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alveolar-capillary membrane of the lung as awhole to transfer CO, differences in area of membrane between persons may account for a large proportion of.
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J. Physiol. (^) (I959) 146, 572-
From (^) the Department of (^) Applied Physiology, London School of Hygiene
The published (^) figures for diffusing capacity for carbon monoxide (^) (D,O) in
by the single-breath (^) D,0 method have been (^) recently reported as (^) follows:
37.3, 30-2 (Marks, Cugell, Cadigan & (^) Gaensler, 1957); 14-4, 33-6, 24-8 (Shep-
differences in technique. Since, however, (^) Dco estimates the capacity of (^) the
corrected by (^) expressing D,o values (^) per unit (^) surface area (e.g. Marks et al. 1957).
The effect of age on (^) Dco has also been reviewed by Forster (1957) who found
maximal (^) Do2. Evidence is (^) presented in this (^) paper that (^) D,o depends on age as well as on
index to (^) Dco.
have reported higher values, ranging from 12 to 62 (^) % more for breath-holding
lung volume on k and on (^) Dco. METHODS
The permeability and diffusing^ capacity^ were measured^ in^ thirty-nine normal male persons by^ the single-breath method of Krogh (1915) using a portable box-bag apparatus (Thomson, 1958). The accuracy of this apparatus appears to be at least as great as for non-portable forms. The single-breath D0o method and the instruments^ used^ for gas analysis^ have been described^ in full by Ogilvie et al. (1957). Briefly, the subject exhales fully into the box and then inspires the test-gas mixture (He 14; CO 0-28; 0, 20; (^) N2 65.72%) from the inspirate bag. The breath is then held for 10 sec and a rapid deep expiration is made, of which the^ first^ 750 ml.^ is^ discarded^ into the box and the remainder, the alveolar sample, is collected in the expirate bag. Analysis of expirate and inspirate is then made using a katharometer for He and an infra-red analyser for^ CO. The katharometer is sensitive to CO,, which must therefore be absorbed^ before^ He determina- tion. The C00-free gas then passes through the infra-red analyser. No correction is^ therefore required when calculating k since the correction factor appears in^ numerator^ and denominator (equation (1) below). In calculating^ D0o a correction factor of 5% has been allowed for oxygen consumption after correcting the inspired volume to^ S.T.P.D.^ It^ should also be^ noted^ that^ calibra- tion of the instruments is not critical when, as in^ these^ calculations, ratios and^ not^ absolute values are required. In all but three subjects the^ tests^ were^ made^ in^ duplicate and^ repeated if duplicates differed by more than 10 %. The subjects were^ invariably seated^ in^ this^ and^ the^ follow- ing trials. In eight persons we ascertained the effect on k and D00 of altering alveolar volume (VA) over the widest range possible, i.e. from total lung capacity to residual volume (RV) + 1200 ml., comprising 750 ml. required to wash out dead space and 450 ml. for^ analysis. Determinations were carried out in duplicate on successive days, as in the first study above, but according to a prearranged plan where (^) VA was randomized with time. On the rare occasions when more than two determinations were made on one day an interval of several hours separated the additional measurements, to allow blood carboxyhaemoglobin to return to within the normal range. Krogh's permeability (k) is the time constant of the exponential decay of CO concentration; during breath-holding. ECO IC from which k = t .In (^) F-= tI FIHe.FEW min
FIHe HEHe^ FkCO, F0co^ are^ respectively^ concentrations of^ He^ and^ CO^ in^ inspirate^ and^ expirate; t =^ time in minutes from beginning of inspiration to time at which expired gas sample was^ col- lected. The diffusing capacity was then found from DC°^ V'^ .k BAp 47 ml/min xmm^ Hg:^ (2) where B.P. =^ barometric (^) pressure in mm (^) Hg; V =^ lung volume in millilitres derived from a 37-
tion to be 18-3 (^) % for (^) D0o and 14-9 (^) % for k. Thus the predictive accuracy is
