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The expiratory flow rate in patients with chronic pulmonary disease
J. chron. Dis. 1968, Vol. 21, pp. 211-219. Pergamon Press. Printed in Great Britain
THE EXPIRATORY FLOW RATE IN PATIENTS WITH CHRONIC PULMONARY DISEASE BRUCEJ. SOBOL,M.D. and CEMILE~~IRGIL,M.D. With the assistance of BEATRICEWEINHEIMER The Cardiopulmonary
Laboratory,
Grasslands
Hospital, Valhalla, N.Y.
(Received 23 October 1967; in revised form 22 January 1968)
THE ETIOLOGY, course and evaluation of therapy in any disease can only be determined with certainty when reliable objective tests for that disease exist. The reliability of any test depends on three things: the validity of the test-that it truly measures what it was designed to measure; the sensitivity of the test-that it can distinguish a test group of subjects from a control group; and lastly the reproducibility of the testthat with repeated testing of the same subject results which are reasonably similar will be obtained. Recent work has suggested that routine ventilatory tests do not conform to the third requirement-they are not reasonably reproducible [l, 21. Furthermore other work [3,4] has indicated that ventilatory tests designed to measure the same function do not correlate well with each other and are therefore open to question as to the first point-that they measure what they were designed to measure. The works cited were performed on normal subjects and the possibility exists that in patients with lung disease, particularly in patients with obstructive lung disease, these tests might prove to be more reliable. Indeed there is some suggestion that this may be the case. [5-l l] In work relating one measure of flow rate to another, better correlations were achieved when the study group included subjects with obstructive pulmonary disease. Over the years simple ventilatory tests have become the mainstay of pulmonary function testing. These tests have enjoyed wide use and their reliability, although recognized to have limitations, has not been seriously questioned in the routine testing of patients with chronic pulmonary disease. It is the purpose of the present work to test, in the patient with pulmonary disease, the reproducibility of certain measures of expiratory flow rate as well as to measure the degree to which one measure of expiratory flow correlates with another. MATERIALS AND METHODS Two groups of adult males form the subjects of this report. The fist group is composed of 155 male subjects without a history of cardiopulmonary disease (including acute illnesses such as pneumonia, bronchitis etc.) were without symptoms, had never used tobacco in any form and had normal chest roentgenograms. These subjects were studied on a mobile chest X-ray truckof the Westchester Tuberculosis and Public Health Association modified to include pulmonary function testing equipment. The equipment consisted of a waterless Wedge spirometer electronically coupled to a 211
212
BRUCE J.SOBOL and CECIL E~GIL
Sanborn twin channel direct writing recorder which displayed the flow and volume outputs of the Wedge. All subjects performed two forced vital capacities (FVC) in rapid succession. Subjects included in the study performed both FVC’s in a proper manner in the judgement of one of us (B.W.) and no subject was included in whom the two FVC’s were not within 10 per cent of each other. This first group is designated as the Normal Group. The second group of subjects was composed of patients who were referred to the cardiopulmonary laboratory at Grasslands Hospital for the evaluation of pulmonary abnormalities during the period of the study. Subjects were only excluded from this group if they were unable to perform pulmonary function tests properly. All females were excluded since they were few in number. No males were excluded, except for poor performance, on the basis of their ventilatory findings. Undoubtedly, some of the subjects, such as the asymptomatic asthmatics, had pulmonary function tests within the usually considered limits of normal. However, since the limits of normal are difficult to define all subjects were included rather than selecting an arbitary method of exclusion. These subjects were tested in the laboratory on the same equipment that had been used in the field study and were tested by the same individual (B.W.). All subjects performed at least 2 satisfactory FVC’s and 39 subjects performed 3 FVC’s. In all there were 49 subjects in this group and they are designated as the Patient Group. Although the setting of the testing was different and the care taken with each subject to assure proper performance was much greater in the laboratory it was deemed valid to compare the performance of the 2 groups if it could be demonstrated that the results obtained in the field were no more variable than those obtained in careful TABLE 1.
