Association Between Serum Folate and Lung Function in People with and without Chronic Obstructive Pulmonary Disease: Results from NHANES 2007–2012.

doi:10.21203/rs.3.rs-3246446/v1

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Association Between Serum Folate and Lung Function in People with and without Chronic Obstructive Pulmonary Disease: Results from NHANES 2007–2012.

https://doi.org/10.21203/rs.3.rs-3246446/v1

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Background

The relationship between serum folate and pulmonary function in individuals with chronic obstructive pulmonary disease (COPD) remains unclear. Our study aims to explore the potential correlation between serum folate levels and pulmonary function.

Methods

We analyzed cross-sectional data from the National Health and Nutrition Examination Survey (NHANES 2007–2012), including individuals aged 40 years and above (n = 1062) with complete post-bronchodilator lung function data and serum folate measurements. COPD was diagnosed based on a post-bronchodilator FEV₁/FVC ratio of less than 0.70. Using a multivariable adjusted linear model, we assessed the association between serum folate levels and lung function indices, stratified by COPD status.

Results

Our study included 493 COPD patients and 569 individuals without spirometry-defined COPD. There were no significant differences in serum folate levels between the two groups. Adjusting for multiple factors, we observed that each 1 nmol/L increase in serum folate was significantly associated with improvements in FEV₁ (2.54 mL, 95% confidence interval [CI] 0.58 to 4.5), FVC (3.58 mL, 95% CI 0.9 to 6.27), and PFE (7.73 mL, 95% CI 2.17 to 13.29) among COPD patients. However, no significant correlation was found between lung function and serum folate levels in non-COPD individuals.

Conclusions

Elevated serum folate levels are associated with better lung function in COPD patients, while folate levels do not significantly impact lung function in individuals without COPD.

COPD

chronic obstructive pulmonary disease

serum folate

lung function

Chronic Obstructive Pulmonary Disease (COPD) is a preventable and treatable disease characterized by chronic respiratory symptoms (dyspnea, cough, sputum production and/or exacerbations) resulting from abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema), leading to persistent, often progressive, airflow obstruction¹. With the development of society, the prevalence of COPD and its socioeconomic burden has been increasing each year². According to global burden of disease studies, COPD is currently the third leading cause of death worldwide, with approximately three million people dying from the disease^3,4.

COPD is a heterogeneous disease^1,5, with its potential pathogenesis involving multiple factors, primarily influenced by environmental, genetic, and lifestyle elements⁶, primarily influenced by smoking, environmental, genetic, and lifestyle elements, including dietary intake. One significant dietary factor is folate, which is widely distributed in foods and participates in various biochemical pathways⁷ in the human body, including the synthesis of amino acids, purines, and pyrimidines. Moreover, folate acts as a methyl donor for DNA methylation⁸. Research has suggested that folate may contribute to the pathogenesis of COPD by influencing DNA methylation and thus modulating the expression of disease susceptibility genes. Some studies propose that variations in serum folate levels may influence oxidative stress and inflammatory responses, subsequently affecting the development and progression of COPD^9–11. Recent epidemiological research has indicated that a high folate intake is beneficial for improving lung function in chronic smokers^12,13. A small-scale study in Japan found that folate intake alleviated respiratory symptoms and improved lung function in COPD patients¹⁴.

However, there is limited research data regarding the correlation between serum folate levels and lung function in COPD patients. In this study, we investigated the distribution characteristics of serum folate levels and their relationship with lung function in COPD patients using data from the National Health and Nutrition Examination Survey (NHANES) conducted in the United States from 2007 to 2012.

Data source

National Health and Nutrition Examination Survey (NHANES) database, conducted by the Centers for Disease Control and Prevention in the United States, is a cross-sectional survey program that collects comprehensive data on the health and nutritional status of the American populatio^15–17. Using a complex stratified sampling design, NHANES selects a representative sample of non-institutionalized individuals, ensuring broad applicability. The database has obtained approval from the National Center for Health Statistics Research Ethics Review Board based on the revised Helsinki Declaration. Participants provide informed consent before data collection and comprehensive health examinations. This database has been extensively employed in studying the COPD patients in the United States. Questionnaires are completed by participants at home, while laboratory measurements and physical examinations, including lung function tests, are conducted at mobile examination centers.

