The study aimed to determine the association between lung function and 10 heavy metals in a typical rural population of northwest China, and to explore the possible effect of solid fuels using behaviors. There are emerging studies on lung function and heavy metals, while most of the study population is occupational population and few studies have examined in rural populations of northwest China. Our study provided evidence on the association between metal mixtures exposure with a lower level of lung function in this population. The results consistently showed that the increase of heavy metals was significantly associated with lung function decline and increased risk of PVD. We discovered that higher concentrations of Hg, Mn, Sb and lower Mo may be risk factors for PVD and lung function decline. Simultaneously, subgroup analyses also showed an increased risk of PVD among people who used solid fuels in multiple heavy metals.
Several cohort studies have shown that some heavy metals were significantly associated with lung function decline and the morbidity of COPD(Dai et al. 2019; Heo et al. 2017; Leem et al. 2014; Zeng et al. 2016). In our study, Hg, Mn and Sb showed hazardous to lung function and increased the risk of PVD. In some animal experiments, epithelial cells and cell fragments were observed in the lungs of Hg exposed rats, leading to occlusion of the bronchiole lumen(Koopsamy Naidoo et al. 2019). At the same time, other studies have shown that type II alveolar cells are susceptible to oxidative stress, and Hg can induce type II epithelial cell damage through oxidative stress-related mitochondrial cell death pathway(Lu et al. 2010). However, our study didn’t involve the corresponding indexes of inflammatory factors, so there are certain limitations in the assessment of internal exposure to heavy metals. In a Korean cohort study of COPD, they found serum Hg level may be a risk factor for reduced lung function and obstructive lung disease(Heo et al. 2017). Elemental mercury is liquid at indoor temperature and can easily evaporate to produce steam(Balali-Mood et al. 2021), and burning coal stoves for heating or cooking can enter the body more easily through the respiratory tract. What’s more, regular alcohol consumption and high Hg concentrations have an enhanced effect(Lee et al. 2017). These results all verify the damage of high concentration of Hg to lung and lead to the decline of lung function, which is consistent with our study.
In addition, our results found that Mn contributed significantly to the effect of metal mixture on lung function decline. A retrospective study of ferromanganese refinery workers showed that manganese dust could impair pulmonary ventilation function in male workers(Wang et al. 2015). Soyseth and Antonini et al found that exposure to manganese dust has adverse effects on lung function, including airflow restriction, bronchitis, airway irritation, and changes in lung function(Antonini 2003; Søyseth et al. 2011). There is evidence that Mn overexposure may be associated with reduced FEV1% and FVC%(Madrigal et al. 2018). This was basically consistent with our results that Mn was significantly negatively correlated with FEV1% and FVC% and the risk of PVD increased significantly with the increase of Mn concentration. Mn and Hg were the main metals affecting FEV1% and FVC% in lung of rural population in northwest China, which may be related to the local heavy metal background value and the use of coals heating in winter(Zhang & Wang 2020). Local residents have been burning coals for heating and cooking for a long time, and their homes did not have effective ventilation facilities or have but did not use them. It is well-known that the particles from coals burning contain trace amounts of heavy metals such as Pb, Hg, As, Cd, Cr, Mn, Sb and so on, which can accumulate in their bodies(Munawer 2018). Moreover, studies have demonstrated the ability of the surface of PM2.5 to adhere to a variety of toxic entities, such as organic compounds and toxic metals(Duan et al. 2012; Li et al. 2021). The indoor pollution level of PM is relatively high in winter(He et al. 2021; Zhou et al. 2016). And our investigation time is in autumn and winter, which may also aggravate the accumulation of heavy metals in their bodies.
However there were very few studies on the effects of Sb on lung function, but earlier studies on the risk of lung cancer in occupational workers highlighted high levels of exposure to Sb compounds and other toxic substances(Cooper & Harrison 2009; McCallum 2005). Studies have shown that Sb has a relatively high mobility of heavy metals in coal ash(Fernandez-Turiel et al. 1994). Therefore, Sb is more likely to be inhaled in daily life. Our study also showed a significantly negative correlation between Sb and FEV1%, but this also need to be further confirmed.
