Environmental project, 1005 – Time Series Study of Air Pollution Health Effects in COPSAC Children

Time Series Study of Air Pollution Health Effects in COPSAC Children

1 Introduction

1.1 Background

The health effects of air pollution exposure have become an area of increasing focus in the recent years. A large body of evidence has demonstrated that there are serious health consequences due to air pollution and that these consequences are not spread equally among the population. Exposure to pollutants such as airborne particulate matter and ozone has been associated with increase in mortality and hospital admission due to respiratory and cardiovascular disease in adults (Brunekreef et al., 2002). Children's exposure to air pollution is however a special concern because their lungs and immune system are not fully developed when exposure begins, raising the possibility of different responses than seen in adults (Schwartz, 2004).

There are several factors that influence relative impact of air pollution on children versus adults. The newborn's lung is not well developed, and development of full functionality does not occur until approximately 6 years of age. During early childhood, the bronchial tree is still developing, resulting in greater permeability of the epithelial layer in young children. Children also have a larger lung surface area per kilogram of body weight than adults and, under normal breathing, breathe 50 % more air per kilogram of body weight than adults. This process of growth and development suggests that there is a critical exposure time when air pollution may have lasting effects on respiratory health.

Infant's immune system, immature at birth, is also developing rapidly in early childhood. Much of recent asthma research as been focused on this development, in particular factors that influence development of TH-2 (humoral immunity dominant) versus TH-1 (cellular immunity dominant).

Children spend more time outdoors than adults, and some of that time is spent in activities that increase ventilation rates. This can increase the exposure to air pollutants compared with adults, as indoor concentrations of air pollutants of outdoor origin are usually lower.

There is growing evidence that the incidence of asthma and inhalant allergies in childhood is increasing in the developed world (Woolcock et al., 1997). Although genetic factors are important determinants of the prevalence and severity of asthma they cannot explain observed increase in prevalence. The environmental factors that have been identified as causative agents of asthma and inhalant allergy in children are sensitization to allergens such as house dust and maternal smoking (Gold, 2000; Arlian et al., 2001; Arshad et al., 1992; Arshad et al., 1993). The effect of outdoor air pollution is less clear. Where the evidence that outdoor air pollution exacerbates preexisting asthma is well established, there is less evidence that outdoor air pollutants increase the incidence of asthma or allergic diseases in children (Wardlaw, 1993; von Mutius, 2001). Recently, however, a Californian cohort study following children from the age of 10 to the age of 18 years showed that a high exposure to PM_2.5 was associated with a high risk of decreased development of lung function (Gauderman et al. 2004). Previously, an association between asthma development and frequent outdoor sports activity in areas with high levels of ozone has been found among Californian children (McConnel et al. 2002).

There is a large body of evidence associating short-term changes in air pollution with short-term changes in pulmonary health in children. Series of summer camp studies illustrated that lung function declined during air pollution episodes, which were combinations of ozone and sulfate particulates (Spektor et al., 1991; Kinney et al., 1989; Berry et al., 1991). Similar wintertime episode studies illustrated decline in lung function during high particulate air pollution (Dockery et al., 1982; Dassen et al., 1986). A number of panel studies, in which children performed daily peak flow tests and answered questions on symptom prevalence, reported significant associations with PM₁₀ (Romieu et al., 1996; Ostro et al., 2001; Pope et al., 1992; Braun-Fahrlander et al., 1992), and ozone (Kinney et al., 2000; Jalaludin et al.,2000; Gold et al., 1999). One study found no significant association with PM₁₀ (Roemer et al., 1999). Two Dutch studies addressed the question of susceptibility, and found stronger associations between particle pollution and peak flow decrements in children with asthma (Van der Zee et al., 1999) and children with bronchial hyperresponsiveness (Boezen et al., 1999), than in those without. Another approach was seen in the studies using more serious outcome requiring physician contact. Pope et al. examined hospital admissions of children in Utah valley during 3 consecutive winters, before, during, and after steel mill strike, and found that air pollution is related to serious asthma exacerbation and to pneumonia exacerbation (1989). Several studies have found associations between day-to-day changes in air pollution and day-to-day fluctuations in childhood hospital admissions (Bates et al., 1989; Burnett et al., 1994; Schwartz et al., 1993; Norris et al., 2000; Tenias et al., 1998; Sunyer et al., 1997). A study looking at emergency house calls by physicians in Paris found that visits for asthma were associated with particulate air pollution and ozone, and that association was stronger for children (Medina et al., 1997).

