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OBJECTIVE: To assess possible ergogenic properties of corticosteroid administration. DESIGN: A balanced, double-blind, placebo-controlled design was used. PARTICIPANTS: 28 well-trained cyclists and rowers. INTERVENTION: 4 weeks' daily inhalation of 800 microg budesonide or placebo. MAIN OUTCOME MEASUREMENTS: The subjects performed three incremental cycle ergometer tests until exhaustion, before and after 2 and 4 weeks of placebo or budesonide administration, to measure maximal power output (W(max)). Once a week they filled in a profile of mood state (POMS) questionnaire. RESULTS: There was no significant difference in W(max) between the placebo (376 (SD 25) W) and the corticosteroid group (375 (36) W) during the preintervention test, and there were no significant changes in either group after 2 and 4 weeks of intervention. No effect of the intervention on mood state was found. CONCLUSION: 4 weeks of corticosteroid or placebo inhalation in healthy, well-trained athletes did not affect maximal power output or mood state. Hence no ergogenic properties of 4 weeks' corticosteroid administration could be demonstrated, which corroborates previous studies of short-term corticosteroid administration.
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Rendimiento Atlético/fisiología , Broncodilatadores/uso terapéutico , Budesonida/uso terapéutico , Resistencia Física/efectos de los fármacos , Administración por Inhalación , Adulto , Método Doble Ciego , Prueba de Esfuerzo , Humanos , Masculino , Resistencia Física/fisiología , Adulto JovenRESUMEN
OBJECTIVE: We developed AsthmaCritic, a non-inquisitive critiquing system integrated with the general practitioners' electronic medical records. The system is based on the guidelines for asthma and chronic obstructive pulmonary disease (COPD) as issued by the Dutch College of General Practitioners. This paper assesses the effect of AsthmaCritic on monitoring and treatment of asthma and COPD by Dutch general practitioners in daily practice. METHODS: A randomized clinical trial in 32 practices (40 Dutch general practitioners) using electronic patient records. An intervention group was given the use of AsthmaCritic, a control group continued working in the usual manner. Both groups had the disposal of the asthma and COPD guidelines routinely distributed by the Dutch College of General Practitioners. We measured the average number of contacts, FEV 1 (forced expiratory volume), and peak-flow measurements per asthma/COPD patient per practice; and, the average number of antihistamine, cromoglycate, deptropine, and oral bronchodilator prescriptions per asthma/COPD patient per practice. RESULTS: The number of contacts increased in the age group of 12-39 years. The number of FEV1 , peak-flow measurements, and the ratio of coded measurements increased, whereas the number of cromoglycate prescriptions decreased in the age group of 12-39 years. CONCLUSIONS: Our study shows that the guideline-based critiquing system AsthmaCritic changed the manner in which the physicians monitored their patients and, to a lesser extent, their treatment behavior. In addition, the physicians changed their data-recording habits.
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Sistemas de Información en Atención Ambulatoria , Asma/tratamiento farmacológico , Sistemas de Apoyo a Decisiones Clínicas , Utilización de Medicamentos , Medicina Familiar y Comunitaria/normas , Adhesión a Directriz , Pautas de la Práctica en Medicina , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Adolescente , Adulto , Niño , Toma de Decisiones , Monitoreo de Drogas , Medicina Familiar y Comunitaria/métodos , Retroalimentación , Femenino , Humanos , Masculino , Sistemas de Registros Médicos Computarizados , Países BajosRESUMEN
Several inhaled drugs for use by cystic fibrosis (CF) patients are formulated for nebulizer use only. This therapy is time consuming and includes the risk of contamination of the nebulizers. Dry powder inhalers (DPI) can be an attractive alternative for CF drugs. Inhaled flow rate and volume, and the device resistance are important determinants for optimal dispersion of drug from a DPI. It is important to understand how these variables interact in the CF population in order to properly design a new DPI formulation targeted for these patients. The objective of this study was to assess the inspiratory variables of a representative population of CF subjects 6 years and older with varying degrees of lung disease while inhaling through resistances that simulate DPI devices. Ninety-six stable CF patients were enrolled, ages 6-54 years, FEV(1) 19-126% predicted. Subjects inhaled forcefully through four different resistances (0.019, 0.024, 0.038, and 0.048 kP(0.5)/LPM, respectively), while inspiratory time (IT(DPI)), peak inspiratory flow (PIF(DPI)), and volumes (V(DPI)) were measured. For any resistance, inspired V(DPI) increased with the older age groups; PIF(DPI) was similar between adults and adolescents but lower in the children. Subjects with lower FEV(1) had lower V(DPI) and PIF(DPI). As resistance increased, PIF(DPI) decreased, IT(DPI) increased, with no significant change in V(DPI). At the lowest resistance mean PIF(DPI) was 105 LPM (range 45-163) for all patients; 112 LPM (range 75-163) in adults; and 89 LPM (45-126) in children. Mean inspired V(DPI) was 1.75 L for all patients; 2.2 L (0.8-3.7) in adults; and 1.2 L (0.5-1.8) in children. At the lowest resistance a minimal flow rate of 30, 45, and 60 LPM was attained in 100%, 99%, and 96% of all patients. Volumes of 1.0, 1.5, and 2.0 L were attained by 85%, 57%, and 30% of the patients. At the highest resistance mean PIF(DPI) was 52 LPM (range 26-70) for all patients; 55 LPM (40-70) in adults; and 47 LPM (26-62) in children. Mean inspired V(DPI) was 1.5 L in all patients; 1.9 L (0.9-3.5) in adults and 1.1 L (0.5-2.3) in children. At the highest resistance, a minimal flow rate of 30, 45, and 60 LPM was attained in 99%, 80%, and 22% of all patients. Volumes of 1, 1.5, and 2 L were attained in 84%, 45%, and 23% of the patients. We defined ranges for inspiratory variables in a diverse CF population for a range of device resistances that bracket those of current DPIs. The recorded inspiratory patterns can be used on the bench to design and test new dry powder formulations and devices to target the largest proportion of the CF population.
