Association of Ambient Ozone Exposure with Airway

Inflammation and Allergy in Adults with Asthma

Sumita B. Khatri, M.D., M.S.1,2, Fernando C. Holguin, M.D.3, P. Barry Ryan, Ph.D.4, David

Mannino, M.D.5, Serpil C. Erzurum, M.D.2, and W. Gerald Teague, M.D.6

1

 Department of Medicine, MetroHealth Medical Center, Case School of Medicine, Cleveland, Ohio

2

 Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio

3

 Department of Medicine Pittsburgh University, Pittsburgh, Pennsylvania

4

 Emory University Rollins School of Public Health, Atlanta, Georgia

5

 University of Kentucky College of Public Health, Lexington, Kentucky

6

 Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia

Abstract

Rationale—Previous studies have demonstrated associations of high ozone levels with increased

epidemiologic as well as lung function measures of asthma activity.

Objectives—In an observational study during the summer months, we hypothesized that higher

ambient ozone levels are associated with more frequent symptoms, higher airway and systemic

inflammation, as well as worse lung function in asthmatics as compared with non-asthmatic

individuals.

Methods—Thirty-eight asthmatics and thirteen healthy control subjects residing in metropolitan

Atlanta were enrolled during peak ozone season. Medical histories, quality-of-life questionnaires,

spirometry, serum immunoglobulin (IgE), peripheral eosinophil counts, and exhaled nitric oxide

(NO) were obtained during study visits. Personal ozone exposures over the 2 days before presentation

were estimated based on location and activity surveys.

Main results—Upper airway symptoms were more frequent in asthmatics. Higher levels of ozone

were associated with worse airflow obstruction, lower quality of life scores, greater eosinophilia, and

higher exhaled NO levels in asthmatics. Finally, both asthmatics and non-asthmatics with allergies

showed associations between air quality and airway inflammation.

Conclusions—In adults with asthma but not controls studied during peak ozone season, increasing

ozone exposure predicted lower lung function and increased biomarkers of respiratory and systemic

inflammation. These associations were enhanced in atopic participants, both with and without

asthma. Importantly, the study findings were noted while atmospheric ozone levels were

predominantly within the current and revised national air quality standards.

Keywords

ozone; asthma; lung function; allergies

*Corresponding author: Sumita B. Khatri. MetroHealth Medical Center/CWRU School of Medicine, 2500, MetroHealth Drive,

Cleveland, OH 44109; skhatri@metrohealth.org.

Declaration of Interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

NIH Public Access

Author Manuscript

J Asthma. Author manuscript; available in PMC 2010 October 1.

Published in final edited form as:

J Asthma. 2009 October ; 46(8): 777–785.

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
Introduction

Atmospheric ozone is an important component of photochemical air pollution that is formed

from interaction of primary pollutants such as volatile hydrocarbons, halogenated organics,

and oxides of nitrogen in the presence of sunlight (1,2). Epidemiologic studies have

demonstrated increased asthma-related morbidity in association with higher levels of

atmospheric ozone. Periods following higher ozone levels are associated with increases in

asthma medication use, number of asthma exacerbations and hospitalizations, and risk of death

(3–9). Large cohort studies have demonstrated worsening of lung function, i.e., decrement in

morning peak flow rates or small airways function, in the days after elevated atmospheric ozone

levels (8,10). Although asthmatics are particularly susceptible to the harmful effects of ozone

air pollution, controlled exposure chamber studies demonstrated acutely diminished lung

function in asthmatics as well as healthy individuals after being exposed to high concentrations

of ozone (11–13). The capacity to induce pulmonary function alterations depends on ozone

levels, duration and pattern of exposure, and respiratory minute volume (14). Some

investigators revealed ozone air pollution’s association with the incidence of asthma in adult

men (15). Also, the incidence of asthma was increased among children playing three or more

outdoor sports in high ozone areas (16).

Although epidemiologic and chamber protocol studies have explored the mechanisms

underlying these associations, some investigators believe that ozone-associated changes in

pulmonary function are greater in natural than in controlled exposure settings (11,17). Studies

of children and adults in natural ozone environments have demonstrated a dose-response

relationship between ambient ozone levels, asthma symptoms, and worse lung function;

however, the mechanisms responsible remain poorly understood (18–22). The body of

literature regarding ozone and lung health underscores the need to further define the

mechanistic relevance of outdoor summer ozone levels with asthma morbidity, even if

pollution levels may be within Environmental Protection Agency (EPA) standards. The

purpose of this study was to use the well-defined high ozone seasons in Atlanta to examine the

associations of summertime ozone levels on airway inflammation in individuals with asthma

and healthy control subjects. We hypothesized that higher ambient ozone levels during the

summer months are associated with increased symptoms, higher airway and systemic

inflammation, as well as worse lung function in asthmatics as compared with non-asthmatic

individuals.

Methods

To test the hypothesis, we conducted a cross-sectional study of asthmatics and healthy control

subjects residing in the metropolitan Atlanta area during May through September 2003, 2005,

and 2006. Before enrollment, participants were asked to review and sign an informed consent

that was approved by the Emory University Institutional Review Board. Asthmatics included

were at least 18 years of age, nonsmokers (less than 5 pack-year smoking history more than 5

years ago), and lived in metropolitan Atlanta. Individuals who were acutely ill or had received

systemic corticosteroids within the last 2 weeks were excluded from participation. The

definition and severity of asthma was based on clinical history and presence of airflow

obstruction and/or documentation of a significant bronchodilator response (23,24). Healthy

control subjects were non-smokers with no history of pulmonary disease or allergic rhinitis

and normal spirometry. A brief medical and medication history was obtained, including

questions about subjective exposures to pollution and allergies. “(Have you been exposed to

pollution in the last 24 or 48 hours? If yes, was the level of exposure low, medium, or

high?)”. Similar questions were asked about exposures to common allergens such as pets,

pollen, mold, and dust. Participants were asked to provide hourly information about their

location by zip codes and level of physical activity for the previous 2 days, subjectively

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qualifying their levels of activity as low (no exertion), medium, and high exertion. Spirometry

was performed according to American Thoracic Society (ATS) standards (24). A peripheral

blood sample was sent to a certified clinical laboratory for leukocyte, eosinophil, and

immunoglobulin E (IgE) levels. The Juniper asthma quality of life questionnaire (QOLQ) was

orally administered to all asthmatic participants (25).

