Dispersion of 0.5- to 2-micron aerosol in microG and hypergravity as a probe of convective inhomogeneity in the lung.

We used aerosol boluses to study convective gas mixing in the lung of four healthy subjects on the ground (1 G) and during short periods of microgravity (microG) and hypergravity ( approximately 1. 6 G). Boluses of 0.5-, 1-, and 2-micron-diameter particles were inhaled at different points in an inspiration from residual volume to 1 liter above functional residual capacity. The volume of air inhaled after the bolus [the penetration volume (Vp)] ranged from 150 to 1,500 ml. Aerosol concentration and flow rate were continuously measured at the mouth. The dispersion, deposition, and position of the bolus in the expired gas were calculated from these data. For each particle size, both bolus dispersion and deposition increased with Vp and were gravity dependent, with the largest dispersion and deposition occurring for the largest G level. Whereas intrinsic particle motions (diffusion, sedimentation, inertia) did not influence dispersion at shallow depths, we found that sedimentation significantly affected dispersion in the distal part of the lung (Vp >500 ml). For 0.5-micron-diameter particles for which sedimentation velocity is low, the differences between dispersion in microG and 1 G likely reflect the differences in gravitational convective inhomogeneity of ventilation between microG and 1 G.     

Measurement of respiratory gas exchange during artificial respiration

This paper reports a new system for the continuous measurements of respiratory gas exchange in ventilated subjects. It involves mixing some of the inspired gas with all of the expired gas and withdrawing the mixture at a constant rate through a dry gas meter that measures the flow. The inspired gas and expired gas mixtures are sampled and O2 and CO2 concentrations measured with a paramagnetic gas analyzer and a capnograph, respectively, to an accuracy of 0.01%. Evidence is presented to confirm the necessary stability and sensitivity of these instruments. It is possible to use the system with high inspired O2 concentrations, with ventilators where there is incomplete separation of inspired and expired gas, and in the presence of intermittent mandatory ventilation, positive end-expiratory pressure, and continuous airway pressure. The system was compared with the N2-dilution method and with the collection of expired gas in a Douglas bag in dog experiments and with patients in the intensive therapy unit. Excellent correlation between these methods was found in all circumstances.     

An assessment of dead space in pulmonary ventilation of the toad Bufo schneideri

The respiratory cycles of Rana and Bufo has been disputed in relation to flow patterns and to the respiratory dead-space of the buccal volume. A small tidal volume combined with a much larger buccal space motivated the "jet steam" model that predicts a coherent expired flow within the dorsal part of the buccal space. Some other studies indicate an extensive mixing of lung gas within the buccal volume. In Bufo schneideri, we measured arterial, end-tidal and intrapulmonary PCO(2) to evaluate dead-space by the Bohr equation. Dead-space was also estimated as: V(D)=(total ventilation-effective ventilation)/f(R), where total ventilation and f(R) were measured by pneumotachography, while effective ventilation was derived from the alveolar ventilation equation. These approaches were consistent with a dead space of 30-40% of tidal volume, which indicates a specific pathway for the expired lung gas.     

Assessment of papain-induced lung injury in isolated lungs by measurements of aerosol deposition and mixing.

Aerosol bolus inspirations were used to assess lung injury in 15 isolated dog lungs exposed to low (0-375 units) or high doses (600-1,200 units) of papain. Effective air space size (EAD) was determined from aerosol deposition during a 5-s breath hold. Convective mixing was assessed by the spreading of the expired bolus with respect to expired volume, quantified by a coefficient of dispersion (CD) equal to the square root of the difference in the variances of the expired and inspired boluses divided by the volumetric penetration of the bolus. After exposure, CD measured with deeply penetrating boluses increased by an average of 2.5% in the low-exposure group (P greater than 0.05) and 28.0% in the high-exposure group (P less than 0.0001). CD measured with shallowly penetrating boluses decreased by 4.3% (P less than 0.0001) in the low-exposure group and increased by an average of 18.3% in the high-exposure group (P less than 0.05). Papain exposure caused EAD to increase in some lungs and decrease in others. For deep bolus penetrations, EAD changed by an average of -0.8% in the low-exposure group (P greater than 0.05) and +21.1% in the high-exposure group (P greater than 0.05). Both EAD and CD appeared to be sensitive to lung injury. However, changes in EAD were less consistent than those in CD, possibly due to changes caused by lung injury in the regional distribution of inspired aerosol.     

