Is rhinitis alone or associated with atopic eczema a risk factor for severe asthma in children?

The objective of this study was to evaluate the role of rhinitis (R) and atopic eczema (E) on asthma severity among asthmatic (A) schoolchildren identified by the International Study of Asthma and Allergies in Childhood written questionnaire (WQ). WQ was applied to parents of 6–7-yr-old schoolchildren (SC, n = 3033), and to adolescents (AD, 13–14 yr old, n = 3487), living in São Paulo, Brazil. An affirmative response to ‘has your child/have you had wheezing/whistling in the last year’ identified those with A, and an affirmative response to ‘the last 12 months has your child/have you had sneezing/runny/blocked nose when he/she you did not have a cold/flu?’ identified those with R. Subjects with an affirmative response to ‘has your child/have you had this itchy rash at any time in the past 12 months?’ were identified as having E. Subjects who had R associated with A were identified as AR and those with A associated with R and E as ARE. A who had at least two affirmative responses to questions for asthma severity: speech disturbance, more than four acute attacks, sleep disturbance, and wheezing with exercise were defined as having severe asthma. 22.1% AD and 24.3% SC were identified as A; 47.1% of those AD and 42.0% SC had AR and 10.0% of those AD and 12.8% of SC had ARE. Considering ARE, AR and A groups, speech disturbance during an acute episode of asthma was significantly higher among ARE AD (20.0% vs. 11.5% vs. 8.7%, p < 0.05), and ARE SC (22.1% vs. 13.9% vs. 10.5%, p < 0.05) in comparison with A. Likewise, more than four acute attacks in the last year was significantly higher among ARE AD (24.0% vs. 14.0% vs. 10.5%, p < 0.05) and ARE SC (32.6% vs. 19.4% vs. 12.8%, p < 0.05) as the frequency of sleep disturbance due to wheezing, for AD (61.3% vs. 42.0% vs. 38.4%, p < 0.05) and SC (77.9% vs. 67.3% vs. 58.4%, p < 0.001) and for ‘wheezing associated with exercise’ for AD (72.0% vs. 47.5% vs. 39.9%, p < 0.001) and SC (36.8% vs. 31.4% vs. 14.1%, p < 0.001). Prevalence of severe asthma was higher among ARE AD (57.3% vs. 31.9% vs. 27.0%, p < 0.05) and ARE SC (52.6% vs. 36.9% vs. 22.5%). In patients with A, the presence of R or E are risk factors for severe asthma, and both together (R and E) are a higher risk.     

Trends in the prevalence and severity of asthma, rhinitis and atopic eczema in 6- to 7- and 13- to 14-yr-old children from the north-east of England

The aims of the present study were to assess time trends in symptoms of asthma, rhinitis and atopic eczema among children in the north-east of England. Two cross- sectional surveys 6 yr apart, 6- to 7- and 13- to 14 yr of age, using the International Study of Asthma and Allergies in Childhood, core questionnaire were performed. There was a general increase in symptoms for all the three conditions in both the age groups. In the age group 6- to 7 yr, the increase was generally the same in boys and girls, while in the age group 13- to 14 yr, the increase was generally more marked among boys. In the younger age group, indices related to lifetime diagnosed ever had asthma and having hay fever increased in girls but not in boys, while indices related to lifetime diagnosis of ever having eczema increased in boys and girls. In the older age group, indices related to lifetime diagnosis of ever had asthma slightly increased in boys but did not change in girls, while lifetime diagnosis of ever having hay fever slightly decreased in girls but did not change in boys. The prevalence of lifetime diagnosis of ever having eczema increased in boys and girls. Changes observed in the present study could be related to the changes in lifestyle or environmental factors, awareness or management of symptoms.     

