Component-resolved diagnostics demonstrates that most peanut-allergic individuals could potentially introduce tree nuts to their diet.

BACKGROUND: Nut allergy varies from pollen cross-allergy, to primary severe allergy with life-threatening symptoms. The screening of IgE antibodies to a wide spectrum of allergens, including species-specific and cross-reactive allergens, is made possible via microarray analysis. OBJECTIVE: We sought to study the association of variable IgE sensitization profiles to clinical response in peanut-challenged children and adolescents in a birch-endemic region. In addition, we studied the avoidance of tree nuts and species-specific sensitizations. METHODS: We studied 102 peanut-sensitized patients who underwent a double-blind placebo-controlled challenge to peanut. We analysed ISAC ImmunoCAP microarray to 112 allergens, singleplex ImmunoCAPs for hazelnut Cor a 14 and cashew Ana o 3, and performed skin prick tests to peanut, tree nuts and sesame seed. We surveyed avoidance diets with a questionnaire. RESULTS: Sensitization to PR-10 proteins was frequent (Bet v 1 90%), but equally high in the challenge negatives and positives. IgE to Ara h 2 and Ara h 6 discriminated peanut allergic (n = 69) and tolerant (n = 33) the best. Avoidance of tree nuts was common (52% to 96%), but only 6% to 44% presented species-specific sensitizations to tree nuts, so a great number could potentially introduce these species into their diet. CONCLUSIONS AND CLINICAL RELEVANCE: PR-10-sensitizations were frequent and strong regardless of peanut allergy status. Component-resolved diagnostics can be employed to demonstrate to patients that sensitization to seed storage proteins of tree nuts is uncommon. Several tree nuts could potentially be reintroduced to the diet.

Burden of allergy diets in Finnish day care reduced by change in practices.

BACKGROUND: Nonessential allergy diets in children with mild symptoms may harm the development of immunological tolerance and impose a burden on families and day care. We aimed to reduce the high prevalence of allergy diets in day care by reforming the practices for inquiring about need of special diets from parents. METHODS: We developed a new special diet form and an information leaflet based on the new allergy guidelines. The new form was implemented into 40 Finnish day care centres in the capital region in 2013-2015. The questionnaires on practices concerning special diets in day care centres and allergy knowledge were collected from the personnel. RESULTS: After 2 years, the new special diet form was used by 64% of families with food-allergic children, and the prevalence of allergy diets in day care centres decreased by 43% to 4.3% (IQ range 3.05-5.96). A significant decrease was found in the prevalence of all basic (milk, grains, egg) and most other allergy diets (P for trend < 0.01). The new practice was well accepted by day care and kitchen personnel. Lack of updated allergy knowledge was noted among day care personnel. CONCLUSIONS: The burden of allergy diets in day care settings could be decreased by simple pragmatic changes based on current allergy guidelines. Old allergy attitudes persisted among day care personnel, indicating the need for continuous education.

Cross-sensitization profiles of edible nuts in a birch-endemic area.

BACKGROUND: Sensitization to birch pollen causes cross-sensitization to nuts, but rarely leads to clinical nut allergy. The aim was to study sensitizations to nuts in individuals sensitized to birch pollen and examine cross-reactivities between birch and nut species. METHODS: All subjects with skin prick tests (SPTs) for birch pollen conducted during 1997-2013 in the Skin and Allergy Hospital in Helsinki (n = 114 572) and their available SPTs for nuts (n = 50 604) were included. Nut sensitizations were analyzed both with and without cosensitization to birch and stratified into age-categories. Cross-reactivities were analyzed with hierarchical clustering. One group of 1589 patients was surveyed for symptoms. Data were gathered also from Lapland to examine sensitizations in an area with less birch-pollen exposure. RESULTS: Of subjects with birch sensitization, 84% were cosensitized to hazelnut, 71% to almond, and 60% to peanut. In a subgroup without birch sensitization, young children (<5 years) were most commonly nut-sensitized (8-40%); and this prevalence decreased in adolescents and further in adults (4-12%). Cashew and pistachio (ρ = 0.66; P < 0.001) and pecan and walnut (ρ = 0.65; P < 0.001) correlated the strongest. The majority of nut-sensitized patients (71% hazelnut, 83% almond, 73% peanut) reported no or mild symptoms. Cosensitizations between nuts and birch were similar in Lapland with its lower birch-pollen exposure. CONCLUSION: Birch-sensitized individuals are frequently cosensitized to hazelnut, almond, and peanut. Among the birch-negatives, prevalences of nut sensitizations decrease from early childhood to adolescence. Cashew and pistachio, and pecan and walnut cross-react the most.

