Mortality and hospitalizations due to cardiovascular and respiratory diseases associated with air pollution in Iran: A systematic review and meta-analysis

Accepted Manuscript Mortality and hospitalizations due to cardiovascular and respiratory diseases associated with air pollution in Iran: A systematic review and meta-analysis Behrooz Karimi, Behnosh shokrinezhad, Sadegh Samadi PII:

S1352-2310(18)30761-1

DOI:

https://doi.org/10.1016/j.atmosenv.2018.10.063

Reference:

AEA 16360

To appear in:

Atmospheric Environment

Received Date: 1 May 2018 Revised Date:

26 September 2018

Accepted Date: 29 October 2018

Please cite this article as: Karimi, B., shokrinezhad, B., Samadi, S., Mortality and hospitalizations due to cardiovascular and respiratory diseases associated with air pollution in Iran: A systematic review and meta-analysis, Atmospheric Environment (2018), doi: https://doi.org/10.1016/j.atmosenv.2018.10.063. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Mortality and hospitalizations due to cardiovascular and respiratory diseases associated

1

with air pollution in Iran: a systematic review and meta-analysis

2 3 4 5

Behrooz Karimia,*, Behnosh shokrinezhada, Sadegh Samadib a

RI PT

6 Department of Environmental Health Engineering, Health Faculty, Arak University of Medical Sciences, Arak, b

SC

Iran; Department of Occupational Health, Health Faculty, Arak University of Medical Sciences, Arak, Iran;

AC C

EP

TE D

M AN U

*Corresponding author; Behrooz Karimi; Department of Environmental Health Engineering, Health Faculty, Arak University of Medical Sciences, Arak, Iran Email: [email protected] Tel & Fax: +98 (0)863368443

1

7 8 9 10 11 12 13 14 15 16 17 18 19

ACCEPTED MANUSCRIPT 20

Air pollution is a major environmental health problem around the world. The purpose of this

21

study was to investigate the relationship between exposure to air pollution with mortality and

22

hospitalizations by conducting a systematic review and meta-analysis.

23

Several databases were searched for studies exploring the relationship between air pollution

24

and the all-cause, cardiovascular and respiratory mortality, as well as hospitalizations. The

25

RI PT

ABSTRACT

26

each study included. Random-effects model was applied to estimate the relative risks of all-

27

cause mortality and mortality/hospitalization due to cardiovascular and respiratory diseases.

28

We found a 0.6% (95% CI 0.5%-0.7%) increase in all-cause, 0.5% (95% CI 0.4%-0.6%)

29

SC

risk of bias assessed by the Office of Health Assessment and Translation (OHAT) Method for

30

per 10 µg/m3 increase of pooled all air pollutants. Moreover, we observed a 0.7% (95% CI

31

0.6%-0.9%) increase in hospitalization due to cardiovascular and respiratory diseases per 10

32

µg/m3 increase of pooled air pollutants. The highest all-cause mortality was associated with

33

exposure to particulates with aerodynamic diameters less than 2.5 µm (PM2.5) (681 deaths or

34

1.5%, 95% CI 1.3%-1.7%), followed by PM10 (253 deaths or 0.7%, 95% CI 0.6%-0.8%).

35

The current study illustrated that all investigated air pollutants were associated with elevated

36

mortality and hospitalization, but the effects of PM2.5 and PM10 were stronger. Thus,

37

TE D

M AN U

increase in cardiovascular, and 0.8% (95% CI 0.6%-0.9%) increase in respiratory mortality

authorities need to pay more attention to establishing the new regulations to apply control

38

measures.

39 40

Keywords: Mortality, Hospitalizations, Air pollution, Meta-analysis

41

EP

Systematic review registration: PROSPERO: CRD42018088770.

42

AC C

43 44 45 46 47 48 49 50 2

ACCEPTED MANUSCRIPT 51

Air pollution is a major environmental health problem around the world (Miri et al., 2016).

52

Rapid urbanization and industrialization are well-known causes of increasing air pollution

53

and subsequently associated with adverse health outcomes (Mannucci and Franchini, 2017;

54

Miri et al., 2016). Air pollution has become the 4th highest-ranking risk factor for death in the

55

world (Brauer, 2016). The world health organization (WHO) in 2016 reported that air

56

pollution of fine particles associated with 4.2 million deaths annually (WHO, 2018). In 2018,

57

this figure increased to be 7 million deaths (WHO, 2018). More than 90% of air pollution-

58

SC

RI PT

1. Introduction

59

Africa. Regarding Middle East, the highest concentrations of air pollution are in the Eastern

60

Mediterranean Region and in South-East Asia, with annual mean concentrations often

61

exceeding more than 5 times WHO limits (WHO, 2018).

62

According to the global ranking, Iran was ranked as the seventh among the most 10 top

63

polluted countries (Heger and Sarraf, 2018). Tehran is ranked as 12th among 26

64

TE D

M AN U

related deaths reported to be occur in low- and middle-income countries, mainly in Asia and

65

Additionally, Tehran as a capital city was the third most top polluted city in the world after

66

Jakarta (Indonesia) and Kolkata (India) (Sefiddashti et al., 2015). Air pollution is a major

67

environmental risk factor for morbidity in Iran including diseases such as respiratory and

68

AC C

EP

megacities in terms of ambient PM10 concentrations (Heger and Sarraf, 2018).

cardiovascular diseases, lung cancer, Alzheimer’s and Parkinson’s diseases (Heger and

69

Sarraf, 2018). The all-cause mortality attributed to air pollution in Tehran estimated to be

70

5388 deaths (40% of all deaths) in 2008 (Joneidi jafari et al., 2010) and this figure was

71

elevated to be 5894 in 2017 (Mohammadi-Zadeh et al., 2017).

72

The concentrations of carbon monoxide (CO), sulfur dioxide (SO2) and nitric oxide (NO) in

73

Tehran had downward trends during the years 2002-2017 (Arhami et al., 2017; Zarandi et al.,

74

2015), while the concentrations of PM2.5, PM10, nitrogen dioxide (NO2) and ozone (O3) had

75

3

ACCEPTED MANUSCRIPT 76

respectively, about 3 and 4 times higher than the national standard limits in 2017

77

(Khodarahmi et al., 2016). Similarly, the concentrations of CO, SO2, NO, NO2 and O3 were

78

reported to be somewhat high as well (Ghozikali et al., 2016).

79

The relationship between air pollution and mortality/hospitalizations in the countries has been

80

well-established (Atkinson et al., 2015; Khaniabadi et al., 2018; Rückerl et al., 2011).

81

Numerous cohort studies suggesting a relationship between long-term exposure to air

82

pollution and mortality in the world, especially with rapid urbanization and industrialization

83

SC

RI PT

rising trends (Jaafari et al., 2017). The mean concentrations of PM2.5 and PM10 were,

84

2016; Fischer et al., 2015; Pope III et al., 2017). Traffic and combustion sources have been

85

previously associated with short-term cardiovascular and respiratory diseases (Bravo et al.,

86

2017; Kim et al., 2012; Samoli et al., 2016). Moreover, there is increasing evidence of the

87

effects of PM with aerodynamic diameters less than 10 and 2.5 µm (PM10 and PM2.5) on

88

cardiovascular disease and respiratory disease (Kloog et al., 2014; Lepeule et al., 2012; Lu et

89

TE D

M AN U

(Ancona et al., 2015; Beelen et al., 2014; Cesaroni et al., 2013; Chen et al., 2013; Chen et al.,

90

associated with air pollution related to mortality and hospitalization in various Iranian cities.

91

However, there is no complete and comprehensive analysis of these data, which together with

92

their integration should generate the precious conclusion. Hence, we decided to do a

93

AC C

EP

al., 2015). Various studies have been carried out concerning the adverse health effects

systematic review and meta-analysis of these data. The objective of this review was to

94

perform a systematic review and meta-analysis of the epidemiological studies to evaluate

95

mortality and hospitalizations due to cardiovascular and respiratory diseases associated with

96

air pollution in Iran.

97 98

2. Methods

99

4

ACCEPTED MANUSCRIPT 100

PROSPERO and is available at https:// www. crd. york. ac. uk/ PROSPERO/ display_record

101

.asp ? ID=CRD42018088770. A complete PRISMA (Preferred Reporting Items for

102

Systematic Reviews and Meta-Analysis) checklist (Moher et al., 2015) is presented in the

103

supplementary material (Table S1).

