Asthma phenotypes in a multi-ethnic Asian cohort.

BACKGROUND: Identification of asthma phenotypes facilitates our understanding of asthma pathobiologies. Phenotypes observed in homogenous Asian cohorts have distinct differences from those described in Caucasian cohorts, suggesting that ethnicity may influence phenotypic expression. Phenotypic clusters in a multi-ethnic Southeast Asian cohort have not been described before, and direct comparisons of these clusters within a single study may reveal how ethnicity affects phenotypic expression. METHODS: Six hundred and thirty adult asthma patients from two healthcare institutions in Singapore were randomly assigned in a 2:1 fashion to a test and validation cohort. Latent class analysis was performed on both cohorts using age of asthma onset, sex, ethnicity, smoking status, body mass index, lung function, blood eosinophil count, asthma control test score, and exacerbation frequency as input variables. Phenotypic clusters between the test and validation cohorts were compared RESULTS: Three clusters were identified in both the test and validation cohorts, with corresponding clusters of each cohort sharing similar characteristics. Ethnic representation and asthma control were significantly different between clusters. Cluster one comprised Chinese females with late-onset asthma and the best asthma control. Cluster two comprised non-Chinese females with obesity and the worst asthma control. Cluster three was multi-ethnic with the greatest proportion of atopic patients. CONCLUSION: We identified three phenotypic clusters in our multi-ethnic Southeast Asian population, with distinct differences in ethnicity which may be attributable to inherent differences in baseline characteristics among ethnic groups.

[Influence of lifestyle, diet and vitamin D on atopy in a population of Afro-descendant Colombian children]. / Influencia del estilo de vida, la dieta y la vitamina D en la atopia en niños colombianos afrodescendientes.

BACKGROUND: Allergic conditions have shown an increase in the past few decades. Hygiene, changes in lifestyle, diet and vitamin D have been blamed for this increase. OBJECTIVE: To determine the role of environment, diet and vitamin D in atopic diseases in a population of Colombian Afro-descendant children. METHODS: Cross-sectional, descriptive, observational study in 200 Afro-descendant children of rural and urban areas from northern Colombia. Lifestyle and diet were established by questionnaires, atopy was assessed with skin tests and total and specific IgE and vitamin D levels were determined by ELISA. RESULTS: Results: Atopy was more prevalent in the urban population (24 % versus 7 %, p < 0.001). Blomia tropicalis was the most common allergen (80.6 %). The PCA indicated two dietary patterns. In the rural area children, the consumption of dairy products and fruit/vegetables was higher, and related with a protective effect on atopy (OR, 0.21 [p < 0.027] and OR, 0.11 [ p < 0.04]). A similar pattern was observed with total IgE and vitamin D levels (2450.73 versus 777.56 kU/mL [p < 0.01] and 59.32 ng/mL versus 31.14 ng/mL [p < 0.001], respectively). CONCLUSION: Allergic conditions were less prevalent in rural area residents, possibly owing to higher consumption of unpasteurized dairy products and fruit/vegetables, as well as higher levels of vitamin D.

Antecedentes: La prevalencia de las enfermedades alérgicas se ha incrementado en las últimas décadas. Se ha responsabilizado de este incremento a cambios en el estilo de vida, la dieta y vitamina D. Objetivo: Determinar el papel del ambiente, dieta y vitamina D en las enfermedades atópicas en una población de niños afrodescendientes colombianos. Métodos: Estudio observacional transversal y descriptivo en 200 niños afrodescendientes de áreas rural y urbana del norte de Colombia. El estilo de vida y la dieta se establecieron por cuestionarios, la atopia por pruebas cutáneas y los niveles de IgE total, específicas y vitamina D por ELISA. Resultados: La atopia fue más prevalente en la población urbana (24 % versus 7 %, p < 0.001). La Blomia tropicalis fue el alérgeno más común (80.6 %). El ACP indicó 2 patrones dietarios. En los niños del área rural fueron más altos el consumo de productos lácteos y de frutas/vegetales, lo cual se relacionó con un efecto protector en la atopia (RM, 0.21 [p < 0.037] y RM, 0.11 (p < 0.04), respectivamente). Un patrón similar se observó respecto a los niveles de IgE total y vitamina D (2450.73 versus 777.56 kU/mL [p < 0.01] y 59.32 ng/mL y 31.14 ng/mL [p < 0.001], respectivamente). Conclusión: las enfermedades alérgicas fueron menos prevalentes en los niños residentes del área rural posiblemente por el mayor consumo de productos lácteos no pasteurizados y frutas y vegetales, así como por mayores niveles de vitamina D.

