Aeroallergen Exposure Research Articles

Targeting the P2Y13 Receptor Suppresses IL-33 and HMGB1 Release and Ameliorates Experimental Asthma.

Rationale: The alarmins IL-33 and HMGB1 (high mobility group box 1) contribute to type 2 inflammation and asthma pathogenesis. Objectives: To determine whether P2Y13-R (P2Y13 receptor), a purinergic GPCR (G protein-coupled receptor) and risk allele for asthma, regulates the release of IL-33 and HMGB1. Methods: Bronchial biopsy specimens were obtained from healthy subjects and subjects with asthma. Primary human airway epithelial cells (AECs), primary mouse AECs, or C57Bl/6 mice were inoculated with various aeroallergens or respiratory viruses, and the nuclear-to-cytoplasmic translocation and release of alarmins was measured by using immunohistochemistry and an ELISA. The role of P2Y13-R in AEC function and in the onset, progression, and exacerbation of experimental asthma was assessed by using pharmacological antagonists and mice with P2Y13-R gene deletion. Measurements and Main Results: Aeroallergen exposure induced the extracellular release of ADP and ATP, nucleotides that activate P2Y13-R. ATP, ADP, and aeroallergen (house dust mite, cockroach, or Alternaria antigen) or virus exposure induced the nuclear-to-cytoplasmic translocation and subsequent release of IL-33 and HMGB1, and this response was ablated by genetic deletion or pharmacological antagonism of P2Y13. In mice, prophylactic or therapeutic P2Y13-R blockade attenuated asthma onset and, critically, ablated the severity of a rhinovirus-associated exacerbation in a high-fidelity experimental model of chronic asthma. Moreover, P2Y13-R antagonism derepressed antiviral immunity, increasing IFN-λ production and decreasing viral copies in the lung. Conclusions: We identify P2Y13-R as a novel gatekeeper of the nuclear alarmins IL-33 and HMGB1 and demonstrate that the targeting of this GPCR via genetic deletion or treatment with a small-molecule antagonist protects against the onset and exacerbations of experimental asthma.

Role of Secretoglobin+ (club cell) NF\u03baB/RelA-TGF\u03b2 signaling in aero-allergen-induced epithelial plasticity and subepithelial myofibroblast transdifferentiation

Repetitive aeroallergen exposure is linked to sensitization and airway remodeling through incompletely understood mechanisms. In this study, we examine the dynamic mucosal response to cat dander extract (CDE), a ubiquitous aero-allergen linked to remodeling, sensitization and asthma. We find that daily exposure of CDE in naïve C57BL/6 mice activates innate neutrophilic inflammation followed by transition to a lymphocytic response associated with waves of mucosal transforming growth factor (TGF) isoform expression. In parallel, enhanced bronchiolar Smad3 expression and accumulation of phospho-SMAD3 was observed, indicating paracrine activation of canonical TGFβR signaling. CDE exposure similarly triggered epithelial cell plasticity, associated with expression of mesenchymal regulatory factors (Snai1 and Zeb1), reduction of epithelial markers (Cdh1) and activation of the NFκB/RelA transcriptional activator. To determine whether NFκB functionally mediates CDE-induced growth factor response, mice were stimulated with CDE in the absence or presence of a selective IKK inhibitor. IKK inhibition substantially reduced the level of CDE-induced TGFβ1 expression, pSMAD3 accumulation, Snai1 and Zeb1 expression. Activation of epithelial plasticity was demonstrated by flow cytometry in whole lung homogenates, where CDE induces accumulation of SMA+Epcam+ population. Club cells are important sources of cytokine and growth factor production. To determine whether Club cell innate signaling through NFκB/RelA mediated CDE induced TGFβ signaling, we depleted RelA in Secretoglobin (Scgb1a1)-expressing bronchiolar cells. Immunofluorescence-optical clearing light sheet microscopy showed a punctate distribution of Scgb1a1 progenitors throughout the small airway. We found that RelA depletion in Secretoglobin+ cells results in inhibition of the mucosal TGFβ response, blockade of EMT and reduced subepithelial myofibroblast expansion. We conclude that the Secretoglobin—derived bronchiolar cell is central to coordinating the innate response required for mucosal TGFβ1 response, EMT and myofibroblast expansion. These data have important mechanistic implications for how aero-allergens trigger mucosal injury response and remodeling in the small airway.

