No abstract

On-line gas exchange monitors have been based on the measurement of both inspired and expired flows (method A) or on the measurement of expired flow only (method B). In both methods, the cancellation of systematic errors is appreciable if calibration errors in the inspiration variables are matched with calibration errors in the corresponding expiration variables. The determination of oxygen consumption (VO2) results in a considerable amplification of random measurement error, which becomes larger as the inspired oxygen fraction (FIO2) is made larger. For example, when in method A all gas compositions and flows are in error by +/- 0.01, the computed value of VO2 will be in error by +/- 0.16 when FIO2 = 0.21 and by +/- 0.40 if FIO2 = 0.50. When air is breathed, method B creates smaller errors than method A, but as FIO2 is increased the error in method B increases sharply and eventually overtakes that of method A. Even at high FIO2 values, the random error in VO2 may be reduced to an acceptable value by estimating it from a sequence of 100 measurement samples requiring a minimum of 5 min to acquire. There is no error amplification in the computation of carbon dioxide production.

The bolus inhalation method was used to measure the fraction of inhaled chlorine (Cl(2)) and ozone (O(3)) absorbed during a single breath as a function of longitudinal position in the respiratory system of 10 healthy nonsmokers during oral and nasal breathing at respired flows of 150, 250, and 1,000 ml/s. At all experimental conditions, <5% of inspired Cl(2) penetrated beyond the upper airways and none reached the respiratory air spaces. On the other hand, larger penetrations of O(3) beyond the upper airways occurred as flow increased and during nasal than during oral breathing. In the extreme case of oral breathing at 1,000 ml/s, 35% of inhaled O(3) penetrated beyond the upper airways and approximately 10% reached the respiratory air spaces. Mass transfer theory indicated that the diffusion resistance of the tissue phase was negligible for Cl(2) but important for O(3). The gas phase resistances were the same for Cl(2) and O(3) and were directly correlated with the volume of the nose and mouth during nasal and oral breathing, respectively.

Risk assessment of inhaled toxicants has typically focused upon adults, with modeling used to extrapolate dosimetry and risks from lab animals to humans. However, behavioral factors such as time spent playing outdoors may lead to more exposure to inhaled toxicants in children. Depending on the inhaled agent and the age and size of the child, children may receive a greater internal dose than adults because of greater ventilation rate per body weight or lung surface area, or metabolic differences may result in different tissue burdens. Thus, modeling techniques need to be adapted to children in order to estimate inhaled dose and risk in this potentially susceptible life stage. This paper summarizes a series of inhalation dosimetry presentations from the U.S. EPA's Workshop on Inhalation Risk Assessment in Children held on June 8-9, 2006 in Washington, DC. These presentations demonstrate how existing default models for particles and gases may be adapted for children, and how more advanced modeling of toxicant deposition and interaction in respiratory airways takes into account children's anatomy and physiology. These modeling efforts identify child-adult dosimetry differences in respiratory tract regions that may have implications for children's vulnerability to inhaled toxicants. A decision framework is discussed that considers these different approaches and modeling structures including assessment of parameter values, supporting data, reliability, and selection of dose metrics.

The fraction of an inspired chlorine (Cl2) bolus absorbed during a single breath (Lambda) was measured as a function of bolus penetration (VP) into the respiratory system of five male and five female nonsmokers during both nasal and oral breathing at a quiet respiratory flow of 250 ml/s. The correspondence between VP and specific anatomic landmarks was found for each subject by a combination of acoustic reflection and nitrogen washout measurements. For both nasal and oral breathing, Lambda reached approximately 0. 95 at the distal end of the upper airways and reached 1.00 within the lower conducting airways. The values of a regional mass transfer parameter computed from the Lambda-VP data indicated that the resistance to Cl2 diffusion in the airway mucosa was negligible compared with the diffusion resistance in the respired gas. Changing the peak inhaled Cl2 concentration from 0.5 to 3.0 parts/million did not significantly affect the distribution of Cl2 absorption, suggesting that the underlying mass transport and chemical reaction processes were linear with respect to Cl2 concentration.