Diffusing capacity for carbon monoxide
- Meredith C McCormack, MD, MHS
Meredith C McCormack, MD, MHS
- Assistant Professor of Medicine
- Medical Director, Pulmonary Function Laboratory Pulmonary and Critical Care Medicine Johns Hopkins University
A test of the diffusing capacity of the lungs for carbon monoxide (DLCO) is one of the most clinically valuable tests of lung function. The DLCO measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in pulmonary capillaries. The DLCO test is convenient and easy for the patient to perform. The ten seconds of breathholding required for the DLCO maneuver is easier for most patients to perform than is the forced exhalation required for spirometry. Completion of two or three DLCO maneuvers also usually takes less time than pre- and post-bronchodilator spirometric tests.
Standards for DLCO instruments, performance of the test, and calculation of the results were initially published by the American Thoracic Society in 1987, and updated in 2005 [1,2]. The indications for DLCO measurement and the interpretation of the results will be discussed here. The use of other pulmonary function tests in the evaluation of respiratory disease in adults and children is discussed separately. (See "Office spirometry" and "Overview of pulmonary function testing in adults" and "Overview of pulmonary function testing in children".)
The diffusing capacity of the lungs for carbon monoxide (DLCO) is designed to reflect properties of the alveolar-capillary membrane, specifically the ease with which oxygen moves from inhaled air to the red blood cells in the pulmonary capillaries. The uptake of most soluble gases (such as nitrous oxide or acetylene) is limited by (and varies with) pulmonary blood flow. In contrast, the strong affinity of hemoglobin for carbon monoxide (CO) combined with the enormous capacity of the red cell mass to absorb CO, make the uptake of CO less dependent on cardiac output. Diseases in which the uptake of oxygen is reduced cause parallel decreases in the uptake of CO, as measured by the DLCO.
Older textbooks suggest that thickening of the alveolar-capillary membrane (in interstitial lung disease) and loss of alveolar membrane surface area (in emphysema) are the primary causes of a low DLCO. However, subsequent experimental data suggest these and most other diseases that influence the DLCO do so by reducing the volume of red blood cells in the pulmonary capillaries. The total volume of blood in the lungs in healthy adults at rest is less than 150 mL. Diseases in which the alveolar-capillary surface area is reduced (eg, idiopathic pulmonary fibrosis and emphysema) lead to a reduction in the blood volume in the lungs.
The volume of blood in the pulmonary capillaries and the DLCO are increased in the following circumstances:
- Single breath carbon monoxide diffusing capacity (transfer factor). Recommendations for a standard technique. Statement of the American Thoracic Society. Am Rev Respir Dis 1987; 136:1299.
- Macintyre N, Crapo RO, Viegi G, et al. Standardisation of the single-breath determination of carbon monoxide uptake in the lung. Eur Respir J 2005; 26:720.
- Crapo RO, Jensen RL, Wanger JS. Single-breath carbon monoxide diffusing capacity. Clin Chest Med 2001; 22:637.
- Morrison NJ, Abboud RT, Ramadan F, et al. Comparison of single breath carbon monoxide diffusing capacity and pressure-volume curves in detecting emphysema. Am Rev Respir Dis 1989; 139:1179.
- Gould GA, Redpath AT, Ryan M, et al. Lung CT density correlates with measurements of airflow limitation and the diffusing capacity. Eur Respir J 1991; 4:141.
- Saydain G, Beck KC, Decker PA, et al. Clinical significance of elevated diffusing capacity. Chest 2004; 125:446.
- Merkus PJ, Govaere ES, Hop WH, et al. Preserved diffusion capacity in children with cystic fibrosis. Pediatr Pulmonol 2004; 37:56.
- Espiritu JD, Ruppel G, Shrestha Y, Kleinhenz ME. The diffusing capacity in adult cystic fibrosis. Respir Med 2003; 97:606.
- Zompatori M, Calabrò E, Chetta A, et al. [Chronic hypersensitivity pneumonitis or idiopathic pulmonary fibrosis? Diagnostic role of high resolution Computed Tomography (HRCT)]. Radiol Med 2003; 106:135.
- Watters LC, King TE, Schwarz MI, et al. A clinical, radiographic, and physiologic scoring system for the longitudinal assessment of patients with idiopathic pulmonary fibrosis. Am Rev Respir Dis 1986; 133:97.
- do Pico GA, Wiley AL Jr, Rao P, Dickie HA. Pulmonary reaction to upper mantle radiation therapy for Hodgkin's disease. Chest 1979; 75:688.