Central compartment sinus disease: A local sinonasal inflammatory response to environmental allergens

Central compartment atopic disease is a recently defined endotype of chronic rhinosinusitis (CRS) with nasal polyps associated with allergic sensitization.1 Aeroallergen exposure in the nasal compartment of sensitized individuals may lead to immunoglobulin (Ig)E-mediated inflammation and middle turbinate edema, a specific endoscopic sign of aeroallergen sensitization.2,3 This disease variant links mucosal changes isolated to the central compartment of the paranasal sinuses with the presence of environmental allergies.

Multi-decade changes in pollen season onset, duration, and intensity: a concern for public health?

BACKGROUND AND AIM: Climate change alters pollen seasons, a public health concern for the growing number of individuals with pollen sensitization. Prior aerobiological research has inconsistently applied definitions of the main pollen season (MPS) and drawn heterogeneous conclusions regarding the magnitude, directionality, and significance of long-term pollen trends. We aimed to better understand long-term shifts in MPS onset, duration and intensity through multi-definition analysis. METHODS: We examined national pollen data in Switzerland between 1990 and 2020, applying six MPS definitions (two retrospective percentage-based, four prospective threshold-based) to twelve relevant allergenic plant species. We analyzed long-term pollen season changes using both linear regression and locally estimated scatterplot smoothing (LOESS). RESULTS:For four of twelve plants, there is unanimity between the six definitions regarding earlier onset of the pollen season (p0.05), with magnitude of 31-year change, dependent on specific MPS definition (hazel: 9-18 days; oak: 5-13 days; grasses: 8-25 days; and nettle/hemp: 6-25 days). There is also consensus for altered MPS duration among hazel (21-104% longer), nettle/hemp (8-52% longer), and ash (18-38% shorter). Between-definition agreement is highest for MPS intensity analysis, showing significant increases in seasonal pollen quantity among hazel, birch, oak, beech, and nettle/hemp. The largest relative intensification is noted for hazel (110-146%) and beech (162-237%). LOESS analysis indicates that these multi-decade pollen changes are typically nonlinear. CONCLUSIONS:Pollen season onset, duration, and intensity have changed for multiple allergenic plants in Switzerland. We found an increase in seasonal pollen quantity emitted for five of twelve species, thus increasing the exposure burden on the allergic population. We identify systematic between-definition differences affecting magnitude and significance of long-term trends, and suggest future studies addressing aeroallergen exposure apply multiple MPS definitions to minimize bias. Further research can determine whether these pollen season shifts correlate with longitudinal differences in population pollen sensitization. KEYWORDS: Climate, Exposure assessment, Environmental epidemiology, Allergies

Evidence for recent climate change and carbon dioxide influence on plant based aero-allergens in the Northern Hemisphere

BACKGROUND AND AIM: Recent and projected assessments of climate change and carbon dioxide may influence plant based aero-allergen characteristics related to pollen load and pollen seasonality METHODS: Characterization and quantification of allergenic plant species related to growth, phenology and allergenicity in the context of rising temperatures and increased carbon dioxide. Methodologies include chamber and open-air assessments of pollen collection, ELISA and historical records. RESULTS:Integration of historical and experimental results from controlled chambers to open-air facilities indicate recent (since the 1970s) and projected changes (to 2100) in climate and CO2, are increasing allergen seasonality and pollen amounts. In addition there is evidence indicating that carbon dioxide per se may increase exine allergen concentration. CONCLUSIONS:These data overall, show a net influence of recent and projected increases in carbon dioxide and global surface temperatures on temporal aspects of aero-allergen exposure, including pollen load, and potential changes in allergenicity. Such changes have significant health consequences for those in the general population who suffer from seasonal allergic rhinitis and asthma. KEYWORDS: aeroallergens, climate change, carbon dioxide, pollen

Climate, Carbon Dioxide, and Plant-Based Aero-Allergens: A Deeper Botanical Perspective.

