Background Uric acid is the most abundant molecule with antioxidant properties found in human blood serum. The relationship with respiratory disease, where oxidative stress from smoking and pollution is thought to play an important role, is currently unknown. We examined the relationship between serum uric acid and the incidence of respiratory disease in the primary care setting including any effect modification by smoking status.

Methods A cohort of 205,484 men and women contributing medical records to The Health Improvement Network (THIN) primary care research database with serum uric acid measured between January 1^st 2000 and December 31^st 2012 was extracted. New diagnoses of chronic obstructive pulmonary disease (COPD) and lung cancer were ascertained based on diagnostic codes entered into the medical records. Multivariable Poisson regression was used to examine the relationships and predict the adjusted incidence rates of COPD and lung cancer for each quintile increase in serum uric acid across smoking strata.

Results During 1,002,496 person years (PYs) of follow-up, there were 3901 COPD diagnoses and 1015 cases of lung cancer. After multivariable adjustment, strong interactions with smoking status were detected with significant negative relationships between serum uric acid and respiratory disease for current smokers but no strong relationships for never or ex-smokers. The relationships were strongest for lung cancer in heavy smokers (≥20 cigarettes per day) with predicted incidence rates 97 per 10,000 PYs (95% CI 68–126) in the lowest serum uric acid quintile (100–250 µmol/L) compared with a predicted 28 per 10,000 PYs (95% CI 14–41) in the highest quintile (438–700 µmol/L) giving a relative risk reduction of 71%. For COPD, the predicted incidence for heavy smokers was 248 per 10,000 PYs (95% CI 207–289) in the lowest serum uric acid quintile compared with 140 per 10,000 PYs (95% CI 107–174) in the highest quintile giving a relative risk reduction of 44%.

Conclusion Low levels of serum uric acid are associated with higher rates of COPD and lung cancer in current smokers after accounting for conventional risk factors. Further work is needed to clarify any causal role of serum uric acid in respiratory disease susceptibility amongst smokers and whether this cheap and accessible assay can improve existing disease risk algorithms in the primary care setting.