Chronic obstructive pulmonary disease (COPD) is a disabling condition produced by chronic bronchitis (airway inflammation and mucus hypersecretion) and emphysema (loss of alveolar surface area). Epidemiologic studies of the workplace have consistently shown an excess of COPD associated with dusty work environments, yet only a few substances (coal, silica, cadmium) causing COPD in the workplace have been characterized based on chemical composition and respirable particle size. These findings suggest that the much broader range of workplace dusts may in certain conditions contribute to COPD based on characteristics other than chemical composition alone. Pulmonary inflammation plays a role in early events leading to COPD. Particles less than 10 micron aerodynamic diameter are considered to be able to penetrate the upper airways and reach the respiratory tract, and are thus designated as being in the respirable range. Ambient fine particles (<2.5um) consist of two fractions: ultrafines (0.01 to 0.1 um) and accumulation mode particles (0.1 to 1.0 um). Recent studies of ambient particulates indicate that ultrafine particles may be more harmful than other fine particles on an equal mass exposure basis. In animal models, ultrafine particles have a higher alveolar deposition fraction, translocate more easily from the airways to the interstitium, induce greater activation of macrophages and cytokine release, and cause greater impairment of macrophage clearance function.One reason for the greater toxicity of equal masses of these smaller particles is their much greater surface area. We hypothesize that the size of inhaled fine particles, in addition to their chemical and other physical characteristics, plays a critical role in determining occupational health effects. To test this we will study early lung and systemic inflammatory responses as well as cardiac effects in adults after carefully controlled inhalation exposure to ultrafine and accumulation mode zinc oxide, a particle we have previously characterized for the dose-response relationship of its short term pulmonary and systemic inflammatory effects. Studies will be conducted in the Environmental Exposure Facility of the Adult General Clinical Research Center. We will compare ultrafine to larger, accumulation mode particles (on an equal mass exposure basis) in their ability to produce symptoms, fever, markers of airway inflammation, antioxidants, systemic acute phase proteins, and alterations in the blood clotting cascade, cytokine release, heart rate, rhythm, and repolarization. We anticipate that the results will help to determine whether there are differential effects for equal mass exposures to fine particles of different size fractions in the pathogenesis of COPD
| Beckett, William S; Chalupa, David F; Pauly-Brown, Andrea et al. (2005) Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults: a human inhalation study. Am J Respir Crit Care Med 171:1129-35 |
