Lung Volume Reference Values for Women and Men

65 to 85 Years of Age
Francisco Garcia-Rio1, Ali Dorgham1, Jose M. Pino1, Carlos Villasante1, Cristina Garcia-Quero1,
and Rodolfo Alvarez-Sala1
1

Servicio de Neumologa, Hospital Universitario La Paz, Madrid, Spain

Rationale: In elderly subjects, static lung volumes are interpreted

using prediction equations derived from primarily younger adult
populations.
Objectives: To provide reference equations for static lung volumes for
European adults 65 to 85 years of age and to compare the predicted
values of this sample with those from other studies including middleaged adults. We compare the lung volumes by plethysmography and
helium dilution in elderly subjects.
Methods: Reference equations were derived from a randomly selected sample from the general population of 321 healthy neversmoker subjects 65 to 85 years of age. Spirometry and lung volume
determinations by plethysmography and multibreath helium equilibration method were performed following the American Thoracic
Society/European Respiratory Society recommendations. Reference
values and lower and upper limits of normal were derived using
a piecewise polynomial model.
Measurements and Main Results: Plethysmography provided higher
values than the dilutional method for all lung volumes, with wide
limits of agreement. In addition to height, our reference equations
confirm the age- and body size dependence of lung volumes in older
subjects. Practically all the estimations performed by extrapolating
reference equations of middle-aged adults overpredicted the true
lung volumes of our healthy elderly volunteers. Middle-aged reference equations classify subjects as being below the total lung
capacity lower limit of normal between 17.9 and 62.5% of the
women and between 12.5 and 42.2% of the men of the current study.
Conclusions: These results underscore the importance of using prediction equations appropriate to the origin, age, and height characteristics of the subjects being studied.
Keywords: lung volume measurement; aged; prediction equations;
total lung capacity; plethysmography

The determination of static lung volumes is essential for the

diagnosis of restrictive or mixed ventilatory defects (1). In
obstructive defects, it may also help to disclose underlying
diseases, to evaluate their functional consequences, and to
assess their severity (13).
Although the proportion of individuals older than 65 years of
age is increasing, many of the reference equations commonly
used for predicting normal lung volume values in North
America and Europe have been derived from studies that
included relatively small numbers of individuals over 65 years
of age (411). In fact, predicted values for older individuals are
often based upon few observations or upon extrapolations from

(Received in original form January 23, 2009; accepted in final form September 3, 2009)
Supported by FIS (99/0218) and NEUMOMADRID grants.
Correspondence and requests for reprints should be addressed to Francisco
Garcia-Rio, Ph.D., Alfredo Marquerie 11, izqda 1A, Madrid, 28034, Spain; E-mail:
fgr01m@gmail.com
This article has an online supplement, which is accessible from this issues table of
contents at www.atsjournals.org
Am J Respir Crit Care Med Vol 180. pp 10831091, 2009
Originally Published in Press as DOI: 10.1164/rccm.200901-0127OC on September 10, 2009
Internet address: www.atsjournals.org

AT A GLANCE COMMENTARY
Scientific Knowledge on the Subject

In elderly subjects, static lung volume measurements are

interpreted using prediction equations derived from primarily younger adult populations. The current international guidelines recommend that reference equations
should not be extrapolated for ages or heights beyond
those covered by the data that generated them.
What This Study Adds to the Field

This study provides the first reported data on reference

equations for static lung volumes in older adults.

data acquired in studies of younger adults. Remarkable differences in these predicted values may be ascribed to the selection
of subjects and to methodologic or technical differences in the
assessment. Moreover, because most of the studies were performed at least two decades ago, they may not fit present-day
populations due to cohort effects.
The main limitation of applying prediction equations derived
from primarily younger adult populations to older adults might
come from the morphologic and functional changes in the
respiratory system related to ageing (12, 13). Structural changes
associated with ageing include smaller airway size, an increase
in alveolar duct diameter with a concomitant change in the
morphology of the alveolar sacs (which become larger), a decrease in lung elastic tissue, and an increase in lung collagen
concentrations and in the proportion of type III collagen (12, 14,
15). These morphologic changes, in addition to a decrease in
chest wall compliance and a decrease in respiratory muscle
strength, produce several changes in the pulmonary function of
elderly subjects, such as a decrease in the static elastic recoil of
the lung, an increase in pulmonary compliance, and small airway
closure resulting in air trapping (13, 16).
In addition to the obvious consequences that these alterations might have on static lung volumes, the calculation of
these volumes might be affected by the measurement procedures used. Because the plethysmographic and dilutional
methods give the same results in healthy adults, the reference
values derived from these techniques are used interchangeably
in adults (5, 6). However, the existence of air trapping in elderly
subjects might result in a significant underestimation of true
lung volumes measured by helium dilution as compared with
plethysmography.
The aims of this paper are to provide reference equations for
static lung volumes for a cohort of healthy never-smoking white
European adults between 65 and 85 years of age and to compare
the predicted values of this sample with those from other studies
including middle-aged adults. In addition, we compare the
measurements of lung volumes by plethysmography and helium
dilution in healthy elderly subjects.

