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Reprinted from the May 1999 issue of RESPIRATORY CARE [Respir Care 1999;44(5):539–546]

AARC Clinical Practice Guideline

Single-Breath Carbon Monoxide Diffusing Capacity, 1999 Update

DLCO 1.0 PROCEDURE Single-breath diffusing capacity for carbon monoxide (DLCOsb), sometimes referred to as the transfer factor for carbon monoxide (TCO).

DLCO 2.0 DESCRIPTION/DEFINITION
The first American Association for Respiratory Care (AARC) single-breath diffusing capacity (DLCOsb) Clinical Practice Guideline (CPG) was published in 1993, and was based largely on the American Thoracic Society (ATS) 1987 recommendations.(1) Since that time, the ATS has published new recommendations.(2) This updated AARC CPG reflects the 1995 ATS recommendations. Various methods are commercially available to perform DLCOsb. This Guideline can be applied in many (perhaps most) cases and is based on experience and research with the traditional method (10-second breathhold with alveolar sample collection). For non-traditional or newer methods, it is the manufacturer's and the scientific community's responsibility to define the comparability of the newer methods with the old.

Diffusing capacity is a measurement of carbon monoxide (CO) transfer from inspired gas to pulmonary capillary blood. During the test, the subject inspires a gas containing CO and one or more tracer gases to allow determination of the gas exchanging capability of the lungs. Although several different methods of measuring DLCO have been described, the most commonly used technique is the single-breath maneuver, or DLCOsb. For purposes of this guideline, recommendations associated with the DLCOsb are referenced.(2) Many of these standards apply indirectly to other methods of measuring diffusing capacity.

2.1 DLCO is usually expressed in mL CO min-1 x torr-1 at standard temperature and pressure dry (STPD).
2.2 The alveolar volume (VA) at which the DLCOsb is measured is also commonly reported; the units for the VA are liters at body temperature and pressure, saturated with water vapor (BTPS).
2.3 The ratio of DLCO to VA is also commonly reported as the DL/VA or simply D/VA.

DLCO 3.0 SETTINGS:

3.1 Pulmonary function laboratories
3.2 Cardiopulmonary laboratories
3.3 Clinics
3.4 Physicians' offices

DLCO 4.0 INDICATIONS:
Tests of diffusing capacity may be indicated for (Specific conditions and direction of change in DLCO are shown in the Appendix.):

4.1 evaluation and follow-up of parenchymal lung diseases including: idiopathic pulmonary fibrosis (IPF, also known as usual interstitial pneumonitis, or UIP) and bronchiolitis obliterans organizing pneumonia (BOOP, or cryptogenic organizing pneumonia, COP), diseases associated with dusts such as asbestos, or drug reactions (eg,from amiodarone) or related to sarcoidosis;(1-3) and for quantification of disability associated with interstitial lung disease; (4)
4.2 evaluation and follow-up of emphysema and cystic fibrosis;(5,6) and differentiating among chronic bronchitis, emphysema, and asthma in patients with obstructive patterns; and for quantification of impairment and disability.
4.3 evaluation of cardiovascular diseases (eg, primary pulmonary hypertension, acute or recurrent thromboembolism, or pulmonary edema);(7,8)
4.4 evaluation of pulmonary involvement in systemic diseases (eg, rheumatoid arthritis, systemic lupus erythematosus);(9-11)
4.5 evaluation of the effects of chemotherapy agents or other drugs (eg, amiodarone, bleomycin) known to induce pulmonary dysfunction;(12-14)
4.6 evaluation of pulmonary hemorrhage;(15)
4.7 as an early indication of certain pulmonary infections (eg, pneumocystis pneumonia);(16)
4.8 prediction of arterial desaturation during exercise in some patients with lung disease.(17,18)

DLCO 5.0 CONTRAINDICATIONS

5.1 Absolute contraindications to performing a diffusing capacity test are
5.1.1 the presence of carbon monoxide toxicity
5.1.2 dangerous levels of oxyhemoglobin desaturation without supplemental oxygen.
5.2 Relative contraindications to performing a diffusing capacity test are
5.2.1 mental confusion or muscular incoordination preventing the subject from adequately performing the maneuver or inability to obtain or maintain an adequate lip seal on the instrument mouthpiece;
5.2.2 a large meal or vigorous exercise immediately before the test;(1)
5.2.3 smoking within 24 hours of test administration (smoking may have a direct effect on DLCO independent of the effect of COHb(19));
5.2.4 decreased lung volumes that would not yield valid test results;
5.2.5 devices that are improperly calibrated or maintained or the unavailability of a qualified operator.