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Fibrosis Quística/tratamiento farmacológico , Fibrosis Quística/fisiopatología , Inhalación , Nebulizadores y Vaporizadores , Adolescente , Adulto , Niño , Sistemas de Liberación de Medicamentos , HumanosRESUMEN
BACKGROUND: Preclinical studies have demonstrated that some second-generation antihistamines have anti-inflammatory effects. It is not known whether these effects are also demonstrable in vivo. In this study we investigated the effect of treatment with desloratadine (DL) on systemic inflammation and on nasal and bronchial mucosal inflammation after nasal allergen provocation (NP) in subjects with grass-pollen-allergic rhinitis and asthma. METHODS: Twenty-six subjects with grass-pollen-allergic rhinitis and asthma were randomly allocated to 8 days of treatment with DL (n = 13) or placebo (n = 13) outside the grass pollen season. On day 7 they underwent nasal provocation with grass pollen allergen. Nasal and bronchial biopsies were taken for immunohistochemical evaluation, and blood samples were analysed. Rhinitis and asthma symptoms, peak nasal inspiratory flow and peak expiratory flow, were also measured at specified times. RESULTS: The number of circulating eosinophils decreased during DL treatment, and there was a reduced increase in circulating eosinophils after NP in these subjects. There was also a significant reduction in early bronchial clinical response. There was no significant lessening in the severity of the nasal symptoms. Nasal and bronchial mucosal inflammation parameters did not alter under DL treatment. CONCLUSION: These data suggest that treatment with DL reduces systemic eosinophilia and prevents the increase in circulating eosinophils after NP. DL also significantly reduces the early bronchial clinical response to NP. However, airway mucosal inflammation is not altered by 1 week of treatment.
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Asma/tratamiento farmacológico , Antagonistas de los Receptores Histamínicos H1 no Sedantes/uso terapéutico , Loratadina/análogos & derivados , Pruebas de Provocación Nasal , Rinitis Alérgica Estacional/tratamiento farmacológico , Adulto , Femenino , Antagonistas de los Receptores Histamínicos H1 no Sedantes/administración & dosificación , Humanos , Inflamación/tratamiento farmacológico , Loratadina/administración & dosificación , Loratadina/uso terapéutico , Masculino , Poaceae/efectos adversos , Poaceae/inmunología , Polen/efectos adversos , Polen/inmunología , Resultado del TratamientoRESUMEN
BACKGROUND: Inhaled corticosteroids are currently regarded as the gold standard in anti-inflammatory therapy, however, leukotriene receptor antagonists have been ascribed anti-inflammatory properties. OBJECTIVE: We directly compared the anti-inflammatory effects of inhaled fluticasone propionate (FP, 100 microg Diskus, twice daily) and oral montelukast (MON 10 mg, nocte) in bronchial biopsies of patients with asthma in a double-blind, double-dummy, parallel-group design. METHODS: Bronchial biopsies, serum and urine samples were collected from 36 atopic asthmatics before and after 8 weeks of treatment. Activated T cells (CD25+), eosinophils (MBP+) and mast cells (tryptase+) were analysed by immunohistochemistry. Serum eosinophil cationic protein (ECP) and IL-5 were analysed by radio and enzyme immunoassay (EIA), respectively. Urinary 9alpha-11beta-PGF2 and leukotriene E4 (LTE4) were measured by EIA. RESULTS: A comparison of changes from baseline [FP/MON ratio (95% confidence interval)] of activated T cells was not different when subjects were treated with FP compared to treatment with MON [1.00 (0.18-4.86); P=0.924]. Following treatment, mast cells in the FP group were significantly lower than in the group treated with MON [0.39 (0.16-0.97); P=0.041]. There was no difference in the number of eosinophils in the lamina propria following either treatment [0.54 (0.05-2.57); P=0.263]. However, treatment with FP resulted in a significantly greater decrease in serum ECP, compared to treatment with MON [0.37 (0.25-0.71); P=0.002]. CONCLUSIONS: FP appears to be superior to MON as an anti-inflammatory therapy in mild asthmatics.