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AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 180

METHODS
Subjects
A random sample of never-smoker subjects without respiratory or
cardiovascular disease was recruited from the elderly population of the
Madrid metropolitan area (17).
Screening was based on a combination of questionnaire on respiratory symptoms (18), physical examination, and chest radiograph
and electrocardiography evaluation. A detailed description of the
exclusion criteria and the subject selection procedure is contained in
the online supplement. The study was approved by the local Ethics
Committee, and informed consent was obtained from all subjects.

Methods
Subjects were weighed and measured while wearing indoor clothing
without shoes, and body mass index (BMI) and body surface area
(BSA) were calculated. Age was recorded to the nearest birthday.
Lung function tests were performed with a MasterLab 4.6 system
(Jaeger, Wurtzburg, Germany). After a spirometry following ATS/
ERS recommendations (19), lung volumes were determined using
a variable-pressure plethysmograph, also in accordance with ATS/
ERS recommendations (20). Thoracic gas volume at the level of
functional residual capacity (FRCpleth) was measured while the subjects made gentle breathing movements against the shutter at a rate of
less than 1/s (5). Expiratory reserve volume (ERV) and inspiratory VC
were measured during the same maneuver. FRCpleth was reported as
the mean of three or more measurements that differed by less than 5%.
Residual volume (RVpleth) was calculated as FRCpleth 2 ERV and
TLCpleth as FRCpleth 1 VC. Airway resistance was computed from
pressure and flow measurements breathing warm, moist air fulfilling
BTPS conditions (21).
Thirty minutes afterward, lung volumes were measured using the
multibreath helium equilibration method. The closed circuit was filled
with a mixture of 10% He, 35% O2, and 55% N2. A helium thermal

2009

conductivity analyzer was used. Helium equilibration was considered

to be complete when the change in helium concentration was less than
0.02% for 30 seconds (5, 20). Rebreathing started from the resting endexpiratory position and ended after 5 to 7 minutes. FRCHe was the
mean of two technically acceptable measurements that agreed by less
than 10%. At the end of rebreathing, a number of ERV and VC
maneuvers were performed to calculate TLCHe and RVHe.

Analysis
Values are expressed as mean 6 SD. Lung volumes were compared
by paired Students t test, and agreement between pairs was analyzed
(21). Independent variables considered for inclusion in the models
were age, standing height, weight, BMI, BSA, and their exponential,
logarithmic, or square root transformations. In the multiple linear
regression analysis, predictor variables were retained only if their
addition significantly improved the fraction of explained variability
(R2). The assumptions of linearity and distributional normality were
controlled. The lower limit of normal (LLN) range was calculated as
follows: predicted value 1.645 3 RSD (where RSD is the residual
standard deviation).
The selection of prediction equations for comparison was based on
common use (410). Differences between observed and predicted
values are given as mean difference, mean squared difference, and
standardized prediction deviation. For comparisons among authors,
LLN was calculated using the RSD of the corresponding equation. The
differences between predicted values based on the prediction equations
from the present study and others are given as Bland and Altman plots.
Statistical significance was assumed for P , 0.05.

RESULTS
A total of 583 subjects underwent clinical evaluation; 201
subjects were excluded due to dyspnea (n 5 24), cough (n 5
17), wheezing (n 5 13), or for several previously undetected

TABLE 1. DESCRIPTIVE DATA

Women (n 5 189)
Age, years
Height, cm
Weight, kg
BMI, kg/m2
BSA, m2
FVC, L
FEV1, L
FEV1/FVC, %
ERV, L
VC, L
IRV, L
IC, L
TLCHe, L
FRCHe, L
RVHe, L
RV/TLCHe, %
FRC/TLCHe, %
TLCpleth, L
FRCpleth, L
RVpleth, L
RV/TLCpleth, %
FRC/TLCpleth, %
IC/TLC pleth, %
Raw, kPa.l21.s
sRaw, kPa/s

Figure 1. Flow chart for subject selection.

