| Background:Allergic rhinitis(AR)is a common disease with high incidence.The prevalence rate of AR in cities of China has been increasing in recent years.Allergic rhinitis could seriously affect the life quality of patients,aggravate social and economic burden,and it has become an important public health problem in China.The occurrence and development of allergic rhinitis are affected by both environmental and genetic factors.Fine particulate matter(PM2.5)can cause respiratory and nasal cell damage through breathing.Exposure to PM2.5 could increase the occurrence of AR related symptoms and scores of nasal symptom.However,the mechanism of how PM2.5 exposure exacerbates the AR-related symptoms remains unclear.The immune imbalance of Thl/Th2 is the main pathogenesis of allergic rhinitis.The JAK/STAT pathway played an important regulating role in Thl/Th2 immune response,and it is related to the occurrence and development of allergic rhinitis.PM2.5 could cause oxidative damage,lead to nasal epithelial damage and barrier dysfunction,and induce the synthesis and release of inflammatory cytokines.Previous studies had suggested that PM2.5 could aggravate allergic airway inflammation and increase the expression of inflammatory cytokines through JAK/STAT pathway.Therefore,it was reasonable to assume that PM2.5 exposure may enlarge the Thl/Th2 immune imbalance in patients with allergic rhinitis by activating the JAK/STAT pathway and promoting the expression of related inflammatory cytokines,thus participate in the aggravation of allergic rhinitis related symptoms.Objective:Through the four repeated measurements of patients with allergic rhinitis,we explored the relationship between PM2.5 concentration and its chemical composition and activation of JAK/STAT pathway and expression of related inflammatory cytokines,aimed to find the possible pathways of PM2.5 exposure to enlarge Th1/Th2 immune imbalance.We hope the result of this study can contribute to the discovery of molecular target for the clinical treatment of allergic rhinitis,further to prevent the onset of allergic rhinitis,to reduce the air pollution effect and suffering of patients.Methods:Before the start of this panel study,the temporal and spatial distribution of PM2.5 pollution from 2013 to 2016 in Taiyuan City was analyzed and a literature review of airborne pollen content in Taiyuan was conducted.60 patients with allergic rhinitis were selected and investigated from June 2017 to January 2018.Four repeated measurements were carried out at the following periods,June,August,and December in 2017,and January in 2018.Ambient PM2.5 samples of three sites(A,B,C)were collected and the compositions of PM2.5 were analyzed during the study period,exposure level to PM2.5 components of subjects in this study was obtained.Based on the data from 8 monitoring stations in Taiyuan City,the individual PM2.5 exposure was assessed using the time activity model combined with the micro-environment monitoring method.Questionnaires were used to obtain the scores of allergic rhinitis related scales.Expression of oxidative stress indicators,inflammatory cytokines,and phosphorylation level of pathway molecules in the nasal irrigating fluids were measured,and routine indicators of blood related to AR were also examined.The mixed effect model was used to analyze the relationship between the individual exposure concentration of PM2.5 and effect indicators.1.Analysis of ambient PM2.5 and its components characteristics in Taiyuan cityBase on the monitoring data from 2013 to 2016,the seasonal distribution characteristics of PM2.5 in Taiyuan City were analyzed,and literature related to pollen content in urban areas of Taiyuan City was also analyzed,to provide a basis for the time schedule of this study.A comparative analysis of air pollution and meteorological factors during four repeated measurements periods were conducted.A mid-flow particle sampler was used at each site to collect daily PM2.5 samples during the four repeated measurements periods.Inductively coupled plasma mass spectrometry(ICP-MS),ion chromatography(IC),and high-performance liquid chromatography(HPLC)were applied to analyze the content of PM2.5 components,to observe the distribution characteristics of the main chemical components of PM2.5 in urban areas of Taiyuan,and to determine the exposure of PM2.5 components of subjects.2.PM2.5 exposure assessment of subjectsBased on the daily PM2.5 concentrations at 8 environmental monitoring stations,spatial interpolation(IDW)was used to obtain the outdoor concentrations of homes and workplaces.The indoor and outdoor PM2.5 concentrations in typical residences and workplaces were monitored and sampled to obtain the indoor/outdoor PM2.5 concentration ratios(I/O ratios)in different measurements periods.Using the outdoor concentration of homes and workplaces,and the corresponding I/O ratio,indoor PM2.5 concentration can be estimated.Finally,combined with the results of the time-activity model,the time-weighted PM2.5 concentrations of various microenvironments were used to estimate individual PM2.5 exposure concentration.3.Relationship between PM2.5 exposure and outcomes of patients with allergic rhinitisThe descriptive statistics of the outcome indicators including the scores of the scales,blood routine indicators,and the expression levels of oxidative stress and inflammatory cytokines