The Prevalence of Asthma among Iranian Children and Adolescent: A Systematic Review and Meta-Analysis

Background Asthma is an important reason for hospitalization in children aged under five years. Information about the current status of asthma in Iranian children can help the Iranian health sector plan carefully and prevent asthma incidence by educating the families. The present systematic review and meta-analysis is aimed at estimating asthma prevalence in Iranian children and adolescents. Method Data were found using keywords such as prevalence, epidemiology, asthma, adolescent, children, pediatrics, Iran in Web of Science, Scopus, PubMed, Cochrane, and Embase databases. Three national databases, including Magiran, Barakat Pharmed Co (Iran medex), and Scientific Information Databank (SID) were searched until 1 October 2020. Cross-sectional and original studies were included in the study, and then, quality assessment was done using the National Institutes of Health's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. A pooled estimated prevalence of asthma was calculated using Der Simonian-Laird random model. Egger's test was used to evaluate publication bias. The data were analyzed using the STATA software version 16. Results 30 studies were selected and investigated. The prevalence of asthma in children and adolescents was 6% and 8%, and the prevalence in boys and girls was 9% and 8%, respectively. Among the asthma symptoms, wheezing had the most prevalence (17% in children and 19% in adolescents) and sleep disturbance had the lowest prevalence (6% in children and 6% in adolescents). Conclusion The prevalence of asthma in Iranian children and adolescents is lower than in the world. Existing strategies should be pursued followed. Also, guidelines for asthma control and prevention should be considered in the future.

400 million persons will experience asthma in the future. The prevalence of asthma in children varies according to geographical variation. However, the global prevalence is from 9.1% to 9.5% in children and from 9.1% to 10.4% in adolescents [2].
It seems that factors such as age, sex, economic status, genetics, and exposure to pollutants can affect asthma prevalence [3]. Asthma causes growth disturbance, increased health care costs, decreased quality of life, absence at school, etc. Implementation of proper strategies for recognizing the epidemiology of asthma and, consequently, appropriate treatment of the disease has effectively decreased disease burden [4].
The prevalence of asthma symptoms in children and adolescents increased worldwide, in recent years, particularly in low-middle income countries [5]. Many studies have been performed to estimate the prevalence of asthma in children and adolescents in various cities in Iran. Heidarnia et al. evaluated 19 studies between 1998 and; all of them used ISSAC protocol. The lowest and the highest prevalence were reported in Kerman (2.7%) and Tehran (35.4%), respectively [6]. The overall prevalence of asthma was estimated to be 13.14%. In another meta-analysis, Ghaffari et al. evaluated 27 studies between 1992 and 2012. They reported asthma prevalence to be 2.7% and 3.5% in children aged 6-7 and 13-14 years, respectively [7]. These two meta-analyses showed a noticeable difference in the total asthma prevalence; also, there is no updated information about asthma status in Iranian children in recent years.
Information about the current status of asthma in Iranian children can help the Iranian health sector plan carefully and prevent asthma incidence by educating the families. It can also help neighboring countries to control the incidence of this disease because management of the health of this generation is important for any country. Due to Iran's geographical variety, the prevalence of this disease varies from region to region. As there is no updated comprehensive study to evaluate asthma prevalence in Iranian children and adolescents, the present systematic review and meta-analysis was performed to estimate asthma prevalence in children and adolescents in Iran.

Method and Material
The present study was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) instruction [8] to examine asthma prevalence among children and adolescents in Iran. . Also, all the big cities searched separately to find the possible related studies. Three national databases, including Magiran, Barakat Pharmed Co (Iran medex), and Scientific Information Databank (SID) were searched until 1 October 2020. All articles published in internationally accredited journals, national conferences, and all available dissertations that attempted to assess the prevalence of asthma in different parts of the country were collected. All references were reviewed manually.

Inclusion Criteria.
Studies that evaluated asthma prevalence in Iranian children were reviewed. The instrument used for data collection was ISSAC or SF-questionnaires, which study participants or their parents completed. Children were categorized as 0 to 10 years old, and those aged 11 to 19 were classified as adolescents. Cross-sectional and original studies were included in the study, and review articles or letter to editors was removed.
2.3. Exclusion Criteria. Unrelated topics, non-Iranian subjects, nonstandard questionnaires, incomplete data, and studies not defined the age group were excluded from the present study. Also, review articles and case-control studies were excluded.
2.4. Quality Assessment. In this step, the papers were independently evaluated by two authors. For quality assessment, we used the National Institutes of Health's Quality Assessment Tool for Observational Cohort and Cross-Sectional    Oxidative Medicine and Cellular Longevity Studies, which resolve past versions' flaws. In this questionnaire, scoring is shown by a scale of "No," "Yes," "cannot be determined", "Not Applicable," and "Not reported" [9].

Data Extraction.
The data extracted from all articles were used in the present study and qualified as a checklist. This checklist includes the author's name, type of study, year of publication, assessment tool, study location, sample size, age, gender, asthma prevalence, and associated risk factors.
2.6. Subgrouping the Outcome. In this study, the prevalence of asthma in children, adolescents, girls, and boys was considered the primary outcome. Other related information such as geographical area and asthma symptoms were considered as the secondary outcome.

