ARTICLE IN PRESS Respiratory Medicine (2007) 101, 1783–1789
Reference values for dynamic and static pulmonary compliance in men W. Galetkea,, C. Feierb, T. Muthb, K.-H. Ruehlec, E. Borsch-Galetkeb, W. Randeratha a
Bethanien Hospital Solingen, Clinic for Pneumology and Allergology, Center for Ventilatory Care and Sleep Medicine, Institute for Pneumology, University Witten/Herdecke, Aufderhoeher Straße 169-175, D–42699 Solingen, Germany b Institute for Occupational and Social Medicine, Heinrich-Heine-University, Duesseldorf, Universita ¨tsstr. 1, D–40225 Du ¨ sseldorf, Germany c Clinic Ambrock, Ambrocker Weg 60, 58091 Hagen, Germany Received 10 September 2006; accepted 19 February 2007 Available online 6 April 2007
KEYWORDS Pulmonary function test; Pulmonary compliance; Static pulmonary compliance; Dynamic pulmonary compliance; Elastic recoil pressure; Reference values
Summary The aim of the present study was to determine new reference values and predictive variables for dynamic and static pulmonary compliance in men. The investigation was conducted as a prospective study in healthy, non-smoking men with normal pulmonary function parameters including spirometry, bodyplethysmography and CO diffusing capacity. The esophageal pressure method was used to measure dynamic compliance (Cdyn), specific dynamic compliance (Cdyn/ITGV), static compliance (Cstat) and specific static compliance (Cstat/ITGV). Lung recoil pressures were recorded at different levels of total lung capacity (TLC). A total of 208 men aged 20–69 years were included in the study. The mean values for the compliance parameters were: Cdyn: 2.9171.08 L/kPa; Cdyn/ITGV: 0.7170.30 kPa1; Cstat: 3.3471.04 L/kPa; Cstat/ITGV: 0.8270.31 kPa1. Cdyn, Cdyn/ITGV and Cstat/ITGV were significantly correlated with age and Cstat was related to height, but in multiple regression analyses the predictability for compliance parameters was very low. Lung recoil pressures at all TLC levels significantly decreased with ageing. In conclusion, we demonstrated that the contribution of anthropometric variables to the regression equations of pulmonary compliance was low. With ageing the static pressure–volume curve of the lung shifted to the left without substantial alteration of the slope. & 2007 Elsevier Ltd. All rights reserved.
Corresponding author. Tel.: +49 212 636040; fax: +49 212 636005.
E-mail address:
[email protected] (W. Galetke). 0954-6111/$ - see front matter & 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.rmed.2007.02.015
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Introduction The elastic properties of the lung along with the airway resistance determine pulmonary mechanics. Lung elasticity can be assessed by different parameters including calculation of pulmonary compliance by analysing the pressure–volume curve of the lung. Measurement of pulmonary compliance is rather seldomly used because of its complexity. Nevertheless, it has been established as an objective evaluation of respiratory function impairment in restrictive pulmonary diseases for years.1–3 In asbestos-induced pleural changes, a reduction of pulmonary compliance is often earlier detectable than other limitations of the pulmonary function tests.4 Determination of pulmonary compliance is also widely used at intensive care units for the adjustment of mechanical ventilation in the acute respiratory distress syndrome5,6 and for weaning procedures.7 Since the study by von Neergaard and Wirz,8 the determination of pulmonary compliance has been methodically developed. Today, the esophageal pressure method with simultaneous registration of transpulmonary pressure and lung volume is regarded as the gold standard.9 There were two main rationale conducting this investigation. Firstly, although today there are numerous applications of pulmonary compliance in the clinical routine and scientific research, the majority of the studies dealing with normal values were performed decades ago and most of them had involved only a small number of participants. Secondly, the question if there might be an age-related decrease of dynamic and static compliance is answered inconsistently. The aim of this study was therefore to determine new reference values and predictive variables for dynamic and static pulmonary compliance in a large group of healthy and non-smoking subjects.
