Chemosphere 222 (2019) 665e670

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Chemosphere
journal homepage: www.elsevier.com/locate/chemosphere

Applying the concept of “number needed to treat” to the formulation

of daily ambient air quality standards
Zengliang Ruan a, Zhengmin (Min) Qian b, Yanjun Xu c, Jun Wu d, Haidong Kan e,
Yin Yang a, Bipin Kumar Acharya a, Chengsheng Jiang f, Kevin M. Syberg b,
Juliet Iwelunmor b, Wenjun Ma g, **, Hualiang Lin a, *
a
Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China
b
College for Public Health and Social Justice, Saint Louis University, Saint Louis, MO, 63104, United States
c
Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 511430, China
d
Program in Public Health, College of Health Sciences, University of California, Irvine, CA, 92697, United States
e
School of Public Health, Fudan University, Shanghai, 200032, China
f
Maryland Institute for Applied Environmental Health, University of Maryland School of Public Health, College Park, MD, 20742, United States
g
Guangdong Provincial Institute of Public Health, Guangzhou, 511430, China

h i g h l i g h t s

There is limited method for air pollution standard formulation.

The “number needed to treat” was proposed as one potential method.

We examined the acute association between PM2.5 and mortality in four Chinese cities.

We then calculated the reduction in air pollution concentrations needed to avoid one death.

Finally, we suggested that 50 mg/m3 should be considered as daily standard of ambient PM2.5 in the study area.

a r t i c l e i n f o a b s t r a c t

Article history: The World Health Organization sets up the Ambient Air Quality Guidelines mainly based on short-term
Received 6 September 2018 and long-term health effects of air pollution. Previous studies, however, have generally revealed a non-
Received in revised form threshold concentration-response relationship between air pollution and health, making it difficult to
25 January 2019
determine a concentration, below which no obvious health effects can be observed. Here we proposed a
Accepted 29 January 2019
Available online 30 January 2019
novel approach based on the concept of “number needed to treat”, specifically, we calculated the
reduction in air pollution concentrations needed to avoid one death corresponding to different hypo-
Handling Editor: R Ebinghaus thetical concentration standards; the one with the smallest value would be the most practical concen-
tration standard. As an example, we applied this approach to the daily standard of ambient PM2.5
Keywords: (particulate matter with aerodynamic diameter 2.5 mm) in four Chinese cities. The calculation was
Ambient air quality standard based on the association between daily mortality and ambient PM2.5, which was examined by a
Particulate matter generalized additive model with adjustment of important covariates. Significant associations were
Number needed to treat observed between PM2.5 and mortality. Our analyses suggested that it is appropriate to have 50 mg/m3 as
China
the daily standard of ambient PM2.5 for the study area, compared to the current standard of which were
directly adopted from the national standard of 75 mg/m3. This novel approach should be considered when
planning and/or revising the ambient air quality guidelines/standards.
© 2019 Elsevier Ltd. All rights reserved.

1. Introduction

* Corresponding author. Numerous studies have consistently reported that both short-
** Corresponding author. term and long-term exposures to ambient air pollution are signif-
E-mail addresses: mawj@gdiph.org.cn (W. Ma), linhualiang@mail.sysu.edu.cn icantly linked to various health outcomes, particularly morbidity
(H. Lin).