COMPARISONOF THE VARIANCEOF DATAIN THIS STUDYWITH TWO OTHERSTUDIES (The maximal midexpiratory flow in normal males) Decade mean age
Number of subjects
MMF mean (k1.S.D.) coeff. of var.
3 27.2
24.3
10
64
5.50
4.68 (1.10) 24%
(1.42) 26%
4.38 (1 .Ol) 23%
5.27 (1.02) 19%
4 34.5
23
38
44.7 j44.4
19
33
5.21 (1.07) 21%
14
20
4.80 (1.05) 22%
34.3
6 54.3
53.5
The forced vital capacity in normal males Correlation coefficient Standard error of the estimate 0.63 0.64 0.58 0.57 In each column the number to the left is from another study, to the right from data obtained during a field study by this laboratory. For the MMF the data is that of LEUALLENand FOWLER [12], and for the Forced Vital Capacity from KORY, et al. [3]. Note the similarity in these tests of scatter. S.D.: Standard Deviation. Coeff. of var. : Coefficient of variation.
The Expiratory Flow Rate in Patients with Chronic Pulmonary Disease
213
studies. Comparison for the vital capacity was made with the results obtained by KORY etal[3] and for a measure of flow rate, the maximal midexpiratory flow (MMF), with those of LEUALLEN and FOWLER. [12] Table 1 illustrates this comparison and demonstrates that the field study used here gave results with no greater variance than that of the laboratories cited above. For the purpose of comparing reproducibility, 49 of the original 155 field study subjects were matched for age against the 49 laboratory subjects. This was done to assure against bias due to age since there was a slight indication that with increasing age there was decreasing reproducibility. [l] In both groups of 49 subjects, the first effort for 1 of 6 measures of flow rate was plotted against the second effort and the correlation coefficient determined. The flow rates measured were the peak flow rate (PFR), the first second volume (FEVl), the volume of the first second divided by the FVC X 100 (per cent FEV& the flow rate at the point when 50 per cent of the FVC had been expelled (50 per cent FR), the flow rate when 75 per cent of the FVC had been expelled (75 per cent FR), and the MMF. In the patient group the maximum expiratory flow rate (MEFR) was also measured. The per cent variability between the first and second effort for each flow rate was determined by the formula: (I El---E2 I/ElSEa/2) X 100 where El= the first effort and ES= the second effort. This formula gives the mean percentage difference for the 49 subjects and was applied to each measure of flow rate. The standard deviation around the mean is not reported since the lower limit is set by zero and the data is skewed. For the 39 subjects who performed 3 FVC’s the mean per cent variation between the first two efforts was computed as well as the mean per cent variation of the largest and smallest value for three efforts. Correlation coefficients for EI : ES were also calculated. At the lower flow rates, MMF, 50 per cent FR and 75 per cent FR there was a tendency of the data to crowd toward the lower values. This crowding was obviated by the use of the logarithms of the observed values. However, the correlation coefficients so obtained did not differ substantially from those obtained with the observed values. Flow rates obtained during the same FVC (the largest obtained were used; if 2 FCV’s were identical the second was used) were plotted against each other and the correlation coefficient determined. If the plot did not meet the requirements for linear regression the data was replotted using semilogarithmic or log-logarithmic coordinates. The correlation coefficient was determined in each case where the graphic plot justified such a determination.
laboratory
RESULTS
Table 2 lists the correlation coefficients and the mean percentage differences between 2 efforts for both groups as well as the mean percentage difference for the 39 subjects in the Patient Group who made 3 efforts. The FVC is included for comparison even though the maximum variance was artificially limited to 10 per cent in the Normal Group. Table 2 contains, what at first glance may appear to be a paradox, that is, that the correlation coefficients for the Patient Group tend to be better than the Normal Group while the per cent variation tends to be worse. Figure 1 is an attempt to clarify
BRUCE3.SOBOL and CWL
214
0
0
ov 0
’
. 10
EMJFRGU
ra0.75
Mean % va49 r = 0.75 Mean96 Vac=lO
20
30
40
50
60
,
70
FIG. I.
