Nonatopic Asthmatic Children Research Articles

Potential Impact of SOD2 (rs4880; p.Val16Ala) Variant with the Susceptibility for Childhood Bronchial Asthma.

Oxidative stress is a sophisticated situation that orignates from the accumulation of reactive free radicals within cellular compartments. The antioxidant mechanism of the MnSOD enzyme facilitates the removal of these lethal oxygen species from cellular components. The main goal of this pertained work is to study the contribution of the SOD2 (rs4880; p.Val16Ala) variant to the development of bronchial asthma among children. The study's design was carried out based on a total of 254 participants including 127 asthmatic children (91 atopic and 36 non-atopic) along with 127 unrelated healthy controls. Allelic discrimination analysis was executed using the T-ARMS-PCR protocol. This potential variant conferred a significant association with decreased risk of bronchial asthmatic children under allelic (OR = 0.56, P-value = 0.002), recessive (OR = 0.32, P-value = 0.011), and dominant (OR = 0.51, P-value = 0.040) models. Additionally, atopic and non-atopic asthmatic children indicated a protection against bronchial asthma development under allelic, and dominant models (p-value < 0.05). Our findings suggested that the SOD2*rs4880 variant was correlated with decreased risk of childhood bronchial asthma.

Dog Ownership in Early Life Increased the Risk of Nonatopic Asthma in Children

Background: It is still debatable whether dog ownership during early childhood is a risk factor for the development of allergic diseases. Objective: We investigated the association of dog ownership in early life with sensitization and asthma in childhood. Methods: Data from the Cohort for Childhood Origin of Asthma and Allergic diseases were used to investigate the association between dog ownership at any time from pregnancy to 1 year of age and sensitization to aeroallergens at 3 and 7 years old, bronchial hyperresponsiveness (BHR), and asthma at 7 years old. We analyzed the cytokine levels in cord blood (CB) and indoor environmental measurement concentrations in the mother’s residence obtained at 36 weeks of pregnancy. Results: Sensitization to dogs at age 3 and 7 did not differ between dog ownership and nonownership, but dog ownership during early life decreased the risk of sensitization to aeroallergens at age 7 (aOR = 0.44, 95% CI 0.21–0.90). Dog ownership significantly increased the risk of nonatopic BHR (aOR = 2.86; 95% CI 1.32–6.21). In addition, dog ownership was associated with asthma, especially nonatopic asthma at 7 years old (aOR = 2.73, 95% CI 1.02–7.32; aOR = 7.05, 95% CI 1.85–26.90, respectively). There were no significant differences in the concentrations of IL-13 or interferon-γ in CB or indoor environmental measurements according to dog ownership during pregnancy. Conclusion: Early-life dog exposure in this birth cohort has been shown to reduce atopy but increase the risk of nonatopic BHR and nonatopic asthma at 7 years old.

Outdoor air pollutants exposure associated with pulmonary function and EBC pH value in atopic asthmatic and non-asthmatic children

Objective Air pollution is associated with the prevalence of respiratory diseases. This study aimed to evaluate the impacts of outdoor air pollutants and indoor Dermatophagoides pteronyssinus 1 (Der p 1) exposure on levels of fractional exhaled nitric oxide (FeNO), exhaled breath condensate (EBC) pH, and pulmonary function in atopic children. Methods This study recruited 59 atopic mild-to-moderate asthmatic children and 23 atopic non-asthmatic children. Data on personal characteristics, FeNO, EBC pH, and pulmonary function were collected. Group 1 allergens of Der p 1 were measured on the tops of mattresses and on bedroom floors in the children’s homes, and outdoor air pollutant concentrations were estimated from air quality monitoring stations, using the ordinary kriging method. Results Exposure levels of outdoor air pollutants, except for particulate matter (PM)2.5, for the recruited children met outdoor air quality standards set by the Taiwan Environmental Protection Agency. The lag effect of outdoor PM10 exposure was negatively associated with the forced expiratory volume in one second (FEV1) [(Lag 1: β=–0.771, p = 0.028), and O3 (Lag 1–7: β=–2.02, p = 0.04, Lag 1–28: β=–3.213, p = 0.029)]. Median pulmonary function parameters differed significantly in forced vital capacity (FVC) (p = 0.004) and FEV1 (p = 0.024) values between atopic asthmatic and non-asthmatic children. No association was found between the FeNO/EBC pH level and exposure to Der p 1 allergen and air pollutants in the recruited children. Conclusions Outdoor PM10 and O3 exposure was associated with reduction in FEV1 in atopic asthmatic and non-asthmatic children.

