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Asthma is quite heterogenous and can be categorized as eosinophilic, mixed granulocytic (presence of both eosinophils and neutrophils in the airways) and neutrophilic. Clinically, mixed granulocytic asthma (MGA) often tends to be severe and requires large doses of corticosteroids. High mobility group box 1 (HMGB1) is one of the epithelium-derived alarmins that contributes to type 2 inflammation and asthma. This study was aimed to investigate the role of glucose transporter 1 (GLUT1) in modulation of airway epithelial HMGB1 production in MGA. Induced sputum and bronchial biopsy specimens were obtained from healthy subjects and asthma patients. BALB/c mice, the airway epithelial cell line BEAS-2B, or primary human bronchial epithelial cells (HBECs) were immunized with allergens. Intracellular and extracellular HMGB1 were both detected. The role of GLUT1 was assessed by using a pharmacological antagonist BAY876. MGA patients have a significant higher sputum HMGB1 level than the health and subjects with other inflammatory phenotypes. Nuclear-to-cytoplasmic translocation of HMGB1 was also observed in the bronchial epithelia. Allergen exposure markedly induced GLUT1 expression in murine lungs and cultured epithelial cells. Pharmacological antagonism of GLUT1 with BAY876 dramatically decreased airway hyperresponsiveness, neutrophil and eosinophil accumulation, as well as type 2 inflammation in murine models of MGA. Besides, the allergen-induced up-regulation of HMGB1 was also partly recovered by BAY876, accompanied by inhibited secretion into the airway lumen. In vitro, treatment with BAY876 relieved the allergen-induced over-expression and secretion of HMGB1 in airway epithelia. Taken together, our data indicated that GLUT1 mediates bronchial epithelial HMGB1 release in MGA., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

In the context of global warming and rapid urbanization, pollen has become a significant public health concern for Chinese citizens. However, there is a paucity of epidemiological research on the impact of pollen on allergen-linked diseases, such as allergic rhinitis and asthma, in China. Using data from the Beijing Chaoyang Hospital between 2013 and 2019, which included allergic rhinitis and asthma incidence, meteorological records, and air pollution data, we employed a Generalized Additive Model (GAM) to examine the relationship between overall and type-specific pollen concentrations in relation to varying population exposures. We found that increased overall pollen concentrations significantly increased the risks of allergic rhinitis and asthma in diverse populations. Notably, the risk of allergic rhinitis was higher than that of asthma at equivalent pollen concentrations. Seasonal trends indicated that spring pollen peaks, primarily from trees, were associated with a lower risk of both allergic rhinitis and asthma than autumn peaks, predominantly from weeds. This study underscores the importance of identifying pollen species that pose heightened risks to different demographic groups across seasons, thereby providing targeted interventions for public health agencies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Fungal sensitization is highly prevalent in severe asthma. The relationship between fungus and asthma, especially Aspergillus fumigatus, has been the subject of extensive research. The ubiquitous presence of A. fumigatus, its thermotolerant nature, the respirable size of its conidia, and its ability to produce potent allergens are pivotal in worsening asthma control. Due to the diverse clinical manifestations of fungal asthma and the lack of specific biomarkers, its diagnosis remains intricate. Diagnosing fungal asthma requires carefully assessing the patient's clinical history, immunological tests, and imaging. Depending on the severity, patients with fungal asthma require personalized treatment plans, including inhaled corticosteroids and bronchodilators, and antifungal therapy. This review provides a comprehensive overview of the association between Aspergillus and asthma by reviewing the relevant literature and highlighting key findings. We discuss the diagnosis of various entities included in fungal asthma. We also debate whether newer definitions, including allergic fungal airway disease, offer any additional advantages over the existing ones. Finally, we provide the current treatment options for the individual entities, including A. fumigatus-associated asthma, severe asthma with fungal sensitization, and allergic bronchopulmonary mycoses., (Copyright © 2023 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Combined allergic rhinitis and asthma syndrome (CARAS) is an allergic airway inflammatory disorder orchestrated by the type 2 immune response. The close gut-lung relationship has been described, however, the effect of gut-modulating agents such as probiotics in allergic airway disorder is unclear. Thus, the goal of this study was to evaluate theLimosilactobacillus fermentumsupplementation in animals with CARAS. Therefore, BALB/c mice were ovalbumin (OVA) -sensitized and -challenged after being supplemented withL. fermentum. Animals, previously probiotic supplemented, showed a decrease (p < 0.05) of inflammatory cell migration, mainly eosinophil, into the nasal (NALF) and the bronchoalveolar (BALF) fluids as well as reduction of the allergic signs such as sneezing, nasal rubbings, and nasal hyperreactivity induced by histamine as compared with non-supplemented animals. In the systemic context,L. fermentumreduced eosinophilia and the serum levels of OVA-specific IgE. The altered histological aspects of nasal and lung tissues of animals with CARAS were effectively ameliorated byL. fermentum. In the BALF, the immunomodulatory effect was due to the decreasing of type 2 and 3 cytokines (IL-4, IL-13, IL-5 and IL-17A) dependent on type 1 (IFN-γ) and Treg (IL-10) cytokine increasing. Indeed,L. fermentumimproved the FOXP3 activation. Additionally, these effects correlate with the amplification of the gut response as increasing short-chain fatty acids (SCFAs) levels, gut epithelium barrier (ZO-1) maintenance, and colon tissue integrity. These data pointed out that animals' probiotic supplemented presented immunomodulatory responses in CARAS experimental model by activating the intracellular transduction signal underlying the IL-10 gene transcription., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

The grass family is responsible for most of peoples pollen allergies, and the severity of pollen-based asthma and allergies is expected to increase with global climate change. Identifying grass species through standard pollen monitoring techniques have limitations due to challenges in species-specific pollen identification. As a result, these monitoring methods end up grouping all Poaceae species together, even though there are hundreds of grass species in Europe with flowering times that may vary drastically among species. Given this lack of specificity, it is hard to know which grass species are responsible for causing allergies over the pollen season, and how different species are affected by climate change. To address these issues, we obtained phenological data from thousands of herbarium specimens collected across Denmark spanning 190 years and used pollen monitoring data collected over the last four decades to determine the response of flowering time to climate change for 12 allergenic grass species, and identify which species are likely the biggest contributors to grass pollen loads throughout the pollen season. We find that pollen season duration is lasting longer and starting earlier, and the maximum pollen loads are occurring earlier in response to climate warming. Herbarium specimens provide taxonomic resolution and reveal that many grass species are flowering earlier in response to warmer spring temperatures. Seven out of the 12 species studied in Denmark are identified as major contributors to airborne pollen based on their flowering times, relative abundance and overlap with the time of the year when maximum pollen loads are detected. Four species (Poa pratensis, Dactylis glomerata, Festuca rubra, Holcus lanatus) significantly shifted their flowering time in response to warming temperatures and are flagged as of particular concern to allergy sufferers. Using data derived from natural history collections can contribute to the advancement of pollen forecasting for asthma and allergy patients under both current conditions and amidst future global changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The reliance of modern society on indoor environments increasing has made them crucial sites for human exposure to microbes. Extensive research has identified ecological drivers that influence indoor microbial assemblages. However, few studies have examined the dispersion of microbes