73
152
61
26.4
1.58
2.29
1.80
78.9
0.83
2.39
0.92
1.57
3.73
2.12
1.40
37.3
57.2
3.91
2.34
1.52
38.7
60.1
39.9
0.49
1.30

6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6

6*
6
7
2.4
0.11
0.47
0.41
5.6
0.40
0.48
0.44
0.47
0.68
0.46
0.40
7.9
8.3
0.69
0.47
0.43
7.7
8.6
8.5
0.29
0.71

Men (n 5 132)
72
166
73
26.6
1.81
3.46
2.65
76.8
1.20
3.65
1.45
2.45
5.41
2.91
1.73
31.7
54.5
5.59
3.14
1.94
34.3
56.8
43.2
0.34
1.21

6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6

5
6
8
2.2
0.12
0.64
0.52
5.5
0.46
0.65
0.66
0.73
1.02
0.60
0.58
8.3
9.1
0.99
0.57
0.56
7.0
8.7
8.7
0.17
0.51

Definition of abbreviations: BMI 5 body mass index; BSA 5 body surface area;
ERV 5 expiratory reserve volume; FRCHe 5 functional residual capacity by helium
dilution; FRCpleth 5 functional residual capacity by plethysmography; IC 5
inspiratory capacity; IRV 5 inspiratory reserve volume; Raw 5 airway resistance;
RVHe 5 residual volume by helium dilution; RVpleth 5 residual volume by
plethysmography; sRaw 5 specific airway resistance; TLCHe 5 total lung capacity
by helium dilution; TLCpleth 5 total lung capacity by plethysmography.
* Values are mean 6 SD.

Garcia-Rio, Dorgham, Pino, et al.: Lung Volumes in Elderly Subjects

diseases, such COPD (n 5 11), asthma (n 5 8), scoliosis (n 5 3),

or obesity (BMI >30 kg/m2) (n 5 125). Of the 382 subjects (231
women and 151 men) who entered into the study, we found
technically acceptable tests for 321 (189 women and 132 men).
Sixty-one subjects (9.8% of men and 13.4% of women) were
excluded from analysis because of claustrophobia (n 5 2),
incapacity to perform satisfactory panting maneuvers (n 5
37), or repeated disconnections from the test gas during
rebreathing (n 5 22) (Figure 1). The elderly subjects who were
excluded or were ineligible for the study were similar in age,
height, and weight as those who were included.
The age distribution of the women and men in the analyzed
sample demonstrates adequate representation of the study
population (see Table E1 in the online supplement). Details
of the anthropometric characteristics, spirometric data, lung
volumes, and airway resistance in both sexes are shown in Table
1. No significant differences in these parameters were found
between excluded subjects and the analyzed sample.

1085

In men and in women, the plethysmographic method provided higher values than the dilutional method for TLC, FRC,
or RV (P , 0.001 in all comparisons) (Table 1). The mean
differences of lung volumes (plethysmographic 2 helium dilution) and their 95% limits of agreement were wide, reflecting
as great a within-subject variability as that from method-related
differences (Figure 2). Because the 95% limits of agreement for
static lung volumes include zero, it is not possible to conclude
that the helium dilution method systematically underestimates
static lung volumes in healthy individuals.
The reference equations for lung volumes from the healthy
older European women and men are given in Tables 2 and 3.
We did not find that the addition of transformations significantly improved the predictability of the regression equations.
No significant interaction between age and height was found.
Analysis of residuals showed that homoscedasticity was present
in all equations. Regression analysis of these residuals showed
neither statistically significant slopes nor correlation coeffi-

Figure 2. Differences between

lung volumes measured by
plethysmography and helium
dilution plotted against the
mean of the two values for
TLC, FRC, and residual volume
(RV) in healthy elderly women
and men. The continuous line
represents the mean difference; the dashed lines represent 2 SD around the mean.

1086

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE VOL 180

2009

TABLE 2. LUNG VOLUME PREDICTION EQUATIONS FOR HEALTHY ELDERLY EUROPEAN WOMEN*
Equation
ERV, L
VC, L
IRV, L
IC, L
TLCpleth, L
FRCpleth, L
RVpleth, L
RV/TLCpleth, %
FRC/TLCpleth, %
IC/TLC, %
Raw, kPa/L/s
sRaw, kPa/s
TLC He, L
FRC He, L
RV He, L
RV/TLC He, %
FRC/TLC He, %

