https://orcid.org/0009-0000-5151-7809
Figures
Abstract
Background
Chronic obstructive pulmonary disease (COPD) has emerged as a leading cause of chronic disease morbidity and mortality globally, posing a substantial public health challenge. Perfluoroalkyl substances (PFAS) are synthetic chemicals known for their high stability and durability. Research has examined their potential link to decreased lung function. Physical activity (PA) has been identified as one of the primary modalities of the non-pharmacological treatment of COPD.
Methods
To investigate the relationship between PFAS and COPD, and whether physical activity could reduce the risk of COPD caused by PFAS exposure, we used data from the NHANES 2013–2018, a cross-sectional study. Logistic regression analysis was used to examine the associations between PFAS and COPD in adult populations, and their associations in different PA types.
Results
We finally included 4857 participants in the analysis, and found that Sm-PFOS (OR: 1.250), PFOA (OR: 1.398) and n-PFOA (OR: 1.354) were closely related to COPD; After stratified by gender, age and smoking, the results showed that Sm-PFOA (OR: 1.312) was related to COPD in female adult, and PFOA (OR: 1.398) and n-PFOA (OR: 1.354) were associated with COPD in male adults; The associations of Sm-PFOS (OR: 1.280), PFOA (OR: 1.481) and n-PFOA (OR: 1.424)with COPD tended to be stronger and more consistent in over 50 years old adults; Sm-PFOS was related to COPD in current smoker (OR: 1.408), and PFOA was related to COPD in former smoker (OR: 1.487); Besides, in moderate-intensity PA group, there were no associations of Sm-PFOS, PFOA and n-PFOA with COPD stratified by gender, age and smoking.
Citation: Pan M, Zou Y, Wei G, Zhang C, Zhang K, Guo H, et al. (2024) Moderate-intensity physical activity reduces the role of serum PFAS on COPD: A cross-sectional analysis with NHANES data. PLoS ONE 19(8): e0308148. https://doi.org/10.1371/journal.pone.0308148
Editor: Avanti Dey, Public Library of Science, UNITED STATES OF AMERICA
Received: February 19, 2024; Accepted: July 18, 2024; Published: August 7, 2024
Copyright: © 2024 Pan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All files are available from the NHANES database.
Funding: This work was financially supported by the National Natural Science Foundation of China (No. 82090015).
Competing interests: The authors declare that there is no conflict of interest regarding the publication of this article.
1. Introduction
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable respiratory disease characterized by persistent symptoms and airflow limitation [1, 2]. It has become a significant cause of chronic morbidity and mortality worldwide, and represents a major public health challenge [3, 4]. The global burden of COPD projected to increase in the coming decades due to continued exposure to COPD risk factors [3]. Perfluoroalkyl substances (PFAS), synthetic chemicals known for their high stability and durability, have been widely used in food contact paper, carpets, furniture, and other household products [5–7]. The National Health and Nutrition Examination Survey (NHANES, 2013–2014) has documented measurable serum levels of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) in over 95% of U.S. general population [8, 9]. Available studies have shown that PFAS may be related to reduced lung function in childhood and adolescence [4, 10, 11]. Pulmonary function decreases to varying degrees with age, especially in older stages [12], and COPD, a typical lung function reduction-related disease, is characterized by non-full irreversible airflow limitation (FEV1/FVC<0.7 post-bronchodilation) [13, 14], and the population suffering from COPD is mostly elderly [15, 16]. PFAS are now have been considered one class of persistent pollutants due to their apparent bioaccumulation and long-range transport potential [17]. Therefore, we hypothesized circumstantially that PFAS levels in blood would be essential for assessing their association with COPD, and we were the first to investigate the relationship between PFAS and COPD.
Physical activity (PA) includes any bodily movement produced by skeletal muscles that requires energy expenditure. It encompasses various activities across four domains: occupational (work-related), domestic (household chores), transportation (walking or cycling to get from one place to another), and leisure time (recreational activities) [18, 19]. PA is recognized as a primary non-pharmacological treatment for COPD and can effectively improve exercise tolerance, clinical symptoms and quality of life of COPD patients [19]. Meanwhile, epidemiological studies by population cohorts have reported longitudinal associations between PA and lung function, attenuated lung function decline and lower COPD incidence [20–22].
Since PFAS and PA can individually affect COPD in opposite directions, it remains unclear whether they have a combined role in regulating COPD. Therefore, we performed an analysis of 2013–2018 National Health and Nutrition Examination Survey (NHANES) data to investigate the association between PFAS and COPD in U.S. adults. Additionally, we assessed whether PA can mitigate the risk of COPD due to PFAS exposure and evaluated the effects of different PA intensities. This study aims to elucidate the relationship between PFAS and COPD and provide scientific evidence for the prevention of COPD through PA in the presence of PFAS exposure.
