs improve chronic respiratory diseases, including COPD, remains to be elucidated. We examined whether human ADSCs (hADSCs) ameliorated elastase-induced emphysema and whether hADSCs differentiated into alveolar epithelial cells in a murine model of COPD. METHODS: Female SCID-beige mice (6 weeks old) were divided into the following four groups according to whether they received an intratracheal injection of phosphate-buffered saline or porcine pancreatic elastase, and whether they received an intravenous injection of saline or hADSCs 3 days after intratracheal injection; Control group, hADSC group, Elastase group, and Elastase-hADSC group. We evaluated the lung function, assessed histological changes, and compared gene expression between hADSCs isolated from the lung of Elastase-hADSC group and naïve hADSCs 28 days after saline or elastase administration. RESULTS: hADSCs improved the pathogenesis of COPD, including the mean linear intercept and forced expiratory volume, in an elastase-induced emphysema model in mice. Furthermore, hADSCs were observed in the lungs of elastase-treated mice at 25 days after administration. These cells expressed genes related to mesenchymal-epithelial transition and surface markers of alveolar epithelial cells, such as TTF-1, ß-catenin, and E-cadherin. CONCLUSION: hADSCs have the potential to improve the pathogenesis of COPD by differentiating into alveolar epithelial cells by mesenchymal-epithelial transition.
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Enfisema , Células Madre Mesenquimatosas , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Animales , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones SCID , Elastasa Pancreática , Enfermedad Pulmonar Obstructiva Crónica/inducido químicamente , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfisema Pulmonar/inducido químicamente , Enfisema Pulmonar/genética , Enfisema Pulmonar/terapia , PorcinosRESUMEN
BACKGROUND: Lung volume reduction with endobronchial coils treatment (ECT), for patients with severe emphysema, has shown modest improvement in exercise capacity and lung functions in clinical trials, yet the benefit of this procedure is still unclear. METHODS: We conducted a multicenter retrospective cohort study including all patients who underwent ECT in Israel and a propensity score matched control group of patients with chronic obstructive pulmonary disease (COPD) that were treated with usual care. The primary outcome was six-minute walk test distance (6MWTD), secondary outcomes were lung function tests and patient survival. RESULTS: Overall, 46 patients were included in the ECT group. Their mean 6MWTD at baseline and at 6 and at 24 months post procedure was 331.0±101.4, 372.9±76.8 and 338.8±104.8, respectively (overall P=0.04, pairwise comparison: baseline to 6 months (P=0.1), baseline to 24 months (P=1.0)). Mean FEV1 values at baseline and at 6 and at 24 months post procedure were 0.86±0.38, 0.92±0.37 and 0.82±0.36 liters, respectively (overall P=0.003, pairwise comparison: baseline to 6 months (P=0.04), baseline to 24 months (P=0.75)). The median 6MWTD for the ECT and control groups at 24 months were 333.0 (262.5-390) and 280 (210-405), respectively (P=0.16). There was no difference in overall survival (P=0.84). Heterogenous emphysema was a significant predictor of treatment success in univariate analysis (p=0.004). CONCLUSION: Lung volume reduction with endobronchial coils may improve the exercise capacity and FEV1 of COPD patients. However, the majority of the effect was diminished after 24 months. The current state of evidence does not support regulatory approval of ECT and warrant its use only after consideration of the benefit-harm ratio in a highly selected patient population.
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Enfisema , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Broncoscopía , Tolerancia al Ejercicio , Volumen Espiratorio Forzado , Humanos , Pulmón , Neumonectomía , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfisema Pulmonar/cirugía , Enfisema Pulmonar/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
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.