Urinary eosinophil protein X in children with asthma: Influence of atopy and airway infections

It has been suggested that urinary eosinophil protein X (U‐EPX) can be used to monitor bronchial inflammation in childhood asthma. However, the influence of atopy and airway infections is not well elucidated. To determine the clinical value of measuring U‐EPX in children with asthma and to evaluate the influence of atopy and airway infections, U‐EPX was measured in 170 children with asthma (mean age 69 months, range 12–179 months), in 79 children with lower or upper respiratory tract infections (mean age 41 months, range 1–165 months), and in 64 controls. U‐EPX was elevated in children with acute asthma (median 132 µg/mmol of creatinine, quartiles 77–195 µg/mmol of creatinine, n = 51, p < 0.001) and chronic asthma (median 93 µg/mmol of creatinine; quartiles 46–149 µg/mmol of creatinine, n = 119, p < 0.01) compared with controls (median 54 µg/mmol of creatinine; quartiles 40–89 µg/mmol of creatinine, n = 39). Atopic children had higher levels of U‐EPX than non‐atopics with acute asthma (median 155 µg/mmol of creatinine, quartiles 113–253 µg/mmol of creatinine, n = 27, vs. median 102 µg/mmol of creatinine, quartiles 56–168 µg/mmol of creatinine, n = 24, p < 0.05), as well as with chronic asthma (median 110 µg/mmol of creatinine, quartiles 65–162 µg/mmol of creatinine, n = 63, vs. median 60 µg/mmol of creatinine, quartiles 39–123 µg/mmol of creatinine, n = 56, p < 0.01). In chronic asthma, children without atopy had levels of U‐EPX similar to values of controls; levels were similar in symptomatic and asymptomatic patients, and not influenced by treatment with inhaled corticosteroids. Moreover, U‐EPX levels were higher in children with pneumonia (median 207 µg/mmol of creatinine, quartiles 111–280 µg/mmol of creatinine, n = 35, p < 0.001), laryngitis (median 109 µg/mmol of creatinine, quartiles 65–161 µg/mmol of creatinine, n = 24, p < 0.01), and rhinitis (median 172 µg/mmol of creatinine, quartiles 123–254 µg/mmol of creatinine, n = 19, p < 0.001) than in controls (median 62 µg/mmol of creatinine, quartiles 41–93 µg/mmol of creatinine, n = 64). There was significant overlap among all groups of children with disease, as well as between children with disease and controls. Hence, U‐EPX may reflect differences in eosinophil involvement and activation between children with atopic and non‐atopic asthma, but the individual spread within groups and the influence of airway infections limits the clinical value of U‐EPX in childhood asthma.     

Wheeze in children: the impact of parental education on atopic and non‐atopic symptoms

de Meer G, Reijneveld SA, Brunekreef B. Wheeze in children: the impact of parental education on atopic and non‐atopic symptoms.
Pediatr Allergy Immunol 2010: 21: 823–830.
© 2009 John Wiley & Sons A/S There is conflicting evidence for the relationship between parental socioeconomic position and their children’s asthma. The aim of this study was to investigate relationships between parental education and respiratory symptoms in their children, distinguishing atopic and non‐atopic symptoms. A cross‐sectional survey among 3262 elementary school children (age 8–13) was performed; data on parental education were obtained for 3213 children. Parents completed a questionnaire on their child’s allergic and respiratory symptoms, and potential explanatory variables including family history, indoor environment, and the child’s medical history. Subsets of children were tested for atopy (n = 1983), lung function (n = 2325), and airway hyperresponsiveness (AHR) (n = 880). Logistic regression was used to assess relationships of health outcomes with parental education. A high parental education was associated with an increased risk of atopic sensitization to indoor allergens (OR 1.31, 95% CI 1.02; 1.69). Studied explanatory variables did not influence the relationship. In contrast, a high parental education protected children from wheeze (OR 0.77, 95% CI 0.61; 0.97). This only applied to non‐atopic wheeze (OR 0.65, 95% CI 0.43; 0.99) and not to atopic wheeze (OR 0.89, 95% CI 0.60; 1.31). The protection from non‐atopic wheeze in children of highly educated parents declined after adjustment for household smoking and breastfeeding (OR 0.96, 95% CI 0.58; 1.57). Similar results were observed for non‐atopic and atopic rhinitis. We conclude that children from highly educated parents are protected from non‐atopic respiratory symptoms, which is largely explained by a lower rate of household smoking and a higher rate of breastfeeding.     