in different locations of identical indoor environments. In this study, we employed PacBio Sequel full-length amplicon sequencing to examine the distribution of microbes at distinct locations in a single home and to identify the potential pathogens and microbial functions. Microbial communities differed considerably among the indoor sampling sites (P < 0.05). In addition, bacterial diversity was influenced by human activities and contact with the external environment at different sites, whereas fungal diversity did not significantly differ among the sites. Potential pathogens, including bacteria and fungi, were significantly enriched on the door handle (P < 0.05), suggesting that door handles may be hotpots for potential pathogens in the household. A high proportion of fungal allergens (34.37 %-56.50 %), which can cause skin diseases and asthma, were observed. Co-occurrence network analysis revealed the essential ecological role of microbial interactions in the development of a healthy immune system. Overall, we revealed the differences in microbial communities at different sampling sites within a single indoor environment, highlighting the distribution of potential pathogens and ecological functions of microbes, and providing a new perspective and information for assessing indoor health from a microbiological viewpoint., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Women show an increased prevalence of adult-onset asthma compared to men and previous studies have shown that testosterone inhibits while estrogen worsens allergen-induced airway inflammation. However, detailed knowledge about the aggravating effects of estrogen on immune responses remain unclear. Defining the effects of physiological levels of estrogen on immune responses in asthma would aid in the development of improved treatment strategies. In this study, the importance of estrogen for the sex difference in asthma was determined using a murine model of house dust mite (HDM)-induced airway inflammation on intact female and male mice, as well as on ovariectomized (OVX) female mice treated with a physiological dose of 17β-estradiol (E2). Innate and adaptive immune responses were defined in bronchoalveolar lavage fluid, mediastinal lymph node (mLN) and lung tissue. The results reveal increased numbers of lung eosinophils, macrophages, and dendritic cells in female but not in male mice after HDM challenge. Females also exhibit higher numbers of Th17 cells in both mLN and lung in response to HDM. However, treatment of OVX mice with physiological levels of E2 does not influence any of the analyzed cell populations. Together, this study confirms the previously reported sex difference in allergen-induced airway inflammation and show that female mice mount stronger innate and adaptive immune responses to HDM challenge, but these effects are not mediated by physiological levels of E2., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Allergen specific immunotherapy (AIT) is the only causal therapeutic option for allergic airway diseases including asthma and allergic rhinitis. AIT has been shown to restore the allergen immune tolerance, can modify both the early and late-onset allergen-specific airway hyperreactivity, helps to achieve disease control/remission and prevents new sensitisations. Recent real life data on long-term effectiveness of house dust mite (HDM) AIT in a large group of patients with HDM-driven asthma further underscored its unique therapeutic potential as well as confirmed previous data with pollen AIT. More widespread use of this causal treatment in select patient populations should further move this promising therapeutic field. In this mini-review, we discuss updates on new insights based on real world patient data., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

When exposed to convective thunderstorm conditions, pollen grains can rupture and release large numbers of allergenic sub-pollen particles (SPPs). These sub-pollen particles easily enter deep into human lungs, causing an asthmatic response named thunderstorm asthma (TA). Up to now, efforts to numerically predict the airborne SPP process and to forecast the occurrence of TAs are unsatisfactory. To overcome this problem, we have developed a physically-based pollen model (DREAM-POLL) with parameterized formation of airborne SPPs caused by convective atmospheric conditions. We ran the model over the Southern Australian grass fields for 2010 and 2016 pollen seasons when four largest decadal TA epidemics happened in Melbourne. One of these TA events (in November 2016) was the worldwide most extreme one which resulted to nine deaths and hundreds of hospital patient presentations. By executing the model on a day-by-day basis in a hindcast real-time mode we predicted SPP peaks exclusively only when the four major TA outbreaks happened, thus achieving a high forecasting success rate. The proposed modelling system can be easily implemented for other geographical domains and for different pollen types., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Asthma is one of the most common chronic diseases. In many cases it is preceded by the development of an immune response to allergens such as animal fur, dust, pollens and etc. In human population this disease is heterogeneous, and no selective drugs are available at the moment for some endotypes of asthma. The role of the adaptive immune system in the pathogenesis of asthma was extensively studied, while the role of innate immune cells, in particular myeloid cells, was not sufficiently addressed. Myeloid cells, such as macrophages and dendritic cells, are characterized by high plasticity, heterogenicity and ability to undergo polarization in response to various pathogenic stimuli, including those engaging innate immune receptors. Recently, special attention was drawn to the link between polarization of macrophages and cell metabolism. We hypothesized that immunometabolic reprogramming of myeloid cells, in particular, of macrophages and dendritic cells during sensitization with an allergen may affect further immune response and asthma development. To test this hypothesis, we generated distinct types of myeloid cells in vitro from murine bone marrow and analyzed their immunometabolic profiles upon activation with house dust mite extract (HDM) and its key active components. We found that the combination of lipopolysaccharide (LPS) and beta-glucan is sufficient to upregulate proinflammatory cytokine production as well as respiratory and glycolytic capacity of myeloid cells, comparably to HDM. This specific immunometabolic phenotype was associated with altered mitochondrial morphology and possibly with increased ROS production in macrophages. Moreover, we found that both TNF production and metabolic remodeling of macrophages in response to HDM are TLR4-dependent processes. Altogether, these results expand our understanding of molecular mechanisms underlying asthma induction and pathogenesis and may potentially lead to new therapeutic strategies for the treatment of this disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Asthma affects over 300 million people globally and is a cause of substantial burden of disease, including both premature death and reduced quality of life in people of all ages. Although both genetic and environmental factors play an important role in the pathogenesis of asthma, the rising trend of asthma and other allergic diseases over recent decades is thought to be largely caused by alteration in environmental conditions. Thus, a considerable amount of attention has been paid to environmental modification for the treatment and management of asthma, including household allergen reduction and/or irritant removal. More advanced environmental modification strategies (e.g., health resort medical rehabilitation, high-altitude climate therapy and multiple-hit interventions) have also been suggested. Research advances have been made over the past decades, but major challenges and opportunities coexist in this emerging field. Concerted efforts are required to tackle these formidable challenges., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: House dust mite allergy constitutes a risk factor for asthma development and is associated with a faster decline of lung function in allergic asthmatics (AAs). To evaluate the effect of Dermatophagoides pteronyssinus (Dp) allergens on the expression of genes involved in inflammation and tissue remodeling by peripheral blood mononuclear cells (PBMCs) isolated from the blood of AAs., Materials and Methods: The cells from AAs, allergic rhinitis without asthma patients (ARs), and healthy controls (HCs) were cultured in the presence of Dp, lipopolysaccharide (LPS), or without any stimulation. The expression of 84 genes was evaluated using a low-density microarray whereas, the quantitative expression analysis of selected genes was performed