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IgE and the Allergy–Asthma Connection in the 23Year Follow-Up of Brown University Students
Abstract
The Hygiene Hypothesis helps to explain the increased epidemiology of atopy, especially asthma and hay fever. This hypothesis depends on two major immunological pathways, the Th1 and the Th2 pathways, which are mutually inhibitory, with the Th2 pathway being the dominant one in fetal life and the newborn. The Th1 leads to a cellular delayed hypersensitive response while the Th2 pathway leads to increased IgE, eosinophilia, atopy, and airway/hyperresponsiveness. The ever-increasing vaccines for immunization against viral and bacterial microorganisms together wit better public health hygiene procedures introduce a bias in favor of the inhibition of the Th1 pathway, thereby allowing the Th2 pathway, wit its IgE hypersensitivity, to predominate. We have attempted to correlate this new hypothesis with data from our Brown University college student longitudinal study. In this study, our data have demonstrated that allergen sensitization (positive pollen skin tests reactions) leads to an increased risk factor for developing asthma. Most of our asthmatic patients in our longitudinal study had positive allergy skin tests. Also, students born in months with high concentrations of atmospheric ragweed pollen had an increased risk of developing sensitization to ragweed and late to develop hay fever, which may led to asthma. There is a strong association of asthma with hay fever (a classic IgE disease). Also hay fever patients have three times the risk for developing asthma than controls. There appear to be several factors needed to express the phenotype of allergic asthma: elevated IgE, eosinophilia, airway hyperresponsiveness, exposure to allergens, and the predominance of the Th2 pathway of immunologic reactions.
... En niños y adultos, la RA es un factor de riesgo para desarrollar asma de acuerdo a un seguimiento de 23 años de estudiantes universitarios. 38 Estos estudios fueron confirmados por otros estudios. 27,[39][40][41][42][43][44][45][46][47][48][49] Algunos de estos estudios mostraron que la rinitis es un factor de riesgo significativo para la aparición de asma en la etapa adulta en sujetos tanto atópicos como no atópicos. ...
Background: There is compelling evidence that the different organs composing respiratory system have a narrow relationship and that they work as a single unit. This interdependence provoques patients presenting multimorbidity to have a negative impact on several areas of airway.
Objective:
To create a multidisciplinar consensus allowing to sintetize the most recent information regarding some pathologies of the Unified Airway model.
Methods:
A literature research was conducted consulting PubMed, Google Scholar and the Cochrane Library databases. Delphi method was used to gather the opinion of 17 experts (including Otolaryngologists, adult and children Allergologists, Pneumologists and Family Physicians, with Methodologists support) in order to compare current evidence and adapt it to mexican context, with the purpose of consensus achievement. Members were requested to complete a survey related to areas of interest such as: diagnosis, treatment and referral criteria to specialists for diverse pathologies of the unified Airway: Allergic Rhinoconjuctivitis, Chronic Rhinosinusitis without nasal polyps, Asthma and Otitis Media with Effusion. This survey was applied via e-mail; 2 live meetings were carried out to present and discuss results of the survey.
Results:
20 questions involvig areas of interest were answered. Based on these, several statements were generated and support texts to back them up.
Conclusions:
Selectig pharmacologic therapeutics combining medications having proved benefits for patients is important so they can diminish probabilities for adverse events and complications.
... A previous population-based study reported that sensitization to dust mites was a significant predisposing factor for asthma, 17 and another study revealed that pollen was another risk factor. 18 In our study, the relationship between asthma and specific allergen sensitivities was partly supported. The self-reported prevalence of asthma was significantly higher in subjects aged 13-19 years (high positivity rate for dust mites) and in those ≥70 years old (high positivity rate for pollen) than among those in their 20 s. ...
Objectives
Currently, epidemiological data on allergic rhinitis collected through the skin prick test are scarce. Moreover, the relationship of age and sex to allergic rhinitis is not comprehensively understood. This study aimed to characterize allergic rhinitis and the associated clinical manifestations by age and sex.
Methods
We retrospectively investigated data from 2883 patients who visited a single university hospital for rhinitis symptoms between January 2003 and December 2014. Of these 2883 patients, 1964 who underwent a skin prick test with 11 standardized allergen extracts and completed a nasal symptom questionnaire were enrolled. The clinical characteristics of allergen sensitization and nasal symptoms were analyzed by sex and age distribution.
Results
The prevalence of allergen sensitization progressively decreased with age after peaking at between 20 and 29 years. The sensitization rate was higher in males than in females ( P = .046). The sensitization rate to house dust mites decreased with age, while sensitization to mugwort and ragweed increased. Six allergens ( Dermatophagoides pteronyssinus, Dermatophagoides farinae, mugwort, trees, ragweed, and cats) were sufficient to identify >96% of patients with allergen sensitization. Nasal obstruction tended to decrease with age and was more prevalent in males ( P = .002) than in females, while rhinorrhea ( P = .007) and itching ( P = .013) were more prevalent in females. Total nasal symptom scores did not differ by sex.
Conclusions
The clinical characteristics of allergic rhinitis, including allergen-sensitization patterns and related symptoms, varied by age and sex. Six common allergens could be sufficient to generate a cost-effective tool to identify allergic rhinitis.
... The Children's Respiratory Study showed that allergic rhinitis in the irst year of life was associated with a risk of developing asthma by 6 years of age [38]. The study by Setipane et al. showed that signiicantly more (10.5%) of the students diagnosed with allergic rhinitis went on the develop asthma compared with those who did not have allergic rhinitis (3.6%) [39]. The presence of bronchial hyperresponsiveness increased the risk for severe symptoms of allergic rhinitis and asthma and earlier development of asthma in children with allergic rhinitis [12]. ...
... 1 It is well established that asthma develops more commonly in patients with allergic rhinitis when compared with children without rhinitis. 2,3 Aeroallergen sensitization, particularly house-dust mite and Aspergillus mold sensitizations, have emerged as independent risk factors for asthma in children. 4 However, different patterns of aeroallergen sensitization are found to be related to varying degrees of asthma risk, 5 and every child with aeroallergen sensitization does not present with asthma symptoms. ...
Background:
Results of epidemiologic studies have determined several risk factors for asthma in school-age children.
Objective:
To examine whether parental and perinatal risk factors, along with infantile feeding patterns, were associated with asthma in children with grass pollen allergy and allergic rhinitis.
Methods:
We retrospectively analyzed the data of our cohort, which consisted of children with allergic rhinitis. Only children with grass pollen sensitization were enrolled. A detailed questionnaire regarding demographic features and perinatal events was given to the parents.
