Fine Particles Are More Strongly Associated than Coarse Particles with Acute Respiratory Health Effects in Schoolchildren

Abstract

Numerous studies have reported associations between airborne particles and a range of respiratory outcomes from symptoms to mortality. Current attention has been focused on the characteristics of these particles responsible for the adverse health effects. We have reanalyzed three recent longitudinal diary studies to examine the relative contributions of fine and coarse particles on respiratory symptoms and peak expiratory flow in schoolchildren. In the Harvard Six Cities Diary Study, lower respiratory symptoms in a two-pollutant model were associated with an interquartile range increment in fine particles [(for 15 μg/m³ particulate matter (PM) <2.5 μm in aerodynamic diameter (PM_2.5), odds ratio = 1.29, 95% confidence limits (CL) = 1.06, 1.57] but not coarse particles (for 8 μg/m³ PM_2.5–10, odds ratio = 1.05, 95% CL = 0.90, 1.23). In Uniontown, PA, we found that peak flow was associated with fine particles (for 15 μg/m³ PM_2.1, peak flow = −0.91 liters/minute, 95% CL = −0.14, −1.68), especially fine sulfate particles, but not with coarse particles (for 15 μg/m³ PM_2.1–10, +1.04 liters/minute, 95% CL = −1.32, +3.40). We found similar results for an equivalent children’s cohort in State College, PA. We conclude that fine particles, especially fine sulfate particles, have much stronger acute respiratory effects than coarse particles.

In recent years, numerous studies have reported associations between airborne particles and a range of respiratory conditions, including respiratory symptoms and pulmonary function deficits, emergency room visits, hospital admissions, and daily deaths. ¹ Most of these studies have been done in urban areas, where variation in daily particle concentrations is dominated by variation in the concentration of fine particulate matter (PM), that is, particles less than 2.5 μm in aerodynamic diameter, denoted PM_2.5. ² Only a small number of studies, however, have directly assessed the relative contributions of different particle sizes to health endpoints.

Schwartz et al³ reported that the association between airborne particles and daily deaths in six eastern U.S. cities was with the fine, and not the coarse, particles. Similar results have been reported for the association with hospital admissions in Toronto. ⁴ Dreher et al⁵ have shown that the pulmonary toxicity of urban particles varied with size, with the greatest toxicity in those smaller than 1.7 μm. This finding suggests that smaller cutpoints than PM_2.5 may be even a better marker of the toxic particle fraction. Other studies have used sulfate aerosols, which are less than 1 micrometer in size, as their exposure, sometimes finding stronger effects than with PM₁₀. ^4,6 On the other hand, the Environmental Protection Agency has noted ⁷ that coarse particles deposit in the upper airways of the lungs and may be more relevant for asthmatic responses and irritation.

To further our understanding of the role of fine vs coarse (between 2.5 and 10 μm in diameter) particles in human health, we have reanalyzed three diary studies of children in which associations have previously been reported between PM₁₀ and respiratory health, using data on fine and coarse mass in each location.

Subjects and Methods

Harvard Six City Diary Study

The Harvard Six City Study of respirable particles and sulfur oxides was a longitudinal study of the effects of exposure on the respiratory health of children and adults. ⁸ As part of that study, we selected a sample of 1,844 school children in grades 2 through 5 from six urban areas in the eastern United States (Watertown, MA; Kingston-Harriman, TN; St. Louis, MO; Steubenville, OH; Portage, WI; and Topeka, KS). Parents completed a daily report on the child’s respiratory symptoms, and these reports were collected every 2 weeks. Further details on these cohorts have been published previously. ⁹ Children kept symptom diaries for a year in each community, but we restricted the analysis to April 1 through August 31 to avoid problems of seasonal variations in ozone and acid aerosols.

A diary day indicating lower respiratory symptoms was defined as any day with a report of at least two of cough, phlegm from chest, pain in chest, or wheezing. A day-at-risk was a diary day following a day with one or no lower respiratory symptom. An incident event was defined as a lower respiratory symptom day that occurred on a day-at-risk. A similar procedure was applied to cough days without any other symptom. By definition, these symptom incidences were independent. The incidence of these symptoms showed no autocorrelation.

We measured air pollution daily during the study period at a single, central-site monitoring station located in a residential area in each community. We collected particulate matter by a dichotomous sampler with an aerodynamic size cut at 10 μm (PM₁₀) and 2.5 μm (PM_2.5). This sampler yielded two daily measurements, one of PM_2.5 and one of coarse particle mass (CM), which were summed daily to produce a PM₁₀ reading. We also measured sulfate on the fine-particle filter and nephelometry, a light-scattering measure of particles less than 1 micrometer in diameter. The previous study focused on PM₁₀, acid aerosols, and the gaseous pollutants. Associations were reported between PM₁₀ and both coughing and lower respiratory symptoms. Ozone was also associated with coughing.