Ara h 2 and Ara 6 are the best predictors of severe peanut allergy: a double-blind placebo-controlled study.

BACKGROUND: Component-resolved diagnostics offers a modern tool in peanut allergy, but studies applying consistently double-blind placebo-controlled challenges are lacking. We aimed to optimize diagnostics for moderate-to-severe peanut allergy in a birch-endemic region and to create an oral-peanut challenge with its allergen activity characterized. METHODS: We performed double-blind placebo-controlled peanut challenges for a referred sample of 6- to 18-year-olds with peanut sensitization or a high suspicion of peanut allergy, including anaphylaxis. We measured specific IgE (sIgE) to Ara h 1, 2, 3, 6, 8, and 9. Testing of allergen activity of the challenge products was by IgE microarray inhibition. RESULTS: Of the 102 patients, 69 were challenge positive: 25 (36%) had severe, 36 (52%) moderate, and 8 (12%) mild symptoms; 38 (37%) received adrenalin. SIgE to Ara h 6 AUC 0.98 (95%CI, 0.96-1.00) was the best marker of moderate-to-severe allergy. When sIgE to Ara h 2 and Ara h 6 was measured together, all (100%) severe reactions at low doses were successfully diagnosable. SIgE to Ara h 8 had no diagnostic value, AUC 0.42 (95%CI, 0.30-0.52). Both nonroasted and roasted peanut inhibited 100% of IgE binding to Ara h 1, 2, 3, and 6. Nonroasted peanut inhibited 87% of IgE binding to Ara h 8, roasted inhibited 30%. The products lacked Ara h 9 activity. CONCLUSION: Co-sensitization to Ara h 2 and Ara h 6 was associated with severe reactions distinguishing severe allergy from mild symptoms. SIgE to Ara h 8 added no diagnostic value. Component-resolved diagnostics reduce the need for oral challenges in peanut allergy.

Wheat allergy in children - new tools for diagnostics.

BACKGROUND: The detection of wheat-specific IgE in children often leads to a suspicion of wheat allergy, but little information is available on the most reliable wheat allergens for predicting clinical reactivity. OBJECTIVE: To evaluate the role of allergenic components of wheat in wheat allergy diagnostics. METHODS: One hundred and eight children (median age 1.5 years; range 0.6-17.3 years) with suspected wheat allergy underwent open or double-blinded, placebo-controlled oral wheat challenges. Responsiveness to different allergenic components of wheat was studied by skin prick tests and by determination of serum IgE antibodies using a semi-quantitative microarray assay. RESULTS: Thirty (28%) children reacted with immediate symptoms, and 27 (25%) with delayed symptoms to ingested wheat, whereas 51 (47%) children exhibited no reactions in oral wheat challenges. Positive IgE responses to any of the 12 allergenic components of wheat was seen in 93%, 41%, and 43% of those with immediate, delayed or no reactions to ingested wheat, respectively (P < 0.001 to P < 0.05 in every comparisons between those with immediate reactions and those with no reactions). Positive IgE responses to ≥5 different allergenic components improved significantly the diagnostic accuracy (with a positive likelihood ratio (LR+) of 5.10). Alpha-amylase inhibitors (AAI), in particular dimeric AAI 0.19 (LR+ 6.12), alpha-, beta-, and gamma-gliadins (LR+ from 3.57 to 4.53), and high-molecular-weight (HMW) glutenin subunits (LR+ 4.37) were the single allergenic components of wheat differentiating most effectively those with immediate symptoms from those who did not exhibit any reactions. CONCLUSIONS AND CLINICAL RELEVANCE: Wheat allergy diagnostics is difficult, even using sophisticated component methods. Our results confirm earlier findings about gliadins and identify the dimeric AAI 0.19, as a relevant allergen in clinically reactive patients when compared to non-reactive subjects. The accuracy of wheat allergy diagnosis may be improved by measuring IgE responses to several components of wheat.