in the nasal irrigation fluid were conducted.The randomized block analysis of variance was used to observe the difference of outcome indicators in four repeated measurements periods.Pearson correlation analysis was used to observe the relationship between PM2.5 and its component concentrations,other air pollutants,meteorological variables and outcome indicators.Finally,a mixed-effect model was used to analyze the association between PM2.5 exposure concentrations and the expression of oxidative stress and inflammatory cytokines,total IgE and phosphorylation level of molecules in JAK/STAT pathway.Results:1.The level of air pollution in Taiyuan was significantly different between non-heating and heating season.PM2.5 concentrations were different in four repeated measurements periods of this study.PM2.5 concentration in the fourth period was higher than those in other three periods from the analysis of monitoring and ambient sampling data.The trend of PM2.5 concentration at eight monitoring stations in the urban area was similar,but the pollution levels at each point were different,the spatial difference of PM2.5 concentration in urban areas of Taiyuan City was existed.The spring peak period of airborne pollen in Taiyuan is from March to May.The autumn peak period of airborne pollen is from late August to late September.The study was conducted from June to early August and from early December to late January,away from the spring and autumn airborne pollen peaks.PM2.5 was significant negative correlated with temperature and ozone,and highly positively correlated with NO2 and SO2.There were regional differences in concentration of metal and metalloid elements and PAHs,the concentration of point A was higher.The addresses of the subjects in this study were located in the downtown area,around points B and C,so the average levels of points B and C can be used to reflect the ambient exposure of PM2.5 component during this study.2.The I/O ratio of residential homes was higher in non-heating season,and the I/O ratio in the fourth period was the lowest.The I/O ratios of workplaces(hospital and office buildings)during the non-heating season were close,but the I/O ratios in the hospital were higher than those in office buildings during heating season,which may be related to the characteristic and ventilation of workplace.Subjects stayed in various indoor environments for most of the daily time.The estimated concentration of individual PM2.5 exposure was still significantly higher in fourth period than other three periods.4.The significant difference of SRS,VAS and RQLQ scores in four repeated measurements periods was not found.But there was a significant correlation between PM2.5lagl and scores of VAS and RQLQ scale and oxidative stress.With PM2.5 concentration increased,the nose and eyes symptoms of AR patients were aggravated,the expression of MDA was increased and the action of SOD was decreased.After adjusted temperature and other potential confounding factors,PM2.5 concentration was still significantly associated with the expression inflammatory cytokines and total IgE.With the increasing of PM2.5 concentrations,IL-4,IL-13,total IgE,IL-6,and IL-17 expression were increased.MDA was positively correlated with IL-4,IL-13,total IgE and IL-6,and SOD was negatively correlated with IL-4,IL-13 and IL-6.After adjusted the potential confounding factors,there was also a link between PM2.5 concentration and the phosphorylation level of JAK/STAT pathway molecules.With the increase of PM2.5 concentration,the phosphorylation levels of JAK1,JAK3,and STAT6 increased.PM2.5 components including polycyclic aromatic hydrocarbons,Cl-,NO3-,NH4+,V,Mn,Fe,Zn,As,Se,Cd,and Pb were related to oxidative stress markers,inflammatory cytokines,and expression levels of pJAKI and pJAK3 There was also a positive correlation between the elements V,Mn,Fe and Zn and the total IgE and pSTAT6.Conclusion:The levels of PM2.5 and its components in Taiyuan urban areas were different in different seasons.PM2.5 concentration was related to other pollutants and meteorological variables.Indoor PM2.5 was different from outdoor,especially in heating season.The participants stayed in various indoor environments for over 81.7%of the daily time,The individual PM2.5 exposure concentration was estimated by using the time activity model combined with the micro-environment monitoring method,differences in PM2.5 concentrations between outdoor,residential and workplace environments were taken into account.So the estimated individual PM2.5 concentration may closer to the actual exposure concentration.In this study,we found that with the increase of PM2.5 concentration,the nasal oxidative stress in patients with allergic rhinitis was significantly increased,Th2 cytokines IL-4 and IL-13 and total IgE expression levels,phosphorylation levels of JAK/STAT pathway molecules also increased,and the symptoms of patients with allergic rhinitis worsened,and the quality of life declined.Therefore,we concluded that PM2.5 exposure may be through oxidative stress and inflammation in the nasal cavity,activated the JAK/STAT pathway,then enhanced the expression level of related inflammatory cytokines,enlarged the Thl/Th2 immune imbalance,increased the synthesis and secretion of IgE,finally aggravated the symptoms of allergic rhinitis. |
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