Allergic rhinitis children with obesity are more vulnerable to air pollution: a cross sectional study.

The association between air pollution, allergic rhinitis (AR), and obesity has not been studied. From 2007 to 2011, 52 obese and 152 non-obese children (7-17 years old) with AR were recruited. Pediatric-Rhinoconjunctivitis-Quality-of-Life Questionnaire (PRQLQ) and nasal peak expiratory flow (NPEF) were tested. Association between the scores and rates of the two tests and mean air pollutant concentrations within 7 days before the tests were compared. When exposed to higher concentrations of CO, PM10, and PM2.5, the rates of worse nasal discomfort were 39.4%, 44.4% and 39.3% in obese children; and 18.0%, 21.9% and 19.7% in non-obese children, respectively. Compare to non-obese children, the rates in obese children were higher for CO (odds ratio (OR) 3.54, 95% confidence interval (CI) 1.15 ~ 10.92); PM10 (OR 3.26, 95% CI 1.01 ~ 10.57) and PM2.5 (OR 3.30; 95% CI 1.03 ~ 10.54). In obese children, correlations between higher concentrations of CO, PM10, PM2.5 and higher nasal discomfort (higher PRQLQ); and correlations between higher concentrations of CO, PM10, PM2.5, NMHC (non-methane hydrocarbon) and higher nasal mucosa inflammation (lower NPEF) were noted. Obesity negatively affected AR severity when AR children experienced higher concentrations of CO, PM10, and PM2.5. Increased nasal inflammation induced by air pollutants might be the underlying mechanism.

Allergic rhinitis is associated with thromboembolic disease in pregnancy.

Finding the risk factors for thromboembolic (TE) disease and preventing its development in pregnant women is important. Allergic rhinitis (AR) is a common chronic disease. We aim to find if AR is a risk factor. From 2004 to 2011, 55,057 pregnant women were recruited from a Taiwan database. They were grouped into AR and non-AR groups. The rate of TE and venous complications during pregnancy and 60 days after childbirth were compared between non-AR and the AR group. Those with AR diagnosed both before and after childbirth, meaning AR was not changed during pregnancy, the rates of TE (OR 2.64) and venous complications (OR 1.35) were higher compared to non-AR subjects. In those who underwent cesarean delivery, the rate was also higher in group 3 (OR 4.14). Those with AR before childbirth, without after, meaning AR was well controlled during pregnancy, the rate of TE was not higher than that of the non-AR subjects. Pregnant women with AR have an increased rate of TE. An increased rate of venous complications in these subjects might explain the increase in TE. If AR is well controlled during pregnancy, the rate of TE does not appear to increase.

Integrated OMICs Approach for the Group 1 Protease Mite-Allergen of House Dust Mite Dermatophagoides microceras.

House dust mites (HDMs) are one of the most important allergy-causing agents of asthma. In central Taiwan, the prevalence of sensitization to Dermatophagoides microceras (Der m), a particular mite species of HDMs, is approximately 80% and is related to the IgE crossing reactivity of Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). Integrated OMICs examination was used to identify and characterize the specific group 1 mite-allergic component (Der m 1). De novo draft genomic assembly and comparative genome analysis predicted that the full-length Der m 1 allergen gene is 321 amino acids in silico. Proteomics verified this result, and its recombinant protein production implicated the cysteine protease and α chain of fibrinogen proteolytic activity. In the sensitized mice, pathophysiological features and increased neutrophils accumulation were evident in the lung tissues and BALF with the combination of Der m 1 and 2 inhalation, respectively. Principal component analysis (PCA) of mice cytokines revealed that the cytokine profiles of the allergen-sensitized mice model with combined Der m 1 and 2 were similar to those with Der m 2 alone but differed from those with Der m 1 alone. Regarding the possible sensitizing roles of Der m 1 in the cells, the fibrinogen cleavage products (FCPs) derived from combined Der m 1 and Der m 2 induced the expression of pro-inflammatory cytokines IL-6 and IL-8 in human bronchial epithelium cells. Der m 1 biologically functions as a cysteine protease and contributes to the α chain of fibrinogen digestion in vitro. The combination of Der m 1 and 2 could induce similar cytokines expression patterns to Der m 2 in mice, and the FCPs derived from Der m 1 has a synergistic effect with Der m 2 to induce the expression of pro-inflammatory cytokines in human bronchial epithelium cells.

