RESUMO
Background: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterized by heterogeneous abnormalities of the airways and lung parenchyma that cause different clinical presentations. The assessment of the prevailing pathogenetic components underlying COPD is not usually pursued in daily practice, also due to technological limitations and cost. Aim: To assess non-invasively the lung emphysema component of COPD by the simultaneous measurement of DLNO and DLCO via a single-breath (sDLNO and sDLCO). Methods: COPD patients aged ≥40 years of both genders were recruited consecutively and labelled by computed tomography as "with significant" emphysema (>10% of CT lung volume) or "with negligible" emphysema otherwise. Current lung function tests such as sDLNO, sDLCO and Vc (the lung capillary blood volume) were measured. All possible subsets of independent spirometric and diffusive parameters were tested as predictors of emphysema, and their predicted power compared to each parameter alone by ROC analysis and area under the curve (AUC). Results: Thirty-one patients with "significant emphysema" were compared to thirty-one with "negligible emphysema". FEV1 and FEV1/FVC seemed to be the best spirometric predictors (AUC 0.80 and 0.81, respectively), while sDLCO and Vc had the highest predicted power among diffusive parameters (AUC 0.92 and 0.94, respectively). sDLCO and Vc values were the parameters most correlated to the extent of CT emphysema. Six subsets of independent predictors were identified and included at least one spirometric and one diffusive parameter. According to goodness-to-fit scores (AIC, BIC, log-likelihood and pseudo R2), RV coupled with sDLCO or Vc proved the best predictors of emphysema. Conclusion: When investigating the parenchymal destructive component due to emphysema occurring in COPD, sDLNO, sDLCO and Vc do enhance the predictive power of current spirometric measures substantially. sDLNO, sDLCO and Vc contribute to phenotype of the main pathogenetic components of COPD easily and with high sensitivity. Organizational problems, radiation exposure, time and costs could be reduced, while personalized and precision medicine could be noticeably implemented.
Assuntos
Pulmão , Valor Preditivo dos Testes , Capacidade de Difusão Pulmonar , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Espirometria , Humanos , Masculino , Feminino , Enfisema Pulmonar/fisiopatologia , Enfisema Pulmonar/diagnóstico , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Volume Expiratório Forçado , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Capacidade Vital , Tomografia Computadorizada por Raios X , Monóxido de Carbono/metabolismo , Monóxido de Carbono/análise , Área Sob a Curva , Curva ROC , Testes Respiratórios/métodos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Giant bullous emphysema is characterized by large bullae occupying at least one-third of the hemithorax and leading to compression of the surrounding lung parenchyma. Overdiagnosis can occur because of the atypical appearance of hyperplastic type II pneumocytes, which may be mistaken for malignant cells. CASE PRESENTATION: A 48-year-old male with a history of smoking and occupational exposure presented with dyspnea and drowsiness. Initial chest X-ray revealed a tension pneumothorax, and subsequent chest CT revealed extensive bullous emphysema and lung cancer in the right middle lobe (RML). Pathologic examination initially indicated resected bullae to metastatic adenocarcinoma, but upon review, it was determined that the reactive alveolar cells were misdiagnosed as malignant. CONCLUSIONS: This case emphasizes the need for thorough histopathological assessment and prudent interpretation of atypical cellular morphology.
Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Enfisema Pulmonar , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma/secundário , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Enfisema Pulmonar/diagnóstico , Tomografia Computadorizada por Raios X , Erros de Diagnóstico , Diagnóstico Diferencial , Vesícula/diagnósticoRESUMO
Vanishing lung syndrome (VLS) or idiopathic giant bullous disease is a rare condition characterized by giant emphysematous bullae, classically presenting as a slowly enlarging bulla that compresses normal lung parenchyma and causes mediastinal shift, leading to increasing dyspnea and reduced exercise tolerance. Intermittent sudden worsening of symptoms may be seen because of secondary pneumothorax due to rupture of these bullae. Here we present three cases of vanishing lung syndrome in children due to tuberculosis (TB). Reports on VLS due to TB are bare minimum. In contrast to most of the published case reports, our cases had a moderate to rapid progression, bilateral extensive bullae and isoniazid which has been traditionally thought to be the causative factor was not used in one of our patients. All three are female patients arising new horizons of research regarding whether there is any sex predominance.
