Impaired pulmonary function increases the risk of gout: evidence from a large cohort study in the UK Biobank

Abstract

Background: Pulmonary function is increasingly recognized as a key factor in metabolic diseases. However, its link to gout risk remains unclear. The study aimed to investigate the relationship between pulmonary function and the risk of developing gout and the underlying biological mechanisms.

Methods: Our study included 420,002 participants with complete pulmonary function data from the UK Biobank. Logistic regression was used to evaluate gout prevalence among individuals with different pulmonary function statuses. Propensity score matching (PSM) created balanced groups, while Cox regression gauged the risk association between reduced lung capacity and gout compared with normal function. Mendelian randomization (MR) analysis was used to verify causal associations. Non-linear correlations were assessed with restricted cubic spline (RCS) analysis, and mediation analysis was used to explore the role of blood biomarkers. Mediation analyses were used to investigate the potential mediating role of biomarkers in the association.

Results: Cross-sectional analysis revealed a higher prevalence of gout in individuals with preserved ratio of impaired spirometry (PRISm) of 6.31% and chronic obstructive pulmonary disease (COPD) of 6.26% than in those with normal pulmonary function (3.45%). After adjustment for covariates, both PRISm (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.17-1.31) and COPD (OR 1.14, 95% CI 1.07-1.22) were significantly associated with gout. Longitudinal analysis confirmed that impaired pulmonary function significantly increased the risk of developing gout (hazard ratio [HR] 1.32, 95% CI 1.24-1.40). MR further revealed a potential causal effect of decreased pulmonary function on an increased risk of gout. Subgroup analysis revealed significant interactions between impaired pulmonary function and several factors, including body mass index (BMI), levels of physical activity, and diabetes status, in their associations with the risk of gout. RCS analysis showed a nonlinear relationship between pulmonary function indicators and gout incidence, characterized by an inverse S-shaped curve. Mediation analysis revealed that urate levels (49.1% mediation proportion), C-reactive protein (CRP) levels (6.62%), monocyte counts (1.33%), and neutrophil counts (4.85%) significantly mediated the relationship between pulmonary function and the risk of gout.

Conclusions: Our study revealed a significant association between impaired pulmonary function and an increased risk of developing gout. The association might be partially mediated by biomarkers including urate levels, inflammatory markers, and immune cell counts.

Keywords: Gout; Immune cell counts; Inflammation; Mediation analysis; Pulmonary function; Spirometry; UK Biobank; Urate levels.

Fig. 1

Flow diagram of participants included in the study. PSM: Propensity score matching

Fig. 2

Kaplan–Meier analysis showing the risk of gout in individuals with impaired pulmonary function and those with normal pulmonary function in model 1 (A), model 2 (B), and model 3 (C). Model 1: Propensity matching by age, sex, Townsend score, and body mass index. Model 2: Propensity matching by age, sex, Townsend score, body mass index, smoking status, alcohol consumption, physical activity, fish consumption, and meat consumption Model 3: Propensity matching by age, sex, Townsend score, body mass index, smoking status, alcohol consumption, physical activity, fish consumption, meat consumption, hypertension, diabetes, CKD, CVD, and asthma. CVD: Cardiovascular disease; CKD: Chronic kidney disease

Fig. 3

Forest plot showing the subgroup analysis of gout risk exposed to impaired pulmonary function compared to normal pulmonary function. HR: Hazard ratio; CVD: Cardiovascular disease; CKD: Chronic kidney disease; BMI: Body mass index

Fig. 4

Association between FVC (% predicted) and FEV1 (% predicted) and the risk of gout in populations. A, B The RCS curves illustrating the nonlinear relationship between pulmonary function and FVC (% predicted) (A) and FEV1 (% predicted) (B). Each hazard ratio was computed with an FVC (% predicted) level of 88% (turning point) and FEV1(% predicted) level of 79% (turning point) as the reference. The solid line and red area represent the estimated values and their corresponding 95% CIs. HR: Hazard ratio; RCS: Restricted cubic spline; FEV1: Forced expiratory volume in 1 s; FVC: Forced vital capacity

Fig. 5

Associations between pulmonary function and incident gout mediated by blood biomarkers and blood cells. Significance (Sig.): ***FDR < 0.001, **FDR < 0.01, *FDR < 0.05; FDR: False discovery rate; HR: Hazard ratio; CI: Confidence interval; PM: Proportion mediated