Progression Of Allergic Diseases Research Articles

Modification of allergic dermatitis on the associations between early-life exposure to size-specific particulate matter and childhood allergic rhinitis

To evaluate the modification of allergic dermatitis on the association between PM exposure and allergic rhinitis in preschool children. This cross-sectional study was based on a questionnaire conducted between June 2019 and June 2020 to caregivers of children aged 3 to 6 years in the kindergartens of 7 Chinese cities to collect information on allergic rhinitis and allergic dermatitis. A mature machine learning-based space-time extremely randomized trees model was applied to estimate early-life, prenatal, and first-year exposure of PM1, PM2.5 and PM10 at 1 km×1 km resolution. A combination of multilevel logistic regression and restricted cubic spline functions was used to quantitatively assess whether allergic dermatitis modifies the associations between size-specific PM exposure and the risk of childhood allergic rhinitis. The results showed that out of 28 408 children, 14 803 (52.1%) were boys and 13 605 (47.9%) were girls; the age of children ranged from 3.1 to 6.8 years, with a mean age of (4.9±0.9) years, of which 3 586 (12.6%) were diagnosed with allergic rhinitis. Among all children, 17 832 (62.8%) were breastfed for more than 6 months and 769 (2.7%) had parental history of atopy. A total of 21 548 children (75.9%) had a mother with an educational level of university or above and 7 338 (29.6%) had passive household cigarette smoke exposure. The adjusted ORs for childhood allergic rhinitis among the children with allergic dermatitis as per interquartile range (IQR) increase in early-life PM1(9.8 μg/m3), PM2.5 (14.9 μg/m3) and PM10 (37.7 μg/m3) were significantly higher than the corresponding ORs among the children without allergic dermatitis [OR: 1.45, 95%CI (1.26, 1.66) vs. 1.33, 95%CI (1.20, 1.47), for PM1; OR: 1.38, 95%CI (1.23, 1.56) vs. 1.32, 95%CI (1.21, 1.45), for PM2.5; OR: 1.56, 95%CI (1.31, 1.86) vs. 1.46, 95%CI (1.28, 1.67), for PM10]. The interactions between allergic dermatitis and size-specific PM exposure on childhood allergic rhinitis were statistically significant (Z value=19.4, all P for interaction<0.001). The similar patterns were observed for both prenatal and first-year size-specific PM exposure and the results of the dose-response relationship were consistent with those of the logistic regression. In conclusion, allergic dermatitis, as an important part of the allergic disease progression, may modify the association between ambient PM exposure and the risk of childhood allergic rhinitis. Children with allergic dermatitis should pay more attention to minimize outdoor air pollutants exposure to prevent the further progression of allergic diseases.

Causal relationships of metabolites with allergic diseases: a trans-ethnic Mendelian randomization study

BackgroundAllergic diseases exert a considerable impact on global health, thus necessitating investigations into their etiology and pathophysiology for devising effective prevention and treatment strategies. This study employs a Mendelian randomization (MR) analysis and meta-analysis to identify metabolite targets potentially associated with allergic diseases.MethodsA two-sample MR analysis was conducted to explore potential causal relationships between circulating and urinary metabolites and allergic diseases. Exposures were derived from a genome-wide association study (GWAS) of 486 circulating metabolites and a GWAS of 55 targeted urinary metabolites. Outcome data for allergic diseases, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma, were obtained from the FinnGen biobank in Europe (cohort 1) and the Biobank Japan in Asia (cohort 2). MR results from both cohorts were combined using a meta-analysis.ResultsMR analysis identified 50 circulating metabolites and 6 urinary metabolites in cohort 1 and 54 circulating metabolites and 2 urinary metabolites in cohort 2 as potentially causally related to allergic diseases. A meta-analysis of the MR results revealed stearoylcarnitine (OR 8.654; 95% CI 4.399−17.025; P = 4.06E-10) and 1-arachidonoylglycerophosphoinositol (OR 2.178; 95% CI 1.388−3.419; P = 7.15E-04) as the most reliable causal circulating metabolites for asthma and AR, respectively. Further, histidine (OR 0.734; 95% CI: 0.594−0.907; P = 0.004), tyrosine (OR 0.601; 95% CI: 0.380−0.952; P = 0.030), and alanine (OR 0.280; 95% CI: 0.125−0.628; P = 0.002) emerged as urinary metabolites with the greatest protective effects against asthma, AD, and AR, respectively.ConclusionsImbalances in numerous circulating and urinary metabolites may be implicated in the development and progression of allergic diseases. These findings have significant implications for the development of targeted strategies for the prevention and treatment of allergic diseases.

