Association of Serum Calcium with the Risk of Chronic Obstructive Pulmonary Disease: A Prospective Study from UK Biobank.

BACKGROUND: Although intracellular calcium had been demonstrated to involve in the pathogenesis of chronic obstructive pulmonary disease (COPD), the association between serum calcium and COPD risk remains unclear. METHODS: We included 386,844 participants with serum calcium measurements and without airway obstruction at the baseline from UK Biobank. The restricted cubic splines were used to assess the dose-response relationship. Multivariable cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of albumin-corrected calcium concentrations with the risk of COPD incidence and mortality. RESULTS: During a median of 12.3 years of follow-up, 10,582 incident COPD cases were documented. A linear positive association was observed between serum calcium concentrations and the risk of COPD incidence. Compared to participants with normal serum calcium (2.19-2.56 mmol/L), a 14% higher risk of COPD was observed in hypercalcemic participants (≥2.56 mmol/L, HR = 1.14; 95% CI: 1.02-1.27). No significant effect modifications were observed in stratified variables. In survival analysis, 215 COPD-specific deaths were documented after a median survival time of 3.8 years. Compared to participants with normal serum calcium, hypercalcemic participants had a 109% (HR = 2.09, 95% CI: 1.15-3.81) increased risk for COPD-specific mortality. CONCLUSION: Our study indicated that hypercalcemia was associated with an elevated risk of COPD incidence and mortality in the European population, and suggested that serum calcium may have a potential impact on the progression of COPD.

Vitamin D status and chronic obstructive pulmonary disease risk: a prospective UK Biobank study.

BACKGROUND: Low vitamin D status has been linked to an increased risk for various inflammatory diseases. Conflicting results have been reported regarding chronic obstructive pulmonary disease (COPD). This study aims to investigate the associations of serum 25-hydroxyvitamin D (25(OH)D) concentrations with COPD risk and survival. METHODS: We included 403 648 participants with serum 25(OH)D measurements and free of COPD at baseline from UK Biobank. Follow-up was until 30 September 2021. Multivariable-adjusted cox regression models were applied to estimate HRs and 95% CIs for the associations of season-standardised 25(OH)D concentrations with COPD risk and survival. The restricted cubic splines were used to assess dose-response relationship. Kaplan-Meier estimation was used to create graphs of the survival curves. RESULTS: During a median follow-up of 12.3 (IQR: 11.4-13.2) years, 11 008 cases of COPD were recorded. We observed a non-linear inverse association between 25(OH)D concentrations and COPD risk. Compared with participants in the fourth quintile of 25(OH)D, those in the lowest quintile were associated with a 23% higher risk (HR, 1.23; 95% CI, 1.16 to 1.31). Stronger associations were observed for the risk in men and current smokers (Both p for interaction <0.05). In survival analyses, compared with the fourth quintile, cases in the lowest quintile had a 38% higher risk for overall death (HR, 1.38; 95% CI, 1.22 to 1.56). CONCLUSION: Our findings indicate that serum 25(OH)D concentrations are non-linearly negatively associated with incidence and mortality of COPD, suggesting a potential protective role of vitamin D in the pathogenesis of COPD.

Associations of diabetes, prediabetes and diabetes duration with the risk of chronic obstructive pulmonary disease: A prospective UK Biobank study.

