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Normal Predicted Values of Single-Breath Diffusing Capacity of the Lung in Healthy Nonsmoking Adults

Article information

Korean J Intern Med. 1986;1(2):178-184
Jeong Ok Park, M.D., In Seon Choi, M.D., Kyung Ok Park, M.D.
Department of Internal Medicine, Chonnam University Medical School, Kwangju, Korea
Address reprint requests: Kyung Ok Park, M.D., Department of Internal Medicine, Chonnam University Medical School, 5 Hakdong Tongku Kwangju Chonnam

Abstract

Prediction equations for the carbon monoxide diffusing capacity of the lung (DLCO) and diffusing capacity per liter of lung volume (DLCO/VA) were derived from 90 normal nonsmoking subjects (40 men and 50 women), using a standardized single-breath technique for determining carbon monoxide diffusing capacity.

The results obtained are as follows:

  1. The mean values for DLCO and DLCO/VA were 28.05±5.07 ml/min/mmHg, 4.569±0.694 ml/min/mmHg/L for men and 20.79±4.03 ml/min/mmHg, 4.695±0.743 ml/min/mmHg/L for women, respectively.

  2. The values for DLCO and DLCO/VA disclosed significantly negative correlation with advancing age and positive correlation with height.

  3. Normal prediction formulas were obtained for diffusing capacity, using age and height.

Men:DLCO=0.3504 H−0.2156 A−23.168DLCO/VA=−0.0205 H−0.0283A+9.0919Women:DLCO=0.2491 H−0.1533 A−11.662DLCO/VA =0.0140 H− 0.0216 A+3.413

Keywords: Diffusing capacity

INTRODUCTION

As diffusing capacity of the lung has been used widely as one of the routine pulmonary function tests, many studies have been done to establish a standardized technique for examination and normal predicted values.

Two methods for estimating DLCO have been reported, one of which is the single-breath test,1,2) a modified Krogh’s breath-holding maneuver, and the other is the steady state method, using Filey’s maneuver.3) It has been known that values of carbon monoxide-diffusing capacity of the lung vary according to the hemoglobin concentration, the height, the body position, exercise, and attitude.4)

In 1975 the Intermountain Thoracic Society (ITS) proposed a standardized modification of the technique of Krogh,5,6) and in 1981 Crapo et al.6) established prediction equations for DLCO and DLCO/VA, using, the ITS technique in normal nonsmoking adults. In this study, in order to establish normal predicted values for the pulmonary-diffusing capacity in Koreans, DLCO and DLCO/VA were measured in 90 healthy nonsmoking adults, and the correlation between diffusing capacity and various physical characteristics, such as age, height, weight, and body surface area were observed. Then regression equations for normal predicted values were derived.

MATERIALS AND METHODS

Ninety subjects (40 men and 50 women) were studied. All subjects lived in Chonnam Province. They were mainly members of the Chonnam University Hospital, medical students, relatives of patients, and persons visiting the hospital for regular physical checkups.

Subjects were screened to select a population of disease-free nonsmokers. Normal was defined as having no history of (1) smoking, (2) asthma, chronic bronchitis, pneumonia or cardiac disease, (3) persistent cough, (4) recent treatment for any respiratory or cardiac symptoms, (5) chest injury or operation, (6) working in a polluted atmosphere for any extended period, finally, no evidence of cardiopulmonary disease on a physical examination, an EKG, or a chest radiograph.

Height, weight, and hemoglobin concentration were measured. The DLCO was measured by the modified Krogh’s single-breath method, using the SRL 1000IV Computerized Pulmonary Function Laboratory, Gould Co., USA.

