TY - JOUR

T1 - Ozone increases airway hyperreactivity and mucus hyperproduction in mice previously exposed to allergen

AU - Larsen, Søren T

AU - Matsubara, Shigeki

AU - McConville, Glen

AU - Poulsen, Steen Seier

AU - Gelfand, Erwin W

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Acute exacerbations of asthma represent a common clinical problem with major economic impact. Air pollutants including ozone have been shown to contribute to asthma exacerbation, but the mechanisms underlying ozone-induced asthma exacerbation are only partially understood. The present study aimed to develop a mouse model to gain insight into the development of airway hyperresponsiveness (AHR) to methacholine (MCh) in mice after exposure to both allergen and ozone. Mice were exposed for 20 min per day for 10 consecutive days to an aerosol of 1% ovalbumin (OVA) or saline followed by a single 3-h exposure to clean air or 100, 250, or 500 ppb ozone. Ozone induced AHR in mice previously exposed to OVA when compared to non-exposed (saline) control mice. After a 10-d exposure to OVA, a single exposure to a low (100 ppb) ozone concentration was sufficient to induce AHR. The AHR response was associated with goblet-cell metaplasia. Even the lowest concentration of ozone tested, 100 ppb, which may be exceeded in urban environments and in the workplace, resulted in a significant increase in AHR, most prominent 24 h after exposure in the OVA-exposed mice.

AB - Acute exacerbations of asthma represent a common clinical problem with major economic impact. Air pollutants including ozone have been shown to contribute to asthma exacerbation, but the mechanisms underlying ozone-induced asthma exacerbation are only partially understood. The present study aimed to develop a mouse model to gain insight into the development of airway hyperresponsiveness (AHR) to methacholine (MCh) in mice after exposure to both allergen and ozone. Mice were exposed for 20 min per day for 10 consecutive days to an aerosol of 1% ovalbumin (OVA) or saline followed by a single 3-h exposure to clean air or 100, 250, or 500 ppb ozone. Ozone induced AHR in mice previously exposed to OVA when compared to non-exposed (saline) control mice. After a 10-d exposure to OVA, a single exposure to a low (100 ppb) ozone concentration was sufficient to induce AHR. The AHR response was associated with goblet-cell metaplasia. Even the lowest concentration of ozone tested, 100 ppb, which may be exceeded in urban environments and in the workplace, resulted in a significant increase in AHR, most prominent 24 h after exposure in the OVA-exposed mice.

KW - Air Pollutants

KW - Allergens

KW - Animals

KW - Asthma

KW - Biological Markers

KW - Bronchial Hyperreactivity

KW - Bronchoalveolar Lavage Fluid

KW - Disease Models, Animal

KW - Drug Interactions

KW - Inhalation Exposure

KW - Leukocyte Count

KW - Leukocytes

KW - Lung

KW - Methacholine Chloride

KW - Mice

KW - Mucus

KW - Ovalbumin

KW - Ozone

KW - Periodic Acid-Schiff Reaction

KW - Respiratory Function Tests

U2 - 10.1080/15287391003614034

DO - 10.1080/15287391003614034

M3 - Journal article

C2 - 20391116

VL - 73

SP - 738

EP - 747

JO - Journal of Toxicology and Environmental Health. Part A: Current Issues

JF - Journal of Toxicology and Environmental Health. Part A: Current Issues

SN - 1528-7394

IS - 11

ER -