With the rapid development of modern industrialization, the air quality around us is increasingly affected (1). The World Health Organization (WHO) estimated that air pollution causes the deaths of 4.2 million people each year, which accounts for 6% of total deaths worldwide (2). Based on the analysis of atmospheric environment in 1,600 cities and regions around the world, it was found that only 12% of the study areas met the safety standards stipulated by WHO (3), indicating that the status and development of global air pollution cannot be ignored. Since the Chinese government implemented China's Action Plan of Prevention and Control of Air Pollution in 2013, atmospheric particulate matter has dropped significantly (4). Nevertheless, along with the rapid development of urban basic infrastructure and growth in motor vehicle number, ozone concentration has dramatically increased recently (5). Ozone is a secondary pollutant, its formation is due to the interaction between the hydrocarbons and oxides of nitrogen released from car exhaust and sunlight (UV), leading to photochemical smog. It can affect air quality at local, regional and even global scales, beside, it has an important impact on animal health, plant growth, climate change and global ecological balance. At the same time, the adverse effects on human life and ecological environment are gradually increasing (6). The more serious the air pollution is, the more the residents' medical expenses will increase (7).

According to the 2020 China Ecological Environment Bulletin, ozone has been become an important pollutant besides particulate matter (PM_2.5, PM₁₀) at the national level (8). Compared with Japan, South Korea, Europe and the United States, the magnitude and frequency of high-ozone events in China are much more significant (9). China experiences high ozone concentrations with highest annual 8-h maximum concentration in eastern China of 78 μg/m³ and was followed by southern (73μg/m³), north-western (69μg/m³), northern (68μg/m³), central (67μg/m³), north eastern (65μg/m³) and south-western China (59μg/m³) (10). The majority of the Chinese population lives in the eastern part of China, especially in the three most developed regions, Jing-Jin-Ji (Beijing-Tianjin-Hebei), the Yangtze River Delta (including Shanghai-Jiangsu -Zhejiang-Anhui), and the Pearl River Delta (including Guangzhou, Shenzhen, and Hong Kong). These regions consistently have the highest emissions of anthropogenic precursors, which have led to severe region-wide air pollution (11). Studies showed that according to monitoring results from 74 Chinese cities, the mean daily 8-h maximum concentrations of ozone increased from approximately 69.5 ppbv in 2013 to 75.0 ppbv in 2015, while the percentage of non-compliant cities increased from 23 to 38% (5, 10). Jiangxi Province lies on the southern bank of the Yangtze River's lower and middle sections, it has a sub-tropical climate, warm and humid. Kan (12) using the data of environmental monitoring stations data in Jiangxi Province from January 2017 to June 2020, showed that from 2017 to 2019, the time and mass concentration of ozone exceeding the limit showed an increasing trend year by year. April to June and August to October were the periods of high incidence of ozone pollution. Nanchang City is the Central City of Jiangxi Province, and it is one of the first cities to implement new ambient air quality standards. The daily 8-hour maximum concentration of ozone in Nanchang from 2013 to 2015 was analyzed, showing that the seasonal variation of ozone was high in spring and summer and low in autumn and winter (13).

Many epidemiological studies had been conducted to assess the characteristics of ozone pollution exposure in China, related research showed that the concentration of ozone in Yangtze River Delta, Beijing-Tianjin-Hebei, Pearl River Delta and Chengdu-Chongqing cities was increasing year by year (14–17). There is a growing interest in studying the potential effect of ozone levels, and its subsequent effects on public health. Epidemiological and toxicological studies had shown that ozone exposure is not only associated with adverse health outcomes (18–22), but also leads to significant economic burdens (23). A series of epidemiological studies reported that short-term ozone exposure is strongly associated with the death risk of cardiovascular diseases (24, 25) and respiratory diseases (26). China recorded 93,351 (95%CI: 11,001–169,898) ozone related premature mortality in 2015 with 42,673 (95%CI: 11,001-69,586) respiratory mortality and 50,678 (95%CI: 0–100,312) cardiovascular mortality. Northern and eastern China recorded high ozone related mortality with 18,230 (95%CI: 4,700–29,727), 12,261 (95%CI: 3,161–19,993) respiratory, 21,662 (95%CI: 0–42 877) and 14,528 (95%CI:0–28 757) cardiovascular deaths respectively (11). Kamal and Anil (27) showed that the proportion of all-cause, cardiovascular and respiratory premature deaths attributed to short-term environmental ozone exposure in China in 2019 increased by 19.6, 19.8, and 21.2% in comparison with those in 2015. Ozone is one of the most powerful oxidizing molecule to which living beings can be exposed. Accordingly, ozone inhalation may cause oxidative damages and inflammation, which could expand from the respiratory system to the periphery and to the brain, for which the nose and olfactory pathway is another portal of entry (28). Animal and human exposure studies had been proved that ozone has a stimulating effect on human mucosa through the eyes, nose, and mouth into the lungs, which will also cause damage to the lung tissue. Therefore, excessive ozone concentration will increase the probability of human suffering from respiratory diseases, and also aggravate the condition of patients with respiratory diseases such as asthma and chronic lung diseases (29). Some scholars pointed out that Short-term ozone exposure at levels was associated with platelet activation and blood pressure increases, suggesting a possible mechanism by which ozone may affect cardiovascular health (30). The proposed mechanisms include systemic inflammation and oxidative stress, autonomic nervous system imbalance, and abnormal epigenetic changes (31).

