Increase in Pulmonary Ventilation–Perfusion Inequality

with Age in Healthy Individuals

JAUME CARDÚS, FELIP BURGOS, ORLANDO DIAZ, JOSEP ROCA, JOAN ALBERT BARBERÀ,
RAMÓN M. MARRADES, ROBERT RODRIGUEZ-ROISIN, and PETER D. WAGNER
Departament de Medicina, Hospital Cinic, Universitat de Barcelona, Barcelona, Spain; and Department of Medicine, University of
California, San Diego, La Jolla, California

Arterial oxygen tension (PaO2) is known to decrease with age, and this is accompanied by a number
of changes in mechanical properties of the lungs, including loss of elastic recoil and increase in clos-
ing volume. The changes in respiratory mechanics with age could induce greater ventilation/perfu-
· ·
sion ( VA/Q ) mismatch and thus explain the decrease in PaO2. In 64 normal subjects aged 18 to 71 yr
· ·
(lifetime nonsmokers with normal spirometry), we measured VA/Q inequality and arterial respiratory
· ·
blood gases (PaO2 and PaCO2) at rest in the seated position. VA/Q mismatch, represented by the sec-
ond moments of the blood flow and ventilation distributions (log SDQ and log SDV) increased with
age, but only slightly (mean log SDQ was 0.36 at age 20 yr and 0.47 at age 70 yr). PaO2 fell by a corre-
spondingly small amount of 6 mm Hg. Previously established upper 95% confidence limits for log
SDQ (0.60) and log SDV (0.65) in subjects at age 20 yr were confirmed. At age 70 yr, the upper limits
of reference for log SDQ are 0.70 and for log SDV 0.75. The study shows that an increased alveolar–
· ·
arterial O2 gradient with age is due to VA/Q inequality rather than to shunting. Cardús J, Burgos F,
Diaz O, Roca J, Barberà JA, Marrades RM, Rodriguez-Roisin R, Wagner PD. Increase in pulmo-
nary ventilation–perfusion inequality with age in healthy individuals.
AM J RESPIR CRIT CARE MED 1997;156:648–653.

The effect of aging on the normal lung has received consider-
able attention over the years. Elastic recoil is progressively re-
duced (1), VC and maximal expiratory flow rates fall (2), clos-
ing volume is increased (3), and PaO2 diminishes (4). Since
PaCO2 does not rise, the decrease in PaO2 must indicate an in-
crease in the alveolar–arterial PO2 difference (AaPO2).
The AaPO2 will increase if any one or more of three forms
of gas-exchange defect develop: (1) right-to-left shunting of
venous blood; (2) diffusion limitation of alveolar–capillary O2
· ·
exchange; or (3) ventilation-perfusion ( VA/Q ) inequality.
Right-to-left shunting can occur within the lungs (or through
defects in the atrial septum), and this form of defect can be
conveniently termed intrapulmonary shunting. In addition,
PaO2 can be reduced by so-called postpulmonary shunting, in
which bronchial or thebesian venous blood enters the oxygen-
ated blood downstream of the lungs. In the first case, mixed
(Received in original form June 4, 1996 and in revised form January 15, 1997 )
Supported by Grants FIS 91/00160602E and FIS 95-0975 from the Fondo de In-
vestigaciones Sanitarias, Grant SGR 95-0446 from the Comissionat per Universi-
tats i Recerca de la Generalitat de Catalunya, ALFA-ETIR [2.042 (8)], and Grant
HL-17731 from the National Heart, Lung and Blood Institute.
Dr. Wagner was a Visiting Professor in the PVI Programme at the Universitat de
Barcelona during 1995 and 1996.
Correspondence and requests for reprints should be addressed to Josep Roca,
M.D., Servei de Pneumologia, Hospital Clinic, Villarroel 170, Barcelona 08036,
Spain.
Am J Respir Crit Care Med Vol. 156. pp. 648–653, 1997
venous blood never sees alveolar gas; in the second case, nor-
mally oxygenated blood passes into the bronchial and myocar-
dial vasculature before it reaches the systemic arterial vessels
as deoxygenated blood.
Each of these varied causes of an increased AaPO2 could oc-
cur in normal subjects. Very few studies have been performed
with methods that can distinguish among them, and those few
have focused mainly on young, active normal volunteers.
Those studies incorporating older subjects have suggested that
· ·
VA/Q inequality may increase significantly with age (5). Intra-
pulmonary shunts have been found to be either small (mainly
less than 1% of the cardiac output) or nonexistent (5), post-
pulmonary shunts appear to be negligible (5–8), and no evi-
dence for diffusion limitation has been found during rest (5–
8). For older subjects, these conclusions are, however, tenta-
tive, having been based on very small numbers of subjects (9).
Since the known changes in lung mechanical properties
· ·
with age referred to earlier could cause VA/Q inequality to in-
crease, the present study was designed to determine whether
· ·
there was indeed an increase in VA/Q mismatching with age,
and if so whether this accounts for any accompanying decline
in PaO2. The principal tool used to answer these questions was
the multiple inert-gas elimination technique (MIGET).
METHODS
Selection of Subjects
Sixty four normal subjects were studied. All were residents of Barce-
lona, Spain, and were lifetime nonsmokers not employed in jobs ex-
Brief Communication 649