0.09238 0.00000059 A3 1 0.000000368 H3 0.00000143 W3

2.773 0.0339 A 1 0.0000006728 H3 0.00000123 W3
1.214 0.0234 A 1 0.892 BSA
1.771 0.0254 A 1 0.00007121 H2
11.495 0.208 A 1 0.00001062 A3 1 0.0002588 H2 21.654 BSA
2.276 1 0.0000008882 H3 1.96 BSA
21.039 1 0.01678 H
29.404 1 0.00002356 A3
36.39 1 0.325 A
63.529 0.324 A
20.923 1 0.0000591 A2 2 0.0000009 W3 1 0.04985 BMI
21.737 1 0.02386 A 1 0.04914 BMI
20.00889 0.0365 A 1 0.05085 H 0.0518 BMI
23.896 1 0.06151 H 2 2.135 BSA
22.07 1 0.02266 H
27.091 1 0.00002554 A3
44.46 1 0.393 A 0.61 BMI

R2

RSD

0.150
0.552
0.162
0.219
0.437
0.304
0.061
0.085
0.047
0.047
0.155
0.069
0.412
0.243
0.120
0.086
0.092

0.3731
0.3214
0.4068
0.4199
0.5238
0.3902
0.4168
7.3748
8.3715
8.3649
0.2659
0.6912
0.5232
0.3999
0.3753
7.5377
7.9339

Definition of abbreviations: A 5 age in years; BMI 5 body mass index in kg/m2; BSA 5 body surface area in m2; H 5 height in
cm; RSD 5 residual standard deviation; W 5 weight in kg.
* The lower limit of normal is computed as: predicted value 1.645 3 RSD. The upper limit of normal is computed as:
predicted value 1 1.645 3 RSD.

cients. The residuals corresponding to these models did not

differ significantly from a Gaussian distribution in all lung
volumes, as determined by the Shapiro-Wilk test. Therefore,
one-sided lower 95% prediction intervals were used to determine the lower limit of normal lung functions (5). Because
the use of weight or weight-related factors for reference
equations would affect to the accuracy of prediction values
among morbidly obese subjects, in Table 4 we provide the
prediction equations for these lung volumes without weightrelated factors.
Tables 5 and 6 show the differences between the observed
values found in the subjects of our study and the values
calculated from several prediction equations. Aside from our
equations, the closest agreements for plethysmographic lung
volumes were with Cordero and colleagues (9) and ECSC (5) in
women and with Crapo and coworkers (4) in men. Regarding
dilutional lung volumes, in women the closest agreements for

TLC were with Crapo and colleagues (4) and ECSC (5),
whereas the closest for FRC was with Cordero and coworkers
(9) and ECSC (5) and for RV with Cordero and colleagues (9)
and Matthys and coworkers (7). In men, the closest TLC
agreements were with Crapo and colleagues (4) and Cordero
and coworkers (9), for FRC with Crapo and coworkers (4) and
Cotes and colleagues (10), and for RV with Matthys and
colleagues (2) and Crapo and coworkers (4).
To compare our reference equations with other prediction
equations, the difference in predicted lung volumes (present
study equation every other equation) by the mean predicted
lung volumes were plotted for women and men, respectively. In
women, Matthys and colleagues (7) and Roca and coworkers
(8) overestimated FRCpleth and FRCHe, whereas Cotes and
coworkers (10) underestimated this lung volume (Figure 3). In
men, the ratio increased proportionally when the present prediction values for FRCpleth were compared with those from

TABLE 3. LUNG VOLUME PREDICTION EQUATIONS FOR HEALTHY ELDERLY EUROPEAN MEN*
Equation
ERV, L
VC, L
IRV, L
IC, L
TLCpleth, L
FRCpleth, L
RVpleth, L
RV/TLCpleth, %
FRC/TLCpleth, %
IC/TLC, %
Raw, kPa/L/s
sRaw, kPa/s
TLC He, L
FRC He, L
RV He, L
RV/TLC He, %
FRC/TLC He, %

A3

W3

1 0.03028 H 0.000000959
23.907 1 0.000001217
2.064 0.00000320 A3 1 0.0000006171 H3
2.037 0.00000257 A3 1 0.0000009746 W3
2.327 0.00000455 A3 1 0.0000004124 H3
2.321 0.00000309 A3 1 0.0000009765 H3
21.425 1 0.02188 A 1 0.0000007418 H3 0.00000103 W3
0.315 1 0.0000003551 H3
11.590 1 0.314 A
32.759 1 0.00006201 A3
67.229 0.0000620 A3
1.717 1 0.005391 A 0.0117 H 1 0.000000414 W3
21.750 1 0.02208 A 1 0.05122 BMI
2.530 1 20.00000352 A3 1 0.0000009212 H3
0.838 1 0.0000004526 H3
22.703 1 0.03978 A 1 0.02261 W
23.79 1 0.00002066 A3
34.716 1 0.00005152 A3

