Effect of aging alone on mechanical of the normal adult human lung
properties
RONALD J. KNUDSON, DUMONT F. CLARK, TIMOTHY C. KENNEDY, AND DWYN E. KNUDSON Division of Respiratory Sciertces, Westend Research Laboratories, University College of Medicine, Tucsun, Arizona 85724
F. CLARK, TIMOTHY C. Effect of aging alone on mechanical properties of the normal adult human lung, J. Appl. Physiol. : Respirat. Environ Exercise Physiol. 43(6): 1054-1062, 1977, - For plethysmographic studies of respiratory mechanics, we selected, from a general population, 51 subjects, aged 25-75 yr, who had never smoked, had no present or past cardiorespiratory symptoms or disease, were al-antitrypsin MM phenotypes, and were normal by physical examination, vectorcardiography, and chest roentgenography. Approximately equal numbers of men and women were represented in each of three age groups; 25-35, 36-64, and 65-75. Both sexes demonstrated loss of lung elastic recoil with age, most significant at high lung volumes, but the rate of loss was less than previously reported. Males had higher lung recoil than females of comparable age, but if lung size was taken into account, there were no sex differences in bulk elastic properties. Maximum expiratory flow diminished with age only at low lung volumes, suggesting that equal pressure points are more centrally located at low lung volumes in the elderly. KNUDSON, KENNEDY,
RONALD AND DWYN
J., DUM~NT E. KNUDSON.
respiratory mechanics; lung elastic recoil; pressure-volume curves; maximum expiratory flow; flow-volume curves; aging of the lung
THE PASSAGE OF TIME, the human lung may be the prey of myriad factors capable of altering its function. When a disease process can be identified, the pathophysiological consequences are often quite apparent. Other factors, however, may exert a more subtle effect on the mechanical properties of the lung. These include the injurious effects of past disease, the potential insult of an altered microenvironment associated with smoking, or genetic factors such as an cr,-antitrypsin deficiency heterozygocity. Dysfunction resulting from such factors may be self-limited or progressive and, if progressive, may represent the beginning of a chronic disease process. Thus the effect of such factors must be distinguished from the effects of aging alone. Several studies have focused on the natural history of the normal lung, but their results have not been consistently in agreement Frank and co-workers examined the mechanical properties of the lung in young (8) and in elderly (7) people but, although they found that elderly subjects demonstrated less lung elastic recoil, they could not attribute
WITH
l
of Arizona
this to aging alone. Permutt and Martin (28) concluded that there was no change in lung recoil with age, but the subsequent study of Turner and associates (30) demonstrated that loss of recoil indeed appeared to be a part of the aging process. Though these studies were based on healthy subjects, the possible past history of respiratory illness was not considered, and some smokers and exsmokers were included among the subjects tested. Two recent studies considered the effect of sex differences, as well as aging, on lung mechanical properties of nonsmokers. Gibson and co-workers (9) concluded that the bulk elastic properties of the lungs of young men and women were identical. Bode and associates (Z), on the other hand, found that young men had greater lung elastic recoil than young women, but lost recoil with age while women did not, Green and co-workers (10) examined maximum expiratory flow-volume (MEFV) curves by age cohort in 59 adults and noted increasing convexity to the volume axis with advancing age. Knudson and associates (19), however, from a study based on optimal composite MEFV curves obtained from 746 nonsymptomatic lifetime nonsmokers in a population survey, were not able to demonstrate a clear, consistent, progressive change in shape of the mean curve by age decade up to 79 yr of age. Because of their strict criteria for defining their “normal” population, they suggested that the previously described changes may have included factors other than aging alone. In attempt to resolve some of these differences and to elucidate the natural history of the normal human lung, the present study was undertaken. Our purpose was to measure the mechanical properties of the respiratory system in a group of adult men and women with the objective of examining the effects of aging alone when the potential influence of disease, insult, injury, and a potentially significant genetic factor are controlled. METHODS
Subjects. Candidates for these studies were drawn from the randomly selected population of Tucson, Ariz., enrolled in a longitudinal epidemiological study of obstructive lung diseases (20). Of 3,115 subjects for whom satisfactory flow-volume data were obtained in the first
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AGING
OF
THE
NORMAL
ADULT
HUMAN
LUNG
