Climate change is causing the spread of common ragweed across Europe, along with rising ground-level ozone (O3) in semi-urban and rural environments. Although elevated O3 has been shown to affect pollen-intrinsic allergenic compounds, here we addressed the lack of in vivo evidence on how ozone-exposed ragweed pollen modulates allergic responses. Ragweed plants were grown in controlled plant growth chambers under control (40 ppb) or elevated (80 ppb and 120 ppb) O3 levels. Aqueous pollen extracts (RWE) from control- or O3-exposed plants were administered in vivo in a murine model for allergic airway inflammation (AAI) and employed in a human in vitro system of monocyte-derived dendritic cells (DCs), key initiators of the allergic response. Adjuvant factors and metabolites in control- and O3-RWE were investigated using ELISA and untargeted metabolomics. Compared to control-RWE, 80 ppb O3 induced a statistically significant enhancement of few AAI parameters, whereas 120 ppb O3 yielded statistically significant dampening effects on AAI. On the same line, in human DCs isolated from atopic donors, RWE O3 80 ppb slightly increased, while RWE O3 120 ppb decreased the expression of maturation markers. Metabolomic profiling revealed pronounced, dose-dependent shifts in pollen primary and secondary metabolites, with moderate stimulation of pro-inflammatory lipid- and protein-derived mediators at 80 ppb, whereas higher O3 levels (120 ppb) induced metabolic degradation resulting in reduced lipid and protein pro-allergenic compounds. Overall, ozone altered ragweed pollen allergenicity in a dose-dependent manner through plant physiological responses to oxidative stress, highlighting the interaction between air pollution and plant physiology in shaping pollen allergenicity in a changing climate.

Background Various mouse models are used to study pollen allergies, but a systematic experimental comparisvon is lacking. We aimed to establish a physiologically relevant adjuvant-free birch pollen allergy model to understand the dynamics of the allergic immune response and to compare the sensitising potential of different self-collected birch pollen extracts in different distinct in vivo and in vitro routes and models. Methods Different intranasal (i. n.) models in BALB/c mice and IL-4 reporter mice (BALB/c:4Get), an intradermal (i. d.) model (BALB/c:4Get), and human dendritic cells (moDCs) were used to investigate the sensitising and inflammatory effects of birch pollen extracts (BPE). A timeseries experiment was performed in the i. n. model to determine the onset of Th2 responses. Bronchioalveolar lavage fluid (BALF), lungs, draining lymph nodes, and serum were analysed for cell infiltrate, cytokines, and antibodies. Results Repeated i. n. instillations of adjuvant-free BPE prepared from commercial pollen resulted in BALF Th2 cells, eosinophilic lung inflammation, and specific serum immunoglobulins in BALB/c mice. After 6 i. n. instillations, eosinophils and CD4+ T cells peaked in BALF, and CD4+IL-4+ and CD4+IL4Rα+ cells peaked in mediastinal lymph nodes. Both, i. n. and i. d. models detected subtle differences in the sensitising potential of BPEs from two self-collected pollen samples. MoDCs showed higher IL-10 release towards the less inflammatory extract. Conclusions Adjuvant-free murine sensitisation models, including intranasal and intradermal routes, as well as a human DC model, covered different aspects of the sensitisation route and temporal resolution. The models may be broadly helpful in screening approaches in studying mechanisms of pollen allergy.

BACKGROUND:Allergen immunotherapy (AIT) is a therapeutic approach to restore allergen tolerance and prevent asthma progression. Previous studies have shown exhaustion of T cells and the induction of T cells expressing IL-17 and FOXP3 early in AIT, which are relevant for the clinical outcome. This study aims to investigate the dynamic transition from type-3 immunity to a regulatory state observed in the first year during allergic inflammation, as well as the subsequent dysfunction of effector cells during AIT. METHODS:Human and experimental models of allergic airway inflammation were used to assess the impact of AIT on Treg, Tr17 and Th17 cell populations using flow cytometry and proliferation assays. Additionally, human blood samples were analysed using single-cell transcriptomics to characterise transcriptional signatures associated with the transition from pro-inflammatory to regulatory states. RESULTS:AIT restored balance of Tr17 and Treg populations and increased their proliferative capacity, whereas Th17 cells remained functionally impaired. Single-cell transcriptomics identified Tr17 cells as intermediate states between pro-inflammatory and regulatory T-cell programs after AIT. In parallel, AIT reprogrammed intracellular communication networks, with TNF/LTA-associated signalling pathways emerging as prominent mediators of tolerogenic signalling. CONCLUSION:These findings highlight that AIT reprograms immune responses by enhancing regulatory dominance, inducing Tr17 plasticity and leveraging TNF/TNFR2-mediated tolerance. Understanding the cellular dynamics during AIT suggests that therapeutic strategies aimed at targeting Th17 functional impairment could further enhance treatment efficacy for allergic airway diseases. This insight opens new avenues for refining immunotherapeutic approaches to more effectively restore immune balance and improve patient outcomes.