TABLE 1
INDIVIDUAL ANTHROPOMETRIC, LUNG FUNCTION, AND GAS EXCHANGE DATA

Age Weight Height FEV1 FEV1 FEV1/FVC PaO2 PaCO2

Subject (yr) Sex (kg) (cm) (L) (% pred) (%) (mm Hg) (mm Hg) Log SDQ Log SDV

1 21 F 77 177 4.12 109 84 107 39.5 0.28 0.28

2 27 M 55 164 3.54 93 87 98 42.7 0.47 0.53
3 20 M 69 175 3.40 101 86 99 40.1 0.50 0.53
4 21 M 74 176 5.19 115 83 103 37.9 0.60 0.65
5 21 M 70 175 4.14 96 90 101 38.8 0.30 0.31
6 22 M 76 179 5.12 116 80 107 35.5 0.37 0.38
7 19 M 77 167 4.25 113 81 107 36.2 0.26 0.27
8 18 M 68 173 3.93 99 82 103 39.9 0.37 0.37
9 20 M 80 177 4.47 94 81 96 37.8 0.28 0.28
10 27 M 75 185 4.66 100 83 92 38.9 0.38 0.53
11 20 M 66 184 5.47 119 94 99 38.2 0.31 0.31
12 21 M 74 172 4.14 96 90 97 38.3 0.33 0.33
13 21 F 57 173 3.63 97 97 98 35.4 0.55 0.63
14 23 F 55 163 3.72 110 92 96 31.3 0.37 0.38
15 27 M 56 161 3.01 83 77 106 37.2 0.33 0.34
16 26 M 75 181 4.94 106 96 93 41.7 0.51 0.45
17 27 M 77 174 4.38 102 83 103 40.3 0.39 0.40
18 34 M 71 174 4.88 118 78 97 33.8 0.37 0.37
19 55 F 59 164 3.39 130 82 111 29.4 0.42 0.46
20 71 M 64 162 2.78 101 84 98 34.3 0.62 0.38
21 58 M 80 172 3.29 93 72 121 28.0 0.49 0.29
22 56 M 75 161 3.48 115 86 105 34.9 0.50 0.30
23 67 F 67 156 1.77 86 70 77 35.5 0.49 0.53
24 52 F 51 153 2.88 124 84 109 33.4 0.36 0.39
25 46 F 67 155 2.47 97 83 83 42.1 0.37 0.39
26 54 M 109 181 3.94 97 84 96 38.8 0.29 0.40
27 38 F 64 155 3.23 118 85 95 33.6 0.30 0.60
28 49 F 58 161 2.53 85 79 107 36.8 0.34 0.43
29 58 M 60 166 2.97 92 75 96 38.5 0.48 0.73
30 52 F 101 170 3.33 116 80 98 29.3 0.47 0.54
31 49 F 76 156 2.89 115 82 97 37.5 0.48 0.56
32 52 F 64 156 2.89 120 86 92 39.8 0.48 0.48
33 57 M 90 167 3.62 110 74 101 33.6 0.46 0.36
34 46 F 62 156 2.78 108 83 108 35.6 0.27 0.38
35 51 M 75 168 3.64 104 83 103 37.5 0.35 0.30
