International Journal of Hygiene and Environmental Health 252 (2023) 114200

Contents lists available at ScienceDirect

International Journal of Hygiene and Environmental Health

journal homepage: www.elsevier.com/locate/ijheh

Seasonal associations between air pollutants and influenza in 10 cities of

southern China
Rui Zhang a, b, Yonghong Li c, Peng Bi d, Siyuan Wu e, Zhibin Peng b, Yujie Meng b, Yu Wang c,
Songwang Wang b, Yushu Huang c, Juan Liang c, Jing Wu a, b, *
a
National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
b
Chinese Center for Disease Control and Prevention, Beijing, China
c
China CDC Key Laboratory of Environment and Population Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention,
Beijing, China
d
School of Public Health, The University of Adelaide, South Australia, Australia
e
Sprott School of Business, Carleton University, Ottawa Ontario, Canada

A R T I C L E I N F O A B S T R A C T

Keywords: Few studies have explored the associations between air pollutants and influenza across seasons, especially at
Influenza large scales. This study aimed to evaluate seasons’ modifying effects on associations between air pollutants and
Air pollutant influenza from 10 cities of southern China. Through scientific evidence, it provides mitigation and adaptation
Season
strategies with practical guidelines to local health authorities and environmental protection agencies. Daily
Distributed lag non-linear model
Attributable fraction
influenza incidence, meteorological, and air pollutants data from 2016 to 2019 were collected. Quasi-Poisson
regression with a distributed lag nonlinear model was used to evaluate city-specific air pollutants and influ­
enza associations. Meta-analysis was used to pool site-specific estimates. Attributable fractions (AFs) of influenza
incidence due to pollutants were calculated. Stratified analyses were conducted by season, sex, and age. Overall,
the cumulative relative risk (CRR) of influenza incidence for a 10-unit increase in PM2.5, PM10, SO2, NO2, and CO
was 1.45 (95% CI: 1.25, 1.68), 1.53 (95% CI: 1.29, 1.81), 1.87 (95% CI: 1.40, 2.48), 1.74 (95% CI: 1.49, 2.03),
and 1.19 (95% CI: 1.04, 1.36), respectively. Children aged 0–17 were more sensitive to air pollutants in spring
and winter. PM10 had greater effect on influenza than PM2.5 in autumn, winter, and overall, lesser in spring. The
overall AF due to PM2.5, PM10, SO2, NO2, and CO was 4.46% (95% eCI: 2.43%, 6.43%), 5.03% (95% eCI: 2.33%,
7.56%), 5.36% (95% eCI: 3.12%, 7.58%), 24.88% (95% eCI: 18.02%, 31.67%), and 23.22% (95% eCI: 17.56%,
28.61%), respectively. AF due to O3 was 10.00% (95% eCI: 4.76%, 14.95%) and 3.65% (95% eCI: 0.50%, 6.59%)
in spring and summer, respectively. The seasonal variations in the associations between air pollutants and
influenza in southern China would provide evidence to service providers for tailored intervention, especially for
vulnerable populations.

1. Introduction health outcomes (Webster and Govorkova 2014).

Influenza is a respiratory infectious disease caused by the influenza
virus that poses serious health risks to the community. Characterized by
high infectivity and rapid transmission. Prominent symptoms of influ­
enza are fever, sore throat, dry coughing, runny nose, headache, muscle
and joint pain, and fatigue (Krammer et al., 2018). While most influenza
patients can recover within a week, people with chronic diseases (e.g.,
kidney disease, diabetes), very young or elderly individuals, gravidas,
and obese people are the most vulnerable which may lead to negative
Air pollution has emerged as a severe global public health problem. It
has been widely recognized that key air pollutants, such as particulate
matters and gaseous pollutants, may contribute to influenza develop­
ment (Loaiza-Ceballos et al., 2022). Previous epidemiological and
experimental studies have shown that particulate matter with a diam­
eter ≤2.5 μm (PM2.5) and particulate matter with a diameter ≤10 μm
(PM10) can carry viruses to infect people and make them susceptible by
reducing the immune system. Sulfur dioxide (SO2), nitrogen dioxide
(NO2), and Ozone (O3) are irritant gases, which could invade respiratory

* Corresponding author. National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention,
Beijing, 100050, China.
E-mail address: wujing@ncncd.chinacdc.cn (J. Wu).

https://doi.org/10.1016/j.ijheh.2023.114200
Received 17 December 2022; Received in revised form 20 May 2023; Accepted 5 June 2023
Available online 15 June 2023
1438-4639/© 2023 Elsevier GmbH. All rights reserved.
R. Zhang et al. International Journal of Hygiene and Environmental Health 252 (2023) 114200

Fig. 1. Location of 10 study cities in southern China.

mucosa, damage epithelial cells, and increase the probability of viral
infections. Carbon monoxide (CO) as another gaseous pollutant com­
petes with oxygen to bind hemoglobin, which enhances the body’s
hypoxic state and reduces cellular immune function and stress (Loai­
za-Ceballos et al., 2022; Tao et al., 2012; Toczylowski et al., 2021).
In addition to air pollutants, climatic factors of different seasons
including temperature, sunlight duration, and precipitation could also
contribute to the seasonality of influenza by affecting the host’s im­
munity, human behavior, and virus survival (Park et al., 2020; Peci
et al., 2019; Yu et al., 2013). Therefore, the heterogeneity of influenza
seasonality might be partly driven by the complex effects of climatic
factors in different seasons (Liu et al., 2019).
Although both air pollutants and climate factors contribute to
influenza transmission, most studies have examined their effects

Fig. 2. Relative risk (RR) for daily incidence of influenza on different lag days for a 10-unit increase in air pollutants: PM2.5 (A), PM10 (B), SO2 (C), NO2 (D), CO (E),
O3 (F).

