Ali Borhan

Prediction of the dose-response behavior of inhaled environmental pollutants in the lung

The toxic effects of inhaled environmental pollutants is an important area of research that greatly benefits from the collaboration of a life scientist with an engineer. In particular, to understand and evaluate the impact of an inhaled substance, the engineer provides the expertise necessary to predict the amount of material that is deposited on sensitive tissues within the respiratory tract while the life scientist evaluates the resulting biological response. This project aims to develop the technical infrastructure and experience necessary for predicting such dose-response behavior in the human lung.

An example of a common air pollutant found in urban smog is ground-level ozone formed by the solar oxidation of hydrocarbon vapors and nitrogen oxides (emitted by combustion of fossil fuels) in outdoor air. Exposure to moderate levels of environmental ozone causes some people to experience difficulty in breathing, often requiring emergency medical assistance. Adverse health effects are particularly severe among children who can suffer impaired lung development, and asthmatics whose lung disease can be exacerbated by environmental exposure to ozone. Recent observations have shown that exposure to ozone can produce intense remodeling in the developing lungs of infant primates, resulting in dramatic loss of conducting airways in the form of substantial reductions (of up to 40%) in airway diameter and length. This is particularly important in light of the catastrophic rise in the incidence of asthma among children that may make them hypersensitive to inhaled ozone.

Absorption of ozone occurs in all regions of the respiratory tract, from the nose to deep in the lung. It has been verified that ozone exposure causes tissue damage in the upper airways (e.g., the nose) as well as in the lower airways (e.g., the trachea and lower breathing tubes of the lung, called the conducting airways). The purpose of this project is to predict the dose-response behavior of ozone in the human lung. In particular, our objectives are to:

  1. Collect magnetic resonance (MR) images of the lungs of healthy individuals of different ages and different states of health using the radiology facilities at Hershey.
  2. Implement three-dimensional computer simulations that predict the respiratory transport and uptake of inhaled ozone within a virtual geometry constructed from the MR images.
  3. Predict the resulting toxicological responses.

The results of this work will have important implications for respiratory delivery of therapeutic gases and vapors to patients, as well as for the federally-mandated setting of air pollution standards to protect human health.



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