Subjects and methods Subjects Two hundred and eight healthy male volunteers aged 20–69 years were examined as part of a study initiated by the trade associations of mining and mechanical engineering. That was the reason for restricting the participants to the male sex. There was an equal number of volunteers in each age decade. All participants were non-smokers and had no evidence of cardiopulmonary, rheumatic or skeletal muscular diseases on history and physical examination. The study was approved by the local Ethics Committee and all participants gave their written consent to take part in the study voluntarily.
Pulmonary function tests Spirometry and bodyplethysmography were performed in each volunteer according to European Respiratory Society recommendations.10 The single-breath method was applied for determination of carbon monoxide transfer factor and coefficient.11 For all the measurements the Body MasterLab& (Viasys, Ho ¨chberg, Germany) was used.
W. Galetke et al.
Assessment of dynamic and static pulmonary compliance The esophageal pressure method was used for the measurement of dynamic and static compliance. An esophageal catheter with a length of 130 cm plus silicone head and an outside diameter of 2.5 mm was used in the study. The balloon had a length of 10 cm and a diameter of 8.6 mm (Viasys, Ho ¨chberg, Germany; version 2.0, item number 780781). All measurements took place in a sitting upright position, which was not different for each volunteer. After introduction through the nare into the nasopharynx the esophageal catheter was carefully advanced into the esophagus while the subject was drinking small amounts of water. After about 5 min of habituation the balloon was emptied by the subject making a maximal expiration. The volunteer was connected to the bodyplethysmograph (MasterLab&, Viasys, Ho ¨chberg, Germany) in order to measure lung volume and to register the pressure–volume curves. A balloon volume of 0.5 ml was used in all measurements. The position of the catheter was adjusted in such a way that both signals ran synchronically and without phase shifts, no heartbeat artefacts appeared, and a negative pressure of 0.5 kPa was registered at the beginning of inspiration. No recordings were made during esophageal contractions. After standardization of volume history by having the subject to make two inspirations to total lung capacity (TLC), the dynamic compliance was registered during quiet breathing and a respiratory rate between 10 and 20 min1. Only closed curves with clearly determined points of reversal at the end of inspiration and expiration were accepted. At least 10 curves of each participant were registered. For statistical analysis only those five curves were chosen where the difference of tidal volume was o10%. The determination of the static compliance was carried out during expiration from TLC level. The volunteer was asked to inspire twice to the TLC before registrating the pressure–volume curves in order to standardize the volume history. After another deep inspiration, the flow during very slow expiration was interrupted automatically for a period of 80 m s after every 200 ml between the TLC and FRC level. At least five technically acceptable curves were registered for each participant. Curves which proved faulty in one of the following ways were not accepted:
less than six usable shutterpoints, sudden drop of the transpulmonary pressure at TLC level because of a glottic closure,
artefacts due to esophagospasms. Transpulmonary pressure was registered at TLC and at 90%, 80%, 70%, 60% TLC (Pel100–60% TLC). The static compliance was calculated by drawing a straight line through the shutterpoints in the quasi-linear part of the pressure–volume curve between FRC and 80% TLC.
Statistical analysis Data are presented as means and standard deviation (SD). Pearson’s correlation coefficient r was computed between
ARTICLE IN PRESS Reference values for pulmonary compliance in men compliance values and age, height, weight and body mass index (BMI). Stepwise multiple linear regression analyses were performed to identify best predictors of pulmonary compliance using age, height, weight, and BMI as independent variables. In the gradual regression analysis, parameter with Po0.05 were included in the model. The value r2 is given as the proportion of variance explained in the model. The 5th and 95th percentiles were calculated using non-parametric methods. Data analyses were performed in SAS statistical software, version 8.0 (SAS Institute Inc., 1999) and in SPSS for Windows, version 11.5 (SPSS Inc., Chicago, IL).
