Development Of Allergic Respiratory Diseases Research Articles

Effect of occupational exposure to ADCA on the incidence of allergic respiratory reactions - a literature review

1,1'-azodi(formamide) (ADCA) is widely used as a blowing agent, a chemical substance designed to induce foaming processes. In Poland, ADCA is manufactured by a company specializing in the production of polyethylene foam bags and laminates used in various industries including home appliances, electronics, construction, furniture, automotive, and sports and leisure. The mechanism of action of ADCA involves thermal decomposition, resulting in nitrogen, carbon monoxide, as well as ammonia and carbon dioxide as the main gaseous decomposition products. These penetrate the polymer matrix, contributing to expansion and foaming properties. Most studies evaluating the relationship between occupational exposure and the development of allergic respiratory diseases focus on workers involved in ADCA production or its use as a blowing agent in plastics. The objective is to assess the respiratory sensitizing effects of ADCA in humans due to occupational exposure, based on literature data. The presented data confirm that long-term occupational exposure to ADCA can lead to persistent bronchial hyperreactivity symptoms in workers. 1,1'-azodi(formamide) can induce occupational asthma, with initial symptoms including nasal congestion, conjunctivitis, wheezing, and cough. Subsequently, symptoms such as chest tightness, dyspnea, and nocturnal cough attacks may appear, with a latency period of several years observed before symptom onset. In some cases, symptom progression was noted with continued ADCA exposure, while in others, exposure was discontinued after initial symptoms, preventing observation of symptom exacerbation. Prior exposure to allergens, such as working in bakeries, appears to accelerate symptom onset. Improvement in allergy symptoms has been noted during weekend breaks from work. There is no safe concentration identified for ADCA that would not result in adverse health effects for workers. A concentration of 0.036 mg/m3 is considered the lowest observed adverse effect concentration, causing critical reduction in lung spirometric parameters. Med Pr Work Health Saf. 2024;75(5).

Climate-Induced Respiratory Challenges: Understanding Allergic Reactions and Asthma Caused by Pollen Allergens

‌In recent years, the impact of climate change on our environment has become increasingly evident. Human activities, particularly the rise in atmospheric concentrations of carbon dioxide (CO2) and other greenhouse gases, are key contributors to this shift. These changes in climate, combined with global warming, have notable effects on weather patterns, influencing the quantity, intensity, and frequency of precipitation. Additionally, climate change is linked to a heightened occurrence of extreme events such as heatwaves, droughts, floods, and hurricanes. A significant concern is the intricate relationship between climate change and respiratory health. In this review, we highlight the association between climate change and respiratory allergies, increased prevalence and severity of asthma, and related allergic diseases. The alterations brought about by climate change significantly contribute to the development of allergic respiratory diseases and asthma. This impact extends to pollen allergies, with changes in their onset, duration, and intensity attributed to climate change. Studies indicate that plants respond to elevated atmospheric CO2 levels with enhanced photosynthesis and reproductive effects, resulting in increased pollen production. Pollen allergies provide valuable insights into the interplay between air pollution and allergic respiratory diseases like rhinitis and asthma. Recognizing the broader health implications, it becomes crucial to address the underlying causes. Implementing measures to reduce greenhouse gas emissions emerges not only as a pivotal step in mitigating climate change but also as a proactive approach with positive health benefits. The need for a comprehensive strategy is underscored by the interconnectedness of environmental and public health concerns in the face of a changing climate.

Climate change and allergic diseases in children and adolescents.