The high molecular weight glutenin subunit Bx7 allergen from wheat contains repetitive IgE epitopes.

BACKGROUND: Wheat is one of the most common food allergen sources for children and adults. The aim of this study was to characterize new wheat allergens using an IgE discovery approach and to investigate their IgE epitopes. METHODS: A cDNA expression library representing the wheat transcriptome was constructed in phage lambda gt11 and screened with IgE antibodies from wheat food allergic patients. IgE-reactive cDNA clones coding for portions of high molecular weight (HMW) glutenin subunits were identified by sequence analysis of positive clones. IgE epitopes were characterized using recombinant fragments from the HMW Bx7 and synthetic peptides thereof for testing of allergic patients' sera and in basophil degranulation assays. RESULTS: We found that the major IgE-reactive areas of HMW glutenins are located in the repetitive regions of the protein and could show that two independent IgE-reactive fragments from HMW Bx7 contained repetitive IgE epitopes. CONCLUSIONS: Our results demonstrate that IgE antibodies from wheat food allergic patients can recognize repetitive epitopes in one of the important wheat food allergens. Recombinant HMW Bx7 may be included into the panel of allergens for component-resolved diagnosis of wheat food allergy.

True adherence with the Turbuhaler in young children with asthma.

OBJECTIVE: To investigate true adherence with a dry powder inhaler, the Turbuhaler (TBH), in children with asthma. True adherence was calculated by multiplying adherence to treatment with inhaler competence, that is correct use of the inhaler. PATIENTS AND DESIGN: In an 18-month study, children aged 5-10 years with asthma received twice daily budesonide via a TBH. Parents and children were trained in the correct use of the inhaler before the study started. For each inhalation, peak inspiratory flow through the TBH (PIF(TBH)) was recorded with an electronic pneumotachograph. The PIF(TBH) recordings were used to calculate true adherence for the first and last 45-day periods in the study by multiplying adherence in using the device (percentage of days with PIF(TBH) recordings) with inhaler competence (correct use of inhaler defined as PIF(TBH) values >40 l/min). MAIN OUTCOME MEASURES: True adherence, adherence, inhaler competence and PIF(TBH). RESULTS: 115 children were treated. The mean (morning and evening) true adherence during the first 45 days was 81.6% (range 78.1-86.4%) and during the last 45 days 57.4% (44.0-66.9%). Mean adherence was 86.0% and 59.3%, whereas mean inhaler competence was 94.7% and 96.2%, respectively. Thus the decline in true adherence was due to the decline in adherence. The largest decline in true adherence occurred in older children. CONCLUSIONS: True adherence with budesonide TBH treatment decreased significantly during the 18-month study due to a decrease in adherence. Inhaler competence with the correct use of the budesonide TBH was high and unchanged over the study period.

Cow's milk allergy as a predictor of bronchial hyperresponsiveness and airway inflammation at school age.

BACKGROUND: Cow's milk allergy (CMA) has been found to be associated with an increased incidence of asthma at school age. However, prospective population-based studies of CMA and the development of airway inflammation and bronchial hyperresponsivess (BHR) are lacking. OBJECTIVE: The aims of this study was to evaluate CMA as a risk factor for BHR and airway inflammation presented later in childhood. METHODS: We followed prospectively 118 children with CMA and invited them to a clinical visit at a mean age of 8.6 years including the measurement of exhaled nitric oxide (FE(NO) ) and bronchial challenge with histamine. Ninety-four patients and 80 control subjects from the same cohort participated. RESULTS: At school age, children with a history of CMA had higher FE(NO) levels (P=0.0009) and more pronounced responsiveness to histamine (P=0.027) than their controls. Stratified analysis showed a significant difference only in IgE-positive CMA. Multinomial logistic regression analysis showed that IgE-positive CMA [odds ratio (OR) 3.51; 95% confidence intervals (CI) 1.56-7.90; P=0.002] and a history of wheeze during the first year of life (OR 2.81; 95% CI 1.16-6.84; P=0.023) were independent explanatory factors for increased FE(NO) , and IgE-positive CMA (OR 3.37; 95% CI 1.03-10.97; P=0.044) and parental smoking (OR 3.41; 95% CI 1.14-10.22; P=0.028) for increased BHR, whereas for IgE-negative CMA, no associations with FE(NO) or BHR were found. In the CMA group, those exposed to CM very early at the maternity hospital, had less BHR (P=0.002). CONCLUSIONS: Compared with their controls, children with a history of IgE-positive CMA show signs of airway inflammation, expressed as higher FE(NO) , and more pronounced bronchial responsiveness to histamine at school age. In contrast to IgE-negative CMA, IgE-positive CMA is a significant predictor of increased FE(NO) and BHR at school age. Very early exposure to CM was associated with less BHR.