[Effects of infant feeding practice on eczema during early childhood in Shanghai, Hohhot, and Fuzhou].

Objective: To estimate the prevalence of eczema in early childhood and effect of infant feeding practice on eczema by different regions of China with diverse climate and dietary patterns. Method: A questionnaire survey was conducted from June 2012 to October 2012 in Shanghai, Hohhot, and Fuzhou. The parent or guardian of the children aged between 2.5 to 3.5 years attending routine health visit in the chosen communities were invited to complete a modified questionnaire of the International Study of Asthma and Allergy in Childhood (ISAAC). Logistic regression model was used to analyze of the family history of allergy, duration of breastfeeding, timing of introduction of complementary foods and other potential confounders. Result: A total of 2 242 children were interviewed, 750 from Shanghai, 716 from Hohhot, and 776 from Fuzhou. The prevalence of eczema in early childhood was significantly different among Shanghai (16.9%, 95%CI 16.87-16.93), Hohhot (34.5%, 95%CI 34.46-34.54)and Fuzhou (44.3%, 95%CI 44.26-44.34). The difference was statistically significant between 3 groups (χ2=72.05, P<0.05). Introducing complementary food after the age of 6 months was associated with a decreased risk for eczema when compared to introduction between 4 to 6 months(odds ratio (OR) 0.58, 95%CI 0.41-0.81) in Fuzhou, while there was no significant association between timing of introduction of complementary foods and eczema in Shanghai and Hohhot. Conclusion: The prevalence of eczema during early childhood is various among three cities. The relationship between timing of introduction of complementary foods and eczema in Fuzhou is different from that in Shanghai and Hohhot. The role of climate and dietary patterns on prevalence of eczema needs further studies.

Atopic allergic conditions and colorectal cancer risk in the Multiethnic Cohort Study.

Studies have provided evidence of an inverse association between atopic allergic conditions (AACs) and invasive colorectal cancer (CRC) incidence and mortality in predominantly white populations. We examined the association between AACs (asthma, hay fever, or allergy) and CRC among white, African-American, Native Hawaiian, Japanese-American, and Latino men and women in the Multiethnic Cohort Study within Hawaii and Los Angeles, California. The prospective analysis included 4,834 incident CRC cases and 1,363 CRC-related deaths ascertained between 1993 and 2010. We examined associations by ethnicity, location, stage, and potential effect modification by CRC risk factors. AACs were associated with a reduced risk of CRC incidence among both men and women (relative risk (RR) = 0.86, 95% confidence interval (CI): 0.80, 0.92). The reduction in risk was noted in all populations except Latinos and was significant in whites (RR = 0.85, 95% CI: 0.73, 0.98), African Americans (RR = 0.81, 95% CI: 0.70, 0.95), Native Hawaiians (RR = 0.72, 95% CI: 0.54, 0.96), and Japanese Americans (RR = 0.87, 95% CI: 0.78, 0.98). Individuals with AACs also had a 20% reduction in CRC-related mortality (P = 0.001). These findings provide evidence for the potential protective role of the reactive immune system in colorectal cancer.

Non-infectious skin disease in Indigenous Australians.

The burden of non-infectious skin disease in the Indigenous Australian population has not been previously examined. This study considers the published data on the epidemiology and clinical features of a number of non-infectious skin diseases in Indigenous Australians. It also outlines hypotheses for the possible differences in the prevalence of such diseases in this group compared with the general Australian population. There is a paucity of literature on the topic but, from the material available, Indigenous Australians appear to have a reduced prevalence of psoriasis, type 1 hypersensitivity reactions and skin cancer but increased rates of lupus erythematosus, kava dermopathy and vitamin D deficiency when compared to the non-Indigenous Australian population. This article profiles the prevalence and presentation of non-infectious skin diseases in the Indigenous Australian population to synthesise our limited knowledge and highlight deficiencies in our understanding.

Prevalence of allergic disease in foreign-born American children.