Modification of Food Allergy on the Associations between Early Life Exposure to Size-Specific Particulate Matter and Childhood Allergic Rhinitis.

Previous studies have reported the association between particulate matter (PM) and childhood allergic rhinitis (AR). However, it is unclear whether food allergy (FA) modifies the PM-AR association. We aimed at evaluating the effect of the modification of FA on PM-AR association in preschool children. We adopted a cross-sectional study and conducted a questionnaire survey among preschool children aged 3-6 years in 7 cities in China from June 2019 to June 2020 to collect information on AR and FA. We used a combination of multilevel logistic regression and restricted cubic spline functions to quantitatively assess whether FA modifies the associations between size-specific PM exposure (1 × 1 km) and the risk of AR. The adjusted odds ratios (ORs) for AR among the children with FA as per a 10 μg/m3 increase in early life PM1, PM2.5, and PM10 were significantly higher than the corresponding ORs among the children without FA [e.g., OR: 1.58, 95% CI: (1.32, 1.90) vs 1.29, 95% CI: (1.18, 1.41), per 10 μg/m3 increase in PM1]. The interactions between FA and size-specific PM exposure and their effects on AR were statistically significant (all p-int < 0.001). FA, as an important part of the allergic disease progression, may modify the PM-AR association in preschool children.

Correlation between allergic rhinitis and asthma

The concept of the „unified respiratory disease” emphasizes the close connection between the upper and lower respiratory pathways in allergic diseases. The structure and function of the upper and lower respiratory pathways are closely interconnected, forming a single morphofunctional entity. Studies show that allergic rhinitis and asthma share the same inflammatory cells and Th2-type cytokines in nasal and bronchial biopsy samples. Additionally, bronchial challenges can induce inflammation in the nasal area and vice versa, suggesting a close link between the two conditions. The epithelial barrier, through its junctions and constituent proteins, plays an essential role in maintaining homeostasis and protection against external factors, and the complex interactions between these two segments of the respiratory pathways are an important research topic. Tight junctions, adhesion junctions, gap junctions, as well as desmosomes contribute to maintaining epithelial integrity and regulating inflammation. The constituent proteins of these junctions and their interactions play crucial roles in the proper functioning of the epithelial barrier. Respiratory allergens such as dust mites, pollen, pets, and fungi are risk factors for both conditions. Recent studies have highlighted numerous environmental factors capable of compromising epithelial integrity and disrupting its barrier function, including allergens with protease activity. Allergenic proteases from various sources, such as dust mites, pollen, fungi, and kitchen cockroaches, have been identified and characterized. Studies have shown the significant role these allergens play in compromising the integrity of the respiratory epithelium and triggering allergic responses. They can activate specific receptors, inducing inflammation and disrupting the epithelium’s barrier function. For example, proteases from dust mites cleave junctional proteins, promoting allergen transport and triggering the release of proinflammatory cytokines. The same effect is observed with pollen, fungi, and kitchen cockroaches. The proteolytic activity of allergens contributes to sensitization and the progression of allergic diseases. Understanding these mechanisms can guide the development of effective therapeutic strategies for preventing and treating these conditions.

A preliminary study on the establishment of a subcutaneous allergen-specific immunotherapy center

Allergic diseases can notably affect a patient's quality of life. World Health Organization (WHO) has identified these diseases as one of the key areas for research and prevention in the 21st century. Currently, allergen-specific immunotherapy is viewed as a potential treatment approach that could modify the natural progression of allergic diseases, thus being recognized as a crucial tactic in their prevention and treatment. Nonetheless, the broad implementation of allergen-specific immunotherapy in clinical settings continues to confront challenges. One significant issue is the absence of standardized centers for subcutaneous allergen-specific immunotherapy. This article presents several perspectives and recommendations for establishing a standardized subcutaneous allergen-specific immunotherapy center.