Study population

Our study utilized data from three NHANES cycles (2007–2012). The primary data collected in this study included demographic information, laboratory data, examination data and questionnaire data. During the initial screening of the NHANES database, we included all participants from 2007 to 2012 (n = 30442). The inclusion criteria for the participants were as follows: (1) Age ≥ 40 years old. (2) Complete serum folate data. (3). Complete and quality-controlled pre- and post-bronchodilator lung function data. The exclusion criteria were as follows: (1) Age < 40 years old. (2) Participants who were pregnant during the examination. (3) Participants without data about covariates at least one of following: body mass index, smoking status, family history of respiratory diseases, occupational exposure, passive smoke. (4) Participants with previous medical history of the following conditions: lung/larynx/windpipe cancer, active tuberculosis, asthma, collapsed lung, chest/abdominal/eye surgery within the past 3 months, stroke/heart attack within the past 3 months and coughed up blood within the past month. (5) Participants without complete and quality-controlled pre- and post-bronchodilator lung function data. (6) Participants without complete serum folate data.

Epidemiological questionnaire

The main contents of epidemiological questionnaire include gender, age (years old), body mass index (kg/m2), race (Mexican American, other Hispanic, non-Hispanic white, non-Hispanic black, other Race), educational status (less than high school, high school, more than high school), hypertension history (Yes, No), diabetes history (Yes, No), smoking status (Whether smoked at least 100 cigarettes in life), history of occupational exposure to dust/gases/fumes (Whether exposure to dust/gases/fumes lasting more than 1 year), family history of respiratory diseases (Whether any parent or sibling diagnosed with chronic bronchitis, emphysema, COPD, asthma, bronchiectasis, or lung cancer, bronchiectasis, interstitial lung disease, cor pulmonale, obstructive sleep apnea hypopnea syndrome), passive smoking (Whether exposure to cigarette smoke at home or at work for more than 1 year), and respiratory symptoms (Chronic cough or chronic phlegm was defined as cough or phlegm not occurring during a “cold” and on most days for as much as 3 months each year for 2 years. Wheezing was the presence of “episodes of wheezing or whistling in the chest associated with a feeling of shortness of breath, in the past 1 year not occurring during a cold.” Wheezy during exercise was defined as the presence of chest sounded wheezy during or after exercise or physical activity).

Measurement of serum folate

Serum folate exists in five forms: tetrahydrofolate, folic acid, 5-methyltetrahydrofolate, 5-formyltetrahydrofolate, 5,10-methenyltetrahydrofolate. In our study, serum total folate concentration represents the overall level of the preceding five forms of folate in the blood. Isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to measure the total serum folate concentration. Detailed protocols on specimen processing and collection can be accessed on the NHANES website (http://www.cdc.gov/nchs/nhanes/).

Spirometry

Spirometry was conducted in the standing position following a standardized protocol recommended by the American Thoracic Society (ATS)^18,19. Lung function in this study was assessed using five key metrics: FVC, FEV₁, PEF, FEV₁/FVC and FEF_25–75%. The results for FEV₁ and FVC were categorized on a scale from A to F, based on the ATS criteria. Our analyses focused exclusively on spirometry data from participants with FEV₁ and FVC values graded as A–C. The diagnosis of COPD was established based on a post-bronchodilator FEV₁/FVC ratio of less than 0.70.

Statistical analysis

All statistical analyses were conducted using IBM SPSS version 26 (Armonk, New York) and R statistical software version 4.1.0. Variable distributions were assessed for normality using the Kolmogorov-Smirnov test. Normally distributed continuous variables were reported as mean ± standard deviation (SD), while skewed variables were presented as median with interquartile range (IQR). Student's t-test was used to compare continuous variables between individuals with and without COPD. Categorical variables were expressed as numbers (percentages), and group comparisons were performed using the chi-square test or Fisher's exact test. Continuous serum folate values were categorized based on their means. Analysis of variance (ANOVA) was used to assess significant differences among different folate level groups. Analysis of covariance was employed to compare pulmonary function parameters (FEV₁, FVC, PEF, FEF_{25 − 75%}, and FEV₁/FVC) between individuals grouped according to mean levels of serum folate. Adjusted variables included age, sex, body mass index, smoking status, family history of respiratory diseases, biomass exposure, occupational exposure, and passive smoke. Multivariable linear models were employed to evaluate the impact of serum folate levels on pulmonary function parameters (FEV₁, FVC, PEF, and FEV₁/FVC). Assumptions of normality, linearity, and homoscedasticity were assessed graphically by examining the relationship between observed and predicted values, as well as residuals and predicted values or observed exposure values. No significant deviations from these assumptions were observed. Sensitivity analysis was conducted to investigate potential gender-based differences in the effects of serum folate, analyzing separate gender groups. Additionally, subgroup analyses were performed based on smoking status. Variables with a p-value < 0.05 were considered statistically significant.

