Uric acid and uric acid to creatinine ratio in the assessment of chronic obstructive pulmonary disease: Potential biomarkers in multicomponent models comprising IL-1beta

Abstract

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease, with oxidative stress and inflammation implicated in its development. Uric acid (UA) could exert anti-oxidative, pro-oxidative or pro-inflammatory effects, depending on the specific context. It was recently shown that soluble UA, and not just its crystals, could activate the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to interleukin (IL)-1β secretion. We aimed to assess the differences in blood levels of UA and its ratio with creatinine (UCR) between COPD patients and healthy subjects, as well as their association with disease severity, smoking status, common COPD comorbidities and therapy regimes. The diagnostic characteristics of UA and UCR were also explored. This study included 109 stable COPD patients and 95 controls and measured white blood cells (WBC), C-reactive protein (CRP), fibrinogen (Fbg), IL-1β, creatinine (CREAT) and UA. All of the parameters were increased in COPD patients, except for CREAT. UA and UCR were positively associated with WBC, CRP and IL-1β. COPD smokers had lower UA and UCR values. Common COPD therapy did not affect UA or UCR, while patients with cardiovascular diseases (CVD) had higher UA, but not UCR, levels. Patients with higher UCR values showed worse disease-related outcomes (lung function, symptoms, quality of life, history of exacerbations, BODCAT and BODEx). Also, UCR differentiated patients with different severity of airflow limitation as well as symptoms and exacerbations. The great individual predictive potential of UCR and IL-1β was observed with their odds ratios (OR) being 2.09 and 5.53, respectively. Multiparameter models of UA and UCR that included IL-1β were able to correctly classify 86% and 90% of cases, respectively. We suggest that UA might be a useful biomarker when combined with IL-1β, while UCR might be even more informative and useful in overall COPD assessments.