2
R. Zhang et al.
separately. It remains unclear how air pollutants affect influenza in
different seasons. This study aimed to assess such associations while
taking into account the seasonal modifying effects. So as to provide
scientific evidence for the refinement of effective influenza control and
prevention strategies.
2. Materials and methods
2.1. Regions of study
Based upon the Qinling Mountains - Huaihe River line (the
geographical boundary between China’s northern and southern regions
and the temperate and subtropical zones), eight provincial capital cities
and two municipalities with independent planning status under the
national social and economic development in southern China were
selected as the study cities (Fig. 1).
2.2. Influenza data
The daily influenza incidence data were obtained by aggregating the
clinical cases reported through the China Information System for Disease
Control and Prevention. Cases were reported online by local health fa­
cilities of 10 cities, including all county-level and above hospitals and all
township hospitals. All of these local health facilities are qualified to
diagnose influenza. The clinical diagnosis of influenza was based on the
diagnostic criteria for influenza (WS285-2008) published by the Na­
tional Health Commission of the People’s Republic of China. Influenza
variables included alleged onset date (AOD), sex (male and female), and
age (≤5, 6–17, 18–59, and ≥60 years). All influenza incidence data in
this study were strictly reviewed by the Chinese Center for Disease
Control and Prevention and adjusted according to the results of the
underreporting rate survey.
2.3. Meteorological and air pollution data
Daily mean temperature (Tmean, ◦ C), daily mean relative humidity
(RHmean, %), and daily precipitation (PPTN, mm) from the 10 cities
over the study period were provided by the China Meteorological
Administration.
We obtained air pollutants data from the local Ecological Environ­
ment Bureau, including daily PM2.5 (24-h mean concentration, μg/m3),
daily PM10 (24-h mean concentration, μg/m3), daily SO2 (24-h mean
concentration, μg/m3), daily CO (24-h mean concentration, mg/m3),
daily NO2 (24-h mean concentration, μg/m3), and daily O3 (maximum 8-
h mean concentration, μg/m3) from 2016 to 2019.
2.4. Statistical analysis
We conducted a two-stage analysis to explore such relationships.
First, a quasi-Poisson regression with a distributed lag nonlinear model
(DLNM) was applied to investigate the association between each air
pollutant and influenza in each city. We chose a linear function for each
air pollutant as they all proved to have a linear effect on influenza after
controlling the daily mean temperature (Zhang et al., 2021). We selected
a cross-basis function with 3 degrees of freedom (df) to capture the lags
of each pollutant and determined the respective lags for each pollutant
according to Fig. 2 (PM2.5:13 days, PM10: 12 days, SO2:11 days, NO2:14
days, CO:11 days, O3: 14 days). We used a natural cubic spline with 3 df
and 21 lag days to control the daily mean temperature. We also adjusted
relative humidity and precipitation as they were prominent climatic
factors of the season. The model was fitted as follows:
logE(Yt ) = α + cb(pollutant) + cb(Tmean) + ns(RHmean, 3df ) + ns(time, 7df
∗ year) + δDOWt + γHolidayt
3
International Journal of Hygiene and Environmental Health 252 (2023) 114200
Where Yt is the number of influenza cases on day t; Tmean is the daily
mean temperature; RHmean indicates the daily mean relative humidity;
time represents the seasonal and long-term trends of air pollutants; DOW
is the day of the week; Holiday is used to control public holidays; cb
refers to the cross-basis function, which simultaneously specifies the
exposure-response and lag-response relationship; ns is the natural cubic
spline; α is the intercept; δ and γ are the coefficients (Gasparrini et al.
2010, 2012; Gasparrini 2011). All df in the model were determined
according to previous studies (Ma et al., 2015; Zhang et al., 2021) and
the minimum principle of Akaike’s information criterion (AIC) (Gas­
parrini et al., 2010).
In the second stage, we used a random effect meta-analysis to pool
site-specific estimates.
We then applied the two-stage approach repeatedly to assess those
associations in spring (April to May), summer (June to October), autumn
(September to November), and winter (December to February),
respectively.
AF (attributable fraction) was calculated to evaluate the incidence
burden of influenza caused by air pollutants. A general definition of the
AFx for a given exposure x can be provided by:
AFx = 1 − exp(− βx )
The parameter βx refers to the association with a specific exposure
intensity x compared to a reference value x0 . Empirical confidence in­
tervals (eCI) were then derived using Monte Carlo simulations (Gas­
parrini and Leone 2014).
To avoid spurious relationships due to multicollinearity, the multi-
meteorological factors model was restricted to variables with Pearson
correlation coefficients <0.6, while air pollutant variables were not
entered into the model simultaneously.
Stratified analyses by season, sex, and age were also conducted. The
tests for statistical significance of differences between subgroups were
conducted by using the formula below:
√̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅̅
2 2
̂1 − Q
(Q ̂ 2 ) ± 1.96 SÊ 1 + SE ̂2
Where Q ̂ 1 and Q
̂ 2 are the estimates for the two categories, and SE
̂ 1 and
SE 2 are their respective standard errors (Chen et al., 2012).
̂
2.5. Sensitivity analysis
Sensitivity analysis for the robustness of the main results was per­
formed by changing the df of RHmean, adjusting and without adjusting
PPTN, and double-pollutant model.
All data analyses were performed by using R software, version 3.62
(R Project for Statistical Computing, Vienna, Austria, http://www.r-pr
oject.org). The distributed lag non-linear model (Gasparrini 2011) and
multivariate meta-analysis (Gasparrini et al., 2012) were fitted by using
the ‘dlnm’ package and ‘mvmeta’ package, respectively. Statistical sig­
nificance was defined as p＜0.05 for all statistical tests.
2.6. Ethics approval
The ethical approval was granted by the Ethics Committee of the
National Institute of Environmental Health, Chinese Center for Disease
Control and Prevention with the approval number 201606.
3. Results
3.1. Descriptive analysis
During the study period, 1,042,308 influenza cases were notified in
the 10 cities, including 549,103 (52.7%) males, 493,205 (47.3%) fe­
males, 367,132 (35.2%) children aged 0–5, and 39,521 (3.8%) people
aged 60 or older. The mean value of the daily incidence of influenza was
R. Zhang et al. International Journal of Hygiene and Environmental Health 252 (2023) 114200