Figure 1 illustrated the study procedures in a flowchart. The study included 1,062 subjects who met the inclusion criteria and had available data, comprising 493 (46.42%) COPD patients defined by spirometry and 569 (53.58%) spirometry-defined healthy individuals. The general clinical characteristics of enrolled subjects were presented in Table 1. Patients with chronic obstructive pulmonary disease (COPD) differed significantly from non-COPD subjects in terms of age, gender, race, smoking status, history of hypertension, occupational dust exposure, and passive smoking. When stratifying the participants into high and low groups based on the mean serum folate levels (42.2nmol/L), significant differences were observed in the low folate group, including younger age, higher male representation, a larger proportion of Non-Hispanic Black and Mexican American individuals, higher prevalence of lower education levels, increased smoking rates, and elevated prevalence of passive smoking (Table 1).

Table 2 revealed a higher occurrence of wheezing in participants with low serum folate levels regarding respiratory symptoms. However, no significant differences were observed between the two groups in terms of chronic cough, expectoration of phlegm, and exercise-induced wheezing. After adjusting for confounding factors like gender and age, body mass index, smoking status, family history of respiratory diseases, biomass exposure, occupational exposure, and passive smoke, a significant association was observed between low serum folate levels and impaired lung function, both before and after bronchodilation.

The distribution of serum folate levels was presented in Figure 2, showing a skewed trend with a mean folate level of 42.2±25.3 nmol/L. There was no significant difference in serum folate levels between COPD patients and non-COPD individuals (43.3 nmol/L vs. 41.1 nmol/L, p=0.16). However, male participants had significantly lower serum folate levels compared to females (40.2 nmol/L vs. 15.8 nmol/L, p<0.001). Additionally, age and smoking status appeared to be closely associated with serum folate levels, whereas the relationship between BMI and folate did not show statistical significance.

After adjusting for multiple confounding variables, we found a significant correlation between serum folate levels and both pre-bronchodilator lung function and post-bronchodilator lung function (Figure 3). Specifically, each 1 nmol/L increase in serum folate was associated with a post-bronchodilator FEV₁ increase of 2.29 mL (95%CI 0.81 to 3.77), a FVC increase of 2.28 mL (95%CI 0.26 to 4.29), a PEF increase of 7.05 mL (95%CI 3.00 to 11.09) and a FEF_25-75% increase of 2.25 mL (95%CI 0.68 to 3.82). Upon stratifying by spirometry, in COPD patients, each 1 nmol/L increase in serum folate was linked to a substantial improvement in post-bronchodilator FEV₁ (2.54 mL, 95% CI: 0.58 to 4.50) and FVC (3.58 mL, 95% CI: 0.90 to 6.27) in COPD patients. However, in non-COPD patients, there was no significant correlation between serum folate levels and lung function (Figure 3; Figure 4). Furthermore, when conducting subgroup analysis based on gender, BMI, and smoking status, we observed a significant association between folate levels and lung function in male patients or those with a BMI greater than 25 kg/m² or who smoked more than 100 cigarettes, among individuals diagnosed with COPD. The detailed results for this analysis were presented in Supplementary Figure A1-A3.

This observational research analyzed 493 COPD patients and 569 individuals without COPD. We observed a positive correlation between serum folate levels and lung function in COPD patients, while no significant correlation was found in the non-COPD group. To our knowledge, this is the first epidemiological research that focuses on exploring the distribution characteristics of serum folate in patients with COPD and the differential effects of serum folate on lung function based on individuals with or without COPD.