2. Materials and methods
2.1. Study design and population
The NHANES, administered by the National Center for Health Statistics (NCHS) of the Centers for Disease Control and Prevention (CDC), is a cross-sectional study employing a multi-stage, random probability sampling design. It was approved by the National Center for Health Statistics (NCHS) Institutional Review Board, and informed consent was obtained from all participants. Health interviews were completed by participants in the household, and physical examinations were conducted at the equipped mobile examination center, where urine and blood samples were collected.
Three sections (2013–2014, 2015–2016 and 2017–2018) with information on demographics, serum PFAS concentration, PA, and COPD (https://www.cdc.gov/nchs/nhanes/index.htm) were combined and analyzed. The detailed process of the participants included in this study is shown in Fig 1. Ultimately, we included 4857 participants aged 18 years and older in the analysis.
2.2. Measurement of PFAS
Nine types of PFAS were detected in the NHANES 2013–2014, 2015–2016, and 2017–2018 cycles, including linear perfluorooctane sulfonate (n-PFOS); monomethyl branched isomers of PFOS (Sm-PFOS); linear perfluorooctanoate (n-PFOA); branched isomers of perfluorooctanoate (Sb-PFOA); pefluorodecanoic acid (PFDA); perfluorohexane sulfonic acid (PFHxS); 2- (N-Methyl- perfluorooctane sulfonamide) acetic acid (nm-PFOSA); perfluorononanoic acid (PFNA) and perflurododecanoic acid (PFDoA). The measurement of PFAS in serum was performed using online-solid phase extraction-high performance liquid chromatography-turbo ion spray ionization-tandem mass spectrometry. Details regarding the analysis methodology are available on the NHANES website (https://wwwn.cdc.gov/Nchs/Nhanes/2017-2018/PFAS_J.htm).
In addition, we calculated total PFOA (PFOA) as the sum of n-PFOA and Sb-PFOA, and total PFOS (PFOS) as the sum of n-PFOS and Sm-PFOS. Following NHANES analysis guidelines, the values below the LLOD were instead of .
2.3. MET and PA calculation
The metabolic equivalent (MET) represents the oxygen consumption necessary to sustain resting metabolism. Based on the energy consumption in a quiet and sitting position, it is a commonly used index to express the relative energy metabolism level. Physical activity (PA) data were collected using the NHANES Physical Activity Questionnaire (PAQ), which assesses participants’ activity levels by inquiring about the frequency, duration, and intensity of various activities performed over a defined period, typically the past week or month. Activities covered include walking, jogging, sports, and household chores, with participants providing details on the days, hours, and minutes spent in each activity. Trained interviewers completed the PAQ at home using the Computer Assisted Personal Interview (CAPI) system. The MET values are varied among different types of physical activities, and NHANES provides recommended MET values for each type. The PAQ survey included Vigorous work-related activity (MET = 8), Moderate work-related activity (MET = 4), Walking or bicycling for Transportation (MET = 4), Vigorous leisure-time PA (MET = 8) and Moderate leisure-time PA (MET = 4). PA can be calculated based on the MET value, activity type, weekly frequency, and duration. We computed the value of PA from the following formula: PA (MET-min/week) = MET × weekly frequency × duration of each physical activity [23, 24]. Subsequently, participants were divided into three groups based on the standard scoring criteria of the International Physical Activity Questionnaire (IPAQ): low (<600 MET-min/week), moderate (600 to 3000 MET-min/week), and high (≥3000 MET-min/week) [23]. The threshold of 600 MET-min/week corresponds to the WHO recommended guidelines for moderate-intensity PA (150 min per week) [25–27].
2.4. Outcome and covariables
COPD diagnosis was determined using the medical conditions data file (MCQ_H) with the question: “Has a doctor or other health professional ever told you that you/she/he had COPD?”. Those who answered “yes” were categorized as COPD, and who answered “no” were categorized as non-COPD.
We adjusted for variables associated with COPD diagnosis or believed to confound the relationship between serum PFAS concentrations and COPD diagnosis. Age (continuous), Race (categorical), Gender (categorical), BMI (categorical), PA (categorical), Covered by health insurance (categorical), NHANES cycle (categorical), Drinking (categorical), Marital (categorical), Household income (categorical) [28, 29], were extracted from the demographic variables and sample weights data file (DEMO_H).