Atopic dermatitis (AD) is an allergic skin disease widespread in children, which later in life can predispose them to asthma. Oriented strand board (OSB), increasingly used in the construction industry, emits volatile organic compounds in the indoor air, some of which may exacerbate AD development in humans. The aim of this study was to evaluate the effects of OSB emissions on the development of AD and lung inflammation. Two different murine AD models, induced by calcipotriol or oxazolone, were exposed to higher- or lower-emitting OSB throughout the experiments. Physiological, biochemical, and immunological parameters of skin disease development, as well as lung inflammatory parameters, were evaluated. Exposure to higher-emitting OSB, characterised especially by high 3-carene emissions, exacerbated some parameters of AD, such as skin barrier function and thickness, with accumulation of eosinophils and 15-lipoxygenase (15-LOX)-driven mediators in both models, whereas IL-4 or 5-LOX-positive cells were increased in only the calcipotriol or oxazolone model, respectively. In the lungs of calcipotriol-treated mice, higher-emitting OSB increased lung eosinophil recruitment. Exposure to lower-emitting OSB had no or even beneficial effects on the skin or lungs of murine AD models. 3-carene in OSB emissions, alone or in combination with other substances, may promote the development of AD and prime the lungs towards an allergic phenotype. Identification and quantification of potentially harmful emitting sources in indoor air may be important for AD prevention or control.

BackgroundAllergen-specific immunotherapy (AIT) is able to restore immune tolerance to allergens in allergic patients. However, some patients do not or only poorly respond to current treatment protocols. Therefore, there is a need for deeper mechanistic insights and further improvement of treatment strategies. The relevance of the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor, has been investigated in several inflammatory diseases, including allergic asthma. However, its potential role in AIT still needs to be addressed.MethodsA murine model of AIT in ovalbumin-induced allergic airway inflammation was performed in AhR-deficient (AhR-/-) and wild-type mice. Furthermore, AIT was combined with the application of the high-affinity AhR agonist 10-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (10-Cl-BBQ) as an adjuvant to investigate the effects of AhR activation on therapeutic outcome.ResultsAlthough AhR-/- mice suffer stronger allergic responses than wild-type mice, experimental AIT is comparably effective in both. Nevertheless, combining AIT with the administration of 10-Cl-BBQ improved therapeutic effects by an AhR-dependent mechanism, resulting in decreased cell counts in the bronchoalveolar fluid, decreased pulmonary Th2 and Th17 cell levels, and lower sIgE levels.ConclusionThis study demonstrates that the success of AIT is not dependent on the AhR. However, targeting the AhR during AIT can help to dampen inflammation and improve tolerogenic vaccination. Therefore, AhR ligands might represent promising candidates as immunomodulators to enhance the efficacy of AIT.

The molecular mechanisms by which worm parasites evade host immunity are incompletely understood. In a mouse model of intestinal helminth infection using Heligmosomoides polygyrus bakeri (Hpb), we show that helminthic glutamate dehydrogenase (heGDH) drives parasite chronicity by suppressing macrophage-mediated host defense. Combining RNA-seq, ChIP-seq, and targeted lipidomics, we identify prostaglandin E2 (PGE2) as a major immune regulatory mechanism of heGDH. The induction of PGE2 and other immunoregulatory factors, including IL-12 family cytokines and indoleamine 2,3-dioxygenase 1, by heGDH required p300-mediated histone acetylation, whereas the enzyme's catalytic activity suppressed the synthesis of type 2-promoting leukotrienes by macrophages via 2-hydroxyglutarate. By contrast, the induction of immunoregulatory factors involved the heGDH N terminus by potentially mediating interactions with cellular targets (CD64 and GPNMB) identified by proteomics. Type 2 cytokines counteracted suppressive effects of heGDH on host defense, indicating that type 2 immunity can limit helminth-driven immune evasion. Thus, helminths harness a ubiquitous metabolic enzyme to epigenetically target type 2 macrophage activation and establish chronicity.

