Exhaled breath condensate eicosanoids and sputum eosinophils in asthmatic children: A pilot study

Cysteinyl leukotrienes (cys-LTs), LTB₄ and 8-isoprostane are increased in the exhaled breath condensate (EBC) from asthmatic patients. The aim of this study was to investigate whether the measurement of cys-LTs, LTB₄ and 8-isoprostane in EBC can reflect the level of airway inflammation assessed by induced sputum in asthmatic children sensitized to house dust mite (HDM) during natural avoidance of HDM allergens. Twelve children were evaluated at the time of admission (T0) and after 3 months of stay (T1) at the Istituto Pio XII (Misurina, Italian Dolomites 1756  m). Sputum eosinophil percentage and measurement of cys-LTs, LTB₄ and 8-isoprostanes in the breath condensate at T0 and T1 were evaluated. Eosinophil percentage in induced sputum was 8.5 ± 1.1% at T0 and 3.5 ± 0.4% at T1 (p = 0.011). Neutrophil percentage in sputum was 1.1 ± 0.5% at T0 and 1.5 ± 1.0% at T1 (ns). Cys-LTs mean level was 14.24 ± 4.53 pg/ml at T0 and 4.65 ± 0.68 pg/ml at T1 (p = 0.0125). LTB₄ level was 2.36 ± 0.19 pg/ml at T0 and 2.41 ± 0.23 pg/ml at T1 (ns). 8-Isoprostane level reduced from 17.47 ± 3.18 pg/ml at T0 to 7.36 ± 3.26 pg/ml at T1 (p = 0.003). This study show that exhaled cys-LTs and 8-isoprostane, as well as eosinophil percentage in induced sputum, are reduced after allergen avoidance in asthmatic children suggesting a potential application of EBC for the non-invasive evaluation of airway inflammation in asthma in allergic asthmatic children.     

Predictive features for persistence of atopic dermatitis in children

Allergen exposure plays an important role in atopic dermatitis (AD). Because immunological mechanisms underlying asthma and AD have great similarities, we evaluated whether features such as allergen sensitization, immune response, disease severity and duration or allergen exposure could be considered predictive for AD persistence. Seventy-one AD children (age range 14–158 months) were enrolled and followed for 3 consecutive years for AD severity using the SCORAD index (SI). At enrollment, reactivity to inhalant and food allergens using the skin prick test (SPT) and house dust mite (HDM) atopy patch test (APT), and HDM allergens in house dust were evaluated. After 3 years, 38 children outgrew their AD (AD^– group), while in 33 AD persisted (AD⁺ group). At enrollment, AD⁺ children had a higher SI, higher rate of positivity to SPT and APT for mites (p = 0.001), and higher environmental exposure to HDM allergens (p = 0.035). The AD⁺ children developed more respiratory symptoms in comparison to AD^– children (p < 0.001). None of the AD^– children presented APT positivity. In our study population, positivity of SPT and APT for HDM, environmental allergen exposure levels and severity of the disease at enrollment presented a significant predictive power towards AD persistence. Subjects with positive skin reactivity to HDM should be considered at risk of AD persistence and of possible development of allergic respiratory disorders.     

Correlation of nitrites in breath condensates and lung function in asthmatic children

We aimed to evaluate the value of exhaled breath condensates in monitoring airway inflammation in childhood asthma before and after high altitude climate therapy.
Forty-eight asthmatic children on regular anti-asthma treatment with a normal FEV₁ and positive skin prick test for house dust mites were recruited. All children had been referred to an alpine clinic for high altitude climate therapy, because of persistent asthmatic symptoms despite use of daily anti-inflammatory treatment. Subjects were assessed on their arrival and before departure from the alpine clinic. Spirometry, bronchial provocation tests and measurements of nitrites in breath condensates were performed.
Median levels of nitrites were significantly higher before than after high altitude climate therapy (1.27 vs. 0.93 μ m ; p = 0.008). In addition, MEF₅₀ improved significantly (p < 0.0005). There was a significant correlation between nitrites in breath condensates and MEF₅₀ (r = −0.63, p < 0.0001), symptoms (r = 0.47, p = 0.0007) and airway hyper-reactivity (AHR) (r = −0.41, p = 0.004).
In summary, we found a reduction in nitrites in breath condensates after a high altitude climate therapy. Significant correlations were found between nitrites and MEF₅₀, AHR and symptoms. We conclude that the measurement of nitrites may be feasible to objectively assess airway inflammation in asthmatic children in order to detect ongoing inflammation in children with normal FEV₁ but persistent symptoms.     