Clinical findings associated with abnormal lung function in children aged 3-26 months with recurrent respiratory symptoms.

AIM: To evaluate whether there are any associations between parentally reported symptoms, clinical findings and lung function in young children with recurrent lower respiratory tract symptoms. METHODS: In 2000-2003, 148 children, aged 3-26 months, with recurrent lower respiratory tract symptoms underwent physical examination, investigation of a chest radiograph, whole body plethysmography and skin prick testing to common food and inhalant allergens. RESULTS: Lung function was considered abnormal (i.e. functional residual capacity z-score of > or =1.65 and/or specific conductance z-score of < or =-1.65) in 83 (56%) children. Findings of increased work of breathing (p < 0.001) and nonspecific noisy breathing sounds (p < 0.001) in the physical examination, as well as an abnormal chest radiograph (p = 0.028) were independently associated with abnormal lung function, explaining up to 34% of the variation in lung function. In contrast, parentally reported respiratory symptoms, environmental exposures or atopic trait were not associated with lung function abnormalities. CONCLUSION: The results of this study emphasize the importance of the meticulous clinical examination in the evaluation of early childhood respiratory disorders. As physical examination alone cannot predict lung function abnormalities reliably in preschool children with troublesome respiratory symptoms, lung function testing may be considered in such patients to obtain additional objective information.

Effects of inhaled corticosteroids on metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 in the airways of asthmatic children.

BACKGROUND: The effects of corticosteroids on the level and expression of matrix metalloproteinase-8 (MMP-8; collagenase-2) and tissue inhibitors of metalloproteinases (TIMPs) in airway tissue are poorly characterized in vivo. METHODS: We compared MMP-8 and TIMP-1 levels in induced sputum and their expression in airway inflammatory cells of healthy children (n = 27) and of children with newly diagnosed asthma with mild (n = 20) or moderate symptoms (n = 19), before and after 6 months of treatment with inhaled budesonide. RESULTS: At baseline, MMP-8 was higher in asthmatic children with moderate symptoms, TIMP-1 was lower and the MMP-8/TIMP-1 ratio was higher in both groups of asthmatic children compared with controls. Inhaled budesonide increased TIMP-1 levels in both groups of asthmatic children and normalized the MMP-8/TIMP-1 ratio, and this paralleled the improvement in forced expiratory volume in 1 s in children with mild symptoms. At baseline, asthmatic children had significantly more MMP-8-positive macrophages than control children, whereas the number of TIMP-1-positive macrophages was almost the same. Budesonide decreased the percentage of MMP-8-positive macrophages and increased that of TIMP-1-positive macrophages; these changes were significant in asthmatic children with mild symptoms. CONCLUSIONS: Inhaled budesonide normalized the MMP-8/TIMP-1 ratio in asthmatic children by upregulation of TIMP-1 production and downregulation of MMP-8 production by airway macrophages. This change may be a biochemical marker of an effect on airway inflammation and possibly of an ongoing remodeling process that should be further investigated using biopsy specimens.

Budesonide improves decreased airway conductance in infants with respiratory symptoms.

