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Exposure to both formaldehyde and high relative humidity exacerbates allergic asthma by activating the TRPV4-p38 MAPK pathway in Balb/c mice
2020
Duan, Jiufei | Xie, Jing | Deng, Ting | Xie, Xiaoman | Liu, Hong | Li, Baizhan | Chen, Mingqing
Some studies have indicated that formaldehyde, a ubiquitous environmental pollutant, can induce or aggravate allergic asthma. Epidemiological studies have also shown that the relative humidity indoors may be an independent and a key factor associated with the aggravation of allergic asthma. However, the synergy of humidity and formaldehyde on allergic asthma and the mechanism underlying this effect remain largely unknown. In this study, we aim to determine the effect of high relative humidity and/or formaldehyde exposure on allergic asthma and explore the underlying mechanisms. Male Balb/c mice were modeled with ovalbumin (OVA) and exposure to 0.5 mg/m3 formaldehyde and/or different relative humidity (60%/75%/90%). Histopathological changes, pulmonary function, Th1/Th2 balance, the status of mucus hypersecretion and the levels of inflammatory factors were detected to assess the exacerbation of allergic asthma. The levels of the transient receptor potential vanilloid 4 (TRPV4), calcium ion and the activation of p38 mitogen-activated protein kinases (p38 MAPK) were detected to explore the underlying mechanisms. The results showed that exposure to high relative humidity or to 0.5 mg/m3 formaldehyde alone had a slight, but not significant, affect on allergic asthma. However, the pathological response and airway hyperresponsiveness (AHR) were greatly aggravated by simultaneous exposure to 0.5 mg/m3 formaldehyde and 90% relative humidity. Blocking TRPV4or p38 MAPK using HC-067047 and SB203580 respectively, effectively alleviated the exacerbation of allergic asthma induced by this simultaneous exposure to formaldehyde and high relative humidity. The results show that when formaldehyde and high relative humidity are present this can enhance the activation of the TRPV4 ion channel in the lung leading to the aggravation of the p38 MAPK activation, resulting in the exacerbation of inflammation and hypersecretion of mucus in the airways.
اظهر المزيد [+] اقل [-]High and low temperatures aggravate airway inflammation of asthma: Evidence in a mouse model
2020
Deng, Linjing | Ma, Ping | Wu, Yang | Ma, Yongsheng | Yang, Xu | Li, Yuguo | Deng, Qihong
Epidemiology suggests ambient temperature is the triggers and potential activator of asthma. The role of high and low temperatures on airway inflammation of asthma, and the underlying molecular mechanism are not yet understood. A mouse model of asthma was adopted in our experiment. The BALB/c mice were exposed at different temperature for 4 h (2 h in the morning and 2 h in the afternoon) on weekday. The exposure temperatures were 10 °C, 24 °C and 40 °C. Ovalbumin (OVA) was used to sensitize the mice on days 14, 18, 22, 26, and 30, followed by an aerosol challenge for 30 min from day 32–38. After the final OVA challenge, lung function, serum protein and pulmonary inflammation were assessed. Comparing the OVA with the saline group at 24 °C, we saw a significant increase in: serum Total-IgE (p < 0.05); OVA-sIgE (p < 0.01); IL-4 (p < 0.05); IL-1β (p < 0.01); IL-6 (p < 0.01); TNF-α (p < 0.01); and the ratio of IL-4/IFN-γ (p < 0.01). At the same time, there was a significant decrease in IFN-γ (p < 0.01). As the temperature increase, there is a U shape for immune proteins and pro-inflammatory factors with a peak value at 24 °C, exception for IFN-γ (inverted U-shape). After the high and low temperature exposure, the Ri and Re increased significantly, while Cldyn decreased significantly compared with the 24 °C group. Histopathological analysis of the OVA groups showed airway remodeling, airway wall thickening and deforming, and subepithelial fibrosis. More obvious changes were found in the high and low temperature exposure groups. The immunohistochemistry suggested that TRPs changed with temperatures. High and low temperatures can aggravate airway inflammation in a mouse model of asthma. TRPs play an important role in temperature aggravation of allergic asthma. The results suggest that asthmatics should avoid exposure to high and low temperatures for too long time.