Testing for Atopy

Atopic status was obtained by skin testing or by history. Skin testing was not performed during

the first year of the study. Historical information or documented testing was used.

Subsequently, presence of allergies was determined by skin prick testing to 12 common

aeroallergens (e.g., dust mite, grass, Aspergillus, etc.) A wheal of 2 mm and flare of 3 mm

were considered positive. Individuals with prior testing within the past 2 years were not

retested.

Exhaled Nitric Oxide Measurement

Exhaled nitric oxide levels (eNO) were collected in participants according to the ATS standards

for offline measurements and analyzed by chemiluminescence analyzer (Sievers 280i, Boulder,

CO) (26–28). Ambient NO samples were also obtained simultaneously. The Mylar collection

balloons were flushed with argon gas between uses and sealed to reduce contamination by

ambient NO.

Quantification of Personal Ambient Ozone Exposure

Peak 1-hour ozone levels, peak 8-hour averaged ozone levels, peak Air Quality Index (AQI)

measurements, as well as temperature and relative humidity of the previous 48-hour and 24-

hour time period, were abstracted from regional air monitoring data. A map of metropolitan

Atlanta was used to visually determine the closest monitoring station to individuals’ reported

locations during each hour of the previous 2 days. Air quality data from that particular station

were then abstracted from the Georgia Department of Natural Resources monitoring website

(http://www.air.dnr.state.ga.us/amp/).

Statistical Analyses

Nonparametric tests (Wilcoxon Rank Sum) were used to evaluate differences between healthy

control subjects and asthmatics with respect to quantitative measures. Linear regression

modeling with biologically plausible and consistent models, excluding collinear variables, was

used to measure associations of clinical parameters with ozone exposure, controlling for

potential confounders. Model variables were selected due to the plausible and likely

independent contributions of each variable to the outcome measure. These variables, such as

subjective levels of exposures to air pollution and common allergens, 8-hour averaged levels

of ozone in the previous days before evaluation, and peripheral eosinophil and IgE levels, were

used as consistently as possible in models evaluated. Potential effect of enrollment year was

addressed by including a “year” variable in all multivariate models; however, primary

outcomes were not appreciably changed. Statistical analyses were performed with SAS version

9.1 (SAS Institute Inc, Gary, NC, USA), with p values ≤ 0.05 considered significant. Nonsignificant trends are also reported in certain instances where p ≤ 0.10.

Results

Patient Characteristics

The study sample included 38 asthmatic patients and 13 healthy control subjects between May

and September. Twelve asthmatic patients and 5 control subjects were studied during the 2003

season (during which 13 days exceeded air quality standards); 20 asthmatic patients and 6

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control subjects were studied in 2005 (during which 17 days exceeded air quality standards),

and 6 asthmatics and 2 healthy control subjects were studied in 2006 (during which 30 days

exceeded air quality standards). One asthmatic individual was not able to reliably perform

spirometry but did provide all other biosamples and clinical information and was therefore

included in the analyses.

Clinical features of enrolled individuals are presented in Table 1. Since a significant number

of men screened for enrollment were smokers, a higher number of women participated in the

study. As expected, participants with asthma demonstrated worse airflow obstruction. Markers

of allergy and inflammation were more prevalent in the asthmatics. Over half of asthmatics

had confirmed allergies by skin testing. However, three control subjects had skin tests positive

as well (Table 1). Fifty percent of the asthmatic group had mild disease, and the rest had

moderate or severe asthma based on Global Initiative for Asthma-GINA criteria (Table 2)

(23). Medication history demonstrated that frequency of controller therapy increased with

severity. A small number of individuals with moderate or severe asthma (8%) were not on any

controller therapy at the time of evaluation.

Ambient Ozone and Activity Levels

Peak 1-hour and peak 8-hour averaged levels recorded by ambient posted monitors nearest to

enrolled individuals in the 24 and 48 hours before study visits were similar in the asthmatic

and non-asthmatic groups (Appendix Table A1). Subjective estimation of high pollution

exposures (“medium” or “high” over prior 48 hours) also did not significantly differ between

the asthma and healthy control group. In any given time period (day of visit, 1 day before, or

2 days before participant evaluation), 8-hour averaged atmospheric ozone levels were inversely

related to relative humidity (R < −0.60, p < 0.001) and correlated with temperature (R > 0.45,

p < 0.01). Reported levels of activity and exertion were also similar between groups over the

previous 2 days (all p > 0.10, data not shown).

Symptoms

Frequency of upper airway symptoms such as itchy eyes, runny nose, sneezing, and congestion

was higher in the asthmatic group, and headaches also tended to be higher (Table 1). Stepwise

logistic regression analyses with symptoms as the outcome variables were performed.

Independent variables included in the model were presence of asthma, use of nasal steroids,

measured ozone levels, and subjective levels of exposure to allergen and pollution. Presence

of asthma and high pollution exposures were significantly associated with itchy eyes (asthma

OR = 12.62 [1.14–139.99], allergen exposure OR = 10.18 [2.12–48.88]). High allergen

exposures was the only independent variable significantly associated with headaches, sneezing,

and congestion (OR 1.67 [1.06–2.61], 1.72 [1.09–2.72], and 2.05 [1.26–3.33], respectively).