In areas with good air quality, ozone has gradually become the main pollution factor affecting the air quality compliance rate, which is closely related to climate change, and its composition is complex and difficult to control. In the preparation of the “14th Five-Year Plan” ecological and environmental protection plan, it is necessary to pay attention to the coordinated treatment of PM_2.5 and ozone in view of the prominent problems of ozone pollution (32). Among China's 2030 climate target, as the largest developing country in the world, China has overcome its own economic and social difficulties, implemented a series of strategies, measures and actions to cope with climate change, participated in global climate governance, and achieved positive results in addressing climate change. China has always attached great importance to non-carbon dioxide greenhouse gas emissions and China has accepted the Kigali Amendment to the Montreal Protocol on Substances that Deplete the Ozone Layer, which has entered a new stage in protecting the ozone layer and responding to climate change (33). Nitrogen oxides (NOx) and volatile organic compounds (VOCs) are important precursors to ozone formation. In order to control ozone pollution during the “14th Five-Year Plan” period, Jiangxi will promote the energy structure, adjustment and optimization of industrial structure and traffic structure to reduce NOx and VOCs emissions from the source (34). Nanchang is an important central city in the middle and lower reaches of the Yangtze River in China, due to the city is a lack of research on the effects of ozone pollution, and the association of human health with ambient ozone have not been fully understood. Therefore, the main objective of this study is to evaluate the association between ozone exposure and respiratory mortality and cardiovascular mortality, at the same time, we aimed to evaluate individual characteristics (sex and age) and season as potential effect modifiers of the ozone-mortality association, which providing a basis for further research and formulation of local environmental prevention and control policies in Nanchang City.

In this study, we found that air pollution has an important correlation with residents' health. This paper describes a approach to evaluate the health effect of ozone exposure on respiratory mortality and cardiovascular mortality in Nanchang City from 2014 to 2020. The exposure-response relationship reflects that ozone has an approximately linear positive correlation with the respiratory mortality and cardiovascular mortality. Studies in many cities in the United States, which showed that daily changes in ambient ozone exposure are linked to premature mortality, even at very low pollution level. And they also found robust evidence of the exposure-response relationship between ozone exposure and mortality showed an approximate linear curve (43). Moreover, the single- and two-pollutant models in our studies were constructed to further analyze the lag-response effect of ozone on the risk of death of residents, it was found a significant association for both O₃-8h and respiratory mortality and cardiovascular mortality with higher effects at the cumulative exposure level.