اظهر المزيد [+] اقل [-]Benefits of influenza vaccination on the associations between ambient air pollution and allergic respiratory diseases in children and adolescents: New insights from the Seven Northeastern Cities study in China
2020
Liu, Kangkang | Li, Shanshan | Qian, Zhengmin (Min) | Dharmage, Shyamali C. | Bloom, Michael S. | Heinrich, Joachim | Jalaludin, Bin | Markevych, Iana | Morawska, L. (Lidia) | Knibbs, Luke D. | Hinyard, Leslie | Xian, Hong | Liu, Shan | Lin, Shao | Leskinen, Ari | Komppula, Mika | Jalava, Pasi | Roponen, Marjut | Hu, Liwen | Zeng, Xiao-Wen | Hu, Wenbiao | Chen, Gongbo | Yang, Bo-Yi | Guo, Yuming | Dong, Guang-Hui
Little information exists on interaction effects between air pollution and influenza vaccination on allergic respiratory diseases. We conducted a large population-based study to evaluate the interaction effects between influenza vaccination and long-term exposure to ambient air pollution on allergic respiratory diseases in children and adolescents.A cross-sectional study was investigated during 2012–2013 in 94 schools from Seven Northeastern Cities (SNEC) in China. Questionnaires surveys were obtained from 56 137 children and adolescents aged 2–17 years. Influenza vaccination was defined as receipt of the influenza vaccine. We estimated air pollutants exposure [nitrogen dioxide (NO2) and particulate matter with aerodynamic diameters ≤1 μm (PM1), ≤2.5 μm (PM2.5) and ≤10 μm (PM10)] using machine learning methods. We employed two-level generalized linear mix effects model to examine interactive effects between influenza vaccination and air pollution exposure on allergic respiratory diseases (asthma, asthma-related symptoms and allergic rhinitis), after controlling for important covariates.We found statistically significant interactions between influenza vaccination and air pollutants on allergic respiratory diseases and related symptoms (doctor-diagnosed asthma, current wheeze, wheeze, persistent phlegm and allergic rhinitis). The adjusted ORs for doctor-diagnosed asthma, current wheeze and allergic rhinitis among the unvaccinated group per interquartile range (IQR) increase in PM1 and PM2.5 were significantly higher than the corresponding ORs among the vaccinated group [For PM1, doctor-diagnosed asthma: OR: 1.89 (95%CI: 1.57–2.27) vs 1.65 (95%CI: 1.36–2.00); current wheeze: OR: 1.50 (95%CI: 1.22–1.85) vs 1.10 (95%CI: 0.89–1.37); allergic rhinitis: OR: 1.38 (95%CI: 1.15–1.66) vs 1.21 (95%CI: 1.00–1.46). For PM2.5, doctor-diagnosed asthma: OR: 1.81 (95%CI: 1.52–2.14) vs 1.57 (95%CI: 1.32–1.88); current wheeze: OR: 1.46 (95%CI: 1.21–1.76) vs 1.11 (95%CI: 0.91–1.35); allergic rhinitis: OR: 1.35 (95%CI: 1.14–1.60) vs 1.19 (95%CI: 1.00–1.42)]. The similar patterns were observed for wheeze and persistent phlegm. The corresponding p values for interactions were less than 0.05, respectively. We assessed the risks of PM1-related and PM2.5-related current wheeze were decreased by 26.67% (95%CI: 1.04%–45.66%) and 23.97% (95%CI: 0.21%–42.08%) respectively, which was attributable to influenza vaccination (both p for efficiency <0.05).Influenza vaccination may play an important role in mitigating the detrimental effects of long-term exposure to ambient air pollution on childhood allergic respiratory diseases. Policy targeted at increasing influenza vaccination may yield co-benefits in terms of reduced allergic respiratory diseases.
