Stephen J. McGeady MDProfessor of Pediatrics

Thomas Jefferson UniversityAI duPont Hosp for Children

Facts about Pediatric AsthmaBetween 1980 and 1995 asthmatic children in the

USA increased from 2.3 million to 5.5 million.Sharpest prevalence increases seen – children

under 5 years of age, in urban areas and among minority children.

Atopy (familial tendency to respond to common allergens with IgE antibody production -allergy) is the most reliable predictor of asthma development.

Wood RA. JAMA 2002; 288: 745-7

Lung Effects of Pollutants Impaired lung development- Lungs continue

to develop until age 18 years, less with pollutants.

Early development of wheezing- not all infants who wheeze are asthmatic, but many are.

Development of IgE sensitization to common environmental allergens.

These effects are most apparent when very young children are exposed.

Pollutants Generated by Traffic

Reactive oxygen species- ozoneParticulates (Diesel exhaust particles-DEP)NO2, NOxSO2Other ?

• The largest single source of airborne PM is diesel exhaust.• Diesel engines emit up to 100 times more exhaust particulate matter than gasoline engines.• Diesel exhaust particulates consist of a carbon core with a large surface area which permits many chemicals and metals to attach.• Most of the deleterious effects of DEP’s are due to the chemicals that are adsorbed onto their surface.

Particulate Matter (PM)

Coarse PM (2.5-10 um)

- regulatory standard = PM10

Fine PM (0.1 – 2.5 um)

- regulatory standard = PM2.5

Ultrafine PM (<0.1 um)

- not regulated

(Human red blood cell = 8 um)

• Exposure to 0.12 ppm ozone decreased the amount of ragweed allergen required to provoke a 20% decrease in FEV1.1

• NO2 exposure has been shown to increase airway hyperresponsiveness to tree pollen.2

• Exposure to PM increases total serum IgE levels. • Nasal histamine levels are increased 3-fold when diesel exhaust

particles are co-administered with allergen. • Exposure to airborne endotoxin enhances response to inhaled

allergen3

1Molfino et al Effect of low concentrations of ozone on inhaled allergen responses in asthmatic subjects. Lancet 1991;338:199-203.2Strand et al Repeated exposure to ambient levels of NO2 enhances asthmatic response to a non-symptomatic allergen dose. Eur Resp J 1998;12:6-12.3 Boehlecke et al, J Allergy Clin Immunol. 2003 Dec;112(6):1241-3

Bronchial Hyperresponsiveness (BHR) and Air Pollutants

•Kreit et al (1) exposed patients with and without asthma to ozone and found an increase in BHR in patients with asthma. •A meta analysis of 20 studies evaluating the effect of NO2 on asthma showed a significant increase in BHR.(2)

(1) Kreit JW et al Ozone induced changes in pulmonary function and bronchial responsiveness in asthmatics. J Appl Physiol 1989;66:217-22.

(2) Folinsbee LJ. Does nitrogen dioxide exposure increase airway responsiveness? Toxicol Indust Health 1992;8:273-83.

Asthma and Air Pollution

Air pollution has been associated with:• Increased bronchial hyperresponsiveness• Increased airway inflammation • Decreased lung function • Increased hospital admissions and ER visits• Enhancing airway inflammation induced by allergen exposure • Priming of the airways to allergic responses (Molfino, Lancet, 1991; Peden, AJRCCM, 1995; Patel & Miller Curr Opin Peds 2009;21:235-242)

1Norris et al An association between fine particles and asthma emergency department visits for children in Seattle. Environ Health Perspect 1999;107:489-93.

2 Romieu et al Effects of urban air pollutants on emergency visits for childhood asthma in Mexico City. Am J Epidemiol 1995;141:546-53.

•Numerous studies have found an association between PM 10 levels and ER visits for asthma.•In Seattle, an increase of 11 µg/m3 in fine PM was associated with an 11% increase in asthma ER visits. (1)• Ozone and SO2 have been associated with ER visits for asthma in Mexico.(2)

1Koenig JQ, et al Effects of SO2 plus NACL aerosol combined with moderate exercise on pulmonary function in asthmatic adolescents. Environ Res 1981;25:340-8.

2Gent et al Association of Low-Level Ozone and Fine Particles with respiratory symptoms in children with asthma. JAMA 2003;290:1859-1867

Lung Function and Air Pollutants

•Inhalation of 1 ppm of SO2 for 10 minutes during moderate exercise decreased FEV1 by 23% in adolescents with asthma. (1)•An association between ambient ozone levels below EPA limits and asthma symptoms was found in children with asthma living in New England. (2)

Lung Function vs. Pollutants

Epidemiologic Studies Of Pollution And Aeroallergens On Causing Asthma

Many studies have investigated the effects of automobile related pollutants in heavily traveled expressways on causing asthma symptoms in allergic children

High vehicle traffic is associated with asthma symptoms in children with known allergen sensitization

Janssen NA, et.al. Environ Health Perspect 2003;111:1512-18.Venn AJ, et.al. Am J Respir Crit Care Med 2001;164:2177-80.Wyler C, et.al. Epidemiology 2000;11:450-6.Nicolai T, et.al. Eur Respir J 2003:21:956-63.

Unanswered Questions

Air quality is better than in the past in many ways-Why is pediatric asthma prevalence increasing?

In grossly polluted East Germany the prevalence of childhood asthma was considerably lower than in West Germany. Why?

Evolution of Hygeine Theory

Early interpretation-Lack of Th1 stimulation allowed excessive Th2 activity.

Later view- Early lack of microbial exposure prevented development of T-reg cells.