Search

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 T H 2-T H 17-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., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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 T H 2-T H 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., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

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., Competing Interests: UZ received payment for manuscripts from Deutsches Aerzteblatt and funds for travel from the European Academy of Allergy and Clinical Immunology (EAACI) and Collegium Internationale Allergologicum (CIA). CS-W received support for research projects from PLS Design, LETI, Zeller AG, and Allergopharma and accepted honoraria for consultancy and seminars from LETI and Allergopharma. He also received travel support from EAACI. AC has consultant arrangements through Technical University Munich with Allergopharma, ALK-Abello, HAL Allergy, Mundipharma, and Lofarma; has conducted clinical studies and received research grants through Technical University Munich from Allergopharma, Novartis, the German Federal Environmental Agency, Bencard/Allergen Therapeutics, ASIT Biotech, and Zeller AG; has received payment for lectures from Allergopharma, ALK-Abello, and GlaxoSmithKline; has received payment for manuscript preparation from Bayerisches Ärzteblatt; and has received travel support from the European Academy of Allergy and Clinical Immunology (EAACI), DGAKI, and SMI. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Musiol, Alessandrini, Jakwerth, Chaker, Schneider, Guerth, Schnautz, Grosch, Ghiordanescu, Ullmann, Kau, Plaschke, Haak, Buch, Schmidt-Weber and Zissler.)

Asthma is a heterogeneous disease with increasing prevalence worldwide characterized by chronic airway inflammation, increased mucus secretion and bronchial hyperresponsiveness. The phenotypic heterogeneity among asthmatic patients is accompanied by different endotypes, mainly Type 2 or non-Type 2. To investigate the pathomechanism of this complex disease many animal models have been developed, each trying to mimic specific aspects of the human disease. Rodents have classically been employed in animal models of asthma. The present review provides an overview of currently used Type 2 vs. non-Type 2 rodent asthma models, both acute and chronic. It further assesses the methods used to simulate disease development and exacerbations as well as to quantify allergic airway inflammation, including lung physiologic, cellular and molecular immunologic responses. Furthermore, the employment of genetically modified animals, which provide an in-depth understanding of the role of a variety of molecules, signaling pathways and receptors implicated in the development of this disease as well as humanized models of allergic inflammation, which have been recently developed to overcome differences between the rodent and human immune systems, are discussed. Nevertheless, differences between mice and humans should be carefully considered and limits of extrapolation should be wisely taken into account when translating experimental results into clinical use., (Copyright © 2020 Alessandrini, Musiol, Schneider, Blanco-Pérez and Albrecht.)