Amino Acid-Based Metabolic Indexes Identify Patients With Chronic Obstructive Pulmonary Disease And Further Discriminates Patients In Advanced BODE Stages

Abstract

Background

The BODE index is a multidimensional grading system for predicting the prognoses of patients with chronic obstructive pulmonary disease (COPD). This study investigated whether an amino acids-based metabolic profile developed for heart failure patients (including histidine, ornithine, phenylalanine, and leucine) could identify COPD patients and further discriminates COPD patients in advanced BODE stages.

Methods

Ultra-performance liquid chromatography was performed on 119 participants, including 75 COPD patients at different BODE stages and 44 normal controls. Albumin, pre-albumin, transferrin, high sensitivity C-reactive protein, and hand grip strength were also measured. Receiver operating characteristic curves and area under curves were used for estimation.

Results

The BODE points in our patients were 3.29 [95% confidence interval (CI) = 2.74–3.85]. Compared to normal controls, COPD patients had lower leucine but higher ornithine levels. A COPD score, developed based on leucine and ornithine, significantly discriminated COPD from normal controls [odds ratio (OR) = 2.71, 95% CI = 1.83–4.04, p <0.001]. A COPD score of ≥ 3.00 had an OR of 15.58 (95% CI = 5.96–40.73, p <0.001). In COPD patients from BODE 1 to BODE 4, the levels of histidine, ornithine and phenylalanine increased significantly. In multivariable analysis, histidine and phenylalanine were independently able to distinguish BODE stages 3 and 4 from BODE 1 and were adopted to develop a metabolic score. Metabolic scores identified patients at BODE 3 and 4 (OR = 2.74, 95% CI =1.41–5.29, p = 0.003) better than hand grip strength, high sensitive C-reactive protein, albumin, pre-albumin, and transferrin value. A metabolic score of ≥9.53 significantly discriminated BODE 3 and 4 from BODE 1 and 2 (OR = 8.56, 95% CI = 2.77–26.39, p <0.001).

Conclusion

Amino acid-based COPD score and metabolic score discriminate COPD patients from normal controls, and identify patients in advanced stages of COPD.

Keywords:

• chronic obstructive pulmonary disease
• BODE
• metabolomics
• amino acids
• heart failure

Acknowledgments

This work was supported by Chang Gung Memorial Hospital (CMRPG2G0621). We thank Yi-Tsen Lin for providing nutritional evaluation support of our study population. We also thank the Healthy Aging Research Center, Chang Gung University and the Featured Areas Research Center Program within the Framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan.

Abbreviations

COPD, Chronic obstructive lung disease; BMI, body mass index; FEV1, forced expiratory volume in one second; mMRC, modified Medical Research Council questionnaire; 6MWD, six-minute walking distance; HF, heart failure; UPLC, ultra-performance liquid chromatography; CAT, chronic obstructive lung disease assessment test; SpO2, oxygen saturation; hsCRP, high sensitive C-reactive protein; Hc, corrected histidine level; Oc, corrected ornithine levels; Pc, corrected phenylalanine levels; ROC, receiver operating characteristic; AUCs, area under curves.

Disclosure

The authors report no conflicts of interest in this work.