RESUMEN
OBJECTIVE: To explore the activities of mast cells, eosinophils, and neutrophils in patients with allergic rhinitis developing common colds and increased responsiveness to allergen following nasal rhinovirus inoculation. METHODS: We have revisited a nasal lavage material obtained from 17 patients who were successfully inoculated with rhinovirus outside the pollen season and received nasal allergen challenges before and after inoculation. We have examined indices of mast cell activity (tryptase), eosinophil degranulation (eosinophil peroxidase; EPO), and neutrophil activation (myeloperoxidase; MPO). RESULTS: Allergen challenges performed before rhinovirus inoculation increased the nasal output of EPO. Notably, this response was significantly greater after rhinovirus inoculation (cf. before inoculation). The output of MPO was also increased following allergen challenge after, but not before, rhinovirus inoculation. Nasal lavage fluid levels of tryptase were increased following allergen challenge similarly before and after rhinovirus inoculation. Also, the viral infection did not affect the baseline levels of tryptase. CONCLUSIONS: The present data demonstrate that rhinovirus infections activate both eosinophils and neutrophils, but that they may not affect mast cell activity. We suggest that common colds in part through stimulation of granulocyte activity potentiate the airway inflammation in allergic diseases.
Asunto(s)
Resfriado Común/complicaciones , Resfriado Común/inmunología , Granulocitos/inmunología , Rinitis Alérgica Estacional/complicaciones , Rinitis Alérgica Estacional/inmunología , Rhinovirus/inmunología , Administración Intranasal , Adulto , Alérgenos/administración & dosificación , Alérgenos/inmunología , Activación Enzimática , Peroxidasa del Eosinófilo , Eosinófilos/enzimología , Eosinófilos/inmunología , Femenino , Granulocitos/enzimología , Humanos , Masculino , Mastocitos/enzimología , Mastocitos/inmunología , Neutrófilos/enzimología , Neutrófilos/inmunología , Peroxidasa/metabolismo , Peroxidasas/metabolismo , Serina Endopeptidasas/metabolismo , TriptasasRESUMEN
Cystic fibrosis (CF) is characterized by the production of abnormally thick secretions in the airways, chronic bacterial endobronchial infections and a chronic, predominantly neutrophilic inflammatory response. Therefore, myeloperoxidase (MPO) and lactoferrin are frequently used as inflammatory markers. Recently, a new protein in the neutrophil granules, human neutrophil lipocalin (HNL) has been discovered. The aim of the present study was to investigate HNL in sera of patients with CF and its relation to MPO and lactoferrin as well as to acute pulmonary exacerbation. Serum concentrations of HNL, MPO and lactoferrin were determined in 42 patients with CF and in 25 healthy subjects. Patients with CF were divided into groups with and without acute pulmonary exacerbation (APE) and also with and without colonization with Pseudomonas aeruginosa (Pa). Median serum levels of HNL (200.5 microg x L(-1)), MPO (595 microg x L(-1)) and lactoferrin (1,356.5 microg x L(-1)) were significantly increased in patients with CF compared to control subjects (57.7, 178 and 478 microg x L(-1), respectively; p<0.0001). CF patients with APE had significantly increased serum concentrations of HNL (321 versus 97.7 microg x L(-1); p<0.0001), MPO (1,125 versus 300 microg x L(-1); p<0.005) and lactoferrin (4,936 versus 980 microg x L(-1); p<0.001) compared with patients in stable clinical condition. Similarly, patients colonized with Pa had significantly higher concentrations of HNL, MPO and lactoferrin than Pa negative patients. These results indicate that in patients with cystic fibrosis, serum concentrations of human neutrophil lipocalin are markedly increased with a strong relationship to myeloperoxidase and lactoferrin. Thus, determination of serum human neutrophil lipocalin concentrations may be another useful diagnostic tool to monitor neutrophil inflammation in cystic fibrosis. The more marked difference in human neutrophil lipocalin compared with myeloperoxidase concentrations with no overlap between patients with acute pulmonary exacerbation and those in stable condition even suggests that human neutrophil lipocalin may be a more sensitive and specific discriminator.