Quality of Life

Of a best possible score of seven, the median total quality-of-life score in our panel of

asthmatics was 5.22, with a range from 2.16 to 7.00. The forced expiratory volume in 1 second

(FEV1) percent predicted was associated with the overall score (R = 0.35, p = 0.04), and the

emotional domain score was especially related (R = 0.50, p < 0.01). Linear regression models

controlling for recent high allergen exposures, activity levels, and atmospheric ozone levels in

the previous 2 days estimated that a 50% increase in baseline % FEV1 would be associated

with an average increase of the quality-of-life score by 1. In contrast, increases in atmospheric

peak ozone levels by only 0.020 ppm (a plausible difference from high to low ozone days) was

associated with an average decrease in the quality of life score by a half a point (Table 3).

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Markers of Allergic Inflammation: Eosinophils, (IgE), and Exhaled NO

Peripheral eosinophilia in asthmatics was higher in association with peak ozone levels the day

before evaluation (Figure 1A), whereas no such association was seen in the healthy control

group (Figure 1B). Linear regression modeling of peripheral eosinophilia and ozone levels,

controlling for FEV1 % predicted tended to demonstrate a lag effect for ozone levels. Increases

in peak 8-hour averaged ozone levels every 0.020 ppm was associated with a 1.6 percent higher

number of eosinophils (Table 4). A similar tendency for a 2-day lag effect was also noted, such

that a 0.020 ppm increase in 8-hour averaged ozone levels was associated with an average 1%

higher peripheral eosinophilia (p ≤ 0.10 for model and ozone variable coefficient).

Exhaled NO values were higher in the asthmatics (n = 29) than healthy control subjects (n =

11) in whom off-line samples were collected (Table 1). Exhaled NO was inversely related to

airflow (FEV1/forced vital capacity [FVC] ratio % predicted, and FEV1 and peak flow %

predicted) and directly correlated with post-bronchodilator changes in FEV1 and FVC

(Appendix Table A2). Interestingly, in asthmatics, exhaled NO also correlated with peak ozone

levels 1 to 2 days before evaluation and tended to correlate with subjective exposures to

pollution (Table 5). Adding allergen exposures did not contribute to the significance of the

model. Correlation between ozone and exhaled NO levels was particularly strong among the

known atopic asthmatics (Figure 2) Linear regressions of exhaled NO and ozone levels,

controlling for FEV1 % predicted, demonstrated that for every 0.020 ppm increase in 8-hour

averaged ozone levels, exhaled NO levels would be higher by nearly 3 ppb (model p = 0.07,

coefficient for zone = 2.78 [C.I. 0.09–5.47], p = 0.05) (Appendix Table A3). Introducing

peripheral eosinophils into the model predicted similar increases in exhaled NO with ozone

levels (data not shown). Adding variables for subjective exposure to high pollution and

eosinophils to the model estimated that a positive response to “high pollution” was associated

with a 7 ppb higher levels of exhaled NO, thereby supporting the premise that individual

estimations of pollutant exposures are likely to be accurate (Table 6).

Associations of Ozone Exposure with Lung Function and Inflammation

Percent predicted FEV1/FVC ratio was inversely related to peak 8-hour ozone levels 2 days

before testing evaluation (R = 0.34, p = 0.04). When controlling for IgE, peripheral

eosinophilia, subjective level of recent allergen and pollution exposures, and 8-hour averaged

ozone levels, eosinophilia and pollution exposures were related to reduced airflow (Table 7).

Subjective exposures to high levels of air pollution, controlling for allergen exposures, was

associated with, on average, a 14-point lower (95% C.I. 3, 25) predicted FEV1/FVC ratio.

Similar associations were seen in the group of all enrolled (asthma and non-asthma), especially

in those with allergies (Appendix Table A4) where subjective exposures to pollution was

associated with an average 16-point lower predicted ratio. In addition, increases in peak 8-hour

averaged levels of ozone by 0.020 were associated with an average 8-point lower % FEV1/

FVC ratio (95% C.I. 3,14). Linear regression modeling demonstrated a trend of reduced

FEV1 percent predicted with subjective reporting of high exposures to air pollution (Table 8).

Adding temperature and relative humidity variables into models predicting FEV1/FVC or

FEV1 % predicted did not demonstrate significant associations or alter the relationships of the

original model. Only in the group of all atopic individuals, it was estimated that every 5%

higher level of relative humidity was associated with a 4-point higher % FEV1/FVC ratio.

Discussion

This study demonstrates an association of ozone lag effects on the morbidity of asthma,

specifically quality-of-life scores, airway inflammation, and lung function. Air quality indices

the days previous to our subjects’ study visits indicate that ozone levels were adequately high

to test our hypothesis, although the predominance of exposure levels were within the current

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and revised standards for peak 1-hour and 8-hour averaged ozone (29). In this panel study,

airway inflammation was associated with higher ozone levels, controlling for factors that are

expected to contribute to airway inflammation. Airways obstruction also appeared to be

associated with higher subjective pollution levels, regardless of estimated levels from posted

ambient ozone monitors. Similar to findings in other studies (30), these asthmatics had more

frequent upper airway symptoms. Also, air pollution exposures were negatively associated

with quality-of-life scores. Prior protocolized experimental studies that have demonstrated

increased allergenicity from ozone priming were underscored by this real world translational

pilot study that demonstrated increased eosinophilia and airway inflammation (as measured

by exhaled NO) in relation to recent higher ozone exposures.

Ground level ozone pollution is formed from motor vehicle exhaust, sunlight, and high

temperatures (2). Ambient ozone levels usually vary between 0.020 and 0.040 parts per million

(ppm). Moderate elevations in levels are usually 0.070 to 0.120 ppm, usually during the peak

ozone months of May through September. The air quality standard for ozone, which is designed

to protect public health with an adequate margin of safety, is 0.080 ppm, averaged over 8 hours,

specifically “the 3-year average of the fourth-highest daily maximum 8-hour average ozone

concentrations measured at each monitor within an area over each year must not exceed 0.080

ppm” (29).