Results:
A total of 293 children (200 boys [68.3%]; with median age, 10.2 years [interquartile range {IQR}, 7.4-13.0 years]) were included. A total of 109 children (37.2%) had accompanying asthma. The median age of onset of rhinitis symptoms was earlier (5.3 years [IQR, 4.0-8.0 years] versus 7.0 years [IQR, 5.0-10.0 years]; p = 0.001), histories of prematurity (16.7 versus 6.5%; p = 0.006), preeclampsia (5.5 versus 0%; p = 0.001), neonatal intensive care unit admission (15.1 versus 6.0%; p = 0.01), phototherapy (17.9 versus 7.1%; p = 0.004), early formula feeding (58.7 versus 41.2%; p = 0.006), and parental asthma (25.0 versus 11.4%; p = 0.002) were more frequent in children with asthma. Multivariate logistic regression analysis revealed prematurity (odds ratio [OR] 2.78 [95% confidence interval [CI],1.24-6.24]; p = 0.013), history of formula feeding (OR 1.81 [95% CI, 1.09-3.01]; p = 0.022), and parental asthma (OR 2.37 [95% CI, 1.22-4.63]; p = 0.011) were associated with asthma in school-age children with grass pollen-induced allergic rhinitis.
Conclusion:
Close monitoring of patients with these risk factors may help with an earlier diagnosis of asthma and prompt initiation of therapeutic interventions in children with allergic rhinitis and who were sensitized to grass pollen.
... nasal blocking, rhinorrhoea) may be differently associated with asthma symptoms [37]. Although testing for allergic sensitisation would have allowed for differentiation between allergic and non-allergic rhinitis, sensitization status is not pivotal since rhinitis symptoms are strongly associated with asthma also in non-sensitized subjects [1,38]. ...
Despite the well-known association between asthma and rhinitis, in Swedish adults the prevalence of rhinitis rose from 22% to 31% between 1990 and 2008 while asthma prevalence was unchanged. We tested whether the association of rhinitis with asthma was stable over time using the same population-based databases.
Two surveys of adults (20-44 years) living in three regions of Sweden, carried out in 1990 (n = 8982) and 2008 (n = 9156) were compared. Identical questions regarding respiratory symptoms, asthma and rhinitis were used. Asthmatic wheeze: Wheeze with breathlessness apart from colds. Current asthma: Asthma attacks and/or asthma medication use.
Subjects with rhinitis had level time trends in asthmatic wheeze, current asthma and most nocturnal respiratory symptoms between 1990 and 2008, adjusted for age, sex, area and smoking. Any wheeze however decreased slightly. In never-smokers asthma symptoms were similarly associated with rhinitis in 1990 and 2008: any wheeze OR 4.0 vs. 4.4 (p = 0.339); asthmatic wheeze OR 6.0 vs. 5.9 (p = 0.937); and current asthma OR 9.6 vs. 7.7 (p = 0.213). In the whole population there were decreases in the asthma symptoms most closely associated to smoking, which decreased by half 1990-2008. Conversely current asthma, which was strongly associated with rhinitis and not with smoking, increased (p < 0.001).
The association of rhinitis with asthma was stable between 1990 and 2008. The pattern in the time trends of asthma outcomes strongly suggests that decreased smoking counterbalanced the driving effect of increased rhinitis on asthma prevalence. The findings illustrate the public health benefits of decreased smoking.
Copyright © 2015 Elsevier Ltd. All rights reserved.
... In the USA, approximately $11.2 billion was spent on AR treatments in 2005. 1 Preschool children and young adults with AR are at increased risk for asthma later in life. 2,3 Early exposure to traffic related air pollutants, specifically diesel exhaust particles (DEP), may enhance risk for aeroallergen sensitization and development of allergic disorders in childhood. 4,5 No prospective study has defined the exact relationship between early DEP exposure and percutaneous aeroallergen sensitization, especially the predictive value of early sensitization, during the first three years of life and the subsequent development of childhood AR. ...
No large, prospective, epidemiologic study has investigated the association between diesel exhaust particle (DEP) exposure and early aeroallergen sensitization and allergic rhinitis (AR) at 4 years of age.
To determine how exposure to traffic exhaust during infancy is associated with aeroallergen sensitization and AR at 4 years of age and the predictive utility of the wheal area at 1 to 3 years of age on AR at 4 years of age.
Infants born to aeroallergen sensitized parents were evaluated annually with skin prick tests to 15 aeroallergens with measurement of wheal areas. At 4 years of age, AR was defined as at least one positive aeroallergen skin prick test result and the presence of sneezing and a runny nose without a cold or flu. Infant (DEP) exposure was estimated using data from 27 air sampling monitors and a land use regression model.
Complete data were available for 634 children at 4 years of age. Prevalence of AR increased annually from 6.9% to 21.9%. A positive trend was observed for high DEP exposure and aeroallergen sensitization at 2 and 3 years of age (odds ratio, 1.40; 95% confidence interval, 0.97-2.0) and (odds ratio, 1.35; 95% confidence interval, 0.98-1.85) but not with AR. At 2 years of age, every 1-mm(2) increase in the wheal area of timothy and Alternaria significantly increased the odds of AR at 4 years of age. At 3 years of age, every 1-mm(2) increase in the wheal area of fescue, dog, and Penicillium significantly increased the odds of AR at 4 years of age.
DEP exposure enhances the risk of early aeroallergen sensitization. Aeroallergen wheal area at 2 and 3 years of age is associated with AR at 4 years of age.
Copyright © 2015 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
... Immunoglobulin E is a proven target molecule for active allergy immunotherapy. 31,32 At present, a humanized anti-IgE mAb [7][8][9] and several recombinant fusion proteins have been reported as vaccine strategies 10-15 for asthma treatment. However, anti-IgE mAb has a short half-life, requires frequent injections, and is expensive, which decreases its clinical utility. ...
The IgE Fcε3 domain is an active immunotherapeutic target for asthma and other allergic diseases. However, previous methods for preparing IgE fusion protein vaccines are complex. Antigen 43 (Ag43) is a surface protein found in E. coli that contains α and β subunits (the α subunit contains multiple T epitopes). Here we constructed a novel antigen 43 (Ag43) surface display system (Ag43 system) to express Ag43 chimeric proteins to disrupt immune tolerance against IgE. The Ag43 system was constructed from the E. coli strain Tan109, in which the Ag43 gene was deleted and a recombinant plasmid (pETAg43) expressing a partial Ag43 gene was introduced. The Fcε3 domain of the IgE gene was then subcloned into plasmid pETAg43, resulting in a recombinant plasmid pETAg43/Fcε3 which was used to transform Tan109 for Ag43/Fcε3 surface expression. Thereafter, Ag43/Fcε3 was investigated as an asthma vaccine in a mouse model. Ag43/Fcε3 was expressed on and could be separated from the bacterial surface by heating to 60°C while retaining activity. Ag43/Fcε3, as a protein vaccine, produced neutralizing auto-antibodies to murine IgE, induced significant anti-asthma effects, and regulated IgE and Th cytokines in a murine asthma model. Data show that Ag43/Fcε3 chimeric protein is a potential model vaccine for asthma treatment, and that the Ag43 system may be an effective tool for novel vaccine preparation to break immune tolerance to other self-molecules.This article is protected by copyright. All rights reserved.
... Furthermore, our data are also consistent with other studies that demonstrate obesity to be a risk factor for incident asthma primarily among women (33)(34)(35)(36)(37)(38). Few longitudinal studies have examined the relationship of atopy (resulting from Th2 pathway of immunologic reactions [39]) to adult-onset asthma. Although atopy is a strong risk factor for pediatric-onset asthma (40), its association with adult-onset asthma is controversial. ...