using a real-time polymerase chain reaction. The concentration of selected proteins in the cell culture supernatants was assessed using ELISA., Results: Stimulation of PBMCs with Dp and LPS resulted in a significant upregulation of 8 and 15 among 84 studied genes, respectively. The greatest upregulation was observed for CCL2 and CCL3 using Dp and LPS, respectively. In comparison with HCs, in AAs, significantly increased upregulation of CCL2 in response to Dp was found. The secretion of CCL2 and CCL3 by PBMCs reflected the pattern of gene expression at the mRNA level. The mean Dp-stimulated secretion of CCL2 by PBMCs of ARs was less than in AAs (p ​< ​0.01), both being notably greater than in the HCs (p ​< ​0.01)., Conclusion: Rapid and potent upregulation of CCL2 expression by PBMCs in response to Dp may constitute an important contribution to the development of allergic asthma., Competing Interests: Declaration of competing interest KK received a lecture fee from: ALK Abello, Astra Zeneca, Berlin Chemie, Emma, Hal Allergy, Orion Pharma, TEVA Pharmaceuticals and royalties from UpToDate. PB, AP and HZ declare no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Benefits for vitamin E intake in diseases with inflammatory components have been described and related in part, to endogenously formed metabolites (long-chain metabolites, LCM). Here, we have evaluated the role of LCM in relieving asthma features. To this aim, the endogenous vitamin E metabolite α-13'-carboxychromanol (α-T-13'-COOH) that acts as potent 5-lipoxygenase inhibitor has been administered either intraperitoneally or by oral gavage to BALB/c mice sensitized by subcutaneous injection of ovalbumin (OVA). We also have taken advantage of the metabolically stable α-T-13'-COOH derivative α-amplexichromanol (α-AC). Intraperitoneal treatment with α-T-13'-COOH reduced OVA-induced airway hyperreactivity (AHR) as well as peri-bronchial inflammatory cell infiltration. α-AC was more efficacious than α-T-13'-COOH, as demonstrated by better control of AHR and in reducing subepithelial. Both compounds exerted their protective function by reducing pulmonary leukotriene C 4 levels. Beneficial effects of α-AC were coupled to inhibition of the sensitization process, as indicated by a reduction of IgE plasma levels, lung mast cell infiltration and Th2 immune response. Metabololipidomics analysis revealed that α-AC raises the pulmonary levels of prostanoids, their degradation products, and 12/15-lipoxygenase metabolites. Following oral administration, the pharmacodynamically different profile in α-T-13'-COOH and α-AC was abrogated as demonstrated by a similar and improved efficacy in controlling asthma features as well as by metabololipidomics analysis. In conclusion, this study highlights a role for LCM and of vitamin E derivatives as pharmacologically active compounds that ameliorate asthmatic features and defines an important role for endogenous vitamin E metabolites in regulating immune response underlying the sensitization process., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Allergen-specific immunoglobulins have a crucial role in allergic diseases. Most wheeze episodes develop before school age, and allergic rhinitis later develops during early elementary school years. However, the clinical background and cytokine/chemokine profiles associated with changes in immunoglobulins during early school-age are poorly understood., Methods: This study used blood samples from children participating in the JECS Pilot Study. We examined nineteen kinds of aeroallergen-specific immunoglobulins (IgE, IgG1, IgG4, and IgA) levels in patients at age 6 and age 8. Fluctuations of Der f 1- and Cry j 1-specific immunoglobulins levels during the two periods were compared to assess the frequency of allergic statuses and clusters of cytokine/chemokine profiles., Results: The medians of aeroallergen-specific IgE levels did not fluctuate, and almost all IgG1 and IgG4 decreased. In IgA, four (e.g., Der f 1) increased, whereas the other four (e.g., Cry j 1) decreased. The ratio of the Der f 1-specific IgG1 level at age 8 to that at age 6 was higher in children with poor asthma control than in children with better asthma control. Moreover, the cytokine/chemokine cluster with relatively lower IL-33 and higher CXCL7/NAP2 was associated with lower Der f 1- and Cry j 1-specific IgG4 levels, but not IgE levels., Conclusions: The cluster of cytokine/chemokine profiles characterized by lower IL-33 and higher CXCL7/NAP2 was associated with the maintenance of aeroallergen-specific IgG4 levels. This result provides a basis for considering the control of aeroallergen-specific immunoglobulins., (Copyright © 2022 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the airways. The majority of patients with mild to moderate BA develop Th2-biased eosinophilic pulmonary inflammation and respond well to corticosteroid treatment. However up to 10% of BA patients develop severe pathology, which is associated with neutrophilic inflammation and resistant to conventional corticosteroid therapy. Contrary to eosinophil-predominant airway inflammation neutrophilic BA is developed through Th1- and Th17-immune responses. However, the etiology of corticoid insensitive neutrophilic BA is still remains unclear. Therefore, in the current study we developed a mouse model of BA with predominant neutrophilic rather than eosinophilic pulmonary inflammation. BALB/c mice were immunized with the mixture of the ovalbumin allergen and Freund's adjuvant, followed by aerosol challenge with the same allergen mixed with E. coli lipopolysaccharide. As a result, mice developed the main BA manifestations: production of allergen specific IgE, development of airway hyperreactivity, airway remodeling and pulmonary neutrophilic inflammation. Moreover, this pathology developed through Th1- and Th17-dependent mechanisms and mice with induced neutrophilic BA phenotype responded poorly to dexamethasone treatment, that coincide to clinical observations. The established mouse model could be useful both for studying the pathogenesis and for testing novel approaches to control neutrophilic BA., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Respiratory tract infection early in life plays a significant role in the pathogenesis of asthma. In the present study we examine, using a murine surrogate, the effects of early life respiratory infection with Streptococcus pneumoniae (SP) on adult asthma induced by sensitisation and exposure to house dust mite (HDM) allergen. Mice (one week old) were infected with SP, then 3 weeks later sensitised to HDM emulsified with Al (OH)3 intraperitoneally and challenged intranasally with same allergen for up to a further 5 weeks to establish the asthma surrogate. Outcome measures were quantified using the FlexiVent apparatus, histology and immunohistology, ELISA and flow cytometry. The murine surrogates of asthma infected with SP early in life exhibited significantly more severe disease compared with the controls of mice without SP infection, as shown by airways responsiveness, inflammatory cellular infiltration of the airways, expression of markers of airways remodelling, serum concentrations of HDM-specific IgE and the concentrations of Th2-type cytokines and the numbers of activated Th2 and ILC2 cells in the lung tissues. These data are compatible with the hypothesis that early-life infection of the airways with SP exacerbates, at least in some individuals, subsequent HDM-induced allergic airways inflammation and associated asthma in adulthood in this murine surrogate., (Copyright © 2022. Published by Elsevier Inc.)

Immune responses that result in asthma exacerbation are associated with allergen or viral exposure. Identification of common immune factors will be beneficial for the development of uniformed targeted therapy. We employed a House Dust Mite (HDM) mouse model of asthma and challenged allergic HDM mice with allergens (HDM, cockroach extract (CRE)) or respiratory syncytial virus (RSV). Purified lung immune cells underwent high-dimensional single-cell RNA deep sequencing (scRNA-seq) to generate an RNA transcriptome. Gene silencing with siRNA was employed to confirm the efficacy of scRNA-seq analysis. scRNA-seq UMAP analysis portrayed an array of cell markers within individual immune clusters. SCENIC R analysis showed an increase in regulon number and activity in CD11b - DC cells. Analysis of conserved regulon factors further identified Creb5 as a shared regulon between the exacerbation groups. Creb5 siRNAs attenuated HDM, CRE or RSV-induced asthma exacerbation. scRNA-seq multidimensional analysis of immune clusters identified gene pathways that were conserved between the exacerbation groups. We propose that these analyses provide a strong framework that could be used to identify specific therapeutic targets in multifaceted pathologies., (© 2022. The Author(s).)