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Acetatos/administración & dosificación , Androstadienos/administración & dosificación , Antiasmáticos/uso terapéutico , Antiinflamatorios/administración & dosificación , Asma/tratamiento farmacológico , Antagonistas de Leucotrieno/administración & dosificación , Quinolinas/administración & dosificación , Administración por Inhalación , Administración Oral , Adulto , Asma/sangre , Asma/orina , Ciclopropanos , Método Doble Ciego , Proteína Catiónica del Eosinófilo/sangre , Femenino , Fluticasona , Humanos , Inmunohistoquímica/métodos , Interleucina-5/sangre , Pulmón/fisiopatología , Masculino , Mastocitos/inmunología , Persona de Mediana Edad , Receptores de Interleucina-2/inmunología , Sulfuros , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Local airway inflammation and airway remodelling are considered important in the clinical expression of allergic asthma. OBJECTIVE: The aim of this study was to compare airway inflammation and remodelling in nasal and bronchial mucosa of subjects with allergic rhinitis with or without asthma. METHODS: Four experimental groups were formed: allergic asthma and rhinitis (n = 19); allergic rhinitis, no asthma (n = 18); atopic subjects, no asthma, no rhinitis (n = 8) and non-allergic healthy control subjects (n = 16). Blood samples, nasal and bronchial biopsy specimens were collected during stable disease. Immunohistochemistry was performed for eosinophils (MBP), mast cells (CD117) and vascular endothelium (CD31). Epithelial loss, reticular basement membrane (RBM) thickness and subepithelial vascularity was assessed with a computer-assisted image analysis system. RESULTS: In nasal and bronchial mucosa, numbers of eosinophils were significantly higher in rhinitis patients with and without asthma than in asymptomatic atopics (P < 0.05) and controls (P < or = 0.01). In bronchial mucosa, the RBM was significantly thickened in rhinitis patients with and without asthma compared to asymptomatic atopics (P < 0.05) and controls (P < 0.01), while in nasal mucosa no differences were seen. Patients with asthma and rhinitis had increased numbers of blood eosinophils (P = 0.05) and skin test reactivity (P = 0.01) compared to patients with rhinitis only. No significant differences could be found between the investigated groups with respect to serum IL-5 and eotaxin levels, the number of mucosal mast cells and the degree of epithelial loss and subepithelial vascularity. Epithelial desquamation was significantly increased in the bronchial mucosa compared to nasal mucosa, not only in asthmatics (P < 0.001), but also in atopics without asthma and rhinitis (P = 0.02). CONCLUSIONS: This study shows that allergic inflammation, increased basement membrane thickness and epithelial desquamation are present in the lower airways of atopic subjects, even before the onset of clinical symptoms. Despite the presence of inflammatory cells, no structural changes could be assessed in nasal mucosa of allergic patients.
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Asma/patología , Mucosa Respiratoria/patología , Rinitis/patología , Adolescente , Adulto , Asma/sangre , Asma/complicaciones , Membrana Basal/patología , Biopsia , Eosinófilos/patología , Femenino , Humanos , Hipersensibilidad Inmediata/sangre , Hipersensibilidad Inmediata/patología , Mediadores de Inflamación/sangre , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Mucosa Nasal/patología , Rinitis/sangre , Rinitis/complicacionesRESUMEN
Symptoms of atopic asthma often disappear around puberty. The authors recently demonstrated that this clinical remission is accompanied with ongoing airways inflammation in most subjects. The discrepancy between lack of symptoms and persistent airway inflammation suggests that perception of the symptoms is unclear. In the present study, young adults in clinical remission of atopic asthma assigned themselves a modified Borg score during methacholine and adenosine-5'-monophosphate induced bronchoconstriction. Borg scores of subjects in clinical remission were compared with those of symptomatic asthmatic subjects. A marked variation in the Borg scores at a 20% fall in the forced expiratory volume in one second was found. Significant differences in Borg scores between remission patients and asthmatics could not be detected. It was concluded that perception of dyspnoea, induced with methacholine and adenosine challenge, is similar in young adults in clinical remission of atopic asthma compared to that of patients with symptomatic asthma. Hence, an unclear perception seems to be an unlikely explanation for the discrepancy between lack of symptoms and ongoing inflammation. Other factors, including both physical and psychological ones, may play a role in the apparent absence of symptoms, thereby potentially leading to undertreatment.