Allergic march: a comprehensive approach to diagnosing, treating and preventing atopic diseases

The article discusses the phenomenon of allergic march, which is a progressive process of atopic disease development in allergic patients. The inflammatory process changes localization, causing various symptoms such as atopic dermatitis, food allergy, asthma, allergic rhinitis and eosinophilic esophagitis. Allergic march has a major impact on the development of asthma and allergic rhinitis. The diversity of allergic march trajectories is due to the interaction of genetic, environmental and psychosocial factors. Understanding these mechanisms is crucial to prevent effectively the progression of allergic diseases. The article also discusses the advantages of sublingual immunotherapy (SILT) in the treatment of allergic diseases. SILT shows safety profile and may be more acceptable treatment option for the patients comparing to the traditional subcutaneous immunotherapy (SCIT). There are evidence of the beneficial effects of SILT in reducing allergy symptoms and improving quality of life in allergic patients.

Indoor aeroallergens from American cockroaches and mites initiate atopic march via cutaneous contact in a murine model.

The progression of allergic diseases from atopic dermatitis in childhood to other allergic conditions such as asthma in later life is often referred to as the atopic march. In order to study the relationship between cutaneous sensitization by aeroallergen and atopic march, we established a mouse model to test the hypothesis using American cockroaches and house dust mites as the model allergens. Mice were sensitized via skin with native cockroach extract (CraA) or recombinant Per a 2 and Der p 2 proteins without adjuvant. Each mouse was subjected to a total of three 1-week patching sensitizations with a 2-week interval in between each application. The resulting immunological variables in sera, scratching behavior, airway hyperresponsiveness (AHR), and pathology of skin lesions and nasal mucosa were evaluated. In mice, application of CraA, rPer a 2, and rDer p 2 aeroallergens through skin patching induced significantly high levels of both total IgE and specific IgEs. The epicutaneous sensitization after a subsequent allergen challenge showed a significant increase in scratch bouts, AHR, epidermal thickness, and eosinophil counts in the skin compared with the control mice. In addition, stimulation of murine splenocytes with allergens increased higher levels of Th2 cytokines, anti-inflammatory cytokines, and chemokines excretion. Our study provides evidence supporting that epicutaneous sensitization to aeroallergens also led to nasal and airway symptoms comparable to atopic march as described in humans. We hope this new allergy model will be useful in the development of new preventive and therapeutic strategies aimed at stopping the atopic march.

Regulation of Dendritic Cell Functions by Vitamins as Promising Therapeutic Strategy for Immune System Disorders.

A functional immune system is crucial for a healthy life, protecting from infections, tumors, or autoimmune disorders; these are accomplished by the interaction between various immune cells. Nourishment, particularly micronutrients, are very important components in the immune system balance, therefore this review emphasizes the vitamins (D, E, A, C) and Dendritic cells' subsets due to vitamins' roles in immune processes, especially on dendritic cells' functions, maturation, and cytokine production. Current studies reveal significant benefits related to vitamins, including vitamin E, which can contribute to the control of dendritic cells' function and maturation. Furthermore, vitamin D plays an immunoregulatory and anti-inflammatory role in the immune system. Metabolite of vitamin A which is called retinoic acid leads to T cells' differentiation to T helper 1 or T helper 17, so low levels of this vitamin exacerbate the menace of infectious diseases, and vitamin C has anti-oxidant effects on dendritic cells and modulate their activation and differentiation program. Additionally, the correlation between the amount of vitamin and the occurrence or progression of allergic diseases and autoimmunity disorders is discussed according to the results of previous studies.

High baseline prevalence of atopic comorbidities and medication use in children treated with allergy immunotherapy in the REAl-world effeCtiveness in allergy immunoTherapy (REACT) study.

