Oh Jee Youn, Lee Young Seok, Min Kyung Hoon, Hur Gyu Young, Lee Sung Yong, Kang Kyung Ho, Rhee Chin Kook, Park Seoung Ju, Khan Adnan, Na Jinhyuk, Park Youngja H, Shim Jae Jeong
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea.
Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea.
Int J Chron Obstruct Pulmon Dis. 2018 Jun 5;13:1809-1818. doi: 10.2147/COPD.S163189. eCollection 2018.
Asthma-COPD overlap (ACO) is heterogeneous in nature and requires a unified diagnostic approach. We investigated the urinary levels of l-histidine, a precursor of histamine related to inflammatory responses, as a new candidate biomarker for diagnosing this condition.
We performed a prospective multicenter cohort study with retrospective analysis of 107 patients, who were divided into three groups: asthma, COPD, and ACO, according to the Spanish guidelines algorithm. Urinary l-histidine levels were measured using liquid chromatography-mass spectrometry. High-resolution metabolomic analysis, coupled with liquid chromatography-mass spectrometry and followed by multivariate statistical analysis, was performed on urine samples to discriminate between the metabolic profiles of the groups.
Urinary l-histidine levels were significantly higher in patients with ACO than in those with asthma or COPD, but the subgroups of ACO, classified according to disease origin, did not differ significantly. High urinary l-histidine level was a significant factor for the diagnosis of ACO even after adjusting for age, sex, and smoking amount. Among patients with airflow obstruction, the urinary l-histidine levels were elevated in patients with a documented history of asthma before the age of 40 years or bronchodilator responsiveness ≥400 mL; bronchodilator responsiveness ≥200 mL of forced expiratory volume in 1 second and exceeding baseline values by 12% on two or more visits; blood eosinophil count ≥300 cells·mm; and frequent exacerbations ( < 0.05).
Urinary l-histidine could be a potential biomarker for ACO, regardless of the diversity of diagnostic definitions used.
哮喘-慢性阻塞性肺疾病重叠综合征（ACO）本质上具有异质性，需要统一的诊断方法。我们研究了与炎症反应相关的组胺前体L-组氨酸的尿水平，将其作为诊断该疾病的一种新的候选生物标志物。
我们进行了一项前瞻性多中心队列研究，并对107例患者进行回顾性分析，根据西班牙指南算法将患者分为三组：哮喘组、慢性阻塞性肺疾病组和ACO组。采用液相色谱-质谱法测定尿L-组氨酸水平。对尿样进行高分辨率代谢组学分析，结合液相色谱-质谱法，随后进行多变量统计分析，以区分各组的代谢谱。
ACO患者的尿L-组氨酸水平显著高于哮喘或慢性阻塞性肺疾病患者，但根据疾病起源分类的ACO亚组之间无显著差异。即使在调整年龄、性别和吸烟量后，高尿L-组氨酸水平仍是ACO诊断的一个重要因素。在气流受限患者中，有40岁前哮喘病史或支气管扩张剂反应性≥400 mL；支气管扩张剂反应性≥1秒用力呼气量200 mL且在两次或更多次就诊时超过基线值12%；血嗜酸性粒细胞计数≥300个细胞·mm；以及频繁急性加重的患者尿L-组氨酸水平升高（P<0.05）。
无论使用何种诊断定义，尿L-组氨酸都可能是ACO的潜在生物标志物。
