Association Between Dietary Selenium Intake and Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study from the National Health and Nutrition Examination Survey 1999–2018

Introduction

Chronic obstructive pulmonary disease (COPD) is a prevalent chronic inflammatory disorder affecting the airways, distinguished by persistent airflow limitation and airway obstruction.¹ Currently, COPD is causing significant economic losses on a global scale, primarily attributed to its high prevalence, considerable morbidity, and mortality rates.^2,3 Research has shown that the risk factors for the disease include exogenous factors such as smoking and nutritional status,⁴ as well as endogenous factors like genetics.¹ These aspects promote inflammation and oxidative stress in the lungs, leading to the development of COPD.⁵ Therefore, early identification of COPD susceptibility factors is crucial for effective prevention. Given the fundamental role of dietary factors in nutritional status and their close association with COPD development,⁶ trace elements may play a significant role in lung health maintenance.^7,8

Selenium, a crucial non-metallic trace element in the human body, plays a fundamental role in the synthesis of various antioxidant selenoproteins, including glutathione peroxidase.⁹ This element exerts antioxidant and anti-inflammatory properties that can effectively suppress oxidative stress responses systemically. Numerous studies have shown that dietary selenium intake enhances immunity,^10,11 fights infection,¹² and exerts protective effects against autoimmune thyroid diseases,¹³ lung cancer,¹⁴ bladder cancer,¹⁵ prostate cancer and other diseases.¹⁶ However, clinical studies have reported that selenium intake not only does not benefit patients with cardiovascular disease,¹⁷ but also increases the risk of diabetes.¹⁸ Previous research has demonstrated that COPD patients exhibit lower serum selenium levels compared to healthy control groups,¹⁹ and their symptoms can be partly alleviated through selenium supplementation.^20,21 Nevertheless, these studies mainly concentrate on selenium supplements among COPD patients, rather than the dietary selenium consumption of the general population. Additionally, the diet is often a complex mixture, and the deficiency of one nutrient may indicate the lack of others. Therefore, inadequate dietary selenium intake could be a sign of deficiencies in other elements. Despite selenium’s potential health benefits, research on the relationship between dietary selenium intake and COPD is still lacking.

To investigate the correlation between dietary selenium intake and COPD, we conducted evaluation among American adults using data from the National Health and Nutrition Examination Survey (NHANES), a comprehensive population-based survey conducted in the United States between 1999 and 2018.

Methods

Study Population

The study obtained its data from the National Center for Health Statistics (NCHS), which is part of the US Centers for Disease Control and Prevention (CDC). NHANES, conducted nationwide, is specifically designed to assess the health and nutritional status of a representative sample of the non-institutionalized US population, offering a comprehensive snapshot of the country’s health landscape.²² Detailed population and sampling survey methods can be found on the NHANES website. It’s worth noting that the NHANES survey protocol has been reviewed and approved by the Ethics Review Committee of the NCHS in the United States. Furthermore, written informed consent was obtained from all participants involved. Considering the Ethical Review Methods for Life Science and Medical Research Involving Human Beings, we have discovered that Article 32 of these regulations explicitly exempts research from needing ethical approval under specific conditions. As stated in Article 32: Ethical approval is not required for research that meets the criteria of (a) using legally obtained public data, or data generated by observation and not interfering with public behavior; and (b) using anonymized informational data to conduct the research. Since this study was based on anonymized publicly available deidentified data and informed consent was waived, ethical approval and consent were not required, so the Ethics Review Committee of the Second People’s Hospital of Banan District exempted the study (ethic number:2022–004). The study was conducted in accordance with the Helsinki Declaration (revised in 2013).

We recruited a total of 55,081 adults aged 20 years and older from 10 cycles of the NHANES study. Participants with incomplete COPD questionnaire data or dietary selenium assessment data, as well as those in a pregnant state, were excluded. Individuals with missing or incomplete data regarding demographics, risk behaviors, comorbid conditions, or dietary intake were excluded from the study. Given the large sample size, missing covariates were excluded directly. The exclusion process is visually represented in Figure 1. A total of 39,654 participants were finally included in the analysis.

Figure 1 Flowchart depicting the screening and enrollment process for study participants. Abbreviation: COPD, chronic obstructive pulmonary disease.

Variables

COPD, as diagnosed by self-report, served as the primary outcome variable in this study.²³ Three self-administered questionnaires were used to verify disease status: “Have you been told you have chronic bronchitis?”, “Have you been told you have emphysema?”, and “Have you been told you have COPD?”. Participants who answered “yes” to any of these questions were placed in the COPD group; those who answered “no” were placed in the non-COPD group.

