Diffusing capacity: Difference between revisions

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The '''single-breath diffusing capacity test''' is the most common way to determine <math>D_L</math>.<ref name="multiple" /> The test is performed by having the subject blow out all of the air that they can, leaving only the [[Lung volumes|residual lung volume]] of gas. The person then inhales a test gas mixture rapidly and completely, reaching the [[Lung volumes|total lung capacity]] as nearly as possible. This test gas mixture contains a small amount of carbon monoxide (usually 0.3%) and a ''[[tracer gas]]'' that is freely distributed throughout the alveolar space but which doesn't cross the alveolar-capillary membrane. [[Helium]] and [[methane]] are two such gasses. The test gas is held in the lung for about 10&nbsp;seconds during which time the CO (but ''not'' the tracer gas) continuously moves from the alveoli into the blood. Then the subject exhales.

The anatomy of the airways means inspired air must pass through the mouth, trachea, bronchi and bronchioles ([[anatomical dead space]]) before it gets to the alveoli where gas exchange will occur; on exhalation, alveolar gas must return along the same path, and so the exhaled sample will be purely alveolar only after a 500 to 1,000&nbsp;ml of gas has been breathed out.{{citation needed|date=April 2018}} While it is algebraically possible to approximate the effects of anatomy (the ''three-equation method''<ref>{{cite journal |vauthors=Graham BL, Mink JT, Cotton DJ | year = 1981 | title = Improved accuracy and precision of single-breath CO diffusing capacity measurements | url = | journal = J Appl Physiol | volume = 51 | issue = 5| pages = 1306–13 | pmid = 7298468 | doi = 10.1152/jappl.1981.51.5.1306 }}</ref>), disease states introduce considerable uncertainty to this approach. Instead, the first 500 to 1,000 ml of the expired gas is disregarded and the next portion which contain gas that has been in the alveoli is analyzed.<ref name="multiple" /> By analyzing the concentrations of carbon monoxide and inert gas in the inspired gas and in the exhaled gas, it is possible to calculate <math>(D_{L_{CO}})</math> according to Equation {{EquationRef|2}}. First, the ''rate'' at which CO is taken up by the lung is calculated according to:

{{NumBlk|::|<math>\dot{V}_{CO} =\frac {\Delta{[CO]} * V_A} {\Delta{t}} </math> . | {{EquationRef|4}} }}

::::The pulmonary function equipment monitors the change in the concentration of CO that occurred during the breath hold, <math>\Delta{[CO]}</math>, and also records the time <math>\Delta{t}</math>.

