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The pulmonary diffusing capacity for carbon monoxide (DLCO) is a standard lung function test that estimates alveolar-capillary diffusion for gases such as O2 and CO2. However, measuring rate-limiting O2 transfer across the alveolar membranes presents technical difficulties that are caused by high background levels of O2. Consequently, CO has been used extensively as a surrogate index of O2 transfer, due primarily to its high affinity for Hb that results in CO being considered a diffusion-limited gas (Chaps. 3 and 9).
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The most widely used DLCO protocol is the single-breath method (Fig. 16.5). After a few normal breaths at rest, subjects exhale to RV and then inhale a standard mixture of gases (FIco = 0.003; FIHe = 0.100; FIo2 = 0.207; FIn2 = 0.690) to TLC. To complete the single-breath test properly, >85% of a subject's VC should consist of this standard gas mixture just inhaled to TLC. While holding at TLC for 10 seconds, subjects should avoid every positive airway pressures that decrease pulmonary blood flow and capillary volume, Vc (see Valsalva maneuver) or extremely negative airway pressures that artifactually increase Q̇ and Vc (see Müller maneuver). After the 10-second breathhold at TLC, the subject exhales completely to RV in a smooth, unforced, and uninterrupted manner. Owing to undiluted gases within the dead space volume, the first liter of exhaled air is discarded. The second liter of gas exhaled by the subject is collected and analyzed to compute both the equilibrated alveolar concentration of CO, FAco and its partial pressure, PAco (Chap. 8) at the end of the breathhold. DLCO is then calculated as the total amount of CO absorbed by the subject from the amount inspired (FIco – FAco) divided by the PAco that served as the driving pressure gradient into the patient's pulmonary capillary blood. Simultaneous measurement of the equilibrium [He] allows an accurate estimate of lung volume by the dilution principles discussed in Chap. 4.
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The DLCO estimated for the entire lung by this test consists of the sequential diffusive capacities of the alveolar-capillary membrane and of pulmonary capillary blood (Chap. 9). Indeed, DLCO is calculated using the equation for resistors in series:
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where DMCO = alveolar membrane diffusing capacity for CO, Vc = pulmonary capillary blood volume (Chap. 7), and ΘCO is the blood transfer conductance coefficient for CO. The ΘCO is the standard rate at which 1 mL of whole blood will take up CO in mL STPD per minute per milliliter of mercury of partial pressure. The unit for DLCO is mL·(min–1·mm Hg–1) or mL·min–1·mm Hg–1, or it can be written as mL/(min·mm Hg). The units for DLCO in most textbooks and research papers report DLCO as mL/min/mmHg (mL/min/kPa in Europe). The most commonly used approximation for ΘCO was derived by Roughton and Forster (1957) who showed that:
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1/ΘCO = 0.73 + {0.0058 · (PAo2) · 14.6/[Hb]}
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where [Hb] is expressed in g/dL of arterial or venous blood. Membrane diffusive resistance, 1/DMCO and red cell resistance, 1/(ΘCO · Vc) usually contribute about equally to the overall diffusive resistance of the lung, 1/DLCO. To estimate the individual contributions made by DMCO and Vc to DLCO, the single-breath method is done twice, at an FIo2 = 0.207 and then at 0.897 to achieve two widely separated values for PAo2 of about 100 mm Hg and 600 mm Hg, respectively. Using the subject's PAo2 measured during each single-breath test, the value of 1/DLCO is plotted on the y-axis and 1/ΘCO is plotted on the x-axis. A straight line drawn through these two points yields the y-intercept (1/DMCO) and the slope (1/Vc) (Fig. 16.6). Sufficient accuracy can usually be achieved with just four to six single-breath tests, usually two to three at low PAo2 and two to three at high PAo2.
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CLINICAL CORRELATION 16.3
In patients with obstructive airway disease or edema, DLCO and DMCO are reduced by the loss or thickening of alveolar-capillary membranes. Patients with anemia also will show a decrease in DLCO. However, some hospitals and research centers today would also correct the DLCO for Hb in these patients. As such, the corrected DLCO would exclude anemia as a factor in DLCO interpretation. In early stage congestive heart failure, pulmonary fibrosis, or severe obesity, DLCO may decrease because of a restrictive ventilatory pattern that decreases the total lung area available for CO diffusion. Patients with polycythemia (including that due to high altitude exposure), Goodpasture's syndrome, late stage congestive heart failure, or intrapulmonary hemorrhage could also have an increased DLCO in proportion to any increase in Vc or circulating [Hb] (by ~0.7% per g Hb/dL).
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No more than five DLCO tests should be performed per session to avoid accumulation of HbCO, since HbCO increases by ~0.7% per single-breath test. For each 1% increase in HbCO, there is an approximate 1% decrease in DLCO due to the reduction in 1/ΘCO that is caused by such dysfunctional hemoglobins. Regular smokers may have an HbCO of 5%-10%, much higher than in nonsmokers, whose HbCO = 0.7%-1.0%. When two DLCO tests fall within 3 mL·min–1·mm Hg–1 of each other, the average of both tests is reported. Normal month-to-month variations in DLCO are about 5 mL·min–1·mm Hg–1. Thus larger variations are clinically meaningful. A classification scheme for severity of a decrease in DLCO compared to normative values is shown in Table 16.3.
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CLINICAL CORRELATION 16.4
Only four contraindications have been established for any of the lung function tests that are described in this chapter: chest or abdominal pain; oral or facial pain; stress incontinence; and dementia. Neither pregnancy nor advanced age is considered a contraindication per se for measurement of pulmonary diffusing capacity using the single breath DLCO technique.