The association between anxiety sensitivity and atopy in adult asthmatics

There is growing evidence linking psychological stress to atopic disease, particularly asthma. Anxiety sensitivity, which is the fear of anxiety-related symptoms, may be particularly important in the study of anxiety and atopic disease. The present study examined the association between atopy and anxiety sensitivity in adult asthmatics. A total of 217 asthma patients who had undergone standard pulmonary function and allergen skin prick testing were included. Participants completed the Anxiety Sensitivity Index, Penn State Worry Questionnaire, Type D Personality Scale-16 and Beck Depression Inventory-II on the day of their asthma clinic visit. Total Anxiety Sensitivity Index score was found to be significantly higher in atopic (M = 17.15, SE = .9) versus non-atopic (M = 12.68, SE = 1.5) asthmatics, independent of age, sex, smoking status, asthma severity, asthma duration, and anxiolytic medication use (F = 6.11, p = .014). There was no evidence for a significant association between any of the other questionnaire scores and atopic status.     

The relationship between anthropometric measurements at birth: asthma and atopy in childhood

BACKGROUND: Recent studies have reported that a large head circumference at birth is associated with an increased risk of raised serum IgE in adult life, and asthma during childhood. OBJECTIVE: To examine the relationship between head circumference and other anthropometric measurements at birth and asthma and indices of atopy in childhood. METHODS: The presence of asthma and measures of atopic status (total serum IgE level and skin prick tests to common allergens) were assessed prospectively in offspring of families participating in a community-based genetic study in Southampton, UK. Measures of perinatal variables including birth weight, head circumference at birth, and gestational age were obtained from hospital records of 239 offspring aged 6-23 years. RESULTS: Children with a head circumference of 37 cm or more at birth had a relative risk of an elevated serum total IgE (> 150 IU) of 3.2 (95% CI 1.0-10.4). There were no consistent relationships between head circumference at birth and either skin prick positivity or the development of clinical asthma. There was no significant association between other perinatal markers and measures of atopic status or clinical asthma. CONCLUSION: The study has identified that a large head circumference at birth is associated with an increased risk of an elevated total serum IgE in childhood. The reasons for this association, and the lack of an association with asthma are unclear and will require further research.     

Interleukin 3 (IL3) polymorphisms associated with decreased risk of asthma and atopy

Cytokines, having central functions in immunological and inflammatory process, are always expected to play important roles in the pathogenesis of various diseases, such as asthma. Genetic polymorphisms of those cytokine and cytokine receptor genes are the focus of genetic association studies. In an effort to identify gene(s) whose variant(s) are involved in the development of asthma, we examined the genetic effects of 19 single nucleotide polymorphisms in eight cytokine and cytokine receptor genes, including IL1A, IL1B, IL2, IL3, IL4, IL8, IL10, and IL5RA, on asthma and atopy. Nineteen single nucleotide polymorphisms in eight cytokine and cytokine receptor genes were genotyped using the single-base extension method in a Korean asthma cohort (n=723). Logistic regression and multiple regressions were used for statistical analyses controlling for smoking, age, and gender as covariables. Genetic association analysis of polymorphisms revealed that one exonic (exon 1), IL3+79T>C (Ser27Pro), showed significant association with the risk of asthma and atopy. The Pro allele had shown dominant and protective effects on development of asthma in nonatopic subjects (P=0.002) and also showed significant association with the risk of atopy in normal control subjects (P=0.007). This information about the genetic association of important genes with asthma might provide valuable insights into strategies for the pathogenesis of asthma and atopy.     