Rationale:
Although asthma is usually considered to originate in childhood, adult-onset disease is being increasingly reported.
Objectives:
To contrast the proportion and natural history of adult-onset versus pediatric-onset asthma in a community-based cohort. We hypothesized that asthma in women is predominantly of adult onset rather than of pediatric onset.
Methods:
This study used data from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort in the United States over a 25-year period. Adult- and pediatric-onset asthma phenotypes were studied, as defined by age at onset of 18 years or older. Subjects with asthma were categorized by sex, obesity, atopy, smoking, and race by mean age/examination year, using a three-way analysis of covariance model. Natural history of disease was examined using probabilities derived from a Markov chain model.
Measurements and main results:
Asthma of adult onset became the dominant (i.e., exceeded 50%) phenotype in women by age 40 years. The age by which adult-onset asthma became the dominant phenotype was further lowered for obese, nonatopic, ever-smoking, or white women. The prevalence trend with increasing time for adult-onset disease was greater among subjects with nonatopic than atopic asthma among both sexes. Furthermore, adult-onset asthma had remarkable sex-related differences in risk factors. In both sexes, the quiescent state for adult-onset asthma was less frequent and also "less stable" over time than for pediatric-onset asthma.
Conclusions:
Using a large national cohort, this study challenges the dictum that most asthma in adults originates in childhood. Studies of the differences between pediatric- and adult-onset asthma may provide greater insight into the phenotypic heterogeneity of asthma.
... Prévalence de l'asthme en fin d'étude montrant que la rhinite est un signe précurseur de l'asthme12 ...
Summary Counselling the allergic apprentice
... The Children's Respiratory Study showed that the presence of doctor-diagnosed AR in infancy was independently associated with a doubling of the risk of developing asthma by 11 years of age. In children and adults, AR as a risk factor for asthma was shown in a 23-year follow up of college students [Settipane and Settipane, 2000]. Significantly more (10.5%) of the students originally diagnosed with AR went on to develop asthma compared with 3.6% of those who did not have rhinitis. ...
Asthma and allergic rhinitis are common health problems that cause major illness and disability worldwide. The prevalence of allergic rhinitis is estimated to range from 10% to 20% in the USA and Europe. Multiple factors contribute to the wide range of reported prevalence rates. These include type of prevalence rate reported (current or cumulative), study selection criteria, age of participants, differences in survey methods, varied geographic locations and socioeconomic status, any of which are significant enough to confound direct comparison between studies. There is no standard set of diagnostic criteria for allergic rhinitis. In most studies, the criteria for diagnosis are based on the subject's reporting, solely by questionnaire and rarely confirmed by skin testing. In addition, most studies focus on hay fever, leaving perennial allergic rhinitis underestimated. Sinus imaging is generally not performed and, therefore, rhinosinusitis not differentiated. Some investigators report 'current' prevalence while others report 'cumulative' or 'lifetime' prevalence. Epidemiologic studies have consistently shown that asthma and rhinitis often coexist in the same patients. The prevalence of asthma is <2% in subjects without rhinitis while it varies from 10% to 40% in patients with rhinitis. Furthermore, the majority of patients with asthma experience rhinitis, which is a factor in the risk for asthma. Despite recognition that allergic rhinitis and asthma are global health problems, there are insufficient epidemiologic data and more data are needed with regard to their etiologic risk factors and natural history. This aim of this review is to enable the reader to discuss prevalence, risk factors and prognosis of allergic rhinitis and asthma.
... Asthma can affect 21%-40% of patients with allergic rhinitis111213. Rhinitis has been reported to be a risk factor for the development of asthma both in atopic and in nonatopic subjects141516. Of note, almost half of the children with rhinitis in Alergológica 2005 had asthma (44.9%). Phase III of the ISAAC study [2] showed that 30% of 13 to 14-year- olds with rhinoconjunctivitis had asthma, as did 35% of 6 to 7-year-olds. ...
Allergic rhinitis is the most frequent chronic allergic disease in children, and may be an important risk factor for the subsequent development of asthma.
To describe the characteristics of patients younger than 14 years of age presenting with rhinitis and the possible association with asthma.
We carried out a prospective, observational, descriptive, cross-sectional epidemiologic study (Alergológica 2005) of 917 patients under the age of 14 consulting for the first time in allergy departments in Spain.
Rhinitis was diagnosed in 42.5% of the children. The association between asthma and rhinitis was significantly higher in children than in adults (44.9% vs 35.5%; P<.05). Time from onset of rhinitis was significantly associated with the development of asthma (2.97 vs 2.06 years; P<.0001). Allergy was the most frequent cause of rhinitis in children with and without asthma. Allergy to epithelia and fungi was more frequent in children with rhinitis and asthma than in children with rhinitis alone. We found no differences in the frequency of treatment with immunotherapy between children with and without asthma.
Rhinitis was frequently associated with asthma in children consulting for the first time at allergy departments. Time since onset of rhinitis and sensitivity to epithelia and fungi were associated with the development of asthma.
... After a mean follow-up of 4.4 years, sensitization to at least one allergen was associated with a significantly increased risk of developing new asthma (OR 3.6). A long-term (23 years) follow-up of university students revealed that sensitization to pollen leads to an increased risk in developing asthma (22). ...
Little is known on the predictive value of sensitization to specific aeroallergens in children with respect to asthma and hay fever incidence in young adulthood. We followed the incidence of asthma and hay fever in children (mean age 11 years) over 9 years, and analyzed the predictive value of sensitization to five common aeroallergens.
Three consecutive surveys were conducted in East German school children. Specific IgE antibodies to birch and timothy grass pollen, house dust mite, cat, and cladosporium were measured. In 1207 out of the 2453 children, the 9-year incidence of asthma and hay fever was assessed by reported doctors' diagnoses. For sensitization, diagnostic parameters were determined and logistic regression analyses controlled for relevant confounders.
A total of 176/78 incident hay fever/asthma cases occurred equaling a cumulative incidence of 1.93/0.86% per year. Incident asthma was associated with previous sensitization to cat [risk ratio (RR) 3.49, 1.57-7.74] and grass pollen (RR 1.79, 1.01-3.19), whereas incident hay fever was associated with each allergen, with grass pollen (RR 6.00, 4.04-8.90) and cat (RR 5.36, 2.87-9.99) exhibiting the strongest associations. When mutually adjusting for all allergens, sensitization to cat remained significantly associated with asthma and hay fever. The latter was also associated with sensitization to grass pollen. The highest positive predictive values for asthma and hay fever were obtained for cat sensitization (10/49 = 20.4% and 23/49 = 46.9%).
Childhood sensitization to cat and grass pollen predicts the incidence of asthma and hay fever in young adulthood. The predictive capacity differs by allergen and manifestation of atopy.
This review is devoted to profilaxis of food allergy in infants. Brest feeding and or partially hydrolized milk formula considered to be mandatory used in infants with high risk of allergy.
