Effects of Body Position and Age on Membrane Diffusing Capacity and Pulmonary Capillary Blood Volume

Effects of Body Position and Age on Membrane Diffusing Capacity and Pulmonary Capillary Blood Volume* Shi-Chuan Chang, M.D., Ph.D., F.C.C.E; Huei-Ing Chang, B.S.; Sheng-Yi uc. B.S.; Guang-Ming Shiao, M.B., F.C.C.E; and Reury-Perng Perng, M.D., Ph.D., F.C.C.E The effects of body position and age on the membrane diffusing capacity (Dm), pulmonary capillary blood volume (Vc), and the single breath carbon monoxide diffusing capacity (Dco) were evaluated in the erect (sitting) and supine positions in 16 nonnal young men (under 40 years old, younger group) and in 13 older men (over 40 years old, older group). Dm and Vc were estimated by several measurements of the 000 at increasing alveolar oxygen tension (PAO.). The results showed that 000, Dm, Vc, and Kco (Dco corrected by alveolar volume) decreased with age in both positions. The differences in Dco, VC, and Kco between the two positions (supine minus the erect position) also decreased with age. The mechanisms of the increases

in Dco in the supine position remain to be explained but may be due to a change in pulmonary capillary shape from an elliptical (erect position) to a circular configuration (supine position) since Vc increased more than Dm on assuming the supine position. The findings may be of clinical importance since many physicians have attempted to utilize a reduction in the positional change in Dco as a potential marker of disease. (Chest 1992; 102:139-42)

Since the initial work of Krogh 1 in 1914, the effect of age on the diffusing capacity of the lung has often been studied, mainly using carbon monoxide (Dco). Early reports showed no significant effect of age on Dco,2.3 but the results of subsequent studies indicated that Dco measured either by the single-breath method or the steady-state method decreased with age. 4-8 The effect of age on the membrane diffusing capacity (Dm) and pulmonary capillary blood volume (Vc) has been studied less often, with variable conclusion. The Vc was observed not to vary or to decrease with age. 7 •9 •10 However, some workers stated that the fall in diffusing capacity with increasing age was associated with a reduction in the Dm. 7 Previous reports demonstrated that Dco measured by the single-breath method increased in the supine position relative to the conventional erect (sitting) position. 2. 11- 13 This has been attributed to a relative underperfusion of the apices in the seated position which become better perfused in the supine position resulting in an increase in Vc by capillary recruitment of upper-lobe capillaries.2.12-14 There are some controversies about the effects of age and body position on Dco and its components. In addition, the influence of age on the postural effect on Dco and its components has not been well-investigated. Ettinger and colleagues" observed that the

positional change in Deo (Keo) decreased with age in nine normal adults. O'Brodovich and coworkers!" noted in the pediatric age group that the positional change in Dco increased with height. Thus, in this study, we intended to evaluate the effects of age and body position on Den and its components, and to evaluate the influence of age on the effect of body position on Dco and its components.

·From the Chest Department, Veterans General Hospital and Institute of Clinical Medicine, National Yang-Ming Medical College, Taipei, Taiwan, Republic of China. Manuscript received July 15; revision accepted October 18. Reprint requests: Dr. Chang, Chest Department, ~terans General Hospital-Taipei, Shih ltli, Taipei, Taiwan 11217 Republic of China

=

=

DM membrane diffusing capacity; Kco D<.'O corrected by alveolar volume; t exchange time; VA alveolar volume; Vc pulmonary capillary blood volume

