Erica S. Schultz

Air Pollution Exposure and Lung Function in Children: The ESCAPE Project.

Background: There is evidence for adverse effects of outdoor air pollution on lung function of children. Quantitative summaries of the effects of air pollution on lung function, however, are lacking due to large differences among studies. Objectives: We aimed to study the association between residential exposure to air pollution and lung function in five European birth cohorts with a standardized exposure assessment following a common protocol. Methods: As part of the European Study of Cohorts for Air Pollution Effects (ESCAPE) we analyzed data from birth cohort studies situated in Germany, Sweden, the Netherlands, and the United Kingdom that measured lung function at 6–8 years of age (n = 5,921). Annual average exposure to air pollution [nitrogen oxides (NO2, NOx), mass concentrations of particulate matter with diameters < 2.5, < 10, and 2.5–10 μm (PM2.5, PM10, and PMcoarse), and PM2.5 absorbance] at the birth address and current address was estimated by land-use regression models. Associations of lung function with estimated air pollution levels and traffic indicators were estimated for each cohort using linear regression analysis, and then combined by random effects meta-analysis. Results: Estimated levels of NO2, NOx, PM2.5 absorbance, and PM2.5 at the current address, but not at the birth address, were associated with small decreases in lung function. For example, changes in forced expiratory volume in 1 sec (FEV1) ranged from –0.86% (95% CI: –1.48, –0.24%) for a 20-μg/m3 increase in NOx to –1.77% (95% CI: –3.34, –0.18%) for a 5-μg/m3 increase in PM2.5. Conclusions: Exposure to air pollution may result in reduced lung function in schoolchildren. Citation: Gehring U, Gruzieva O, Agius RM, Beelen R, Custovic A, Cyrys J, Eeftens M, Flexeder C, Fuertes E, Heinrich J, Hoffmann B, de Jongste JC, Kerkhof M, Klümper C, Korek M, Mölter A, Schultz ES, Simpson A, Sugiri D, Svartengren M, von Berg A, Wijga AH, Pershagen G, Brunekreef B. 2013. Air pollution exposure and lung function in children: the ESCAPE project. Environ Health Perspect 121:1357–1364; http://dx.doi.org/10.1289/ehp.1306770

Traffic-related air pollution and lung function in children at 8 years of age: a birth cohort study

RATIONALE Long-term exposure to air pollution has been related to lung function decrements in children, but the role of timing of exposure remains unknown. OBJECTIVES To assess the role of long-term exposure to air pollution on lung function in school-age children. METHODS More than 1,900 children in the Swedish birth cohort BAMSE were followed with repeated questionnaires, dynamic spirometry, and IgE measurements until 8 years of age. Outdoor concentrations of particulate matter with an aerodynamic diameter less than 10 μm (PM(10)) from road traffic were estimated for residential, day care, and school addresses from birth and onward using dispersion modeling. The relationship between time-weighted average exposure during different time windows and FEV at 8 years was analyzed by linear regression, adjusting for potential confounding factors, including short-term exposure to air pollution. MEASUREMENTS AND MAIN RESULTS A 5th to 95th percentile difference in time-weighted average particulate matter less than 10 μm in aerodynamic diameter exposure during the first year of life was associated with a reduced FEV(1) of -59.3 ml (95% confidence interval, -113 to -5.6) at 8 years of age. The negative association was particularly pronounced in children concomitantly sensitized to common inhalant or food allergens (-136.9 ml; 95% confidence interval, -224.1 to -49.7). Exposure after the first year of life seemed to have less impact on lung function at 8 years. CONCLUSIONS Our results indicate that exposure to traffic-related air pollution during infancy affects lung function in children up to 8 years of age and particularly in those sensitized to common inhalant or food allergens.

Early growth characteristics and the risk of reduced lung function and asthma : A meta-analysis of 25,000 children

