One of the main goals of this study was to determine the association between PM2.5 exposure and survival of lung cancer patients after surgery. Although not all our results were significant, the overall trend suggested that high postoperative levels of PM2.5 reduced the survival of lung cancer patients. Our data suggest that for every 10 μg/m3 additional monthly PM2.5 exposure in the first and second postoperative months, the risk of death increases (HR: 1.043, 95% CI: 1.019−1.067 and HR: 1.036, 95% CI: 1.013−1.060, respectively). Fu et al. identified a positive association between PM2.5 exposure and lung cancer mortality rates (Fuet al., 2015). They found an overall trend that provinces in China with higher PM2.5 exposure had higher rates of death among lung cancer patients. Postoperative complications are common, and patients may experience fatigue, dyspnea, pain, and impaired lung function after surgery. Consequently, they are more vulnerable to PM2.5 exposure.
Patients’ demographic characteristics that may affect survival (sex, age, marital status, occupation, length of hospitalization, and medical insurance type) were controlled for in multivariate analyses. To adjust for the effects of other air pollutants, specific monthly O3 exposure was also integrated in the Cox regression model in the sensitivity analysis. The PM2.5 and O3 data of this study come from the near-real-time TAP in China. We used the Baidu Maps API to convert residential addresses into coordinates and estimate the daily PM2.5 and O3 exposure. Thus, we were able to accurately assess the exposure of patients at an individual level. However, there are several limitations to our survey. First, data on the tumor-node-metastasis stage and pathological classification, which are important for forecasting the survival of patients with lung carcinoma (Goldstrawet al., 2007), were unavailable. Therefore, we used the length of hospitalization to control for disease severity. Second, the influence of indoor air pollution was not taken into consideration because of a lack of related data. However, a former study showed that a high level of indoor air pollution may induce respiratory symptoms and impair lung function (Leeet al., 2020). Last, because of the small sample size, the impact of PM2.5 concentration on the survival of cancer patients was not statistically significant in some subgroups.
The causal relationship between PM2.5 concentration and carcinogenic risk has been well demonstrated by epidemiological studies. Studies performed in the past decade have mostly focused on the development of exposure-response models to assess the lung cancer mortality and morbidity risks in relation to PM2.5 exposure. However, to our knowledge, no prior study has examined the relationship between ambient PM2.5 exposure and the survival of lung cancer patients after surgery. In this study, we found that increases in PM2.5 exposure in the first and second months after surgery increased the risk of mortality. In a previous study in China, there was a 5.2% increase in lung cancer mortality for every 10 μg/m3 increase in PM2.5 concentration (Caoet al., 2018). This was comparable to the results of the present study. Stronger correlations between PM2.5 exposure and mortality in lung cancer patients have been reported in North America (Hamraet al., 2014; Huanget al., 2017). The average PM2.5 concentration in this study was 55.91 μg/m3, which is higher than the levels in most previous studies in Western populations, which had mean concentrations ranging from 6.6 μg/m3 to 13.0 μg/m3 (Olssonet al., 2011; Raaschou-Nielsenet al., 2013; Huanget al., 2021). The higher levels of PM2.5 may increase the effect of PM2.5 on the survival of lung cancer patients. However, these differences may also be because of geographical diversity and patient heterogeneity.
Another noteworthy result was that PM2.5 exposure has a significant effect on patients with longer hospital stays. This is primarily because the efficacy of the immune system decreases as disease severity increases (Budisanet al., 2021). Therefore, patients with longer hospital stays are more vulnerable to health effects caused by air pollution (Shumakeet al., 2013). Previous studies have reported that every 10 μg/m3 increase in the concentration of PM2.5 is linked to an increase in mortality of 15–27% in lung cancer patients, particularly in former and current smokers (Turneret al., 2011; Huang, et al., 2021). However, in our study, PM2.5 exposure affected the survival of patients of never-smokers but not that of ever-smokers. This may because smoking produces particulates also contained in PM2.5, which are directly absorbed into the body when smoking and cause health effects (Yueet al., 2015). Therefore, the effect of PM2.5 was obscured by smoking.
Our results also showed that there was a relatively stronger correlation between survival and PM2.5 concentration in the younger population than in the older population, which was different from the results of a previous study (Yue, et al., 2015). This could be because younger patients have a higher rate of recovery and more outdoor physical activity; therefore, they are more easily exposed to PM2.5 (Jonssonet al., 2019).
Several possible mechanisms for the correlation between PM2.5 concentration and lung cancer development have been proposed. Under exposure to PM2.5, epigenetic and microenvironmental alterations mediated by microRNA dysregulation, DNA methylation, cell autophagy, and apoptosis may activate oncogene-associated pathways to induce carcinomatosis of the lung (Liet al., 2018). Chao et al. found that chronic PM2.5 exposure induced lung cancer development by enhancing interleukin-17a (IL- 17a)-regulated proliferation and metastasis and increased the risk of non-small cell lung cancer progression (Chaoet al., 2020). In their study, PM2.5 exposure resulted in significant lung damage. However, IL-17a-knockout mice displayed significantly less pulmonary impairment after PM2.5 exposure. Therefore, PM2.5 exposure may reduce survival through IL-17a signaling.
Intermediate actions are required to enhance air quality and minimize the impact of PM2.5 on patients (Martenieset al., 2015). The regulation of PM2.5 is an urgent issue for the Chinese government. Our results suggest that China needs to change its economic development pattern to promote air quality. Economic growth should be combined with the protection of the environment to build a sustainable economic development pattern. Moreover, patients who undergo pulmonary lobectomy should be transferred to areas with better air quality to prolong their survival time.