36 52 F 63 156 2.52 104 78 111 33.4 0.57 0.30
37 55 F 76 149 2.23 105 77 103 36.3 0.32 0.92
38 64 M 96 171 3.41 101 74 80 37.3 0.37 0.72
39 50 M 69 170 3.45 96 77 95 42.2 0.32 0.49
40 43 M 85 178 3.53 85 75 102 38.3 0.37 0.67
41 38 M 85 177 4.32 102 72 109 31.3 0.37 0.49
42 60 F 66 148 2.27 115 79 85 34.7 0.72 0.48
43 25 M 67 171 1.98 119 85 104 40.9 0.43 0.28
44 36 M 91 178 4.56 106 78 100 37.5 0.38 0.35
45 24 M 84 175 4.63 105 88 99 44.2 0.29 0.69
46 20 M 75 181 4.97 113 78 100 39.3 0.31 0.32
47 20 M 92 176 4.93 99 83 115 35.8 046 0.37
48 24 M 64 173 4.20 100 81 101 36.3 0.38 0.32
49 27 F 51 158 3.47 111 89 111 36.0 0.38 0.34
50 23 M 71 175 4.49 102 82 106 35.1 0.39 0.39
51 29 M 72 176 4.15 95 91 93 31.3 0.30 0.49
52 34 M 80 181 3.99 89 89 107 36.6 0.50 0.59
53 38 M 73 167 3.91 105 93 86 38.3 0.47 0.68
54 33 M 64 166 3.99 106 93 93 36.0 0.22 0.22
55 41 F 50 159 2.63 94 81 101 33.8 0.34 0.35
56 44 F 76 156 2.99 114 82 111 33.7 0.51 0.54
57 33 M 76 174 4.15 100 75 94 36.8 0.27 0.27
58 32 M 69 162 3.42 96 91 105 40.5 0.54 0.59
59 39 M 66 168 4.92 132 80 104 34.6 0.39 0.39
60 43 M 74 173 4.64 119 84 97 38.7 0.36 0.38
61 34 M 75 167 4.15 110 79 108 36.8 0.47 0.50
62 38 F 64 157 2.56 91 82 111 34.7 0.31 0.32
63 30 F 61 171 3.74 109 89 103 35.1 0.33 0.34
64 32 M 76 184 5.70 122 82 91 42.6 0.44 0.56
Mean 37.3 21 F/43 M 72 169 3.81 105 83 100 36.7 0.40 0.44
SD 14.3 12 9 0.89 11 6 8 3.3 0.10 0.14

Definition of abbreviations: F 5 female; M 5 male; log SDQ and log SDV correspond to the second moment of blood flow and ventilation distributions on a logarithmic scale. These
parameters quantify the amount of ventilation–perfusion inequality.
650 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL. 155 1997

