RESUMEN
Vitronectin, a multifunctional glycoprotein, is involved in coagulation, inhibition of the formation of the membrane attack complex (MAC), cell adhesion and migration, wound healing, and tissue remodeling. The primary cellular source of vitronectin is hepatocytes; it is not known whether resident cells of airways produce vitronectin, even though the glycoprotein has been found in exhaled breath condensate and bronchoalveolar lavage from healthy subjects and patients with interstitial lung disease. It is also not known whether vitronectin expression is altered in subjects with asthma and COPD. In this study, bronchial tissue from 7 asthmatic, 10 COPD and 14 control subjects was obtained at autopsy and analyzed by immunohistochemistry to determine the percent area of submucosal glands occupied by vitronectin. In a separate set of experiments, quantitative colocalization analysis was performed on tracheobronchial tissue sections obtained from donor lungs (6 asthmatics, 4 COPD and 7 controls). Vitronectin RNA and protein expressions in bronchial surface epithelium were examined in 12 subjects who undertook diagnostic bronchoscopy. Vitronectin was found in the tracheobronchial epithelium from asthmatic, COPD, and control subjects, although its expression was significantly lower in the asthmatic group. Colocalization analysis of 3D confocal images indicates that vitronectin is expressed in the glandular serous epithelial cells and in respiratory surface epithelial cells other than goblet cells. Expression of the 65-kDa vitronectin isoform was lower in bronchial surface epithelium from the diseased subjects. The cause for the decreased vitronectin expression in asthma is not clear, however, the reduced concentration of vitronectin in the epithelial/submucosal layer of airways may be linked to airway remodeling.
Asunto(s)
Asma/metabolismo , Bronquios/metabolismo , Regulación de la Expresión Génica , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Vitronectina/metabolismo , Adulto , Anciano , Asma/genética , Asma/patología , Bronquios/patología , Estudios de Casos y Controles , Células Epiteliales/metabolismo , Glándulas Exocrinas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/patología , Vitronectina/genética , Adulto JovenRESUMEN
We hypothesised that biomass smoke exposure is associated with an airway-predominant chronic obstructive pulmonary disease (COPD) phenotype, while tobacco-related COPD is associated with an emphysema-predominant phenotype. In this cross-sectional study, female never-smokers with COPD and biomass exposure (n=21) and female ex-cigarette smokers with COPD without biomass exposure (n=22) completed computed tomography (CT) at inspiration and expiration, pulmonary function, blood gas, exercise tolerance, and quality of life measures. Two radiologists scored the extent of emphysema and air trapping on CT. Quantitative emphysema severity and distribution and airway wall thickness were calculated using specialised software. Women in the tobacco group had significantly more emphysema than the biomass group (radiologist score 2.3 versus 0.7, p=0.001; emphysema on CT 27% versus 19%, p=0.046; and a larger size of emphysematous spaces, p=0.006). Women in the biomass group had significantly more air trapping than the tobacco group (radiologist score 2.6 and 1.5, respectively; p=0.02) and also scored lower on the symptom, activities and confidence domains of the quality of life assessment and had lower oxygen saturation at rest and during exercise (p<0.05). Biomass smoke exposure is associated with less emphysema but more air trapping than tobacco smoke exposure, suggesting an airway-predominant phenotype.
Asunto(s)
Contaminación del Aire/efectos adversos , Nicotiana/efectos adversos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/etiología , Humo/efectos adversos , Fumar/efectos adversos , Anciano , Análisis de los Gases de la Sangre , Culinaria , Estudios Transversales , Diagnóstico por Computador , Enfisema/complicaciones , Enfisema/diagnóstico , Tolerancia al Ejercicio , Femenino , Volumen Espiratorio Forzado , Humanos , México , Persona de Mediana Edad , Análisis Multivariante , Fenotipo , Enfermedad Pulmonar Obstructiva Crónica/etnología , Calidad de Vida , Pruebas de Función Respiratoria , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: The use of biomass as a cooking fuel is commonplace in developing countries and has been associated with chronic bronchitis and obstructive airway disease. METHODS: A cross-sectional survey was done in the village of Solis, close to Mexico City. Lifelong nonsmoking women 38 yr of age or older (n=841) completed a questionnaire on respiratory symptoms and illnesses and on cooking fuel use, and performed spirometry in their homes. Particulate matter concentration was measured with a nephelometer in the kitchen for 1 h, while the subject was cooking. RESULTS: The peak indoor concentration of particulate matter (PM10, particles with a diameter of 10 microm or less) often exceeded 2 mg/m3. Compared with those cooking with gas, current use of a stove burning biomass fuel was associated with increased reporting of phlegm (27 vs. 9%) and reduced FEV1/FVC (79.9 vs. 82.8%). Levels of FEV1 were 81 ml lower and cough was more common (odds ratio, 1.7; 95% confidence interval, 1.0-2.8) in women from homes with higher PM10 concentrations. All women found with moderate airflow obstruction (Global Initiative for Chronic Obstructive Lung Disease stage II and above) were cooking with biomass stoves. CONCLUSION: Women cooking with biomass fuels have increased respiratory symptoms and a slight average reduction in lung function compared with those cooking with gas.
Asunto(s)
Contaminación del Aire Interior/efectos adversos , Biomasa , Culinaria/métodos , Volumen Espiratorio Forzado/fisiología , Enfermedades Respiratorias , Población Rural , Adulto , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Incidencia , México/epidemiología , Persona de Mediana Edad , Pruebas de Función Respiratoria , Enfermedades Respiratorias/epidemiología , Enfermedades Respiratorias/etiología , Enfermedades Respiratorias/fisiopatología , Estudios Retrospectivos , Encuestas y CuestionariosRESUMEN
We established a specific genotyping assay for HLA-A*01, which is one of the most frequently found HLA-A alleles in the Caucasian population. This assay uses the polymerase chain reaction (PCR) with allele group-specific primers (ASP). HLA-A*01 group-specific primers were designed for exon 3 of the HLA-A gene, based on the recent HLA-sequence alignment. Both sense and anti-sense primers were designed with completely matched sequences to each specific HLA-A*01 allele, but mismatched by at least 1 nucleotide to all other known class I HLA alleles. By the use of these primers and stringent PCR conditions, we successfully genotyped the HLA-A*01 group alleles and achieved greater accuracy than previous methods.