NOS1 polymorphism is associated with atopy but not exhaled nitric oxide levels in healthy children

Exhaled nitric oxide (FE_NO) is raised in atopy. The mechanism for this is unclear. The aim of this study was to investigate whether the number of AAT repeats in intron 20 of the NOS1 gene, recently associated with variations in FE_NO in adults with asthma and cystic fibrosis, was associated with the raised FE_NO in healthy atopic children. Eighty-seven healthy children (44 girls, 42 atopic, age range 6–18 years) underwent measurements of FE_NO, spirometry, airway responsiveness and skin prick testing. Genotyping was carried out to determine the number of AAT repeats. There was no association between the number of AAT repeats and FE_NO in either the whole sample of healthy children (n = 87) or in the subsample of healthy atopics (n = 42). However, a greater number of atopic children had two high repeat alleles compared with non-atopic children (33.3% vs. 13.6%, respectively, p = 0.03). This suggests that variations in the NOS1 gene may contribute to atopy without this relationship being reflected by FE_NO.     

Fractional exhaled nitric oxide in infants during cow's milk food challenge

Cow's milk allergy (CMA) is the most common food allergy in early childhood. The golden standard for the diagnosis of CMA is a food challenge after a period of elimination. Increased levels of fractional exhaled nitric oxide (FE_NO) have been shown after bronchial allergen provocation. We evaluated whether FE_NO may also be a predictor of a positive reaction during cow's milk challenge in infants. Forty-four infants [mean age (range): 4.2 (3.7–4.6) months] suspected of CMA underwent an open food challenge with cow's milk formula administered in ascending quantities, starting with 2 ml and then 6, 20, 60 and 200 ml until a clinical reaction occurred. Off-line FE_NO samples were obtained during tidal breathing by means of a facemask covering infants' nose and mouth. FE_NO was measured twice before the challenge (baseline), immediately before each new dose of milk and after a positive reaction or after the last dose of milk. Eleven children showed immediate positive clinical responses to cow's milk, whereas 13 infants presented only a late-type reaction. FE_NO values before or after a positive reaction (either immediate or late) were not different from FE_NO values at baseline. Baseline FE_NO in infants with a positive reaction did not differ from FE_NO in infants without a reaction at any time point. We conclude that FE_NO values are not predictive and not related to the occurrence of a positive reaction during a cow's milk challenge in infants, suggesting that a positive reaction may not result from eosinophilic activation.     

Wheezing in school children is not always asthma

Our objective was to study whether children with reported asthma differed from children with wheeze but without asthma, and from children with neither asthma nor wheeze, regarding lung function, bronchial hyper‐responsiveness (BHR) using methacholine inhalation, exercise‐induced bronchoconstriction (EIB), and skin prick test (SPT) reactivity. School children (n=2188), enrolled in a survey of asthma, were classified into three mutually exclusive groups by parental report of: asthma, wheeze, and no asthma/no wheeze. A random sample of 80 children in each group was tested (n=240). Among asthmatics, 68% (95% confidence interval (CI), 57–79) had a BHR (measured as PD₂₀ forced expiratory volume in 1 s (FEV₁) ≤ 8.16 μmol using methacholine) compared to 31% (CI 20–42%) and 30% (CI 19–40%) in the wheeze and no asthma/no wheeze groups. The dose–response slope (DRS) confirmed the PD₂₀ data and distinguished equally between groups. EIB (≥10% fall in FEV₁) was more frequent (40%, CI 29–52%) among asthmatics than among children with wheeze (12%, CI 4–19%) and no asthma/no wheeze (7%, CI 1–13%). The prevalence of at least one positive SPT was twice as high in the asthma group (58%, 47–69%) than in the wheeze (27%, CI 16–37%) and the no asthma/no wheeze (25%, 15–35%) groups. These results indicate that children with asthma differ from children with wheeze and children with no asthma/no wheeze regarding lung function, BHR, EIB, and SPT reactivity. Children with wheeze are more similar to children with no asthma/no wheeze with respect to these parameters.     