Uniontown and State College Diary Studies

As part of the Harvard/Health Canada 24-City Study, cross-sectional studies of respiratory symptoms and pulmonary function in fourth- and fifth-grade children were conducted in the Pennsylvania communities of Uniontown and State College. During the summer of 1990, we enrolled from the cross-sectional cohort a stratified sample of 83 children living in Uniontown to participate in twice-daily measurements of peak expiratory flow rate from June 10 through August 23. ¹⁰ This design was repeated among 108 children living in State College from June 29 through August 20, 1991. ¹¹ In both studies, peak expiratory flow rates were measured with a Mini-Wright Peak Flow Meter (Armstrong Medical Industries, Lincolnshire, IL). Each child performed and recorded three unsupervised measurements in the standing position twice daily, once upon arising in the morning and again in the evening before bedtime.

We measured air pollution daily during the study period at a single, central-site monitoring station located in a residential area in each community. We collected particulate matter (in μg/m ³) with two collocated samplers, one with an aerodynamic size cut at 10 μm (PM₁₀) and one with an aerodynamic size cut at 2.1 μm (PM_2.1). The difference between these measurements was an estimate of CM. Sulfate particles (in nmol/m ³) were measured by an annular denuder/filter pack over two 12-hour periods, daytime (8:00 am to 8:00 pm) and overnight (8:00 pm to 8:00 am). These previous studies focused on PM_2.1, acid aerosols, and the gaseous pollutants. Sulfate particles and particle-strong acidity were associated with cough and with decrements in peak expiratory flow rates. Ozone was also associated with peak flow decrements. In State College, the reanalysis was restricted to the first 4 weeks of the 8-week study period.

Analytic Strategy

We have chosen to replicate the models used in the previous studies so that any differences in results can be unambiguously attributed to the difference in the pollution variables. Hence, for each study, we first replicated the originally reported results and then repeated the analyses using the different available particle measurements. Because the ability to differentiate between different particle measures depends on the correlation among the measures, we have assessed that correlation in each of the studies. In the Harvard Six City Diary Study, the logistic regression model for the daily symptom incidence rates in each location included dummy variables for city, day of the week, and linear and quadratic temperature terms. In Uniontown and State College, separate linear regression models for the mean deviation in the peak expiratory flow rate in each location adjusted for linear trend, a binary indicator of morning or evening reporting period, the 12-hour average daytime temperature and second-order autocorrelation. Mean deviation was defined as the daily average of the deviation of each subject’s peak flow on that day from the subjects average peak flow. Both morning and evening peak flow measurements were included in the model, but an association with particles was observed only for the evening measurements. The peak flow results for each location were combined using inverse variance weights. In all locations, we have computed effect sizes for an increment in exposure approximately equal to an interquartile range in the pollutant.

Results

In the Harvard Six City Dairy Study, the correlation among the various fine-particle measures (PM_2.5, sulfates, and nephelometry) was high, as expected (Table 1). The correlation between CM and PM_2.5 was moderate (0.41) and was lower with the sulfate and nephelometry measures. Because PM_2.5 contains some crustal dust, this finding is not unexpected. These low correlations allow an exploration of the independent effects of fine vs coarse mass. Table 2 shows a comparison of the results from the Harvard Six City Diary Study using CM and the fine-particle measures (PM_2.5, sulfates, and nephelometry) as exposures. For lower respiratory symptoms, the association was stronger for all of the fine-particle measures than for CM in single-pollutant regressions. A model including both CM and PM_2.5 resulted in a substantial reduction in the effect of CM, with little evidence that the remaining effect was different from zero. For cough symptoms, the strongest effect was for nephelometry, closely followed by CM. In two-pollutant models, both nephelometry and CM made independent contributions to explaining cough incidence, with only modest reductions in effect size. In contrast, PM_2.5 made little independent contribution to explaining cough symptoms in a two-pollutant model with CM.

Table 1: Correlation among the Particle Measures in the Three Diary Studies^*

Table 2: Association of Respiratory Symptoms with Coarse Particle Mass (CM) and Measures of Fine Particles (PM_2.5, Sulfate, Nephelometry) in the Harvard Six City Diary Study^*

In both Uniontown and State College, fine particles, especially fine sulfate particles, were poorly correlated with CM (Table 1) and were associated with decreased evening peak expiratory flow rates (Table 3). The effect estimates for fine particles were more similar across locations than those for coarse particles and were close to the combined effect estimate. When we scaled each pollutant to its approximate interquartile range, fine-sulfate particle concentrations showed almost twice the decrement in evening peak flow rates as fine-particle mass concentrations. Conversely, coarse particles had little association with evening peak flow in either location, with a combined effect estimate very close to the null value.

Table 3: Association of Evening Peak Expiratory Flow Rates with Coarse Particle Mass (CM) and Measures of Fine Particles (PM_2.1, Sulfate) in the Uniontown and State College Diary Studies^*

Discussion

In both the Harvard Six Cities Diary Study and the Uniontown-State College diaries, fine-particle measures were much more strongly associated with asthma-related responses (increased lower respiratory symptoms and decreased peak flow) than coarse particle mass. Moreover, an interquartile range increment in fine sulfate particles was associated with a larger change in both outcomes than was an interquartile range increment in total PM_2.5 mass. This result indicates that the sulfate component of fine particles is a better proxy for the toxic particle constituents than total fine mass. The fine fraction contains constituents other than sulfates, and these may be responsible for the observed health effects of fine particles.