Asunto(s)
Proteínas de Fase Aguda , Proteínas Portadoras/sangre , Fibrosis Quística/diagnóstico , Proteínas Oncogénicas , Adolescente , Biomarcadores/sangre , Estudios de Casos y Controles , Fibrosis Quística/sangre , Fibrosis Quística/microbiología , Femenino , Humanos , Lactoferrina/sangre , Lipocalina 2 , Lipocalinas , Masculino , Neutrófilos , Peroxidasa/sangre , Proteínas Proto-Oncogénicas , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Eosinophils are involved in the chronic inflammatory response in asthma and their basic proteins are thought to play a major pathophysiological role in this process. While serum levels of basic proteins have been used to monitor the ongoing allergic disease, little is known about the intracellular expression of these proteins in clinical situations. OBJECTIVE: The aim of the study was to determine the intracellular expression of eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) in asthmatic children and control subjects and relate it to serum levels of both proteins, lung function tests and immunoglobulin (Ig)E levels. METHODS: Serum ECP and EPO concentrations were determined by immunoassays in 13 asthmatic children (mean age: 9 +/- 1 years, mean FEV1: 92 +/- 10% predicted, geometric mean PC20 histamine 0.5 mg/mL) and 10 age-matched, healthy control subjects. A flow cytometric single cell assay was employed to detect intracellular ECP and EPO in peripheral blood eosinophils. RESULTS: While serum concentrations of both ECP (asthma: median 15.0 microg/L [range 3.6-57.7] vs control: 5.9 microg/L [2.7-9.1]; P = 0.02) and EPO (22.9 microg/L [5.2-82.5] vs 7. 2 microg/L [2.5-12.7]; P = 0.008) were significantly elevated in asthmatics, the intracellular expression of ECP and EPO (measured as mean fluorescence intensity) was decreased (EG1: 55.3 [17.7-120.8] vs 100.3 [46.5-264.4]; P = 0.01; EG2: 80.2 [24.1-135.3] vs 133.7 [32. 1-244.9]; P = 0.04 and EPO: 49.7 [23.1-155.8] vs 94.9 [28.8-115.2]; P = 0.03). In asthmatics there was a significant correlation of FEV1 with intracellular ECP and of bronchial hyperresponsiveness with serum EPO and ECP. Furthermore, total IgE levels were positively correlated with serum EPO only. CONCLUSION: We conclude that in asthmatics the intracellular content of ECP and EPO in peripheral eosinophils is reduced possibly due to degranulation. Epitope masking in activated eosinophils or a shift to early bone marrow-derived progenitors with less granule proteins are further possible explanations.
Asunto(s)
Asma/sangre , Proteínas Sanguíneas/metabolismo , Eosinófilos/metabolismo , Peroxidasas/metabolismo , Ribonucleasas , Asma/inmunología , Niño , Proteínas en los Gránulos del Eosinófilo , Peroxidasa del Eosinófilo , Eosinófilos/inmunología , Femenino , Humanos , Inmunoglobulina E/sangre , Masculino , Pruebas de Función RespiratoriaRESUMEN
Several studies have confirmed the presence of animal dander allergens in school dust but the effect of this indirect animal exposure on health has not been evaluated. In this study we investigated bronchial reactivity and markers of eosinophil activity and inflammation during two separate weeks of school in 10 children with mild asthma and a positive skin prick test to cat and dog. At the beginning and the end of the first week the children underwent bronchial challenges with methacholine, and at the beginning and the end of the second week they underwent nasal lavages (NAL) and induced sputum samplings. Blood and urine samples for analysis of inflammatory markers were obtained before and after both school weeks. Peak expiratory flow (PEF) and symptoms of asthma and allergy were recorded daily, and spirometry was performed on each visit. The exposure to animal dander allergens was estimated from dust samples obtained in the subjects' schools and homes. Bronchial sensitivity to methacholine increased in the week when this was measured. The proportion of eosinophils in peripheral blood, and urinary eosinophil protein X (EPX), decreased in both weeks. There was a trend towards an increase of eosinophil peroxidase (EPO) and myeloperoxidase (MPO) in sputum in the week when these proteins were measured. The concentrations of cat (Fel d1) and dog (Can f1) allergens were higher in dust collected in schools than in homes. Our results show that in children with mild asthma and animal dander allergy, there is a significantly increased bronchial sensitivity to methacholine after one school week. There is also a significant decrease in the number of circulating eosinophils and a trend towards an increase of sputum EPO, which could correlate with the early phase of eosinophil recruitment to the lungs. These effects may be related to the continuous exposure to animal allergens in school dust.
Asunto(s)
Alérgenos/efectos adversos , Asma/inmunología , Polvo/efectos adversos , Ribonucleasas , Adolescente , Alérgenos/análisis , Animales , Antígenos de Plantas , Asma/sangre , Asma/fisiopatología , Asma/orina , Biomarcadores/sangre , Biomarcadores/orina , Proteínas Sanguíneas/análisis , Proteínas Sanguíneas/orina , Hiperreactividad Bronquial/diagnóstico , Pruebas de Provocación Bronquial , Broncoconstrictores , Gatos , Niño , Perros , Peroxidasa del Eosinófilo , Neurotoxina Derivada del Eosinófilo , Eosinófilos , Femenino , Glicoproteínas/análisis , Humanos , Leucotrieno E4/orina , Masculino , Cloruro de Metacolina , Líquido del Lavado Nasal/química , Peroxidasa/análisis , Peroxidasas/análisis , Peroxidasas/sangre , Esputo/enzimologíaRESUMEN
BACKGROUND: Recently, increased serum levels of eosinophil cationic protein (ECP) in cystic fibrosis (CF) have been reported which were closely related to the levels in sputum. In the present study we investigated other eosinophil proteins such as eosinophil peroxidase (EPO) and eosinophil protein X (EPX) in sera of patients with CF and their relation to pulmonary function. METHODS: Serum samples from 42 patients with CF and from 25 healthy control subjects were measured for ECP, EPO and EPX. Lung function tests were performed by using whole body plethysmographic technique, and the results were correlated with the levels of eosinophil granule proteins. RESULTS: Serum ECP (median: 20.9 microg/L), EPO (median: 30.3 microg/L) and EPX (median: 37.9 microg/L) levels were significantly increased in CF compared with healthy controls (3.5 microg/L, P < 0.0001, 5.6 microg/L, P < 0.0001 and 14.6 microg/L, P < 0.0001, respectively) whereas eosinophil counts were not different. There was a strong correlation between the levels of eosinophil proteins and variables of pulmonary function, like between ECP and forced vital capacity (r = -0.764, P < 0.0001). In addition, ECP concentrations were significantly related to the levels of EPO and EPX, albeit, in some patients with low ECP levels, increased EPO and EPX concentrations were observed. CONCLUSION: These results indicate that in patients with CF, ECP, EPO and EPX concentrations also were increased with a significant relationship between these three eosinophil proteins. Since eosinophil activity in patients with CF is strongly correlated with pulmonary function, the assessment of eosinophil granule proteins might be useful for clinical monitoring in CF.