Previous studies have shown that the total serum folate levels in women are significantly higher than in men in the United States²⁰, and they are more prone to developing folate deficiency²¹. These findings are consistent with the results of our research. Furthermore, our study fills the knowledge gap regarding the relationship between serum folate levels and gender in patients with COPD. Based on previous research findings, smoking status can alter the body's inflammatory state and serum folate levels²². The higher proportion of male smokers may partially explain the gender difference in serum folate levels. Our study found that serum folate levels of participants aged 60 and above were significantly higher than those of participants below the age of 60, which was broadly consistent with previous research findings²⁰. Low serum folate was inversely associated with age, with a prevalence of 43.4% among the 30-year-olds and 18.3% among those aged 60 years²¹. Previously reported findings showed that higher BMI was associated with lower serum total folate concentration (and higher red blood cell total folate)²³. This led to the hypothesis that BMI may alter folate cellular uptake and tissue distribution^20,23. Huemer²⁴ and Paulina et al²⁵. found that subjects with higher BMI tended to show lower levels of folate and cobalamin (vitamin B12). In our study, we found that serum folate levels in overweight and obese COPD patients were lower than those in patients with normal body weight, but the difference was not statistically significant. This may be attributed to differences in the selection of study populations. Therefore, further investigation was needed to explore the relationship between body mass index and serum folate levels.

This study investigated the association between serum folate levels and lung function in COPD patients. After adjusting for other variables, we found that subjects with higher serum folate levels had significantly better lung function. A 10 ng/ml decrement in total folate was associated with a 0.28 decrement in FEV₁/FVC z-score in a prior study of asthmatic children²⁶. Another study revealed that in current smokers, higher serum folate levels were significantly associated with better lung function¹³. Chang et al. also confirmed a significant positive correlation between serum folate levels and FEV₁, FEV₁/FVC, and FEF _25−75% in Korean elderly men aged 60 years and above²⁷. These research results were consistent with our findings. In contrast, a study conducted on Danish adults found no association between total folate and lung function²⁸. Some studies also indicated that the relationship between total folate levels and lung function differs between children and adults²⁹. The variations in these research results may be attributed to differences in the populations included in various studies and variations in inflammatory states. The pathophysiological mechanisms by which folate improves lung function or prevents lung function decline can be explained through various pathways. It is known that folate possesses antioxidant activity, which helps to eliminate free radicals and is associated with the inhibition of oxidative stress-induced cell apoptosis³⁰. This antioxidant activity may prevent lung function deterioration by reducing inflammation pathways relevant to the pathogenesis of COPD in patients³¹. The sensitivity of folate to oxidative stress may help reduce airway inflammation in COPD patients, as airway inflammation is involved in the pathogenesis of COPD³². Furthermore, folate is involved in DNA methylation, which suppresses the expression of key immune regulatory genes and plays multiple roles in cellular functions related to the pathogenesis of allergic sensitization. These mechanisms may contribute to the beneficial effects of folate on lung function and its potential role in preventing lung function decline^33,34. Unlike previous studies, this research focuses on whether the subjects have chronic obstructive pulmonary disease. In different disease states, patients may have different inflammatory conditions, which could have an impact on the association between serum folate levels and lung function. This also partly explained why there is a positive correlation between serum folate levels and lung function in COPD patients, while there was no correlation in individuals with normal lung function.

The strengths of this study primarily include the following aspects. Firstly, the study population was derived from the NHANES database, which used a sophisticated stratified sampling design and selected a representative sample of non-institutionalized individuals, making the population highly representative. Secondly, the study had good generalizability, allowing for potential application to broader populations. Thirdly, we conducted stratified analysis based on whether the subjects had chronic obstructive pulmonary disease and adjusted for various factors that may influence lung function. Additionally, we performed subgroup analysis considering factors such as gender, body mass index, and smoking status.

However, our study has several limitations. Firstly, serum folate levels mainly reflect the short-term folate status of the body, and it includes various active forms. Therefore, the association between serum folate levels and lung function in COPD patients requires longitudinal cohort studies and analyses at multiple time points to draw specific conclusions. Secondly, our study lacks detailed data on patient diets, and certain dietary factors may influence the serum folate levels of patients. Thirdly, this is a cross-sectional study, and the causal relationship between serum folate and lung function requires further investigation through prospective studies.

Elevated serum folate levels are associated with better lung function in COPD patients, while folate levels do not significantly impact lung function in individuals without COPD. Future longitudinal studies are needed to explore the biological mechanisms of the effect of serum folate on pulmonary function in COPD patients.