year of the project (19), 746 met the following criteria defining “normal.” In a self-administered health questionnaire, they answered in the negative all questions relating to shortness of breath, cough, or sputum production. They denied any current or previous cardiorespiratory disease, either suspected or physician-confirmed, and denied having any serious respiratory problems in childhood. In addition, they had never smoked cigarettes. From this segment of the population, which had now been tested for each of three successive years, only subjects who were able to expire at least 75% of the forced vital capacity in the 1st second were considered. In the 2nd year of the population study, vectorcardiograms (VCG) had been obtained in all adults. For this study, a normal VCG was a required selection criterion. Of the remaining candidates, only those who were MM phenotype (protease inhibitor phenotype PiM), based on analysis of blood samples drawn for cw,-antitrypsin screening, were eligible for participation, Subject selection was also based on sex and age. With the objective of studying approximately 60 subjects including equal numbers of men and women in three age groups between 25 and 75 yr, a random list of eligible persons was constructed and subjects then approached in sequence to request their participation. Of 73 persons approached, 70 agreed to participate. The selected candidates who agreed to participate were interviewed by a physician, a physical examination was performed, and chest roentgenograms were taken. If this final screening yielded nothing suggestive of any cardiorespiratory abnormality, the subject was judged to have met our criteria for study. Reasons for rejecting subjects at this stage included slight but noticeable kyphoscoliosis, prominent pulmonary vasculature by chest roentgenogram, hypertension, or clinical observations suggestive of mild cardiorespiratory disorder. It was also required that a subject had been free from any symptoms of acute upper respiratory infection for at least 1 mo prior to the time of testing. Full studies were completed on 51 subjects. Satisfactory data were obtained on 18 young people, aged 2535, and on 18 elderly subjects, aged 65-75. The remaining 15 subjects were in the broad middle-aged group, 36-64 yr of age. Data coLLection. Subjects were seated in an air-conditioned pressure-corrected, integrated flow, volume displacement body plethysmograph (J. H. -Emerson Co.). Volume was measured by the electrical integration of flow measured as the pressure drop (Validyne MP-45) across a flow-resistive element in the anterior wall of the plethysmograph. Pressure compensation was achieved by adding an appropriate proportion of this pressure drop to its own integral. This was adjusted to achieve a frequency-amplitude response which was flat through 15 Hz. When the subject was enclosed in the plethysmograph and the air conditioning set to obtain thermal stability, the negative bias flow of 0.5 1 s-l, which was to be used during measurements to reduce apparatus dead space to that of the mouthpiece alone, was directed through the DlethvsmomaDh and used for final adiustl
1055 ment of the volume calibration. Mouth flow was measured with a Fleisch pneumotachograph in conjunction with a differential pressure transducer (Sanborn 270). The bias flow, exiting near the mouthpiece, drew room air through the pneumotachograph and was offset electrically. Transpulmonary pressure (Pst(L)) was measured as the difference between mouth pressure and esophageal pressure sensed by a differential pressure transducer (Hewlett-Packard model 268B). Static deflation pressure-volume (PV) curves were obtained by interrupting expiratory flow during slow expiration from total lung capacity (TLC) to residual volume (RV). A constant volume history was assured by having the subject take three deep breaths to TLC, and recording PV data during the third expiration after which TLC was verified by a final maximal inspiration. The final PV curve was drawn as the best fit by eye to points derived from at least three sets of static deflation data. Esophageal pressure, as an index of pleural pressure (Ppl), was measured in the manner described by MilicEmili and co-workers (25) using an esophageal ballooncatheter passed transnasally. The balloons were 10 cm long, 3.5 cm in perimeter, and approximately 0.06 mm in wall thickness, mounted on PE-200 tubing, 110 cm long. For each subject, the balloon was positioned to the depth at which the pleural pressure was most negative with minimal cardiac artifact. The distance from balloon tip to nares varied from 34 to 46 cm in this study and depended to a considerable extent on the height of the subject. For the initial studies, a standard balloon volume of 0.4 ml of air was used. However, we observed considerable intersubject variability in the PV curves, even among subjects of the same sex and similar age. Therefore, these subjects were recalled and the studies repeated, and all subsequent subjects were studied employing trials with two different balloon volumes. For each esophageal balloon-catheter system, the optimal balloon volume was determined by the water immersion technique suggested by Lemen and associates (21). For none of the balloons used in this study did this volume exceed 0.2 ml. Separate measurements were made with this optimal volume and the standard volume of 0.4 ml. In almost all subjects, Ppl measured with the 0.4-ml balloon volume was more positive, and the PV curve consequently shifted to the left, compared to the smaller optimal balloon volume. This is consistent with the earlier findings of Milic-Emili and co-workers (25). However, the magnitude of the difference was not consistent when subjects were compared. Because the evidence suggests that pressures measured with the optimal balloon volume more accurately reflect pleural pressures (25) and introduce less variability in PV diagrams, only these pressures are used in describing the results that follow. Thoracic gas volume at FRC was measured by the technique of DuBois and associates (6) followed by full inspiration and subsequent full expiration permitting calculation of TLC and RV. Data were recorded on a multichannel oscillograph (Hewlett-Packard model 7788A),