DLCO 6.0 HAZARDS/COMPLICATIONS:

6.1 DLCOsb requires breathholding at total lung capacity (TLC); some patients may perform either a Valsalva (higher than normal intrathoracic pressure) or Müller (lower than normal intrathoracic pressure) maneuver. Either of these can result in alteration of venous return to the heart and pulmonary capillary blood volume.
6.2 Interruption of supplemental oxygen may result in oxyhemoglobin desaturation.
6.3 Transmission of infection is possible via improperly cleaned mouthpieces or as a consequence of the inadvertent spread of droplet nuclei or body fluids (patient-to-patient or patient-to-technologist).

DLCO 7.0 LIMITATIONS OF METHODOLOGY/VALIDATION OF RESULTS:

7.1 Limitations of the common methods used for DLCO include:
7.1.1 DLCO should be corrected for hemoglobin (Hb) level according to the method described by Cotes and co-workers.(20)
7.1.1.1 For adolescent boys(>= 15 years of age) and adult men, the Hb is adjusted to a value of 14.6 g/dL:
Hb-adjusted DLCO = observed DLCO (10.22 + Hb)/1.7 Hb.
7.1.1.2 For children < 15 years of age and women the Hb is adjusted to a value of 13.4 g/dL:
Hb-adjusted DLCO = observed DLCO (9.38 + Hb)/1.7 Hb.
7.1.2 For purposes of interpretation, DLCO should be corrected for the effects of COHb present in the subject's blood.(1)
COHb-adjusted DLCO = measured DLCO (1+ [%COHb/100]).
7.1.3 DLCO increases with increasing altitude and appropriate correction for the alveolar or inspired oxygen pressures are recommended.(1)
Altitude-adjusted DLCO = measured DLCO (1.0 + 0.0035(PAO2 - 120])
or
Altitude-adjusted DLCO = measured DLCO (1.0 + 0.0031(PIO2 - 150])
(where estimated PIO2 = 0.21 [PB - 47 torr].)
7.1.4 A 4-minute minimum interval should elapse between subsequent maneuvers to allow test gas to be eliminated from the lungs.(1)
7.1.5 DLCO varies with body position; the upright seated position is recommended.
7.1.6 Abnormal breathholding maneuvers (Valsalva or Müller) alter DLCO.(21)
7.1.7 Other factors that may alter measurement of DLCO include recent alcohol consumption,(22) vigorous exercise, smoking, diurnal variation, and bronchodilators.(23)
7.1.8 Pregnancy (first trimester only) has been reported to be associated with an increase in DLCO.(24) Menstruation may also influence DLCO.(25)
7.1.9 Breathhold time should be calculated using the method of Jones-Meade.(2) Other methods may produce significantly different results.
7.2 Large interlaboratory differences in measured DLCO and in percent-of-predicted DLCO have been observed(26,27) and are attributed to variations in testing techniques and computational algorithms and errors in gas analysis. The choice of equipment may also influence the measured DLCO.(27,28)
7.3 Choice of reference equations may affect the final interpretation of measured DLCO values.(29)
7.4 Validation of the testing technique and equipment may include but is not limited to
7.4.1 Volume accuracy of spirometer should be < ± 3% over an 8-L volume (ie, meets or exceeds all ATS recommendations(2)) and must be checked each day that the test is performed, using a 3.00 L (minimum) syringe. Spirometer must maintain accuracy with varying gas concentrations.
7.4.2 Gas analyzers should be subjected to a 2-point calibration before each test. Manufacturers should be encouraged to provide software and techniques by which analyzer linearity may be easily checked (eg, dilution technique). Gas analyzer linearity should be
7.4.2.1 within ± 1%, from zero to full span, of maximal value over the duration of the test,
7.4.2.2 formally checked at least quarterly.(30)
7.4.3 Timing device should be checked every 3 months30 and be accurate within ± 1% over a 10-second period.
7.4.4 The entire circuit resistance should be < 1.5 cm H2O/L/s at a flow of 6 L/s. The addition of in-line filters may cause the circuit resistance to exceed recommendations.
7.4.5 The apparatus dead space should be < 0.1 L. In-line filters need to be accounted for when determining entire system dead space as well as discard volume (before alveolar collection).
7.4.6 Demand valve sensitivity of < 10 cm H2O is required for 6 L/s flow through a valve and circuit (if a compressed gas source is used).
7.4.7 Chemical absorbers (for CO2 and H2O) or selectively permeably tubing should be replaced at the frequency recommended by the manufacturer, when saturated (as indicated by color change) or sooner. In addition, the chemical absorbers should be placed in the proper order (ie, CO2 absorber should precede H2O absorber), should be replaced when exhausted, and should be arranged according to how alveolar gas is analyzed.
7.4.8 Normal standard subjects (biologic controls) may be used to establish intrasubject coefficient of variation and to serve as a quality control population.(2)