اظهر المزيد [+] اقل [-]Multi-city study on air pollution and hospital outpatient visits for asthma in China
2020
Lü, Peng | Zhang, Yongming | Lin, Jiangtao | Xia, Guoxin | Zhang, Wenyi | Knibbs, Luke D. | Morgan, Geoffrey G. | Jalaludin, Bin | Marks, Guy | Abramson, Michael | Li, Shanshan | Guo, Yuming
The proportion of asthma patients with mild to moderate exacerbations is far greater than the number who experience episodes that are severe enough to require emergency room visits or hospital admission. However the routinely collected data from hospitals is absent in the past.To evaluate associations between short-term exposures to air pollutants and hospital outpatient visits for asthma in China.We obtained data for 143,057 asthma outpatient visits from the largest hospitals in 17 Chinese cities, between Jan 01 2013 and Dec 31 2015. We used daily concentrations of air pollutants measured by the China National Environmental Monitoring Centre. We used a time-stratified case-crossover design, and fitted conditional logistic regression models to determine the associations.Particulate matter ≤10μm in diameter (PM10) and nitrogen dioxide (NO2) were associated with increased risks of hospital outpatient visits for asthma on the same day, while the effects were delayed for particulate matter ≤2.5μm in diameter (PM2.5) and sulphur dioxide (SO2). For the cumulative effect model at lag05 days, 10 μg/m3 increase in air pollutants concentrations were correlated with hospital outpatient visits for asthma with odds ratios (ORs) and 95% confidence intervals 1.004 (1.000-1.008) for PM2.5, 1.005 (1.002-1.008) for PM10, 1.030 (1.021-1.040) for NO2, and 1.015 (1.008-1.021) for SO2. Almost one in nine (10.9%; 7.7, 13.9%) hospital outpatient visits for asthma were attributable to NO2.Short-term exposures to PM2.5, PM10, NO2 and SO2 were associated with hospital outpatient visits for asthma in China.
اظهر المزيد [+] اقل [-]Sargassum horneri extract containing mojabanchromanol attenuates the particulate matter exacerbated allergic asthma through reduction of Th2 and Th17 response in mice
2020
Herath, Kalahe Hewage Iresha Nadeeka Madushani | Kim, Hyo-jin | Mihindukulasooriya, Suyama Prasansali | Kim, Areum | Kim, Hyun Jung | Jeon, You-Jin | Jee, Youngheun
Airborne particulate matter (PM) has become a serious health issue causing pulmonary diseases such as asthma. Due to the side effects and non-specificity of conventional drugs, there is a need to develop natural-product-based alternative treatments. Sargassum horneri is a brown alga shown to have anti-oxidant, anti-inflammatory, and anti-allergic effects. Thus, we sought to determine whether ethanol extract of Sargassum horneri (SHE) mitigates the effect of PM exposure on asthma development. To establish a mouse model of asthma, BALB/c mice were sensitized with ovalbumin (OVA, 10 μg) and challenged with PM (5 mg/m³) for 7 days consecutively. SHE (200, 400 mg/kg), Prednisone (5 mg/kg), or PBS was daily administrated orally before PM exposure. SHE mitigated PM exacerbated dendritic cell activation. More importantly, SHE restrained Th2 polarization by attenuating transcription factors GATA3 and STAT5, which further mitigated the expression of Th2 cytokines interleukin (IL)-4, IL-5, and IL-13 in the lung homogenates of PM-exacerbated asthmatic mice. SHE further attenuated PM-exacerbated eosinophil infiltration in the lung, trachea, and BALF. In addition, SHE markedly mitigated the activation of mast cells and the IgE level in serum. Concomitantly, SHE further restrained the Th17 cell response in PM-exposed allergic mice through attenuating expression of transcription factors RORγT, STAT3 and expression of relevant effector cytokines IL-17a. This resulted in mitigated neutrophil infiltration in the lung. Taken together, SHE significantly suppressed PM-exacerbated hypersecretion of mucus in asthmatic mice. These results suggest that SHE has therapeutic potential for treating PM-exacerbated allergic asthma through concomitantly inhibiting Th2/Th17 responses.
اظهر المزيد [+] اقل [-]The immunomodulatory effects of diesel exhaust particles in asthma
2020
de Homdedeu M, | Cruz, Mj | Sanchez-Díez, S. | I, Ojanguren | Romero-Mesones, C. | J, Vanoirbeek | Velde G, Vande | X, Muñoz
Ammonium persulfate (AP) causes occupational asthma (OA) and diesel exhaust particles (DEP) exacerbate asthma; however, the role of DEP in asthma due to chemical agents has not been assessed to date. Therefore, the present work aims to study the immunomodulatory effects of DEP in a mouse model of chemical asthma. BALB/c ByJ mice were randomly divided into four experimental groups. On days 1 and 8, mice were dermally sensitized with AP or saline. On days 15, 18 and 21, they received intranasal instillations of AP or saline. Two experimental groups received DEP on every of the three challenges. Airway hyperresponsiveness (AHR), lung mechanics, pulmonary inflammation in bronchoalveolar lavage, leukocyte numbers in total lung tissue, oxidative stress and optical projection tomography (OPT) studies were assessed. The AP-sensitized and challenged group showed asthma-like responses, such as airway hyperresponsiveness, increased levels of eosinophils and NKs and lower numbers of monocytes and CD11b-Ly6C- dendritic cells (DCs). Mice exposed to DEP alone showed increased levels of neutrophils and NKs, reduced numbers of monocytes and alveolar macrophages, and increased levels of CD11b + Ly6C- DCs. The AP sensitized and AP + DEP challenged group also showed asthma-like symptoms such as AHR, as well as increased numbers of eosinophils, neutrophils, CD11b + Ly6C- DCs and decreased levels of total and alveolar macrophages and tolerogenic DCs. Particle deposition was visualised using OPT. In the DEP group the particles were distributed relatively evenly, while in the AP + DEP group they were seen mainly in the large conducting airways. The results show that DEP exposure activates the innate immune response and, together with AP, exacerbates asthma immune hallmarks. This mouse model provides the first evidence of the capacity of DEPs to increase CD11b + Ly6C- (Th2-related) DCs. This study also demonstrates, for the first time, a differential deposition pattern of DEP in lungs depending on asthma status.