Asunto(s)
Proteínas Sanguíneas/biosíntesis , Fibrosis Quística/diagnóstico , Fibrosis Quística/metabolismo , Pulmón/fisiología , Peroxidasas/biosíntesis , Ribonucleasas , Adolescente , Aspergilosis Broncopulmonar Alérgica/metabolismo , Bacterias/crecimiento & desarrollo , Infecciones Bacterianas/metabolismo , Niño , Proteínas en los Gránulos del Eosinófilo , Peroxidasa del Eosinófilo , Neurotoxina Derivada del Eosinófilo , Eosinófilos/citología , Eosinófilos/metabolismo , Femenino , Volumen Espiratorio Forzado , Humanos , Hipersensibilidad Inmediata/metabolismo , Hipersensibilidad Inmediata/microbiología , Inmunoglobulina E/sangre , Recuento de Leucocitos , Masculino , Infecciones del Sistema Respiratorio/metabolismo , Infecciones del Sistema Respiratorio/microbiologíaRESUMEN
The severity of asthma can be graded from mild intermittent to severe persistent. Airway inflammation is a feature of persistent asthma. We compared several markers of inflammation in mucosal biopsies and bronchoalveolar lavage fluid (BAL fluid) from 12 healthy control subjects, 24 patients with intermittent asthma, and 18 patients with mild-to-moderate persistent asthma. Epithelial shedding, eosinophil (EG2-positive cells), and activated T-cell (UCHL1) counts in biopsies, and ECP levels in BAL fluids were significantly increased in patients with intermittent asthma by comparison with control subjects and this increase was significantly greater for patients with persistent asthma. Alveolar macrophage activation (percentage of hypodense cells) and the thickness of the basement membrane were significantly increased in asthmatic subjects as compared with controls but there was no difference between the two asthmatic groups. Hyaluronic acid levels in BAL fluids were significantly increased in patients with persistent asthma by comparison with control subjects and patients with intermittent asthma. Mast cell numbers (toluidine blue) in biopsies and histamine or levels in BAL fluids were similar in the three groups. This study shows that airways inflammation is present in patients with intermittent asthma but to a lesser extent than in patients with persistent asthma.
Asunto(s)
Asma/complicaciones , Asma/fisiopatología , Bronquitis/etiología , Adulto , Asma/patología , Biopsia , Bronquios/patología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Inmunohistoquímica , Mediadores de Inflamación/análisis , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
The aim of this investigation was to study the seasonal variation in the serum levels of eosinophil cationic protein (S-ECP). The study population comprised a general population sample of 379 individuals (range: 20-45 years) who were investigated with blood sample for the measurement of S-ECP, skin prick test and methacholine challenge. The examination took place between May and October 1991. Of the 379 subjects investigated, 137 (36%) were atopic. A significant seasonal variation in S-ECP was found in the group of birch-pollen-positive subjects (P < 0.05), but not in the non-atopic or birch-negative atopic group. The mean level of S-ECP in birch-positive subjects was about twice as high in June as in birch atopic subjects examined during other months. It is concluded that seasonal variation in birch-pollen-positive subjects must be taken into account when using S-ECP clinically or in epidemiological research.
Asunto(s)
Proteínas Sanguíneas/metabolismo , Hipersensibilidad/sangre , Mediadores de Inflamación/metabolismo , Ribonucleasas , Estaciones del Año , Adulto , Proteínas Sanguíneas/análisis , Pruebas de Provocación Bronquial , Broncodilatadores , Proteínas en los Gránulos del Eosinófilo , Humanos , Hipersensibilidad/inmunología , Mediadores de Inflamación/análisis , Cloruro de Metacolina , Persona de Mediana Edad , Polen , Pruebas CutáneasRESUMEN
We have recently phenotyped inflammation in non-infectious allergic and non-allergic chronic maxillary sinusitis using sinus biopsies and lavage fluids. In this first paper, we have concentrated our work on the eosinophil, T cell, mast cell and macrophage infiltrates. However, many unresolved questions remain and particularly the role of neutrophils needed to be addressed. In the present study, we focused on the neutrophilic inflammation: myeloperoxidase (MPO) and interleukin-8 (IL-8) were measured by immunoassays and neutrophils were enumerated by conventional staining in the sinus lavage fluids of 16 patients with chronic sinusitis and six control subjects. Both MPO and IL-8 levels were significantly higher in patients than in controls (P < 0.01 and 0.005, respectively). There was a significant correlation between MPO levels and neutrophil numbers, and between MPO and IL-8 levels in the sinus lavage fluid (P < 0.0001, Spearman rank correlation). The presence of high levels of IL-8 in the lavage fluids of patients suffering from chronic sinusitis, levels which correlate with those of MPO, suggests that this cytokine may activate neutrophils in this chronic disease.
