The DLCO is the one pulmonary function test of the three main types in use that has the greatest effect on the workup and treatment of shortness of breath when the cause is unknown. Its underlying principles and many uses reveal why. Spirometry and lung plethysmography – the other main types of lung function tests – have their places. But DLCO is the game changer.
DLCO is an acronym for diffusing capacity of the lung for carbon monoxide. Even though it measures the uptake of carbon monoxide (CO), it serves as an indicator of the ability of the lungs to perform gas exchange in general. Most importantly, it indirectly assesses the ability of the lungs to transfer inhaled oxygen (O2) to blood. CO is the gas of choice for the test because it has a much stronger affinity (natural attraction) for hemoglobin (HGB) than O2 does. In fact, it is 200 to 250 times greater.
There are two main physiologic factors that determine DLCO. They are the total surface area of the lungs available for gas exchange (VA) and the rate of uptake of CO across the alveolar-capillary membrane. VA is the symbol for the total surface area of the lungs available for gas exchange. KCO is the symbol for the rate at which CO passes from the lungs into the blood.
KCO depends on four factors. One is the partial pressure gradient across the alveolar capillary membrane. Since the partial pressure of CO in capillary blood is close to 0 this factor is for the most part the partial pressure of CO in the alveoli alone. The partial pressure of CO in the blood remains zero or almost because CO binds to the HGB of red blood cells. Thus, unbound HGB is the main driver of CO diffusion from the lungs into the blood. Since HGB is in blood, the amount of blood flow to the lungs also determines the rate of CO diffusion from the lungs into the blood. The fourth factor that determines the extent to which CO and other gases can diffuse from the lungs into the bloodstream is the thickness of the alveolar capillary membrane barrier, which in some disease states is increased.
How DLCO Is Determined
DLCO is a determination which the test machine makes based on the VA and KCO which it calculates from measurements it makes. The equation on which the determination is based is DLCO = VA x KCO. In other words DLCO is a product of two measurements. It is the total lung surface area for gas exchange times the rate of transfer of CO into the blood of nearby capillaries.
The test measures alveolar volume (VA) based on the dilution of an inhaled inert gas that does not enter the blood from the lungs and the rate of decay of inhaled CO over a specified period of time (KCO). Depending on the test facility, the inert gas is usually helium or methane.
Standard DLCO Test Procedure and Rationale
During the test the patient breathes through a mouthpiece with nose clips. The most commonly used technique for the test is to have the patient swiftly inhale a single-breath mixture of gases consisting of .3% CO, either 10% helium or .3% methane and the remaining portions of room air from RV to TLC; hold the breath for 10 seconds; then exhale back to RV in less than 4 seconds.
The test machine eliminates a volume of the exhaled gas estimated to be equal to the anatomical dead space of the test subject. The term for this step is the washout. It then calculates the concentration of the inert gas exhaled. The total amount of helium or methane inhaled would not change since neither enters the blood from the lungs. Thus, any change in the concentration of the exhaled sample of gas compared to the inhaled mixture is strictly a reflection of redistribution of the inhaled gas into a larger volume which in this case is VA.
If the test uses helium as the inert gas the amount of it that ends up in the gas-exchanging alveoli will be the same as the amount inhaled even though the concentration will be less. The reason is it does not diffuse into the blood. Since the concentration of He is the amount divided by the volume and the amount is unchanged the following equation holds true:
VI is the volume of gas inhaled minus the estimated dead space. The test allows for dead space during inhalation also because it is the part of the lung volume not involved in gas exchange. Hei is the concentration of helium inhaled. Hee is the concentration of helium exhaled.
Since the volume and concentration of helium inhaled are known and the DLCO machine analyzer can measure Hee, it can calculate VA based on the following re-arrangement of the above equation as follows:
The machine also calculates the rate of CO uptake (KCO) based on an equation using alveolar concentration of CO immediately after inhalation of the gas mixture (CO0) and at the end of 10 seconds of breath holding (COe). The machine can’t measure CO0 directly. But since the inhaled CO concentration (COi) is known and since CO dilutes as it enters the lungs in proportion to helium it is calculated via the following equation:
CO0 = COi (Hee/Hei)
Performance Criteria for Test Validity
In order for the test to be valid the patient performance must meet the following criteria:
- The volume of inspired gas must be at least 85% of vital capacity recorded during preceding spirometry
- The inspiration from RV to TLC should be less than 4 seconds
- Expiration should be 4 seconds or less, but not forced
- The expired sample volume should be between .5 and 1.0 L
- The breath hold should be 10 seconds
- There must be two valid DLCO measurements within 10% of each other
What DLCO Reveals
The test provides clues to the pathophysiology of a disease process based on the equation DLCO = VA x KCO. When rearranged KCO = DLCO/VA. The test machine calculates and prints out DLCO/VA which is the rate of diffusion of CO across the alveolar-capillary membrane. It is not an adjustment of DLCO as some suppose. It is a part of DLCO, not a correction of it.