2.5. Statistical analysis
All analyses were performed using R software. PFOA and PFOS were analyzed as the sum of the respective linear and branched polymers (Total PFOS (PFOS) = Sm-PFOS + n-PFOS, Total PFOA (PFOA) = Sb-PFOA + n-PFOA). Continuous variables were represented by Median ± Inter quartile range (Median ± IQR), and categorical variables were denoted by N (%). Differences in continuous variables between COPD and non-COPD participants were assessed using t-tests. Moreover, chi-square tests were applied to evaluate the differences in categorical demographic. Serum PFAS distributions were usually right-skewed. Therefore, ln-transformation was performed in the regression analysis to ensure the linearity of the relationship between the predictors and the logit of the outcome. The associations between PFAS and COPD risk were investigated by univariate and multivariate logistic regression analysis. The results were presented with odds ratios (OR) and 95% confidence intervals (95% CI). First, the study of the Crude model was carried out. Then, Model 1 adjusted for age, race, gender, BMI, smoking, PA, covered by health insurance, cycle (referring to NHANES Cycle). Model 2 adjusted for drinking, marital, household income. Then, we analyzed the relationships between serum PFAS concentrations and COPD risk among subpopulation stratified by age, gender or smoking, adjusting for age, race, gender, BMI, smoking, physical activity, covered by health insurance, Cycle, drinking, marital, household income. Moreover, to explore the effect of various types of PA(Low-intensity physical activity, Moderate-intensity physical activity, High-intensity physical activity) on the relationship between serum PFAS concentrations and COPD risk, we screened serum PFAS concentrations that are correlated with COPD among subpopulation stratified by age, gender or smoking, and used multivariate logistic regression to analyze the correlation between serum PFOS concentration and COPD at different intensities of physical activity. The probabilities (P values) were bilateral for all reports, and P<0.05 was regarded as statistically significant.
3. Results
3.1. Basic characteristics of participants
The characteristics of the study participants are summarized in Table 1. The final number of participants included in the analysis was 4857, comprising 2304 men and 2553 women. With all participants being adults ≥18 years old, 1962 (40.4%) were between the ages of 18 and 44, 1713 (35.27%) were between the ages of 45 and 64, and the rest were over 65 years old. There were 929 (19.15%) current smokers and 1120 (23.08%) former smokers. In addition, 1967(40.5%) made low-intensity PA, 1363 (28.1%) had moderate-intensity PA, 1495 (30.8%) had high-intensity PA, and 200 was diagnosed with COPD.
Among all participants, the distributions of several key characteristics were markedly higher in COPD patients compared to non-COPD patients. These characteristics included age (65 and over), race (Non-Hispanic White), household income (<$20,000), marital status (Divorced and Widowed), smoking status (Current smoker and Former smoker), physical activity level (Low-intensity), health insurance coverage (Yes), and type of health insurance (Medicare).
3.2. Serum PFAS and COPD
The associations between individual PFAS and COPD in adults are presented in Table 2. After adjusting confounding variables (Age, Race, Gender, BMI, Smoking, PA, covered by health insurance and Cycle) in Model 1, an ln-unit increase in Sm-PFOS was associated with COPD (OR: 1.189, 95% CI: 1.008–1.409). In Model 2, we further adjusted for Drinking, Marital and Household income, and found that the relationship between Sm-PFOS and COPD persisted (an ln-unit increase, OR: 1.250, 95% CI: 1.040–1.511). Additionally, both PFOA (an ln-unit increase, OR: 1.398, 95% CI: 1.078–1.819) and n-PFOA (an ln-unit increase, OR: 1.354, 95% CI: 1.068–1.729) were shown to be closely related to COPD. Thus, the concentrations of serum Sm-PFOS, PFOA and n-PFOA are associated with COPD, respectively.
3.3. Serum PFAS and COPD stratified by gender, age and smoking
Stratification by gender showed that an ln-unit increase in Sm-PFOS was associated with COPD in female adults (OR: 1.312, 95% CI: 1.015–1.721), but not in male adults; For PFOA and n-PFOA, the positive effect estimates were found in male adults (PFOA, an ln-unit increase, OR: 1.398, 95% CI: 1.078–1.819; n-PFOA, an ln-unit increase, OR: 1.354, 95% CI: 1.068–1.729), but not in female adult (Table 3). Then, stratification by age (50 years old as the limit) indicated stronger and more consistent positive effect estimates for Sm-PFOS, PFOA, and n-PFOA in over 50 years old adults (Sm-PFOS, an ln-unit increase, OR: 1.280, 95% CI: 1.052–1.569; PFOA, an ln-unit increase, OR: 1.481, 95% CI: 1.125–1.960; n-PFOA, an ln-unit increase, OR: 1.424, 95% CI: 1.107–1.847), but not in less than 50 years old adult (Table 4). Finally, stratification by smoking status (including never smoker, former smoker and current smoker) indicated that an ln-unit increase in Sm-PFOS was correlated with COPD in current smoker (OR: 1.408, 95% CI: 1.016–1.992), and an ln-unit increase in PFOA was associated with COPD in former smoker (OR: 1.487, 95% CI: 1.003–2.219) (Table 5).