DLCO 8.0 ASSESSMENT OF NEED (see Section 4.0 Indications)

DLCO 9.0 ASSESSMENT OF TEST QUALITY:
Individual test maneuvers and results should be evaluated according to the ATS recommendations.(2)

9.1 Use of proper quality-controlled equipment.
9.2 Provision of test instructions before testing commences and determination that the subject is able to follow commands.
9.3 Inspiratory volume exceeding 90% of the largest previously measured vital capacity (FVC or VC), attained in < 2.5 s in healthy subjects and within 4 s in patients with moderate to severe airway obstruction.
9.4 Breathhold times of 9-11 seconds, with no evidence of leaks or Valsalva or Müller maneuvers.
9.5 After the breathhold, there should be appropriate clearance of dead space (anatomic plus system) and proper collection and analysis of alveolar gas.
9.5.1 The washout volume (ie, dead space) should be 0.75-1.00 L or 0.50 L if the subject's VC is less than 2.0 L. If a washout volume other than 0.75-1.00 L must be used, it should be noted.
9.5.2 If an in-line filter is used, when determining discard volume, the filter dead space must be accounted for.
9.5.3 For alveolar-gas sample-bag systems, the volume of the alveolar gas sample should be 0.5-1.0 L obtained in < 4 seconds.
9.6 Two or more acceptable tests should be averaged; the DLCO values should be reproducible to within 10% or 3 mL CO x min -1 x torr -1, whichever is greater. We recommend empirically that no more than 4-6 maneuvers be performed.
9.7 The subject should have refrained from smoking for 24 hours prior to the test; however, because subjects do not always comply, the time of the last smoking event should be recorded.
9.8 Corrections for Hb, COHb should be included as noted above (Sections 7.1.1 and 7.1.2); correction for tests performed at altitude is recommended. If Hb correction is made, both the corrected and uncorrected DLCO values should be reported.

DLCO 10.0 RESOURCES

10.1 Equipment:
10.1.1 Volume-measuring device must meet or exceed ATS recommendations.
10.1.2 Appropriate gas analyzers dependent on the methodology employed; certified calibration gases for use before each series of measurements.
10.1.3 COoximeter for analysis of total Hb and COHb is strongly recommended.
10.2 Personnel: Diffusing capacity tests should be performed under the direction of a physician trained in pulmonary function testing. The value of diffusing capacity results can be compromised by poor patient instruction secondary to inadequate technologist training. Thus, technologists should have documented training, with continued competency assessments in diffusing capacity administration and recognition of errors encountered in the testing process as well as a sound understanding of pulmonary pathophysiology. Diffusing capacity testing may be performed by persons who meet criteria for either Level I or Level II.
10.2.1 Level I: The technologist performing DLCO should be a high school graduate or equivalent with a demonstrated ability to perform basic pulmonary function studies such as spirometry (and DLCOsb). Level I personnel should perform DLCO tests only under the supervision of a Level II individual or a physician.
10.2.2 Level II: Personnel supervising DLCO testing should have formal education and training (as a part of a program in respiratory therapy or pulmonary function technology or 2 years of college in biological sciences and mathematics) and 2 or more years performing spirometry, lung volumes, and diffusing capacity tests.(31) One or more of the following credentials is recommended: RPFT, CPFT, RRT, CRT.