Table 1 CO, and O3 was founded in the city of Xiamen, Xiamen, Xiamen, Xiamen,
Descriptive statistics of influenza cases in different seasons, sex, and age groups Xiamen, and Nanning with a mean and standard deviation of 26 ± 13
in 10 cities of southern China, 2016–2019. μg/m3, 46 ± 21 μg/m3, 9 ± 5 μg/m3, 29 ± 14 μg/m3, 0.6 ± 0.2 mg/m3,
Cases Daily incidence of influenza and 75 ± 34 μg/m3, respectively.
Mean ± SD P25 P50 P75
The correlations between meteorological factors and air pollutants
were not big enough leading to possible multicollinearity (Figure S1).
Total 1042308 (100%) 71 ± 252 2 8 28
Sex
Male 549103 (52.7%) 38 ± 132 1 4 15 3.2. Associations between air pollutants and influenza in different seasons
Female 493205 (47.3%) 34 ± 120 1 4 13
Age group (years) Table 4 shows that, overall, except for O3, the other five air pollut­
367132 (35.2%) 25 ± 76 1 3 12
ants had increased risks on the daily incidence of influenza after con­
≤5
6–17 430386 (41.3%) 29 ± 144 0 2 8
18–59 205269 (19.7%) 14 ± 46 0 1 5 trolling the effects from daily mean temperature and relative humidity.
≥60 39521 (3.8%) 3±9 0 0 2 The cumulative relative risk (CRR) of influenza incidence for a 10-unit
Seasons increase in PM2.5, PM10, SO2, NO2, and CO was 1.45 (95% CI: 1.25,
Spring 229744 (22.0%) 62 ± 140 3 10 34
1.68), 1.53 (95% CI: 1.29, 1.81), 1.87 (95% CI: 1.40, 2.48), 1.74 (95%
Summer 83095 (8.0%) 23 ± 63 1 4 16
Autumn 88642 (8.5%) 24 ± 101 2 5 15 CI: 1.49, 2.03), and 1.19 (95% CI: 1.04, 1.36), respectively. In spring, the
Winter 640827 (61.5%) 178 ± 455 6 18 120 CRR of influenza incidence for a 10-unit increase in PM2.5, NO2, CO, and
O3 was 1.14 (95% CI: 1.01, 1.29), 1.21 (95% CI: 1.09, 1.33), 1.21 (95%
CI: 1.10, 1.34), and 1.28 (95% CI: 1.13, 1.45), respectively. In summer,
71 with a standard deviation of 252 cases. During the study period, the the increase in the concentration of air pollutants tended to reduce the
number of influenza cases was the highest in winter (61.5%), followed risks of catching influenza in certain subgroups, i.e. females, 0–5, and
by spring (22.0%), autumn (8.5%), and summer (8.0%) (Table 1). ≥60 years old with PM2.5, females and ≥60 years old with PM10, 18–59
Table 2 shows influenza and characteristics data for the 10 cities years old with SO2, and 6–59 years old with CO. In autumn, the CRR of
during 2016–2019. Guangzhou had the highest number of influenza influenza incidence for a 10 μg/m3 increase in PM10 and NO2 was 1.19
cases with 235,953 and Kunming had the lowest with 11,803. The (95% CI: 1.04, 1.35) and 1.29 (95% CI: 1.10, 1.50), respectively. In
highest daily average value of temperature, relative humidity, and winter, the CRR of influenza incidence for a 10 μg/m3 increase in PM2.5,
precipitation was founded in the city of Guangzhou, Chengdu, and PM10, SO2, and NO2 was 1.32 (95% CI: 1.12, 1.56), 1.33 (95% CI: 1.11,
Changsha with a mean and standard deviation of 22.2 ± 6.0 ◦ C, 82 ± 1.59), 1.61 (95% CI: 1.23, 2.10), and 1.68 (95% CI: 1.44, 1.98),
9%, and 5.7 ± 2.1 mm, respectively. The lowest daily average value of respectively. Children aged 0–17 were more sensitive to PM2.5, PM10,
temperature, relative humidity, and precipitation was founded in the SO2, NO2, and CO for influenza development, especially in winter. And
city of Kunming, Kunming, and Chengdu with a mean and standard children aged 0–5 were more sensitive to air pollutants than other age
deviation of 16 ± 4.8 ◦ C, 71 ± 14%, and 2.6 ± 1.8 mm, respectively. groups. Among people over 60 years old, in all seasons, the increase in
Statistical descriptions of air pollutants for the 10 cities during the concentration of air pollutants (SO2, NO2, and CO) tended to reduce
2016–2019 are shown in Table 3. The highest daily average concen­ the risks of catching influenza. There was no significant difference be­
tration of PM2.5, PM10, SO2, NO2, CO, and O3 was founded in the city of tween male and female.
Chengdu, Chengdu, Kunming, Chengdu, Wuhan, and Hangzhou with a
mean and standard deviation of 53 ± 37 μg/m3, 86 ± 56 μg/m3, 14 ± 5
3.3. The attributable fractions of influenza incidence due to air pollutants
μg/m3, 49 ± 16 μg/m3, 1.0 ± 0.3 mg/m3, and 98 ± 54 μg/m3, respec­
tively. The lowest daily average concentration of PM2.5, PM10, SO2, NO2,
Table 5 shows that overall, AFs of influenza incidence due to NO2

