肥胖与哮喘共同决定了一个独特的呼吸系统代谢表型
2017/05/10
摘要
背景：流行病学与临床证据支持一个肥胖相关的哮喘表型的存在。迄今尚无明显的病理生理因素或特殊的生物标志物被识别，但是增加的氧化应激已有被报道。
目的：我们旨在验证肥胖哮喘病人、正常体重哮喘病人和肥胖非哮喘受试者呼出气冷凝物中的代谢物是否可以识别一个单独“哮喘-肥胖”呼吸系统代谢表型，这里被定义为“代谢型”的特殊并经统计学验证的生物学标志物。
方法学：25例肥胖哮喘病人（OA），30例肥胖非哮喘受试者（LA）和30例轻-中度年龄匹配的正常体重哮喘病人（ONA）参与了这一横断面研究。核磁共振资料通过偏最小二乘判别分析法经行分析，并且结果在一个独立病人集群中被验证。
结果：通过核磁共振资料，我们获得了强回归模型显著区别OA组与LA组（质量参数：拟合优度参数R2 = 0.81和预测优度参数Q2 = 0.79），OA组与ONA组（R2 = 0.91 和Q2 = 0.89）。所有组间比较（R2 = 0.86 和 Q2 = 0.83）表明OA组具有一个与在其它组别病人中获得的完全相异的呼吸系统代谢成分。我们也鉴别了组间分类中独立于临床偏移的特殊生物学标志物。它们涉及到甲烷、丙酮酸盐、乙醛酸盐和二元羧酸盐代谢路径。
结论：基于核磁共振的代谢组学表明OA患者具有完全不同于受哮喘和肥胖独立影响病人的一个呼吸系统代谢指纹图谱特征。这样的表型差异强烈提示独特的病理生理路径参与成人肥胖受试者中哮喘的发病机制。此外，肥胖哮喘代谢型可以明确基于非偏倚生物学标志物的病人分层管理策略，并且有重要的诊断和治疗启示。
Coexistence of obesity and asthma determines a distinct respiratory metabolic phenotype
Maniscalo M, Paris D, Melck DJ, D’Amato M, Zedda A, Sofia M, Stellato C, Motta A
J Allergy Clin Immunol.2016 Oct 14. pii: S0091-6749(16)31122-8.
Abstract
BACKGROUND: Epidemiologic and clinical evidence supports the existence of an obesity-related asthma phenotype. No distinct pathophysiologic elements or specific biomarkers have been identified thus far, but increased oxidative stress has been reported
OBJECTIVE: We aimed at verifying whether metabolomics of exhaled breath condensate from obese asthmatic (OA) patients, lean asthmatic (LA) patients, and obese nonasthmatic (ONA) subjects could recognize specific and statistically validated biomarkers for a separate "asthma-obesity" respiratory metabolic phenotype, here defined as "metabotype."
METHODS: Twenty-five OA patients, 30 ONA subjects, and 30 mild-to-moderate LA age-matched patients participated in a cross-sectional study. Nuclear magnetic resonance (NMR) profiles were analyzed by using partial least-squares discriminant analysis, and the results were validated with an independent patient set.
RESULTS: From NMR profiles, we obtained strong regression models that distinguished OA patients from ONA subjects (quality parameters: goodness-of-fit parameter R2 = 0.81 and goodness-of-prediction parameter Q2 = 0.79), as well as OA patients from LA patients (R2 = 0.91 and Q2 = 0.89). The all-classes comparison (R2 = 0.86 and Q2 = 0.83) indicated that OA patients possess a respiratory metabolic profile fully divergent from those obtained in the other patient groups. We also identified specific biomarkers for between-class separation, which are independent from clinical bias. They are involved in the methane, pyruvate, and glyoxylate and dicarboxylate metabolic pathways.
CONCLUSIONS: NMR-based metabolomics indicates that OA patients are characterized by a respiratory metabolic fingerprint fully different from that of patients independently affected by asthma or obesity. Such a phenotypic difference strongly suggests unique pathophysiologic pathways involved in the pathogenesis of asthma in adult obese subjects. Furthermore, the OA metabotype could define a strategy for patient stratification based on unbiased biomarkers, with important diagnostic and therapeutic implications.