Time efficacy of a single dose of montelukast on exercise-induced asthma in children

The aim of this study was to evaluate the timing of onset and the duration of action of a single oral-dose treatment with montelukast in comparison to placebo on exercise-induced asthma (EIA) in asthmatic children. Nineteen children (7–13 years) with stable asthma were evaluated. Patients undertook three consecutive treadmill exercise tests, respectively, 2, 12 and 24 h after a single-dose administration. A double-blind randomized, single-dose, placebo-controlled, crossover design was used. To assess bronchoconstriction after the exercise challenge, the maximal percentage fall in FEV₁ (ΔFEV₁) from the baseline value was considered. Two hours after dosing, ΔFEV₁ was −15.33  ±  2.93 for placebo and −13.33  ±  2.03 for montelukast. At 12 h, ΔFEV₁ was −18.69  ±  2.83 for placebo, −9.78  ±  1.85 for montelukast (p < 0.005). No difference was observed between placebo (ΔFEV₁−10.21  ±  2.07) and montelukast (ΔFEV₁−9.10  ±  2.02) at 24 h. Analysis of the degree of protection showed a significant efficacy of montelukast (p = 0.02) in comparison with placebo only at 12 h. Montelukast showed a significant protective effect 12 h after dosing, but no effect after 2 and 24 h. In mild asthmatics, the timing of administration of single dosage before exercise should be strictly considered in order to obtain the drug protective effects.     

The effect of high-efficiency and standard vacuum-cleaners on mite, cat and dog allergen levels and clinical progress

The major triggers for allergic asthma are exposure to allergens of the house dust mite, Dermatophagoides pteronyssinus , and of pets. Unfortunately studies of techniques designed to reduce house dust mite and pet allergens have had mixed results. However, new so-called 'improved' products continue to appear on the market and require subjective evaluation. The homes of 60 house dust mite-allergic patients were studied to compare the effects of high-efficiency and standard vacuum-cleaners on allergen concentration. Der p 1 (house dust mite), Fel d 1 (cat) and Can f 1 (dog) allergens were measured in four separate locations in each home. Clinical analysis was by lung function, bronchodilator usage and histamine challenge techniques. There was a significant reduction in Fel d 1 (ng/m²) in dust samples from the living-room carpet (p = 0.046), bedroom carpet (p = 0.003) and mattress (p = 0.013) and living-room sofa (p = 0.005) after 12 months of using the high-efficiency cleaners, but only in the mattress sample using the standard cleaners (p = 0.014). Can f 1 (ng/g dust) was reduced in the mattress sample after using the high-efficiency vacuum-cleaners (p = 0.028), but not at other sites. Der p 1 levels were not significantly changed over this period. Clinically, patients in the high-efficiency group showed improvements in peak expiratory flow rate (PEFR) (p = 0.004), FEV₁ (p = 0.026) and bronchodilator usage (p = 0.005) after 12 months. When the cat-sensitive patients were analyzed separately, improvements in histamine PC₂₀ (p = 0.039) were also seen. Reducing Fel d 1 concentrations, in the absence of any change in Der p 1 concentrations, can produce significant improvements in the lung function of atopic, asthmatic patients. This effect was primarily achieved in those patients with cat sensitivity, but who did not possess a cat themselves.     