https://doi.org/10.1016/j.chemosphere.2019.01.175
0045-6535/© 2019 Elsevier Ltd. All rights reserved.
666 Z. Ruan et al. / Chemosphere 222 (2019) 665e670
and mortality from cardiovascular and respiratory diseases (Crouse
et al., 2015; Chen et al., 2017; Li et al., 2018; Qiu et al., 2018). This
evidence has served as an important scientific basis for the devel-
opment of the ambient air quality guidelines/standards used by the
World Health Organization (WHO) and different countries (World
Health Organization, 2006; Ministry of Environmental Protection
of China, 2012).
Additionally, these findings have also been used by the WHO to
establish interim targets in some countries with different air
pollution levels (World Health Organization, 2006). However, most
of these guidelines were based on the concentrations at which
there were observed health impacts (Krzyzanowski and Cohen,
2008). The current evidence generally reported an approximately
linear concentration-response relationship between air pollution
exposure and health; meaning that no concentration thresholds
were identified (Pope et al., 2006), making it hard to set up a
specific concentration standard (Wu et al., 2018).
Hypothetically, we have the same daily concentration standard
for two cities with the same air pollution level (for example, with a
daily mean concentration of 35 mg/m3 for PM2.5), and one city may
have substantial health benefits by obtaining the standard if there
is a considerable population exposed to PM2.5 higher than 35 mg/
m3. However, the potential health benefits may be limited if only a
limited population is exposed to PM2.5 higher than 35 mg/m3 in
another city. As a result, a more appropriate approach to the
formulation of air quality guideline/standards is urgently needed.
We thus proposed a novel approach by incorporating the con-
cepts of “number needed to treat (NNT)” to complement the air
quality standard formulation. Specifically, this concept consists of
calculating the air pollution concentrations needed to prevent one
mortality for different hypothetical concentration standards, in
particular, we compared the air pollution concentrations needed to
prevent each one mortality for a few hypothetical concentration
standards, the one with the lowest value would be the proposed
standard due to the cost and feasibility. We applied this approach in
four Chinese cities in Guangdong Province to calculate the standard
of daily concentration of ambient PM2.5.
2. Methods
2.1. Study area
Four Chinese cities of Guangzhou, Foshan, Dongguan, and
Jiangmen were selected from Guangdong Province for this study.
These cities have a typical subtropical and monsoon climate with
an annual temperature of 23  C and an annual relative humidity of
76%. As the capital city of Guangdong Province, Guangzhou is the
largest city and economic center in southern China in 2015 with a
population of 16.7 million; Dongguan is a major manufacturing hub
for electronics and communications equipment with approxi-
mately 8.3 million residents; Foshan has a large number of elec-
tronic appliance factories and a population of approximately 7.2
million residents; and Jiangmen's economy mainly relies on
manufacturing sectors and has approximately 4.5 million residents.
2.2. Mortality data
The daily mortality time series data were derived from the death
registration system of the health department of Guangdong Prov-
ince during the period between January 18, 2013 and December 31,
2016. We extracted the following data from the death certificate:
age, sex, education, and cause of death. We used standard quality
assurance and quality control to ensure data quality (Lu et al.,
2007). Using the Tenth Revision of the International Classification
of Diseases (ICD-10) as a guide, we classified mortality data for this
analysis into the following: all-natural diseases (ICD10: A00eR99),
cardiovascular diseases (ICD10: I00eI99), and respiratory diseases
(ICD10: J00eJ99).
2.3. Air pollution data
The 24-h mean concentrations of ambient air pollution were
monitored in the four cities from January 19, 2013 through
December 31, 2016. There are 11 air monitoring stations in
Guangzhou, four in Jiangmen, eight in Foshan, and five in Dong-
guan. These air monitoring stations regularly monitor the daily
concentration of PM2.5, nitrogen dioxide (NO2), sulfur dioxide (SO2)
and ozone (O3). The mean concentrations across the stations in
each city were used for analysis. Previous studies indicated that the
monitoring stations represents the current general air pollution
situation in these cities (Lin et al., 2016a). Our time series data had
53 days of missing data for PM2.5, SO2, NO2, and 35 days of missing
data for O3, respectively.
The daily meteorological data were retrieved from the city-
specific weather stations, including mean temperature ( C) and
relative humidity (%).
2.4. Statistical analysis
The association between PM2.5 and mortality was firstly exam-
ined for each city using a generalized additive time series model; a
quasi-Poisson link was selected to deal with the over-dispersion of
the daily mortality data. A few important covariates were adjusted
in the model including public holidays, day of the week, temporal
trend and meteorological factors. The former two variables were
treated as categorical variables. Penalized smoothing splines were
used to address non-linear patterns of seasonal pattern and long-
term trend, as well as meteorological parameters such as temper-
ature and relative humidity (Lin et al., 2016b). Model specifications
were constructed in accordance with guidelines established in
previous air pollution time series studies (Tian et al., 2013). For
example, degrees of freedom (df) of 6 per year for smoothing
functions of temporal trends, a df 6 for the current day's temper-
ature (Temp0) and moving average of previous 3 days' mean tem-
perature (Temp1e3), and a df 3 for the current day's relative
humidity (Humidity0) were applied. The statistical model can be
specified as:
log [E(Yt)] ¼ b*PM2.5 þ s (t, df ¼ 6/year) þ s (Temp0, df ¼ 6) þ s
(Temp1e3, df ¼ 6) þ s (Humidity0, df ¼ 3) þ b1*day of the
week þ b2*public holidays þ a.
where E (Yt) is the expected daily mortality count on day t, s ()
indicates a smoother based on penalized smoothing splines, df is
the degree of freedom, t represents time to adjust for long-term
trend and seasonality, b is the regression coefficient, day of week
is a variable with values from 1 to 7, public holidays is a binary
variable of 0 and 1, and a is the model intercept.
After checking the linearity of the association between PM2.5
and mortality using a smoothing function, estimates of the
magnitude of the associations with different lag days including
both single lag days (from the same day (lag0) up to three lag days
(lag3)) and multiple lag days (moving averages for the same day and
previous one, two and three days (lag03)) were calculated. In
addition to the single-pollutant models that only included PM2.5,
we applied two-pollutant models that adjusted for the potential
confounding effects of gaseous air pollutants, where PM2.5 and SO2
(or NO2, O3) were simultaneously included at the same model.
A few sensitivity analyses were used to check the robustness of
the results from the main models. Alternative dfs for smoothing
 Z. Ruan et al. / Chemosphere 222 (2019) 665e670 667