Hypothetical relationships between the correlation coeEcient and the mean per cent variation. The heavy black line indicates the regression line for all points. Light solid lines indicate the variance for 0 and l . Broken lines indicate the variance for x . The variance for 0 and l is the same, 5, while for x it is 10. The correlation coefficient for 0 and e are the same while the per cent variation is much Larger for 0. This is due to the fact that the absolute values for 0 are small and for Olarge, while the variance is the same for both. On the other hand the variance for x is twice that for 0, 10, giving a poorer correlation coefhcient, but since the absolute values of the numbers are larger the average per cent variation is smaller.
this. It is a representation of severa hypothetical relationships illustrating the type of divergence which is possible between the correlation coefficient and the mean per cent variation. Figure 2 demonstrates graphically the type of scatter and correlation which is presented in Table 2. These two flow rates were chosen merely to demonstrate one of the more reproducible and one of the least reproducible flow rates. Also quite evident from these graphs is that there is no tendency for the second effort to produce a higher Aow rate than the first, either in the Normal or Patient Group. As a matter of fact there was no tendency for a third effort to be superior to the first 2 in those subjects with 3 FVC’s. For example there were only 9 subjects in the Patient Group whose third effort was superior to the first 2 for the PFR and MMF (not the same 9 subjects) out of 39. This does not suggest a learning factor with repeated efforts even in those exposed to the spirogram for the first time-the Normal Group.
The Expiratory TABLE 2.
215
Flow Rate in Patients with Chronic Pulmonary Disease
CORRELATION COEFRCIENTS AND PER CENT VARIATION BETWEENSEQUENTIAL EFFORTS FOR
SEVENMEASURES OF FLOWBATE
Av. % diff.
r FVC PFR 50% FR 75% FR MMF FEVl % FEVr MEFR
0.98 0.79 0.81 0.87 0.81 0.96 0.82 -
39 Patients
49 Patients
49 Normals
3.3 17.5 18.1 17.3 17.1 4.6 4.9 -
r
0.97 0.93 0.98 0.92 0.96 0.99 0.97 0.96
Av. % diff. 6.1 12.8 16.7 25.7 17.3 6.1 7.7 12.8
2 Efforts Av. % diff.
3 Efforts Av. % diff.
6.9 13.1 17.5 25.8 18.0 6.2 8.1 12.5
9.7 18.2 23.9 34.3 24.2 9.9 12.8 20.5
The number at the top of each column indicates the number of subjects. r=Correlation coefficient. Av. % DifI. = Average per cent difference. Definitions of flow rate abbreviations given in text. MEFR was not measured on the normal subjects. Note the improvement in correlation between sequential efforts of the patients as against normal subjects. Note the worsening per cent difference. between efforts when 3 rather than 2 efforts are compared.
Table 2 illustrates a point that has been previously made on a different set of subjects, [l] namely that there is nothing to choose from in terms of reproducibility between the early-PFR, mid-50 per cent FR, or later-75 per cent FR of the expiratory effort. In the Patient Group there is a tendency for the reproducilibity to get worse toward the terminal portion of the effort. Table 3 demonstrates the dramatic improvement in correlation between flow rates obtained during a single expiratory effort when one is dealing with subjects with TABLE 3.
CORRELATIONCOEFFICIENTSOF VARIOUS FLGW MEASUREMENTS OBTAINEDDURING THE PERFORMANCE OF A SINGLEFORCEDVITALCAPAClTY PFR
MMF
50%
75%
MEFR
FEV,
‘XFEV, 0.31
I
75%
-
-
-
E
MEFR
N
FEV,
0.88
0.95
0.96
-
T
%FEVr
0.80
0.91
0.89
-
-
PFR
N
MEFR
A
The correlations for the various pairs of flow rates are obtained by relating the flow rate listed across the top with a flow rate on the left for subjects with pulmonary disease, or a flow rate on the right for normal subjects. Values above the diagonal line, therefore, represent correlations for normal subjects while those below for patients with pulmonary disease. Underlined numbers indicate linear correlations, others are logarithmic-logarithmic. *These correlations taken from KORY et al [3], the other correlations on normals are taken from this laboratory[ll]-the entire group of 155 subjects. The slash indicates correlations which are not available while the horizontal line indicates relationships which would not permit the use of a correlation coe5cient. see text. Note the marked improvement in correlation between various measures of flow rate when these determinations are made on pulmonary patients.