104

RI PT

The protocol information for present systematic review and meta-analysis were registered on

2.1. Study selection

SC

Two investigators (B.K and B.S) simultaneously searched the databases of PubMed,

105 106 107 108

MagIran, IranMedex and Scientific Information Databank (SID). The databases were

109

searched from January 1980 to January 2018 for studies investigating the all-cause mortality

110

as well as mortality and hospitalization relevant to cardiovascular and respiratory diseases

111

which linked with exposure to air pollution. The following search keywords were used “air

112

pollution”, “air pollutant”, “particulate”, “particles”, “PM10”, “PM2.5”, “carbon monoxide”,

113

TE D

M AN U

EMBASE, Web of Science, Scopus, Ovid, Google Scholar; and Iranian databases including

“CO”, “nitrogen dioxide”, “NO2”, “nitric oxide”, “nitrogen oxide”, “nitrogen monoxide”,

114

“NO”, “sulfur dioxide”, “sulphur dioxide”, “SO2”, “ozone” or “O3” linked with “mortality”,

115

“cardiopulmonary

“hospital

116

admission” or “human health”. The reference lists of eligible articles were explored to find

117

“respiratory

mortality”,

“hospitalization”,

AC C

EP

mortality”,

the most relevant articles as well. Using PRISMA guidelines, article titles and abstracts were

118

first judged independently by two authors to choose the appropriate studies. The final

119

inclusion of studies was made on the basis of full article investigation. In cases of

120

uncertainties and inconsistency, the differences were resolved by a third author (SS).

121

Publications were judged to be included in this review study if following inclusion criteria

122

applied: they reported a risk estimate for the relationship between exposure to air pollution

123

and all-cause mortality as well as mortality/hospitalization due to cardiovascular and

124

5

ACCEPTED MANUSCRIPT respiratory diseases (Supplementary Table S2). Letters to the editor, systematic review

125

studies, and review studies were excluded.

126 127 128

Information for each study was extracted by two authors independently, including the name

129

of the first author, study design, year of study, sample size, concentrations of air pollutants,

130

the main findings of mortality or hospitalization, latitude, province, city, and year of

131

publication (Supplementary Table S1, Appendix A). The following extracted information for

132

SC

RI PT

2.2. Data extraction

133

pollutants, relative risk (RR) with 95% confidence interval (CI), numbers of all-cause

134

mortality, as well as mortality/hospitalization due to cardiovascular and respiratory diseases.

135

2.3. Risk of bias assessment

M AN U

the present review study was used: mean concentrations and standard deviations of air

TE D

The risk of bias of each study was evaluated using the Office of Health Assessment and

136 137 138 139

Sciences-National Toxicology program (NIEHS-NTP) and the Navigation Guide from the

140

University of California, San Francisco (OHAT, 2015). The risks of bias were assessed for

141

following items: selection bias, confounders, exposure assessment, outcome assessment,

142

AC C

EP

Translation (OHAT) method presented by the National Institutes of Environmental Health

incomplete outcome data, selective reporting, and conflict of interest (Table 2 and more

143

analytically in Table S2 Appendix B and C). With regards to pre-specific criteria, the risk of

144

bias per each item was given as “low”, “probably low”, “probably high”, “high”, or “not

145

applicable”.

146 147

2.4. Data analysis

148

6

ACCEPTED MANUSCRIPT 149

College Station, TX) and R software version 3.3.2 (R Core Team 2015). The heterogeneity of

150

studies was assessed by both Q test (P<0.10 as significant) and the coefficient of

151

inconsistency (I2). The value of I2 equals 25% indicating low heterogeneity and if it exceeds

152

75% suggesting high heterogeneity. Random-effects models and fixed-effect models were

153

applied to calculate the effect size of studies based on Mantel-Haenszel and DerSimonian

154

methods, respectively (DerSimonian and Laird, 1986). The pooled effect estimates of the

155

concentration of all air pollutants and the RR with 95% CI for mortality/hospitalization were

156

SC

RI PT

Statistical analyses were performed with STATA software version 12 (STATA Corporation,

157

were computed according to the following formula.

158

M AN U

calculated using the random-effects models. The percent changes in mortality/hospitalization

159

The publication bias was examined by constructing funnel plots of the log risk ratio versus

160

the standard error (SE). The source of heterogeneity was investigated by the application of

161

meta-regression analysis for geographical latitude, year of study and sample size.

162

TE D

Percent change (%) = (ln (RR-1)) × 100%

163

and the causes of mortality and hospitalization. Begg’s and Egger’s tests were used for the

164

regression asymmetry test (P<0.10 as significant) and adjusted for publication bias following

165

the “Trim and Fill” method if needed. Sensitivity analysis was performed to determine the

166

AC C

EP

Additionally, the subgroup analyses were performed by study design, type of air pollutants,

effect of removing each study.

167 168

3. Results

169

3.1. Included studies

170

With a preliminary search of national and international databases, 1704 peer-reviewed studies

171

were identified. Of them, 197 articles were excluded because of the overlap between

172

databases. By reviewing the remaining articles, 1424 articles were removed since they were

173

7

ACCEPTED MANUSCRIPT 174

read and after a qualitative assessment, 45 articles were also excluded. Finally, 38 articles

175

were fulfilled the quality assessment criteria and they were included in this meta-analysis

176

(Fig. 1). Of which, 36 studies were cross-sectional and 2 time-series. Twenty four articles

177

simultaneously examined both mortality and hospitalization, 2 studies only explored all-cause

178

mortality, 3 studies investigated mortality related to both cardiovascular and respiratory

179

diseases, and 4 studies explored hospitalization related to both cardiovascular and respiratory

180

diseases (Table 1). Table 2 shows the risk of bias for each selected study. Further details of

181

SC

RI PT

unrelated to the aim of this study. The full texts of the remaining 83 articles were completely

182

Concerning the exposure assessment, the risk of bias was ‘low’ in the most of cases,

183

‘probably low’ risk or ‘probably high’ risk in some cases, and only two studies had ‘high’

184

risk.

185

TE D

Table 1. Studies included in the meta-analysis

M AN U

individual studies are given in supplementary material (Table S2, Appendix B, and C).

186 187 188

Table 2. Risk of bias rating for each study.

189

EP

Fig.1. PRISMA flowchart for literature selection and study identification (Moher et al., 2015)

190 191

Table 3 provides the pooled mean concentrations of O3, PM2.5, PM10, NO2, NOx, SO2 and

192

AC C

3.2. Concentrations of air pollutants

CO. As shown in Table 3, the pooled mean concentrations of CO and PM10 were the highest

193

exposure (2620 mg/m3 and 112.3 µg/m³), followed by NOx (95.9 µg/m³). The forest plots of

194

pooled concentrations of O3, PM2.5, PM10, NO2, NOx, SO2, and CO are given in

195

supplementary material (Figs. S1-4, Appendix C). Fig. 2 shows the mean concentration of

196

PM10 and the mean number of mortalities caused by PM10 derived from studies. The highest

197

concentrations of PM10 were observed in cities located in the western part of Iran.

198 199

8

ACCEPTED MANUSCRIPT Fig. 2. Pooled mean concentrations of PM10 and the mean number of mortality associated with PM10 based on

200

locations.

201 202

Table 3. Pooled mean concentrations of O3, PM2.5, PM10, NO2, NOx, SO2 and CO derived from studies.

203

RI PT

204

3.3. All-cause mortality

205 206

in Table 3. The highest all-cause mortality was associated with exposure to PM2.5. The forest

207

plots of the association between all-cause mortality and exposure to O3, PM2.5, PM10, NO2,

208

NOx, SO2, CO are presented in supplementary material (Figs. S5-10, Appendix D). Using

209

M AN U

SC

The association between the pooled amounts of all-cause mortality and air pollutants is given

210

46.4 µg/m³ which was responsible for the high mortality rate (680 deaths), and PM10 with a

211

pooled mean concentration of 112.3 µg/m³ attributed to the second highest mortality rate (253

212

deaths) (Table 4). An increasing of concentrations of PM10 and PM2.5 were associated with an

213

elevating of all-cause mortality after considering the quartile of mortality rate (Fig. 3 (A) and

214

(B)). The pooled percent changes for all-cause mortality rate in relation to exposure to all air

215

pollutants were 0.6% (95% CI 0.5%-0.7%). For all-cause mortality, the highest percent

216

EP

TE D

random-effects model, the results showed that the pooled mean concentration of PM2.5 was

217

changes in all-cause mortality rates with regard to the type of air pollutants are illustrated in

218

AC C

change (1.5%, 95% CI 1.3%-1.7%) was related to PM2.5 exposure. The pooled percent

Fig. 4 (A).

219 220

Table 4. The pooled numbers of all-cause mortality related to O3, PM2.5, PM10, NO2, NOx, SO2 and CO.

221 222

Fig. 3. The association between (A) PM10 and (B) PM2.5 and number of all-cause mortality.