The studies on the epidemiology of allergic diseases indicate at the difference in prevalence depending on the place of residence. The study Epidemiology Allergic Diseases in Poland (ECAP) showed that citizens have a higher prevalence of asthma and allergic diseases. Research compared the major Polish cities and rural areas of Zamojszczyzna. Observations of patients living in Pomeranian region suggest to the mixed character of the rural Pomeranian area and similar prevalence as in the Tri-City agglomeration.
The aim of the study was to determine the prevalence of diseases (asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, urticaria, food allergies, allergy to insect venom and drugs) in the population of the province of Pomerania, among patients living in the city and countryside. The second objective was to evaluate the significance of the factors predisposing to the development of asthma and allergy (sex, smoking, having a bird or cat, housing conditions).
The analysis was based on the research questionnaire containing questions used in epidemiological studies ISAC, ECHRS, ECAP constructed for the study. Statistical analysis of the collected results was made in the program Statistica v.12, χ2 test. The research group consisted of 619 people – 457 women and 162 men, 180 residents of villages and 439 urban residents.
A statistically significant difference and a higher incidence were found in patients with food allergies (p = 0.0002); urticaria (p = 0.009); atopic dermatitis (p = 0.0025); allergies to drugs (p = 0.0001). There were no differences in the prevalence, depending on the place of residence, of asthma (p = 0.5), allergic rhinitis (p = 0.056), allergic conjunctivitis (p = 0.33), allergic reactions to insect venom (p = 0.13), smoking (p = 0.1), sex (p = 0.054). More frequent development of asthma was observed in patients treated for allergic rhinitis OR = 4.29 (CI 1.02–18.03). The differences in the prevalence of the risk factors such as smoking, having a bird or a cat, and the living conditions were statistically insignificant.
The prevalence of the risk factors of allergic diseases as well as asthma, allergic rhinitis and drug allergies were similar in urban and rural areas. The prevalence of food and drug allergy, urticarial and atopic dermatitis were higher among the residences of the cities.
Allergic rhinitis is the most frequent atopic disease and is an important health problem that causes impairment in patients activities, social functioning, sleep, school and work. Asthma prevalence ranges from 5 to 20% of the population in different countries and most patients with asthma have rhinitis supporting the concept of "one airway one disease". Epidemiologic studies have shown that asthma and rhinitis often coexist in the same patient. Moreover, patients with moderate/severe persistent allergic rhinitis may be more likely to suffer from asthma than those with intermittent allergic rhinitis and/or a milder form of the disease. The coexistence of rhinitis with asthma appears to impair asthma control. The presence of allergic rhinitis commonly exacerbates asthma increasing the risk of asthma attacks, emergency visits and hospitalizations for asthma. In April 2008 an Update of ARIA (Allergic Rhinitis and Its Impact on Asthma) guidelines have been published in which classification of rhinitis and management recommendations were validated. In ARIA 2008 document the links between asthma and allergic rhinitis have been confirmed and accented. The epidemiologic evidence and common risk factors were reviewed. The similarities and differences of nasal and bronchial mucosa and mechanisms of allergic inflammation in asthma and rhinitis were presented. In this article, it is aimed to summarize the newly updated and published version of "Allergic Rhinitis and its Impact on Asthma (ARIA) 2008" and to present the diagnostic and therapeutic consequences of ARIA guidelines. According to them patients with allergic rhinitis should be evaluated for asthma, because the treatment of rhinitis reduces asthma severity and optimize asthma control.
Allergic rhinitis (AR) is a symptomatic disorder of the nose based on chronic allergic inflammation. AR is a global health problem that causes major illness and disability and inadequately treated, of which prevalence is about 20% of general population. In general, AR is rarely found in isolation and has been associated with numerous comorbidities, including bronchial asthma, allergic conjunctivitis, otitis media with effusion, sinusitis with polyp, chronic cough, adenoid hypertrophy and consequent sleep disturbance. In particular, coexistence of AR and asthma is a common feature, suggesting the concept of 'one airway, one disease'. Poorly controlled AR can develop or trigger exacerbations of these comorbidities because they often share pathophysiologic pathways in common with AR. Thus, AR should be regarded as a spectrum of systemic disease and treatment requires a systemic approach with considering its comorbidities.
Seeking to understand the individual in his symptomatic totality has been the aim of homeopathy since its very beginning and even then there were warnings that inadequate treatment of acute diseases in childhood may lead to future chronic diseases. Since this conduct upsets the organism’s vital reaction, Hahnemann cautioned that by treating acute diseases with allopathic medicine, with strong doses of heroic drugs, or suppressing local symptoms of those diseases, there would be risk of developing future chronic diseases. At the end of the XIX century, Burnett came up with the theory of vaccinosis and warned of chronic manifestations subsequent to small pox vaccination. In the middle of the last century, French homeopaths, seeking the physiopathological origin of chronic diseases, correlated it to the abnormal reaction of the reticuloendothelial system (R.E.S.). Through the study of experimental pathology, Maffei attributed every symptomatic manifestation to the imbalance between the immunological phenomena of allergy and immunity. This broadened the view of illness as an altered reaction of the R.E.S. He placed the sensitizing and pathogenic effects of medications and vaccines in the phenomena of metalergy and paralergy, respectively. With the modern hygiene hypothesis, there is extensive evidence that the imbalance of immunological response in childhood, more specifically among the Th1 and Th2 lymphocyte subpopulations, is responsible for the development of some allergic and chronic diseases in the future. The deranging factor for the prevalence of future allergic response (Th2) is in the impediment of natural manifestations of infectious diseases (Th1 response) in pre-school children. As homeopathic treatment induces an equilibrated vital reaction, corresponding to an integrative physiological response (neuro-immuno-endocrin-metabolic), we believe it acts to regulate Th1/Th2 imbalance, as is proven by the cure of innumerable allergic and chronic diseases. However, clinical trials to support this hypothesis are lacking.
RESUMO: Buscando compreender o indivíduo em sua totalidade sintomática, prerrogativa do modelo homeopático, desde os primórdios da Homeopatia existem advertências de que o tratamento inadequado de doenças agudas na infância propiciariam o surgimento de doenças crônicas futuras. Por desequilibrar a reação vital do organismo, Hahnemann alertava para o perigo de se tratarem doenças agudas com medicamentos alopáticos, com doses fortes de medicamentos heróicos ou suprimindo externamente os sintomas locais das mesmas, com o risco do desenvolvimento de doenças crônicas futuras. Burnett, ao final do século XIX, levanta a teoria das vacinoses, alertando para o surgimento de manifestações crônicas após a vacinação da varíola. Em meados do século passado, homeopatas franceses, buscando a origem fisiopatológica das doenças crônicas, correlacionam-na à reação anormal do Sistema reticuloendotelial (S.R.E.). Maffei, através do estudo da patologia experimental, atribui toda manifestação sintomática ao desbalanço entre os fenômenos imunológicos da alergia e da imunidade, ampliando a visão de enfermidade como reação alterada do S.R.E., situando nos fenômenos da metalergia e da paralergia os efeitos sensibilizantes e patogênicos dos medicamentos e das vacinas, respectivamente. Com a hipótese higiênica moderna, são inúmeras as evidências de que o desbalanço da resposta imunológica na infância, mais especificamente entre as subpopulações de linfócitos Th1 e Th2, é responsável pelo desenvolvimento de algumas doenças alérgicas e crônicas futuras, estando no impedimento da manifestação natural de doenças infecciosas (resposta Th1) na idade pré-escolar o fator desequilibrante do predomínio da resposta alérgica (Th2) futura. Em vista do tratamento homeopático induzir uma reação vital equilibrada, correspondente a uma resposta fisiológica integrativa (neuro-imuno-endócrino-metabólica), acreditamos que ela atue regulando o desbalanço Th1/Th2, comprovado pela cura de inúmeras doenças alérgicas e crônicas, faltando ensaios clínicos que comprovem esta hipótese.
Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations.
In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease.
This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work.
The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available.
Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed.
The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.
Allergic rhinitis (AR) is recognized as a major health problem worldwide, and its prevalence depends on the age range of the subjects. The aims of this study were to determine the current prevalence of AR, effects of age on the prevalence of IgE sensitization to inhalant allergens, and serum total IgE levels in Japanese subjects.
We conducted a survey of 1,540 subjects between 20 and 49 years of age in 2006 and 2007 and examined the prevalence of AR and sensitization to 7 common aeroallergens. We measured serum total IgE and specific IgE to 7 aeroallergens. AR was determined based on symptoms, predominantly in the nose and eyes, caused by aeroallergens as mentioned in a questionnaire and sensitization to any of the 7 aeroallergens as assessed by measurement of serum specific IgE.
The prevalence of AR was 44.2% (681 of the 1,540 subjects) and there was no difference among age decades. Of the 1,540 subjects, 1,073 (69.7%) were sensitized to at least 1 of the 7 aeroallergens. The most common allergen in AR was Japanese cedar pollen (89.6%, 610 of the 681 with AR) in all the age decades examined. The sensitization rate to mites was significantly higher in the younger subjects.
Our data suggest that the prevalence of AR between 20 and 49 years of age has increased by nearly 10% during the last 10 years. Cedar pollen and mites were predominant allergen sources among the 7 aeroallergens in the Japanese population.
B AC K G R O U N D Even though not a life-threatening disease, pollen allergic rhinitis (AR) has a remarkable social impact and cannot be left to its natural course. Pollens appear seasonally and are reflected in the symptoms of patients with AR living in temperate climates as in Turkey. Our aim was to determine prospectively the clinical characteristics of the patients diagnosed with pollen allergic persistent rhinitis and their risk factors for asthma in our allergy clinic. M ET H O D; A prospective study was conducted among 102 pollen AR patients with persistent symptoms in GATA Haydarpafla Hospital, Department of Allergy, between March 2005-September 2006. Participants were evaluated for allergic respiratory diseases, then were skin tested using the prick test method. A serum sample was analyzed for total IgE and peripheral blood eosinophil counts. R E S U LT S The mean age of the pat ients was 30.64±7.9 years and 69.6% were male. The most acc o mp a nying sens it iv i t y was against house dust mites (62.7%). Mon os e nsitiz at ion was found to be prot e ct ive factor for the dev el o pment of mod er at e - s ev ere dis e ase. The common acc o mpanying all e rgic dis e ase, asthma, was observed in 46 (45.1%) of the pat ients, 13 of whom had pos it ive fam i l y h i story of asthma. IgE levels and total eos in o phil cou n t s were signif icantly higher in the non-asth m atic patients. CO N C L U S I O N S Patients with AR were admitted to allergy clinics quite late, especially when persistent symptoms emerged. This might be due to AR not being considered as a serious disease. High IgE level and/or total eosinophil count were found to be protective factors for the development of asthma.
The aim of this study is to determine what factors have been shown, in prospective studies, to predict the incidence of asthma.
We performed a systematic review of peer-reviewed literature from 1994 to 2004 to determine what factors predict the development of asthma in both children and adults. This search strategy yielded 40 studies, with 36 providing some estimate of asthma incidence for the total sample and or a specific subgroup.
Annual estimated incidence of physician-diagnosed asthma ranged from 0.6 to 29.5 per 1000 persons. Risk factors for incident asthma among children included: male sex, atopic sensitization, parental history of asthma, early-life stressors and infections, obesity, and exposure to indoor allergens, tobacco smoke and outdoor pollutants. Risk factors for adult-onset asthma included female sex, airway hyperresponsiveness, lifestyle factors, and work-related exposures.
Risk factors for asthma include both modifiable and nonmodifiable ones, and they vary between children and adults. This review of prospective evidence supports tobacco and smoke avoidance as an intervention for the primary prevention of childhood asthma. During adolescence and adulthood, targeting lifestyle factors like obesity and smoking or reducing occupational exposures are the best opportunities for asthma prevention. Before specific public health recommendations can be made, however, additional longitudinal research is needed to better characterize target populations and identify appropriate settings for multifaceted asthma interventions.
Airway allergic diseases are regulated by interleukin (IL)-5, which causes infiltration of eosinophils into the bronchial epithelium, and by IL-4 which increases serum immunoglobulin E (IgE) production and promotes CD30 expression on Th cells. CD30 generates a costimulatory signal involved in apoptosis or cell proliferation, depending on the microenvironment. Our aims were: (i) to analyze if CD4+ CD30+ T cells from allergic patients proliferate in response to Dermatophagoides pteronyssinus, and (ii) if upon stimulation this cell population produces IL-4 and IL-5.
Peripheral blood mononuclear cell (PBMC) from 17 allergic rhinitis and mild allergic asthma patients and 12 healthy nonallergic individuals were stimulated with allergen in the presence or absence of anti-IL-4, anti-IL-5 or anti-IL-4Ralpha monoclonal antibodies (mAbs). TdT-mediated dUTP nick end-labeling (TUNEL) assay, 7-aminoactinomycin-D (7-AAD) intercalation, and flow cytometry were used to determine the CD4+ CD30+ blasts percentage, cell proliferation, apoptosis, and intracellular cytokines after 7 culture days.
Cell proliferation induced with allergen showed that 90% of the allergen-stimulated blasts were CD4+, 50% of which were CD30+. Allergen-stimulated PBMC showed a progressive increase (mean: from 7% to 23%) of CD4+ CD30+IFN-gamma+ and CD4+ CD30+IL-4+ blasts which diminished (mean: 6%) after 5 culture days. In contrast, CD4+ CD30+IL-5+ blasts showed a continuous progression (from 12% to 24%) that maintained after 7 culture days. The vast majority of CD4+ CD30+ blasts were negative to 7-AAD or TUNEL. Additionally, a significant decrease (34%) was observed in the number of CD4+ CD30+ blasts when IL-4 was neutralized.
These data suggest that specific allergen stimulation of PBMC isolated from allergic patients generates a nonapoptotic CD4+ CD30+ blast subset that produces IL-5.