Clusterin in atopic and non-atopic childhood asthma

Several biomarkers have been studied to diagnose or to detect the phenotype of asthma. Clusterin is a sensitive cellular biosensor of oxidative stress and has been studied as a biomarker for inflammatory diseases. We aimed to study serum clusterin level in atopic versus non-atopic childhood asthma and its relation to disease severity. This case-control study included 160 children; 120 stable asthmatic children and 40 apparently healthy children. Asthmatic children were further subdivided into atopic and non-atopic. All children were subjected to medical history taking, clinical examination, and laboratory investigations including complete blood count, serum IgE, serum clusterin level and spirometry before and after bronchodilator therapy. In comparison to controls, patients had significantly higher eosinophils count which was higher in atopic than non-atopic group, also serum IgE level was higher in the atopic asthmatics (118.1 ± 16.2 U/ml) than in both the non-atopic asthmatics (81.2 ± 6.1 U/ml) and the controls (76.3 ± 11.6 U/ml). There was statistical significant difference in serum levels of Clusterin which were highest in the atopic group (182.5 ± 33.5 ng/l), followed by the non-atopic patients (127.5 ± 32.5 ng/l) and lowest in the controls (46.09 ± 7.01 ng/l). Moreover, the higher the severity of asthma, the higher was the level of serum clusterin. In conclusion serum level of clusterin was higher in atopic than non-atopic asthmatic children and it increases significantly with increased severity of the disease.

Progressive increase of FcεRI expression across several PBMC subsets is associated with atopy and atopic asthma within school-aged children.

Antigen-specific IgE binds the Fcε receptor I (FcεRI) expressed on several types of immune cells, including dendritic cells (DCs). Activation of FcεRI on DCs in atopics has been shown to modulate immune responses that potentially contribute to asthma development. However, the extent to which DC subsets differ in FcεRI expression between atopic children with or without asthma is currently not clear. This study aimed to analyse the expression of FcεRI on peripheral blood mononuclear cells (PBMCs) from atopic children with and without asthma, and non-atopic/non-asthmatic age-matched healthy controls. We performed multiparameter flow cytometry on PBMC from 391 children across three community cohorts and one clinical cohort based in Western Australia. We confirmed expression of FcεRI on basophils, monocytes, plasmacytoid and conventional DCs, with higher proportions of all cell populations expressing FcεRI in atopic compared to non-atopic children. Further, we observed that levels of FcεRI expression were elevated across plasmacytoid and conventional DC as well as basophils in atopic asthmatic compared to atopic non-asthmatic children also after adjusting for serum IgE levels. Our data suggest that the expression pattern of FcεRI on DC and basophils differentiates asthmatic from non-asthmatic atopic children. Given the significant immune modulatory effects observed as a consequence of FcεRI expression, this altered expression pattern is likely to contribute to asthma pathology in children.

Innate Lymphoid Cells Mediate Pulmonary Eosinophilic Inflammation, Airway Mucous Cell Metaplasia, and Type 2 Immunity in Mice Exposed to Ozone

