Lung physiology and controlled exposure study design.

Abstract

Provide an overview of normal lung physiology and common controlled human inhalation exposure (CHIE) study designs and methods, and identify opportunities to apply physiological and scientific principles to design more robust CHIE studies in the future. Summarized the physiology of the lung; methods for characterizing lung function and lung conditions; sources of variability; interpretations of normal, adaptive responses relative to adverse responses; and factors affecting testing outcomes critical to designing and interpreting CHIE studies results. CHIE studies provide a unique opportunity to conduct formal experiments to examine the human health effects of airborne pollutants. Lung function, easily measured using spirometry, is a common physiological variable often utilized in these studies. By design, CHIE studies only induce mild and reversible acute effects, which may or may not predict adverse effects that may develop under chronic exposure conditions. There is substantial inter- and intra-individual variability in functional capacity and symptoms such as chest tightness and dyspnea, which are complex variables that are affected by individual perception, physiological lung impairment, and other variables (e.g., concomitant health conditions, and level of conditioning/fitness). Thus, the design of the CHIE study and physiological and environmental factors of study participants can affect each CHIE study s results. Researchers can address many of these critical issues in the problem formulation phase of CHIE studies, utilizing existing information on the expected effects of the substance of interest and possible modes of action. Thoughtful design and interpretation of CHIE studies will increase their utility for evaluating and setting environmental health policy.