Results Subjects The volunteers’ anthropometric data and the results of their pulmonary function tests were reported in Table 1. All volunteers had normal pulmonary function parameters according to published reference values.12–14
Dynamic compliance The mean dynamic pulmonary compliance Cdyn was 2.9171.08 L/kPa. A small, but significant decrease of Cdyn with age could be demonstrated, but no significant correlations between Cdyn and the other anthropometric parameters were found (Table 2). The mean specific dynamic compliance (Cdyn/ITGV) was 0.7170.30 kPa1. A more clearly negative correlation between the specific dynamic compliance and age was shown. There was no relationship between Cdyn/ITGV and height, weight and BMI, respectively (Table 2). The multiple linear regression analysis resulted in the following regression equations: Cdyn ðL=kPaÞ ¼ 0:014 age þ 3:4149
ðr 2 ¼ 0:023; Po0:05Þ;
Cdyn =ITGV ðkPa1 Þ ¼ 0:0048 age þ 0:9302 2
ðr ¼ 0:057; Po0:001Þ: Following these regression equations, a reference interval of Cdyn and Cdyn/ITGV could be demonstrated with the fifth percentile as the lower and the 95th percentile as the upper range (Figs. 1a and b).
Static compliance The mean static pulmonary compliance Cstat was 3.3471.04 L/kPa. There was no correlation with age, but a weak, yet significant positive correlation was found between Cstat and height (Table 2). Mean specific static pulmonary compliance ðCstat =ITGVÞ was 0:8270:31 kPa1 : A negative correlation between Cstat/ITGV and age was shown, even though that was only a weak correlation. There was no significant relationship between Cstat/ITGV and height, weight and BMI, respectively (Table 2).
1785 The multiple linear regression analysis lead to the following equations: Cstat ðI=kPaÞ ¼ 0:0267 height ðcmÞ 1:4385 ðr 2 ¼ 0:028; Po0:05Þ; Cstat =ITGV ðkPa1 Þ ¼ 0:0042 age þ 1:0102 ðr 2 ¼ 0:037; Po0:01Þ: Analogous to the dynamic compliance, the reference intervals of Cstat and Cstat/ITGV are shown in Figs. 2a and b. The mean transpulmonary pressure (‘‘recoil pressure’’) at TLC level (Pel 100% TLC) was 2.5670.68 kPa. Mean Pel at 90%, 80%, 70% and 60% TLC were 1.1470.36, 0.8270.31, 0.5970.28 and 0.4170.25 kPa, respectively. There was a significant decrease of the recoil pressures at all TLC levels with ageing. In addition, Pel 100% TLC was significantly Table 1
Subject characteristics (n ¼ 208).
Characteristics
Mean7SD
Range
Age (years) Height (cm) Weight (kg) Body mass index (kg/m2) TLC (L) IVC (L) FEV1 (L) Reff (kPa/L/s) TLCO (mmol/ min/kPa)
44.8714.6 179.276.5 81.7710.3 25.472.6
20–69 165.0–198.0 56.0–108.0 19.3–33.1
7.570.9 5.170.8 4.370.8 0.1470.05 10.572.2
5.0–9.9 2.9–7.9 2.2–7.1 0.04–0.3 6.5–18.5
SD: standard deviation; TLC: total lung capacity; IVC: inspiratory vital capacity; FEV1: forced expiratory volume in the first second; Reff: effective resistance; TLCO: transfer factor for carbon monoxide.
Table 2 Correlations between pulmonary compliance and anthropometric parameters. Age Cdyn r P
Height
Weight
BMI
0.153 o0.05
0.129 0.062
0.120 0.861
0.076 0.278
Cdyn/ITGV r 0.238 P 0.001
0.018 0.792
0.072 0.304
0.071 0.305
0.102 0.144
0.167 o0.05
0.035 0.618
0.078 0.261
Cstat/ITGV r 0.193 P o0.01
0.035 0.621
0.091 0.189
0.081 0.243
Cstat r P
BMI ¼ body mass index; Cdyn ¼ dynamic pulmonary compliance; Cstat ¼ static pulmonary compliance; ITGV ¼ intrathoracic gas volume.
ARTICLE IN PRESS 1786
W. Galetke et al.
Dynamic compliance (l/kPa)
8
!
Cdyn = - 0.014 age + 3.4149
!
6 ! !
! !
! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! 4 ! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !! ! ! !! ! !!! ! ! !!!! ! ! ! ! ! ! ! !! ! ! ! ! ! !!!!!!! ! ! ! !! !! ! !!! ! !! ! ! ! ! ! ! !! ! ! ! !!! ! ! ! ! !! ! ! ! ! !! ! !! !! ! ! !!! ! !! ! ! !! ! ! !! ! 2 !! ! !! ! ! ! !! ! ! ! !! !! ! !! ! ! ! ! ! !! ! !! ! ! !! ! ! ! !! ! ! ! !! ! ! ! !