Building characteristics affect the risk of allergy development

Damp dwellings increase the risk for house dust mite (HDM) infestation in temperate climate zones and may be associated with an increased risk for allergic disease. The aim of the study was to assess possible relationships between allergen levels in house dust, characteristics of residence buildings and allergic diseases in children. A subsample of 12-yr-old children, having the same address in 1991 and 1996, was selected from a population-based sample of children from the Göteborg area. Health inspectors examined the residences of all the 109 children and several different building characteristics including humidity and indoor temperature were collected. Dust samples for analysis of HDM allergens were collected from the children's beds, and for analysis of cat and dog allergens from the living room. Current health status was assessed by questionnaires, interviews and skin prick tests (SPT). Dog or cat allergens were found in all houses, even in houses without such animals. HDM allergens were found in 60% of the houses, but only six of them had levels exceeding 2 μg/g dust. There was a strong association between HDM-infestation and wheeze, but not with specific sensitization to HDM. The type of building (houses when compared with flats), the ventilation system and the presence of a basement had all major implications on respiratory symptoms, atopy and HDM infestation. We can conclude that dog or cat allergens were found in all houses, and a strong association between HDM infestation and indoor environment. Building construction affected both respiratory morbidity and sensitisation independently, suggesting not only worsening of symptoms but also a causative relationship with disease development.     

A 3-year longitudinal analysis of changes in fitness, physical activity, fatness and screen time

Aim:  To analyse whether changes in physical activity index (PAI), screen time (ST: television, computer) and body mass index (BMI) made a contribution to longitudinal changes in fitness of children and adolescents. Additionally, we analysed the interaction between baseline fitness level and changes in fitness.
Methods:  This is a 3-year longitudinal study of 345 high school students aged 11–19 years. Students performed curl-ups, push-ups and 20-m shuttle run tests from Fitnessgram. PA and ST were evaluated using a standard questionnaire. Standardized scores of fitness tests were summed. Changes over time were calculated as Δ₁ (2007 minus 2006), Δ₂ (2008 minus 2007) and Δ₃ (2008 minus 2006).
Results:  Changes in PAI were positively and independently associated with changes in fitness in Δ₁, Δ₂ and Δ₃. Changes in BMI were negatively associated with changes in fitness in Δ₃. Participants highly fit at baseline were those who showed positive changes in PAI over Δ₃, decreased changes in ST and had the lowest increase in BMI over 3 years compared with those low-fit at baseline.
Conclusions:  Changes in BMI were associated with changes in fitness over 3 years. However, changes in PAI were the best predictor for changes in fitness in each year and over the 3 years of evaluation in youth.     

Transforming growth factor-β1 is elevated in unpasteurized cow's milk

Unpasteurized milk consumption was associated with less atopy prevalence. Not only microbial load but also fatty acids and cytokines such as transforming growth factor-β₁ (TGF-β₁) may play a role on the effect of unpasteurized milk. Levels of TGF-β₁ in different cow's milk samples were evaluated: we consider raw unpasteurized milk before and after boiling, commercial pasteurized and micro-filtrated cow's milk and different commercially available cow's milk formulas. TGF-β₁ concentration in raw unpasteurized cow's milk was 642.0 ± 52.9 pg/ml before boiling and decreased significantly after boiling (302.7 ± 50.59 pg/ml) (p < 0.05). TGF-β₁ concentrations were also significantly lower in commercial pasteurized milk (246.2 ± 43.15 pg/ml) and in commercial micro-filtrated milk (213.0 ± 31.6 pg/ml) in comparison to unpasteurized unboiled milk (p = 0.002). The levels of TGF-β₁ in all formula samples were below the threshold of detectability for the assays. As TGF-β₁ in the milk may contribute to the development of the immature gastrointestinal tract by influencing IgA production and oral tolerance induction, we suggest to consider not only the microbial compounds but also the cytokine patterns to explain the protective effect of unpasteurized cow's milk on allergic disorders.     

Evaluation of clinical and immunological effects of inactivated influenza vaccine in children with asthma

