RESUMEN
BACKGROUND: The prevalence of asthma and bronchial hyper-responsiveness is greater in elite athletes than in the general population, and its association with mild airway inflammation has recently been reported. OBJECTIVE: To study the relationship between the type of sport practised at the highest levels of competition (on land or in water) and sputum induction cell counts in a group of healthy people and people with asthma. MATERIAL AND METHODS: In total, 50 athletes were enrolled. Medical history, results of methacholine challenge tests and sputum induced by hypertonic saline were analysed RESULTS: Full results were available for 43 athletes, who were classified by asthma diagnosis and type of sport (land or water sports). Nineteen were healthy (10 land and 9 water athletes) and 24 had asthma (13 land and 11 water athletes). Although the eosinophil counts of healthy people and people with asthma were significantly different (mean difference 3.1%, 95% CI 0.4 to 6.2, p = 0.008), analysis of variance showed no effect on eosinophil count for either diagnosis of asthma or type of sport. However, an effect was found for neutrophil counts (analysis of variance: F = 2.87, p = 0.04). There was also a significant correlation between neutrophil counts and both duration of training and bronchial hyper-responsiveness among athletes exposed to water (Spearman's rank correlations, 0.36 and 0.47, p = 0.04 and 0.04, respectively). CONCLUSIONS: Elite athletes who practice water sports have mild neutrophilic inflammation, whether or not asthma is present, related to the degree of bronchial hyper-reactivity and the duration of training in pool water.
Asunto(s)
Asma/fisiopatología , Hiperreactividad Bronquial/fisiopatología , Neutrófilos/metabolismo , Aptitud Física/fisiología , Deportes/fisiología , Adulto , Análisis de Varianza , Pruebas de Provocación Bronquial , Femenino , Humanos , Inflamación/fisiopatología , Masculino , Pruebas Cutáneas , Espirometría , Esputo/química , AguaRESUMEN
The objective of the present study was to investigate the kinetics of high doses of inhaled steroid fluticasone in comparison with oral steroid prednisone on plasma protein leakage and bronchial eosinophilia in adults with moderate asthma exacerbations. The study design was a randomised, double-blind, placebo-controlled prospective trial. In total, 45 patients treated at the emergency department for moderate asthma exacerbations were recruited and 39 were assigned to receive fluticasone and placebo of prednisone (19 patients), or prednisone and placebo of fluticasone (20 patients). Medication was administered to all patients via a metered-dose inhaler and spacer (16 puffs; 4,000 microg.day(-1) or placebo) plus one pill (prednisone 30 mg.day(-1) or placebo). Spirometry and induced sputum for differential cell counts, albumin and alpha(2)-macroglobulin levels and blood eosinophils, interleukin-5 and granulocyte-macrophage colony-stimulating factor levels were obtained before treatment and at 2, 6 and 24 h after treatment. Symptoms clearly improved after 24 h in both groups. No differences were seen between groups in peak expiratory flow or forced expiratory flow in one second, which improved progressively but then decayed slightly after 24 h. Eosinophil counts in sputum also improved over time in both groups. The effect was faster with fluticasone than with prednisone, but was partially lost at 24 h. However, plasma proteins in sputum and eosinophil count in blood both decreased until 24 h, with no significant differences between groups. There was no correlation between eosinophil counts and plasmatic protein levels. In conclusion, both treatments improved symptoms, airway obstruction and inflammation, and plasma protein leakage at 24 h. Prednisone reduced blood eosinophil counts, while fluticasone reduced airway eosinophil counts, suggesting that the anti-inflammatory performance of fluticasone is exerted locally.