AIM: To investigate the associations of diabetes, prediabetes and diabetes duration with chronic obstructive pulmonary disease (COPD) risk and survival in the UK Biobank. MATERIALS AND METHODS: We conducted a prospective analysis among 452 680 participants without COPD at baseline using UK Biobank data. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox regression models. The dose-response relationship was explored using restricted cubic splines. A separate survival analysis was conducted for 12 595 patients with incident COPD. RESULTS: Over a median follow-up of 12.3 years, 12 595 cases of COPD were documented. Compared with the reference group, those with prediabetes and diabetes were associated with an 18% (HR 1.18 [95% CI: 1.13-1.24]) and 35% (HR 1.35 [95% CI: 1.24-1.47]) higher risk of COPD, respectively. Diabetes duration was associated with COPD risk, with multivariable HRs (95% CIs) of 1.23 (1.05-1.44), 1.20 (1.04-1.39) and 1.18 (1.01-1.37) for diabetes duration of 7 years or longer, 3 to less than 7 years, and 1 to less than 3 years versus less than 1 year, respectively. Dose-response analysis revealed a non-linear relationship between diabetes duration and COPD risk. Regarding COPD survival, COPD patients with prediabetes and diabetes had a 9% (HR 1.09 [95% CI: 1.00-1.19]) and 21% (HR 1.21 [95% CI: 1.05-1.41]) higher risk of overall death, respectively. Compared with the cases with a diabetes duration of less than 1 year, those with a diabetes duration of 7 years or longer were associated with a 46% higher risk of overall death (HR 1.46 [95% CI: 1.11-1.92]). CONCLUSIONS: Our findings indicate that diabetes, prediabetes and a longer diabetes duration are associated with a higher risk of and worse survival for COPD. Future studies are warranted to determine the optimal way of diabetes control that might reduce COPD risk.

Circulating liver function markers and the risk of COPD in the UK Biobank.

Objective: To investigate the associations of circulating liver function marker levels with the risk of chronic obstructive pulmonary disease (COPD). Methods: We leveraged the data of 372,056 participants from the UK Biobank between 2006 and 2010. The assessed circulating liver function markers included alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), total bilirubin (TBIL), albumin (ALB), and total protein (TP). Incident COPD was identified through linkage to the National Health Service registries. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a median follow-up period of 12.3 (interquartile range:11.4-13.2) years, we documented 10,001 newly diagnosed COPD cases. Lower levels of ALT, TBIL, ALB, and TP and higher levels of GGT and ALP were nonlinearly associated with elevated COPD risk. The HR (95% CI) for decile 10 vs. 1 was 0.92 (0.84-1.01) for ALT, 0.82 (0.75-0.89) for TBIL, 0.74 (0.67-0.81) for ALB, 0.96 (0.88-1.04) for TP, 1.45 (1.31-1.62) for GGT, and 1.31 (1.19-1.45) for ALP. Restricted cubic spline analyses suggested a U-shaped relationship between AST levels and COPD risk (P for nonlinearity <0.05). Conclusion: We observed that all seven circulating liver function markers were nonlinearly associated with the risk of COPD, indicating the importance of liver function in COPD.

Age-adjusted reference values and influencing factors of cystatin C in healthy Chinese population.

BACKGROUND: Normative distribution of serum cystatin C and relationship with sex and age in healthy adult Chinese population is unknown. METHODS: This is a prospective cohort study. Adult subjects (18 years of age and older) who underwent annual health examination at the Health Management Center in Sir Run Run Hospital were eligible. Subjects with major diseases, e.g., hypertension, diabetes, chronic kidney disease, obesity (body mass index ≥ 28 kg/m2) were excluded from the analysis. Multivariate logistic regression analysis was conducted to identify risk factors of elevated cystatin C (> 1.03 mg/L). Data are shown as median and 95% confidence interval (CI). RESULTS: The final analysis included a total of 10,640 subjects (40 ± 12 years, 52% men). The median serum cystatin C concentration was 0.73 mg/L (95% CI 0.52-1.03 mg/L) in the overall analysis, 0.79 (95% CI 0.59-1.07 mg/L) in men, and 0.67 (95% CI 0.49-0.95 mg/L) in women. In the multivariate regression analysis, elevated cystatin C was independently associated with the male sex (odds ratio 1.94; 95% CI 1.07-3.52), older age (odds ratio 1.04 every year; 95% CI 1.02-1.06), higher body mass index (odds ratio 1.70; 95% CI 1.01-2.83), uric acid (odds ratio 1.00; 95% CI 1.00-1.01), and ß2-microglobulin (odds ratio 39.35; 95% CI 22.90-67.64). CONCLUSION: The median serum cystatin C concentration was 0.73 (95% CI 0.52-1.03 mg/L) in healthy adult Chinese population, 0.79 (95% CI 0.59-1.07 mg/L) in men, and 0.67 (95% CI 0.49-0.95 mg/L) in women. Elevated cystatin C was associated with the male sex, older age and higher body mass index.