The results of survey showed that a correlation between O₃-8h and respiratory mortality and cardiovascular mortality, with percent changes in excessive risk of 1.04% (95%CI: 0.40 ~ 1.68%) and 1.26% (95%CI: 0.68 ~ 1.83%) for a 10 μg/m³ increase in O₃-8h at lag0 and at lag1, respectively. The multi-day moving average lag effect showed that the greatest excessive risk of respiratory mortality and cardiovascular mortality at lag05 and lag03 increased by 1.77% (95%CI: 0.99 ~ 2.57%), 1.68% (95%CI: 0.93 ~ 2.45%), respectively, which is similar to the effect value of related research at home and abroad (42, 44, 45). In our studies, we found that ozone exposure had immediate effect on respiratory mortality and cardiovascular mortality, and the risk of death of cardiovascular diseases was especially susceptible to ozone pollution. But with the cumulative lag effect, it is worth noting that ozone has a greater impact on respiratory mortality. The association between O₃-8h exposure and respiratory mortality and cardiovascular mortality has been well documented in the epidemiological literature. Chao (41) also found that for every 10 μg/m³ increase in O₃-8h concentration, a single-day lag of 1st-2nd day and multi-day cumulative lag of 3rd day had the greatest effect on cardiovascular disease mortality in Jiangsu Province. Qi's (21) research in Nanjing city discovered that the risk of cardiovascular mortality increased by 1.25% (95%CI: 0.78 ~ 1.72%) for a 10 μg/m³ increase in O₃-8h, while the effect of O₃-8h on the risk of respiratory mortality was not statistically significant. A study in Sichuan Province (46) consider that for every 10 μg/m³ increase in ozone, respiratory mortality would increase by 0.78%(95%CI: 0.12 ~ 1.44%). The same environmental and health cohort study followed up in Canada for 16 years showed that (47), for every 10 μg/m³ increase in ozone on respiratory mortality and cardiovascular mortality will increase by 0.97%(95%CI: 0.95 ~ 0.99%) and 1.03% (95%CI: 1.03 ~ 1.05%), respectively. The inconsistency of research results in different regions may be related to temperature (5), population composition, geographical structure and urbanization scale (16, 39, 44). In our studies, in the dual-pollution model, after adjusting for SO₂, NO₂, CO, PM_2.5, and PM₁₀, the death risk of respiratory diseases had no significant change, while the death risk of cardiovascular diseases caused by O₃-8h decreased by 0.23, 0.23, 0.35, 0.38, and 0.27%, respectively. Qi (21) and Yebin (25) discovered that O₃ had a certain degree of reduction in the risk of cardiovascular mortality after adjusting for PM_2.5,PM₁₀, NO₂, SO₂ and CO; Lihong (35) found that after adding PM_2.5 and NO₂, the risk of respiratory diseases was not significantly different from the effect value of O₃ single pollutant, which is consistent with our findings. Furthermore, there was a research showed (48) that after incorporating other pollutants into the single pollutant model, there was no difference in the impact on the health of residents before and after. The reason for the difference may be related to the constructed model, or the single air pollutant may be only considered in the single pollution model effect, and the effect of air pollutant may be affected by the co-linearity or spatial nature of other air pollutants (47).

Regarding gender differences, the effect of ozone exposure on excessive risk of respiratory mortality and cardiovascular mortality in female was greater than in male. It has been proved that females were more likely to suffer from the mortality of respiratory diseases and cardiovascular diseases than males, and females are more susceptible to O₃-8h than males, which is similar to the results of previous studies at home and abroad (48, 49). The reason for this result may be females have higher gas sensitivity, shorter respiratory tract and more susceptible to air pollutants compared with males (5, 37, 44). However, there is also evidence that males are more vulnerable to the effects of ozone on respiratory mortality than females. A study conducted in Li et al. (50) explained that pneumonia and bronchitis are more common in males with a history of smoking and exposure to different occupations, which may exacerbate the impact of O₃-8h on respiratory mortality in males. Mechanistically, as a result of reduced uptake of ozone into conducting airways, cigarette smoking may shift the longitudinal distribution of ozone uptake distally toward the respiratory airways, thereby leading to respiratory diseases in the population (51). However, there is no detailed study on whether the smoking rate of adults will affect the association between ozone exposure and cardiovascular diseases. Our studies have also exhibited that the elevated concentration of O₃-8h significantly increased the risk of respiratory mortality among residents aged ≥65 years (compared to aged <65 years), which is consistent with the results of previous studies (5, 19–22, 44). The structure of the respiratory system changes as we age, with decreased chest wall compliance, respiratory muscle strength, and vital capacity, which could lead to the risk of death of respiratory diseases in older people (52). As for the risk of cardiovascular mortality, the effect value of residents aged <65 years is higher than that of residents aged ≥65 years, which is inconsistent with previous researches found that people aged ≥65 years were more closely related to cardiovascular mortality risks (37, 48, 50). On the one hand, the younger with these cardiometabolic conditions had a higher prevalence of cardiovascular diseases in association with higher air pollution exposures than individuals without these cardiometabolic conditions (53). On the another hand, some scholars detected stronger associations between air pollutants and cardiometabolic risk factors in younger participants and for those with a family history of cardiovascular diseases (54). In summary, ozone exposure is closely related to the risk of respiratory mortality and cardiovascular mortality in people of different ages and sexes. Among them, females and people aged ≥65 years are sensitive groups. Nevertheless, ozone as an important air pollutant, we also should also be paid attention to the health risk of people aged <65 years because they are more closely linked to cardiovascular mortality for a 10 μg/m³ increase in O₃-8h.

