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1.  Genetic and Environmental Contributions to Allergen Sensitization in a Chinese Twin Study 
Allergic disease is on the rise worldwide. Effective prevention of allergic disease requires comprehensive understanding of the factors that contribute to its intermediate phenotypes, such as sensitization to common allergens.
To estimate the degree of genetic and environmental contributions to sensitization to food or aeroallergens.
Sensitization was defined as a positive skin prick test to an allergen. We calculated the zygosity-specific concordance rates and odds ratios (ORs) for sensitization to food and aeroallergens in 826 Chinese twin pairs (472 MZ and 354 DZ) aged 12 to 28 years. We also applied structural equation modeling procedures to estimate genetic and environmental influences on sensitization.
The concordance rates and risk of sensitization in one twin given the presence vs. the absence of sensitization in the other twin were higher in MZ twins than those in DZ twins. However, a large number of MZ twins were discordant in sensitization to common allergens. These observations suggest both genetic and environmental factors influence sensitization. Consistently, the estimated heritability and individual environmental components of the liability to sensitization ranged from 0.51 to 0.68 and 0.32 to 0.49, respectively, based on the best-fitted structural equation model. We also observed high phenotypic correlations between sensitization to two aeroallergens (cockroach and dust mite: 0.83) and two food allergens (peanut and shellfish: 0.58), but only moderate correlations for the pairs between sensitization to a food and an aeroallergen (0.31-0.46). The shared genetic and environmental factors between paired sensitizations contribute to the observed correlations.
We demonstrated that sensitization to common food and aeroallergens were influenced by both genetic and environmental factors. Moreover, we found that paired allergen sensitizations might share some common sets of genes and environmental factors. This study underscores the need to further delineate unique and/or pleiotropic genetic and environmental factors for allergen sensitization.
PMCID: PMC2756049  PMID: 19302247
Twin; sensitization; positive SPT; structural equation modeling; heritability; environmental factors
2.  Asthma, allergy, and atopy in three south-east Asian populations. 
Thorax  1994;49(12):1205-1210.
BACKGROUND--Whilst many recent reports have suggested a rise in the prevalence of asthma and allergic disease in Western countries, little is known about the epidemiology of these common conditions in south-east Asia. This study compared the prevalence of asthma and allergic disease amongst secondary school students in three south-east Asian populations--Hong Kong, Kota Kinabalu in Malaysia, and San Bu in China--and investigated the associations with atopy and family history. METHODS--Secondary school students were given standard questionnaires on respiratory and allergic symptoms for completion by parents with response rates of 89.2% in Hong Kong (611 male, 451 female; mean (SD) age = 13.9 (1.8 years), 87.6% in Kota Kinabalu (134 male, 275 female; 15.5 (2.1) years), and 98.6% in San Bu (492 male, 245 female; 16.4 (1.8) years). Skin tests were performed in a subsample of students to determine atopic status. RESULTS--The respective prevalence (and 95% CI) for hayfever, eczema, and wheeze or asthma were 15.7% (13.5, 17.9), 20.1% (17.7, 22.5), 11.6% (9.3, 13.9) in Hong Kong, 11.2% (8.2, 14.3), 7.6% (5.0, 10.1), 8.2% (5.5, 10.9) in Kota Kinabalu, and 2.1% (1.2, 3.1), 7.2% (5.4, 9.1), 1.9% (0.7, 3.1) in San Bu. Atopy was common and was present in 49.0-63.9% of subjects in the three populations. Dust mite and cockroach were the commonest allergens that gave positive reactions in 42.8-60.5% and 25.7-35.9% of students respectively. A higher proportion of students in Hong Kong had severe degree of reactivity on skin test than the other two populations. Family history was associated with asthma and allergic symptoms in the three populations conferring a 3-80-fold increase in risk to family members and was a stronger predictor for asthma and allergy than atopy. CONCLUSIONS--Prevalence of asthma and allergic disease is low compared with Western countries, but considerable differences exist between the three south-east Asian populations despite similar rates of atopy. Asthma and allergic disease are more strongly associated with family history than atopy, which suggests that genetic and environmental factors common to the family, other than aeroallergen sensitisation, are important in the pathogenesis of asthma and allergy in the region.
PMCID: PMC475324  PMID: 7878553
3.  Effects of geohelminth infection and age on the associations between allergen-specific IgE, skin test reactivity and wheeze: a case-control study 
Most childhood asthma in poor populations in Latin America is not associated with aeroallergen sensitization, an observation that could be explained by the attenuation of atopy by chronic helminth infections or effects of age.
To explore the effects of geohelminth infections and age on atopy, wheeze, and the association between atopy and wheeze.
A case-control study was done in 376 subjects (149 cases and 227 controls) aged 7–19 years living in rural communities in Ecuador. Wheeze cases, identified from a large cross-sectional survey, had recent wheeze and controls were a random sample of those without wheeze. Atopy was measured by the presence of allergen-specific IgE (asIgE) and skin prick test (SPT) responses to house dust mite and cockroach. Geohelminth infections were measured in stools and anti-Ascaris IgE in plasma.
The fraction of recent wheeze attributable to anti-Ascaris IgE was 45.9%, while those for SPT and asIgE were 10.0% and 10.5% respectively. The association between atopy and wheeze was greater in adolescents than children. Although Anti-Ascaris IgE was strongly associated with wheeze (adj. OR 2.24 (95% CI 1.33–3.78, P = 0.003) and with asIgE (adj. OR 5.34, 95% CI 2.49–11.45, P < 0.001), the association with wheeze was independent of asIgE. There was some evidence that the association between atopy and wheeze was greater in uninfected subjects compared with those with active geohelminth infections.
Conclusions and clinical relevance
Atopy to house dust mite and cockroach explained few wheeze cases in our study population, while the presence of anti-Ascaris IgE was an important risk factor. Our data provided only limited evidence that active geohelminth infections attenuated the association between atopy and wheeze in endemic areas or that age modified this association. The role of allergic sensitization to Ascaris in the development of wheeze, independent of atopy, requires further investigation.
PMCID: PMC3563216  PMID: 23278881
allergen skin test reactivity; allergen-specific IgE; atopy; geohelminths; wheeze
4.  Risk Factors Associated with the Development of Atopic Sensitization in Indonesia 
PLoS ONE  2013;8(6):e67064.
The prevalence of allergic diseases has increased not only in high income but also in low-to-middle income countries. However, risk factors for their development are still not well established, particularly in the latter.