posing them to known pulmonary toxins. The subject’s ages ranged Arterial Blood-gas Measurements
from 18 to 71 yr; there were 21 females and 43 males. None had any Immediately after each inert gas sample was collected as described
history of respiratory, cardiovascular, or systemic disease other than above, a 3-ml arterial blood sample was taken into a heparinized sy-
occasional upper-respiratory infections. No such episode had oc- ringe. Bubbles were removed and the sample was iced prior to mea-
curred within 2 mo prior to study. Physical examination was within surements, which were made within 30 min. PO2, PCO2, pH, O2 satura-
normal limits, and pulmonary function tests (Model 1070; Med- tion, and [Hb] were measured directly from each sample (BG3 and
Graphics, St. Paul, MN) revealed normal forced spirometry (Table 1). IL482; Instrumentation Laboratories, Milan, Italy). Values were cor-
No FEV1 values were less than 80% predicted. Mean FEV1 was 105 6 rected to body temperature measured once prior to connecting the
11% predicted. The decrease in the ratio of FEV1 to FVC with age subject to the mouthpiece of the spirometer.
was 0.2 per year, which was within the expected range for healthy sub-
jects.
Statistical Analysis
Subject Preparation Results given in the text are expressed as mean 6 SD. Linear regres-
We performed clinical evaluations and pulmonary function testing af- sion was used to analyze relationships between principal variables.
ter giving the subjects an explanation of all procedures and receiving Measured and calculated values of cardiac output were compared
their informed consent. Within a week, each subject then returned af- with Student’s paired t test. Both PaO2 expected from the measured
· ·
ter an overnight fast for the principal study of gas exchange. After ad- amount of intrapulmonary shunting and VA/Q inequality were calcu-
equate ulnar collateral arterial bloodflow was assured, a 20-gauge can- lated (12) and compared with the measured PaO2 value for each sub-
nula was placed in the radial artery of the nondominant hand. A ject with Student’s paired t test.
catheter was placed into a vein on the contralateral arm. In both cases,
sterile technique and local anesthesia (1% lidocaine) were used. Not
less than 30 min after the beginning of an intravenous infusion of a RESULTS
sterile mixture of dissolved inert gases (for the MIGET; see the subse- · ·
VA/Q Inequality
quent discussion), the subject was connected through a nonrebreath- · ·
ing valve to a heated 10 L volume metallic mixing box (10). Ventila- Figure 1 shows the principal dispersion data for the VA/Q dis-
tion was continuously recorded with a calibrated Wright respirometer, tribution (log SDQ and log SDV). The two variables explicitly
and mixed expired O2 and CO2 concentrations were continuously
measured with a calibrated respiratory mass spectrometer (SensorLab
N/S V12866; Fisons, Cheshire, UK). These measurements provided a
continuous record of O2 uptake and CO2 elimination. These data were
also used to confirm a steady state of gas exchange both by constancy
of values to within 6 5% and by values of the respiratory exchange ra-
tio lying with physiologic limits, an important requirement for inter-
·
pretation of any gas-exchange data. V O2 was used to estimate cardiac
output according to the Fick principle and an assumed arteriovenous
O2 difference of 50 ml · dl21. This was necessary for the seven subjects
(of the total of 64) in whom direct cardiac output measurements re-
quired for applying the MIGET were unavailable; correlations of
measured and computed cardiac output values for the 57 other sub-
jects provided validation for the computed values as a reasonable sub-
stitute in these seven.

Cardiac Output Measurements

The indocyanine green dye technique was used to measure cardiac
output. To inscribe the dye curve, 5 mg of dye in 1 ml of water was
rapidly flushed into the venous catheter and arterial blood was with-
drawn at a constant rate of 20 ml · min21. In these resting subjects, ad-
equate curves were obtained prior to recirculation for the conventional
Stewart–Hamilton analysis with a cardiac output computer (DC-410;
Waters Instruments Inc., Rochester, MN). Duplicate measurements
requiring about 40 ml blood in all were made and the results averaged.