The Anthropocene is used to describe the most recent period where major disruptions in Earth's system processes have resulted from humanity's increasing ecological footprint. Climate change affects the social and environmental determinants of good health, such as clean air, stable ecosystems, safe drinking water, and sufficient and safe food, and they seem to be closely related to air pollution. This article aims to review the evidence of how extreme weather events and indoor and outdoor pollution are associated with insufficient lung growth in early life, changes in lung function, and the increase in respiratory infections, favoring the development of allergic respiratory diseases. Non-systematic review of English, Spanish, and Portuguese articles published in the last ten years in databases such as PubMed, EMBASE, and SciELO. The terms used were air pollution OR climate changes OR smoke, AND health OR allergic disease. Climate change and air pollution are the leading contributors to health emergencies around the world. On a global scale, those most at risk of adverse health effects associated with climate change include children, the elderly, and other vulnerable groups. Climate change and air pollution have adverse impacts on respiratory allergies, and the mechanisms are complex and interactive. Health professionals must receive information and education necessary to establish effective mitigation and adaptation strategies to minimize the effects of climate changes on the respiratory health of their patients.

Early infant feeding and allergic respiratory diseases in Ibb city, Yemen

BackgroundAllergic respiratory diseases (ARD) are a highly prevalent health problem affecting infants and children in Yemen. Early infant feeding predisposition to the development of ARD has been a controversial question. The aim of this study is to investigate the association between early feeding before 6 months of age and the development of ARD among children attending Childhood and Maternity Public Hospital (CMPH), Ibb, Yemen Republic.Subjects and methodsThe study population included 151 child patients attending the pediatric clinic at CMPH. Upon clinical and laboratory examinations, 72 out of 151 patients had ARD, while the other 79 had diseases other than ARD; all of them were used in risk assessment. Fifteen blood samples from healthy volunteers were used in laboratory investigations as a control. Complete blood count and IgE level were investigated for all participants. Children's parents were requested to give an informed consent and fill questionnaire about demography and history details.ResultsEarly infant feeding was a significant risk factor for the development of ARD with an odds ratio (OR) of 6.8 and 95% confidence interval (CI) 3.0 to 15.3. Artificial milk particularly was risk factor with an OR of 6.1 and 95% confidence interval 2.7 to 13.5. Artificial milk exhibited more wheezing and asthma attack than others (OR 4.3, 95% CI 1.9 to 9.4 and OR 7.6, 95% CI 3.5 to 16.3, respectively). The risk of wheezing and asthma attack also increase with early feeding generally (OR 3.0, 95% CI 1.3 to 7.2 and OR 4.8, 95% CI 2.2 to 8.1, respectively). The patients had a higher sensitization markers than the control, such as eosinophil count and total serum IgE. The highest levels of IgE ever reported existed among early fed patients with artificial milk.ConclusionsEarly infant feeding, particularly with artificial milk, is a risk factor predisposing infants to the development of allergic respiratory disease presented with more clinical features of wheezing and asthma attack.

The perinatal use of probiotics, prebiotics, and synbiotics for the primary prevention of allergic diseases in children: A systematic review

Given the increasing prevalence of allergic diseases, as well as the extensive burden on society caused by these conditions, there is a need for strategies aimed at primary prevention. Probiotics, prebiotics, and synbiotics, when administered perinatally, have been shown to reduce the incidence of allergic diseases in children. However, there are many unanswered questions in terms of the optimal timing, duration, dosage, and composition of probiotics, prebiotics, or both (synbiotics). The objective of this systematic review is to audit the current medical literature on the effects of the perinatal administration of probiotics, prebiotics or synbiotics for the primary prevention of allergic disease in childhood. PubMed, Web of Science, and SCOPUS medical databases were systematically searched for relevant studies, published from the year 2000 to May 2020, assessing the effects of probiotics, prebiotics or synbiotics administered during the perinatal period on the prevention of allergy in children. A total of 38 studies met inclusion criteria for the systematic review. The use of probiotics, when administered during the third trimester of pregnancy and continued for the first three to six months of life, consistently reduced the incidence of atopic dermatitis, but not allergic respiratory disease or allergic sensitization. Mixtures of probiotics, in a dose of 109 to 1010 cfu/day, were most effective at reducing the incidence of atopic dermatitis. Prebiotics, administered in the postpartum period, with or without the perinatal administration of probiotics, did not consistently reduce the incidence of allergic diseases in children. Probiotics started during the third trimester of pregnancy and continued for the first three months of life, administered as a mixture of different species in the amount of 109 to 1010 cfu/day, reduces the incidence of atopic dermatitis in children. There is no consistent protective effect on the development of allergic respiratory diseases or allergic sensitization. The addition of prebiotics, other than those obtained from breastfeeding, do not appear to provide additional protection against the development of allergic disease in children.