If DLCO is low but DLCO/VA is normal or slightly increased the cause of the low DLCO is a loss of alveolar volume. With combining of the above equations DLCO = VA x DLCO/VA. Thus, if both DLCO and DLCO/VA (KCO) are low, the reason for the low CO diffusing capacity is a low rate of diffusion ± reduced alveolar volume.
DLCO Classification and Severity Guidelines
There are five designations for DLCO based on the test reading. They are as follows:
- High – greater than 140% of predicted
- Normal – >75% of predicted, up to 140%
- Mild decrease – 60% to 74%
- Moderate decrease – 40% to 59%
- Severe decrease – less than 40%
The actual reported units are in milliliters of CO per minute per mmHg (STPD). STPD is an abbreviation for standard temperature and pressure, dry. It denotes the expression of the volume of gas as if it were at standard temperature (0°C); standard pressure (760 mmHg); and under dry conditions.
A DLCO of <30% of predicted is a Social Security criterion for total disability.
Interpretation and Diagnostic Implications
Proper interpretation of the DLCO test helps doctors make early diagnoses and provide timely treatment of a number of diseases that can cause shortness of breath. The key to proper interpretation of the test is an understanding of the factors that affect VA and KCO and how they correlate with certain disease states.
COPD with emphysema is a case in point. It often features a decreased DLCO even when spirometry and lung volumes are normal. The decrease is due to both a loss of VA and a decrease in KCO. The reason is the loss of alveoli and the capillary beds within them. In the case of COPD with chronic bronchitis alone or asthma DLCO is normal though, because alveoli volume and blood flow are intact; accordingly, VA and KCO are normal.
The test can also distinguish between pulmonary arterial diseases such as pulmonary hypertension and those that affect only the lung parenchyma. The reason is KCO is low but VA is normal when disease affects only alveolar blood flow; whereas, the opposite is true when it involves the lung parenchyma but not the blood vessels. The reason for the latter is the diversion of blood flow from lost alveolar units to previously less-perfused ones.
In the normal state there is diversion of blood from lesser to greater air-filled alveoli. Alveoli are more air-filled in the (bases) lower regions of the lungs and less so in the apices (upper portions). Consequently, blood flow is greatest in the bases of the lungs and least in the apices when one is in an upright position. This variable blood flow is the lungs’ means of ensuring that O2 uptake is as uniform as possible throughout the lungs. Similarly, the same process occurs as lung volumes fall from TLC to RV so as to keep KCO relatively constant.
Blood flow diversion also occurs when there are decreased amounts of air in alveoli due to disease. It results in improved perfusion of involved alveolar units and supernormal perfusion of ones not involved. The net effect is a decrease in DLCO which is less than expected because of an increase in KCO (DLCO/VA) as a result of the net increase in blood flow.
Contrary to some views, DLCO does not help distinguish restrictive lung disease (RLD) from COPD. The reason is it can be normal or low depending on the cause of the RLD. It can be helpful though in diagnosing the cause of the restriction.
DLCO is normal in cases of RLD due to factors outside of the lungs such as obesity or neuromuscular disease. The reason is the increase in KCO resulting from the diversion of alveolar blood flow mentioned above.
When RLD is due to disease of lung tissue such as ILD it usually features decreased DLCO due to reduced VA and KCO. But a reduction in KCO usually precedes a drop in VA in the early stages of the disease. The reduced rate of diffusion is usually due to decreased alveolar blood flow. But in some forms (particularly pulmonary fibrosis) an increase in the thickness of the alveolar-capillary membrane is also a factor.
The DLCO test provides clues for a variety of other medical conditions and factors that affect it, the enumeration and discussion of which is beyond the scope of this article. Most cause a drop in the DLCO. But some cause it to rise. At any rate, the test is a valuable tool which if properly interpreted and used can improve patient outcomes.