216
BRUCEJ. SOBOLand CECIL EMIRGIL
PFR
FEV,
NORMALS
NORMALS
. .
13
.
r.0.79
i
.
.
a.
11 -
45
rz0.96
. .
.
9. 9-
.
.*
8"
s*
a*
.
41)
l
.
.
.*,r . ..
.:
%
+
l
: J-
0.
.*
. 9
.
*
7-
s-
l
. .
. .
1
I
I
I
1
3
I
5
I
,
,
,
7
9
,
,
Ii
,
.
’ ij
PATIENTS
PATIENTS
I1 -
. .
r : 0.93
4D .
r :0.99
. 0.
9-
.
.
a0
.
.
7-
l
. i
?
5-
01
0
SECOND FIG. 2.
The relationship
,
, 1.0
I
,
,
2.0
, 31)
,
(
4.0
EFFORT
of the first to second effort for two flow rates in normals and patients.
PFR: Peak flow rate FEV, : 1 Second forced expiratory volume Note the lack of any impressive tendency for the second effort to be superior to the first.
pulmonary disease as against normals. This has also been observed recently in the Veterans Administration Cooperative Study [8] in which they point out that the correlation between FEVl and MEFR went from 0.17 in normals to 0.89 in subjects with obstructive pulmonary disease. Also pointed out by this group was the excellent
The Expiratory Flow Rate in Patients with Chronic Pulmonary Disease
217
correlation between FEVl and other measures of expiratory flow rate. In this study FEVl had the best correlation with the other measures of flow rate as well. DISCUSSION
that in a group of subjects, a majority of whom have obstructive pulmonary disease, the correlation of one measure of expiratory flow rate with another is far superior to that observed with normal subjects. [2,4] However, it is also equally apparent that in terms of the reproducibility of flow rates with sequential expiratory efforts, there is little to choose from between the Normal Group and the Patient Group. Naturally, since the flow rates of the Normal Group are higher, the absolute variation between the 2 efforts will be larger. However, when one is attempting to follow the course of a disease or assess the value of therapy it is usually the per cent change which is of concern. Furthermore, one must bear in mind that the data presented here are the average per cent changes for each flow rate in each group. Obviously, the more severely impaired the individual is the larger his per cent difference will be since the variance along the regression lines of the data presented here is fairly constant, Fig. 2. For example, the average per cent difference between paired efforts in the Patient Group for the MMF was 17.3 per cent. However, some patients had an MMF that ranged between 0.1 to 0.2 for the two efforts, a change of 100 per cent (67 per cent by the formula used here). In other words, if one is interested in assessing the benefits of therapy on individual patients one is forced to follow long term trends rather than establishing arbitrary criteria of improvement. It is interesting to note that there was no tendency for the second or third effort to produce a higher flow rate than the first. This is not the same as saying that many efforts are not more likely to produce a higher flow rate than a single effort. What it does imply is that the likelihood of getting the highest flow rate on the first effort is entirely random and that perhaps the benefits of training and familiarity with the spirogram have been over-emphasized in the past. Whether random or not, however, it is certainly evident that the more efforts the subject makes the more likely one is to find a higher variance between the largest and smallest effort. And the variance is discouragingly high. Why one measure of flow rate should be less variable than another remains a matter of speculation. However, there are inherent in the methods of measuring flow rates certain factors which would incline one to suspect that one measure might be superior to another. For example, certain measures of flow rate are dependent not only on the force of the expiratory effort but on the volume expired as well. These are represented by the MMF, the 50 per cent FR and the 75 per cent FR as well as all portions of the timed vital capacity, such as the per cent FEVl. Under such circumstances one would expect more variability, since both a change in effort and a change in the duration of the effort would vary the value obtained. On the other hand the PFR, which is not dependent on the volume expired, is extremely sensitive to varying effort and one might expect considerable variation from this fact alone. The FEVl and the MEFR are not dependent on the volume expired and are therefore free from the requirement of an adequate terminal effort. They would also appear to have the advantage that they are in a sense “averages”, the FEVl an average of volume and the MEFR an average of time. One would suspect that this might tend to “smooth out” variations in the point in time in which the maximum effort occurs. The fact that they correlate so well It is quite apparent