=

=

=

METHODS ANI) MATERIALS

Twenty-nine male adults were studied. Sixteen younger subjects (age under 40 years old, younger group) were professional employees of our hospital (students and residents), and 13 older subjects (age over 40 years old, older group) were selected from the patients who were admitted to the hospital previously fi)r physical check-up. None had a history of cardiopulmonary disease and all denied respiratory symptoms such as cough or dyspnea. Their physical examination, chest roentgenogram, electrocardiogram, and the usual lung function tests-e-Iorced vital capacity (FVC), forced expiratory volume at 1 s (FEV.), and FEV/FVC-sho\\'ed no abnormalities. All were nonsmokers, Spirometry was performed in a the erect position in all subjects a minimum of three times (usin~ CPI 5000 I~ Gould, Houston, Tex). The hest values of FVC and FEV. were selected for analysis. The diffusing capacity of the lung for carbon monoxide (1)<"'0) was measured by single-breath method with minor modification'" (usin~ a CPI 5000 I~ Gould, Houston, Tex). The exchange time, t, is the sum of the breath-holding time plus two thirds of the inspiratory time and one half of the collection time of the expired sample." The breath-holding time was 10 s. The C(> hack pressure was not corrected because all the studied subjects were nonsmokers. The gas mixtures used for the test contained 10 percent helium and 0.3 percent carbon monoxide with the balance consisting of various proportions of O 2 and N:z. Each test was done three times at three different inspired oxygen levels (20.5 percent and 50 percent O 2 in nitrogen, and 100 percent 02) at 10- to 15-Juin intervals in an order of increased inspired oxygen concentration. CHEST I 102 I 1 I JUL'f, 1992

139

Table 1-PhyBictJl and l'ulmontJry Functional

RESULTS

ChtJrlJCteriBtica*

Age, yr Height, cm FEV.,L % ofpred FVC,L %ofpred FEV/FVC, % Dco, mllmin/mm Hg VA,L

Younger Group (n= 16)

Older Group (n= 13)

28.1 ±5.3 167.0±7.0 3.60±0.46 95.2±7.4 4.14±0.45 94.1 ±5.4 86.7±3.1 29.59 ± 3.94 5.90±0.76

6O.3±5.3 169.2±7.2 2.57±0.38 95.6± 13.4 3.23±0.45 89.9±7.7 79.5±6.8 23.02 ± 2.54 5.21±0.58

*The values of mean and SD are given. FEV. = forced expiratory volume at 1 s: FVC = forced vital capacity; nco = diffusing capacity; VA = alveolar volume. The tests in erect and supine positions were done in random order at 2- to 3-h intervals. The estimations of Om and Vc were done by the method of Roughton and Forster," 1IDco = lIDm + INc X cpCO, where the numeric value of the reaction rate coefficient for erythrocytes, q>CO, was calculated by the equation, lIq>CO=a+0.0057 POI. We postulate, therefore, that the ratio, ~, of membrane permeability to that of the erythrocyte interior has an inGnite value. The coefficient, a, is then equal to 0.33. The estimations of Om and Vc based on the previous equation were calculated from nine determinations of Dco at three increasing levels of PAOI. The data were accepted when the correlation coefficient, r, of 1IDco and lIeo was more than 0.95. Statistical comparison of the data between younger and older groups was carried out by using unpaired Students t test. The effect of age on Deo, Dm, Vc, and Kco (Dco corrected by alveolar volume) was examined by using the linear correlation coefficient. The effect of body position on Deo and its components were examined by using paired Students t test. The effects of age and height on positional changes in Dco and its components were examined by using the linear correlation coefficient and stepwise multiple linear regression.

The general data about the physical and functional characteristics of the 29 male subjects are given in Table 1. The younger group consisted of 16 male subjects with an age range from 22 to 39 years (mean±SD, 28.1±5.3 years). In the older group, there were 13 male subjects with an age range from 53 to 70 years (mean± SD, 6O.3±5.3 years). The values of Dco, Dm, Vc, Kco, and VA (alveolar volume) obtained in the erect and supine positions were significantly higher in younger group than in older group (Table 2). The DmlVc obtained in either erect or supine position was not significantly different in the younger vs older group. In the younger group, Dco, Dm, Vc, DmlVc, and Kco were significantly higher in the supine compared with the erect position. In contrast, VA was significantly lower in the supine than in the erect position. In the older group, Dco, Vc, and Kco were also significantly higher in the supine than in the erect position. Similarly, the value of VA was significantly lower in the supine position. No significant differences in Dm and DmlVc were found between the two positions in older group (Table 2). The effect of age on Dco and its components obtained in the supine and erect positions was evaluated by using the linear correlation coefficient. A significantly negative correlation between age and Deo, Dm, Vc, Keo, and VA obtained in the two positions was found (Table3). There was no significant correlation between age and DmlVc. The differences in Dco, Dm, Vc, and Kco between the supine and erect positions (the data obtained in