Effect of combination treatment with Lactobacillus rhamnosus and corticosteroid in reducing airway inflammation in a mouse asthma model.

BACKGROUND: Asthma is a complex multifactorial chronic airway inflammatory disease with diverse phenotypes and levels of severity and is associated with significant health and economic burden. In a certain population of asthma patients, the symptoms cannot be well controlled with steroid. There has been long standing interest in the use of probiotics for treating allergic diseases. The purpose of this study is to investigate whether the combination of Lactobacillus rhamnosus GG (LGG) with prednisolone could reduce the dosage of glucocorticoid in controlling airway inflammation in a murine model for allergic asthma. MATERIAL AND METHODS: We used Der p 2-sensitized asthma model in female BALB/c mice. The animals were treated with 75 µl or 50 µl oral prednisolone or combination treatment of these two doses of oral prednisolone with LGG. Airway hyperresponsiveness, serum specific IgE/IgG1/IgG2a, infiltrating inflammatory cells in lung and cytokines were assessed. RESULTS: Compared to 75 µl prednisolone, a lower dose of prednisolone with 50 µl was less satisfactory in suppressing airway hyperresponsives, serum IgE and IgG1, Th2 cytokines and inflammatory cytokines such as IL-6, IL-8 and IL-17 as well as infiltrating inflammatory cells. However, combination of 50 µl prednisolone and LGG decreased airway resistance and serum IgE and IgG1, inhibited the production of IL-4, IL-5, IL-6, IL-8, IL-13 and IL-17, upregulated serum IgG2a and enhanced Th1 immune response. CONCLUSIONS: LGG may reduce the dosage of prednisolone and thus may be beneficial in the treatment of asthma.

Effect of the Fungal Immunomodulatory Protein FIP-fve in the Neutrophilic Asthma Animal Model.

BACKGROUND: Asthma animal models provide valuable information about the pathogenesis and the treatment of asthma. An ovalbumin (OVA)/complete Freund's adjuvant (CFA)-sensitized model was developed to induce neutrophil-dominant asthma and to investigate whether fungal immunomodulatory peptide-fve (FIP-fve) could improve asthma features in the OVA/CFA-sensitized model. METHODS: We used female BALB/c mice and sensitized them intraperitoneally with OVA/CFA on days 1, 2, and 3. On days 14, 17, 21, 24, and 27, they were challenged with intranasal OVA. The airway hyper-responsiveness (AHR) was detected by BUXCO, inflammatory cells were stained with Liu's stain, the cytokines were detected using ELISA, and the airway inflammation was analyzed with hematoxylin and eosin stain. RESULTS: According to the results, OVA/CFA sensitization could induce AHR, high levels of IgE, and inflammatory cells especially neutrophils infiltration in the lung and airway inflammation. IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17, IL-25, IL-33, and transforming growth factor-ß (TGF-ß) increased in the OVA/CFA-sensitized mice. OVA/CFA-sensitized mice treated with FIP-fve not only increased IL-12 and IFN-γ but also decreased IL-4, IL-5, IL-6, IL-8, IL-13, IL-17, IL-25, IL-33, and TGF-ß in the bronchoalveolar lavage fluid. Moreover, FIP-fve significantly decreased neutrophil infiltration in the lung. CONCLUSION: The OVA/CFA model induced neutrophilic asthma successfully, and FIP-fve improved neutrophil-dominant asthma.

Systematic Characterization of the Group 2 House Dust Mite Allergen in Dermatophagoides microceras.