Dietary selenium intake is the main predictor variable. It was obtained through two rounds of 24-hour dietary recall interviews. Participants, excluding those from the 1999–2000 and 2001–2002 cycles, underwent both interviews. During the first recall, respondents completed a test conducted at the NHANES mobile testing center, followed by a telephone interview conducted between 3 and 10 days later during the second recall. To ensure data completeness and accuracy, this analysis utilized the average dietary selenium intake from the two interviews. In cases where data from the second interview was missing, data from the first interview was used as a substitute.

In the NHANES database, data on dietary supplements were collected during household interviews. From 2007 to 2018, participants were asked if they had taken dietary supplements in the past 30 days, and detailed information on the supplements was provided. To calculate the average daily intake of nutrients from supplements, researchers divided the total intake of all supplements by 30 days. The total selenium intake was calculated by adding dietary intake and supplement intake.

Covariates were selected based on literature review and clinical experience,^23,24 including sex, age, race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American, other), education level (< 9 years, 9–12 years, > 12 years), marital status (married, living with partner or living alone), ratio of income to poverty (PIR) (low: ≤ 1.3, medium: > 1.3 to 3.5, high: > 3.5),²⁵ smoking status (never, former, or current), drinking status (defined as significant alcohol intake for ≥ 12 glasses of alcohol per year, and non-significant alcohol intake otherwise), body mass index (BMI, kg/m²), complications (diabetes, hypertension), dietary supplement intake and total daily energy intake. Total energy was obtained from two 24-hour dietary recalls. We used questionnaires to assess a history of diabetes and hypertension.

Statistical Analysis

This study conducted secondary analysis on publicly available datasets, and statistical analysis was performed following the survey methods and NHANES analysis guidelines. Categorical variables were described using numbers (percentages), and inter-group comparisons were conducted using the chi-square test. Continuous variables were described as mean ± standard deviation (SD) if normally distributed, or as median and interquartile range (IQR) if skewed. We developed a multivariable logistic regression model to estimate the odds ratio (OR) and corresponding 95% confidence interval (95% CI), examining the association between selenium intake and COPD. The model consisted of three parts: an unadjusted model, a minimally adjusted model (including age, sex, race/ethnicity), and a fully adjusted model (including age, sex, race/ethnicity, marital status, PIR, education level, BMI, physical activity, smoking and drinking status, hypertension, diabetes, dietary supplements, and total energy intake). To confirm the results obtained as continuous variables in unadjusted and multivariable adjusted models, we calculated p-values for trends. To explore the potential nonlinear association between dietary selenium intake and COPD, we utilized a restricted cubic spline (RCS) model, treating selenium intake as a continuous variable with four knots (5th, 35th, 65th, and 95th percentiles) to capture smoothed curves. Additionally, we conducted subgroup analyses considering variables including sex, age, education level, marital status, PIR and BMI. To assess subgroup heterogeneity and interactions, logistic regression models were employed, and likelihood ratio tests were performed. In addition to dietary intake, supplements are also an important source of selenium. To investigate the effect of supplemental selenium on COPD, we conducted an additional analysis among participants who consumed selenium supplements (> 0.01 μg/day).

As the sample size was solely determined by available data, no prior statistical power estimates were obtained. All analyses were performed using R 3.3.2 statistical software (http://www.R-project.org, The R Foundation) and Free Statistics software version 1.9 (Beijing Free Clinical Medical Technology Co., LTD). A two-tailed of p < 0.05 was regarded statistically significant.

Results

Baseline Characteristics

Table 1 presents an overview of the baseline demographics and characteristics of the 39,654 individuals included in the study. The average age was 50.0 (± 17.9) years, with males representing 50.2% and females accounting for 49.8%. Notably, 3,160 (8.0%) participants self-reported COPD. Participants with higher dietary selenium intake generally consisted of those who were young, male, non-Hispanic white, married or living with a partner, and had the habit of drinking but not smoking. Higher dietary selenium intake was also associated with higher education levels and family income, supplement usage, increased energy intake, and lower rates of hypertension and diabetes.

Table 1 Population Characteristics by Categories of Dietary Selenium Intake

Association Between Dietary Selenium Intake and Chronic Obstructive Pulmonary Disease

When considering dietary selenium intake as a categorical variable (tertiles), we constructed three logistic regression models to investigate its association with COPD (Table 2). Across all models, we observed a higher risk of COPD in the group with the highest dietary selenium intake, followed by the moderate intake group, showing a consistent trend (p < 0.001). After adjusting age, sex, race/ethnicity, marital status, PIR education level, BMI, smoking and drinking status, physical activity, diabetes, hypertension, dietary supplements, total energy (Model 3), compared to the reference T1 (< 81.6 μg/day) group, the ORs for the T2 (81.6–122.0 μg/day) and T3 (> 122.0 μg/day) groups were 0.89 (95% CI: 0.81–0.98) and 0.80 (95% CI: 0.71–0.91), respectively, with all p-values < 0.05.