High birth weight, asthma and atopy at the age of 16 yr

The association between high birth weight and asthma has been suggested. The Northern Finland Birth Cohort 1986, a longitudinal cohort originally including 9479 participants, has been followed up since birth until the age of 16 yr. Using the data of this study, we analyzed the association of high birth weight with asthma and atopic sensitization at the age of 16 yr. The analysis included the 5995 subjects with complete skin prick test data and the 5500 subjects with data on doctor-diagnosed asthma (written questionnaire) at the age of 16 yr. Atopy was defined as at least one positive skin prick test reaction, which definition was also used to separate atopic and non-atopic asthma. There was a significant association between high birth weight (>4510 g) and asthma among the atopic subjects (OR 2.40, 95% CI 1.33–4.32). When looking at atopy, the highest risk was observed among the subjects with highest birth weight category (>4510 g) (OR 1.44, 95% CI 1.05–1.97) and the adjacent (4200–4500 g) birth weight category (OR 1.24, 95% CI 1.01–1.53), when compared with the reference category (2500–3340 g). Our results support the notion that high birth weight is associated with an increased risk of asthma and suggest that the association is mostly explained by an increased risk of atopy. The biological mechanisms behind the associations are unknown, but they could be related to obesity.     

Inflammation markers and symptom activity in children with bronchial asthma. Influence of atopy and eczema

Background. Eosinophil cationic protein (ECP) has been reported to reflect the eosinophil inflammatory activity in asthma. However, the relative impact of asthma symptoms and atopic eczema upon serum (s)-ECP in asthmatic children has not been established.
Objectives. To examine s-ECP levels and s-myeloperoxidase (MPO) in relation to asthma symptoms and atopic eczema in asthmatic children.
Methods. S-ECP and s-MPO were assessed in relation to symptom activity, lung function, exercise induced bronchoconstriction and bronchial responsiveness in 101 children; median age 9 years, range 1-16 years; with moderate to severe asthma, admitted to Voksentoppen Center.
Result. S-ECP was significantly higher in children with persistent compared to episodic or no asthma symptoms in the past four weeks, S-ECP was also higher in children with atopic compared to non-atopic asthma, as well as in those with active compared to past history of no history of atopic eczema. SMPO was higher in children with persistent asthma symptoms, but did not differ in relation to atopy of eczema state. Persistent asthma symptoms had the greatest impact upon s-ECP levels, followed by atopy and active eczema.
Conclusion. S-ECP may be used in assessing symptom activity in asthmatic children, but with the realisation that active eczema and the presence of atopy may also influence levels.     

Allergy: a systemic disease? The HUNT and Young–HUNT study,Norway.

A systemic nature of allergic diseases has been hypothesized. As part of this discussion, we studied if adolescent allergic wheeze and increasing combinations of allergic organ involvements (lung, nose and skin) would also increase the reporting of other health problems (headache, muscle pain and abdominal pain). In addition, we studied if parental asthma was associated with adolescent clustering of allergic expressions and if parental asthma with additional health problems (headache or muscle pain) was associated with adolescent reporting allergy in combination with headache, muscle pain and abdominal pain. Adolescents 13–19 yr (n = 8817, 89%) participated in the Young–HUNT study, Norway, 1995–97. Parental data on asthma were eligible in n = 5620. Health and lifestyle were measured by questionnaires and interviews. Associations with additional health problems were significantly strengthened with combinations of wheeze and other allergic expressions. Odds Ratio for associations ‘wheeze only’, ‘wheeze and rhinitis’ and ‘wheeze, rhinitis and eczema’ were for headache 2.1, 3.4 and 3.7; for muscle pain 2.8, 3.2 and 4.9; for abdominal pain 3.6, 4.0 and 4.9. All p for trend were <0.010. Similar results were obtained when studying allergic wheeze; p for trend <0.001. Parental asthma was associated with clustering of adolescent allergic expressions, and parental asthma with headache or muscle pain was significantly associated with reported allergy combined with similar health problems in their offspring. The results indicate that allergy may be expressed beyond organs commonly viewed as part of an allergic disease, and hence may support a hypothesis of a systemic nature of allergic diseases.     