Asunto(s)
Interleucina-8/metabolismo , Peroxidasa/metabolismo , Sinusitis/metabolismo , Adolescente , Adulto , Anciano , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Líquido del Lavado Nasal , Fenotipo , Sinusitis/enzimología , Sinusitis/inmunologíaRESUMEN
Eosinophilic inflammation has been observed in the airways of patients with chronic obstructive pulmonary disease (COPD). A subset of patients clinically diagnosed as having COPD show a reversibility of airflow obstruction when treated with corticosteroids, and may consist of patients with features of asthma including reticular basement membrane thickening and eosinophilic inflammation. Twenty-five unselected patients clinically diagnosed as having COPD received a daily oral dose of 1.5 mg/kg body weight of prednisolone for 15 d to assess the relationships between the functional response to corticosteroids and the presence of features of asthma. Eosinophilic inflammation was characterized before the course of corticosteroid therapy by enumerating eosinophils in peripheral blood, bronchoalveolar lavage fluid (BALF), and bronchial biopsies, using EG2 monoclonal antibody, and by measurement of eosinophil cationic protein (ECP) in BALF. A response to treatment was defined by an increase in FEV1 of at least 12% from baseline values and an absolute value of 200 ml measured at the end of the treatment. Twelve of 25 patients responded to the treatment. By comparison with nonresponders, responders had a significantly larger number of eosinophils (p < 0.015), and higher levels of ECP (p = 0.013) in their BALF. The responders had a thicker reticular basement membrane than the nonresponders (p < 0.04). These results indicate that a response to prednisolone in patients diagnosed as having COPD might occur more readily in a subset of patients presenting with features of asthma.
Asunto(s)
Asma/diagnóstico , Glucocorticoides/uso terapéutico , Enfermedades Pulmonares Obstructivas/fisiopatología , Prednisona/uso terapéutico , Ribonucleasas , Adulto , Anciano , Asma/tratamiento farmacológico , Proteínas Sanguíneas/análisis , Bronquios/patología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Proteínas en los Gránulos del Eosinófilo , Eosinófilos , Femenino , Volumen Espiratorio Forzado , Humanos , Inflamación , Mediadores de Inflamación/análisis , Enfermedades Pulmonares Obstructivas/diagnóstico , Enfermedades Pulmonares Obstructivas/tratamiento farmacológico , Enfermedades Pulmonares Obstructivas/patología , Masculino , Persona de Mediana Edad , Ventilación Pulmonar/efectos de los fármacosRESUMEN
Allergen avoidance is regarded as an important approach to management of atopic asthma. The effect of Intervent bed covering systems on house dust mite (HDM) allergen exposure, asthma symptoms and markers of inflammation was investigated in 31 HDM sensitive asthmatic children. Dust concentrations of Dermatophagoides pteronyssinus allergen 1 (Der p 1) were monitored before and after covering the mattress, duvet and pillow with active and placebo covers for 3 months, in a single-blind, cross-over trial. Twice daily peak expiratory flow rate (PEFR), daily symptom scores and treatment schedule were recorded. Bronchial hyperresponsiveness was monitored by histamine challenge (provocative concentration of histamine causing a 20% fall in forced expiratory volume in one second (PC20)), and inflammation by measuring eosinophil cationic protein (ECP), eosinophil protein X (EPX), eosinophil peroxidase (EPO), and soluble interleukin-2 receptor (sIL-2R) in serum. There was a significant reduction in Der p 1 when the mattress, duvet and pillow were covered with the active bedding. There was no significant improvement in symptoms of asthma, PEFR, bronchodilator usage of PC20. Also, ECP, EPX, sIL-2R concentrations did not change for either treatment. EPO concentrations were significantly lower in the active compared to the placebo period. The active bed covers reduced retrievable Dermatophagoides pteronyssinus allergen 1 (Der p 1) from the bedding, with short term clinical benefit.