Table 2-CompariBon ofDco and Ita componentl in the Erect and Supine POIitioru between Youngerand Older Groupa* Younger Group

Older Group

(n= 16)

p Value

29.60±3.94 34.08±3.98

<0.001

54.42± 11.73 57.60± 11.87

p Value

p Value

23.02±2.54 23.72±2.85

<0.05

<0.001 <0.001

<0.05

41.95±5.22 4O.20±4.95

NS

<0.001 <0.001

71.62± 10.88 91.22± 17.03

<0.001

57.52±9.77 64.88± 15.09

<0.05

<0.001 <0.001

0.78±0.22 0.66±0.21

<0.01

0.74±0.12 0.65±0.17

NS

NS NS

5.05±0.54 6.10±0.79

<0.001

4.56±0.88 5.05±0.94

<0.001

<0.05 <0.01

5.90±0.76 5.64±0.75

<0.001

5.15±0.68 4.78±0.63

<0.001

<0.001 <0.001

(n= 13)

Oro, mllmin/mm Hg

Erect Supine Om, mllmin/mm Hg Erect Supine VC,ml Erect Supine DroNc Erect Supine Kco, mllmin/mm HgIL Erect Supine VA,L Erect Supine

*The values of men and SD are given. Oro = diffusing capacity; Dm = membrane diffusing capacity; Vc = pulmonary capillary blood volume; Kco = Dco corrected by alveolar volume; VA = alveolar volume; NS = not significant.

140

Effectsof Body Positionand Age on Membrane DiffusingC8pacity (Chang at eI)

Table 3-Correlation betweenAge and Dco and Ita comporIBfIU in the Erect and Supine PoaitionI in !9

Normal Subjecta*

Correlation Coefficient

p Value

-0.7475 -0.8371

<0.001 <0.001

Erect

- 0.6316 -0.7375

<0.001 <0.001

Erect

-0.5334 -0.5896

<0.01 <0.001

-0.2123 -0.1329

NS NS

-0.3679 -0.5125

<0.05 <0.01

000, mVminlmm Hg Erect Supine Om, mVminlmm Hg Supine VC,ml Supine DroNc Erect Supine Keo, mVmin/mm HWL Erect Supine

*Dco=diffusing capacity; Dm=membrane diffusing capacity; Vc = pulmonary capillary blood volume; Keo = 000 corrected by alveolar volume; NS = not signi6cant.

the supine position minus those in the erect position) were significantly higher in the younger group than in older group (Iable 4). Postural differences in DmNc and VA showed no significant difference between the two groups. The effects of age and height on the postural effect on Dco and its components were evaluated by using the linear correlation coefficient and stepwise multiple linear regression. A significantly negative correlation between age and the differences in the data of Dco, Vc, and Kco obtained in the supine and erect positions was found (Iable 5). There was no significant correlation between age and the differences in Dm, Dm/Vc, and VA in the two positions. Our results showed that body height did not affect the positional changes in Dco and its components (data not shown). DISCUSSION

Dco has been shown to decrease with age in Table 4-Compariaon of the Poaural DiJfrmmca in Dco GfId Ita Componenta between Younger and 0lJer Groupa*

Dco-SE Dm-SE Vc-SE DroNc-SE Kco-SE VA-SE

Younger Group (n= 16)

Older Group (n= 13)

p Value

4.48±1.79 3.18±7.10 19.60± 12.60 -0.12±0.15 1.05±0.53 -0.25±0.23

0.70± 1.26 -1.75±5.40 7.30± 12.48 -0.09±0.21 0.49±0.37 -0.36±0.26

<0.()01 <0.05 <0.01 NS <0.01 NS

*The values of mean and SD are given. SE = data in the supine position minus those in the erect position; Dco = diffusing capacity; Dm = membrane diffusing capacity; Vc = pulmonary capillary blood volume; Keo = 000 corrected by alveolar volume; NS = not significant.