PTGDR is not a major candidate gene for asthma and atopy in Chinese children

Airway sensitization requires the expression of prostanoid DP receptor in mice. Recent studies reported that polymorphisms in the gene encoding prostanoid DP receptor (PTGDR) were associated with asthma in White people and Black people, but this association could not be replicated among Latinos and Koreans. This study investigated the association between asthma‐related traits and six single nucleotide polymorphisms (SNPs) of PTGDR in Chinese children, consisted of 308 asthmatics and 368 non‐allergic controls. Plasma total and aeroallergen‐specific immunoglobulin E were measured by immunoassays. PTGDR SNPs were determined by multiplex SNaPshot? genotyping. All polymorphic markers followed Hardy–Weinberg equilibrium except G1044A in the controls (p = 0.021). The linkage disequilibrium (LD) scores for these SNPs were moderate to high, and in particular, T‐549C and C‐441T were in strong LD. Significant interethnic variations in PTGDR alleles and haplotypes (up to 41%) were found in our subjects when compared with White people or Latinos. Asthma diagnosis, atopy and aeroallergen sensitization did not differ among children with different PTGDR genotypes (p > 0.15 for all). Linear regression showed weakly significant associations between T‐197C and G1044A of PTGDR and spirometric variables. PTGDR haplotypes were not associated with asthma and atopy phenotypes (p > 0.09 for all). Our results do not support PTGDR to be a major candidate gene for asthma traits in Chinese children.     

Environmental and dietary risk factors for infantile atopic eczema among a Slovak birth cohort

Infantile atopic eczema (AE) is a risk marker for future asthma. This study assesses the contribution of modifiable exposures to infantile AE. If modifiable exposures contribute substantially to infantile AE, its prevention might be a sensible approach to asthma prevention. Pregnant women (n = 1978) were systematically recruited from maternity hospitals of the Slovak Republic; their birthed cohort of 1990 children were prospectively followed for 1 yr. Children's exposures to selected environmental and dietary factors were assessed via maternal questionnaires administered at delivery and 1 yr of age. A child was considered to have AE, based on physical examination (SCORAD index >2) or mother's report of a previous physician diagnosis. Multivariate logistic regression was used to calculate adjusted odds ratios and percent total regression scores (TRS) for each variable. At 1 yr of age 1326 (67%) of the children remained in the cohort and 207 (15.6%) developed AE. Various modifiable environmental and dietary exposures increased the likelihood of AE (ownership of cats; consumption of infant formula, eggs, and fish) while others decreased the likelihood of AE (ownership of livestock; exclusive breast feeding for > or =4 months). Overall, modifiable exposures contributed less to the TRS than did non-modifiable exposures (38% vs. 62%, respectively). The modifiable exposure category that contributed most to the TRS was infant feeding practices (27.5% TRS). Modifiable exposures -- especially those related to infant feeding practices -- significantly contribute to infantile AE, although modifiable factors contribute less overall than do non-modifiable exposures.     

Early environmental determinants of asthma risk in a high-risk birth cohort

Environmental exposures during early life have been suggested to have the greatest impact on childhood asthma. Our aim was to evaluate the risk factors associated with asthma at age 7 yr in a high-risk cohort that participated in a randomized controlled study on the primary prevention of asthma. Indoor exposures were characterized before birth and at 2 weeks, 4, 8, 12, 18, and 24 months after birth and again at 7 yr. Nasal scrapings for respiratory viruses were done at the same intervals during the first 2 yr. At age 7, the children were assessed by a pediatric allergist and had allergy skin tests. Logistic regression analysis was undertaken to evaluate the effect of exposures on asthma for the entire cohort with adjustment for group allocation. In addition to the lower risk of asthma in the intervention group, we found a higher prevalence of asthma at age 7 for males, those having a positive history of asthma in mother, father, or older siblings, for children residing in Winnipeg and for atopic subjects. Upon adjustment for intervention group assignment and baseline factors, significant environmental risk factors during year 1 included dog ownership and respiratory syncytial viral infection detected at 12 months while maternal smoking was protective. Dog ownership was a significant risk factor in year 2, but highly correlated with dog ownership in year 1. Indoor environmental exposures during year 7 were not associated with asthma at age 7. Maternal smoking at year 7 was associated with a reduced risk of asthma at 7 yr. Early-life exposures were more important determinants than those in later years. A 'window of opportunity' exists for intervention measures to be applied.     