COPD, chronic obstructive pulmonary disease;

Non-COPD, without chronic obstructive pulmonary disease

FEV₁, forced expiratory volume in one second

FVC, forced vital capacity

PEF, peak expiratory flow

FEF_25-75%, forced expiratory flow 25%-75%

BMI, body mass index

ATS, American Thoracic Society

Data availability statement

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: http://www.cdc.gov/nchs/nhanes/.

Ethics statement

The studies involving human participants were reviewed and approved by the National Centers for Disease Control (CDC) and Prevention National Health Statistics Center. The patients/participants provided their written informed consent to participate in this study.

Author contributions

XW conducted the study design, data extraction, statistical analysis, drafted the manuscript, and revision of the paper. HJY conducted data extraction, statistical analysis, and revision of the paper. LYW conducted the study design, statistical analysis, drafted the manuscript, and revision of the paper. All authors contributed to the article and approved the submitted version.

Acknowledgments

The NHANES protocol was approved by the NCHS Research Ethics Review Board.

Conflict of interest

The authors declare that they have no competing interests.

Patient consent for publication

Not applicable.

Celli B, Fabbri L, Criner G, et al (2022) Definition and Nomenclature of Chronic Obstructive Pulmonary Disease: Time for its Revision. Am J Respir Crit Care Med 206(11):1317-1325.
Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 3(11):e442.
Halpin DMG, Celli BR, Criner GJ, et al (2019) The GOLD Summit on chronic obstructive pulmonary disease in low- and middle-income countries. Int J Tuberc Lung Dis 23(11):1131-41.
Meghji J, Mortimer K, Agusti A, et al (2021) Improving lung health in low-income and middle-income countries: from challenges to solutions. Lancet 397(10277):928-40.
Yang IA, Jenkins CR, Salvi SS (2022) Chronic obstructive pulmonary disease in never-smokers: risk factors, pathogenesis, and implications for prevention and treatment. Lancet Respir Med 10(5):497-511.
Cho MH, Hobbs BD, Silverman EK (2022) Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorder. Lancet Respir Med 10(5):485-96.
Naderi, N.; House, J.D (2018) Recent Developments in Folate Nutrition. Adv. Food Nutr. Res. 83:195–213.
Naderi N, House JD (2018) Recent developments in folate nutrition. Adv Food Nutr Res 83:195–213.
Nakano, E.; Higgins, J.A.; Powers, H.J, et al (2001) Folate protects against oxidative modification of human LDL. Br. J. Nutr. 86(6):637-9
Cui, S; Lv, X; Li, W, et al (2018) Folic acid modulates VPO1 DNA methylation levels and alleviates oxidative stress-induced apoptosis in vivo and in vitro. Redox Biol 19:81-91.
Angelis, N.; Porpodis, K.; Zarogoulidis, P, et al (2014) Airway inflammation in chronic obstructive pulmonary disease. J. Thorac. Dis 6:S167–S172.
Leng, S.; Picchi, M.A.; Tesfaigzi, Y.; Wu, G, et al (2017) Dietary nutrients associated with preservation of lung function in Hispanic and non-Hispanic white smokers from New Mexico. Int. J Chron. Obstruct. Pulmon. Dis 12:3171–3181.
Kim T, Oak CH, Jung MH, et al (2020) High Serum Folate Concentration Is Associated with Better Lung Function in Male Chronic Obstructive Pulmonary Disease Patients Who Are Current Smokers: Analysis of Nationwide Population-Based Survey. Nutrients 12(8):2219.
Hirayama, F.; Lee, A.H.; Terasawa, K, et al (2010) Folate intake associated with lung function, breathlessness and the prevalence of chronic obstructive pulmonary disease. Asia Pac. J. Clin. Nutr 19:103–109.