Exposure to elevated levels of ambient ozone in photochemical smog is associated with eosinophilic airway inflammation and nonatopic asthma in children. In the present study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced nonatopic asthma by using lymphoid cell-sufficient C57BL/6 mice, ILC-sufficient Rag2-/- mice (devoid of T and B cells), and ILC-deficient Rag2-/-Il2rg-/- mice (depleted of all lymphoid cells including ILCs). Mice were exposed to 0 or 0.8 parts per million ozone for 1 day or 9 consecutive weekdays (4 hr/day). A single exposure to ozone caused neutrophilic inflammation, airway epithelial injury, and reparative DNA synthesis in all strains of mice, irrespective of the presence or absence of ILCs. In contrast, 9-day exposures induced eosinophilic inflammation and mucous cell metaplasia only in the lungs of ILC-sufficient mice. Repeated ozone exposures also elicited increased messenger RNA expression of transcripts associated with type 2 immunity and airway mucus production in ILC-sufficient mice. ILC-deficient mice repeatedly exposed to ozone had no pulmonary pathology or increased gene expression related to type 2 immunity. These results suggest a new paradigm for the biologic mechanisms underlying the development of a phenotype of childhood nonatopic asthma that has been linked to ambient ozone exposures.

The relationships among Dermatophagoides pteronyssinus exposure, exhaled nitric oxide, and exhaled breath condensate pH levels in atopic asthmatic children

This study examined seasonal changes in indoor Dermatophagoides pteronyssinus 1 (Der p 1)/Blattella germanica 1 (Bla g 1) antigen concentrations in the homes of atopic asthmatic and atopic nonasthmatic children. Possible associations between environmental allergen exposure and levels of exhaled breath indices were also evaluated.A total of 38 atopic children were recruited for this cross-sectional study: 22 were asthmatic and 16 were nonasthmatic. Home visits were conducted for indoor air and dust sampling each season. Exhaled nitric oxide (eNO)/spirometric measurements were taken and exhaled breath condensate (EBC) was collected after sampling of the domestic environment.The highest Der p 1 concentrations were on the top of mattresses in the homes of recruited children. The floors of kitchens and living rooms had the highest Bla g 1 concentrations in the homes of atopic asthmatic children. A positive correlation was found between Der p 1 exposure of mattress, bedroom floor, and living room floor and eNO levels in the atopic asthmatic children. The Der p 1 concentrations on the surfaces of mattress and bedroom floor were positively related to high eNO levels in the atopic asthmatic children after adjusting for season. No association was found between Der p 1 exposure and EBC pH values in the recruited children.A positive correlation was found between Der p 1 exposure and high eNO levels in atopic asthmatic children, especially in Der p 1 exposure of mattress and bedroom floor.

IL-5, IL-8 and MMP -9 levels in exhaled breath condensate of atopic and nonatopic asthmatic children

Asthma is a heterogeneous disease, and a great majority of pediatric patients with asthma demonstrate atopic characteristics and develop a Th2 type cytokine response. Nonatopic asthma, on the other hand, is seen more rarely. In this study, levels of IL-5, IL-8 and MMP-9 were measured in exhaled breath condensate (EBC) of the subjects to demonstrate the extent of tissue damage as well as eosinophilic and neutrophilic inflammation in children with atopic and nonatopic asthma. A total of 37 children with atopic asthma and 37 children with nonatopic asthma were enrolled in the study. Patients who exhibited protease positive aeroallergen (House dust mite, mould mix, olea, grass mix) sensitivity in allergen skin prick test were included in the atopic asthma group. To evaluate the EBC, the fluid content of the breath was collected by having the patients exhale into an EBC device, after which the IL-5, IL-8 and MMP-9 levels were assayed using the ELISA method. The atopic asthmatics exhibited significantly higher IL-5 levels in their EBC samples than the nonatopic asthmatics (0.271 [0.198-0.489]pg/ml and 0.198 [0.125-0.344]pg/ml, respectively, p=0.04), while no significant differences were observed in the levels of IL-8 and MMP-9 in the EBC samples of the atopic and nonatopic asthmatics. IL-5 levels, as a marker of eosinophilic inflammation, were demonstrated to be higher in the children with atopic asthma when compared to those with nonatopic asthma in EBC. The fact that no significant difference was apparent in the IL-8 levels between the groups suggests that it is the severity of the disease rather than the atopic state that plays an important role in IL-8 levels. Since no difference was recorded between the groups interms of MMP-9 levels, lung damage in asthma sufferers seems to develop independent of atopia.

The Association of Lung Function, Bronchial Hyperresponsiveness, and Exhaled Nitric Oxide Differs Between Atopic and Non-atopic Asthma in Children.