To assess prevalence and identify risk factors for sensitization to two major inhalant allergens among children from semi-urban and rural areas in Indonesia.
A cross-sectional survey was performed among 1,674 school children aged 5–15 years old. Information on potential risk factors and reported allergic symptoms were obtained by questionnaire. Helminth infections were assessed. Skin prick tests (SPT) were performed, total IgE as well as allergen-specific IgE for house dust mite (HDM) and cockroach were measured.
The prevalence of allergic skin sensitization to both aeroallergens was significantly higher in the semi-urban than in the rural area. However, serum IgE against HDM and cockroach as well as total IgE were significantly lower in semi-urban than in rural children. In the semi-urban area, there was a significant positive association between SPT to HDM and higher paternal education but a negative one with hookworm infection. The risk factors linked to cockroach sensitization were different: being of a farmer offspring and lacking access to piped water were associated with an increased risk for a positive SPT to cockroach. No significant associations between measured risk factors and having a positive SPT were found in the rural area.
Sensitization to HDM and cockroach is common in Indonesia, more often translating into a positive SPT in the semi-urban than in the rural setting. Whereas high paternal education and low hookworm infection were associated with increased risk of SPT to HDM, we were surprised to find parameters of lower SES were identified as risk factor for cockroach SPT.
PMCID: PMC3686782  PMID: 23840583
5.  Prevalence of allergen sensitization among patients with allergic diseases in Guangzhou, Southern China: a four-year observational study 
The distribution of allergens may vary with different geographic areas, suggesting the importance of local epidemiological data to support evidence-based prevention and management of allergic diseases. We investigated the distribution of common allergens in allergic patients in Guangzhou, southern China.
7,047 patients with allergic symptoms were examined for serum sIgE to 15 common allergens in this region, based on the protocol of reversed enzyme allergosorbent test.
4,869 (69.09%) of the subjects tested positive for sIgE to at least one of the 15 common allergens. There was no statistical difference in the overall rate of positive sIgE detection between males (3128/4523, 69.16%) and females (1741/2524, 68.98%). Der pteronyssinus and Der farinae were the most common aeroallergens, while eggs and cow’s milk the most common food allergens, responsible for higher positive rates of sIgE responses. A good correlation in positive sIgE response was found between Der pteronyssinus and Der farinae. By age-group analysis, we noted several peaks of sensitization to certain allergens: Der pteronyssinus, Der farinae, and Blomiatropicalis at age between 9 and 12; Blattellagermanica and mosquito at age between 15 and 18, cow’s milk before age 3; eggs and flour at age between 3 and 6; crabs and shrimps at age between 12 and 15. Along with older age, there was an ascending tendency in the overall positive rate of sIgE response to house dust mites among subjects who tested positive for sIgE to eggs or cow’s milk.
Der pteronyssinus, Der farinae, cow’s milk, and eggs are major allergens in Guangzhou. Sensitization to eggs and cow’s milk is more common at younger age, and then gives place to the increasing prevalence of sensitization to Der pteronyssinus and Der farinae at older age. Such a sequence of events may be a result of allergy march. Knowledge on the prevalence of allergen sensitization in different age groups would help early diagnosis and intervention of allergic diseases in this large geographical region.
PMCID: PMC3898259  PMID: 24428953
Allergy; Distribution; Prevalence; Specific immunoglobulin E
6.  Adiposity, serum lipid levels, and allergic sensitization in Chinese men and women 
Obesity and allergic diseases have increased dramatically in recent decades. While adiposity has been associated with asthma, associations with allergic sensitization have been inconsistent.
To examine the association of adiposity and lipid profiles with allergic sensitization.
This study included 1,187 rural Chinese twins (653 men) aged 18-39 years, with skin prick tests (SPT), anthropometric and DEXA-assessed adiposity measures, and lipid assessments. Allergic sensitization was defined as positive SPT to ≥1 allergen (9 foods and 5 aeroallergens tested). We applied gender-stratified generalized estimating equations to assess the association of adiposity and serum lipids with allergic sensitization, and structural equation models to estimate the genetic/environmental influences on any observed associations.
Males had lower percent body fat (%BF) (13.9% vs. 28.8%) but higher rates of allergic sensitization (56.2% vs. 36.7%) than females. Males in the highest %BF quartile were 2.1 times more likely sensitized than the lowest quartile (95%CI 1.3-3.5, P-trend=0.003). In males, the risk of allergic sensitization increased with HDL<40 mg/dl (OR=4.0, 95%CI 1.8-9.2) and higher LDL quartiles (P-trend=0.007). This appeared to be partially explained by shared genetic factors between serum lipid levels and allergic sensitization. In females, lower HDL was associated with increased risk of allergic sensitization.
In this relatively lean Chinese population, higher %BF, lower HDL and higher LDL were associated with greater risk of allergic sensitization, most notable in males. The observed associations between adiposity, serum lipids and allergic sensitization in males appear to be partially explained by common genetic influences on these traits.
PMCID: PMC2697621  PMID: 19135238
DEXA; Body mass index; Adiposity; Serum lipids; Sensitization
7.  Sensitization to airborne allergens among adults and its impact on allergic symptoms: a population survey in northern Vietnam 
The knowledge about allergic sensitization and its relationship with clinical symptoms and diseases among adults in South-East Asia is poor. The aim of this study was to investigate the prevalence and pattern of allergic sensitization and the association with asthma and allergic rhinitis in adults in urban and rural Vietnam.
Among 5,782 responders to a questionnaire survey in northern Vietnam, a random sample was invited to a clinical follow-up and 684 (46%) participated. The methods included a structured interview using a modified GA2LEN study questionnaire on symptoms and possible determinants for diseases. Skin prick test (SPT) with ten common airborne indoor and outdoor allergens, lung function test, and methacholine test was performed among subjects ≤60 years of age.
In total, one third of subjects had a positive SPT reaction to at least one allergen, 36.9% of men and 31.0% of women (n.s.). The most common sensitizer was the storage mite B. tropicalis (men 27.7%; women 18.7%) followed by house dust mite D. pteronyssinus (men 16.5%; women 10.6%), and D. farinae (men 15.3%; women 6.3%), and cockroach (men 16.5%; women 10.2%). Sensitization to all major allergens were significantly more common among men and among subjects ≤45 years compared with women and subjects >45 years, respectively. The prevalence of sensitization to animals, pollen and molds were low. The majority of cockroach-sensitized subjects were also sensitized to mites. Sensitization to any allergen and all major allergens were significantly associated with rhinitis, but not with asthma. However, bronchial hyper-reactivity was significantly associated with increasing number of positive SPTs (p = 0.047).
