Name: combining volumetric capnography and barometric plethysmography to measure the lung structure-function relationship
Uploaded: 2019-01-08T13:00:00
Description: Watch this Scientific Journal Video about Combining Volumetric Capnography And Barometric Plethysmography To Measure The Lung Structure-function Relationship at JoVE.com

This work was funded by the Departments of Health and Human Physiology and Internal Medicine at the University of Iowa. This work was also supported by the Old Gold Fellowship (Bates) and Grant IRG-15-176-40 from the American Cancer Society, administered through The Holden Comprehensive Cancer Center at The University of Iowa (Bates)

This protocol has been previously approved by and follows the guidelines set by the University of Iowa Institutional Review Board. Data shown were collected as part of a project approved by the Institutional Review Board at the University of Iowa. Participants gave informed consent and the studies were performed in accordance with the Declaration of Helsinki.
1. Equipment
<ol>
	<li>Check the equipment table to verify that all required equipment is available. Double check the configuration us...

<ol>
	<li>Robinson, P. D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Consensus+statement+for+inert+gas+washout+measurement+using+multiple-+and+single-+breath+tests.">Consensus statement for inert gas washout measurement using multiple- and single- breath tests.</a> European Respiratory Journal. 41 (3), 507-522 (2013).</li><li>Verbanck, S., Paiva, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Gas+mixing+in+the+airways+and+airspaces.">Gas mixing in the airways and airspaces.</a> Comprehensive Physiology. 1 (2), 809-834 (2011).</li><li>Bates, M. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pulmonary+function+responses+to+ozone+in+smokers+with+a+limited+smoking+history.">Pulmonary function responses to ozone in smokers with a limited smoking history.</a> Toxicology and Applied Pharmacology. 278 (1), 85-90 (2014).</li><li>Bates, M. L., Brenza, T. M., Ben-Jebria, A., Bascom, R., Ultman, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Longitudinal+distribution+of+ozone+absorption+in+the+lung:+comparison+of+cigarette+smokers+and+nonsmokers.">Longitudinal distribution of ozone absorption in the lung: comparison of cigarette smokers and nonsmokers.</a> Toxicology and Applied Pharmacology. 236 (3), 270-275 (2009).</li><li>Reeser, W. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Uptake+of+ozone+in+human+lungs+and+its+relationship+to+local+physiological+response.">Uptake of ozone in human lungs and its relationship to local physiological response.</a> Inhalation Toxicology. 17 (13), 699-707 (2005).</li><li>Taylor, A. B., Lee, G. M., Nellore, K., Ben-Jebria, A., Ultman, J. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Changes+in+the+carbon+dioxide+expirogram+in+response+to+ozone+exposure.">Changes in the carbon dioxide expirogram in response to ozone exposure.</a> Toxicology and Applied Pharmacology. 213 (1), 1-9 (2006).</li><li>Baker, L. G., Ultman, J. S., Rhoades, R. 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The Respiratory Dead Space.</a> American Journal of Physiology-Legacy Content. 154 (3), 405-416 (1948).</li><li>Eberlein, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Supranormal+Expiratory+Airflow+after+Bilateral+Lung+Transplantation+Is+Associated+with+Improved+Survival.">Supranormal Expiratory Airflow after Bilateral Lung Transplantation Is Associated with Improved Survival.</a> American Journal of Respiratory and Critical Care Medicine. 183 (1), 79-87 (2011).</li><li>Eberlein, M., Schmidt, G. A., Brower, R. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chest+wall+strapping.+An+old+physiology+experiment+with+new+relevance+to+small+airways+diseases.">Chest wall strapping. An old physiology experiment with new relevance to small airways diseases.</a> Annals of the American Thoracic Society. 11 (8), 1258-1266 (2014).</li><li>Taher, H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Chest+wall+strapping+increases+expiratory+airflow+and+detectable+airway+segments+in+computer+tomographic+scans+of+normal+and+obstructed+lungs.">Chest wall strapping increases expiratory airflow and detectable airway segments in computer tomographic scans of normal and obstructed lungs.