PurposeAlthough many previous studies have attempted to identify differences between atopic asthma (AA) and non-atopic asthma (NAA), they have mainly focused on the difference of each variable of lung function and airway inflammation. The aim of this study was to evaluate relationships between lung function, bronchial hyperresponsiveness (BHR), and the exhaled nitric oxide (eNO) levels in children with AA and NAA.MethodsOne hundred and thirty six asthmatic children aged 5-15 years and 40 normal controls were recruited. Asthma cases were classified as AA (n=100) or NAA (n=36) from skin prick test results. Lung function, BHR to methacholine and adenosine-5'-monophosphate (AMP), eNO, blood eosinophils, and serum total IgE were measured.ResultsThe AA and NAA cases shared common features including a reduced small airway function and increased BHR to methacholine. However, children with AA showed higher BHR to AMP and eNO levels than those with NAA. When the relationships among these variables in the AA and NAA cases were evaluated, the AA group showed significant relationships between lung function, BHR to AMP or methacholine and eNO levels. However, the children in the NAA group showed an association between small airway function and BHR to methacholine only.ConclusionsThese findings suggest that the pathogenesis of NAA may differ from that of AA during childhood in terms of the relationship between lung function, airway inflammation and BHR.

Association between vitamin D receptor gene FokI polymorphism and atopic childhood bronchial asthma

ObjectiveTo investigate the association between vitamin D receptor (VDR) gene FokI polymorphism and atopic bronchial asthma in Egyptian children. Material and methodsPolymerase chain reaction-restriction fragment length polymorphism was used to determine VDR gene FokI polymorphism in 180 asthmatic children (atopic, n=90 and non-atopic, n=90) and 180 age and gender matched healthy children. Serum levels of total IgE were measured by ELISA. Skin prick test was performed on all patients. ResultsThe frequency of FF genotype was significantly higher in healthy children (n=90, 50%) versus asthmatic children (n=39, 21.7%, χ2=5.852, OR=0.23, 95% CI=0.07–0.78, p=0.016). The frequency of FF genotype was significantly higher among healthy children (n=90, 50%) compared to atopic asthmatic children (n=12, 13.4%, χ2=9.745, OR=0.11, 95% CI=0.02–0.46, p=0.002). Also, its frequency was significantly higher among non-atopic asthmatic children (n=27, 30%) compared to atopic asthmatic children (n=12, 13.4%, χ2=4.394, OR=0.21, 95% CI=0.04–0.94, p=0.041). Total IgE differed significantly among the three VDR gene FokI polymorphic genotypes in children with atopic asthma (p=0.007) and the highest median level was detected in ff genotype. ConclusionOur findings raise the susceptibility of VDR gene to be a candidate gene for atopic childhood bronchial asthma.

Prevention – what is the most promising approach?

Prevention – what is the most promising approach?

Prematurity, atopy, and childhood asthma in Puerto Ricans

Puerto Rican children share a disproportionate burden of prematurity and asthma in the United States. Little is known about prematurity and childhood asthma in Puerto Rican subjects. We sought to examine whether prematurity is associated with asthma in Puerto Rican children. We performed a case-control study of 678 children aged 6 to 14 years with (n = 351) and without (n = 327) asthma living in San Juan, Puerto Rico. Prematurity was defined by parental report for our primary analysis. In a secondary analysis, we only included children whose parents reported prematurity that required admission to the neonatal intensive care unit. Asthma was defined as physician-diagnosed asthma and wheeze in the prior year. We used logistic regression for analysis. All multivariate models were adjusted for age, sex, household income, atopy (≥1 positive IgE level to common allergens), maternal history of asthma, and early-life exposure to environmental tobacco smoke. In a multivariate analysis there was a significant interaction between prematurity and atopy on asthma (P = .006). In an analysis stratified by atopy, prematurity was associated with a nearly 5-fold increased odds of asthma in atopic children (adjusted odds ratio, 4.7; 95% CI, 1.5-14.3; P = .007). In contrast, there was no significant association between prematurity and asthma in nonatopic children. Similar results were obtained in our analysis of prematurity requiring admission to the neonatal intensive care unit and asthma. Our results suggest that atopy modifies the estimated effect of prematurity on asthma in Puerto Rican children. Prematurity might explain, in part, the high prevalence of atopic asthma in this ethnic group.