- Theuws JC, Muller SH, Seppenwoolde Y, et al. Effect of radiotherapy and chemotherapy on pulmonary function after treatment for breast cancer and lymphoma: A follow-up study. J Clin Oncol 1999; 17:3091.
- Luursema PB, Star-Kroesen MA, van der Mark TW, et al. Bleomycin-induced changes in the carbon monoxide transfer factor of the lungs and its components. Am Rev Respir Dis 1983; 128:880.
- Crawford SW, Pepe M, Lin D, et al. Abnormalities of pulmonary function tests after marrow transplantation predict nonrelapse mortality. Am J Respir Crit Care Med 1995; 152:690.
- Ewert R, Opitz C, Wensel R, et al. Abnormalities of pulmonary diffusion capacity in long-term survivors after kidney transplantation. Chest 2002; 122:639.
- Mitchell DM, Fleming J, Pinching AJ, et al. Pulmonary function in human immunodeficiency virus infection. A prospective 18-month study of serial lung function in 474 patients. Am Rev Respir Dis 1992; 146:745.
- Nieman RB, Fleming J, Coker RJ, et al. Reduced carbon monoxide transfer factor (TLCO) in human immunodeficiency virus type I (HIV-I) infection as a predictor for faster progression to AIDS. Thorax 1993; 48:481.
- Schachter LM, Dixon J, Pierce RJ, O'Brien P. Severe gastroesophageal reflux is associated with reduced carbon monoxide diffusing capacity. Chest 2003; 123:1932.
- Schwartz DA, Van Fossen DS, Davis CS, et al. Determinants of progression in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 1994; 149:444.
- Steenhuis LH, Groen HJ, Koëter GH, van der Mark TW. Diffusion capacity and haemodynamics in primary and chronic thromboembolic pulmonary hypertension. Eur Respir J 2000; 16:276.
- Fernandez-Bonetti P, Lupi-Herrera E, Martinez-Guerra ML, et al. Peripheral airways obstruction in idiopathic pulmonary artery hypertension (primary). Chest 1983; 83:732.
- Tashkin DP, Clements PJ, Wright RS, et al. Interrelationships between pulmonary and extrapulmonary involvement in systemic sclerosis. A longitudinal analysis. Chest 1994; 105:489.
- Hills EA, Geary M. Membrane diffusing capacity and pulmonary capillary volume in rheumatoid disease. Thorax 1980; 35:851.
- Songür N, Songür Y, Tüzün M, et al. Pulmonary function tests and high-resolution CT in the detection of pulmonary involvement in inflammatory bowel disease. J Clin Gastroenterol 2003; 37:292.
- Herrlinger KR, Noftz MK, Dalhoff K, et al. Alterations in pulmonary function in inflammatory bowel disease are frequent and persist during remission. Am J Gastroenterol 2002; 97:377.
- Wang JS. Relationship of carbon monoxide pulmonary diffusing capacity to postoperative cardiopulmonary complications in patients undergoing pneumonectomy. Kaohsiung J Med Sci 2003; 19:437.
- Datta D, Lahiri B. Preoperative evaluation of patients undergoing lung resection surgery. Chest 2003; 123:2096.
- Beckles MA, Spiro SG, Colice GL, et al. The physiologic evaluation of patients with lung cancer being considered for resectional surgery. Chest 2003; 123:105S.
- Iwasaki A, Yosinaga Y, Kawahara K, Shirakusa T. Evaluation of lung volume reduction surgery (LVRS) based on long-term survival rate analysis. Thorac Cardiovasc Surg 2003; 51:277.
- National Emphysema Treatment Trial Research Group. Patients at high risk of death after lung-volume-reduction surgery. N Engl J Med 2001; 345:1075.
- Sue DY, Oren A, Hansen JE, Wasserman K. Diffusing capacity for carbon monoxide as a predictor of gas exchange during exercise. N Engl J Med 1987; 316:1301.
- Hadeli KO, Siegel EM, Sherrill DL, et al. Predictors of oxygen desaturation during submaximal exercise in 8,000 patients. Chest 2001; 120:88.
- Mohsenifar Z, Lee SM, Diaz P, et al. Single-breath diffusing capacity of the lung for carbon monoxide: a predictor of PaO2, maximum work rate, and walking distance in patients with emphysema. Chest 2003; 123:1394.
- Jensen RL, Crapo RO. Diffusing capacity: how to get it right. Respir Care 2003; 48:777.
