RESUMEN

INTRODUCTION: Bronchial hyper-responsiveness is usually measured with direct stimuli such as methacholine (MCh) or histamine. Adenosine 5'-monophosphate (AMP), which acts indirectly via the secondary release of mediators, is another stimulus to measure bronchial hyper-responsiveness. AIM: To investigate whether provocation with inhaled AMP itself initiates an inflammatory response resulting in an influx of eosinophils into the airway lumen. METHODS: We have included 21 non-smoking atopic asthmatic subjects (mean FEV1 101% predicted, mean age 34 years). Each subject performed three sputum inductions on different days, at least seven days apart: one without previous provocation, one hour after PC20 methacholine, and one hour after PC20 AMP. RESULTS: After provocation with AMP, but not methacholine, the percentage of sputum eosinophils increased significantly (from 1.9+/-0.5% to 4.5+/-1% (P<0.01) and 1.9+/-0.5% (P=0.89)). No changes in the percentages of neutrophils, lymphocytes, macrophages, or bronchial epithelial cells were found. CONCLUSION: A provocation test with AMP leads to an increased percentage of sputum eosinophils. This observation cannot be explained by a non-specific response of the airways to a vigorous bronchoconstriction, since methacholine had no effect on inflammatory cells.

Asunto(s)

Asunto(s)

RESUMEN

It has been suggested in cross-sectional studies that provocation with adenosine 5'-monophosphate (AMP) more closely reflects the inflammatory process in asthma than does provocation with methacholine or histamine. We investigated whether the steroid-induced improvement in the provocative concentration of AMP producing a 20% decline in FEV1 (PC20 AMP) is more closely associated with the concomitant reduction in airway inflammation than is the improvement in PC20 methacholine. In 120 asthmatic patients, we measured PC20 methacholine and PC20 AMP as well as sputum induction and nitric oxide (NO) in exhaled air before and after 2 weeks of treatment with corticosteroids. Improvement in PC20 AMP was solely related to reduction in airway inflammation (i.e., change in the number of sputum eosinophils, lymphocytes, epithelial cells, and concentration of NO in exhaled air). In contrast, improvement in PC20 methacholine was related to both reduction in airway inflammation (i.e., change in the number of sputum eosinophils and lymphocytes) and increase in FEV1 %predicted. The total explained variance of the improvement in bronchial hyperresponsiveness was greater for AMP than for methacholine (36% versus 22%, respectively). We conclude that PC20 AMP is more sensitive to changes in acute airway inflammation than is PC20 methacholine, further reinforcing the notion that PC20 AMP can be a useful tool for monitoring the effects of antiinflammatory therapy.

Asunto(s)

RESUMEN

Inhalation of a direct stimulus such as histamine or methacholine is generally used to measure bronchial hyperresponsiveness (BHR). Provocation with adenosine 5'-monophosphate (AMP), an indirect airway challenge, has been suggested to be a better marker of airway inflammation than direct challenges. However, so far little information on this subject is available. The aim of our study was to assess whether the concentration of AMP causing the FEV(1) to drop by 20% (PC(20)) is more closely associated with inflammatory parameters in asthma than PC(20) methacholine. In 120 patients with atopic asthma (median FEV(1) 81% predicted [pred], median age 27 yr), PC(20) methacholine and PC(20) AMP as well as sputum induction, blood sampling, and measurement of nitric oxide in exhaled air were performed. PC(20) methacholine was predominantly predicted by FEV(1) %pred (explained variance [ev] = 18%) with the percentage of peripheral blood monocytes being a weak additional independent predictor (total ev = 23%). By contrast, PC(20) AMP was predominantly predicted by the percentage of eosinophils in sputum (ev = 25%), while FEV(1) %pred was only an additional independent predictor (total ev = 36%). PC(20) AMP reflects more closely the extent of airway inflammation due to asthma than PC(20) methacholine.

Asunto(s)

RESUMEN

BACKGROUND: In asthmatic inflammation, TH2 cells play an important role. TH2 cells specifically secrete cytokines like IL-4 and IL-5. IL-4 stimulates IgE production and IL-5 is involved in hemopoiesis, chemotaxis, priming and activation of eosinophils. IFNgamma, produced by TH1 cells, has an inhibitory action on IgE production. OBJECTIVES: To investigate the TH1/TH2-cell pattern in the cytokine production of peripheral blood of asthmatic children. We determined IL-4, IFNgamma and IL-5 in serum and in supernatants of unstimulated and stimulated (24 h with Concanavaline A) cultures of peripheral blood mononuclear cells (PBMCs) in 22 children with moderate asthma (mean age 9.3 years) and in 17 healthy controls (mean age 10.3 years). All children visited the out-patient department (OPD) where history taking, physical examination and blood sampling took place. Children younger than 8 years of age performed symptom and peak flow registration during 1 week after the visit to the OPD. RESULTS: The number of eosinophils were significantly higher in children with asthma, compared with healthy controls. The concentration of IFNgamma in supernatants of cultures of stimulated PBMCs was significantly lower and the ratio of IL-4/IFNgamma was significantly higher in children with asthma compared with healthy controls. The FEV1 was directly and IgE was inversely related to the concentration of IFNgamma in supernatants of cultures of stimulated PBMCs. CONCLUSION: IFNgamma may play an important role in the pathophysiology of childhood atopic asthma.