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Asma/psicología , Disnea/psicología , Percepción , Adenosina Monofosfato , Adulto , Asma/diagnóstico , Asma/inmunología , Hiperreactividad Bronquial/diagnóstico , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/psicología , Broncoconstrictores , Estudios Transversales , Disnea/diagnóstico , Disnea/inmunología , Femenino , Volumen Espiratorio Forzado/efectos de los fármacos , Humanos , Masculino , Cloruro de Metacolina , Remisión EspontáneaRESUMEN
Symptoms of atopic asthma often disappear at puberty. However, asthmatic subjects in clinical remission will frequently have a relapse later in life. The aim of this study was to investigate whether subjects in clinical remission of atopic asthma have persistent airway inflammation and/or airway remodeling. Bronchial biopsies were obtained from subjects in clinical remission, asthmatic subjects, and healthy control subjects. The presence and/or activation state of eosinophils, mast cells, macrophages, T lymphocytes, interleukin (IL)-5, eotaxin, and inducible nitric oxide synthase (iNOS) were analyzed. Results were compared with less invasive indicators of airway inflammation. Also aspects of airway remodeling were determined. Eosinophils, T cells, mast cells, and IL-5 were significantly elevated in the airway mucosa of subjects in remission compared with control subjects. Also, blood eosinophil cell counts were significantly higher in subjects in clinical remission. Blood eosinophil cell counts, exhaled nitric oxide (eNO) levels, and bronchial response to adenosine-5'-monophosphate correlated significantly with the quantity of tissue eosinophils. Significant airway remodeling was found in subjects in clinical remission. Our study has shown ongoing airway inflammation and airway remodeling in adolescents in clinical remission of atopic asthma. Subclinical airway inflammation may well determine the risk of an asthma relapse later in life.
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Asma/inmunología , Asma/patología , Hipersensibilidad Inmediata/inmunología , Hipersensibilidad Inmediata/patología , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/patología , Adenosina Monofosfato/farmacología , Adolescente , Adulto , Factores de Edad , Asma/sangre , Biopsia , Pruebas Respiratorias , Estudios de Casos y Controles , Eosinófilos/inmunología , Femenino , Humanos , Hipersensibilidad Inmediata/sangre , Inmunohistoquímica , Inflamación , Interleucina-5/análisis , Interleucina-5/inmunología , Recuento de Leucocitos , Macrófagos/inmunología , Masculino , Mastocitos/inmunología , Óxido Nítrico/análisis , Recurrencia , Remisión Espontánea , Mucosa Respiratoria/química , Factores de Riesgo , Linfocitos T/inmunologíaRESUMEN
Mast cells and basophils are cells that play an important role in the initiation and control of allergic inflammation in asthma and rhinitis. This study was undertaken to determine the presence and dynamics of mast cells and basophils in the nasal and bronchial mucosa of allergic rhinitis patients after segmental bronchial provocation (SBP). Eight nonasthmatic, grass pollen-allergic rhinitis patients and eight healthy controls were included. Bronchial and nasal biopsies, as well as blood samples, were taken before (T(0)) and 24 h (T(24)) after SBP. Immunohistochemical staining was performed for mast cells (tryptase and chymase; phenotypes MC(T), MC(TC), MC(C)) and basophils (BB1). In the bronchial mucosa, the number of BB1(+) cells increased significantly (p < 0.05) in allergic rhinitis patients after SBP. In the nasal mucosa, the numbers of MC(C) and MC(TC) cells decreased significantly, whereas the numbers of [BB1(+)] cells increased significantly in allergic rhinitis patients after SBP (p < 0.05). In blood, the number of basophils decreased (p < 0.05) and the level of interleukin (IL)-5 increased (p < 0.05) in atopic patients after SBP. No significant changes could be observed in healthy controls. This study shows that SBP in nonasthmatic allergic rhinitis patients reduces numbers of mast cells in the nose as a result of enhanced degranulation. At the same time, there is evidence for an influx of basophils from the blood into the nasal and bronchial mucosae.
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Basófilos , Pruebas de Provocación Bronquial/métodos , Mastocitos , Mucosa Respiratoria/inmunología , Rinitis/inmunología , Adolescente , Adulto , Bronquios/inmunología , Recuento de Células , Femenino , Humanos , Masculino , Mucosa Nasal/inmunologíaRESUMEN
BACKGROUND: Allergic rhinitis (AR) and asthma are characterized by means of a similar inflammatory process in which eosinophils are important effector cells. The migration of eosinophils from the blood into the tissues is dependent on adhesion molecules. OBJECTIVE: To analyze the aspects of nasobronchial cross-talk, we studied the expression of adhesion molecules in nasal and bronchial mucosa after nasal allergen provocation (NP). METHODS: Nine nonasthmatic subjects with seasonal AR and 9 healthy control subjects underwent NP out of season. Bronchial and nasal biopsy specimens were taken before (T(0)) and 24 hours after NP (T(24)). Mucosal sections were analyzed for the presence of eosinophils, IL-5, eotaxin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and human endothelium (CD31). RESULTS: At T(24), an influx of eosinophils was detected in nasal epithelium (P =.01) and lamina propria (P <.01), as well as in bronchial epithelium (P =.05) and lamina propria (P <.05), of the patients with AR. At T(24), increased expression of ICAM-1, as well as increased percentages of ICAM-1+, VCAM-1+, and E-selectin+ vessels, were seen in nasal and bronchial tissue of patients with AR. The number of mucosal eosinophils correlated with the local expression of ICAM-1, E-selectin, and VCAM-1 in patients with AR. CONCLUSION: This study shows that NP in patients with AR results in generalized airway inflammation through upregulation of adhesion molecules.