3.4. Regulation of PA on PFAS and COPD
Based on the relationship between PFAS and COPD stratified by gender, age, and smoking, we further explored these associations in different PA groups (Table 6). we further explored these associations in different PA groups (Table 6). We found that male adults in the low-intensity PA group (PA = 0) were at higher risk of COPD associated with PFOA (OR: 2.312, 95% CI: 1.051, 5.665), female adults in the low-intensity PA group (PA = 0) were at higher risk of COPD associated with Sm-PFOS (OR: 1.616, 95% CI: 1.012, 2.73), and male adults in high-intensity PA group (PA = 2) were at highest risk of COPD associated with PFOA (OR: 3.111, 95% CI: 1.217, 8.872) and n-PFOA (OR: 2.92, 95% CI: 1.206, 7.912); For adults over the age of 50, the risks of COPD associated with Sm-PFOS(OR: 1.448, 95% CI: 1.031, 2.078), PFOA(OR: 2.103, 95% CI: 1.051, 5.665) and n-PFOA(OR: 1.935, 95% CI: 1.231, 3.158) were highest in the low-intensity PA group (PA = 0); For current smoker, high-intensity PA group (PA = 2) were at the highest risk of COPD associated with Sm-PFOS(OR: 4.862, 95% CI: 1.664, 25.292), and For former smoker, high-intensity PA group (PA = 2) were at the highest risk of COPD associated with PFOA (OR: 7.661, 95% CI: 2.147, 34.929); Additionally, in the moderate-intensity PA group (PA = 1), there were no associations between Sm-PFOS, PFOA, and n-PFOA and COPD in adult populations stratified by gender, age, and smoking, indicating that moderate-intensity PA could mitigate PFAS-related COPD.
4. Discussion
In this study indicated that PFAS (including Sm-PFOS, PFOA and n-PFOA) were associated with COPD in adult populations. Interestingly, these associations varied across different adult populations stratified by gender, age and smoking status. For example, Sm-PFOA was related to COPD in female adults, and PFOA and n-PFOA were associated with COPD in male adults; Sm-PFOS, PFOA and n-PFOA were more strongly and consistently associated with COPD in over 50 years old adults, but not in less than 50 years old adults; Sm-PFOS was related to COPD in current smoker, and PFOA was associated with COPD in former smoker. Furthermore, moderate-intensity PA appeared to mitigate the associations of Sm-PFOS, PFOA, and n-PFOA with COPD in adult populations.
Currently, there are relatively few studies exploring the associations between PFAS and respiratory diseases, mainly focused on asthma, airway inflammation and infection [30–32]. This study is the first to reveal the consistent and positive correlation between PFAS (including Sm-PFOS, PFOA, and n-PFOA) and COPD in adult populations. Actually, the presence of incomplete reversible airflow limitation is required for COPD to be diagnosed by performing spirometry and a post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ≤0.7 [33]. It has been proved that the concentrations of PFOA and PFOS in cord blood were correlated with decreasing lung function in childhood [34], indirectly supporting the associations of Sm-PFOS, PFOA, and n-PFOA with COPD.
As adults age, their lung function tends to increase first and then decrease, and by age 50, the rate of decline slows down [35, 36]. Therefore, this study stratified COPD patients by age, and indicated that Sm-PFOS, PFOA and n-PFOA were related to COPD in over 50 years old adults. Still, these associations were not shown in less than 50 years old adults, which indicated that people over 50 years old should pay more attention to avoid the harm of PFAS related to COPD. Given that the most intensively studied risk factor for COPD was cigarette smoking [37], this study divided the COPD patients into three groups: non-smoker, former smoker and current smoker, then explored the associations of Sm-PFOS, PFOA and n-PFOA with these three COPD patients. And we found that Sm-PFOS was related to COPD in current smoker, but not in non-smoker or former smoker, PFOA was related to COPD in the former smoker, but not in non-smoker or current smoker, indicating that smoking could promote the occurrence of PFAS-related COPD, and even smoking in the past and not smoking now has a promoting effect. Thus, to prevent the occurrence of PFAS-related COPD, smoking should be banned, because smoking could also lead to the event of PFAS-related COPD. In addition, gender-related differences in immune pathways and airway damage patterns [38, 39]; therefore, we further evaluated the associations of Sm-PFOS, PFOA and n-PFOA with COPD in female and male adults, respectively. And we found that PFOA and n-PFOA were associated with COPD in male adults, but not in female adults; and Sm-PFOS was associated with COPD in female adults, but not in male adults. These results indicated that male adults should pay more attention to avoiding the harm of COPD related to PFOA, and female adults should pay more attention to preventing the harm of COPD related to PFOS. As for the underlying mechanisms of the differently outcomes for Sm-PFOS, PFOA and n-PFOA in female and male adults, respectively, further scrupulously studies are needed.