Asunto(s)
Androstadienos/administración & dosificación , Androstadienos/uso terapéutico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Administración por Inhalación , Administración Oral , Adulto , Anciano , Albúminas/metabolismo , Androstadienos/farmacología , Antropometría , Antiinflamatorios/farmacología , Asma/fisiopatología , Recuento de Células Sanguíneas , Proteínas Sanguíneas , Eosinófilos/citología , Eosinófilos/efectos de los fármacos , Femenino , Fluticasona , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Interleucinas/sangre , Masculino , Inhaladores de Dosis Medida , Persona de Mediana Edad , Ápice del Flujo Espiratorio/efectos de los fármacos , Prednisona/farmacología , Ventilación Pulmonar/efectos de los fármacos , Espirometría , Esputo/citología , Esputo/efectos de los fármacosRESUMEN
OBJECTIVE: Airway remodeling in chronic obstructive pulmonary disease (COPD) has been linked to the equilibrium between matrix metalloproteinase (MMP) 9 and its inhibitor, tissue inhibitor of metalloproteinase (TIMP) 1. However, that equilibrium has not been analyzed in healthy smokers. The aim of this study was to assess the equilibrium between MMP-9 and TIMP-1 in induced sputum from healthy smokers, healthy nonsmokers (controls), and patients with COPD. PATIENTS AND METHODS: Samples of induced sputum were obtained from 35 individuals: 12 healthy smokers, 12 controls, and 11 patients with COPD. In each sample, a differential cell count was performed and enzyme-linked immunosorbent assays were used to analyze the concentrations of MMP-9 (total and active fraction) and TIMP-1. RESULTS: Compared with controls, healthy smokers were found to have a higher mean (SD) concentration of total MMP-9 (273 [277] ng/mL vs 128 [146] ng/mL) and a higher ratio of total MMP-9 to TIMP-1 (0.16 [0.14] vs 0.08 [0.06]). However, the ratio of active MMP-9 to TIMP-1 was similar in the 2 groups. Samples from patients with COPD had the highest concentrations of total MMP-9 (477 [262] ng/mL) and active MMP-9 (178 [126] ng/mL) and the lowest concentrations of TIMP-1 (1.044 [1.036] microg/mL). When all groups were considered together, there was an inverse relationship between the MMP-9/TIMP-1 ratio and the forced expiratory volume in the first second (FEV1). The relationship between the active MMP-9/TIMP-1 ratio and FEV1 was even stronger, and the relation of both ratios with FEV1 became stronger still when smoking was considered. CONCLUSIONS: Healthy smokers had a higher concentration of total MMP-9 and that concentration was correlated with their exposure to tobacco smoke. Maintenance of the active MMP-9/TIMP-1 ratio in healthy smokers may explain the absence of progressive airway obstruction. Measurement of active MMP-9 concentration could be useful for assessment of airway remodeling.
Asunto(s)
Metaloproteinasa 9 de la Matriz/análisis , Fumar , Esputo/química , Inhibidor Tisular de Metaloproteinasa-1/análisis , Adulto , Biomarcadores/análisis , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/enzimología , Sistema RespiratorioRESUMEN
OBJECTIVE: Cell cultures provide a good model for studying lung diseases but they are difficult to reproduce and the number of cells obtained is limited. The aim of this study was to develop a way to increase the production of human bronchial epithelial cells (BEC) in primary cultures. MATERIAL AND METHODS: A total of 12 samples (9 from surgical specimens and 3 from endoscopic biopsies) were processed on plates coated with type I collagen with growth medium supplemented for BEC. When cell proliferation started, the explants were removed for successive subculturing. The remaining cells were left to proliferate and were trypsinized after 50% confluence. We recorded the number of cells obtained, cell viability, and the percentage positive for cytokeratin 7. RESULTS: The total number of cells obtained by this method was 3-fold the number of human BEC obtained with simple primary cultures. The maximum number of subcultures was 5, mean (SD) cell viability was 91.9% (11.7%), and the percentage of cells positive for cytokeratin 7 was 30.71% (10.68%). CONCLUSIONS: The described method for expanding primary BEC cultures increases cell production.