218
BRUCBJ. SOBOLand CECIL EMIRGIL
with each other, r =O. 98 would tend to support this view although certainly not substantiate it. Although the reasons for the superiority of one measure of flow-rate over another are speculative, it is evident from the data presented here that the FEVl is superior to the other measures of flow rate, in that it has the smallest per cent variation for both normals and patients and it correlates best with the other measures of flow rate. This latter may be discounted to some extent since it is not important that a good measure of airway resistant ecorrelate well with a poorer one. If one accepts this then there is little to choose from between the FEVl and the per cent FEVL Furthermore, previous work has shown that they correlate equally well with airway conductance/ unit lung volume (CA/V). (13). Between the two the per cent FEVl has the advantage of more widespread use with a more or less universally accepted lower range of normal. In contradistinction to this the FEVl is less widely used and the normal values will vary with the subject’s vital capacity. In conclusion some statistical observations seem pertinent. In the first place one must be cautious of slavish adherence to the correlation coefficient in choosing a test which will provide the most useful information. As pointed out in Fig. 1 a simple correlation coefficient can be misleading. In choosing any test of ventilatory function one might do well to choose that test which provides the least variability regard1 ess of the correlation coefficient. In the second place, because of the easy access to computers which exists today, there is a temptation to skip the arduous business of graphically plotting the data prior to any statistical analysis. Under such circumstances one can mathematically develop correlation coefficients which have no valid meaning. In the work presented here, Table 3, 6 correlations in the Patient Group have not been included because the linear, semilogarithmic and the log-logarithmic plots did not permit the use of the correlation coefficient, and only 3 out of the 15 correlations developed were linear on linear coordinates. If the data had not been graphed 21 correlation coefficients could have been presented only 3 of which would have been legitimate, the other 18 would have been invalid by reasons of curvilinearity, poor dispersion or inconstant variance. Acknowle&ements-The authors acknowledge with gratitude the help of ALEIERTAVARBLZ in the preparation of this manuscript. This work was supported by a Grant from the State of New York Department of Health. REFERENCES 1. 2. 3. 4. 5. 6. 7.
SOBOL,B. J. and &IIRGIL C.: Subject effort and the expiratory
flow rate. Am. Rev. resp. Dis. 89,402-408,1964. SOUL, B. J.: Assessment of ventilatory abnormality in the asymptomatic subject-an exercise in futility. Thorax, 31,445-449, 1966. KORY, R. C., CALLAHAN,R. Q., BORENH. G. and SYNER.J. C. : The veterans administrationarmy cooperative study of pulmonary function I. Am. J. Med. 30,243-258, 1961. SOBOL, B. J. and EMIRGIL. C.: The expiratory flow rate in normal subjects. Rev. AlZergy (accepted for publication). Boaaows, B., STRAUSSR. H. and NIDEN. A. H.: Chronic obstructive lung disease III. Am. Rev. resp. Dis. 91, 861-868, 1965. FAIRBAIRN,A. S., FLETCHER,C. M. TINKER C. M. and WOOD. C. H.: A comparison of spirometric and peak expiratory flow measurements in men with and without chronic bronchitis. Thorax 17,16&174, 1962. IIALLEIT, W. Y. and MARTIN.C. J. : Obstructive pulmonary disease testing in hospital patients. Am, Rev. resp. Dis. 86, 686-696, 1962.
The Expiratory Flow Rate in Patients with Chronic Pulmonary Disease 8. 9. 10. 11. 12. 13.
