Ozone exposure and pulmonary effects in panel and human clinical studies: Considerations for design and interpretation

Figures & data

Table 1. Summary of post-2000 panel studies that evaluated associations between ozone and pulmonary effects in children or adults

Reference	Location	Study period	Study population	Ozone metric(s)	Mean ozone concentration (ppb) (SD)	Lag(s)	Outcome(s)	Primary results	Multipollutant models
Altug et al. 2013	3 different areas in Eskisehir, Turkey	2 weeks in 2 seasons in 2008 and 2009	1880 students aged 9–13 years	Average of two 1-week integrated samples collected outside at studied schools	23.9 (6.9) to 55.0 (13.9) depending on season/location	—	FVC, FEV1, PEF, MMEF, FEV1/FVC%, symptoms	Significantly reduced lung function for girls in summer season; no other results significant.	—
Altug et al. 2014	3 different areas in Eskisehir, Turkey	2 weeks in March 2009	695 students aged 9–13 years	1-week avg	23.9 (6.9), 39.3 (13.0), and 43.9 (13.2) for three locations	—	FVC, FEV1, PEF, MMEF, FeNO, upper respiratory tract complaints, medication use	Significant association with upper respiratory tract complaints; significant negative association with PEF in children without respiratory tract complaints. No significant associations for FeNO.	—
Castro et al., 2008	Rio de Janeiro, Brazil	3 months in 2004	118 children aged 6–15 years	24-hr avg	40.5 (18.8)	1-, 2-, and 3-day; 2- and 3-day MAs	PEF	Significant increase in peak flow at lag 1; no significant associations for any other lags.	—
Chan and Wu 2005	Taichung City, Taiwan	November-December 2001	43 mail carriers	8-hr avg, 8-hr max (both during carriers’ working periods)	8-hr avg: 35.6 (12.1); 8-hr max: 52.6 (18.8)	0-, 1-, 2-, and 3-day	Nightime PEFR; nighttime PEFR deviation	8-hr average ozone significantly associated with nighttime PEFR (and deviation) at lags 0, 1, and 2 days; 8-hr max ozone significantly associated with both measures at lags 0 and 1 day.	No change in results with PM10 and NO2.
Dales et al. 2009	Windsor, Canada	28 days in 2005	182 asthmatic children aged 9–14 years	24-hr avg; 24-hr max	24-hr avg: 14.1 (6.0); 24-hr max: 27.2 (8.6)	—	FEV1	No significant associations for either ozone measure.	No change in results with PM2.5, NO2, or SO2.
Delfino et al. 2002	Alpine, CA	March-April, 1996	22 asthmatic children aged 9–19 years	1-hr max, 8-hr max	1-hr max: 69 (16); 8-hr max: 60 (12)	0-, 1-, 2-, 3-, 4-, 5-day; various moving averages selected based on individual lag results	Symptoms (none or not bothersome vs. interfering with daily activities)	No significant associations for either ozone measure at any lag, or in groups of children on or not on medication.	Interactions between ozone and NO2 observed, but risk estimates not reported.
Delfino et al. 2003	Los Angeles, CA	Up to 3 months, 1999–2000	22 Hispanic children with asthma, aged 10–16 years	1-hr max, 8-hr max	1-hr max: 25.4 (9.6); 8-hr max: 17.1 (7.2)	0-, 1-day	Symptoms (0 = none; 1 = not bothersome; 2 = bothersome or more severe), PEF	Significant increase in ORs for symptom scores >2 for 1-hr and 8-hr max ozone at lag 0; no significant associations for symptom scores >1. Results for PEF not reported.	—
Escamilla-Nunez et al. 2008	Mexico City, Mexico	Average of 22 weeks during 2003–2005	147 asthmatic children (6–14 yrs), 50 healthy children (6–14 yrs)	1-hr max	86.5 (34.4)	0 and 1 day; 2–5 day MAs	Presence/absence of cough and wheeze; medication use	Significant increase in cough, wheeze,and bronchodilator use at lag 1 (cough also at lag 0) and cumulative lags 2–5 in asthmatic children. No significant associations in healthy children.	With PM2.5 and NO2, results similar.
Jalaludin et al. 2000	Sydney, Australia	11 months in 1994	125 children with history of wheeze (mean age 9.6 years)	Daytime avg (06:00–21:00); daily max	avg: 12.0 (6.8); max: 26.0 (14.4)	0, 1, 2, 3, 4; 2- and 5- day average	Daily mean variation in PEFR (ΔPEFR)	Significant negative association between daily average ozone and ΔPEFR; no significant association for daily max ozone.	With PM10 and NO2, little change in coefficients.
Jalaludin, O’Toole, and Leeder 2004	Sydney, Australia	11 months in 1994	125 children with history of wheeze (mean age 9.6 years)	Daytime avg (06:00–21:00); daily max	avg: 12.0 (6.8); max: 26.0 (14.4)	0, 1, 2, 3, 4; 2- and 5- day average	Symptoms, medication use, doctor visits for asthma	No significant associations for any outcome.	With PM10 and NO2, little change in coefficients.
Just et al. 2002	Paris, France	3 months in 2006	82 asthmatic children (mean age 10.9 years)	8-hr avg	29.5 (12.3)	0, 1, 2; average of 0–2 days and 0–4 days	Symptoms, PEF	Significant association between increase in PEF variability and 0–2 day average ozone.	BS not significant in model with BS, O3 and int term between O3 and temperature. O3 not significant in model with NO2, O3 and int term between O3 and temperature.
