Aeroallergen Exposure Research Articles

Targeting the ICOS/ICOS‐L pathway in a mouse model of established allergic asthma disrupts T follicular helper cell responses and ameliorates disease

BackgroundAllergic asthma is characterized by chronic inflammation and remodelling of the airways, associated with dysregulated type 2 immune responses and allergen‐specific IgE. T follicular helper cells (TFH) are crucial in T‐dependent B‐cell responses and have been implicated in allergic airway disease (AAD). TFH, unlike other CD4+ T cells, are uniquely reliant on continuous ICOS signalling to maintain their phenotype after T‐cell priming; therefore, disrupting this signal can impair TFH responses. However, the contribution of TFH to disease during chronic aero‐allergen exposure and the therapeutic potential of targeting these cells have not been evaluated.MethodsTo establish AAD, female BALB/c mice were repeatedly exposed to house dust mite or Alternaria alternata three times a week for up to 5 weeks. To examine the impact of TFH on AAD, mice were allergen exposed for 5 weeks and co‐administered anti‐ICOS Ligand‐targeted antibodies, three times a week for the last 2 weeks.Results TFH were first observed in the lung‐draining lymph nodes and with further exposure were also found locally within the lungs. TFH accumulated with sustained allergen exposure, alongside germinal centre (GC) B cells. Blockade of ICOS signalling after AAD establishment successfully depleted TFH but did not affect the differentiation of other CD4+ T‐cell subsets. This reduced GC responses, allergen‐specific IgE, inflammation, pulmonary IL‐13 and airway hyper‐responsiveness.Conclusions TFH are crucial in the regulation of AAD and the ICOS/ICOS‐L pathway could represent a novel therapeutic target in allergic asthma.

CME Exam: Aeroallergen Exposure and Spread in the Modern Era

CME Exam: Aeroallergen Exposure and Spread in the Modern Era

ANAPHYLAXIS SECONDARY TO AN EMULSIFIER IN ALMOND YOGURT IN A CASHEW/PISTACHIO SENSITIZED PATIENT

Introduction Pectin is an emulsifier derived from fruits and has been recognized as an occupational aeroallergen exposure. It more recently has been implicated as a food allergen with cross-reactivity to cashew and pistachio. To our knowledge, all published cases of anaphylaxis following pectin ingestion have occurred in cashew or pistachio sensitized patients. Case Description A 6-year-old male with a known food allergy to peanut and avoidance of cashew/pistachio due to sensitization developed a rash and emesis immediately after ingestion of strawberry flavored almond yogurt and peaches. The patient was seen by an outside allergist who performed skin prick testing (SPT) to strawberry, almond, peach, and a sample of the yogurt. All SPT's were negative, apart from positive SPT to the yogurt itself. The patient was referred for a second opinion. Review of yogurt ingredients identified citrus pectin as a possible culprit. We performed SPT to the fruit and seed of lemon, orange, and grapefruit. SPT's to orange and lemon seeds demonstrated sensitization of 30mm/53mm (wheal/flare) and 24mm/35mm respectively with negative SPT's to the fruits and grapefruit seed, as suspected as the fruits without seeds were previously tolerated. Therefore, pectin was thought to be the likely trigger of the episode. Discussion To our knowledge, this is the fifth described anaphylactic reaction following ingestion of pectin derived from citrus fruit. All identified patients have had known sensitization to cashews or pistachios. Cross-reactivity should be explored in cases of unexplained anaphylaxis in patients with known food allergies. The clinical management of these patients remain a practical dilemma.

Mucosal bromodomain-containing protein 4 mediates aeroallergen-induced inflammation and remodeling