!
0 20
30
40
50 Age (years)
60
70
80
Specific dynamic compliance (kPa-1)
3 sCdyn = - 0.0048 age + 0.9302
!
2.5
!
2 1.5
!
! !!
!
!
!
!
!!
! ! !! !! !! !! ! ! ! !! ! ! ! ! ! ! ! !! ! ! !! !!! ! !!! !! ! !! !! ! !! !! ! ! ! ! !! ! !! ! !! !!! ! !! ! ! ! ! ! !! !!! !!! !! !!! !! ! !!! ! ! !!!!!! !!!! !!! !!! !! !! !! !! ! ! ! ! !!!! !! !!!!! 0.5 !!! ! !! ! ! ! ! !!!! !! ! ! ! !! !! ! ! ! ! ! !! ! !! ! 0 20 30 40 50 60 Age (years) 1 !
!
! ! !! !! ! !! ! !!! !!! ! 70
80
Figure 1 Reference intervals for dynamic pulmonary compliance (a) and specific dynamic pulmonary compliance (b) in men. Dashed lines represent the 95th percentile as the upper and the 5th percentile as the lower range.
correlated with height and Pel 60% TLC significantly diminished with increasing BMI (Table 3). However, in multivariate analyses using age, height, weight and BMI as independent variables, only age significantly contributed to the regression equations (Table 4).
Discussion To our knowledge this is the largest study dealing with reference values of pulmonary compliance. Predictive equations for pulmonary compliance variables are presented based on multiple regression analysis. One of the main findings was that, although significant for age in dynamic compliance, specific dynamic compliance and specific static compliance and for height in static compliance, the contribution of anthropometric variables to the regression equations was not relevant. On the other hand, a significant decrease of static transpulmonary pressures at lung volumes between 60% and 100% TLC with ageing was demonstrated. As a result, in elderly people the static pressure–volume curve of the lung performed a shift to the left without alteration in the slope of the curve. In this study, careful selection of the participants occurred according to recently published guidelines.13 All
volunteers were lifelong non-smokers, had no evidence of past or present respiratory disease and were even distributed with respect to age. Their pulmonary function test results were within the normal range of published reference values.12–14 The esophageal pressure method was used by simultaneous recording the change of intrapleural pressure and lung volume during slow expiration. This quasi-static method of short interruptions of the airflow to register the transpulmonary pressure was described firstly in 197015 and recommended as the standard procedure by the European Respiratory Society.16 The average mean of the dynamic pulmonary compliance Cdyn in our study was 2.9171.08 L/kPa, thus proving the results of previous studies. In these studies the mean dynamic compliance was between 2.68 and 3.10 L/ kPa.17–19 Attinger et al.20 and Frank et al.21 reported considerably lower values of dynamic compliance (1.6570.41 and 1.5370.28 L/kPa, respectively). In contrast to the present study, the participants of their studies were smaller and had a lower mean vital capacity of 4.7 and 3.86 L, respectively. Regression analyses of dynamic pulmonary compliance were rarely performed in previous studies. In 1957, Butler et al.18 tested 26 healthy men aged 19–75 years and could not prove a decrease of dynamic compliance with ageing.
ARTICLE IN PRESS Reference values for pulmonary compliance in men
1787
!
Static compliance (l/kPa)
8 !
6
! !
! ! ! ! ! ! !! !!! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !! ! !
4
2
0 160
! !
!
! ! !! !! ! ! ! ! ! !
!! ! ! ! ! !! ! !
170
Cstat = 0.0267 height – 1.4385
!
! !! !! ! !! !!
! ! !
!
!
!
! ! !! ! ! ! ! ! !!! ! !! !! !! ! ! ! !! !! ! ! ! !!!! ! ! ! ! ! ! ! !! ! ! !! ! !! ! ! !
!
! ! ! ! ! !! !! ! !
! ! !
! ! !! ! ! !!! !!! ! !! !!! ! ! !
180 Height (cm)
!
!!
190
!
200
Speific static compliance (kPa-1)
3.5 sCstat = - 0.0042 age + 1.0102
!