Demonstration of airway closure in man.

After partial equilibration of the lung with a N2O gas mixture absorption of N2O by the pulmonary circulation results in a flow of gas into the lungs during breath holding. A bolus of 133Xe introduced at the mouth at the beginning of the breath hold is carried in by the gas flow and distributed according to regional perfusion. In three subjects, breath holding at FRC, apex-to-base distribution of a 133Xe bolud delivered by N2O absorption (Xecar) was similar to that of a bolus injected intravenously (Xeiv). Near RV however, much less of Xecar penetrated into dependent zones than expected from the distribution of Xeiv. In fact, distribution of Xecar did not differ from that of a slowly inhaled bolus. Correction for Compton scatter in the chest wall, measured in one subject, accounted only in part for the radioactivity recorded over dependent lung regions. The findings indicate that near RV some but not all of the dependent airways must be closed. Furthermore, the distribution of airway closure completely accounts for the distribution of a bolus inhaled from RV.     

Calculation of regional deposition of aerosol in the respiratory tract

The removal of air-borne particles in the respiratory tract is treated to enable regional deposition to be inferred from measurement of expired aerosol as well as predicted from theory of the primary removal processes. The analysis uses the analogy of a continuous tubular filter-bed and includes consideration of respiratory pauses and the mechanical mixing of gas flow. Derived equations relate regional deposition, distribution of aerosol in the expired air, and efficiency of removal at different depths in the respiratory tract.     

Convective and diffusive gas transport in canine intrapulmonary airways.

The significance of convective and diffusive gas transport in the respiratory system was assessed from the response of combined inert gas and particle boluses inhaled into the conducting airways. Particles, considered as "nondiffusing gas," served as tracers for convection and two inert gases with widely different diffusive characteristics (He and SF6) as tracers for convection and diffusion. Six-milliliter boluses labeled with monodisperse di-2-ethylhexyl sebacate droplets of 0.86-microns aerodynamic diameter, 2% He, and 2% SF6 were inspired by three anesthetized mechanically ventilated beagle dogs to volumetric lung depths up to 170 ml. Mixing between inspired and residual air caused dispersion of the inspired bolus, which was quantified in terms of the bolus half-width. Dispersion of particles increased with increasing lung depth to which the boluses were inhaled. The increase followed a power law with exponents less than 0.5 (mean 0.39), indicating that the effect of convective mixing per unit volume was reduced with depth. Within the pulmonary dead space, the behavior of the inert gases He and SF6 was similar to that of the particles, suggesting that gas transport was almost solely due to convection. Beyond the dead space, dispersion of He and SF6 increased more rapidly than dispersion of particles, indicating that diffusion became significant. The gas and particle bolus technique offers a suitable approach to differential analysis of gas transport in intrapulmonary airways of lungs.     

Lung gas mixing during expiration following an inspiration of air

The airway system of the lung from the mouth to the pulmonary membrane is modelled by matching a cylindrical model of a pathway through the respiratory region of the lung onto a one-dimensional trumpet model for the conducting airways. The concentration of O₂ in gas expired from this model airway system is investigated following an inspiration of air at two different flow rates (10 litres/min and 85 litres/min). In each case, expiration occurs at the same constant flow rate as that during the previous inspiration. The inspirations, which are studied in an earlier paper, are each of 2 sec duration and begin at a lung volume of 2300 ml and a lung oxygen tension of 98 mm Hg. The equations are solved numerically and plots of expired O₂ concentration against time and against expired volume are shown. It is found that at 85 litres/min, gas mixing in the lung is complete after about 0.7 sec of expiration whereas at 10 litres/min, about 2.6 sec of expiration is required for complete equilibration. It is suggested that the experimental alveolar plateau slope is not in general caused by a slow approach to equilibrium of gas concentrations; except at very low flow rates in the early part of the concentration/time plateau.     