The MIGET
Using methods described previously from this laboratory (11), we
· ·
used the MIGET to assess VA/Q relationships in subjects at rest in
· ·
the seated upright position. To measure VA/Q inequality, we used
previously described indices (10), principally the second moment of
the distributions of ventilation and blood flow on a logarithmic scale
log SDV and log SDQ, respectively. The analysis separately yields a
value for the intrapulmonary shunt as the fraction of the cardiac out-
· ·
put perfusing regions with a VA/Q ratio below 0.005, the lower limit of
resolution of the method (12, 13). The total perfusion to areas with
· ·
subnormal ventilation (low VA/Q areas) was defined as the percent
· ·
perfusion to lung units with a VA/Q ratio above 0.005 and below 0.1.
Duplicate or triplicate measurements were attempted in order to com-
pute the intrasubject variance of the outcome variables with a previ- · ·
ously described approach involving the pooling of normalized data Figure 1. Ventilation–perfusion ( VA/Q) inequality increases with
from many subjects (9). Such sequential samples were taken 5 min age. Upper panel shows a slight increase in dispersion of the blood
apart, with the inert gas infusion continuing, and including catheter flow distribution (log SDQ) with age, and lower panel a similar in-
dead space, each sample required 10 ml of blood. In all, 159 samples crease for the ventilation distribution (log SDV). In each graph, the
were successfully taken and processed from the 64 subjects. regression line is indicated by a continuous line.
Brief Communication
exclude contributions of intrapulmonary shunting, which were
generally very small and which are analyzed later. Very few
data lay above the previously reported reference limits for
young normal subjects (9). Thus, in only two cases was log
SDQ above the reference limit of 0.6, and in only six cases was
log SDV above its limit of 0.65. Nevertheless, an in-depth
analysis of extreme data points did not yield any insight into
the mechanisms that were involved.
· ·
The dispersion of VA/Q distributions increases with age.
The rates of increase are similar for both log SDQ and log
SDV, but it must be emphasized that the magnitude of the age
effect is on average physiologically small and clinically not sig-
nificant. For example, from the log SDQ regression line, mean
values would be only 0.36 at age 20 yr and 0.47 at age 70 yr. As
shown by West (14), these values of dispersion correspond to
an AaPO2 of only about 5 mm Hg and 15 mm Hg, respectively,
or to arterial PO2 values of about 95 to 100 mm Hg and 85 to
90 mm Hg, respectively, depending on the arterial PCO2. Con-
sequences for arterial O2 saturation would be very small. In
contrast, patients with severe lung disease often develop log
SDQ values of 2.0 or greater (15); a perfectly homogeneous
lung would have a log SDQ of 0.
The variance in both log SDQ and log SDV is considerable,
as Figure 1 shows. The sources of this variance are discussed
subsequently, but the low correlation coefficients of 0.35 and
0.24 for each variable indicate that only 12% of the total vari-
ance is age-related.
The impact of intrasubject variance due to a combination
of experimental errors and biologic change in samples taken
5 min apart was examined by normalizing and then pooling
the dispersion parameters for each subject (9). In the present
study, this approach indicated that only 11% of the total vari-
ance of the dispersion indices (Figure 1) was due to intra-
· ·
subject variation. The majority of the variance in VA/Q dis-
Figure 2. Combined perfusion of unventilated and low VA/Q ratio regions in percentage of cardiac output
as a function of age. Most subjects had less than 0.75% perfusion in such abnormal areas. Only about
10% had more than 1% perfusion, and 5% had more than 1.5%; the maximal value is less than 3%.
651
persion therefore remained unexplained, but must have been
of intersubject origin. An obvious candidate for the cause of
such intersubject variance is the range of spirometric values (Ta-
ble 1). However, when log SDQ values were plotted against ei-
ther FEV1 as %predicted or against the FEV1/FVC ratio, no
evidence was found that these spirometric variables had any
· ·
relationship to VA/Q inequality. We were therefore unable to
· ·
account for the majority of the observed variance in VA/Q in-
equality through any physiologic variable or possible mea-
sured source of variability such as age, height, weight, expira-
tory flow rates, or experimental errors.
Since log SDQ and log SDV do not reflect unventilated re-
gions (nor intrapulmonary shunting), we examined the amount
· ·
of blood flow perfusing areas with a subnormal VA/Q ratio
· ·
(i.e., areas of VA/Q , 0.1). It is these areas that contribute most
to the size of the AaPO2 and which would therefore cause a de-
crease in arterial PO2. Expressed as a percentage of the cardiac
· ·
output, this low VA/Q area perfusion is shown in Figure 2. In
all but seven of the 64 subjects, there was no more than 0.75%
of the cardiac output in such areas, a trivial amount in terms of
arterial oxygenation. No subject had more than 3% of the car-
· ·
diac output in low VA/Q regions.
Arterial Blood-gas Data
PaO2 fell with age as expected, but only slightly (Figure 3). Be-
cause of variance, the slope of the regression line was only just
significantly negative (p 5 0.05, one-tailed test), and indicated
a mean decrease of about 6 mm Hg, from 102.3 mm Hg at age
20 yr to 96.5 mm Hg at age 70 yr. However, and unexpectedly,
arterial PCO2 also fell with age, by almost 4 mm Hg, from a
mean of 38.0 mm Hg to 34.3 mm Hg over the same age range
(p 5 0.02). When the alveolar gas equation was used to calcu-
late a PaO2 that would have existed had the arterial PCO2 been
40 mm Hg in every subject, rather than tending to fall with
· ·
652 AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL. 155 1997