There is global evidence of a general increase in the incidence and prevalence of respiratory diseases including allergic rhinitis and associated asthma. This increase in turn, has been related, in part, to concurrent increases in carbon dioxide (CO2) and temperature on pollen production and allergic disease generated from plant-based sources of pollen. Such links to anthropogenic climate change has suggested three significant and interrelated consequences associated with respiratory allergies or disease. First, warmer temperatures and a longer frost-free growing season can influence pollen season length and temporal exposure to airborne aeroallergens. Second, both warmer temperatures and additional CO2 can increase the amount of pollen, the seasonal intensity, from spring through fall. Thirdly, there is evidence from oak and ragweed that rising levels of CO2 could increase the allergen concentration of the pollen and symptom severity. However, while these outcomes are of obvious consequence, they do not fully encompass all of the plant derived changes that could, directly or indirectly, influence aeroallergen production, exposure, and consequences for public health. In this overview, I will delve deeper into other plant-based links to climate/CO2 that are consequential either directly or indirectly to allergic rhinitis and associated disease. Such interactions range from pollen morphology to fire occurrence, from volatile organic compounds to potential changes in pesticide usage. The goal in doing so is to provide a broader context and appreciation for the interactions between plant biology and climate that can also affect allergen production and human impact but which, to date, have received little recognition or research.

Associations between the spatiotemporal distribution of Kawasaki disease and environmental factors: evidence supporting a multifactorial etiologic model

The etiology of Kawasaki Disease (KD), the most common cause of acquired heart disease in children in developed countries, remains elusive, but could be multifactorial in nature as suggested by the numerous environmental and infectious exposures that have previously been linked to its epidemiology. There is still a lack of a comprehensive model describing these complex associations. We present a Bayesian disease model that provides insight in the spatiotemporal distribution of KD in Canada from 2004 to 2017. The disease model including environmental factors had improved Watanabe-Akaike information criterion (WAIC) compared to the base model which included only spatiotemporal and demographic effects and had excellent performance in recapitulating the spatiotemporal distribution of KD in Canada (98% and 86% spatial and temporal correlations, respectively). The model suggests an association between the distribution of KD and population composition, weather-related factors, aeroallergen exposure, pollution, atmospheric concentration of spores and algae, and the incidence of healthcare encounters for bacterial pneumonia or viral intestinal infections. This model could be the basis of a hypothetical data-driven framework for the spatiotemporal distribution of KD. It also generates novel hypotheses about the etiology of KD, and provides a basis for the future development of a predictive and surveillance model.

The association between outdoor allergens – pollen, fungal spore season and high asthma admission days in children and adolescents

ABSTRACT Periods when asthma admissions peaks have serious implications for asthma sufferers and hospitals. We assessed the association between aeroallergen exposure and childhood asthma peak periods during two grass pollen seasons using the Melbourne Air Pollen Children and Adolescent Health (MAPCAH) study conducted in Melbourne, Australia. Two peak periods were identified. Effect modifications by atopy and sex were considered. All pollen 2 days prior was associated with increased odds of these peak periods. Same day fungal spores, but not pollen, were important. Grass at lag 2 was associated with increased odds 1.03 (95%CI 1.01, 1.05) as was the same day Alternaria 1.02 (1.00, 1.04) per spore/m3 for boys. In addition to pollen, fungal spores particularly Alternaria may result in days of high exacerbations during pollen seasons. Further guidance is needed to better prepare families/carers with information about the increased risk of asthma attacks in children prior to pollen seasons.