The effects of climate change on respiratory allergy and asthma induced by pollen and mold allergens.

The impact of climate change on the environment, biosphere, and biodiversity has become more evident in the recent years. Human activities have increased atmospheric concentrations of carbon dioxide (CO2 ) and other greenhouse gases. Change in climate and the correlated global warming affects the quantity, intensity, and frequency of precipitation type as well as the frequency of extreme events such as heat waves, droughts, thunderstorms, floods, and hurricanes. Respiratory health can be particularly affected by climate change, which contributes to the development of allergic respiratory diseases and asthma. Pollen and mold allergens are able to trigger the release of pro-inflammatory and immunomodulatory mediators that accelerate the onset the IgE-mediated sensitization and of allergy. Allergy to pollen and pollen season at its beginning, in duration and intensity are altered by climate change. Studies showed that plants exhibit enhanced photosynthesis and reproductive effects and produce more pollen as a response to high atmospheric levels of carbon dioxide (CO2 ). Mold proliferation is increased by floods and rainy storms are responsible for severe asthma. Pollen and mold allergy is generally used to evaluate the interrelation between air pollution and allergic respiratory diseases, such as rhinitis and asthma. Thunderstorms during pollen seasons can cause exacerbation of respiratory allergy and asthma in patients with hay fever. A similar phenomenon is observed for molds. Measures to reduce greenhouse gas emissions can have positive health benefits.

Determinants of Allergic Sensitization, Asthma and Lung Function: Results from a Cross-Sectional Study in Italian Schoolchildren.

Prenatal smoking exposure and early-life respiratory infections are major determinants of asthma during childhood. We investigate the factors influencing allergic sensitization (AS), asthma, and lung function in children and the balance between individual and environmental characteristics at different life stages. 1714 children aged 7–16 years and living in southern Italy were investigated using a parental questionnaire, skin prick tests, and spirometry. We found 41.0% AS prevalence: among children without parental history of asthma, male sex, maternal smoking during pregnancy (MatSmoke), and acute respiratory diseases in the first two years of life (ARD2Y) were significant risk factors for AS. MatSmoke was associated (OR = 1.79) with ARD2Y, and this association was influenced by sex. ARD2Y was, in turn, a significant risk factor (OR = 8.53) for childhood current asthma, along with AS (OR up to 3.03) and rhinoconjuctivitis (OR = 3.59). Forced mid-expiratory flow (FEF25–75%) was negatively affected by ARD2Y, with a sex-related effect. Thus, males exposed to MatSmoke had significantly lower FEF25–75% than unexposed males. Despite the difficulty of discriminating among the complex interactions underlying the development of allergic respiratory diseases, ARD2Y appears to strongly influence both asthma and lung function during childhood. In turn, ARD2Y is influenced by prenatal exposure to tobacco smoke with a sex-dependent effect.

The effect of residential urban greenness on allergic respiratory diseases in youth: A narrative review