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Moléculas de Adhesión Celular/biosíntesis , Eosinofilia/etiología , Pruebas de Provocación Nasal , Adulto , Biomarcadores/sangre , Biopsia , Bronquios , Selectina E/sangre , Eosinófilos/química , Eosinófilos/citología , Femenino , Humanos , Inmunohistoquímica , Mediadores de Inflamación/sangre , Interleucina-5/sangre , Recuento de Leucocitos , Masculino , Membrana Mucosa/química , Membrana Mucosa/patología , Mucosa Nasal/química , Mucosa Nasal/patología , Dimensión del Dolor , Rinitis Alérgica Estacional/sangre , Rinitis Alérgica Estacional/diagnóstico , Molécula 1 de Adhesión Celular Vascular/sangreRESUMEN
Chronic inflammation and extracellular remodeling of the airway wall characterize asthma. The purpose of this study was to examine whether these features cause a change in airway mechanical properties. We examined 14 healthy and 10 young adults with long-lasting asthma, the latter treated with inhaled bronchodilators and corticosteroids. To obtain area-versus-transmural pressure (A-Ptm) curves during forced expiration (Pedersen, O. F., et al. J. Appl. Physiol. 1982;52:357-369), we used an esophageal balloon and a Pitot static probe positioned at five locations between the right lower lobe and midtrachea. Cross-sectional area (A), airway compliance (Caw = dA/dPtm), and specific airway compliance (sCaw = Caw/A) were obtained from the A-Ptm curves. Results showed that: (1) A was larger in males than in females; (2) Caw and sCaw decreased with a more downstream position; and (3) Caw and sCaw were significantly lower in the patients with asthma, with the differences between the asthmatic patients and the healthy subjects becoming smaller toward the trachea. The lower Caw and sCaw in the patients with long-lasting asthma support the concept that chronic inflammation and remodeling of the airway wall may result in stiffer dynamic elastic properties of the asthmatic airway.
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Resistencia de las Vías Respiratorias/fisiología , Asma/fisiopatología , Rendimiento Pulmonar/fisiología , Adulto , Bronquios/fisiopatología , Elasticidad , Femenino , Humanos , Mediciones del Volumen Pulmonar , Masculino , Síndrome de Respuesta Inflamatoria Sistémica/fisiopatología , Tráquea/fisiopatologíaRESUMEN
Symptoms of atopic asthma often decrease or even seem to disappear around puberty. The aim of this study was to investigate whether this so-called clinical remission is accompanied by remission of airway inflammation, since symptoms relapse in a substantial proportion of subjects later in life. To assess indicators of inflammation and/or structural damage of the airways, exhaled nitric oxide (eNO) and bronchial responsiveness to adenosine-5'-monophosphate (AMP) and methacholine (MCh) were determined in 21 subjects in clinical remission of atopic asthma. Clinical remission was defined as complete absence of symptoms of asthma without the use of any medication in the year preceding the study. Results were compared with those of 21 patients with current asthma and 18 healthy control subjects. We found significantly higher eNO values in the remission group than in healthy controls (geometric mean, 18.9 and 1.0 ppb, respectively; p < 0.001) whereas eNO values of the remission group and those of the subjects with current asthma (geometric mean, 21.9 ppb) were similar (p = 0.09). The responsiveness to both AMP and MCh of subjects in clinical remission was significantly higher as compared with responsiveness of healthy controls, and lower than responsiveness of subjects with current asthma. A significant correlation could be established between eNO and responsiveness to AMP, but not between eNO and responsiveness to MCh. The results of this study are suggestive of persistent airway inflammation during clinical remission of atopic asthma. We speculate that subclinical inflammation is a risk factor for asthma relapse later in life, and that eNO and responsiveness to both AMP and MCh can be used as different, noninvasive indices of the inflammatory process of the airways.
