RESUMEN
Some patients with severe asthma cannot be controlled with high doses of inhaled steroids (ICS), which may be related to ongoing environmental allergen exposure. We investigated whether 10 weeks of high altitude allergen avoidance leads to sustained benefits regarding clinical and inflammatory markers of disease control in adolescents with persistent asthma despite treatment with high dose ICS. Eighteen atopic asthmatic adolescents (12-18 yr, 500-2000 microg ICS daily) with established house dust mite allergy, participated in a parallel-group study. Quality of life (PAQL), lung function, bronchial hyperresponsiveness (BHR) to adenosine and histamine, induced sputum and urine samples were collected repeatedly from 10 patients during a 10-week admission period to the Swiss Alps (alt. 1560 m) and at 6 weeks after return to sea level. Results were compared with those in eight patients, studied in their home environment at sea level for a similar time period. Throughout the study, asthma medication remained unchanged in both groups. During admission to high altitude, PAQL, lung function, BHR to adenosine and histamine, and urinary levels of eosinophil protein X (U-EPX), leukotriene E4 (U-LTE4) and 9alpha11beta prostaglandin F2 (U-9alpha11beta PGF2) improved significantly (P < 0.05), with a similar tendency for sputum eosinophils (P < 0.07). Furthermore, the changes in PAQL and BHR to adenosine and histamine were greater in the altitude than in the control group (P < 0.05). At 6 weeks after renewed allergen exposure at sea level, the improvements in PAQL (P < 0.05), BHR to adenosine (P < 0.07) and histamine (P < 0.05), as well as U-EPX (P < 0.05) and U-LTE4 (P < 0.05) were maintained. A short period of high altitude allergen avoidance, on top of regular treatment with ICS and long-acting beta2-agonists, results in improvement of asthma, as assessed by clinical and inflammatory markers of disease severity. These findings indicate that short-term, rigorous allergen avoidance can improve the long-term control of severe asthma over and above what can be achieved even by high doses of inhaled steroids.
Asunto(s)
Alérgenos , Asma/tratamiento farmacológico , Esteroides/administración & dosificación , Administración por Inhalación , Adolescente , Alérgenos/inmunología , Animales , Asma/inmunología , Polvo , Femenino , Humanos , Hipersensibilidad Inmediata/inmunología , Masculino , Ácaros/inmunologíaRESUMEN
This study examined the safety of sputum induction and the relation between sputum cell counts and clinical parameters in adolescents with severe persistent asthma. Within 5 days, induced sputum and reversibility in forced expiratory volume in one second (FEV1), quality of life, provocative concentration causing a 20% fall in FEV1 (PC20) of adenosine monophosphate and histamine, exercise-induced bronchoconstriction, overall asthma severity index, and blood eosinophils were collected in 20 atopic adolescents with moderate-to-severe persistent asthma (12-18 yrs of age, FEV1 65-110% of predicted, on 500-2,000 microg inhaled steroids daily). FEV1 was reversible by 13.3-2.3% pred. After sputum induction, FEV1 was still increased by 9.0+/-2.6% pred as compared to the pre-salbutamol baseline. Sputum contained, median (range): 12.4 (0.4-59.5)% squamous cells, 47.3 (6.8-84.0)% macrophages, 39.0 (4.6-84.8)% neutrophils, 4.8 (1.0-12.4)% lymphocytes, 0.4 (0-10.8)% eosinophils and 3.6 (0-23.4)% bronchial epithelial cells. Sputum eosinophils showed a trend towards a significant association with the overall asthma severity index (r=0.46, p=0.06) and correlated inversely with baseline FEV1 (r=-0.51, p=0.03). In conclusion, sputum can be induced safely in adolescents with moderate-to-severe persistent asthma, if pretreated with beta2-agonists. Despite relatively low sputum eosinophil counts in these patients on inhaled steroids, the association of eosinophil numbers with baseline forced expiratory volume in one second and asthma severity index favours a role of induced sputum in monitoring adolescents with severe asthma.