The mechanism by which PFAS causes COPD has not been elucidated, but limited evidence suggests that the inflammatory response may be a critical link in mediating PFAS-induced COPD. On the one hand, the chronic inflammatory response could not only induce the destruction of parenchymal tissue leading to emphysema, but also disrupt the regular repair and defence mechanisms of the lung leading to small airway fibrosis, which eventually resulted in gas trapping and progressive airflow limitation, the pathological manifestations of COPD [40]; On the other hand, PFAS exposure could induce an inflammatory response in multiple organs. For example, a study using data from the NHANES 2005–2012 found that PFOA and PFOS were significantly associated with percentage increases in lymphocyte counts, and increased serum albumin, meaning these chemicals were related to chronic inflammation [41]; the odds of developing nonalcoholic steatohepatitis (NASH) increased significantly for each interquartile range (IQR) increase of PFOS compared to children with steatosis alone [42]; higher PFAS was associated with a lower degree of gut inflammation [43]; PFAS concentration was associated with a positive marker “FeNO>25 ppb” of eosinophilic airways inflammation [30].
Additionally, we found an interesting result that the low- or high-intensity PA group (PA = 0 or 2) was at the highest risk of COPD related to serum PFAS, and moderate-intensity PA has no risk of COPD related to serum PFAS. This finding is consistent with the study of David et al., which discovered that high-intensity PA did not produce any reduced risk for COPD [44]. This phenomenon may be caused by the fact that PA is a well-recognized determinant that reduces the incidence of COPD and inhibits the progression of COPD [29, 45], but high-intensity PA can bring burden to the body [46], which may have no effect on COPD or further exacerbate COPD. Therefore, our results were very plausible, indicating that moderate-intensity PA could eliminate the risk of COPD under PFAS exposure.
There were some limitations of this study. First, this study relied on self-reported questionnaires to identify COPD, which may result in missed diagnosis of the outcome, thus potentially attenuating these results. Second, although PA is a habitual human behavior and the data collected are reliable, recall bias cannot be ruled out for some of the data because they were collected through questionnaires. Additionally, for populations younger than 50 years, the number of people diagnosed with COPD will be smaller, which can lead to extremely imbalance between the COPD and non-COPD groups, resulting in biased and inaccurate results in the statistical analysis. To reduce this bias, we stratified by age (limited to 50 years), showing stronger positive effect estimates for PFAS in adults over 50 years old (Table 3), consistent with the results on the association between individual PFAS and COPD (Table 2). Finally, NHANES is a cross-sectional survey which limits the ability to establish the temporality of the exposure and outcome sequence. PFAS can persist in the body for years [47].
COPD is now among the top three causes of death worldwide, with 90% of these deaths occurring in low- and middle-income countries [48]. More than 3 million people died of COPD in 2012, accounting for 6% of all deaths globally [3]. COPD is a major cause of chronic morbidity and mortality throughout the world, representing a significant public health challenge [3]. And in our study, we found that the serum of the participants contained various types of PFAS contaminants. More importantly, PFAS has been classified as persistent organic pollutants (POPs) and can bind to proteins in the body, affecting homeostasis and ultimately leading to disease [47]. Thus, this association warrants further investigation. Future prospective cohort studies could explore the causal relationship between PFAS exposure and COPD development.
5. Conclusion
Sm-PFOS, PFOA and n-PFOA were associated with COPD in adults. PFOA and n-PFOA were associated with COPD in male adults, the associations of Sm-PFOS, PFOA and n-PFOA with COPD were stronger and more consistent in over 50 years old adults, and Sm-PFOS and PFOA were related to COPD in the current or former smoker. In addition, moderate-intensity PA could reduce the risk of COPD under PFAS exposure.
Supporting information
S1 Checklist. STROBE statement—Checklist of items that should be included in reports of cross-sectional studies.
https://doi.org/10.1371/journal.pone.0308148.s001
(DOC)
Acknowledgments
We extend our appreciation to the editor and the anonymous reviewers for their invaluable and constructive comments. We would like to thank the National Health and Nutrition Examination Survey (NHANES) for providing the data used in this study.
References
- 1. Qin W, Huang H, Dai Y, Han W, Gao Y. Proteome analysis of urinary biomarkers in a cigarette smoke-induced COPD rat model. Respir Res. 2022;23(1):156. Epub 2022/06/16. pmid:35705945.