Association of atopic and non‐atopic asthma with emotional symptoms in school children

To date, there is conflicting evidence whether the association between asthma and depression depends on the atopic or non-atopic asthma phenotype. This study investigates associations between emotional symptoms and atopic and non-atopic asthma in school-aged children. Cross-sectional data on asthma and allergic diseases at the 10-year follow-up of two birth cohorts were collected by parent-reported physician diagnoses. Specific IgE levels including most common inhalant allergens (SX1) and food allergens (FX5) were measured by RAST-CAP FEIA. Atopic asthma was defined as asthma ever and positive specific IgE test, non-atopic asthma as asthma ever and no IgE sensitization. Emotional symptoms were assessed by parent-reported strength and difficulty questionnaire. Logistic regression modeling were applied to determine likelihood of emotional symptoms in children with atopic and non-atopic asthma controlling for socio-demographic factors, body mass index, atopic eczema, allergic rhinitis, and pubertal development. Non-atopic asthma was associated with about 3-fold higher likelihood of emotional symptoms compared to children with no asthma (ORadj=2.90, CI95%=1.46-5.73). Atopic asthma was not associated with emotional symptoms (ORadj=1.35, CI95%=0.81-2.26). Atopic and non-atopic asthma in children might have different etiologies, whereas for non-atopic asthma, emotional symptoms are relevant, this is not the case in atopic asthma. The relationship between the non-atopic asthma phenotype and emotional symptoms might be dependent on gender.

Genetic variants in Protocadherin‐1, bronchial hyper‐responsiveness, and asthma subphenotypes in German children

Recently, Protocadherin-1 (PCDH1) was reported as a novel susceptibility gene for bronchial hyper-responsiveness (BHR) and asthma. PCDH1 is located on chromosome 5q31-33, in the vicinity of several known candidate genes for asthma and allergy. To exclude that the associations observed for PCDH1 originate from the nearby cytokine cluster, an extensive linkage disequilibrium (LD) analysis was performed. Effects of polymorphisms in PCDH1 on asthma, BHR, and related phenotypes were studied comprehensively. Genotype information was acquired from Illumina HumanHap300Chip genotyping, MALDI-TOF MS genotyping, and imputation. LD was assessed by Haploview 4.2 software. Associations were investigated in a population of 1454 individuals (763 asthmatics) from two German study populations [MAGICS and International Study of Asthma and Allergies in Childhood phase II (ISAAC II)] using logistic regression to model additive effects. No relevant LD between PCDH1 tagging polymorphisms and 98 single nucleotide polymorphisms within the cytokine cluster was detected. While BHR was not associated with PCDH1 polymorphisms, significant associations with subphenotypes of asthma were observed. Protocadherin-1 polymorphisms may specifically affect the development of non-atopic asthma in children. Functional studies are needed to further investigate the role of PCDH1 in BHR and asthma development.

Deficient antiviral immune responses in childhood: Distinct roles of atopy and asthma

