Increased urinary L-histidine in patients with asthma–COPD overlap: a pilot study
Received 19 January 2018
Accepted for publication 19 March 2018
Published 5 June 2018 Volume 2018:13 Pages 1809—1818
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 2
Editor who approved publication: Dr Richard Russell
Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Adnan Khan,4 Jinhyuk Na,4 Youngja H Park,4 Jae Jeong Shim1
1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea; 4Metabolomics Laboratory, College of Pharmacy, Korea University, Sejong, Republic of Korea
Purpose: 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.
Patients and methods: 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.
Results: 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−3; and frequent exacerbations (P < 0.05).
Conclusion: Urinary l-histidine could be a potential biomarker for ACO, regardless of the diversity of diagnostic definitions used.
Keywords: asthma, COPD, ACO, urinary L-histidine, metabolomics, inhaled corticosteroid
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