Asunto(s)
Asma/diagnóstico , Proteínas Sanguíneas/análisis , Mediadores de Inflamación/análisis , Ribonucleasas , Esputo/citología , Adolescente , Albuterol , Biomarcadores/análisis , Pruebas de Provocación Bronquial , Recuento de Células , Estudios Transversales , Técnicas y Procedimientos Diagnósticos/efectos adversos , Proteínas en los Gránulos del Eosinófilo , Femenino , Humanos , Masculino , Monitoreo Fisiológico/métodos , Pronóstico , Calidad de Vida , Reproducibilidad de los Resultados , Pruebas de Función Respiratoria , Esputo/químicaRESUMEN
Asthma is now considered as an inflammatory airway disease. There is evidence that allergen avoidance reduces clinical symptoms in atopic asthma. We investigated the effect of a month's stay in the hypoallergenic environment of Davos, Switzerland (1560 m) which is relatively free of house dust mite (HDM) on changes in bronchial hyperresponsiveness (BHR), using the challenge tests of adenosine 5'-monophosphate (AMP), exercise and methacholine to test for BHR. Thirteen asthmatic children with an allergy to HDM participated in the study. We measured BHR on admission to the Davos Asthma Center and after 1 month in the house dust-free environment. The medications used by the patients at the time of admission were kept unchanged during this month. No significant difference in BHR was found to methacholine challenge after a 1-month stay at high altitude (P > 0.05). By contrast, the response to AMP was significantly different as indicated by displacement of the dose-response curve to the right by 2.15 doubling concentrations (P = 0.005). We also observed a significant difference in response to exercise (P = 0.03). These results indicate that a month's stay in a hypoallergenic environment caused a reduction in BHR to AMP and exercise, but not to methacholine. In addition, the results support the concept of differences in trigger mechanisms for BHR, and that responses to a methacholine challenge are not the same as responses to an exercise challenge. The observed reduction in BHR in asthmatic children to the indirect bronchial stimuli of AMP and exercise suggest reduced airway inflammation following avoidance of house dust aeroallergens. AMP and exercise challenges may therefore be better indicators of asthmatic airway inflammation than the direct stimulus of methacholine.
Asunto(s)
Adenosina Monofosfato , Alérgenos/inmunología , Asma/prevención & control , Asma/fisiopatología , Hiperreactividad Bronquial , Pruebas de Provocación Bronquial , Broncoconstrictores , Prueba de Esfuerzo , Cloruro de Metacolina , Ácaros/inmunología , Adolescente , Altitud , Animales , Asma Inducida por Ejercicio , Niño , Ambiente Controlado , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Improvement of allergic asthma is seen at high altitude partly because of low concentrations of allergen, especially house dust mite. To investigate the effect of a hypoallergenic environment (Davos, 1560 m) on airways inflammation, the changes in bronchial hyperresponsiveness measured with methacholine and adenosine 5'-monophosphate (AMP), blood eosinophils, eosinophil cationic protein (ECP), and serum IgE were studied. METHODS: In 16 allergic asthmatic children tests were performed on admission and after one month. Medication was kept unchanged during the month of investigation and the patients performed peak expiratory flow (PEF) measurements twice daily. RESULTS: After one month at high altitude a considerable improvement was seen in the provocative concentration of AMP causing a 20% fall in forced expiratory volume in one second (PC20 AMP), but not with methacholine. There was also a reduction in total blood eosinophils and ECP. No change in serum IgE was observed. Peak flow variability decreased. CONCLUSIONS: After one month at high altitude a reduction in airways inflammation occurs. The results indicate that AMP responsiveness is a more accurate marker of disease activity in relation to inflammation in asthma than methacholine. The benefits of allergen avoidance at high altitude have important clinical implications for children with allergic asthma.