Peter W. Scherer

Numerical modeling of nasal obstruction and endoscopic surgical intervention: Outcome to airflow and olfaction

Background Mechanical obstruction of odorant flow to the olfactory neuroepithelium may be a primary cause of olfactory loss in nasal-sinus disease patients. Surgical removal of nasal obstruction may facilitate the recovery of olfactory ability. Unfortunately, quantifying the functional impact of nasal obstruction and subsequent surgical outcomes using acoustic rhinometry, rhinomanometry, or CT scans is inadequate. Methods Using computational fluid dynamics (CFD) techniques, we can convert patient CT scans into anatomically accurate 3D numerical nasal models that can be used to predict nasal airflow and odorant delivery rates. These models also can be rapidly modified to reflect anatomic changes, e.g., surgical removal of polyps. Results CFD modeling of one patients nose pre- and postsurgery showed significant improvement in postsurgical ortho- and retronasal airflow and odorant delivery rate to olfactory neuroepithelium (<1000 times), which correlated well with olfactory recovery. Conclusion This study has introduced a novel technique (CFD) to calculate nasal airflow dynamics and its effects on olfaction, nasal obstruction, and sinus disease. In the future, such techniques may provide a quantitative evaluation of surgical outcome and an important preoperative guide to optimize nasal airflow and odorant delivery.

Flow visualization of steady streaming in oscillatory flow through a bifurcating tube

A steady streaming displacement of fluid elements is observed to occur during oscillatory flow through a Y-shaped tube bifurcation model at Womersley and Reynolds numbers that can exist in the human bronchial tree. The cause of the displacement is the effect of the asymmetric geometry on the oscillating velocity vector field. The steady streaming displacement is greatest for fluid elements that experience the highest velocity through the bifurcation junction. The maximum displacement observed increases with Re and a up to a Re of about 100 and a of about 5, after which a levelling off and gradual decline occur. Photographs of low-Re and low-a: cxpcrimcnts show the effects of secondary components of the steady-streaming displacement field which contribute to a complex circulation.

Volumetric capnography in children : influence of growth on the alveolar plateau slope

Background Lung growth in children is associated with dramatic increases in the number and surface area of alveolated airways. Modelling studies have shown the slope of the alveolar plateau (phase III) is sensitive to the total cross‐sectional area of these airways. Therefore, the influence of age and body size on the phase III slope of the volumetric capnogram was investigated. Methods Phase III slope (alveolar dcCO2/dv) and airway deadspace (VDaw) were derived from repeated single‐breath carbon dioxide expirograms collected on 44 healthy mechanically ventilated children (aged 5 months‐18 yr) undergoing minor surgery. Ventilatory support was standardized (VT = 8.5 and 12.5 ml/kg, [florin] = 8–15 breaths/min, inspiratory time = 1 s, end‐tidal partial pressure of carbon dioxide = 30–45 mmHg), and measurements were recorded by computerized integration of output from a heated pneumotachometer and mainstream infrared carbon dioxide analyzer inserted between the endotracheal tube and anesthesia circuit. Experimental data were compared to simulated breath data generated from a numeric pediatric lung model. Results An increased VDaw, a smaller VDaw/VT, and flatter phase III slope were found at the larger tidal volume (P < 0.01). Strong relationships were seen at VT = 12.5 ml/kg between airway deadspace and age (R2 = 0.77), weight (R2 = 0.93), height (R2 = 0.78), and body surface area (R2 = 0.89). The normalized phase III slopes of infants were markedly steeper than that of adolescents and were reduced at both tidal volumes with increasing age, weight, height, and body surface area. Phase III slopes and VDaw generated from modelled carbon dioxide washout simulations closely matched the experimental data collected in children. Conclusions Morphometric increases in the alveolated airway cross‐section with lung growth is associated with a decrease of the phase III slope. During adolescence, normalized phase III slopes approximate those of healthy adults. The change in slope with lung growth may reflect a decrease in diffusional resistance for carbon dioxide transport within the alveolated airway resulting in diminished acinar carbon dioxide gradients.