اظهر المزيد [+] اقل [-]Home environmental and lifestyle factors associated with asthma, rhinitis and wheeze in children in Beijing, China
2020
Huang, Shaodan | Garshick, Eric | Weschler, Louise B. | Hong, Chuan | Li, Jing | Li, Linyan | Qu, Fang | Gao, Dewen | Zhou, Yanmin | Sundell, Jan | Zhang, Yinping | Koutrakis, Petros
The prevalence of asthma and allergic diseases has increased rapidly in urban China since 2000. There has been limited study of associations between home environmental and lifestyle factors with asthma and symptoms of allergic disease in China.In a cross-sectional analysis of 2214 children in Beijing, we applied a two-step hybrid Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to identify environmental and lifestyle-related factors associated with asthma, rhinitis and wheeze from a wide range of candidates. We used group LASSO to select variables, using cross-validation as the criterion. Effect estimates were then calculated using adaptive LASSO. Model performance was assessed using Area Under the Curve (AUC) values.We found a number of environmental and lifestyle-related factors significantly associated with asthma, rhinitis or wheeze, which changed the probability of asthma, rhinitis or wheeze from −5.76% (95%CI: −7.74%, −3.79%) to 27.4% (95%CI: 16.6%, 38.3%). The three factors associated with the largest change in probability of asthma were short birth length, carpeted floor and paternal allergy; for rhinitis they were maternal smoking during pregnancy, paternal allergy and living close to industrial area; and for wheeze they were carpeted floor, short birth length and maternal allergy. Other home environmental risk factors identified were living close to a highway, industrial area or river, sharing bedroom, cooking with gas, furry pets, cockroaches, incense, printer/photocopier, TV, damp, and window condensation in winter. Lifestyle-related risk factors were child caretakers other than parents, and age<3 for the day-care. Other risk factors included use of antibiotics, and mother’s occupation. Major protective factors for wheeze were living in a rural/suburban region, air conditioner use, and mother’s occupation in healthcare.Our findings suggest that changes in lifestyle and indoor environments associated with the urbanization and industrialization of China are associated with asthma, rhinitis, and wheeze in children.
اظهر المزيد [+] اقل [-]Exposure to air pollution during the first 1000 days of life and subsequent health service and medication usage in children
2020
Evidence of health effects following early life exposure to short-to-medium duration of high pollution levels is extremely limited.We aimed to evaluate the associations between: 1. intrauterine exposure to fine particulate matter (PM2.5) from coal mine fire emissions and the frequencies of general practitioner attendances and dispensations of prescribed asthma inhalers, steroid skin creams, and antibiotics during the first year of life; 2. infant exposure and those outcomes during the year following the fire.All participants were recruited from the Latrobe Valley of Victoria, Australia. Participants’ 24-h average and hourly peak mine fire-specific PM2.5 exposures from 09/02/2014 to 31/03/2014 were estimated using chemical transport modelling. Outcome data were obtained from the Australian Medicare Benefits Schedule and Pharmaceutical Benefits Scheme from each child’s birth to 31/12/2016. We used negative binomial and logistic regression models to independently assess risks of the outcomes associated with every 10 and 100 μg m−3 increase in average or peak PM2.5 exposure, respectively, while adjusting for potential confounders.We included 286 of 311 children whose parents consented to be linked, comprising 77 with no exposure, 88 with intrauterine exposure and 121 with exposure in infancy. 10- and 100- μg m−3 increases in average and peak PM2.5 exposure during infancy were associated with greater incidence of antibiotics being dispensed during the year following the fire: the adjusted incidence rate ratios were 1.24 (95% CI 1.02, 1.50, p = 0.036) and 1.14 (1.00, 1.31, p = 0.048) respectively. No other significant associations were observed.Exposure to coal mine fire emissions during infancy was associated with increased dispensing of antibiotics. This could reflect increased childhood infections or increased prescriptions of antibiotics in the year following the fire.