Allergic conjunctivitis in children with asthma, rhinitis and eczema in a secondary outpatient clinic

Little evidence is available on the prevalence of allergic conjunctivitis in pediatric populations. The objective of this study was to assess the cumulative prevalence of allergic conjunctivitis in children with rhinitis, asthma and eczema in a secondary pediatric outpatient clinic. Children aged 5-15 yr referred during the period of 2002-2004 in whom allergic conjunctivitis, asthma, allergic rhinitis or eczema was diagnosed were included in a retrospective survey. At referral patient characteristics, history, symptoms, signs and results of type 1 allergy tests were entered into an electronic form. Four hundred and fifty-eight children with a mean age of 9.4 yr were studied. Of 316, 324 and 149 children with rhinitis, asthma or eczema, respectively, 133 (42%), 78 (24%) and 45 (30%) had concomitant allergic conjunctivitis. One hundred and thirty-seven (30%) had allergic conjunctivitis, of whom 133 (97%) also had allergic rhinitis, 77 (56%) asthma and 45 (33%) eczema. One hundred and twenty-five (91%) of the children with allergic conjunctivitis had positive allergy tests to one or more allergens, sensitization to house dust mites being more frequent in chronic allergic conjunctivitis than in acute allergic conjunctivitis (95% vs. 53%; p < 0.01). Sensitization to grass was more frequent in children with acute allergic conjunctivitis (78% vs. 57%; p = 0.03). In a secondary pediatric outpatient clinic allergic conjunctivitis is a frequent co-morbidity to allergic rhinitis and to asthma and eczema. Allergic conjunctivitis need to be included as an important co-morbidity in future guidelines on asthma, rhinitis and eczema management.     

Prevalence of specific allergic diseases in school children as related to parental atopy

BACKGROUND: Our objective was to investigate the influence of parental allergy on the manifestations and course of allergic disease in children. METHODS AND RESULTS: A total of 15,234 school children aged 6 and 9 years were evaluated by means of questionnaires completed by their parents in a cross-sectional survey conducted in Tokushima, Japan. The prevalence and relative risk ratio (RRR) for parental allergy in children with atopic dermatitis, asthma and allergic rhinitis were 6.4% (RRR 2.5), 3.2% (RRR 2.4) and 15% (RRR 2.4), respectively. The risk of atopic dermatitis was particularly high in children whose parent had atopic dermatitis, with an RRR of 2.8 (father) and 3.7 (mother). Children with a parental history of asthma also had a high risk of that disorder (RRR of father 5.3, mother 6.2). However, the risk of allergic rhinitis was no different in children with a parental history of allergic rhinitis or from children with a parental history of asthma and atopic dermatitis. A history of allergic disease in both parents, especially of asthma and atopic dermatitis, increased the risk of allergic disease in the child. Milder symptoms, such as wheezy bronchitis, in schoolchildren were similarly related with the same hereditary tendency as the identical allergic disease. The disappearance of allergic symptoms with age also related to a hereditary component, being less likely in children with a history of parental allergy than in those without such an atopic history. CONCLUSIONS: The manifestations and course of allergic disease in school children relate to parental allergic disease.     

