Determinants Of Allergy Research Articles

The hygiene hypothesis for allergy - conception and evolution.

In 1989, a short paper entitled "Hay fever, hygiene and household size" observed that British children from larger families were less likely to develop hay fever and suggested that this could be because early exposure to infection prevents allergy. This sibship size association for hay fever, since replicated many times in Britain and other affluent countries and confirmed by objective measures of atopy, prompted what has come to be known as the "hygiene hypothesis for allergy", although that term was not specifically used in the 1989 paper. The present paper reviews the historical roots of the "hygiene hypothesis" and charts its development over more than 30 years. Initial scepticism among immunologists turned to enthusiasm in the mid-1990s as the Th1/Th2 paradigm for allergic sensitisation emerged from animal experiments and the concept of "immunological old friends" became popular from the early 2000s. From the late 1990s, observations of reduced allergy risk among children of anthroposophic families and those brought up on farms suggested that the sibship size effects formed part of a broader range of "hygiene-related" determinants of allergy. Children from large families with farming exposure have approximately sixfold reduction in prevalence of hay fever, indicating the potential strength and epidemiological importance of these environmental determinants. During the 21st century, a wide range of specific microbial, environmental and lifestyle factors have been investigated as possible underlying mechanisms, but sadly none have emerged as robust explanations for the family size and farming effects. Thus, while the "hygiene hypothesis" led to a fundamental reappraisal of our relationship with our microbial environment and to the concept that early exposure, rather than avoidance, is beneficial for developing a healthy immune system, the underlying mechanism for variations in allergy prevalence with family size remains, in Churchillian terms, "a riddle wrapped in a mystery inside an enigma".

Conurbation, Urban, and Rural Living as Determinants of Allergies and Infectious Diseases: Royal College of General Practitioners Research and Surveillance Centre Annual Report 2016-2017.

BackgroundLiving in a conurbation, urban, or rural environment is an important determinant of health. For example, conurbation and rural living is associated with increased respiratory and allergic conditions, whereas a farm or rural upbringing has been shown to be a protective factor against this.ObjectiveThe objective of the study was to assess differences in general practice presentations of allergic and infectious disease in those exposed to conurbation or urban living compared with rural environments.MethodsThe population was a nationally representative sample of 175 English general practices covering a population of over 1.6 million patients registered with sentinel network general practices. General practice presentation rates per 100,000 population were reported for allergic rhinitis, asthma, and infectious conditions grouped into upper and lower respiratory tract infections, urinary tract infection, and acute gastroenteritis by the UK Office for National Statistics urban-rural category. We used multivariate logistic regression adjusting for age, sex, ethnicity, deprivation, comorbidities, and smoking status, reporting odds ratios (ORs) with 95% CIs.ResultsFor allergic rhinitis, the OR was 1.13 (95% CI 1.04-1.23; P=.003) for urban and 1.29 (95% CI 1.19-1.41; P<.001) for conurbation compared with rural dwellers. Conurbation living was associated with a lower OR for both asthma (OR 0.70, 95% CI 0.67-0.73; P<.001) and lower respiratory tract infections (OR 0.94, 95% CI 0.90-0.98; P=.005). Compared with rural dwellers, the OR for upper respiratory tract infection was greater in urban (OR 1.06, 95% CI 1.03-1.08; P<.001) but no different in conurbation dwellers (OR 1.00, 95% CI 0.97-1.03; P=.93). Acute gastroenteritis followed the same pattern: the OR was 1.13 (95% CI 1.01-1.25; P=.03) for urban dwellers and 1.04 (95% CI 0.93-1.17; P=.46) for conurbation dwellers. The OR for urinary tract infection was lower for urban dwellers (OR 0.94, 95% CI 0.89-0.99; P=.02) but higher in conurbation dwellers (OR 1.06, 95% CI 1.00-1.13; P=.04).ConclusionsThose living in conurbations or urban areas were more likely to consult a general practice for allergic rhinitis and upper respiratory tract infection. Both conurbation and rural living were associated with an increased risk of urinary tract infection. Living in rural areas was associated with an increased risk of asthma and lower respiratory tract infections. The data suggest that living environment may affect rates of consultations for certain conditions. Longitudinal analyses of these data would be useful in providing insights into important determinants.

Epigenetic determinants of allergy and tolerance

Not only genetics and environmental factors are responsible for the development of allergies. Epigenetic mechanisms – that are master regulators of gene transcription and thus of the accessibility and use of genome information – have been identified as a third power that is key in determining many features of allergy. So far, three epigenetic mechanisms have been identified in humans: histone modification, DNA methylation, and posttranscriptional modification by microRNA (miRNA) or small interfering RNA (siRNA). In recent years, it became clear that epigenetic regulation of gene function does not only play a role in the development of allergy but may also play a key role in the induction of tolerance against allergens, holding the promise to truly heal or prevent atopic diseases in the future.