- 2. Zhang J, Chen F, Wang Y, Chen Y. Early detection and prediction of acute exacerbation of chronic obstructive pulmonary disease. Chinese Medical Journal Pulmonary and Critical Care Medicine. 2023;1(2):102–7. %U http://dx.doi.org/10.1016/j.pccm.2023.04.004.
- 3. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med. 2006;3(11):e442. Epub 2006/11/30. pmid:17132052; PubMed Central PMCID: PMC1664601.
- 4. Hurst JR, Skolnik N, Hansen GJ, Anzueto A, Donaldson GC, Dransfield MT, et al. Understanding the impact of chronic obstructive pulmonary disease exacerbations on patient health and quality of life. European Journal of Internal Medicine. 2020;73:1–6. pmid:31954592
- 5. Becanova J, Melymuk L, Vojta S, Komprdova K, Klanova J. Screening for perfluoroalkyl acids in consumer products, building materials and wastes. Chemosphere. 2016;164:322–9. Epub 2016/09/07. pmid:27592321.
- 6. Buck RC, Franklin J, Berger U, Conder JM, Cousins IT, de Voogt P, et al. Perfluoroalkyl and polyfluoroalkyl substances in the environment: terminology, classification, and origins. Integr Environ Assess Manag. 2011;7(4):513–41. Epub 2011/07/28. pmid:21793199; PubMed Central PMCID: PMC3214619.
- 7. Conder JM, Hoke RA, De Wolf W, Russell MH, Buck RC. Are PFCAs bioaccumulative? A critical review and comparison with regulatory criteria and persistent lipophilic compounds. Environ Sci Technol. 2008;42(4):995–1003. Epub 2008/03/21. pmid:18351063.
- 8. Calafat AM, Kato K, Hubbard K, Jia T, Botelho JC, Wong LY. Legacy and alternative per- and polyfluoroalkyl substances in the U.S. general population: Paired serum-urine data from the 2013–2014 National Health and Nutrition Examination Survey. Environ Int. 2019;131:105048. Epub 2019/08/04. pmid:31376596; PubMed Central PMCID: PMC7879379.
- 9. Wang Y, Aimuzi R, Nian M, Zhang Y, Luo K, Zhang J. Perfluoroalkyl substances and sex hormones in postmenopausal women: NHANES 2013–2016. Environ Int. 2021;149:106408. Epub 2021/02/07. pmid:33548847.
- 10. Manzano-Salgado CB, Granum B, Lopez-Espinosa MJ, Ballester F, Iniguez C, Gascon M, et al. Prenatal exposure to perfluoroalkyl substances, immune-related outcomes, and lung function in children from a Spanish birth cohort study. Int J Hyg Environ Health. 2019;222(6):945–54. Epub 2019/07/03. pmid:31262703.
- 11. Qin XD, Qian ZM, Dharmage SC, Perret J, Geiger SD, Rigdon SE, et al. Association of perfluoroalkyl substances exposure with impaired lung function in children. Environ Res. 2017;155:15–21. Epub 2017/02/09. pmid:28171771.
- 12. Cho SJ, Stout-Delgado HW. Aging and Lung Disease. Annu Rev Physiol. 2020;82:433–59. Epub 20191115. pmid:31730381; PubMed Central PMCID: PMC7998901.
- 13. Halpin DMG, Criner GJ, Papi A, Singh D, Anzueto A, Martinez FJ, et al. Global Initiative for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease. The 2020 GOLD Science Committee Report on COVID-19 and Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2021;203(1):24–36. pmid:33146552; PubMed Central PMCID: PMC7781116.
- 14. Chen D, Curtis JL, Chen Y. Twenty years of changes in the definition of early chronic obstructive pulmonary disease. Chinese Medical Journal Pulmonary and Critical Care Medicine. 2023;1(2):84–93. %U http://dx.doi.org/10.1016/j.pccm.2023.03.004.
- 15. Lange P, Celli B, Agusti A, Boje Jensen G, Divo M, Faner R, et al. Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease. N Engl J Med. 2015;373(2):111–22. pmid:26154786.
- 16. Incalzi RA, Scarlata S, Pennazza G, Santonico M, Pedone C. Chronic Obstructive Pulmonary Disease in the elderly. European Journal of Internal Medicine. 2014;25(4):320–8. pmid:24183233
- 17. Wang Z, DeWitt JC, Higgins CP, Cousins IT. A Never-Ending Story of Per- and Polyfluoroalkyl Substances (PFASs)? Environ Sci Technol. 2017;51(5):2508–18. Epub 2017/02/23. pmid:28224793.