With the subjects in the sitting position, their noses were clamped and initial maximal exhalation was followed by maximal inhalation of the test gas (contained 0.3%CO and 10%He). After a 10-second holding of the breath the exhaled gas was collected in a sample bag, and the sampling was analyzed for CO and He. Then the DLCO was calculated as follows:

DLCO=VA×60(PB−47) (t2−t1) × Ln(FACOt 1)(FACOt 2)

  • VA: Alveolar volume (STPD)

  • 60: Correction from seconds to minutes

  • PB: Barometric pressure

  • 47: Water vapor pressure (PH2O)

  • t2–t1: Breath holding interval

  • Ln: Natural logarithm

  • FACOt1: Fraction of CO in alveolar gas before diffusion

  • FACOt2: Fraction of CO in alveolar gas at the end of diffusion

Because the inspired gas was dry, an ATPD to BTPS correction factor was used. Units for DLCO were ml CO(STPD)/min/mmHg, and for DLCO/VA, ml CO(STPD)/min/mmHg/L(BTPS). Because changes in the hemoglobin concentration have a calculable effect on total CO diffusion, the measured DLCO and DLCO/VA were normalized to a standard hemoglobin value according to Cotes equation.8)

Corrected DLCO=Hgb+10.221.7 Hgb × measured DLCO

The correlations based on the diffusion capacity of the lung and the physical characteristics, such as age, height, weight and body surface area were observed. And prediction formulas were derived from the variables for both sexes, using a computer system (SPSS Batch System).

RESULTS

A total of 90 healthy nonsmoking men and women were included in the study. The distribution by decades of age is shown in Table 1.

Distribution of Subjects by Decades

The mean and standard deviations for age, height, weight, body surface area, DLCO, DLCO/VA, and hemoglobin concentration for each sex are listed in Table 2. The mean DLCO was higher in men than in women, but there was no significant difference for DLCO/VA.

Mean Values and Standard Deviations for Physical Characteristics and DLCO in Healthy Nonsmokers

Correlation coefficients between DLCO and each physical characteristic for each sex are shown in Tables 3 and 4. Negative correlations were obtained between DLCO and age (Tables 3 and 4, Fig. 1 and 2). Height was directly related to DLCO, but not to DLCO/VA.

Correlation Coefficients of Physical Characteristics and DLCO for Healthy Male Nonsmokers

Correlation Coefficients of Physical Characteristics and DLCO for Healthy Female Nonsmokers

Fig. 1.

Correlation between DLCO and age in healthy nonsmokers.

Fig. 2.

Correlation between DLCO/VA and age in healthy nonsmokers.

Because DLCO and DLCO/VA showed correlation with age and height, prediction equations were derived for the variables for both sexes. The prediction formulas are listed in Tables 5 and 6.

Prediction Formulas with Correlation Coefficient (r) and Standard Error of Estimate (SEE) for DLCO

Prediction Formulas with Correlation Coefficient(r) and Standard Error of Estimate(SEE) for DLCO/VA

Comparisons of the present study with previous studies reported from abroad regarding prediction formulas are shown in Tables 7 and 8, which indicate the differences between the predicted mean and the observed mean values. The mean values of age and height from the present study were substituted in the formulas of previous studies in calculating the predicted mean. The observed means are those that were calculated from the total sample of the present study. The predicted mean using the formulas of the present study was lower than those using the formulas of previous studies for western peoples.6,9–12)

Comparison of Prediction Formulas for DLCO Using Mean Values for Age and Height from Present Study

Comparison of Prediction Formulas for DLCO/VA Using Mean Values for Age and Height from Present Study

The percentage of predicted values above which 95 per cent of the “normal” population fell were calculated as lower limits of the normal (Table 9).

The Normal Range (Low 95th percentiles of percent predicted)

DISCUSSION

As an index of pulmonary gas exchange, the test for DLCO, as well as the other lung function tests has been widely accepted in clinical practices or epidemiologic studies of disease of the respiratory system. It is quite valuable in the early diagnosis and evaluation of severity of pulmonary interstitial diseases and it may be used in epidemiologic studies of occupational lung diseases, such as asbestosis and berylliosis.4)

Because the diffusing capacity of the lung depends chiefly on the area and thickness of the alveolar-capillary membrane available for diffusion (Dm) and the pulmonary capillary blood volume (Vc), it may decrease in patients with various cardiopulmonary disorders that affect Dm, Vc, or both.13) And it depends also on changes in the hemoglobin concentration,14) altitudes,15) and the partial pressure of carbon monoxide in the blood.16) For example, anemia reduces DLCO, the increased Vc by elevated pulmonary arterial pressures in persons who live at high altitudes increase and the high carbon monoxide blood level in smokers lowers it. These factors should be taken into account when the values are estimated.