Frequent exacerbations of allergic asthma lead to airway remodeling and a decrease in pulmonary function, producing morbidity. Cat dander is an aeroallergen associated with asthma risk. We sought to elucidate the mechanism of cat dander-induced inflammation-remodeling. We identified remodeling in mucosal samples from allergic asthma by using quantitative RT-PCR. We developed a model of aeroallergen-induced experimental asthma using repetitive cat dander extract exposure. We measured airway inflammation using immunofluorescence, leukocyte recruitment, and quantitative RT-PCR. Airway remodeling was measured by using histology, collagen content, myofibroblast numbers, and selected reaction monitoring. Inducible nuclear factor κB (NF-κB)-BRD4 interaction was measured by using a proximity ligation assay in situ. Enhanced mesenchymal signatures are observed in bronchial biopsy specimens from patients with allergic asthma. Cat dander induces innate inflammation through NF-κB signaling, followed by production of a profibrogenic mesenchymal transition in primary human small airway epithelial cells. The IκB kinase-NF-κB signaling pathway is required for mucosal inflammation-coupled airway remodeling and myofibroblast expansion in the mouse model of aeroallergen exposure. Cat dander induces NF-κB/RelAto complex with and activate BRD4, resulting in modifying the chromatin environment of inflammatory and fibrogenic genes through its atypical histone acetyltransferase activity. Anovel small-molecule BRD4 inhibitor (ZL0454) disrupts BRD4 binding to the NF-κB-RNA polymerase II complex and inhibits its histone acetyltransferase activity. ZL0454 prevents epithelial mesenchymal transition, myofibroblast expansion, IgE sensitization, and fibrosis in airways of naive mice exposed to cat dander. NF-κB-inducible BRD4 activity mediates cat dander-induced inflammation and remodeling. Therapeutic modulation of the NF-κB-BRD4 pathway affects allergen-induced inflammation, epithelial cell-state changes, extracellular matrix production, and expansion of the subepithelial myofibroblast population.

C3a is required for ILC2 function in allergic airway inflammation.

Aberrant type 2 responses underlie the pathologies in allergic diseases like asthma, yet, our understanding of the mechanisms that drive them remains limited. Recent evidence suggests that dysregulated innate immune factors can perpetuate asthma pathogenesis. In susceptible individuals, allergen exposure triggers the activation of complement, a major arm of innate immunity, leading to the aberrant generation of the C3a anaphylatoxin. C3 and C3a have been shown to be important for the development of Th2 responses, yet remarkably, the mechanisms by which C3a regulates type 2 immunity are relatively unknown. We demonstrate a central role for C3a in driving ILC2-mediated inflammation in response to allergen and IL-33. Our data suggests that ILC2 recruitment is C3a-dependent. Further, we show that ILC2s directly respond to C3a, promoting type 2 responses by specifically: 1) inducing IL-13 and GM-CSF, while inhibiting IL-10 production from ILC2; and 2) enhancing their antigen-presenting capability during ILC-T cell crosstalk. In summary, we identify a novel mechanism by which C3a can mediate aberrant type 2 responses to aeroallergen exposure, which involves a yet unrecognized crosstalk between two major innate immune components – complement and group 2 innate lymphoid cells.

The Clinical Utility of Pollen Counts.

In this review, we describe how pollen counts are performed, the health effects caused by exposure to varying amounts of pollen, the clinical utility of reporting pollen counts to the public, and how that information can be used by patients who have allergies to improve their health. The public is very interested in pollen counts, particularly if the counts provide a forecast of expected pollen exposure for the next few days. Traditional pollen counts are labor-intensive; poorly distributed; and, since the counts are usually 1-day-old, do not provide forecasts that can be acted on. New methods that provide short- and long-term pollen forecasts can provide this information to allergic individuals so that they can respond to changing outdoor conditions. Studies of the relationship between artificial and natural exposure to pollen and development of symptoms have provided improved understanding into how much pollen it takes to cause symptoms. Thresholds for pollen counts that trigger symptoms vary by pollen type, sensitivity of the population, and interactions with other atmospheric exposures. Strategies to inform the public when the pollen count poses a health risk have been proposed along with computerized systems that provide personalized pollen alerts. The best performing public notification system was a "traffic light system" that reported pollen exposure as low, 0-30; intermediate, 31-50; or high, 51-150. This system outperformed other threshold systems used in Sweden and in Britain/Denmark. Continued improvements in pollen forecasting models combined with data provided by automated pollen counters and better public reporting should permit allergic individuals and urban planners to adapt effectively to changes in outdoor aeroallergen exposures.