Cyclosporin A liposome aerosol: Particle size and calculated respiratory deposition

Abstract Treatment of pulmonary diseases with the immunosuppressive drug Cyclosporin A (CsA) is limited, in part, by poor penetration into the lung following oral or intravenous administration, and by the development of limiting renal, hepatic, and other toxicity following prolonged administration. CsA aerosol delivery may provide an alternate route of local administration that could improve treatment and reduce systemic toxicity. The total CsA dosage administered via aerosol would be less than the conventional oral or intravenous dosage routes. In the present study, lipophilic CsA was prepared with different phosphatidylcholine (PC) liposome formulations. CsA-liposome small particle aerosols generated using continuous jet nebulizers were compared according to particle size range, efficiency of drug delivery, and calculated amounts of respiratory tract deposition. Five different CsA-PC liposome formulations were tested in aerosol with varying degrees of efficiency of drug delivery. CsA-PC liposomes prepared using PC with phase transition temperatures ( T c ) below 16–17°C nebulized more efficiently than those with higher T c . Based on its size range an efficiency, CsA-DLPC was selected as the best formulation for aerosol delivery to the lung. Using the Puritan Bennett 1600, twin jet nebulizer modified to a single jet, the particle size, mass median aerodynamic diameter (MMAD), was 0.82 μ m ± geometric standard deviation (GSD) = 1.7. A computer model of inhaled particle deposition in Weibels lung generations 0–16 and 17–23 was utilized to predict the anatomical delivery of CsA. A calculated 11.6% of inhaled CsA-DLPC liposomes will deposit in the respiratory tract, almost exclusively in Weibel generations 17–23. The remainder, 88.4%, will be exhaled. A dosage of about 2 mg/h will deposit in the adult model respiratory tract used for calculations. Local delivery of CsA by aerosol may provide more efficient treatment of immunologically-mediated pulmonary diseases without systemic toxicity common with intravenous or oral therapy.

Sensitivity of CO2 washout to changes in acinar structure in a single-path model of lung airways.

A numerical solution of the convection-diffusion equation with an alveolar source term in a single-path model (SPM) of the lung airways simulates steady state CO2 washout. The SPM is used to examine the effects of independent changes in physiologic and acinar structure parameters on the slope and height of Phase III of the single-breath CO2 washout curve. The parameters investigated include tidal volume, breathing frequency, total cardiac output, pulmonary arterial CO2 tension, functional residual capacity, pulmonary bloodflow distribution, alveolar volume, total acinar airway cross sectional area, and gas-phase molecular diffusivity. Reduced tidal volume causes significant steepening of Phase III, which agrees well with experimental data. Simulations with a fixed frequency and tidal volume show that changes in blood-flow distribution, model airway cross section, and gas diffusivity strongly affect the slope of Phase III while changes in cardiac output and in pulmonary arterial CO2 tension strongly affect the height of Phase III. The paper also discusses differing explanations for the slope of Phase III, including sequential emptying, stratified inhomogeneity, and the issue of asymmetry, in the context of the SPM.

Noninvasive recovery of acinar anatomic information from CO2 expirograms

A numerical single path model of respiratory gas exchange with distributed alveolar gas sources was used to estimate the anatomical changes in small peripheral airways such as occur in chronic obstructive pulmonary diseases (COPD). A previous sensitivity analysis of the single path model showed that decreasing total acinar airway cross-sectional area by an area reduction factor, R, results in computed gas expirograms with Phase III steepening similar to that observed in COPD patients. From experimental steady state CO2 washout data recorded from six healthy subjects and six COPD patients, optimized area reduction factors for the single path model were found that characterize peripheral airway anatomy for each subject. Area reduction factors were then combined with measured functional residual capacity data to calculate the normalized peripheral airspace diameters in a given subject, relative to the airspace diameters in the generations of an idealized standard lung. Mean area reduction factors for the patient subgroup were 63% of those for the healthy subgroup, which is related to the gas transport limitation observed in disease. Mean airspace sizes for the patient subgroup were 235% of the healthy subgroup, which characterizes the increase in size and reduction in number of peripheral airspaces due to tissue erosion in emphysema. From these results, the air-phase diffusive conductance in COPD patients was calculated to be 32% of the mean value in the healthy subjects. These findings correlated well with standard pulmonary function test data for the patients and yield the recovery of acinar airway information from gas washout by combining the single path model with experimental measurements.

DIFFUSIVITY, RESPIRATORY RATE AND TIDAL VOLUME INFLUENCE INERT GAS EXPIROGRAMS

We modified, and developed software for, a computer-controlled quadrupole mass spectrometer to measure complete breath-by-breath expirograms of helium (He) and sulfur hexafluoride (SF6) exhaled during the infusion of saline saturated with the inert gases. He and SF6 have similar blood solubilities but very different gas phase diffusivities allowing examination of the influence of gas phase diffusivity on steady state inert gas expirograms. We studied six normal human volunteers in nine separate studies and examined the influence of tidal volume (VT) and breathing frequency (f) on the airways dead space (VDaw) and alveolar plateau slope (phase III) for the inert gases and CO2. The experimental data showed a reduction in VDaw with rapid shallow breathing, while phase III slope increased by a factor of two to three. We critically evaluated the data and methodology of these and previously reported studies of continuous and single breath washout of He and SF6. In general the 15 to 20 ml differences in VDaw between He and SF6 were in keeping with previous studies by others. The ratio of phase III slopes of SF6 to He reported by us previously (Scherer et al., J. Appl. Physiol. 64: 1022-1029, 1988) was 3.13. In the current study, which includes the analysis of more than 400 He and SF6 breaths, the ratio of SF6 to He slope was 1.85. The difference between the two studies was largely related to the improved methodology of the current study, particularly for the measurement of He. The results support the conclusion that diffusivity is an important component of both phase II and phase III of the expirogram. However, the difference in phase III between He and SF6 is somewhat less than previously reported.