Respiratory allergy, commonly manifesting as allergic rhinitis (AR) and asthma, is a chronic progressive disease that frequently starts in childhood. Allergy immunotherapy (AIT) is the only causal treatment for respiratory allergy with the potential to modify the underlying cause of allergy and, ultimately, prevent disease progression. This analysis aimed to determine if AIT is received sufficiently early to halt the progression of allergic disease, by characterizing the burden and progression of disease in children prior to AIT initiation in real-life clinical practice. The REAl-world effeCtiveness in allergy immunoTherapy (REACT) study was a large retrospective cohort study using German claims data between 2007 and 2017. Characteristics of two pre-defined AIT age cohorts from the REACT study - children (aged <18 years) and adults (aged ≥18 years) - were evaluated during the 1-year period before the first AIT prescription. For comparison, a control group of all subjects with a confirmed diagnosis of AR and without prescriptions for AIT was included. Burden of disease was assessed using diagnostic codes for atopic comorbidities [e.g., atopic dermatitis (AD), asthma, and acute allergic conjunctivitis] and non-atopic comorbidities (e.g., migraine, headache); medication use, recorded as prescriptions for symptom-relieving AR medication and reliever/controller medication for asthma, was also assessed. Data were analyzed descriptively, using summary statistics. Both children (n = 11,036) and adults (n = 30,037) showed a higher prevalence of atopic comorbidities and a greater drug burden prior to AIT initiation compared to AR patients not treated with AIT (n = 1,003,332). In the two age-specific AIT cohorts, children consistently showed the highest prevalence of atopic comorbidities compared to adults (AIT children, AIT adults - asthma: 41.4%, 34.5%; AD: 19.9%, 10.2%; acute allergic conjunctivitis: 13.6%, 10.2%). Generally, prescriptions per year for symptom-relieving AR and asthma treatments were also higher for children initiating AIT vs. adults (AIT children, AIT adults - AR prescriptions per subject: 1.72, 0.73; asthma prescriptions per subject: 1.42, 0.79). Children with AR who are offered AIT in real-life show considerable disease burden prior to initiation. As AIT may alleviate the burden and halt the progression of allergic disease, considering AIT earlier in the disease course may be warranted.

The ketone body β-hydroxybutyrate mitigates ILC2-driven airway inflammation by regulating mast cell function.

Ketone bodies are increasingly understood to have regulatory effects on immune cell function, with β-hydroxybutyrate (BHB) exerting a predominantly anti-inflammatory response. Dietary strategies to increase endogenous ketone body availability such as the ketogenic diet (KD) have recently been shown to alleviate inflammation of the respiratory tract. However, the role of BHB has not been addressed. Here, we observe that BHB suppresses group 2 innate lymphoid cell (ILC2)-mediated airway inflammation. Central to this are mast cells, which support ILC2 proliferation through interleukin-2 (IL-2). Suppression of the mast cell/IL-2 axis by BHB attenuates ILC2 proliferation and the ensuing type 2 cytokine response and immunopathology. Mechanistically, BHB directly inhibits mast cell function in part through GPR109A activation. Similar effects are achieved with either the KD or 1,3-butanediol. Our data reveal the protective role of BHB in ILC2-driven airway inflammation, which underscores the potential therapeutic value of ketone body supplementation for the management of asthma.

Regulatory T Cells, a Viable Target Against Airway Allergic Inflammatory Responses in Asthma.

Asthma is a multifactorial disorder characterized by the airway chronic inflammation, hyper-responsiveness (AHR), remodeling, and reversible obstruction. Although asthma is known as a heterogeneous group of diseases with various clinical manifestations, recent studies suggest that more than half of the clinical cases are ‘‘T helper type 2 (Th2)-high’’ type, whose pathogenesis is driven by Th2 responses to an inhaled allergen from the environmental exposures. The intensity and duration of inflammatory responses to inhaled allergens largely depend on the balance between effector and regulatory cells, but many questions regarding the mechanisms by which the relative magnitudes of these opposing forces are remained unanswered. Regulatory T cells (Tregs), which comprise diverse subtypes with suppressive function, have long been attracted extensive attention owing to their capability to limit the development and progression of allergic diseases. In this review we seek to update the recent advances that support an essential role for Tregs in the induction of allergen tolerance and attenuation of asthma progression once allergic airway inflammation established. We also discuss the current concepts about Treg induction and Treg-expressed mediators relevant to controlling asthma, and the therapies designed based on these novel insights against asthma in clinical settings.

Epithelial Barrier: Protector and Trigger ofAllergic Disorders.

The epithelial barrier has classically been considered as the only first line of defense against irritants, pathogens, and allergens. However, it is now known to play an essential role in the immune response to exogenous agents. In fact, recent reports postulate the epithelial barrier hypothesis as a possible explanation for the increasing incidence and severity of allergic diseases. The epithelial barrier preserves the isolation of internal tissues from potential external threats. Moreover, a coordinated interaction between epithelial and immune cells ensures the unique immune response taking place in mucosal tissues, which is reported to be dysregulated in allergic diseases. We and others have demonstrated that in severe allergic phenotypes, the epithelial barrier undergoes several histological modifications, with increased infiltration of immune cells, leading to dysfunction. This is common in atopic dermatitis, asthma, and food allergy. However, the precise role of the epithelial barrier in mucosal biology during progression of allergic diseases is not well understood. In this review, we aim to compile recent knowledge regarding the histological structure and immunological function of the epithelial barrier and to shed light on the role of this compartment in the onset and progression of allergic diseases.