Pediatric asthma exacerbations during the COVID-19 pandemic: Absence of the typical fall seasonal spike in Washington, DC

Pediatric asthma exacerbations during the COVID-19 pandemic: Absence of the typical fall seasonal spike in Washington, DC

Persistan Atopik Dermatit'li İnfantlarda Beklenmeyen Kedi Alerjisi

Atopic dermatitis is a chronic, recurrent inflammatory skin disease usually caused by genetic predisposition, immune dysregulation, epidermal barrier dysfunction and interaction of environmental factors. Atopic dermatitis is part of atopic march and is often accompanied by food allergy. Aeroallergenic sensitization at early age is not an expected finding. Here, we present five cases with moderate-severe atopic dermatitis during infancy, in whom food allergy was detected and the symptoms improved only partially despite elimination and treatment. Sensitization was investigated in patients with a history of intense exposure to cats by specific IgE and skin prick test in infants with atopic dermatitis who had food allergy and persistant findings. Egg allergy was detected in four of the cases, wheat allergy in one. Cat allergy was present in all. Elimination diet was started in all cases. When exposure to cats was reduced, a marked improvement in the findings of atopic dermatitis was observed in all cases. Allergic diseases are increasing day by day. Unexpected aeroallergenic sensitization is now more common in the early stages of life. Allergic patients, regardless of age, should be questioned in detail for aeroallergen exposure. If it is detected; necessary preventive measures should be taken.

Describing fluctuating indoor aerosol dust measurements with application to house dust mite allergens

Measuring house dust mite aeroallergen concentrations is essential in understanding mite allergen exposure. Physically, the aerolized house dust mite faeces are part of indoor particulate matter. We studied the statistical ways of summarizing measurements of fluctuating mite aeroallergen exposure inside homes through indoor particulate matter. To study emissions from beddings, we measured the time-related airborne dust concentration after shaking a duvet. Analysis was performed both by a method based on the estimated mean and by a non-linear model. Twenty-eight studies reported a sum of concentrations; only one also reported the peak. In our four experiments on shaking a duvet (245 to 275 measurements each), the peak value was two to four times higher than the mean. The mean-based and non-linear models both predicted the sum of concentrations exactly. A 1% upper prediction bound and the non-linear model predicted the peak emission rate moderately well (64 to 92%, and 63 to 93%, respectively). Mean levels of indoor particulate matter measurements differ substantially from peak concentrations. The use of the mean is only sufficient to predict the sum of concentrations. We suggest that, mite aeroallergen measurements should include information on the peak as well as the mean.

The Indoor Environment and Childhood Asthma.

Sensitization and exposure to triggers in the indoor environment, including aeroallergens, indoor air pollution, and environmental tobacco smoke, have a significant role in asthma development and morbidity. This review discusses indoor environmental exposures and their effect on children with asthma as well as environmental interventions and their role in improving asthma morbidity. Recent research has emphasized the role of aeroallergen sensitization and exposure in asthma morbidity and the importance of the school indoor environment. There is an established association between indoor exposures and asthma development and morbidity. Recent evidence has highlighted the importance of the indoor environment in childhood asthma, particularly the role of the school indoor environment. While home environmental interventions have had mixed results, interventions in the school environment have the potential to significantly impact the health of children, and ongoing research is needed to determine their effectiveness.

Neonatal endotoxin stimulation is associated with a long-term bronchiolar epithelialexpression of innate immune and anti-allergic markers that attenuates the allergic response.

Allergic asthma is the most common phenotype of the pathology, having an early-onset in childhood and producing a Th2-driven airways remodeling process that leads to symptoms and pathophysiological changes. The avoidance of aeroallergen exposure in early life has been shown to prevent asthma, but without repeated success and with the underlying preventive mechanisms at the beginning of asthma far to be fully recognized. In the present study, we aimed to evaluate if neonatal LPS-induced boost in epithelial host defenses contribute to prevent OVA-induced asthma in adult mice. To this, we focused on the response of bronchiolar club cells (CC), which are highly specialized in maintaining the epithelial homeostasis in the lung. In these cells, neonatal LPS administration increased the expression of TLR4 and TNFα, as well as the immunodulatory/antiallergic proteins: club cell secretory protein (CCSP) and surfactant protein D (SP-D). LPS also prevented mucous metaplasia of club cells and reduced the epidermal growth factor receptor (EGFR)-dependent mucin overproduction, with mice displaying normal breathing patterns after OVA challenge. Furthermore, the overexpression of the epithelial Th2-related molecule TSLP was blunted, and normal TSLP and IL-4 levels were found in the bronchoalveolar lavage. A lower eosinophilia was detected in LPS-pretreated mice, along with an increase in phagocytes and regulatory cells (CD4+CD25+FOXP3+ and CD4+IL-10+), together with higher levels of IL-12 and TNFα. In conclusion, our study demonstrates stable asthma-preventive epithelial effects promoted by neonatal LPS stimulation, leading to the presence of regulatory cells in the lung. These anti-allergic dynamic mechanisms would be overlaid in the epithelium, favored by an adequate epidemiological environment, during the development of asthma.