R2

RSD

0.139
0.476
0.179
0.435
0.354
0.282
0.095
0.059
0.403
0.402
0.136
0.091
0.335
0.132
0.187
0.054
0.278

0.4299
0.4738
0.6054
0.5545
0.8001
0.4865
0.5369
6.8354
6.7594
6.7669
0.1564
0.4901
0.8429
0.5626
0.6184
8.1326
7.7813

Definition of abbreviations: A 5 age in years; BMI 5 body mass index in kg/m2; BSA 5 body surface area in m2; H 5 height in
cm; RSD 5 residual standard deviation; W 5 weight in kg.
* The lower limit of normal is computed as: predicted value 1.645 3 RSD. The upper limit of normal is computed as:
predicted value 1 1.645 3 RSD.

Garcia-Rio, Dorgham, Pino, et al.: Lung Volumes in Elderly Subjects

1087

TABLE 4. LUNG VOLUME PREDICTION EQUATIONS WITHOUT WEIGHT-RELATED FACTORS*

Women
ERV, L
VC, L
IRV, L
TLCpleth, L
FRCpleth, L
Raw, kPa/L/s
sRaw, kPa/s
TLC He, L
FRC He, L
FRC/TLC He, %
Men
ERV, L
IRV, L
FRCpleth, L
Raw, kPa/L/s
sRaw, kPa/s
RV He, L

Equation

R2

RSD

0.07476 0.0000002534 H3
2.90 0.03375 A 1 0.0000005504 H3
1.932 0.02309 A 1 0.0000001885 H3
12.383 0.243 A 1 0.00001271 A3 1 0.0001824 H2
0.563 1 0.0000004998 H3
0.546 1 0.009432 A 0.00003178 H2
20.542 1 0.02527 A
21.690 0.03779 A 1 0.05354 H
22.427 1 0.02976 H
29.951 1 0.372 A

0.080
0.524
0.149
0.416
0.233
0.100
0.041
0.379
0.159
0.060

0.3859
0.3301
0.4099
0.5223
0.4083
0.2735
0.6996
0.5358
0.4199
8.0392

0.098
0.143
0.251
0.056
0.043
0.037

0.4384
0.6162
0.4949
0.1621
0.5008
0.5313

22.131
2.543
21.215
1.443
20.204
0.771

1 0.000001359 A3 1 0.01691 H
0.00000285 A3
1 0.02434 A 1 0.0000005659 H3
0.006653 H
1 0.01949 A
1 0.0000002113 H3

Definition of abbreviations: A 5 age in years; BMI 5 body mass index in kg/m2; BSA 5 body surface area in m2; H 5 height in
cm; RSD 5 residual standard deviation; W 5 weight in kg.
* The lower limit of normal is computed as: predicted value 1.645 3 RSD. The upper limit of normal is computed as:
predicted value 1 1.645 3 RSD.

ECSC (5), whereas it decreased proportionally with respect to

Cordero and coworkers (9) and Cotes and colleagues (10)
(Figure 4). Roca and coworkers (8) and Matthys and colleagues
(7) clearly overestimated FRCpleth in men. For women and for
men, all the analyzed adult-derived reference equations overpredicted TLCpleth, TLCHe, and RVpleth (Figures E1E12).

DISCUSSION
To our knowledge, the current study provides the first data in
the international literature on reference values for static lung
volumes and airway resistance in healthy older adults. Our

results confirm that reference equations should not be extrapolated, in general, for ages or heights beyond those covered by
the data that generated them. For patients over 65 years of age,
the current study shows that the most commonly used sets of
reference equations may lead to inaccurate interpretations.
The exact definition of a healthy group is difficult to agree
upon. Although criteria to define subjects as healthy have been
established in previous ATS statements (22), previous studies
have used many different criteria. The ECSC reference equations (5, 6) were not based on original data; rather, they were
derived from previously published reference equations. Moreover, the data on TLC, RV, and FRC are derived from

TABLE 5. COMPARISON BETWEEN OBSERVED PLETHYSMOGRAPHIC LUNG VOLUMES AND THE PREDICTED VALUES DERIVED FROM
DIFFERENT REFERENCE EQUATIONS
Women

TLC
Present
ECSC (5)
Crapo (4)
Cordero (9)
Roca (8)
Matthys (7)
FRC
Present
ECSC (5)
Crapo (4)
Cordero (9)
Roca (8)
Matthys (7)
Cotes (10)
RV
Present
ECSC (5)
Crapo (4)
Cordero (9)
Roca (8)
Matthys (7)