BACKGROUND Children born preterm or with a small size for gestational age are at increased risk for childhood asthma. OBJECTIVE We sought to assess the hypothesis that these associations are explained by reduced airway patency. METHODS We used individual participant data of 24,938 children from 24 birth cohorts to examine and meta-analyze the associations of gestational age, size for gestational age, and infant weight gain with childhood lung function and asthma (age range, 3.9-19.1 years). Second, we explored whether these lung function outcomes mediated the associations of early growth characteristics with childhood asthma. RESULTS Children born with a younger gestational age had a lower FEV1, FEV1/forced vital capacity (FVC) ratio, and forced expiratory volume after exhaling 75% of vital capacity (FEF75), whereas those born with a smaller size for gestational age at birth had a lower FEV1 but higher FEV1/FVC ratio (P < .05). Greater infant weight gain was associated with higher FEV1 but lower FEV1/FVC ratio and FEF75 in childhood (P < .05). All associations were present across the full range and independent of other early-life growth characteristics. Preterm birth, low birth weight, and greater infant weight gain were associated with an increased risk of childhood asthma (pooled odds ratio, 1.34 [95% CI, 1.15-1.57], 1.32 [95% CI, 1.07-1.62], and 1.27 [95% CI, 1.21-1.34], respectively). Mediation analyses suggested that FEV1, FEV1/FVC ratio, and FEF75 might explain 7% (95% CI, 2% to 10%) to 45% (95% CI, 15% to 81%) of the associations between early growth characteristics and asthma. CONCLUSIONS Younger gestational age, smaller size for gestational age, and greater infant weight gain were across the full ranges associated with childhood lung function. These associations explain the risk of childhood asthma to a substantial extent.

Early-Life Exposure to Traffic-related Air Pollution and Lung Function in Adolescence

RATIONALE Exposure to air pollution during infancy has been related to lung function decrements in 8-year-old children, but whether the negative effects remain into adolescence is unknown. OBJECTIVES To investigate the relationship between long-term air pollution exposure and lung function up to age 16 years. METHODS A total of 2,278 children from the Swedish birth cohort BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiological Survey) performed spirometry at age 16 years. Levels of outdoor air pollution from local road traffic were estimated (nitrogen oxides [NOx] and particulate matter with an aerodynamic diameter of <10 μm [PM10]) for residential, daycare, and school addresses during the lifetime using dispersion modeling. Associations between exposure in different time windows and spirometry indexes were analyzed by linear regression and mixed effect models. MEASUREMENTS AND MAIN RESULTS Exposure to traffic-related air pollution during the first year of life was associated with FEV1 at age 16 years of -15.8 ml (95% confidence interval [CI], -33.6 to 2.0 for a 10 μg/m(3) difference in NOx), predominately in males (-30.4 ml; 95% CI, -59.1 to -1.7), and in subjects not exposed to maternal smoking during pregnancy or infancy. Later exposures appeared to have had an additional negative effect. High exposure during the first year of life was also associated with odds ratios for FEV1 and FVC less than the lower limit of normal (LLN) (defined as a z-score < -1.64 SD) of 3.8 (95% CI, 1.3-10.9) and of 4.3 (95% CI, 1.2-15.0), respectively. The results for PM10 were similar to those for NOx. CONCLUSIONS Exposure to traffic-related air pollution in infancy is negatively associated with FEV1 at age 16 years, leading to increased risk of clinically important deficits.

Lung Function at 8 and 16 Years After Moderate-to-Late Preterm Birth: A Prospective Cohort Study

BACKGROUND AND OBJECTIVE: Knowledge regarding lung function after moderately preterm birth is limited. We therefore investigated lung function at early school age and adolescence among children born moderately preterm. METHODS: Data were used from the Swedish prospective birth cohort BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology study; N = 4089), with a 4.8% prevalence of moderate to late preterm birth defined as a gestational age of 32 to 36 weeks. Participants underwent spirometry at ages 8 and 16 years, and impulse oscillometry additionally at age 16 years. In total, 2621 children (149 preterm and 2472 term) provided lung function data. RESULTS: At age 8 years, adjusted forced expiratory volume in 1 second was lower in preterm female subjects (–64 mL [95% confidence interval (CI): –118 to –10]) compared with term female subjects but not in preterm male subjects. At age 16 years, both genders in the preterm group demonstrated lower forced expiratory volume in 1 second (female subjects: –116 mL [95% CI: –212 to –20]; male subjects: –177 mL [95% CI: –329 to –25]) compared with the term group. For the preterm group, impulse oscillometry demonstrated higher adjusted resistance at 5 Hz (female subjects: 31.3 Pa·L–1·s−1 [95% CI: 6.3 to 56.3]; male subjects: 34.9 Pa·L–1·s−1 [95% CI: 12.0 to 57.7]) and frequency dependence of resistance (resistance at 5 and 20 Hz) for male subjects (20.9 Pa·L–1·s−1 [95% CI: 9.8 to 31.9]) compared with the term group. CONCLUSIONS: Measures of airway function assessed in adolescence were reduced in children born moderate to late preterm, and no catch-up in lung function between ages 8 and 16 years was observed.