Asunto(s)
Alérgenos , Asma/fisiopatología , Ropa de Cama y Ropa Blanca , Ácaros , Hipersensibilidad Respiratoria/fisiopatología , Ribonucleasas , Adolescente , Animales , Antígenos Dermatofagoides , Asma/sangre , Asma/terapia , Proteínas Sanguíneas/análisis , Hiperreactividad Bronquial , Pruebas de Provocación Bronquial , Niño , Preescolar , Estudios Cruzados , Polvo/análisis , Proteínas en los Gránulos del Eosinófilo , Peroxidasa del Eosinófilo , Neurotoxina Derivada del Eosinófilo , Eosinófilos , Femenino , Glicoproteínas/análisis , Histamina , Humanos , Mediadores de Inflamación/análisis , Masculino , Ápice del Flujo Espiratorio , Peroxidasas/análisis , Receptores de Interleucina-2/sangre , Hipersensibilidad Respiratoria/sangre , Hipersensibilidad Respiratoria/terapia , Método Simple CiegoRESUMEN
Interleukin 8 (IL-8) is a chemoattractant cytokine having a distinct target specificity for the neutrophil. However, it was also found to be active on primed eosinophils. IL-8 was measured by enzyme immunoassay in the bronchoalveolar lavage fluid (BALF) of 9 control subjects, 19 asthmatics and 36 chronic bronchitis patients. Its levels were correlated with neutrophil and eosinophil counts as well as levels of myeloperoxidase (MPO) and eosinophil cationic protein in the BALF. Asthmatic and chronic bronchitis patients had elevated levels of IL-8 in comparison with normal subjects. There was no correlation between the severity of asthma or chronic bronchitis and IL-8 levels. In asthmatic subjects there was a correlation between IL-8 and MPO levels (p < 0.0001, Spearman test). There was no significant correlation between eosinophils and IL-8. In chronic bronchitis there was a correlation between IL-8 and MPO levels as well as between IL-8 and neutrophil counts (p < 0.004 and p < 0.0152, respectively, Spearman test). IL-8 is involved in neutrophilic inflammation in asthma and chronic bronchitis, but differences in the IL-8 regulation of neutrophils were observed in both diseases.
Asunto(s)
Asma/inmunología , Bronquitis/inmunología , Líquido del Lavado Bronquioalveolar/química , Interleucina-8/análisis , Adolescente , Adulto , Anciano , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Recuento de Células , Eosinófilos/inmunología , Humanos , Persona de Mediana Edad , Neutrófilos/inmunología , Peroxidasa/análisis , Índice de Severidad de la EnfermedadRESUMEN
Recently, bronchial brush biopsy (BBB) has been introduced as a complimentary method to bronchial forceps biopsy for the study of bronchial epithelial cells. We wanted to determine whether epithelial inflammatory cells in bronchial brush biopsies can reflect mucosal inflammation assessed indirectly by levels of cellular activation markers in bronchial lavage fluid. We studied 15 healthy controls, 11 asthmatics with regular steroid inhalation therapy, 13 asthmatics without steroids, and 10 smokers with nonobstructive chronic bronchitis. Differential counts of epithelial and inflammatory cells were made from the BBB material. Bronchial lavage levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), tryptase, hyaluronan and interleukin-8 (IL-8) were measured as indirect markers for inflammatory cell activation. We found an increased percentage of eosinophil granulocytes in the BBB from the steroid-untreated asthmatic patients (1.16%) in comparison to the other groups (0.11%, 0.09% and 0.02%, respectively; p<0.01). In the steroid-untreated asthmatic patients, the percentage of eosinophils correlated with ECP in bronchial lavage fluid (r=0.73; p<0.01), indicating that the BBB method can reflect the degree of eosinophilic activation. A negative correlation was found for the percentage of eosinophils in BBB with levels of provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) for the asthmatic patients in the study (r= -0.67; p<0.003). The bronchial brush biopsy method appears to give information on the changes present in superficial bronchial epithelium in inflammatory airways disease. These changes appear to relate to the degree of inflammatory activity and disease severity in asthma.
Asunto(s)
Asma/patología , Biopsia/métodos , Bronquitis/patología , Administración por Inhalación , Adulto , Asma/tratamiento farmacológico , Biomarcadores/análisis , Líquido del Lavado Bronquioalveolar , Enfermedad Crónica , Células Epiteliales , Epitelio/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Sensibilidad y Especificidad , Esteroides/administración & dosificación , Esteroides/uso terapéuticoRESUMEN
BACKGROUND: Lung function tests, including forced expiratory volume in one second (FEV1), forced expiratory flow at 25-75% of vital capacity (FEF25-75%) and provocation concentrations of histamine which reduce FEV1 by 20% (PC20), are used as indicators of airway form and function in bronchial asthma. Recently, markers of eosinophil activation in bronchial lavage and serum have been suggested as a measure of eosinophil mediated inflammation in the airways. These include eosinophil cationic protein (ECP), eosinophil protein X (EPX) (also known as eosinophil derived neurotoxin) and eosinophil peroxidase (EPO). Similarly, serum tryptase has been used as a marker of mast cell activation in systemic anaphylaxis. OBJECTIVES: We measured both sets of indices in a group of children with moderately severe asthma to assess the contribution of eosinophil and mast cell mediated events to airflow limitation and bronchial hyperresponsiveness. METHODS: Forty-eight children aged 5-10 years had spirometric assessments, histamine challenges and blood sampling on the same occasion. After analysis of sera, the indices were compared. RESULTS: The eosinophil markers ECP and EPX correlated very well with each other. They showed a moderate negative correlation with PC20 for histamine. EPX was also found to negatively correlate with FEV1 and FEF25-75%. Serum tryptase levels showed no such correlates with airway function. CONCLUSION: These results suggest that serum markers of eosinophil activation correlate with airway function in childhood asthma, and may be of value in assessing the severity of the disease. It further supports the notion that childhood asthma has a similar immunopathology to that occurring in adults, with predominance of eosinophil mediated inflammation.