</a> Journal of Applied Physiology. , (2017).</li><li>Verscheure, S., Massion, P. B., Verschuren, F., Damas, P., Magder, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volumetric+capnography:+lessons+from+the+past+and+current+clinical+applications.">Volumetric capnography: lessons from the past and current clinical applications.</a> Critical Care. 20 (1), 184 (2016).</li><li>Suarez-Sipmann, F., Bohm, S. H., Tusman, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volumetric+capnography:+the+time+has+come.">Volumetric capnography: the time has come.</a> Current Opinion in Critical Care. 20 (3), 333-339 (2014).</li><li>Wanger, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standardisation+of+the+measurement+of+lung+volumes.">Standardisation of the measurement of lung volumes.</a> European Respiratory Journal. 26 (3), 511-522 (2005).</li><li>Culver, B. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recommendations+for+a+Standardized+Pulmonary+Function+Report.+An+Official+American+Thoracic+Society+Technical+Statement.">Recommendations for a Standardized Pulmonary Function Report. An Official American Thoracic Society Technical Statement.</a> American Journal of Respiratory and Critical Care Medicine. 196 (11), 1463-1472 (2017).</li><li>Goldman, H. I., Becklake, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Respiratory+function+tests;+normal+values+at+median+altitudes+and+the+prediction+of+normal+results.">Respiratory function tests; normal values at median altitudes and the prediction of normal results.</a> Am Rev Tuberc. 79 (4), 457-467 (1959).</li><li>Shim, S. S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lumen+area+change+(Delta+Lumen)+between+inspiratory+and+expiratory+multidetector+computed+tomography+as+a+measure+of+severe+outcomes+in+asthmatic+patients.">Lumen area change (Delta Lumen) between inspiratory and expiratory multidetector computed tomography as a measure of severe outcomes in asthmatic patients.</a> J The Journal of Allergy and Clinical. , (2018).</li><li>Smith, B. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Human+airway+branch+variation+and+chronic+obstructive+pulmonary+disease.">Human airway branch variation and chronic obstructive pulmonary disease.</a> Proceedings of the National Academy of Sciences of the United States of America. 115 (5), E974-E981 (2018).</li><li>Farmery, A. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Volumetric+Capnography+and+Lung+Growth+in+Children+-+a+Simple-Model+Validated.">Volumetric Capnography and Lung Growth in Children - a Simple-Model Validated.</a> Anesthesiology. 83 (6), 1377-1379 (1995).</li><li>Scherer, P. W., Neufeld, G. R., Aukburg, S. J., Hess, G. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Measurement+of+Effective+Peripheral+Bronchial+Cross-Section+from+Single-Breath+Gas+Washout.">Measurement of Effective Peripheral Bronchial Cross-Section from Single-Breath Gas Washout.</a> Journal of Biomechanical Engineering-Transactions of the Asme. 105 (3), 290-293 (1983).</li><li>Sinha, P., Soni, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Comparison+of+volumetric+capnography+and+mixed+expired+gas+methods+to+calculate+physiological+dead+space+in+mechanically+ventilated+ICU+patients.">Comparison of volumetric capnography and mixed expired gas methods to calculate physiological dead space in mechanically ventilated ICU patients.</a> Intensive Care Medicine. 38 (10), 1712-1717 (2012).</li><li>Bourgoin, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Assessment+of+Bohr+and+Enghoff+Dead+Space+Equations+in+Mechanically+Ventilated+Children.">Assessment of Bohr and Enghoff Dead Space Equations in Mechanically Ventilated Children.</a> Respiratory Care. 62 (4), 468-474 (2017).</li></ol>

Here, a protocol for the measurement of VD and airways homogeneity (slope) is provided. These measurements can be made at FRC, or as a function of lung volume. Measuring FRC before the start of the experiment and after a perturbation allows VD and slope to be plotted as a function of lung volume and may provide useful information about the structure-function relationship of the lung that is not obtained from capnography at FRC alone.
Airways volume and high-resolution str...