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1056
KNUDSON,
Each subject performed at least three forced vital capacity maneuvers yielding reproducible MEFV curves. Flow measured by the pneumotachograph at the mouth was displayed against plethysmographic volume on a cathode ray storage oscilloscope (Tektronix 564B) and the resulting image traced on centimeter graph paper using a beam splitter. For subsequent tabulation, maximum expiratory flow (V,,,) values were recorded at selected percent increments of both vital capacity and TLC. TABLE Subj
1. Individual Age,
Yr
KNUDSON
Age, sex, height, volume, pressure, and flow data for eachof the 51 subjects studied appear in Table 1. Mean
data on all subjects Pst(L) at %TLC,
cmH,O
VC,
FRC,
liters
liters
liters
100%
90%
6.70 6.40 5.75 6.10 5.10 4.16 6.30 6,OO 6,54
2,81 3*14 3.07 3.35 2.05 2.44 3.30 2.42 4.14
44*0 35*7 48.0
18.0 20.3
13.8 16.4
10.9
19.2 18.0 19.1
13.8 14.2
10.8 11.5
8,6 9.2
16.5 25,5
14*7 13.4 18.5
11.8 11.2 14.7
9.7 9.2 12.0
19.8
15.7
12.7
9.9
15.6
12.1
9.7
7.7
80%
70%
90%
80%
70%
60%
50%
40%
9*3
8.1 9.2
6.0 7.5 5.2 5-8 6.3 4.0 7.5 5.3 3.2
10.4 9.0
10.6
9.4
6.9
5.2
3.4
10.5 10.2 13.0
7,8 9.5 8.8 11.2 6.5 8.8 9.8 10.8
6,4 7.6 7.4 9.8 4.9 7.8 7.8 4.4
5.6 5.1 5.0 8.4 3.4 6.6 5.7 3.6
3.3 3.8 3.1 5.8 2.2 5.0 4.6 3.0
2.3 2.6 1,8 4.2 1.2 3.1 3.3 2,O
8.3 8.4 5.0 2.5 5.8 4.1 6.8 6.2 3.9
6.9 7.4 3.5 -0.4 2,6 Z-5 5.0 4.3
5.2 7.2 4.6 7.8 7.0 7.2 5.0 5.6 7.0
5,6 7.2 6.6 7.8 7.3 8.1 7.8 5.7 7.2
5,5 4.8 6.4 6.2 6.1 6.8 7.0 5.1 6.3
4.2 3.7 5.4 4.4 5.4 5.3 6.1 3.6 5.5
3.1 2.7 4.1 2.6 3.8 3.9 4.2 2.7 3.2
2.2 1.8 2.6
7.4 8.3 8.5 8.2 6.5 5.6 5.6
5.5 7.0 7.3 6.7 4.1 3.2 3.5
9.4 11.7 9.4 9.9
7.6
5.4
4.0
3.0
1.6
11.0 10.5
7.9 8.0
6.2 5.4
4.6 3.8
2.8 2.3
9.8
9.5
3.7
5.2
3.2
10.0
10.9
9.5
4.5
2.5
0.4
6.5 7.1
7.6 5.7
5.3 4.1
4.0 3*1
2,O L4
0.2 0.4
4.6 5.2 5*4 9.5 7.2 4.9 3.7 4.5
2.6 3.6 4.0 6.6 5.1 3.2
7.9 6.1 5.7 6.4 6.3 6.1 6.1 5.4
8.2 5.8 4.3 5.9 5,5 6.3 4.6 4.6
6.2 5.0 4.1 4.4 3.5 5.1 4.0 2.1
4.6 4.0 3.6 2.4 2.3 3.3 3.4
3.2 2.8 2.0 1.2 1.2 2.1 1.6
1.8 1.4 0.9 0.4 0.5 0.6 0.5
1.0
0.3
0.1
6.8 9.0 5.8 4.4 8.5 7.5 5.0 3.5
5.2
9.0 8.1 7.1 7.5 11.4 7*7 5.9 9.6
8.0 6.0 7.2 8.6 8.0 8.4 6.6 8.5
6.5 3.7 5.6 6.1 5.0 4.9 5.4 5.3
4.5 2.0 3.8 3.5 3.6 3.4 3.8
2.9 0.4 2.0 1.2 1.5 1.6
1.2
2.9
1.1 1.1
0.2 0.2
7.8 3.1 6.5 4.3 5.8 4.2 5.7 5.9 7.8 4.9
6.6
6.6 6.4 7.0 7.1 6.4 5.7 5.7 5.5 6.2 3.4
5.1
3.1
4.0 6.5 7.5 6.2 5.2 4.5 4.1
3.1 5.7 4,9 4.9 4.0 3.3 3.4 3.8 2.2
1.6 1.9
0.5 0.8
3.8 2.9 3.1 2.3 2.7 2.7 Z-5 0.6
2.2 1.6
0.1 0.2 1.0
173 173 183 173 183
7.68 6.95 6.46 7.54 5.39 5.24 7.47 6.35 8.10
YFl YF2 YF3 YF4 YF5 YF6 YF7 YF8 YF9
25 27 27 28 29 31 31 32 33
163 160 162 168 173 168 168 163 173
5.18 4,08 4.67 5.30 4.58 4.64 4.28 3.88 5*79
4.70 3.61 4.34 4.32 3.70 4.00 3.60 2.95 5.04
2.02 L87 1.54 2.66 2.45 2.44 1.78 2.20 2.79
33.5 28-O 36.0 36.0 43.0 35.0 48.0 33.0 35.0
18.6 17.6 15.4 13.5 17.1 17.0 21.0
14*3 13.7 11.2 9.2 12.5 12.0 15.3
11.4 11.6 8.3 6.6 9.4 9.0 11.7
9.5 9.9 6.6 4.2 8.0 6.0 8.8
18.9
14.2
10.7
8,2
18.6
13.4
9.6
6.5
MM1 MM2 MM3 MM4 MM5 MM6 MM7
37 39 42 48 56 59 60
175 178 175 173 173 168 170
5.36 7.84 6.68 5.57 5.92 5.88 5.37
4.45 6.70 5*90 4.70 4.90 3*95 3.76
2.21 3.36 2,40 1.88 2.24 2.28 2.50
21.5 48.0 27.0 28.5 36.0 38.0 32.0
15.5 22.2
12.8 16.5
11.0
15.9
13.3
11.4
9.9
17.4 17.8 15.0 14.8
14.0 13.2 11.8 11.6
11.7 10.5 9.6 9.4
9.8 8.3 7.6 7-4
MFl MF2 MF3 MF4 MF5 MF6 MF? MF8
36 43 43 50 52 53 57 64
170 163 160 162 160 165
4.36 3.82 3.83 3.49 3.80 3.35 3.63 2.63
2.95 2.22 2.32 3.06
28.5 27.5 21.0 28.8
17.3 14.5 13.3
12.2 11.3 10.8
9.1
6.7
8.8 8.4
6.8 6.7
16.6 14.1
11.8
21.8
19.2 17,8
14.2
la99 1.97 2.18 2.09
20.0 28.0 30.0
12.4 14.0 12.4
9.7 10.4
11.4 7.8 7.8
9,3 6.1 5.7
160
5.43 4.62 4.59 5.14 5.09 4.22 4.50 4.13
10.0
8.2
6.5
EM1 EM2 EM3 EM4 EM5 EM6 EM7
170 165 168 178 173 180 170 180
6.35 5.21 7,12 5.78 8.05 6.69 5.21 7.06
5.70 3.31 5.13 4.10 6.10 5.15 3.53 4.90
2.38 2.44 3.37 2.70 3.86 2.88 2.47 3.58
27.0 40.0 32.0 32.0 42.2 36,O 38.0 17.0
14.0 21.3 16.7 14.3 17.8 17.5 15.0 10.7
11.2 16.6 12.3 lo,7
9.3 13.4 9,5 8.2
13.9
11.2
9.7
EM8
65 67 68 68 70 72 73 73
13.1 11.4 8.2
10.5 9.0 6+3
8.8 6.8 5-O
EFl EF2 EF3 EF4 EF5 EF6 EF7 EF8 EF9 EFlO
68 70 71 71 71 71 71 71 72 75
163 157 165 157 163 150 157 157 160 147
4.43 3.75 3.94 5.01 4.54 3.90 4.16 3.46 3.99 3.32
3.24 2.62 3.10 4.20 3.40 2.50 2.70 2.72 3.10
2.26 2.12 2.06 2.17 2.14 2.01 2.37 1.86 1.82
16.0 11.8 11-4 12.5 13.6 12.8 14.0 13.8 15.2
12.4 8.6 9.6 9.2
10.4 6.0 8.3 6.8
9.0 4.3 7,3 5.2
lO*O
8.1
6.8
9.0 11.3 11.7
6.8 9.0 9.7
5.3 7.3 7.9
2.19
1.99
28.0 18.0 21.0 22.0 21.0 23.0 24.0 25.0 23.0 31.6
11.9 9.3
9.7 7.5
8.6 6.2
44.0 25.0 39.0 32.0 24.0
11.9
13.0
1 as-1
40%
183
31.5
at %TLC,
50%
25 25 28 28 29 31 33 33 33
13.4
Lx
--
60%
YMl YM2 YM3 YM4 YM5 YM6 YM7 YM8 YM9
157
AND
RESULTS
TLC,
185
KENNEDY,
For each subject, data were tabulated, entered on punch cards, and for each sex/age group, distributions, mean values, standard deviations (SD), and standard errors of the mean (SE) were derived by computer analysis. Computer techniques were employed for subsequent statistical analyses.
HL cm
183 I75
CLARK,
11.2
9*0 10.5
8.1
11.0 7.5 6.2
6.7 7.5 8.0 7.2 9.5 7.4 5.8
1.0
4.2 2.7 6.5 6.4 3.2
5.4 3.8 4.6
3.8 7.3
10.0 10.9 10.6 8.3
5.9 3.4
1.1 1.6 2.5 2.8 1.8 2.1
0.6 0.2 0.3 0.5
0.4
1.1
0.3
0.4 1.5
0.2
1.1 1.1
0.3 0.2
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AGING
OF
THE
NORMAL
ADULT
HUMAN
LUNG
TABLE
2. Mean values by ugelsex groups
--
-P-
I
Females
Males Young n=9
Age,
yr
Height, cm TLC, liters VC, liters FRC, liters RV/TLC, % Pst(ti
Middle-Aged n=7
-
Young n=9
Elderly n=8
Middle-Aged n=B
Elderly n = 10
x
SD
SE
s
SD
SE
ii.
SD
SE
ii
SD
SE
ii.
