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Effect of fexofenadine hydrochloride on allergic rhinitis aggravated by air pollutants.

ABSTRACT: In recent decades, seasonal allergic rhinitis (SAR) prevalence has increased and recent studies have shown that air pollutants, such as diesel exhaust particles (DEP), can increase inflammatory and allergic biomarkers. The aim of this study was to investigate the effects of DEP on SAR symptoms induced by ragweed and to evaluate the efficacy and safety of fexofenadine HCl 180 mg versus placebo. This phase 3, single-centre, sequential, parallel-group, double-blind, randomised study (NCT03664882) was conducted in an environmental exposure unit (EEU) during sequential exposures: Period 1 (ragweed pollen alone), Period 2 (ragweed pollen+DEP), and Period 3 (ragweed pollen+DEP+single-dose fexofenadine HCl 180 mg or placebo). Efficacy and safety were evaluated in Period 3. Primary endpoints were the area under the curve (AUC) of total nasal symptom score (TNSS) from baseline to hour 12 (AUC_0-12) during Period 1 and Period 2; and the AUC of the TNSS from hour 2 to 12 (AUC_2-12) during Period 3. 251 out of 257 evaluable subjects were included in the modified intent-to-treat population. Least squares mean difference (95% CI) for TNSS Log AUC_0-12 in Period 2 versus Period 1 was 0.13 (0.081-0.182; p<0.0001). Least squares mean difference in TNSS Log AUC_2-12 for fexofenadine HCl versus placebo during Period 3 was -0.24 (-0.425--0.047; p=0.0148). One fexofenadine HCl-related adverse event was observed. SAR symptoms evoked by ragweed were aggravated by DEP. Fexofenadine HCl 180 mg was effective in relieving pollen-induced, air pollution-aggravated allergic rhinitis symptoms.

SUBMITTER: Ellis AK

PROVIDER: S-EPMC8021806 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Allergic rhinitis (AR) is a common chronic inflammatory disease of the upper respiratory tract. Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and belongs to environmental endocrine disruptors (EDCs). It can be entered the human body which is harmful to health. The relationship between DEHP and AR is still inconclusive. This study aims to investigate the effect of environmental pollutants DEHP on AR. By examining DEHP metabolites in the urine of AR patients and building an AR model. 24 BALB/c mice were used as the study subjects, and ovalbumin (OVA) and DEHP (3 mg/kg/body) were used for intragastric administration. They were divided into control group, DEHP group, OVA group and OVA?+?DEHP group. Examination, behavioral scoring, inflammatory factor testing, oxidative stress testing, detection of aryl hydrocarbon receptor (AhR) and signaling pathways CYP1A1 and CYP1B1 related proteins and mRNA. The concentrations of 3 metabolites of DEHP (MEHHP, MEOHP, and MEHP) in urine of AR patients were higher. And HE-staining showed that for the control group, many chronic inflammatory cell infiltration and nasal mucosal destruction were observed in the OVA?+?DEHP group and were more severe than the OVA group. Allergic symptom scores were obtained from sneezing, scratching, number of scratching, and nose flow. The scores of the OVA group and the OVA?+?DEHP group were higher than 7 points. Serum ELISA and nasal mucosal oxidative stress tests are more serious in the OVA?+?DEHP group. The expression of AhR protein and its mRNA was increased in the DEHP group, OVA group and OVA?+?DEHP group. The OVA?+?DEHP group was more significant in the OVA group and DEHP group. And the mRNAs of the AhR-related signaling pathways CYP1A1 and CYP1B1 were also more prominent in the OVA?+?DEHP group. DEHP may aggravate its inflammatory response through the AhR pathway closely related to the environment. When combined with OVA, DEHP can further aggravate the OVA-induced nasal inflammatory response and make the nasal cavity have undergone severe changes, and many inflammatory cells have infiltrated. DEHP has shown an adjuvant effect, and the AhR-related signaling pathways CYP1A1 and CYP1B1 may be critical.

