| Background:Asthma is a chronic airway inflammatory disease involving a variety of inflammatory and structural cells.It usually manifests as a wide range of reversible airflow obstruction in association with airway hyperresponsiveness(AHR).Patients may experience recurrent wheezing,cough,chest tightness and shortness of breath,which often occur or worsen in the morning and at night.Uncontrolled asthma will present irreversible airway narrowing and remodeling,which seriously affect the life quality of patients.In recent decades,the worldwide prevalence of asthma has been increasing year by year.There are more than 300 million asthma patients across the world,and more than 30 million in China.Asthma brings great psychological and economic burden to the patients and the society.Thus,it is very important to study the cause and risk factors of asthma.The occurrence of asthma is thought to be a combination of genetic and environmental factors.Asthma is a polygenic hereditary disease with a distinct tendency to flock.The external environment we are exposed to,such as allergens,atmospheric pollutants,meteorological factors,pathogenic microorganisms,are considered to be closely related to the occurrence and development of asthma.In addition to the external environment,the microenvironment inside also plays a vital role.The series of combined effects of external and internal environment both have an impact on the development of the immune system,especially in childhood,thus leading to the occurrence of asthma.The internal environment of the organism is mainly composed of the symbiotic microbiota.In addition to the well-known gastrointestinal tract,the skin,respiratory tract,urinary tract and other systems also have specific microbial colonization.Imbalance of the microbiome may lead to occurrence of some diseases,such as inflammatory bowel disease,atopic dermatitis,metabolic disease and cardiovascular disease.Studies have shown that early life is a "critical window" for the development and maturation of the microbiome.At this stage,the disturbance of some external factors will lead to imbalance of the microbiome,which will then affect the health of the whole body.Among these factors,the application of antibiotics become more and more common for children.Application of antibiotics can effectively destroy the pathogenic bacteria,and also alters the internal microbiome,causing temporary or continuous imbalance of the microbiome,which then lead to immune system disorders or the occurrence and development of immune-related diseases.The external environment is also closely related to the occurrence of asthma.Air pollution is a representative factor,such as the particulate matter(PM2.5).PM2.5 directly goes into the bronchioles and alveoli,interfere with the gas exchange in the lungs,causing a series of respiratory diseases.At the same time,the global warming also leads to a series of concomitant effects.Therefore,it is meaningful to explore the relationship between meteorological factors and the occurrence and development of asthma.In this study,we discuss the relationship between internal and external environment and the development of asthma,trying to provide theoretical basis and new insight for the early prevention and treatment of asthma.Method:(1)A retrospective questionnaire was conducted for children with asthma and healthy control children.The contents of the questionnaire include basic conditions,asthma incidence,personal and family allergy history,birth feeding history,antibiotic intervention,and cigarette exposure.Using statistical methods,we identified risk factors that may be associated with asthma in genetic background,lifestyle,and antibiotics exposure.(2)The C57BL/6 mice were treated with vancomycin in early-life,and an OVA-induced asthma model was established at 6 weeks of age,at which time the vancomycin intervention is terminated.Total cell number in the alveolar lavage fluid and the cell classification were detected.The lung pathological sections were used to evaluate the inflammatory cells infiltration and mucus secretion in the airway.The expression of related cytokines was detected by Q-PCR to observe the effect of vancomycin intervention on the development of airway inflammation in subsequent asthma.At the same time,16S rDNA sequencing was performed to analyze the composition of intestinal and airway microbiome,and to explore the changes leading by vancomycin exposure in early-life.(3)The monthly average data of meteorological factors(temperature,PM2.5,PM 10)and the outpatient and emergency visits of asthmatic children in the children's hospital of zhejiang university school of medicine from 2014 to 2017 were collected.Correlation analysis was conducted between meteorological factors and the visits of asthmatic children to explore the relationship between them.(4)C57BL/6 mice were raised respectively under different temperature conditions(10?,20?,30?),and a HDM-induced asthma model was established and short-term exposure of PM2.5 was conducted.Airway inflammation was evaluated with the above methods.Results:(1)We found that respiratory tract infection was the most common inducing factor of asthma attack in children,and most children were susceptible to asthma attacks in winter.The incidence of allergic disease in asthmatic children was significantly higher than that in healthy children.Allergic rhinitis is most common in asthmatic children.The positive rate of family history and allergen detection in asthmatic children was higher than that in healthy children.Dust mite was the most common allergen for asthmatic children.The time of first exposure to antibiotics for asthmatic children was earlier than that for healthy children,and antibiotics were used more frequently within 1 to 3 years of age in children with asthma.At the same time,the longest course of antibiotic intervention in asthmatic children within 3 years of age was significantly longer than that in healthy children.Logistic regression analysis revealed that positive allergen test,family history of allergy,and times of antibiotics intervention under 3 years old were the risk factors for children's asthma.(2)Vancomycin intervention in early-life aggravated airway inflammation in subsequent asthma in adult mice.At the same time,vancomycin exposure induced the imbalance of intestinal and airway microbiome,in which the decrease of Firmicutes in intestinal and the decrease of Clostridiaceae-1 and Micrococcaceae in the airway may be related to the up-regulation of Th2 immune response and airway inflammation.But short term of vancomycin administration in early-life did not aggravate airway inflammation in subsequent asthma in adult mice.(3)After the analysis of the correlation between meteorological factors(temperature,PM2.5,PM 10)and asthma indicated that the average temperature was negatively correlated with the outpatient and emergency visits of children with asthma,which was more obvious in children younger than 6 years old.There is a significant positive correlation between PM2.5 concentration and emergency visits of asthmatic children.Among children under 6 years old,the percentage of asthma visits to total hospital visits is also related to PM2.5 concentration.There was also a moderate positive correlation between PM10 concentration and asthma emergency visits and outpatient visits,and the correlation was more obvious in children under 6 years old.(4)There were no differences in the airway inflammatory of the asthma mice,which were raised under different environment temperature.Short-term exposure of PM2.5 to HDM-induced asthma models increased the number of inflammatory cells and mucus secretion in the airway,as well as the expression of GM-CSF,IL-33 and Th2-related cytokines.Conclusions:(1)Positive aeroallergens,family history of allergy and frequency of antibiotics used within 3 years old were risk factors for the occurrence of childhood asthma.(2)Vancomycin intervention in early-life may lead to increased airway inflammation in subsequent asthma models by altering intestinal and airway microecology and upregulating Th2 immune responses in mice.(3)The average monthly ambient temperature,PM2.5 and PM 10 concentration may be related to the onset of asthma,especially in children under 6 years old.(4)Different temperature conditions did not cause changes in airway inflammation in asthmatic mice.Short-term exposure to PM2.5 increased the expression of GM-CSF,IL-33 and Th2-related cytokines in lung tissues,and aggravate the airway inflammation in the HDM-induced asthma model in mice. |
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