Transfer Factor (DLCO)

Standard Spirometry gives an estimate of pulmonary function based on anatomical lung volumes. It does not give an estimate of physiological function which may be affected by fibrosis, bullae or oedema. The single breath carbon monoxide diffusion capacity is a test of alveolar respiratory function.

Technique

    1. A single breath of carbon monoxide is inhaled. The amount of CO exhaled is then measured by .... . An estimate of that not exhaled is an estimate of the ability of the gas to diffuse or transfer across the alveolar wall into the blood stream.

  2. Measurements

    1. DLCO - carbon monoxide diffusion capacity of the lung.

    2. DLCO (corrected) is the measured DLCO corrected for haemoglobin etc

    3. DLCO (corrected alv) or DL/VA is the measured DLCO corrected for alveolar volume. KCO is the equivalent of the DL/VA.

  3. What does it measure?

  4. •measure of lungs' overall capacity to transfer gas rather than just diffusing capacity of alveolar-capillary membrane

  5. •gas transfer factor = volume of gas taken up/(PAGas - PcGas)

Why Carbon Monoxide?

  1. •gas is usually carbon monoxide: rate of diffusion resembles oxygen and so completely taken up by Hb. That means capillary pressure is effectively zero

  2. •value given as ml/min/mmHg of alveolar pressure of CO

What factors affect TLCO:

  1. •epithelial-endothelial surface area (increases with size of subject)

  2. •pulmonary capillary blood volume and Hb concentration (increases in polycythaemia and pulmonary capillary distension; decreases with PE)

  3. •rate of reaction of CO with Hb

  4. •thickness of alveolar-capillary membrane

  5. •distribution of ventilation and ventilation-perfusion relationships


Differentiating parenchymal destruction from fibrosis:

  1. •effect of lung volume or unevenly distributed ventilation can be corrected by dividing TL by effective alveolar volume (VA). The latter is the volume into which CO distributes during measurement of TL. It is determined by helium dilution. 10% helium is administered during test along with CO and air

  2. •in parenchymal disease characterised by destruction or diffuse infiltration both TL and TL/VA decreased while in diseases characterized by loss of lung tissue (eg fibrotic replacement) TL decreases but TL/VA may be normal.

DLCO as predictor of postoperative morbidity and mortality

    1. Ferguson tested 376 patients having 284 lobectomies and 92 pneumonectomies and  demonstrated

        1. Predicted postoperative diffusing capacity was best predictor of mortality or morbidity.

    2. It had predictive power independent of spirometry, therefore useful at borderline values of FEV1.

    3. Reference: Diffusion capacity for CO: Transfer factor. (Ferguson MK. J Thorac Cardiovasc Surg 1995;109:275-83.)

  2. DLCO as predictor of postoperative lung function

    1. Wernly and Demeester performed Xenon 133 ventilation scans, technetium 99m perfusion scans, and preop. spirometry  in 85 patients undergoing 45 pneumonectomies and 40 lobectomies.

    2. In calculating predicted FEV1 after pneumonectomy, the actual post-operative result correlates better with perfusion scans than ventilation scan. Matched V-P scans also have a good correlation. I suspect that most patients requiring pneumonectomy have central hilar node disease. Nodes tend to obstruct pulmonary arteries before obstructing bronchi so perfusion scans best predict the extent of the disease.

    3. Predicted FEV1 = Preop. FEV1  x % perfusion

    4. For predicted FEV1 after lobectomy, calculation using ventilation or perfusion scans was no more accurate than using a simple subtraction method link.

    5. References:

    6. Wernly and Demeester J Thorac Cardiovasc Surg 1980;80:535-43.

    7. Alessandro Brunelli, Majed Al Refai, Michele Salati, Armando Sabbatini, Nicholas J. Morgan-Hughes, and Gaetano Rocco. Carbon monoxide lung diffusion capacity improves risk stratification in patients without airflow limitation: evidence for systematic measurement before lung resection. Eur. J. Cardiothorac. Surg., Apr 2006; 29: 567 - 570.


The following explanation of Transfer Factor is from eMedicine:

http://www.emedicine.com/med/topic2972.htm

by  Author: Kevin McCarthy, R-CPT, Technical Director, Pulmonary Function Laboratories, Section of Pulmonary Function, Department of Pulmonary and Critical Care, The Cleveland Clinic Foundation

Coauthor(s): Raed A Dweik, MD, FACP, FCCP, FRCPC, Associate Professor of Medicine, The Cleveland Clinic, Lerner College of Medicine; Director, Pulmonary Vascular Program, Department of Pulmonary, Allergy and Critical Care Medicine, The Cleveland Clinic Foundation


Synonyms

Transfer factor (TL, mmol/min/kilopascal, Europe); DLCO; diffusing capacity of lung (DL, mL/min/mmHg); diffusing capacity of lung/alveolar volume (DL/VA); rate of carbon monoxide (CO) uptake (KCO), which is equivalent to the DL/VA; and alveolar volume (VA, L), which is the single-breath estimate of the TLC determined by the dilution of the helium concentration

Contraindications

Inability to follow instructions is a contraindication to a DLCO test (CPT code 94070). Patients should be alert, oriented, able to exhale completely and inhale to total lung capacity, able to maintain an airtight seal on a mouthpiece, and able to hold a large breath for 10 seconds.