BACKGROUND: Allergic asthma, a chronic airway inflammatory disease, is a critical public health problem. Indoor house dust mites (HDMs) could cause allergic asthma. The prevalence of sensitization to Dermatophagoides microceras (Der m) was approximately 80% and is related to the immunoglobulin E crossing-reactivity of mites belonging to the same genus, Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farina (Der f). However, studies on Der m are scant. METHODS: We used integrated OMICs approaches to identify and characterize the group 2 mite allergen-like protein in Der m (Der m 2). We established a Der m 2-induced allergic asthma mouse model and treated the mice with a fungal immunomodulatory protein (FIP-fve) isolated from Flammulina veluptipes to evaluate the allergenicity of Der m 2 and the immunomodulatory effects of FIP-fve. RESULTS: By performing de novo draft genome assembly and comparative genome analysis, we identified the putative 144-amino acid Der m 2 in silico and further confirmed its existence through liquid chromatography-tandem mass spectrometry. Der m 2 is a lipopolysaccharides (LPS)-binding protein. Thus, we examined the LPS-binding activity of recombinant Der m 2 by performing molecular docking analysis, co-immunoprecipitation (Co-IP), and a pull-down assay. Der m 2 elicited the production of pro-inflammatory cytokines, interleukin (IL)-6, and IL-8 in BEAS-2B cells, a human bronchial epithelial cell line, and induced airway hyperresponsiveness in mice. Furthermore, in mice sensitized with Der m 2, the administration of FIP-fve in either the earlier stage or the late stage, FIP-fve alleviated allergic asthma by moderating airway inflammation and remodeling. CONCLUSIONS: Der m 2 induced inflammatory responses in cell and mouse models. FIP-fve alleviated inflammation in Der m 2-induced asthma in mice by exerting an immunomodulatory effect.

Role of biomarkers and effect of FIP-fve in acute and chronic animal asthma models.

BACKGROUND: Asthma is a consequence of complex gene-environment interactions. Exploring the heterogeneity of asthma in different stages is contributing to our understanding of its pathogenesis and the development of new therapeutic strategies, especially in severe cases. OBJECTIVE: This study aimed to further understand the relationship between manifestations of acute and chronic asthma and various endotypes, and explore the severity of lung inflammation, cell types, cytokine/chemokine differences, and the effects of FIP-fve. MATERIALS AND METHODS: Acute and chronic OVA-sensitization mouse asthma models, based on our previously published method, were used and FIP-fve was used to evaluate the effect on these two models. BALF cytokines/chemokines were detected according to the manufacturer's protocol. RESULTS: Seventeen cytokine/chemokine secretions were higher in the chronic stage than in the acute stage. Whether in acute stage or chronic stage, the FIP-fve treatment groups had reduced airway hyperresponsiveness, infiltration of airway inflammatory cells, secretion of cytokines, chemokines by Th2 cells, and TNF-α, IL-8, IL-17, CXCL-1, CXCL-10, CCL-17, and CCL-22, and it was also found that the Treg cell cytokine IL-10 had increased significantly. PCA (Principal Component Analysis) was also used to compare statistics and laboratory data to find the important biomarkers in different stages and after treatment with FIP-fve. CONCLUSIONS: There are many different immune responses in the different stages of the asthma process. Drug treatment at the appropriate times might help reduce the worsening of asthma.

Effect of Lactobacillus rhamnosus GG immunopathologic changes in chronic mouse asthma model.