Background: the built environment in urban areas may have side effects on children's respiratory health, whilst less is known for adulthood., Aim: to assess the association between increasing exposure to grey spaces and allergic status in an adult general population sample., Methods: 2070 subjects (age range 15-84 yrs), living in Pisa/Cascina, Italy, were investigated in 1991-93 through a questionnaire on health status and risk factors, skin prick test (SPT), serum Immunoglobulins E (IgE), and serum antibodies to benzo(a)pyrene diol epoxide (BPDE)-DNA adducts. Land-cover exposure within a 1000 m buffer from each subject's home address was assessed through the CORINE Land Cover program (CLC 1990) within the FP7/HEALS project (2013-2018). Participants' residential addresses were geocoded and the proportion of surrounding grey spaces was calculated. Through logistic regression models, adjusting for potential confounding factors, the effect of a 10% increase in grey spaces exposure on allergic biomarkers/conditions was assessed; the relationship with serum antibodies to BPDE-DNA adducts positivity was also analyzed., Results: A 10% increase in grey spaces coverage was associated with a higher probability of having SPT positivity (OR 1.07, 95% CI 1.02-1.13), seasonal SPT positivity (OR 1.12, 1.05-1.19), polysensitization (OR 1.11, 1.04-1.19), allergic rhinitis (OR 1.10, 1.04-1.17), co-presence of SPT positivity and asthma/allergic rhinitis (OR 1.16, 1.08-1.25), asthma/allergic rhinitis (OR 1.06, 1.00-1.12), presence of serum antibodies to BPDE-DNA adducts positivity (OR 1.07, 1.01-1.14)., Conclusions: grey spaces have adverse effects on allergic status and are related to a biomarker of polycyclic aromatic hydrocarbons exposure in adulthood. Thus, they may be used as a proxy of urban environmental exposure., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: The role of infectious agents in allergy development is ambivalent. On one hand, there are reports of an association between a previous infection (especially a viral respiratory tract infection) and developing hypersensitivity to inhaled allergens, which in turn may increase the risk of developing allergic reactions. On the other hand, there are reports emphasizing a protective effect of a number of infectious agents against allergy development. The aim the study was to find possible associations between a past infectious or parasitic disease and an allergic condition., Material and Methods: The study population was a group of 18,648 subjects. The study, which was a part of the project: 'Implementation of a System for the Prevention and Early Detection of Allergic Diseases in Poland', was conducted in 9 selected regions of Poland and used the ECRHS and ISAAC questionnaires adapted for Europe. The following statistical tools were used: Pearson's chi-squared test, Fisher's exact test, and logistic regression., Results: This research was an attempt to clear association between a history of measles or viral hepatitis and the likelihood of developing asthma, especially in males (χ 2 = 5.29; p<0.05). Past parasitic disease showed a clear association with a suspected allergic rhinitis in various groups of patients (differing both in terms of sex and age)., Conclusions: A history of some forms of either infectious or parasitic diseases has a measurable effect on the risk of developing allergies., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2021 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Pollinosis and allergic asthma are respiratory diseases of global relevance, heavily affecting the quality of life of allergic subjects. Since there is not a decisive cure yet, pollen allergic subjects need to avoid exposure to high pollen allergens concentrations. For this purpose, pollen forecasting is an essential tool that needs to be reliable and easily accessible. While forecasting methods are rapidly evolving towards more complex statistical and physical models, the use of simple and traditional methods is still preferred in routine predictions. In this review, we summarise and explain the main parameters considered when forecasting pollen, and classify the different forecasting methods in two groups: observation-based and process-based. Finally, we compare these approaches based on their usefulness to allergic patients, and discuss possible future developments of the field., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Potential triggers for equine asthma are allergens from hay and straw dusts, mold spores and storage mites. The contribution of these environmental trigger factors to equine asthma is still largely uncertain. The aim of this study was to compare results of four allergy tests from healthy and asthma-affected horses, and to evaluate the clinical relevance of allergens tested positive via specific inhalation provocation test. Fifteen horses were classified using a clinical scoring system as asthmatic (n = 9) or control (n = 6). Four different allergy tests (functional in vitro test, intradermal test, Fc-epsilon receptor test, and ELISA for allergen-specific IgE) were compared. A histamine inhalation provocation test as positive control was performed in all horses and the interpleural pressure was measured. In addition, two individual allergens were chosen for the allergen inhalation provocation test based on the results of the allergy tests and inhaled in increasing concentrations, until signs of dyspnea occurred. None of the four allergy tests could differentiate reliably between controls and asthma-affected horses. There was no agreement among the results of the four allergy tests. The interpleural pressure results showed a large individual variability. A clear positive reaction on the allergen inhalation provocation test was only detected in two asthma-affected horses 6 hours after allergen inhalation with Aspergillus fumigatus and Cladosporium herbarum. In most cases a purely type I immediate reaction is unlikely to be involved in causing the clinical signs of equine asthma. Because of a delayed reaction after allergen provocation in two horses, the involvement of cell-mediated type III or IV hypersensitivity may be possible. As all allergy tests used in this study can only detect IgE-mediated hypersensitivity, these tests are probably not suitable for an etiological diagnosis of equine asthma., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Exposure to environmental pollutants such as diesel exhaust particles (DEP) increases the risk of asthma and asthma exacerbation. However, the exact mechanisms inducing asthma to low doses of allergens remain poorly understood. The present study aimed to analyse the immunomodulatory effect of the inhalation of DEP in a mouse model exposed to non-asthmagenic doses of soybean hull extract (SHE)., Material and Methods: BALB/c ByJ mice were randomly divided into four experimental groups. Two groups received nasal instillations of saline and the other two groups received 3 mg ml -1 SHE during 5 days per week for 3 weeks. One group in each pair also received 150 μg of DEP in the same instillations 3 days per week. SHE-specific IgE levels, oxidative stress, leukocyte pattern and optical projection tomography (OPT) imaging studies were assessed., Results: Inhalation of SHE and/or DEP increased levels of H 2 O 2 in BAL, while coexposure to SHE and DEP increased SHE-specific IgE levels in serum. Inhalation of SHE alone increased eosinophils, B cells, total and resident monocytes and decreased levels of NK cells, while inhalation of DEP increased neutrophils and decreased total monocytes. Regarding dendritic cells (DC), the inhalation of SHE and/or DEP increased the total population, while the inhalation of SHE alone increased Th2-related DCs (CD11b + Ly6C-) and decreased tolerogenic DCs (CD11b-Ly6C-). However, coexposure to SHE and DEP increased oxidative stress-sensitive DCs (CD11b-Ly6C+) and decreased Th1-related DCs (CD11b + Ly6C+). As regards macrophages, inhalation of SHE and DEP decreased total and alveolar populations. DEP deposition in lung tissue did not differ between groups., Conclusion: Coexposure to DEP activates the asthmatic response to low doses of soy by triggering the immune response and oxidative stress., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: In epidemic thunderstorm asthma (ETSA) events a large number of people develop asthma symptoms over a short period of time. This is thought to occur because of a unique combination of high amounts of pollen and certain meteorological conditions. However, the exact cause and mechanism of epidemic thunderstorm asthma remains unclear., Objectives: The objective of this study was to test the hypothesis that convergence lines may be a causative factor in ETSA events, by investigating whether convergence line weather events are associated with the occurrence of high asthma presentations days during the Victorian grass pollen season (October-December)., Methods: A case control method was used. All public hospitals within 75 km of the Melbourne weather radar were included, and data were taken from 2009 to 2017 during the Victorian grass pollen season. Cases hospital days were hospitals with a high number of asthma presentations within a 24-h period, and controls were hospitals with an expected number of asthma presentations. Exposure was defined as geographical proximity of a convergence line to the hospital case or control., Results: Eighty-one case hospital days and 157 hospital day controls were included in the study. The odds of exposure to a convergence line were significantly higher for cases than for controls at all exposure distances. At 4 km, 80 of the 81 cases had been exposed to a convergence