The Role of the Environment in Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease with incompletely understood pathogenesis. Though disease manifestations were initially ascribed to a delayed reaction to food allergens, emerging evidence suggests that modifiable host factors and environmental allergen exposure may also play critical roles in the pathogenesis and ongoing manifestations of EoE. As with other atopic diseases, lack of early-life exposure to microbial pathogens leads to an immune tolerance defect and reprograms the commensal gut microflora toward a type 2 T helper (Th2) phenotype; the esophageal microbiota, a rich environment consisting of diverse bacterial species, is greatly altered by inflammation. Although multiple early life microbiome-altering factors are associated with EoE development, no causative, direct relationships have been identified. Interestingly, large, cross-sectional analyses of several populations identify an inverse relationship between Helicobacter pylori presence and EoE, likely via virulence factors that downregulate Th2 inflammation, though causality has not been proven. In regard to environmental allergens, some studies support seasonal variation in EoE diagnosis and flares, and EoE can be generated after a large, identifiable aeroallergen exposure. Examples include mouse models of intranasal Aspergillus dosing and following initiation of oral immunotherapy to foods or environmental allergens. Conversely, treatment of allergic rhinoconjunctivitis may improve EoE symptoms, though data is limited to case reports and small series. Unfortunately, biologic therapies for atopic conditions have failed to improve EoE symptoms despite improvement in esophageal eosinophil count, though dupilumab shows promise in ongoing studies. Overall, this chapter shows that EoE pathogenesis is likely multifactorial, and the environment is a key component in our understanding of EoE.

Cow's Milk and Immune Function in the Respiratory Tract: Potential Mechanisms.

During the last decades, the world has witnessed a dramatic increase in allergy prevalence. Epidemiological evidence shows that growing up on a farm is a protective factor, which is partly explained by the consumption of raw cow’s milk. Indeed, recent studies show inverse associations between raw cow’s milk consumption in early life and asthma, hay fever, and rhinitis. A similar association of raw cow’s milk consumption with respiratory tract infections is recently found. In line with these findings, controlled studies in infants with milk components such as lactoferrin, milk fat globule membrane, and colostrum IgG have shown to reduce respiratory infections. However, for ethical reasons, it is not possible to conduct controlled studies with raw cow’s milk in infants, so formal proof is lacking to date. Because viral respiratory tract infections and aeroallergen exposure in children may be causally linked to the development of asthma, it is of interest to investigate whether cow’s milk components can modulate human immune function in the respiratory tract and via which mechanisms. Inhaled allergens and viruses trigger local immune responses in the upper airways in both nasal and oral lymphoid tissue. The components present in raw cow’s milk are able to promote a local microenvironment in which mucosal immune responses are modified and the epithelial barrier is enforced. In addition, such responses may also be triggered in the gut after exposure to allergens and viruses in the nasal cavity that become available in the GI tract after swallowing. However, these immune cells that come into contact with cow’s milk components in the gut must recirculate into the blood and home to the (upper and lower) respiratory tract to regulate immune responses locally. Expression of the tissue homing-associated markers α4β7 and CCR9 or CCR10 on lymphocytes can be influenced by vitamin A and vitamin D3, respectively. Since both vitamins are present in milk, we speculate that raw milk may influence homing of lymphocytes to the upper respiratory tract. This review focuses on potential mechanisms via which cow’s milk or its components can influence immune function in the intestine and the upper respiratory tract. Unraveling these complex mechanisms may contribute to the development of novel dietary approaches in allergy and asthma prevention.

Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics

Atopic asthma is a persistent disease characterized by intermittent wheeze and progressive loss of lung function. The disease is thought to be driven primarily by chronic aeroallergen-induced type 2-associated inflammation. However, the vast majority of atopics do not develop asthma despite ongoing aeroallergen exposure, suggesting additional mechanisms operate in conjunction with type 2 immunity to drive asthma pathogenesis. We employed RNA-Seq profiling of sputum-derived cells to identify gene networks operative at baseline in house dust mite-sensitized (HDMS) subjects with/without wheezing history that are characteristic of the ongoing asthmatic state. The expression of type 2 effectors (IL-5, IL-13) was equivalent in both cohorts of subjects. However, in HDMS-wheezers they were associated with upregulation of two coexpression modules comprising multiple type 2- and epithelial-associated genes. The first module was interlinked by the hubs EGFR, ERBB2, CDH1 and IL-13. The second module was associated with CDHR3 and mucociliary clearance genes. Our findings provide new insight into the molecular mechanisms operative at baseline in the airway mucosa in atopic asthmatics undergoing natural aeroallergen exposure, and suggest that susceptibility to asthma amongst these subjects involves complex interactions between type 2- and epithelial-associated gene networks, which are not operative in equivalently sensitized/exposed atopic non-asthmatics.

