Ozone Concentration and Pulmonary Response Relationships for 6.6-Hour Exposures with Five Hours of Moderate Exercise to 0.08, 0.10, and 0.12 ppm

Horstman, Donald H.; Folinsbee, Lawrence J.; Ives, Phillip J.; Abdul-Salaam, Sa'id; McDonnell, William F.

doi:10.1164/ajrccm/142.5.1158

Cited by 221 publications

(142 citation statements)

References 5 publications

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“…A remarkably high variability in response to ozone has been observed (23)(24)(25), and genetic factors have been implicated in this variability. Human SP-A plays a role in inflammation by regulating cytokine production by macrophages.…”

Section: Discussionmentioning

confidence: 99%

The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production.

Wang

Umstead

Phelps

et al. 2002

Environ Health Perspect

124

197

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Ozone exposure can cause inflammation and impaired lung function. Human surfactant protein A (SP-A) may play a role in inflammation by modulating cytokine production by macrophages. SP-A is encoded by two genes, SP-A1 and SP-A2, and several allelic variants have been characterized for each gene. These allelic variants differ among themselves in amino acids that may exhibit differential sensitivity to ozone-induced oxidation and this may produce functional differences. We studied the effects of SP-A variants before and after ozone exposure on the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-8. These are important proinflammatory cytokines and are expressed by the macrophage-like THP-1 cells. Eight variants were expressed in vitro, characterized by gel electrophoresis, and studied. These included six single-gene SP-A alleles and two SP-A variants derived from both genes. Variants were exposed to ozone at 1 ppm for 4 hr at 37 degrees C, and we compared their ability to stimulate cytokine (TNF-alpha and IL-8) production by THP-1 cells to air-exposed and unexposed SP-A variants. We found that a) SP-A2 variants (1A, 1A(0), 1A(1) stimulate significantly more TNF-alpha and IL-8 production than SP-A1 variants (6A, 6A(2), 6A(4); b) coexpressed SP-A variants (1A(0)/6A(2), 1A(1)/6A(4) have significantly higher activity than single gene products; c) after ozone exposure, all SP-A variants showed a decreased ability to stimulate TNF-alpha and IL-8 production, and the level of the decrease varied among SP-A variants (26-48%); and d) human SP-A from patients with alveolar proteinosis exhibited a minimal decrease (18% and 12%, respectively) in its ability to stimulate TNF-alpha and IL-8 after in vitro ozone exposure. We conclude that biochemical and functional differences exist among SP-A variants, that ozone exposure modulates the ability of SP-A variants to stimulate cytokines by THP-1 cells, and that SP-As from bronchoalveolar lavage (BAL) fluid of certain alveolar proteinosis patients may be oxidized in vivo.

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Section: Discussionmentioning

confidence: 99%

The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production.

Wang

Umstead

Phelps

et al. 2002

Environ Health Perspect

124

197

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“…Ozone has been of particular concern, as it provokes airway inflammation at very low levels (Aris et al 1993). In addition, ozone increases airway reactivity (Horstman et al 1990;Kreit et al 1989), and there is evidence to suggest that ozone may potentiate the effects of allergens (Molfino et al 1991). Ozone levels have been related to increases in asthma admissions and emergency room visits among children in Atlanta, Georgia (White et al 1994), New Jersey (Cody et al 1992), and Mexico City (Romieu et al 1995).…”

Section: Risks At Different Agesmentioning

confidence: 99%

Children's health and the environment: public health issues and challenges for risk assessment.

Landrigan

Kimmel

Correa

et al. 2004

Environ Health Perspect

364

206

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Infants and children are not little adults. They are uniquely vulnerable to environmental toxicants. To protect infants and children against toxicants, the National Research Council in 1993 called for development of an approach to risk assessment that considers children's unique patterns of exposure and their special vulnerabilities to pesticides. Many aspects of that call were codified into federal law in the Food Quality Protection Act (FQPA) of 1996. This report highlights the central elements needed for development of a child-protective approach to risk assessment: a) improved quantitative assessment of children's exposures at different life stages, from fetal life through adolescence, including acute and chronic exposures, exposures via multiple routes, and exposures to multiple agents; b) development of new approaches to toxicity testing of chemicals that can detect unanticipated and subtle outcomes and that evaluate experimental subjects over the entire life span from early exposure to natural death to replicate the human experience; c) development of new toxicodynamic and toxicokinetic models that account for the unique physiologic characteristics of infants and children; d) development of new approaches to assessment of outcomes, functional, organ, cellular and molecular, over the entire life span; these measures need to be incorporated into toxicity testing and into long-term prospective epidemiologic studies of children; and e) application of uncertainty and safety factors in risk assessment that specifically consider children's risks. Under FQPA, children are presumed more vulnerable to pesticides than adults unless evidence exists to the contrary. Uncertainty and safety factors that are protective of children must therefore be incorporated into risk assessment when data on developmental toxicity are lacking or when there is evidence of developmental toxicity. The adequate protection of children against toxic agents in the environment will require fundamental and far-reaching revisions of current approaches to toxicity testing and risk assessment.

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“…It is well known that ozone (03), an air pollutant, and exposure to humans (11), dogs (12), rats (13), guinea pigs (14) and other animals can cause transient AHR and airway inflammation. Therefore, 03-induced AHR is used as a tool for investigating AHR.…”

Section: Airway Hyperresponsivenessmentioning

confidence: 99%

Importance of Impairment of the Airway Epithelium for Ozone-Induced Airway Hyperresponsiveness in Guinea Pigs

Matsubara¹,

Fushimi

Kaminuma³

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-We examined the relationship between ozone (03)-induced airway hyperresponsiveness (AHR) and inflammation in guinea pigs. Inhalation of methacholine (MCh) was adopted in the time course study of AHR that was assessed by measuring pulmonary inflation pressure after 03 exposure (3 ppm, for 2 hr) because the degree of AHR detected by inhalation of MCh was greater than that detected by i.v. administration. AHR was detected up to 5 hr after 03 exposure and was not observed at 24 and 48 hr. In the bronchoalveolar lavage (BAL) study, the numbers of neutrophils, eosinophils, lymphocytes and macrophages in BAL fluid (BALF) reached maximum at 24 hr or later. On the other hand, the number of airway epithelial cells in the BALF significantly increased at 2 and 5 hr. In the histological study, disorder and impairment of the airway epithelium in the trachea and lung were observed at 2 and 5 hr. Changes in the airway epithelium were recovered at 48 hr, although an increase in leukocytes was observed in the lung. These results indicate that 03-induced AHR in guinea pigs is most probably associated with impairment of the epithelium rather than with infiltration of inflammatory cells in the airway.

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Ozone Concentration and Pulmonary Response Relationships for 6.6-Hour Exposures with Five Hours of Moderate Exercise to 0.08, 0.10, and 0.12 ppm

Cited by 221 publications

References 5 publications

The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production.

The effect of ozone exposure on the ability of human surfactant protein a variants to stimulate cytokine production.

Children's health and the environment: public health issues and challenges for risk assessment.

Importance of Impairment of the Airway Epithelium for Ozone-Induced Airway Hyperresponsiveness in Guinea Pigs

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