Although annual influenza vaccinations are recommended by many authorities, some doctors may be reluctant to vaccinate asthmatic children because of the risk of inducing bronchial reactivity and exacerbating the asthma. In this study, the effect of split influenza vaccine on clinical symptoms, airway responsiveness and its influence on T lymphocytes was evaluated. Twenty-one asthmatic children with stable asthma were recruited and divided into two groups. Eleven patients who received the influenza vaccine formed the vaccination group and 10 patients who received a placebo formed the placebo group. Forced expiratory volume in 1 s ( FEV ₁), airway response (PC₂₀ methacholine, PC₂₀ = provocation concentration causing a 20% fall in FEV ₁) and the T lymphocyte subset ratio (Th1/Th2) were recorded on day 1 pre-vaccination and day 14 post-vaccination. Patients were also asked to record their peak expiratory flow (PEF) every morning and evening and to complete daily symptom scores over the period of 2 weeks. There were no significant changes in PC₂₀, FEV ₁, PEF variability, symptom scores and the Th1/Th2 ratio between the vaccination and placebo groups between day 1 pre-vaccination and day 14 post-vaccination. Similar results of PEF variability and asthma symptom score were obtained when the analysis was restricted to the day 1 pre-vaccination and day 3 post-vaccination. Immunization with split influenza vaccine does not exacerbate asthma in children either with a clinical or immunological effect. These results suggest that children with stable asthma can safely be immunized with a split influenza vaccine.     

The effect of montelukast on allergen-induced cutaneous responses in house dust mite allergic children

The benefits of a leukotriene modifier on allergen-induced cutaneous responses have not been studied in children. We hypothesized that a leukotriene-receptor antagonist would provide protection against allergen-induced early and/or late phase cutaneous responses in susceptible children. In a randomized, double-blind, placebo-controlled, cross-over study in 6- to 15-year-old house dust mite allergic children, we compared the benefit of either montelukast or a matching placebo for 2 days on cutaneous responses induced by intradermal injection of house dust mite extract. Responses were measured as the mean of the longest diameter and its longest perpendicular of the induration response after 10, 20 min, 4 h and 6 h of the challenge. A total of 30 children were randomized to placebo or montelukast. The mean decline from baseline was significantly greater (p = 0.04) in the montelukast-treated children [−5.20 mm (−12.03–1.63)][median (95% CI)] than in the placebo-treated children [0.13 mm (−6.46–6.73] at 6th hour of the challenge, as was the mean diameter (p = 0.04), but did not differ in the remaining time points. We concluded that in house dust mite allergic children, montelukast 5 mg provided significant improvement in allergen-induced cutaneous late-phase responses, suggesting its contribution to allergic skin responses and its potential therapeutic value.     

Environmental exposures and exhaled nitric oxide in children with asthma

OBJECTIVE: To evaluate the relation of environmental factors with exhaled nitric oxide (FENO) concentrations among asthmatic children. STUDY DESIGN: Cross-sectional analysis of 170 tobacco smoke-exposed children, ages 6 to 12 years, who have doctor-diagnosed asthma using measures of FENO, medication use, and exposures to settled indoor allergens and tobacco smoke. RESULTS: In multivariable analysis, child's age, uncarpeted flooring, not owning a cat, higher income, dust mite exposure, and being sensitized to any allergens were associated with higher FENO concentrations. Children who were sensitized to indoor allergens had an adjusted geometric mean FENO of 15.4 ppb (95% CI, 13.1, 18.2) compared with 10 ppb (95% CI, 8.2, 12.2) for unsensitized children. There was no statistically significant association of serum cotinine, hair cotinine, or reported corticosteroid therapy with FENO. CONCLUSIONS: FENO is higher among children who are sensitized to indoor allergens and exposed to dust mites. The results hold promise for the use of FENO as a tool to manage childhood asthma by using both pharmacologic and environmental treatments.     

Total and allergen-specific IgE levels in serum reflect blood eosinophilia and fractional exhaled nitric oxide concentrations but not pulmonary functions in allergic asthmatic children sensitized to house dust mites

Although elevated levels of serum immunoglobulin E (IgE) are considered the hallmark of atopic diseases, their clinical value in evaluating subjects with allergic disorders is under debate. To evaluate possible relationships between serum IgE levels and a variety of clinical parameters, 83 mild asthmatic children [10.98-year-old (2.95)], sensitized to house dust mites (HDM) Dermatophagoides pteronyssinus (Dp) or D. farinae (Df), were enrolled. As compared with normal control reference values detected in our laboratory, children with allergic asthma had higher blood eosinophil counts (expressed both as percentage and as absolute number) and higher fractional exhaled nitric oxide ( FeNO) levels but similar values in pulmonary function parameters. In the allergic asthmatic population, serum levels of total, Dp-specific or Df-specific IgE correlated positively with eosinophil counts (Rho ≥ 0.30, p < 0.01, each correlation) and FeNO levels (Rho ≥ 0.33, p < 0.01, each correlation) but not with pulmonary function parameters (p > 0.1, each correlation). Finally, significant correlations, although moderate, were found in the allergic asthmatic population between eosinophil counts and FeNO levels (Rho ≥ 0.42, p < 0.001, each correlation). Thus, in atopic children sensitized to HDM with mild intermittent asthma, IgE levels in blood appear to reflect systemic (blood eosinophils) and organ-specific (FeNO) markers of allergic inflammation but not pulmonary volumes or the degree of airflow limitation.     