223 224

3.4. Cardiovascular mortality

225

9

ACCEPTED MANUSCRIPT 226

increase in all air pollutants. The same increase (0.5%, 95% CI 0.4%-0.6%) in cardiovascular

227

mortality per 10 µg/m3 increase in PM2.5 was observed as well. The highest percent change

228

increase in cardiovascular mortality (35.5%, 95% CI 8.5%-58.5%) was related to CO

229

exposure. The second highest percent change in cardiovascular mortality (0.8%, 95% CI

230

0.6%-1.0%) was related to SO2 exposure. The pooled percent changes in cardiovascular

231

mortality rates with regard to the type of air pollutants are illustrated in Fig. 4 (B). The

232

association between the pooled numbers of cardiovascular mortality and air pollutants is

233

SC

RI PT

We obtained a 0.50% (95% CI 0.4%-0.6%) increase in cardiovascular mortality per 10 µg/m3

234

to O3, PM2.5, PM10, NO2, NOx, SO2, and CO are presented in supplementary material (Fig.

235

S11, Appendix D).

236

M AN U

given in Table 3. The forest plots of cardiovascular mortality rates associated with exposure

3.5. Respiratory mortality

237 238

pollutants are illustrated in Fig. 4(C). A 10 µg/m3 increase in all air pollutants corresponded

239

TE D

The pooled percent changes in respiratory mortality rates with regard to the type of air

240

respiratory mortality (2.4%, 95% CI -5.8%-10.7%) was related to CO exposure, the second

241

highest percent change in respiratory mortality (1%, 95% CI, 0.6%-1.3%) was related to

242

PM10 exposure. The association between the pooled numbers of respiratory mortality and air

243

AC C

EP

to a 0.8% (95% CI 0.6%-0.9%) in respiratory mortality. The highest percent change in

pollutants is given in Table 3(C). Among all air pollutants, the highest respiratory mortality

244

rate was associated with exposure to PM2.5 (490 deaths). The forest plots of all-cause

245

mortality rates associated with exposure to O3, PM2.5, PM10, NO2, NOx, SO2, and CO are

246

presented in supplementary material (Fig. S12, Appendix D).

247 248

3.6. Hospitalization due to cardiovascular and respiratory diseases

10

249

ACCEPTED MANUSCRIPT 250

and respiratory diseases in relation to exposure to all air pollutants were 0.7% (95% CI 0.6%-

251

0.9%). The highest pooled percent change for hospitalization was related to CO exposure

252

(17.3%, 95% CI 3.0%-31.5%), and the second highest percent change was related to SO2

253

exposure (1.3%, 95% CI 0.1%-2.5%). The association between the pooled numbers of

254

hospitalization and air pollutants is given in Table 3 (D). Among all air pollutants, the highest

255

hospitalization was associated with exposure to PM2.5 (1558 cases), followed by PM10 (563

256

cases). The forest plots of hospitalization associated with exposure to O3, PM2.5, PM10, NO2,

257

NOx, SO2, and CO are presented in supplementary material (Fig. S13, Appendix D).

258

M AN U

SC

RI PT

As shown in Fig. 4(D), the pooled percent changes for hospitalization due to cardiovascular

259

Fig. 4. Pooled percent changes in (A) all-cause, (B) cardiovascular and (C) respiratory mortality, and (D)

260

hospitalization in relation to pooled concentrations of CO, NO2, O3, PM10, PM2.5, and SO2 with 95% CI.

261

TE D

3.8. Additional analyses

262 263 264

significant source of heterogeneity (p<0.05), while the year of study and sample size were

265

not. Funnel plot was slightly asymmetric and the result of Egger's test was significant

266

EP

Using a meta-regression model, the findings showed that only geographical latitude was a

267

method showed that 57 studies required to obtain a full symmetry in Funnel plot (Q=421 and

268

AC C

(p<0.001) (supplementary material, Figs. S14-16, Appendix D). Using the trim and fill

p<0.001) (supplementary material, Fig. S17, Appendix D). The sensitivity analysis test

269

showed that there was no significant change in the results (supplementary material, Fig. S18,

270

Appendix E).

271 272

4. Discussion

273

The results of this study showed a significant relationship between mortality and

274

hospitalization with exposure to air pollutants of O3, PM2.5, PM10, NO2, NOx, SO2, and CO.

275

11

ACCEPTED MANUSCRIPT 276

60.1, 46.4, 112.3, 58.0, 95.9 and 34.8 µg/m³. Among these air pollutants, the pooled mean

277

concentration of PM10 (112.3 µg/m3) was the highest exposure and this concentration was

278

2.26 times greater than the concentration (50 µg/m3) suggested by the WHO guideline (Miri

279

et al., 2016). The pooled mean concentration of PM2.5 (46.4 µg/m3) was 1.85 times greater

280

than the concentration (25 µg/m³) proposed by WHO guideline (Miri et al., 2016). Beelen et

281

al. in a study found that a concentration of about 20 µg/m³ of PM2.5, slightly lower than the

282

concentration (25 µg/m³) suggested by WHO guideline, associated with an increased risk of

283

SC

RI PT

The pooled mean concentrations for O3, PM2.5, PM10, NO2, NOx, and SO2 were, respectively;

284

considerably high concentrations of PM2.5 and PM10 (Goudarzi et al., 2017; Goudarzi et al.,

285

2015b; Shahsavani et al., 2012). Shahsavani et al. in a study found substantially higher

286

concentrations of PM10 (319.6 ± 407 µg/m3) and PM2.5 (69.5 ± 83.2 µg/m3) (Shahsavani et

287

al., 2012). Similarly, Goudarzi et al. in two studies measured a remarkably high concentration

288

of PM10 which was probably related to dust storms (in respectively 261 and 360 µg/m3)

289

TE D

M AN U

mortality (Beelen et al., 2014). Three studies we included in this meta-analysis, they reported

290

concentrations of PM2.5 and PM10 reported by these 3 studies could be contributed to high

291

pooled concentrations of PM2.5 and PM10 observed in this meta-analysis. In agreement with

292

remarkably high pooled concentrations of PM2.5 and PM10 in this review, a study carried out

293

AC C

EP

(Goudarzi et al., 2017; Goudarzi et al., 2015b). Thus, findings of considerably high

by Draxler et al. in countries located in the west and south of Iran, the concentrations of

294

PM10 reported to be very high (3000 µg/m3) (Draxler et al., 2001). However, this

295

concentration was almost 27 times higher than the pooled mean concentration of PM10

296

obtained from this study. Meng and Lu found that the mean concentration of PM2.5 was 217

297

µg/m3 (Meng and Lu, 2007) which were 4 times higher than the pooled mean concentration

298

of PM2.5 in the present study. These findings proposed that probably dust storms in this meta-

299

analysis could be an important source of high concentrations of PM10. The other possible

300

12

ACCEPTED MANUSCRIPT 301

close to cities.

302

We observed an association between the increasing concentration of PM2.5 and the elevating

303

risks of the all-cause, cardiovascular and respiratory mortality. In parallel to our findings,

304

Beelen et al. reported that the most cases of mortality due to particulate matter were related to

305

PM2.5, while coarse particles had less effect (Beelen et al., 2014). The same results were also

306

reported in nurses’ health study (Puett et al., 2009). The association between the percent

307

changes in all-cause, cardiovascular and respiratory mortality and PM10 and PM2.5 for 10-

308

µg/m3 increase in this study has been compared with other studies in Table 5.

309

M AN U

SC

RI PT

sources could be particulate matters released from cars as well as industries which located

310

Table 5. The percent change of all-cause, cardiovascular and respiratory mortality (95% CI) for a 10-µg/m3

311

increase in the average concentration of PM10 and PM2.5 in this study compared with other studies

312

TE D

We found that the pooled RR of all-cause mortality based on 10 µg/m³ increase of PM2.5 was

313 314 315

the RRs of mortality from long-term exposure to PM2.5 were 1.04, 1.06, and 1.13,

316

respectively; which were slightly higher than our results (Ballester et al., 2008; Beelen et al.,

317

EP

1.015. Three studies conducted by Ballester et al., Pope et al. and Beelen et al. showed that

318

Society Study on Los Angeles population reported being much higher (Jerrett et al., 2005).

319

AC C

2014; Pope III et al., 2002). The RR of mortality (1.17) related to PM2.5 exposure in cancer

In the present study, the health effects reported by studies differed. The discrepancy in

320

relation to the estimating of the health effects between studies might be explained by different

321

definitions used for health effects. Other factors such as population size, sources of air

322

pollution, the intensity of exposure, and the components of PMs might be responsible for

323

observed health effects. The underlying mechanisms of health effects associated with PMs

324

are poorly understood. Nonetheless, PMs are well-known causing biochemical stresses such

325

as systemic inflammation and oxidative stress (Møller et al., 2014). Chronic inflammation

326

13

ACCEPTED MANUSCRIPT 327

known as indicators of the biological aging of cells (Karimi et al., 2017). To confirm this,

328

McCracken et al. in a study among the elderly population found that the prolonged exposure

329

to PM in high traffic areas associated with a shortened length of telomere (McCracken et al.,

330

2010).