An Overview of Rising CO₂ and Climatic Change on Aeroallergens and Allergic Diseases.

There are a number of implications of climate change in regard to human health. Among these, the role of rising carbon dioxide (CO2) and temperature in aeroallergen exposure and associated changes in the start, duration and intensity of the pollen season, and associated consequences in aeroallergens and allergic disease are a primary concern. This review is intended to provide a synopsis of CO2 and climate factors associated with likely changes in aeroallergen biology (indoor and outdoor), including changes in the demography of flowering plants, pollen seasonality, aeroallergen production, and potential biotic and abiotic interactions. These factors, in turn, are compared to clinical trials that have linked aeroallergens to allergic disease and associated health impacts. Finally, suggestions to address unmet needs and critical knowledge gaps are offered. Such recommendations are not meant to be inclusive, but to serve as a spur for the additional research and resources that will be necessary to acquire a better understanding of climate change, CO2, aeroallergens and associated allergic diseases. Such resources will be critical to derive time-relevant scientific and policy solutions that will minimize public health consequences in a changing climate.

Targeting inducible epigenetic reprogramming pathways in chronic airway remodeling.

Allergic asthma is a chronic inflammatory airway disease whose clinical course is punctuated by acute exacerbations from aeroallergen exposure or respiratory virus infections. Aeroallergens and respiratory viruses stimulate toll-like receptor (TLR) signaling, producing oxidative injury and inflammation. Repetitive exacerbations produce complex mucosal adaptations, cell-state changes, and structural remodeling. These structural changes produce substantial morbidity, decrease lung capacity, and impair quality of life. We will review recent systems-level studies that provide fundamental new insights into how repetitive activation of innate signaling pathways produce epigenetic ‘training’ to induce adaptive epithelial responses. Oxidative stress produced downstream of TLR signaling induces transient oxidation of guanine bases in the regulatory regions of inflammatory genes. The epigenetic mark 8-oxoG is bound by a pleiotropic DNA repair enzyme, 8-oxoguanine DNA glycosylase (OGG1), which induces conformational changes in adjacent DNA to recruit the NFκB·bromodomain-containing protein 4 (BRD4) complex. The NFκB·BRD4 complex not only plays a central role in inflammation, but also triggers mesenchymal transition and extracellular matrix remodeling. Small molecule inhibitors of OGG1-8-oxoG binding and BRD4–acetylated histone interaction have been developed. We present studies demonstrating efficacy of these in reducing airway inflammation in preclinical models. Targeting inducible epigenetic reprogramming pathway shows promise for therapeutics in reversing airway remodeling in a variety of chronic airway diseases.

Allergic Comorbidity in Eosinophilic Esophagitis: Mechanistic Relevance and Clinical Implications.

