This birth cohort study had daily air pollutant data for 5 months each year, respiratory outcomes over a 10-year calendar period, and individual-level time-varying home environmental factors on > 1,000 children. It is the first study to relate a large database of ambient PAH measurements to respiratory disease.
Early childhood respiratory illnesses account for much of the morbidity in the youngest segments of the population. LRIs are more serious than illnesses affecting upper airways, often resulting in lost workdays for employed parents. In this study, LRI incidence was 8.3 per 1,000 child-months, more than one event per year per child, on average.
Our major finding is a clear demonstration that PAHs were associated with a greater incidence of physician-diagnosed LRIs, particularly bronchitis, in preschool children, even after adjustment for temperature, season, calendar time trends, and multiple individual characteristics. The strongest associations were observed in preschool children ≥ 2 years of age; this group may have been either more susceptible or more highly exposed for a given ambient level. Exposures from ambient air pollution sources might be greater in the older children if infants and young toddlers were kept indoors more, especially in winter months when pollutant levels are higher. Associations of PM2.5 with bronchitis in this age group were weaker and less consistent than for PAHs. Croup was not associated with these pollutants after adjustment for confounders.
Preschoolers > 1 year of age have been studied very little: Research based on parental reports of symptoms showed elevated rates of cough without a cold and wheeze in association with PM10
(Pierse et al. 2006
), and of ear, nose, and throat infections in association with higher PM2.5
(Brauer et al. 2002
). A study similar to ours (Pino et al. 2004
) used physician diagnoses of Chilean infants from 4 months to 1 year of age and reported that an average 10-μg/m3
increase in fine particles, lagged 9 days, was associated with a 9% increased risk of wheezing bronchitis.
We observed a similar increase of 7% for all bronchitis when we calculated the RR for a 10-μg/m3
increment averaged over 14 days with no lag; our results were stronger for longer averaging periods (≥ 30 days), which Pino and colleagues did not examine. We are aware of only a few other investigations of children in which measurements of PAHs were obtained. Miller et al. (2004)
followed pregnant women in New York City who wore personal monitors for 48 hr during the third trimester, and found that maternally reported respiratory symptoms during the first 2 years of life increased with PAHs among those children who were also postnatally exposed to environmental tobacco smoke. Using a similar study design in Poland, with monitoring during the second trimester, researchers observed high relative risks for maternally reported barking cough, wheezing without cold, and other symptoms, as well as longer duration of respiratory symptoms (Jedrychowski et al. 2005
Hospital admissions (Gouveia and Fletcher 2000
) and mortality (Loomis et al. 1999
) in the first year of life are significantly increased after episodes of high air pollution. Post-neonates were the most vulnerable to total and respiratory mortality in a Korean study of PM10
(Ha et al. 2001
). Two studies of linked birth–infant death files also found that post-neonatal mortality from respiratory illness was increased by high exposures to ambient particles: Ritz et al. (2006)
examined average concentrations of PM10
for periods of 2 weeks to 6 months before deaths of infants up to 12 months of age; Woodruff and colleagues (2006)
analyzed infants’ lifetime average exposure to PM2.5
. Both studies observed a doubling of postneonatal mortality in relation to particulate matter concentrations. A systematic review of 15 studies of infant mortality and air pollution concluded that results are most consistent for respiratory deaths in postneonates (Glinianaia et al. 2004a
). No overall association was observed between hospitalizations of infants with bronchiolitis, primarily from respiratory syncytial virus, and acute exposures to PM2.5
, but elevated risks were found for lags of 3–5 or 6–8 days among those born at < 29 weeks gestation (Karr et al. 2006
). However, subchronic exposures, defined as exposures in the month preceding hospitalization, were associated with higher risks for bronchiolitis in the first year of life: An increase in PM2.5
of 10 μg/m3
was associated with a relative risk of 1.09 (95% CI, 1.04–1.14) (Karr et al. 2007
). Interestingly, if converted to the increment used in our analyses, namely 25 μg/m3
, the relative risk for PM2.5
is 1.24, quite similar to the 1.30 that we obtained for the first 2 years of life.
Temperature and air pollution are correlated with each other, and both are associated with lower respiratory illness. Regardless of the temperature adjustment, the association of PAH exposures with bronchitis was strongest for the 30-day pollutant average. PAHs were significant in all 25 models fit to the data on 2- to 4.5-year-olds, and in 21 of 25 models in the younger age group. In contrast, associations of PM2.5 with bronchitis were significant primarily for 30- and 45-day averages in the younger age group, and for 3-to 30-day averages in 2- to 4.5-year-olds, after adjustment for long averaging periods of temperature.