Karakatsani et al. 2012	Amsterdam, The Netherlands; Athens, Greece; Birmingham, UK; Helsinki, Finland	6-month period in 2002–2004	136 adults aged ≥ 35 years diagnosed with asthma, COPD, or chronic non-specific lung disease	24-hr avg	Helsinki 21.3; Athens 23.5; Amsterdam 16.6; Birmingham 18.7 (all medians)	0-, 1-, 2-day; average of lag 0–6	Symptoms	Significant increase in waking with breathing problems at lag 0 in total study group; significant negative association with shortness of breath at lags 1 and 2 in asthmatic group; significant increase in cough at lags 0, 1, and 2 in total study group and asthmatic group	—
Lagorio et al. 2006	Rome, Italy	May–June and November–December 1999	29 adults with COPD (11), asthma (11), or IHD (7)	24-hr avg	33.1 (5.8) in spring; 7.5 (3.8) in winter	1-day, cumulative 2- and 3-day	FEV1, FVC	No significant associations for ozone and any endpoint.	—
Lewis et al. 2005	Detroit, MI	Six 2-week periods in 2001–2002	86 asthmatic children aged 7–11 years	24-hr avg	24-hr avg 27.6 (12.5); peak 8-hr avg 40.4 (18.2) (for Eastside site; concentrations similar at Southwest site)	1- and 2-day; 3–5 day average	FEV1	No significant associations with 24-hr average ozone among children not using maintenance corticosteroids (CS); daily 8-hr peak ozone significantly associated with FEV1 decrements at lag 2.	With PM2.5, significant association at lag 3–5; with PM10, significant association at lags 1, 2, and 3–5.
Mortimer et al. 2002	Eight urban areas in the United States	Summer 1993	846 asthmatic children aged 4–9 years	8-hr avg	Values not provided; Figure 1 in this paper shows mean ranging from ~40–60 depending on urban area. Mean over all 8 areas = 48.	1-, 2-, 3-, 4-, 5-, 6-day; 1–5 day average; 1–4 day average, 0–4 day average, 0–3 day average	Symptoms, PEFR	Significant associations between decline in morning PEFR and 5-day average ozone, increased morning symptoms and 4-day average ozone. No associations for evening measures.	For morning symptoms, addition of SO2 to the model removed ozone significance.
Ostro et al. 2001	Los Angeles and Pasadena, CA	August–November, 1993	138 African-American children with asthma, aged 8–13 years	1-hr max	Los Angeles: 59.5 (31.4); Pasadena: 95.8 (49)	0-, 1-, 2-, 3-day; 4-day moving average	Symptoms, medication use	No significant associations for shortness of breath, cough, or wheeze. In moderate and severe asthmatics, 2-day moving average ozone and lag 1 day significantly assocated with extra medication use.	—
Peacock et al. 2003	3 schools in Medway, England	13 weeks in 1996–1997	179 children aged 7–13	8-hr max moving avg, 1-hr max	8-hr max MA: 21.6 (11.1) for rural; 19.0 (10.6) for urban. 1-hr max: 25.8 (11.1) for rural, 23.1 (10.2) for urban.	0, 1, 2 days; 1–4 day average	PEFR	Either null or significantly protective associations between ozone and PEFR when all schools analyzed together.	—
Samoli et al. 2017	Athens and Thessaloniki, Greece	5 weeks in 2013–2014	186 children aged 10–11 years at schools in low- and high-ozone areas	24-hr avg personal and fixed site	Athens, fixed site: 22.3 (9.4) to 32.1 (11.1); personal: 4.1 (3.9) to 5.4 (3.9). Thessaloniki lower.	0, 1 day	PEF, symptoms	Significantly increased odds of stuffy nose with personal but not fixed-site data; no significant associations with other symptoms or with PEF.	With PM10, no change.
Schachter et al. 2016	New York, NY	Two 2-week periods in summer and winter seasons during 2008–2009	36 asthmatic children aged 6–14 years	24-hr avg	Summer: 25.3 (8.7); winter: 16.6 (9.0)	—	Symptoms, PEF	Ozone significantly associated with symptoms and reduced morning FEV1 in summer but not winter.	—
Schildcrout et al. 2006	8 North American cities	1993–1995; followed for median of 2 months	990 children aged 5–12 years	1-hr max (warm season)	Means not provided; median ranged from 43.0 to 65.8 depending on city	0, 1, 2 days; 0–3 day average	Symptoms, medication use	No significant associations for any outcome.	—
Ward et al., 2002	Birmingham and Sandwell, England	Two 8-week periods (summer and winter) in 1996	162 children aged 9 years	24-hr avg	Means not provided; winter median 13.0, summer median 22.0	0, 1, 2, 3 days; 0–7 day average	Symptoms, PEF	In winter, significant associations for DPEF in morning at 0–7 average lag; some significant associations for symptoms. In summer, significant association for DPEF in morning at 2 day lag and 0–8 day average lag, some significant associations with wheeze.	—
Yoda et al. 2014	Tokyo, Japan	2 weeks during summer 2012	21 healthy female students aged 20–23 years	24-hr avg	Values not provided; Figure 2 in this paper shows range of ~10–60 ppb	lag 0, 1; 2 to 5 day average	PEF, FEV1, EBC pH, FeNO	Significant reduction in EBC pH at all lags; nonsignificant associations for FeNO, PEF, FEV1	Ozone association for EBC pH significantly decreased after adjusting for NO2 or suspended PM.