Assuntos
Tuberculose Pulmonar , Humanos , Feminino , Tuberculose Pulmonar/complicações , Criança , Antituberculosos/uso terapêutico , Enfisema Pulmonar/complicações , Síndrome , Tomografia Computadorizada por Raios X , Vesícula , AdolescenteRESUMO
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.
Assuntos
Enfisema Pulmonar , Deficiência de alfa 1-Antitripsina , alfa 1-Antitripsina , Humanos , Deficiência de alfa 1-Antitripsina/complicações , Deficiência de alfa 1-Antitripsina/diagnóstico , Deficiência de alfa 1-Antitripsina/tratamento farmacológico , Deficiência de alfa 1-Antitripsina/fisiopatologia , alfa 1-Antitripsina/administração & dosagem , Enfisema Pulmonar/fisiopatologia , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/terapia , Masculino , Pessoa de Meia-Idade , Feminino , Índice de Gravidade de Doença , Resultado do Tratamento , Medicina de Precisão , Adulto , Progressão da Doença , IdosoRESUMO
Reduced skeletal muscle mass and oxidative capacity coexist in patients with pulmonary emphysema and are independently associated with higher mortality. If reduced cellular respiration contributes to muscle atrophy in that setting remains unknown. Using a mouse with genetically induced pulmonary emphysema that recapitulates muscle dysfunction, we found that reduced activity of succinate dehydrogenase (SDH) is a hallmark of its myopathic changes. We generated an inducible, muscle-specific SDH knockout mouse that demonstrates lower mitochondrial oxygen consumption, myofiber contractility, and exercise endurance. Respirometry analyses show that in vitro complex I respiration is unaffected by loss of SDH subunit C in muscle mitochondria, which is consistent with the pulmonary emphysema animal data. SDH knockout initially causes succinate accumulation associated with a down-regulated transcriptome but modest proteome effects. Muscle mass, myofiber type composition, and overall body mass constituents remain unaltered in the transgenic mice. Thus, while SDH regulates myofiber respiration in experimental pulmonary emphysema, it does not control muscle mass or other body constituents.
Assuntos
Respiração Celular , Camundongos Knockout , Contração Muscular , Músculo Esquelético , Enfisema Pulmonar , Succinato Desidrogenase , Animais , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/genética , Enfisema Pulmonar/patologia , Enfisema Pulmonar/etiologia , Succinato Desidrogenase/metabolismo , Succinato Desidrogenase/genética , Camundongos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Complexo II de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/genética , Modelos Animais de Doenças , Camundongos Transgênicos , Mitocôndrias Musculares/metabolismo , Mitocôndrias Musculares/patologia , Consumo de OxigênioRESUMO
Iatrogenic pneumothorax is a relevant complication of computed tomography (CT)-guided percutaneous lung biopsy. The aim of the present study was to analyze the prognostic significance of texture analysis, emphysema score and muscle mass derived from CT-imaging to predict postinterventional pneumothorax after CT-guided lung biopsy. Consecutive patients undergoing CT-guided percutaneous lung biopsy between 2012 and 2021 were analyzed. Multivariate logistic regression analysis included clinical risk factors and CT-imaging features to detect associations with pneumothorax development. Overall, 479 patients (178 females, mean age 65 ± 11.7 years) underwent CT-guided percutaneous lung biopsy of which 180 patients (37.5%) developed pneumothorax including 55 patients (11.5%) requiring chest tube placement. Risk factors associated with pneumothorax were chronic-obstructive pulmonary disease (COPD) (p = 0.03), age (p = 0.02), total lung capacity (p < 0.01) and residual volume (p = 0.01) as well as interventional parameters needle length inside the lung (p < 0.001), target lesion attached to pleura (p = 0.04), and intervention duration (p < 0.001). The combined model demonstrated a prediction accuracy of the occurrence of pneumothorax with an AUC of 0.78 [95%CI: 0.70-0.86] with a resulting sensitivity 0.80 and a specificity of 0.66. In conclusion, radiomics features of the target lesion and the lung lobe CT-emphysema score are predictive for the occurrence of pneumothorax and need for chest insertion after CT-guided lung biopsy.