Asunto(s)
Bronquios/citología , Técnicas de Cultivo de Célula , Células Cultivadas , Células Epiteliales/citología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Although altered vascular permeability and edema of the bronchial mucosa are associated with asthma attack, their influence on its severity remains unknown. We address this issue by comparing relative indices for the concentration of albumin (RIAlb) and alpha2-macroglobulin (RIalpha2M) in induced sputum and peripheral blood from patients with exacerbated asthma, patients with stable asthma, and control subjects. PATIENTS AND METHODS: Forty-six volunteers participated in the study: 14 with exacerbated asthma (forced expiratory volume in the first second [FEV1] 74.3% [SD, 20.8%] of reference), 23 with stable asthma (FEV1 93.6% [7.5%]), and 9 controls (FEV1 101.1% [9.9%]). The concentrations of albumin and alpha2-macroglobulin were quantified by immunoturbidimetry and immunonephelometry, respectively. The relative index was then calculated by dividing the concentration in sputum supernatant by the concentration in peripheral blood. RESULTS: The mean RIAlb was 1.2 (1.1) in the control group, 2.9 (3.1) in the stable asthma group, and 6.0 (6.7) in the exacerbated asthma group. The RIalpha2M values were 11.7 (10.9), 11.9 (14.7), and 3.2 (3.8) for the control group and stable and exacerbated asthma groups, respectively. The increases in the RIAlb values between all groups, and the decrease in the RIalpha2M value between the exacerbated asthma and control groups were statistically significant (P<.05). The percentage of neutrophils, but not of eosinophils, in sputum was correlated with the RIAlb (r=0.39; P=.008) but not the RIalpha2M (r=-0.035; P=.82). FEV1 displayed an inverse relationship with the RIAlb (r=-0.43; P=.009) but not with the RIalpha2M (r=-0.206; P=.24). No correlation was found between oxyhemoglobin saturation and either the RIAlb (r=-0.33; P=.19) or the RIalpha2M (r=-0.12; P=.84). CONCLUSIONS: Vascular permeability is altered during asthma exacerbations and appears to be correlated with the presence of neutrophils and the degree of bronchial obstruction.
Asunto(s)
Asma/fisiopatología , Proteínas Sanguíneas/análisis , Bronquios/fisiopatología , Exudados y Transudados/química , Enfermedad Aguda , Adolescente , Adulto , Asma/sangre , Recuento de Células Sanguíneas , Pruebas de Provocación Bronquial , Permeabilidad Capilar , Eosinófilos , Exudados y Transudados/citología , Femenino , Volumen Espiratorio Forzado , Humanos , Macrófagos , Masculino , Cloruro de Metacolina , Persona de Mediana Edad , Nefelometría y Turbidimetría , Neutrófilos , Albúmina Sérica/análisis , Esputo/química , alfa-Macroglobulinas/análisisRESUMEN
BACKGROUND: The correlation between total IgE in induced sputum (IS) and serum is not well defined. The aim of this study was to investigate the relationship between total IgE in IS and total IgE in serum and airway inflammation. METHODS: Twenty-one patients with stable asthma and thirteen healthy controls were studied. Clinical and spirometric data were collected and a skin prick test to the 13 most common aeroallergens in our area was performed in all subjects. Total IgE in IS and serum was determined by the UNICAP immunoanalysis system (Pharmacia Uppsala, Sweden) while albumin concentration in IS and serum was determined using the Cobas Integra turbidimetric method (Roche Diagnostics, Basel, Switzerland). RESULTS: The percentage of eosinophils in EI was 8.7 (11.8) in asthmatic subjects and was 0.5 (1) in healthy controls. Total IgE (KU/L) was 43.2 (23) in asthmatics vs 25.6 (3) in healthy controls in IS, and was 329 (413) in asthmatics vs 57 (78) in controls in serum. Total IgE in IS was significantly correlated with total IgE in serum; r = 0.71 (p = 0.048), but not with the albumin relative index. No correlation was found between IgE and the number of eosinophils in IS. CONCLUSIONS: Total IgE can be measured in IS. Total IgE in IS is mildly correlated with total IgE measured in serum. The lack of correlation between total IgE and albumin in IS suggests that IgE in IS could be locally produced, at least in part.