Small bronchiolar histopathological changes related to prolonged diabetes / Pequeños cambios histopatológicos bronquiolares relacionados con la diabetes prolongada

SUMMARY: Diabetes mellitus increases the risk of developing chronic obstructive pulmonary disease (COPD). The small bronchiole is a prominent site of airflow obstruction that causes increased airway resistance in patients with the COPD. Therefore, the histological and ultrastructural changes in small bronchioles in streptozotocin (STZ)-induced chronic diabetes were determined. Twenty-four weeks after STZ induction, rats were sacrificed, and the right and left lungs were collected for examination by light and electron microscopy. The alterations to the small bronchioles were the same in both lungs of these diabetic rats. The bronchiolar epithelial cells, both ciliated and secretory club cells, showed pyknotic nuclei and damaged cytoplasmic organelles. Increased thickening of the bronchiolar wall occurred in diabetic rats due to smooth muscle layer thickening, inflammatory cell infiltration, and increased numbers of myofibroblasts with collagen deposition.These results indicated that chronic diabetes caused extreme damage to small bronchioles, which may lead to chronic small airway obstruction and ultimately increase the likelihood of COPD progression. This basic knowledge provides a better understanding of the progression of pathogenesis in the small airways of patients with prolonged diabetes.

RESUMEN: La diabetes mellitus aumenta el riesgo de desarrollar enfermedad pulmonar obstructiva crónica (EPOC). El bronquiolo es un sitio prominente de obstrucción del flujo de aire que causa una mayor resistencia de las vías respiratorias en pacientes con EPOC. Por lo tanto, se determinaron los cambios histológicos y ultraestructurales en los bronquiolos en la diabetes crónica inducida por estreptozotocina (STZ). 24 semanas después de la inducción de STZ, se sacrificaron las ratas y se analizaron los pulmones derecho e izquierdo por microscopía óptica y electrónica. Las alteraciones de los pequeños bronquiolos fueron las mismas en ambos pulmones de estas ratas diabéticas. Las células epiteliales bronquiolares, tanto ciliadas como secretoras, mostraban núcleos picnóticos y orgánelos citoplasmáticos dañados. Se produjo un aumento del engrosamiento de la pared bronquiolar en ratas diabéticas debido al engrosamiento de la capa de músculo liso, infiltración de células inflamatorias y un mayor número de miofibroblastos con colágeno. Estos resultados indicaron que la diabetes crónica causaba daño extremo a los pequeños bronquiolos, lo que puede conducir a una obstrucción crónica de las vías respiratorias pequeñas y además aumentar la probabilidad de progresión de la EPOC. Esta información proporcionará un mejor conocimiento de la patogénesis en las vías respiratorias pequeñas de los pacientes con diabetes prolongada.

Coxsackie-virus and adenovirus receptor expression in lung cancer bronchiole-alveolar carcinoma features and its significance / 中国肿瘤临床

Objective:This study aims to investigate the protein expression of coxsackie-virus and adenovirus receptor (CAR) in partial subtypes of pulmonary adeno-carcinoma, as well as its expression with clinico-pathological factors and prognosis. Methods:CAR expression was immunohistochemically assessed in 137 cases of lung cancer with bronchiole-alveolar carcinoma (PWBF) fea-tures, and analyzed in relation to various clinico-pathological parameters. All data were analyzed using SPSS statistics software, and Ka-plan-Meier survival curves were constructed. A Log-rank test was also conducted. Results: The CAR positive rates in PWBF, other types of lung cancer, and normal lung tissue were 71.5%, 50.0%, and 13.3%, respectively. The difference was statistically significant (P<0.05). In addition, a statistically significant difference was observed between the positive expression of CAR and other clini-co-pathologic parameters, such as pathological type and histological differentiation. No statistical significance was observed in other pa-rameters, such as gender, age, smoking, and tumor diameter. Patients with CAR positivity were characterized by longer survival times than the others;however, this difference did not reach statistical significance. Conclusion:CAR is related to the occurrence and devel-opment of lung cancer, especially PWBF. The higher expression of CAR in PWBF for gene therapy with adenovirus vectors opened a broader space. The conspicuous regulation of CAR may be reliable evidence and may bright future for the gene therapy of other types of lung cancer.

Cigarette Smoke Extract-induced Reduction in Migration and Contraction in Normal Human Bronchial Smooth Muscle Cells

The proliferation, migration, cytokine release, and contraction of airway smooth muscle cells are key events in the airway remodeling process that occur in lung disease such as asthma, chronic obstruction pulmonary disease, and cancer. These events can be modulated by a number of factors, including cigarette smoke extract (CSE). CSE-induced alterations in the viability, migration, and contractile abilities of normal human airway cells remain unclear. This study investigated the effect of CSE on cell viability, migration, tumor necrosis factor (TNF)-alpha secretion, and contraction in normal human bronchial smooth muscle cells (HBSMCs). Treatment of HBSMCs with 10% CSE induced cell death, and the death was accompanied by the generation of reactive oxygen species (ROS). CSE-induced cell death was reduced by N-acetyl-l-cysteine (NAC), an ROS scavenger. In addition, CSE reduced the migration ability of HBSMCs by 75%. The combination of NAC with CSE blocked the CSE-induced reduction of cell migration. However, CSE had no effect on TNF-alpha secretion and NF-kappaB activation. CSE induced an increase in intracellular Ca2+ concentration in 64% of HBSMCs. CSE reduced the contractile ability of HBSMCs, and the ability was enhanced by NAC treatment. These results demonstrate that CSE treatment induces cell death and reduces migration and contraction by increasing ROS generation in normal HBSMCs. These results suggest that CSE may induce airway change through cell death and reduction in migration and contraction of normal HBSMCs.

Multiple Small Nodular Lung Lesions with Severe Dyspnea / 결핵

Diffuse panbronchiolitis is a chronic inflammatory lung disease of unknown etiology which is characterized by chronic airflow limitation and airway inflammation, predominantly localized in the respiratory bronchioles with infiltration of inflammatory cells, and has typical clinical, radiological and pathological features. Obstructive respiratory functional impairment, occasional symptoms of wheezing, and also cough and sputum resemble the feature of emphysema, bronchial asthma, or chronic bronchitis, respectively. We experienced a case of pathologically proven advanced diffuse panbronchiolitis in a 55-year-old man with productive cough and exertional dyspnea. The chest radiography showed multiple tiny nodular densities on whole lung fields. It was confirmed by thoracoscopy-guided lung biopsy and the patient was improved after initiation of treatment with low-dose erythromycin

Bronchiole-alveolar Carcinoma-Analysis of 10 Autopsy Cases / 第三军医大学学报

Ten autopsy cases of bronchiole-alveolar carcinoma (BAC) were reported. Grossly, BAC may be divided into 3 types, i. e. finely nodular, coarsely nodular and diffuse type. Histologic pattern falls into 2 categories: ' (1) alveolar type, (2) papillary type. Metastasis is most frequently mediated through lymphatics, spreading to the regional lymph nodes. Next, they are spread by blood stream. Brain (meningeal carcinomatosis),bone and adrenal glands are the frequent metastasized sites. Pulmonary fibrosis and scar formation seem to be the predisposing factors to BAC.