Effect of season of birth on cord blood IgE and IgE at birth: A systematic review and meta-analysis

BackgroundElevated cord blood IgE is important on the pathway to allergic disease. The association between season of birth and infant cord blood IgE is not well-established. Study findings differ on which birth season is associated with higher cord blood IgE risk and its magnitude. We conducted a systematic review and meta-analysis of studies on season of birth and cord blood IgE. MethodsWe searched Medline, Web of Science, Scopus and ProQuest Health databases, and reviewed reference lists of articles that met the inclusion criteria. All included studies measured IgE as a binary variable using various cut-off values. We performed multivariate-random-effects meta-analysis to handle an exposure with multiple categories of Season of Birth. ResultsOur search identified 275 records and 10 had sufficient data to be included in a meta-analysis. Relative to summer, winter birth had the greatest odds of high IgE (≥ 0.1IU/ml), meta-analysis OR = 1.24 (95%CI: 1.01–1.52). A similar OR, was found for IgE ≥ 0.5 IU/ml, OR = 1.30 (95%CI: 0.99–1.71). ConclusionsA winter season of birth was associated with statistically significant higher odds of elevated cord blood IgE at cut-off ≥ 0.1IU/ml but borderline at cut-off ≥ 0.5IU/ml. This winter effect is likely to be a marker for a range of other environmental exposures during specific stages of pregnancy, such as aeroallergen exposures, maternal infections and vitamin D levels. Further research is required to support our finding and to identify the exact mechanisms that lead to the winter season of birth effect on circulating IgE levels, as this may have implications for allergic disease prevention.

Environmental Tobacco Smoke (ETS) and Climate Change Influencing the Incidence of Allergic Diseases such as Asthma: in vivo Studies using Murine Model Exposed to Cigarette Smoke

Today the air we breathe in is loaded with aeroallergens (such as pollen, fungal spores etc.) and different air pollutants including cigarette smoke, carbon dioxide, nitrogen oxide, sulphur dioxide, ozone etc. which are all above the standards prescribed by the government and are extremely harmful for human health. Increased aeroallergen exposures as a result of global warming in combination with pollutants exposure can act synergistically to enhance allergic diseases. Climate change also influences the concentration of airborne pollutants which alone and in conjugation with aeroallergens could exacerbate symptoms of allergic diseases. Smoking pollutes the air and is a widely acknowledged danger to human health. Experimental evidence suggests that complex organic molecules from cigarette smoke may act as allergic adjuvants through the production of oxidative stress in airway cells. Exposure to environmental tobacco smoke (also known as passive smoking or second-hand smoke) is an important factor in indoor exposures leading to allergic and asthmatic effects. In our study, we illustrate how ETS, outdoor air pollutants and climate change may act as environmental risk factors for development of asthma. We chose ETS as indoor pollutant in our lab using murine model because atleast some degrees of exposure to ETS is very common worldwide. Mice were exposed to the side stream smoke generated by burning cigarettes in specially designed smoking chamber and lab animal ultrastructural/histopathological studies have demonstrated that mice exposed to cigarette smoke could induce inflammation in the airways. However, more studies are needed to understand the association between environmental factors and development of asthma.

Airway Epithelial KIF3A Regulates Th2 Responses to Aeroallergens.