High levels of urinary eosinophil protein X in young asthmatic children predict persistent atopic asthma

Levels of urinary eosinophil protein X (U-EPX) and eosinophil counts were measured in 32 children (12–36 months of age) who were hospitalized for acute asthma, and the U-EPX levels were measured in 20 healthy children of the same age. The ability of these parameters to predict persistent asthma (at least one wheezing episode during the last 6 months) and atopic asthma (a positive skin-prick test [SPT]), was evaluated at a follow-up 2 years later. On admission, levels of U-EPX were higher in children with asthma (median: 120 µg/mmol of creatinine; quartiles: 67–123 µg/mmol of creatinine) than in controls (60 µg/mmol of creatinine, 38–74 µg/mmol of creatinine; p< 0.001). The U-EPX level was higher in those with persistent atopic asthma at follow-up (173 µg/mmol of creatinine, 123–196 µg/mmol of creatinine, n = 16), than in those with persistent non-atopic asthma (73 µg/mmol creatinine, 46–105 µg/mmol of creatinine, n = 8; p< 0.05), and higher than in those with transient asthma (no symptoms at follow-up) (106 µg/mmol creatinine; 42–167 µg/mmol of creatinine, n = 8; p< 0.05). By multiple logistic regression analysis, U-EPX was the only parameter able to predict persistent atopic asthma; eosinophil counts, parental atopy, age or gender could not. Parental atopy was the only parameter predictive for persistent asthma, regardless of atopic status. In conclusion, levels of U-EPX, but not eosinophil counts, measured in young children hospitalized with acute asthma can predict the persistence of atopic asthma 2 years later.     

Non-atopic asthma in children is related to maternal bronchial hyperreactivity

Data on the pathogenic mechanisms underlying the development of non-atopic asthma in children are scarce. Our aim was to evaluate the association and compare the atopic status, pulmonary functions, bronchial hyperresponsiveness and serum total immunoglobulin E (IgE) levels of parents of atopic and non-atopic asthmatic children by using objective methods. Fifty-one asthmatic children aged 4–16 yr and their parents were included into the study. Initially the American Thoracic Society's Respiratory Disease questionnaire inquiring data on symptoms of asthma, rhinitis and past medical history was filled in. Afterwards, skin prick test with aeroallergens, pulmonary function and methacholine bronchial provocation tests and serum sampling for total IgE level determinations were carried out. Bronchial hyperresponsiveness to methacholine was significantly more common in the mothers of non-atopic children compared to those of atopic ones, although no significant difference was observed in the skin prick test reactivity, pulmonary function test parameters and serum IgE levels. Questionnaire data revealed that the presence of asthmatic symptoms such as wheezing and phlegm and doctor-diagnosed asthma were more common in the mothers of non-atopic children. Meanwhile, asthmatic symptoms were also found to be significantly more common in fathers of non-atopic children. Logistic regression analyses revealed that maternal PC₂₀ was the only predictive factor for the risk of displaying non-allergic asthma in children. The results demonstrate that among the risk factors studied, maternal bronchial hyperreactivity was associated with the development of asthma in non-atopic children.     

Intrabdominal fat is related to metabolic risk factors in Hispanic Americans, African Americans and in girls

Aim:  This study aimed to test the association of individual adipose depots on cardiometabolic outcomes, whether the association varied by depot and if the associations differed by race/ethnicity or gender in early pubertal children.
Methods:  Three hundred and twenty children (53% male) aged 7–12 years self-identified as African American (AA; n = 114), European American (EA; n = 120) or Hispanic American (HA; n = 86) participated. Insulin dynamics were assessed by intravenous glucose tolerance test; body composition with DXA; fat distribution with CT.
Results:  AA had the least fat in each depot and HA had the most. Fat accumulation negatively impacted cardiometabolic outcomes independent of race/ethnicity or gender. AA and females were reproductively more mature. In AA and HA, each measure of adiposity influenced the insulin sensitivity index (S_I), whereas intra-abdominal adipose tissue (IAAT) did not contribute to S_I in EA. IAAT was positively associated with blood pressure in AA only. In females, adiposity adversely influenced cardiometabolic outcomes such that total fat mass, IAAT and/or SAAT was inversely associated with S_I, and positively associated with blood pressure and fasting insulin.
Conclusion:  IAAT is uniquely related to metabolic risk factors in Hispanic Americans, African Americans and girls, suggesting that either the threshold for adverse effects of IAAT is lower, or the IAAT metabolism differs in these groups.     