Pinewood, increasingly used in construction and interior fittings, emits high amounts of volatile organic compounds (VOCs), which tend to accumulate in indoor air. Whether indoor VOCs affect the development of atopic dermatitis (AD) is a matter of debate. We aimed to evaluate the effects of pinewood VOCs on the development of AD-like inflammatory phenotype and linked microbiome alterations, both hallmarks of AD. An oxazolone-induced mouse model of AD was exposed to three different VOC concentrations emitted by pinewood plates throughout the experiment. The disease course and associated immunological and microbiological changes were evaluated. To validate and translate our results to humans, human keratinocytes were exposed to a synthetic pinewood VOCs mixture in an AD environment. Pinewood emitted mainly terpenes, which at a total concentration of 5 mg/m3 significantly improved oxazolone-induced key AD parameters, such as serum total IgE, transepidermal water loss, barrier gene alteration, inflammation, and dysbiosis. Notably, exposure to pinewood VOCs restored the loss of microbial richness and inhibit Staphylococci expansion characteristic of the oxazolone-induced mouse AD model. Most beneficial effects of pinewood VOCs were dose-dependent. In fact, lower (< 3 mg/m3) or higher (> 10 mg/m3) pinewood VOC levels maintained only limited beneficial effects, such as preserving the microbiome richness or impeding Staphylococci expansion, respectively. In the human in-vitro model, exposure of keratinocytes grown in an AD environment to a pinewood VOCs mixture reduced the release of inflammatory markers. In conclusion, our results indicate that airborne phytochemicals emitted from pinewood have beneficial effects on an AD-like phenotype and associated dysbiosis. These investigations highlight the effects of terpenes as environmental compounds in the prevention and/or control of atopic skin disease.

BACKGROUND:The rise in asthma has been linked to different environmental and lifestyle factors including dietary habits. Whether dietary salt contributes to asthma incidence, remains controversial. We aimed to investigate the impact of higher salt intake on asthma incidence in humans and to evaluate underlying mechanisms using mouse models. METHODS:Epidemiological research was conducted using the UK Biobank Resource. Data were obtained from 42,976 participants with a history of allergies. 24-h sodium excretion was estimated from spot urine, and its association with asthma incidence was assessed by Cox regression, adjusting for relevant covariates. For mechanistic studies, a mouse model of mite-induced allergic airway inflammation (AAI) fed with high-salt diet (HSD) or normal-salt chow was used to characterize disease development. The microbiome of lung and feces (as proxy for gut) was analyzed via 16S rRNA gene based metabarcoding approach. RESULTS:In humans, urinary sodium excretion was directly associated with asthma incidence among females but not among males. HSD-fed female mice displayed an aggravated AAI characterized by increased levels of total IgE, a TH2-TH17-biased inflammatory cell infiltration accompanied by upregulation of osmosensitive stress genes. HSD induced distinct changes in serum short chain fatty acids and in both gut and lung microbiome, with a lower Bacteroidetes to Firmicutes ratio and decreased Lactobacillus relative abundance in the gut, and enriched members of Gammaproteobacteria in the lung. CONCLUSIONS:High dietary salt consumption correlates with asthma incidence in female adults with a history of allergies. Female mice revealed HSD-induced T-cell lung profiles accompanied by alterations of gut and lung microbiome.

[This corrects the article DOI: 10.3389/fimmu.2023.1157373.].