Childhood asthma and exposure to indoor allergens: lowmite levels are associated with sensitivity

The prevalence and level of sensitivity to indoor allergens were studied in relation to current exposure at home in 124 children with perennial asthma living in three climatic zones of Sweden. The house dust mite (HDM) allergen levels were higher in the South than in the North (p < 0.001), while cat and dog allergen levels tended to be higher in the North than the South (n. s.). Thirty-four percent of the children were sensitive to the HDM Dermatophagoides pteronyssinus , as determined by IgE antibodies in vitro, 27% were sensitive to D. farinae , 57% to cat and 55% to dog. Sensitivity to HDM was significantly more prevalent in Southern, than in Central and Northern Sweden (p=0.001) where the children were more often sensitive to pets (cat p=0.005, dog p= 0.002). A significant association between the concentration of Der p I and Derf I in the house dust and both the prevalence of sensitivity to HDM and the IgE antibody levels against mites was found even at concentrations well below the commonly suggested risk level for sensitisation of 2 μg/g dust. No relationship was found between pet allergen concentration in the home dust and sensitivity to pets, possibly because of exposure outside home, e. g. in schools and meeting places for leisure activities. Similarly, there was no consistent association between the level of mite or pet allergen exposure at home and asthma severity as judged by symptom and medication score. The study indicates that there is no threshold value for sensitisation to mite allergens in asthmatic children, and therefore, dust allergen levels at home should be kept as low as possible in homes of children at risk for asthma.     

Low‐dose budesonide improves exercise‐induced bronchospasm in schoolchildren

The aim of this study was to compare the clinical efficacy of low‐dose inhaled budesonide (once or twice daily) and placebo, administered via Turbuhaler^®, on exercise‐induced bronchoconstriction (EIB) in children with mild asthma. Fifty‐seven steroid‐naive children (7–16 years old; 41 boys, 16 girls) with EIB participated in this sub‐population study according to the following inclusion criterion: a maximum fall in forced expiratory volume in 1 s ( FEV ₁) ≥ 10% after a standardized treadmill test. Mean baseline FEV ₁ was 100.3% of predicted, and mean maximum fall in FEV ₁ after the standardized exercise test was 22%. The study was a double‐blind, randomized, parallel‐group design. After 2 weeks of run‐in, the children received inhaled budesonide 100 µg or 200 µg once daily in the morning, 100 µg twice daily, or placebo, for 12 weeks. After 12 weeks of treatment, the fall in FEV ₁ after the exercise test was significantly less in all three budesonide groups (7.2–7.8%) vs. placebo (16.7%). Daytime symptom scores were significantly lower in all three budesonide groups compared with placebo (p < 0.02). The three budesonide groups did not differ significantly, and no significant change in lung function was found in any group. Therefore children with mild asthma, but with significant EIB, improved their exercise tolerance and symptom control after 3 months of treatment with a low dose of inhaled budesonide given once or twice daily.     