Patient care/preparations

Refrain from smoking for several hours before the test. Alcohol vapors can affect the accuracy of some fuel cell types of CO analyzers, and alcoholic beverages should be withheld for 8 hours.

Test

DLCO, also known as the transfer factor of the lung for CO (TLCO), is a measurement of the ease of transfer for CO molecules from alveolar gas to the hemoglobin of the red blood cells in the pulmonary circulation. It often is helpful for evaluating the presence of possible parenchymal lung disease when spirometry and/or lung volume determinations suggest a reduced vital capacity, RV, and/or TLC.

Most pulmonary laboratories in the United States perform this test by the single-breath technique (DLCO SB) because it is quicker to perform and more reproducible than other techniques. Other techniques, such as the rebreathing technique, are not commonly available and are not described here. In the single-breath technique, the subject exhales to RV and then inspires the test gas (10% helium, 0.3% CO, 21% oxygen, and balance nitrogen) briskly to TLC. This vital capacity size breath is held for 10 seconds and then exhaled into a sample bag after an initial discard of 0.5-0.75 L to account for dead space.

The grab sample (0.5-1 L) then is analyzed for helium and CO. The helium dilution of the vital capacity breath of test gas by the patient's RV provides both a means to estimate the initial alveolar concentration of CO and to estimate the patient's TLC. The rate of diffusion of the CO can be estimated by the change from this initial alveolar level to that of the expired grab sample. This change in the CO concentration is then multiplied by the single-breath estimate of TLC to calculate the diffusing capacity. Abnormal hemoglobin (Hb) levels can affect the diffusing capacity and, if known, should be used to mathematically correct the measured diffusing capacity to normal Hb.


•Adjusted DLCO (adolescent males and men): Hb adjusted DLCO (DLCOc) = measured DLCO ([10.22 + Hb g/dL]/[1.7 Hb])


•Hb adjusted DLCO (children <15 y and women): Hb adjusted DLCO (DLCOc) = measured DLCO ([9.38 + Hb g/dL]/[1.7 Hb])

The measured DLCO also can be adjusted for elevated levels of carboxyhemoglobin, as follows:


•Carboxyhemoglobin-adjusted DLCO (DLCOc) = measured DLCO (1 + [%CO Hb/100])

The diffusing capacity is a measure of the conductance of the CO molecule from the alveolar gas to Hb in the pulmonary capillary blood. The transfer of the CO molecule is limited by both perfusion and diffusion. CO (and oxygen) must pass through the alveolar epithelium, tissue interstitium, capillary endothelium, blood plasma, and red cell membrane and cytoplasm before attaching to the Hb molecule.

Results

Reported parameters typically include the DLCO (mL/min/mm Hg) and the DL/VA, the average inspiratory vital capacity (IVC) of 2 reproducible measurements and the average calculated alveolar volume (VA), and Hb-corrected and carboxyhemoglobin-corrected values.

Interpretation

Because the DLCO is directly proportional to VA (the single-breath dilutional estimate of TLC), nonpulmonary processes that reduce the TLC cause reductions in the DLCO. If VA can be assessed accurately, these reductions produce a normal or elevated DL-to-VA ratio. Examples of this include lung resection, thoracic cage abnormalities (eg, kyphoscoliosis), and small lungs. DLCO is reduced in pulmonary emphysema; however, because of the poor distribution of the inspired test gas, the VA may grossly underestimate the TLC, and the resultant DL/VA may be normal. A reduced DLCO and a reduced DL-to-VA ratio suggest a true interstitial disease such as pulmonary fibrosis or pulmonary vascular disease. Recent work has shown that, in normal patients, the DL/VA is increased to above normal levels when the DLCO test is performed at volumes less than the TLC. This suggests that a low DLCO and a normal DL/VA may be a function of an inappropriately low predicted value for DL/VA when TLC is reduced.

The pattern of a low DLCO and a normal DL/VA may not be sufficient to rule out the presence of parenchymal disease. The recent works of Johnson and Chinn et al advocate the volume correction of the predicted value for DLCO by using the measured VA to "correct" the predicted DLCO for low or high lung volumes. Further work is warranted, but studies demonstrating the nonlinearity of the relationship between lung volume and DLCO are sufficiently convincing that the practice of interpreting a low DLCO and a normal DL/VA as normal should not be performed. The degree of severity of reduction in the diffusing capacity can be assigned according to the following scheme: less than the lower limit of normal (LLN) but greater than 60% of predicted is mild, between 40 and 60% of predicted is moderate, and less than 40% is severe.

Nonperfusion of ventilated alveoli, such as in pulmonary vascular disease, produces reduction of both the DLCO and the DL/VA. Anemia produces a virtual reduction in pulmonary capillary blood volume that causes a reduction in DLCO that can be adjusted mathematically for the reduced Hb. The DLCO may be reduced temporarily in a variety of disorders such as pneumonia, interstitial infiltrative disorders, and alveolar proteinosis. The importance of obtaining an inspiratory vital capacity (IVC) greater than 90% of the best measured VC from the day of the test cannot be overemphasized. Inability to achieve an IVC of greater than or equal to 90% of the largest VC measured that day must be noted on the report.