Hence, for acute asthma-related responses as well as daily mortality, fine particles are a stronger predictor of response than are coarse particles. Sulfate particles clearly play an important and perhaps the predominant role in those health associations. Sulfate particles in these study locations are primarily related to the long-range transport of sulfur emissions from coal-burning power plants.

Cough in the absence of any other symptoms was the only response in which coarse particles appeared to contribute to an adverse health effect. For cough-only symptom episodes, both submicron particles (as measured by nephelometry) and coarse particle mass appeared to make independent contributions. This coarse particle effect may be due to particle deposition and irritation in the upper airways.

Airborne particles are a complex mixture of particles differing by size, chemical composition, and structure. Most particles produced in nature are the product of mechanical processes, such as erosion. These are generally referred to as coarse particles and have typical mass median diameters of about 7 μm. The median diameter varies by location; some crustal particles are less than 2.5 μm in aerodynamic diameter. Fine particles are predominantly generated by controlled combustion processes. Substantial human exposure to combustion particles only began with the domestication of fire, and these particles differ in size and depositional pattern from the coarse particles. They typically have mass median diameters of about 0.7 μm and are more likely to deposit in the alveolar region than coarse particles. The U.S. Environmental Protection Agency estimates ⁸ that the fraction of the total aerosol deposited in the alveolar region of a general population that derives from particles less than 2.5 μm in diameter ranges from 98%, in locations with aerosols similar to Philadelphia, to 80% for aerosols similar to Phoenix.

Combustion particles also differ in physiochemical properties from the coarse particles. They contain higher concentrations of sulfates and nitrates, organic compounds, and more bioavailable transition metals than coarse particles. ^5,12,13 These transition metals are factors in the toxicity of the particles. Li et al¹⁴ and Gilmour et al¹⁵ in 1996 reported that the instillation of 50 to 125 μg of particles removed from PM₁₀ filters in Edinburgh increased the recruitment of neutrophils into the lung and that cultured bronchoalveolar lavage cells produced excess quantities of tumor necrosis factor alpha and major inflammatory protein 2 (MIP2), which are proinflammatory cytokines. Pretreatment with a metal chelating agent reduced the inflammatory response to the urban particles, indicating the role of metals in the inflammatory process.

Costa and Dreher ¹⁶ have reported that urban particles produce pulmonary toxicity, with the level of toxicity related to the amount of transition metals that the particles contain. In contrast, Schapira et al¹⁷ found that coarse particles from the ash of the Mount St. Helens volcano had less soluble transition metals and showed less toxicity when instilled at the same dose. The toxicity of the combustion particles was substantially reduced when they were washed to remove the soluble metals before instillation in the rat lungs.

Recent studies have directly compared the toxicity of fine particles with that of coarse particles. Dreher et al⁵ placed fine particles and coarse particles collected from the air in Washington, DC, in the lungs of animals and found substantial toxicity from the fine particles but much less from the coarse particles. Osornio-Vargas et al¹⁸ found that particles from a region in Mexico City where combustion particles dominate were much more toxic than the particles from a region where windblown dust is also an important contributor to PM₁₀.

Another recent study used concentrated fine ambient particles ¹⁹ drawn from the outside air in Boston, MA. After 3 days of exposure to concentrated ambient particles (6 hours per day at 228–288 μg/m ³), mortality was 37% among rats with induced chronic bronchitis, 19% among rats with monocrotyline-induced inflammation, and none among normal rats. ²⁰ These rats also had elevated levels of tumor necrosis factor alpha and MIP2 in their lungs, and MIP2 in their hearts. Other reports suggest that particles of residual oil fly ash produce pulmonary inflammation in vitro²¹ and in vivo, ¹³ that the inflammation was characterized by an alveolar influx of neutrophils that peaked 24 hours after exposure, ²² and that particle toxicity was increased by preexisting inflammation. ²³

Human studies generally point in a similar direction. A recent chamber study of exposure to diesel particles at concentrations of 300 μg/m ³ for 1 hour reported increased neutrophils in the lung and in peripheral blood. ²⁴ The great London smog episode of 1952 saw high concentrations of combustion-related fine particles that occurred in stagnant air conditions that would result in low coarse mass levels.

The Mount St. Helens eruption produced high concentrations (10,000 μg/m ³) of dust (coarse particles). Few adverse health effects were seen. A similar result was reported in a study of a dust storm in southeastern Washington State, where particle concentrations exceeded 1,000 μg/m ^{3. 25} Another study examined 17 dust storm episodes in Spokane, WA, and found no increase in mortality during those episodes. ²⁶ In contrast, an episode in West Germany in 1985 of combustion-derived fine particles at half those concentrations was associated with a substantial increase in daily deaths, hospital admissions, and ambulance calls, ²⁷ as well as increases in plasma viscosity. ²⁸ This finding suggests that the coarse particles are of lesser concern.

In summary, toxicologic and epidemiologic studies indicate that ambient toxic particles are primarily in the fine-particle fraction and that fine sulfate particles from coal combustion are important contributors to these adverse health effects.