There are many technical problems in measuring DLCO as in other lung function tests. They include the variability of the breath-hold-interval, and the difficulties in estimating the amount of exhaled gas, and the concentration of carbon monoxide.

Many studies have been done to establish normal predicted values for the diffusing capacity of the lung, but the normal standard values have not been settled on yet. An agreed upon set of normal standard values for Koreans is needed.

Ogilvie et al4). (1957), Burrow et al17). (1961), and Samet et al18). (1979) have reported normal values already, but they selected subjects irrespective of smoking history. Recently Crapo et al6). (1981) and Miller et al19). (1983) measured DLCO for healthy nonsmoking adults. In these studies normal values for DLCO and DLCO/VA varied with sex, age and height, and the values for women were lower than those for men of the same age and height, and the values decreased with advancing age and increased with height.

Now, the use of the regression equations for normal predicted values by Crapo et al6), and Miller et al19), are widely recommended, and the normal values in these studies are slightly higher than those of authors. Although these differences are presumed to be due to racial difference, Cotes et al.20) claimed that the estimated values for DLCO had no racial differencies; the inverse was the case in the estimated values for lung volumes and spirometry.

Miller et al.19) reported that correlation coefficients between DLCO and age were −0.55 for men and −0.35 for women, and between DLCO and height, 0.27 for men and 0.28 for women. However, in the present study, the correlation coefficients between DLCO and age were −0.66 for men and −0.58 for women, and between DLCO and height, 0.55 for men and 0.43 for women. Thus, the values for DLCO showed negative correlation with age and positive correlation with height.

Ogilvie et al.4) and Burrow et al.17) reported that values for DLCO had significant correlations with body surface area, but in this study the correlation coefficients were low: 0.33 for men and 0.23 for women. Double correlation coefficients for DLCO with age and height were slightly higher (0.727 for men, 0.621 for women) than those of single correlations with age, and a similar result was obtained with age and body surface area.

As Crapo et al.6) and Miller et al.19) have suggested, better regression of DLCO could be obtained by using both age and height.

References

1. Forster RE, Fowler WS, Bates DV, Van Lingen B. The absorption of carbon monoxide by the lung during breath holding. J Clin Invest 33:1135. 1954;
2. Forster RE, Cohn JE, Bricoe WA, Blakemore WS, Riley RL. A modification of the Krogh carbon monoxide breathholding technique for estimating the diffusing capacity of the lung: a comparison with three other methods. J Clin Invest 34:1417. 1955;
3. Filey GF, MacIntosh DJ, Wright GW. Carbon monoxide uptake and pulmonary diffusing capacity in normal subjects at rest and during exercise. J Clin Invest 33:530. 1954;
4. Ogilvie CM, Forster RE, Blakemore WS, Morton JW. A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest 36:1. 1957;
5. Kanner RE, Morris AH, eds. Clinical pulmonary function testing: a manual of uniform laboratory procedures for the intermountain area Salt Lake City: Intermountain Thoracic Society. IVp. 1. 1975.
6. Crapo RO, Morris AH. Standard single breath normal values for carbon monoxide diffusing capacity. Am Rev Respir Dis 123:185. 1981;
7. Medical Research Council’s Committee on the Aetiology of Chronic Bronchitis: Standardized-questionnaires on respiratory symptoms. Br Med J 2:1665. 1960;
8. Cotes JE. Lung function Oxford: Blackwell scientific publications. 2411975.
9. Teculescu DB, Stanescu DC. Lung diffusing capacity. Normal values in male smokers and nonsmokers using the breathholding technique. Scand J Respir Dis 51:137. 1970;
10. Salorinne Y. Single breath pulmonary diffusing capacity; Reference values and application in connective tissue diseases and in various lung diseases. Scand J Respir Dis 56:165. 1975;
11. Frans A, Stanescu DC, Veriter C, Clerbaux T, Brasseur L. Smoking and pulmonary diffusing capacity. Scand J Respir Dis 56:165. 1975;
12. Hall AM, Heywood C, Cotes JE. Lung function in healthy British women. Thorax 34:359. 1979;
13. Roughton FJW, Forster RE. Relative importance of diffusion and chemical reaction rates in determining rate of exchange of gases in the human lung, with special reference to true diffusing capacity of pulmonary membrane and volume of blood in lung capillary. J Appl Physiol 11(2):290. 1957;
14. Dinkara P, Blumenthal WS, Johnston RF, Kauffman LA, Solnick PB. The effect of anemia on pulmonary diffusing capacity with deviation of a correction equation. Am Rev Respir Dis 102:965. 1970;
15. DeGraff AC Jr, Grover RF, Johnson RS Jr, Hammond JW Jr, Miller JM. Diffusing capacity of the lung in Caucasians native to 3100m. J Appl Physiol 29:71. 1970;
16. Martt JM. Pulmonary diffusing capacity in cigarette smokers. Ann Intern Med 56:39. 1962;
17. Burrows B, Kasik JE, Niden AH, Barclay WR. Clinical usefulness of the single breath pulmonary diffusing capacity test. Am Rev Respir Dis 84:789. 1961;
18. Samet JM, Epler GR, Gaensler EA, Rosner B. Absence of synergism between exposure to asbestos and cigarette smoking in asbestosis. Am Rev Respir Dis 120:75. 1979;
19. Miller A, Thomton JC, Raphel W, Anderson H, Teirstein AS, Selikoff IJ. Single breath diffusing capacity in a representative sample of the population of Michigan, a large industrial state. Am Rev Respir Dis 127:270. 1983;
20. Cotes JE, Hall AM. The transfer factor of the lung: normal values in adults. In : Arcangeli P, ed. Normal values for respiratory function in man Torino: Panminerva Med. p. 327. 1970.