Interestingly, lower dose of heavy metals is common in our environment and diet, and even some of them are essential for health benefit. For example, organisms require different amounts of heavy metals, some trace elements such as Mo, Co, Cu, Zn, all of which are required by humans(Fernandez-Luqueno et al. 2013). Generally speaking, Cu and Zn at low concentrations have been confirmed to be components of various proteins and enzymes and participate in redox reactions(Jomova & Valko 2011). However, the subjects in this study also lived near a mining area and non-ferrous metals smelting area. Although production has been stopped at present, there were still high levels of environmental pollution, in which Co, Cu and Zn residues in the soil were still high(Liu et al. 2017; Zhang et al. 2022). In general, heavy metals would produce toxic effects when their concentration exceeds a certain threshold(Rahman & Singh 2019). Thus, it is reasonable that Co and Cu were negatively correlated with FEV1/FVC in our study. Previous studies have shown that heavy metals are mostly harmful to human body through the soil-grain-human system, and grain consumption is one of the main ways of human exposure to toxic elements(Liu et al. 2017; Liu et al. 2013). Most of these grains were consumed by local residents, so it was likely that feeding on these grains had a negative impact on the health of our study population.
There was a study in American Indian adults showed that Mo was associated with a decrease in FVC%, and Mo was the most influential metal in restrictive ventilatory lung disease among diabetics(Sobel et al. 2022). Whereas, in our study, Mo and Pb showed a potential protective effect. This may be related to the fact that Mo are essential trace elements in human body(Fernandez-Luqueno et al. 2013). And Low levels of Pb exposure have been reported to have immune-stimulating effects compared to higher exposures that normally lead to immunosuppression(Mishra 2009). At present, there were relatively few studies using BKMR models to assess the relationship between metals co-exposure and lung function. Wu et al. conducted a study on the association between metals co-exposure and lung function in welders, and the results showed that the joint exposure of heavy metals was related to the decline of lung function of workers(Wu et al. 2022), which was consistent with our results.
Further subgroup analysis found that the population using solid fuels, males and BMI ≥ 24kg/m2 were associated with a higher risk of PVD among Co, Zn and Hg. This may be explained by the higher smoking rate in males than females, where accompanied by the synergistic effect between nicotine and heavy metals(Perez et al. 2020; Wei et al. 2021). Furthermore, studies have shown that obesity significantly interferes with respiratory function by reducing lung volume, especially expiratory reserve and functional residual volume(Mafort et al. 2016). Therefore, people with BMI ≥ 24kg/m2 may be more susceptible to heavy metal damage to lung function. In our study, we used the clinically commonly used indicators FEV1, FVC and FEV1/FVC to evaluate lung function. Moreover, FEV1 and FEV1/FVC can represent the small airway limitation; peak expiratory flow (PEF) can only reflect central airway obstruction. Sometimes when PEF is normal, FEV1 has decreased(Luo et al. 2021; Wu et al. 2022).
In this study, we found a relationship between metal mixtures and lung function using several statistical methods, especially among people who use solid fuels, facilitating a more comprehensive and accurate analysis. We obtained the same results from various analysis, which proved the validity of the conclusion. In this population, the prevention and control of the harm caused by heavy metals mainly apply to the government intervention to install effective ventilation equipment, and regular health education for the local population to know the harm of indoor coals burning. In addition, there are some limitations in this study. Firstly, this study was a cross-sectional study, so we could not determine the causal relationship between heavy metals exposure and lung function. In the next place, urinary heavy metals sometimes do not reflect individual exposure, and blood samples may be more representative. Thirdly, recall bias may exist because questionnaire data were self-reported. However, face-to-face surveys were conducted by trained investigators to a uniform standard, as well as each completed questionnaire was logically checked. Fourthly, this study was only targeted at the population in the rural areas of northwest China, and the sample size was too small to be representative. Then, since the source of food is not very clear in this study, this aspect was not involved in this study. In addition, this study did not analyze the specific sources of heavy metals, which should be strengthened in future studies so as to carry out targeted prevention and control of heavy metal pollution.