line., Conclusion: Convergence lines appear to be a necessary, but not sufficient, element in the cause of epidemic thunderstorm asthma. This is the first study to show a clear link between epidemic thunderstorm asthma and convergence lines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Neutrophils can regulate adaptive immune responses and contribute to chronic inflammation including asthma. However, the roles and mechanisms of neutrophils in initiating eosinophilic airway inflammation remain incompletely understood. Neutrophil elastase (NE) is a component of azurophilic granules and a serine protease with potent functions during inflammation. Here, we showed that neutrophils were early recruited at the onset of asthmatic inflammation by related chemokines. Furthermore, neutrophils could capture allergens and release NE to promote neutrophil aggregation at first. Then they prompt eosinophil infiltration and amplify type 2 immune responses in later phases. Also, this process can be rescued by administration of the NE inhibitor (GW311616). Our data collectively indicate that neutrophils could contribute to asthmatic inflammation by releasing NE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Thunderstorm asthma is defined as epidemics of asthma occurring shortly after a thunderstorm. While grass pollen has been implicated in thunderstorm asthma events, little is known about the role of fungi and studies have not been synthesised., Objective: This systematic review aims to evaluate whether grass pollen is necessary in thunderstorm asthma events and whether fungi also play a part in these associations., Methods: We conducted a systematic search using six electronic databases (i.e. CINAHL, Medline (Ovid), Web of Science, ProQuest Central, EMBASE and Google Scholar) and checked reference lists. The search terms used were pollen AND thunderstorm* AND asthma. The inclusion criteria were studies published in English with original human data relating to outdoor pollen and thunderstorm asthma., Results: Twenty of 2198 studies were eligible. Reported findings differed due to variation in methodological approaches and a meta-analysis was not possible. Nonetheless, of the 20 studies included, 15 demonstrated some relationship with nine demonstrating lagged effects up to four days for increasing grass pollen counts associated with increased risk of thunderstorm asthma. Of the 10 studies that examined fungi, nine demonstrated a positive relationship with thunderstorm asthma. The fungal taxa involved varied, depending on whether measurements were recorded before, during or after the thunderstorm. Nevertheless, none of the studies considered fungi as a potential effect modifier for the pollen-thunderstorm asthma association., Conclusion: We found evidence to suggest that grass pollen was a necessary factor for thunderstorm asthma but there are other as yet unrecognised environmental factors that may also be important. Further research is required to examine the role of fungi and other environmental factors such as air quality as potential effect modifiers of the association., Competing Interests: Declaration of competing interest Michael Abramson holds investigator-initiated grants from Pfizer and Boehringer-Ingelheim for unrelated research. He has also undertaken an unrelated consultancy for Sanofi., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Introduction: In Portugal, data on the role of Der p 1 and Der p 2 in patients with house dust mite (HDM) allergy are scarce. Allergen-specific immunotherapy (sIT) is the only treatment that improves symptoms, reduces the need for pharmacological therapy and modifies the natural history of the disease. With this study, the authors aim to understand the local epidemiology and to clarify if the molecular assay of major allergens is advantageous in deciding and/or modifying the decision to initiate sIT in children with clinical indication which are sensitized to Dermatophagoides pteronyssinus., Methods: Retrospective study with analysis of patients with asthma and/or rhinitis., Study Period: January/2013-December/2016., Inclusion Criteria: 1) positive prick-test to Dermatophagoides pteronyssinus; and 2) clinically relevant disease under treatment. Assay Der p 1 and Der p 2 values ≥0.35 kUA/L were considered positive. Statistical significance was set at P<.05., Results: The clinical files of 279 patients. Mean ages 9.55 years (min.4-max.17). Asthma was present in 199 children (71.3%) and rhinitis in 245 (87.8%). Der p 1 and Der p 2 was <0.35kUA/L in 29 (10,4%) patients. The value of Der p 1/Der p 2 correlated with the size of the prick-test papule, the value of the eosinophils and the total IgE., Conclusions: Der p 1 and Der p 2 are dominant allergens in our population and there may be benefits in determining these molecular allergen levels in patients with a positive prick-test and a clinical indication for sIT prior to a decision of initiating sIT or not., (Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Studies have reported protective and adverse associations between microbial exposure and childhood asthma. However, among children with asthma the relationships between endotoxin and exercise-induced bronchospasm (EIB) is less clear., Objective: We investigated the association between exposure to endotoxin in house dust with atopy and EIB in children with asthma., Methods: A cross-sectional survey was conducted among schoolchildren (aged 7-17 years) in the province of Saskatchewan, Canada. A subpopulation with asthma (n = 116) were identified from 335 participants using a validated asthma algorithm. We determined atopy among the asthma subpopulation by skin prick testing (SPT) while EIB was evaluated using exercise challenge testing (ECT). Dust samples were collected from mattress and play area floors, and endotoxin was measured in dust extracts. Logistic regression analyses were used to explore associations between endotoxin with atopy and EIB., Results: Among the 116 children with asthma, 99 completed SPT and all had completed ECT. Of these, 71/99 (71.7%) were atopic and 26/116 (22.4%) had EIB. Exposure to high play area endotoxin concentration [adjusted odds ratio (aOR) = 0.15, 95% CI: 0.03-0.85] and load (aOR = 0.11, 95% CI: 0.02-0.73) were negatively associated with atopy. In contrast, EIB was positively associated with high mattress endotoxin concentration (aOR = 6.01, 95% CI: 1.20-30.13)., Conclusion: Indoor microbial endotoxin exposure has varied associations with atopy and exercise-induced bronchospasm among children with asthma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Pollen exposure has acute adverse effects on sensitized individuals. Information on the prevalence of respiratory diseases in areas with different pollen concentrations is scanty., Aim: We performed an ecologic analysis to assess whether the prevalence of allergic rhinitis and asthma in young adults varied across areas with different pollen concentrations in Italy., Methods: A questionnaire on respiratory diseases was delivered to random samples of 20-44year-old subjects from six centers in 2005-2010. Data on the daily air concentrations of 7 major allergologic pollens (Poaceae, Urticaceae, Oleaceae, Cupressaceae, Coryloideae, Betula and Ambrosia) were collected for 2007-2008. Center-specific pollen exposure indicators were calculated, including the average number of days per year with pollens above the low or high concentration thresholds defined by the Italian Association of Aerobiology. Associations between pollen exposure and disease prevalence, adjusted for potential confounders, were estimated using logistic regression models with center as a random-intercept., Results: Overall, 8834 subjects (56.8%) filled in the questionnaire. Allergic rhinitis was significantly less frequent in the centers with longer periods with high concentrations of at least one (OR per 10days=0.989, 95%CI: 0.979-0.999) or at least two pollens (OR=0.974, 95%CI: 0.951-0.998); associations with the number of days with at least one (OR=0.988, 95%CI: 0.972-1.004) or at least two (OR=0.985, 95%CI: 0.970-1.001) pollens above the low thresholds were borderline significant. Asthma prevalence was not associated with pollen concentrations., Conclusions: Our study does not support that the prevalence of allergic rhinitis and asthma is greater in centers with higher pollen concentrations. It is not clear whether the observed ecologic associations hold at the individual level., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Viral respiratory infections have been associated with up to 80% of wheezing episodes and asthma exacerbations. However, studies on the role of these viruses in asthmatic patients in the interval between exacerbations are sparse. This study aimed to determine the presence of respiratory viruses, without symptoms of infection, in the airways of young asthmatics as compared to healthy controls., Material and Methods: Patients 10-35 years of age with stable asthma and a group of healthy controls were analyzed regarding the presence of RNA from common respiratory viruses in nasopharyngeal aspirates by PCR. Self-reported asthma control and quality of life, fraction of exhaled nitric oxide (FeNO), spirometry, and bronchial responsiveness to methacholine were recorded. Blood samples were collected to assess IgE sensitisation and eosinophil cationic protein (ECP) levels., Results: In 354 patients with asthma and 108 healthy controls, human rhinovirus (HRV) was the only virus detected (4.5% of asthmatics vs. 0.9% of controls; p = 0.08). HRV(+) asthma patients had a higher degree of aeroallergen IgE sensitisation (median 37.7 vs. 10.4 kUA/L, p = 0.04), and a tendency for