Sphingolipid profiles and their relationship with inflammatory factors in asthmatic patients of different sexes

Background:Asthma is a heterogeneous disease with distinct prevalence and manifestation between sexes.This study was to identify sex-specific features of asthma via metabolomic analysis of sphingolipids.Methods:Forty-two asthma patients(27 women and 15 men)admitted to the Peking University Third Hospital from January 2015 to December 2015 were enrolled.Peripheral venous blood was collected for metabolomic analysis by targeted liquid chromatography-mass spectrometry.Sex hormones(estradiol,progesterone,testosterone,and androstenedione)and multiple inflammatory factors(periostin,leptin,IgE,IL-4,IL-5,IL-10,IL-13,IL-17A,and IFN-γ)were also assessed.The eosinophil percentage in induced sputum was also detected.All these data were applied to comparative analysis between sexes.Results:Testosterone was negatively related to periostin(ρ=-0.420,P=0.009)and IL-5(ρ=-0.540,P=0.012),while estradiol was positively related to the blood eosinophil percentage(ρ=0.384,P=0.025).Among the eighteen species of sphingolipids detected in the 42 patients,five ceramide(Cer)species(Cer16:0,Cer:20:0,Cer22:0,Cer24:0,and Cer26:0)and one sphingomyelin(SM)species(SM38:0)were significantly higher in male than in female patients.Further investigation found that the correlation between Cer20:0 and IL-5 was positive in males(ρ=0.943,P=0.005)but negative in females(ρ=-0.561,P=0.030).Conclusions:Testosterone was negatively correlated with eosinophil inflammatory factors,but estradiol was positively correlated.Male asthma patients had higher ceramide and sphingomyelin levels than female patients.Different sexes had opposite correlations with ceramide and IL-5,respectively,suggesting that therapeutic strategies targeting ceramide should be different between sexes.