Among adults in northern Vietnam sensitization to mite and cockroach most common in both rural and urban areas. The dominant sensitizer was the storage mite B. tropicalis, which should be included in future studies and also in clinical practice, owing to its association with clinical symptoms. As in the Western world allergic sensitization was associated with rhinitis and bronchial hyper-reactivity. The lack of association with asthma in South-East Asia needs to be studied further.
PMCID: PMC3923743  PMID: 24512828
Allergic sensitization; Asthma; Allergic rhinitis; Storage mite; Vietnam
8.  Exercise-Induced Bronchospasm and Atopy in Ghana: Two Surveys Ten Years Apart 
PLoS Medicine  2007;4(2):e70.
Asthma and allergic diseases have increased in the developed countries. It is important to determine whether the same trends are occurring in the developing countries in Africa. We aimed to determine the time trend in the prevalence of exercise-induced bronchospasm (EIB) and atopic sensitisation over a ten-year period in Ghanaian schoolchildren.
Methods and Findings
Two surveys conducted using the same methodology ten years apart (1993 and 2003) among schoolchildren aged 9–16 years attending urban rich (UR), urban poor (UP), and rural (R) schools. Exercise provocation consisted of free running for six minutes. Children were skin tested to mite, cat, and dog allergen. 1,095 children were exercised in 1993 and 1,848 in 2003; 916 were skin tested in 1993 and 1,861 in 2003. The prevalence of EIB increased from 3.1% (95% CI 2.2%–4.3%) to 5.2% (4.3%–6.3%); absolute percentage increase 2.1% (95% CI 0.6%–3.5%, p < 0.01); among UR, UP, and R children EIB had approximately doubled from 4.2%, 1.4%, and 2.2% to 8.3%, 3.0% and 3.9% respectively. The prevalence of sensitisation had also doubled from 10.6%, 4.7%, and 4.4% to 20.2%, 10.3%, and 9.9% (UR, UP, and R respectively). Mite sensitisation remained unchanged (5.6% versus 6.4%), but sensitisation to cat and dog increased considerably from 0.7% and 0.3% to 4.6% and 3.1%, respectively. In the multiple logistic regression analysis, sensitisation (odds ratio [OR] 1.77, 95% CI 1.12–2.81), age (OR 0.88, 95% CI 0.79–0.98), school (the risk being was significantly lower in UP and R schools: OR 0.40, 95% CI 0.23–0.68 and OR 0.54, 95% CI 0.34–0.86, respectively) and year of the study (OR 1.73, 95% CI 1.13–2.66) remained significant and independent associates of EIB.
The prevalence of both EIB and sensitisation has approximately doubled over the ten-year period amongst 9- to 16-year-old Ghanaian children irrespective of location, with both EIB and atopy being more common among the UR than the UP and R children.
The prevalence of both exercise-induced bronchospasm and sensitisation has approximately doubled over the ten-year period amongst 9- to 16-year-old Ghanaian children
Editors' Summary
The proportion of children with asthma is thought to be increasing worldwide, and particularly among children that live in more developed countries. However, it is not clear why this is, since many different aspects of lifestyle and the environment have been linked with the onset of asthma. In Africa, asthma has typically been thought of as being very uncommon, and indeed in many African dialects there is no word for asthma or the symptoms, such as wheezing, that asthmatic children experience. However, some research studies have suggested that asthma might be becoming more common in Africa and that this could be linked to ongoing economic and social changes.
Why Was This Study Done?
The researchers here wanted to understand whether the trend for childhood asthma to be on the increase worldwide was also the case in Africa. Economic growth is bringing about rapid changes in lifestyle in many developing countries, and at the same time the burden of disease is changing. In order to make sure that health systems are appropriately resourced, it's important to anticipate future changes in the burden of different diseases.
What Did the Researchers Do and Find?
This study was based on a comparison between two surveys, carried out ten years apart, of children attending three schools in Ghana's second largest city, Kumasi. The surveys were done in 1993 and 2003, and the schools surveyed were a rich city school, a poor city school, and a school in the nearby countryside. The same methods were used in the two different surveys. Importantly, the researchers used an exercise test as an indicator for asthma, because language differences meant they could not find out whether children were indeed asthmatic. In the exercise test, the schoolchildren ran outdoors for six minutes, and the researchers measured how fast the children could breathe out before and after exercise (their “peak flow”). Children whose drop in peak flow was more than 12.5% were classified as having exercise-induced bronchospasm, which is thought to predict asthma. The children were also tested for their response to extracts that commonly cause allergic reactions, such as from dust mites and cat and dog hair. 1,095 children were studied in 1993 and 1,848 in 2003, paralleling the growth of the city, which also meant that by 2003 the rural school had become incorporated into the city. Over this period of time, the proportion of children with exercise-induced bronchospasm increased in all three schools; overall this proportion went up from 3.1% to 5.2%. Children from the rich city school were most likely to have exercise-induced bronchospasm at either survey date. However, children from the poor city school experienced the biggest change over the time period studied, with more than double the proportion of children having exercise-induced bronchospasm in 2003 as compared to 1993. The researchers also saw similar trends in children who had allergic reactions to common substances.
What Do These Findings Mean?
The researchers observed substantial increases in the rate of exercise-induced bronchospasm, and allergic reactions, between the two survey dates. This finding suggests that asthma is likely to have become much more common in that time. However, exercise-induced bronchospasm is not an exact indicator of asthma so it is not possible to be certain about this. These changes are likely to be linked with the adoption of westernized lifestyles, but which precise factors are responsible for the increase is not clear. Factors linked to the development of asthma include a lower rate of childhood infections, a lower rate of breast-feeding, environmental pollution, and many others. Links between the increase in exercise-induced bronchospasm and any of these factors were not examined in this study. However, these results suggest that if the findings here are common to other African cities as well, a greater proportion of African health budgets will need to be devoted to asthma care in the future.
Additional Information.