331

RI PT

and oxidative stress are associated with shortened telomeres, and subsequently, they are

332

1.001–1.004), which was lower than those RR values reported by Beelen et al. (1.01, 95% CI

333

0.99–1.03) and Mills et al. (1.007, 95% CI 1.004–1.010) (Beelen et al., 2014; Mills et al.,

334

SC

In the present study, the RR value for all-cause mortality due to NO2 was 1.003 (95% CI

335

respiratory diseases such as asthma and subsequently the number of hospitalizations due to

336

respiratory diseases increased (Mohammadi et al., 2016). Since most of the Iranian people

337

often use their own cars, the high exposure to NO2 in the present study could be explained by

338

the high number of cars used and also the intense traffic jam.

339

The trend of O3 concentration in Iran has been steadily increased over the last two decades,

340

TE D

M AN U

2015) A study reported that exposures to NO2 were associated with the prevalence increase of

341

elevated concentration of 10 µg/m3 of O3 resulted in an increase of 0.4% in all-cause

342

mortality. This finding was roughly close to those results reported by four studies: a meta-

343

analysis study conducted by WHO (0.3%), a systematic review of Chinese studies (0.48%),

344

AC C

EP

with higher concentrations in the warm seasons (Zarandi et al., 2015). We revealed that the

the Chinese PAPA study (0.31%), and a Canadian cohort study with a follow-up of 16 years

345

(0.34%)(Anderson et al., 2004; Crouse et al., 2015; Shang et al., 2013; Wong et al., 2008). In

346

contrast, Carey et al. and Ghorbani et al. observed a negative relationship between the annual

347

mean concentration of O3 and the mortality rate (both RR=0.98) (Carey et al., 2013;

348

Ghorbani et al., 2017).

349

Among the air pollutants, an increase of 10 mg/m3 in CO concentration was significantly

350

associated with an elevated RR of hospitalization (1.173, 95% CI 1.030–1.315). Zheng et al.

351

14

ACCEPTED MANUSCRIPT 352

findings found that the RR of hospitalization related to CO exposure was 1.045 (95% CI

353

1.029-1.061) which was somewhat lower than our RR value, while a considerably higher RR

354

(1.490, 95% CI 1.250-1.770) was found by Shahi et al. (Shahi et al., 2014). The mechanism

355

of health effects related to CO is poorly understood. Nonetheless, CO quickly bonds with

356

hemoglobin and interferes with oxygen release in tissues. Then, cardiovascular dysfunction

357

includes myocardial infarction, arrhythmia and angina could occur (Lee et al., 2015).

358

The estimates derived from this study could be applied to health risk assessments of air

359

SC

RI PT

(Zheng et al., 2015) in a systematic review and meta-analysis study in accordance of our

360

effectively synthesize existing data of all types and design data collection efforts in a variety

361

of research contexts. However, evidence of mortality and hospitalizations, especially for

362

chronic obstructive pulmonary disease (COPD) and myocardial infarction, is still insufficient

363

for meta-analysis.

364

TE D

5. Conclusions

M AN U

pollutants in Iran and a meta-analysis is a versatile tool that can help researchers more

365 366 367

associated with air pollution in Iran. All investigated air pollutants were associated with

368

increased risk of mortality and hospitalization due to cardiovascular and respiratory diseases,

369

AC C

EP

This is the first systematic review and meta-analysis of mortality and hospitalization

but the effects of PM2.5 and PM10 were stronger. So identifying the concentrations and

370

sources of air pollutants will help to establish the new regulations for control measures. This

371

subsequently leads to the diminishing of mortality and hospitalization. Moreover, further

372

cohort-based studies in this field are needed to be conducted to better investigate the effects

373

of air pollution on health effects.

374 375

Acknowledgments: This study was supported by Arak University of Medical Sciences, Iran. The authors will

376

like to thank Dr. Masoud Behzadfar for providing us the additional analyses.

377

15

ACCEPTED MANUSCRIPT 378 Supplementary data

379

Supplementary data to this article can be found in Tables S1-2 and Figs S1-18.

380 381 382

Ancona, C., Badaloni, C., Mataloni, F., Bolignano, A., Bucci, S., Cesaroni, G., Sozzi, R., Davoli, M., Forastiere, F., 2015. Mortality and morbidity in a population exposed to multiple sources of air pollution: A retrospective cohort study using air dispersion models. Environmental research 137, 467-474. Anderson, H.R., Atkinson, R.W., Peacock, J., Marston, L., Konstantinou, K., Organization, W.H., 2004. Meta-analysis of time-series studies and panel studies of particulate matter (PM) and ozone (O3): report of a WHO task group. Arhami, M., Hosseini, V., Shahne, M.Z., Bigdeli, M., Lai, A., Schauer, J.J., 2017. Seasonal trends, chemical speciation and source apportionment of fine PM in Tehran. Atmospheric Environment 153, 70-82. Atkinson, R.W., Mills, I.C ,.Walton, H.A., Anderson, H.R., 2015. Fine particle components and health—a systematic review and meta-analysis of epidemiological time series studies of daily mortality and hospital admissions. Journal of Exposure Science and Environmental Epidemiology 25 , .208 Bahrami Asl, F., Kermani, M., Aghaei, M., Karimzadeh, S., Salahshour Arian, S., Shahsavani, A., Goudarzi, G., 2015. Estimation of Diseases and Mortality Attributed to NO2 pollutant in five metropolises of Iran using AirQ model in 2011-2012. Journal of Mazandaran University of Medical Sciences 24, 239-249. Ballester, F., Medina, S., Boldo, E., Goodman, P., Neuberger, M., Iñiguez, C., Künzli, N., 2008. Reducing ambient levels of fine particulates could substantially improve health: a mortality impact assessment for 26 European cities. Journal of Epidemiology & Community Health 62, 98-105. Beelen, R., Raaschou-Nielsen, O., Stafoggia, M., Andersen, Z.J., Weinmayr, G., Hoffmann, B., Wolf, K., Samoli, E., Fischer, P., Nieuwenhuijsen, M., 2014. Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project. The Lancet 383, 785-795. Brauer, M., 2016. The global burden of disease from air pollution, 2016 AAAS Annual Meeting (February 11-15, 2016). aaas. Bravo, M.A., Ebisu, K., Dominici, F., Wang, Y., Peng, R.D., Bell, M.L., 2017. Airborne fine particles and risk of hospital admissions for understudied populations: effects by urbanicity and short-term cumulative exposures in 708 US counties. Environmental health perspectives 125, 594. Carey, I.M., Atkinson, R.W., Kent, A.J., Van Staa, T., Cook, D.G., Anderson, H.R., 2013. Mortality associations with long-term exposure to outdoor air pollution in a national English cohort. American journal of respiratory and critical care medicine 187, 1226-1233. Cesaroni, G., Badaloni, C., Gariazzo, C., Stafoggia, M., Sozzi, R., Davoli, M., Forastiere, F., 2013. Longterm exposure to urban air pollution and mortality in a cohort of more than a million adults in Rome. Environmental health perspectives 121, 324. Chen, H., Goldberg, M.S., Burnett, R.T., Jerrett, M., Wheeler, A.J., Villeneuve, P.J., 2013. Long-term exposure to traffic-related air pollution and cardiovascular mortality. Epidemiology 24, 35-43. Chen, X., Zhang, L.-w., Huang, J.-j., Song, F.-j., Zhang, L.-p., Qian, Z.-m., Trevathan, E., Mao, H.-j., Han, B., Vaughn, M., 2016. Long-term exposure to urban air pollution and lung cancer mortality: A 12-year cohort study in Northern China. Science of The Total Environment 571, 855-861. Crouse, D.L., Peters, P.A., Hystad, P., Brook, J.R., van Donkelaar, A., Martin, R.V., Villeneuve, P.J., Jerrett, M., Goldberg, M.S., Pope III, C.A., 2015. Ambient PM2. 5, O3, and NO2 exposures and