A mechanical approach to the longitudinal dispersion of gas flowing in human airways

The aim of this work is to contribute to elucidating the mechanism underlying gas mixing in the human pulmonary airways. For this purpose, a particular attempt is made to analyse the fluid mechanical aspects of gaseous dispersion using bolus response methods. The experiments were performed on five normal subjects by injection of 10 cm3 bolus of He, Ar and SF6 into the latter part of the inspired airstream, in such a way that the whole bolus entered the inspiratory flow and was recovered during the following expiration. The results, presented in a logarithmic plot of dimensionless variance (dispersion of the output bolus) against the Peclet number, show that gaseous dispersion is only slightly dependent on the nature of the tracer gas but is strongly related to flow velocity. This is in agreement with the theory of turbulent or disturbed dispersion; however, it seems that Taylor laminar dispersion does not play a significant role in the airways.     

Validity of inspiratory and expiratory methods of measuring gas exchange with a computerized system.

The accuracy of a computerized metabolic system, using inspiratory and expiratory methods of measuring ventilation, was assessed in eight male subjects. Gas exchange was measured at rest and during five stages on a cycle ergometer. Pneumotachometers were placed on the inspired and expired side to measure inspired (VI) and expired ventilation (VE). The devices were connected to two systems sampling expired O(2) and CO(2) from a single mixing chamber. Simultaneously, the criterion (Douglas bag, or DB) method assessed VE and fractions of O(2) and CO(2) in expired gas (FE(O(2)) and FE(CO(2))) for subsequent calculation of O(2) uptake (VO(2)), CO(2) production (VCO(2)), and respiratory exchange ratio. Both systems accurately measured metabolic variables over a wide range of intensities. Though differences were found between the DB and computerized systems for FE(O(2)) (both inspired and expired systems), FE(CO(2)) (expired system only), and VO(2) (inspired system only), the differences were extremely small (FE(O(2)) = 0.0004, FE(CO(2)) = -0.0003, VO(2) = -0.018 l/min). Thus a computerized system, using inspiratory or expiratory configurations, permits extremely precise measurements to be made in a less time-consuming manner than the DB technique.     

A source of experimental underestimation of aerosol bolus deposition.

We examined the measurement error in inhaled and exhaled aerosol concentration resulting from the bolus delivery system when small volumes of monodisperse aerosols are inspired to different lung depths. A laser photometer that illuminated approximately 75% of the breathing path cross section recorded low inhaled bolus half-widths (42 ml) and negative deposition values for shallow bolus inhalation when the inhalation path of a 60-ml aerosol was straight and unobstructed. We attributed these results to incomplete mixing of the inhaled aerosol bolus over the breathing path cross section, on the basis of simultaneous recordings of the photometer with a particle-counter sampling from either the center or the edge of the breathing path. Inserting a 90 degrees bend into the inhaled bolus path increased the photometer measurement of inhaled bolus half-width to 57 ml and yielded positive deposition values. Dispersion, which is predominantly affected by exhaled bolus half-width, was not significantly altered by the 90 degrees bend. We conclude that aerosol bolus-delivery systems should ensure adequate mixing of the inhaled bolus to avoid error in measurement of bolus deposition.     

The effect of inspired oxygen concentration on the ventilation-perfusion distribution in inhomogeneous lungs

The coupled conservation of mass equations for oxygen, carbon dioxide and nitrogen are written down for a lung model consisting of two homogeneous alveolar compartments (with different ventilation-perfusion ratios) and a shunt compartment. As inspired oxygen concentration and oxygen consumption are varied, the flux of oxygen, carbon dioxide and nitrogen across the alveolar membrane in each compartment varies. The result of this is that the expired ventilation-perfusion ratio for each compartment becomes a function of inspired oxygen concentration and oxygen consumption as well as parameters such as inspired ventilation and alveolar perfusion. Another result is that the "inspired ventilation-perfusion ratio and the "expired ventilation-perfusion ratio differ significantly, under some conditions, for poorly ventilated lung compartments. As a consequence, we need to distinguish between the "inspired ventilation-perfusion distribution, which is independent of inspired oxygen concentration and oxygen consumption, and the "expired ventilation-perfusion distribution, which we now show to be strongly dependent on inspired oxygen concentration and less dependent oxygen consumption. Since the multiple inert gas elimination technique (MIGET) estimates the "expired ventilation-perfusion distribution, it follows that the distribution recovered by MIGET may be strongly dependent on inspired oxygen concentration.     