Asthma phenotypes and lung function up to 16 years of age-the BAMSE cohort.

Asthma is a disease affecting many locations throughout the airway. Most studies have used spirometry as the primary assessment of airway obstruction, a method that may be less sensitive in regard to peripheral airway obstruction. The aim of this study was to elucidate the associations between asthma phenotypes based on age of onset and duration of symptoms, and (i) spirometry and (ii) small airway involvement measured by impulse oscillometry (IOS) in adolescence.

Prevalence of severe childhood asthma according to the WHO

BACKGROUND The World Health Organization (WHO) recently proposed a new definition of severe asthma to facilitate standardized characterization of patients, and enable more accurate estimations of the prevalence of severe asthma. The aim of this study was to estimate the prevalence of severe asthma according to the WHO definition in children aged 12 years, in Stockholm, Sweden. METHODS The birth cohort BAMSE enrolled 4089 children during 1994-96. Parental questionnaires provided information on asthma-related symptoms, diagnosis and medication from 3015 enrolled children at the age of 12 years. Severe asthma was defined as the presence of asthma, as well as continuous treatment with inhaled corticosteroids and long-acting beta-2 agonists, based on information from the Swedish prescribed drug register demonstrating prescriptions of at least 800 μg budesonide daily (or equivalent). RESULTS The prevalence of asthma was 11% among 12-year-olds (n = 329). Based on information from the Swedish prescribed drug register, seven children with asthma fulfilled the definition of severe asthma. The estimated prevalence corresponds to 0.23% (95% CI, 0.06-0.4) of the population, or 2.1% (95% CI, 0.5-3.7) of children with asthma. Based on assessed markers of asthma control, 3/7 with severe asthma were considered to have controlled asthma and 4/7 had partly or uncontrolled asthma. CONCLUSION Severe asthma appears rare both among 12-year-old schoolchildren with asthma and in the general population. Combining self-reported information from a population-based birth cohort with data from a drug register seems trustworthy in estimating severe asthma as defined by the WHO.

Effects of Long-Term Exposure to Traffic-Related Air Pollution on Lung Function in Children

Lung function in early life has been shown to be an important predictor for peak lung function in adults and later decline. Reduced lung function per se is associated with increased morbidity and mortality. With this review, we aim to summarize the current epidemiological evidence on the effect of traffic-related air pollution on lung function in children and adolescents. We focus in particular on time windows of exposure, small airway involvement, and vulnerable sub-groups in the population. Findings from studies published to date support the notion that exposure over the entire childhood age range seems to be of importance for lung function development. We could not find any conclusive data to support evidence of sup-group effects considering gender, sensitization status, and asthma status, although a possibly stronger effect may be present for children with asthma. The long-term effects into adulthood of exposure to air pollution during childhood remains unknown, but current studies suggest that these deficits may be propagated into later life. In addition, further research on the effect of exposure on small airway function is warranted.

Risk factors and markers of asthma control differ between asthma subtypes in children

There is limited understanding about risk factors for asthma, and few studies have presented an overall picture of factors associated with asthma subtypes in schoolchildren. The aim of this study was to evaluate risk factors and markers of asthma control associated with asthma subtypes up to preadolescence.

Early life determinants of lung function change from childhood to adolescence

RATIONALE Little is known about how perinatal and childhood factors influence lung function change between childhood and adolescence. OBJECTIVES To investigate possible early life predictors of change in FEV1 between age 8 and 16 years. In addition, to investigate possible predictors of having persistently low lung function (FEV1 <25th percentiles both at age 8 and 16) up to adolescence. METHODS The BAMSE birth cohort study collected data throughout childhood on environmental factors, individual characteristics, and spirometric measures at 8 and 16 years (n = 1425). Associations between early life predictors (n = 31) and FEV1 increase between 8 and 16 years were assessed with linear regression. Predictors of having persistently low lung function were examined. RESULTS Few factors were consistently associated with altered lung function growth, although low birth weight, asthma heredity (paternal), secondhand smoke in infancy, and season of birth had a significant impact (p-value ≤0.01). The majority of subjects stayed however within the same category of lung function between ages 8 and 16 years (in total 821/1425 = 58%). Predictors associated with having persistently low lung function were gestational age, secondhand smoke (at 2 and 8 years of age), and factors related to lower respiratory tract infections in infancy. CONCLUSIONS In summary, rather few exposures in childhood were identified to have a significant impact on lung function growth between childhood and adolescence. Our data support previous study findings indicating that lung function development is influenced by factors before birth and in infancy, including second hand tobacco smoke.