Impaired immune response to viral infections in atopic asthmatic patients has been recently reported and debated. Whether this condition is present in childhood and whether it is affected by atopy per se deserves further investigation. We sought to investigate airway interferon production in response to rhinovirus infection in children who are asthmatic, atopic, or both and its correlation with the airway inflammatory profile. Bronchial biopsy specimens and epithelial cells were obtained from 47 children (mean age, 5 ± 0.5 years) undergoing bronchoscopy. The study population included asthmatic children who were either atopic or nonatopic, atopic children without asthma, and children without atopy or asthma. Rhinovirus type 16 induction of IFN-λ and IFN-β mRNA and protein levels was assessed in bronchial epithelial cell cultures. The immunoinflammatory profile was evaluated by means of immunohistochemistry in bronchial biopsy specimens. Rhinovirus type 16-induced interferon production was significantly reduced in atopic asthmatic, nonatopic asthmatic, and atopic nonasthmatic children compared with that seen in nonatopic nonasthmatic children (all P< .05). Increased rhinovirus viral RNA levels paralleled this deficient interferon induction. Additionally, IFN-λ and IFN-β induction correlatedinversely with the airway T(H)2 immunopathologic profile (eosinophilia and IL-4 positivity: P< .05 and r= -0.38 and P< .05 and r= -0.58, respectively) and with epithelial damage (P< .05 and r= -0.55). Furthermore, total serum IgE levels correlated negatively with rhinovirus-induced IFN-λ mRNA levels (P< .05 and r= -0.41) and positively with rhinovirus viral RNA levels (P< .05 and r= 0.44). Deficient interferon responses to rhinovirus infection are present in childhood in asthmatic subjects irrespective of their atopic status and in atopic patients without asthma. These findings suggest that deficient immune responses to viral infections are not limited to patients with atopic asthma but are present in those with other T(H)2-oriented conditions.

292 The Relationship Between Maternal Atopy and Childhood Asthma

BackgroundThe diagnostic difficulty of childhood asthma leads to widespread under-diagnosis, which negatively affects the quality of life of asthmatic children. The presence of atopy in children is often used as a clinical tool to assist in making the diagnosis. However, local studies have demonstrated that atopy occurs in fewer asthmatic children than previously thought. This brings into question the association between allergy and asthma. The purpose of this study was to determine if a family history of allergy is predictive of atopic asthma in children, by comparing allergy, history of asthma and allergic symptoms, in mothers of atopic versus non-atopic asthmatic children.MethodsA random sample of children and their mothers attending the Children's Chest and Allergy Clinic at Steve Biko Academic Hospital were enrolled. Skin-prick testing or radioallergosorbent test results, of the children were obtained from the child's hospital records. Mothers completed a detailed questionnaire which included demographic details, a history of symptoms suggestive of ‘atopy’ and allergic diseases and a history of asthma. Skin prick testing was performed on the mothers.Results100 children and their parents were enrolled. 64 mothers to atopic children were used as the study group and 36 mothers to non-atopic children were used as the control group. Of the 48 mothers with a positive skin prick test, 30 (64%) had atopic children (P = 0.836). Of the 16 mothers with asthma, 14 (88%) had atopic children (P = 0.045). Of the 70 mothers with a history of symptoms suggestive of an allergic disease, 45 (64%) had children with atopic asthma (P = 1.0). Of the 77 mothers who were considered to be allergic, 50 (65%) had children with atopic asthma (P = 0.806).ConclusionsBoth maternal skin prick positivity and a history of symptoms suggestive of allergic disease, are poor predictors of atopic asthma in children. This is true even in the mothers were considered to be allergic. However maternal asthma is a specific predictor of childhood atopic asthma with a good positive predictive and a high odds ratio. Further studies need to be conducted to compare the epidemiology of allergic asthma in different population groups.

SP1-40 Maternal mental health and social support: effects on atopic and non-atopic asthma in children

IntroductionAlthough there is evidence that atopic and non-atopic asthma have distinct risk factors and immunological mechanisms, there are few studies that consider the effect of psychosocial factors on these asthma...

Indoor particulate matter increases asthma morbidity in children with non-atopic and atopic asthma

Compared with atopic asthma, fewer environmental modifications are recommended for non-atopic asthma in children. To better understand the role of indoor pollutants in provoking non-atopic asthma, we investigated the effect of in-home particulate matter on asthma symptoms among non-atopic and atopic children living in inner-city Baltimore. A cohort of 150 children ages 2 to 6 years with asthma underwent home environmental monitoring for 3-day intervals at baseline, 3, and 6 months. Children were classified as non-atopic if they were skin test negative to a panel of 14 aeroallergens. Caregivers completed questionnaires assessing symptoms and rescue medication use. Longitudinal data analysis included regression models with generalized estimating equations. Children were primarily African American from lower socioeconomic backgrounds and spent most of their time in the home. Thirty-one percent were non-atopic, and 69% were atopic. Among non-atopic and atopic children, increased in-home fine (PM2.5) and coarse (PM2.5-10) particle concentrations were associated with significant increases in asthma symptoms and rescue medication use ranging from 7% (95% confidence interval [CI], 0-15) to 14% (95% CI, 1-27) per 10 μg/m(3) increase in particle concentration after adjustment for confounders. In-home particles similarly cause increased symptoms of asthma in non-atopic and atopic children. Environmental control strategies that reduce particle concentrations may prove to be an effective means of improving asthma outcomes, especially for non-atopic asthma, for which there are few environmental control practice recommendations.