BackgroundEnvironmental exposures across the life course may be a contributor to the increased worldwide prevalence of respiratory and allergic diseases occurring in the last decades. Asthma and rhinoconjunctivitis especially contribute to the global burden of disease. Greenness has been suggested to have beneficial effects in terms of reduction of occurrence of allergic respiratory diseases. However, the available evidence of a relationship between urban greenness and childhood health outcomes is not yet conclusive. The current review aimed at investigating the current state of evidence, exploring the relationship between children's exposure to residential urban greenness and development of allergic respiratory diseases, jointly considering health outcomes and study design. MethodsThe search strategy was designed to identify studies linking urban greenness exposure to asthma, rhinoconjunctivitis, and lung function in children and adolescents. This was a narrative review of literature following PRISMA guidelines performed using electronic search in databases of PubMed and Embase (Ovid) from the date of inception to December 2018. ResultsOur search strategy identified 2315 articles; after exclusion of duplicates (n = 701), 1614 articles were screened. Following review of titles and abstracts, 162 articles were identified as potentially eligible. Of these, 148 were excluded following full-text evaluation, and 14 were included in this review. Different methods for assessing greenness exposure were found; the most used was Normalized Difference Vegetation Index. Asthma, wheezing, bronchitis, rhinoconjunctivitis, allergic symptoms, lung function, and allergic sensitization were the outcomes assessed in the identified studies; among them, asthma was the one most frequently investigated. ConclusionsThe present review showed inconsistencies in the results mainly due to differences in study design, population, exposure assessment, geographic region, and ascertainment of outcome. Overall, there is a suggestion of an association between urban greenness in early life and the occurrence of allergic respiratory diseases during childhood, although the evidence is still inconsistent. It is therefore hard to draw a conclusive interpretation, so that the understanding of the impact of greenness on allergic respiratory diseases in children and adolescents remains difficult.

Passport of sensitization of schoolchildren as a tool for the prevention of asthma

Molecular allergy diagnosis allows to identify sensitization to a large range of respiratory allergens, which is important in the diagnosis of allergic asthma. Moreover, based on the reactive IgE profile detected at an early age, it is possible to predict the development of allergic respiratory diseases even at the preclinical stage. The goal of the pilot project was to create a children's passport sensitization using a multiplex panel to be able to identify groups at risk for the development of asthma in children of early school age. Materials and methods. Parents of 33 students studying in the second grade of the Tashkent gymnasium were questioned using the ISAAC questionnaire for the clinical manifestations of respiratory diseases in their children. Their children’s sera were tested for the presence of IgE to various allergenic molecules using the MeDALL research method. Results. 30% of children were sensitized to at least one allergen, and 30% of them were born by Caesarean section. and 30% of them were born by Caesarean section. In total, 68 of the 176 allergenic molecules located on the MeDALL microchip were recognized. 80% of sensitized children had a genuine polysensitization to 3 or more major allergens. In 18% of children, IgE to household molecules of the risk of developing asthma, such as Alt a 1, Bla g 1, Bla g 2, Can f 1, Fel d 1, were detected. Conclusions. In general, clinical manifestations in the form of wheezing and obstruction were detected in 60% of sensitized children, but only 40% of these children were under the supervision of an allergist or received symptomatic treatment. In 20% of already sensitized children, clinical symptoms were absent. Molecular testing of the profile of IgE sensitization and the creation of an allergic passport allows us to identify a group of children at risk for developing asthma. This information can be used to assign therapy and secondary prevention of asthma in the early school years.

Bronchial asthma in children in the practice of a family doctor

The objective: substantiation of the most significant risk factors for the development of bronchial asthma (BA) in children living in Kiev and the Ternopil region.Materials and methods. Descriptive and analytical methods of epidemiological study of the influence of a complex of factors on public health were used. One of the stages of identifying the risk of allergic respiratory diseases and asthma in children is a screening survey that covered 657 children aged 3 to 14 years, residents of Kiev and Ternopil region. Two qualitatively different groups of the children's population were examined: with allergic diseases of respiratory organs and clinically healthy ones.Results. As a result of the study, it was proved that the technique developed for practical investigation of the risk groups for the development of allergic respiratory diseases, in particular asthma, in children, can be used in healthcare institutions for the timely detection and prevention of this pathology.The conclusion. The most significant risk factors for the development of allergic respiratory diseases and bronchial asthma in children are complications of antenatal development, heredity, allergy to juices, manifestations of exudative catarrhal diathesis, the incidence of acute respiratory viral infection, concomitant pathology, spontaneous manifestations of choking in the middle of the night,