Analysis of reactive carbonyls in the expired air of transgenic mice.

Methods for the determination of trace levels of volatile carbonyl compounds in air expired from mice were developed and validated. Tumor bearing transgenic mice or nontransgenic control mice were placed into a glass chamber through which air was passed continuously at 90 ml/min for 1 h. The effluent gas stream was bubbled into an aqueous cysteamine solution or an aqueous methylhydrazine solution. Formaldehyde, acetaldehyde, and acetone in expired air were derivatized to thiazolidine with cysteamine and malonaldehyde was derivatized to 1-methyl-2-pyrazole with methylhydrazine. The derivatized compounds were analyzed by capillary gas chromatography with flame photometric or nitrogen-phosphorous-specific detection. The lowest level quantitated was 4 micrograms/ml thiazolidine, equivalent to 1.35 micrograms/ml formaldehyde. Formaldehyde was recovered at a level of 1356 +/- 234 nmol/kg0.75 (mean +/- SD) from mice with tumors and 898 +/- 97 nmol/kg0.75 from mice without tumors, suggesting that tumor bearing transgenic mice expired significantly more formaldehyde than did tumor free controls. Amounts of expired acetaldehyde and acetone were not different among mice. Malonaldehyde was not detected in either group of mice.     

Monte Carlo simulation of simultaneous gas flow and diffusion in an asymmetric distal pulmonary airway model

In order to evaluate the effect of anatomic asymmetries on the gas concentration distribution in the pulmonary airways, a Monte Carlo simulation of combined bulk flow and molecular diffusion was carried out in a realistic distal airway model (Parkeret al., 1971). This airway model, composed of branches distal to the 0.5-ram diameter airways, contained an upper symmetric segment consisting of four generations of conducting airways and a lower asymmetric segment of alveolar ducts and sacs arranged in five transport paths of varying lengths. In accounting for the volume increases of these ducts and sacs occurring during normal respiration, uniform alveolar filling rates and a fixed length-to-diameter ratio of all airways were assumed. For a pulse injection of inert tracer gas, the simulation was employed to determine the longitudinal concentration profiles in the conducting airways. In the alveolated airways, not only were the longitudinal profiles determined along each path, but radial transport from the core to the periphery of the airways was considered. The results of the simulations indicate that geometric asymmetries alone contribute substantially to regional concentration variations in the distal airways. For example, when a gas bolus is injected at mid*inspiration, there are concentration differences as great as 40% between two points along different transport paths located equi-distant from the proximal end of the model. As viewed from the terminal end of the model (acinus), average concentration differences as large as 6-to-1 exist between the longest and shortest transport paths respectively for gas boli introduced near the end of inspiration. The results further indicate because of large radial diffusion rates, no significant concentration differences exist between the periphery a-ld the central core of alveolated airways. Simulation of the expired concentration profiles indicate that boll injected very late during inspiration exhibit a sloping tail, unlike the earlier injected boll whose tails are virtually horizontal. Through the use of superposition teehniqnes, it was found that these sloping tails correspond to an alveolar slope of 1.5 vol% between 750 and 1250 ml expired for a continuous washing of tracer. This result is in disagreement with other transport analyses which did not directly account for the effect of geometric asymmetries.     

Influence of cycle exercise on acetone in expired air and skin gas

Abstract

This study investigated the influence of cycle exercise on acetone concentration in expired air and skin gas. The subjects for this experiment were eight healthy males. Subjects performed a continuous graded exercise test on a cycle ergometer. The workloads were 360 (1.0 kg), 720 (2.0 kg), 990 (2.75 kg) kgm/min, and each stage was 5 min in duration. A pedaling frequency of 60 rpm was maintained. Acetone concentration was analyzed by gas chromatography. The acetone concentration in expired air and skin gas during exercise at 990 kgm/min intensity was significantly increased compared with the basal level. The skin-gas acetone concentration at 990 kgm/min significantly increased compared with the 360 kgm/min (P < 0.05). The acetone excretion of expired air at 720 kgm/min and 990 kgm/min significantly increased compared with the basal level (P < 0.05). Acetone concentration in expired air was 4-fold greater than skin gas at rest and 3-fold greater during exercise (P < 0.01). Skin gas acetone concentration significantly related with expired air (r = 0.752; P < 0.01). This study confirmed that the skin-gas acetone concentration reflected that of expired air.     