- Punjabi NM, Shade D, Patel AM, Wise RA. Measurement variability in single-breath diffusing capacity of the lung. Chest 2003; 123:1082.
- Sansores RH, Abboud RT, Kennell C, Haynes N. The effect of menstruation on the pulmonary carbon monoxide diffusing capacity. Am J Respir Crit Care Med 1995; 152:381.
- Sansores RH, Pare PD, Abboud RT. Acute effect of cigarette smoking on the carbon monoxide diffusing capacity of the lung. Am Rev Respir Dis 1992; 146:951.
- Graham BL, Mink JT, Cotton DJ. Effects of increasing carboxyhemoglobin on the single breath carbon monoxide diffusing capacity. Am J Respir Crit Care Med 2002; 165:1504.
- Sansores RH, Pare P, Abboud RT. Effect of smoking cessation on pulmonary carbon monoxide diffusing capacity and capillary blood volume. Am Rev Respir Dis 1992; 146:959.
- Crapo RO, Morris AH. Standardized single breath normal values for carbon monoxide diffusing capacity. Am Rev Respir Dis 1981; 123:185.
- Johnson DC. Importance of adjusting carbon monoxide diffusing capacity (DLCO) and carbon monoxide transfer coefficient (KCO) for alveolar volume. Respir Med 2000; 94:28.
- Fitting JW. Transfer factor for carbon monoxide: a glance behind the scene. Swiss Med Wkly 2004; 134:413.
- Hughes JM, Pride NB. Examination of the carbon monoxide diffusing capacity (DL(CO)) in relation to its KCO and VA components. Am J Respir Crit Care Med 2012; 186:132.
- Kanengiser LC, Rapoport DM, Epstein H, Goldring RM. Volume adjustment of mechanics and diffusion in interstitial lung disease. Lack of clinical relevance. Chest 1989; 96:1036.
- Miller A, Thornton JC, Warshaw R, et al. 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. Am Rev Respir Dis 1983; 127:270.
- Rijcken B, Schouten JP, Xu X, et al. Airway hyperresponsiveness to histamine associated with accelerated decline in FEV1. Am J Respir Crit Care Med 1995; 151:1377.
- Kitaichi M, Nishimura K, Itoh H, Izumi T. Pulmonary lymphangioleiomyomatosis: a report of 46 patients including a clinicopathologic study of prognostic factors. Am J Respir Crit Care Med 1995; 151:527.
- Coulter TD, Stoller JK. What causes an elevated diffusing capacity? Respir Care 2000; 45:531.
- Stewart RI. Carbon monoxide diffusing capacity in asthmatic patients with mild airflow limitation. Chest 1988; 94:332.
- Drummond MB, Schwartz PF, Duggan WT, et al. Intersession variability in single-breath diffusing capacity in diabetics without overt lung disease. Am J Respir Crit Care Med 2008; 178:225.
- Mushtaq M, Hayton R, Watts T, et al. An audit of pulmonary function laboratories in the West Midlands. Respir Med 1995; 89:263.
- Hegewald MJ, Markewitz BA, Wilson EL, et al. Single-breath diffusing capacity for carbon monoxide instrument accuracy across 3 health systems. Respir Care 2015; 60:430.
- Hathaway EH, Tashkin DP, Simmons MS. Intraindividual variability in serial measurements of DLCO and alveolar volume over one year in eight healthy subjects using three independent measuring systems. Am Rev Respir Dis 1989; 140:1818.
- Robson AG, Innes JA. Short term variability of single breath carbon monoxide transfer factor. Thorax 2001; 56:358.
- Cramer D. Standardization of the measurement of transfer factor. Eur Respir J 1993; 6:1577.
- Jensen RL, Teeter JG, England RD, et al. Instrument accuracy and reproducibility in measurements of pulmonary function. Chest 2007; 132:388.
- Jensen RL, Teeter JG, England RD, et al. Sources of long-term variability in measurements of lung function: implications for interpretation and clinical trial design. Chest 2007; 132:396.
- Obstructive disease
- Restrictive disease
- Pulmonary vascular disease
- Prior to lung resection surgery
- Disability evaluation
- Need for oxygen therapy
- Carboxyhemoglobin and cigarette smoking
- High altitude
- Volume correction
- Low DLCO due to cigarette smoking
- Low DLCO with obstruction
- Low DLCO with restriction
- Normal DLCO with restriction
- Low DLCO with normal spirometry
- Increased DLCO
- USING DLCO TO MONITOR DISEASE COURSE
- MAINTENANCE OF QUALITY
- SUMMARY AND RECOMMENDATIONS