1. Effects Of Obesity On Lung Function In Allergic And Non-allergic Asthmatic Children. 2. Effects Of Macrophage Ablation On Airway Inflammation And Airway Hyperresponsiveness In Obese Mice

Objective: To investigate whether the effect of obesity on lung function is different between nonallergic and allergic asthmatic children.Methods: We conducted a cross sectional study involving 230 pre-pubertal children who were newly diagnosed with mild-to-moderate asthma.The study population was divided into allergy and nonallergic groups according to their SPT test result.Furthermore,based on different body mass index(BMI)Z score,they were also divided into allergic normal weight group,allergic overweight group,allergic obese group,nonallergic normal weight group,nonallergic overweight group and nonallergic obese group.The effect of BMI on lung function in asthmatic children with different allergic status was analysized.The influence of gender on the effect of obesity on lung function in allergic and nonallergic asthmatic children was studied respectively.Results: There were significant differences in peak expiratory flow(PEF),maximal expiratory flows at the 75% of vital capacity(MEF75),MEF50,MEF25,and maximal mid expiratory flow(MMEF)among different groups of mild-to-moderate asthmatic children,and the levels of all above markers were the lowest in nonallergic obese group,followed by nonallergic overweight group(P<0.05).There was no correlation between the BMI-Zscore and the indexes of allergic asthma(P>0.05).The pulmonary function indexes(PEF,MEF75,MEF50,MEF25 and MMEF)of nonallergic asthma children were negatively correlated with BMI-Z score(r=-0.314?-0.273,P all <0.01).A stronger negative association between BMI Z score and function parameters was observed in nonallergic boys(P<0.01)than nonallergic girls(P>0.05).Conclusions: The effect of obesity on lung function in asthmatic children with different atopic status is different.Obesity has a stronger impact on lung function in nonallergic asthma children,and mainly affects ventilation function.Gender could affect the relationship between BMI and function parameters in nonallergic children.It was stronger in boys than that in girls.Objective: To investigate whether macrophage was involved in the mechanism of obesity induced airway responsiveness and inflammation.Methods: Obesity model was established by reducing the number of mouse when they were fed by mother mouse.When they were 150 day old,4 m M 2-CA(Sigma-Aldrich)in a volume of 40 ul was administered by intranasal delivery everyday for a week in macrophage depleted obesity group.The normal weight control group and obesity control group were treated with saline in the same volume.Airway resistance was performed 24 hours after the last administration.To verify whether macrophage was depleted successfully,bronchoalveolar lavage fluid were obtained to count total and classified inflammatory cells.Hematoxylin & Eosin(HE)staining and Q-PCR for TNF-??IL-6 and TGF?1 in lung tissue were done to investigate the effect of depleting macrophage on lung inflammation induced by obesity.Results: The mouse in obesity control group displayed a higher airway responsiveness to Methacholine which was reduced by depleting macrophage to some extend.Total cells especially macrophages in bronchoalveolar lavage in obesity group were significantly higher than those in normal weight groups,and macrophages were significantly reduced by administration of 2-CA.What more,more inflammation cells infiltrated around the alveolar in obesity groups while the macrophage depleted obesity group and the normal weight control group displayed fewer inflammation cells around the alveolar.Lung TNF-? IL-6?TGF-?1 m RNA expression were significantly increased in obesity groups while TNF-? was significantly reduced after macrophage was depleted.Conclusion: Macrophage may be involved in the mechanism of obesity induced airway hyperresponsiveness and inflammation.