Short-term Effects of Different PM2.5 Thresholds on Daily All-cause Mortality in Jinan, China


 To examine the effects of different PM2.5 limits on daily all-cause mortality, 8,768 all-cause deaths were recorded in the database of the Jinan Center for Disease Control and Prevention. Data on the levels of air pollutants (PM2.5 and O3) were provided by the Jinan Environment Monitoring Center. The Jinan Bureau of Meteorology provided air temperatures and relative humidity. The relative risk of all-cause mortality was assessed using a quasi-Poisson regression model after adjusting Interference factors. There was a significant positive association between exposure concentrations (35 µg/m³, 75 µg/m³, and 150 µg/m³) and all-cause deaths, with a mortality increase of 1.07 (1.01, 1.13), 1.03 (1.00, 1.05), and 1.05 (1.01, 1.08), respectively. It had a significant correlation between all-cause deaths and a PM2.5 limit of 35 µg/m³ in men. All-cause mortality in women and individuals aged ≥ 60 years increased significantly with exposure to PM2.5 levels of 75, 115, and 150 µg/m³. There was no significant relationship between PM2.5 exposure and all-cause deaths in individuals aged < 60 years. Exposure to PM2.5 (35 µg/m³) increased the mortality risk. Women and individuals aged ≥ 60 years were more sensitive to the effects of PM2.5 than men and individuals aged < 60 years.


Introduction
The adverse effects of airborne particulate matter ≤ 2.5 µm (PM 2.5 ) on public health, especially in the respiratory and cardiovascular systems, have been studied for nearly half a century. The formation of PM 2.5 and its adverse impact on public health are evident in both developed and developing countries [1][2][3][4] .
Various studies in Europe, the United States, and developing countries such as China, India, and Korea found that entire populations were affected by short-term exposure to ne particulate matter and that there was a positive correlation between PM 2.5 levels and mortality [5][6][7][8][9] . In addition, substantial epidemiological evidence demonstrates that ground-level ne particulate matter is linked to various respiratory diseases, including asthma, chronic obstructive pulmonary disease, lung cancer 10,11,12 , and cardiovascular mortality 10,13,14 .
However, the results of all-cause mortality associated with exposure to PM 2.5 are inconsistent; therefore, public awareness of the risk of this type of exposure is low 15,16,17 . Moreover, few studies to date investigated the PM 2.5 limit that poses no health risk. For this reason, a recommended PM 2.5 concentration is needed to minimize the adverse health effects 18 .
The objective of this study is to examine the effects of different PM 2.5 thresholds on all-cause mortality and provide public health recommendations to avoid exposure of PM 2.5 .

Data source
Daily levels of PM 2.5 in 24-hour intervals and ozone (O 3 ) in 1-hour intervals averaged from 14 permanent monitoring stations in urban areas of Jinan, China, from 2013 to 2015 were provided by the Jinan Environment Monitoring Center. Daily mean air temperatures and relative humidity in the corresponding period were provided by the Jinan Bureau of Meteorology.
Data on the daily mortality of the registered population of Jinan for the period 2013-2015 were recorded in the database of the Jinan Center for Disease Control and Prevention. Detailed demographic information, including age, gender, date of hospital admission, date of hospital discharge, admission diagnosis, discharge diagnosis codes, and current residence were extracted from the Jinan Qilu Hospital registry. Mortality data on total non-accidental causes (codes A00-R99), cardiovascular disease (codes I00-I99), and respiratory disease (codes J00-J98) were classi ed according to Diseases Revision 10 (ICD-10). The data on all-cause mortality were strati ed by gender (male and female) and age (< 60 and ≥ 60 years). A quasi-Poisson regression model with natural splines was used to assess the impact of different PM 2.5 limits on daily all-cause mortality because the daily death counts in Jinan approximately followed a Poisson distribution. This regression model is used to adjust inference for overdispersion 19 . The natural cubic spline for mean temperatures with 5 degrees of freedom and relative air humidity with 3 degrees of freedom (df) was controlled to analyze all-cause mortality based on Akaike's Information Criterion (AIC) for lag effects of up to 3 days 20 . Confounding factors such as day of the week and holidays were included as dummy variables.
The natural cubic spline smoothing function degree of freedom for mean temperature and relative air humidity is determined as follows: Yt represents the death counts on day t. E(Yt) represents the expected death counts on day t, ns stands for the natural cubic spline smoothing function, Temp represents the mean temperature, RH represents the relative air humidity, DOW and Holiday stands for the day of the week effect and legal holidays respectively, β 1 and β 2 is the coe cient of DOW and Holiday respectively. The degree of freedom of the mean temperature factor is N (N = 2,3,...6). Obtain the magnitude of the corresponding AIC of the equation when N is different, and the minimum value of AIC is the optimal degree of freedom. Different PM 2.5 limits were added into the above basic model to establish a single-pollutant model. O 3 was included in the single-pollutant models of PM 2.5 with multi-day moving average lag structures [from a lag of 0 to 1 day (mean) to a lag of 0 to 3 days (mean)] were used for sensitivity analysis to determine the stability of the model.
The relative risk (RR) and corresponding 95% con dence interval (CI) were estimated to assess the impact of different PM 2.5 limits on daily counts of all-cause mortality. P-values smaller than 0.05 were considered statistically signi cant.
Strati ed analyses of exposure to different PM 2.5 limits based on gender (male or female) and age (< 60 years and ≥ 60 years) were performed to nd associations with daily all-cause mortality.