functions of temporal trends (7e9 df/year) and of the weather Table 1

factors (5 and 7 df for temperature and 4 and 5 df for relative hu- Descriptive summary of daily mortality, air pollution, and weather factors in the four
cities in Guangdong Province, China, 2013e2016.
midity) were used. The magnitude of the association was measured
using percentage increase in daily mortality associated with each Dongguan Foshan Guangzhou Jiangmen Mean
10 mg/m3 increment in ambient PM2.5. Days 1441 1461 1461 1455 1454
Based on the above estimated associations, the avoidable Daily death counts
number of mortality when daily mean concentration of PM2.5 All 31 53 126 72 70
CVD 15 22 52 39 32
reached a certain concentration threshold was calculated. As the
Respiratory 3 8 20 8 10
current standard for daily concentration of PM2.5 was 75 mg/m3 in Number of monitors 5 8 11 4 7
China, the hypothetical standards were thus set from 70 mg/m3 to Air pollution, mg/m3
25 mg/m3 with a decrement interval of 5 mg/m3. The potential PM2.5 40.7 43.4 43.3 40.8 42.1
mortality reduction was calculated for each 1 mg/m3 reduction in SO2 18.7 22.6 16.7 20.1 19.5
NO2 38.4 43.9 46.0 33.0 40.3
the standards. For example, when setting the standard at 65 mg/m3, O3 63.7 49.9 53.1 50.4 54.3
the formula can be specified as (Li et al., 2016): Weather
Temperature ( C) 23.0 21.5 21.9 23.0 22.4
Mortality reduction ¼ baseline mortality Humidity (%) 76.8 78.2 79.7 81.3 79.0
Xn
 ðexpðb*DAPCk Þ  1Þ Abbreviations: CVD ¼ cardiovascular disease; PM2.5 ¼ particulate matter with an
k¼1 aerodynamic diameter less than or equal to 2.5 mm; SO2 ¼ sulfur dioxide;
NO2 ¼ nitrogen dioxide; O3 ¼ ozone.
where the baseline mortality is defined as the daily mortality count
on the days with daily PM2.5 concentrations around 65 mg/m3; b is
the regression coefficient of the PM2.5-mortality association; △APC in PM2.5 was associated with an increase in all natural mortality of
is the difference between the observed PM2.5 concentrations and 2.29% (95% confidence interval (CI): 1.80%, 3.30%) in Dongguan,
65 mg/m3 across the observation days with the concentrations 2.53% (95% CI: 1.88%, 3.20%) in Foshan, and 1.71% (95% CI: 1.19%,
above 65 mg/m3. 2.22%) in Guangzhou. For the cardiovascular mortality, each 10 mg/
The denominator, namely the overall concentration*days, was m3 increase in PM2.5 was associated with an increased risk of 3.32%
further calculated. For example, one day with daily PM2.5 concen- (95% CI: 2.09%, 4.54%) in Dongguan, 3.05% (95% CI: 2.19%, 3.91%) in
tration of 72 mg/m3 would contribute to (72-65) ¼ 7 excessive Foshan, and 2.26% (95% CI: 1.65%, 2.88%) in Guangzhou. With regard
concentration unit*days (abbreviated as concentration*days to the respiratory mortality, the risk was 2.15% (95% CI: 0.83%,
thereafter), and one day with daily PM2.5 concentration of 69 mg/m3 3.47%) in Foshan, 1.89% (95% CI: 0.95%, 2.83%) in Guangzhou and
would contribute to (69-65) ¼ 4 concentration*days. The sum of 1.91% (95% CI: 0.43%, 3.41%) in Jiangmen. For the regional overall
the concentration*days would be the denominator, this calculation effects, the meta-analysis reported that each 10 mg/m3 increase of
was in line with one previous study (Goggins et al., 2015). ambient PM2.5 concentration was associated with an increased risk
Finally, the PM2.5 concentrations needed to avoid one excessive of 1.99% (95% CI: 1.51%, 2.48%) in all natural mortality, 2.53% (95%
mortality was calculated as the ratio of the overall concen- CI: 1.90%, 3.16%) in cardiovascular mortality, and 1.85% (95% CI:
tration*days and the overall mortality reduction for each hypo- 1.20%, 2.50%) in respiratory mortality, respectively.
thetical standard; the one with the smallest value was suggested as Different values of PM2.5 concentrations needed to reduce to
the most practical concentration standard, meaning that, to avoid prevent death against different hypothetical concentration