Epidemiologic studies have demonstrated that asthmatics are particularly susceptible to poor

air quality, and multiple mechanisms may account for that association. The immediate effect

appears to be transient and neurally mediated. FEV1 and FVC return to pre-exposure levels

within 12 to 24 hours. However, airway resistance remains elevated, indicating a longer-term

consequence of exposure (31,32). The association with air pollution appears to be with a lageffect, particular with ozone (5,6,8,9). Changes in lung function after ozone exposure are

associated with an exuberant airway inflammatory response. The magnitude of this response

is heightened in individuals with asthma, with infiltration of both neutrophils and eosinophils

into the airways (2,32–35). Furthermore, the asthmatic response to inhaled allergen is amplified

with pre-exposure to ozone (17,36,37).

The similar peak ozone exposures in our healthy and asthmatic cohorts during their routine

every-day activities in Atlanta provided an ideal real-life opportunity to evaluate symptoms,

lung function, and airway inflammation between the two groups. In addition, this study was

performed in the natural environment with particular attention to activity level-sand provides

complementary data and validation of findings in controlled experimental studies. Other

investigators have suggested that the mechanism of chronic allergic inflammation and

susceptibility to ozone-related airway inflammation are related (38). In addition, responses to

inhaled allergen are also enhanced after exposure to ozone (36). In our study, individuals with

asthma tended to demonstrate worse airflow obstruction and enhanced biomarkers of allergic

inflammation associated with ozone exposure, with increased eosinophilia and exhaled NO

levels, even controlling for lung function.

The importance of self-reported exposures was evident in this study and may be partially

explained by heightened perception of exposures by those who are most affected (39).

However, in this study, objective clinical markers underscored the validity of their reports.

Therefore, personal immediate exposures and subjective sense of exposures are important and

cannot be estimated by distant and generalized measures alone. Asthmatics’ exhaled NO levels

were higher in association to perceptions of high pollution exposure (even controlling for

allergen exposure). In addition, individuals’ perceptions of recent exposures to high pollution

levels were related to lung function. Prior studies have described changes in FEF25–75, peak

expiratory flows, and %FEV1 after ambient exposure (10,40,41). Recent measured ozone

levels did not demonstrate a direct relationship to %FEV1 in asthmatic participants in this study.

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However, individual perception of pollution exposures appeared to play a role. The lack of

correlation of larger airways function to ozone levels in our cohort may be due to tolerance

developed over the ozone season or insufficient subjects. Ozone chamber studies show that

changes in FEV1 and FVC normalize after 12 to 24 hours of ozone exposure but that the increase

in airway resistance often persists (31). No airway resistance measurements were made in this

study; therefore, such associations may have been missed, perhaps accounting for worse

quality-of-life scores with higher ozone levels, even after controlling for lung function.

The role of other pollutants in increasing morbidity related to chronic lung diseases should not

be underestimated. Particulate matter (PM), which is the most common type of pollution

associated with industrial and traffic-related sources, refers to solid particles or droplets that

are suspended in the air. These particles can come from natural sources or industrial sources

and are categorized by size (fine particles are those less than 2.5 microns or less in diameter)

(42,43). Epidemiologic and experimental evidence has supported associations of PM and

asthma morbidity (42–46). For example, children attending schools within 400 meters of major

highways and freeways had increased respiratory symptoms suggestive of asthma (42).

Although this current study was not designed to evaluate the role of PM pollution with asthma

symptoms and airway inflammation, there were some individuals in whom PM contribution

could be estimated with geographic modeling and home addresses. The spatial relationships

of PM are more relevant than in ozone due to dispersion and individuals’ immediate

environments; therefore, firm conclusions cannot be drawn. Despite those limitations, 24- and

48-hour prior measures of ozone and PM were significantly correlated (R > 0.65, p < 0.001)

for all instances in which PM were able to be determined. All models for lung function with

ozone were run including PM values, and no significant plausible contributions were noted.

As stated in the hypothesis, this study was designed to evaluate associations between air quality

(ozone levels) and asthma activity and inflammation. However, there are certainly limitations

to this panel study. Although air pollution levels between groups were similar, individuals were

recruited over three high ozone seasons and were evaluated in a cross-sectional and not serial

manner. Another limitation is that despite attempts to keep enrollment equal between genders,

there was a predominance of women enrolled in the study. In addition, the asthmatic cohort

was predominantly African American. We may in part be demonstrating some phenomenon

that may be enhanced in certain ethnic populations and that requires further study. As of now,

there is no literature of antioxidant defenses and racial background affecting responses to air

pollution. However, it is known that areas of increased pollution owing to traffic and urban

development are frequently worse in areas where minorities reside (47–49). Next, most, but

not all, asthmatics were atopic; therefore some misclassification did occur. However, models

did allow for atopy to be evaluated, and subjective levels of allergen exposure were included

in most models. Atopy did not play a significant role in any associations except for exhaled

NO levels. A reasonable conclusion is that even if smaller groups are evaluated in such

translational exposure studies, real-world ozone levels did demonstrate biologically and

scientifically plausible associations, underscoring other investigators’ premise that controlled

chamber studies likely underestimate the effects of true outdoor air pollutants (11,17). Ambient

posted monitors have been used thus far to evaluate lung health and ozone levels (20,50). Based

on our results, it appears that a combination of exposure measures, such as measured outdoor,

personal monitor levels, and subjective levels of exposure, will show the most accurate

estimates of associations of pulmonary effects of air quality in real-world field studies.

Conclusion

In conclusion, in this real-world observational study, we demonstrate that asthmatics exposed

to ambient atmospheric ozone levels during high ozone season experienced worse symptoms

and had lower quality-of-life scores, worse lung function with increased airflow obstruction,

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and enhanced allergic inflammation. Although other factors potentially play a role in pollutantrelated airway inflammation, such as baseline lung function or individual antioxidant

capability, the associations seen in this study were evident with mean pollutant levels within

the current air quality standards (22,29).