383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425

AC C

EP

TE D

M AN U

SC

RI PT

References

16

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

associations with mortality over 16 years of follow-up in the Canadian Census Health and Environment Cohort (CanCHEC). Environmental health perspectives 123, 1180. Dadbakhsh, M., Khanjani, N., Bahrampour, A., 2015. Death from respiratory diseases and air pollutants in Shiraz, Iran (2006-2012). Journal of Environment Pollution and Human Health 3, 4-11. Daryanoosh, M., Goudarzi, G., Rashidi, R., Keishams, F., Hopke, P.K., Mohammadi, M.J., Nourmoradi, H., Sicard, P., Takdastan, A., Vosoughi, M., 2017. Risk of morbidity attributed to ambient PM10 in the western cities of Iran. Toxin Reviews, 1-6. DerSimonian, R., Laird, N., 1986. Meta-analysis in clinical trials. Controlled clinical trials 7, 177-188. Draxler, R.R., Gillette, D.A., Kirkpatrick, J.S., Heller, J., 2001 .Estimating PM 10 air concentrations from dust storms in Iraq, Kuwait and Saudi Arabia. Atmospheric Environment 35, 4315-4330. Fischer, P.H., Marra, M., Ameling, C.B., Hoek, G., Beelen, R., de Hoogh, K., Breugelmans, O., Kruize, H., Janssen, N.A., Houthuijs, D., 2015. Air pollution and mortality in seven million adults: the Dutch Environmental Longitudinal Study (DUELS). Environmental health perspectives 123, 697. Geravandi, S., Goudarzi, G., Yari, A.R., Idani, E., Yousefi, F., Soltani, F., Mohammadi, M.J., Salmanzadeh, S., Nashibi, R., Khishdost, M., 2016. An estimation of COPD cases and respiratory mortality related to ground-level ozone in the metropolitan Ahvaz during 2011. Archives of Hygiene Sciences Volume 5. Geravandi, S., Zallaghi, E., Goudarzi ,G., Yari, A.R., Soltani, F., Shireigi, E., Mohammadi, M.J., Kalantar, F., Mohamadrezai Esfarjani, N., Shaghayegh Alavi, S., 2015. Effects of PM10 on human health in the western half of Iran (Ahwaz, Bushehr and Kermanshah Cities). Archives of Hygiene Sciences 4, 179186. Ghanbari Ghozikali, M., Mosaferi, M., Nadafi, K., 2014. Quantification Of The Health Effects Of Exposure To Ozone In Tabriz By Using AIRQ Model. Urmia Medical Journal 25, 521-530. Gharehchahi, E., Mahvi, A.H., Amini, H., Nabizadeh, R., Akhlaghi, A.A., Shamsipour, M., Yunesian, M., 2013. Health impact assessment of air pollution in Shiraz, Iran: a two-part study. Journal of Environmental Health Science and Engineering 11, 11. Gholampour, A., Nabizadeh, R., Naseri, S., Yunesian, M., Taghipour, H., Rastkari, N., Nazmara, S., Faridi, S., Mahvi, A.H., 2014. Exposure and health impacts of outdoor particulate matter in two urban and industrialized area of Tabriz, Iran. Journal of Environmental Health Science and Engineering 12, 27. Ghorbani, N ,.Yazdani Charati, J., Etemadinejad, S., 2017. Relationship between Air Pollution and Mortality Rate due to Cardiovascular Diseases in Mashhad, Iran 2011. Journal of Mazandaran University of Medical Sciences 26, 47-55. Ghozikali, M.G., Heibati, B., Naddafi ,K., Kloog, I., Conti, G.O., Polosa, R., Ferrante, M., 2016. Evaluation of chronic obstructive pulmonary disease (COPD) attributed to atmospheric O 3, NO 2, and SO 2 using Air Q Model (2011–2012 year). Environmental research 144, 99-105. Goudarzi, G., Daryanoosh, S., Godini, H., Hopke, P., Sicard, P., De Marco, A., Rad, H., Harbizadeh, A., Jahedi, F., Mohammadi, M., 2017. Health risk assessment of exposure to the Middle-Eastern Dust storms in the Iranian megacity of Kermanshah. public health 148, 109-116. Goudarzi, G., Geravandi, S., Foruozandeh, H., Babaei, A.A., Alavi, N., Niri, M.V., Khodayar, M.J., Salmanzadeh, S., Mohammadi, M.J., 2015a. Cardiovascular and respiratory mortality attributed to ground-level ozone in Ahvaz, Iran. Environmental monitoring and assessment 187, 487. Goudarzi, G., Geravandi, S., Saeidimehr, S., Mohammadi, M., Vosoughi Niri, M., Salmanzadeh, S., Ahmadi Angali, K., Neisi, A., Babaei, A., 2015b. Estimation of health effects for PM10 exposure using of Air Q model in Ahvaz City during 2009. Iranian Journal of Health and Environment 8, 117-126. Goudarzi, G., Mohammadi, M.J., Angali, K.A., Neisi, A.K., Babaei, A.A., Mohammadi, B., Soleimani, Z., Geravandi, S., 2012. Estimation of health effects attributed to no2 exposure using airq model. Archives of Hygiene Sciences Volume 1. Heger, M., Sarraf, M., 2018. Air Pollution in Tehran: Health Costs, Sources, and Policies. World Bank. http://documents.worldbank.org/curated/en/160681527012587818/pdf/126402-NWP-PUBLICTehran-WEB-updated.pd [accessed 26 September 2018].

17

426 427 428 429 430 431 432 433 434 435 436 437 438 439 440 441 442 443 444 445 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

Hosseini, G., Maleki, A., Amini, H., Mohammadi, S., Hassanvand, M.S., Giahi, O., Gharibi, F., 2014. Health impact assessment of particulate matter in Sanandaj, Kurdistan, Iran. Journal of Advances in Environmental Health Research 2. Jaafari, J., Naddafi, K., Yunesian, M., Nabizadeh, R., Hassanvand, M.S., Ghozikali, M.G., Nazmara, S., Shamsollahi, H.R., Yaghmaeian, K., 2017. Study of PM10, PM2. 5, and PM1 levels in during dust storms and local air pollution events in urban and rural sites in Tehran. Human and Ecological Risk Assessment: An International Journal, 1-12. Jerrett, M., Burnett, R.T., Ma, R., Pope III, C.A., Krewski, D., Newbold, K.B., Thurston, G., Shi, Y., Finkelstein, N., Calle, E.E., 2005. Spatial analysis of air pollution and mortality in Los Angeles. Epidemiology 16, 727-736. Joneidi jafari, Zohor A, Rezaie R, Malekafzali Sh, A, S., 2010. Estimation of hearty and respiration dead by air pollution of Tehran city based on particulate matter Teb and tazkie journal 74-75, 37-47 Karimi, B., Nabizadeh, R., Yunesian, M., Mehdipour, P., Rastkari, N., Aghaie, A., 2017. Foods, Dietary Patterns and Occupational Class and Leukocyte Telomere Length in the Male Population. American journal of men's health, 1557988317743385. Kermani, M., Aghaei, M., 2016. Estimation of cardiovascular death, myocardial infarction and chronic obstructive pulmonary disease) COPD) attributed to PM and SO2 in the air of Tehran metropolis. Journal of Research in Environmental Health 2, 116-126. Kermani, M., Aghaei, M., Dolati, M., 2016a. Estimation the Number of Mortality Due to Cardiovascular and Respiratory disease, Attributed to pollutants O3, and NO2 in the Air of Tehran. Journal of health research in community 1, 1-11. Kermani, M., Aghaei, M., Gholami, M., Asl, F., Karimzadeh, S., Jokandan, S., Dowlati, M., 2016b. Estimation of mortality attributed to PM2. 5 and CO exposure in eight industrialized cities of Iran during 2011. Iran Occupational Health 13, 49-61. Kermani, M., Bahrami Asl, F., Aghaei, M., Karimzadeh, S., Arfaeinia, H., Godarzi, G., Salahshour Arian, S., 2015. Quantification of Health Effects Attributed to Ozone in Five Metropolises of Iran Using AirQ Model. Journal of Health 6, 266-280. Khamutian, R., Sharafi, K., Najafi, F., Shahhoseini, M., 2014. Association of Air Pollution and Hospital Admission for Cardiovascular Disease: A. Khaniabadi, Y.O., Goudarzi, G ,.Daryanoosh, S.M., Borgini, A., Tittarelli, A., De Marco, A., 2017a. Exposure to PM10, NO2, and O3 and impacts on human health. Environmental Science and Pollution Research 24, 2781-2789. Khaniabadi, Y.O., Hopke, P.K., Goudarzi, G., Daryanoosh, S.M., Jourvand, M., Basiri, H., 2017b. Cardiopulmonary mortality and COPD attributed to ambient ozone. Environmental research 152, 336-341. Khaniabadi, Y.O., Sicard, P., Takdastan, A., Hopke, P.K., Taiwo, A.M., Khaniabadi, F.O., De Marco, A., Daryanoosh, M., 2018 .Mortality and morbidity due to ambient air pollution in Iran. Clinical Epidemiology and Global Health. Khanjani, N., Ranadeh Kalankesh, L., Mansouri, F., 2012. Air pollution and Respiratory Deaths in Kerman, Iran (from 2006 till 2010). Iranian Journal of Epidemiology 8, 58-65. Khodarahmi, F., Soleimani, Z., Yousefzadeh, S., Alavi, N., Babaei, A.A., Mohammadi, M.J., Goudarzi, G., 2016. Levels of PM10, PM2. 5 and PM1 and Impacts of Meteorological Factors on Particle Matter Concentrations in Dust Events and non Dusty Days. International Journal of Health Studies 1, page: 7-12. Kim, S.-Y., Peel, J.L., Hannigan, M.P., Dutton, S.J., Sheppard, L., Clark, M.L., Vedal, S., 2012. The temporal lag structure of short-term associations of fine particulate matter chemical constituents and cardiovascular and respiratory hospitalizations. Environmental health perspectives 120, 1094. Kloog, I., Nordio, F., Zanobetti, A., Coull, B.A., Koutrakis, P., Schwartz, J.D., 2014. Short term effects of particle exposure on hospital admissions in the Mid-Atlantic states: a population estimate. PloS one 9, e88578.

