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.

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.

OBJECTIVE: To compare the serum glycerophospholipid levels in the inflammatory subtypes of asthma by using targeted metabolomic analysis. METHODS: Demographic and clinical data were collected from 51 patients with asthma between January 2015 and December 2015. Routine blood and sputum induction tests were performed. Eosinophilic asthma was defined as induced sputum containing ⪖ 3% eosinophils, and neutrophilic asthma, as induced sputum containing ⪖ 71% neutrophils. Serum metabolic glycerophospholipid profile was determined by liquid chromatography-mass spectrometry. Differences in glycerophospholipid levels between eosinophilic and non-eosinophilic asthma and between neutrophilic and non-neutrophilic asthma were analyzed using partial least squares discriminant analysis. RESULTS: The serum lysophosphatidylglycerol level was significantly higher in the group with ⪖ 3% eosinophils in sputum than in the group with < 3% eosinophils in sputum. The area under the receiver-operating characteristic curve was ⪖ 70%. There was no significant difference in the serum metabolic glycerophospholipid profile between the group with sputum neutrophils ⪖ 71% and the group with sputum neutrophils < 71%. CONCLUSION Serum lysophosphatidylglycerol is produced abundantly in eosinophilic asthma and may be a biomarker of eosinophilic asthma. This information is helpful for identifying and tailoring treatment for the common asthma subtypes.
Adult ; Asthma ; blood ; immunology ; Eosinophils ; immunology ; Female ; Glycerophospholipids ; blood ; Humans ; Male ; Metabolomics ; Middle Aged ; Neutrophils ; immunology ; Sputum ; cytology ; immunology