each one death, it needs the least resources to reduce the air thresholds were observed in the four cities (Fig. 2), ranging from
pollution concentrations from the existing level. 4.51 for the hypothetical standard of 50 mg/m3 in Guangzhou to
Besides the city-specific analysis, a random effect meta-analysis 14.24 for the hypothetical standard of 45 mg/m3 in Dongguan. Based
to estimate the overall association between PM2.5 and mortality on this result, setting up the daily PM2.5 standard at 50 mg/m3 in
across the four cities (Hunter and Schmidt, 2000) was conducted. Dongguan and Guangzhou, 65 mg/m3 in Foshan, and 45 mg/m3 in
Estimates of the most practical daily PM2.5 standard for the study Jiangmen is suggested. The combined analysis with data from all
region were calculated from this meta-analysis. P values < 0.05 four cities suggested that 50 mg/m3 would be an appropriate daily
were viewed as statistically significant. concentration standard of ambient PM2.5 in the study region.
The associations remained similar in a series of sensitivity an-
alyses, including further adjustment for gaseous air pollutants in
3. Results
two-pollutant models (SO2, NO2 and O3), changing the degree of
freedom in the smoothing functions (Table s2). When we calculated
A total of 408,743 deaths from all-natural diseases were recor-
the PM2.5 concentrations needed to reduce cardiovascular and
ded in the four cities during the study period. Table 1 shows the
respiratory mortality (Fig. s1), a minimal value at 50 mg/m3 of PM2.5
descriptive statistics of the daily mortality, air pollution, and
in the study region was also observed.
weather variables in the study cities. The daily average count of
mortality varied across the cities and ranged from 31 to 126 for all-
natural diseases, including 15e52 for cardiovascular diseases and 4. Discussion
3e20 for respiratory diseases. The daily average concentrations of
ambient PM2.5 over the entire study period across the cities ranged This study proposed a novel approach to combining the health
from 40.7 mg/m3 in Dongguan to 43.4 mg/m3 in Foshan. The mean effects of air pollution and the concept of “NNT”. As a further step,
temperature ranged from 21.5  C to 23.0  C and relative humidity this approach was applied to four Chinese cities, where proposed
ranged from 76.8% to 81.3%. daily ambient concentration standard of PM2.5 was calculated for
Fig. 1 presents the results of the regression models. Varying each of the cities. We suggest the use of this approach when
magnitudes of the associations were observed across the four cities revising the ambient air quality standard in these cities and beyond.
and across different lag days and the causes of death. As indicate in The concept of NNT has been widely applied in clinical and
Fig. 1 and Table s1, PM2.5 at lag03 had the strongest city-specific and pharmaceutic research. It evaluates the effectiveness of a new
regional overall associations. For example, each 10 mg/m3 increase treatment or a new drug. A more effective treatment/drug results in
668 Z. Ruan et al. / Chemosphere 222 (2019) 665e670
Fig. 1. The short-term associations between ambient PM2.5 and mortality in the four cities.
lower NNTs. The most ideal NNT is one, meaning that everyone
receiving the treatment/drug benefits (Sedgwick, 2015). This study,
for the first time, applied the “number needed to treat” concept to
the formulation of air quality standard. For example, a value of 10
would mean that 10 mg/m3 reduction in air pollution would be
needed in order to prevent one person to die prematurely. In
general, the smaller the value, the more achievable the proposed
standard based on the existing air quality level would be.
This new approach possessed a few unique advantages and
important implications. It considered the temporal variation in
daily mean PM2.5 concentrations in each city, as well as the health
effects of air pollution. At the same time, it is based on the attrib-
utable mortality number due to exposure to ambient PM2.5 at