Epigenetic determinants of allergy and tolerance

Epigenetic determinants of allergy and tolerance

Asthma diagnosis and treatment – 1017. Prevalence and determinants of allergy and asthma amongst Indian children

Methods Schools at various centres were randomly selected. Children of eligible age group were included in the study after confirming with the school records. Two groups of children aged between 6-7 year and 13-14 year were selected and questionnaires were given. Parents of the younger age group children answered the questionnaire. The 13-14 year aged children answered the questions themselves along with an additional video questionnaire. The questionnaire included questions regarding exposure to traffic pollution and environmental tobacco smoke. Bivariate analysis was used to calculate the odds ratio.

Validation of Basophil CD164 Upregulation for Pollen Allergy Diagnosis

The aim of the study was to evaluate the sensitivity and specificity of allergen-induced basophil CD164 upregulation in patients with seasonal allergic rhinitis caused by allergy to grass pollens. This study was performed in 24 patients with allergy to grass pollens, and in 25 healthy controls. The protocol for allergen-induced basophil CD164 upregulation consisted of whole blood samples processing and staining with anti-CCR3/anti-CD164 antibodies added to a buffer at the beginning of stimulation. We observed dose-dependent allergen-induced basophil CD164 upregulation with 100% of specificity in both used allergen concentrations (12 and 1.2ng/ml). Higher allergen concentration resulted in 100% and lower concentration in only 70.83% sensitivity. We have observed in the patients statistically significant correlations between anti-IgE stimulation and both allergen concentrations (for 12ng/ml, r=0.71, p<0.0001; and for 1.2ng/ml, r=0.64, p<0.001). We conclude that assessment of allergen-induced basophil CD164 upregulation is a very useful method for in vitro determination of allergy to grass pollens. This method seems to be a very promising tool in laboratory testing of allergies to other allergens.

Elevated Atopy Among Obese Women Not Related To Habitual Physical Activity

Atopy (a predisposition of the immune system toward allergic disorders including asthma) has increased dramatically in the US in the last twenty years. Epidemiological studies have found body mass index (body weight kg/height m2) to be a positive independent correlate of atopy in women and not men. The effect of habitual physical activity (HPA) on this relationship is not known. PURPOSE Investigate the prevalence of atopy among healthy obese (OB) and non-obese (NO) women and its relationship to fat mass (FM), insulin resistance (IR), plasma concentrations of 17 β-estradiol (E), IL-4 and leptin, and HPA. METHODS A cross-sectional study of 21 OB (>30% body fat) and 22 NO (<30% body fat) women (18–41y) was performed. The following measurements were taken: FM by plethysmography; atopy by Phadiatop® blood glucose, insulin, C-peptide, E, sex hormone binding globulin (SHBG), and IL-4, using commercial kits. Insulin sensitivity was determined using fasting insulin resistance index (FIRI) and by oral glucose tolerance test. Information about HPA was obtained through self-administered Baecke questionnaires, which have been shown to be valid and reliable for measurement of HPA in epidemiological studies. RESULTS Frequency of atopy was almost three times higher among OB than NO (p=0.008). Plasma concentrations of E (P=0.06), ratio of E:SHBG (P=0.02), and leptin (P<0.001) were higher among OB vs NO women. FIRI and C-peptide were higher among OB than NO (p<0.05) after adjustment for oral contraceptive use. All factors correlated positively with FM. No statistical differences in HPA were found (p=0.291), but OB tended to have lower scores, indicative of lower HPA. Logistic regression showed FM to be the only positive predictor of atopy (P=0.01); leptin tended to correlate negatively (P=0.06). CONCLUSIONS Findings show for the first time, a direct effect of adiposity on atopy in women. Percentage body fat mass may be a determinant of allergy and asthma development in women. Although self-reported HPA did not appear to be independently related to atopy, further study is necessary to determine the effect of duration and intensity of exercise on the relationship between adiposity and atopy in women.