Please access these Web sites via the online version of this summary at
Wikipedia has an entry on asthma (Wikipedia is an internet encyclopedia anyone can edit)
The World Health Organization's Ghana minisite has information on this country
Patient information from NHS Direct on asthma
An accompanying PLoS Medicine Essay by Matthias Wjst and Daniel Boakye discusses research on asthma in Africa
PMCID: PMC1808098  PMID: 17326711
9.  Role of Skin Prick Test in Allergic Disorders: A Prospective Study in Kashmiri Population in Light of Review 
Indian Journal of Dermatology  2013;58(1):12-17.
Skin prick test (SPT) is the most effective diagnostic test to detect IgE mediated type I allergic reactions like allergic rhinitis, atopic asthma, acute urticaria, food allergy etc. SPTs are done to know allergic sensitivity and applied for devising immunotherapy as the therapeutic modality.
Materials and Methods:
This prospective study was conducted in the department of Immunology and Molecular medicine at SKIMS. A total of 400 patients suffering from allergic rhinitis, asthma and urticaria were recruited in this study. SPT was performed with panel of allergens including house dust mite, pollens, fungi, dusts, cockroach, sheep wool and dog epithelia. Allergen immunotherapy was given to allergic rhinitis and asthmatic patients as therapeutic modality.
In our study, age of patients ranged from 6 to 65 years. Majority of patients were in the age group of 20-30 years (72%) with Male to female ratio of 1:1.5. Of the 400 patients, 248 (62%) had urticaria, 108 (27%) patients had allergic rhinitis and 44 (11%) patients had asthma. SPT reaction was positive in 38 (86.4%) with allergic asthma, 74 (68.5%) patients with allergic rhinitis and 4 (1.6%) patient with urticaria, respectively. Allergen immunotherapy was effective in 58% patients with allergic rhinitis and 42% allergic asthma.
Identifiable aeroallergen could be detected in 86.4% allergic asthma and 68.5% allergic rhinitis patients by SPT alone. Pollens were the most prevalent causative allergen. There was significant relief in the severity of symptoms, medication intake with the help of allergen immunotherapy.
PMCID: PMC3555364  PMID: 23372205
Allergic rhinitis; asthma; Kashmir; skin prick test
10.  Skin Prick Test Reactivity to Common Aero and Food Allergens among Children with Allergy 
Background: The prevalence of allergic diseases has risen in the last decades. The objective of this study was to determine the common allergens in children via the skin prick test.
Methods: This cross-sectional study recruited 313 allergic children (4 months to 18 years old) referred to the Asthma and Allergy Clinic of Children’s Medical Center in Tehran. A questionnaire containing demographic data and patient history was completed. The Skin Prick Test (SPT) was selected according to the patients’ history of food and/or aeroallergen sensitivity.
Results: Patients (62.4% male, 37.6% female) with symptoms of asthma (n=141, 57.1%), allergic rhinitis (n=50, 20.4%), atopic dermatitis (n=29, 11.7%), and urticaria (n=20, 8.1%) were studied. Positive skin prick test to at least one allergen was 58.1%. The most prevalent allergens were tree mix (26%), Alternaria alternata (26%), weed mix (23.6%), Dermatophagoides farinae (22.9%), Dermatophagoides pteronyssinus (22.9%), milk (21.7%), eggs (20%), and wheat flour (18.3%). Also, common allergens in the patients with different symptoms of allergic disorders were as follows: asthma (tree mix, weed mix, and Dermatophagoides farinae); allergic rhinitis (Dermatophagoides farinae, tree mix, and Dermatophagoides pteronyssinus); and atopic dermatitis (Alternaria alternata, Dermatophagoides pteronyssinus, and cockroaches).
Conclusion: Identifying allergens in each area is necessary and has an important role in the diagnosis and management of allergic disorders and possibility of performing immunotherapy. In this study, the most common aeroallergens were tree mix, Alternaria alternata, and weed mix and also the most common food allergens were milk, eggs, and wheat. Considering these data, appropriate preventive strategies can decrease the cost and morbidity of therapeutic actions.
PMCID: PMC3895892  PMID: 24453391
Allergens; Children; Skin test
11.  Sensitization to Food and Inhalant Allergens in Relation to Age and Wheeze Among Children with Atopic Dermatitis 
Atopic dermatitis (AD) is common in children; however, persistence of AD with or without asthma, is less common. Longitudinal studies remain limited in their ability to characterize how IgE antibody responses evolve in AD, and their relationship to asthma.
To use a cross-sectional study design of children with active AD to analyze age-related differences in IgE antibodies and relation to wheeze.
IgE antibodies to food and inhalant allergens were measured in children with active AD (5 months to 15 years of age, n=66), with and without history of wheeze.
Whereas IgE antibodies to foods persisted at a similar prevalence and titer throughout childhood, IgE antibodies to all aeroallergens rose sharply into adolescence. From birth, the chance of sensitization for any aeroallergen increased for each 12-month increment in age (OR≥1.21, p≤0.01), with the largest effect observed for dust mite (OR=1.56, p<0.001). A steeper age-related rise in IgE antibody titer to dust mite, but no other allergen, was associated with more severe disease. Despite this, sensitization to cat was more strongly associated with wheeze (OR=4.5, p<0.01), and linked to Fel d 1 and Fel d 4, but not Fel d 2. Comparison of cat allergic children with AD to those without, revealed higher titers to Fel d 2 and Fel d 4 (p<0.05), but not Fel d 1.
Conclusions and Clinical Relevance
Differences in sensitization to cat and dust mite among young children with AD may aid in identifying those at increased risk for disease progression and development of asthma. Early sensitization to cat and risk for wheeze among children with AD may be linked to an increased risk for sensitization to a broader spectrum of allergen components from early life. Collectively, our findings argue for early intervention strategies designed to mitigate skin inflammation in children with AD.
PMCID: PMC3801418  PMID: 24074334
Atopic dermatitis; asthma; wheeze; IgE antibodies; age; food allergy; aeroallergens; cat; dust mite
12.  Characterization of aeroallergen sensitivities in children with allergic rhinitis and chronic rhinosinusitis 
Allergy & Rhinology  2014;5(3):e143-e145.