18

477 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

Lee, F.-Y., Chen, W.-K., Lin, C.-L., Kao, C.-H., 2015. Carbon monoxide poisoning and subsequent cardiovascular disease risk: a nationwide population-based cohort study. Medicine 94. Lepeule, J., Laden, F., Dockery, D., Schwartz, J., 2012. Chronic exposure to fine particles and mortality: an extended follow-up of the Harvard Six Cities study from 1974 to 2009. Environmental health perspectives 120, 965. Lu, F., Xu, D., Cheng ,Y., Dong, S., Guo, C., Jiang, X., Zheng, X., 2015. Systematic review and metaanalysis of the adverse health effects of ambient PM2. 5 and PM10 pollution in the Chinese population. Environmental research 136, 196-204. Mannucci, P.M., Franchini, M., 2017 .Health effects of ambient air pollution in developing countries. International journal of environmental research and public health 14, 1048. Marzouni, M.B., Alizadeh, T., Banafsheh, M.R., Khorshiddoust, A.M., Ghozikali, M.G., Akbaripoor, S., Sharifi, R ,.Goudarzi, G., 2016. A comparison of health impacts assessment for PM 10 during two successive years in the ambient air of Kermanshah, Iran. Atmospheric Pollution Research 7, 768-774. McCracken, J., Baccarelli, A., Hoxha, M., Dioni, L., Melly, S., Coull ,B., Suh, H., Vokonas, P., Schwartz, J., 2010. Annual ambient black carbon associated with shorter telomeres in elderly men: Veterans Affairs Normative Aging Study. Environmental health perspectives 118, 1564. Meng, Z., Lu, B., 2007. Dust events as a risk factor for daily hospitalization for respiratory and cardiovascular diseases in Minqin, China. Atmospheric Environment 41, 7048-7058. Mills, I.C., Atkinson, R.W., Kang, S., Walton, H., Anderson, H., 2015. Quantitative systematic review of the associations between short-term exposure to nitrogen dioxide and mortality and hospital admissions. BMJ open 5, e006946. Miri, M., Derakhshan, Z., Allahabadi, A., Ahmadi, E., Conti, G.O., Ferrante, M., Aval, H.E., 2016. Mortality and morbidity due to exposure to outdoor air pollution in Mashhad metropolis, Iran. The AirQ model approach. Environmental research 151, 451-457. Mohammadi-Zadeh, M.J., Karbassi, A., Bidhendi, G.N., Abbaspour, M., Padash, A., 2017. An Analysis of Air Pollutants’ Emission Coefficient in the Transport Sector of Tehran. Open Journal of Ecology 7, 309. Mohammadi, A., Azhdarpoor, A., Shahsavani, A., Tabatabaee, H., 2015. Health Impacts of Exposure to PM 10 on Inhabitants of Shiraz, Iran. Health Scope 4. Mohammadi, A., Azhdarpoor, A., Shahsavani ,A., Tabatabaee, H., 2016. Investigating the health effects of exposure to criteria pollutants using AirQ2. 2.3 in Shiraz, Iran. Aerosol and Air Quality Research 16, 1035-1043. Moher, D., Shamseer, L., Clarke, M., Ghersi, D., Liberati, A., Petticrew, M ,.Shekelle, P., Stewart, L.A., 2015. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Systematic reviews 4, 1. Mokhtari, M., Miri, M., Mohammadi, A., Khorsandi, H., Hajizadeh, Y., Abdolahnejad, A., 2015 . Assessment of air quality index and health impact of PM10, PM2. 5 and SO2 in Yazd, Iran. Journal of Mazandaran University of Medical Sciences 25, 14-23. Møller, P., Danielsen, P.H., Karottki, D.G., Jantzen, K., Roursgaard, M., Klingberg, H., Jensen, D.M ,. Christophersen, D.V., Hemmingsen, J.G., Cao, Y., 2014. Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles. Mutation Research/Reviews in Mutation Research 762, 133-166. Naddafi, K., Hassanvand, M.S., Yunesian, M ,.Momeniha, F., Nabizadeh, R., Faridi, S., Gholampour, A., 2012. Health impact assessment of air pollution in megacity of Tehran, Iran. Iranian journal of environmental health science & engineering 9, 28. Nikoonahad, A., Naserifar, R., Alipour, V., Poursafar, A., Miri, M., Ghafari, H.R., Abdolahnejad, A., Nemati, S., Mohammadi, A., 2017. Assessment of hospitalization and mortality from exposure to PM10 using AirQ modeling in Ilam, Iran. Environmental Science and Pollution Research 24, 2179121796.

19

527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 571 572 573 574 575

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

SC

RI PT

Nourmoradi, H., Goudarzi, G., Daryanoosh, S.M., Omidi-Khaniabadi, F., Jourvand, M., OmidiKhaniabadi, Y., 2015. Health Impacts of Particulate Matter in Air using AirQ Model in Khorramabad City, Iran. Journal of Basic Research in Medical Sciences 2, 44-52. Nourmoradi, H., Khaniabadi, Y.O., Goudarzi, G., Daryanoosh, S.M., Khoshgoftar, M., Omidi, F., Armin, H., 2016. Air quality and health risks associated with exposure to particulate matter: a crosssectional study in Khorramabad, Iran. Health Scope 5. OHAT, 2015 .Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration. Office of Health Assessment and Translation, Division of National Toxicology Program, National Institute of Environmental Health Sciences. Omidi, Y., Goudarzi, G., Heidari, A.M., Daryanoosh, S.M., 2016. Health impact assessment of shortterm exposure to NO2 in Kermanshah, Iran using AirQ model. Environmental Health Engineering and Management Journal. Pope III, C.A., Burnett, R.T., Thun, M.J., Calle, E.E., Krewski, D., Ito, K., Thurston, G.D., 2002. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. Jama 287, 1132-1141. Pope III, C.A., Krewski, D., Gapstur, S.M., Turner, M.C., Jerrett, M., Burnett, R.T., 2017. Fine Particulate Air Pollution and Mortality: Response to Enstrom’s Reanalysis of the American Cancer Society Cancer Prevention Study II Cohort. Dose-Response 15, 1559325817746303. Puett, R.C., Hart, J.E., Yanosky, J.D., Paciorek, C., Schwartz, J., Suh, H., Speizer, F.E., Laden, F., 2009. Chronic fine and coarse particulate exposure, mortality, and coronary heart disease in the Nurses’ Health Study. Environmental health perspectives 117, 1697. Rückerl, R., Schneider, A., Breitner, S., Cyrys, J., Peters, A., 2011. Health effects of particulate air pollution: a review of epidemiological evidence. Inhalation toxicology 23, 555-592. Samoli, E., Atkinson, R.W., Analitis, A., Fuller, G.W., Green, D.C., Mudway, I., Anderson, H.R., Kelly, F.J., 2016. Associations of short-term exposure to traffic-related air pollution with cardiovascular and respiratory hospital admissions in London, UK. Occup Environ Med, oemed-2015-103136. Sefiddashti, S.E., Sari, A.A., Ghazanfa, S., 2015. The Impact of Air Pollution on Emergency Admissions of Heart Attack Cases in Tehran: 2007-2012. Journal of Health and Development 4, 190-199. Shahi, A.M., Omraninava, A., Goli, M., Soheilarezoomand, H.R., Mirzaei, N., 2014. The effects of air pollution on cardiovascular and respiratory causes of emergency admission. Emergency 2, 107. Shahsavani, A., Naddafi, K., Haghighifard, N.J., Mesdaghinia, A., Yunesian, M., Nabizadeh, R., Arahami, M., Sowlat, M., Yarahmadi, M., Saki, H., 2012. The evaluation of PM 10, PM 2.5 ,and PM 1 concentrations during the Middle Eastern Dust (MED) events in Ahvaz, Iran, from April through September 2010. Journal of Arid Environments 77, 72-83. Shang, Y., Sun, Z., Cao, J., Wang, X., Zhong, L., Bi, X., Li, H., Liu, W., Zhu, T., Huang, W .2013 ,. Systematic review of Chinese studies of short-term exposure to air pollution and daily mortality. Environment international 54, 100-111. WHO (World Health Organization), 2018. World Health Organization releases new global air pollution data. Geneva, Switzerland. http://www.ccacoalition.org/en/news/world-healthorganization-releases-new-global-air-pollution-data [accessed 26 September 2018]. Wong, C.-M., Vichit-Vadakan, N., Kan, H., Qian, Z., 2008. Public Health and Air Pollution in Asia (PAPA): a multicity study of short-term effects of air pollution on mortality. Environmental health perspectives 116, 1195. Zallaghi, E., 201 .4Assessment of health impacts attributed to PM10 exposure during 2011 in Kermanshah City, Iran. Journal of Advances in Environmental Health Research 2. Zallaghi, E., Geravandi, S., Haddad, M.N., Goudarzi, G., Valipour, L., Salmanzadeh, S., Hashemzadeh , B., Zahedi, A., Mohammadi, M.J., Soltani, F., 2015. Estimation of health effects attributed to nitrogen dioxide exposure using the AirQ model in Tabriz City, Iran. Health Scope 4. Zallaghi, E., Goudarzi, G., Geravandi, S., Mohammadi, M.J., 2014. Epidemiological indexes attributed to particulates with less than 10 micrometers in the air of Ahvaz City during 2010 to 2013. Health Scope 3.