Allergic eosinophilic esophagitis (EoE) is a chronic, allergen-mediated inflammatory disease of the esophagus, and the most common cause of prolonged dysphagia in children and young adults in the developed world. While initially undistinguished from gastroesophageal reflux disease-associated esophageal eosinophilia, EoE is now recognized as a clinically distinct entity that shares fundamental inflammatory features of other allergic conditions and is similarly increasing in incidence and prevalence. The clinical and epidemiologic associations between EoE and other allergic manifestations are well established. In addition to exaggerated rates of atopic dermatitis, IgE-mediated food allergy, asthma, and allergic rhinitis in EoE patients, each of these allergic manifestations imparts individual and cumulative risk for subsequent EoE diagnosis. As such, EoE may be a member of the "allergic march"-the natural history of allergic manifestations during childhood. Several determinants likely contribute to the relationship between these conditions, including shared genetic, environmental, and immunologic factors. Herein, we present a comprehensive review of allergic comorbidity in EoE. We discuss areas of the genome associated with both EoE and other allergic diseases, including the well-studied variants encoding thymic stromal lymphopoietin and calpain 14, among other "atopic" regions. We summarize ways that environmental factors (such as microbiome-altering pressures and aeroallergen exposure) may predispose to multiple allergic conditions including EoE. Finally, we touch onsome fundamental features of type 2 inflammation, and the resulting implications for the development of multiple allergic manifestations. We conclude with an analysis of the "type 2" biologics, and how mechanistic similarities between EoE and the other allergic manifestations have important implications for screening and treatment of the allergic patient.

Comparative responses of paediatric airway epithelium to viral and allergen insult

Asthma affects over a million children in the UK. Early age viral infection, allergen sensitization, atopy and genetic predisposition increases the likelihood of developing asthma. Our aim is to understand the consequences of allergen exposure (house-dust mite; HDM) and/or RSV infection on innate immune responses, cytopathogenesis and virus replication in paediatric airway epithelium. Well-differentiated primary paediatric nasal epithelial cell (WD-PNEC) cultures derived from newborn or pre-school children were infected with RSV before or after stimulation with HDM. Virus growth kinetics, cytopathology and innate immune responses were analysed. HDM pre-treatment did not affect the culture integrity or RSV growth. Preliminary RT-qPCR analysis revealed upregulation of irf9 in RSV infected/HDM treated and HDM pre-treated/RSV infected cultures at 24 and 96 h post-infection (hpi). Isg15 was also upregulated in HDM pre-treated/RSV infected cultures at 24 hpi in newborns only. At 96 hpi, irf9, isg15, ifi6, duox2 and duoxA2 were upregulated in RSV infected cultures. Surprisingly, HDM treatment alone did not induce any significant upregulation of these genes compare to untreated/uninfected controls. However, data from more donors will be required to confirm these preliminary data. IL-29/IFNλ1 secretion was also significantly reduced following HDM pre-treatment of RSV infected cultures, while there was a trend towards reduced IL-6 secretion. These results suggest that HDM exposure modulates the innate immune responses to RSV infection of airway epithelium. The preliminary data are consistent with our over-arching hypothesis that our model of aeroallergen exposure and viral infection of airway epithelium will help elucidate mechanisms by which pre-school wheeze develops.

Mood Worsening on Days with High Pollen Counts is associated with a Summer Pattern of Seasonality.

Background:Summer/spring-type seasonal affective disorder (S-SAD) is the less common subtype of seasonal affective disorder and evidence regarding potential triggers of S-SAD is scarce. Recent reports support association of airborne-pollen with seasonal exacerbation of depression (mood seasonality) and timing of suicidal behavior. Therefore, we hypothesized that Old Order Amish (OOA) with summer/spring pattern of seasonality (abbreviated as summer pattern) and S-SAD will have significant mood worsening on high pollen days.Methods:A seasonal pattern of mood worsening and SAD parameters were estimated using Seasonal Pattern Assessment Questionnaire (SPAQ). Age- and gender-adjusted ANCOVAs and post hoc analyses were conducted to compare mood worsening on days with high pollen counts between summer-pattern vs no-summer-pattern of mood worsening, S-SAD vs no-S-SAD, winter-pattern vs no-winter-pattern of mood worsening, and W-SAD vs no-W-SAD groups.Results:The prevalence of S-SAD was 0.4%, while 4.5% of individuals had a summer pattern of mood seasonality. A statistically significant difference for mood worsening on high pollen days was observed between summer-pattern vs no-summer-pattern of mood worsening (p = 0.006). The significant association between S-SAD vs no-SAD groups (p = 0.032) for mood worsening on high pollen days did not withstand Bonferroni adjustment for multiple comparisons. No significant association was found for winter-pattern vs no-winter-pattern of mood worsening (p = 0.61) and for W-SAD vs no-W-SAD (p = 0.19) groups.Conclusion:Our results are consistent with previous studies implicating links between aeroallergen exposure and summer pattern of seasonality, but not the winter pattern of seasonality.