E.S. Ford, D.M. Mannino, A.G. Wheaton, Croft, et al (2013) Trends in the prevalence of obstructive and restrictive lung function among adults in the United States: findings from the national health and nutrition examination surveys from 1988-1994 to 2007-2010. Chest 143(5):1395-1406.
E. Diaz-Guzman, M. Khosravi, D.M. Mannino, et al (2011) Asthma, chronic obstructive pulmonary disease, and mortality in the U.S. population. COPD 8(6):400-7.
A.A. Diaz, C.E. Come, D.M. Mannino, et al (2014) Obstructive lung disease in Mexican Americans and non-Hispanic whites: an analysis of diagnosis and survival in the National Health and Nutritional Examination Survey III Follow-up Study. Chest 145(2):282-289.
M.R. Miller, J. Hankinson, V. Brusasco, et al (2005) Standardization of spirometry. Eur. Respir. J 26(2):319-38.
Bakke PS, Ronmark E, Eagan TM, et al (2012) Recommendations for epidemiological studies on COPD. Eur Respir J 39(5):1278–1279.
Pfeiffer CM, Sternberg MR, Fazili Z, et al (2015) Folate status and concentrations of serum folate forms in the US population: National Health and Nutrition Examination Survey 2011-2. Br J Nutr 113(12):1965-77.
Thuesen BH, Husemoen LL, Ovesen L, et al (2010) Lifestyle and genetic determinants of folate and vitamin B12 levels in a general adult population. Br J Nutr. 103(8):1195-204.
Vardavas, C.I., Linardakis, M.K., Hatzis, C.M., et al (2008) Smoking status in relation to serum folate and dietary vitamin intake. Tob. Induc. Dis 4(1):8.
Tinker SC, Hamner HC, Berry RJ, et al (2012) Does obesity modify the association of supplemental folic acid with folate status among nonpregnant women of childbearing age in the United States? Birth Defect Res A Clin Mol Teratol 94:749–755.
Huemer M., Vonblon K., Födinger M., et al (2006) Total Homocysteine, Folate, and Cobalamin, and Their Relation to Genetic Polymorphisms, Lifestyle and Body Mass Index in Healthy Children and Adolescents. Pediatr. Res 60:764–769.
Kreusler P, Vogel M, Willenberg A, et al (2021) Folate and Cobalamin Serum Levels in Healthy Children and Adolescents and Their Association with Age, Sex, BMI and Socioeconomic Status. Nutrients 13(2):546.
Nicholson A, Pollard SL, Lima JJ, et al (2017) Serum folate concentrations, asthma, atopy, and asthma control in Peruvian children. Respir Med 133:29–35.
Chang SW, Kim MB, Kang JW, et al (2022) High serum folate level is positively associated with pulmonary function in elderly Korean men, but not in women. Sci Rep 12(1):4523.
Thuesen BH, Husemoen LL, Ovesen L, et al (2010) Atopy, asthma, and lung function in relation to folate and vitamin B (12) in adults. Allergy 65:1446–54.
Han YY, Forno E, Rosser F, et al (2020) Serum folate metabolites, asthma, and lung function in a nationwide US study. J Allergy Clin Immunol 146(1):220-222.e8.
Paniz C, Bertinato JF, Lucena MR, et al (2017) A daily dose of 5 mg folic acid for 90 days is associated with increased serum unmetabolized folic acid and reduced natural killer cell cytotoxicity in healthy Brazilian adults. J. Nutr 147(9):1677–1685.
Nicholson A, Pollard SL, Lima JJ, et al (2017) Serum folate concentrations, asthma, atopy, and asthma control in Peruvian children. Respir. Med 133:29–35.
Angelis N, Porpodis K, Zarogoulidis P, et al (2014) Airway inflammation in chronic obstructive pulmonary disease. J. Thorac. Dis 6:S167–S172.
Lovinsky-Desir S, Miller RL, et al (2012) Epigenetics, asthma, and allergic diseases: A review ofthe latest advancements. Curr Allergy Asthma Rep 12(3):211–20.
Blatter J, Han YY, Forno E, et al (2013) Folate and asthma. Am J Respir Crit Care Med 188(1):12–7.

Table 1. The Association of Baseline Participant Characteristics with serum folate and COPD (N=1062)