Table 2 Association Between Dietary Selenium Intake and COPD

The relationship between dietary selenium intake and COPD was elucidated through RCS analysis, illustrating the fitting curve between dietary selenium intake and COPD (Figure 2). The results revealed a linear association between the variables (non-linearity p = 0.531) following adjustments in Model 3. The impact across various levels of dietary selenium intake was found to be consistent.

Figure 2 Restricted cubic spline plot between dietary selenium intake and odds ratio of COPD. The bar chart illustrates the distribution of the population. Solid and dashed lines denote predicted values with 95% confidence intervals. Reference.point, the median selenium intake. Data represents 99% of the sample. Adjusted for age, sex, race/ethnicity, marital status, education level, body mass index, ratio of income to poverty, physical activity, smoking and drinking status, hypertension, diabetes, total energy intake. Abbreviation: COPD, chronic obstructive pulmonary disease.

Subgroup Analyses

We further investigated potential associations between dietary selenium intake and COPD across various demographic factors, including sex, age, education level, marital status, PIR, and BMI. Consistent patterns were observed across all subgroups after adjusting for all covariates. To visually represent these findings, we included a Forest plot (Figure 3). Specifically, dietary selenium intake was linked to COPD, with a stronger association observed among individuals aged below 60 years (OR, 0.76; 95% CI, 0.65–0.90) and a weaker association among those aged 60 years and above (OR, 0.82; 95% CI, 0.68–0.98). Moreover, higher levels of education were significantly inversely correlated with COPD (OR, 0.72; 95% CI, 0.61–0.80), while this correlation attenuated in lower education strata (OR, 0.88; 95% CI, 0.74–1.04). Despite observing a statistically significant interaction between age and education level (p for interaction < 0.05), the clinical relevance of this finding remains uncertain due to the implications of multiple testing and the similarity in the direction of the associations.

Figure 3 Forest plot illustrating the multivariable-adjusted association between dietary selenium intake and COPD. Each square represents the OR, and the horizontal lines represent the 95% CI. The top of the plot represents the overall summary estimate. Adjustments were made for age, sex, race/ethnicity, marital status, education level, body mass index, ratio of income to poverty, physical activity, smoking and drinking status, hypertension, diabetes, total energy intake. Abbreviations: BMI, body mass index; CI, confidence interval; OR, odds ratio; PIR, ratio of income to poverty; dietary selenium intake tertiles (μg /day): T1 (< 81.6); T2 (81.6–122.0); T3 (> 122.0).

Sensitivity Analysis

In addition to dietary intake, supplements play a significant role in providing selenium. Therefore, we also investigated the association between selenium supplement intake and COPD. Out of the 39,654 participants included in this study, 2,906 individuals increased their selenium intake (≥ 0.01 μg/day) through these supplements. The study population taking dietary selenium supplements was divided into tertiles. Compared to T1 (< 19.8 μg/day), the adjusted OR for COPD in T2 (19.8–54.6 μg/day) and T3 (> 54.6 μg/day) were 0.94 (95% CI: 0.66–1.32, p = 0.704) and 0.85 (95% CI: 0.61–1.20, p = 0.361), respectively. Similarly, when total selenium intake was categorized into tertiles, the adjusted OR for COPD in T2 (120.0–177.5 μg/day) was 0.65 (95% CI: 0.46–0.91, p = 0.013) and in T3 (> 177.5 μg/day) was 0.77 (95% CI: 0.52–1.14, p = 0.195). For more detailed information, please consult Table 3.

Table 3 Association Between Selenium Dietary Supplement Intake and COPD

Discussion

The presence of co-existing diseases contributes to the elevated prevalence and mortality rates of COPD. Consequently, comprehensive identification of the risk factors for COPD is crucial for early prevention and timely intervention of the disease, ultimately mitigating excessive medical resource utilization and alleviating the financial burden on nations. Our study revealed a negative linear association between dietary selenium intake and COPD, indicating that higher selenium intake may be associated with a lower risk of COPD. The dietary intake of selenium holds promise as a protective factor in the prevention and management of COPD.