Longitudinal Phenotypes of Respiratory Health in a High-Risk Urban Birth Cohort.

Characterization of patterns of wheezing and allergic sensitization in early life may allow for identification of specific environmental exposures impacting asthma development. To define respiratory phenotypes in inner-city children and their associations with early-life environmental exposures. Data were collected prospectively from 442 children in the URECA (Urban Environment and Childhood Asthma) birth cohort through age 7 years, reflecting symptoms (wheezing), aeroallergen sensitization, pulmonary function, and body mass index. Latent class mixed models identified trajectories of wheezing, allergic sensitization, and pulmonary function. Cluster analysis defined nonoverlapping groups (termed phenotypes). Potential associations between phenotypes and early-life environmental exposures were examined. Five phenotypes were identified and mainly differentiated by patterns of wheezing and allergic sensitization (low wheeze/low atopy; low wheeze/high atopy; transient wheeze/low atopy; high wheeze/low atopy; high wheeze/high atopy). Asthma was most often present in the high-wheeze phenotypes, with greatest respiratory morbidity among children with frequent wheezing and allergic sensitization. These phenotypes differentially related to early-life exposures, including maternal stress and depression, antenatal environmental tobacco smoke, house dust microbiome, and allergen content (all P < 0.05). Prenatal smoke exposure, maternal stress, and depression were highest in the high-wheeze/low-atopy phenotype. The high-wheeze/high-atopy phenotype was associated with low household microbial richness and diversity. Early-life aeroallergen exposure was low in high-wheeze phenotypes. Patterns of wheezing, allergic sensitization, and lung function identified five respiratory phenotypes among inner-city children. Early-life environmental exposure to stress, depression, tobacco smoke, and indoor allergens and microbes differentially associate with specific phenotypes.

Seasonal exacerbation of eosinophilic esophagitis histologic activity in adults and children implicates role of aeroallergens

BackgroundDisease activity may correlate with environmental aeroallergen exposure in eosinophilic esophagitis. The association between seasons and flares of eosinophilic esophagitis (EoE) histologic activity has not been extensively studied. ObjectiveWe aimed to assess the frequency of seasonal exacerbations of eosinophilic esophagitis, as well as changes in symptom reporting, endoscopic findings, and histologic findings attributed to aeroallergens in an EoE cohort. MethodsIn this retrospective cohort study, we analyzed EoE patients in histologic remission (<15 eosinophil/high-power field) but who doubled the esophageal eosinophil count between seasons without change in eosinophilic esophagitis–specific therapy. Outcomes were: symptomatic global worsening (yes/no); change in endoscopic severity (EREFS scoring system); and histologic change (peak eosinophil count). ResultsOf 782 patients, 13 (4%) met inclusion criteria (mean age: 36.2; 85% male; 86% white; 85% atopic disease diagnosis), and 14 exacerbations were recorded. Of these, 71% occurred in fall and summer months. Peak eosinophil counts increased from 6.8 to 86.8 eosinophil per high-power field (P < .001). Four patients (31%) reported worsening of seasonal allergies and 5 (38%) a global worsening of symptoms. Endoscopic severity was also significantly worse during seasonal exacerbations (total EREFS 3.7 vs 1.7; P = .01). Baseline features differed by atopic diagnoses and endoscopic findings between patients with and without seasonal exacerbations. ConclusionSeasonal exacerbations of eosinophilic esophagitis were uncommon in this cohort and most commonly recorded over the summer and fall months. These data support a role of aeroallergens in the pathogenesis of eosinophilic esophagitis in some patients, and clinicians should consider aeroallergens as a potential cause of disease exacerbation.