In recent years the morbidity and mortality of asthma has increased, although the etiology is still poorly understood. Most patients with asthma suffer acute attacks that are commonly treated in hospital emergency rooms (ER). In the present study, asthma in adults was studied with acute attacks as a marker for the disease; 102 patients first observed at a university hospital ER with acute airway obstruction were compared to 118 patients observed at the same ER with any diagnosis other than shortness of breath to evaluate allergy as a risk factor for asthma in adults. Sera were assayed for IgE antibody (Ab) to dust mites, cockroach, cat dander, and grass and ragweed pollen. The results demonstrate that in adults younger than 50 years of age, the prevalence of IgE Abs was fourfold greater among subjects with asthma than among control subjects (46/67 versus 12/81; odds ratio, 10.1; 95% confidence interval, 4.9 to 20.7). The population attributable risk for the presence of IgE Ab to one of the five allergens was greater than 50%. Among individuals older than 50 years of age, the prevalence of serum IgE Abs was not significantly increased among patients with acute airway obstruction. In the whole group, the prevalence of IgE Abs to different allergens demonstrated significant seasonal and socioeconomic differences, suggesting that the associated risk is related to exposure to those allergens. The results establish that, with acute attacks of asthma as a marker for adult asthma, the presence of serum IgE Abs to common inhalant allergens is a major risk factor.(ABSTRACT TRUNCATED AT 250 WORDS)
Excessive production of interleukin (IL)-4, IL-5, IL-10, and IL-13 is thought to be important in the development of allergy and asthma. The objective of this investigation was to study Th1/Th2-like cytokine profiles in vitro in seven patients allergic to birch pollen and six nonallergic controls during the birch-pollen season.
Peripheral blood mononuclear cells (PBMC) were isolated and cultured with birch-pollen extract (BPE) or tetanus toxoid (TT) for 7 days, harvested, and restimulated with the mitogens phytohemagglutinin (PHA) and phorbol 12-myristate 13-acetate (PMA) for 24 h. Cytokine production was determined by ELISA, and logarithmic cytokine ratios were compared between the two groups and between the antigens.
In the allergic group, the cultures prestimulated with BPE had a more Th2-like cytokine response than the TT-prestimulated cultures; i.e., lower IFN-gamma and higher IL-10 production (P<0.05), as well as higher IL-5/IFN-gamma and IL-13/ IFN-gamma ratios (P<0.05). There were also significantly higher IL-4/IFN-gamma (P<0.005) and IL-5/IFN-gamma (P<0.05) ratios in BPE-stimulated cultures in the allergic group than in the control group. The IL-4 and IL-13 production in vitro correlated with the specific serum IgE levels.
BPE stimulation induces a Th2-like cytokine response by PBMC isolated during the pollen season from birch-pollen-allergic patients, indicating a Th2-type immune response to birch pollen in vivo.
Viruses cause asthmatic exacerbations in schoolchildren. We tested the hypothesis that children who wheezed with viral respiratory tract infections secrete higher levels of the type 1 cytokine interferon-gamma (IFN-) in the peripheral circulation than children who had never wheezed. Blood was taken from 13 children (eight atopic) with episodic wheeze and 11 controls. CD4 and CD8 cells were separated from peripheral blood mononuclear cells and stimulated with phorbol 12-myrisate 13-acetate (PMA) and ionomycin for 24 h. IFN-, IL-4, and IL-5 were measured in the supernatant by ELISA. IFN- production by CD4 and CD8 cells was lower in children with a history of wheeze (CD4, P=0.046; CD8, P=0.037). These children were then analysed according to atopic status. CD4 and CD8 IFN- production in nonatopic wheezy children was reduced (CD4, P=0.009; CD8, P=0.003). IFN- production by atopic wheezy children was lower than by controls, but the differences were not significant (CD4, P=0.2831; CD8, P=0.1372). CD8 IL-5 was lower in children who wheezed (P=0.012). Release of IL-4 and IL-5 by CD4 cells did not differ between the three groups. We propose that defective IFN- secretion by CD4 and CD8 cells may contribute to viral-induced wheeze in nonatopic children.
Nine hundred three former college freshmen were followed 7 yr after entering college by means of a detailed allergy questionnaire. Original data collected from the students as freshmen, including a history of atopy and allergy skin test results, were evaluated in relation to the frequency of developing new allergies. During the 7-yr follow-up period, new cases of hay fever occurred in 12.6%, nonseasonal allergic rhinitis in 4.8%, and new asthma in 2.5%. The risks of developing asthma and allergic rhinitis are both significantly associated with a prior positive allergy skin test. The risk of developing asthma, not hay fever, is significantly associated with a prior history of atopy. The association of positive allergy skin tests with the development of new cases of allergy remains significant throughout the 7-yr follow-up period. However, individuals who had all negative skin tests developed significantly fewer new cases of clinical allergy during the first 3 yr of follow-up; in the next 4 yr of the 7-yr follow-up, increased numbers of individuals with negative scratch tests developed new cases of allergy. Thus, negative skin tests proved of less prognostic value during the last 4-yr period of this 7-yr study, although significant differences still are apparent between the positive and negative reactor groups.
We investigated the association of self-reported asthma or allergic rhinitis with serum IgE levels and skin-test reactivity to allergens in 2657 subjects in a general-population study. Regardless of the subjects' status with respect to atopy or their age group, the prevalence of asthma was closely related to the serum IgE level standardized for age and sex (P less than 0.0001), and no asthma was present in the 177 subjects with the lowest IgE levels for their age and sex (greater than 1.46 SD below the mean). The log odds ratio increased linearly with the serum IgE level after we controlled for possible confounders and the degree of reactivity to skin tests. In contrast, allergic rhinitis appeared to be associated primarily with skin-test reactions to common aeroallergens, independently of the serum IgE level. We conclude that asthma is almost always associated with some type of IgE-related reaction and therefore has an allergic basis, although not all the allergic stimuli that cause asthma appear to have been included in the battery of common aeroallergens we used to assess atopic status. These findings challenge the concept that there are basic differences between so-called allergic ("extrinsic") and nonallergic ("intrinsic") forms of asthma.
Allergic conditions were evaluated for 2 successive years among 1,836 Brown University and Pembroke College freshmen (99.2 per cent). Students gave personal allergic histories and family histories of allergy, and information was supplemented by parents. Some type of allergy was present in 34.8 per cent of the population. A total of 25.0 per cent of students had a history of asthma, seasonal hay fever, or nonseasonal allergic rhinitis. The frequency of each of these conditions was 5.3 per cent for asthma, 21.1 per cent for seasonal hay fever, and 5.2 per cent for nonseasonal allergic rhinitis. Positive family histories of asthma and/or allergic rhinitis were found to localize among students who had these conditions. Skin scratch tests with 15 commercial allergens and a control were performed on 1,243 students (67.7 per cent); 30.9 per cent showed at least one positive reaction, with localization found among the allergic group. No association between scratch test reaction and family history was observed.