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Asma/fisiopatología , Hiperreactividad Bronquial/fisiopatología , Óxido Nítrico/fisiología , Hipersensibilidad Respiratoria/fisiopatología , Adenosina Monofosfato , Adolescente , Adulto , Asma/diagnóstico , Pruebas Respiratorias , Bronquios/fisiopatología , Hiperreactividad Bronquial/diagnóstico , Pruebas de Provocación Bronquial , Estudios Transversales , Femenino , Humanos , Masculino , Cloruro de Metacolina , Remisión Espontánea , Hipersensibilidad Respiratoria/diagnósticoRESUMEN
Allergic rhinitis and asthma often coexist and share a genetic background. Pathophysiologic connections between the nose and lungs are still not entirely understood. This study was undertaken to compare allergic inflammation and clinical findings in the upper and lower airways after segmental bronchial provocation (SBP) in nonasthmatic allergic rhinitis patients. Eight nonasthmatic, grass pollen-sensitive patients with allergic rhinitis and eight healthy controls were included. Bronchial biopsies and blood samples were taken before (T(0)) and 24 h (T(24)) after SBP. Nasal biopsies were obtained at T(0), 1 h after SBP (T(1)), and T(24). Immunohistochemical staining was performed for eosinophils (BMK13), interleukin (IL)-5, and eotaxin. The number of eosinophils increased in the challenged and unchallenged bronchial mucosa (p < 0.05) and in the blood (p = 0.03) of atopic subjects at T(24). We detected an increase of BMK13-positive and eotaxin-positive cells in the nasal lamina propria and enhanced expression of IL-5 in the nasal epithelium of atopic subjects only at T(24) (p < 0.05). SBP induced nasal and bronchial symptoms as well as reductions in pulmonary and nasal function in the allergic group. No significant changes could be observed in healthy controls. The study shows that SBP in nonasthmatic allergic rhinitis patients results in peripheral blood eosinophilia, and that SBP can induce allergic inflammation in the nose.
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Pruebas de Provocación Bronquial , Quimiocinas CC , Mucosa Nasal/inmunología , Rinitis Alérgica Estacional/inmunología , Adulto , Asma/diagnóstico , Asma/inmunología , Biopsia , Quimiocina CCL11 , Citocinas/metabolismo , Eosinófilos/inmunología , Femenino , Humanos , Interleucina-5/metabolismo , Recuento de Leucocitos , Masculino , Mucosa Nasal/patología , Rinitis Alérgica Estacional/diagnóstico , Factores de RiesgoAsunto(s)
Asma/enzimología , Bronquios/enzimología , Antígenos CD13/fisiología , Dipeptidil Peptidasa 4/fisiología , Neprilisina/fisiología , Inflamación Neurogénica/enzimología , Neuropéptidos/metabolismo , Animales , Antiasmáticos/farmacología , Antiinflamatorios/farmacología , Asma/patología , Líquido del Lavado Bronquioalveolar , Células Dendríticas/enzimología , Eosinófilos/enzimología , Glucocorticoides/farmacología , Antagonistas de Hormonas/farmacología , Humanos , Mifepristona/farmacología , Inflamación Neurogénica/patología , Fagocitos/enzimología , Receptores de Glucocorticoides/efectos de los fármacos , Receptores de Glucocorticoides/fisiología , Fumar/efectos adversos , SolubilidadRESUMEN
The nature of the micro-flora present in sputa of six different cystic fibrosis (CF) patients was assessed using routine microbiological culture and molecular methods. Bacterial genes for the small subunit ribosomal RNA (ssu rDNA) were specifically amplified from DNA extracted from the sputum samples, cloned and characterised by hybridisation and DNA sequencing. A large number of clones from six sputa were screened. Initially, oligonucleotide hybridisation was performed with five probes, specific for Gram-positives and Gram-negatives in general and the main pathogens for the CF patient (Staphylococcus aureus, Pseudomonas aeruginosa and Haemophilus influenzae). For a single sputum sample, the results were fully congruent when culture and molecular methods were compared. In the other five sputa, discrepancies for S. aureus and/or H. influenzae were documented. Although S. aureus DNA and H. influenzae DNA was detected in three and four sputa, respectively, strains could not be cultured. Although the PCR approach is not capable of distinguishing viable from dead bacteria, all of the CF patients had a history of S. aureus infections, while one of the CF patients once had cultivable H. influenzae in the sputum as well. A number of clones for probe-unidentified Gram-negative or Gram-positive bacterial species were further analysed by sequencing and additional potential pathogens were identified. Although routine culture of sputum frequently points to mono-specific exacerbations, our molecular data indicate that the other CF-related pathogens appear to be persistently present as well. We conclude that routine culture for bacterial pathogens from CF sputa yields limited microbiological information since it frequently fails to identify a number of pathogenic bacterial species that are potentially present in a viable status in the lungs of these patients.