20

576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 616 617 618 619 620 621 622 623 624 625 626

ACCEPTED MANUSCRIPT Zarandi, S.M., Alimohammadi, M., Moghaddam, V.K., Hasanvand, M.S., Miranzadeh, M.B., Rabbani, D., Mostafaii, G.R., Sarsangi, V., Hajiketabi, S., Tehrani, A.M., 2015. Long-term trends of Nitrogen oxides and surface ozone concentrations in Tehran city, 2002–2011. Journal of Environmental Health Science and Engineering 13, 63. Zheng, X.-y., Ding, H., Jiang, L.-n., Chen, S.-w ,.Zheng, J.-p., Qiu, M., Zhou, Y.-x., Chen, Q., Guan, W.-j., 2015. Association between air pollutants and asthma emergency room visits and hospital admissions in time series studies: a systematic review and meta-analysis. PloS one 10, e0138146.

627 628 629 630 631 632 633

AC C

EP

TE D

M AN U

SC

RI PT

634

21

ACCEPTED MANUSCRIPT Table 1. Studies included in the meta-analysis. Type of study Cross- sectional

Pollutants O3

Kerman, 2006 - 2010

Time series

3

(Mokhtari et al., 2015)

Yazd, 2013-2014

ecological

PM10, CO, NO, NO2, NOx, O3, SO2 PM10, PM2.5, SO2

4

(Daryanoosh et al., 2017)

Ahvaz, Khorramabad, Ilam

Cross- sectional

PM10

5

(Goudarzi et al., 2015b)

Ahvaz, during 2009

Cross- sectional

PM10

6

(Kermani et al., 2015)

Cross-sectional

O3

7

(Kermani et al., 2016b)

Mashhad, Tabriz, Shiraz, Isfahan and Arak, 2011. 8 industrial cities of Iran, 2011

Cross-sectional

PM2.5, CO

8

(Kermani and Aghaei, 2016)

Tehran, 2012

Cross-sectional

PM10, PM2.5, SO2

9

(Ghorbani et al., 2017)

Mashhad, 2012

Cross-sectional

10

(Kermani et al., 2016a)

Tehran, 2014

CO, SO2, NOx, NO2, NO, O3 NO2, O3

11 12

(Ghozikali et al., 2016) (Miri et al., 2016)

Tabriz, 2011–2012 Mashhad, 2012

13 14 15 16 17 18 19

(Goudarzi et al., 2017) (Shahsavani et al., 2012) (Marzouni et al., 2016) (Omidi et al., 2016) (Goudarzi et al., 2015a) (Khaniabadi et al., 2017a) (Nikoonahad et al., 2017)

Kermanshah, 2014 - 2015 Ahvaz, 2010 Kermanshah, 2011- 2012 Kermanshah Ahvaz Kermanshah, 2014– 2015 Ilam, 2014–2015

Cross- section Cross- section Cross- section Cross- section Cross-sectional Cross-sectional Cross-sectional

20 21 22 23 24 25 26 27

(Mohammadi et al., 2016) (Naddafi et al., 2012) (Gholampour et al., 2014) (Zallaghi et al., 2014) (Mohammadi et al., 2015) (Khaniabadi et al., 2017b) (Bahrami Asl et al., 2015) (Dadbakhsh et al., 2015)

Shiraz, 2012 Tehran, 2012 Tabriz, 2012 - 2013 Ahvaz 2010 - 2013 Shiraz, 2013 Kermanshah, 2014 - 2015 five metropolises, 2011-2012 Shiraz, 2006-2012

Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional

28 29 30 31 32 33 34 35 36 37

(Nourmoradi et al., 2015) (Hosseini et al., 2014) (Geravandi et al., 2016) (Goudarzi et al., 2012) (Zallaghi, 2014) (Geravandi et al., 2015) (Zallaghi et al., 2015) (Nourmoradi et al., 2016) (Gharehchahi et al., 2013) (Shahi et al., 2014)

Khorramabad, 2014 Sanandaj, Kurdistan, 2013 Ahvaz 2011 Ahvaz 2009 Kermanshah 2011 Ahwaz, Bushehr, Kermanshah, 2011 Tabriz, 2015 Khorramabad Shiraz, 2008-2010 Tehran, 2012

Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Cross-sectional Time series

38

(Khamutian et al., 2014)

Kermanshah, 2010-2011

Cross-sectional

SC

RI PT

Location/Period Tabriz, Iran: 2014

2

Study (Ghanbari Ghozikali et al., 2014) (Khanjani et al., 2012)

Cross-sectional

Cross-sectional Cross- section

M AN U

TE D

EP

AC C

# 1

O3, SO2 NO2 PM10, PM2.5, O3, NO2, SO2 PM10 PM10, PM2.5 PM10 NO2, O3 O3 PM10, NO2, O3 PM10 PM10, SO2, NO2, O3 O3, NO2, PM10, SO2 PM2.5, PM10 PM10 PM10 O3 NO2 O3, SO2, CO, PM10, NO, NO2, NOx PM10 PM10 O3 NO2 PM10 PM10, NO2 NO2 PM10 PM10, SO2, NO2 O3, NO2, SO2, PM10, PM2.5, CO NO, PM10, CO, O3, SO2

ACCEPTED MANUSCRIPT Table 2. Risk of bias rating for each study

23 24 25

Zallaghi et al. 2010

26 27 28

Bahrami et al. 2011

29 30

Hosseini et al. 2014

31

Goudarzi et al. 2011

32 33 34 35

Zallaghi et al. 2009

36

Gharehchahi et al. 2008

37

Shahi et al. 2012

Omidi et al. 2014 Goudarzi et al. 2012 Omidi et al. 2014 Nikoonahad et al. 2014 Mohammadi et al. 2012 Naddafi et al. 2012

Selection bias

Incomplete outcome data

Selective outcome reporting

Conflict of interest

Other

TE D

Gholampour et al. 2012 Mohammadi et al. 2013 Omidi et al. 2014

AC C

Dadbakhsh et al. 2009 Nourmoradi et al. 2006

Confounding

RI PT

Ghanbari et al. 2014 Khanjani et al. 2014 Mokhtari et al. 2013 Daryanoosh et al. 2014 Goudarzi et al. 2009 Kermani et al. 2011 Kermani et al. 2011 Kermani et al. 2013 Ghorbaniet al. 2011 Kermani et al. 2014 Ghanbari et al. 2011 Miri et al. 2015 Goudarzi et al. 2014 Shahsavani et al. 2010 Bagherian et al. 2011

Outcome assessment

SC

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

Exposure assessment

M AN U

Study

EP

#

Geravandi et al. 2013

Geravandi et al. 2011 Zallaghi et al. 2012

Nourmoradi et al. 2015

38 Khamutian et al. 2010 Risk of bias rating

Low

Probably Low

Probably high

High

ACCEPTED MANUSCRIPT

Table 3. Pooled mean concentrations of O3, PM2.5, PM10, NO2, NOx, SO2 and CO derived from studies.