Allergic rhinitis is a common comorbid condition in pediatric chronic rhinosinusitis (CRS). Testing for aeroallergen sensitization should therefore be considered in the evaluation of children with CRS. At present the aeroallergen sensitivity profile of children with CRS remains uncharacterized. In this study, we retrospectively identify a consecutive series of children with CRS and allergic rhinitis who have undergone joint otolaryngology and allergy evaluation at a single tertiary care center. We describe the aeroallergen sensitivity profiles (based upon formal skin testing) of these children, stratifying them according to co-morbidity status: 1) CRS with cystic fibrosis (CF), 2) CRS with immune deficiency and 3) uncomplicated CRS (without co-morbid CF, immune deficiency or primary ciliary dyskinesia). We identify 208 children (average age 9.3 years, standard deviation 4.8 years) with CRS and allergic rhinitis meeting inclusion criteria, 140 with uncomplicated CRS, 64 with co-morbid immune deficiency and 4 with co-morbid CF. The prevalence of indoor aeroallergen sensitivities (62.9–100.0%) was more common than that of outdoor aeroallergen sensitivities (43.8–50.0%) in all three cohorts of children. In all three cohorts, the most common indoor aeroallergen sensitivity was to dust mites (50.0–75.0%) and the most common outdoor aeroallergen sensitivity was to tree pollens (43.8–50.0%). The aeroallergen sensitivity profile of children with CRS and allergic rhinitis appears to be similar to that of the general pediatric population with allergic rhinitis, and parallels the aeroallergen sensitivities previously described for adults with CRS and allergic rhinitis. Knowledge of the aeroallergen sensitivities in children with CRS and allergic rhinitis will enhance both diagnostic and treatment strategies.
PMCID: PMC4275460  PMID: 25565050
Aeroallergen; allergic rhinitis; chronic rhinosinusitis; epidemiology; pediatric; sensitivities; skin testing
13.  Lower Expression of TLR2 and SOCS-3 Is Associated with Schistosoma haematobium Infection and with Lower Risk for Allergic Reactivity in Children Living in a Rural Area in Ghana 
Helminth infections are prevalent in rural areas of developing countries and have in some studies been negatively associated with allergic disorders and atopy. In this context little is known of the molecular mechanisms of modulation involved. We have characterized the innate immune responses, at the molecular level, in children according to their helminth infection status and their atopic reactivity to allergens.
Methodology/Principal Findings
The mRNA expression of several genes of the innate immune system that have been associated with microbial exposure and allergy was examined in 120 school children in a rural area in Ghana. Helminth infections were common and atopy rare in the study area. The analysis of gene expression in ex vivo whole blood samples reflected the levels of corresponding proteins. Using this approach in a population of school children in whom the presence of Schistosoma haematobium infection was associated with protection from atopic reactivity, we found that the level of TLR2 and SOCS-3, genes associated with atopy in the children, were significantly downregulated by presence of S. haematobium infection.
S. haematobium infections modulate the expression of genes of the innate immune system (TLR2 and SOCS-3); these are genes that are associated with increased allergic inflammatory processes, providing a molecular link between the negative association of this infection and atopy in rural children in Ghana.
Author Summary
Inflammatory diseases such as atopic disorders are a major health problem in the Western world, but their prevalence is also increasing in developing countries, especially in urban centres. There is increasing evidence that exposure to a rural environment with high burden of compounds derived from parasites and microorganisms is associated with protection from atopic disorders. Since urbanisation is progressing at a rapid pace, particularly in less-developed nations, there is a need to understand the molecular processes that control the progress towards the development of allergic diseases in developing countries. In this study we have examined a population of school children living in a rural area of Ghana, where helminth (worm) infections are prevalent and associated with protection from skin reactivity to house dust mite. Blood samples were collected from these children and analysed for the expression levels of several genes involved in the development of a pro allergic immune system. The results point at a potential molecular link that might explain the negative association between schistosome infections and allergies.
PMCID: PMC2291570  PMID: 18414649
14.  Food allergies in developing and emerging economies: need for comprehensive data on prevalence rates 
Although much is known today about the prevalence of food allergy in the developed world, there are serious knowledge gaps about the prevalence rates of food allergy in developing countries. Food allergy affects up to 6% of children and 4% of adults. Symptoms include urticaria, gastrointestinal distress, failure to thrive, anaphylaxis and even death. There are over 170 foods known to provoke allergic reactions. Of these, the most common foods responsible for inducing 90% of reported allergic reactions are peanuts, milk, eggs, wheat, nuts (e.g., hazelnuts, walnuts, almonds, cashews, pecans, etc.), soybeans, fish, crustaceans and shellfish. Current assumptions are that prevalence rates are lower in developing countries and emerging economies such as China, Brazil and India which raises questions about potential health impacts should the assumptions not be supported by evidence. As the health and social burden of food allergy can be significant, national and international efforts focusing on food security, food safety, food quality and dietary diversity need to pay special attention to the role of food allergy in order to avoid marginalization of sub-populations in the community. More importantly, as the major food sources used in international food aid programs are frequently priority allergens (e.g., peanut, milk, eggs, soybean, fish, wheat), and due to the similarities between food allergy and some malnutrition symptoms, it will be increasingly important to understand and assess the interplay between food allergy and nutrition in order to protect and identify appropriate sources of foods for sensitized sub-populations especially in economically disadvantaged countries and communities.
PMCID: PMC3551706  PMID: 23256652
Food allergy; Food hypersensitivity; Nutrition; Developing countries
15.  81 Dose Response Relationship Between Ascaris Sensitisation and Atopy and Bronchial Hyper-Responsiveness but not Allergic Diseases in Black South Africans 
The World Allergy Organization Journal  2012;5(Suppl 2):S43-S44.
The relationship between sensitisation to helminths and atopy, bronchial-hyperresponsiveness and allergic diseases may differ depending on many factors, including the genes of the population studied. We sought to examine this relationship in an African cohort.
Urban Xhosa children were tested for ascaris IgE levels, bronchial hyper-responsiveness (BHR) by methacholine challenge, atopic sensitisation (skin tests to aeroallergens) and allergic disease (asthma, eczema and rhinitis) assessed by questionnaire.
Ascaris sensitisation was strongly associated with BHR but not with asthma, eczema or rhinitis. There was a dose-response relationship between increasing class of ascaris IgE and increased BHR (Prevalence ratio (PR) 1.75; CI 1.09-2.82). Higher levels of ascaris IgE were seen in those with BHR. Ascaris IgE was associated with atopic sensitisation to aeroallergens. There was a dose-response relationship between increasing class of ascaris IgE and sensitisation to one or more allergen (PR 1.65; CI, 1.27-2.13), sensitisation to house dust mites (HDM) (PR 1.79; CI, 1.29-2.46) and grass (PR 2.66; CI, 1.24-5.71) and number of positive skin prick tests (PR 1.78; CI, 1.27-2.49). Presence of any sensitisation to ascaris was associated with more than doubling the prevalence of HDM sensitisation (41.5 vs 18.5%) and almost quadrupling the prevalence of grass sensitisation (10.8 vs 2.8%).