Table 5-Correlation between Age and the Diffenmca in

Dco and Ita Componenta in the Erect and Supine POBitionI

ira !9 Normal Subjecta*

Dco-SE Dm-SE Vc-SE DmNc-SE Kco-SE VA-SE

Correlation Coefficient

p Value

-0.7080 -0.3498 -0.4054 0.0726 -0.4389 -0.2446

<0.001 NS <0.05 NS <0.02 NS

*SE = data in the supine position minus those in the erect position; Dco = diffusing capacity; Dm = membrane diffusing capacity; Vc = pulmonary capillary blood volume; Keo= Dco corrected by alveolar volume; VA = alveolar volume; NS = not significant.

adults.v" This has been attributed variously to changes in Dm and Vc. Our results confirmed the observation that Dco decreased with age. The influence of age on Dco could not be explained by the reduction of VA with age, because Kco also decreased with age. The effect of age on the components of Dco, Dm, and Vc were studied less often. There were some controversies about the effect of age on Dm and VC. 7 ,9,10 In this study, Dm and Vc decreased with age (Tables 2 and 3). The decrease in Dco with age was not due to a change in DmNc. Dco increases when changing from the erect to the supine position. 2 ,l1 -13 This has been attributed variously to changes in Dm, Vc, or DmNc. Our results confirm this and also demonstrate that Kco increases in the supine vs the erect position. However, controversy exists as to whether the increase in Dco in the supine position stems primarily from an increase in Dm or Vc, or from a change in DmNC. 2 , I2- 14 In this study, both Dm and Vc increased in the supine vs the erect position in the younger group. In the older group, however, Vc but not Dm increased significantly in the supine position (Table 2). The finding that Vc is more important than Dm in explaining the effect of body position on Dco is in agreement with some investigators. 2 , Ii -I4 Nevertheless, Dm did play some role in accounting for the increase in Dco in the supine position in young male subjects. The role of Dm in the effect of body position on Dco became less with increasing age. The differences in Dco, Dm, Vc, and Kco between the two positions (the data obtained in the supine position minus those in the erect position) was significantly higher in the younger than in the older group (Table 4). In addition, we found that the differences in Dco, Keo, and Vc between the two positions decreased with age (Table 5). Our results failed to find a significant correlation between age and the differences in Dm and DmNc. This finding further supports the finding that the Vc, not Dm or Dm/Vc, is the major factor to account for the increase in Dco in the supine position. CHEST I 102 I 1 I JUL'(. 1992