Note. max, Maximum; avg, average

Altug, H., E.O. Gaga, T. Dogeroglu, O. Ozden, S. Ornektekin, B. Brunekreef, K. Meliefste, G. Hoek, and W. Van Doorn. 2013. Effects of air pollution on lung function and symptoms of asthma, rhinitis, and eczema and primary school children. Environ. Sci. Pollut. Res. International 20:6455–67. doi:10.1007/s11356-013-1674-1.

 PubMed Web of Science ®Google Scholar

Altug, H., E.O. Gaga, T. Dogeroglu, B. Brunekreef, G. Hoek, and W. Van Doorn. 2014. Effects of ambient air pollution on respiratory tract complaints and airway inflammation in primary school children. Sci. Total Environ. 479–480:201–09. doi:10.1016/j.scitotenv.2014.01.127.

 PubMed Web of Science ®Google Scholar

Chan, -C.-C., and T.-H. Wu. 2005. Effects of ambient ozone exposure on mail carriers’ peak expiratory flow rates. Environ. Health Perspect. 113:735–38. doi:10.1289/ehp.7636.

 PubMed Web of Science ®Google Scholar

Dales, R., L. Chen, A.M. Frescura, L. Liu, and P.J. Villeneuve. 2009. Acute effects of outdoor air pollution on forced expiratory volume in 1 s: A panel study of schoolchildren with asthma. Eur. Respir. J. 34 (2):316–23. doi:10.1183/09031936.00138908.

 PubMed Web of Science ®Google Scholar

Delfino, R.J., R.S. Zeiger, J.M. Seltzer, D.H. Street, and C.E. McLaren. 2002. Association of asthma symptoms with peak particulate air pollution and effect modification by anti-inflammatory medication use. Environ. Health Perspect. 110 (10):A607–17. doi:10.1289/ehp.021100607.

 PubMed Web of Science ®Google Scholar

Delfino, R.J., J.H. Gong, W.S. Linn, E.D. Pellizzari, and Y. Hu. 2003. Asthma symptoms in Hispanic children and daily ambient exposures to toxic and criteria air pollutants. Environ. Health Perspect. 111 (4):647–56. doi:10.1289/ehp.5992.

 PubMed Web of Science ®Google Scholar

Escamilla-Nunez, M.C., A. Barraza-Villarreal, L. Hernandez-Cadena, H. Moreno-Macias, M. Ramirez-Aguilar, J.J. Sienra-Monge, M. Cortez-Lugo, J.L. Texcalac, B. Del Rio-Navarro, and I. Romieu. 2008. Traffic-related air pollution and respiratory symptoms among asthmatic children, resident in Mexico City: The EVA cohort study. Respir. Res. 9:74. doi:10.1186/1465-9921-9-74.

 PubMed Web of Science ®Google Scholar

Jalaludin, B.B., T. Chey, B.I. O’Toole, W.T. Smith, A.G. Capon, and S.R. Leeder. 2000. Acute effects of low levels of ambient ozone on peak expiratory flow rate in a cohort of Australian children. Int. J. Epidemiol. 29 (3):549–57. doi:10.1093/intjepid/29.3.549.