Project description:With the continuous rapid urbanization process over the last three decades, outdoors air pollution has become a progressively more serious public health hazard in China. To investigate the possible associations, lag effects and seasonal differences of urban air quality on respiratory health (allergic rhinitis) in Changchun, a city in Northeastern China, we carried out a time-series analysis of the incidents of allergic rhinitis (AR) from 2013 to 2015. Environmental monitoring showed that PM2.5 and PM10 were the major air pollutants in Changchun, followed by SO?, NO? and O?. The results also demonstrated that the daily concentrations of air pollutants had obvious seasonal differences. PM10 had higher daily mean concentrations in spring (May, dust storms), autumn (October, straw burning) and winter (November to April, coal burning). The mean daily number of outpatient AR visits in the warm season was higher than in the cold season. The prevalence of allergic rhinitis was significantly associated with PM2.5, PM10, SO? and NO?, and the increased mobility was 10.2% (95% CI, 5.5%-15.1%), 4.9% (95% CI, 0.8%-9.2%), 8.5% (95% CI, -1.8%-19.8%) and 11.1% (95% CI, 5.8%-16.5%) for exposure to each 1-Standard Deviation (1-SD) increase of pollutant, respectively. Weakly or no significant associations were observed for CO and O?. As for lag effects, the highest Relative Risks (RRs) of AR from SO?, NO?, PM10 and PM2.5 were on the same day, and the highest RR from CO was on day 4 (L4). The results also indicated that the concentration of air pollutants might contribute to the development of AR. To summarize, this study provides further evidence of the significant association between ambient particulate pollutants (PM2.5 and PM10, which are usually present in high concentrations) and the prevalence of respiratory effects (allergic rhinitis) in the city of Changchun, located in Northeastern China. Environmental control and public health strategies should be enforced to address this increasingly challenging problem.

Project description:Pollen is the main factor causing asthma and allergic rhinitis (AR). However, the key indoor and outdoor factors associated with childhood symptoms of allergic rhinitis (SAR) to pollen are unclear. We investigate the association of exposure to outdoor air pollution and indoor environmental factors with childhood SAR to pollen and consider SAR to pollen in different seasons. A cross-sectional study of 2598 preschool children aged 3-6 was conducted in Changsha, China (2011-2012). The prevalence of SAR to pollen in children and information on indoor environmental factors were obtained by questionnaire. Children's exposure to outdoor air pollutants (PM10, SO2, and NO2) was estimated from the monitored concentrations. The association of exposure to indoor environmental factors and outdoor air pollution with childhood SAR to pollen was estimated by multiple logistic regression models using odds ratio (OR) and a 95% confidence interval (CI), and the relationship between outdoor air pollutants and childhood SAR to pollen was investigated using restricted cubic splines. We found that early-life and current exposure to outdoor air pollution were significantly associated with childhood SAR to pollen in autumn, including exposure to SO2 one year before conception (OR = 1.60, 95% CI = 1.08-2.37) and during entire pregnancy (OR = 1.49, 95% CI = 1.01-2.20) periods, exposure to PM10 during the current period (OR = 1.78, 95% CI = 1.07-2.96), and exposure to NO2 during the early-life (one year before conception and entire pregnancy) and current periods with ORs (95% CI) of 1.72 (1.10-2.71), 1.82 (1.17-2.83), and 1.94 (1.11-3.40), respectively. Further, we found significant associations of both prenatal and postnatal exposure to window condensation with childhood SAR to pollen, with ORs (95% CI) = 1.37 (1.05-1.77) and 1.38 (1.02-1.88), respectively. We encourage SAR to pollen sufferers to stay indoors due to outdoor air pollution and higher pollen concentration outdoors, but indoor ventilation should be maintained.

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Effect of fexofenadine hydrochloride on allergic rhinitis aggravated by air pollutants.

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