Assuntos
Tubos Torácicos , Biópsia Guiada por Imagem , Pneumotórax , Enfisema Pulmonar , Tomografia Computadorizada por Raios X , Humanos , Pneumotórax/diagnóstico por imagem , Pneumotórax/etiologia , Pneumotórax/epidemiologia , Feminino , Masculino , Tomografia Computadorizada por Raios X/métodos , Idoso , Enfisema Pulmonar/diagnóstico por imagem , Biópsia Guiada por Imagem/métodos , Biópsia Guiada por Imagem/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Fatores de Risco , RadiômicaRESUMO
The antitumor and antimetastatic activity of dopamine D2 receptor antagonists spiperone was studied in C57BL/6 mice in a model of combined pathology (emphysema and lung cancer). Emphysema was induced by administration of LPS and cigarette smoke extract. Lung cancer was induced by injection of Lewis lung carcinoma cells into the lung. It has been shown that under conditions of combined lung pathology, spiperone prevents inflammatory infiltration and emphysematous expansion of the lungs and reduces the size of the primary tumor node, the number of metastases, and the area of the lungs affected by metastases. Spiperone reduces the number of cancer stem cells (CSCs) in the lungs and blood of mice with combined pathology. CSCs isolated from the lungs and blood of mice with combined pathology treated with spiperone had a significantly lower potential to form a tumorosphere in vitro than CSCs from untreated mice with emphysema and lung carcinoma. Thus, blockade of dopamine D2 receptors is a promising approach for correcting combined lung pathology and can be used in the development of a method for treating lung cancer in patients with emphysema.
Assuntos
Carcinoma Pulmonar de Lewis , Neoplasias Pulmonares , Camundongos Endogâmicos C57BL , Células-Tronco Neoplásicas , Enfisema Pulmonar , Espiperona , Animais , Espiperona/farmacologia , Espiperona/uso terapêutico , Camundongos , Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Lewis/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Enfisema Pulmonar/tratamento farmacológico , Enfisema Pulmonar/patologia , Enfisema Pulmonar/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Antineoplásicos/farmacologia , Masculino , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Antagonistas dos Receptores de Dopamina D2/farmacologia , Antagonistas dos Receptores de Dopamina D2/uso terapêutico , Receptores de Dopamina D2/metabolismo , Lipopolissacarídeos/toxicidadeRESUMO
Chronic obstructive pulmonary disease is a common chronic lung disease with an ever-increasing incidence. Despite years of drug research and approvals, we are still not able to halt progress or restore normal lung function. Our previous studies have demonstrated that liver growth factor-LGF has an effect on the repair of the affected tissue in a mouse model of cigarette smoke exposure, but by what pathways it achieves this is unknown. The present study aimed to identify differentially expressed genes between emphysematous mice treated with LGF to identify potential therapeutic targets for the treatment of pulmonary emphysema. The emphysema mouse model was induced by prolonged exposure to cigarette smoke. To determine the gene expression profile of the lung in smokers treated or not with LGF, lung messenger RNA gene expression was assessed with the Agilent Array platform. We carried out differentially expressed gene analysis, functional enrichment and validated in treated mouse lung samples. The treated group significantly improved lung function (~35%) and emphysema level (~20%), consistent with our previous published studies. Microarray analysis demonstrated 290 differentially expressed genes in total (2.0-fold over or lower expressed). Injury repair-associated genes and pathways were further enhanced in the lung of LGF treated mice. The expression trends of two genes (Zscan2 and Bag6) were different in emphysematous lungs treated with LGF compared to untreated lungs. Therefore, Zscan2 and Bag6 genes could play a role in regulating inflammation and the immune response in the lung that undergoes partial lung regeneration. However, further studies are necessary to demonstrate this causal relationship.