Statistical Analysis.
A pooled estimated prevalence of asthma was calculated using Der Simonian-Laird random model [10], and the results were reported by 95% confidence interval (CI). To examine the heterogeneity, I 2 threshold was used [11]. Also, subgroup was done based on asthma symptoms and geographical areas. For finding the possible reasons of heterogeneity, metaregression was used based on the sample size and publication years. Sensitivity analysis was performed to ensure the stability of the results. Egger's test was used to evaluate publication bias [12]. The data were analyzed using the STATA software version 16.

Search Results.
In the first stage, 1270 articles were found; by reviewing the articles, 1090 duplicate and irrelevant articles with inadequate data and other exclusion factors were removed and finally, 30 articles were selected for this systematic review study (Figure 1).      Figure 3: Prevalence of asthma in Iranian adolescent (11)(12)(13)(14)(15)(16)(17)(18)(19).  Table 3 shows the prevalence of asthma in the four groups of children, adolescents, boys, and girls in the selected articles. As shown in Table 3, the prevalence of asthma in children was 7% (95% CI: 5-9) with heterogeneity of 98.37% (Figure 2). The prevalence of asthma in adolescents was 9% (95% CI: 7-11) with heterogeneity of 99.32% (Figure 3). The prevalence of asthma in girl and boy were 8% (95% CI: 6-10) and 9% (95% CI: 7-11), respectively. The odds ratio for male/female and children/adolescents was 0.13 and 0.82, respectively. Sensitivity analysis showed that the results before and after this analysis did not change, and the findings were stable.   Iran's geographic areas were divided into five groups: North, South, Central, West, and East. The outbreak of asthma in the studies in each region was estimated as presented in Table 4. The highest prevalence of asthma in children and adolescents were in the Center and the East, respectively. The lowest prevalence of asthma was in children and adolescents in the West.

The Overall Prevalence of Asthma.
3.6. The Prevalence of Asthma Symptoms. As shown in Table 5, the outbreak of asthma symptoms and their effects were evaluated in this study. Among asthma symptoms in children and adolescents, wheezing had the most prevalence (17% in children and 19% in adolescents) and sleep disturbance had the lowest prevalence (6% in children and 6% in adolescents).