Figure 3. Respiratory-gas data as a function of age, showing measured PaO2 and PCO2 (top panels) and PaO2 corrected in every subject to a
normal PCO2 of 40 mm Hg (lower left). AaPO2 differences appear at lower right. PO2 decreases slightly but significantly with age, as does
PCO2, PO2 corrected to a PCO2 of 40 mm Hg shows this more clearly. Although AaPO2 appears to increase, the large variance results in lack
of significance.

age, a more clear-cut effect of age became apparent (Figure 3,
lower left panel ). When this was done, the mean corrected ar-
terial PO2 fell by 10 mm Hg, from 100 mm Hg at age 20 yr to 90
mm Hg by age 70 yr. It is not apparent why older subjects
hyperventilated, but it is evident that this should be consid-
ered in interpreting age-dependent changes in PaO2. Owing to
the very large relative variance, the apparently positive slope
of AaPO2 with age (Figure 3, lower right panel) was not signifi-
cant. The variance of AaPO2 is expected to be relatively large,
since AaPO2 is the generally small difference between two
large numbers, alveolar and arterial PO2. This consequence of
normal error propagation also explains the negative values of
AaPO2, which are to be expected on occasion in the normal
population. However, despite the large variance in PO2 and in
AaPO2, the inert-gas data and those for O2 are internally con-
sistent with each other.
Additionally, the mean value of PaO2 for all 64 subjects
(100 6 8 mm Hg) was not significantly different from the PaO2
predicted from the measured combination of shunting plus
· ·
perfusion of low VA/Q areas as recovered from the inert-gas
data (98 6 11.6 mm Hg). Had there been significant alveolar–
capillary diffusion limitation of O2, and/or bronchial venous or
thebesian (postpulmonary) shunts reducing PaO2, the mea-
sured PaO2 would have been systematically lower than the
value predicted by the inert gas data. That this was not the
case argues against the presence of such phenomena to any
measurable degree.
DISCUSSION
· ·
VA/Q Inequality, O2 Exchange, and Age: Main Findings
· ·
The principal findings of this study are: (1) that VA/Q inequal-
ity, but not intrapulmonary shunting, does indeed increase
with age as previously expected; (2) that based on our group
of 64 subjects aged from 18 to 71 yr, the increase over the span
of about 50 yr is physiologically very small; (3) that most of
· ·
the variance in VA/Q mismatch over the age range of the group
is not due to aging, and remains unexplained; and (4) that the
decrease PaO2 with age is also quite small but is internally
· ·
consistent with the VA/Q changes measured independently.
· ·
VA/Q inequality was characterized in most subjects by a
narrow distribution that widened slightly with age, together
with a very small shunt of less than 1% of the cardiac output in
90% of cases. Both log SDQ and log SDV increased by about
0.1 between the ages of 20 yr and 70 yr. Thus, log SDQ in-
creased from 0.36 to 0.47, which is consistent with a decrease
Brief Communication
in PaO2 of only about 6 mm Hg. The cause(s) of the increase in
· ·
VA/Q mismatch with age were examined as far as possible
from the data collected. Only about 10% of the total variance
in dispersion was attributable to age. A similar amount was
due to intrasubject variability, but none was due to variation
in FEV1 % predicted, the FEV1/FVC ratio, weight, or height.
· ·
It is certainly possible that age could increase VA/Q inequality
as a result of increases in closing volume (3), such that in older
subjects some airways are closed during normal tidal breath-
· ·
ing, reducing local ventilation and hence producing VA/Q mis-
matching. We did not measure closing volume, but since this
· ·
mechanism is highly unlikely to compromise VA/Q relation-
ships in young normal subjects, we would argue that closing