Article information Continued

Copyright © 1986 The Korean Association of Internal Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Fig. 1.

Fig. 1.

Correlation between DLCO and age in healthy nonsmokers.

Fig. 2.

Fig. 2.

Correlation between DLCO/VA and age in healthy nonsmokers.

Table 1.

Distribution of Subjects by Decades

Age (years) Number of subjects
Men Women
20–29 11 10
30–39 14 12
40–49 8 16
50–59 4 6
60–69 3 6
Total 40 50

Table 2.

Mean Values and Standard Deviations for Physical Characteristics and DLCO in Healthy Nonsmokers

Men
Women
Mean SD Mean SD
Age, years 37.15 13.01 41.44 12.94
Height, cm 169.00 4.62 155.78 3.72
Weight, kg 60.95 7.30 56.30 10.06
BSA, m2 1.697 0.106 1.543 0.125
Hemoglobin, g/dl 14.93 0.73 13.78 1.06
DLCO, ml/min/mmHg 28.05 5.07 20.79 4.03
DLCO/VA, ml/min/mmHg/L 4.569 0.694 4.695 0.743
*

BSA; body surface area

Mean temperature; 24.10±1.34°C in men, 24.48±1.07°C in women

Mean pressure; 750.20±2.73mmHg in men, 751.28±2.10 mmHg in women

Table 3.

Correlation Coefficients of Physical Characteristics and DLCO for Healthy Male Nonsmokers

Age Height Weight BSA DLCO DLCO/VA
Age, years 1.00 −0.09 −0.17 −0.26 −0.66 −0.48
Height, cm −0.09 1.00 0.09 0.15 0.51 0.04
Weight, kg −0.17 0.09 1.00 0.95 0.19 −0.10
BSA, m2 −0.26 0.15 0.95 1.00 0.33 −0.06
DLCO −0.66 0.51 0.19 0.33 1.00 0.55
DLCO/VA −0.48 0.04 −0.10 −0.06 0.55 1.00
*

BSA; Body surface area

Table 4.

Correlation Coefficients of Physical Characteristics and DLCO for Healthy Female Nonsmokers

Age Height Weight BSA DLCO DLCO/VA
Age, years 1.00 −0.40 −0.03 −0.11 −0.58 −0.40
Height, cm −0.40 1.00 0.36 0.54 0.43 0.22
Weight, kg −0.03 0.36 1.00 0.98 0.16 0.05
BSA, m2 −0.11 0.54 0.98 1.00 0.24 0.11
DLCO −0.58 0.43 0.16 0.24 1.00 0.70
DLCO/VA −0.40 0.22 0.05 0.11 0.70 1.00
*

BSA; Body surface area

Table 5.