The use of mutually exclusive categories for atopic sensitization: A contrasting effect for family size on house dust mite sensitization compared with ryegrass sensitization

Our aim was to examine the relative importance of family size on sensitization to two different allergens: ryegrass and house dust mite (HDM), using a mutually exclusive classification for allergen-specific sensitization. An 8-year follow-up birth cohort study of children born between 1988–89 was conducted. The follow-up sample consisted of 498 children residing in Northern Tasmania in 1997 (84% of eligible). Outcome measures included skin prick test (SPT) reaction to nine aeroallergens and parental questionnaire. Family size was defined as sibling number in 1997. Children with a positive SPT to either Der p or Der f house dust mite but not ryegrass were classified as HDM-exclusive (n = 84). Children with a positive SPT to ryegrass but not HDM were classified as ryegrass-exclusive (n = 43). Family size was associated with reduced ryegrass-exclusive sensitization [AOR 0.57 (0.39, 0.84) per increase in sibling number] but not HDM-exclusive sensitization [AOR 0.97 (0.77,1.23)]. The difference in the family size effect on these sensitization outcomes was significant (p = 0.02). Similarly, family size tended to be associated with reduced asthma among ryegrass-exclusive sensitized children [AOR 0.45 (0.18,1.12)] but not HDM-exclusive sensitized children [(AOR 1.46(0.80–2.65)]. Large family size was strongly associated with reduced sensitization for ryegrass allergens but not HDM allergens using mutually exclusive sensitization categories. If this difference is confirmed in other studies, the contrasting effect of family size may reflect differences between these allergens with regard to level or timing of early life exposure, differences in allergen -specific potentiation for sensitization or unidentified confounding. The use of mutually exclusive categories for allergen sensitization will assist future work on child atopic disease.     

Leukotriene C4 in Children with Atopic Asthma I. Plasma Levels in Acute Asthma

The leukotrienes C₄, D₄ and E₄ are potent biologic mediators, and are thought to play an important role in obstructive airways disease such as asthma. In this study, plasma im-munoreactive LTC₄ (iLTC₄) levels in asthmatic children were measured using radio-immunoassay after Sep-pak extraction in order to determine whether LTC₄ is released in vivo during an asthmatic attack. In 10 non-atopic children, the mean ± SEM of plasma iLTC₄ level was 0.031 ± 0.013 pmol/ml. Significantly higher plasma iLTC₄ levels were recognized at all stages in asthmatic children, both in remission (p<0.01) and during an attack (p<0.01). PaO₂ levels during an attack were significantly lower in the high iLTC₄ group. In 15 asthmatic children, the plasma iLTC₄ levels during an attack (0.134 ± 0.017 pmol=ml) significantly decreased during recovery (0.078 ± 0.012 pmol/ml) (p<0.05). Plasma iLTC₄ levels correlated closely with lung function (p<0.01). The high iLTC₄ levels in plasma in asthmatic children suggest a role for LTC₄ in the pathophysiology of asthma.     

CC chemokine receptor expression in childhood asthma is influenced by natural allergen exposure

Chemokines and their receptors may play an important role for leukocyte trafficking in allergic inflammation. Aim was to evaluate whether expression of chemokine receptors CCR4 and CCR8 on cells obtained by sputum induction from asthmatic allergic children may be influenced by house dust mite (HDM) allergen natural exposure. Twenty-one children (7-13 yr) with moderate asthma and sensitized to HDM were evaluated during a prolonged period of allergen avoidance (T0) and after a period of natural allergen exposure (T1). At each time point of sputum induction, lung function evaluation, exhaled nitric oxide (eNO) measurements were performed. At T1, CCR4 and CCR8 expression on sputum-induced cells increased from 28.4% +/- 2.9% and 25.8% +/- 1.9%, to 41.1% +/- 4.2% and 37.5% +/- 2.0%, respectively (p < 0.05 and p = 0.01). After allergen exposure, both sputum eosinophils (from 5.2% +/- 2.0% to 12.1% +/- 4.1%, p < 0.01) and eNO (from 15.1 +/- 2.2 ppb to 24.2 +/- 5.8 ppb, p < 0.05) showed significant increase. Lung function tests presented significant deterioration of Forced Expiratory Flow at 25-75% of Vital Capacity (FEF(25--75)) (p < 0.05) and increase of residual volume (p = 0.002). Significant changes in CC chemokine receptor expression in sputum-induced cells in asthmatic children in response to HDM exposure have been observed leading to consider the relevance of CCR4 and CCR8 in allergic asthmatic inflammation.     