volume is not a strong candidate for causing the variance in
· ·
VA/Q matching. In a very much smaller number of subjects
consisting of both young and middle-aged volunteers studied
for other reasons, differences in closing volume were apparent
· ·
as a function of age, but there were no evident effects on VA/Q
mismatching of increasing closing volume by water immersion
to the neck (16). When both dry and immersed, the older sub-
· ·
jects had greater VA/Q mismatching than the younger sub-
jects. Taken together, these findings also do not support a role
· ·
for airway closure as an explanation for age-related VA/Q in-
equality.
Even though no cause for the effects of age were identified,
· ·
approximate upper limits to VA/Q inequality could be defined
across the 50-yr span from age 20 yr to 70 yr. Figure 1 shows
that the 95% upper confidence limits found previously for
young (20 to 40 yr old) normal subjects (9) can be retained.
For log SDQ, this limit is 0.60, and for log SDV it is 0.65. With
the 0.1 increase in both parameters by age 70 yr, a reasonable
estimate of the 95% upper confidence limit at age 70 yr would
be 0.1 units greater for each parameter, at 0.70 for log SDQ
and 0.75 for log SDV. These estimates are compatible with the
95% confidence interval (CI) calculated from individual data in
Figure 1, although greater precision would require a greater
number of subjects, an undertaking that is probably not justified.
The establishment of such upper confidence limits is of
clinical utility. Most studies of patients with lung disease are
done with older subjects because most of the diseases of inter-
est are more common as age increases.
· ·
It was something of a surprise that both PaO2 and VA/Q in-
equality changed so little with age, especially in light of prior
work showing larger decreases in PO2 with age (17). However,
more recent data (18–20) are more in line with our findings.
Whether the differences between earlier and more recent work
reflect methodologic differences or differences in subject se-
lection cannot be answered.
In summary, this study of 64 normal subjects aged 18 to 71
· ·
yr has confirmed earlier suspicions that VA/Q inequality in-
creases with age. The effects of age are, however, very small,
with dispersion (i.e., log SDQ) increasing on average by only
about 0.1, from 0.36 at age 20 yr to 0.47 at age 70 yr. The data
fit well with concurrently measured indices of arterial oxygen-
ation, which showed a small decline of only about 6 mm Hg
· ·
over this age range. There was far more variance in VA/Q ine-
quality among the subjects than could be explained by age, and
candidates for sources of this variance such as experimental
errors and differences in spirometric indices, body weight, and
height were excluded. The explanation remains to be found.
Although previously established 95% upper confidence limits
· ·
for the VA/Q dispersion parameters log SDQ and log SDV in
young subjects continue to fit the younger subjects in the
· ·
present group, the increase in VA/Q mismatching with age sug-
gests that these limits of normality be raised for older subjects.
Thus, at age 20 yr, the upper limit of reference for log SDQ is
653
0.60, whereas at age 70 yr it would be 0.70. The upper limits
for log SDV are 0.65 at 20 yr and, if raised, 0.75 at 70 yr, and
for subjects of intermediate age, linear interpolation between
these values is reasonable. These limits should be useful from
· ·
now on for interpreting VA/Q dispersion data in older subjects
with cardiopulmonary diseases.
Acknowledgment : The authors are grateful to Conxi Gistau, Teresa Lecha,
Maite Simó, and Carmen Argaña of the Lung Function Laboratory of the
Hospital Clínic for their outstanding technical support.
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