Impact of air pollution in respiratory allergic diseases

Allergic respiratory disease, which includes allergic rhinoconjunctivitis and asthma, is one of the most common diseases, with a major impact on a patient's quality of life. Air pollution is one of the main factors associated with the development of allergic respiratory disease, it has been shown to impair lung development in children and adolescents. The origins of particulate matter produced from various sources, including those issued by traffic and the burning of fuels such as coal, gasoline and diesel. Diesel emissions represent the majority of the particulate matter in urban air pollution. It has been found that the co-exposure of diesel emissions and airborne allergens increases allergen-specific IgE levels, severity of asthma, inflammation and airway hyper-responsiveness. In vivo and in vitro studies have reported the activation of anti-transcription and pro-inflammatory mediators. Polycyclic aromatic hydrocarbons, metal components or metabolites may increase due to the formation of oxygen reactive species that interact with DNA, producing different types of damage as oxidative damage.

The characteristics of indoor and outdoor fungi and their relation with allergic respiratory diseases in the southern region of Turkey.

Indoor and outdoor fungal exposure has been shown to be associated with the development of allergic respiratory diseases. The aim of the study was to investigate the types and concentrations of airborne fungi inside and outside homes and evaluate the association between fungal levels and allergic diseases in the southern region of Turkey. A total of 61 children admitted with respiratory complaints to the pediatric allergy clinic between September 2007 and November 2008 were included in this study. The air samples were obtained using the Air IDEAL volumetric air sampler longitudinally for 1year. A comprehensive questionnaire was used for medical history and housing conditions. Skin prick test was performed to determine fungal sensitivity and spirometric indices were employed. The predominant indoor fungal species were Cladosporium (69.3%), Penicillium (18.9%), Aspergillus (6.5%), and Alternaria (3.1%). A strong correlation between indoor and outdoor fungal levels was detected for the Cladosporium species (p < 0.001, r = 0.72) throughout the year. Living in a detached home (p = 0.036) and the presence of cockroaches (p = 0.005) were associated with total indoor fungal levels. The presence of cockroaches (aOR 3.5; 95% CI 0.95-13.10, p = 0.059) was also associated with fungal sensitization at the edge of significance. The statistical cutoff values of indoor and outdoor Cladosporium levels to predict symptomatic asthma were found to be >176CFU/m(3) (p = 0.003, AUC 0.696; sensitivity 65.5%; specificity 68.7%) and >327CFU/m(3) (p = 0.038; AUC 0.713; sensitivity 66.6%; specificity 76.9%), respectively. Children with respiratory symptoms are exposed to a considerable level of fungi inside and outside their homes. The prevention of fungal exposure may provide valuable intervention for respiratory diseases.

MOULDS IN THE INDOOR ENVIRONMENT AND POSSIBLE HEALTH EFFECTS

Moulds are multicellular fungi that are ubiquitous in indoor and outdoor environment. Exposure to moulds can occur through inhalation, ingestion, and touching mouldy surfaces. Adverse health effects may occur through allergic, infectious, irritant, and toxic processes. In our review we elucidated some possible harmful mechanisms of moulds on the health of the population and some preventive recommendation. A systematic literature review was carried out in two bibliographic databases, Science Direct and PubMed, in the period from 1985 to February 2015. We systematically observed also the internet pages from CDC (Centers for Diseases Control and Prevention) and EPA (Environmental Protection Agency). Out of websites we accepted the roles for recommendation in case of moulds indoor buildings. Epidemiological studies all over the world have shown associated mould sensitivity, with the development, persistence and severity of asthma and other respiratory allergic diseases. Recent studies suggest that host immune response to environmental moulds and genetic factors may play an important role in the development of allergic respiratory diseases. This new knowledge could help us to prevent and cure these diseases. There are also studies about the potential toxic reactions to the micotoxins. The prevention of developing moulds in indoor environment is still the most important for the well-being of all population.