SD
SE
x
SD
SE
29 179 6.80 5.89 2.97 13.02
3.09 4.99 0.944 0.760 0.588 5.97
1.03 1.66 0.315 0.253 0.196 1.99
49 173 6.09 4.91 2.41 19.84
8.98 3.09 0.828 0.374 0.427 8.15
3.39 1.17 0.313 0.141 0.161 3.08
70 173 6.43 4.74 2.84 26.72
2.82 5.36 0.934 0.770 0.548 7.92
0.997 1.90 0.330 0.272 0.194 2.80
29 166 4.71 4.03 2.19 14.68
2.54 4.47 0.580 0.604 0.399 5.29
0.847 1.41 0.193 0.201 0.133 1.76
50 162 4.72 3.61 2.35 23.41
8.30 3.72 0.432 0.466 0.396 7.45
2.93 1.32 0.153 0.165 0.140 2.56
71 158 4.05 2.98 2.08 26.83
1.64 5.40 0.375 0.538 0.161 6.75
0.519 1.70 0.119 0.170 0.051 2.14
35.90 19.10 14.70 11.90 9.64 7.71 5.64
8.53 2.84 1.89 1.52 1.30 1.16 1.43
2.840 0.945 0.631 0.506 0.432 0.386 0.478
33.00 16.90 13.30 10.90 8.93 7.16 5.33
8.65 2.59 1.64 1.25 1.20 1.26 1.73
3.270 0.977 0.620 0.473 0.454 0.477 0.654
33.00 15.90 12.20 9.68 7.89 6.31 4.70
2.87 3.16 2.48 2.11 1.94 1.97 1.60
2.860 1.120 0.876 0.745 0.686 0.697 0.655
36.40 17.50 12.90 9.81 7.52 5.67 3.64
5.84 2.16 1.86 1.72 1.84 2.00 2.57
1.950 0.721 0.622 0.572 0.614 0.667 0.856
25.70 15.10 11.90 9.46 7.45 5.62 4.18
4.04 2.63 2.37 2.24 2.06 1.86 1.45
1.430 0.929 0.838 0.791 0.728 0.658 0.592
23.70 13.30 10.30 8.23 6.79 5.60 5.25
3.85 1.51 1.39 1.46 1.54 1.53 1.46
1.220 0.477 0.438 0.462 0.485 0.483 0.597
10.30 9.31 7.28 5.59 4.00 2.66
1.30 1.52 1.81 1.58 1.20 0.93
0.434 0.506 0.604 0.527 0.402 0.311
9.14 9.01 7.10 4.41 3.21 1.56
1.79 2.05 2.16 1.06 1.39 1.25
0.675 0.775 0.818 0.401 0.524 0.471
8.29 7.66 5.31 3.44 1.48 0.40
1.69 0.96 0.84 0.74 0.74 0.37
0.598 0.340 0.298 0.260 0.262 0.132
6.29 7.03 6.02 4.84 3.37 2.06
1.18 0.90 0.75 0.89 0.64 0.54
0.393 0.300 0.248 0.296 0.213 0.180
6.25 5.65 4.30 3.80 1.80 0.78
0.74 1.26 1.22 1.13 0.93 0.56
0.262 0.444 0.430 0.400 0.330 0.200
6.00 5.24 3.84 2.41 1.03 0.30
1.06 1.28 1.05 0.88 0.64 0.29
0.335 0.406 0.333 0.279 0.203 0.096
at %TLC, CmH~O
100% 90% 80% 70% 60% 50% 40%
TLC TLC TLC TLC TLC TLC TLC
r’,,,
at %TLC, 1 -s--l 90% TLC 80% TLC 70% TLC 60% TLC 50% TLC 40% TLC
data for the three age groups are snown ror males and females, respectively, in Table 2. In these tables, Pst(L) and maximum expiratory flow (v,,,) values are given for volumes at decile increments of each subject’s TLC, but presented as means in Table 2. Because measurements of pleural pressure by the esophageal balloon technique may be unreliable at low lung volumes (25), no data are reported for volumes less than 40% of TLC. Static deflation PV curves based on mean values for each age/sex group are shown in Fig. 1. To standardize for lung size, volume is expressed at %TLC though Pst(L) is given in absolute units of cmH,O. Inspection of these PV curves reveals age-related changes within each sex. With advancing age, there is progressive loss of lung elastic recoil and, at least in women, a change in the slope of the PV curve. From these data, age regressions were developed separately for men and for women and also for all subjects collectively. In Table 3 these age regressions are shown for Pst(L) at decile increments of TLC. In women, age-related decrease in Pst(L) does not appear to be significant at volumes below 60% TLC. At 40% TLC, the loss of lung elastic recoil is of only minimal significance in men and of no significance when all subjects are considered. Static compliance was taken as the chord slope of the static deflation PV curve between FRC and FRC + 0.5 liters. This value did not show a significant change with age. Dynamic compliance during quiet breathing (mean frequency = 14.5 breaths/min) also showed no change with age. As anticipated, the RV/TLC ratio increased with age. Using values for flow at decile and quartile increments of the expired VC, mean MEFV curves were reconstructed for each of the sex/age groups. These mean MEFV curves are shown in Fig. 2 where only the descending or effort-independent portions are shown.
ae FEMALES
------elderly -middle
20
aged
----young
o!
1 0
10 Pst(L)
I
.
I
20
30
40
Hz01
km
FIG. 1. Mean pressure-volume curves for males and females by age group. To compensate for differences in size, volume is expressed as %TLC.
To compensate for differences in lung size among the groups, flow is expressed at TLC s-l and volume as percent expired VC, with RV equal to 100% of expired VC. Although inspection of these curves suggests that there is an age-related decrease in V,,, at low lung volumes, the degree of significance of this change in shape of the MEFV curve is not immediately apparent. However, when the data were subjected to further analysis, the decrease in v,,, with age was found to be l
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1058
KNUDSON,
3. Age regressions I
TABLE
TLC TLC
TLC TLC
TLC 50%TLC 40% TLC
A
B
37.48
- 0.0698
8.18
21.41 16.75 13.71 11.27 9.17 6.96
-0.0826 -0.0679 -0.0588 -0.0499 -0.0431 -0.0360
3.09 2.24 1.85 1.64 1.56 1.55
A = regression
constant;
SD
B = slope; Pst(L)
R
0.154 0.482 0.547 0.572 0.551 0.500 0.407
Q
4 cc
0.472(M) 0.017 0.006 0.003 0.005 0.013 0.060
A
B
SD
R
42.13 20.30 14.70 11.03 8.18 5.88 2.56
-0.2680 -0.0994 -0.0605 -0.0376 -0.0188 -0.0050 0.0370
7.28 2.71 2.12 1.87 1.77 1.72 2.04
0.683 0.681 0.531 0.373 0.197 0.054 0.326
deviation
1.5
MALES
*.--. 1 -9.
FEMALES
1.0 0.5 0 20
0
%
40
Expired
60
100
VC
2. Maximum expiratory flow-volume curves females by age group. To compensate for differences expressed as TLC mS-I and volume as percent expired effort-independent portions of the curves are shown. FIG.