Assuntos
Modelos Animais de Doenças , Pulmão , Doença Pulmonar Obstrutiva Crônica , Fatores de Transcrição , Animais , Masculino , Camundongos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos Endogâmicos C57BL , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Enfisema Pulmonar/genética , Enfisema Pulmonar/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
PURPOSE: Latent TGF-ß binding protein 4 (LTBP4) is involved in the production of elastin fibers and has been implicated in LTBP4-related cutis laxa and its complication, emphysema-like changes. Various factors have been implicated in the pathogenesis of emphysema, including elastic degeneration, inflammation, cellular senescence, mitochondrial dysfunction, and decreased angiogenesis in the lungs. We investigated the association between LTBP4 and emphysema using human lung fibroblasts with silenced LTBP4 genes. METHODS: Cell contraction, elastin expression, cellular senescence, inflammation, anti-inflammatory factors, and mitochondrial function were compared between the LTBP4 small interfering RNA (siRNA) and control siRNA. RESULTS: Under the suppression of LTBP4, significant changes were observed in the following: decreased cell contractility, decreased elastin expression, increased expression of the p16 gene involved in cellular senescence, increased TNFα, decreased GSTM3 and SOD, decreased mitochondrial membrane potential, and decreased VEGF expression. Furthermore, the decreased cell contractility and increased GSTM3 expression observed under LTBP4 suppression were restored by the addition of N-acetyl-L-cysteine or recombinant LTBP4. CONCLUSION: The decreased elastin expression, cellular senescence, inflammation, decreased antioxidant activity, mitochondrial dysfunction, and decreased VEGF expression under reduced LTBP4 expression may all be involved in the destruction of the alveolar wall in emphysema. Smoking is the most common cause of emphysema; however, genetic factors related to LTBP4 expression and other factors may also contribute to its pathogenesis.
Assuntos
Senescência Celular , Fibroblastos , Proteínas de Ligação a TGF-beta Latente , Humanos , Proteínas de Ligação a TGF-beta Latente/genética , Proteínas de Ligação a TGF-beta Latente/metabolismo , Senescência Celular/fisiologia , Fibroblastos/metabolismo , Elastina/metabolismo , RNA Interferente Pequeno , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/genética , Enfisema Pulmonar/patologia , Células Cultivadas , Pulmão/metabolismo , Pulmão/patologia , Enfisema/metabolismo , Enfisema/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
There is limited evidence regarding the causal inference of emphysema and functional small airway disease in the subsequent progression of chronic obstructive pulmonary disease (COPD). Patients consisting of two independent cohorts diagnosed with COPD and underwent two serial chest CT scans were included. Total percent emphysema (PRMEmph) and fSAD (PRMfSAD) was quantified via PRM. To investigate the progression of emphysema, we divided COPD patients with PRMEmph < 10% into low and high PRMfSADgroup, matched with similar baseline characteristics, and conducted nonparametric hypothesis tests based on randomization inference using Wilcoxon signed rank test and Huber's M statistics. In patients with baseline PRMEmph < 10%, there were 26 and 16 patients in the low PRMfSA group and 52 and 64 patients in the high PRMfSA in the derivation and validation cohorts, respectively. In the both low and high PRMfSAD groups, there were 0.11 and 1.43 percentage point increases (Huber's M statistic p = 0.016) and 0.58 and 2.09 percentage point increases (p = 0.038) in the proportion of emphysema in the derivation and validation cohorts, respectively. On the contrary, among patients with baseline PRMfSAD < 20%, there was no significant differences in the interval changes of PRMfSAD between the low and high PRMEmph groups in both cohorts. In COPD patients with low emphysema, group with baseline high PRMfSAD showed greater change of PRMEmph than those with low PRMfSAD in both the derivation and validation cohorts. Imaging-based longitudinal quantitative analysis may provide important evidence that small airway disease precedes emphysema in CT-based early COPD patients.