背景：流行病学与临床证据支持一个肥胖相关的哮喘表型的存在。迄今尚无明显的病理生理因素或特殊的生物标志物被识别，但是增加的氧化应激已有被报道。
目的：我们旨在验证肥胖哮喘病人、正常体重哮喘病人和肥胖非哮喘受试者呼出气冷凝物中的代谢物是否可以识别一个单独“哮喘-肥胖”呼吸系统代谢表型，这里被定义为“代谢型”的特殊并经统计学验证的生物学标志物。
方法学：25例肥胖哮喘病人（OA），30例肥胖非哮喘受试者（LA）和30例轻-中度年龄匹配的正常体重哮喘病人（ONA）参与了这一横断面研究。核磁共振资料通过偏最小二乘判别分析法经行分析，并且结果在一个独立病人集群中被验证。
结果：通过核磁共振资料，我们获得了强回归模型显著区别OA组与LA组（质量参数：拟合优度参数R2 = 0.81和预测优度参数Q2 = 0.79），OA组与ONA组（R2 = 0.91 和Q2 = 0.89）。所有组间比较（R2 = 0.86 和 Q2 = 0.83）表明OA组具有一个与在其它组别病人中获得的完全相异的呼吸系统代谢成分。我们也鉴别了组间分类中独立于临床偏移的特殊生物学标志物。它们涉及到甲烷、丙酮酸盐、乙醛酸盐和二元羧酸盐代谢路径。
结论：基于核磁共振的代谢组学表明OA患者具有完全不同于受哮喘和肥胖独立影响病人的一个呼吸系统代谢指纹图谱特征。这样的表型差异强烈提示独特的病理生理路径参与成人肥胖受试者中哮喘的发病机制。此外，肥胖哮喘代谢型可以明确基于非偏倚生物学标志物的病人分层管理策略，并且有重要的诊断和治疗启示。
(刘影1 张红萍1 王刚 四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（J Allergy Clin Immunol.2016 Oct 14. pii: S0091-6749(16)31122-8.）
（J Allergy Clin Immunol.2016 Oct 14. pii: S0091-6749(16)31122-8.）
Coexistence of obesity and asthma determines a distinct respiratory metabolic phenotype
Maniscalo M, Paris D, Melck DJ, D’Amato M, Zedda A, Sofia M, Stellato C, Motta A
J Allergy Clin Immunol.2016 Oct 14. pii: S0091-6749(16)31122-8.
Abstract
BACKGROUND: Epidemiologic and clinical evidence supports the existence of an obesity-related asthma phenotype. No distinct pathophysiologic elements or specific biomarkers have been identified thus far, but increased oxidative stress has been reported
OBJECTIVE: We aimed at verifying whether metabolomics of exhaled breath condensate from obese asthmatic (OA) patients, lean asthmatic (LA) patients, and obese nonasthmatic (ONA) subjects could recognize specific and statistically validated biomarkers for a separate "asthma-obesity" respiratory metabolic phenotype, here defined as "metabotype."
METHODS: Twenty-five OA patients, 30 ONA subjects, and 30 mild-to-moderate LA age-matched patients participated in a cross-sectional study. Nuclear magnetic resonance (NMR) profiles were analyzed by using partial least-squares discriminant analysis, and the results were validated with an independent patient set.
RESULTS: From NMR profiles, we obtained strong regression models that distinguished OA patients from ONA subjects (quality parameters: goodness-of-fit parameter R2 = 0.81 and goodness-of-prediction parameter Q2 = 0.79), as well as OA patients from LA patients (R2 = 0.91 and Q2 = 0.89). The all-classes comparison (R2 = 0.86 and Q2 = 0.83) indicated that OA patients possess a respiratory metabolic profile fully divergent from those obtained in the other patient groups. We also identified specific biomarkers for between-class separation, which are independent from clinical bias. They are involved in the methane, pyruvate, and glyoxylate and dicarboxylate metabolic pathways.
CONCLUSIONS: NMR-based metabolomics indicates that OA patients are characterized by a respiratory metabolic fingerprint fully different from that of patients independently affected by asthma or obesity. Such a phenotypic difference strongly suggests unique pathophysiologic pathways involved in the pathogenesis of asthma in adult obese subjects. Furthermore, the OA metabotype could define a strategy for patient stratification based on unbiased biomarkers, with important diagnostic and therapeutic implications.
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中性粒细胞胞外诱捕网在哮喘和慢性阻塞性肺疾病中的作用
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基质金属蛋白酶-1活化促进气道平滑肌生长并加重哮喘严重程度
