Diagnosing atopic dermatitis in infancy using established diagnostic criteria: a cohort study.

BACKGROUND: Diagnosing atopic dermatitis (AD) in infants is challenging. OBJECTIVES: To determine the incidence and persistence of eczema and AD in infants using the UK Working Party (UKWP) and Hanifin and Rajka (H&R) criteria. METHODS: A cohort of 1834 infants was examined clinically at 3, 6 and 12 months of age. AD was diagnosed by UKWP (3, 6 and 12 months) and H&R (12 months) criteria. Logistic regression models were used to assess the relationship between AD and eczema. RESULTS: Eczema was observed in 628 (34·2%) infants (n = 240, n = 359 and n = 329 at 3, 6 and 12 months, respectively), with AD diagnosed in 212 (33·7%) infants with any eczema and in 64/78 (82%) infants with eczema at all three visits. The odds of AD were lower with first presentation of eczema at 6 [odds ratio (OR) 0·33, 95% confidence interval (CI) 0·22-0·48] or 12 months (OR 0·49, 95% CI 0·32-0·74) than at 3 months, and higher in infants with eczema at three (OR 23·1, 95% CI 12·3-43·6) or two (OR 6·5, 95% CI 4·3-9·9) visits vs. one visit only. At 12 months, 156/329 (47·4%) fulfilled the UKWP and/or H&R criteria; 27 (8%) fulfilled the UKWP criteria only and 65 (20%) only the H&R criteria. Of the 129 infants who fulfilled the H&R criteria, 44 (34·1%) did not meet the itch criterion. CONCLUSIONS: Used in combination and at multiple timepoints, the UKWP and H&R criteria for AD may be useful in clinical research but may have limited value in most other clinical settings.

Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy.

BACKGROUND: Loss-of-function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. OBJECTIVES: To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy. METHODS: FLG mutations were analysed in 1836 infants in the Scandinavian population-based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age. RESULTS: FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3 g m-2  h-1 ) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95-4·28; P < 0·001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69-10·68) vs. 8·24 (95% CI 7·97-8·15), P < 0·01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25-2·80; P = 0·002 and OR 2·44, 95% CI 1·51-3·95; P < 0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04-2·22; P = 0·028 and OR 1·74, 95% CI 1·17-2·57; P = 0·005). FLG mutations were associated with eczema and AD in infancy. CONCLUSIONS: FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months.

Telomere length was similar in school-age children with bronchopulmonary dysplasia and allergic asthma.

AIM: Inflammation is a major factor in the pathophysiology of bronchopulmonary dysplasia (BPD), and it contributes to accelerated telomere shortening and cellular ageing. This study aimed to determine its effect on telomere length and lung function in school-aged children born preterm with BPD. METHODS: We examined 29 children with BPD, born preterm in Stockholm county 1998-99, along with 28 children with allergic asthma born at term matched for age and gender. At 10 years of age, we measured relative telomere length (RTL) in blood by quantitative polymerase chain reaction, lung function by spirometry and inflammation by fractional exhaled nitric oxide and blood cytokines. RESULTS: RTL was not different in preterm born with BPD compared to term born children with asthma. The gender effect was strong in both groups; girls had significantly longer median RTL than boys (1.8 versus 1.5, p < 0.01). Short RTL was associated with low forced expiratory flow, also after adjusting for gender, but was not affected by severity of BPD or ongoing inflammation. CONCLUSION: Telomere length was similar in 10-year-old children born preterm with a history of BPD and term born children with allergic asthma. However, impaired lung function and male gender were associated with short telomeres.

Allergy testing in children with persistent asthma: comparison of four diagnostic methods.