Acknowledgments

Supported by a K12 grant from NIH National Center for Research Resources K12 RR 017643 and a grant from The

Carlyle Fraser Heart Center, Emory Crawford Long Hospital.

The author gratefully acknowledges the support and consultation of Professor Regis McFadden and statistical

assistance from Jeff Hammel. Technical assistance was provided by Smita Patel, Catherine Romano, Marianne Foster,

Jeanette Peabody, Samira Savill, Smitha Battula, Eric Hunter, Nancy Twum-Baah, Joseph Gram Praytor, EunjunYi,

Cindy Newman, and Ann Vander Schrier.

References

1. National Ambient Air Quality Standards (NAAQS). 2008. Retrieved 3 November 2008 from

http://epa.gov/air/criteria.html

2. Mudway IS, Kelly FJ. Ozone and the lung: A sensitive issue. Mol Aspects Med 2000;21:1–48.

[PubMed: 10804262]

3. Sunyer J, Basagana X, Belmonte J, Anto JM. Effect of nitrogen dioxide and ozone on the risk of dying

in patients with severe asthma. Thorax 2002;57:687–693. [PubMed: 12149528]

4. Jaffe DH, Singer ME, Rimm AA. Air pollution and emergency department visits for asthma among

Ohio Medicaid recipients, 1991–1996. Environ Res 2003;91:21–28. [PubMed: 12550084]

5. Friedman MS, Powell KE, Hutwagner L, Graham LM, Teague WG. Impact of changes in transportation

and commuting behaviors during the 1996 Summer Olympic Games in Atlanta on air quality and

childhood asthma. JAMA 2001;285:897–905. [PubMed: 11180733]

6. Pande JN, Bhatta N, Biswas D, Pandey RM, Ahluwalia G, Siddaramaiah NH, Khilnani GC. Outdoor

air pollution and emergency room visits at a hospital in Delhi. Indian J Chest Dis Allied Sci

2002;44:13–19. [PubMed: 11845928]

7. Ostro B, Lipsett M, Mann J, Braxton-Owens H, White M. Air pollution and exacerbation of asthma

in African-American children in Los Angeles. Epidemiology 2001;12:200–208. [PubMed: 11246581]

8. Mortimer KM, Neas LM, Dockery DW, Redline S, Tager IB. The effect of air pollution on inner-city

children with asthma. Eur Respir J 2002;19:699–705. [PubMed: 11999000]

9. Villeneuve PJ, Chen L, Rowe BH, Coates F. Outdoor air pollution and emergency department visits

for asthma among children and adults: A case-crossover study in northern Alberta, Canada. Environ

Health 2007;6:40. [PubMed: 18157917]

10. Romieu I, Meneses F, Ruiz S, Sienra JJ, Huerta J, White MC, Etzel RA. Effects of air pollution on

the respiratory health of asthmatic children living in Mexico City. Am J Respir Crit Care Med

1996;154(2 Pt 1):300–307. [PubMed: 8756798]

11. Higgins IT, D’Arcy JB, Gibbons DI, Avol EL, Gross KB. Effect of exposures to ambient ozone on

ventilatory lung function in children. Am Rev Respir Dis 1990;141(5 Pt 1):1136–1146. [PubMed:

2339836]

12. Koenig JQ. Effect of ozone on respiratory responses in subjects with asthma. Environ Health Perspect

1995;103 (suppl 2):103–105. [PubMed: 7614933]

13. Kreit JW, Gross KB, Moore TB, Lorenzen TJ, D’Arcy J, Eschenbacher WL. Ozone-induced changes

in pulmonary function and bronchial responsiveness in asthmatics. J Appl Physiol 1989;66:217–222.

[PubMed: 2917924]

14. McDonnell WF, Stewart PW, Smith MV, Pan WK, Pan J. Ozone-induced respiratory symptoms:

Exposure-response models and association with lung function. Eur Respir J 1999;14:845–853.

[PubMed: 10573232]

15. McDonnell WF, Abbey DE, Nishino N, Lebowitz MD. Long-term ambient ozone concentration and

the incidence of asthma in nonsmoking adults: The AHSMOG Study. Environ Res 1999;80(2 Pt 1):

110–121. [PubMed: 10092402]

Khatri et al. Page 8

J Asthma. Author manuscript; available in PMC 2010 October 1.

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
16. McConnell R, Berhane K, Gilliland F, London SJ, Islam T, Gauderman WJ, Avol E, Margolis HG,

Peters JM. Asthma in exercising children exposed to ozone: A cohort study. Lancet 2002;359(9304):

386–391. [PubMed: 11844508]

17. Spektor DM, Lippmann M, Lioy PJ, Thurston GD, Citak K, James DJ, Bock N, Speizer FE, Hayes

C. Effects of ambient ozone on respiratory function in active, normal children. Am Rev Respir Dis

1988;137:313–320. [PubMed: 3341625]

18. Korrick SA, Neas LM, Dockery DW, Gold DR, Allen GA, Hill LB, Kimball KD, Rosner BA, Speizer

FE. Effects of ozone and other pollutants on the pulmonary function of adult hikers. Environ Health

Perspect 1998;106:93–99. [PubMed: 9435151]

19. Mulholland JA, Butler AJ, Wilkinson JG, Russell AG, Tolbert PE. Temporal and spatial distributions

of ozone in Atlanta: Regulatory and epidemiologic implications. J Air Waste Manag Assoc

1998;48:418–426. [PubMed: 9602552]

20. Tolbert PE, Mulholland JA, MacIntosh DL, Xu F, Daniels D, Devine OJ, Carlin BP, Klein M, Dorley

J, Butler AJ, Nordenberg DF, Frumkin H, Ryan PB, White MC. Air quality and pediatric emergency

room visits for asthma in Atlanta, Georgia, USA. Am J Epidemiol 2000;151:798–810. [PubMed:

10965977]

21. Girardot SP, Ryan PB, Smith SM, Davis WT, Hamilton CB, Obenour RA, Renfro JR, Tromatore KA,

Reed GD. Ozone and PM2.5 exposure and acute pulmonary health effects: A study of hikers in the

Great Smoky Mountains National Park. Environ Health Perspect 2006;114:1044–1052. [PubMed:

16835057]

22. Nickmilder M, Carbonnelle S, de Burbure C, Bernard A. Relationship between ambient ozone and

exhaled nitric oxide in children. JAMA 290:2546–2547. [PubMed: 14625330]

23. NHLBI/WHO. GINA (Global Initiative for Asthma) Workshop Report, Global Strategy for Asthma

Management and Prevention. NIH publication 95–3659. 2004. NHLBI/WHO Workshop Report.