Allergic inflammation of the airways such as allergic asthma is a major health problem with growing incidence world-wide. One cardinal feature in severe type 2-dominated airway inflammation is the release of lipid mediators of the eicosanoid family that can either promote or dampen allergic inflammation. Macrophages are key producers of prostaglandins and leukotrienes which play diverse roles in allergic airway inflammation and thus require tight control. Using RNA- and ATAC-sequencing, liquid chromatography coupled to mass spectrometry (LC-MS/MS), enzyme immunoassays (EIA), gene expression analysis and in vivo models, we show that the aryl hydrocarbon receptor (AhR) contributes to this control via transcriptional regulation of lipid mediator synthesis enzymes in bone marrow-derived as well as in primary alveolar macrophages. In the absence or inhibition of AhR activity, multiple genes of both the prostaglandin and the leukotriene pathway were downregulated, resulting in lower synthesis of prostanoids, such as prostaglandin E2 (PGE2), and cysteinyl leukotrienes, e.g., Leukotriene C4 (LTC4). These AhR-dependent genes include PTGS1 encoding for the enzyme cyclooxygenase 1 (COX1) and ALOX5 encoding for the arachidonate 5-lipoxygenase (5-LO) both of which major upstream regulators of the prostanoid and leukotriene pathway, respectively. This regulation is independent of the activation stimulus and partially also detectable in unstimulated macrophages suggesting an important role of basal AhR activity for eicosanoid production in steady state macrophages. Lastly, we demonstrate that AhR deficiency in hematopoietic but not epithelial cells aggravates house dust mite induced allergic airway inflammation. These results suggest an essential role for AhR-dependent eicosanoid regulation in macrophages during homeostasis and inflammation.

BACKGROUND:The rates of obesity, its associated diseases, and allergies are raising at alarming rates in most countries. House dust mites (HDM) are highly allergenic and exposure often associates with an urban sedentary indoor lifestyle, also resulting in obesity. The aim of this study was to investigate the epidemiological association and physiological impact of lung inflammation on obesity and glucose homeostasis.METHODS:Epidemiological data from 2207 adults of the population-based KORA FF4 cohort were used to test associations between asthma and rhinitis with metrics of body weight and insulin sensitivity. To obtain functional insights, C57BL/6J mice were intranasally sensitized and challenged with HDM and simultaneously fed with either low-fat or high-fat diet for 12 weeks followed by a detailed metabolic and biochemical phenotyping of the lung, liver, and adipose tissues.RESULTS:We found a direct association of asthma with insulin resistance but not body weight in humans. In mice, co-development of obesity and HDM-induced lung inflammation attenuated inflammation in lung and perigonadal fat, with little impact on body weight, but small shifts in the composition of gut microbiota. Exposure to HDM improved glucose tolerance, reduced hepatosteatosis, and increased energy expenditure and basal metabolic rate. These effects associate with increased activity of thermogenic adipose tissues independent of uncoupling protein 1.CONCLUSIONS:Asthma associates with insulin resistance in humans, but HDM challenge results in opposing effects on glucose homeostasis in mice due to increased energy expenditure, reduced adipose inflammation, and hepatosteatosis.

Background: Infectious agents can reprogram or "train "macrophages and their progenitors to respond more readily to subsequent insults. However, whether such an inflammatory memory exists in type 2 inflammatory conditions such as allergic asthma was not known. Objective: We sought to decipher macrophage-trained immunity in allergic asthma. Methods: We used a combination of clinical sampling of house dust mite (HDM)-allergic patients, HDM-induced allergic airway inflammation in mice, and an in vitro training setup to analyze persistent changes in macrophage eicosanoid, cytokine, and chemokine production as well as the underlying metabolicand epigenetic mechanisms. Transcriptional and metabolic profiles of patient-derived and in vitro trained macrophages were assessed by RNA sequencing or metabolic flux analysis and liquid chromatography-tandem mass spectrometry analysis,respectively. Results: We found that macrophages differentiated from bone marrow or blood monocyte progenitors of HDM-allergic mice or asthma patients show inflammatory transcriptional reprogramming and excessive mediator (TNF-alpha, CCL17, leukotriene, PGE2, IL-6) responses upon stimulation. Macrophages from HDM-allergic mice initially exhibited a type 2 imprint, which shifted toward a classical inflammatory training over time. HDM-induced allergic airway inflammation elicited a metabolically activated macrophage phenotype,producing high amounts of 2-hydroxyglutarate (2-HG). HDM-induced macrophage training in vitro was mediated by a formyl peptide receptor 2-TNF-2-HG-PGE(2)/PGE(2) receptor 2 axis,resulting in an M2-like macrophage phenotype with high CCL17 production. TNF blockade by etanercept or genetic ablation of Tnfin myeloid cells prevented the inflammatory imprinting of bone marrow-derived macrophages from HDM-allergic mice. Conclusion: Allergen-triggered inflammation drives a TNF-dependent innate memory, which may perpetuate and exacerbate chronic type 2 airway inflammation and thus represents a target for asthma therapy.