What evidence is there that these associations are plausible? An important study showed that exposure to urban particles exacerbated pneumonia in an animal model (Zelikoff et al., 1999). Other evidence points to a role for pollution in increasing lung inflammation in children, particularly in those with asthma. A study found that increases in several air pollutant levels were associated with increased levels of exhaled nitric oxide (NO) (Fischer et al., 2002), a good marker of lung inflammation in individuals with asthma (Kharitonov et al., 1995; Massaro et al., 1996). A similar study found that exhaled NO concentrations in the urban children with asthma were more than double of those in children with asthma living in national parks, and found no difference in exhaled NO between children with asthma in the park and healthy children in the city (Giroux et al., 2001). Finally, there is strong evidence that changing air pollution in the short term produces immediate reductions in asthma exacerbations, such as in the Utah (Pope et al., 1989) and the Atlanta (Friedman et al., 2001) study .

Although there is a considerable database of time-series studies of acute effects of air pollution in children very few of these have addressed the smallest children for whom the risk could potentially be greatest. A British population based study covering one year in a part of London found borderline significant associations between daily counts of emergency room appearances with wheezing and daily levels of ozone, PM₁₀, SO₂, NO₂ and some hydrocarbons (Buchdahl et al. 2000). The associations with ozone and some hydrocarbons were significant among children younger than two years. The only published panel based study of infants is from Santiago, Chile, and it included 504 children followed from 4 to 12 months of age (Pino et al. 2004). The daily incidence of wheezing bronchitis was associated with daily concentrations of PM_2.5 with lag-time up till 10 days. Among children with familiar asthma the response was approximately 10% (95% CI 2-20% with lag-time 2 days) increased risk per 10 µg/m³ PM_2.5 through the 10 days lag-time, whereas children without predisposition for asthma the response was smaller during the first 8 days of lag-time, e.g. 4% (95% CI: 0-8%) lag 1 day and 2% (95% CI: 0.98-1.06) increased risk per 10 µg/m³ PM_2.5 lag 2 days. There were no consistent associations with daily concentrations of SO₂ or NO₂, although PM_2.5 was described as mainly associated with traffic in Santiago, which is heavily polluted with e.g. 107 days per year with levels above 65 µg/m³ PM_2.5.

Only one Danish study has investigated the relationship between air pollution and respiratory illness in children and it included a wide age range (Keiding et al., 1995). In this study outdoor concentration of nitrogen oxide, sulfur dioxide, carbon moNO_xide, NO_x, ozone and black smoke were used as a measure of air pollution. No Danish epidemiological study has so far used PM₁₀ or PM_2.5 concentrations as a measure of air pollution or focused on infants. Since the extrapolation of data from other geographical areas to Danish conditions involves many uncertainties, it is very important to make a valid risk investigation of air pollution due to fine particles and gases in the Danish environment. Moreover, the data on infants with a potentially specifically high risk are very limited internationally.

1.2 Purpose of the Study

The purpose of this study is to:

Study the association between particulate and gaseous air pollution and development of acute respiratory symptoms in small children (0-18 months) susceptible to asthma living in Denmark.
Evaluate the time window within which air pollution has effect on the development of respiratory symptoms in small children
Consider and discuss study designs issues in time series studies of air pollution health effects, relevant to defining study population according to study subjects' proximity to exposure source.

The project was funded and done in collaboration with COPSAC study group. More details about COPSAC cohort can be found at their website http://www.copsac.dk/.