different levels. This approach provides a new way for the envi-
ronmental health workers including health departments to
formulate the daily air quality standard in a more efficient and
accountable way.
The WHO and various countries have developed ambient air
quality guidelines/standards based on health effects (Basagan ~a
et al., 2015; Samoli et al., 2016; Zhang et al., 2017a, 2017b). For
example, the WHO guideline of 25 mg/m3 for the 24-h mean PM2.5
concentration was mainly based on the epidemiological studies
from Europe and North America, which observed significant health
effects at the low range of the air pollution concentrations among
the study areas (World Health Organization, 2006). However, that
guideline may not be applicable to every country and region,
though interim targets have also been proposed considering het-
erogeneity in air pollution levels, emission sources, composition of
pollutant mixture, populations and vulnerable subpopulations, and
feasibility to comply with the guideline (World Health
Organization, 2006). From the perspective of public health pro-
tection, an approach is needed to incorporate the potential health
benefits resulting from the reduced air pollution levels. With this in
mind, this study proposed reductions in air pollution concentra-
tions that are needed to avoid each one mortality, as a novel indi-
cator that can be used when planning a new or revising an existing
air quality standard.
The calculated values of concentrations need to reduce varied
across the four studied cities, indicating that to prevent one indi-
vidual death, the efforts to reduce the air pollution concentration
would be different in the four cities. The underlying reasons include
the distribution of the PM2.5 concentrations, other environmental
exposures or stressors that make some cities more vulnerable to
PM2.5 exposure than others, as well as the baseline mortality. The
differences, especially in the effect estimates of the associations,
have also been reported in a few other multi-city air pollution
epidemiology studies (Lin et al., 2016a; Nwanaji-Enwerem et al.,
2017).
A few limitations are acknowledged in this study. The exposure
assessment is one important concern. The city-wide average air
pollution concentration was used as the exposure variable, which
might have resulted in exposure misclassification, and possibly
inaccurate effect estimates of the PM2.5-mortality association. It
should be also noted that one underlying assumption of the new
approach was that resources and efforts to reduce each one unit of
PM2.5 concentration were similar at different concentration levels,
 Z. Ruan et al. / Chemosphere 222 (2019) 665e670
Fig. 2. The estimated PM2.5 concentrations needed to reduce one death in the four cities.
which may not be the case in reality. Usually it may take more
resources at lower levels. Further studies should take this issue into
consideration. Lastly, due to insufficient data, the current study did
not consider the chemical components of PM, which are important
determinants of the health effects of PM pollution (Lin et al.,
2016b). Future studies are warranted in respect to these limitations.
5. Conclusions
This study proposes a new approach based on the concept of
“number needed to treat” for the formulation of the daily ambient
air quality standards. We applied this method and suggest that
50 mg/m3 would be appropriate for the four cities in Guangdong
Province. This approach should be considered in future air quality
standard formulation and revision.
Funding
This work was supported by the National Key R&D Program of
China (grant number: 2018YFA0606200).
Declarations of interest
None.
669
Acknowledgments
We thank all the reviewers for their careful reviewing the
manuscript and the insightful comments and suggestions.
Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.chemosphere.2019.01.175.
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