Table 2
City-specific daily incidence of influenza and meteorological factors in 10 cities of southern China, 2016–2019.
Cities Cases Daily incidence of influenza Tmean (◦ C) Rhmean (%) PPTN (mm)

Mean ± P25 P50 P75 Mean ± P25 P50 P75 Mean ± P25 P50 P75 Mean ± P25 P50 P75
SD SD SD SD

1 Chengdua 132964 91 ± 242 1 4 17 16.7 ± 9.9 17 23 82 ± 9 76 83 89 2.6 ± 1.8 1 3 4

7.4
2 Guangzhoua 235953 162 ± 15 39 195 22.2 ± 17.8 23.3 27.3 81 ± 10 76 83 89 5.1 ± 1.9 3.7 4.9 6.2
314 6.0
3 Hangzhoua 193640 133 ± 2 6 39 18.2 ± 10.5 18.9 25.2 74 ± 14 64 74 84 4.7 ± 1.4 3.7 4.5 5.5
468 8.8
a
4 Hefei 19878 14 ± 29 2 5 13 16.9 ± 8.8 17.4 24.6 76 ± 12 68 77 85 4.4 ± 1.4 3.4 4.2 5.1
9.4
5 Kunminga 11803 8 ± 12 2 4 9 16 ± 4.8 12.3 16.8 20 71 ± 14 62 73 81 5.5 ± 1.9 4.1 5.2 6.5
6 Nanninga 17920 12 ± 42 1 4 10 22 ± 6.3 17.2 23.6 27.4 80 ± 12 74 82 88 5.3 ± 1.7 4 5.1 6.3
7 Ningbob 121887 83 ± 213 5 13 47 17.8 ± 10.7 18 25 80 ± 12 72 81 89 3.3 ± 2.2 1 4 5
8.5
8 Xiamenb 14907 10 ± 22 0 2 10 21.8 ± 6 16.7 22.4 27.4 77 ± 13 68 79 87 5.5 ± 1.8 4.5 5.2 6.2
9 Wuhana 81739 56 ± 178 5 11 29 17.4 ± 9.2 18.1 25.5 79 ± 10 72 79 87 4.1 ± 1.5 3 3.8 5
9.4
10 Changshaa 211617 145 ± 10 26 98 17.6 ± 10.1 18.3 25 79 ± 14 69 81 91 5.7 ± 2.1 4.2 5.4 7
381 8.8

Note.
Tmean = daily mean temperature.
RHmean = daily mean relative humidity.
PPTN = daily mean precipitation.
a
Provincial capital city.
b
Municipality with independent planning status under the national social and economic.

4
R. Zhang et al. International Journal of Hygiene and Environmental Health 252 (2023) 114200

Table 4

P75

126

127

137

131

107

122

127

125
Cumulative relative risk (CRR) and 95% confidence interval of stratified daily

97

99
incidence of influenza associated with a 10-unit increase of air pollutants in
P50 different season layers in 10 cities of southern China, 2016–2019.

