Childhood Asthma/Tobacco Smoke

Introduction

Characteristics

Fate and Transport

Exposure Pathway

Methods for Monitoring in the Environment

Methods for Measuring Human Exposure

Strategies for Preventing or Controlling Exposure


Respiratory Harmful Effects

Deposition, Absorption, and Metabolism

Dose-Response Relationship

Organ Sites of Toxicity

Biomarkers

Risk Assessment/Risk Management Considerations

References

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Dose-Response relationship of Environmental Tobacco Smoke (ETS) and Childhood Respiratory Effects

  • Dose of ETS exposure can be measured in humans through questionnaires
    • For children, mothers are asked how often they smoke, how much per day, where they smoke and so forth
    • However, these questionnaires may not properly estimate exposure because mother may lie about how much she smoked during and after pregnancy
    • But, smokers often know how much they smoke a day
    • Questionnaires given to the parent is the most used method for assessing dose of ETS exposure in children (i.e., 10 cigarettes per day)
    • In addition not clear what type of biological response on a cellular level occurs in human when exposed to a particular ETS dose
  • Dose of ETS exposure measured in animals (reviewed in Witschi, Joad and Pinkerton, 1997)
    • Effects of SS (1mg/m^3 of Total Suspended Particles (TSPs), 6h/day, 5 days/week) on bronchiolar epithelial cell development and expression of cytochrome P450 isoenzyme 1A1 protein in postnatal rat lung
      • ETS interferes with production of epithelial cells in the terminal bronchioles
      • Acclerates and maintains expression of cytochrome P450 isoenzyme in Clara cells during postnatal lung development
    • The Clara cells are nonciliated, nonmucous, secretory cells containing characteristic peptidergic granules; they constitute up to 80% of the epithelial cell of the distal airways
      • This response is important to note because Clara cells are involved in metabolism of chemicals by the lung and it is probably target for inhaled and systemically delivered agents in the lung
    • Effects of SS (1mg/m^3 of TSPs, 6h/day, 5 days/week) from age 2 days of life to 8-15 weeks in rats
      • ETS did not change lung resistance, compliance, lung weight/body weight ratio
      • Study did show that rats exposed from 2 days to 11 weeks had an airway hyporesponsiveness to serotonin
      • This response important because the rats may eventually have down-regulation of serotonin-receptors which may decrease airways ability to constrict
      • Effect of SS (1mg/m^3 of TSPs, 6h/day, 5 days a week) on pregnant Sprague-Dawley rats from day 3 of gestation to birth, the female pups were then exposed for 7-10 weeks postnatally compared to those rats exposed to filtered air
        • Results showed that pups lungs were less compliant and more reactive to methacholine (test for asthma), and had 22-fold more pulmonary endocrine cells
        • This response is important because it shows exposure both pre- and postnatally led to changes in airways and lungs
      • Effect of SS(1mg/m^3 of TSP’s, 6h/day, 5 days/week) on guinea pigs from 8 days to 43 days of life
        • Results showed lungs had increased compliance, but decreased airway reactivity of C-fiber system without changing neurotransmitter substance P
        • C-fibers are stimulated by constituents of ETS, like nicotine, acrolein and oxidants
        • This response shows there may be decreased response to ETS through coughing, but there is still mucous production and bronchoconstriction
      • Tissue dose-response relationship (Carty et al., 1996)
      • Smooth muscle cells, which surround the airways, exposed to varying concentrations of nicotine and cotinine The concentrations ranged from 10^-9 mol/L to 10^-6 mol/L
      • Both nicotine and cotinine stimulated production of basic fibroblast growth factor (bFGF)
      • The resulting shape of the curve is an upside down U, where a lower response is seen in the lowest and highest concentration, but a higher response is seen in the middle concentrations (10^-8 and 10^-9)

Taken from Carty et al. (1996) Figure 1. bFGF found in conditioned medium of human SMCs (smooth muscle cells) after 24 hours of incubation with different concentrations of nicotine or cotinine dissolved in no-growth medium.