Modelling steady state pulmonary elimination of He, SF6 and CO2: effect of morphometry.

We studied the influence of acinar morphometry on the shape of simulated expirograms computed from a single path convection-diffusion model that includes a source term for gas evolution from the blood (Scherer et al., J. Appl. Physiol. 64: 1022-1029, 1988). Acinar structure was obtained from published data of 3 different lung morphometries. The simulations were performed over a range of tidal volumes (VT) and breathing frequencies (f) comparable to those observed in a previously reported human study. Airways dead space (VDaw) increased with VT in all the morphometric models tested and in the experimental data. The increase in VDaw with VT was inversely related to the diffusivity of the evolving gas and to the rate of increase in airway cross-section of the most mouthward (proximal) alveolated generations of the models. Normalized phase III slope for all the gases decreased with increasing VT in all the models as was previously reported for healthy human subjects. In the model simulations, the greatest sensitivity of phase III slope to VT was seen with the least diffusible gas using the airway morphometry with the smallest cross-sectional areas in the proximal alveolated generations. We conclude that both VDaw and phase III slope of an evolving gas are sensitive to the geometry of the proximal acinar airways and that this is manifest by their dependence on tidal volume, breathing frequency, molecular diffusivity and alveolar/blood source emission rate. The model simulations indicate that heterogeneity of gas washout is not required to explain the magnitude of the phase III slope in healthy human subjects.

Microemboli reduce phase III slopes of CO2 and invert phase III slopes of infused SF6

We investigated the effect of increasing doses of intravenously infused glass microspheres (mean diameter 125 microns) on gas exchange in anesthetized, heparinized, mechanically ventilated goats (VT = 16-18 ml/kg). Breath-by-breath CO2 expirograms were collected using a computerized system (Study A) during the infusion of a total of 15 g of microspheres. We found a 50% decrease in extravascular lung water by indicator dilution with a corresponding doubling of alveolar dead space (VDalv). Airways deadspace (VDaw) decreased by 13 ml (10%) and mean normalized phase III slope for CO2 decreased from 0.23 to -0.08 L-1 becoming negative in 3 of 5 animals. In a second study (Study B), simultaneous breath-by-breath CO2 and infused SF6 expirograms were collected using an infrared CO2 analyzer and a mass spectrometer. Under baseline conditions VDaw for CO2 was smaller than for SF6 and the ratio of the phase III slope for SF6 to the phase III slope for CO2 was 1.39. Following embolization there were no differences in VDaw between the two gases, however, the phase III slope for CO2 became either slightly negative or extremely flat, while the phase III slope for SF6 became negative in 73% of the breaths (-0.17 L-1, P < 0.05). Negative phase III slopes have been predicted by a single path model when blood flow is confined to the most mouthward generations of the acinus (Schwardt et al., Ann. Biomed. Engin, 19: 679-697, 1991). The agreement between the numerical model and the experimental data is consistent with a serial distribution of blood flow within the acinus.

Predicted combustion product deposition in the human airway

Fires involving modern polymeric materials produce toxic vapours and particles of widely varying composition and size depending on available oxygen and localized temperatures. Adverse health effects of inhaled combustion-generated particles depend on physiological interactions at the airway deposition site. The present work is a theoretical investigation into the importance of airway humidity and temperature profiles, initial particle size, particle size distribution and ionic concentration on airway particle deposition. A modified numerical model accounting for hygroscopic particle growth was used to predict airway deposition of 0.1-10.0 microm mass median aerodynamic diameter (MMAD) particles. Dynamic humidity profiles were generated with an unsteady state model of heat and water vapour transport. Results suggest that for hygroscopic particles < 2.0 microm, MMAD dynamic end-inspiratory humidity profiles produce up to 250% greater predicted nasopharyngeal deposition than steady state humidity profiles. Assuming combustion products are hygroscopic, these results also suggest that less pulmonary deposition will occur than previously predicted. In addition, higher upper airway concentrations of combustion products may have significant health consequences independent of pulmonary deposition patterns.