higher levels of serum ECP (median 17.2 vs. 12.6 μg/L, p = 0.07), as compared to their HRV(-) counterparts., Conclusions: Absence of symptoms of respiratory tract infection notwithstanding, HRV seems to be more prevalent in the airways of adolescents and young adults with asthma and a high degree of aeroallergen IgE sensitisation than in controls. The presence of HRV seems also to be related to systemic eosinophilic inflammation despite ongoing treatment with inhaled corticosteroids., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Environmental factors may play important roles in asthma, but findings have been inconsistent., Objective: The goal of this study was to determine the associations between early life exposures, environmental factors, and asthma in urban and rural children in southeast China., Methods: A screening questionnaire survey was conducted in 7,164 children from urban Guangzhou and 6,087 from rural Conghua. In the second stage, subsamples of 854 children (419 from Guangzhou, 435 from Conghua) were recruited for a case-control study that included a detailed questionnaire enquiring on family history, early life environmental exposures, dietary habits, and laboratory tests (including histamine airway provocation testing, skin prick tests, and serum antibody analyses). House dust samples from 76 Guangzhou families and 80 Conghua families were obtained to analyze levels of endotoxins, house dust mites, and cockroach allergens., Results: According to the screening survey, the prevalence of physician-diagnosed asthma was lower in children from Conghua (3.4%) than in those from Guangzhou (6.9%) (P < .001). A lower percentage of asthma was reported in rural subjects compared with urban subjects (2.8% vs. 29.4%; P < .001) in the case-control study. Atopy (OR, 1.91 [95% CI, 1.58-2.29]), parental atopy (OR, 2.49 [95% CI, 1.55-4.01]), hospitalization before 3 years of age (OR, 2.54 [95% CI, 1.37-4.70]), high consumption of milk products (OR, 1.68 [95% CI, 1.03-2.73]), and dust Dermatophagoides farinae group 1 allergen (OR, 1.71 [95% CI, 1.34-2.19]) were positively associated with asthma. Living in a crop-farming family at < 1 year of age (OR, 0.15 [95% CI, 0.08-0.32]) and dust endotoxin levels (OR, 0.69 [95% CI, 0.50-0.95]) were negatively associated with asthma., Conclusions: Rural children from an agricultural background exhibited a reduced risk of asthma. Early life exposure to crop farming and high environmental endotoxin levels might protect the children from asthma in southern China., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Kinin B1 receptors are implicated in asthmatic airway inflammation. Here we tested this hypothesis by examining the anti-inflammatory effects of BI113823, a novel non-peptide orally active kinin B1 receptor antagonist in mice sensitized to ovalbumin (OVA). Male Balb-c mice were randomly assigned to four study groups: (1) control, (2) OVA+vehicle, (3) OVA+BI113823, (4) OVA+dexamethasone. Mice were sensitized intraperitoneally with 75μg ovalbumin on days 1 and 8. On days 15-17, mice were challenged intranasally with 50μg of ovalbumin. Mice received vehicle, BI113823, or dexamethasone (positive control) on days 16-18. On day 19, bronchoalveolar lavage (BAL) and lung tissue were collected for biochemical and immuno-histological analysis. Compared to controls treatment with BI113823 significantly reduced the numbers of BAL eosinophils, macrophages, neutrophils and lymphocytes by 58.3%, 61.1%, 66.4% and 56.0%, respectively. Mice treated with dexamethasone showed similar reductions in BAL cells. Treatment with BI113823 and dexamethasone also significantly reduced total protein content, IgE, TNF-α and IL-1β in lavage fluid, reduced myeloperoxidase activity, mucus secretion in lung tissues, and reduced the expression of B1 receptors, matrix metalloproteinase (MMP)-2 and cyclooxygenase (COX)-2 compared to vehicle-treated mice. Only BI113823 reduced MMP-9 and inducible nitric oxide synthase (iNOS). BI113823 effectively reduced OVA-induced inflammatory cell, mediator and signaling pathways equal to or greater than that seen with steroids in a mouse asthma model. BI113823 might be useful in modulating inflammation in asthma., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The role of interleukin (IL)-23 in asthma pathophysiology is still controversial. We examined its role in allergic airway inflammation in response to two distinct antigens using IL-23-deficient mice., Methods: Allergic airway inflammation was evaluated in wild-type and IL-23p19(-/-) mice. Mice were sensitized to ovalbumin (OVA) or house dust mite (HDM) by intraperitoneal injection of antigen and their airways were then exposed to the same antigen. Levels of antigen-specific immunoglobulins in serum as well as cytokines in bronchoalveolar or peritoneal lavage fluid and lung tissue were determined by enzyme-linked immunosorbent assay and/or quantitative polymerase chain reaction., Results: Deficiency of IL-23p19 decreased eosinophils and Th2 cytokines in bronchoalveolar lavage fluid (BALF) of OVA-treated mice, while it increased BALF eosinophils of HDM-treated mice. Peritoneal injection of OVA with alum, but not of HDM, induced local synthesis of IL-6, IL-10, and IL-23. Systemic production of antigen-specific IgG1 was partially dependent on IL-23. In contrast, airway exposure to HDM, but not to OVA, induced IL-23p19 mRNA expression in the lungs. In IL-23p19-deficient mice, HDM-exposed lungs did not exhibit the induction of IL-17A, which negatively regulates eosinophilic inflammation., Conclusions: Different antigens induced IL-23 at different part of the body in our similar asthma models. Endogenous IL-23 production at the site of antigen sensitization facilitates type-2 immune responses, whereas IL-23 production and subsequent IL-17A synthesis in the airways suppresses allergic inflammation., (Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Work-related asthma is common and yet remains a challenge to diagnose. Access to a listing of agents associated with work-related asthma has been suggested as useful in assisting in the diagnosis., Methods: The Association of Occupational and Environmental Clinics (AOEC) developed criteria that were used to review the peer-reviewed medical literature published in English. Based on this review, substances were designated either as a sensitizing agent or an irritant. The reviews were conducted by a board certified internist/pulmonologist/occupational medicine specialist from 2002 to 2007 and a board certified internist/occupational medicine physician from 2008- date. All reviews were then reviewed by the nine member AOEC board of directors., Results: The original list of agents associated with new onset work-related asthma was derived from the tables of a text book on work-related asthma. After 13 years of review, there are 327 substances designated as asthma agents on the AOEC list; 173 (52.9%) coded as sensitizers, 35 (10.7%) as generally recognized as an asthma causing agent, four (1.2%) as irritants, two (0.6%) as both a sensitizer and an irritant and 113(34.6%) agents that still need to be reviewed., Conclusions: The AOEC has developed a readily available web based listing of agents associated with new onset work-related asthma in adults. The listing is based on peer-reviewed criteria. The listing is updated twice a year. Regular review of the peer-reviewed medical literature is conducted to determine whether new substances should be added to the list. Clinicians should find the list useful when considering the diagnosis of work-related asthma., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Inhalation of antigen in atopic asthma induces early (EAR) and late asthmatic responses (LARs), inflammatory cell infiltration and airways hyperresponsiveness (AHR). Previously, we have established a protocol of sensitisation and subsequent ovalbumin (Ova) inhalation challenge in guinea-pigs which induced these 4 features (Smith & Broadley, 2007). However, the responses of guinea-pigs to Ova challenge have recently declined, producing no LAR or AHR and diminished EAR and cells. By making cumulative modifications to the protocol, we sought to restore these features., Methods: Guinea-pigs were sensitised with Ova (i.p. 100 or 150 μg) on days 1 and 5 or days 1, 4 and 7 and challenged with nebulised Ova (100 or 300 μg/ml, 1h) on day 15. Airway function was measured in conscious guinea-pigs by whole-body plethysmography to record specific airway conductance (sGaw). Airway responsiveness to aerosolized histamine (0.3mM) was determined before and 24h after Ova challenge. Bronchoalveolar lavage was performed for total and differential inflammatory cell counts. Lung sections were stained for counting of eosinophils., Results: Lack of AHR and LAR with the original protocol was confirmed. Increasing the Ova challenge concentration from 100 to 300 μg/ml restored AHR and eosinophils and increased the peak of the EAR. Increasing the number of sensitisation injections from 2 to 3 did not alter the responses. Increasing the Ova sensitisation concentration from 100 to 150 μg significantly increased total cells, particularly eosinophils. A LAR was revealed and lymphocytes and eosinophils increased when either the Al(OH)3 concentration was increased or the duration between the final sensitisation injection and Ova challenge was extended from 15 to 21 days., Discussion: This study has shown that declining allergic responses to Ova in guinea-pigs could be restored by increasing the sensitisation and challenge conditions. It has also demonstrated an important dissociation between EAR, LAR, AHR and inflammation., (Copyright © 2014. Published by Elsevier Inc.)