Gas washout techniques have been used for decades to provide important information about the structure and uniformity of the airway tree. The lung is classically described as having two compartments &#8211; a conducting zone that is comprised of the anatomic dead space and the respiratory zone where gas exchange occurs in the alveoli. The conducting airways are termed as &#8220;dead space&#8221; because they do not participate in the exchange of oxygen and carbon dioxide. In the single breath gas washout method, the concentration profile of an exhaled gas can be used to determine the volume of the anatomic dead space and to derive information about the uniformity of ventilation. Some methods rely on the breathing of inert gases to make these measures (N2, argon, He, SF6, etc.). The use of inert gas is well-established, supported by scientific consensus statements1, and there are available commercial equipment with user friendly interfaces. However, the exhaled profile of carbon dioxide (CO2) can be used to derive similar information. Evaluating the profile of CO2 as a function of the exhaled volume, or volumetric capnography, does not require the participant to breathe special gas mixtures and allows the investigator to gather additional information flexibly about metabolism and gas exchange with minimal adjustment to the technique.
During a controlled exhalation, the concentration of CO2 can be plotted against the total exhaled volume. At the beginning of an exhalation, the dead space is filled with atmospheric gas. This is reflected in Phase I of the exhaled CO2 profile where there is an undetectable amount of CO2 (Figure 1, top). Phase II marks the transition to the alveolar gas, where gas exchange occurs and CO2 is abundant. The volume at the midpoint of Phase II is the volume of the anatomic dead space (VD). Phase III contains alveolar gas. Because airways with different diameters empty at different rates, the slope (S) of Phase III provides information about airways uniformity. A steeper slope of Phase III suggests a less uniform airway tree proximal to the terminal bronchioles, or convection-dependent inhomogeneity2. In the case where a perturbation may change the rate of CO2 production, and to make comparisons between individuals, the slope can be divided by the area under the curve to normalize for differences in metabolism (NS or normalized slope). Volumetric capnography has been used previously to evaluate the changes in airways volume and uniformity following air pollutant exposure3,4,5,6.
Gas transport in the lung is governed by both convection and diffusion. Single breath washout measures are highly dependent on air flow and the measured value of VD occurs at the convection-diffusion boundary. Changing the flow rate of the exhalation or preceding inhalation changes the location of that boundary7. Capnography is also highly dependent on the volume of the lung immediately preceding the maneuver. Larger lung volumes distend the airways, resulting in larger values of VD8. One solution is to consistently make the measurement at the same lung volume &#8211; usually functional residual capacity (FRC). An alternative, described here, is to couple volumetric capnography with barometric plethysmography, in order to obtain the relationship between VD and lung volume. The participant then performs the maneuver at constant flow rates, while varying the lung volume. This still allows for classic capnographic measures to be made at FRC, but also for the relationship between the lung volume and dead space volume and between the lung volume and homogeneity to be derived. Indeed, the added value of coupling capnography with plethysmography comes from the ability to test hypotheses about the distensibility of the airways tree and the structure-function relationship of the lung. This may be a valuable tool for investigators aiming to quantify the influence of airways mechanics versus lung compliance and elastance on pulmonary function in healthy and diseased populations9,10,11. Furthermore, accounting for the absolute lung volume at which the volumetric capnographic measurements are being performed allows investigators to characterize the effects of conditions that can alter the inflation state of the lung, such as obesity, lung transplant, or interventions like chest wall strapping. Volumetric capnography may ultimately have clinical utility in the intensive care setting12,13.