- 18. Peterman JE, Loy S, Carlos J, Arena R, Kaminsky LA. Increasing physical activity in the community setting. Prog Cardiovasc Dis. 2021;64:27–32. Epub 2020/11/02. pmid:33130191.
- 19. Ambrosino P, Di Minno MND, D’Anna SE, Formisano R, Pappone N, Mancusi C, et al. Pulmonary rehabilitation and endothelial function in patients with chronic obstructive pulmonary disease: A prospective cohort study. European Journal of Internal Medicine. 2023;116:96–105. pmid:37349204
- 20. Behrens G, Matthews CE, Moore SC, Hollenbeck AR, Leitzmann MF. Body size and physical activity in relation to incidence of chronic obstructive pulmonary disease. CMAJ. 2014;186(12):E457–69. Epub 2014/07/09. pmid:25002559; PubMed Central PMCID: PMC4150732.
- 21. Fuertes E, Carsin AE, Anto JM, Bono R, Corsico AG, Demoly P, et al. Leisure-time vigorous physical activity is associated with better lung function: the prospective ECRHS study. Thorax. 2018;73(4):376–84. Epub 2018/01/08. pmid:29306902; PubMed Central PMCID: PMC5870462.
- 22. Pelkonen M, Notkola IL, Lakka T, Tukiainen HO, Kivinen P, Nissinen A. Delaying decline in pulmonary function with physical activity: a 25-year follow-up. Am J Respir Crit Care Med. 2003;168(4):494–9. Epub 2003/06/07. pmid:12791579.
- 23. Chen L, Cai M, Li H, Wang X, Tian F, Wu Y, et al. Risk/benefit tradeoff of habitual physical activity and air pollution on chronic pulmonary obstructive disease: findings from a large prospective cohort study. BMC Med. 2022;20(1):70. Epub 2022/03/01. pmid:35220974; PubMed Central PMCID: PMC8883705.
- 24. Ran J, Zhang Y, Han L, Sun S, Zhao S, Shen C, et al. The joint association of physical activity and fine particulate matter exposure with incident dementia in elderly Hong Kong residents. Environ Int. 2021;156:106645. Epub 2021/05/21. pmid:34015665.
- 25. Bull FC, Al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, et al. World Health Organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports Med. 2020;54(24):1451–62. Epub 2020/11/27. pmid:33239350; PubMed Central PMCID: PMC7719906.
- 26. Burge AT, Cox NS, Abramson MJ, Holland AE. Interventions for promoting physical activity in people with COPD. Cochrane Database of Systematic Reviews. 2017.
- 27. Yin P, Zhang M, Li Y, Jiang Y, Zhao W. Prevalence of COPD and its association with socioeconomic status in China: findings from China Chronic Disease Risk Factor Surveillance 2007. BMC Public Health. 2011;11:586. Epub 2011/07/26. pmid:21781320; PubMed Central PMCID: PMC3152537.
- 28. Cai Y, Schikowski T, Adam M, Buschka A, Carsin A-E, Jacquemin B, et al. Cross-sectional associations between air pollution and chronic bronchitis: an ESCAPE meta-analysis across five cohorts. Thorax. 2014;69(11):1005–14. pmid:25112730
- 29. Garcia-Aymerich J, Lange P, Benet M, Schnohr P, Anto JM. Regular physical activity modifies smoking-related lung function decline and reduces risk of chronic obstructive pulmonary disease: a population-based cohort study. Am J Respir Crit Care Med. 2007;175(5):458–63. Epub 2006/12/13. pmid:17158282.
- 30. Averina M, Brox J, Huber S, Furberg AS, Sorensen M. Serum perfluoroalkyl substances (PFAS) and risk of asthma and various allergies in adolescents. The Tromso study Fit Futures in Northern Norway. Environ Res. 2019;169:114–21. Epub 2018/11/18. pmid:30447498.
- 31. Jackson-Browne MS, Eliot M, Patti M, Spanier AJ, Braun JM. PFAS (per- and polyfluoroalkyl substances) and asthma in young children: NHANES 2013–2014. Int J Hyg Environ Health. 2020;229:113565. Epub 2020/06/03. pmid:32485600; PubMed Central PMCID: PMC7492379.
- 32. Kvalem HE, Nygaard UC, Lodrup Carlsen KC, Carlsen KH, Haug LS, Granum B. Perfluoroalkyl substances, airways infections, allergy and asthma related health outcomes—implications of gender, exposure period and study design. Environ Int. 2020;134:105259. Epub 2019/11/17. pmid:31733527.
- 33. Celli BR, MacNee W, Force AET. Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper. Eur Respir J. 2004;23(6):932–46. Epub 2004/06/29. pmid:15219010.