O3 PM2.5 PM10 NO2 NOx SO2 CO

mean

lower

upper

Standard

Heterogeneity

df

P

I-squared

Tau-squared

60.1 46.4 112.3 57.9 95.8 34.8

45.7 31.3 73.0 46.4 24.1 19.7

74.4 61.5 151.6 69.5 167.6 49.8

2620.3

1569.1

3672.6

159 35 150 100 196 10000

66.5 2.3 89.9 28.1 0.41 28.8 5.7

19 14 26 20 2 12 5

0.00 1 0.00 0.10 0.80 0.004 0.34

71.40% 0.00% 71.10% 11.90% 0.00% 58.30% 89.70%

479.9 0 5500 0.16 0 296.8 201.8

RI PT

Pollutants

Heterogeneity

df

P

I-squared

Tau-squared

273.5 178.6 871.0 267.6 242.8 92.4 4.8 72.8

3898.1 3.6 834.3 15597.8 1930.2 650.9 56.6 34822.1

47 3 15 98 22 22 7 227

0 0.312 0 0 0 0 0 0

98.8% 15.9% 98.2% 99.4% 98.9% 96.6% 87.6% 99.3%

13000 768.1665 140000 3300 9500 898.475 3.6099 114.7866

297.3 187.1 140.7 4.8 281.4 335.5 28.2

779.7 1428.4 174.6 56.6 714.6 6970.9 12951.7

13 18 6 7 8 2 61

0 0 0 0 0 0 0

98.3% 98.7% 96.6% 87.6% 98.9% 100.0% 99.5%

2.40E+04 2.00E+03 2.20E+03 3.6099 1.30E+04 77.235 44.0957

259.3 53.6 50.5 430.5 812.0 86.4

492.7 830.5 129.7 3.8 0.0 2202.0

13 18 6 1 0 44

0 0 0 0.052 . 0

97.4% 97.8% 95.4% 73.5% .% 98.0%

6.80E+03 276.4695 320.9848 7.80E+03 0 570.446

381.9 645.6 244.7 768.9 2485.5 398.2

431.0 8851.2 401.4 40.8 0.0 10918.4

7 41 5 3 0 64

0 0 0 0 . 0

98.4% 99.5% 98.8% 92.6% .% 99.4%

2.70E+04 6.20E+04 1.90E+04 1.10E+05 0 1.70E+04

TE D

M AN U

upper

AC C

EP

Pollutants mean lower A) All-cause mortality O3 236.8 200.1 TSP 114.0 49.5 PM2.5 680.5 490.1 PM10 252.9 238.2 NO2 199.2 155.5 SO2 76.5 60.5 CO 3.0 1.3 Overall 70.1 67.5 B) Cardiovascular mortality O3 211.0 124.7 PM10 159.8 132.4 SO2 99.5 58.3 CO 3.0 1.3 NO2 204.0 126.6 PM2.5 167.0 10.0 Overall 25.3 22.3 C) Respiratory mortality O3 209.3 159.2 PM10 43.2 32.8 SO2 35.1 19.6 NO2 291.7 153.0 PM2.5 490.0 168.0 Overall 76.9 67.4 D) Hospitalization O3 246.5 111.0 PM10 563.4 481.2 NO2 128.6 12.5 SO2 418.6 68.3 PM2.5 1558.0 630.5 Overall 60.9 323.7

SC

Table 4. Pooled numbers of all-cause mortality related to O3, PM2.5, PM10, NO2, NOx, SO2 and CO.

ACCEPTED MANUSCRIPT Table 5. The percent change of all-cause, cardiovascular and respiratory mortality (95% CI) for a 10-µg/m3 increase in the average concentration of PM10 and PM2.5 in this study compared with other studies cardiovascular mortality 0.9%, 95% CI 0.3%–1.4% 0.43%, 95% CI 0.37%–0.5% 0.9%, 95% CI 0.5%–1.3% 0.58, 95% CI 0.22%–0.93% 0.44, 95% CI 0.19%–0.68% 0.7%, 95% CI 0.4%–1% – 0.44%, 95% CI 0.33%–0.54% 0.58, 95% CI 0.22%–0.93% 0.44, 95% CI 0.19%–0.68% 0.5%, 95% CI 0.1%–2.0%

AC C

EP

TE D

M AN U

SC

(Atkinson et al., 2012) (Shang et al., 2013) (Anderson et al., 2004) (Wong et al., 2008)(4 cities) (Wong et al., 2008) (3 Chinese cities) This study Study (Franklin et al., 2007) (Shang et al., 2013) (Wong et al., 2008)(4 cities) (Wong et al., 2008) (3 Chinese cities) This study

PM10 all-cause mortality 0.3%, 95% CI 0.1%–0.4% 0.32, 95% CI 0.28%–0.35% 0.6%, 95% CI 0.4%–0.8% 0.55, 95% CI 0.26%–0.85% 0.37, 95% CI 0.21%–0.54% 0.7%, 95% CI 0.6%–0.8% PM2.5 1.21%, 95% CI 0.29%– 2.14% 0.38%,95% CI 0.31%– 0.45% 0.55, 95% CI 0.26%–0.85% 1.37, 95% CI 0.21%–1.54% 1.5%, 95% CI 1.3%–1.7%

respiratory mortality 0.4%, 95% CI 0.1%–0.6% 0.32, 95% CI 0.23%–0.40% 1.3%, 95% CI 0.5%–2.0% 0.62, 95% CI 0.22%–1.02% 0.60, 95% CI 0.16%–1.04% 1.0%, 95% CI 0.6%–1.3%

RI PT

Study

1.03% 95% CI 0.02%–2.04% 0.51% 95% CI 0.30%–0.73% 0.62, 95% CI 0.22%–1.02% 0.60, 95% CI 0.16%–1.04% 0.8%, 95% CI 0.4%–1%

Identification

ACCEPTED MANUSCRIPT Records identified through database searching (N =1675)

Additional records identified through other sources (N =29; from reference)

Records screened (N =1507)

Records excluded (N =1424)

Full-text articles excluded, with reasons: Not relevant studies to CVD or Respiratory and COPD, N = 30 Abstract only, N= 5 Small sample sizes, N= 8 Letter comments, correspondence, N = 2

M AN U

SC

Eligibility

Full-text articles assessed for eligibility (N =83)

RI PT

Screening

Records after duplicates removed (N =197)

Included

Studies included in qualitative synthesis (N =38)

TE D

Studies included in quantitative synthesis (metaanalysis) (N =38)

AC C

EP

Fig 1. PRISMA Flowchart for literature selection and Study identification (Moher et al., 2015)

ACCEPTED MANUSCRIPT

( ! Ardabil

East Azerbaijan

Golestan

( ! Gilan

! (

Kurdistan

Hamadan ( !

5

Kermanshah

PM10 (µg/m3) 20 - 60

( ! Markazi

! (

( ! Ilam

Lorestan

! (

! (

Tehran

( Isfahan!

Yazd

! (

( and Bakhtiari Chaharmahal!

Khosestan

! (

( Boyer-Ahmad ! Kohgiluyeh and

Mortality ( !

! (

40 - 70

71 - 360

! (

361 - 1109

! (

1110 - 2141

EP ( ! Bushehr

( ! South Khorasan

Kerman ( !

! (Fars

AC C

131 - 269

! (

( ! Semnan

( ! Qom

61 - 100

101 - 130

Razavi Khorasan

SC

( ! Qazvin

( ! Mazandaran

M AN U

( ! Zanjan

TE D

West Azerbaijan

( ! North Khorasan

( !

RI PT

! (

( !

( !

Hormozgan ( !

Sistan and Baluchestan

ACCEPTED MANUSCRIPT

A

80

M AN U

PM2.5 (µg/m3)

200

100

Lower 230

Between 231-645

EP

TE D

60

All-cause mortality

Higher 642

AC C

PM10 (µg/m3)

100

SC

300

RI PT

B

40

Lower 210

Between 211-770

All-cause mortality

Higher 770

ACCEPTED MANUSCRIPT

A 

B 2

1

0

M AN U

0.5 

SC

1.0 

RI PT

% Change 

% Change 

1.5 

-1

NO2 

O3 

SO2 

PM10 

CO

C 

AC C

5 

0 

Pooled

PM2.5

PM10

SO2 

O3 

NO2 

NO 

NOx

D  2.5 2.0

% Change 

EP

10 

% Change 

PM2.5

TE D

Pooled 

1.5 1.0 0.5

-5 

0.0 Pooled 

CO 

NOx 

NO2 

NO 

SO2 

PM10 

O3

Pooled

SO2

NO

PM2.5 

PM10 

O3

NO2  

ACCEPTED MANUSCRIPT Highlights The relationship between exposure to air pollution with mortality and hospitalizations by conducting a systematic review and meta-analysis The risk of bias assessed by the Office of Health Assessment and Translation (OHAT) Method for each study included

AC C

EP

TE D

M AN U

SC

RI PT

The percent change of all-cause, cardiovascular and respiratory mortality and hospitalization (95% CI) for a 10-µg/m3 increase in the PM10, PM2.5, O3 and CO (per each 10 mg/m3)