Aerosol bolus dispersion and convective mixing in human and dog lungs and physical models.

The dispersion of aerosol boluses in the lung is a probe for convective mixing and has been proposed as a marker for abnormal lung function. To better understand the factors underlying this phenomenon, aerosol dispersion was compared in human subjects, dogs, and various physical models. In all systems, dispersion increased with the volumetric penetration of the aerosol bolus. The rate of this increase was 83% greater in humans compared with dogs. Dispersion in dogs was close to that in a packed bed with beads of 2.5 mm. Aerosol dispersion decreased with increasing flow rate in human subjects. An artificial larynx inserted into the straight tube caused a 33% increase in dispersion. In humans, aerosol dispersion was significantly correlated with forced expired flow between 25 and 75% of vital capacity. A 2-s pause between inspiration and expiration increased dispersion 23-58% in three isolated dog lungs but did not affect dispersion in the packed bed. The data suggest that lung geometry, flow rate, particle mobility, and the larynx all significantly affect aerosol dispersion by influencing the reversibility of aerosol transport between inspiration and expiration.     

Bioelectronic sniffers for ethanol and acetaldehyde in breath air after drinking

Two kinds of bioelectronic gas sensors (bio-sniffer) incorporating alcohol oxidase (AOD) and aldehyde dehydrogenase (ALDH) were developed for the convenient analysis of ethanol and acetaldehyde in expired gas, respectively. The sniffer devices for gaseous ethanol and acetaldehyde were constructed by immobilizing enzyme on electrodes covered with filter paper and hydrophilic PTFE membrane, respectively. The AOD and ALDH sniffers were used in the gas phase to measure ethanol vapor from 1.0 to 500 ppm, and acetaldehyde from 0.11 to 10 ppm covering the concentration range encountered in breath after alcohol consumption. Both bio-sniffers displayed good gas selectivity which was attributed to the substrate specificity of the relevant enzymes (AOD and ALDH) as gas recognition material. From the results of physiological application, the bio-sniffers could monitor the concentration changes in breath ethanol and acetaldehyde after drinking. The ethanol and acetaldehyde concentrations in expired air from ALDH2 [-] (aldehyde dehydrogenase type 2 negative) subjects were higher than that of the ALDH2 [+] (positive) subjects. The results indicated that the lower activity of ALDH2 induced an adverse effect on ethanol metabolism, leading to ethanol and acetaldehyde remaining in the human body, even human expired air.     

Distal projection of insufflated gas during tracheal gas insufflation.

Tracheal gas insufflation (TGI) flushes expired gas from the ventilator circuitry and central airways, augmenting CO2 clearance. Whereas a significant portion of this washout effect may occur distal to the injection orifice, the penetration and mixing behavior of TGI gas has not been studied experimentally. We examined the behavior of 100% oxygen TGI injected at set flow rates of 1-20 l/min into a simulated trachea consisting of a smooth-walled, 14-mm-diameter tube. Models incorporating a separate coaxial TGI injector, a rough-walled trachea, and a bifurcated trachea were also studied. One-hundred percent nitrogen, representing expiratory flow, passed in the direction opposite to TGI at set flow rates of 1-25 l/min. Oxygen concentration within the "trachea" was mapped as a function of axial and radial position. Three consistent findings were observed: 1) mixing of expiratory and TGI gases occurred close to the TGI orifice; 2) the oxygenated domain extended several centimeters beyond the endotracheal tube, even at high-expiratory flows, but had a defined distal limit; and 3) more distally from the site of gas injection, the TGI gas tended to propagate along the tracheal wall, rather than as a central projection. We conclude that forward-directed TGI penetrates a substantial distance into the central airways, extending the compartment susceptible to CO2 washout.     

Longitudinal distribution of chlorine absorption in human airways: a comparison to ozone absorption.

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.