Men

Mean
Difference (%)

Mean
Squared
Difference

Standardized
Prediction
Deviation

% Observed
Values below the
LLN or over ULN*

Rank

Mean
Difference (%)

Mean
Squared
Difference

Standardized
Prediction
Deviation

% Observed
Values Below the
LLN or over ULN*

Rank

24.0
217.8
223.6
214.8
236.8
228.9

0.552
0.745
0.851
0.699
1.098
0.956

20.094
21.308
21.826
21.043
22.826
22.156

5.7
23.4
40.8
17.9
62.5
50.0

1
3
4
2
6
5

22.2
213.3
211.6
213.3
225.7
218.4

0.731
0.832
0.808
0.842
1.063
0.922

0.001
20.689
20.571
20.698
21.464
21.024

4.3
16.4
12.5
15.6
42.2
25.0

1
3
2
4
6
5

23.3
216.0
216.8
24.8
222.0
217.9
21.5

0.402
0.599
0.612
0.476
0.666
0.624
0.665

20.035
20.809
20.843
0.146
21.137
20.866
1.363

1.3
1.6
1.1
5.4
0
0
22.8

1
3
4
2
7
5
6

22.5
212.9
24.2
212.9
216.4
214.3
211.8

0.583
0.651
0.595
0.641
0.685
0.666
0.634

20.005
20.593
20.100
20.660
20.848
20.716
20.592

3.9
0.8
2.3
0.8
0.8
0.8
0.8

1
5
2
4
7
6
3

23.5
238.2
247.7
221.7
246.2
231.1

0.497
0.710
0.778
0.597
0.765
0.660

20.003
21.447
21.749
20.894
21.728
21.173

2.2
0
0
0
0
0

1
4
6
2
5
3

211.4
246.8
229.9
234.8
247.9
229.1

0.571
0.750
0.628
0.645
0.755
0.627

0.002
21.072
20.564
20.724
21.134
20.536

2.3
0
0
0
0
0

1
5
3
4
6
2

* Lower limit of normal (LLN) range was calculated as predicted value RSD 3 1.645. Upper limit of normal (ULN) range was calculated as predicted value 1 RSD 3
1.645. Rank of the mean square difference is shown. Upper limit of normal is applicable to FRC and RV.

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TABLE 6. COMPARISON BETWEEN OBSERVED DILUTIONAL LUNG VOLUMES AND THE PREDICTED VALUES DERIVED FROM
DIFFERENT REFERENCE EQUATIONS*
Women

TLC
Present
ECSC (5)
Crapo (4)
Cordero (9)
Roca (8)
Matthys (7)
FRC
Present
ECSC (5)
Crapo (4)
Cordero (9)
Roca (8)
Matthys (7)
Cotes (10)
RV
Present
ECSC (5)
Crapo (4)
Cordero (9)
Roca (8)
Matthys (7)

Men

Rank

Mean
Difference %

Mean
Squared
Difference

Standardized
Prediction
Deviation

% Observed
Values below the
LLN or over ULN

Rank

4.3
31.9
48.6
23.9
75.4
60.1

1
3
4
2
6
5

1.6
213.3
211.6
213.3
225.7
218.4

0.756
0.832
0.808
0.842
1.063
0.922

0.260
20.689
20.571
20.698
21.464
21.024

3.1
16.4
12.5
15.6
42.2
25.0

1
3
2
4
6
5

20.084
21.035
21.125
20.462
21.401
21.183
0.975

4.3
1.4
0.0
2.2
0.0
0.0
26.1

1
4
5
2
7
6
3

24.8
212.9
25.2
212.9
216.4
214.3
211.8

0.422
0.651
0.595
0.641
0.685
0.666
0.634

0.151
20.593
20.200
20.660
20.848
20.716
20.592

3.3
1.6
2.3
0.8
0.8
0.8
0.8

1
5
2
4
7
6
3

20.079
21.636
21.943
21.099
21.891
21.417

3.6
0
0
1.4
0
0

1
4
6
2
5
3

8.3
246.8
229.9
234.8
247.9
229.1

0.581
0.750
0.628
0.645
0.755
0.627

0.509
21.072
20.564
20.724
21.134
20.536

5.0
0
0
0
0
0

1
5
3
4
6
2

Mean
Difference %

Mean
Squared
Difference

Standardized
Prediction
Deviation

% Observed
Values below the
LLN or over ULN

23.1
219.8
225.2
217.3
238.4
230.9

0.546
0.790
0.893
0.744
1.107
0.993

20.117
21.202
21.582
21.053
22.461
21.938

24.8
224.4
226.4
212.2
232.0
228.7
16.2

0.521
0.645
0.671
0.552
0.739
0.705
0.605

210.1
254.5
263.9
239.1
261.7
248.6

0.484
0.741
0.813
0.624
0.794
0.700

* Lower limit of normal range (LLN) was calculated as predicted value RSD 3 1.645. Upper limit of normal range (ULN) was calculated as predicted value 1 RSD 3
1.645. Rank of the mean square difference is shown.

