The Relation between Ambient Temperature and Asthma Exacerbation in Children : A Systematic Review

Background: Asthma is one of the most common chronic noncommunicable diseases which is seen more in the developed than developing countries of the world. Recurrence and exacerbations of the disease are common among patients and often lead to hospitalization and therapeutic interventions. Ambient air temperature might be related to the relapse of asthma. This review was conducted to investigate the relation between ambient temperature and exacerbations of asthma in children.


Introduction
Asthma is one of the most common chronic airway and non-communicable diseases worldwide and its prevalence has increased in recent years 1 .This disease is characterized by chronic inflammation and obstruction of the airways.According to the WHO report, 235 million people suffer from this disease 2 .
Recurrence and exacerbations of this disease are common among patients, which often leads to hospitalization and therapeutic interventions for improving lung function 3 .Several studies have been conducted to investigate the relation between air pollutants such as ozone and fine particulate matter and the progression and exacerbations of asthma.There is also evidence that exposure to environmental factors such as ambient temperature is associated with recurrence of asthma 4 , and even deterioration and death due to respiratory failure 5,6 .
Average global temperature has increased 0.85 •C , between 1880 and 2012 7 .Nowadays all world countries are affected by global warming and its effect is not limited to a specific region of the world 8 .
Air temperature may directly or indirectly be related to the recurrence of asthma.Cold air may directly affect airways and cause hyper-responsiveness.It might also indirectly trigger asthma by predisposing people to viral diseases, or air pollution.Air conditioners used in warm weather may also trigger the recurrence of asthma 9 .Several studies have been conducted in different countries to investigate the relation between ambient temperature variations and the incidence and/or recurrence of asthma.Studies have reported clusters of asthma recurrence and hospitalization in some seasons 10 .Children are one of the sensitive groups affected by environmental factors.These factors might cause asthma recurrence and hospitalization in sensitive children 11 .
Understanding the environmental factors that trigger asthma recurrence and hospitalization in children can help prevent these attacks by modifying lifestyle or reducing exposure to these environmental factors 12 .Various studies have reported different results about the role of ambient temperature on the occurrence of asthma.These studies have been conducted in different geographic, social and racial regions and have examined the effect of low or high temperatures, or heat/cold waves, on the exacerbation of asthma 13,14 .These studies have reported various associations and it is necessary to provide an overall conclusion from these studies to help public health policymaking.Although a systematic review was recently conducted about ambient temperature and childhood asthma by Xu et al 15 , but this review did not include some articles 4,[16][17][18][19][20][21][22][23][24][25][26][27][28][29] .
This review study was conducted to investigate the relation between ambient temperature and asthma focusing on recurrence and exacerbation of the disease in children.

Inclusion Criteria
Studies were included in this review if they had considered at least one temperature index as an exposure, had evaluated the age group under 17 years separately, the outcome was investigated in humans, and recurrence or hospitalization due to exacerbation of asthma was reported as a consequence.Also, papers were included which had included at least one year data.

Search Strategy
PubMed, Web of Science, Science Direct, and Scopus databases were searched for relevant articles.No time limit was implemented.
The final search was done on October 1, 2018.In order to retrieve all related articles which included various age groups, we did not use "Children" as a keyword.Hence, we screened full-text articles to see if they had included children as a separate category.

Study selection
After searching different databases, the titles and abstracts of the retrieved articles were imported into EndNote software and duplicates were removed based on title, author and year of publication.
Initially, the relevance of the articles was examined based on title and abstract.Out of 2633 articles, 88 were selected for full-text evaluation.The full-text articles were evaluated using the inclusion and exclusion criteria.
The author's name, study period, population size, type of study, type of exposure variable and outcome, statistical analysis, and the main results were extracted from the finally selected articles.
Due to the differences in study methodologies, statistical analysis, and different temperature indices, conducting a meta-analysis was not possible.

Result
After screening through several steps, shown in Figure 1, 23 articles were selected for the review.The characteristics of these articles are summarized in Table 1.The studies were from different parts of the world including Europe, America and Asia, but no study was conducted in Africa.The studies had been conducted in countries.

Different definitions had been used to define the
According to the World Economic Situation and Prospects 38 , most studies (16 studies) had been conducted in developed countries; including Croatia, the US, Japan, Australia, Greece, Malta and Spain; and seven studies had been conducted in developing countries, including China, Trinidad and Tobago, Hong Kong, Israel and Brazil 17, 19, 21-23, 31, 32 , while no study had been conducted in less developed countries.