Elevated Atopy Among Obese Women Not Related To Habitual Physical Activity

Atopy (a predisposition of the immune system toward allergic disorders including asthma) has increased dramatically in the US in the last twenty years. Epidemiological studies have found body mass index (body weight kg/height m2) to be a positive independent correlate of atopy in women and not men. The effect of habitual physical activity (HPA) on this relationship is not known. PURPOSE Investigate the prevalence of atopy among healthy obese (OB) and non-obese (NO) women and its relationship to fat mass (FM), insulin resistance (IR), plasma concentrations of 17 β-estradiol (E), IL-4 and leptin, and HPA. METHODS A cross-sectional study of 21 OB (>30% body fat) and 22 NO (<30% body fat) women (18–41y) was performed. The following measurements were taken: FM by plethysmography; atopy by Phadiatop® blood glucose, insulin, C-peptide, E, sex hormone binding globulin (SHBG), and IL-4, using commercial kits. Insulin sensitivity was determined using fasting insulin resistance index (FIRI) and by oral glucose tolerance test. Information about HPA was obtained through self-administered Baecke questionnaires, which have been shown to be valid and reliable for measurement of HPA in epidemiological studies. RESULTS Frequency of atopy was almost three times higher among OB than NO (p=0.008). Plasma concentrations of E (P=0.06), ratio of E:SHBG (P=0.02), and leptin (P<0.001) were higher among OB vs NO women. FIRI and C-peptide were higher among OB than NO (p<0.05) after adjustment for oral contraceptive use. All factors correlated positively with FM. No statistical differences in HPA were found (p=0.291), but OB tended to have lower scores, indicative of lower HPA. Logistic regression showed FM to be the only positive predictor of atopy (P=0.01); leptin tended to correlate negatively (P=0.06). CONCLUSIONS Findings show for the first time, a direct effect of adiposity on atopy in women. Percentage body fat mass may be a determinant of allergy and asthma development in women. Although self-reported HPA did not appear to be independently related to atopy, further study is necessary to determine the effect of duration and intensity of exercise on the relationship between adiposity and atopy in women.

Early life factors related to clinical manifestations of atopic disease but not to skin-prick test positivity in young children.

The relative influence of early life events in the development of IgE-mediated allergy is still undetermined. We investigated early life factors in relation to skin-prick test positivity (SPT) and clinical manifestations of atopic disease in a population-based sample of 201 Italian children (3 months-5 years), after considering their interactions with known determinants of allergy. Among them, 143 children had SPT performed to common allergens. Threatened abortions, general anesthesia at delivery, prematurity, birthweight < 2500 g, maternal smoking, dampness and gas heating exposure were all significantly related to an increased risk of frequent rhinitis in the absence of cold (18%). In utero smoking, threatened abortions, fetal health complications, infantile colic, maternal smoking in childhood (satisfactorily correlated with maternal expired CO during the survey) and respiratory infections were all independent determinants of frequent wheezing (23%). Doctor's diagnosis of asthma (3%) was related to in utero smoking, being born in spring, infantile colic and respiratory infections. A simultaneous exposure to in utero smoking and infantile colic put the infants to a fourfold higher risk of frequent wheezing and to a ninefold risk of asthma, respectively. Having a pet and washing blankets at < 60 degrees C were inversely related to frequent wheezing. Data confirmed also that maternal phenotype influences the inheritance of atopic disease. No event, except a low intake of fruit (< 3/week), was significantly associated with positive SPT (20%) or eczema. Besides allergic sensitization, other events, which occur early in life, seem critical to the development of IgE-mediated allergy.

Intra-species cross-reactivity of house dust mite allergens separated by protein blotting and detected by selective elution of mite components and IgE antibodies.

A complex and varied antibody response to allergens, in particular Dermatophagoides pteronyssinus, is observed in the serum of allergic patients. To examine the role of cross-reacting antigenic determinants in allergy, a strategy has been devised for isolating antibody populations that bind to individual polypeptides of an allergen source separated by sodium dodecyl sulfate-polyacrylamide electrophoresis and electroblotted to nitrocellulose. Polypeptides are identified on the blots, desorbed and coupled to CNBr-activated paper discs. The coupled discs are then used as immunoadsorbent surfaces for the binding of antibodies from allergic sera. Antibodies eluted from the polypeptide immunoadsorbents are then used to reprobe protein blots of the allergen. Results are presented which demonstrate strong cross-reaction between two major mite allergens, Der p I and Der p III, and some weaker intra-species cross-reactivities.

Role of the quaternary ammonium ion determinants in allergy to muscle relaxants

Anaphylaxis to muscle relaxants appears to be a very useful model to study the IgE-dependent mechanisms of mediator release in humans. The serum IgE binding sites of the drugs appeared to be the ammonium ion determinants. In patients allergic to suxamethonium, one of the most frequently used muscle relaxants for general anesthesia, significant histamine release could be obtained in each case with simple diammonium salts. The length of the chain linking the ammonium groups appears to play an important role. In fact, when the length was less than or equal to 4 A, no significant histamine release could be obtained, whereas the optimal length for histamine release appeared to be greater than or equal to 6 A. Furthermore, muscle relaxants with a rigid backbone between the ammonium determinants (such as pancuronium) are less active than flexible molecules (such as suxamethonium) in initiating mediator release. This study suggests that small divalent molecules can induce anaphylactic shock in sensitized patients and that the length and the flexibility of the chain bearing the haptenic determinants appear to be important factors in the elicitation of mediator release.