3 !
2.5 2
!
!
! ! ! ! ! ! ! ! ! ! ! ! ! !! ! !!! ! ! ! !! !! ! ! !! ! !! !! ! ! ! ! ! ! ! !! 1 ! ! ! !! ! ! ! !! ! ! !! ! !! !! ! ! ! ! !!!!! ! ! ! ! ! ! !!! ! ! !!!!! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !! ! ! ! ! ! ! !!! !!! ! ! !! ! !! !!! ! ! ! ! !!!!! ! !!! ! ! !!! ! ! ! !! 0.5 ! ! !! ! !!!! ! ! !! !!! !
1.5 ! !
!
!
! !! ! !!!!!! ! ! !! ! !
0 20
30
40
50 Age (years)
60
70
80
Figure 2 Reference intervals for static pulmonary compliance (a) and specific static pulmonary compliance (b) in men. Dashed lines represent the 95th percentile as the upper and the 5th percentile as the lower range.
Table 3 Correlations between transpulmonary pressures at different TLC levels and anthropometric parameters. Age
Height
Weight
BMI
Pel 100% TLC r 0.556 P o0.001
0.177 0.034
0.040 0.638
0.076 0.366
Pel 90% TLC r 0.509 P o0.001
0.133 0.118
0.038 0.654
0.049 0.565
Pel 80% TLC r 0.493 P o0.001
0.023 0.789
0.052 0.545
0.079 0.359
Pel 70% TLC r 0.495 P o0.001
0.075 0.388
0.036 0.679
0.098 0.258
Pel 60% TLC r 0.404 P o0.001
0.119 0.202
0.082 0.382
0.194 0.036
BMI ¼ body mass index; Pel 100%, 90%, 80%, 70%, 60% TLC ¼ transpulmonary pressure (‘‘recoil pressure’’) at 100%, 90%, 80%, 70%, 60% total lung capacity.
Pielesch et al.19 found a correlation between Cdyn and age, height, weight and intrathoracic gas volume (ITGV), respectively, but the statistical analysis was described only incompletely. They measured the dynamic compliance at breathing frequencies of 25 and 50 min1, which was remarkably higher than in other studies. In the present study, only age was significantly related to Cdyn, but the contribution to the regression equation was negligible. ITGV had a considerable influence on pulmonary compliance in previous studies.22,23 However, the correlation between the specific dynamic pulmonary compliance Cdyn/ITGV and age did not change substantially, indicating that increasing age has only a small influence on the dynamic pulmonary compliance in healthy, non-smoking men. In the present study, the mean static pulmonary compliance was 3.3471.04 L/kPa. Some previous studies reported remarkable lower values between 1.9270.52 and 2.1370.33 L/kPa.21,24,25 The participants in the study by Frank et al.24 were smaller and had a lower vital capacity than the volunteers in the present study. Gillissen et al.25 tested only 22 non-smoking men, who were older and smaller than the population in the actual study. This might explain the discrepant results and emphasizes the importance of the specific static pulmonary compliance Cstat/ITGV thus eliminating the influence of the lung size on pulmonary compliance. As in dynamic pulmonary compliance, in the
ARTICLE IN PRESS 1788
W. Galetke et al.
Table 4 analysis.
Predictive equations for transpulmonary pressures at different lung volumes derived from multiple regression
Regression equation Pel Pel Pel Pel Pel
100% TLC 90% TLC 80% TLC 70% TLC 60% TLC
0.026 0.013 0.011 0.011 0.007
age+3.822 age+1.777 age+1.335 age+1.062 age+0.746
r2
P-value
SE
0.309 0.259 0.243 0.245 0.162
o0.001 o0.001 o0.001 o0.001 o0.001
0.563 0.315 0.267 0.243 0.230
r2 ¼ variability of transpulmonary pressures explained by age; SE ¼ standard error; Pel 100%, 90%, 80%, 70%, 60%; TLC ¼ transpulmonary pressure (‘‘recoil pressure’’) at 100%, 90%, 80%, 70%, 60% total lung capacity.