ULN is applicable to FRC and RV.

populations that include smokers and exsmokers (6); therefore,

these equations may not be representative of a healthy nonsmoking population. In the study by Cotes and colleagues (10),
some exsmoker women were included in the reference group. In
contrast, all of the current study patients were lifelong nonsmokers. Also, notable differences exist in the technique used to
determine lung volumes. In some cases, the reference equations
were obtained from measurements for single-breath helium
dilution (4), in others from multiple breath helium dilution (5,
9, 10), and in others by plethysmography (7, 8).
Although it has been proposed to use the same reference
values for plethysmographic and dilutional methods in middleaged adults (6), the comparison of lung volumes measured by
plethysmography and helium dilution shows statistically significant differences despite substantial interindividual variation
(see Table 1; Figure 2). As a consequence of the reduction in
supporting tissue around the airways, distal airways begin to
close at a higher lung volume in elderly people than in younger
people (12). Despite the absence of airway obstruction in our
subjects, the existence of poorly- or nonventilated airspaces or
a premature closure of the airways during tidal breathing (13)
could explain the lower lung volumes obtained by helium
dilution. In any case, the differences obtained between plethysmography and helium dilution are notable, as demonstrated
by the wide limits of agreement for TLC (20.29 to 0.73 L in
women and 20.22 to 0.79 L in men) (see Figure 2). Because the
difference obtained between the two procedures is not calculable beforehand, it seems necessary to use specific sets of
reference equations for every procedure in elderly subjects.
Usually, lung volumes are related to body size, with standing
height being the most important factor (19), but our results
support the importance of other factors.
Although many reference equations for FRC only consider
age and height (47), those of Cordero (9), Roca (8), and Cotes
(10) include other body measurements, such as weight, BMI, or

BSA. In our case, we verify that body size is an important factor

related to FRC, expressed essentially as BSA. This result is
consistent with the clinical observation that obesity has the
greatest effect on FRC because the effect of body fat on lung
volumes is determined by the decrease of total and chest wall
compliance (13), which reduces FRC (23). However, the inclusion of BSA in the prediction equations for FRC may lead to
misinterpretation of the results. Likewise, it has been suggested
that the incorporation of body composition measurements,
especially fat-free mass index, increases the accuracy of the
reference equations for lung volumes (10). Nevertheless, it is
difficult to recommend the incorporation of these measurements
in all routine explorations, except in the most sophisticated lung
function laboratories. The application of our reference equations
to morbidly obese subjects might reduce their accuracy, and this
would result in a significant tendency toward misclassification of
obesity-associated restriction by undepredicting lung volumes.
To avoid this problem, we have generated another set of
reference equations without weight-related factors (see Table
4). The use of both prediction equations allows for distinguishing
if high weight is the sole cause for a low lung volume or whether
there is some other contributing process.
In addition to height dependence, our reference equations
confirm the importance of incorporating age in the prediction of
TLC in women and in elderly men. The age-related decrease in
diaphragmatic strength (24) reduces maximal respiratory pressures in healthy elderly subjects (25) and can consequently
reduce inspiratory capacity. A reduction in diaphragmatic
strength, by about 25% in healthy elderly subjects compared
with young adults (25), must have some effect on TLC.
Similarly, age was directly related to RV in women and in
men. In addition to the increased closing volume, this can be
justified by the age-related weakness of the expiratory muscles.
Previously, it has been demonstrated that the expiratory intercostal muscles undergo atrophy with a decrease of approx-

Garcia-Rio, Dorgham, Pino, et al.: Lung Volumes in Elderly Subjects

1089

Figure 3. Difference between plethysmographic FRC and mean FRC predicted by the present study versus (A) ECSC and colleagues (5), (B) Crapo
and colleagues (4), (C) Cordero and colleagues (9), (D) Roca and colleagues (8), (E) Matthys and colleagues (7), and (F) Cotes and colleagues (10) in
women.