DLCO 11.0 MONITORING: (Also see Section 9.0 Assessment of Test Quality) The following should be evaluated during the performance of the DLCO measurement to assess the validity of the results:

11.1 Acceptability of the maneuvers and reproducibility of DLCOsb:
11.1.1 patient positioning: subjects should be seated for at least 5 minutes prior to testing and should remain seated throughout the DLCO testing session,
11.1.2 interval between tests: at least 4 minutes between sequential tests to allow elimination of tracer gas,
11.1.3 reproducibility, with at least 2 acceptable tests that are within ± 10% or 3 mL CO(STPD)/min/mm Hg of the average DLCO.
11.2 Level of understanding (of test instructions), effort and cooperation by the subject.
11.3 Equipment function or malfunction (eg, calibration), with equipment quality control performed as recommended, any time accuracy is suspect or if the equipment is moved to a different location.
11.3.1 Volume calibration and leak testing performed on a daily basis,
11.3.2 Gas analyzer linearity checked quarterly,
11.3.3 Timer tested quarterly
11.3.4 Tests on standard subjects (biologic controls, or bio-QC) should be performed at least on a quarterly basis and any time accuracy is suspect.(2)
11.3.4.1 Standard subjects should be tested more frequently initially to establish statistical variation for comparison.
11.3.4.2 It is advantageous to perform Bio-QC at weekly or semi-monthly intervals.(32)
11.4 Reference equations: each laboratory should select reference equations appropriate for the methods and the population tested.
11.5 Inspired oxygen concentration: test gas concentration should be 20.93% and at sea level pressure. Subjects should remain off supplemental oxygen for at least 5 minutes prior to performing the first test. Technologists should document (in the final report)a patient's inability to remain off supplemental oxygen for the allotted time.
11.6 The final report should contain a statement about test quality.
11.7 The final report should contain the DLCO, the corrected DLCO (Hb, COHb, altitude), and the Hb value used for correction. The alveolar volume (VA) and DL/VA (ie, the ratio of diffusing capacity to the lung volume at which the measurement was made) may be included in the report. These values are helpful for purposes of interpretation. The final report should indicate which method was used to correct the raw DLCO value and for what the DLCO value is being corrected [eg, corr DLCO (Hb), corr DLCO (CO)].
11.8 DLCOsb results should be subject to ongoing review by a supervisor, with feedback to the technologist. Quality assurance (QA) and/or quality improvement (QI) programs should be designed to monitor the technologist both initially and on an ongoing basis.

DLCO 12.0 FREQUENCY:
The frequency at which DLCO measurements should be repeated depends on the clinical question(s) to be answered.

DLCO 13.0 INFECTION CONTROL:
Diffusing capacity tests are relatively safe procedures, but the possibility of cross-contamination exists, either from the patient-patient or patient-technologist interface.(33)

13.1 Technologists should exercise Standard Precautions for all patients, follow recommendations of the Centers for Disease Control and Prevention for control of exposure to tuberculosis and droplet nuclei, and, in addition, institute appropriate precautions empirically for airborne, droplet, and contact agents pending confirmation of diagnosis in patients suspected of having serious infections.(33)
13.2 Proper use of barrier devices (eg, protective gloves) may be useful to prevent spread of contagion via direct contact. Hand washing must always be performed between patients, and protective gloves must be worn if there are open cuts, or sores, on the technologist's hands.(2)
13.3 Due to the nature of the DLCO maneuvers and the likelihood of coughing when the test is performed by subjects with known or suspected active infection with Mycobacterium tuberculosis or other airborne organisms, recommended precautions are:(34)
13.3.1 The room in which the DLCO test is performed should meet or exceed the recommendations of U.S. Public Health Service(33,35) for air changes and ventilation. The ideal situation is to establish an area in the testing department specially ventilated for isolation patients. We strongly recommend that, if this is not possible, the patient be returned to the isolation room as soon as possible, and the testing room be closed for a minimum of 1 to 2 hours.
13.3.2 Pulmonary function technologists performing procedures on patients with potentially infectious airborne diseases should wear a personal respirator that meets OSHA recommendations, especially if the testing itself induces coughing.(35)
13.4 The mouthpiece, tubing, and any parts of the system that come into contact with the subject should be disposable or sterilized between patients. If sterilization is not feasible, then high-level disinfection should be performed. It is unnecessary to routinely clean the interior surface of the spirometer.
13.4.1 Visible condensation, from expirate, warrants cleaning of the system before testing another patient.
13.4.2 Bacterial filters that allow rebreathing may be used in circuit, although their efficacy is not well documented. However, such filters may impose added resistance during inspiration or expiration and affect the timing of the DLCO maneuver. If a filter is used, the filter dead-space volume should be considered in the calculation of DLCO and VA.