KIF3A, the gene encoding kinesin family member 3A, is a susceptibility gene locus associated with asthma; however, mechanisms by which KIF3A might influence the pathogenesis of the disorder are unknown. In this study, we deleted the mouse Kif3a gene in airway epithelial cells. Both homozygous and heterozygous Kif3a gene-deleted mice were highly susceptible to aeroallergens from Aspergillus fumigatus and the house dust mite, resulting in an asthma-like pathology characterized by increased goblet cell metaplasia, airway hyperresponsiveness, and Th2-mediated inflammation. Deletion of the Kif3a gene increased the severity of pulmonary eosinophilic inflammation and expression of cytokines (Il-4, Il-13, and Il-17a) and chemokine (Ccl11) RNAs following pulmonary exposure to Aspergillus extract. Inhibition of Kif3a disrupted the structure of motile cilia and impaired mucociliary clearance, barrier function, and epithelial repair, demonstrating additional mechanisms by which deficiency of KIF3A in respiratory epithelial cells contributes to pulmonary pathology. Airway epithelial KIF3A suppresses Th2 pulmonary inflammation and airway hyperresponsiveness following aeroallergen exposure, implicating epithelial microtubular functions in the pathogenesis of Th2-mediated lung pathology.

Association Between Allergen Exposure in Inner-City Schools and Asthma Morbidity Among Students

ImportanceHome aeroallergen exposure is associated with increased asthma morbidity in children, yet little is known about the contribution of school aeroallergen exposures to such morbidity.ObjectiveTo evaluate the effect of school-specific aeroallergen exposures on asthma morbidity among students, adjusting for home exposures.Design, Setting, and ParticipantsThe School Inner-City Asthma Study was a prospective cohort study evaluating 284 students aged 4 to 13 years with asthma who were enrolled from 37 inner-city elementary schools in the northeastern United States between March 1, 2008, and August 31, 2013. Enrolled students underwent baseline clinical evaluations before the school year started and were then observed clinically for 1 year. During that same school year, classroom and home dust samples linked to the students were collected and analyzed for common indoor aeroallergens. Associations between school aeroallergen exposure and asthma outcomes during the school year were assessed, adjusting for home exposures.ExposuresIndoor aeroallergens, including rat, mouse, cockroach, cat, dog, and dust mites, measured in dust samples collected from inner-city schools.Main Outcomes and MeasuresThe primary outcome was maximum days in the past 2 weeks with asthma symptoms. Secondary outcomes included well-established markers of asthma morbidity, including asthma-associated health care use and lung function, measured by forced expiratory volume in 1 second.ResultsAmong 284 students (median age, 8 years [interquartile range, 6-9 years]; 148 boys and 136 girls), exposure to mouse allergen was detected in 441 (99.5%) of 443 school dust samples, cat allergen in 420 samples (94.8%), and dog allergen in 366 samples (82.6%). Levels of mouse allergen in schools were significantly higher than in students’ homes (median settled dust level, 0.90 vs 0.14 µg/g; P < .001). Exposure to higher levels of mouse allergen in school (comparing 75th with 25th percentile) was associated with increased odds of having an asthma symptom day (odds ratio, 1.27; 95% CI, 1.05-1.54; P = .02) and 4.0 percentage points lower predicted forced expiratory volume in 1 second (95% CI, –6.6 to –1.5; P = .002). This effect was independent of allergic sensitization. None of the other indoor aeroallergens were associated with worsening asthma outcomes.Conclusions and RelevanceIn this study of inner-city students with asthma, exposure to mouse allergen in schools was associated with increased asthma symptoms and decreased lung function. These findings demonstrate that the school environment is an important contributor to childhood asthma morbidity. Future school-based environmental interventions may be beneficial for this important public health problem.

PARP inhibition treatment in a nonconventional experimental mouse model of chronic asthma.

Allergic asthma is an immunological disease that occurs as a consequence of aeroallergen exposure. Inhibition of poly(ADP-ribose) polymerases (PARPs) in conventional models of asthma-like reaction has emerged as an effective anti-inflammatory and airway remodeling intervention. In a house dust mite (HDM) exposure mouse model, we investigated the impact of PARP inhibition on allergic airway inflammation, sensitization, and remodeling. Mice were intranasally exposed to a HDM extract for 5days per week for up to 5weeks. Mice were administered, or not, by PARP inhibitors 3-aminobenzamide (3-ABA) or 5-aminoisoquinolinone (5-AIQ) during the last 2weeks of HDM treatment. Mice treated with PARP inhibitors after HDM stimulation showed a significant decrease in the number of total cells and eosinophils detectable in the bronchoalveolar lavage fluid as compared with the HDM-stimulated ones. In vitro HDM-stimulated splenocyte culture produced considerable amounts of the Th2 cytokines that were not affected by treatment with PARP inhibitors. Immunoglobulin levels in the serum were also unchanged. In the lung tissue, collagen deposition was decreased, whereas α-smooth muscle actin thickening was not significantly affected. Moreover, in HDM-stimulated PARP inhibitor-treated groups, we found a downregulation in the activation of signal transducer and activator of trascription-6 (STAT-6) and a significant decrease in the mRNA levels of C-C motif chemokine 11 (CCL11). In this mouse model of chronic asthma PARP inhibition treatment, although it does not affect sensitization, it effectively reduces the allergic airway inflammation and affects the remodeling through a mechanism involving STAT6 and CCL11.