Asunto(s)
Asma/metabolismo , Asma/fisiopatología , Bronquios/fisiopatología , Eosinófilos/metabolismo , Mediadores de Inflamación/metabolismo , Ribonucleasas , Biomarcadores , Proteínas Sanguíneas/metabolismo , Líquido del Lavado Bronquioalveolar/química , Recuento de Células , Niño , Preescolar , Quimasas , Proteínas en los Gránulos del Eosinófilo , Peroxidasa del Eosinófilo , Neurotoxina Derivada del Eosinófilo , Eosinófilos/patología , Volumen Espiratorio Forzado , Humanos , Mastocitos/metabolismo , Flujo Espiratorio Medio Máximo , Peroxidasas/metabolismo , Serina Endopeptidasas/sangre , TriptasasRESUMEN
BACKGROUND: Bronchial asthma is associated with elevated serum levels of eosinophil products, such as eosinophil protein X (EPX), but the occurrence in urine of this substance in patients with asthma has not previously been studied. OBJECTIVE: This study was performed to clarify whether increased amounts of eosinophil granulocyte proteins in urine and serum reflect ongoing asthmatic inflammation and whether decreasing values reflect successful treatment. METHODS: Twelve children with a median age of 12.5 years who had mild or moderate atopic asthma were studied for 3 months. At the time of inclusion in the study, treatment with inhaled budesonide was initiated. Nine children of the same age without atopic disease served as control subjects. Levels of EPX, eosinophil cationic protein (ECP), and myeloperoxidase in serum and in urine (urinary EPX) were determined at inclusion and then after 3 months of treatment. Spirometry was performed on the same occasions. RESULTS: At the time of inclusion, urinary EPX and serum ECP were significantly higher in children with atopic asthma than in the control subjects (mean, 116.4 vs 43.0 micrograms/mmol creatinine [p = 0.004] and 37.0 vs 14.8 micrograms/L [p = 0.004]). In the asthma group urinary EPX, as well as serum ECP, decreased significantly after 3 months of treatment with budesonide (116.4 to 68.4 micrograms/mmol creatinine [p = 0.005] and 37.0 to 24.0 micrograms/L [p = 0.04]). At the same time, peak expiratory flow values increased significantly in the children with asthma (76.0% to 87.8% of predicted value [p = 0.005]) but not in the control subjects (87.0% to 90.1%). In the asthma group the levels of myeloperoxidase were similar to those in the control group, both at inclusion and after 3 months. CONCLUSION: Increased urinary EPX and serum ECP levels seem to reflect active atopic asthma, whereas decreased levels after antiinflammatory treatment probably reflect normalization of airway inflammation, and indirectly, improved lung function.
Asunto(s)
Asma/orina , Proteínas Sanguíneas/orina , Ribonucleasas , Adolescente , Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Biomarcadores , Proteínas Sanguíneas/metabolismo , Niño , Proteínas en los Gránulos del Eosinófilo , Neurotoxina Derivada del Eosinófilo , Eosinófilos/fisiología , Femenino , Humanos , Recuento de Leucocitos , Masculino , Ventilación PulmonarRESUMEN
Do markers of eosinophil activation differ in their ability to detect subjects with atopy or bronchial hyper-responsiveness (BHR)? Comparisons of serum levels of eosinophil peroxidase (S-EPO), of eosinophil cationic protein (S-ECP) and the blood eosinophil count (B-Eos) have been made between 154 subjects aged 20-44 years, participating in the European Community Respiratory Health Survey in Uppsala, Sweden. Subjects with atopy had significantly higher levels of S-EPO and S-ECP than those without atopy (P <0 center dot 001). Subjects with BHR had significantly higher levels of S-EPO (P <0 center dot 001) and B-Eos (P <0 center dot 01) than subjects without BHR. Persons reporting asthma-related symptoms had significantly higher levels of S-EPO and B-Eos than subjects without such symptoms (P <0 center dot 001 and P <0 center dot 01, respectively). Asthma symptom score correlated significantly to S-EPO (r = 0 center dot 26, P <0 center dot 01), S-ECP (r = 0 center dot 20, P <0 center dot 05) and B-Eos (r = 0 center dot 18, P <0 center dot 05). Finally, S-EPO was significantly more sensitive than S-ECP for detecting subjects with BHR (P <0 center dot 05) and significantly more sensitive than B-Eos for detecting both subjects with BHR and subjects with a combination of atopy and BHR (P <0 center dot 05). It is concluded that S-EPO is a promising marker with a higher sensitivity for BHR than S-ECP or B-Eos. Further studies are needed to define the value of S-EPO when following disease activity.