Discussion
Most of the studies showed that extreme ambient air temperature has a relation with the recurrence or hospitalization of children due to asthma.For example, in Tokyo, as temperature decreased 12 , and in New York, as temperature increased, the incidence of asthma attacks in children increased 4 .The average daily temperature in Tokyo is 11 °C, while in New York City during cold spells it is -15 °C4 and New York has colder winters in comparison to Tokyo.Probably children with asthma during the winter season and during the cold spell, because of medical orders, changed their behavior and were less likely to expose themselves to the cold environment or use a mask to prevent asthma attacks.
Cold and hot temperatures affect the respiratory system through different mechanisms.Warm weather may cause microorganisms, mites and cockroaches to grow in the interior of human dwellings, or warm air can cause increased air pollution such as an increase in ozone and PM 10 .This, maybe one of the factors associated with inflammation of the respiratory tract and the recurrence of asthma.
Studies have also shown that cold and dry air increases the risk of airway inflammation, reduces lung function and reduces lung capacity 37,[39][40][41] .Cold weather can decrease moisture in the mucosal membrane of the respiratory tract, predispose it to irritation by allergens, cause sensitivity to viral and bacterial infections and increase the risk of asthma attacks 42 .
Studies conducted in Japan and America reported a direct relation between temperature changes, one day before the recurrence of asthma in children 18,24,26,27,29,35,36 .But, children under 5 years of age were less likely to be affected by air temperature changes due to less contact with the outside and environmental triggers 31,34,35 .
However, the high recurrence rate of asthma in school age children can be due to temperature changes and the transition from summer to autumn and due to the easier transmission of respiratory diseases after school opens.Respiratory pathogens in these children affect the relation outcome in different articles.Although all studies were conducted after the release of the Ninth Revision of the International Classification of Diseases, only 8 studies had used ICD9 4,16,25,27,28,30,31,34 .Five studies had used code 493.00 and 3 studies had used code 493.00 to 493.99.Also, two studies had used ICD10-(J45) as the outcome variable 17,35 .The rest of the studies measured outcome based on physicians' assessment, the presence of asthmarelated symptoms and the administration of nebulized bronchodilators.Two studies did not report how the asthmatic attack was diagnosed 26,29 .
The results of 10 studies showed that the number of cases of asthma exacerbation was higher in boys than girls, while two studies reported a higher number of cases of asthma in girls than boys 4,27 , and one study reported an equal number of cases 36 .
Studies had considered different lag periods between exposure and outcome, which varied from 0 to 60 days, but 8 studies did not include lag time 19-21, 23, 24, 26-28 .In many studies, the temperature was not the only risk factor considered; and demographic factors such as sex, race and meteorological factors such as barometric pressure, relative humidity, wind speed, rainfall and air pollutants, such as PM 10 , PM 2.5 , O 3 , NO X , were also examined.But these variables were different in different studies.
Fourteen studies were simple ecological studies, and two were case-crossover studies 27,34 .Two studies had used the time-series method 24,31 .Seven studies had used correlation coefficients 16,17,19,20,24,28,29 and four studies had used relative risks to examine the relation between air temperature and asthma exacerbations 12,25,27,31 .
Studies in Malta and Spain showed that the increase in the incidence of asthma in the 5-14 age group was associated with the school re-opening season, and with a two-week lag after the start of the school year, recurrence of asthma increased in this age group 19,20,22,30 .
Among the papers reviewed, 11 papers had examined the effect of seasons on the recurrence of asthma in children.Based on the Köppen−Geiger Climate Classification 16 studies were conducted in a warm-temperate climate 4,12,16,19,20,[23][24][25][26][29][30][31][32][33][34][35] .Three articles were from the equatorial region 12,25,34 and three articles were from the snow region 13, between air temperature and the recurrence of asthma.Students can transmit these respiratory diseases to other family members, and a recurrence of asthma may be seen in other age groups as well 16,20,22,30 .
The reason for the difference in recurrence of asthma in different times of the year can be due to the effects of various climatic or demographic variables, air pollutants, viral infections, and indoor aeroallergens 43 .In spring, the increased incidence of asthma may be related to fungal spores and pollen grains, while in autumn it may be due to rapid changes in temperature 44,45 .
Most of the studies used in this review were ecological studies and one of the limitations of these studies was the assumption that the level of exposure was equal throughout the population and in different social and economic classes; and as well as the amount of time spent outdoors, and the use of air conditioner, heater and humidifiers.Also, in these studies, the reference population of patients visiting the hospitals under investigation was not clear.Only two studies used postal codes to determine the patients› location of residence and excluded children who were not living in that area 34,36 .
Another limitation was not using the same patient classification system in the studies, as only 10 studies used the International Classification of Diseases 4,16,17,25,27,30,31,34,35 .Other studies used physician's assessment, the presence of asthma symptoms, or a history of using asthma drugs; for diagnosing asthma attacks.Two studies did not report the criteria used for diagnosing asthma attacks 26,29 .

Conclusion
Ambient air temperature is probably related to the recurrence and hospitalization of child asthmatic patients.The results of some studies have shown that extremely hot and cold temperatures both increase the incidence of asthma in children.However, hot and cold temperature cause asthma attacks through different mechanisms.

Figure 2 :
Figure 2: Distribution of studies across five Köppen Geiger climate zones (A-E).Study numbers on the map are defined in Table1.

Table 1 .
Summary of the studies included in this systematic review Figure 1: Search results and study selection * TVN: Temperature variation between neighboring days *NR: Not Reported 18, 37