IMPORTANCE: Improved understanding of allergic disease epidemiology lead to novel therapeutic and prevention strategies. OBJECTIVES: To study the association between US birthplace and prevalence of childhood allergic disease and to determine the effects of prolonged US residence on allergic disease. DESIGN, SETTING, PARTICIPANTS: Cross-sectional questionnaire distributed to 91, 642 children aged 0 to 17 years enrolled in the 2007-2008 National Survey of Children's Health. EXPOSURE: Place of birth. MAIN OUTCOME AND MEASURE: Prevalence of allergic disease, including asthma, eczema, hay fever, and food allergies. RESULTS: Children born outside the United States had significantly lower odds of any atopic disorders than those born in the United States (logistic regression OR, 0.48; 95% CI, 0.38-0.61), including ever-asthma (0.53; 0.39-0.72), current-asthma (0.34; 0.23-0.51), eczema (0.43; 0.30-0.61), hay fever (0.39; 0.27-0.55), and food allergies (0.60; 0.37-0.99). The associations between child's birthplace and atopic disorders remained significant in multivariate models including age, sex, race/ethnicity, annual household income, residence in metropolitan areas, and history of child moving to a new address. Children born outside the United States whose parents were also born outside the United States had significantly lower odds of any atopic disorders than those whose parents were born in the United States (P = .005). Children born outside the United States who lived in the United States for longer than 10 years when compared with those who resided for only 0 to 2 years had significantly higher odds of developing any allergic disorders (adjusted OR, 3.04; 95% CI, 1.08-8.60), including eczema (4.93; 1.18-20.62; P = .03) and hay fever (6.25; 1.70-22.96) but not asthma or food allergies (P ≥ .06). CONCLUSIONS AND RELEVANCE: Children born outside the United States have a lower prevalence allergic disease that increases after residing in the United States for 1 decade.

Factors associated with degree of atopy in Latino children in a nationwide pediatric sample: the Genes-environments and Admixture in Latino Asthmatics (GALA II) study.

BACKGROUND: Atopy varies by ethnicity, even within Latino groups. This variation might be due to environmental, sociocultural, or genetic factors. OBJECTIVE: We sought to examine risk factors for atopy within a nationwide study of US Latino children with and without asthma. METHODS: Aeroallergen skin test responses were analyzed in 1830 US Latino subjects. Key determinants of atopy included country/region of origin, generation in the United States, acculturation, genetic ancestry, and site to which subjects migrated. Serial multivariate zero-inflated negative binomial regressions stratified by asthma status examined the association of each key determinant variable with the number of positive skin test responses. In addition, the independent effect of each key variable was determined by including all key variables in the final models. RESULTS: In baseline analyses African ancestry was associated with 3 times (95% CI, 1.62-5.57) as many positive skin test responses in asthmatic participants and 3.26 times (95% CI, 1.02-10.39) as many positive skin test responses in control participants. Generation and recruitment site were also associated with atopy in crude models. In final models adjusted for key variables, asthmatic patients of Puerto Rican (exp[ß] [95% CI], 1.31 [1.02-1.69]) and mixed (exp[ß] [95% CI], 1.27 [1.03-1.56]) ethnicity had a greater probability of positive skin test responses compared with Mexican asthmatic patients. Ancestry associations were abrogated by recruitment site but not region of origin. CONCLUSIONS: Puerto Rican ethnicity and mixed origin were associated with degree of atopy within US Latino children with asthma. African ancestry was not associated with degree of atopy after adjusting for recruitment site. Local environment variation, represented by site, was associated with degree of sensitization.

Determinants of, and reference equation for, exhaled nitric oxide in the Chinese population.