Histories of allergy were obtained from 1,836 freshmen college students, and 1,243 of these students were also scratch tested with 15 allergens. Three years later, 1,352 of these students participated in a follow-up study designed to determine new allergies which had developed since their entrance into college as freshmen. Sixty-four new cases of hay fever, nonseasonal allergic rhinitis, and/or bronchial asthma were identified in the population. The frequency of new hay fever that developed among 614 senior students who had no clinical manifestation of allergy as freshmen is over ten times higher in students with initially positive pollen scratch tests (18.2 per cent) than in students with negative pollen scratch tests (1.7 per cent). Students with a 2+ or greater pollen scratch test reaction subsequently developed hay fever significantly more frequently than students with no positive pollen scratch tests. The data also suggest that the positive pollen scratch test reaction precedes the onset of clinical symptoms of hay fever. Cumulative prevalence rates of asthma, nonseasonal allergic rhinitis, and seasonal hay fever by age of onset of each condition are given. Of the students who first had onset of hay fever and were at risk to develop asthma, only 5.3 per cent have subsequently developed asthma.
Serum IgE levels were measured by a paper-disc radioimmunoassay technique (PRIST) in 425 nonallergic subjects and in 570 patients with asthma, 244 with allergic rhinitis, 48 with asthma and eczema (atopic dermatitis), 49 with eczema but without asthma, and 57 with chronic urticaria. The data are presented for age groups in geometric means and standard deviations and by modal distribution. Normal mean IgE levels for the total sample were 32 IU/ml with highest levels (mean of 51 IU/ml) in school-age children. The highest IgE levels were found in patients with both asthma and eczema (mean of 985 IU/ml), followed by asthma alone (305 IU/ml), eczema alone (273 IU/ml), and allergic rhinitis (171 IU/ml). The values for our United States population were higher than those reported from Scandinavian countries but lower than those reported from Canada. The geometric mean plus 1 SD (64 IU/ml for infants, 150 IU/ml for schoolchildren, and 100 to 120 IU/ml for all other age groups) appears to be the most useful limit of normalcy. Overlaps with normal values are largest for urticaria, eczema, and allergic rhinitis and least for patients with allergic asthma.
In the initial study of 23 years ago, 1836 college freshmen were prospectively evaluated by questionnaires, interviews, and physical examinations for medical conditions which included the presence of asthma, allergic rhinitis, and positive allergy skin tests to a battery of pollens, animal extracts, and mold. In a 23-year follow-up study, 1021 (64%) returned their completed questionnaires. Of these, 738 (72%) had been skin tested as freshmen. The results of this follow-up study revealed that the frequency of asthma and allergic rhinitis continue to increase as the individuals become older. Allergic rhinitis and positive allergy skin tests are significant risk factors for developing new asthma. Individuals with either of these diagnoses are about three times more likely to develop asthma than negative controls. Positive allergy skin tested students have more than twice (2.3x) the risk of developing new hay fever than do negative skin tested students over a 23-year period.
The purpose of this study is to examine the co-existence of asthma and allergic rhinitis among former college students who were diagnosed with these diseases either before or after their freshman year. A total of 738 former Brown University students (69% males and 31% females) who were evaluated and underwent skin testing during their freshman year completed a 23-year follow-up questionnaire inquiring of their history of allergies and asthma. The mean age of the participants at the time of the follow-up study was 40 years. In this group, the cumulative incidence of asthma was 11.3% (84/738), hay fever was 41.5% (306/738), and nonseasonal allergic rhinitis was 14.0% (103/738). The cumulative incidence of allergic rhinitis (hay fever) and/or nonseasonal allergic rhinitis (was 45.8% (338/738). Among the 84 individuals with a cumulative incidence of asthma, 63 (75.0%) had a history of hay fever, 27 (32.1%) had a history of nonseasonal allergic rhinitis, and 72 (85.7%) had a history of allergic rhinitis. Among the 306 participants with a cumulative incidence of hay fever, 63 (20.6%) had a history of asthma. Twenty-seven (26.2%) of the 103 individuals with a history of nonseasonal allergic rhinitis had a cumulative incidence of asthma. Among the 338 individuals with a cumulative incidence of allergic rhinitis 72 (21.3%) had a history of asthma. Among the participants with a history of both asthma and hay fever, 44.8% developed hay fever first, 34.5% developed asthma first, and 20.7% developed both diseases at the same time. Among the individuals with a history of asthma and nonseasonal allergic rhinitis, 38.5% developed nonseasonal allergic rhinitis first, 30.8% developed asthma first, and 30.8% developed both diseases at the same time. This study further demonstrates the frequent co-existence of asthma and allergic rhinitis. Among asthmatics, allergic rhinitis occurred in 85.7%. Only 14.3% of asthmatics did not have allergic rhinitis. Among individuals with allergic rhinitis, asthma occurred in 21.3%. Also, allergic rhinitis often precedes or occurs at the same time as asthma.
Interleukin-5 (IL-5) is the predominant cytokine associated with antigen-induced eosinophilic inflammation in the lung. The activation of TH2 cells leads to the production of IL-5. The proeosinophilic effects of IL-5 include 1) enhanced replication and differentiation of eosinophilic myelocytes; 2) enhanced degranulation of eosinophils; 3) prolonged survival time of eosinophils; and 4) enhanced adhesion of eosinophils. The effects of IL-5 are mediated via the interaction of IL-5 with receptors (Il-5R) expressed on the eosinophil cell membrane. Intracellular signaling produced by occupation of the IL-5R by IL-5 occurs via the JAK-STAT system. IL-5 is a 45kD glycoprotein that consists of two identical polypeptide chains. The 5'-promoter region of the IL-5 gene contains elements that are down-regulated by glucocorticoids. A 16-mer deoxyoligonucleotide, antisense to IL-5 mRNA and with two phosphorothioate modifications, produced, at 20 micromolar concentration, complete inhibition of IL-5 secretion by human peripheral blood mononuclear cells. The targeted 16-mer sequence of the IL-5 mRNA did not display complete homology with any other known human gene sequences. These results suggest that the 16-mer phosphorothioate antisense IL-5 provides the basis for a non-glucocorticoid, sequence-specific inhibitor of IL-5.
Infection with Mycobacterium tuberculosis induces a type-1 immune response, whereas intestinal parasites elicit a type-2 response. Given that type-1 and type-2 responses inhibit each other, we investigated if M tuberculosis downregulates serum IgE, a marker of a type-2 response.
A prospective study was done in the Western Cape Province of South Africa, where tuberculosis and intestinal-parasite infection are common. Total serum IgE was determined for 37 controls and for 33 adolescent patients at presentation with tuberculosis and after successful completion of treatment. IgE specific for ascaris and allergens were measured in a subset of these individuals. Mantoux skin tests were done on 35 controls and on 31 patients at diagnosis.
Total IgE concentrations were high in controls (mean 313 kU/L) and in patients before treatment (mean 457 kU/L, p=0.085) and declined in all patients following successful treatment (mean 175 kU/L, p<0.0001). Posttreatment IgE concentrations did not differ from concentrations in controls. Ascaris-specific IgE was lower in controls (mean 1.73 kU/L) than in patients before treatment (4.62 kU/L, p=0.023) and was 2.39 kU/L in patients after treatment (p=0.0625). Tuberculin induration correlated inversely with IgE in patients but not in controls.