Interactions between breast-feeding, specific parental atopy, and sex on development of asthma and atopy

BACKGROUND: The influence of breast-feeding on the risk of developing atopy and asthma remains controversial. OBJECTIVE: To examine asthma and atopy outcomes by sex, reported specific parental history of atopy, and breast-feeding. METHODS: In a birth cohort, we examined childhood asthma and atopy (positive skin prick tests) by sex and breast-feeding in relation to maternal and paternal atopy. Interactions were explored in logistic regression models. RESULTS: For boys, breast-feeding (odds ratio [OR], 1.63; 95% CI, 0.93-2.87; P = .09) and maternal atopy (OR, 1.95; 95% CI, 0.93-4.08; P = .08) were each associated with atopy at age 13 years. Breast-feeding increased the risk for atopy among boys with paternal atopy (OR, 7.39; 95% CI, 2.21-24.66) compared with non-breast-fed boys with paternal atopy, but did not significantly further increase risk among subjects with maternal atopy. For girls, breast-feeding (OR, 0.74; 95% CI, 0.41-1.31) and maternal and paternal atopy were not independent risk factors for atopy at age 13 years. However, breast-feeding increased the risk for atopy in girls with maternal atopy (OR, 3.13; 95% CI, 1.20-8.14) compared with non-breast-fed girls with maternal atopy. There was no such effect among subjects with paternal atopy. Results for the outcome of asthma followed a similar pattern. CONCLUSION: The influence of breast-feeding on development of atopy and asthma differs by sex and by maternal and paternal atopy, and is most significant among subjects at lower baseline risk. CLINICAL IMPLICATIONS: Analyses of environmental risk factors for asthma and atopy should be stratified by specific parental atopy and sex.     

Perinatal influences on the development of asthma and atopy in childhood

BackgroundIn most children with asthma and atopy, onset of disease occurs early in life, indicating a crucial role of in utero and early childhood environment. However, only a small part of this burden of disease established early in life has been explained.ObjectiveTo examine the effects of early environmental exposures on the development of asthma and atopy within the setting of an affluent urban population.MethodsThe authors followed 526 German children from birth to 5 years of age. Parental interviews in pregnancy and then yearly assessed the health of the child and environmental characteristics. Endotoxin and allergens in house dust were measured at 3 months. Atopic sensitization was assessed at 1 and 5 years.ResultsIn atopic mothers, acute atopic symptoms during pregnancy were associated with increased risk of early atopic dermatitis (adjusted odds ratio [aOR] 1.74, 95% confidence interval [CI] 1.00–3.02) and allergic rhinitis at 5 years (aOR 2.11, 95% CI 1.01–4.41). Further, maternal illnesses during pregnancy (ie, repeated common colds) increased the risk of asthma at 5 years (aOR 2.31, 95% CI 1.12–4.78). Endotoxin in the child's mattress was inversely associated with atopic sensitization (aOR 0.79, 95% CI 0.64–0.97) and asthma (aOR 0.71, 95% CI 0.55–0.93). A contrasting effect of early endotoxin and mite exposure was observed for mite sensitization: mite exposure increased the risk of mite sensitization at 5 years (aOR 1.30, 95% CI 1.11–1.53), whereas endotoxin exposure was inversely associated with mite sensitization (aOR 0.73, 95% CI 0.57–0.95).ConclusionFactors affecting the in utero environment, such as maternal atopy and infections, and bacterial exposure in pregnancy or early life may act as immunomodulators enhancing or inhibiting the development of asthma and atopy in childhood.     

Contributions of the intestinal microbiome in lung immunity

The intestine is a critical site of immune cell development that not only controls intestinal immunity but extra‐intestinal immunity as well. Recent findings have highlighted important roles for gut microbiota in shaping lung inflammation. Here, we discuss interactions between the microbiota and immune system including T cells, protective effects of microbiota on lung infections, the role of diet in shaping the composition of gut microbiota and susceptibility to asthma, epidemiologic evidence implicating antibiotic use and microbiota in asthma and clinical trials investigating probiotics as potential treatments for atopy and asthma. The systemic effects of gut microbiota are partially attributed to their generating metabolites including short chain fatty acids, which can suppress lung inflammation through the activation of G protein‐coupled receptors. Thus, studying the interactions between microbiota and immune cells can lead to the identification of therapeutic targets for chronic lower respiratory diseases.     