Ascaris sensitisation was strongly associated with BHR and with atopy, but not with allergic diseases. Possible explanations might be that the type of ascaris infection that causes high levels of ascaris IgE in this genetic population may also favour the development of atopy or that atopics in Africa have upregulation of their defence system against parasitic infection. These hypotheses are not mutually exclusive.
PMCID: PMC3512651
16.  Impact of helminth infection on childhood allergic diseases in an area in transition from high to low infection burden 
Asia Pacific Allergy  2012;2(2):122-128.
The effect of helminth infections on allergic diseases is still inconclusive. Furthermore, the effect of helminth infections on childhood allergic diseases in a tropical area where prevalence of helminth infections has undergone dramatic changes is not well documented.
To investigate the relationship between allergic diseases and helminth infection in a cohort of schoolchildren in an area that has undergone dramatic changes in intensity of helminth infections.
Children attending grade 5 were recruited from 17 schools in Western Province of Sri Lanka. They were assessed for allergic diseases using the International Study of Asthma and Allergies in Childhood questionnaire. Their serum total IgE (tIgE) and allergen-specific IgE (sIgE) for five common aeroallergens were measured by ImmunoCAP® method and stools were examined for the presence of helminth infections.
A total of 640 children (mean age 10 years) were recruited to the study. Of them, 33.7% had evidence of allergic disease and 15.5% had helminth infections. Majority of infections (68.9%) were of low intensity. A significant relationship between allergic disease and helminth infections was not observed, however, a trend toward protective role of helminth infections against allergic diseases was noted. Multivariate analysis showed helminth infections to be an independent predictor of high tIgE levels whereas allergic disease was not. Allergic sensitization (atopy) was a significant risk factor for allergic disease only among non-infected children (odds ratio 3.025, p = 0.022) but not in infected children. The ratio of sIgE to tIgE was higher in non-infected children.
Though not significant, a reduced risk of allergy in helminth-infected children was observed in this population. A Decrease in intensity of helminth infections may have contributed to the reduced capacity of immune-modulation by helminths in this paediatric population.
PMCID: PMC3345325  PMID: 22701862
Allergy; Atopy; Children; IgE; Helminth infections
The Journal of pediatrics  2006;149(4):505-511.
To present methodology to identify atopic parents and determine the prevalence of sensitization to 15 aeroallergens in their infant offspring.
Study design
A birth cohort of infants was identified from birth records; an infant was enrolled if 1 of the parents reported allergy respiratory symptoms and had a positive skin prick test (SPT) to a common aeroallergen. At age 1 year, these infants were tested to the same aeroallergens.
Of the 680 enrolled infants, 28.4% were SPT+ to 1 or more aeroallergens and/or food, and 18.0% were positive to 1 or more aeroallergens. By category of allergens, 9.7% were sensitized to pollens, 7.5% to molds, 4.3% to house dust mite and/or cockroach, and 3.4% to dog and/or cat. Of the infants who were positive to an aeroallergen, 65.7% remained positive at age 2 years.
Infants born to atopic parents with percutaneous sensitization to aeroallergens are at increased risk for aeroallergen sensitization during infancy, which persists to age 2 years. These findings suggest that current clinical practices, which generally avoid skin testing before age 2 years, be reassessed in this population of high-risk children.
PMCID: PMC2233934  PMID: 17011322
18.  167 Allergen Sensitization in Children with Allergic Rhinitis and Asthma in Guatemala 
The World Allergy Organization Journal  2012;5(Suppl 2):S72-S73.
There are no previous studies published reporting allergen sensitizations in the population of most Central American countries, including Guatemala. There are many types of climates in different regions, with variable altitude, humidity, etc. The purpose of this study was to determine the most common allergen sensitizations in children with Allergic Rhinitis and Asthma in 4 different regions.
The study was performed on 461 children aged 5 to 15 years, from 4 different regions in Guatemala. A questionnaire was given to record information regarding family history of atopic disease and symptoms of Rhinitis and Asthma. The diagnosis was made in the presence of at least 3 symptoms of each disease. Scratch testing was performed using a commercially available device and a panel of 8 allergen extracts: Cypress Arizona, Dog, Cat, Dermatophagoides farinae and pteronyssinus, Cockroach Mix, Mold Mix and Bermuda grass.
Patient average age was 8.3 years, 55% male and 45% female. Patient distribution by region was 35% from Huehuetenango, 29% Chiquimula, 18% Mazatenango and 18% Quetzaltenango. Family history of allergic rhinitis was present in 46% of patients, asthma in 51% and atopic dermatitis in 33%. The most common diagnosis was rhinitis in 86% of patients, 52% had asthma and 43%, both rhinitis and asthma. 98% had a positive Histamine Control and all a Negative Saline Control. 36% of patients had no allergy sensitization to allergens tested and 64% showed positive skin tests. The most frequent allergic sensitization was to Dermatophagoides pteronyssinus (44%) and farinae (43%), followed by Cockroach (28%). We also found less frequently, positive skin tests to grass (14%), Cat (14%), Mold (10%), Dog (8%) and Cypress (6%). The regions with higher dust mite sensitization were Quetzaltenango (51–55%) and Huehuetenango (45–51%).
The most common allergen sensitizations in children with allergic rhinitis and asthma in Guatemala are dust mites and cockroach. Family history of either rhinitis or asthma is present in a significant amount of patients (46–51%) with atopic disease and allergic sensitization, showing that it is an important risk factor in Guatemala. In 36% of patients in this study, allergic sensitization does not seem to contribute to their rhinitis and asthma symptoms.
PMCID: PMC3512912
19.  Dust mite, cockroach, cat, and dog allergen concentrations in homes of asthmatic children in the northeastern United States: impact of socioeconomic factors and population density. 
Environmental Health Perspectives  2002;110(4):419-425.
