Lysophosphatidic acid species are associated with exacerbation in chronic obstructive pulmonary disease.
BMC Pulm Med
; 21(1): 301, 2021 Sep 23.
Article
em En
| MEDLINE
| ID: mdl-34556083
ABSTRACT
BACKGROUND:
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 (LPA160, 180, 181, 182, 204) as biomarkers of COPD exacerbation. PATIENTS ANDMETHODS:
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.RESULTS:
The levels of LPA species were intercorrelated (rho 0.29-0.91). Patients with low and medium levels of LPA (LPA160, 204) had significantly higher exacerbation rate compared to the respective LPA-high patients [estimated rate per patient per year (95% CI)] LPA160-low = 1.2 (0.8-1.9) (p = 0.019), LPA160-medium = 1.3 (0.8-2.0) (p = 0.013), LPA160-high = 0.5 (0.2-0.9); LPA204-low = 1.4 (0.9-2.1) (p = 0.0033), LPA204-medium = 1.2 (0.8-1.8) (p = 0.0089), LPA204-high = 0.4 (0.2-0.8). These patients also had earlier time to first exacerbation (hazard ratio (95% CI) LPA160-low = 2.6 (1.1-6.0) (p = 0.028), LPA160-medium = 2.7 (1.2-6.3) (p = 0.020); LPA20.4-low = 2.8 (1.2-6.6) (p = 0.017), LPA204-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)] LPA160-low = 3.1 (1.1-8.8) (p = 0.030), LPA160-medium = 3.0 (1.1-8.3) (p = 0.031); LPA204-low = 3.8 (1.3-10.9) (p = 0.012), LPA204-medium = 3.3 (1.2-9.5) (p = 0.025). For the other LPA species (LPA180, 181, 182), the results were mixed; patients with low and medium levels of LPA180 and 182 had increased exacerbation rate, but only LPA180-low patients had significant increase in exacerbation risk and earlier time to first exacerbation compared to the LPA180-high subgroup.CONCLUSIONS:
The study provided evidence of association between systemic LPA levels and exacerbation in COPD. Patients with low and medium levels of specific LPA species (LPA160, 204) 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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Lisofosfolipídeos
/
Doença Pulmonar Obstrutiva Crônica
Tipo de estudo:
Clinical_trials
/
Risk_factors_studies
Limite:
Aged
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
BMC Pulm Med
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos