Editing Diffusing capacity (section)

== 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 | 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 = 1 November 2024 }}</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 | 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) | journal = Eur Respir J Suppl | volume = 16 | pages = 41–52 | pmid = 8499053 | doi = 10.1183/09041950.041s1693 | s2cid = 54555111 | doi-access = free }}</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 | 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 | journal = Respir. Med. | volume = 105 | issue = 1| pages = 15–23 |pmid=20889322 | doi=10.1016/j.rmed.2010.07.020| doi-access = free }} 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 | journal = Respirology | volume = 2 | issue = 2| pages = 143–9 | pmid = 9441128 | doi=10.1111/j.1440-1843.1997.tb00070.x| s2cid = 31037816 }}</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 | journal = Int J Circumpolar Health | volume = 66 | issue = 5| pages = 449–57 | pmid = 18274210 | doi = 10.3402/ijch.v66i5.18316 | s2cid = 22302973 | doi-access = free }}</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 | journal = Respirology | volume = 12 | issue = 4| pages = 599–606 | doi = 10.1111/j.1440-1843.2007.01084.x | pmid = 17587430 | date=July 2007| s2cid = 5897844 }}</ref>

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

In heavy smokers, blood CO is great enough to influence the measurement of <math>D_{L_{CO}}</math>, and requires an adjustment of the calculation when COHb is greater than 2% of the whole.

{{bold div|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 | 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}} }}

{{bold div|Any change in <math>V_c</math> alters <math>D_{L_{CO}}</math>}}

The volume of blood in the lung capillaries, <math>V_c</math>, changes appreciably during ordinary activities such as [[Physical exercise|exercise]].  Simply breathing in brings some additional blood ''into'' the lung because of the negative intrathoracic pressure required for inspiration.  At the extreme, inspiring against a closed glottis, the [[Müller's maneuver]], pulls blood ''into'' the chest.  The opposite is also true, as exhaling increases the pressure within the thorax and so tends to push blood out; the [[Valsalva maneuver]] is an exhalation against a closed airway which can move blood ''out'' of the lung. So breathing hard during exercise will bring extra blood into the lung during inspiration and push blood out during expiration. But during exercise (or more rarely when there is a [[Atrioventricular septal defect|structural defect]] in the heart that allows blood to be shunted from the high pressure, systemic circulation to the low pressure, pulmonary circulation) there is also increased blood flow throughout the body, and the lung adapts by recruiting extra capillaries to carry the increased output of the heart, further increasing the quantity of blood in the lung.  Thus <math>D_{L_{CO}}</math> will appear to increase when the subject is not at rest, particularly during inspiration.

In disease, [[Pulmonary hemorrhage|hemorrhage]] into the lung will increase the number of haemoglobin molecules in contact with air, and so measured <math>D_{L_{CO}}</math> will increase. In this case, the carbon monoxide used in the test will bind to haemoglobin that has bled into the lung. This does not reflect an increase in diffusing capacity of the lung to transfer oxygen to the systemic circulation.

Finally, <math>V_c</math> is increased in '''[[obesity]]''' and when the subject lies down, both of which increase the blood in the lung by compression and by gravity and thus both increase <math>D_{L_{CO}}</math>.

{{bold div|Reasons why <math>\theta</math> varies}}

The rate of CO uptake into the blood, <math>\theta</math>, depends on the concentration of hemoglobin in that blood, abbreviated [[Hemoglobin|Hb]] in the CBC ([[Complete Blood Count]]).  More hemoglobin is present in [[polycythemia]], and so <math>D_{L_{CO}}</math> is elevated.  In [[anemia]], the opposite is true.  In environments with high levels of CO in the inhaled air (such as [[smoking]]), a fraction of the blood's hemoglobin is rendered ineffective by its tight binding to CO, and so is analogous to anemia.  It is recommended that <math>D_{L_{CO}}</math> be adjusted when blood CO is high.<ref name="multiple" />

The lung blood volume is also reduced when blood flow is interrupted by blood clots ([[pulmonary emboli]]) or reduced by bone deformities of the thorax, for instance [[scoliosis]] and [[kyphosis]].

Varying the ambient concentration of oxygen also alters <math>\theta</math>.  At high altitude, inspired oxygen is low and more of the blood's hemoglobin is free to bind CO; thus <math>\theta</math> is increased and <math>D_{L_{CO}}</math> appears to be increased.  Conversely, supplemental oxygen increases Hb saturation, decreasing <math>\theta</math> and <math>D_{L_{CO}}</math>.

{{bold div|Lung diseases that reduce <math>D_M</math> and <math>\theta * V_c</math>}}

Diseases that alter lung tissue reduce both <math>D_M</math> and <math>\theta * V_c</math> to a variable extent, and so decrease <math>D_{L_{CO}}</math>.
# Loss of lung parenchyma in diseases like [[emphysema]].
# Diseases that scar the lung (the [[interstitial lung disease]]), such as [[idiopathic pulmonary fibrosis]], or [[sarcoidosis]]
# Swelling of lung tissue ([[pulmonary edema]]) due to [[heart failure]], or due to an acute inflammatory response to allergens ([[acute interstitial pneumonitis]]).
# Diseases of the blood vessels in the lung, either inflammatory ([[Vasculitis|pulmonary vasculitis]]) or hypertrophic ([[pulmonary hypertension]]).

{{bold div|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.|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|s2cid=27264342|doi-access=free}}</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>