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== Interpretation ==

In general, a healthy individual has a value of <math>D_{L_{CO}}</math> between 75% and 125% of the average.<ref name=uppsala>LUNGFUNKTION - Practice compendium for semester 6. Department of Medical Sciences, Clinical Physiology, Academic Hospital, Uppsala, Sweden. Retrieved 2010.</ref> However, individuals vary according to age, sex, height and a variety of other parameters. For this reason, reference values have been published, based on populations of healthy subjects<ref>{{cite journal |vauthors=Miller A, Thornton JC, Warshaw R, Anderson H, Teirstein AS, Selikoff IJ | year = 1983 | title = Single breath diffusing capacity in a representative sample of the population of Michigan, a large industrial state. Predicted values, lower limits of normal, and frequencies of abnormality by smoking history | url = | journal = Am Rev Respir Dis | volume = 127 | issue = 3| pages = 270–7 | pmid = 6830050 | doi = 10.1164/arrd.1983.127.3.270 | doi-broken-date = 2019-12-12 }}</ref><ref>{{cite journal |vauthors=Knudson RJ, Kaltenborn WT, Knudson DE, Burrows B | year = 1987 | title = The single-breath carbon monoxide diffusing capacity. Reference equations derived from a healthy nonsmoking population and effects of hematocrit | url = | journal = Am Rev Respir Dis | volume = 135 | issue = 4| pages = 805–11 | pmid = 3565929 | doi=10.1164/arrd.1987.135.4.805}}</ref><ref>{{cite journal |vauthors=Cotes JE, Chinn DJ, Quanjer PH, Roca J, Yernault JC | year = 1993 | title = Standardization of the measurement of transfer factor (Diffusing capacity) | url = | journal = Eur Respir J Suppl | volume = 16 | issue = | pages = 41–52 | pmid = 8499053 | doi = 10.1183/09041950.041s1693 }}</ref> as well as measurements made at altitude,<ref>{{cite journal |vauthors=Crapo RO, Morris AH, Gardner RM | year = 1982 | title = Reference values for pulmonary tissue volume, membrane diffusing capacity, and pulmonary capillary blood volume | url = | journal = Bull Eur Physiopathol Respir | volume = 18 | issue = 6| pages = 893–9 | pmid = 6927541 }}</ref> for children<ref>{{cite journal |vauthors=Koopman M, Zanen P, Kruitwagen CL, van der Ent CK, Arets HG | year = 2011 | title = Reference values for paediatric pulmonary function testing: The Utrecht dataset | url = | journal = Respir. Med. | volume = 105 | issue = 1| pages = 15–23 |pmid=20889322 | doi=10.1016/j.rmed.2010.07.020}} Erratum in ''Respir. Med.'' 2011 Dec;105(12):1970-1.</ref> and some specific population groups.<ref>{{cite journal |vauthors=Chin NK, Ng TP, Hui KP, Tan WC | date = Jun 1997 | title = Population based standards for pulmonary function in non-smoking adults in Singapore | url = | journal = Respirology | volume = 2 | issue = 2| pages = 143–9 | pmid = 9441128 | doi=10.1111/j.1440-1843.1997.tb00070.x}}</ref><ref>{{cite journal |vauthors=Piirilä P, Seikkula T, Välimäki P | year = 2007 | title = Differences between Finnish and European reference values for pulmonary diffusing capacity | url = | journal = Int J Circumpolar Health | volume = 66 | issue = 5| pages = 449–57 | pmid = 18274210 | doi = 10.3402/ijch.v66i5.18316 }}</ref><ref>{{cite journal |vauthors=Ip MS, Lam WK, Lai AY, etal | title = Hong Kong Thoracic Society. Reference values of diffusing capacity of non-smoking Chinese in Hong Kong | url = | journal = Respirology | volume = 12 | issue = 4| pages = 599–606 | doi = 10.1111/j.1440-1843.2007.01084.x | pmid = 17587430 | date=July 2007}}</ref>

===Blood CO levels may not be negligible===

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====The two components of <math>D_{L_{CO}}</math>====

While <math>(D_L)</math> is of great practical importance, being the overall measure of gas transport, the interpretation of this measurement is complicated by the fact that it does not measure any one part of a multi-step process. So as a conceptual aid in interpreting the results of this test, the time needed to transfer CO from the air to the blood can be divided into two parts. First CO crosses the alveolar capillary membrane (represented by <math>D_M</math> ) and then CO combines with the hemoglobin in capillary red blood cells at a rate <math>\theta</math> times the volume of capillary blood present (<math>V_c</math>).<ref>{{cite journal |vauthors=Roughton FJ, Forster RE | year = 1957 | title = Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in the human lung, with special reference to true diffusing capacity of pulmonary membrane and volume of blood in the lung capillaries | url = | journal = J Appl Physiol | volume = 11 | issue = 2| pages = 290–302 | pmid = 13475180 | doi = 10.1152/jappl.1957.11.2.290 }}</ref> Since the steps are in series, the conductances add as the sum of the reciprocals:

{{NumBlk|::|<math>\frac {1} {D_{L_{CO}}} =\frac {1} {D_M} + \frac {1} {\theta * V_c}</math> . | {{EquationRef|3}} }}

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====Lung conditions that increase <math>D_{L_{CO}}</math>.====