Direct aeroallergen exposure disrupts the oxidant and antioxidant balance in human bronchial epithelial cells

Abstract Exposure to aeroallergens is a major risk factor for asthma development. Allergen possessing proteolytic activity is capable of disrupting airway epithelium. Increasing evidence pointing to asthma as an epithelial disease, however, the underlying mechanisms that drive asthma are not fully elucidated. Here, we investigated the DNA damage potential of aeroallergens on human bronchial epithelial cells BEAS-2B, and elucidated the damaging mechanisms. We exposed BEAS-2B cells to house dust mite (HDM), and measured DNA damage by CometChip and DNA double strand breaks (DSBs) by γH2AX staining. Intracellular oxidative stress was evaluated by staining cells with CellROS and MitoTracker. Antioxidant genes expression were determined using RT-PCR. Cell viability was determined by XTT assay. Cell death was studied using flow cytometry. To elucidate the underlying mechanism, cells were treated with Toll-like receptor 4 (TLR4) agonist or antagonist, or antioxidants glutathione or catalase. BEAS-2B cells exposed to HDM showed enhanced DNA damage, elevated ROS production, and increased mitochondrial oxidative stress and nitrite level. Expression of Nrf2-dependent antioxidant genes was reduced by HDM exposure. HDM also reduced cell viability and induced cell death. Importantly, HDM-induced DNA damage could be prevented by antioxidants. Our results suggest that direct HDM exposure to bronchial epithelial cells leads to production of RONS that damage DNA and induce cytotoxicity. Antioxidants can prevent HDM-induced DNA damage, revealing a novel role for antioxidants in preventing genotoxicity. [This study was partially supported by NMRC/CBRG/0027/2012, NUHS Seed Grant R-184-000-238-112, NRF, NIEHS R44-ES0211116 and Trevigen Inc.]

Recent advances in environmental controls outside the home setting.

It has been well studied that aeroallergen, mold, and airborne pollutant exposure in the inner-city home environment is associated with significant childhood asthma morbidity. Although the home environment has been extensively studied, the school environment is less well understood. In this article, we discuss the relationship between environmental exposures within the school and daycare environment and pediatric asthma morbidity and novel environmental interventions designed to help mitigate pediatric asthma morbidity. Studies assessing environmental exposures outside the home environment and interventions to mitigate these exposures have the potential to reduce pediatric asthma morbidity. Further study in this area should focus on the complex cost benefit analyses of environmental interventions outside the home setting, while controlling for the home environment.

Early indoor aeroallergen exposure is not associated with development of sensitization or allergic rhinitis in high-risk children.

Allergen exposure is associated with the development of allergic sensitization in childhood as reflected by global variations in sensitization patterns. However, there is little evidence to support a direct association. To investigate the association between perinatal aeroallergen exposure and sensitization and rhinitis to such allergens later in childhood. Allergic sensitization to cat, dog, and house dust mites was diagnosed longitudinally using skin prick tests and specific IgE measurements at ½, 1½, 4, 6, and 13 years in 399 children from the Copenhagen Prospective Study on Asthma in Childhood2000 birth cohort. Rhinitis was diagnosed at 7 and 13 years. Allergen exposure was defined as dog or cat in the home during the 3rd trimester of pregnancy or the first year of life and as allergen levels of dog, cat, and house dust mite in bed dust samples at 1 year. Associations between exposure and outcomes were analyzed by logistic regression and stratified for eczema status and test method (skin prick test and specific IgE). We found no association between dog or cat exposure in perinatal life and sensitization or rhinitis during childhood. Similarly, there was no association between levels of allergens in bed dust samples and sensitization or rhinitis during childhood. Perinatal indoor aeroallergen exposure does not seem to affect development of allergic sensitization or rhinitis during childhood questioning the relevance of allergen avoidance as a preventive measure. Other factors such as timing of allergen exposure or other environmental adjuvants may contribute in a more complex pathway to sensitization.