Measurement of fractional exhaled nitric oxide concentration (FeNO) has been proposed as a useful biomarker for monitoring and management of airway diseases. Limited information is available regarding reference levels of FeNO levels in Chinese adults. This study aimed to investigate the reference equation and determinants of FeNO in Chinese adults. 1093 (577 males) healthy nonsmoking subjects aged 18-90 years were recruited. FeNO was measured online using a chemiluminescence analyser. Other assessments included spirometry, skin prick tests, total serum IgE levels and eosinophil count in peripheral blood. The geometric mean FeNO was 32.6 (95% reference interval (RI) 31.4-33.7) ppb for all subjects. FeNO values were higher in males than females (geometric mean (95% RI) 38.3 (36.5-40.2) ppb versus 27.1 (25.8-28.5) ppb, p<0.0001), and in atopic than nonatopic subjects (34.6 (33.0-36.3) ppb versus 29.8 (28.3-31.4) ppb, p<0.0001). FeNO correlated with age (r(2) = 0.23), height (r(2) = 0.20), IgE level (r(2) = 0.18) and percentage eosinophil count (r(2) = 0.18) (all p<0.0001), but not with spirometric parameters. Based on multiple regression modelling, the reference equation of FeNO value was: log(FeNO) = 0.781 + 0.104(sex) + 0.004(age) + 0.084(atopy) + 0.003(height in cm), where for sex 1 = male and 0 = female, age is measured in years, for atopy 1 = atopic and 0 = nonatopic, and height is measured in cm. The FeNO of Chinese adults is higher than that of the Caucasian population, and is affected by age, sex, height and atopic status. This study provides useful references for the interpretation of FeNO.

A study of IgE sensitization and skin response to histamine in Asian-Pacific American adults.

Allergic disorders and skin response to histamine have been noted to vary in different ethnicities. We investigated IgE-mediated allergic sensitization and skin response to histamine in Asian Pacific Americans (APAs), black and Hispanic Americans, and white adults. A retrospective questionnaire-based study was performed of 2222 adults presenting at a New York City allergy referral center from 1994 to 2003. Questionnaire data included sex, age, and ethnicity and personal and family history of atopic disorders. Skin-prick test (SPT) data included saline and histamine controls and response to a standardized panel of 10 aeroallergens. APA patients had a lower odds of asthma (adjusted odds ratio [aOR], 0.68; 95% confidence interval [CI], 0.52-0.89; p = 0.005) and/or animal allergies (aOR, 0.64; 95% CI, 0.50-0.82; p = 0.0003). Histamine response was not significantly different in APA (aOR, 0.90; 95% CI, 0.73-1.12; p = 0.36) or Hispanic Americans (aOR, 1.03; 95% CI, 0.85-1.24; p = 0.76), but was higher in black Americans (aOR, 2.32; 95% CI, 1.67-3.21; p < 0.0001). APA had higher odds of a positive SPT to trees (aOR, 1.49; 95% CI, 1.16-1.91; p = 0.002), grasses (aOR, 1.32; 95% CI, 1.05-1.43; p = 0.02), feathers (aOR, 1.65; 95% CI, 1.31-2.09; p < 0.0001), and cockroaches (aOR, 1.37; 95% CI, 1.10-1.62; p = 0.005). Moreover, APA had a higher total number of positive SPTs when compared with white patients (5.5 ± 3.2 versus 4.9 ± 3.3; aOR, 1.34; 95% CI, 1.10-1.62 p = 0.004). APA adults in our patient population had more IgE sensitizations but not an increased skin response to histamine. In contrast, black Americans had increased skin response to histamine.

[Bronchoconstriction induced by exercise in the black African athlete]. / L'Asthme Induit Par L'Exercice De L'Athlete En Climat Chaud Et Humide.

INTRODUCTION: The bronchoconstriction induced by exercise (BIE) in urban black Africans is poorly known. The warm moist air would be a mitigating factor for its occurrence. The objective of this study was to measure the prevalence and determine the associated factors. SUBJECTS AND METHODS: A prospective descriptive and analytical involving 40 student-athletes was conducted from September 12 to 24, 2010. The test was considered positive when the percentage fall in FEV from baseline in pre-test and the smallest value in post-test exceeded 10%. RESULTS: The prevalence of bronchoconstriction induced by exercise was 40% CI (26.3-55.4). The presence of symptoms of atopy was higher in athletes with an BIE than in those without (66% vs. 33.33% p NS). CONCLUSION: The proportion of the BIE in the middle of the black African athlete is as important as that observed in other countries, highlighting the weak influence of climate on its occurrence.

No association between genetic ancestry and susceptibility to asthma or atopy in Canary Islanders.