79

87

90

94

80

73

92

79

87

86
Overall Spring Summer Autumn Winter
P25

CRR (95% CRR CRR CRR (95% CRR

51

52

56

62

62

51

67

61

52

56
O3（μg/m3）

CI) (95% (95% CI) (95%

CI) CI) CI)
91 ± 53

93 ± 53

98 ± 54

98 ± 47

84 ± 32

75 ± 34

96 ± 43

81 ± 29

92 ± 50

92 ± 47
Mean ±

PM2.5 Total 1.45 (1.25, 1.14 0.94 1.05 (0.94, 1.32

SD

1.68) (1.01, (0.83, 1.16) (1.12,

1.29) 1.08) 1.56)
Sex
P75

1.1

1.0

1.0

1.0

1.0

1.1

0.9

0.7

1.2

1.0
Male 1.47 (1.25, 1.10 1.00 1.09 1.22
1.72) (0.96, (0.84, (0.97,1.23) (1.01,
P50

0.9

0.8

0.8

0.8

0.8

0.9

0.7

0.6

1.0

0.8
1.28) 1.18) 1.48)
Female 1.46 (1.24, 1.14 0.81 1.01 (0.90, 1.22
1.71) (0.98, (0.70, 1.13) (1.00,
P25

0.7

0.7

0.7

0.7

0.7

0.8

0.6

0.5

0.8

0.7
1.32) 0.93) 1.50)
CO（mg/m3）

Age
1.47 (1.22, 1.12 0.84 1.23 (1.07, 1.26
Mean ±

≤5
1.76) (0.95, (0.71, 1.42) (1.01,
1.0 ±

0.9 ±

0.8 ±

0.9 ±

0.9 ±

0.9 ±

0.8 ±

0.6 ±

1.0 ±

0.9 ±
0.3

0.2

0.2

0.3

0.2

0.2

0.2

0.2

0.3

0.2
SD

1.33) 0.98) 1.59)

6–17 1.21 (1.01, 0.93 0.81 0.87 (0.75, 1.33
1.44) (0.78, (0.62, 1.02) (1.01,
P75

59

56

55

56

37

38

47

36

59

45

1.11) 1.04) 1.75)

18~59 1.24 (1.00, 1.13 0.90 0.93 (0.82, 0.18
P50

1.53) (0.94, (0.74, 1.05) (0.15,

47

43

41

40

30

29

34

26

43

32

1.36) 1.11) 0.21)

≥60 1.09 (0.81, 1.21 0.65 0.97 (0.82, 0.87
P25

37

34

31

31

25

23

24

19

31

23

1.45) (0.76, (0.46, 1.14) (0.55,

NO2（μg/m3）

1.90) 0.93) 1.36)

PM10 Total 1.53 (1.29, 1.06 0.98 1.19 (1.04, 1.33
49 ± 16

48 ± 20

43 ± 17

45 ± 19

33 ± 13

37 ± 17

29 ± 14

47 ± 20

36 ± 17
Mean ±

31 ± 9

1.81) (0.93, (0.85, 1.35) (1.11,

1.21) 1.12) 1.59)
SD

Sex
Male 1.50 (1.25, 0.96 1.03 1.25 (1.08, 1.23
P75

13

12

12

13

16

12

12

11

12

14

1.81) (0.83, (0.87, 1.45) (1.00,

1.10) 1.22） 1.51)
P50

Female 1.55 (1.28, 1.11 0.86 1.14 (0.99, 1.33

10

13

10
9

1.88) (0.95, (0.74, 1.32) (1.06,

1.31) 0.99) 1.67)
P25

10

Age
SO2（μg/m3）

≤5 1.52 (1.23, 1.11 0.90 1.40 (1.18, 1.27

1.86) (0.92, (0.76, 1.67) (1.01,
Mean ±

10 ± 5

10 ± 4

10 ± 4

10 ± 6

14 ± 5

11 ± 4

10 ± 4

10 ± 6

11 ± 7

1.33) 1.07) 1.61)

9±5

6–17 1.24 (1.01, 0.75 0.80 1.04 (0.85, 1.18

SD

1.52) (0.63, (0.62, 1.27) (0.88,

0.91) 1.03) 1.58)
City-specific of daily mean air pollutants in 10 cities of southern China, 2016–2019.

P75

110

103

110
70

90

68

72

70

57

90

18~59 1.08 (0.88, 0.88 0.94 0.98 (0.85, 0.56

1.33) (0.74, (0.77, 1.13) (0.43,
1.05) 1.16) 0.72)
P50

71

49

62

74

49

49

47

42

76

61

≥60 0.81 (0.63, 0.51 0.60 1.00 (0.83, 0.45

1.04) (0.35, (0.42, 1.21) (0.30,
P25
PM10（μg/m3）

0.74) 0.84) 0.68)

46

36

43

51

37

36

32

31

51

41

SO2 Total 1.87 (1.40, 1.12 0.89 1.23 (0.98, 1.61

2.48) (0.94, (0.74, 1.54) (1.23,
86 ± 56

56 ± 27

71 ± 39

81 ± 40

54 ± 23

58 ± 30

55 ± 32

46 ± 21

84 ± 47

70 ± 41
Mean ±

1.34) 1.07) 2.10)