Characteristics	All Participants (n=1062)	Non-COPD (n=569)	COPD (n=493)	P value	Low serum folate (n=633)	High serum folate (n=429)	P value
Age, years	50.7±16.6	44.0±16.1	58.6±13.3	<0.001^*	47.2±16.3	56.1±16.6	<0.001^*
Males, n (%)	691 (65.1)	328 (57.6)	363 (73.6)	<0.001^*	436 (68.9)	255 (59.4)	0.002^*
Body mass index, kg/m²	27.5±5.7	27.5±5.8	27.4±5.5	0.93	27.7±5.8	27.1±5.5	0.07
Race/ethnicity, n (%)				<0.001^*			<0.001^*
Non-Hispanic white	627 (59.0)	286 (50.3)	341 (69.2)		339 (53.6)	288 (67.1)
Non-Hispanic black	181 (17.4)	99 (17.4)	82 (16.6)		133 (21.0)	48 (11.2)
Mexican American	112 (10.5)	87 (15.3)	25 (5.1)		79 (12.5)	33 (7.7)
Other Hispanic	72 (6.8)	51 (9.0)	21 (4.3)		44 (7.0)	28 (6.5)
Other Race	70 (6.6)	46 (8.1)	24 (4.9)		38 (6.0)	32 (7.5)
Education level, n (%)				0.24			<0.001^*
Less than high school	269 (25.3)	144 (25.3)	125 (25.4)		187 (29.6)	82 (19.1)
High school	255 (24.0)	128 (22.5)	127 (25.8)		154 (24.3)	101 (23.5)
More than high school	538 (50.7)	297 (52.2)	241 (48.9)		292 (46.1)	246 (57.4)
Comorbidity, n (%)
Hypertension	334 (31.5)	140 (24.6)	194 (39.4)	<0.001^*	172 (27.2)	162 (37.8)	<0.001^*
Diabetes	104 (9.8)	49 (8.6)	55 (11.2)	0.16	61 (9.6)	43 (10.0)	0.83
Smoked at least 100 cigarettes in life, n (%)	678 (63.8)	305 (53.6)	373 (75.7)	<0.001^*	438 (69.2)	240 (55.9)	<0.001^*
Family history of respiratory diseases, n (%)	208 (19.6)	106 (18.6)	102 (20.6)	0.39	122 (19.3)	86 (20.0)	0.76
Occupational exposure, n (%)	660 (62.1)	330 (58.0)	330 (66.9)	<0.001^*	408 (64.5)	252 (58.7)	0.06
Passive smoke, n (%)	281 (26.5)	125 (22.0)	156 (31.6)	<0.001^*	208 (32.9)	73 (17.0)	<0.001^*

Data are mean ± standard deviation or n (%). Abbreviations: COPD, chronic obstructive pulmonary disease; Non-COPD, without chronic obstructive pulmonary disease. ^*p value less than 0.05.

Table 2. Effect of serum folate levels on respiratory symptoms and spirometry.

Characteristics	Low serum folate (n=633)	High serum folate (n=429)	P value
Respiratory Symptoms
Chronic cough, n (%)	64 (10.1)	44 (10.3)	0.93
Expectoration of phlegm, n (%)	53 (8.4)	46 (10.7)	0.20
Wheezing, n (%)	158 (25.0)	75 (17.5)	0.005^*
Wheezy during exercise, n (%)	66 (10.4)	39 (9.1)	0.47
Spirometry
Before bronchodilator use ^a
FEV₁, mL	2573±30	2678±35	0.006^*
FVC, mL	3912±42	4021±48	0.040^*
FEV₁/FVC, %	65.5±0.3	66.3±0.3	0.026^*
PEF, mL /s	6625±85	6984±98	0.001^*
FEF_25-75%, mL /s	1451±25	1526±29	0.017^*
After bronchodilator use ^a
FEV₁, mL	2742±30	2850±35	0.005^*
FVC, mL	3940±41	4036±47	0.06
FEV₁/FVC, %	69.4±0.3	70.3±0.4	0.022^*
PEF, mL /s	7220±82	7610±95	<0.001^*
FEF_25-75%, mL/s	1814±32	1913±36	0.015^*

Data are mean ± standard error (Mean ± SE) or n (%),

Notes: ^aAnalysis of covariance; Adjusted variables included age, sex, body mass index, smoking status, family history of respiratory diseases, biomass exposure, occupational exposure, and passive smoke. ^*p value less than 0.05.

Abbreviations: FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; PEF, peak expiratory flow; FEF_25-75%, forced expiratory flow 25%-75%.

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Association Between Serum Folate and Lung Function in People with and without Chronic Obstructive Pulmonary Disease: Results from NHANES 2007–2012.

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Study population

Epidemiological questionnaire

Measurement of serum folate

Spirometry

Statistical analysis

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Tables

Supplementary Files

Status:

Version 1