Asthma is a complex respiratory disease characterized by chronic inflammation of airways and frequently associated with atopic symptoms. The population from the Canary Islands, which has resulted from a recent admixture of North African and Iberian populations, shows the highest prevalence of asthma and atopic symptoms among the Spanish populations. Although environmental particularities would account for the majority of such disparity, genetic ancestry might play a role in increasing the susceptibility of asthma or atopy, as have been demonstrated in other recently African-admixed populations. Here, we aimed to explore whether genetic ancestry was associated with asthma or related traits in the Canary Islanders. For that, a total of 734 DNA samples from unrelated individuals of the GOA study, self-reporting at least two generations of ancestors from the Canary Islands (391 asthmatics and 343 controls), were successfully genotyped for 83 ancestry informative markers (AIMs), which allowed to precisely distinguishing between North African and Iberian ancestries. No association was found between genetic ancestry and asthma or related traits after adjusting by demographic variables differing among compared groups. Similarly, none of the individual AIMs was associated with asthma when results were considered in the context of the multiple comparisons performed (0.005 ≤ p value ≤ 0.042; 0.221 ≤ q value ≤ 0.443). Our results suggest that if genetic ancestry were involved in the susceptibility to asthma or related traits among Canary Islanders, its effects would be modest. Larger studies, examining more genetic variants, would be needed to explore such possibility.

Serum retinoic acid and atopy among children of different ethnic origin living in Germany.

We hypothesized that higher provitamin A carotenoid serum levels may be associated with higher concentrations of all-trans retinoic acid (ATRA) and atopy. Concentration of ATRA was measured by high-performance liquid chromatography in sera from German domestic and Turkish migrants' children. ATRA serum levels were significantly higher in German children if compared with Turkish children and correlated with those of ß-carotene (rs = 0.692) and other provitamin A carotenoids. They did not differ significantly between atopic and nonatopic individuals. Serum levels of ATRA are related to those of provitamin A carotenoids but are not directly related to atopy in the present study.

Relationship of serum cholesterol levels to atopy in the US population.

BACKGROUND: Cholesterol promotes Th2 immunity and allergic inflammation in rodents; whether this occurs in humans is unclear. Reports of both direct and inverse associations between serum cholesterol and atopy in different populations suggest that race and/or other demographic variables may modify these relationships. AIMS OF THE STUDY: To determine the relationships between levels of three serum cholesterol measures [total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), and non-HDL-C] and atopy in a sample representative of the US population. METHODS: Cross-sectional study of 6854 participants aged > or =6 years from the 2005-2006 National Health and Nutrition Examination Survey. RESULTS: In the overall population, adjusted odds ratios (AORs) per two-standard deviation increase in TC and non-HDL-C for biochemical atopy (defined as > or =1 allergen-specific IgE to 19 allergens) were 1.17 [95% confidence interval (CI), 1.00-1.38] and 1.19 (95% CI, 1.03-1.39), respectively. Interactions by race were noted for the two relationships (interaction P = 0.004 and P = 0.009, respectively) with non-Hispanic Whites (NHWs) having direct relationships [TC: AOR 1.27 (95% CI, 1.03-1.57); non-HDL-C: AOR 1.27 (95% CI, 1.03-1.56)] and non-Hispanic Blacks (NHBs) inverse relationships [TC: AOR 0.77 (95% CI, 0.62-0.95); non-HDL-C: AOR 0.86 (95% CI, 0.69-1.08)]. The adjusted HDL-C-atopy relationship was nonsignificant for NHWs and inverse for NHBs [AOR 0.77 (95% CI, 0.61-0.96)]. Relationships were independent of body mass index and serum C-reactive protein and unmodified by corticosteroid or statin usage. Results were similar using current hay fever/allergy as the atopy outcome. CONCLUSIONS: There are marked inter-racial differences in the relationship between serum cholesterol and atopy in the US population.

Mouse to human comparative genetics reveals a novel immunoglobulin E-controlling locus on Hsa8q12.