Sex
SD

Male 1.86 (1.38, 1.00 0.88 1.12 (0.87, 1.63

2.49) (0.82, (0.70, 1.44) (1.23,
P75

1.23) 1.12) 2.16)

68

43

54

65

35

44

43

32

65

64

Female 1.87 (1.37, 1.18 0.89 1.04 (0.79, 1.51

2.55) (0.95, (0.71, 1.37) (1.14,
P50

43

30

36

43

25

29

29

23

42

41

1.47) 1.11) 2.02)

Age
P25
PM2.5（μg/m3）

0.78 (0.62, 1.07 0.84 1.11 (0.83, 1.11

26

21

25

29

18

18

19

16

28

27

≤5
0.99) (0.84, (0.66, 1.50) (0.82,
1.35) 1.06) 1.50)
53 ± 37

34 ± 19

43 ± 26

51 ± 32

28 ± 13

34 ± 21

34 ± 22

26 ± 13

51 ± 33

50 ± 34
Mean ±

6–17 1.74 (1.23, 0.85 0.84 0.93 (0.69, 1.25

2.47) (0.67, (0.57, 1.26) (0.89,
SD

1.08) 1.22) 1.76)

18~59 0.96 (0.74, 0.86 0.67 1.00 (0.63, 1.23
Guangzhou

1.25) (0.67, (0.51, 1.58) (0.94,

Hangzhou

Changsha
Kunming
Chengdu

Nanning

Xiamen

1.12) 0.87) 1.62)

Ningbo

Wuhan
Cities

Hefei

≥60 0.46 (0.37, 0.51 0.80 0.34 (0.23, 0.84

0.58) (0.32, (0.42, 0.51) (0.63,
Table 3

0.83) 1.53) 1.10)

10
1

(continued on next page)