141

Dco could increase in the supine vs erect position either by increasing Dm or Vc or both. An increase in Dm with supine position could be due to an increase in the effective area available for diffusion by perfusion of areas ventilated but not previously perfused, or by ventilation of areas perfused but not previously ventilated. The Vc could be increased either by perfusion of additional capillaries or by an increase in the volume of blood in those capillaries already perfused. If an increase in Vc results from a significant increase in the number of capillaries perfused, Dm should also increase proportionally because of a proportional increase in the surface area available for diffusion. If capillaries that are already open expand by an increase in circumference or by changing shape (from elliptical to circular cylinders), the Vc should increase to a greater degree than the Dm. In this study, Dm increased to a smaller degree than Vc on assuming the supine position. This is compatible with the concept that Dco is increasing primarily in response to changes in shape or circumference of the pulmonary capillaries rather than in response to recruitment of capillaries. As age increased, arteriosclerotic changes of the pulmonary capillaries could increase the rigidity of the pulmonary vessels. This might explain our finding that the effect of body position on Dco was attenuated with increasing age. In the pediatric health subjects, O'Brodovieh and eoworkers'" observed that the position change in Dco (supine minus the erect position) increased in height. At variance with the results of the report, our results showed that height had no effect on the postural differences in Dco and its components between the two positions in healthy adults. The reasons for the discordance may be explained by the difference in the studied subjects. In summary, our results show that age and body position affect Dco and its components. Dco, Dm, Vc, and Kco decrease with increasing age. Dco, Dm, Vc, and Kco increase on changing from the erect to the supine position. The effect of body position on Dco and its components depended on age, the postural effect on Dco and its components decreasing with increasing age. The increase in Dco in the supine position was primarily due to an increase in Vc. The mechanism for the increase in Dco in the supine position might be due to a change in pulmonary capillary shape from an elliptical (erect position) to a circular configuration (supine position). The findings may be of clinical importance since numerous authors have attempted to utilize a reduction in positional change in Dco as a potential marker of disease. 15,16,19,20 The effect of age must be considered when considering the significance of positional changes in Dco in the disease. 142

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7 Hamer NAJ. The effect of age on the components of the pulmonary diffusing capacity. Clio Sci 1962; 23:85-93 8 McGrath M~ Thomson ML. The effect of age, body size and lung volume change on alveolar-capillary permeability and diffusing capacity in man. J Physiol (London) 1959; 146:572-82 9 Krumholz RA. Pulmonary membrane diffusing capacity and pulmonary capillary blood volume: an appraisal of their clinical usefulness. Am Rev Respir Dis 1966; 94:195-200 10 Georges R, Saumon G, Loiseau A. The relationship of age to pulmonary membrane conductance and capillary blood volume. Am Rev Respir Dis 1978; 117:1069-78 11 Bates D~ Pearce JF. The pulmonary diffusing capacity: a comparison of methods of measurement and a study of the effect of body position. J Physioll956; 132:232-38 12 Lewis BM, Lin TH, Noe FE, Komisaruk R. The measurement of pulmonary capillary blood volume and pulmonary membrane diffusing capacity in normal subjects: the effects of exercise and position. J Clio Invest 1958; 37:1061-70 13 Daly WJ, Giammona ST, Boss JC, Feignebaum H. Effects of pulmonary vascular congestion on postural changes in the perfusion and filling of the pulmonary vascular bed. J Clio Invest 1964; 43:68-76 14 Newman F. The effect of change in posture on alveo1aJ'.capillary diffusion and capillary blood volume in the human lung. J Physioll962; 162:29Jl.31P 15 Ettinger WH, WISe RA, Stevens MB, Wigley EM. Absence of positional change in pulmonary diffusing capacity in systemic sclerosis. Am J Med 1983; 75:305-12 16 O'Brodovteh HM, Mellins RB, Mansell AL. Effects of growth on the diffusion constant for carbon monoxide. Am Rev Respir Dis 1982; 125:670-73 17 Roughton F~ 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 the lung capillaries. J Appl Physioll957; 11:290-302 18 Jones RS, Meade F. A theoretical and experimental analysis of anomalies in the estimation of pulmonary diffusing capacity by the single breath method. Q J Exp Physioll961; 46:131-43 19 Hyland RH, Krastins IRB, Aspin N, Mansell AL, Zamel N. Effect of body position on carbon monoxide diffusing capacity in asymptomatic smokers and nonsmokers. Am Rev Respir Dis 1978; 117:1045-53 20 Cotton OJ, Graham BL, Mink IT. Pulmonary diffusing capacity in adult cystic fibrosis: reduced positional changes are partially reversed by hyperoxia. Clio Invest Med 1990; 13:82-91

Effec18 of Body PoeItion and AIJ8 on MembraneDiIIusing Capacity (Chang et aI)