Relationship between adipokines and manifestations of childhood asthma

Although the prevalences of asthma and obesity are increasing substantially in recent decades, very little is known about the possible association between them. We evaluated the roles of leptin, adiponectin, and resistin, which are adipokines produced by adipose tissue, on childhood asthma, and their association with pulmonary function and bronchial hyperresponsiveness. We studied 149 atopic asthmatic children, 37 non-atopic asthmatic children, and 54 healthy children. Body mass index was calculated using height and weight, which were measured on the same day that pulmonary function tests and methacholine challenge tests were performed. Skin prick tests were performed, and total eosinophil count, total serum immunoglobulin E (IgE), serum eosinophil cationic protein, leptin, adiponectin, and resistin were measured in all subjects. Atopic asthmatics had lower resistin levels compared with non-atopic asthma and control groups, but leptin and adiponectin did not show any difference among these three groups. Resistin demonstrated positive correlation with methacholine PC₂₀ and negative correlations with eosinophil count and serum total IgE. Leptin and adiponectin showed associations with forced expiratory volume in 1 s or forced expiratory flow between 25–75%. Multiple regression analysis revealed that resistin was a significant predictive factor for asthma. There was no direct association between asthma and leptin or adiponectin. Our findings suggest that resistin may play a negative predictive role in asthma. Adiponectin and leptin showed close associations with pulmonary function and may have disease-modifying effects in children with asthma.     

Role of atopy in the natural history of wheeze and bronchial hyper-responsiveness in childhood

The role of atopy in the development of asthma has become increasingly recognised. We have been prospectively following a birth cohort of children of atopic parents to document the development of atopic disease. Our aim in this study was to document the natural history of BHR and wheeze at 10 years of age and to relate this to atopy. We reviewed 47 of our original cohort of 79 infants at 10 years of age and documented their clinical history of atopic disease and performed allergen skin prick tests and BHR to histamine. Thirty-three (70%) children wheezed at some time during their 10 years of life, with 13 commencing in infancy. Twenty-two children (47%) had current wheeze at 10 years of age. Wheeze in infancy was a poor predictor (RR 1.23, Cl₉₅ 0.66–2.23) of current wheeze while wheeze commencing after infancy was a good predictor (RR 2.89, Cl₉₅ 1.45–5.2). In contrast both atopy in infancy (RR 2.94, Cl₉₅ 1.92–4.53) and current atopy (RR 3.58, Cl₉₅ 1.43–9.03) were strong predictors of current wheeze. Analysis of BHR confirmed the importance of atopy in predicting its occurrence and severity. Sensitisation to D. pteronyssinus appeared to be the strongest predictor of both current wheeze and BHR. These observations confirm the importance of atopy in predicting outcome in children with asthma and suggest that wheezing in infancy and wheezing in later childhood may have different pathogenetic mechanisms.     

Urinary leukotriene E4 levels in children with allergic rhinitis treated with specific immunotherapy and anti-IgE (Omalizumab)

Recently, we were able to demonstrate that Omalizumab, a humanized monoclonal anti-IgE antibody, reduces in vitro leukotriene (LT) release of peripheral leukocytes stimulated with allergen in children with allergic rhinitis undergoing allergen immunotherapy. The aim of this study was to investigate the effect of anti-IgE in combination with specific immunotherapy (SIT) on urinary leukotriene E₄ (LTE₄) levels. Children and adolescents with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a phase III, placebo-controlled, multicenter clinical study. Within the four-arm study, patients were randomized to receive SIT for either birch or grass pollen and to receive either subcutaneous anti-IgE or placebo for 24 weeks during the pollen season. From a total population of 225 children, we collected three urine samples in a subgroup of 19 children [n = 12 boys (63%); mean age 11.8 years; range 7.2–17.5 years; Group A (n = 10): SIT (grass or birch) + anti-IgE; Group B (n = 9): SIT (grass or birch) + placebo]. Urine samples were collected before, during and at the end of treatment. Endogenous urinary LTE₄ was separated by high-performance liquid chromatography (HPLC) and determined by enzyme immunoassay with a specific antibody. No differences in urinary LTE₄ concentrations were observed between the anti-IgE and the placebo groups before (A: 35.2; B: 36.5 nmol/mol creatinine), during (A: 27.0; B: 29.3) and after treatment (A: 28.9; B: 26.5 nmol/mol creatinine). We conclude that urinary LTE₄ levels are not helpful in monitoring patients treated with anti-IgE and SIT.     

