Defining asthma in genetic studies.

Genetic studies have been hampered by the lack of a gold standard to diagnose asthma. The complex nature of asthma makes it more difficult to identify asthma genes. Therefore, approaches to define phenotypes, which have been successful in other genetically complex diseases, may be applied to define asthma in genetic studies. These approaches include narrowing of the disease definition and use of intermediate phenotypes of asthma. Future studies are required to apply these approaches in genetic studies of asthma and, most likely, this will facilitate the search for genes for asthma.

Seasonal variations in house dust mite influence the circadian peak expiratory flow amplitude.

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.

Exogenous stimuli and circadian peak expiratory flow variation in allergic asthmatic children.

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.

Long-term circadian effects of salmeterol in asthmatic children treated with inhaled corticosteroids.

The present study was set up to investigate whether salmeterol in children with asthma already treated with inhaled corticosteroids (ICS) leads to a sustained bronchodilator effect and decreased bronchial responsiveness, both during the day and night. Furthermore, we investigated whether cessation of salmeterol leads to a rebound increase in bronchial responsiveness. Forty children with asthma (aged 7-15 yrs) using ICS participated in a randomized, double-blind, parallel study. They received either twice daily 50 micrograms salmeterol or placebo. FEV1 and provocative concentration of methacholine that caused a 20% fall in FEV1 (PC20) were measured at 4:00 P.M. and 4:00 A.M. at baseline and after 16 wk. The same measurements were performed at 4:00 P.M. at 8 h after the first dose, and after 1 and 8 wk. After cessation of the study drug, FEV1 and PC20 were measured at 12 and 20 h and after 1 wk. Overall mean FEV1 from 1 to 16 wk of treatment was significantly higher in the salmeterol group than in the placebo group (difference, 4.9 +/- 2.0%, p = 0.01). Evolution in time of FEV1 did not differ significantly between the two groups (p = 0.09). Overall mean PC20 from 1 to 16 wk of treatment was not significantly higher with salmeterol than with placebo (difference, 0.7 +/- 0.4 doubling dose [DD] p = 0.07); evolution in time of PC20 did not differ significantly between the two groups (p = 0.58).(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency of nocturnal symptoms in asthmatic children attending a hospital out-patient clinic.

Since nocturnal symptoms indicate more severe asthma, we investigated their frequency in a hospital-based population of asthmatic children. Recognition of these symptoms offers the possibility to introduce appropriate treatment. We studied 796 consecutive children with asthma (mean (SD) age 9 (4) yrs) attending a hospital clinic, to determine whether these nocturnal symptoms predicted that daytime activities would be affected, and also the patients' perception of disease severity. At the end of a regular out-patient clinic visit, the answers to seven different questions concerning nocturnal symptoms in the previous 3 weeks were recorded. The forced expiratory volume in one second (FEV1) was > or = 90% predicted in 98% of the population that was able to perform lung function measurements (72% of the total population). In 38% of the patients with nocturnal symptoms, these symptoms were reported spontaneously. When asked for, nocturnal symptoms were reported by 47% of the children; 6% every night and 34% at least once a week. Cough was the most frequently reported symptom (31%). Children with nocturnal symptoms had a lower FEV1, scored their perception of asthma as more severe, and had their daytime activities affected more than those without nocturnal symptoms. Doctors should specifically ask about nocturnal symptoms, as not all patients with nocturnal symptoms report them spontaneously and they predict more severe disease.

House dust mite exposure in asthmatic and healthy children: the difference is carpeting.

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.

Epidemiology and the concept of underlying mechanisms of nocturnal asthma.

Nocturnal symptoms are common in asthma, even when patients are regularly seen at an outpatient clinic. Inflammation is generally accepted as a general feature of asthma and the severity of this basic inflammatory process can be increased by exogenous triggers such as exposure to allergens and nonallergic stimuli. Superimposed endogenous circadian rhythms may play a more important and intricate role in the circadian modulation of the inflammatory process by changing the number of cells, their release of mediators and/or the susceptibility of airway smooth muscle and vasculature. For instance, an increase in vagal tone may induce nocturnal bronchoconstriction which is further enhanced by falling catecholamine levels. Together, the reduced nocturnal catecholamine levels and the diminished bronchodilating capacity of the NANC system and the low cortisol levels oppose possible protection against inflammatory processes leading to nocturnal airflow obstruction.