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Hiperreactividad Bronquial/enzimología , Eosinófilos/enzimología , Peroxidasas/sangre , Adulto , Asma/enzimología , Biomarcadores/sangre , Hiperreactividad Bronquial/inmunología , Peroxidasa del Eosinófilo , Femenino , Volumen Espiratorio Forzado , Humanos , Hipersensibilidad Inmediata/enzimología , Inmunoglobulina E/análisis , Masculino , Cloruro de Metacolina , Ápice del Flujo Espiratorio , Sensibilidad y Especificidad , Pruebas CutáneasRESUMEN
BACKGROUND: Despite the wide use of antihistamines in the treatment of allergic rhinitis, little is known about effects of these drugs on airway mucosal indices, which specifically reflect either mast cell release activity (tryptase) or microvascular-epithelial exudation of bulk plasma (alpha 2-macroglobulin). OBJECTIVE: This study, involving subjects with seasonal allergic rhinitis, examines the effects of loratadine treatment on allergen-induced nasal mucosal output of tryptase and alpha 2-macroglobulin. Effects on nasal symptoms and eosinophils are also examined. METHODS: Placebo and loratadine (20 mg) were given orally once daily for 5 days at 6-week intervals. Nasal diluent and allergen challenges were carried out on day 5. The mucosa was lavaged with saline solution after each challenge, and nasal lavage fluid levels of tryptase and alpha 2-macroglobulin were determined. Nasal symptoms were scored, and nasal peak expiratory flow rates were measured. Superficial cells (eosinophils) were obtained with a brush device before and 24 hours after the allergen challenges. RESULTS: Allergen dose-dependently increased the nasal symptoms and the lavage fluid levels of alpha 2-macroglobulin and tryptase. Allergen also reduced the nasal peak expiratory flow rates. Loratadine inhibited the exudation of alpha 2-macroglobulin and reduced tryptase levels, nasal symptoms, and obstruction, but did not affect the number of eosinophils. CONCLUSION: The inhibitory effects of loratadine on nasal lavage fluid levels of alpha 2-macroglobulin suggest that histamine, through effects on microvascular H1-receptors, mediates allergen challenge-induced exudation of bulk plasma in acute allergic rhinitis. The reduced lavage fluid levels of tryptase suggest either that loratadine directly attenuates mast cell release activity or that loratadine, through inhibition of the exudation process, simply attenuates luminal entry of tissue solutes (in this case, tryptase).
Asunto(s)
Alérgenos/inmunología , Loratadina/uso terapéutico , Mucosa Nasal/metabolismo , Rinitis Alérgica Estacional/metabolismo , Serina Endopeptidasas/metabolismo , alfa-Macroglobulinas/metabolismo , Adolescente , Adulto , Recuento de Células , Quimasas , Estudios Cruzados , Relación Dosis-Respuesta Inmunológica , Método Doble Ciego , Eosinófilos/patología , Femenino , Humanos , Mediadores de Inflamación/metabolismo , Masculino , Mucosa Nasal/patología , Ápice del Flujo Espiratorio , Rinitis Alérgica Estacional/patología , Rinitis Alérgica Estacional/fisiopatología , TriptasasRESUMEN
BACKGROUND: Bronchial inflammation in chronic bronchitis has not been characterised as well as in asthma. The present study was undertaken to assess whether a characteristic pattern of bronchial inflammatory markers could be found in patients with chronic bronchitis. METHODS: Bronchoscopy with bronchial lavage was performed in 42 patients with chronic bronchitis and in 13 healthy controls. Twenty three of the patients had non-obstructive chronic bronchitis and 19 had chronic bronchitis and chronic obstructive pulmonary disease (COPD). Eighteen of the patients with bronchitis had recurrent infective exacerbations and 24 did not. Intrabronchial bacterial cultures were taken with a protected specimen brush. RESULTS: Increased activity of neutrophils, fibroblasts, and eosinophils was found in the patients with chronic bronchitis as assessed by the levels of myeloperoxidase (MPO) and interleukin-8 (IL-8), hyaluronan, and eosinophil cationic protein (ECP), respectively. The levels of tryptase did not differ from the controls. High correlations were found between the levels of MPO and IL-8, as well as ECP and IL-8. No differences were found between the patients with COPD and those with non-obstructive chronic bronchitis. CONCLUSIONS: Recruitment and activation of both neutrophils and eosinophils seem to be a characteristic of chronic bronchitis. This activation is associated with IL-8. The patients with intrabronchial cultures of Streptococcus pneumoniae had the highest individual levels of MPO, ECP, and IL-8 of all subjects in the study, indicating that colonisation with S pneumoniae could promote bronchial inflammation.
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Bronquitis/patología , Líquido del Lavado Bronquioalveolar/química , Ribonucleasas , Adulto , Anciano , Biomarcadores/análisis , Proteínas Sanguíneas/análisis , Bronquitis/microbiología , Líquido del Lavado Bronquioalveolar/microbiología , Enfermedad Crónica , Proteínas en los Gránulos del Eosinófilo , Eosinófilos/patología , Fibroblastos/patología , Humanos , Ácido Hialurónico/análisis , Interleucina-8/análisis , Enfermedades Pulmonares Obstructivas/patología , Persona de Mediana Edad , Neutrófilos/patología , Peroxidasa/análisis , Streptococcus pneumoniae/aislamiento & purificaciónRESUMEN
The levels of serum eosinophil cationic protein (ECP) in asthmatic patients have been shown to be increased in acute and undertreated asthma as a result of inflammation. ECP is released during in vitro clotting of peripheral blood. The exposure of the atopic individual to an offending allergen stimulates the activation of the blood eosinophils and their release of ECP into serum. Serum ECP levels reflect avoidance of the allergen, and successful treatment of asthma inflammation with corticosteroids cause a reduction of the inflammation in the lung. When individual patients with asthma are followed, the level of serum ECP can be used (1) as an early indicator of the degree of inflammation, (2) for monitoring the efficacy of corticosteroid therapy, and (3) for possible noncompliance with treatment.