Various studies observed that selenium may have an effect on COPD. Both a cross-sectional study involving 479 British individuals and another involving 2,460 Chinese community residents found a positive correlation between selenium and lung function.^26,27 Furthermore, a longitudinal study in the United States examined lung function among 1,641 men over an average of three years and reported that selenium was associated with a reduced decline in FEF_25-75 among current smokers.²⁸ Another clinical cohort study in Portugal, including 45 patients, found lower plasma selenium levels in those with COPD.¹⁹ Additionally, numerous randomized double-blind controlled trials have indicated that selenium supplementation, either orally or intravenously, has the potential of alleviating specific symptoms in COPD patients.^20,21,29 Despite the accumulating evidence above, the impact of dietary selenium intake on COPD remains underexplored.

Recently, only two large-scale studies have been conducted on the American population, suggesting a potential beneficial effect of elevated serum selenium concentrations on lung health.^30,31 However, these studies, which relied on data from 1988 to 1994, did not delve into the specific linkage between dietary selenium intake and COPD. Hence, our study aimed to bridge this knowledge gap by employing updated clinical data to conduct a comprehensive analysis of dietary selenium intake. Through multivariable logistic regression and RCS analysis, we identified an inverse association between dietary selenium intake and COPD. Selenium intake typically comes from the consumption of foods such as fish, meat, poultry, wheat, bread, grains, and selenium supplements.³² Our findings reveal a beneficial role for selenium in the management of COPD, thus underscoring the importance of considering dietary selenium intake based on its potential benefits for respiratory health.

Although the association between dietary selenium intake and COPD remains unclear at present, these observations are bolstered by relevant evidence. Selenium, a crucial component of antioxidant proteins like glutathione peroxidase, exerts a favorable influence on the therapy, alleviation, and prognosis of various oxidative stress-related diseases.³³ For instance, in rheumatoid arthritis, dietary selenium intake may alleviate joint pain and injury.³⁴ Similarly, selenium treatment shows promise in relieving pain and controlling the disease in patients with pancreatitis.³⁵ The impact of selenium on oxidative stress in the respiratory system is mediated by the antioxidant activity of glutathione peroxidase 1 (GPX1). Cellular and animal studies have demonstrated that decreased selenium intake leads to reduced GPX1 activity, increased oxidative stress in the lung,³⁶ and excessive mucus synthesis.³⁷ Oxidative stress and excessive mucus production are closely linked to the pathogenesis of chronic inflammatory airway diseases, such as asthma and COPD.^38,39 Therefore, we postulate that selenium’s antioxidant and anti-inflammatory properties may underlie its beneficial impact on COPD.

Notably, the stratified analysis revealed a stronger association between dietary selenium intake and COPD among individuals aged below 60 years compared to those aged 60 years and above. This finding suggests that selenium plays a more direct role in maintaining lung health among younger and middle-aged adults. However, there may be a decline in selenium absorption and utilization efficiency with age, possibly attributed to weakened gastrointestinal function.⁴⁰ Additionally, comorbidities and complex medication regimens among older adults may further impair the protective effect of selenium against COPD.⁴¹ On the other hand, the study also demonstrated a significant inverse relationship between educational level and COPD, which attenuated as education level decreased. The result possibly indicated that individuals with lower education levels face greater health challenges and lifestyle limitations, contributing to an increased COPD risk.⁴² Although a statistical interaction between sex and educational level was observed, the clinical significance of this finding remains to be validated.

Given the substantial role of selenium supplements in overall selenium intake, a sensitivity analysis was conducted to investigate the relationship between selenium supplementation and COPD. The results revealed a negative correlation between the combined intake of selenium from both dietary and supplemental sources and the occurrence of COPD. Future studies on detailed mechanisms underlying selenium’s role in COPD are warranted to further elucidate this association.

Strengths and Limitations

The strength of this study resides in its substantial sample size, utilization of individual-level data, and construction of a reliable multivariate logistic regression model. This comprehensive analysis considers both dietary selenium intake and supplementation, adjusting for multiple confounders. The findings offer valuable insights into the potential role of selenium in COPD prevention and treatment strategies, adding to the existing knowledge base in this crucial area. However, there are also limitations that warrant caution. Initially, due to the nature of acquiring dietary selenium intake through the 24-hour recall method, it is impractical to entirely eliminate recording errors and recall biases. Conversely, we opted against utilizing food frequency surveys due to their limited ability to capture comprehensive information on food types and quantities consumed.⁴³ Additionally, as a secondary analysis of open databases, this study may be susceptible to interference from residual confounding effects, including genetic factors, despite the adjustment for numerous confounding factors. Lastly, this cross-sectional study can only describe phenomena, and causal or consequential associations cannot be inferred. Therefore, future longitudinal studies are crucial to deeply explore the causal link between dietary selenium intake and COPD.

Conclusion

Our study observed a negative correlation between dietary selenium intake and COPD among American adults, indicating a possible association between higher selenium intake and a lower risk of COPD. However, further research is warranted to confirm these findings.