BACKGROUND: Asthma is a heterogeneous inflammatory disorder of the airway. A Th2 response usually contributes to high levels of allergen-specific IgE and eosinophilic airway inflammation. Several findings have demonstrated that neutrophils, not eosinophils, are the major inflammatory cells in chronic asthma patients with steroid-resistance. Lactobacillus rhammosus GG (LGG) exhibits anti-inflammatory properties on OVA-induced acute airway inflammation. OBJECTIVE: We hypothesized that orally administrated LGG should reduce airway remodeling in chronic experimental models. METHODS: Female Balb/c mice were sensitized with OVA. LGG was used to investigate whether oral administrations of LGG inhibited OVA-induced airway inflammation in a chronic asthma model and the different intervention times between LGG pre-treatment and post-treatment groups. BALF was analyzed with Liu's stain and ELISA assay. Lung histopathology was assayed with HE, IHC and Masson's trichrome staining. Lung tissues were assayed with PCR (T-bet, GATA3, RORrt and Foxp3). Many cytokines were detected in the serum and BALF. RESULTS: LGG significantly decreased the number of infiltrating inflammatory cells. We also found that the oral LGG group suppressed not only Th2 cytokine, but also IL-17, TNF-α and HMGB1 in the BALF levels. However, GATA3 and RORrt decreased significantly in the RNA level in the LGG groups, but the T-bet and Foxp3 increased in the RNA level. CONCLUSIONS: LGG not only had anti-inflammatory effects on OVA-induced airway inflammation, but also improved airway remodeling and collagen expression in the chronic asthma mouse model. Moreover, LGG might be an additional or supplementary therapy for allergic airway diseases.

Fungal immunomodulatory protein-fve could modulate airway remodel through by affect IL17 cytokine.

BACKGROUND: Asthma is one of the most common allergic diseases. Our previous studies have reported that FIP-fve in acute allergic mouse model can reduce inflammation, improve the balance of the Th1/Th2 system. However, the effects of reducing airway remodeling on FIP-fve is still unknown. OBJECTIVE: We hypothesized that orally administrated FIP-fve should be able to reduce airway remodeling in chronic allergic models. METHODS: The chronic asthma animal model was established with 6-8 weeks female Balb/c mice. After intranasal challenges with OVA, the airway inflammation and AHR were determined by a BUXCO system. BALF was analyzed with Liu's stain and ELISA assay. Lung histopathologic changes and Collagen deposition were assayed with H&E, Masson's trichrome and IHC stain. RESULTS: FIP-fve significantly decreased the number of infiltrating inflammatory cells and Th2 cytokines and increased Th1 cytokines in BALF and serum compared with the OVA sensitized mice. FIP-fve had a better effect than corticosteroid could reduce infiltrating cells in lung especially neutrophils and eosinophils. We also found that the oral FIP-fve group suppressed IL-17 and enhanced IL-22 in the serum and BALF. In addition, oral FIP-fve decreased MMP9 expression, collagen expression and airway remodeling in lung tissues. CONCLUSION: FIP-fve had anti-inflammatory effects on OVA-induced airway inflammation and an effect to inhibited Th17 cells to reduced airway remodeling and collagen expression. Moreover, FIP-fve might be a potential alternative therapy for allergic airway diseases.

Effects of immunomodulatory supplementation with Lactobacillus rhamnosus on airway inflammation in a mouse asthma model.

BACKGROUND: Asthma is a common allergic disease. In previous studies, probiotics improved the balance of intestinal microbes, reduced inflammation, and promoted mucosal tolerance. This study investigated whether oral administrations of Lactobacillus rhamnosus GG (LGG) inhibited allergen (ovalbumin or OVA)-induced airway inflammation in a mouse asthma model. METHODS: The allergy/asthma animal model in this study was sensitization with OVA. After intranasal challenge with OVA, the airway inflammation and hyper-responsiveness were determined by a Buxco system, bronchoalveolar lavage fluid analysis with Liu stain, and enzyme-linked immunosorbent assay. Histopathologic changes in the lung were detected by hematoxylin and eosin staining and immunohistochemistry staining. RESULTS: Both pre- and post-treatment with LGG suppressed the airway hyper-responsiveness to methacholine and significantly decreased the number of infiltrating inflammatory cells and Th2 cytokines in bronchoalveolar lavage fluid and serum compared with the OVA-sensitized mice. In addition, LGG reduced OVA-specific IgE levels in serum. Oral LGG decreased matrix metalloproteinase 9 expression in lung tissue and inhibited inflammatory cell infiltration. CONCLUSION: LGG had an anti-inflammatory effect on OVA-induced airway inflammation and might be an additional or supplementary therapy for allergic airway diseases.