80
for males and in size, flow is VC. Only the
of statistical significance only at volumes below 70% expired VC. By analysis of variance, significance (P) was well above 0.5 at volumes greater than 60% VC, but was less than 0.015 at volumes after 70% VC had been expired. This age-related change in size-compensated flow was observed when vmax was expressed as either TLC s-l or VC s-4 l
KNUDSON
P
properties
RONALD J. KNUDSON, DUMONT F. CLARK, TIMOTHY C. KENNEDY, AND DWYN E. KNUDSON Division of Respiratory Sciertces, Westend Research Laboratories, University College of Medicine, Tucsun, Arizona 85724
F. CLARK, TIMOTHY C. Effect of aging alone on mechanical properties of the normal adult human lung, J. Appl. Physiol. : Respirat. Environ Exercise Physiol. 43(6): 1054-1062, 1977, - For plethysmographic studies of respiratory mechanics, we selected, from a general population, 51 subjects, aged 25-75 yr, who had never smoked, had no present or past cardiorespiratory symptoms or disease, were al-antitrypsin MM phenotypes, and were normal by physical examination, vectorcardiography, and chest roentgenography. Approximately equal numbers of men and women were represented in each of three age groups; 25-35, 36-64, and 65-75. Both sexes demonstrated loss of lung elastic recoil with age, most significant at high lung volumes, but the rate of loss was less than previously reported. Males had higher lung recoil than females of comparable age, but if lung size was taken into account, there were no sex differences in bulk elastic properties. Maximum expiratory flow diminished with age only at low lung volumes, suggesting that equal pressure points are more centrally located at low lung volumes in the elderly. KNUDSON, KENNEDY,
RONALD AND DWYN
J., DUM~NT E. KNUDSON.
respiratory mechanics; lung elastic recoil; pressure-volume curves; maximum expiratory flow; flow-volume curves; aging of the lung
THE PASSAGE OF TIME, the human lung may be the prey of myriad factors capable of altering its function. When a disease process can be identified, the pathophysiological consequences are often quite apparent. Other factors, however, may exert a more subtle effect on the mechanical properties of the lung. These include the injurious effects of past disease, the potential insult of an altered microenvironment associated with smoking, or genetic factors such as an cr,-antitrypsin deficiency heterozygocity. Dysfunction resulting from such factors may be self-limited or progressive and, if progressive, may represent the beginning of a chronic disease process. Thus the effect of such factors must be distinguished from the effects of aging alone. Several studies have focused on the natural history of the normal lung, but their results have not been consistently in agreement Frank and co-workers examined the mechanical properties of the lung in young (8) and in elderly (7) people but, although they found that elderly subjects demonstrated less lung elastic recoil, they could not attribute
WITH
l
of Arizona
this to aging alone. Permutt and Martin (28) concluded that there was no change in lung recoil with age, but the subsequent study of Turner and associates (30) demonstrated that loss of recoil indeed appeared to be a part of the aging process. Though these studies were based on healthy subjects, the possible past history of respiratory illness was not considered, and some smokers and exsmokers were included among the subjects tested. Two recent studies considered the effect of sex differences, as well as aging, on lung mechanical properties of nonsmokers. Gibson and co-workers (9) concluded that the bulk elastic properties of the lungs of young men and women were identical. Bode and associates (Z), on the other hand, found that young men had greater lung elastic recoil than young women, but lost recoil with age while women did not, Green and co-workers (10) examined maximum expiratory flow-volume (MEFV) curves by age cohort in 59 adults and noted increasing convexity to the volume axis with advancing age. Knudson and associates (19), however, from a study based on optimal composite MEFV curves obtained from 746 nonsymptomatic lifetime nonsmokers in a population survey, were not able to demonstrate a clear, consistent, progressive change in shape of the mean curve by age decade up to 79 yr of age. Because of their strict criteria for defining their “normal” population, they suggested that the previously described changes may have included factors other than aging alone. In attempt to resolve some of these differences and to elucidate the natural history of the normal human lung, the present study was undertaken. Our purpose was to measure the mechanical properties of the respiratory system in a group of adult men and women with the objective of examining the effects of aging alone when the potential influence of disease, insult, injury, and a potentially significant genetic factor are controlled. METHODS
Subjects. Candidates for these studies were drawn from the randomly selected population of Tucson, Ariz., enrolled in a longitudinal epidemiological study of obstructive lung diseases (20). Of 3,115 subjects for whom satisfactory flow-volume data were obtained in the first
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AGING
OF
THE
NORMAL
ADULT
HUMAN
LUNG