Aim: Lung function tests are essential for the diagnosis and management of bronchial asthma. Impulse oscillation (IOS) system is an alternative way to measure lung mechanics for some patients. We investigated the relative sensitivities of IOS, body plethysmography and spirometry in detecting allergen- and methacholine-induced bronchoconstriction., Method: Twenty-two subjects had single allergen inhalation and 8 subjects had 3 methacholine challenges. The tests were stopped when FEV1 fell by 20%. Lung function was measured using IOS (R5, R20, R5-R20, X5, AX, fres), plethysmography (sRaw, sGaw, FRC, lung volumes) and spirometry (FEV1, FVC, PEF, FEF50%) during inhalation challenges, and expressed as percent change from pre-challenge baseline., Results: All subjects were non-smoking adults with mild allergic asthma. Following allergen challenges, the most sensitive IOS index was R5-R20 and the most sensitive plethysmography and spirometry measurements were sRaw, sGaw and FEF50%. Following methacholine challenge the most sensitive IOS index was AX, the most sensitive plethysmography measurement was sRaw. Overall, IOS (R5-R20, AX, X5Hz) proved to be more sensitive than plethysmography and spirometry measurements following allergen-induced and methacholine-induced bronchoconstriction., Conclusion: Our result shows that IOS is more sensitive than other lung function tests following allergen and methacholine challenge. In addition, IOS can act as an alternative measurement technique of airway resistance and obstruction in patients where manoeuvres involved in plethysmography and spirometry prove difficult to perform., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Pulmonary inflammation causes multiple alterations within the lung, including mucus production, recruitment of inflammatory cells, and airway hyperreactivity (AHR). Measurement of AHR by direct, invasive means (eg, mechanical ventilation) or noninvasive techniques, like whole body plethysmography (WBP), assesses the severity of pulmonary inflammation in animal models of inflammatory lung disease. Direct measurement of AHR is acknowledged as the most accurate method for assessing airway mechanics, but analysis of all data obtained from WBP may offer insights into which inflammatory aspects of the lung are altered along with AHR. Using WBP, we compared the respiratory parameters of two groups of mice sensitized with cockroach allergen. One group was treated with dexamethasone (Dex) before final challenge (Dex-Asthma), while the other group received vehicle treatment (Asthma). Respiratory parameters from plethysmography revealed that Dex-Asthma mice compensated to maintain high minute ventilation, whereas Asthma mice showed significant impairment in minute ventilation despite increased peak expiratory flow (103 ± 5 ml/min vs. 69 ± 70 ml/min). The WBP data suggest that enhanced air exchange in the Dex-Asthma mice results from significant decreases in airway mucus production. Additional studies with quantitative morphometry of histological sections confirmed that Dex reduced airway mucus. In conclusion, a detailed examination of WBP parameters can accurately assess the respiratory health of mice and will help direct additional studies.

Purpose: A considerable body of non clinical evidence has accumulated to support peroxisomal proliferator-activated receptor gamma agonists as candidate anti-inflammatory drugs in asthma. We utilized rosiglitazone as a tool compound in the inhaled allergen challenge model of asthma., Methods: A single centre, double-blind, randomised, placebo controlled, two period cross-over study. Subjects received rosiglitazone 4mg and placebo twice daily for 28 days in random order. On day 28, inhaled allergen challenge was performed 1 hour post-dose. A methacholine challenge was performed on day 29 and an adenosine monophosphate challenge on day 14. Exhaled nitric oxide was measured on days 1, 14, 28, 29. Blood was collected pre dose on days 1, 14 and 28 and analysed for markers associated with PPAR activity and systemic markers of inflammation., Results: The late asthmatic reaction (LAR) change from post saline FEV(1) from 4-10 hrs post allergen on day 28 was statistically significant for the weighted mean LAR. The difference in weighted mean was 0.06 L (95% CI 0.01 to 0.11) which equates to a 15% attenuation of the response during placebo treatment. This was accompanied by trends in other markers of efficacy and anti-inflammatory activity but none were considered major effects., Discussion: Treatment with a PPARgamma agonist (rosiglitazone) was associated with a modest (15%) reduction in the late asthmatic reaction in the allergen challenge model of asthma. Based on the results of this study, PPARgamma agonist monotherapy is unlikely to represent a clinically useful intervention in human asthma. Registered with www.clinicaltrials.gov (NCT00318630).

Objectives: This study aimed at characterizing the nature, severity, and timing of nasal and ocular symptoms in subjects with work-exacerbated asthma (WEA)., Methods: Among the 363 subjects referred to a tertiary-care hospital for the investigation of work-related asthma symptoms, 105 subjects who demonstrated non-specific bronchial hyperresponsiveness to histamine, but a negative response to a specific inhalation challenge with the suspected occupational agent(s) were considered as having WEA. Their characteristics were compared with those of 172 subjects with occupational asthma (OA), ascertained by a positive response to a specific inhalation challenge., Results: A high proportion of subjects with WEA (83%) and OA (90%) reported at least one nasal symptom at work. Sneezing/itching and rhinorrhea were more frequent in subjects with OA (78% and 70%, respectively) than in those with WEA (61%, p = 0.004 and 57%, p = 0.038, respectively), while post-nasal discharge was more common in WEA (30%) than in OA (18%, p = 0.019). Nasal symptoms were less severe in WEA (median [25th-75th percentiles] global severity score: 4 [2-6]) as compared to OA (5 [4-7], p < 0.001). Nasal symptoms preceded less frequently those of asthma in subjects with WEA (17%) than in subjects with OA (43%, p = 0.001)., Conclusions: Nasal symptoms are highly prevalent in subjects with WEA, although their clinical pattern differs from that found in OA. Further investigations of the health and socio-economic impacts of upper airways symptoms in WEA are required to improve the understanding and management of this common condition., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Sauchinone, a lignan compound isolated from the root of Saururus chinensis, has been recently demonstrated to exhibit anti-inflammatory activity via the suppression of NF-kB p65 activity in vitro. In an effort to evaluate the in vivo anti-inflammatory function of sauchinone, we have evaluated the effects of sauchinone on allergen-induced airway inflammation using a murine model of allergic asthma. We observed that marked eosinophilic and lymphocyte infiltration in the BAL fluid were suppressed to a significant degree by sauchinone, and that mucus-secreting goblet cell hyperplasia and collagen deposition in the airways were also ameliorated by administration of sauchinone treatment. Moreover, gene expression of the inflammatory cytokines, IL-13, and IL-5 and eotaxin in the lung, and IL-5 in the draining lymph node were significantly decreased in sauchinone-treated mice. We demonstrated that sauchinone repressed Th2 cell development in vitro and IL-4 production by Th2 cells, and also inhibited GATA-3-mediated IL-5 promoter activity in a dose-dependent manner. Collectively, sauchinone ameliorated allergen-induced airway inflammation, in part, by repressing GATA-3 activity for Th2 cell development, indicating the possible therapeutic potential of sauchinone in airway inflammatory diseases including allergic asthma and rhinitis.