Phages and their potential to modulate the microbiome and immunity

Bacteriophages (hence termed phages) are viruses that target bacteria and have long been considered as potential future treatments against antibiotic-resistant bacterial infection. However, the molecular nature of phage interactions with bacteria and the human host has remained elusive for decades, limiting their therapeutic application. While many phages and their functional repertoires remain unknown, the advent of next-generation sequencing has increasingly enabled researchers to decode new lytic and lysogenic mechanisms by which they attack and destroy bacteria. Furthermore, the last decade has witnessed a renewed interest in the utilization of phages as therapeutic vectors and as a means of targeting pathogenic or commensal bacteria or inducing immunomodulation. Importantly, the narrow host range, immense antibacterial repertoire, and ease of manipulating phages may potentially allow for their use as targeted modulators of pathogenic, commensal and pathobiont members of the microbiome, thereby impacting mammalian physiology and immunity along mucosal surfaces in health and in microbiome-associated diseases. In this review, we aim to highlight recent advances in phage biology and how a mechanistic understanding of phage–bacteria–host interactions may facilitate the development of novel phage-based therapeutics. We provide an overview of the challenges of the therapeutic use of phages and how these could be addressed for future use of phages as specific modulators of the human microbiome in a variety of infectious and noncommunicable human diseases.     

Phenotype stability in asthma and atopy in childhood

The asthma phenotype can be described using a combination of the following: symptom type, pattern and severity; markers of atopy; and measurement of bronchial responsiveness. Because of the very nature of the disease, symptoms of asthma are variable in both the short- and the long-term, and the natural history of the disease is such that symptoms in an individual may evolve over time through different patterns. Although atopy appears to be a life-long attribute resulting from an early life switching to a TH₂ immune response, the surrogate markers of atopy each are subject to their own time-related determinants and patterns of change with age. Bronchial responsiveness in childhood is neither specific nor sensitive for asthma, and although showing good short-term repeatability, can vary widely when measured over a period of months or years. Stimuli for responsiveness testing should be chosen which can be inhaled safely in high doses so as to allow an end point to be reached by as many subjects within a population as possible, and individuals may have to be tested repeatedly over time so as to avoid misclassification.     

The complexities of defining atopy in severe childhood asthma

Background Defining atopy in children with severe, therapy‐resistant asthma is complex. There is currently no gold standard test; both skin prick testing (SPT) and allergen‐specific IgE (sIgE) are used. Furthermore, atopy is increasingly considered to be a spectrum, not an all‐or‐none phenomenon. Hypothesis SPTs and sIgE cannot be used interchangeably, and if both tests are not performed, opportunities for intervention will be missed. Furthermore, the severity of atopy will be defined differently by the two tests. Methods Cross‐sectional study of 47 children with severe, therapy‐resistant asthma, mean age 11.8 years, range 5.3–16.6 years, who underwent SPT, and measurement of total and sIgE as part of their clinical work‐up. Results Overall, 42/47 (89%) were atopic (defined as either one positive SPT or sIgE). There was 98% concordance between the two tests in classifying atopy. When each allergen was considered individually, in 40/200 (20%), the SPT and sIgE results were discordant, most commonly in 25/200 (12.5%), the SPT was negative and the sIgE was positive. House dust mite and cat sensitization were more likely detected by sIgE, but dog sensitization by SPT. When atopy was quantified, the sum of sIgEs compared with the sum of SPT weal diameter showed a moderate correlation (r²=0.44, P<0.001). Total IgE increased with an increasing number of positive sIgEs (P=0.028), but not significantly with increasing numbers of positive SPTs. Conclusion and Clinical Relevance SPT and sIgE identify group prevalence of atopy equally well; however, for individual allergens, concordance is poor, and when used to quantify atopy, SPTs and sIgE were only moderately correlated. In a clinical setting, if allergen avoidance is contemplated in children with severe, therapy‐resistant asthma, both tests should be performed in order to detect sensitization. Cite this as: J. Frith, L. Fleming, C. Bossley, N. Ullmann and A. Bush, Clinical & Experimental Allergy, 2011 (41) 948–953.     