5
R. Zhang et al. International Journal of Hygiene and Environmental Health 252 (2023) 114200

Table 4 (continued ) Table 5

Overall Spring Summer Autumn Winter
Attributable fraction (AF) of influenza due to air pollutants in different season
layers in 10 cities of southern China, 2016–2019.
CRR (95% CRR CRR CRR (95% CRR
CI) (95% (95% CI) (95% Overall Spring Summer Autumn Winter
CI) CI) CI) AF (95% AF (95% AF (95% AF (95% AF (95%
NO2 Total 1.74 (1.49, 1.21 1.06 1.29 (1.10, 1.68 eCI, %) eCI, %) eCI, %) eCI, %) eCI, %)
2.03) (1.09, (0.94, 1.50) (1.44, PM2.5 4.46 (2.43, 5.56 0.02 2.01 3.71 (2.23,
1.33) 1.19) 1.98) 6.43) (2.26, (− 1.01, (− 1.15, 5.25)
Sex 8.78) 1.09) 5.17)
Male 1.72 (1.46, 1.13 1.05 1.21 (1.02, 1.68 PM10 5.03 (2.33, 3.87 0.40 4.70 6.57 (4.05,
2.02) (1.01, (0.91, 1.45) (1.42, 7.56) (1.08, (− 1.00, (0.66, 9.14)
1.27) 1.22) 1.99) 6.40) 1.72) 8.49)
Female 1.72 (1.45, 1.24 1.01 1.26 (1.04, 1.70 SO2 5.36 (3.12, 5.98 1.08 2.92 3.75 (0.77,
2.03) (1.10, (0.88, 1.52) (1.42, 7.58) (3.25, (− 1.00, (0.48, 6.57)
1.40) 1.15) 2.03) 8.42) 3.40) 5.18)
Age NO2 24.88 14.90 1.83 14.88 22.02
≤5 1.50 (1.28, 1.06 0.93 1.13 (0.93, 1.80 (18.02, (9.06, (− 4.44, (7.55, (10.96,
1.77) (0.93, (0.80, 1.36) (1.47, 31.67) 20.36) 8.39) 21.58) 30.84)
1.20) 1.07) 2.21) CO 23.22 5.53 − 0.50 7.72 28.80
6–17 1.55 (1.27, 1.11 1.03 1.26 (0.99, 1.44 (17.56, (2.18, (− 3.16, (1.84, (20.06,
1.89) (0.96, (0.82, 1.61) (1.12, 28.61) 8.53) 2.22) 13.30) 36.30)
1.29) 1.29) 1.86) O3 − 4.46 10.00 3.65 9.05 − 11.08
18~59 0.99 (0.85, 1.09 1.04 0.81 (0.62, 1.45 (− 15.58, (4.76, (0.50, (− 3.40, (− 27.86,
1.16) (0.95, (0.86, 1.06) (1.21, 4.32) 14.95) 6.59) 19.33) 2.01)
1.25) 1.25) 1.75) Note.
0.47 (0.42, 1.12 0.87 0.53 (0.39, 0.94
Bold values are statistically significant.
≥60
0.53) (0.81, (0.59, 0.72) (0.79,
1.54) 1.30) 1.11)
COa Total 1.19 (1.04, 1.21 0.96 1.12 (0.94, 0.99 and CO were greater than PM2.5, PM10, SO2, and O3, reaching 24.88%
1.36) (1.10, (0.86, 1.32) (0.89, (95% eCI: 18.02%, 31.67%) and 23.22% (95% eCI: 17.56%, 28.61%),
1.34) 1.07) 1.10)
respectively. In spring, AF of NO2 was the greatest at 14.90% (95% eCI:
Sex
Male 1.22 (1.05, 1.24 0.93 1.11 (0.91, 1.01 9.06%, 20.36%), followed by it of O3 at 10.00% (95% eCI: 4.76%,
1.41) (1.10, (0.82, 1.35) (0.90, 14.95%). In summer, O3 was the only pollutant with a significant AF of
1.40) 1.06) 1.13) 3.65% (95% eCI: 0.50%, 6.59%). In autumn, AF of NO2 was the greatest
Female 1.17 (1.02, 1.13 0.94 1.07 (0.87, 0.96
at 14.88% (95% eCI: 7.55%, 21.58%), followed by it of CO at 7.72%
1.36) (1.01, (0.82, 1.33) (0.86,
1.27) 1.08) 1.08) (95% eCI: 1.84%, 13.30%). In winter, AF of CO was the greatest at
Age 28.80% (95% eCI: 20.06%, 36.30%), followed by it of NO2 at 22.02%
≤5 1.20 (1.02, 1.17 0.88 1.04 (0.83, 1.19 (95% eCI: 10.96%, 30.84%).
1.42) (1.01, (0.77, 1.30) (1.03,
1.34) 1.01) 1.38)
6–17 1.28 (1.05, 1.19 0.68 0.64, 0.51, 0.78 3.4. Sensitivity analysis
1.56) (1.02, (0.56, 0.80) (0.66,
1.39) 0.84) 0.92)
18~59 0.86 (0.74, 1.12 0.79 0.93 (0.68, 0.88 The sensitivity analysis results (Table S1) showed that the CRRs
1.01) (0.98, (0.68, 1.28) (0.78, remained almost unchanged, which indicated that the models were
1.29) 0.92) 0.99) stable.
≥60 0.80 (0.64, 1.15 0.82 0.54 (0.37, 0.99
0.99) (0.81, (0.64, 0.77) (0.83,
1.64) 1.06) 1.19) 4. Discussion
O3 Total 0.96 (0.85, 1.28 1.09 1.17 0.91
1.08) (1.13, (0.96, (0.98,1.39) (0.83, To our best knowledge, this is the first multi-site and comprehensive
1.45) 1.23) 1.00)
study examining the effects of air pollutants on influenza infection risks
Sex
Male 0.94 1.20 1.08 1.19 (0.96, 0.91
in different seasons with sub-tropical climates. After controlling the
(0.83,1.06) (1.05, (0.93, 1.47) (0.83, possible contributions from climate factors, we revealed that seasons
1.38) 1.25) 1.01) modified the associations between air pollutants and influenza in
Female 0.94 (0.83, 1.32 1.04 1.02 (0.83, 0.90 southern China.
1.07) (1.14, (0.90, 1.27) (0.81,
Overall, we found that except for O3, the increasing in concentration
1.54) 1.20) 0.99)
Age of PM2.5, PM10, SO2, NO2, and CO raised the influenza infection risks.
≤5 1.00 (0.87, 1.18 1.04 1.26 (0.99, 0.82 The results are consistent with previous studies (Croft et al., 2019; Liang
1.16) (1.00, (0.89, 1.59) (0.74, et al., 2014; Seah et al., 2023; Su et al., 2019).
1.40) 1.21) 0.90) Biologically, exposure to air pollutants can affect the respiratory
6–17 0.52 (0.47, 1.11 0.91 0.99 (0.73, 1.03
0.57) (0.93, (0.72, 1.34) (0.88,
system by inducing inflammatory states, modulating the immune sys­
1.31) 1.14) 1.21) tem, and increasing the expression of molecules that favor respiratory
18~59 1.12 (0.94, 1.27 1.04 0.61 (0.47, 0.77 virus pathogenesis (Loaiza-Ceballos et al., 2022). Also, pollutants could
1.35) (1.06, (0.87, 0.80) (0.70, induce oxidative stress, leading to the production of free radicals. These,
1.52) 1.24) 0.85)
in turn, could have damaging effects on the respiratory system, thereby
≥60 1.17 (0.87, 0.51 0.97 0.66 (0.41, 0.88
1.59) (0.37, (0.66, 1.07) (0.75, lowering the resistance of the tissues to viral and bacterial infections
0.70) 1.41) 1.03) (Ciencewicki and Jaspers 2007).
Seasonal stratification analyses revealed that seasonality modified
Note.
Bold values are statistically significant. the effects of the pollutants on influenza incidence. The greatest effects
a
CRR for a 10 μg/m3 increase in CO are shown in Table S2. from PM2.5, PM10, SO2, and NO2 on incidence occurred in winter. This
result is in line with previous studies (Kan et al., 2008; Lai et al., 2013;