<table>
	<tbody>
		<tr>
			<td>Computer with dual monitor</td>
			<td>Dell Instruments</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>PowerLab 8/35*</td>
			<td>AD Instruments</td>
			<td>PL3508</td>
			<td></td>
		</tr>
		<tr>
			<td>LabChart Data Acquisition Software*</td>
			<td>AD Instruments</td>
			<td>Version 8</td>
			<td></td>
		</tr>
		<tr>
			<td>Gemini Respiratory Gas Analyzer* (upgraded option)</td>
			<td>CWE, Inc</td>
			<td>GEMINI 14-10000</td>
			<td>*indicates that part is available in the Exercise Physiology package from AD Instruments</td>
		</tr>
		<tr>
			<td>Heated Pneumotach with Heater Controller* (upgraded option)</td>
			<td>Hans Rudolph, Inc</td>
			<td>MLT3813H-V</td>
			<td></td>
		</tr>
		<tr>
			<td>3L Calibration Syringe</td>
			<td>Vitalograph</td>
			<td>36020</td>
			<td></td>
		</tr>
		<tr>
			<td>Nose Clip*</td>
			<td>VacuMed</td>
			<td>Snuffer 1008</td>
			<td></td>
		</tr>
		<tr>
			<td>Pulse Transducer*</td>
			<td>AD Instruments</td>
			<td>TN1012/ST</td>
			<td></td>
		</tr>
		<tr>
			<td>Barometer</td>
			<td>Fischer Scientific</td>
			<td>15-078-198</td>
			<td></td>
		</tr>
		<tr>
			<td>Flanged Mouthpiece*</td>
			<td>AD Instruments</td>
			<td>MLA1026</td>
			<td></td>
		</tr>
		<tr>
			<td>Nafion drying tube with three-way stopcock*</td>
			<td>AD Instruments</td>
			<td>MLA0343</td>
			<td></td>
		</tr>
		<tr>
			<td>Desiccant cartridge (optional for humid environments)*</td>
			<td>AD Instruments</td>
			<td>MLA6024</td>
			<td></td>
		</tr>
		<tr>
			<td>Resistor</td>
			<td>Hans Rudolph, Inc</td>
			<td>7100 R5</td>
			<td></td>
		</tr>
		<tr>
			<td>Flow head adapters*</td>
			<td>AD Instruments</td>
			<td>MLA1081</td>
			<td></td>
		</tr>
		<tr>
			<td>Modified Tubing Adapter (optional)</td>
			<td>AD Instruments</td>
			<td>SP0145</td>
			<td></td>
		</tr>
		<tr>
			<td>Two way non-rebreather valve (optional)*</td>
			<td>AD Instruments</td>
			<td>SP0146</td>
			<td></td>
		</tr>
		<tr>
			<td>Plethysmograph</td>
			<td>Vyaire</td>
			<td>V62J</td>
			<td></td>
		</tr>
		<tr>
			<td>High Purity Helium Gas</td>
			<td>Praxair</td>
			<td>He 4.8</td>
			<td></td>
		</tr>
		<tr>
			<td>6% CO2 and 16% O2 Calibration Gas</td>
			<td>Praxair</td>
			<td>Custom</td>
			<td></td>
		</tr>
		<tr>
			<td>Microsoft Excel</td>
			<td>Microsoft</td>
			<td>Office 365</td>
			<td></td>
		</tr>
	</tbody>
</table>

combining volumetric capnography and barometric plethysmography to measure the lung structure-function relationship

Tools to measure lung and airways volume are critical for pulmonary researchers interested in evaluating the impact of disease or novel therapies on the lung. Barometric plethysmography is a classic technique to evaluate the lung volume with a long history of clinical use. Volumetric capnography utilizes the profile of exhaled carbon dioxide to determine the volume of the conducting airways, or dead space, and provides an index of airways homogeneity. These techniques may be used independently, or in combination to evaluate the dependence of airways volume and homogeneity on lung volume. This paper provides detailed technical instructions to replicate these techniques and our representative data demonstrates that the airways volume and homogeneity are highly correlated to lung volume. We also provide a macro for the analysis of capnographic data, which can be modified or adapted to fit different experimental designs. The advantage of these measures is that their advantages and limitations are supported by decades of experimental data, and they can be made repeatedly in the same subject without expensive imaging equipment or technically advanced analysis algorithms. These methods may be particularly useful for investigators interested in perturbations that change both the functional residual capacity of the lung and airways volume.

Representative plethysmography results are given in Figure 4. This participant required four attempts in order to collect three FRC values with &#60;5% variability from the mean.%Ref reflects the percent of the predicted value for each variable based on population regression equations that take into account sex, age, race, height and weight
Figure 1 (top) shows a repres...

Watch this Scientific Journal Video about Combining Volumetric Capnography And Barometric Plethysmography To Measure The Lung Structure-function Relationship at JoVE.com

Combining Volumetric Capnography And Barometric Plethysmography To Measure The Lung Structure-function Relationship

Here, we describe two measures of pulmonary function &#8211; barometric plethysmography, which allows the measurement of lung volume, and volumetric capnography, a tool to measure the anatomic dead space and airways uniformity. These techniques may be used independently or combined to assess airways function at different lung volumes.

Tools to measure lung and airways volume are critical for pulmonary researchers interested in evaluating the impact of disease or novel therapies on the ...

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