24. Standardization of Spirometry, Update. American Thoracic Society. Am J Respir Crit Care Med

1994;152:1107–1136.

25. Juniper EF, Buist AS, Cox FM, Ferrie PJ, King DR. Validation of a standardized version of the Asthma

Quality of Life Questionnaire. Chest 1999;115:1265–1270. [PubMed: 10334138]

26. Silkoff PE. Noninvasive measurement of airway inflammation using exhaled nitric oxide and induced

sputum. Current status and future use. Clin Chest Med 2000;21:345–360. [PubMed: 10907593]

27. Recommendations for standardized procedures for the on-line and off-line measurement of exhaled

lower respiratory nitric oxide and nasal nitric oxide in adults and children-1999. This official

statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999.

Am J Respir Crit Care Med 1999;160:2104–2117. [PubMed: 10588636]

28. Barreto M, Villa MP, Martella S, Falasca C, Guglielmi F, Pagani J, Darder MT, Ronchetti R. Offline exhaled nitric oxide measurements in children. Pediatr Pulmonol 2001;32:159–167. [PubMed:

11477733]

29. Clean Air Scientific Advisory Committee Recommendation Concerning the Proposed National

Ambient Air Quality Standards for Particulate Matter. EPA-CASAC-LTR-06-002 Letter to Stephen

L. Johnson. Mar 21. 2006

30. Rodriguez C, Tonkin R, Heyworth J, Kusel J, De Klerk N, Sly PD, Franklin P, Runnion T, Blockley

A, Landau L, Hinwood AL. The relationship between outdoor air quality and respiratory symptoms

in young children. Int J Environ Health Res 2007;17:351–360. [PubMed: 17924263]

31. McDonnell WF, Horstman DH, Hazucha MJ, Seal E Jr, Haak ED, Salaam SA, House DE. Pulmonary

effects of ozone exposure during exercise: Dose-response characteristics. J Appl Physiol

1983;54:1345–1352. [PubMed: 6863094]

32. Nightingale JA, Rogers, Barnes PJ. Effect of inhaled ozone on exhaled nitric oxide, pulmonary

function, and induced sputum in normal and asthmatic subjects. Thorax 1999;54:1061–1069.

[PubMed: 10567624]

33. Peden DB, Boehlecke B, Horstman D, Devlin R. Prolonged acute exposure to 0.16 ppm ozone induces

eosinophilic airway inflammation in asthmatic subjects with allergies. J Allergy Clin Immunol

1997;100(6 Pt 1):802–808. [PubMed: 9438490]

Khatri et al. Page 9

J Asthma. Author manuscript; available in PMC 2010 October 1.

NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
34. Peden DB, Setzer RW Jr, Devlin RB. Ozone exposure has both a priming effect on allergen-induced

responses and an intrinsic inflammatory action in the nasal airways of perennially allergic asthmatics.

Am J Respir Crit Care Med 1995;151:1336–1345. [PubMed: 7735583]

35. Balmes JR, Aris RM, Chen LL, Scannell C, Tager IB, Finkbeiner W, Christian D, Kelly T, Hearne

PQ, Ferrando R, Welch B. Effects of ozone on normal and potentially sensitive human subjects. Part

I: Airway inflammation and responsiveness to ozone in normal and asthmatic subjects. Res Rep

Health Eff Inst 1997:1–37. discussion 81–99. [PubMed: 9387195]

36. Molfino NA, Wright SC, Katz I, Tarlo S, Silverman F, McClean PA, Szalai JP, Raizenne M, Slutsky

AS, Zamel N. Effect of low concentrations of ozone on inhaled allergen responses in asthmatic

subjects. Lancet 1991;338(8761):199–203. [PubMed: 1676776]

37. Jenkins HS, Devalia JL, Mister RL, Bevan AM, Rusznak C, Davies RJ. The effect of exposure to

ozone and nitrogen dioxide on the airway response of atopic asthmatics to inhaled allergen: Doseand time-dependent effects. Am J Respir Crit Care Med 1999;160:33–39. [PubMed: 10390376]

38. Peden DB. Air pollution in asthma: Effect of pollutants on airway inflammation. Ann Allergy Asthma

Immunol 2001;87(6 suppl 3):12–17. [PubMed: 11770676]

39. Kuehni CE, Strippoli MP, Zwahlen M, Silverman M. Association between reported exposure to road

traffic and respiratory symptoms in children: Evidence of bias. Int J Epidemiol 2006;35:779–786.

[PubMed: 16513809]

40. Romieu I, Sienra-Monge JJ, Ramirez-Aguilar M, Moreno-Macias H, Reyes-Ruiz NL, Estela del RioNavarro B, Hernandez-Avila M, London SJ. Genetic polymorphism of GSTM1 and antioxidant

supplementation influence lung function in relation to ozone exposure in asthmatic children in

Mexico City. Thorax 2004;59:8–10. [PubMed: 14694237]

41. Romieu I, Sienra-Monge JJ, Ramirez-Aguilar M, Tellez-Rojo MM, Moreno-Macias H, Reyes-Ruiz

NI, del Rio-Navarro BE, Ruiz-Navarro MX, Hatch G, Slade R, Hernandez-Avila M. Antioxidant

supplementation and lung functions among children with asthma exposed to high levels of air

pollutants. Am J Respir Crit Care Med 2002;166:703–709. [PubMed: 12204869]

42. Janssen NA, Brunekreef B, van Vliet P, Aarts F, Meliefste K, Harssema H, Fischer P. The relationship

between air pollution from heavy traffic and allergic sensitization, bronchial hyperresponsiveness,

and respiratory symptoms in Dutch schoolchildren. Environ Health Perspect 2003;111:1512–1518.