Discussion
The purpose of this systematic review and meta-analysis was to evaluate the prevalence of asthma among children and adolescents in Iran. This systematic review and metaanalysis investigated 30 studies from 2000 to 2020. The global outbreak of asthma has been increasing over the past decades. As a chronic disease that usually starts in early childhood, it imposes a heavy burden on these people's lives, caregivers, and the community. Despite significant progress in health care in the last decades, there is still ongoing disagreement between countries.
The prevalence of asthma in Iranian children and adolescents was 6% (95% CI: 5-8) and 8% (95% CI: [6][7][8][9][10][11]. The global prevalence of asthma in children and adolescents has increased. Prevalence of ever asthma worldwide was 9.1% to 9.5% in children and 9.1% to 10.4% in adolescents [2]. The prevalence of asthma in children was reported to be The prevalence of asthma in adolescents was 19.8%, 6.05%, 6.1%, and 25.9% in Oman, India, Thailand, and Costa Rica, respectively [13][14][15][16][17][18]. The prevalence of asthma in Iran in the present study is lower than the reported value in other countries (such as Brazil, Oman, Costa Rica, and Portugal), but it was higher than Indian children and adolescents in Thailand and India. Many types of researches in Iran have examined the prevalence of asthma, leading to control of asthma incidence. Differences in variables such as climate, lifestyle, nutrition, ethnicity, and cultures in Iran compared to other countries can also affect asthma prevalence.
Many studies have been performed to estimate the prevalence of asthma in children and adolescents in various cities in Iran. Heidarnia et al. evaluated 19 studies between 1998 and, and the overall prevalence of asthma was estimated to be 13.14%, which was higher than our study [6]. In another meta-analysis, Ghaffari et al. evaluated 27 studies between 1992 and 2012. They reported asthma prevalence to be 2.7% and 3.5% in children aged 6-7 and 13-14 years, respectively [7]. In Hassanzadeh et al.'s study, just guidance school children were evaluated between 1997 and 2009. The overall outbreak was 3.9% [19]. Varmaghani et al. evaluated 10 studies between 1990 and 2015; they reported the asthma prevalence to be 8.80% [20]. Compared with the present results, these reports showed that asthma prevalence increased in recent years in Iran.
According to the present systematic review and metaanalysis, the prevalence of asthma in adolescents was higher than in children (OR = 0:82, CI: 0.64-1.06, and P < 0:001). This was consistent with several studies, such as Soto-Martínez et al., Al-Herz, de Oliveira et al., and Singh et al. [13,17]. This may be because adolescents spend more time outside the home and are more exposed to contaminants and other allergens and pollen. This finding may also be due to changes during puberty, since hormonal changes at this age can affect the incidence and severity of asthma [3].
Smoking as well is more common in this age group and can increase the prevalence of asthma. Other causes of increased asthma prevalence in adolescents could include increased consumption of foods and drinks containing preservatives.
In this systematic review and meta-analysis, the prevalence of asthma was found to be higher in boys (9%, 95% CI: 7-11) than in girls (8%, 95% CI: 6-10) (OR = 0:13, CI: -0.04-0.30, and P < 0:001). Several studies were similar to the present study, such as the study of Chinratanapisit et al. in Bangkok, and other studies in Turkey and Korea [16,21,22]. Also in Japan, the prevalence of asthma was higher in boys (6%) than girls (4%) [23]. These gender differences might be ascribed to a narrower airways caliber in males than females in early life due to different hormonal factors. Other reasons include physical and social differences. Since smoking is more prevalent in boys than in girls, it can influence this disease [24].
The other causes of the difference in asthma prevalence include climate dispersal in a different region of Iran. In the present systematic review and meta-analysis, among region  Oxidative Medicine and Cellular Longevity subgroups, the highest and lowest prevalence of asthma in children was 8% and 3% in the Center and the West of Iran, respectively. Also, the highest and lowest prevalence of asthma in adolescent were 13% in the East and 4% in the West of Iran. As a result, the central region's prevalence was higher, which may be due to air pollution and contaminants in central populated cities such as Tehran. According to Lashanizand and Gholamrezaie's study, atmospheric conditions directly and indirectly affect the prevalence of asthma, and ambient moisture reduces asthma attacks, according to the present study. It can be concluded that the northern and southern regions of the sea margin have suitable ambient humidity, which results in a lower prevalence of asthma in these regions [25]. In addition to climate change, air pollution and vehicle overcrowding in crowded cities, diet in different areas, and genetic changes can also affect asthma prevalence. Also, scattering vegetation in different cities and exposure to pollen in different seasons can affect asthma prevalence. As shown in the study of Zhang et al., SO 2 , relative humidity and sunshine are associated with asthma prevalence [26]. Descriptive information including wheezing, dry cough, sleep disturbance, wheezing attacks, and exercise wheeze was estimated in the present study. The prevalence of asthma symptoms in children and adolescents worldwide increased from 11.1% to 11.6% and from 13.2% to 13.7%, respectively, between ISAAC phase I and phase III. According to the present systematic review and meta-analysis, wheezing prevalence was higher in Iranian adolescents than in children (17% in children and 19% in adolescents). In a study in Thailand (Southeast Asia), wheezing was reported 14.6% in children and 12.5% in adolescents [16]. A study by Mallol et al. reported the prevalence of wheezing from 11.11% in 1994 to 13.4% in 2015 among adolescents [3]. It was 35.1% in children and 35.4% in adolescent in Costa Rica [17]. The prevalence of wheezing in Thailand was lower than in the present study but higher in Brazil and Costa Rica than in the present study. It was higher in adolescents than children in the present study; this is in line with Costa Rica study. The prevalence of dry cough was higher in adolescents than in children (11% in children and 17% in adolescents). The prevalence of dry cough in a study in Thailand (24.2% in children and 29.9 in adolescents) was similar to the present study; however, the result of Costa Rica study (28.5% in children and 24.4% in adolescent) was different with our result [16,17]. In Mallol et al.'s study (2015), it was reported to be 33.1% in adolescents. The prevalence of dry cough in the present study was lower than studies done in Thailand, Costa Rica, and South-Santiago. The prevalence of exerciseinduced wheezing was higher in adolescents than in children (7% in children and 16% in adolescents). In Chinratanapisit et al.'s study in Thailand, it was 3% in children and 14.8% in adolescents [16], which was higher than the amount reported in the present study.
The prevalence of wheezing attacks was significantly higher in adolescents than in children, and this finding is in line with a study in Thailand [16]. Having stress during this period of life is more than childhood and can affect asthma wheezing attacks. The prevalence of wheezing attacks in the present study was lower than in children and higher than in adolescents in Thailand. As shown, the prevalence of asthma symptom in adolescent was higher than children. The reasons can also be attributed to the increased prevalence of asthma in adolescents than children.
Publication bias of the asthma prevalence was significant. The quality of the papers affects the bias. Most of the studies did not mention blinding of the outcome assessors. Also, most of them did not mention the research's timing in the title. The results may affect by some limitation in the researches. Also, heterogeneity was encountered perhaps due to various center settings, populations enrolled, etc. In some parts of the country, we do not find any research; few studies have been done in other parts. This limitation may affect the results and cause publication bias. This study was not registered in PROSPERO.

Conclusion
Overall, the present study showed that asthma prevalence in Iranian children and adolescents is lower than in regions in 9 Oxidative Medicine and Cellular Longevity the world. Given that the disease affects the quality of life of the studied age group and the quality of their education and economic situation, the existing strategies should be pursued as well, on the provision of medicines and the cost of treatment. Also, guidelines for asthma control should be considered in the future, such as providing asthma medicines throughout the country (especially villages), measures to reduce air pollution, and training parents to quit smoking, alternatively, smoking in a place far away from their children.

Data Availability
All data generated or analyzed during this study are included in this published article.

Conflicts of Interest
The authors declare that they have no conflicts of interest.