Asunto(s)
Bacterias/aislamiento & purificación , Fibrosis Quística/microbiología , Esputo/microbiología , Adulto , Bacterias/genética , Bacterias/crecimiento & desarrollo , Técnicas Bacteriológicas , Medios de Cultivo , Fibrosis Quística/complicaciones , ADN Bacteriano/análisis , ADN Bacteriano/aislamiento & purificación , ADN Ribosómico/genética , Infecciones por Haemophilus/complicaciones , Infecciones por Haemophilus/diagnóstico , Haemophilus influenzae/genética , Haemophilus influenzae/aislamiento & purificación , Humanos , Reacción en Cadena de la Polimerasa , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/aislamiento & purificación , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Infecciones Estafilocócicas/complicaciones , Infecciones Estafilocócicas/diagnóstico , Staphylococcus aureus/genética , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
BACKGROUND: Neuropeptides may be involved in the pathogenesis of asthma by evoking neurogenic inflammation. Since the effects of neuropeptides are limited by peptidases, reduced activity of peptidases may contribute to the inflammatory process. OBJECTIVE: We hypothesized that soluble peptidase activities are decreased in asthmatics and that inhaled glucocorticoids exert part of their anti-inflammatory action by increasing soluble peptidase activities. METHODS: Serum and bronchoalveolar lavage (BAL) fluid was obtained from non-smoking and smoking volunteers and from allergic asthmatics both before and after treatment for 12 weeks with placebo or inhaled fluticasone propionate. Activities of neutral endopeptidase (NEP), aminopeptidase N (APN) and dipeptidyl peptidase IV (DPP IV) were determined using colourometric assays. RESULTS: Reduced DPP IV activity in serum and reduced NEP activity in BAL fluid were found in healthy smokers compared with non-smokers. In contrast, no differences in peptidase activities in serum or BAL fluid were observed between allergic asthmatics and healthy non-smokers. Fluticasone propionate treatment did not affect peptidase activities in the asthmatic patients. CONCLUSIONS: We conclude that reduced peptidase activities in serum or BAL fluid can be found in healthy smokers, but not in allergic asthmatics, and that inhaled glucocorticoids do not affect peptidase activities in BAL fluid or serum of asthmatics. Our results do not support the hypothesized dysfunction of peptidases in the asthmatic airways.
Asunto(s)
Asma/enzimología , Líquido del Lavado Bronquioalveolar/química , Antígenos CD13/metabolismo , Dipeptidil Peptidasa 4/metabolismo , Hipersensibilidad/enzimología , Neprilisina/metabolismo , Administración por Inhalación , Administración Tópica , Adolescente , Adulto , Androstadienos/administración & dosificación , Androstadienos/uso terapéutico , Antialérgicos/administración & dosificación , Antialérgicos/uso terapéutico , Antiasmáticos/administración & dosificación , Antiasmáticos/uso terapéutico , Antiinflamatorios/administración & dosificación , Antiinflamatorios/uso terapéutico , Asma/tratamiento farmacológico , Antígenos CD13/análisis , Antígenos CD13/sangre , Dipeptidil Peptidasa 4/análisis , Dipeptidil Peptidasa 4/sangre , Femenino , Fluticasona , Glucocorticoides , Humanos , Hipersensibilidad/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Neprilisina/análisis , Neprilisina/sangre , Valores de Referencia , FumarRESUMEN
Asthma is characterized by both local infiltration of eosinophils in the bronchial mucosa and bronchial hyperreactivity (BHR). A detailed characterization of BHR implies analysis of a histamine or methacholine dose-response curve yielding not only the dose at 20% fall of baseline forced expiratory volume in 1 s (FEV1), but also a plateau (P) representing the maximal narrowing response in terms of percent change in FEV1 and reactivity as the steepest slope at 50% of P (%FEV1/doubling dose). In the baseline condition, the specific airway conductance (sGaw) may be considered closely related to airway lumen diameter. In 20 nonsmoking asthmatic patients, methacholine dose-response curves were obtained, and a sigmoid model fit yielded the BHR indexes. Immunohistochemistry with the monoclonal antibodies (EG1 and EG2) was used to recognize the total number of eosinophils and activated eosinophils, respectively. The number of activated eosinophils was significantly correlated to both P (r = 0.62; P < 0.05) and sGaw (r = -0.52; P < 0.05), whereas weaker and nonsignificant correlations were found for dose at 20% fall of baseline FEV1 and the total number of eosinophils. We conclude that the number of activated eosinophils can be considered a marker of the inflammation-induced decrease of airway lumen diameter as represented by the plateau index and sGaw.