[PubMed: 12948892]

43. Brauer M, Hoek G, Van Vliet P, Meliefste K, Fischer PH, Wijga A, Koopman LP, Neijens HJ,

Gerritsen J, Kerkhof M, Heinrich J, Bellander T, Brunekreef B. Air pollution from traffic and the

development of respiratory infections and asthmatic and allergic symptoms in children. Am J Respir

Crit Care Med 2002:1661092–1661098.

44. Pope CA III, Dockery DW. Health effects of fine particulate air pollution: Lines that connect. J Air

Waste Manag Assoc 2006;56:709–742. [PubMed: 16805397]

45. Pope CA III. Respiratory disease associated with community air pollution and a steel mill, Utah

Valley. Am J Public Health 1989;79:623–628. [PubMed: 2495741]

46. Pope CA III. Respiratory hospital admissions associated with PM10 pollution in Utah, Salt Lake, and

Cache Valleys. Arch Environ Health 1991;46:90–97. [PubMed: 2006899]

47. Brown P, Mayer B, Zavestoski S, Luebke T, Mandelbaum J, McCormick S. The health politics of

asthma: Environmental justice and collective illness experience in the United States. Soc Sci Med

2003;57:453–464. [PubMed: 12791488]

48. Claudio L, Torres T, Sanjurjo E, Sherman LR, Landrigan PJ. Environmental health sciences

education–a tool for achieving environmental equity and protecting children. Environ Health Perspect

1998;106 (suppl 3):849–855. [PubMed: 9646048]

49. Gunier RB, Hertz A, Von Behren J, Reynolds P. Traffic density in California: Socioeconomic and

ethnic differences among potentially exposed children. J Expo Anal Environ Epidemiol

2003;13:240–246. [PubMed: 12743618]

50. O’Neill MS, Ramirez-Aguilar M, Meneses-Gonzalez F, Hernandez-Avila M, Geyh AS, SienraMonge JJ, Romieu I. Ozone exposure among Mexico City outdoor workers. J Air Waste Manag

Assoc 2003;53:339–346. [PubMed: 12661692]

Khatri et al. Page 10

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Appendix

Table A1

Peak levels of ozone (ppm) days prior to evaluation.

Asthmatics Controls p value*

8-hour averaged ozone

levels 2 days prior

0.061 (.032–.074) 0.056 (.037–.064) 0.97

1-hour ozone levels 2 days

prior

0.072 (.045–.087) 0.066 (.050–.082) 0.99

8-hour averaged ozone

levels 1 day prior

0.059 (.044–.073) 0.065 (.057–.083) 0.35

1-hour ozone levels 1 day

prior

0.070 (.049–.080) 0.077 (.070–.094) 0.28

Air Quality index†

2 days prior 75 (53–101) 76 (61–111) 0.53

1 day prior 75 (55–103) 97 (70–121) 0.18

Subjective exposure to

high pollution‡

26 (68%) 6 (46%) 0.17

Data presented as median (IQR);

*

p-value based on wilcoxon rank sum testing

†

AQI defined as the index of air quality as determined by the highest level of criteria pollutants: PM, Ozone, sulfur dioxide,

nitrogen dioxide, and carbon monoxide.

‡

Those reporting exposure to medium to high levels of pollution during prior 2 days.

Table A2

Exhaled NO and lung function in asthma.

Exhaled NO and R (Spearman) p Numbers

FEWFVC Ratio −0.567 0.002 28

% Pred Ratio −0.53 0.003 28

%FEV1 −0.436 0.021 28

%PEFR −0.437 0.020 28

%FEF −0.567 0.002 28

Change FEV1 post BD 0.649 0.0006 24

Change FVC post BD 0.468 0.021 24

Table A3

Exhaled NO and air pollution in asthma (model p = 0.07).

Parameter estimate 95% C.I. p

*

Intercept 16.69 1.83,31.55 0.04

FEV1 % predicted −0.12 −0.28, .04 0.18

Change of 0.02 ppm of 8-hour averaged ozone

levels 2 days prior

2.78 0.09, 5.47 0.05

*

p value: significance of parameter estimate in linear regression model.

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Table A4

Predicted ratio in allergic asthmatics and nonasthmatics (model p = 0.02).

Parameter estimate Std Errp

Intercept 148.64 16.46 <0.01

Subjective exposure to high allergen

*

−1.60 1.87 0.41

Subjective exposure to high pollution

*

−16.44 6.81 0.04

Change of 0.02 ppm of 8-hour averaged ozone

levels 2 days prior

−8.33 2.80 0.02

Peripheral blood % eosinophils−215.00 1.94 0.30

Serum IgE level−0.006 0.003 0.07

Asthmatic−12.57 11.46 0.30

*

Those reporting exposure to “medium” to “high” levels of pollution or allergen during prior 2 days.

*p value: significance of parameter estimate in linear regression model.

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Figure 1.

Eosinophilia and prior ozone levels in asthmatics (a) R = 0.41, p = 0.03 vs. controls (b) R =

0.12, p = 0.73.

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Figure 2.

Correlation in atopic asthmatics between ozone levels 2 days prior and exhaled NO levels, R

= 0.60, p = 0.014.

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Table 1

Subject characteristics.