Assuntos
Progressão da Doença , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Tomografia Computadorizada por Raios X , Humanos , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Masculino , Feminino , Idoso , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Enfisema Pulmonar/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pulmão/patologiaRESUMO
Purpose: We compared pulmonary function indices and quantitative CT parameters of airway remodeling, air trapping, and emphysema in asthmatic patients and patients with COPD and asthma-COPD overlap (ACO) and explored their relationships with airflow limitation. Patients and Methods: Patients with asthma (n=48), COPD (n=52), and ACO (n=30) and controls (n=54) who completed pulmonary function tests and HRCT scans were retrospectively enrolled in our study. Quantitative CT analysis software was used to assess emphysema (LAA%), airway wall dimensions (wall area (WA), luminal area (LA), and wall area percentage (WA%)), and air trapping ((relative volume change of -860 HU to -950 HU (RVC-860 to-950) and the expiration-to-inspiration ratio of the mean lung density (MLDE/I))). Differences in pulmonary function and HRCT parameters were compared among the groups. Spearman correlation analysis and regression analysis were utilized to explore structureâfunction relationships. Results: The LAA% in COPD and ACO patients was significantly greater than that in asthmatic patients and controls. The WA% and WA in COPD and ACO patients were greater than those in controls, whereas the WA% and LA between asthmatic patients and controls reached statistical significance. The RVC-860 to -950 levels decreased in the following order: ACO, COPD, and asthma. RVC-860 to -950 independently predicted FEV1% in asthmatic patients; LAA% and MLDE/I in COPD patients; and LAA%, WA% and RVC-860 to -950 in ACO patients. Conclusion: Comparable emphysema was observed in patients with COPD and ACO but not in asthmatic patients. All patients exhibited proximal airway remodeling. The bronchi were thickened outward in COPD and ACO patients but are thickened inward in asthmatic patients. Furthermore, air trapping in ACO patients was the most severe among all the groups. Indirect lung densitometry measurements might be more predictive of the degree of airflow limitation than direct airway measurements in obstructive airway diseases.
Assuntos
Remodelação das Vias Aéreas , Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma , Asma , Pulmão , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Estudos Retrospectivos , Asma/fisiopatologia , Asma/diagnóstico por imagem , Asma/complicações , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/complicações , Idoso , Enfisema Pulmonar/fisiopatologia , Enfisema Pulmonar/diagnóstico por imagem , Volume Expiratório Forçado , Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma/fisiopatologia , Síndrome de Sobreposição da Doença Pulmonar Obstrutiva Crônica e Asma/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Capacidade Vital , Testes de Função Respiratória , Tomografia Computadorizada MultidetectoresRESUMO
Endoscopic lung volume reduction (ELVR) is an established treatment option for patients with severe emphysema. Not all patients are candidates for this type of intervention, and in the context of significant airway secretions, they may be excluded from treatment. Bronchial Rheoplasty (BR) was developed to treat mucus hypersecretion by delivering nonthermal pulsed electric fields to the airway epithelium and submucosa. The literature to date demonstrates that patients treated with BR in clinical studies have a reduction in airway goblet cell hyperplasia as well as substantive clinical improvement in the setting of chronic bronchitis (CB). In this case series, we present four patients treated at three different institutions who had previously undergone ELVR with beneficial outcome. However, over time, these patients subsequently developed worsening clinical issues, including complaints of increased and thickened mucus, along with exacerbations in the setting of a loss of some ELVR-associated benefits. These patients then underwent exploratory treatment with BR with the intent of reducing their secretion burden and potentially restoring the efficacy associated with the initial placement of the airway valves. All BR procedures were well tolerated, and three of the four patients showed substantial improvement in their symptom burden. Airway examinations during the second of the two BR procedures also revealed what appeared to be less airway mucosal inflammation and a decrease in the quantity of airway secretions. Therefore, treatment with BR may have the potential to improve and restore the initial benefits associated with ELVR, thus enhancing long-term outcomes. Further clinical studies with sufficient follow-up are warranted to assess this in a larger cohort of patients, and to determine whether treatment with BR prior to ELVR may make more patients eligible for this treatment through reduction in their secretions and/or symptoms.