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Asma/inmunología , Proteínas Sanguíneas/análisis , Hipersensibilidad/diagnóstico , Mediadores de Inflamación/análisis , Ribonucleasas , Antiinflamatorios/metabolismo , Antiinflamatorios/uso terapéutico , Asma/diagnóstico , Pruebas de Provocación Bronquial/métodos , Niño , Preescolar , Proteínas en los Gránulos del Eosinófilo , Glucocorticoides/metabolismo , Glucocorticoides/uso terapéutico , Humanos , Hipersensibilidad/metabolismo , Cooperación del Paciente , Sensibilidad y Especificidad , EsteroidesRESUMEN
How are the serum concentration of eosinophil cationic protein (S-ECP) and the blood eosinophil count (B-Eos) related to symptoms of asthma, allergy, and bronchial hyperresponsiveness (BHR)? We measured S-ECP, B-Eos, and total and specific IgE in serum in blood samples from 699 randomly selected persons 20-44 years old. They also underwent a structured interview, spirometry, a methacholine provocation test, and skin prick tests as part of the European Community Respiratory Health Survey. B-Eos and S-ECP were found to be closely related to asthma symptom score (P < 0.001), total IgE (P < 0.001), and BHR (P < 0.001). On the basis of the results, the subjects were divided into four groups: healthy controls, patients with allergic rhinitis, patients with nonallergic asthma, and patients with allergic asthma. There were significant differences in both B-Eos and S-ECP among the groups (P < 0.001), the highest values being found in the allergic asthma group. B-Eos and S-ECP each had an additive value in predicting the occurrence of asthma. Among persons with high concentrations of both variables, asthma was eight times more common than in those with low concentrations. Allergy and BHR were also found to be independently related to B-Eos and S-ECP levels. Furthermore, both B-Eos and S-ECP showed good correlation to subjective and objective measures of asthma activity. We conclude that both B-Eos and S-ECP and their interrelationship may be of value in assessing the activity of asthma. However, their role in disease management was not established in this cross-sectional study.
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Asma/sangre , Proteínas Sanguíneas/análisis , Hiperreactividad Bronquial/sangre , Eosinófilos , Inmunoglobulina E/sangre , Rinitis Alérgica Perenne/sangre , Ribonucleasas , Adulto , Factores de Edad , Asma/diagnóstico , Asma/epidemiología , Asma/inmunología , Biomarcadores/sangre , Hiperreactividad Bronquial/diagnóstico , Hiperreactividad Bronquial/epidemiología , Hiperreactividad Bronquial/inmunología , Pruebas de Provocación Bronquial , Estudios Transversales , Proteínas en los Gránulos del Eosinófilo , Europa (Continente) , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Prevalencia , Rinitis Alérgica Perenne/diagnóstico , Rinitis Alérgica Perenne/epidemiología , Rinitis Alérgica Perenne/inmunología , Pruebas Cutáneas , Fumar/efectos adversos , SueciaRESUMEN
BACKGROUND AND AIM: Pathologic examination of the sinus mucosa and titration of inflammatory mediators in the sinus fluid were carried out to characterize inflammation in chronic sinusitis and determine whether patients with chronic allergic rhinitis (CAR) and sinusitis differ from patients with chronic nonallergic rhinitis (CNAR) and sinusitis. METHODS: Nine control subjects (patients requiring ear, nose, and throat surgery not related to sinusitis), 12 patients with CAR and sinusitis, and 13 patients with CNAR and sinusitis were investigated. Eosinophil cationic protein, tryptase, myeloperoxidase, histamine, and prostaglandin D2 were measured in the sinus lavage fluids, and cells were enumerated. The cellular infiltrate was studied by immunohistochemistry with monoclonal antibodies against eosinophil cationic protein (eosinophils), tryptase (mast cells), neutrophil elastase (neutrophils), CD3 (lymphocytes), CD68 (macrophages), and proliferating cell nuclear antigens. RESULTS: Neutrophils were not increased in sinusitis. In comparison with control subjects, patients with CAR and CNAR with sinusitis showed significant increases in eosinophils and macrophages in biopsy specimens and in eosinophil cationic protein in sinus lavage fluids. In comparison with patients with CNAR, patients with CAR had an increased number of intraepithelial mast cells and lymphocytes. CONCLUSIONS: These findings suggest that patients with CNAR and sinusitis can be distinguished from patients with CAR and sinusitis, which resembles nonallergic rhinitis with eosinophilia syndrome.