BACKGROUND: Multiple allergic sensitizations are common in persistent childhood asthma, and thorough assessment of allergy is crucial for optimal care of these children. Microarray testing offers opportunities for improved sIgE characterization, which has been projected to be useful in the management of multisensitized patients. OBJECTIVE: The aim of this study was to investigate the accuracy and information obtained by two microarray platforms applied on a well-characterized pediatric asthma cohort. METHODS: Seventy-one children were recruited from a nationwide Swedish study on severe childhood asthma. Severe (n = 40) and controlled (n = 31) asthmatics were assessed for allergic sensitization by two microarray systems (Microtest and ISAC) and by two standard diagnostic methods (ImmunoCAP and skin prick test). Data on clinical history, physical examination, spirometry, asthma control test, and doctor's diagnosis were collected. Results from the four diagnostic methods were analyzed and compared. RESULTS: A high prevalence of allergic sensitization was observed in this cohort. The pairwise concordance between two methods was 90-92% independently of methods compared. The sensitivity of the four methods against doctor's diagnosis was 0.77-0.88, and the specificity was 0.97-0.99. Microarray methods provided new information in 47% of the sensitized children in comparison with results obtained by standard diagnostic methods. CONCLUSION: The high prevalence of food and respiratory sensitization supports the clinical guideline recommendation that allergies should be evaluated in all children with suspected asthma. The microarray platforms studied here demonstrated acceptable accuracy and provided refined IgE characterization in 47% of the patients compared to standard extract-based methods.

IgE antibodies to animal-derived lipocalin, kallikrein and secretoglobin are markers of bronchial inflammation in severe childhood asthma.

BACKGROUND: Component-resolved allergy diagnostics enables the detection of crossreactive or species-specific allergen components. This study analysed Immunoglobulin E (IgE) profiles to single allergen components in relation to bronchial inflammation in severe childhood asthma. METHODS: Ninety-five schoolchildren were assessed, 39 with controlled mild-to-moderate asthma and 56 uncontrolled severe asthmatics. Allergen components (n = 111) of food allergens, pollen and perennial aeroallergens were analysed using an immunosolid-phase allergen chip. Blood eosinophils (10(9) × l(-1)), bronchial inflammation (FeNO, ppb), lung function (FEV(1)%) and bronchial hyper-responsiveness (BHR) (dose-response slope of methacholine challenge) were measured. RESULTS: A specific IgE response to more than three animal-derived components--lipocalin (nMus m 1, rEqu c 1, Fel d 4, rCan f 1, 2), kallikrein (rCan f 5) and secretoglobin (rFel d 1)--was more common among severe asthmatics compared to children with controlled asthma (n = 14 vs n = 3, P = 0.030). These subjects also displayed higher blood eosinophils (0.65 vs 0.39, P = 0.021), higher Fractional exhaled nitric oxide (38 ppb vs 25 ppb, P = 0.021) and increased BHR (112 vs 28, P = 0.002) compared to other severe asthmatics positive to fewer lipocalin/kallikrein/secretoglobin components. Among all sensitized subjects, there were correlations between specific IgE levels for rFel d 4 and nMus m 1 (r = 0.751, P ≤ 0.001) and for rFel d 4 and rEqu c 1 (r = 0.850, P ≤ 0.001). CONCLUSION: Multi-sensitization towards lipocalin, kallikrein and secretoglobin components is associated with increased bronchial inflammation in severe asthmatics. In addition, crossreactive patterns were observed between different lipocalin components.

The clinical benefit of evaluating health-related quality-of-life in children with problematic severe asthma.

AIM: To evaluate health-related quality-of-life (HR-QoL) and the asthma control test (ACT) in children with problematic severe asthma and those with controlled asthma and to identify whether clinical characteristics show correlations with these measurements. METHODS: This multicentre cross-sectional study included 93 children in total, 54 with problematic severe asthma and 39 age-matched with controlled asthma. Subjects completed the Paediatric Asthma Quality-of-Life Questionnaire as well as a standardized health questionnaire and the ACT. Objective measurements of exhaled nitric oxide, specific sensitization, pulmonary function and bronchial hyper-responsiveness to methacholine were also taken. RESULTS: HR-QoL was reduced in children with problematic severe asthma (5.4 vs. 6.7, p < 0.001), particularly for girls (5.1 vs. 5.6 for boys, p = 0.02), and their ACT scores were also lower (17 vs. 23, p < 0.001) compared with those of subjects with controlled asthma. A HR-QoL score <6.2 discriminated problematic severe asthma from controlled asthma with 85% sensitivity and 97% specificity, as did the ACT score <20 (79% sensitivity and 94% specificity). Objective measures and other clinical characteristics were weakly associated with HR-QoL or ACT score. CONCLUSION: Subjective measurements of HR-QoL and asthma control are both equally useful in differentiating children with problematic severe asthma from those with controlled asthma.