Assuntos
Broncoscopia , Pulmão , Pneumonectomia , Enfisema Pulmonar , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Broncoscopia/métodos , Volume Expiratório Forçado , Pulmão/fisiopatologia , Pulmão/cirurgia , Muco/metabolismo , Pneumonectomia/efeitos adversos , Pneumonectomia/métodos , Enfisema Pulmonar/cirurgia , Enfisema Pulmonar/fisiopatologia , Enfisema Pulmonar/diagnóstico , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: This is a retrospective cohort study from a single center of Chest Medical District of Nanjing Brain Hospital Affiliated to Nanjing Medical University, Jiangsu Province, China. It was aim to evaluate the diagnostic value of radial endobronchial ultrasound (R-EBUS) combination with rapid on-site evaluation (ROSE) guided transbronchial lung biopsy (TBLB) for peripheral pulmonary lesions in patients with emphysema. METHODS: All 170 patients who underwent PPLs with emphysema received an R-EBUS examination with or without the ROSE procedure, and the diagnostic yield, safety, and possible factors influencing diagnosis were analyzed between the two groups by the SPSS 25.0 software. RESULTS: The pooled and benign diagnostic yields were not different in the two groups (P = 0.224, 0.924), but the diagnostic yield of malignant PPLs was significantly higher in the group with ROSE than the group without ROSE (P = 0.042). The sensitivity of ROSE was 79.10%, the specificity, 91.67%, the positive predictive value, 98.15%, and the negative predictive value, 84.62%. The diagnostic accuracy, was 95.52%. In the group of R-EBUS + ROSE, the procedural time and the number of times of biopsy or brushing were both significantly reduced (all P<0.05). The incidence of pneumothorax (1.20%) and bleeding (10.84%) in the group of R-EBUS + ROSE were also less than those in the group of R-EBUS (P<0.05). The lesion's diameter ≥ 2 cm, the distance between the pleura and the lesion ≥ 2 cm, the positive air bronchograms sign, the location of the ultrasound probe within the lesion, and the even echo with clear margin feature of lesion ultrasonic image, these factors are possibly relevant to a higher diagnostic yield. The diagnostic yield of PPLs those were adjacent to emphysema were lower than those PPLs which were away from emphysema (P = 0.048) in the group without ROSE, however, in the group of R-EBUS + ROSE, there was no such difference whether the lesion is adjacent to emphysema or not (P = 0.236). CONCLUSION: Our study found that the combination of R-EBUS and ROSE during bronchoscopy procedure was a safe and effective modality to improve diagnostic yield of PPLs with emphysema, especially for malignant PPLs. The distance between the pleura and the lesion ≥ 2 cm, the positive air bronchograms sign, the location of the ultrasound probe within the lesion, and the even echo with clear margin feature of lesion ultrasonic image, these factors possibly indicated a higher diagnostic yield. Those lesions' position is adjacent to emphysema may reduce diagnostic yield but ROSE may make up for this deficiency.
Assuntos
Broncoscopia , Endossonografia , Neoplasias Pulmonares , Enfisema Pulmonar , Humanos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Enfisema Pulmonar/diagnóstico por imagem , Endossonografia/métodos , Broncoscopia/métodos , China , Avaliação Rápida no Local , Sensibilidade e Especificidade , Pulmão/diagnóstico por imagem , Pulmão/patologia , Valor Preditivo dos Testes , Biópsia Guiada por Imagem/métodosRESUMO
BACKGROUND: Endoscopic lung volume reduction with valves is a minimally invasive treatment strategy for patients with severe pulmonary emphysema. Two valve systems are currently available: Zephyr and Spiration valves. As these can be implanted simultaneously in the same procedure, the question arose as to the effect on lung function, exercise capacity and subjective disease perception after combined valve treatment. METHODS: We conducted a retrospective analysis of 108 patients with combined, simultaneous treatment of Zephyr and Spiration valves. The decision on which and how many valves to implant was based on the individual patient anatomy. Effects on lung function, exercise capacity and atelectasis formation as well as complications were evaluated 90- and 180-days post-treatment (90d-FU and 180d-FU). RESULTS: At 90d-FU (n = 90), the mean change was 86.7 ± 183.7 mL for FEV1 and -645.3 ± 1276.5 mL for RV, with responder rates of 39.8 % and 46.5 %, respectively. Complete atelectasis occurred in 16.7 % and partial atelectasis in 25.5 % of patients. Six-minute walking distance increased by 27.00 m [-1.50 - 68.50m]. The rates of pneumothorax (10.2 %) 6 months after treatment were not higher than in randomized controlled trials (RCTs). Likely due to the inclusion of high-risk patients, there was a higher incidence of severe COPD exacerbation (21.3 %) and pneumonia (12.0 %) compared to RCTs. CONCLUSIONS: The combined implantation of Zephyr and Spiration valves resulted in significant clinical and functional improvements with an acceptable risk profile. Therefore, the ability to combine both valve types in severe emphysema could be a promising option in endoscopic lung volume reduction.
