Lysophosphatidic acid species are associated with exacerbation in chronic obstructive pulmonary disease

• Published in: BMC pulmonary medicine Vol. 21; no. 1; p. 301
• Main Authors: Li, Qingling, Wong, Weng, Birnberg, Andrew, Chakrabarti, Arindam, Yang, Xiaoying, Choy, David F, Olsson, Julie, Verschueren, Erik, Neighbors, Margaret, Sandoval, Wendy, Rosenberger, Carrie M, Grimbaldeston, Michele A, Tew, Gaik W
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 23-09-2021; BioMed Central; BMC
• Subjects: Aged; Antibiotics; Asthma; Biomarkers; Biomarkers - blood; Blood; Body mass index; Bronchitis; Chronic obstructive pulmonary disease; Clinical trials; Development and progression; Diagnosis; Disease Progression; Drug development; Emphysema; Exacerbation; Female; Humans; Lipidomic; Lipids; Logistic Models; Lung diseases; Lung diseases, Obstructive; Lysophosphatidic acid; Lysophospholipids - blood; Male; Mass spectrometry; Middle Aged; Obstructive lung disease; Patients; Placebos; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive - blood; Pulmonary Disease, Chronic Obstructive - physiopathology; Pulmonology; Questionnaires; Randomized Controlled Trials as Topic; Respiratory tract diseases; Risk factors; Risk groups; Scientific imaging; Serum lysophosphatidic acid species; Severity of Illness Index; Species; Steroids; United States; Exacerbation; Chronic obstructive pulmonary disease; Serum lysophosphatidic acid species; Lipidomic
• ISSN: 1471-2466; 1471-2466
• DOI: 10.1186/s12890-021-01670-9

Chronic obstructive pulmonary disease (COPD) exacerbations are heterogenous and profoundly impact the disease trajectory. Bioactive lipid lysophosphatidic acid (LPA) has been implicated in airway inflammation but the significance of LPA in COPD exacerbation is not known. The aim of the study was to investigate the utility of serum LPA species (LPA16:0, 18:0, 18:1, 18:2, 20:4) as biomarkers of COPD exacerbation.
LPA species were measured in the baseline placebo sera of a COPD randomized controlled trial. Tertile levels of each LPA were used to assign patients into biomarker high, medium, and low subgroups. Exacerbation rate and risk were compared among the LPA subgroups.
The levels of LPA species were intercorrelated (rho 0.29-0.91). Patients with low and medium levels of LPA (LPA16:0, 20:4) had significantly higher exacerbation rate compared to the respective LPA-high patients [estimated rate per patient per year (95% CI)]: LPA16:0-low = 1.2 (0.8-1.9) (p = 0.019), LPA16:0-medium = 1.3 (0.8-2.0) (p = 0.013), LPA16:0-high = 0.5 (0.2-0.9); LPA20:4-low = 1.4 (0.9-2.1) (p = 0.0033), LPA20:4-medium = 1.2 (0.8-1.8) (p = 0.0089), LPA20:4-high = 0.4 (0.2-0.8). These patients also had earlier time to first exacerbation (hazard ratio (95% CI): LPA16:0-low = 2.6 (1.1-6.0) (p = 0.028), LPA16:0-medium = 2.7 (1.2-6.3) (p = 0.020); LPA20.4-low = 2.8 (1.2-6.6) (p = 0.017), LPA20:4-medium = 2.7 (1.2-6.4) (p = 0.021). Accordingly, these patients had a significant increased exacerbation risk compared to the respective LPA-high subgroups [odd ratio (95% CI)]: LPA16:0-low = 3.1 (1.1-8.8) (p = 0.030), LPA16:0-medium = 3.0 (1.1-8.3) (p = 0.031); LPA20:4-low = 3.8 (1.3-10.9) (p = 0.012), LPA20:4-medium = 3.3 (1.2-9.5) (p = 0.025). For the other LPA species (LPA18:0, 18:1, 18:2), the results were mixed; patients with low and medium levels of LPA18:0 and 18:2 had increased exacerbation rate, but only LPA18:0-low patients had significant increase in exacerbation risk and earlier time to first exacerbation compared to the LPA18:0-high subgroup.
The study provided evidence of association between systemic LPA levels and exacerbation in COPD. Patients with low and medium levels of specific LPA species (LPA16:0, 20:4) had increased exacerbation rate, risk, and earlier time to first exacerbation. These non-invasive biomarkers may aid in identifying high risk patients with dysregulated LPA pathway to inform risk management and drug development.