Association of Childhood Obesity With Atopic and Nonatopic Asthma: Results From the National Health and Nutrition Examination Survey 1999–2006

Background. Obesity and asthma prevalence have both risen among children over the last several decades, and research efforts increasingly suggest that obesity is associated with asthma. Some, but not all, studies have shown that the effect of obesity on asthma is stronger among nonatopic individuals than among those with atopy. Systemic inflammation may be a factor in this relationship. Objective. To examine the association of obesity with atopic and nonatopic asthma among U.S. children and to assess the role of C-reactive protein. Design. Nationally representative data from the National Health and Nutrition Examination Survey (NHANES) were used to examine the relationship of weight to current asthma using logistic regression. Overweight was defined as ≥85th percentile of body mass index (BMI)-for-age and obesity was defined as ≥95th percentile of BMI-for-age. The presence of at least one positive allergen-specific immunoglobulin E (IgE) was used to stratify the relationship by atopic status in 2005–2006 data (n = 3387). Setting and Participants. Stratified, multistage probability sampling was used to identify survey participants. This analysis includes children ages 2–19 (n = 16,074) from the 1999–2006 NHANES who have information on BMI and current asthma. Main Outcome Measure. Self-report of doctor-diagnosed current asthma. Results. Obesity was significantly related to current asthma among children and adolescents (odds ratio [OR]: 1.68, 95% confidence interval [CI]: 1.33, 2.12). The association was stronger in nonatopic children (OR: 2.46, 95% CI: 1.21, 5.02) than in atopic children (OR: 1.34, 95% CI: 0.70, 2.57) (interaction p value = .09). C-reactive protein levels were associated with current asthma in nonatopic children, but not after adjusting for BMI. Conclusion. Excess weight in children is associated with higher rates of asthma, especially asthma that is not accompanied by allergic disease.

MMP-9 gene variants increase the risk for non-atopic asthma in children

BackgroundAtopic and non-atopic wheezing may be caused by different etiologies: while eosinophils are more important in atopic asthmatic wheezers, neutrophils are predominantly found in BAL samples of young children with wheezing. Both neutrophils as well as eosinophils may secrete matrix metalloproteinase 9 (MMP-9). Considering that MMP-9 plays an important role in airway wall thickening and airway inflammation, it may influence the development of obstructive airway phenotypes in children. In the present study we investigated whether genetic variations in MMP-9 influence the development of different forms of childhood asthma.MethodsGenotyping of four HapMap derived tagging SNPs in the MMP-9 gene was performed using MALDI-TOF MS in three cross sectional study populations of German children (age 9-11; N = 4,264) phenotyped for asthma and atopic diseases according to ISAAC standard procedures. Effects of single SNPs and haplotypes were studied using SAS 9.1.3 and Haploview.ResultsSNP rs2664538 significantly increased the risk for non-atopic wheezing (OR 2.12, 95%CI 1.40-3.21, p < 0.001) and non-atopic asthma (OR 1.66, 95%CI 1.12-2.46, p = 0.011). Furthermore, the minor allele of rs3918241 may be associated with decreased expiratory flow measurements in non-atopic children. No significant effects on the development of atopy or total serum IgE levels were observed.ConclusionsOur results have shown that homozygocity for MMP-9 variants increase the risk to develop non-atopic forms of asthma and wheezing, which may be explained by a functional role of MMP-9 in airway remodeling. These results suggest that different wheezing disorders in childhood are affected differently by genetic alterations.