# Alveolar hemorrhage [[Goodpasture's syndrome]],<ref>{{cite journal|last=Greening|first=AP|author2=Hughes, JM|title=Serial estimations of carbon monoxide diffusing capacity in intrapulmonary haemorrhage.|journal=Clinical Science|date=May 1981|volume=60|issue=5|pages=507–12|pmid=7249536|doi=10.1042/cs0600507}}</ref> [[polycythemia]],<ref>{{cite journal|last=Burgess|first=J. H.|author2=Bishop, J. M.|title=PULMONARY DIFFUSING CAPACITY AND ITS SUBDIVISIONS IN POLYCYTHEMIA VERA|journal=Journal of Clinical Investigation|volume=42|issue=7|pages=997–1006|doi=10.1172/JCI104804|pmc=289367|pmid=14016987|title=Pulmonary Diffusing Capacity and ITS Subdivisions in Polycythemia Vera|year=1963}}</ref> left to right [[Cardiac shunt|intracardiac shunts]],<ref>{{cite journal|last=AUCHINCLOSS JH|first=Jr|author2=GILBERT, R |author3=EICH, RH |title=The pulmonary diffusing capacity in congenital and rheumatic heart disease.|journal=Circulation|date=February 1959|volume=19|issue=2|pages=232–41|pmid=13629784|doi=10.1161/01.cir.19.2.232}}</ref> due increase in volume of blood exposed to inspired gas.

# [[Asthma]] due to better perfusion of apices of lung. This is caused by increase in pulmonary arterial pressure and/or due to more negative pleural pressure generated during inspiration due to bronchial narrowing.<ref>{{cite journal|last=Collard|first=P|author2=Njinou, B |author3=Nejadnik, B |author4=Keyeux, A |author5= Frans, A |title=Single breath diffusing capacity for carbon monoxide in stable asthma.|journal=Chest|date=May 1994|volume=105|issue=5|pages=1426–9|pmid=8181330|doi=10.1378/chest.105.5.1426}}</ref>

==History==

In one sense, it is remarkable that DL_CO has retained such clinical utility. The technique was invented to settle one of the great controversies of pulmonary physiology a century ago, namely the question of whether oxygen and the other gases were actively transported into and out of the blood by the lung, or whether gas molecules diffused passively.<ref>{{cite journal | author = Gjedde A | year = 2010 | title = Diffusive insights: on the disagreement of Christian Bohr and August Krogh | url = http://advan.physiology.org/content/34/4/174.full#content-block | journal = Adv Physiol Educ | volume = 34 | issue = 4| pages = 174–185 | doi = 10.1152/advan.00092.2010 | pmid = 21098384 }}</ref> Remarkable too is the fact that both sides used the technique to gain evidence for their respective hypotheses. To begin with, [[Christian Bohr]] invented the technique, using a protocol analogous to the steady state diffusion capacity for carbon monoxide, and concluded that oxygen was actively transported into the lung. His student, [[August Krogh]] developed the single breath diffusion capacity technique along with his wife [[August Krogh|Marie]], and convincingly demonstrated that gasses diffuse passively,<ref>Krogh A. 1910 On the oxygen metabolism of the blood. Skand Arch Physiol 23: 193–199</ref><ref>Krogh A. 1910 On the mechanism of the gas-exchange in the lungs of the tortoise. Skand Arch Physiol 23: 200–216.</ref><ref>Krogh A. 1910 On the combination of hæmoglobin with mixtures of oxygen and carbonic acid. Skand Arch Physiol 23: 217–223.</ref><ref>Krogh A. 1910 Some experiments on the invasion of oxygen and carbonic oxide into water. Skand Arch Physiol 23: 224–235</ref><ref>Krogh A. 1910 On the mechanism of gas exchange in the lungs. Skand Arch Physiol 23: 248–278</ref><ref>Krogh A, Krogh M. 1910 On the tensions of gases in arterial blood. Skand Arch Physiol 23: 179–192.</ref><ref>Krogh A, Krogh M. 1910 Rate of diffusion into lungs of man. Skand Arch Physiol 23: 236–247</ref> a finding that led to the demonstration that capillaries in the blood were recruited into use as needed – a Nobel Prize–winning idea.<ref>https://www.nobelprize.org/nobel_prizes/medicine/laureates/1920/krogh-bio.html</ref>

==See also==