imately 20% in the mean cross-sectional area after the fifth

decade (26). Moreover, with increasing age, the chest wall
becomes less compliant, and the lungs become more distensible.
As a result of the diminished lung elastic recoil, an increase in
RV by approximately 50% between 20 and 70 years of age has
been reported (13).
Practically all the estimations made by extrapolation of
reference equations for middle-aged adults overpredicted the
true lung volumes of our healthy elderly volunteers. An increase in static lung volume has been reported during normal
ageing as a consequence of the decrease in the elastic recoil of
the lung secondary to changes in the lung connective tissue (12).
However, it is possible that these changes mimic those observed
in emphysema and are of a lesser magnitude than expected.
Biochemical studies suggest that the total lung content of
collagen and elastin does not change with ageing and that the
collagen becomes more stable because of increased numbers of
intermolecular crosslinks (27). Morphometric studies in senescence-accelerated animal models have not shown evidence of

cellular infiltration or a decrease in the ratio of lung weight to

body weight, suggesting little or no lung destruction, as opposed
to what is seen in emphysema (28). As a consequence of
changes in the spatial arrangement or crosslinking of the elastic
fiber network (29), a homogeneous enlargement of air spaces
occurs, followed by discrete lung hyperinflation. The changes
observed in senile lungs are morphologically and histologically
different from emphysema, and their major consequences seem
to be a tendency toward small airway collapse and a decrement
in expiratory flow with ageing (13, 17).
An example of the overprediction of lung volumes is provided by the estimation of healthy subjects below or over the
limits of normal. Because prediction equations derived from
cross-sectional data are primarily used as a screening tool to
identify individuals with lung function outside the expected
range, the utility of any particular reference equation depends
upon its ability to correctly identify individuals with lung
function below the lower limit of normal (LLN) or over the
upper limit of normal. Some authors have defined the LLN as

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Figure 4. Difference between plethysmographic FRC and mean FRC predicted by the present study versus (A) ECSC and colleagues (5), (B) Crapo
and colleagues (4), (C) Cordero and colleagues (9), (D) ROCA and colleagues (8), (E) Matthys and colleagues (7), and (F) Cotes and colleagues (10)
in men.

that value above which the results of 95% of the normal

population lie, working under the assumption that larger values
have larger variances. However, if skewed distributions are
transformed to normalize their shape, the subtraction of 1.645
SD may still be used to estimate the LLN. Middle-aged
reference equations classify subjects as being below the plethysmographic TLC LLN between 11.8 and 55.5% of the
women and between 14.1 and 25.9% of the men of the current
study. In contrast, only 0.6 to 1.7% of the women and 0.1 to
0.3% of the men were above the upper limit of normal of
plethysmographic RV.
In conclusion, we have developed reference equations for
the prediction of static lung volumes in older adults. Differences
among studies in predictions of lung volumes or in the
identification of individuals with lung function values outside
the limits of normal may be due to differences in the age range
of the reference subjects but are also likely to be contributed to
by different measurement methods and other differences in the
underlying populations. These results underscore the impor-

tance of using prediction equations appropriate to the age and

height characteristics of the population to whom inferences are
to be applied. Our reference equations may be used for the
prediction of lung volumes in white patients 65 to 85 years of
age with standing heights for women between 144 and 174 cm
and men between 152 and 181 cm. The use of our reference
equations beyond these age and height limits may lead to
inaccuracies.
Conflict of Interest Statement: F.G-R. has participated as a speaker in scientific
meetings or courses organized and financed by various pharmaceutical companies (GlaxoSmithKline, AstraZeneca, Pfizer, Boehringer Ingelheim, and Merck
Sharp & Dohme), serves as a consultant to Pfizer and GlaxoSmithKline and on an
advisory board for Boehringer Ingelheim, and has received research grants
sponsored by GlaxoSmithKline and CarburosMedica. A.D. does not have
a financial relationship with a commercial entity that has an interest in the
subject of this manuscript. J.M.P. does not have a financial relationship with
a commercial entity that has an interest in the subject of this manuscript. C.V.
does not have a financial relationship with a commercial entity that has an
interest in the subject of this manuscript. C.G-Q. does not have a financial
relationship with a commercial entity that has an interest in the subject of this
manuscript. R.A-S. does not have a financial relationship with a commercial entity
that has an interest in the subject of this manuscript.

Garcia-Rio, Dorgham, Pino, et al.: Lung Volumes in Elderly Subjects

Acknowledgment: The authors thank A. Alvarez. P. Libran, A. Perez, and C.
Suarez for technical assistance.

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