Allergen-Specific CD4+T Cells in Human Asthma

In allergic asthma, aeroallergen exposure of sensitized individuals mobilizes robust innate and adaptive airway immune responses, stimulating eosinophilic airway inflammation and the activation and infiltration of allergen-specific CD4(+) T cells into the airways. Allergen-specific CD4(+) T cells are thought to be central players in the asthmatic response as they specifically recognize the allergen and initiate and orchestrate the asthmatic inflammatory response. In this article, we briefly review the role of allergen-specific CD4(+) T cells in the pathogenesis of human allergic airway inflammation in allergic individuals, discuss the use of allergen-major histocompatibility complex class II tetramers to characterize allergen-specific CD4(+) T cells, and highlight current gaps in knowledge and directions for future research pertaining to the role of allergen-specific CD4(+) T cells in human asthma.

Aeroallergen sensitization and allergic disease phenotypes in Asia.

Allergic diseases are on the rise in Asia. Aeroallergen exposure is a strong risk factor for sensitization, development and severity of atopic diseases, especially in the Asian paediatric population. Geographical and seasonal variations in aeroallergen sensitization are seen even within Asian countries and changes in aeroallergen sensitization patterns have been observed over time. Some possible reasons include climate change as well as rapid urbanization and improved sanitation which follow socioeconomic development. House dust mite allergy is present in up to 90% of Asian atopic patients, far exceeding that which is seen in Western populations which report prevalences of only 50% to 70%. Pollen and animal dander affect less than 10% of Asian patients as compared to 40-70% of individuals with asthma and allergic rhinitis living in the West, a burden almost equivalent to the dust mite burden in those regions. There is thus a pressing need for preventive measures to reduce dust mite sensitization in Asian children today.

Seasonal recurrence of food bolus obstruction in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a newly recognised condition that is apparently increasing in prevalence, and the aetiology is poorly understood. The role of aeroallergens in EoE is controversial, given the success of dietary therapy. Massive aeroallergen exposure leading to food bolus obstruction events (FBOE) has been described, and the diagnosis of EoE by esophageal biopsy noted to be more common in the pollen season according to previous case series. To determine if a seasonal variation and a geographical variation occurred in EoE presenting as FBOE in adults, and to track the prevalence of FBOE and EoE over time. A retrospective case-control study analysis was performed from January 2002 to January 2012 to identify all FBOE in adults presenting to five tertiary hospitals in Melbourne, Australia. Endoscopy, histopathological reports, case notes and blood tests were examined, and postcodes recorded. Records of pollen counts were obtained. Cases were defined according to esophageal biopsy and grouped based on month of diagnosis. All other causes of FBOE served as controls. One thousand, one hundred and thirty-two FBOE were identified. Biopsies were only performed in 278 of these cases, and 85 patients were found to have EoE after biopsy. Patients with EoE were younger (mean age 38 years, range 18-72) compared with those with alternative diagnosis (mean age 64.4 range 22-92), more likely to be male (M : F = 4:1 compared with 1.68:1 ) and had a higher eosinophil count in venous blood. Overall no seasonality was demonstrated in FBOE secondary to any diagnosis, although the six cases of recurrent FBOE secondary to EoE mainly occurred in the grass pollen season in subsequent years. FBOE cases were evenly distributed throughout metropolitan Melbourne irrespective of population density. EoE as a percentage of FBOE increased over time. Seasonal aeroallergens may be important for a subgroup of patients with EoE presenting as recurrent FBOE. Esophageal biopsies are performed in a minority of patients, representing a significant departure from ideal management and contributing to recurrent unnecessary FBOE. EoE is an increasingly important cause of FBOE.