Asunto(s)
Asma/patología , Asma/fisiopatología , Bronquios/patología , Eosinófilos/fisiología , Cloruro de Metacolina/farmacología , Adulto , Asma/inmunología , Biopsia , Bronquios/fisiopatología , Hiperreactividad Bronquial/inducido químicamente , Hiperreactividad Bronquial/fisiopatología , Broncoconstrictores/farmacología , Relación Dosis-Respuesta a Droga , Eosinófilos/efectos de los fármacos , Eosinófilos/patología , Femenino , Volumen Espiratorio Forzado , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Membrana Mucosa/efectos de los fármacos , Membrana Mucosa/patología , Membrana Mucosa/fisiopatología , Análisis de RegresiónRESUMEN
Congenital bilateral absence of the vas deferens (CBAVD) is found in 1-2% of infertile males and in most male cystic fibrosis (CF) patients. CF and some of the CBAVD cases were found to share the same genetic background. In this study, 21 males with CBAVD had extensive physical and laboratory testing for symptoms of CF. Possible defective cellular chloride transport was measured by interstitial current measurement of rectal suction biopsies. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation analysis was performed for 10 common CFTR mutations. CF-related symptoms were found in six men. On laboratory testing slightly abnormal liver and pancreatic function was found in seven patients. The sweat test was found to be abnormal in four patients; interstitial current measurement showed defective chloride excretion in 11 patients. CFTR gene mutations were found in 66% of the patients: eight were compound heterozygotes; in six, only one common mutation could be detected. The 5T allele in one copy of intron 8 was found in four men. CBAVD appears to be a heterogeneous clinical and genetic condition. A CFTR gene mutation was found in both copies of the allele or interstitial current measurement showed defective chloride excretion in 14/21 cases. Genetic counselling is clearly indicated for couples seeking pregnancy through epididymal or testicular sperm aspiration and intracytoplasmic sperm injection.
Asunto(s)
Fibrosis Quística/complicaciones , Conducto Deferente/anomalías , Adulto , Alelos , Transporte Biológico/fisiología , Cloruros/metabolismo , Fibrosis Quística/genética , Fibrosis Quística/fisiopatología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Electrofisiología , Humanos , Masculino , Mutación/genéticaRESUMEN
BACKGROUND: There has been an increasing interest in the potential systemic effects of inhaled corticosteroids. METHODS: The effect of locally inhaled corticosteroids in the nose and lung on blood lymphocytes was measured in two studies. In the first study, budesonide (BUD) (200 and 800 microg), fluticasone propionate (FP) (200 and 800 microg), and placebo were administered in the nose, and BUD (1600 microg) and FP (1500 microg) were inhaled into the lungs in a blinded, randomized fashion by 12 healthy volunteers. Blood samples were taken before and 4 h after the administration of the drug, and total lymphocyte count and different subpopulations were determined. In the second study, 15 healthy volunteers were randomized to BUD (1600 microg), FP (1600 microg), or placebo inhaled into the lungs. Blood samples were taken before and 4, 8, 24, 48, and 148 h (=7 days) after inhalation of the medication. RESULTS: Neither the nasal applications nor the inhalation of FP (1500 microg/1600 microg) showed significant differences in total lymphocyte count or different subpopulations between baseline and 4 h after the administration. In both studies, a significant reduction was found in the total lymphocyte count, B cells, T cells, and the CD4+ and the CD8+ fractions 4 h after application of BUD 1600 microg. CONCLUSIONS: Nasal application of BUD or FP in doses up to 800 microg do not induce lymphopenia. BUD 1600 microg inhalation in the lung reduces lymphocytes and their subfractions. Further studies have to be done to determine whether the results obtained in this study in healthy volunteers will also be found in patients with diseased mucosa and whether there is any correlation with adverse effects such as growth inhibition or osteoporosis.
Asunto(s)
Corticoesteroides/administración & dosificación , Recuento de Linfocitos/efectos de los fármacos , Subgrupos Linfocitarios/efectos de los fármacos , Administración por Inhalación , Administración Intranasal , Adulto , Androstadienos/farmacología , Budesonida/farmacología , Estudios Cruzados , Método Doble Ciego , Femenino , Fluticasona , Humanos , MasculinoRESUMEN
Asthma is considered a Th2-like disease, characterized by locally increased levels of interleukin (IL) 4. The bronchial epithelium plays an important role in the initiation and perpetuation of inflammatory reactions within the airways. However, little is known about the presence of IL-4 receptors on human bronchial epithelial cells, or the effects of IL-4 on these cells. In this report, definitive evidence of IL-4 receptor expression on human bronchial epithelial cells using several methods is presented. IL-4 receptor expression on human bronchial epithelial cells in vivo was demonstrated using in situ hybridization and immunohistochemistry. No difference in IL-4 receptor protein expression was observed between bronchial biopsies of healthy subjects compared to allergic asthmatics. Cultured human bronchial epithelial cells also expressed IL-4 receptor mRNA and protein (as determined by RT-PCR analysis and flow cytometry, respectively). IL-4 receptor protein expression by bronchial epithelial cells could be increased by stimulation with PMA+calcium ionophore, whereas IL-1beta and IL-6 decreased IL-4 receptor expression. A cyclic AMP analogue and IL-4 had no effect. Finally, it is shown that the IL-4 receptor is functionally active as IL-4 stimulates the release of IL-8, monocyte chemoattractant protein 1, and particularly IL-1 receptor antagonist by human bronchial epithelial cells. It is concluded that human bronchial epithelial cells express IL-4 receptors both in vivo and in vitro. Stimulation of human bronchial epithelial cells by IL-4 may result in the release of both pro- and anti-inflammatory mediators known to be upregulated in asthmatic airways.