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.     

Increased eosinophil cationic protein levels in bronchoalveolar lavage from wheezy infants

Although studies examining the serum suggest a role for eosinophils in wheezing episodes in infants and toddlers, the presence of a chronic eosinophilic inflammation within their airways remains to be demonstrated. In this study we investigated whether eosinophil cationic protein (ECP) levels are increased in BAL fluid (BALF) from infants and toddlers with recurrent wheezing episodes, during an asymptomatic period. The levels of ECP in BALF were quantitated by radioimmunoassay in 61 children (36 with severe recurrent episodes of wheezing and 25 who were non-wheezy), aged 6–36 months, in whom flexible bronchoscopy was clinically indicated. BALF eosinophil counts were ≤ 1% in all patients and did not differ in wheezers, compared to non-wheezers. In contrast, ECP levels in BALF were ≥ 2.2 µg/l in 18 of 36 (50%) wheezy infants but in only three of 25 (12%) control infants (p < 0.01). Neutrophil counts were significantly higher in the wheezer group than in the non-wheezer group (8.1 × 10³ cells/ml vs. 3.0 × 10³ cells/ml). ECP levels in the BALF were not correlated with the absolute number of eosinophils ( r  = 0.03; p = 0.8) but were correlated with the absolute number of neutrophils ( r  = 0.54; p = 0.001). There was no association between high ECP levels in BALF and the atopic status of the wheezers. In conclusion, ECP levels are increased in BALF from young children with recurrent wheezing episodes, even during relatively quiescent periods, suggesting a chronic increased cell activation in the lower airways.     

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 costs of atopy and asthma in children: Assessment of direct costs and their determinants in a birth cohort

The aim of this study was to estimate costs accrued by the health care of children with asthma in comparison to children with atopic eczema and seasonal rhinitis and to investigate cost determinants. From the multicenter cohort study (MAS-90), we selected children with an asthma, atopic eczema and/or seasonal rhinitis diagnosis during the first 8 years of life, and overall 8-year health care utilization was estimated retrospectively by reviewing medical records. Asthma treatment (n = 76) incurs an average cost of US$ 627 per year, 44% due to hospital stays. Atopic eczema treatment (n = 91) cost on average US$ 219 and seasonal rhinitis (n = 69) US$ 57 per year. In asthma and atopic eczema, costs increase significantly with disease severity. Allergy diagnostics use accounts for only 1% of total costs. Costs for asthma and atopic eczema treatment are highest in those years when topical steroids are used for the first time, but decrease with every further year of steroid use. A remarkable 25% of asthmatic children with severe symptoms were not treated according to national guidelines, so that most steroid treatment was initiated during the first hospital stay. In the case of asthma, total direct costs increased until the 3rd year of the disease, and then decreased with further years of diagnosis, while steroid use continued to increase. These results indicate a 'learning effect' in the treatment of asthma and atopic eczema for each patient as well as considerable cost-saving potential by preventing severe asthma. Moreover, the importance of considering cost-driving factors and using cohort or longitudinal designs in cost-of-illness approaches is emphasized.     

Exhaled nitric oxide in children with asthma and sinusitis

Exhaled nitric oxide (FE_NO) is a surrogate marker of eosinophilic airway inflammation. The measurement of this gas can be easily performed in children and the result is immediately available. Because of these characteristics, measurement of FE_NO is slowly becoming part of the routine clinical evaluation of an asthmatic patient. FE_NO measurement may have a role both in the diagnosis of asthma and as a guide in therapy algorithms. For example when FE_NO levels are persistently normal and the asthmatic child is asymptomatic, the steroid therapy may be decreased or even stopped. In patients with acute or chronic rhinosinusitis the levels of nasal nitric oxide (nNO) are significantly decreased, while they rise up after a course of antibiotics. The measurement of nasal NO has been proposed as a functional test to evaluate sinus ventilation. Nasal NO is significantly reduced also in primary ciliary dyskinesia and can be used as a screening tool to identify patients affected by this condition.     