Atopy is a predisposition to hyperproduction of immunoglobulin E (IgE) against common environmental allergens. It is often associated with development of allergic diseases such as asthma, rhinitis, and dermatitis. Production of IgE is influenced by genetic and environmental factors. In spite of progress in the study of heredity of atopy, the genetic mechanisms of IgE regulation have not yet been completely elucidated. The analysis of complex traits can benefit considerably from integration of human and mouse genetics. Previously, we mapped a mouse IgE-controlling locus Lmr9 on chromosome 4 to a segment of <9 Mb. In this study, we tested levels of total IgE and 25 specific IgEs against inhalant and food allergens in 67 Czech atopic families. In the position homologous to Lmr9 on chromosome 8q12 marked by D8S285, we demonstrated a novel human IgE-controlling locus exhibiting suggestive linkage to composite inhalant allergic sensitization (limit of detection, LOD = 2.11, P = 0.0009) and to nine specific IgEs, with maximum LOD (LOD = 2.42, P = 0.0004) to plantain. We also tested 16 markers at previously reported chromosomal regions of atopy. Linkage to plant allergens exceeding the LOD > 2.0 was detected at 5q33 (D5S1507, LOD = 2.11, P = 0.0009) and 13q14 (D13S165, LOD = 2.74, P = 0.0002). The significant association with plant allergens (quantitative and discrete traits) was found at 7p14 (D7S2250, corrected P = 0.026) and 12q13 (D12S1298, corrected P = 0.043). Thus, the finding of linkage on chromosome 8q12 shows precision and predictive power of mouse models in the investigation of complex traits in humans. Our results also confirm the role of loci at 5q33, 7p14, 12q14, and 13q13 in control of IgE.

Netherton syndrome: mutation analysis of two Taiwanese families.

Netherton syndrome (NS) is a severe autosomal recessive skin disorder characterized by congenital ichthyosiform erythroderma, hair shaft abnormalities, and atopic diathesis. Recently, pathogenic mutations were identified in serine protease inhibitor Kazal-type 5 (SPINK5), the gene that encodes lympho-epithelial Kazal-type related inhibitor (LEKTI), a type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. In the present report, we describe the mutation analysis of two Taiwanese patients with NS. Patient 1 has heterozygous mutations; the maternal allele has novel T808I (C-T transition in codon 808) and the paternal allele has recurrent R790X (C-T transition in codon 790). Patient 2 is homozygous for a novel polymorphism R267Q (G-A transition in codon 267). The change was not detected in the patient's father. Haplotype analysis revealed that the patient was homozygous for the 5 single nucleotide polymorphisms in the genomic sequence of SPINK5 as well as the flanking (GT)(17) and D5S413, in addition to the discrepancy of R267Q. Nevertheless real-time quantitative PCR analysis revealed no microdeletion in the genomic sequence of SPINK5. Thus uniparental disomy of maternal SPINK5 allele was indicated.

Allergen-specific IgG1 provides parsimonious heritability estimates for atopy-associated immune responses to allergens.

Although serum total immunoglobulin E (IgE) is generally elevated in atopic conditions, it is an unreliable trait for dissecting the genetic and environmental components contributing to atopic immune responses, because it can be significantly confounded by demographic factors (age, gender, and race) and clinical status (atopic vs nonatopic). Allergen-specific IgE is a discontinuous trait present only in those with sensitivity to allergens. However, all people will produce allergen-specific immunoglobulin G1 (IgG1), which is elevated among those atopically sensitized to specific allergens. We screened 91 Caucasian nuclear families (N = 367) with medical histories of atopic diseases and used variance components analysis to compare heritability estimates for total IgE and IgG1 produced against the common major allergen from house dust mite Dermatophagoides pteronyssinus (Der p 1). An estimate of total IgE heritability was about 48%, although this was significantly confounded by age, gender, and clinical atopic status. In contrast, Der p 1-IgG1 demonstrated a significant inherited component of about 62% that was not influenced by age, gender, or clinical status. For genetic studies of atopic humoral responses, allergen-specific IgG1 may be a more reliable quantitative trait than serum IgE. Moreover, atopy is an inherited deregulation of immune responses to noninfectious antigens, involving antibody isotypes other than IgE.

Genetic epidemiology of health disparities in allergy and clinical immunology.

The striking racial and ethnic disparities in disease prevalence for common disorders, such as allergic asthma, cannot be explained entirely by environmental, social, cultural, or economic factors, and genetic factors should not be ignored. Unfortunately, genetic studies in underserved minorities are hampered by disagreements over the biologic construct of race and logistic issues, including admixture of different races and ethnicities. Current observations suggest that the frequency of high-risk variants in candidate genes can differ between African Americans, Puerto Ricans, and Mexican Americans, and this might contribute to the differences in disease prevalence. Maintenance of certain allelic variants in the population over time might reflect selective pressures in previous generations. For example, significant associations between markers in certain candidate genes (eg, STAT6, ADRB2, and IFNGR1) for traits such as high total IgE levels observed in resistance to extracellular parasitic disease in one population and atopic asthma in another supports the common disease/common variant model for disease. Herein is a discussion of how genetic variants might explain, at least in part, the marked disparities observed in risk to allergic asthma.