Assuntos
Pneumonectomia , Enfisema Pulmonar , Humanos , Enfisema Pulmonar/cirurgia , Enfisema Pulmonar/fisiopatologia , Masculino , Estudos Retrospectivos , Feminino , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Pneumonectomia/métodos , Pneumonectomia/efeitos adversos , Tolerância ao Exercício , Volume Expiratório Forçado , Atelectasia Pulmonar/etiologia , Testes de Função Respiratória , Próteses e Implantes , Teste de CaminhadaRESUMO
Senescent cells contribute to tissue aging and underlie the pathology of chronic diseases. The benefits of eliminating senescent cells have been demonstrated in several disease models, and the efficacy of senolytic drugs is currently being tested in humans. Exercise training has been shown to reduce cellular senescence in several tissues; however, the mechanisms responsible remain unclear. We found that myocyte-derived factors significantly extended the replicative lifespan of fibroblasts, suggesting that myokines mediate the anti-senescence effects of exercise. A number of proteins within myocyte-derived factors were identified by mass spectrometry. Among these, pigment epithelium-derived factor (PEDF) exerted inhibitory effects on cellular senescence. Eight weeks of voluntary running increased Pedf levels in skeletal muscles and suppressed senescence markers in the lungs. The administration of PEDF reduced senescence markers in multiple tissues and attenuated the decline in respiratory function in the pulmonary emphysema mouse model. We also showed that blood levels of PEDF inversely correlated with the severity of COPD in patients. Collectively, these results strongly suggest that PEDF contributes to the beneficial effects of exercise, potentially suppressing cellular senescence and its associated pathologies.
Assuntos
Senescência Celular , Proteínas do Olho , Pulmão , Fatores de Crescimento Neural , Condicionamento Físico Animal , Serpinas , Serpinas/metabolismo , Fatores de Crescimento Neural/metabolismo , Animais , Proteínas do Olho/metabolismo , Camundongos , Pulmão/metabolismo , Pulmão/patologia , Humanos , Condicionamento Físico Animal/fisiologia , Masculino , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Fibroblastos/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Feminino , Músculo Esquelético/metabolismo , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/patologiaRESUMO
Background Pre-existing emphysema is recognized as an indicator of future worsening in patients with chronic obstructive pulmonary disease (COPD) when observed through CT imaging. However, it remains uncertain whether additional factors, such as the spatial compactness of CT emphysema, might also serve as predictors of disease progression. Purpose To evaluate the relationship between the compactness of CT emphysema voxels and emphysema progression. Materials and Methods This secondary analysis uses data from the prospective Canadian Cohort Obstructive Lung Disease (CanCOLD) study, examining CT images obtained in participants with and without COPD at baseline and a 3-year follow-up time point (November 2009 to November 2018). Measurements of forced expiratory volume in first second of expiration (FEV1) and diffusing capacity of lung for carbon monoxide (DLco) were collected. The normalized join-count (NJC) measurement from baseline CT images and lung density (LD) changes were analyzed. Emphysema progression was defined as an annualized LD change of less than half an SD below the mean of the participants without COPD with no smoking history. Multivariable linear and logistic regression models were used to assess the association between baseline CT NJC measurements and the annualized change in LD, FEV1, DLco, and emphysema progression versus nonprogression. Results A total of 524 participants (mean age, 66 years ± 10 [SD]; 293 male) (FEV1 percent predicted, 88% ± 19; FEV1/FVC, 67% ± 9; DLco percent predicted, 105% ± 25) were analyzed, 187 (36%) of whom had COPD. CT NJC was associated with the annualized change in LD (P < .001), FEV1 (P = .02), and DLco (P = .01). Additionally, CT NJC predicted emphysema progression versus nonprogression (odds ratio, 2.24; 95% CI: 1.37, 3.50; P < .001). Conclusion The spatial distribution, or "compactness," of CT emphysema voxels predicted emphysema progression in individuals with and without COPD. ClinicalTrials.gov Identifier: NCT00920348 © RSNA, 2024 Supplemental material is available for this article.