TABLE 1. (^) Lung function measurements and physical characteristics of thirty-nine male subjects vital Age (^) Weight Height SA capacity (^) VA Subject (yr) (kg) (^) (cm) (m2) (ml.) (ml.) 1 2 3 4 5 6 7 8 9
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 Mean
15 15 17 17 17 17 18 18 22 22 23 24 27 28 30 32 32 35 36 38 38 40 43 44 49 51 53 57 58 60 62 63 63 65 65 65 66 72 75 40-
44- 57- 75- 86- 75- 65- 79- 69- 66- 64- 75- 78- 66- 72- 79- 72- 68- 70- 93- 71- 59- 66- 79- 71- 58- 72- 68- 49- 52- 70- 88- 77- 82- 64- 54- 46- 54- 74-
155 158 180 174 170 168 186 i 178 177 186 174 177 177 177 160 175 175 170 188 177 177 178 184 165 170 164 173 172 174 183 170 184 170 158 165 173 165
1- 1- 1- 1- 1- 1- 2- 1- 1- 1- 2- 1- 1- 1- 1- 1- 1- 1- 1- 2- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 2- 1- 2- 1- 1- 1- 1- 1- 1-
2750 3800 3250 3950 4280 5520 4400 5360 4800 5310 4600 5430 4900 6040 4800 5620 4200 5010 4900 6330 5070 6680 4950 5700 4250 4820 3900 5050 4180 5460 3450 4600 4100 5270 3750 4660 4050* 5820* 3500 4730 4700 6840 3550 5830 3650 5260 4300 5630 4950 6880 3650 4780 (^4300 ) 2800 3880 3150 4270 3600 4840 2450* 3960* 2800* 4540* 3800 6260 3150 4540 3350 5260 2400 3740 3530 5210 2550 4440 2500 4210 3827 5161
(ml.) (min-) min x mm Hg) 1080 5-14 24- 780 4-31 21- 1360 4-25 30- 1060 5-40 37- 640 5-57 (^) 41- 980 4-96 37- (^780) 5-50 42- 1260 5-89 42- 900 6-34 40- 1530 5-20 42- 1650 5-56 47- 1480 4-66 34- 840 4-63 28- 1220 4-78 31- 1430 3-75 26- 1170 4.44 26- 1320 4-96 33* 1340 4-05 26- 1770* 4-11* 26-80* 1450 4-52 27- 2290 5-24 45- 2400 3-20 23- 1680 3-27 22- 1480 4-25 33- 2230 3 39 32- 1200 3-66 22- 1840 4.26 32- (^1270) 4-38 22- (^1370) 3-47 18- 1700 2-70 (^) 17- 1510* 4.15* (^) 20- 1760* 3.20* 18-83* 2580 2-89 24- 2120 3-65 23- 1970 4-15 28- 1820 4-25 20- 1850 2-26 15- 1920 3-07 17- 1700 3-20 16- 1506 4-27 28- The formsV' (mean alveolar volume) (^) RV' (mean (^) residual volume) and D'0 (^) (diffusing capacity) are used to indicate that these values are based on the (^) method of (^) single-breath He dilution.
I E x C E E
i^8
0 10 20 30 40 50 60 70 80 90 Age (yr) Fig. 1. (^) Relationship between diffusing capacity, age and body surface area for (^) thirty-nine male subjects. SA, 2-1-1-9 (^) m2, C]; 1-9-1-7 (^) m2, A; 1-7-1-5 (^) m2, 0; 1-5-1-3 (^) m2, v. Solid (^) signs indicate smokers.
0 6 - v
o 5 0 00
4 C 4~~~~~~~~~~ 0~~~
3
0
2
10 20 30 40 50 60 70 80 Age (yr) Fig. 2. Relationship between^ permeability (k) and^ age for^ thirty-nine male^ subjects. Single observations, O; mean^ of^ two^ or more^ observations, 0. Solid^ signs indicate smokers.
been drawn in Fig. 3 (lower right) together with the corresponding (Dc0, Vi), graphs (^) (D,o =^ k V'J713).^ There^ is^ theoretical^ justification,^ discussed^ below,
The form of the (^) (D'0, VA) graphs is more variable than that of the (k, VA)
attained for each subject has been calculated for k and (^) D'o so as to compare the
4.6% and 8.6% for k and Do0 respectively. Although the number^ of^ points was small these were, without exception, higher for (^) D'o than for k and the
Marshall (1958) showed in one subject that (^) D,0 by single-breath method^ at
breath (^) D,0 was due to the different lung volumes at which the tests were carried out. The mean (^) Do, of our eight subjects at^ total^ lung capacity was
above in the introduction (39 (^) %) to confirm this explanation.
DISCUSSION There is fairly good agreement between the rise of (^) D,0 with surface area given
face area only
The regression of (^) Dco on SA from our results becomes
Estimating diffusing capacity of the diseased (^) lung
breath VA should be used in calculating breath-holding (^) D,O. The rationale
on the nature of the abnormality. Thus (^) D,o based on VA +X is likely to be a
than (^) D,0 in the abnormal lung. If, however, the total capacity to transfer gas is required, the clinician may use, for calculating (^) D,o, V[ together with that
relationship for lung volumes-greater than v has been represented in Fig. 3
SUMMARY
We are very grateful to Professor G. P. Crowden and to Dr P. (^) Armitage for (^) advice, to the staff of the School who acted as subjects, and to the University of London Central Research Fund for a (^) grant for apparatus.
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