Wheeze in preschool children and its relation with doctor diagnosed asthma

OBJECTIVE--To describe the characteristics of wheeze and its relation with doctor diagnosed asthma in children aged 5 years and under. DESIGN--Questionnaire survey of population based random sample of children registered on Leicestershire Health Authority's child health index for immunisation; questionnaire completed by parents. SUBJECTS--1650 white children born in 1985 to 1989 who were surveyed in 1990. MAIN OUTCOME MEASURES--Age distribution, severity, precipitants, seasonal characteristics, and diurnal variation of wheeze, family history of asthma/atopy, and their association(s) with doctor diagnosed asthma. RESULTS--There were 1422 replies (86.2%). Two hundred and twenty two (15.6%) were reported to have wheezed and of these 121 (8.6%) had formally been diagnosed as having asthma. More than 80% of the former had recurrences of wheeze and 40% (72) had three or more episodes in the preceding 12 months. Age, number of episodes per year, the severity of shortness of breath with attacks, and precipitants other than colds were the major factors determining the probability that a wheezy child will be diagnosed as having asthma. The data also suggest that despite the strong association of symptom based criteria with the label asthma, asthma was not diagnosed by these same severity criteria in one quarter of cases. CONCLUSIONS--Clinical and physiological follow up studies of children identified as asthmatic by the above criteria during the preschool years should validate or refute the predictive value of these measures of wheeze severity.     

Exposure to pets and atopic dermatitis during the first two years of life. A cohort study

The aim of this study was to assess the association between keeping pets in early childhood and the occurrence of atopic dermatitis in an ongoing birth cohort followed up to the age of 2 years. We analyzed data of 4578 children in the intervention and observation part of an ongoing cohort study. The children were recruited at birth in the two study regions Wesel and Munich between January 1996 and June 1998. Information on atopic diseases and pet ownership was obtained by questionnaire at the child's first and second birthday. The logistic regression model showed a negative association between 'keeping any pet' and in particular 'keeping dogs' in the 1st year of life and the development of atopic dermatitis in the 1st and the 2nd years of life. The protective effects remained statistically significant after adjusting for several possible confounding variables (1st year_{any pet} OR 0.71, 95% CI [0.55;0.92], 1st year_dog OR 0.62, 95% CI [0.39;0.98], 2nd year_{any pet} OR 0.74, 95% CI [0.57;0.97], 2nd year_dog OR 0.63, 95% CI [0.40;0.98]). Ownership of small furred pets (hamster, rabbit and guinea pig) also showed a borderline protective effect for the 1st year. We assume an association between keeping pets and undefined environmental factor(s) that contribute protectively to the development of atopic dermatitis in early life, presumably by effects on the maturation of the immune system.     

Use of Phadiatop® Infant in diagnosis of specific sensitization in young children with wheeze or eczema

Wheezing and eczema are common symptoms in young children and it is important to disclose sensitization for correct management. The objective of this study was to assess the diagnostic values of Phadiatop Infant, an in vitro test for graded determination of immunoglobulin E (IgE) antibodies to food and inhalant allergens. One-hundred and forty-nine children (median age 1.4 yr) with symptoms of wheezing (51%) eczema (28%) or a combination of both (21%) were classified as atopic or non-atopic based on case history, atopic history, physical examination and determination of IgE antibodies. The clinical performance of Phadiatop Infant was evaluated for 145 children against this classification in a blinded manner to the allergist. Fifty-one children were classified as atopic of which Phadiatop Infant identified 49. Ninety-four were non-atopic of which the test identified 90. This resulted in a sensitivity of 96%, a specificity of 96%, a positive and a negative predictive value of 94% and 98%, respectively. Logistic regression showed that probability had to be assessed as atopic increased with increasing Phadiatop Infant values. These results suggest that Phadiatop Infant can be recommended as an adjunct to the clinical information in the differential diagnosis on IgE-mediated allergy in young children. The test thus provides an opportunity for early correct diagnosis and identification of subjects at risk for whom intervention may be necessary.     

