Serum Methylarginines and Spirometry-Measured Lung Function in Older Adults

Rationale
Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans.
Objectives
This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures.
Methods
Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity.
Measurements and Main Results
In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function.
Conclusions
After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function.

研究背景
甲基精氨酸是内源性一氧化氮合酶（nitric oxide synthase）抑制剂，已有动物模型研究提示其与肺部疾病存在关联，但此前尚未有研究探讨其与人类肺功能肺量测定指标的关联。

研究目的
本研究针对社区居住的老年成人代表性样本，检测不对称二甲基精氨酸（asymmetric dimethylarginine）与对称二甲基精氨酸（symmetric dimethylarginine）的血清浓度，并分析其与肺量测定法所得肺功能指标的关联。

研究方法
本研究基于澳大利亚亨特社区研究（Hunter Community Study）的老年人群样本，收集了临床、生活方式、人口统计学特征、甲基化精氨酸以及L-精氨酸（采用液相色谱-串联质谱法LC-MS/MS检测）的相关数据。本研究纳入的5项核心肺功能结局指标包括：1秒用力呼气容积（Forced Expiratory Volume in 1 second, FEV1）、用力肺活量（Forced Vital Capacity, FVC）、1秒用力呼气容积/用力肺活量比值（Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, FEV1/FVC）、1秒用力呼气容积占预计值百分比（Percent Predicted Forced Expiratory Volume in 1 second, %pred FEV1）以及用力肺活量占预计值百分比（Percent Predicted Forced Vital Capacity, %pred FVC）。

测量指标与主要结果
在校正混杂因素的分析中，存在具有统计学意义的独立关联：a) 血清不对称二甲基精氨酸水平升高与1秒用力呼气容积降低、用力肺活量降低相关；b) 血清L-精氨酸/不对称二甲基精氨酸比值降低与1秒用力呼气容积降低、1秒用力呼气容积占预计值百分比降低以及用力肺活量占预计值百分比降低相关。与之相反，未观察到对称二甲基精氨酸与肺功能指标存在显著关联。

研究结论
在校正临床、人口统计学、生化及药理学混杂因素后，血清不对称二甲基精氨酸水平升高与核心肺功能指标降低独立相关。未来仍需开展进一步研究，以明确甲基精氨酸是否可预测肺功能的下降。