Goat Milk–Derived Lipids Restrain NK T Cell–Dependent Eosinophilic Inflammation in a Murine Model of Atopic Dermatitis

Atopic dermatitis (AD) is a debilitating disease that disproportionately affects infants and young children and is considered the first step of the atopic march—the age-related progression of allergic disease. Consequently, there is an urgent unmet need to elucidate the root causes of AD and evaluate potential prevention mechanisms.

The Presence of Atopic March in Patients Diagnosed with Atopic Dermatitis

Objective: Atopic march is a model that explains the progression of allergic diseases from atopic dermatitis (AD) to allergic asthma and rhinitis. In our study, while evaluating the presence of allergen sensitivity and allergic diseases in patients who were diagnosed with AD and followed up until the age of at least 5 years, we wanted to investigate how much the definition of classical atopic gait responded to expectations. Material and Methods: We retrospectively reviewed the file records of patients diagnosed with atopic dermatitis, whose ages were 2 years and under at the time of application and followed up regularly until at least 5 years of age. We recorded the clinical and laboratory findings. We noted the allergic disease status and allergen sensitivity of the patients when they were 5 years old. Results: Forty-one patients with a diagnosis of AD who met the criteria were identified. During the application, we found food sensitivity in 28 (68.3%) patients. When 41 patients reached the age of 5, 13 (31.7%) were diagnosed with asthma and 12 (29.2%) were diagnosed with allergic rhinitis. Conclusion: We found the frequency of asthma and allergic rhinitis higher in patients with AD than in the normal population. However, we could not show a relationship between food sensitivity and the development of asthma and/or allergic rhinitis. Effective skin care in AD can be protective for developing of allergic diseases. In order for clinicians to understand the heterogeneity of atopic disease models in children and to eliminate this variability, infants with AD should be followed up in later life.

The risk of atopic comorbidities and atopic march progression among Black and White children with mild-to-moderate atopic dermatitis: A cross-sectional study

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with the sequential propagation of atopic comorbidities, such as asthma and allergic rhinitis. This atopic march has been depicted as a homogenous progression of allergic diseases, but patient factors such as race may reveal heterogeneity in this process. The goal of our cross-sectional study was to evaluate differences in atopic illnesses and subsequent atopic march progression among a national cohort of Black and White children with physician-diagnosed mild-to-moderate AD.

Atopic March: Dermatologic Perspectives.

The progression of allergic diseases with the development of atopic dermatitis and food allergy in infancy and subsequent asthma and allergic rhinitis in the later childhood is known as 'atopic march'. There have been many arguments in favour of and against this concept. This article reviews the latest epidemiology, immunological mechanisms and translational implications in clinical practice and research, which is relevant to the dermatologists. The role of skin as a site of initiation and the potential for interventions on skin that may prevent subsequent allergic diseases is also highlighted.

Inhibition of Chitinase-3-like-1 by K284-6111 Reduces Atopic Skin Inflammation via Repressing Lactoferrin.

Chitinase-3-like-1 (CHI3L1) is known to induce inflammation in the progression of allergic diseases. Previous our studies revealed that 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7-dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide (K284-6111; K284), the CHI3L1 inhibiting compound, has the anti-inflammatory effect on neuroinflammation. In this study, we investigated that K284 treatment could inhibit the development of atopic dermatitis (AD). To identify the effect of K284, we used phthalic anhydride (5% PA)-induced AD animal model and in vitro reconstructed human skin model. We analyzed the expression of AD-related cytokine mediators and NF-κB signaling by Western blotting, ELISA and quantitative real-time PCR. Histological analysis showed that K284 treatment suppressed PA-induced epidermal thickening and infiltration of mast cells. K284 treatment also reduced PA-induced release of inflammatory cytokines. In addition, K284 treatment inhibited the expression of NF-κB activity in PA-treated skin tissues and TNF-α and IFN-γ-treated HaCaT cells. Protein-association network analysis indicated that CHI3L1 is associated with lactoferrin (LTF). LTF was elevated in PA-treated skin tissues and TNF-α and IFN-γ-induced HaCaT cells. However, this expression was reduced by K284 treatment. Knockdown of LTF decreased the expression of inflammatory cytokines in TNF-α and IFN-γ-induced HaCaT cells. Moreover, anti-LTF antibody treatment alleviated AD development in PA-induced AD model. Our data demonstrate that CHI3L1 targeting K284 reduces AD-like skin inflammation and K284 could be a promising therapeutic agent for AD by inhibition of LTF expression.