present study the contribution of anthropometric variables to the regression equation of static compliance was insignificant or negligible. Only height was significantly correlated to Cstat, but no predictability was given with a r2 value of 0.03. In contrast, elderly participants had slightly, but significantly lower specific static pulmonary compliance. However, in multiple regression analysis, the contribution of age was irrelevant suggesting that the slope of the pressure–volume curve of the lung do not change substantially with ageing. Previous studies reported conflicting results in this issue. Frank et al.24 and Yernault et al.26 could not prove a decrease of static compliance with ageing in their small study populations. Some years later, Yernault et al.26 studied a group of 119 volunteers aged 7–64 years involving smokers and non-smokers. As in the present study, the static compliance was poorly related to height and ageing, particularly in the male group. The regression equation was only slightly significant with a r2 value of 0.08.22 Other authors described a significant correlation between Cstat and age, but the reference population appeared small and inhomogeneous.19,25 There is only one study calculating a regression equation of specific static compliance Cstat/ITGV. In this analysis, only age correlated with Cstat/ITGV, but the contribution to the regression equation was insignificant thus confirming the results of the present study.26 In the present study, lung recoil pressures, measured at fixed percentages of TLC, significantly diminished with ageing at all TLC-levels. That was true especially for Pel 100% TLC and Pel 90% TLC. Other anthropometric variables failed to demonstrate a relevant correlation with lung recoil. In a small study, Turner et al.27 first described that aging was associated with a loss of lung recoil. Bode et al.28 further reported not only an association with age, but also a sex difference with higher recoil pressures in young males than in young females. In the latter study, males progressively lost lung recoil with ageing whereas females did not, resulting in similar elastic recoil pressures in the older age groups of both sexes. These results were confirmed by other authors.29,30 As in the present study, Yernault et al.22 found age to be the only parameter significantly correlated with recoil pressures, but the reference group included smokers as well. The diminished lung recoil in elderly people, shifting the pressure–volume curve to the left, is apparently very near balanced by a reduction in chest-wall compliance. Mittman et al.31 and Cherniack et al.32 firstly demonstrated
a significant decrease of the chest-wall compliance and the total compliance of the respiratory system with ageing. In consequence, TLC remains almost constant in the elderly, even though there is an increased ease of lung expansion with reduction of recoil pressures. There are a few potential drawbacks to this study. The selection of volunteers is always crucial in studies dealing with reference values. In the present study participants were asked about their smoking habits and physical disorders, but it cannot be excluded, that the reference population contained a few smokers or ex-smokers. However, the pulmonary function test results of all volunteers were within published guidelines virtually excluding that this would have an influence on the pulmonary compliance parameters. Second, the authors realize that fitting a straight line through a relative large part of the static expiratory compliance curve may be a simplification. Some investigators have modeled the pressure–volume curve as an exponential curve which has the advantage of using all available data.33,34 However, because these mathematical models are complex and routinely not available in most of the pulmonary function labs, for practical reasons we preferred the common method analysing the pressure–volume curve. Third, the respiratory muscle forces were not measured in our study. Since inspiratory muscle strength has a notable influence on the recoil pressure at TLC-level,35 volunteers with an inspiratory muscle weakness would have reduced values of Pel 100% TLC. In fact, the presence of a normal TLC and VC in all participants reasonably excludes any significant respiratory muscle disorder. Another limitation of the study is the fact that we only studied male volunteers. When initiating the study, the rationale for involving only male was the fact, that insurance companies were very interested in new reference values for their asbestos workers, who are predominantly male. Because previous studies reported a remarkable difference in pulmonary compliance between female and male subjects,22,30 our results cannot be easily transmitted to healthy women. Additional work is absolutely necessary to establish new reference values for pulmonary compliance not only in women but also in elderly people. In summary, the present study provides new reference values for dynamic and static pulmonary compliance in men aged 20–70 years. Dynamic compliance, specific dynamic compliance and specific static compliance diminished with ageing, while height was the only variable significantly
ARTICLE IN PRESS Reference values for pulmonary compliance in men related to static compliance. However, the level of predictability for pulmonary compliance parameters by regression equations was very low. In older men, lung recoil pressures at all TLC levels were remarkably lower than in younger men. Consequently, the static pressure–volume curve of the lung shifted to the left with ageing without substantial alteration of the slope.
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