 PubMed Web of Science ®Google Scholar

Jalaludin, B.B., B.I. O’Toole, and S.R. Leeder. 2004. Acute effects of urban ambient air pollution on respiratory symptoms, asthma medication use, and doctor visits for asthma in a cohort of Australian children. Environ. Res. 95 (1):32–42. doi:10.1016/S0013-9351(03)00038-0.

 PubMed Web of Science ®Google Scholar

Just, J., C. Segala, F. Sahraoui, G. Priol, A. Grimfeld, and F. Neukirch. 2002. Short-term health effects of particulate and photochemical air pollution in asthmatic children. Eur. Respir. J. 20 (4):899–906. doi:10.1183/09031936.02.00236902.

 PubMed Web of Science ®Google Scholar

Karakatsani, A., A. Analitis, D. Perifanou, J.G. Ayres, R.M. Harrison, A. Kotronarou, I.G. Kavouras, J. Pekkanen, K. Hämeri, G.P. Kos, J.J. De Hartog, G. Hoek, and K. Katsouyanni. 2012. Particulate matter air pollution and respiratory symptoms in individuals having either asthma or chronic obstructive pulmonary disease: A European multicentre panel study. Environ. Health 11:75. doi:10.1186/1476-069X-11-75.

 PubMed Web of Science ®Google Scholar

Lagorio, S., F. Forastierez, R. Pistelli, I. Iavarone, P. Michelozzi, V. Fano, A. Marconi, G. Ziemacki, and B.D. Ostro. 2006. Air pollution and lung function among susceptible adult subjects: A panel study. Environ. Health 5:11. doi:10.1186/1476-069X-5-11.

 PubMedGoogle Scholar

Lewis, T.C., T.G. Robins, J.T. Dvonch, G.J. Keeler, F.Y. Yip, G.B. Mentz, X. Lin, E.A. Parker, B.A. Israel, L. Gonzalez, and Y. Hill. 2005. Air pollution-associated changes in lung function among asthmatic children in Detroit. Environ. Health Perspect. 113:1068–75. doi:10.1289/ehp.7533.

 PubMed Web of Science ®Google Scholar

Mortimer, K.M., L.M. Neas, D.W. Dockery, S. Redline, and I.B. Tager. 2002. The effect of air pollution on inner-city children with asthma. Eur. Respir. J. 19 (4):699–705. doi:10.1183/09031936.02.00247102.

 PubMed Web of Science ®Google Scholar

Ostro, B., M. Lipsett, J. Mann, H. Braxton-Owens, and M. White. 2001. Air pollution and exacerbation of asthma in African-American children in Los Angeles. Epidemiology 12 (2):200–08. doi:10.1097/00001648-200103000-00012.

 PubMed Web of Science ®Google Scholar

Peacock, J.L., P. Symonds, P. Jackson, S.A. Bremner, J.F. Scarlett, D.P. Strachan, and H.R. Anderson. 2003. Acute effects of winter air pollution on respiratory function in schoolchildren in southern England. Occup. Environ. Med. 60 (2):82–89. doi:10.1136/oem.60.2.82.

 PubMed Web of Science ®Google Scholar

Samoli, E., K. Dimakopoulou, D. Evangelopoulos, S. Rodopoulou, A. Karakatsani, L. Veneti, M. Sionidou, I. Tsolakoglou, I. Krasanaki, G. Grivas, D. Papakosta, and K. Katsouyanni. 2017. Is daily exposure to ozone associated with respiratory morbidity and lung function in a representative sample of schoolchildren? Results from a panel study in Greece. J. Expos. Sci. Environ. Epidemiol. 27 (3):346–51. doi:10.1038/jes.2016.32.

 PubMed Web of Science ®Google Scholar

Schachter, E.N., E. Moshier, R. Habre, A. Rohr, J. Godbold, A. Nath, A. Grunin, B. Coull, P. Koutrakis, and M. Kattan. 2016. Outdoor air pollution and health effects in urban children with moderate to severe asthma. Air Qual. Atmos. Health 9 (3):251–63. doi:10.1007/s11869-015-0335-6.

 Web of Science ®Google Scholar

Schildcrout, J.S., L. Sheppard, T. Lumley, J.C. Slaughter, J.Q. Koenig, and G.G. Shapiro. 2006. Ambient air pollution and asthma exacerbations in children: An eight-city analysis. Am. J. Epidemiol. 164 (6):505–17. doi:10.1093/aje/kwj225.

 PubMed Web of Science ®Google Scholar

Yoda, Y., N. Otani, S. Sakurai, and M. Shima. 2014. Acute effects of summer air pollution on pulmonary function and airway inflammation in healthy young women. J. Epidemiol. 24:312–20. doi:10.2188/jea.JE20130155.

 PubMed Web of Science ®Google Scholar