Bioactive metabolites of arachidonic acid control chronic inflammation, particularly in therapy-resistant airway diseases. Helminth products have been suggested as natural immunoregulators for treating inflammatory diseases. Here, we identified an anti-inflammatory glutamate dehydrogenase (GDH) in the larval extract of the helminth Heligmosomoides polygyrus bakeri (Hpb). We particularly assessed whether Hpb GDH regulates type 2 immune responses by modulating immune cell metabolism. Effects of Hpb GDH on the metabolism of monocyte derived macrophages (MDM), were quantified by mediator profiling by LC-MS/MS (eicosanoids, TCA metabolites) and seahorse analysis. Moreover, Hpb GDH treated MDM were subjected to RNA sequencing to assess effects on gene expression profile. For characterization of immune regulatory effects in vivo, mice were treated with Hpb GDH during house dust mite (HDM)-induced allergic airway inflammation or during infection with Hpb. In macrophages, Hpb GDH induced the production of prostanoids and 2-hydroxyglutarate, which contributed to the suppression of cysteinyl leukotrienes. Moreover, Hpb GDH treated MDM showed an induction of regulatory and type 2 suppressive genes, which partially depended on histone acetylation via p300 HAT. Treatment of mice with Hpb GDH attenuated allergic airway inflammation in mice, while treatment during Hpb infection results in a significant increase in worm burden, suggesting that Hpb GDH regulates type 2 immune responses by modulating the metabolism as well as gene expression in macrophages. Thus, anti-inflammatory modulation of macrophages by Hpb GDH may be translated into new immunomodulatory strategies for the treatment of airway diseases.

The lung epithelial barrier serves as a guardian towards environmental insults and responds to allergen encounter with a cascade of immune reactions that can possibly lead to inflammation. Whether the environmental sensor aryl hydrocarbon receptor (AhR) together with its downstream targets cytochrome P450 (CYP1) family members contribute to the regulation of allergic airway inflammation remains unexplored. By employing knockout mice for AhR and for single CYP1 family members, we found that AhR -/- and CYP1B1 -/- but not CYP1A1 -/- or CYP1A2 -/- animals display enhanced allergic airway inflammation compared to WT. Expression analysis, immunofluorescence staining of murine and human lung sections and bone marrow chimeras suggest an important role of CYP1B1 in non-hematopoietic lung epithelial cells to prevent exacerbation of allergic airway inflammation. Transcriptional analysis of murine and human lung epithelial cells indicates a functional link of AhR to barrier protection/inflammatory mediator signaling upon allergen challenge. In contrast, CYP1B1 deficiency leads to enhanced expression and activity of CYP1A1 in lung epithelial cells and to an increased availability of the AhR ligand kynurenic acid following allergen challenge. Thus, differential CYP1 family member expression and signaling via the AhR in epithelial cells represents an immunoregulatory layer protecting the lung from exacerbation of allergic airway inflammation.

Background Cutaneous bacterial dysbiosis is a characteristic hallmark of atopic dermatitis (AD), and it decisively influences the severity of the disease. Despite this, frequently used murine models of AD have not been characterized regarding the changes in skin microbiome communities. Objective To analyse the skin microbiome of two frequently used murine models for AD for assessing their applicability in translational research. Methods AD was induced in mice by topical application of calcipotriol or oxazolone. Following comparable elicitation of AD-like dermatitis, including IgE induction, the skin microbial communities were analysed and compared with human AD. Results We detected critical differences in the microbiota composition of diseased skin. In contrast to calcipotriol treatment, application of oxazolone induced significant changes in the cutaneous microbiota and a drastic drop of bacterial richness. Furthermore, an expansion of Staphylococci, particularly S. xylosus, was observed in the oxazolone group, also displaying positive correlations with AD key markers including pH, TEWL, IL-4, TSLP and IL-33. Conclusions In this article, we show that (a) the model of choice to investigate AD needs to be characterized for the cutaneous microbiota if applicable and (b) the oxazolone-mediated mixed Th1-Th2 immune response triggers microbiota-induced alterations which share similarities to dysbiosis in human AD and represents therefore a suitable model for translational research on AD if alterations of the microbiome are in the focus of the investigation.