Mode of delivery is associated with asthma and allergy occurrences in children.

PURPOSE: A growing body of evidence indicates that perinatal factors modulate immune development and thereby may affect childhood asthma risk. In this study, we examined the associations between birth by cesarean section (C-section) and atopic disease occurrence in childhood. METHODS: Subjects were born in California between 1975 and 1987 and were 8 to 17 years old during their enrollment in the Children's Health Study. Our analysis was restricted to 3464 children born at or after 37 weeks of gestation with a birth weight of 2500 g or greater based on birth certificate data. Information about sociodemographic factors, reported physician-diagnosed asthma, and other atopic diseases was obtained by using a self-administered structured questionnaire. Logistic regression models were fitted to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Children born by C-section were at increased risk for asthma (OR, 1.33; 95% CI, 1.01-1.75), hay fever (OR, 1.57; 95% CI, 1.24-1.99), and allergy (OR, 1.26; 95% CI, 1.03-1.53) compared with those born vaginally. Risk associated with C-section was the same for children regardless of family history of asthma or allergy. CONCLUSION: We conclude that birth by C-section or processes associated with it may increase the risk for atopic disease in childhood.

Asthma phenotypes in Niue Islanders.

OBJECTIVE: The aim of this study was to identify asthma phenotypes in patients of Niue Island ancestry that might be suitable for susceptibility gene mapping studies. METHODOLOGY: Two hundred and sixteen Niue Islanders with physician-diagnosed asthma that was not secondary to other medical conditions were recruited through community organisations. Fifty-one of the subjects with asthma were resident on Niue Island and 165 in New Zealand. Each subject was interviewed and tested for atopy, serum [IgE] (5% quantile, median, 95% quantile) and lung function. RESULTS: There were two groups of subjects defined by an age of onset of asthma less than 12 years of age (childhood-onset, boys:girls 64:65) and greater than 12 years of age (adult-onset, men:women 11:76). A positive response (wheal > 3 mm) to at least one aeroallergen was seen in 181 patients, with 168/181 (92.8%) responding to house dust mite. Twenty-eight subjects with asthma were non-atopic (no detectable wheal) and the atopy status of seven subjects with asthma could not be determined (wheal < 3 mm). In childhood-onset asthma, serum IgE levels were higher (P < 0.0001) in subjects with atopic than in subjects with non-atopic asthma. In adult-onset asthma, serum IgE levels were higher (P < 0.0001) in subjects with atopic asthma than in either subjects with non-atopic asthma or matched non-atopic subjects without asthma. The asthma phenotypes in Niue Island and New Zealand residents were similar. CONCLUSIONS: Both atopic and non-atopic asthma phenotypes exist in Niue Islanders resident in Niue and New Zealand. The potential for mapping asthma susceptibility genes in this isolated population is discussed.

Dynamic changes in sensitization to specific aeroallergens in children raised in a desert environment.

BACKGROUND: Allergen skin test reactivity and total serum IgE are objective measures used to characterize and help diagnose allergic diseases. Cross-sectional studies have shown that overall aeroallergen skin test reactivity increases throughout childhood. However, little attention has been paid to whether individual aeroallergen remittance occurs, which could distort or mask relationships to disease. OBJECTIVE: To access the incidence and remittance of skin test reactions to individual allergens in children aged 6-11 years. METHODS: Longitudinal sensitization to six aeroallergens and total IgE were assessed in 828 children raised in the semi-arid US southwest at ages 6 and 11 years. RESULTS: New sensitization (to any allergen) between 6 and 11 years occurred in 30.2% of children compared with 39.7% before age 6 years. The rate of complete remittance from positive to negative between ages 6 and 11 years was 8.2%, and total IgE at age 6 years was not predictive. Remittance rates for individual allergens were high and variable (19-49%). The perennial allergens Bermuda and Alternaria were early sensitizers and had low remittance rates. Early sensitization to the four seasonal allergens was less common and more subject to remittance with the bulk of sensitization occurring between 6 and 11 years. CONCLUSION: This study shows that sensitization to individual aeroallergens in childhood is dynamic and indicates the limitation of single point assessment of skin test reactivity.