Climate change has a negative impact on human health due to increased exposure to adverse climate-related stresses (55). According to the climatic characteristics and the analysis of daily average temperature and daily average relative humidity of Nanchang City during the study period, it is known that the higher the temperature in the warm season (spring, summer), the greater the humidity. When considering differential effects by season, it had been reported that seasonal changes will affect the impact of air pollutants on human health (56). We conducted that season-specific associations for the mortality risk of respiratory diseases showed stronger associations in winter and spring for a 10 μg/m³ increase in O₃-8h, which is in agreement with the finding of the study by Yuqi (42) in Lishui district. And the risk of cardiovascular mortality was stronger associated with O₃-8h in summer and winter. In summer, ozone precursors in the air produce ozone more quickly with the increase of temperature (57). The reduced levels of nitrogen dioxide and carbon monoxide in summer months can be attributed to the contribution of these compounds to photochemical reactions occurring under the influence of solar radiation which result in the formation of ozone (58). Most importantly, we indicated the excessive risk of ozone pollution on respiratory mortality and cardiovascular mortality occurred earlier and had a greatest effect in winter than in the warm season. Higher levels of ozone pollution in winter months may also be associated with increased low emissions from local home furnaces, as well as more frequent in these periods, inversion of temperature resulting in smog events (59).

This study has several limitations that should be addressed. First, the air pollution exposure data of the study is the monitoring point data, which may be affected by distance, climate and other reasons, and cannot fully reflect the individual exposure (39, 40, 48), may overestimate the impact of air pollutants on the death of residents. Second, there exists another source of misclassification of ozone concentrations as this study did not use personal ozone exposure, because some personal behavior factors were not taken into consideration, such as air conditioner use, and time spent outdoors (60). Third, this study was conducted in a single city (Nanchang), thus, our findings cannot be generalized to other cities with different environmental and economic characteristics. Finally, the research only examined the correlation of respiratory mortality and cardiovascular mortality and ozone pollution, we were not able to involve more diseases, which is also a limitation of this study. As an important pollutant, ozone has independent health hazards. According to the source and changes of ozone in Nanchang city, government departments should strengthen the monitoring and control of ozone pollutant emissions, actively formulate energy-saving and emission reduction measures for ozone to reduce the heavy burden. In this vein, government departments also should promote actions and measures to enhance numerous aspects around the subject. Boosting education, training and public participation are some of the relevant actions for maximizing the opportunities to achieve the targets and goals on the crucial matter of ozone pollution. Without any doubt, technological improvements makes our world easier and it seems difficult to reduce the harmful impact caused by gas emissions, we could limit its use by seeking reliable approaches (61). When carrying out the prevention and control of ozone pollution, the relationship between PM_2.5 and ozone is often discussed. In winter, PM_2.5 treatment should be carried out, and in summer, the synergy between ozone and PM_2.5 should be explored. As a secondary pollutant, ozone has a complex reaction mechanism, and it is necessary to implement multi-target and multi-pollutant coordinated control. In the entire prevention and control work, more emphasis should be placed on the importance of atmospheric oxidation (62). Last but not least, taking appropriate protective measures for the entire population, sensitive groups, and high-risk groups to improve residents' awareness of self-protection. At the same time, identifying vulnerable subpopulations and the impact of ozone on these subpopulations will help in establishing air quality standards that will better protect these groups (53). A study (63) have shown that masks containing activated carbon interlayer have good protection against ozone at different pollution levels.

This study provides evidence of evaluating the effects of O₃-8h exposure on respiratory mortality and cardiovascular mortality in Nanchang city from 2014 to 2020. To our knowledge, results confirm that ozone pollution would increase the risk of respiratory mortality and cardiovascular mortality. Our findings complement previous studies that are lacking by revealing that ozone pollutants have a lag effect on the health of the population in Nanchang city, China. With the rapid of economic growth and the development of processing industries such as electric power, gas and non-ferrous metal smelting in Nanchang city, the government should introduce corresponding control policies, take actions to reduce air pollution and make interventions for sensitive individuals to improve our health.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

HW and JF conceived and designed the work. HW led the study, carried out the time-series studies, analyzed the data, and approved the version to be published. KL involved in the study design and the interpretation of the results. JF helped to conceptualize the study, provided intellectual advice, and revise various drafts of the manuscript. All authors read and approved the final manuscript.

This work was funded by Science and Technology Plan of Jiangxi Health Commission (20204847).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.