We defined illness events using ICD-coded physician diagnoses. Thus, the event must impel the parent to bring the child to a physician, who must then make a correct diagnosis. All Czech citizens are entitled to free, readily available medical care. Families usually remain with one pediatrician. We attribute the low refusal rate in the follow-up study (5.4% for births in 1994–1996, without incentives, and 2.5% in 1997–1998 births, when incentives were offered) to the close relationships between the family and the physician and nurses. Ready access to and high utilization of physicians are demonstrated by the completeness of immunizations: 98% of the children received a complete series of four DPT (diphtheria–pertussis–tetanus) injections, compared with 81% of U.S. children in 1997 (Centers for Disease Control and Prevention 1999
Studies of child morbidity often rely on parental reports, usually collected retrospectively, which can be inaccurate and highly subjective (Lara et al. 1998
). In contrast, the validation survey we conducted with 25 pediatricians indicated strong consistency in coding symptoms of bronchitis and croup, and no differences between districts (survey instrument and results available on request). Whatever their limitations, physician diagnoses are recorded at the time of the consultation and are more objective than parental reports and more complete than hospitalizations alone. Moreover, because visits to specialists or hospitals are forwarded to the primary physician in the Czech Republic, diagnoses in this study included virtually all contacts with health care providers.
We focused on episodes of LRI, which are more likely to result in contact with the health care system than, for instance, the occurrence of less serious illness, such as an upper respiratory infection. However, because our primary air pollution comparisons are temporal, not spatial, variation in health care utilization or diagnostic practices (Howel et al. 2001
) is less likely to be associated with pollution and hence would not result in confounding. We also assessed possible shifts in diagnostic practices or health care–seeking behavior (results available on request), but found little evidence for time trends or differences across districts. Had they existed, statistical adjustment for calendar time and district would have controlled for them. We did observe that children born in 1995 or 1996 appeared to experience higher illness rates, respiratory and nonrespiratory, before 2 years of age. Because both years were characterized by particularly high levels of pollution, peri-natal exposures may have influenced the health of these birth cohorts.
Concentrations of organic pollutants and particles in this study were, as previously reported (Hertz-Picciotto et al. 2005
), comparable to those recorded in a number of U.S., European, and Asian cities (Naumova et al. 2002
; Pinto et al. 2004
). This similarity in ambient air pollutant levels supports generalizability of our findings. Moreover, whereas many air pollution studies have measurements only every sixth day, we obtained daily data on PM2.5
and on both gaseous and particle-bound PAHs for 5 months each year for 10 years, and every-third-day measurements for another 5 months per year. Major findings were similar or stronger in analyses of months with daily data only. Availability of frequent measurements permitted accurate differentiation of effects for different averaging periods.
We chose to examine fine rather than coarse particles because, with only one monitor in each district, exposure misclassification error would likely be lower. The striking findings for PAHs but not for PM2.5 are unlikely to be an artifact; when we limited analyses to children residing at closer distances or not separated from monitors by topography, the patterns were similar: The RR for 30-day PAHs increased from 1.56 to 1.74 in children > 2 years of age, and the nonsignificant findings for PM2.5 remained so.
Potential mechanisms by which PAHs or PM2.5
may increase LRIs are numerous, including oxidative stress, structural damage, efficient transport of pathogenic microbes, and immune dysregulation. Oxidative stress is strongly correlated with organic carbon components, specifically PAHs (Li et al. 2003
). PAH constituents of diesel exhaust particles catalytically generate reactive oxygen species, causing stress to biological systems (Hiura et al. 1999
). Several metabolic and cellular activation pathways appear linked to PAHs, and may affect cytokine and chemokine expression. (D’Arena et al. 1998
). Particles can also impair alveolar macrophage superoxide production (Kleinman et al. 2003
), which may in turn compromise the lung’s ability to kill some respiratory pathogens. Pathways involving immunologic alterations are supported by our previous finding that PM2.5
exposures during the 14 days before delivery were associated with reduced T-lymphocyte percentages and elevated B-lymphocyte percentages (Hertz-Picciotto et al. 2005
Sensitivity analyses exploring different averaging periods for pollutants and temperature, different covariance assumptions, the impact of imputation, and so forth, yielded consistent patterns of results. Such robustness of the principal results to analytic decisions strengthens the plausibility of a causal link. Overall data validity was supported by confirmation of established risk and protective factors (e.g., current breast-feeding, presence of other children in the household, low maternal education, child’s sex, and ETS exposure) (Koch et al. 2003
; Pino et al. 2004
To summarize, this study demonstrated strong associations of PAHs with lower respiratory illnesses, especially bronchitis, in children between birth and 4.5 years of age. These associations are unlikely to have been confounded, subject to the caveat that we did not examine other components of ambient air pollution or meteorologic covariates besides temperature. Strengths of the study include participation of all physicians and high retention rates, which minimized the possibility of selection bias; the high quality and intensive air monitoring program; and a wealth of covariate data that were well controlled in the statistical analysis, including breast-feeding, day care attendance, indoor sources of air pollution, ambient temperature, and season. The case for generalizability of the results, should they prove to be causal, is strong, given that the analysis accounted for sampling fractions and that exposure levels were comparable to those in cities throughout western Europe, the United States, and elsewhere. Experimental research suggests that a causal relationship with PAHs and PM2.5 is plausible, though our data support the former more than the latter. Whereas ambient air quality standards focus on particulate matter and gaseous pollutants such as SO2, CO, and O3, PAHs are ubiquitous, and few epidemiologic studies have examined their associations with morbidity. This study indicates that short-term exposures to PAHs may represent a significant public health threat to children.