- 34. Kung YP, Lin CC, Chen MH, Tsai MS, Hsieh WS, Chen PC. Intrauterine exposure to per- and polyfluoroalkyl substances may harm children’s lung function development. Environ Res. 2021;192:110178. Epub 2020/09/30. pmid:32991923.
- 35. Ong BA, Li J, McDonough JM, Wei Z, Kim C, Chiavacci R, et al. Gene network analysis in a pediatric cohort identifies novel lung function genes. PLoS One. 2013;8(9):e72899. Epub 2013/09/12. pmid:24023788; PubMed Central PMCID: PMC3759429.
- 36. Wang L, Yu C, Liu Y, Wang J, Li C, Wang Q, et al. Lung Cancer Mortality Trends in China from 1988 to 2013: New Challenges and Opportunities for the Government. Int J Environ Res Public Health. 2016;13(11). Epub 2016/11/02. pmid:27801859; PubMed Central PMCID: PMC5129262.
- 37. Wheaton AG, Liu Y, Croft JB, VanFrank B, Croxton TL, Punturieri A, et al. Chronic Obstructive Pulmonary Disease and Smoking Status—United States, 2017. MMWR Morb Mortal Wkly Rep. 2019;68(24):533–8. Epub 2019/06/21. pmid:31220055; PubMed Central PMCID: PMC6586372 potential conflicts of interest. No potential conflicts of interest were disclosed.
- 38. Bel EH, Ten Brinke A. New Anti-Eosinophil Drugs for Asthma and COPD: Targeting the Trait! Chest. 2017;152(6):1276–82. Epub 2017/06/07. pmid:28583618.
- 39. Gal-Oz ST, Maier B, Yoshida H, Seddu K, Elbaz N, Czysz C, et al. ImmGen report: sexual dimorphism in the immune system transcriptome. Nat Commun. 2019;10(1):4295. Epub 2019/09/22. pmid:31541153; PubMed Central PMCID: PMC6754408.
- 40. Zhang Y, Tu YH, Fei GH. The COPD assessment test correlates well with the computed tomography measurements in COPD patients in China. Int J Chron Obstruct Pulmon Dis. 2015;10:507–14. Epub 2015/03/19. pmid:25784797; PubMed Central PMCID: PMC4356707.
- 41. Omoike OE, Pack RP, Mamudu HM, Liu Y, Strasser S, Zheng S, et al. Association between per and polyfluoroalkyl substances and markers of inflammation and oxidative stress. Environ Res. 2021;196:110361. Epub 2020/11/03. pmid:33131681.
- 42. Jin R, McConnell R, Catherine C, Xu S, Walker DI, Stratakis N, et al. Perfluoroalkyl substances and severity of nonalcoholic fatty liver in Children: An untargeted metabolomics approach. Environ Int. 2020;134:105220. Epub 2019/11/21. pmid:31744629; PubMed Central PMCID: PMC6944061.
- 43. Xu Y, Li Y, Scott K, Lindh CH, Jakobsson K, Fletcher T, et al. Inflammatory bowel disease and biomarkers of gut inflammation and permeability in a community with high exposure to perfluoroalkyl substances through drinking water. Environ Res. 2020;181:108923. Epub 2019/11/25. pmid:31759646.
- 44. Donaire-Gonzalez D, Gimeno-Santos E, Balcells E, de Batlle J, Ramon MA, Rodriguez E, et al. Benefits of physical activity on COPD hospitalisation depend on intensity. Eur Respir J. 2015;46(5):1281–9. Epub 2015/07/25. pmid:26206873.
- 45. Gimeno-Santos E, Frei A, Steurer-Stey C, de Batlle J, Rabinovich RA, Raste Y, et al. Determinants and outcomes of physical activity in patients with COPD: a systematic review. Thorax. 2014;69(8):731–9. Epub 2014/02/22. pmid:24558112; PubMed Central PMCID: PMC4112490.
- 46. Tian X, Xue B, Wang B, Lei R, Shan X, Niu J, et al. Physical activity reduces the role of blood cadmium on depression: A cross-sectional analysis with NHANES data. Environ Pollut. 2022;304:119211. Epub 2022/03/29. pmid:35341822.
- 47. Jansen A, Muller MHB, Gronnestad R, Klungsoyr O, Polder A, Skjerve E, et al. Decreased plasma levels of perfluoroalkylated substances one year after bariatric surgery. Sci Total Environ. 2019;657:863–70. Epub 2019/01/27. pmid:30677951.
- 48. Halpin DMG, Celli BR, Criner GJ, Frith P, Lopez Varela MV, Salvi S, et al. The GOLD Summit on chronic obstructive pulmonary disease in low- and middle-income countries. Int J Tuberc Lung Dis. 2019;23(11):1131–41. Epub 2019/11/14. pmid:31718748.