Assuntos
Progressão da Doença , Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Canadá , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Valor Preditivo dos TestesRESUMO
Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. Macrophages release IL-1ß and orchestrate airway inflammation in COPD. Previously, we explored the role of a new lncRNA, LincR-PPP2R5C, in regulating Th2 cells in asthma. Here, we established a murine model of COPD and explored the roles and mechanisms by which LincR-PPP2R5C regulates IL-1ß in macrophages. LincR-PPP2R5C was highly expressed in pulmonary macrophages from COPD-like mice. LincR-PPP2R5C deficiency ameliorated emphysema and pulmonary inflammation, as characterized by reduced IL-1ß in macrophages. Unexpectedly, in both lung tissues and macrophages, LincR-PPP2R5C deficiency decreased the expression of the IL-1ß protein but not the IL-1ß mRNA. Furthermore, we found that LincR-PPP2R5C deficiency increased the level of ubiquitinated IL-1ß in macrophages, which was mediated by PP2A activity. Targeting PP2A with FTY720 decreased IL-1ß and improved COPD. In conclusion, LincR-PPP2R5C regulates IL-1ß ubiquitination by affecting PP2A activity in macrophages, contributing to the airway inflammation and emphysema in a murine model of COPD. PP2A and IL-1ß ubiquitination in macrophages might be new therapeutic avenues for COPD therapy.
Assuntos
Modelos Animais de Doenças , Interleucina-1beta , Camundongos Endogâmicos C57BL , Doença Pulmonar Obstrutiva Crônica , RNA Longo não Codificante , Ubiquitinação , Animais , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Interleucina-1beta/metabolismo , Camundongos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteína Fosfatase 2/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Humanos , Masculino , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/imunologia , Enfisema Pulmonar/patologia , Enfisema Pulmonar/genética , Pulmão/patologia , Pulmão/imunologia , Camundongos KnockoutRESUMO
Chronic obstructive pulmonary disease (COPD), an inflammatory lung disease, causes approximately 3 million deaths each year; however, its pathological mechanisms are not fully understood. In this study, we examined whether HX110B, a mixture of Taraxacum officinale, Dioscorea batatas, and Schizonepeta tenuifolia extracts, could suppress porcine pancreatic elastase (PPE)-induced emphysema in mice and its mechanism of action. The therapeutic efficacy of HX110B was tested using a PPE-induced emphysema mouse model and human bronchial epithelial cell line BEAS-2B. In vivo data showed that the alveolar wall and air space expansion damaged by PPE were improved by HX110B administration. HX110B also effectively suppresses the expression levels of pro-inflammatory mediators including IL-6, IL-1ß, MIP-2, and iNOS, while stimulating the expression of lung protective factors such as IL-10, CC16, SP-D, and sRAGE. Moreover, HX110B improved the impaired OXPHOS subunit gene expression. In vitro analysis revealed that HX110B exerted its effects by activating the PPAR-RXR signaling pathways. Overall, our data demonstrated that HX110B could be a promising therapeutic option for COPD treatment.
Assuntos
Elastase Pancreática , Extratos Vegetais , Transdução de Sinais , Animais , Transdução de Sinais/efeitos dos fármacos , Camundongos , Elastase Pancreática/metabolismo , Humanos , Extratos Vegetais/farmacologia , Enfisema Pulmonar/tratamento farmacológico , Enfisema Pulmonar/metabolismo , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/patologia , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Modelos Animais de Doenças , Linhagem Celular , Masculino , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Camundongos Endogâmicos C57BL , SuínosRESUMO
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.