Prediction Formulas with Correlation Coefficient (r) and Standard Error of Estimate (SEE) for DLCO

Prediction formula r SEE
Men
  DLCO=−0.2563A+37.545 0.661 3.835
  DLCO=0.3504H−0.2156A−23.168 0.727 3.578
  DLCO=8.1464B−0.2392A+23.091 0.681 3.791
Women
  DLCO=−0.1818A+28.327 0.584 3.300
  DLCO=0.2491H−0.1533A−11.662 0.621 3.221
  DLCO=5.9807B−0.1758A+18.845 0.613 3.249
*

A; Age in years, H; Height in cm, B; Body surface area in m2

Table 6.

Prediction Formulas with Correlation Coefficient(r) and Standard Error of Estimate(SEE) for DLCO/VA

Prediction formula r SEE
Men
  DLCO/VA=−0.0258A+5.529 0.484 0.615
  DLCO/VA=−0.0205H−0.0283A+9.0919 0.501 0.616
  DLCO/VA=−1.3361B−0.0286A+7.900 0.523 0.607
Women
  DLCO/VA=−0.0232A+5.658 0.405 0.686
  DLCO/VA=0.0140H−0.0216A+3.413 0.410 0.692
  DLCO/VA=0.4096B−0.0228A+5.009 0.410 0.692
*

A; Age in years, H; Height in cm, B; Body surface area in m2

Table 7.

Comparison of Prediction Formulas for DLCO Using Mean Values for Age and Height from Present Study

Investigators Sex Prediction formula SEE Pred. Mean Obs. Mean Differ
Park et al* M 0.3504H−0.2156A− 23.168 3.578 28.05 28.05 0
Crapo et al6)** M 0.410H−0.210A−26.31 4.82 34.15 28.05 −6.10
Teculescu9) M 0.333H−0.298A−12.26 4.17 32.11 28.05 −4.06
Salorinne10) M 0.142H−0.232A+16.30 3.57 31.32 28.05 +3.27
Frans11) M 0.285H−0.140A+10.30 4.20 52.55 28.05 +24.50
Park et al* F 0.2491H−0.1533A−11.662 3.221 20.79 20.79 0
Crapo et al6)** F 0.282H−0.157A−10.89 3.60 26.53 20.79 +5.74
Hall12) F 0.283H−0.185A−8.28 4.07 28.14 20.79 +7.35
Salorinne10) F 0.219H−0.115A−5.97 2.75 23.38 20.79 +2.59

Key; A: Age in years, H: Height in cm

*

Corrected to a standard hemoglobin of 14.7 g/dl, according to Cotes

**

Corrected to a standard hemoglobin of 14.6 g/dl, according to Cotes

Table 8.

Comparison of Prediction Formulas for DLCO/VA Using Mean Values for Age and Height from Present Study

Investigators Sex Prediction formula SEE Pred. Mean Obs. Mean Differ
Park et al* M 5.529−0.0258A 0.615 4.571 4.569 −0.002
Crapo et al6)** M 6.930−0.0030A 0.83 5.693 4.569 −1.124
Teculescu9) M 8.50−0.0510A 0.89 6.605 4.569 +2.036
Frams11) M 6.18−0.0296A+0.000157(A2) 0.73 5.297 4.569 +0.728
Salorinne10) M 12.5−0.029A−0.0353H 0.63 5.545 4.569 −0.976
Park et al* F 5.658−0.0232A 0.696 4.697 4.695 −0.002
Crapo et al6) F 6.940−0.0280A 0.80 5.780 4.695 +1.085
Salorinne10) F 12.39−0.0131A−0.0396H 0.74 5.678 4.695 −0.983

Key; A: Age in years, H: Height in cm

*

Corrected to a standard hemoglobin of 14.7g/dl, according to Cotes

**

Corrected to a standard hemoglobin of 14.6g/dl, according to Cotes

Table 9.

The Normal Range (Low 95th percentiles of percent predicted)

Age, years 20–29 30–39 40–49 50–59 60–69 Total
Men
  DLCO 72.11 72.27 70.46 76.23 79.66 64.76
  DLCO/VA 72.40 83.95 78.97 85.25 36.53 70.23
Women
  DLCO 69.04 65.69 75.21 58.08 73.43 62.01
  DLCO/VA 68.81 80.64 76.29 53.12 66.08 68.98