Home exposures to aeroallergens are an important environmental factor in allergic sensitization and in the development and exacerbation of asthma. We assessed variations in home concentrations of dust mite, cockroach, cat, and dog allergens in dust collected in the main living areas of asthmatics' homes by family income, mother's education, dwelling type, population density, household population density, and ethnicity in Connecticut and south-central Massachusetts. Dust samples were collected at the time of home interview in 999 homes as part of an ongoing longitudinal birth cohort study of 1,002 infants and their asthmatic siblings. The analysis employed lower and upper cut points for group 1 dust mite (> or = 2.0 microg/g and > or = 10 microg/g), cockroach (> or = 1.0 U/g and > or = 4.0 U/g), cat (> or = 1.0 microg/g and > or = 8.0 ug/g), and dog (> or = 2.0 microg/g and > or = 10.0 microg/g) allergens. Subject residences were geocoded to assess population density from the U.S. Census, and multiple logistic regression was used to control for confounding. The portion of homes at the lower cut point for dust mite, cockroach, cat, and dog allergens were 46.9%, 24.9%, 42.2%, and 35.6%, respectively; the upper cut point for each of the allergens was reached in 22.4%, 13.4%, 21.0%, and 22.9% of the homes, respectively. In all, 86.0% of the homes had at least one allergen at the lower cut point, and 58.0% had at least one allergen at the upper cut point. Forty-nine percent of the homes had two or more allergens at the lower cut point, and 19.7% had two or more allergens at the upper cut point. Higher education of the mother, higher household income, living in a single-family home in a less densely populated area with fewer people per room, and being a white household were associated with elevated dust mite, cat, and dog allergens and low cockroach allergen. In contrast, low income, living in a multifamily home in a high population density area with a higher occupancy rate per room, and being a Hispanic or black household were associated with elevated cockroach allergens and low concentrations of dust mite, cat, and dog allergens. Although the presence of an individual allergen is more likely associated with one or more socioeconomic or ethnic factors, most homes typically have multiple allergen burdens in excess of concentrations thought to be associated with sensitization and exacerbation of asthma. Mite and cockroach allergens have distinct and opposite associations with socioeconomic factors and population density.
PMCID: PMC1240806  PMID: 11940461
20.  233 The Evaluation of Allergen Sensitivity in Allergic Rhinoconjunctivitis and Allergic Asthma Patients in Antalya, Turkey 
The World Allergy Organization Journal  2012;5(Suppl 2):S93-S94.
Allergic rhinitis is a common health problem which has 2 forms; seasonal and perennial. The prevalence and etiology of allergic rhinitis varies from region to region and affect 10 to 20% of the population approximately. The prevalences of asthma, allergic rhinitis and allergic eye disease were detected as 8.2%, 10.8% and 7.5% respectively in Antalya, the south coast of Turkey.
The study was conducted in Antalya between 10th of November 2009 and 20th of September 2010. 866 of 2862 patients who had allergic rhinoconjunctivitis and asthma were enrolled in the study due to having high total IgE levels in blood conducted at the Allergy-Immunology Division of Antalya Research and Training Hospital. Allergen-spesific subcutaneous immunotherapy was given 626 of 866 patients.
Of the 866 patients studied, 66.1 % were females. Most of the cases had declaired that the rhinitis symptomes were due to pollens and house dust the second most common irritant. Also the cases have said that their symptoms got worse with exposure to dust, smoke, heavy odors, perfumes, and detergents. Most of the patients have said that air pollution was the most important factor that exacerbated the symptoms of rhinitis and asthma. While there is a comparison between the age and SPT positivity, Aspergillus fumigatus and Dpteronyssinus sensitivity was statistically different in the mites and fungal mixture dermal test groups. As a result, in the study group of 866 allergic rhinitis patients, only the Plantagolanceolata, Corylusavellana, Aspergillus fumigatus, Dpteronyssinus and cockroach sensitivity was significantly varies with the age.
In allergic diseases; we all know that allergens may have regional variations. That's why; the allergen profiles of the regions must be determined and the dermal Prick tests must be prepared accordingly. Mostly grass and cereal mixtures and mites are responsible from the allergic rhinitis cases due to our observations in our clinic. The other important allergens that are linked to the flora and climate of the region are olive and the cockroaches. High asthma prevalence in people living in shanties and in housewives may be due to exposure to house dust mites.
PMCID: PMC3512677
21.  434 Frequency of Food-sensitization by Prick-to-Prick Test and Atopy Patch Test in Allergic Children 
Food-allergy is a substantial and evolving health issue. We evaluate the frequency of food sensitization by prick-to-prick and atopy patch test (APT) in allergic children in a tertiary pediatric care center.
Cross-sectional retrospective study of prick-to-prick and APT tests made in atopic children attending to the Pediatric Allergy and Clinical Immunology outpatient clinic aged 6 months to 19 years. Patients were stratified in 4 groups according to age (<1, 1–5, 6–10 and >11 years), and by atopy-related diagnosis (asthma, rhinitis, food allergy, atopic dermatitis and eosinophilic gastroenteropathy).
Total of 170 prick-to-prick with fresh foods were made, 135 were positive with the next distribution: milk 28.8%, (95% CI, 21.3-36.3%), egg white 20.1% (95% CI, 13.5-26.8%), banana 19.4% (95% CI, 12.8-26%). Sensitization to milk was most common in children aged 1 to 5 years old with 26.9% (95% CI, 17.1-36.8%) compared with corn, nuts and peanuts P < 0.05. Sensitization to milk was the most frequent in the food allergy diagnosis group with 27.1% (95% CI,15.8-38.5%) compared with wheat, corn and peanuts P < 0.05.
A total of 140 APT tests were made, 105 were positive with the next distribution: soybeans 53.3% (95% CI,43.8-62.8%), peanut and chocolate both with 50.5% (95% CI,40.9-60,.0). This finding was sustained in patients with atopic dermatitis with soybean 55.6% (95% CI,36.8-74.3) compared to egg yolk. Sensitization to soybeans was most common in children aged 1 to 5 years old with 52.1% (95% CI,40.6-63.6) compared to rice and egg yolk P < 0.05. A different distribution was found for the 6 to 10 years old aged group: peanut 41.9% (95% CI,27.1-56.6) compared with egg yolk P < 0.05.
Milk is the most common food-allergen found by prick-to-prick in children independent of age or allergic diagnosis, with statistical significant difference, when compared to other food-allergens, in the group of food-allergy diagnosis and in the 1 to 5 years old age-group. Soybean is the most common food-allergen found in atopy patch test in the groups <1, 1 to 5 and >11 years old, independent of atopy related diagnosis, with statistical significant difference, when compared to other food-allergens in the group of atopic dermatitis and in the 1 to 5 years old age-group. For the 6 to 10 years old group peanut was the most common food-allergen found by APT, independent of atopy related diagnosis
PMCID: PMC3513170
22.  Association of pediatric asthma severity with exposure to common household dust allergens 
Environmental research  2009;109(6):768-774.
Reducingexposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma.
To examine the dose response relationships and health impact of five common household dust allergens on disease severity, quantified using both symptom frequency and medication use, in atopic and non-atopic asthmatic children.
Asthmatic children (N=300) aged 4–12 years were followed for one year. Household dust samples from two indoor locations were analyzed for allergens including dust mite (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1). Daily symptoms and medication use were collected in monthly telephone interviews. Annual disease severity was examined in models including allergens, specific IgE sensitivity and adjusted for age, gender, atopy, ethnicity, and mother’s education.
Der p 1 house dust mite allergen concentration of 2.0 + μg/g from the main room and the child’s bed was related to increased asthma severity independent of allergic status (respectively, OR 2.93, 95% CI 1.37, 6.30 for 2.0 –10.0 μg/g and OR 2.55 95% CI 1.13, 5.73 for ≥ 10.0 μg/g). Higher pet allergen levels were associated with greater asthma severity, but only for those sensitized (cat OR 2.41 95% CI 1.19, 4.89; dog OR 2.06 95% CI 1.01, 4.22).
Higher levels of Der p 1 and pet allergens were associated with asthma severity, but Der p 1 remained an independent risk factor after accounting for pet allergens and regardless of Der p 1 specific IgE status.
PMCID: PMC2706291  PMID: 19473655
pediatric asthma; household dust allergens; Der p1; dust mite; pet allergens
23.  Determinants of Allergic Rhinitis in Young Children with Asthma 
PLoS ONE  2014;9(5):e97236.
In the preschool period, allergic rhinitis (AR) is infrequent and thus under-diagnosed. However, recent works have highlighted the occurrence of AR in toddlers although the causes of AR in this young population remain unknown. The objective of this study was to identify determinants of AR in young children with asthma.
We carried out a case-control study of 227 children with active asthma and enrolled in the Trousseau Asthma Program. AR and other allergic diseases (asthma, food allergy and eczema) were diagnosed by medical doctors using standardized questionnaires. Parental history of AR and asthma, biological markers of atopy (total IgE, blood eosinophilia, allergic sensitization towards food and aeroallergens) and environmental parameters were also collected.
Forty one of the children (18.1%) had AR. By univariate logistic regression analysis, AR was mainly associated with peanut sensitization (OR = 6.75; p = 0.002); food allergy (OR = 4.31; p = 0.026); mold exposure (OR = 3.81 p<0.01) and parental history of AR (OR = 1.42; p = 0.046). Due to the strong link between food allergy and peanut sensitization three models of multivariate logistic regression were performed and confirmed that AR is associated with peanut sensitization but also food allergy and mold exposure. A random forest analysis was also performed to explain AR. The results reinforced the logistic analysis that peanut sensitization and mold exposure were the principal determinants of AR.
Conclusions & Clinical Relevance
These results stress the importance of investigating AR in young children with asthma to potentially diagnose a particularly severe allergic asthmatic phenotype. Moreover, these data evoke the hypothesis that peanut could be an aeroallergen.
PMCID: PMC4022721  PMID: 24831804
24.  Association between Short Sleep Duration and the Risk of Sensitization to Food and Aero Allergens in Rural Chinese Adolescents 
Both long and short sleep duration have been associated with obesity, cardiovascular disease, and diabetes. However, there have been no previous studies investigating the potential relationship between altered sleep duration and allergen sensitization.
To explore the association between sleep duration and sensitization to food and aeroallergens.
This study includes 1534 rural Chinese adolescent twins aged 12 to 21 years who completed standard sleep questionnaires and skin prick tests (SPTs) to 9 food and 5 aeroallergens. Total sleep time was defined as the interval from bedtime to wake-up time minus sleep latency. Sensitization was defined as having at least one positive SPT.
Compared to individuals with the highest (3rd) tertile of sleep duration, those who slept less were more likely to be sensitized to any food allergen with odds ratios (ORs) of 1.9 (95% confidence interval(CI):1.3–2.7) and 1.4 (95%CI:1.0–1.9) for the 1st and 2nd tertiles (trend test Ptrend=3×10−4), respectively. The corresponding ORs for sensitization to any aeroallergen were 1.5 (95%CI: 1.1–2.0) and 1.3 (95%CI:1.0–1.7) (Ptrend=8×10−3). These associations were independent of percent body fat. In addition, we observed a significant dose-response association between the number of positive SPTs and percentage of shortest sleep duration (1st tertile) (Ptrend=1×10−3).
Conclusions and Clinical Relevance
In this sample of relatively lean rural Chinese adolescents, we found that short sleep duration was associated with increased risk of sensitization to food and aeroallergens, independent of percent body fat. Longitudinal studies are needed to further determine the temporal and causal relationships. If short sleep duration indeed is one of the risk factors for allergic sensitization, the global burden of allergic diseases could be dramatically reduced by providing appropriate guidance on sleep duration for youth.
PMCID: PMC3056931  PMID: 21255141
sleep duration; skin prick test; allergen; sensitization; adolescent
25.  Food Allergy--Lessons from Asia 
This is a review on published data available on food allergy in East Asia and a discussion on the insights that it offers.
PubMed searches were made for terms food allergy and anaphylaxis, in combination with Asia.
There is a paucity of population-based prevalence studies on food allergy in Asia. Certain unique food allergens, such as buckwheat, chestnuts, chickpeas, bird's nest, and royal jelly, which are consumed extensively by certain Asian populations have resulted in clinical food allergy of little importance in other populations. Crustacean shellfish is of importance in this region relative to other common food allergens. The high consumption of these foods and possibly coupled with cross-reactive tropomyosins from dominant inhalant dust mite and cockroach allergens in this region may explain this phenomenon. In contrast, the prevalence of peanut allergy is relatively low in this region. The reasons for this difference are not apparent. However, this may be a reflection of the general reduced propensity in this region to allergic diseases as seen with asthma.
Further research on food allergy in Asia is warranted because it offers unique opportunities to further our understanding on the influence of population and environment.
PMCID: PMC3650988  PMID: 23282480
food allergy; Asia; shellfish allergy; peanut allergy; buckwheat; bird's nest; chickpeas; royal jelly

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