Umbilical cord-blood transplantations from unrelated donors in patients with inherited metabolic diseases: Single-institute experience

Abstract:  We evaluated the feasibility of UCBT from unrelated donors and a myeloablative preparative regimen that did not involve anti-thymocyte globulin in five children with lysosomal and peroxisomal diseases. Patients with MPS II (n = 1), adrenoleukodystrophy (n = 1), metachromatic leukodystrophy (n = 2), and Krabbe disease (n = 1) received UCBT between December 2001 and September 2005. All patients received oral Bu (600 mg/m²), CY (200 mg/kg IV), and fludarabine (180 mg/m² IV). Prophylaxis for GVHD consisted of a combination of tacrolimus and a short methotrexate course. Neutrophil engraftment occurred a median of 24 days (range, 21–25) after transplantation. None had graft rejection. One patient developed grade III acute GVHD and the other four patients had grade I acute GVHD; none had extensive chronic GVHD. One patient developed hemorrhagic cystitis. There were no treatment-related deaths. Although one child with MPS II died of PTLD 10 months after the UCBT, four of the five children are alive 14, 20, 31, and 55 months after transplantation with complete donor chimerism. These results suggest the feasibility of the UCBT with Bu, fludarabine, and CY-preparative regimen for patients with inherited metabolic diseases.     

Correction of bronchial challenge data for age and size may affect the results of genetic association studies in children

Meaningful studies of asthma genetics require careful definition of airway hyperresponsiveness (AHR). In children, several studies have emphasized the need for correction of bronchial challenge data for baseline parameters, such as age, gender, lung function and atopic status, when undertaking airway responsiveness measurements. However, few studies have suggested how this should be performed in practice. This study describes a method for the correction of dose–response slopes (DRS) and PC₂₀ values for baseline parameters in children, and illustrates the effect of such corrections on the association of AHR with the glutathione S-transferase GSTP1 Ile105Val polymorphism in children. Skin prick and methacholine challenge testing, measurement of total serum IgE concentration and GSTP1 genotyping were performed in 145 unrelated British children aged 7–18 years. Correction of bronchial challenge results, expressed as both DRS and PC₂₀ values, for age, gender, baseline lung function and atopic status was performed using linear regression and discriminant analysis, respectively. Adjusting bronchial challenge results for the age and size of the child altered AHR status, defined as a PC₂₀ methacholine <8 mg/ml, in 37% of children. Correction for baseline parameters also resulted in a significant reduction in mean DRS (original uncorrected DRS 83.6, corrected DRS _c 27.4). This had a marked effect on the results of the association study, unmasking a previously unidentified association between the GSTP1 genotype and AHR in children. Age and size adjustment of bronchial challenge data has a significant effect on AHR status and may influence the results of genetic association studies in children.     

Cutaneous lymphocyte‐associated antigen expression in children with atopic dermatitis and non‐atopic healthy children

Cutaneous lymphocyte‐associated antigen (CLA) is a cell surface glycoprotein which has been implicated in the homing of lymphocytes to cutaneous sites. It is postulated to play an important role in T‐cell migration to skin in atopic dermatitis; however, the expression of CLA in both normal children and children with atopic dermatitis has not been extensively studied. If CLA expression on T cells were important in the traffic of lymphocytes to atopic dermatitis skin lesions, it might be expected that the proportion of CLA⁺ T cells in unstimulated peripheral blood from children with atopic dermatitis would be elevated. We have examined the proportion of CLA⁺ T cells in children with atopic dermatitis and non‐atopic age‐matched controls. The proportion of CLA⁺ T cells in non‐atopic children was highly associated with and increased with increasing age ( r  = 0.88, p < 0.001). There was no difference between the proportion of T cells expressing CLA in the unstimulated PBMC from children with severe or mild/moderate atopic dermatitis and age‐matched non‐atopic controls (p = 0.18, p = 0.3, respectively). Despite this, children with atopic dermatitis did show evidence of perturbation of CLA expression, as unlike the non‐atopic children the proportion of CLA⁺ T cells in the atopic children did not correlate with age. These findings suggest that while CLA expression may play a role in atopic dermatitis, other as yet undefined surface markers are likely to principally determine the migration of T cells to skin in atopic dermatitis.