OBJECTIVE: Inhaled corticosteroids (ICS) are commonly used to treat wheezing disorders in children, but few studies have investigated the effect of ICS on lung function in infants. We evaluated the efficacy of inhaled budesonide for decreased specific airway conductance (sGaw) as an indication of bronchial obstruction in very young children with recurrent cough and/or wheeze. PATIENTS, DESIGN AND INTERVENTIONS: Functional residual capacity (FRC) and sGaw of steroid-naive children aged 3-26 months with respiratory symptoms were measured using an infant whole-body plethysmograph. Clinically indicated bronchoscopy was performed in 79% of the patients to exclude anatomical abnormalities before randomisation. Children with abnormal lung function and respiratory symptoms were randomised into two treatment groups, receiving either inhaled budesonide (400 microg/day) or placebo with NebuChamber for 6 weeks. Inhaled terbutaline 0.25 mg/dose was used as a rescue medication. Lung function measurements were repeated after 6 weeks. MAIN OUTCOME MEASURE: Lung function. RESULTS: 44 children with a median age of 11.3 months (range 3.7-25.9) completed the study. Median sGaw improved from a z score of -3.6 to -1.2 (p<0.001) in the budesonide group and from -3.2 to -2.6 (p = 0.033) in the placebo group; between group difference p = 0.014. Improvement in sGaw was more pronounced in children with atopy (p = 0.017). Symptom-free days increased in both the budesonide and placebo groups with no difference between groups. CONCLUSION: Treatment with inhaled budesonide for 6 weeks improved sGaw in young children with chronic cough or wheeze and bronchial obstruction.

Effect of adenoidectomy on respiratory function: a randomised prospective study.

OBJECTIVE: Risk of childhood asthma is increased in children with recurrent otitis media. This may be associated with recurrent respiratory tract infections in these children, but the role of adenoidectomy, a frequent operation during childhood, is unknown. Therefore, the role of adenoidectomy in the development of atopy and respiratory function changes characteristic of asthma was evaluated. DESIGN: Randomised controlled study. SETTING: Tertiary care centre. PATIENTS: 166 children aged 12-48 months who had recurrent or persistent otitis media and who were followed-up for 3 years after randomisation. INTERVENTION: Randomisation to undergo insertion of tympanostomy tubes with or without adenoidectomy. MAIN OUTCOME MEASURES: The primary outcome measure was exercise-induced bronchoconstriction as evaluated by impulse oscillometry. The secondary outcome measures were bronchial inflammation as evaluated by exhaled nitric oxide and atopy as evaluated by skin prick tests. During the 3-year follow-up period otitis media episodes were documented in patient diaries. RESULTS: Adenoidectomy did not significantly influence baseline lung function, exercise-induced bronchoconstriction, exhaled nitric oxide concentration, the development of positive skin prick tests, or doctor-diagnosed asthma. Adenoidectomy did not significantly prevent otitis media. Recurrent otitis media (>or=4 episodes) during the first follow-up year was associated with an abnormal exercise-induced bronchoconstriction (OR 6.62, 95% CI 1.27 to 34) and an elevated exhaled nitric oxide concentration (OR 3.26, 95% CI 0.98 to 10.8) regardless of adenoidectomy. CONCLUSIONS: Adenoidectomy did not promote asthma or allergy. Recurrent respiratory tract infections during early childhood are associated with the risk of bronchial hyper-reactivity.

Bronchial response pattern of antigen presenting cells and regulatory T cells in children less than 2 years of age.

BACKGROUND: In early childhood, the ability to mount protective immune responses in the airways is impaired, with increased risk of allergic sensitisation to inhaled allergens. Antigen presenting cells (APC) and regulatory T cells (Treg) are important modifiers of T cell immunity but little is known about their distribution in bronchial mucosa at this age. Here the subset distribution of APC and the appearance of Foxp3(+) Treg and bronchus associated lymphoid tissue (BALT) were examined immunohistochemically in children less than 2 years of age with chronic asthma-like symptoms of the lower airways. METHODS: Immunophenotyping was performed in situ on bronchial biopsy specimens obtained from 45 infants, 4-23 months of age, under investigation for airway disease. RESULTS: A well developed HLA-DR(+) network of APC was present in all samples, approximately 50% of the cells being CD68(+) macrophages and the remainder various subsets of dendritic cells. The density of HLA-DR(+) cells increased significantly with age but was not related to atopy, clinical symptoms or lung function. Comparing the density of APC subsets and clinical parameters, only the number of intraepithelial CD1a(+) dendritic cells was significantly increased in infants who had recently suffered a respiratory infection. BALT structures were identified in 22 children, with no relation to lung function, atopic status or human rhinovirus positivity. Plasmacytoid dendritic cells and Foxp3(+) Treg were located primarily within these isolated lymphoid follicles. CONCLUSION: A bronchial network of dendritic cells and macrophages develops quite rapidly after birth, apparently independent of clinical symptoms or atopy. The high frequency of BALT structures containing putative tolerogenic dendritic cells and Treg suggests that these lymphoid follicles play an important role in bronchial immune homeostasis during infancy.

Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study).

OBJECTIVE: To compare the effect of inhaled budesonide given daily or as-needed on mild persistent childhood asthma. Patients, design and INTERVENTIONS: 176 children aged 5-10 years with newly detected asthma were randomly assigned to three treatment groups: (1) continuous budesonide (400 microg twice daily for 1 month, 200 microg twice daily for months 2-6, 100 microg twice daily for months 7-18); (2) budesonide, identical treatment to group 1 during months 1-6, then budesonide for exacerbations as needed for months 7-18; and (3) disodium cromoglycate (DSCG) 10 mg three times daily for months 1-18. Exacerbations were treated with budesonide 400 microg twice daily for 2 weeks. MAIN OUTCOME MEASURES: Lung function, the number of exacerbations and growth. RESULTS: Compared with DSCG the initial regular budesonide treatment resulted in a significantly improved lung function, fewer exacerbations and a small but significant decline in growth velocity. After 18 months, however, the lung function improvements did not differ between the groups. During months 7-18, patients receiving continuous budesonide treatment had significantly fewer exacerbations (mean 0.97), compared with 1.69 in group 2 and 1.58 in group 3. The number of asthma-free days did not differ between regular and intermittent budesonide treatment. Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed. The latter was associated with catch-up growth. CONCLUSIONS: Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed. The dose of ICS could be reduced as soon as asthma is controlled. Some children do not seem to need continuous ICS treatment.

Airway responsiveness: associated features in infants with recurrent respiratory symptoms.

Increased airway responsiveness (AR) is one of the main pathophysiological manifestations of asthma. The present study aimed to define the clinical features associated with increased AR in infants with recurrent lower respiratory tract symptoms. AR was evaluated by performing a novel dosimetric methacholine challenge test. Increased AR to methacholine, defined as a methacholine dose of < or =0.90 mg producing a 40% fall (PD(40)) in the maximal flow at functional residual capacity (V'(max,FRC)), was associated with atopy (odds ratio (OR) 4.1; 95% confidence interval (CI) 1.3-13.3), a history of physician-confirmed wheezing with respiratory syncytial virus (OR 32.9; 95% CI 2.5-428.8) or of a nonspecified aetiology (OR 4.9; 95% CI 1.1-22.5), functional residual capacity z-score > or =2 (OR 36.8; 95% CI 2.9-472.6), and V'(max,FRC) z-score (OR 0.5; 95% CI 0.2-0.9) at baseline, when compared with infants with only mild or no responsiveness to methacholine (PD(40) V'(max,FRC) >0.90 mg). In conclusion, in recurrently symptomatic infants, increased airway responsiveness is associated with reduced baseline lung function, an atopic trait of the child, a history of physician-confirmed wheeze and viral aetiology of wheeze. Future intervention studies are needed to confirm the role of airway responsiveness in respiratory morbidity during infancy.

Induced sputum in children with newly diagnosed mild asthma: the effect of 6 months of treatment with budesonide or disodium cromoglycate.

BACKGROUND: There are few controlled studies on the effects of anti-inflammatory treatment on airway inflammation in newly diagnosed childhood asthma. METHODS: Sixty children with newly diagnosed mild persistent asthma, 5-10 years of age, and 17 healthy control subjects were studied. Asthmatic children were randomized into an open study with two treatment groups: (1) budesonide 400 microg twice daily for 1 month, 200 microg twice daily for 5 months and (2) disodium cromoglycate (DSCG) 10 mg three-times daily for 6 months. All exacerbations were treated with budesonide 400 microg twice daily for 2 weeks. Symptoms and lung function were recorded throughout the study. RESULTS: Sputum induction was safe and the overall success rate was 71%. This improved with age and decreased after treatment. At baseline, the asthmatic children had more eosinophils in blood (0.26 vs 0.18 x 10(9)/l, P = 0.03) and sputum (1.1 vs 0.0 %, P = 0.0001) than the control subjects. The numbers of sputum eosinophils correlated with bronchial responsiveness (R = -0.58, P = 0.0002). Eosinophils were higher in children with atopic asthma than with nonatopic asthma (P < 0.0001), and in children with a history wheezing than in children without wheezing (P = 0.02). Six months of budesonide treatment, but not of DSCG, improved lung function (P = 0.007), decreased symptoms (P = 0.007) and sputum eosinophils (P = 0.003). The effects of budesonide were pronounced in children with intense sputum eosinophilia (>3%). CONCLUSION: Sputum eosinophilia is present in children with newly diagnosed mild persistent asthma. Treatment with inhaled budesonide, but not with DSCG, decreases sputum eosinophils along with clinical and functional improvement.

Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma.

BACKGROUND: Respiratory function and airway inflammation can be evaluated in preschool children with special techniques, but their relative power in identifying young children with asthma has not been studied. This study was undertaken to compare the value of exhaled nitric oxide (FE(NO)), baseline lung function, and bronchodilator responsiveness in identifying children with newly detected probable asthma. METHODS: Ninety six preschool children (age 3.8-7.5 years) with asthmatic symptoms or history and 62 age matched healthy non-atopic controls were studied. FE(NO) was measured with the standard online single exhalation technique, and baseline lung function and bronchodilator responsiveness were measured using impulse oscillometry (IOS). RESULTS: Children with probable asthma (n=21), characterised by recent recurrent wheeze, had a significantly higher mean (SE) concentration of FE(NO) than controls (22.1 (3.4) ppb v 5.3 (0.4) ppb; mean difference 16.8 ppb, 95% CI 12.0 to 21.5) and also had higher baseline respiratory resistance, lower reactance, and larger bronchodilator responses expressed as the change in resistance after inhalation of salbutamol. Children with chronic cough only (n=46) also had significantly raised mean FE(NO) (9.2 (1.5) ppb; mean difference 3.9 ppb, 95% CI 0.8 to 7.0) but their lung function was not significantly reduced. Children on inhaled steroids due to previously diagnosed asthma (n=29) differed from the controls only in their baseline lung function. The analysis of receiver operating characteristics (ROC) showed that FE(NO) provided the best power for discriminating between children with probable asthma and healthy controls, with a sensitivity of 86% and specificity of 92% at the cut off level of 1.5 SD above predicted. CONCLUSIONS: FE(NO) is superior to baseline respiratory function and bronchodilator responsiveness in identifying preschool children with probable asthma. The results emphasise the presence of airway inflammation in the early stages of asthma, even in young children.

Acceptability, reproducibility, and sensitivity of forced expiratory volumes and peak expiratory flow during bronchial challenge testing in asthmatic children.

OBJECTIVES: To compare the acceptability, reproducibility, and sensitivity of spirometric outcome measures of airway caliber during challenge testing in children. DESIGN: FEV(1), forced expiratory volume in 0.75 s, forced expiratory volume in 0.5 s, and peak expiratory flow (PEF) were recorded during stepwise dosimetric histamine challenge tests. The responses were compared, and the reproducibility at baseline and from duplicate measurements at each challenge step was determined. PATIENTS: One hundred five children with newly diagnosed asthma, aged 5 to 10 years. RESULTS: Compared to PEF, FEV(1) showed better baseline reproducibility (p = 0.002) and higher sensitivity (p < 0.0001) during challenge testing, determined as the change normalized to the baseline variation, while the forced expiratory volumes were not significantly different in these respects. During challenge testing in subjects with acceptable flow-volume tracings, paired recordings of FEV(1) agreed within 0.1 L in 85% and within 0.2 L in 93% of measurements. During challenge testing, the reproducibility of FEV(1) measurements was not better than that of the other indexes. Failure to exhale long enough precluded the use of FEV(1) in 16 of the children, particularly the youngest children. CONCLUSIONS: The results demonstrated that the recently published guidelines for FEV(1) measurements during challenge tests can be applied to children. During challenge tests in asthmatic children, the advantage of the shorter fractions of forced expiratory volume was that they were more often acceptably recorded than FEV(1), while they showed as good reproducibility and were also equally sensitive in assessing changes in airway obstruction.