year of the project (19), 746 met the following criteria defining “normal.” In a self-administered health questionnaire, they answered in the negative all questions relating to shortness of breath, cough, or sputum production. They denied any current or previous cardiorespiratory disease, either suspected or physician-confirmed, and denied having any serious respiratory problems in childhood. In addition, they had never smoked cigarettes. From this segment of the population, which had now been tested for each of three successive years, only subjects who were able to expire at least 75% of the forced vital capacity in the 1st second were considered. In the 2nd year of the population study, vectorcardiograms (VCG) had been obtained in all adults. For this study, a normal VCG was a required selection criterion. Of the remaining candidates, only those who were MM phenotype (protease inhibitor phenotype PiM), based on analysis of blood samples drawn for cw,-antitrypsin screening, were eligible for participation, Subject selection was also based on sex and age. With the objective of studying approximately 60 subjects including equal numbers of men and women in three age groups between 25 and 75 yr, a random list of eligible persons was constructed and subjects then approached in sequence to request their participation. Of 73 persons approached, 70 agreed to participate. The selected candidates who agreed to participate were interviewed by a physician, a physical examination was performed, and chest roentgenograms were taken. If this final screening yielded nothing suggestive of any cardiorespiratory abnormality, the subject was judged to have met our criteria for study. Reasons for rejecting subjects at this stage included slight but noticeable kyphoscoliosis, prominent pulmonary vasculature by chest roentgenogram, hypertension, or clinical observations suggestive of mild cardiorespiratory disorder. It was also required that a subject had been free from any symptoms of acute upper respiratory infection for at least 1 mo prior to the time of testing. Full studies were completed on 51 subjects. Satisfactory data were obtained on 18 young people, aged 2535, and on 18 elderly subjects, aged 65-75. The remaining 15 subjects were in the broad middle-aged group, 36-64 yr of age. Data coLLection. Subjects were seated in an air-conditioned pressure-corrected, integrated flow, volume displacement body plethysmograph (J. H. -Emerson Co.). Volume was measured by the electrical integration of flow measured as the pressure drop (Validyne MP-45) across a flow-resistive element in the anterior wall of the plethysmograph. Pressure compensation was achieved by adding an appropriate proportion of this pressure drop to its own integral. This was adjusted to achieve a frequency-amplitude response which was flat through 15 Hz. When the subject was enclosed in the plethysmograph and the air conditioning set to obtain thermal stability, the negative bias flow of 0.5 1 s-l, which was to be used during measurements to reduce apparatus dead space to that of the mouthpiece alone, was directed through the DlethvsmomaDh and used for final adiustl
1055 ment of the volume calibration. Mouth flow was measured with a Fleisch pneumotachograph in conjunction with a differential pressure transducer (Sanborn 270). The bias flow, exiting near the mouthpiece, drew room air through the pneumotachograph and was offset electrically. Transpulmonary pressure (Pst(L)) was measured as the difference between mouth pressure and esophageal pressure sensed by a differential pressure transducer (Hewlett-Packard model 268B). Static deflation pressure-volume (PV) curves were obtained by interrupting expiratory flow during slow expiration from total lung capacity (TLC) to residual volume (RV). A constant volume history was assured by having the subject take three deep breaths to TLC, and recording PV data during the third expiration after which TLC was verified by a final maximal inspiration. The final PV curve was drawn as the best fit by eye to points derived from at least three sets of static deflation data. Esophageal pressure, as an index of pleural pressure (Ppl), was measured in the manner described by MilicEmili and co-workers (25) using an esophageal ballooncatheter passed transnasally. The balloons were 10 cm long, 3.5 cm in perimeter, and approximately 0.06 mm in wall thickness, mounted on PE-200 tubing, 110 cm long. For each subject, the balloon was positioned to the depth at which the pleural pressure was most negative with minimal cardiac artifact. The distance from balloon tip to nares varied from 34 to 46 cm in this study and depended to a considerable extent on the height of the subject. For the initial studies, a standard balloon volume of 0.4 ml of air was used. However, we observed considerable intersubject variability in the PV curves, even among subjects of the same sex and similar age. Therefore, these subjects were recalled and the studies repeated, and all subsequent subjects were studied employing trials with two different balloon volumes. For each esophageal balloon-catheter system, the optimal balloon volume was determined by the water immersion technique suggested by Lemen and associates (21). For none of the balloons used in this study did this volume exceed 0.2 ml. Separate measurements were made with this optimal volume and the standard volume of 0.4 ml. In almost all subjects, Ppl measured with the 0.4-ml balloon volume was more positive, and the PV curve consequently shifted to the left, compared to the smaller optimal balloon volume. This is consistent with the earlier findings of Milic-Emili and co-workers (25). However, the magnitude of the difference was not consistent when subjects were compared. Because the evidence suggests that pressures measured with the optimal balloon volume more accurately reflect pleural pressures (25) and introduce less variability in PV diagrams, only these pressures are used in describing the results that follow. Thoracic gas volume at FRC was measured by the technique of DuBois and associates (6) followed by full inspiration and subsequent full expiration permitting calculation of TLC and RV. Data were recorded on a multichannel oscillograph (Hewlett-Packard model 7788A),
