Increased urinary l-histidine in patients with asthma–COPD overlap: a pilot study

Abstract

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

Acknowledgments

We thank SY Hwang for the excellent statistical support. AstraZeneca supported this study.

Author contributions

All authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.