特异质与慢性持续期哮喘儿童呼出气一氧化氮相关性研究

目的评估特异质对慢性持续期哮喘儿童呼出气一氧化氮(FeNO)水平的影响。方法选取同时完成皮肤点刺试验和FeNO检测的慢性持续期哮喘患儿52例,按皮肤点刺试验结果分为非特异质组和特异质组,按有无合并过敏性鼻炎分为鼻炎组和无鼻炎组;另选择78例健康儿童作为对照组,比较各组FeNO水平;并比较32例予吸入型糖皮质激素治疗3个月患儿的FeNO水平变化。结果 40例特异质组、12例非特异质组和对照组的FeNO水平差异有统计学意义(H=33.29,P=0.000);特异质组FeNO水平高于对照组和非特异质组,差异有统计学意义(P0.05)。11例无鼻炎组、41例鼻炎组和对照组的FeNO水平差异有统计学意义(H=30.63,P=0.000);鼻炎组FeNO水平高于对照组,差异有统计学意义(P0.05);鼻炎组与无鼻炎组差异无统计学意义(P0.05)。特异质组患儿FeNO水平与屋尘螨、粉尘螨皮肤点刺致敏风团直径无相关性(r=2.05、1.58,P均0.05)。32例患儿经吸入糖皮质激素治疗3个月后FeNO水平显著下降,与其治疗前第一次检测结果比较,差异有统计学意义(Z=2.05,P=0.041)。结论特异质对慢性持续期哮喘儿童FeNO水平有重要影响,吸入糖皮质激素可显著降低致敏哮喘儿童FeNO水平。     

MBL2 variants in relation to common childhood infections and atopy-related phenotypes in a large German birth cohort

Mannose-binding lectin (MBL) is considered an important component of innate immunity. Four functional MBL2 alterations in codons 52, 54, 57 and in the promoter at position c.1-290 are correlated with significantly lowered MBL serum levels. These variants have been associated with susceptibility to a variety of infectious agents as well as with various immunologic disorders including asthma. To reassess these observations, we analysed the four above mentioned MBL2 variants in 749 children, who were recruited by the German Multicenter Allergy Study and were prospectively evaluated for common respiratory childhood infections and atopy-related phenotypes from birth up to the age of 11 yr. We performed genotyping by melting curve analysis using fluorescence resonance energy transfer probes and the LightCycler. In contrast to previous studies, we found an association of MBL2 variants neither with the frequency of common respiratory childhood infections at any age nor with asthma or other atopy-related phenotypes. Our data suggest that MBL deficiency does not represent a pre-disposing factor for respiratory infections or atopic disorders in infants and children.     

Antibody levels to Bordetella pertussis in 10-yr-old children with atopy and atopic asthma

Suboptimal immune responses to vaccination have been suggested among atopic infants. The aim of this study was to assess the influence of atopy and atopic asthma on the humoral response to Bordetella pertussis vaccination. Immunoglobulin (Ig)G and IgA specific antibodies were measured by enzyme linked-immunosorbent assay in 102, 10-yr-old atopic children (66 of them also being asthmatics) and compared with 76 non-atopic and 53 non-atopic non-asthmatic controls of similar age. The levels of antibodies and the percentage of positives to B. pertussis were comparable in all groups. Children with a very high total serum immunoglobulin (Ig)E (Percentile (Pct) > 90th) showed higher (p = 0.01) IgG pertussis antibodies than children with very low serum IgE (Pct < 10th). In conclusion, we found normal pertussis antibody levels in atopic and in atopic asthmatic children in late childhood, thus overriding any possible suboptimal response during infancy.     

Atopy in Children with and without a Family History of Atopy

ABSTRACT. The influence of a family history of atopy on atopic morbidity, and relationships between diet in infancy and allergic manifestations at the ages of one and five years were prospectively studied in 91 children. A control group consisted of 72 children with no family history of atopy. At the age of one year, atopic manifestations were found in 19 % of 163 children, in 23 % of those with a family history of atopy and in 14 % of those with no such history. Skin problems were more common in children with a family history of atopy (43 %) than in the control children (19 %). Of the children with a family history of atopy, 23 % had prolonged rhinorrhoea during infancy. The corresponding figure in children with no family history of atopy was 10 %. Prolonged rhinorrhoea during infancy correlated with parental smoking only in children with a family history of atopy (47 % vs. 18 %). At the age of five years, atopic disease was found in 17 % of 128 children, 24 % of those with a family history of atopy and 9 % of those with no such history. Atopic eczema was more common in children with a family history of atopy, irrespective of the diet consumed during infancy. Atopic signs were found in about half of all the children with a family history of atopy. If atopy had been present in the family, the child usually exhibited the same manifestation. Onset of atopic manifestations was not prevented or delayed.