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1056
KNUDSON,
Each subject performed at least three forced vital capacity maneuvers yielding reproducible MEFV curves. Flow measured by the pneumotachograph at the mouth was displayed against plethysmographic volume on a cathode ray storage oscilloscope (Tektronix 564B) and the resulting image traced on centimeter graph paper using a beam splitter. For subsequent tabulation, maximum expiratory flow (V,,,) values were recorded at selected percent increments of both vital capacity and TLC. TABLE Subj
1. Individual Age,
Yr
KNUDSON
Age, sex, height, volume, pressure, and flow data for eachof the 51 subjects studied appear in Table 1. Mean
data on all subjects Pst(L) at %TLC,
cmH,O
VC,
FRC,
liters
liters
liters
100%
90%
6.70 6.40 5.75 6.10 5.10 4.16 6.30 6,OO 6,54
2,81 3*14 3.07 3.35 2.05 2.44 3.30 2.42 4.14
44*0 35*7 48.0
18.0 20.3
13.8 16.4
10.9
19.2 18.0 19.1
13.8 14.2
10.8 11.5
8,6 9.2
16.5 25,5
14*7 13.4 18.5
11.8 11.2 14.7
9.7 9.2 12.0
19.8
15.7
12.7
9.9
15.6
12.1
9.7
7.7
80%
70%
90%
80%
70%
60%
50%
40%
9*3
8.1 9.2
6.0 7.5 5.2 5-8 6.3 4.0 7.5 5.3 3.2
10.4 9.0
10.6
9.4
6.9
5.2
3.4
10.5 10.2 13.0
7,8 9.5 8.8 11.2 6.5 8.8 9.8 10.8
6,4 7.6 7.4 9.8 4.9 7.8 7.8 4.4
5.6 5.1 5.0 8.4 3.4 6.6 5.7 3.6
3.3 3.8 3.1 5.8 2.2 5.0 4.6 3.0
2.3 2.6 1,8 4.2 1.2 3.1 3.3 2,O
8.3 8.4 5.0 2.5 5.8 4.1 6.8 6.2 3.9
6.9 7.4 3.5 -0.4 2,6 Z-5 5.0 4.3
5.2 7.2 4.6 7.8 7.0 7.2 5.0 5.6 7.0
5,6 7.2 6.6 7.8 7.3 8.1 7.8 5.7 7.2
5,5 4.8 6.4 6.2 6.1 6.8 7.0 5.1 6.3
4.2 3.7 5.4 4.4 5.4 5.3 6.1 3.6 5.5
3.1 2.7 4.1 2.6 3.8 3.9 4.2 2.7 3.2
2.2 1.8 2.6
7.4 8.3 8.5 8.2 6.5 5.6 5.6
5.5 7.0 7.3 6.7 4.1 3.2 3.5
9.4 11.7 9.4 9.9
7.6
5.4
4.0
3.0
1.6
11.0 10.5
7.9 8.0
6.2 5.4
4.6 3.8
2.8 2.3
9.8
9.5
3.7
5.2
3.2
10.0
10.9
9.5
4.5
2.5
0.4
6.5 7.1
7.6 5.7
5.3 4.1
4.0 3*1
2,O L4
0.2 0.4
4.6 5.2 5*4 9.5 7.2 4.9 3.7 4.5
2.6 3.6 4.0 6.6 5.1 3.2
7.9 6.1 5.7 6.4 6.3 6.1 6.1 5.4
8.2 5.8 4.3 5.9 5,5 6.3 4.6 4.6
6.2 5.0 4.1 4.4 3.5 5.1 4.0 2.1
4.6 4.0 3.6 2.4 2.3 3.3 3.4
3.2 2.8 2.0 1.2 1.2 2.1 1.6
1.8 1.4 0.9 0.4 0.5 0.6 0.5
1.0
0.3
0.1
6.8 9.0 5.8 4.4 8.5 7.5 5.0 3.5
5.2
9.0 8.1 7.1 7.5 11.4 7*7 5.9 9.6
8.0 6.0 7.2 8.6 8.0 8.4 6.6 8.5
6.5 3.7 5.6 6.1 5.0 4.9 5.4 5.3
4.5 2.0 3.8 3.5 3.6 3.4 3.8
2.9 0.4 2.0 1.2 1.5 1.6
1.2
2.9
1.1 1.1
0.2 0.2
7.8 3.1 6.5 4.3 5.8 4.2 5.7 5.9 7.8 4.9
6.6
6.6 6.4 7.0 7.1 6.4 5.7 5.7 5.5 6.2 3.4
5.1
3.1
4.0 6.5 7.5 6.2 5.2 4.5 4.1
3.1 5.7 4,9 4.9 4.0 3.3 3.4 3.8 2.2
1.6 1.9
0.5 0.8
3.8 2.9 3.1 2.3 2.7 2.7 Z-5 0.6
2.2 1.6
0.1 0.2 1.0
173 173 183 173 183
7.68 6.95 6.46 7.54 5.39 5.24 7.47 6.35 8.10
YFl YF2 YF3 YF4 YF5 YF6 YF7 YF8 YF9
25 27 27 28 29 31 31 32 33
163 160 162 168 173 168 168 163 173
5.18 4,08 4.67 5.30 4.58 4.64 4.28 3.88 5*79
4.70 3.61 4.34 4.32 3.70 4.00 3.60 2.95 5.04
2.02 L87 1.54 2.66 2.45 2.44 1.78 2.20 2.79
33.5 28-O 36.0 36.0 43.0 35.0 48.0 33.0 35.0
18.6 17.6 15.4 13.5 17.1 17.0 21.0
14*3 13.7 11.2 9.2 12.5 12.0 15.3
11.4 11.6 8.3 6.6 9.4 9.0 11.7
9.5 9.9 6.6 4.2 8.0 6.0 8.8
18.9
14.2
10.7
8,2
18.6
13.4
9.6
6.5
MM1 MM2 MM3 MM4 MM5 MM6 MM7
37 39 42 48 56 59 60
175 178 175 173 173 168 170
5.36 7.84 6.68 5.57 5.92 5.88 5.37
4.45 6.70 5*90 4.70 4.90 3*95 3.76
2.21 3.36 2,40 1.88 2.24 2.28 2.50
21.5 48.0 27.0 28.5 36.0 38.0 32.0
15.5 22.2
12.8 16.5
11.0
15.9
13.3
11.4
9.9
17.4 17.8 15.0 14.8
14.0 13.2 11.8 11.6
11.7 10.5 9.6 9.4
9.8 8.3 7.6 7-4
MFl MF2 MF3 MF4 MF5 MF6 MF? MF8
36 43 43 50 52 53 57 64
170 163 160 162 160 165
4.36 3.82 3.83 3.49 3.80 3.35 3.63 2.63
2.95 2.22 2.32 3.06
28.5 27.5 21.0 28.8
17.3 14.5 13.3
12.2 11.3 10.8
9.1
6.7
8.8 8.4
6.8 6.7
16.6 14.1
11.8
21.8
19.2 17,8
14.2
la99 1.97 2.18 2.09
20.0 28.0 30.0
12.4 14.0 12.4
9.7 10.4
11.4 7.8 7.8
9,3 6.1 5.7
160
5.43 4.62 4.59 5.14 5.09 4.22 4.50 4.13
10.0
8.2
6.5
EM1 EM2 EM3 EM4 EM5 EM6 EM7
170 165 168 178 173 180 170 180
6.35 5.21 7,12 5.78 8.05 6.69 5.21 7.06
5.70 3.31 5.13 4.10 6.10 5.15 3.53 4.90
2.38 2.44 3.37 2.70 3.86 2.88 2.47 3.58
27.0 40.0 32.0 32.0 42.2 36,O 38.0 17.0
14.0 21.3 16.7 14.3 17.8 17.5 15.0 10.7
11.2 16.6 12.3 lo,7
9.3 13.4 9,5 8.2
13.9
11.2
9.7
EM8
65 67 68 68 70 72 73 73
13.1 11.4 8.2
10.5 9.0 6+3
8.8 6.8 5-O
EFl EF2 EF3 EF4 EF5 EF6 EF7 EF8 EF9 EFlO
68 70 71 71 71 71 71 71 72 75
163 157 165 157 163 150 157 157 160 147
4.43 3.75 3.94 5.01 4.54 3.90 4.16 3.46 3.99 3.32
3.24 2.62 3.10 4.20 3.40 2.50 2.70 2.72 3.10
2.26 2.12 2.06 2.17 2.14 2.01 2.37 1.86 1.82
16.0 11.8 11-4 12.5 13.6 12.8 14.0 13.8 15.2
12.4 8.6 9.6 9.2
10.4 6.0 8.3 6.8
9.0 4.3 7,3 5.2
lO*O
8.1
6.8
9.0 11.3 11.7
6.8 9.0 9.7
5.3 7.3 7.9
2.19
1.99
28.0 18.0 21.0 22.0 21.0 23.0 24.0 25.0 23.0 31.6
11.9 9.3
9.7 7.5
8.6 6.2
44.0 25.0 39.0 32.0 24.0
11.9
13.0
1 as-1
40%
183
31.5
at %TLC,
50%
25 25 28 28 29 31 33 33 33
13.4
Lx
--
60%
YMl YM2 YM3 YM4 YM5 YM6 YM7 YM8 YM9
157
AND
RESULTS
TLC,
185
KENNEDY,
For each subject, data were tabulated, entered on punch cards, and for each sex/age group, distributions, mean values, standard deviations (SD), and standard errors of the mean (SE) were derived by computer analysis. Computer techniques were employed for subsequent statistical analyses.
HL cm
183 I75
CLARK,
11.2
9*0 10.5
8.1
11.0 7.5 6.2
6.7 7.5 8.0 7.2 9.5 7.4 5.8
1.0
4.2 2.7 6.5 6.4 3.2
5.4 3.8 4.6
3.8 7.3
10.0 10.9 10.6 8.3
5.9 3.4
1.1 1.6 2.5 2.8 1.8 2.1
0.6 0.2 0.3 0.5
0.4
1.1
0.3
0.4 1.5
0.2
1.1 1.1
0.3 0.2
Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (163.015.154.053) on October 30, 2018. Copyright © 1977 American Physiological Society. All rights reserved.
AGING
OF
THE
NORMAL
ADULT
HUMAN
LUNG
TABLE
2. Mean values by ugelsex groups
--
-P-
I
Females
Males Young n=9
Age,
yr
Height, cm TLC, liters VC, liters FRC, liters RV/TLC, % Pst(ti
Middle-Aged n=7
-
Young n=9
Elderly n=8
Middle-Aged n=B
Elderly n = 10
x
SD
SE
s
SD
SE
ii.
SD
SE
ii
SD
SE
ii.