Diffusion Capacity Working Group

Carl Mottram RRT RPFT, Chairman, Rochester MN
Susan Blonshine BS RRT RPFT, Mason MI
Robert A Brown BS RRT RPFT, Waunakee WI
Gregg L Ruppel MEd RRT RPFT, St Louis MO
Jack Wanger MBA RRT RPFT, Lenexa KS

REFERENCES
  1. American Thoracic Society. Single breath carbon monoxide diffusing capacity (transfer factor): recommendations for a standard technique. Am Rev Respir Dis 1987;136:1299-1307.
  2. American Thoracic Society. Single breath carbon monoxide diffusing capacity (transfer factor): recommendations for a standard technique¬1995 update. Am J Respir Crit Care Med 1995;152;2185-2198.
  3. Weinberger SE, Johnson TS, Weiss ST. Clinical significance of pulmonary function tests: use and interpretation of the single-breath diffusing capacity. Chest 1980;78:483-488
  4. Epler GR, Saber FA, Gaensler EA. Determination of severe impairment (disability) in interstitial lung disease. Am Rev Respir Dis 1980;121:647-659.
  5. Ogilvie C. The single-breath carbon monoxide transfer test 25 years on: a reappraisal. 2. Clinical considerations (editorial). Thorax 1983;38:5-9.
  6. Morris AH, Kanner RE, Crapo RO, Gardner RM. Clinical pulmonary function testing: a manual of uniform laboratory procedures, 2nd ed. Salt Lake City: Intermountain Thoracic Society, 1984.
  7. Knudson RJ, Kaltenborn W, Burrows B. Single breath carbon monoxide transfer factor in different forms of chronic airflow obstruction in a general population sample. Thorax 1990;45:514-519.
  8. Light RW, George RB. Serial pulmonary function in patients with acute heart failure. Arch Intern Med 1983;143:429-43.
  9. Gibson GJ, Edmunds JP, Hughes GRV. Diaphragm function and lung involvement in systemic lupus erythematosus. Am J Med 1977;63:926-932.
  10. Gross M, Esterly JR, Earle RH. Pulmonary alterations in systemic lupus erythematosus. Am Rev Respir Dis 1972;105:572-577.
  11. Frank ST, Weg JG, Harkeroad LE, Fitch RF. Pulmonary dysfunction in rheumatoid disease. Chest 1973;63:27-34.
  12. Comis RL. Bleomycin pulmonary toxicity: current status and future directions. Sem Oncol, 1992;19(Suppl 5):64-70.
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  15. Crapo RO, Forster RE 2nd. Carbon monoxide diffusing capacity. Clin Chest Med 1989;10(2):187-198.
  16. Mitchell DM, Fleming J, Pniching AJ, Harris JR, Moss FM, Veale D, Shaw RJ. Pulmonary function in human immunodeficiency virus infection; a prospective 18-month study of serial lung function in 474 patients. Am Rev Respir Dis 1992;146:745-751.
  17. Owens GR, Rogers RM, Pennock BE, Levin D. The diffusing capacity as a predictor of arterial oxygen desaturation during exercise in patients with chronic obstructive pulmonary disease. N Engl J Med 1984;310:1218-1221.
  18. Nordenfelt I, Svensson G. The transfer factor (diffusing capacity) as a predictor of hypoxaemia during exercise in restrictive and chronic obstructive pulmonary disease. Clin Physiol 1987;7:423-430.
  19. 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(4):951-958.
  20. Cotes JE. Lung function: assessment and application in medicine, 4th ed. Oxford: Blackwell Scientific Publications, 1979:203,329.
  21. Smith TC, Rankin J. Pulmonary diffusing capacity and the capillary bed during Valsalva and Müller maneuvers. J Appl Physiol 1969;27:826-833.
  22. Peavy HH, Summer WR, Gurtner G. The effects of acute ethanol ingestion on pulmonary diffusing capacity. Chest 1977;4:488-492.
  23. Lawson WH. Effect of drugs, hypoxia, and ventilatory maneuvers on lung diffusion for CO in man. J Appl Physiol 1972;32:788-794.