اظهر المزيد [+] اقل [-]Co-exposure to polycyclic aromatic hydrocarbons, benzene and toluene may impair lung function by increasing oxidative damage and airway inflammation in asthmatic children
2020
Kuang, Hongxuan | Liu, Jian | Zeng, Yingwei | Zhou, Wenji | Wu, Peiqiong | Tan, Jianhua | Li, Yonghong | Pang, Qihua | Jiang, Wenhui | Fan, Ruifang
As previous studies found that the direct associations between urinary polycyclic aromatic hydrocarbon (PAH), benzene and toluene (BT) metabolites and the decreased lung function were not conclusive, we further investigated relationship of oxidative damage and airway inflammation induced by PAHs and BTs exposure with lung function. A total of 262 children diagnosed with asthma and 72 heathy children were recruited. Results showed that asthmatic children had higher levels of PAHs and BTs exposure, as well as Malonaldehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) compared with healthy children. Furthermore, binary logistic regression showed that each unit increases in level of urinary 2-&3-hydroxyfluorene (2-&3-OHF), 2-hydroxyphenanthrene (2-OHPhe), 1-hydroxyphenanthrene (1-OHP) and S-phenylmercapturic acid (S-PMA) were significantly associated with an elevated risk of asthma in children with odds ratios of 1.5, 2.3, 1.7 and 1.4, respectively, suggesting that PAHs and BTs exposure could increase the risk of asthma for children. Neither PAH nor BT metabolite could comprehensively indicate the decreased lung function as only 2-&3-OHF and 1-OHP were significantly and negatively correlated with forced vital capacity (FVC). Moreover, levels of most individual PAH and BT metabolite were significantly correlated to MDA and 8-OHdG. Further hierarchical regression analysis indicated that MDA and 8-OHdG levels did not show significant effects on the decreased lung function, suggesting that they are not the suitable biomarkers to indirectly indicate the altered lung function induced by PAHs and BTs. Urinary 2-OHPhe and 1-&9-hydroxyphenanthrene (1-&9-OHPhe) were significantly correlated with fractional exhaled nitric oxide (FeNO). Moreover, FeNO significantly contributed to decreased lung function and explained 7.7% of variance in ratio of forced expiratory volume in 1 s (FEV₁) and FVC (FEV₁/FVC%). Hence, FeNO, rather than oxidative damage indicators or any urinary PAH and BT metabolite, is more sensitive to indirectly reflect the decreased lung function induced by PAHs and BTs exposure for asthmatic children.
اظهر المزيد [+] اقل [-]Associations between observed formaldehyde concentrations and smoking, environmental tobacco smoke, and self-reported cancers and asthma: data for US children, adolescents, and adults
2020
Jain, Ram B.
For the first time, the National Health and Nutrition Examination Survey (NHANES) released data on hemoglobin adducts of formaldehyde (HCHO) in public domain for US children aged 6–11 years, adolescents aged 12–19 years, and adults aged > = 20 years for 2015–2016. This study was undertaken to evaluate the associations between concentrations of HCHO in whole blood and smoking, exposure to environmental tobacco smoke (ETS), and self-reported diagnoses of cancers and asthma. Adult smokers were found to have higher adjusted concentrations of HCHO than nonsmokers (127.7 vs. 125.1 pmol/g Hb, p = 0.02). Exposure to ETS was not found to affect the adjusted concentrations of HCHO. No associations were observed between HCHO concentrations and self-reported diagnosis of “ever” cancer as well as self-reported presence of asthma at the time of participation in NHANES. HCHO concentrations were not found to differ across genders and racial/ethnic groups for children and adolescents. Among adults, non-Hispanic blacks (120.0 pmol/g Hb) had lower adjusted concentrations (p < = 0.01) of HCHO than non-Hispanic whites (128.8 pmol/g Hb), Mexican Americans (129.4 pmol/g Hb), other Hispanics (130.3 pmol/g Hb), and non-Hispanic Asians (127.9 pmol/g Hb). In conclusion, self-reported diagnoses of cancer and asthma were not found to be associated with observed concentrations of HCHO in whole blood.
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