Steroid-sensitive indices of airway inflammation in children with seasonal allergic rhinitis

Previous studies involving adults have demonstrated that airway glucocorticosteroids inhibit plasma exudation and eosinophil activity in allergic rhinitis. This study explores the possibility that plasma exudation, exudative responsiveness, and the occurrence of eosinophil activity-related proteins are glucocorticosteroid-sensitive nasal mucosal indices in allergic children. Using a placebo-controlled, parallel-group design effects of nasal budesonide (64 µg per nasal cavity b.i.d) were determined in children with seasonal allergic rhinitis. Nasal lavage fluid levels of eotaxin, eosinophil cationic protein (ECP), and α₂-macroglobulin, indicating plasma exudation, were determined, the latter with and without challenge with topical histamine. Nasal lavage fluid levels of α₂-macroglobulin and ECP increased significantly during the pollen season, and the acute plasma exudation response to histamine was significantly greater during than outside the season. There was a trend towards a seasonal increase in nasal lavage fluid levels of eotaxin. Budesonide significantly inhibited the seasonal increase in α₂-macroglobulin as well as the exudative hyperresponsiveness to histamine. Any tendency of increases in mucosal output of eotaxin and ECP was abolished by the glucocorticosteroid treatment. We conclude that mucosal exudation of plasma, as a global sign of active inflammatory processes, is a glucocorticosteroid-sensitive facet of allergic rhinitis in children. Exudative hyperresponsiveness, potentially caused by several weeks of mucosal inflammation, emerges as a significant feature of allergic rhinitis in children, and its development is prevented by local treatment with a glucocorticosteroid drug. The seasonal increase in ECP and the trend for an increase in eotaxin were absent in the glucocorticosteroid-treated subjects.     

Leukotriene C4 in Children with Atopic Asthma II. Plasma Levels in Bronchial Challenge with Specific Allergen

Peptide leukotrienes C₄, D₄ and E₄ are considered to be major mediators of hypersensitivity reactions. In this study, immunoreactive leukotriene C₄ (iLTC₄) in plasma, taken from asthmatic children who had undergone bronchial challenge with a specific allergen, was measured using radioimmunoassay in order to determine whether LTC₄ is released in duo during human allergic reactions. With regard to the bronchial challenge of 10 asthmatic children, plasma iLTC₄ levels at the postchallenge stage (0.131 ± 0.037 pmol/ml) were significantly elevated compared to the prechallenge stage (0.065 ± 0.016 pmol/ml) (p <0.01). The bronchial response was not directly related to the increased plasma iLTC₄ levels, but the strength of the bronchial response did relate to the plasma iLTC₄ levels at the pre-challenge (p<0.05) and postchallenge (p<0.01) states. The prechallenge levels are relevant to bronchial reactivity, and the post-challenge levels are relevant to bronchocon-striction caused by exposure to allergens. The in vivo release of LTC₄ following exposure to a specific allergen suggests that leukotrienes are important in the pathogenesis of asthma.     

Reduced IL-2-induced IL-12 responsiveness in atopic children

Atopy may be associated with a reduced T-cell function particularly regarding maturation of T helper 1 (Th1) responses. We hypothesized that atopic children may have a reduced capacity to up-regulate the β₂ subunit of the interleukin-12 (IL-12) receptor (IL-12Rβ₂, the signal-transducing component). The study included 38 children followed from birth to the age of 7 years. Twenty one had a cumulative history of atopic disease, whereas 17 had none. Sixteen out of 21 children also had atopic symptoms within the past year (current), out of whom 10 children had atopic airway symptoms. The expression of IL-12Rβ₂ mRNA was analyzed by quantitative real-time PCR and the secretion of interferon-γ (IFN-γ), IL-5 and IL-10 was assessed by enzyme-linked immunosorbent assay (ELISA). Children with current atopic airway symptoms and high levels of total IgE up-regulated IL-12Rβ₂ mRNA expression less than non-atopic children with low IgE levels after IL-2 stimulation. This was accompanied by a low IL-2- and IL-12-induced IFN-γ production, possibly reflecting the reduced capacity of atopic children to up-regulate the IL-12 receptor. As IL-2 is needed to initiate and sustain immune responses and IL-12 promotes Th1 responses, this may contribute to the Th2-skewed pattern in atopic children.