TGF-β1 is known to have a pro-inflammatory impact by inducing Th9 and Th17 cells, while it also induces anti-inflammatory Treg cells (Tregs). In the context of allergic airway inflammation (AAI) its dual role can be of critical importance in influencing the outcome of the disease. Here we demonstrate that TGF-β is a major player in AAI by driving effector T cells, while Tregs differentiate independently. Induction of experimental AAI and airway hyperreactivity in a mouse model with inducible genetic ablation of the gene encoding for TGFβ-receptor 2 (Tgfbr2) on CD4+T cells significantly reduced the disease phenotype. Further, it blocked the induction of pro-inflammatory T cell frequencies (Th2, Th9, Th17), but increased Treg cells. To translate these findings into a human clinically relevant context, Th2, Th9 and Treg cells were quantified both locally in induced sputum and systemically in blood of allergic rhinitis and asthma patients with or without allergen-specific immunotherapy (AIT). Natural allergen exposure induced local and systemic Th2, Th9, and reduced Tregs cells, while therapeutic allergen exposure by AIT suppressed Th2 and Th9 cell frequencies along with TGF-β and IL-9 secretion. Altogether, these findings support that neutralization of TGF-β represents a viable therapeutic option in allergy and asthma, not posing the risk of immune dysregulation by impacting Tregs cells.

Allergen-specific immunotherapy (AIT) is the only currently available curative treatment option for allergic diseases. AIT often includes depot-forming and immunostimulatory adjuvants, to prolong allergen presentation and to improve therapeutic efficacy. The use of aluminium salts in AIT, which are commonly used as depot-forming adjuvants, is controversially discussed, due to health concerns and Th2-promoting activity. Therefore, there is the need for novel delivery systems in AIT with similar therapeutic efficacy compared to classical AIT strategies. In this study, a triblock copolymer (hydrogel) was assessed as a delivery system for AIT in a murine model of allergic asthma. We show that the hydrogel combines the advantages of both depot function and biodegradability at the same time. We further demonstrate the suitability of hydrogel to release different bioactive compounds in vitro and in vivo. AIT delivered with hydrogel reduces key parameters of allergic inflammation, such as inflammatory cell infiltration, mucus hypersecretion, and allergen-specific IgE, in a comparable manner to standard AIT treatment. Additionally, hydrogel-based AIT is superior in inducing allergen-specific IgG antibodies with potentially protective functions. Taken together, hydrogel represents a promising delivery system for AIT that is able to combine therapeutic allergen administration with the prolonged release of immunomodulators at the same time.

BACKGROUND:Dietary carbohydrates and fats are intrinsically correlated within the habitual diet. We aimed to disentangle the associations of starch and sucrose from those of fat, in relation to allergic sensitization, asthma and rhinoconjuctivitis prevalence in humans, and to investigate underlying mechanisms using murine models.METHODS:Epidemiological data from participants of two German birth cohorts (age 15) were used in logistic regression analyses testing cross-sectional associations of starch and sucrose (and their main dietary sources) with aeroallergen sensitization, asthma and rhinoconjunctivitis, adjusting for correlated fats (saturated, monounsaturated, omega-6 and omega-3 polyunsaturated) and other covariates. For mechanistic insights, murine models of aeroallergen-induced allergic airway inflammation (AAI) fed with a low-fat-high-sucrose or -high-starch versus a high-fat diet were used to characterize and quantify disease development. Metabolic and physiologic parameters were used to track outcomes of dietary interventions and cellular and molecular responses to monitor the development of AAI. Oxidative stress biomarkers were measured in murine sera or lung homogenates.RESULTS:We demonstrate a direct association of dietary sucrose with asthma prevalence in males, while starch was associated with higher asthma prevalence in females. In mice, high-carbohydrate feeding, despite scant metabolic effects, aggravated AAI compared to high-fat in both sexes, as displayed by humoral response, mucus hypersecretion, lung inflammatory cell infiltration and TH 2-TH 17 profiles. Compared to high-fat, high-carbohydrate intake was associated with increased pulmonary oxidative stress, signals of metabolic switch to glycolysis and decreased systemic anti-oxidative capacity.CONCLUSION:High consumption of digestible carbohydrates is associated with an increased prevalence of asthma in humans and aggravated lung allergic inflammation in mice, involving oxidative stress-related mechanisms.