Study Objectives: To investigate the relationship between current and early life factors and airway responsiveness to inhaled methacholine in children with a median age of 7.0 years., Participants: Study subjects were a subset of a prospective birth cohort of children in the Boston area at high risk for atopy., Methods: One hundred thirty-one children underwent both skin-prick testing to a panel of aeroallergens and a methacholine challenge test between 6.5 years and 8.8 years of age. Telephone questionnaires were performed at set intervals, and home dust samples were collected in the first year of life., Results: Of the 131 participating children, 51% (67 patients) had at least one positive skin-prick test response and 28% (37 patients) had airway hyperresponsiveness (AHR) [provocative concentration of methacholine causing a 20% fall in FEV(1) of < 4 mg/mL]. After adjusting for relevant covariates, AHR was strongly associated with sensitization to at least four aeroallergens (odds ratio [OR], 13.41; 95% confidence interval [CI], 3.03 to 59.42). In separate adjusted models, sensitization to cat (OR, 14.73; 95% CI, 3.64 to 59.55), dust mite (OR, 5.13; 95% CI, 1.94 to 13.56), cockroach (OR, 4.00; 95% CI, 1.19 to 13.50), and ragweed (OR, 10.08; 95% CI, 2.31 to 44.10) were significant predictors of AHR. However, no relationship was found with early life exposure to perennial aeroallergens or other perinatal and first-year-of-life factors., Conclusions: Among young children at risk for atopy, sensitization to specific aeroallergens, but not early life exposures, is associated with increased airway responsiveness.

Background: Asthma development and prognosis have been studied extensively in at-risk populations, but knowledge of the natural history of asthma in the general population is limited., Objective: To describe the incidence and remission of asthma and its predictors, data from a 12-year follow-up study of a random population sample (n = 291; age range, 7 to 17 years) at enrollment, were analyzed., Methods: The sample was examined in 1986 and in 1998. A case history, including data on asthma, allergic diseases, and lifestyle factors, was obtained by questionnaire and interview. Airway hyperresponsiveness (AHR) to histamine, lung function, and skin-prick test reactivity to a standard panel of 10 aeroallergens were measured., Results: The point prevalence of asthma increased from 4.1% at the first survey to 11.7% at follow-up, at which point 19.6% of the sample had ever experienced asthma symptoms. Of the subjects with ever-asthma, 40% had remitted at follow-up. Asthma developed in 45 subjects (16.1%) during the follow-up period, which was predicted by the following factors: wheezing in childhood (odds ratio [OR], 3.61; 95% confidence interval [CI], 1.34 to 9.75), AHR (OR, 4.94; 95% CI, 2.42 to 10.08), allergic sensitization to house dust mites (OR, 3.23; 95% CI, 1.00 to 10.40), and dermatitis (OR, 2.94; 95% CI, 1.22 to 7.11). The simultaneous presence of more than one of these risk factors was associated with a high probability of developing asthma at follow-up (61.5%). In subjects without any risk factors, such as AHR, allergic sensitization, rhinitis, dermatitis or wheezing in childhood; paternal/maternal allergy, or asthma, asthma developed in only 4% during follow-up., Conclusion: The presence of AHR and concomitant atopic manifestations in childhood increase the risk of developing asthma in adulthood, and should be recognized as markers of prognostic significance, whereas the absence of these manifestations predicts a very low risk of future asthma.

Objective: Parental atopy and environmental exposures at home have been recognized risk factors for adulthood asthma. However, the relative contributions of specific risk factors and the overall contributions of heredity or home exposure remain unexplored. The purpose of this study was to identify predictors and estimate the population attributable risk (PAR) of each exposure for typical asthma symptoms among 26- to 50-year-old Taiwanese. We also investigated whether an interactive effect existed between parental atopy and home exposures on the occurrence of asthma symptoms in adulthood., Design: A cross-sectional study with retrospective components., Setting: Elementary and middle schools in Southern Taiwan., Subjects: Between March and October 2004, we conducted a cross-sectional survey among schoolchildren's parents from 94 elementary and middle schools in Southern Taiwan. The main outcome measure was typical asthma-like symptoms occurring within the preceding 5 years. Information on hereditary and home exposures was collected by using a self-administered questionnaire., Results: After excluding unqualified questionnaires, data from 24,784 subjects were left for analysis. New-onset asthma was reported for 0.83% of male (n = 80 of 9,662) and 1.36% of female subjects (n = 206 of 15,122). Besides parental atopic factors, environmental tobacco smoke or pet avoidance and visible mold on walls at home were independently associated with the occurrence of asthma symptoms. Mutually adjusted models produced statistically significant associations between any home exposure (odds ratio [OR], 1.80; 95% confidence interval [CI], 1.08 to 3.23; PAR, 28.04%), parental atopy (OR, 4.47; 95% CI, 3.47 to 5.75; PAR, 31.38%), and new-onset asthma. However, there was no interaction between parental atopy and home exposures., Conclusions: Home exposures and parental atopy both increased the risks of new-onset asthma in adulthood but did not show an interactive effect. These two exposure categories approximately contributed equally to the adulthood asthma.

Objective: To evaluate the impact of a multifaceted environmental and educational intervention on the indoor environment and health in 5-12-year-old children with asthma living in urban environments., Design: Changes in indoor allergen levels and asthma severity measurements were compared between children who were randomized to intervention and delayed intervention groups in a 14-month prospective field trial. Intervention group households received dust mite covers, a professional house cleaning, and had roach bait and trays placed in their houses., Results: Of 981 eligible children, 410 (42%) were enrolled; 161 (40%) completed baseline activities and were randomized: 84 to intervention and 77 to delayed intervention groups. At the study's end, dust mite levels were 163% higher than at baseline for the delayed intervention group. Overall asthma severity scores did not change. However, the median functional severity score (FSS) component of the severity score improved more in the intervention group (33% vs. 20%) than in the delayed intervention group. At the study's end, the median FSSs for the intervention group improved 25% compared with the delayed intervention group, (p<0.01). Differences between groups for medication use, emergency department (ED) visits or hospitalization were not significant., Conclusions: Despite low retention, the intervention resulted in decreased dust mite allergen levels and increased FSSs among the intervention group. The interventions probably contributed to the improvements, especially among the more severely affected children. This study highlights the complexities of designing and assessing the outcomes from a multifaceted asthma intervention.