Diet as a risk factor for atopy and asthma

It has been hypothesized that decreasing antioxidant (fruit and vegetables), increased n-6 polyunsaturated fatty acid (PUFA; (margarine, vegetable oil), and decreased n-3 PUFA (oily fish) intakes have contributed to the recent increases in asthma and atopic disease. Epidemiologic studies in adults and children have reported beneficial associations between dietary antioxidants and lipids and parameters of asthma and atopic disease. The associations with n-6 and n-3 PUFA appear to be very complex and might differ between asthma and atopic dermatitis. Dietary antioxidants are probably exerting antioxidant and nonantioxidant immunomodulatory effects. Dietary lipids exert numerous complex effects on proinflammatory and immunologic pathways. It has also been suggested that atopic dermatitis is associated with an enzyme defect in lipid metabolism. In spite of this, the results of interventional supplementation studies in established disease have been disappointing, and there is now increasing interest in the possibility that dietary antioxidant and lipid intakes might be important in determining expression of disease during pregnancy and early childhood and that dietary interventions should be targeted at these groups. It also seems likely that there is individual variation in the responses of individuals to lipid, and probably antioxidant, supplementation. Further research to determine whether dietary intervention can reduce the risk of asthma and atopic disease is justified.     

Respiratory illnesses in early life and asthma and atopy in childhood

BACKGROUND: The relation between respiratory illnesses in early life and the development of asthma and atopy in childhood is incompletely understood. OBJECTIVE: We sought to examine the relationship between respiratory illnesses in early life and atopic diseases at school age. METHODS: We performed a prospective birth cohort study of the relationship between respiratory illnesses in the first year of life and asthma, atopy (sensitization to >or=1 allergen), and allergic rhinitis at school age in 440 children with a parental history of atopy. Logistic regression was used to examine the relationship between respiratory illnesses and asthma, atopy, and allergic rhinitis. The relationship between respiratory illnesses in early life and repeated measures of wheezing between the ages of 1 and 7 years was investigated by using a proportional hazards models. RESULTS: Physician-diagnosed croup (adjusted odds ratio [OR], 0.30; 95% CI, 0.12-0.72) and having 2 or more physician-diagnosed ear infections (adjusted OR, 0.58; 95% CI, 0.35-0.98) in the first year of life were inversely associated with atopy at school age. Physician-diagnosed bronchiolitis before age 1 year was significantly associated with asthma at age 7 years (adjusted OR, 2.77; 95% CI, 1.23-6.22). Recurrent nasal catarrh (>or=3 episodes of a runny nose) in the first year of life was associated with allergic rhinitis at age 7 years (adjusted OR, 2.99; 95% CI, 1.03-8.67). CONCLUSION: The relationship between early-life respiratory illnesses and asthma and atopy is complex and likely dependent on the type of infection and immune response it initiates. CLINICAL IMPLICATIONS: Certain respiratory illnesses in early life modify the risk of atopy and asthma at school age.     

The role of genetics in the development of asthma and atopy

PURPOSE OF REVIEW: The mapping of complex traits such as asthma and atopy is one of the most important and central areas of human genetics. This article will present an overview of the current status of genetic studies of asthma and atopy using genome screens and association studies that have occurred in the literature since January 2003. RECENT FINDINGS: Many regions of the genome have been found to have linkage with the phenotypes of asthma and atopy. Over 70 variants in candidate genes have been reported to be associated with these phenotypes. The main regions these variants have been found are on chromosomes 2q, 5q, 6p, 11q, 12q, 16q and 17q. Five potential asthma susceptibility genes or complexes have been identified using a positional approach. These are ADAM33, DPP10, PHF11 and SETDB2, GPRA and SPINK5. It is evident that environmental factors will influence the expression of genes and the ultimate clinical phenotype of asthma and atopy. SUMMARY: The development of asthma and atopy involves many genes and environmental factors. An understanding of their genetic basis has great implications for their management.