Plesni v notranjem okolju in možni učinki na zdravje

Moulds are multicellular fungi that are ubiquitous in indoor and outdoor environment. Exposure to moulds can occur through inhalation, ingestion, and touching mouldy surfaces. Adverse health effects may occur through allergic, infectious, irritant, and toxic processes. In our review we elucidated some possible harmful mechanisms of moulds on the health of the population and some preventive recommendation. A systematic literature review was carried out in two bibliographic databases, Science Direct and PubMed, in the period from 1985 to February 2015. We systematically observed also the internet pages from CDC (Centers for Diseases Control and Prevention) and EPA (Environmental Protection Agency). Out of websites we accepted the roles for recommendation in case of moulds indoor buildings. Epidemiological studies all over the world have shown associated mould sensitivity, with the development, persistence and severity of asthma and other respiratory allergic diseases. Recent studies suggest that host immune response to environmental moulds and genetic factors may play an important role in the development of allergic respiratory diseases. This new knowledge could help us to prevent and cure these diseases. There are also studies about the potential toxic reactions to the micotoxins. The prevention of developing moulds in indoor environment is still the most important for the well-being of all population.

Advances in environmental and occupational disorders in 2008

Substantial progress in understanding the role of environmental factors in allergic disease and asthma has been made in the past year. A number of new allergens have been described, and the impact of exposure to indoor allergens in the development of allergic respiratory disease is further confirmed. Exposures to environmental pollutants, particularly tobacco smoke in children, have furthered our knowledge of the detrimental effects of these exposures. This review highlights key advances in environmental and occupational exposures that contribute to the burden of allergic respiratory disease.

Indoor allergens, environmental avoidance, and allergic respiratory disease

Indoor allergen exposure to sources such as house-dust mites, pets, fungi, and insects plays a significant role in patients with allergic rhinitis and asthma. The identification of the major allergens has led to methods that can quantitate exposure, e.g., immunoassays for Der p 1 in settled dust samples. Sensitization and the development of allergic respiratory disease result from complex genetic and environmental interactions. New paradigms that examine the role of other environmental factors, including exposure to proteases that can activate eosinophils and initiate Th2 responses, and epigenetics, are being explored. Recommendations for specific environmental allergen avoidance measures are discussed for house-dust mites, cockroaches, animal dander, and fungi. Specific measures to reduce indoor allergen exposure when vigorously applied may reduce the risk of sensitization and symptoms of allergic respiratory disease, although further research will be necessary to establish cost-effective approaches.

Relationship between cord blood level of IL-12 in preterm newborns and development of wheezing

Purpose :Abnormal activation patterns of Th1/Th2-cells have been suggested to increase the prevalence of allergic diseases. Prevention is regarded as an important corner stone in the management of allergic diseases. In this study, we have investigated the relationship between cord blood levels of IL-4, IL-10, and IL-12 in preterm newborns and the development of allergic respiratory diseases in infancy Methods :Forty-six preterm newborns born at the Ewha Womans University Mokdong Hospital between January 2003 and July 2005, were enrolled for this study, and consent was obtained to test their cord blood samples. Clinical history was obtained from the hospital records. Cord blood was obtained at birth and kept frozen until it was tested. The levels of IL-4, IL-10, and IL-12 were determined by enzyme-linked immunosorbent assay (ELISA). Results :All infants were followed-up for a median of 16.0 months±13.2 d (range, 12.0 to 36.0 months). Eighteen infants who developed wheezing showed lower cord blood levels of IL-12 (366.60±140.40 vs 435.09±91.20 pg/mL, P=0.009). Cord blood levels of IL-4 and IL-10 showed no significant difference between the two groups. Four newborns who later developed asthma, and infants with asthma showed lower IL-12 level in the cord blood than other groups. Conclusion :Lower concentration of cord blood levels of IL-12 in newborns who later developed wheezing and asthma suggested that they had abnormal activation patterns of Th1/Th2-cells at the time of birth, and cord blood IL-12 level can be used as a predictor of allergic respiratory diseases. (Korean J Pediatr 2008;51:754-759)