Asthmatics Controls p value

*

N 38 13Age 44 (31–50) 40 (29–55) 1.00Gender F:M 32:6 12:1BMI 32 (25–40) 30 (23–41) 0.49Race-ethnicity

Caucasian 11 4African- American 26 8Asian 0 1Other 1 0

Lung function

% FEV1/FVC ratio 91 (81–101) 97 (96–102) 0.04% FEV1 79 (69–90) 88 (82–94) 0.07%PEF 78 (66–99 83 (66–88) 0.52

Markers of blood leukocytes (× 10

3

) 6.8 (5.7–8.6) 5.3 (4.8–6.4) 0.07

Eosinophils (%) 2 (2–4) 2 (1–2) 0.07Neutrophils (%) 62 (53–68) 53 (41–62) 0.09

IgE (lU/mL) 134 (50–324) 34 (14–74) <0.01eNO (ppb) 11.4 (9.8–17.0) 7.1 (6.3–12.5) 0.03Results of allergen skin tests:

>1/12 positive 20 11/12 positive 3 20/12 positive 8 5History of atopy (no skin test) 7 5

Frequency of upper respiratory symptoms

Itchy eyes 22/34 64 1/12 8 <0.01Runny nose 16/34 47 0/12 0 <0.01Sneezing 17/34 50 1/12 8 0.02Congestion 15/38 39 1/13 8 0.04

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Asthmatics Controls p value

*

Headaches 13/38 34 1/13 8 0.08

Data presented as median (IQR);*

p value based on Wilcoxon Rank Sum,

+

p value based on Fischer Exact Test.

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Table 2

Asthmatic Global Initiative for Asthma (GINA) Classification (n = 37)

* by severity and medication.

Severity

N ICS only ICS +LTRA LTRA only Neither ICS nor LTRA

Mild (%FEV1 > 80) 18 6 3 4 5Moderate asthma (%FEV1 60–80) 13 5 5 1 2Severe (%FEV1 < 60) 6 4 1 0 1

Total 37 15 9 5 8

*

One asthmatic patient was unable to adequately perform spirometry.

ICS = inhaled corticosteroids; LTRA = leukotriene receptor antagonist.

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Table 3

Asthma quality-of-life scores and exposures (model p = 0.07).

Parameter estimate 95% C.I. p

Intercept 2.97 −0.58, 6.52 0.11

FEV1% predicted 0.02 0.00, 0.04 0.05

Subjective exposure to high allergen* activity levels 2 days prior 0.08 −0.19, 0.35 0.57

0.05 −0.05, 0.15 0.40

Change of 0.02 ppm of 8-hour averaged ozone levels 2 days prior −0.46 −0.85, −0.07 0.03

*

Those reporting exposure to “medium” to “high” levels of pollution or allergen during prior 2 days.

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Table 4

Eosinophilia and air pollution in asthmatics (model p = 0.03).

Pararmeter estimate 95% C.I. p

Intercept 1.95 −4.79, 8.69 0.58

FEV1 %predicted −0.04 −0.12,0.04 0.26

Change of 0.02 ppm of 8-hour averaged ozone levels 1 day prior 1.63 0.41,2.85 0.02

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Table 5

Exhaled NO and air quality in asthmatics, atopic asthmatics.

Correlations of exhaled NO and air quality R (Spearman’) p Numbers

All asthmatics:

Peak 8-hour avg ozone levels 2 days prior 0.428 0.21 29

Peak 1-hour ozone levels 2 days prior 0.415 0.025 29

Subjective exposure to high pollution* 0.34 0.07 29

Atopic asthmatics:

Peak 8-hour avg ozone levels 2 days prior 0.601 0.014 16

Peak 1-hour ozone levels 2 days prior 0.546 0.028 16

Subjective exposure to high pollution* 0.39 0.13 16

*

Those reporting exposure to “medium” to “high” levels of pollution during prior 2 days.

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Table 6

Exhaled NO and air pollution in asthma (model p=0.02).

Parameter estimate Std Err p

Intercept −5.70 11.31 0.62

FEV1 % predicted 0.0005 0.0969 1

Change of 0.02 ppm of 8-hour averaged ozone levels 2 days prior 3.10 1.40 0.04

Subjective exposure to high pollution* peripheral blood % eosinophils 7.88 3.56 0.04

2.56 1.17 0.04

*

Those reporting exposure to “medium” to “high” levels of pollution during prior 2 days.

*

p value: significance of parameter estimate in linear regression model.

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Table 7

FEV1/FVC ratio (% predicted) in asthmatics (model p < 0.01).

Parameter estimate 95% Cl p

Intercept 119.22 104.77, 133.67 <0.01

Subjective exposure to high allergen* −0.70 −4.52, 3.12 0.72

Subjective exposure to high pollution* −13.65 −24.76, −2.54 0.03

Change of 0.02 ppm of 8-hour averaged ozone levels 2 days prior −3.14 −7.78, 1.48 0.20

Peripheral blood % eosinophils −2.24 −3.96, −0.52 0.02

Serum IgE level −0.007 −0.013, −0.001 0.04

*

Those reporting exposure to “medium” to “high” levels of pollution or allergen during prior 2 days.

*

p value: significance of parameter estimate in linear regression model.

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Table 8

FEV1 percent predicted in asthmatics (model p = 0.04).

Parameter estimate 95% Cl p

*

Intercept 97.00 77.30, 116.70 <0.01

Subjective exposure to high allergen* 1.65 −45.4, 48.69 0.50

Subjective exposure to high pollution* −11.84 −25.21, 1.53 0.10

Change of 0.02 ppm of 8-hour averaged ozone levels 2 days prior 1.28 −4.55, 7.10 0.67

Peripheral blood % eosinophils −0.95 −3.09, 1.19 0.39

Serum IgE level −0.010 −0.018, −0.002 0.02

On inhaled corticosteroid treatment −12.08 −24.45, −0.29 0.07

*

Those reporting exposure to “medium” to “high” levels of pollution or allergen during prior 2 days.

*

p value: significance of parameter estimate in linear regression model.

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