Infection with M tuberculosis as such is not incompatible with a prominent IgE response. IgE concentrations decreased after successful treatment of tuberculosis, showing that IgE concentrations in human beings can be downregulated under these circumstances, presumably due to enhancement of a type-1 response.
Over the past several years, a number of cytokines with chemoattractive properties (chemokines) have been identified. These low molecular weight molecules have been shown to be important leukocyte chemical attractants to sites of inflammation and infection. Chemokines act on leukocytes through selective receptors and are now known to function also in leukocyte maturation, trafficking, and homing of these cells. RANTES and eotaxin (among other chemokines) are important chemoattractants for eosinophils. Since eosinophils seem to play a critical role in the production of allergic inflammation, an understanding of the mechanism of action of these chemokines may lead to new therapies for asthma and other allergic processes.
Patients with asthma and concomitant allergic rhinitis are among the most costly patients. A survey of over 34,000 patients with asthma indicated that the cost of those patients who have asthma alone without allergic rhinitis was roughly half the overall cost of patients who had concomitant allergic rhinitis and asthma. Asthma and allergic rhinitis are linked in several ways. The shared immunologic pathogenesis are nasal bronchial reflex, allergen sensitization, and epidemiologic studies that link asthma and allergy. There is an interrelatedness of the upper and lower airway function, the link operating directionally from the sinuses to the lungs. In addition, there is a co-occurrence of asthma and allergic rhinitis in the population. Furthermore, both conditions respond to similar treatments, including antihistamine-containing therapies that may ameliorate allergic rhinitis and also potentially help alleviate asthma symptoms.
In the last few years strong evidence has accumulated to suggest that allergen-reactive type-2 T helper (T(H)2) cells play an important role in the induction and maintenance of the allergic inflammatory cascade. First, cytokines and chemokines produced by T(H)2 cells (GM-CSF, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, macrophage-derived chemokine) and those produced by other cell types in response to T(H)2 cytokines or as a reaction to T(H)2-related tissue damage (eotaxin, transforming growth factor-beta, IL-11) account for most pathophysiologic aspects of allergic disorders (production of IgE antibodies; recruitment or activation of mast cells, basophils, and eosinophils; mucus hypersecretion; subepithelial fibrosis; and tissue remodeling). The T(H)2 hypothesis may also explain the complex genetic background responsible for allergic disorders. Several genes are involved in the development and regulation of T(H)2 cells and may provide the reason why the prevalence of atopic allergy is increasing in Western countries. Indeed, a dramatic change has occurred in the last several decades in the "microbial" environment of children, thus probably altering the balance between T(H)1 and T(H)2 responses to "innocuous" antigens (allergens) in favor of T(H)2 responses. Finally, the T(H)2 hypothesis offers exciting opportunities for the development of novel immunotherapeutic strategies targeted to address allergen-specific T(H)2 cells or T(H)2-derived effector molecules in atopic individuals.
Bacterial endotoxin is known to induce interferon gamma and interleukin 12 production, and therefore has the potential to decrease allergen sensitisation. To find out the role of early chronic endotoxin exposure in the development of allergen sensitisation and asthma, we compared concentrations of endotoxin in house dust with allergen sensitisation in infants at high risk for developing asthma.
61 infants 9-24 months old with at least three physician-documented episodes of wheezing were studied. Concentrations of house-dust endotoxin and allergens were measured in the infants' homes. Allergen sensitisation was measured by skin-prick testing with a panel of common inhalant and food allergens. In a subset of these infants, proportions of T lymphocytes producing interferon gamma, and interleukins 4, 5, and 13 were calculated by cell-surface and intracellular cytokine staining, with flow cytometry.
House-dust endotoxin concentrations ranged from 104 to 10,000 endotoxin units (EU) per mL (geometric mean 912 EU/mL). Concentrations did not vary significantly over a 6-month interval. Ten infants (16%) were sensitised to at least one allergen. The homes of allergen-sensitised infants contained significantly lower concentrations of house-dust endotoxin than those of non-sensitised infants (mean 468 vs 1035 EU/mL, respectively; p=0.01). Increased house-dust endotoxin concentrations correlated with increased proportions of interferon-gamma-producing CD4 T cells (p=0.01). Such concentrations did not correlate with proportions of cells that produced interleukins 4, 5, or 13.
This study may provide the first direct in-vivo evidence that indoor endotoxin exposure early in life may protect against allergen sensitisation by enhancing type 1 immunity.
A major function of the immune system is to protect the body from infection and the diseases caused by infectious agents. The immune system also provides protection against cancer cells, for once they arise, cancers can essentially behave as "foreign" cells capable of causing pathology. In contrast, allergy is a manifestation of the immune response to certain environmental cells or molecules that are usually neither a threat for infection nor cancer. Allergic reactions are generally an annoynance, even life-threatening. I will focus on type I allergy, characterized in part by induction of IgE antibody responses to allergens. It should be noted that not all IgE responses cause allergic symptoms. There is even evidence that IgE responses to tropical helminthic parasites offer a degree of immunity to reinfection. I have three objectives: (1) review T cell differentiation leading to the Th1/Th2 paradigm; (2) evaluate the increased prevalence of atopy, including asthma, as a consequence of a Th2-dominated immune system; (3) relate the high prevalence of asthma in inner city United States black children to the relatively recent migration of their ancestors from tropical regions of Africa, where genetically biased Th2-dependent IgE responses may be important in protection against high burdens of parasitic worms.
Listeria monocytogenes causes sepsis and meningitis in immunocompromised hosts and a devastating maternal/fetal infection in pregnant women. In recent years a more benign gastroenteritis in normal hosts has been described. Listeria has been increasingly identified as a food-borne pathogen, and large-scale contamination of processed foods with resulting outbreaks has occurred in recent years, possibly as a result of consolidation of the food industry. Experimental listeriosis in mice has proven to be an extraordinarily useful model for analyzing cell-mediated immune host defenses. Contrary to original concepts, we found that neutrophils, not macrophages, are the prime effectors during early infection. CD8+ T cells are then responsible for lysing infected hepatocytes through perforin-related (early primary and secondary infection) or Fas-L/Fas mechanism (late primary). Of interest, non-classical MHC class Ib restricted recognition mechanisms exist early, whereas MHC class Ia mechanisms can be detected throughout infection.
Cytokines are glycoproteins that are secreted and that regulate immunologic inflammation. The cytokine system is characterized by much redundancy and cross-reactivity. Of the more than 100 cytokines that have been identified, interleukin-5 (IL-5) and the chemokine (chemotactic cytokine), eotaxin, are the most selective for cells of eosinophilic origin. Because of this relative specificity, and because of their important immunoregulatory roles, IL-5, eotaxin, and their receptors IL-5R and CCR3 are potential targets for non-glucocorticosteroid pharmacological treatment of eosinophilic inflammation.