Distribution of ambient pollutants and weather data
The mean daily concentrations of PM 2. 5  in the database of the Jinan Center for Disease Control and Prevention. The percentage of individuals aged < 60 and ≥ 60 years was 38.79% (3401/8768) and 61.21% (5367/8768), respectively. The distribution of the daily concentration on air pollutants, weather parameters, and deaths is shown in Table 1.   (Table 3). Strati ed analysis based on gender and age indicated that there was a signi cant relationship between all-cause mortality and a PM 2.5 threshold of 35 µg/m³ in men in lags 1 and 01. All-cause deaths in women signi cantly increased with exposure to 75 µg/m³, 115 µg/m³, and 150 µg/m³ in lag 1; lags 0 and 01; and lags 0, 1, 01, 02, and 03, respectively. There were no signi cant associations between PM 2.5 exposure and all-cause mortality in individuals aged < 60 years. All-cause deaths in individuals aged ≥ 60 years were signi cantly correlated with exposure to 75 µg/m³, 115 µg/m³, and 150 µg/m³ in lags 1 and 01; lags 1 and 01; and lags 0 and 01, respectively (Fig. 2).
The results of sensitivity analysis indicated that there were no signi cant changes in the RR at different PM 2.5 limits for daily all-cause mortality after including O 3 in the multi-day moving average lag structures.
Therefore, the effect of this single-pollutant model was robust (Fig. 3).

Discussion
To our knowledge, this epidemiologic study is the rst to examine the association of PM 2.5 limits with allcause mortality in Asia. The results indicated that, except for the PM 2.5 threshold of 115 µg/m³, the concentrations of 35 µg/m³, 75 µg/m³, and 150 µg/m³ were signi cantly associated with mortality from all causes, and the effects of PM 2.5 were stronger as the levels increased. In addition, consistent with other studies, there was no evidence of a limit at which PM 2.5 exposure does not affect mortality, even for concentrations lower than 35 µg/m³, demonstrating that PM 2.5 is a signi cant risk factor for all-cause mortality, and the adverse impacts on public health do not decrease as pollutant levels decrease [21][22][23] .
The association between all-cause deaths and PM 2.5 exposure was statistically signi cant at 35 µg/m³, 75 µg/m³, and 150 µg/m³, and this result maybe because of the relatively fewer deaths between 75 µg/m³ and 115 µg/m³. Furthermore, the daily temperature corresponding to each of these concentrations was higher than that of other thresholds. The impact of different PM 2.5 limits on mortality may be due to high temperatures 24,25 .
The results of a previous study on the gender-speci c effects of particulate matter were inconsistent 26 . The results of the gender-strati ed analysis demonstrated that female patients were more sensitive to the PM 2.5 levels of 75 µg/m³, 115 µg/m³, and 150 µg/m³, whereas male patients were more sensitive to a concentration of 35 µg/m³, indicating that men are more susceptible to lower PM 2.5 concentrations than women.
Smoking is a critical environmental risk factor, and one study suggested that the estimated impact of air pollution might be stronger in nonsmokers than smokers 27 . A potential reason for this difference may be that women have slightly stronger airway reactivity and smaller airways than men 28 . Moreover, the adverse impacts of additional exposure to PM 2.5 may be overcome by the oxidative and in ammatory effects of smoking 29 .
Older individuals had increased susceptibility to PM 2.5 levels of 75 µg/m³, 115 µg/m³, and 150 µg/m³ compared with younger individuals, possibly because the former group has a weaker immune system and higher sensitivity to these particles 30,31

Conclusions
For all-cause mortality, PM 2.5 presented adverse effects on health even at a low concentration (35 µg/m³), and the impact of PM 2.5 on mortality was higher as the concentration was increased. Women and individuals aged ≥ 60 years were more sensitive to the effects of PM 2.5 than men and individuals aged < 60 years.

Declarations
Financial support This work was supported by the Major scienti c and technological innovation projects of Shandong Province (grant number 2019JZZY020904 and QYPY2019NSFC0603) and the National Key Research and Development Program (2019YFE0117800).
Con ict of Interest: The authors declare that they have no con ict of interest.
Authors' contributions: Ma Zhixiang designed/performed most of the investigation, data analysis and wrote the manuscript; Chen Cai and Meng Xiangwei contributed to scoping and structuring the paper and guided method development. Li Wei provided pathological assistance; Zhang Chuanzhen contributed to the interpretation of the data and analyses. All of the authors have read and approved the manuscript  Lag structures of age and gender-speci c relative risk (RR) of daily mortality from exposure to different PM2.5 thresholds. a35 μg/m3, b75 μg/m3, c115 μg/m3, d150 μg/m3. *p<0.05