Association between prenatal polycyclic aromatic hydrocarbons and infantile allergic diseases modified by maternal glutathione S-transferase polymorphisms: results from the MOCEH birth cohort.

BackgroundPrenatal exposure to polycyclic aromatic hydrocarbons (PAH) has been linked to allergic disease onset. Variations in the glutathione S-transferase (GST) gene family can impact the progression of allergic diseases. We sought to examine the association between prenatal PAH exposure and infantile allergic diseases in 6-month-old infants, and how maternal glutathione S-transferase M1 (GSTM1) or T1 (GSTT1) polymorphism affects the association between prenatal PAH exposure and allergic diseases in the Mothers and Children's Environmental Health (MOCEH) study.MethodsThe study sample comprised 349 infants and their mothers from the MOCEH study, for whom 1-hydroxypyrene (1-OHP) and 2-naphthol were measured in both the early period of pregnancy and late period of pregnancy. An infant was deemed to be affected by an allergic disease if diagnosed with or if developed at least one of the allergic diseases. A logistic regression analysis was performed to study the association between urinary 1-OHP and 2-naphthol levels during pregnancy and allergic diseases in 6-month-old infants. Furthermore, analyses stratified by maternal GSTM1 or GSTT1 present/null polymorphisms were performed.ResultsThe risk of allergic diseases in 6-month-old infants was significantly increased in accordance with an increase in urinary 1-OHP during the early period of pregnancy (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.05, 3.23; by one log-transformed unit of 1-OHP μg/g creatinine). The increased risk of infantile allergic diseases associated with urinary 1-OHP during the early period of pregnancy was limited to the maternal GSTT1 null type (OR: 2.69; 95% CI: 1.17, 6.21, by one log-transformed unit of 1-OHP μg/g creatinine); however, the Relative Excess Risk due to Interaction was not statistically significant.ConclusionsThe present study found that infantile allergic diseases could be affected by intrauterine PAH exposure, particularly in the early prenatal period and the risk was limited to the maternal GSTT1 null type.

Clinical efficacy and safety of combined house dust mite subcutaneous immunotherapy and omalizumab in five cases of allergic rhinitis and asthma

Allergen immunotherapy (AIT) is a well-recognized treatment for altering the natural course of respiratory allergy which builds immune tolerance and prevents progression of allergic diseases. In our five cases of house dust mite (HDM)-driven allergic rhinitis and asthma, combined HDM Subcutaneous Immunotherapy (HDM-SCIT) for 2 years with omalizumab for more than 12 months has achieved disease remission in four cases and disease control in one case along with long-term effect for 3 years after discontinuation of AIT. We hypothesize that combining HDM-SCIT and omalizumab is a promising strategy as it is effective, safe, and synergistic having immune-modifying activity in cases of HDM-driven Allergic Rhinitis and Asthma.

Environmental exposures and mechanisms in allergy and asthma development.

Environmental exposures interplay with human host factors to promote the development and progression of allergic diseases. The worldwide prevalence of allergic disease is rising as a result of complex gene-environment interactions that shape the immune system and host response. Research shows an association between the rise of allergic diseases and increasingly modern Westernized lifestyles, which are characterized by increased urbanization, time spent indoors, and antibiotic usage. These environmental changes result in increased exposure to air and traffic pollution, fungi, infectious agents, tobacco smoke, and other early-life and lifelong risk factors for the development and exacerbation of asthma and allergic diseases. It is increasingly recognized that the timing, load, and route of allergen exposure affect allergic disease phenotypes and development. Still, our ability to prevent allergic diseases is hindered by gaps in understanding of the underlying mechanisms and interaction of environmental, viral, and allergen exposures with immune pathways that impact disease development. This Review highlights epidemiologic and mechanistic evidence linking environmental exposures to the development and exacerbation of allergic airway responses.