  24. Milne JA, Mills RJ, Coutts JRT, MacNaughton MC, Moran F, Pack AI. The effect of human pregnancy on the pulmonary transfer factor for carbon monoxide as measured by the single breath method. Clin Sci Mol Med 1977;53:271-276.
  25. Sansores R, Gibson N, Abboud R. Variation of pulmonary CO diffusing capacity (DLCO) during the menstrual cycle (abstract). Am Rev Respir Dis 1991;143(4, Part 2):A759.
  26. Clausen J, Crapo R, Gardner RM. Interlaboratory comparisons of pulmonary function testing (abstract). Am Rev Respir Dis 1984;129(4, Part 2):A37.
  27. Wanger J, Irvin C. Comparability of pulmonary results from 13 laboratories in a metropolitan area. Respir Care 1991;36:1375-1382.
  28. Hathaway EH, Tashkin DP, Simmons MS. Intra-individual variability in serial measurements of DLCO and alveolar volume over one year in eight healthy subjects using three independent systems. Am Rev Respir Dis 1989;140:1818-1822.
  29. Crapo RO, Gardner RM. DLCO reference equations: a perspective (editorial). Am Rev Respir Dis 1986;134:856.
  30. American Thoracic Society. Quality assurance in pulmonary function laboratories. (position paper). Am Rev Respir Dis 1986;134:625-627.
  31. American Thoracic Society. Pulmonary function laboratory personnel qualifications. Am Rev Respir Dis 1986;134(3):623-624.
  32. American Thoracic Society. Pulmonary function laboratory management. Wanger J, Crapo RO, Irvin CG, editors. American Thoracic Society 1998.
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  34. Garner JS, Hospital Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. Guidelines for Isolation Precautions in Hospitals. Atlanta GA: Centers for Disease Control and Prevention, 1-01-1996. www.cdc.gov
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APPENDIX
Factors that Result in a Decrease in DLCO
Factor Condition Giving Rise to Factor
Deficiency in red blood cells
Loss of pulmonary capillary bed with relatively normal lung volume
Anemia
Multiple pulmonary emboli, early collagen-vascular disease, early sarcoidosis, miliary tuberculosis
Loss of functioning alveolar-capillary (A-C) bed with increased lung volume Emphysema
Loss of functioning A-C bed with decreased lung volume Parenchymal restrictive processes including pulmonary resection, idiopathic interstitial fibrosis, asbestosis, scleroderma lung disease, histiocytosis-X, sarcoidosis, pneumonia
Failure of inspired air to reach alveoli, or poor distribution of ventilation with low, normal or increased lung volume Seen occasionally with severe obstruction during asthmatic or bronchitic attack; seen frequently with emphysema and poor effort


Factors that Result in an Increase in DLCO
Factor Condition Giving Rise to Factor
Increase in pulmonary capillary blood volume Increase in red blood cells
Left heart failure, left-to-right shunt (atrial septal defect, anomalous pulmonary venous return), exercise Early polycythemia


Specific Abnormalities Leading to an Increase in DLCO*
Abnormality Precipitation Condition

Lung compression

Increased airway resistance

Pulmonary vascular congestion

Intrapulmonic hemorrhage

'Physiologic' leaks

Scoliosis, obesity, pectus excavatum

Asthma, cystic fibrosis, central airway lesions

Congestive heart failure, regurgitative valvular disease

Pulmonary hemosiderosis, Goodpasture's syndrome, hemothorax

*The clinician should be suspicious if a patient with any of the abnormalities and/or precipitating condition listed proves to have a normal diffusing capacity.


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Reprinted from the May 1999 issue of RESPIRATORY CARE [Respir Care 1999;44(5):539–546]

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