Probiotics in the atopic march: highlights and new insights

The frequent development of allergic respiratory diseases in patients with histories of atopic dermatitis (AD) in early childhood has been known for a long time. At school age, AD has been associated with an increased risk of asthma, and was thus regarded as one of the first steps in a successive “atopic march” leading from AD to asthma. Probiotics are cultures of potentially beneficial bacteria that positively affect the host by enhancing the microbial balance and therefore restore the normal intestinal permeability and gut microecology. They also improve the intestine's immunological barrier function and reduce the generation of proinflammatory cytokines characteristic of allergic inflammation. In clinical trials probiotics appear to be useful for the treatment of various clinical conditions such as food allergy, AD and allergic rhinitis, and in primary prevention of atopy. We can hypothesize that it may be possible, in the future, to use probiotics in primary prevention of asthma.

Initial High-Dose Nasal Allergen Exposure Prevents Allergic Sensitization to a Neoantigen

Primary allergic sensitization--IgE formation after Ag exposure--is fundamental in the development of allergic respiratory disease. With the rising prevalence of asthma and allergic rhinitis, improved understanding of the determining factors for allergic sensitization is needed. Human epidemiologic studies suggest high-dose allergen exposure may paradoxically protect against sensitization. Prospective human studies of allergen dose effect on primary allergic sensitization are lacking. We prospectively examined the effect of respiratory Ag dose exposure on the rate of primary allergic sensitization to a neoantigen, keyhole limpet hemocyanin, using a unique model of human nasal allergic sensitization. Atopic human subjects were exposed to 0.1-, 10-, 1,000-, or 100,000-mug doses of intranasal keyhole limpet hemocyanin in conjunction with adjuvant intranasal diesel exhaust particles. Ag-specific IgE, IgG, and IgG4 were measured in nasal lavage samples at the conclusion of the sensitization protocol. Allergic sensitization rates for the 0.1-, 10-, 1,000-, and 100,000-mug dose groups were 0, 100, 57, and 11%, respectively. All subjects produced Ag-specific IgG with the highest levels observed in the high-dose group. These results provide direct evidence that primary allergic sensitization may be prevented by initial high levels of respiratory Ag exposure through induction of a modified, nonallergic immune response. This Ag dose effect was capable of overcoming the well-established allergic adjuvant effects of diesel exhaust particle exposure. Whether this immune response represents durable allergic tolerance is not yet known. Studies investigating the molecular mechanisms of this non-IgE response may be useful in developing therapy to prevent allergic sensitization.

Initial high-dose nasal allergen exposure prevents allergic sensitization to a neoantigen

Primary allergic sensitization--IgE formation after Ag exposure--is fundamental in the development of allergic respiratory disease. With the rising prevalence of asthma and allergic rhinitis, improved understanding of the determining factors for allergic sensitization is needed. Human epidemiologic studies suggest high-dose allergen exposure may paradoxically protect against sensitization. Prospective human studies of allergen dose effect on primary allergic sensitization are lacking. We prospectively examined the effect of respiratory Ag dose exposure on the rate of primary allergic sensitization to a neoantigen, keyhole limpet hemocyanin, using a unique model of human nasal allergic sensitization. Atopic human subjects were exposed to 0.1-, 10-, 1,000-, or 100,000-mug doses of intranasal keyhole limpet hemocyanin in conjunction with adjuvant intranasal diesel exhaust particles. Ag-specific IgE, IgG, and IgG4 were measured in nasal lavage samples at the conclusion of the sensitization protocol. Allergic sensitization rates for the 0.1-, 10-, 1,000-, and 100,000-mug dose groups were 0, 100, 57, and 11%, respectively. All subjects produced Ag-specific IgG with the highest levels observed in the high-dose group. These results provide direct evidence that primary allergic sensitization may be prevented by initial high levels of respiratory Ag exposure through induction of a modified, nonallergic immune response. This Ag dose effect was capable of overcoming the well-established allergic adjuvant effects of diesel exhaust particle exposure. Whether this immune response represents durable allergic tolerance is not yet known. Studies investigating the molecular mechanisms of this non-IgE response may be useful in developing therapy to prevent allergic sensitization.