SD
SE
x
SD
SE
29 179 6.80 5.89 2.97 13.02
3.09 4.99 0.944 0.760 0.588 5.97
1.03 1.66 0.315 0.253 0.196 1.99
49 173 6.09 4.91 2.41 19.84
8.98 3.09 0.828 0.374 0.427 8.15
3.39 1.17 0.313 0.141 0.161 3.08
70 173 6.43 4.74 2.84 26.72
2.82 5.36 0.934 0.770 0.548 7.92
0.997 1.90 0.330 0.272 0.194 2.80
29 166 4.71 4.03 2.19 14.68
2.54 4.47 0.580 0.604 0.399 5.29
0.847 1.41 0.193 0.201 0.133 1.76
50 162 4.72 3.61 2.35 23.41
8.30 3.72 0.432 0.466 0.396 7.45
2.93 1.32 0.153 0.165 0.140 2.56
71 158 4.05 2.98 2.08 26.83
1.64 5.40 0.375 0.538 0.161 6.75
0.519 1.70 0.119 0.170 0.051 2.14
35.90 19.10 14.70 11.90 9.64 7.71 5.64
8.53 2.84 1.89 1.52 1.30 1.16 1.43
2.840 0.945 0.631 0.506 0.432 0.386 0.478
33.00 16.90 13.30 10.90 8.93 7.16 5.33
8.65 2.59 1.64 1.25 1.20 1.26 1.73
3.270 0.977 0.620 0.473 0.454 0.477 0.654
33.00 15.90 12.20 9.68 7.89 6.31 4.70
2.87 3.16 2.48 2.11 1.94 1.97 1.60
2.860 1.120 0.876 0.745 0.686 0.697 0.655
36.40 17.50 12.90 9.81 7.52 5.67 3.64
5.84 2.16 1.86 1.72 1.84 2.00 2.57
1.950 0.721 0.622 0.572 0.614 0.667 0.856
25.70 15.10 11.90 9.46 7.45 5.62 4.18
4.04 2.63 2.37 2.24 2.06 1.86 1.45
1.430 0.929 0.838 0.791 0.728 0.658 0.592
23.70 13.30 10.30 8.23 6.79 5.60 5.25
3.85 1.51 1.39 1.46 1.54 1.53 1.46
1.220 0.477 0.438 0.462 0.485 0.483 0.597
10.30 9.31 7.28 5.59 4.00 2.66
1.30 1.52 1.81 1.58 1.20 0.93
0.434 0.506 0.604 0.527 0.402 0.311
9.14 9.01 7.10 4.41 3.21 1.56
1.79 2.05 2.16 1.06 1.39 1.25
0.675 0.775 0.818 0.401 0.524 0.471
8.29 7.66 5.31 3.44 1.48 0.40
1.69 0.96 0.84 0.74 0.74 0.37
0.598 0.340 0.298 0.260 0.262 0.132
6.29 7.03 6.02 4.84 3.37 2.06
1.18 0.90 0.75 0.89 0.64 0.54
0.393 0.300 0.248 0.296 0.213 0.180
6.25 5.65 4.30 3.80 1.80 0.78
0.74 1.26 1.22 1.13 0.93 0.56
0.262 0.444 0.430 0.400 0.330 0.200
6.00 5.24 3.84 2.41 1.03 0.30
1.06 1.28 1.05 0.88 0.64 0.29
0.335 0.406 0.333 0.279 0.203 0.096
at %TLC, CmH~O
100% 90% 80% 70% 60% 50% 40%
TLC TLC TLC TLC TLC TLC TLC
r’,,,
at %TLC, 1 -s--l 90% TLC 80% TLC 70% TLC 60% TLC 50% TLC 40% TLC
data for the three age groups are snown ror males and females, respectively, in Table 2. In these tables, Pst(L) and maximum expiratory flow (v,,,) values are given for volumes at decile increments of each subject’s TLC, but presented as means in Table 2. Because measurements of pleural pressure by the esophageal balloon technique may be unreliable at low lung volumes (25), no data are reported for volumes less than 40% of TLC. Static deflation PV curves based on mean values for each age/sex group are shown in Fig. 1. To standardize for lung size, volume is expressed at %TLC though Pst(L) is given in absolute units of cmH,O. Inspection of these PV curves reveals age-related changes within each sex. With advancing age, there is progressive loss of lung elastic recoil and, at least in women, a change in the slope of the PV curve. From these data, age regressions were developed separately for men and for women and also for all subjects collectively. In Table 3 these age regressions are shown for Pst(L) at decile increments of TLC. In women, age-related decrease in Pst(L) does not appear to be significant at volumes below 60% TLC. At 40% TLC, the loss of lung elastic recoil is of only minimal significance in men and of no significance when all subjects are considered. Static compliance was taken as the chord slope of the static deflation PV curve between FRC and FRC + 0.5 liters. This value did not show a significant change with age. Dynamic compliance during quiet breathing (mean frequency = 14.5 breaths/min) also showed no change with age. As anticipated, the RV/TLC ratio increased with age. Using values for flow at decile and quartile increments of the expired VC, mean MEFV curves were reconstructed for each of the sex/age groups. These mean MEFV curves are shown in Fig. 2 where only the descending or effort-independent portions are shown.
ae FEMALES
------elderly -middle
20
aged
----young
o!
1 0
10 Pst(L)
I
.
I
20
30
40
Hz01
km
FIG. 1. Mean pressure-volume curves for males and females by age group. To compensate for differences in size, volume is expressed as %TLC.
To compensate for differences in lung size among the groups, flow is expressed at TLC s-l and volume as percent expired VC, with RV equal to 100% of expired VC. Although inspection of these curves suggests that there is an age-related decrease in V,,, at low lung volumes, the degree of significance of this change in shape of the MEFV curve is not immediately apparent. However, when the data were subjected to further analysis, the decrease in v,,, with age was found to be l
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1058
KNUDSON,
3. Age regressions I
TABLE
TLC TLC
TLC TLC
TLC 50%TLC 40% TLC
A
B
37.48
- 0.0698
8.18
21.41 16.75 13.71 11.27 9.17 6.96
-0.0826 -0.0679 -0.0588 -0.0499 -0.0431 -0.0360
3.09 2.24 1.85 1.64 1.56 1.55
A = regression
constant;
SD
B = slope; Pst(L)
R
0.154 0.482 0.547 0.572 0.551 0.500 0.407
Q
4 cc
0.472(M) 0.017 0.006 0.003 0.005 0.013 0.060
A
B
SD
R
42.13 20.30 14.70 11.03 8.18 5.88 2.56
-0.2680 -0.0994 -0.0605 -0.0376 -0.0188 -0.0050 0.0370
7.28 2.71 2.12 1.87 1.77 1.72 2.04
0.683 0.681 0.531 0.373 0.197 0.054 0.326
deviation
1.5
MALES
*.--. 1 -9.
FEMALES
1.0 0.5 0 20
0
%
40
Expired
60
100
VC
2. Maximum expiratory flow-volume curves females by age group. To compensate for differences expressed as TLC mS-I and volume as percent expired effort-independent portions of the curves are shown. FIG.
80
for males and in size, flow is VC. Only the
of statistical significance only at volumes below 70% expired VC. By analysis of variance, significance (P) was well above 0.5 at volumes greater than 60% VC, but was less than 0.015 at volumes after 70% VC had been expired. This age-related change in size-compensated flow was observed when vmax was expressed as either TLC s-l or VC s-4 l
KNUDSON
P