Asunto(s)

RESUMEN

The aim of the study was to investigate whether seasonal differences in house dust mite (HDM) allergen exposure influence the circadian peak expiratory flow (PEF) amplitude in asthmatic children. Asthmatic children (n = 25) with a solitary allergy to HDM were studied in spring and in autumn. All used inhaled corticosteroids (ICS) regularly. Six days after withdrawal of ICS, PEF amplitude (every 4 h during 24 h, highest-lowest/percentage of mean value) was assessed. HDM allergen (HDMA) in living rooms, bedrooms, and mattresses was collected. HDMA levels were not always highest in autumn. PEF amplitudes in spring and autumn did not correlate with HDMA levels in the same season. However, the seasonal difference in PEF amplitude (autumn value - spring value) correlated positively and significantly with the seasonal difference in HDMA exposure levels from the mattresses (rho = 0.34, p < 0.05). Multivariate analysis showed that the seasonal difference in HDMA exposure in the mattress was the single parameter explaining seasonal difference in PEF amplitudes by 21.0% (p = 0.02). Our cross-sectional study showed a higher PEF amplitude not to be significantly associated with higher HDMA exposure in mattresses in a group of HDM-allergic asthmatic children. However, the change in HDMA exposure over seasons contributed significantly to the change in PEF amplitude after withdrawal of ICS in HDM-allergic asthmatic children.

Asunto(s)

RESUMEN

The influence of exogenous factors in the home on the circadian variation of airway obstruction has not been fully assessed in children with asthma. The aim of the present study was to investigate the contribution of exogenous stimuli to the degree of peak expiratory flow (PEF) variability during 24 h. Fifty-five children (33 boys and 22 girls; mean age, 9.3 +/- 1.7 yr) with symptoms of asthma, increased bronchial responsiveness, and a solitary allergy to house dust mite (HDM) participated. Their asthma symptoms were well-controlled for at least 4 mo with daily inhaled corticosteroids (ICS) and beta 2-adrenergic drugs if needed. Symptoms, peripheral blood eosinophils, total IgE, and specific IgE to HDM were assessed. Spirometry and PC20 histamine were performed. PEF amplitudes during 24 h (highest minus lowest as a percentage of the day's mean value) were obtained at home during and 6 d after withdrawal of ICS. Dust samples were collected from the total area of the living rooms, bedrooms, mattresses (n = 25), and classrooms to obtain the HDM allergen (HDMA) exposure to Der p I and Der p II. Family smoking habits, presence of pets, and types of floor-covering were recorded on a checklist. Mean PEF amplitude did not increase after withdrawal of ICS, but absolute PEF values were significantly lower (p = 0.05) at midnight and 4:00 A.M. Twenty-six children (47%) were exposed to environmental tobacco smoke (ETS), and 23 (42%) kept pets. Mattresses contained significantly higher amounts of HDMA compared with other locations. PEF amplitude after withdrawal of ICS was significantly higher in children exposed to ETS, a pet, or a high HDMA level in their mattress than in children who were not exposed (ETS: 29.7% [3.9 to 56.6] versus 19.4% [0.0 to 56.6], p < 0.05; pets: 31.4% [9.7 to 52.5] versus 21.9% [0.0 to 56.6], p < 0.05; high HDMA level in the mattress: 35.5% [10.2 to 56.6] versus 21.4% [3.9 to 56.6], p < 0.05). These factors combined with age and PC20 histamine and its interaction with ETS, especially in mild to moderate asthma, explained 48.4% of the variance of the PEF amplitude after withdrawal of ICS. Exogenous stimuli such as exposure to ETS, pets, and high HDMA levels in mattresses contribute to an increased circadian PEF amplitude after withdrawal of ICS and therefore to nocturnal worsening of asthma in HDM-allergic asthmatic children. Moreover, ETS exposure seems to especially worsen PEF variability in children with mild to moderately severe bronchial responsiveness.

Asunto(s)

RESUMEN

AIM: To determine whether house dust mite (HDM) exposure in living rooms and bedrooms is higher in asthmatic children than in those of age and sex matched healthy children, living in the same area. METHODS: Types of floor-coverings were recorded and dust samples were collected by vacuum cleaning the total area of living rooms and bedrooms; Der p I and Der p II per gram fine dust concentrations were assessed. Twenty-five asthmatic children (RAST HDM > or = class 3, age 6-12 years) and 25 healthy children participated in the study. RESULTS: The frequency of cleaning and prevalence of smooth floor-coverings in bedrooms of asthmatic children were significantly higher. There were no differences in living rooms in this respect. The amount of fine dust/m2 floor space was significantly lower in bedrooms of asthmatic children. Concentrations of HDM were low and no differences in Der p I and Der p II concentrations were observed between the two groups (asthmatic children: Der p I living room: 1.1 (0.04-59.4 micrograms/g), bedroom: 0.5 (below detection--19.3 micrograms/g); nonasthmatic children: Der p I living room: 1.4 (below detection--27.5 micrograms/g), bedroom: 0.9 (below detection--68.8 micrograms/g. Smooth floor coverings contained significantly less fine dust, Der p I, and Der p II than carpeted floors. CONCLUSIONS: Low HDM concentrations are a general finding in Dutch dwellings in the present generation of children. We observed a higher cleaning frequency, and more smooth floor coverings in bedrooms of asthmatic children than of healthy children, yet HDM concentrations were not significantly different. The latter can be explained by the observation that only 40% of the asthmatic children had smooth floor coverings in their bedrooms. Smooth floor coverings contain less fine dust and lower concentrations of Der p I and Der p II than carpeted floors.

Asunto(s)