6
R. Zhang et al.
Qian et al., 2010). This may be due to the fact that air pollution increases
every winter, making influenza viruses surviving longer. Besides, viruses
spread easier when people tend to stay inside. (Somayaji et al., 2020).
Biologically, pollutants in winter are more irritating to the respiratory
tract and cause inflammation of the respiratory system due to lower
temperatures. Additionally, shorter duration of sunlight during winter,
along with stronger blockage of sunlight by increased concentrations of
PMs, lead to low immunity due to vitamin D deficiency (Cannell et al.,
2008; Siddiqui et al., 2020). All of these may increase the susceptibility
to air pollutants, thus making infection risks greater in winter (Juze­
niene et al., 2010; Lofgren et al., 2007; Mora et al., 2008).
Influenza viruses can be attached to PMs and floating in the air, so
that they can remain airborne long enough to be inhaled into the res­
piratory tract of a susceptible host (Feng et al., 2016). The risk of
influenza infection from increasing in PM10 concentration was signifi­
cant in winter but not in spring. This may be due to the humid and rainy
spring in southern China, where precipitation lower the PM10 levels,
thus reduced the chance of the influenza viruses spreading in the
external environment (Kan et al., 2008; Moriyama et al., 2020; Qian
et al., 2010). The minuscule particle size of PM2.5, mainly acting on the
lower respiratory tract and alveoli, produces less short-term acute effects
than that of PM10 which directly infects the upper respiratory tract
(Loaiza-Ceballos et al., 2022). This fact might explain the finding of
greater influenza infection risks from PM10 overall.
The results suggest that increasing concentrations of O3 are nega­
tively associated with the risks of catching influenza, which may be
specifically related to the bactericidal properties of O3 (Song et al.,
2021). Moreover, epidemiological studies have shown that O3 levels are
directly driven by weather, as ozone-generating photochemical re­
actions of air pollutants require high temperatures and bright sunlight,
which are the typical conditions in summer (De Sario et al., 2013). O3
concentrations are highest in summer and lowest in winter, while the
trend for influenza incidence is the opposite, so the negative correlation
may be explained.
In the age subgroup analysis, the age group of 0–17 was more sen­
sitive to air pollutants for influenza development in spring and winter.
The reason could be that children aged 0–17 have immature immune
systems, making this group more vulnerable to influenza viruses (Feng
et al., 2016). Therefore, more attention should be paid to preschool and
school-aged children, such as reducing their outdoor activities to lessen
the exposure to air pollutants and influenza viruses. In terms of health
promotion, hygiene, and symptom monitoring in kindergartens and
schools should be enhanced, especially during the influenza seasons.
The AFs for a particular exposure-outcome order is defined as the
proportion of preventable outcomes in the population if the exposure
was completely eliminated. The AFs of influenza incidence due to NO2
and CO were greater than that of other pollutants, especially in winter.
This suggests that symptom monitoring should be intensified simulta­
neously for influenza incidence, NO2 and CO concentration. In addition,
more attention should be paid to O3 concentrations to prevent spring
and summer epidemics of influenza.
Several limitations should be acknowledged. First, the influenza data
from disease notifications were based on hospital reports, which may
have underreporting bias. Second, the study was based on sub-tropical
climates in southern China, so the results may not be generalizable to
regions with other climates. Third, because the coverage of influenza
vaccine data was not available, we could not exclude the influence from
this variable. Fourth, due to the lack of individual reporting information
and exposure information, this study employed an ecological study
design rather than individual-based models (e.g., conditional logistic
regression models) to analyze the data.
5. Conclusion
Our findings have updated the scientific evidence of the seasonal
associations between air pollutants and influenza in southern China.
7
International Journal of Hygiene and Environmental Health 252 (2023) 114200
These findings may facilitate local health authorities and environmental
protection agencies to optimize influenza warning systems, to imple­
ment interventions, and to distribute clinical and public health
resources.
Authorship contribution statement
Rui Zhang: Methodology, Software, Writing- Original draft prepa­
ration, Funding acquisition Yonghong Li: Funding acquisition, Project
administration, Supervision Peng Bi: Writing- Reviewing and Editing
Siyuan Wu: Writing- Reviewing and Editing Zhibin Peng: Formal
analysis, Resources Yujie Meng: Software, Formal analysis Yu Wang:
Software, Formal analysis Songwang Wang: Funding acquisition,
Software, Validation Yushu Huang: Software, Formal analysis Juan
Liang: Software, Formal analysis Jing Wu: Funding acquisition,
Conceptualization, Methodology, Supervision, Writing- Reviewing, and
Editing.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Acknowledgments
This work was supported by the National Key Research and Devel­
opment Program of China [2022YFC2602301], the 2022 Key Strategic
Research and Consulting Project of the Chinese Academy of Engineer­
ing: National Health Management Engineering Research [2022-XBZD-
21-02], the Science and Technology Fundamental Resources Investiga­
tion Program [2017FY101201], and the National Science and Technol­
ogy Major Project [2017ZX10305501-009].
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.ijheh.2023.114200.
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