219
RENZET~,A. D., McCLEMENT .I. H. and Lrrr. B. D.: The veterans administration cooperative study of pulmonary function III. Am. J. Med. 41,115-129,1966. Rrrcmx, B.: A comparison of forced expiratory volume and peak flow in clinical practice. Lancer 2,271-273, 1962. ROSENBLAIT, G., ALKALAY, I., MCCANNP. D. and Smr~. M. : The correlation of peak flow rate with maximal expiratory flow rate, one second forced expiratory volume, and maximal breathing capacity. Am. Rev. resp. Dis. 87, 589-591, 1963. SHEPHARD, R. J.: Some observations on peak expiratory flow. Thorax 17, 39-48, 1962. LEU.ULZ.N, E. C and FOWLER,W. S.: Maximal midexpiratory flow. Am. Rev. Tuberc. pulm. Dis. 72,783-800, 1955. Sono~, B. J. and E~GIL, C.: Airway resistance as measured by body plethysmograph versus measurements of expiratory flow rate. Am. Rev. resp. Dis. 96, 275-283, 1967.
THE EXPIRATORY FLOW RATE IN PATIENTS WITH CHRONIC PULMONARY DISEASE BRUCEJ. SOBOL,M.D. and CEMILE~~IRGIL,M.D. With the assistance of BEATRICEWEINHEIMER The Cardiopulmonary
Laboratory,
Grasslands
Hospital, Valhalla, N.Y.
(Received 23 October 1967; in revised form 22 January 1968)
THE ETIOLOGY, course and evaluation of therapy in any disease can only be determined with certainty when reliable objective tests for that disease exist. The reliability of any test depends on three things: the validity of the test-that it truly measures what it was designed to measure; the sensitivity of the test-that it can distinguish a test group of subjects from a control group; and lastly the reproducibility of the testthat with repeated testing of the same subject results which are reasonably similar will be obtained. Recent work has suggested that routine ventilatory tests do not conform to the third requirement-they are not reasonably reproducible [l, 21. Furthermore other work [3,4] has indicated that ventilatory tests designed to measure the same function do not correlate well with each other and are therefore open to question as to the first point-that they measure what they were designed to measure. The works cited were performed on normal subjects and the possibility exists that in patients with lung disease, particularly in patients with obstructive lung disease, these tests might prove to be more reliable. Indeed there is some suggestion that this may be the case. [5-l l] In work relating one measure of flow rate to another, better correlations were achieved when the study group included subjects with obstructive pulmonary disease. Over the years simple ventilatory tests have become the mainstay of pulmonary function testing. These tests have enjoyed wide use and their reliability, although recognized to have limitations, has not been seriously questioned in the routine testing of patients with chronic pulmonary disease. It is the purpose of the present work to test, in the patient with pulmonary disease, the reproducibility of certain measures of expiratory flow rate as well as to measure the degree to which one measure of expiratory flow correlates with another. MATERIALS AND METHODS Two groups of adult males form the subjects of this report. The fist group is composed of 155 male subjects without a history of cardiopulmonary disease (including acute illnesses such as pneumonia, bronchitis etc.) were without symptoms, had never used tobacco in any form and had normal chest roentgenograms. These subjects were studied on a mobile chest X-ray truckof the Westchester Tuberculosis and Public Health Association modified to include pulmonary function testing equipment. The equipment consisted of a waterless Wedge spirometer electronically coupled to a 211
212
BRUCE J.SOBOL and CECIL E~GIL
Sanborn twin channel direct writing recorder which displayed the flow and volume outputs of the Wedge. All subjects performed two forced vital capacities (FVC) in rapid succession. Subjects included in the study performed both FVC’s in a proper manner in the judgement of one of us (B.W.) and no subject was included in whom the two FVC’s were not within 10 per cent of each other. This first group is designated as the Normal Group. The second group of subjects was composed of patients who were referred to the cardiopulmonary laboratory at Grasslands Hospital for the evaluation of pulmonary abnormalities during the period of the study. Subjects were only excluded from this group if they were unable to perform pulmonary function tests properly. All females were excluded since they were few in number. No males were excluded, except for poor performance, on the basis of their ventilatory findings. Undoubtedly, some of the subjects, such as the asymptomatic asthmatics, had pulmonary function tests within the usually considered limits of normal. However, since the limits of normal are difficult to define all subjects were included rather than selecting an arbitary method of exclusion. These subjects were tested in the laboratory on the same equipment that had been used in the field study and were tested by the same individual (B.W.). All subjects performed at least 2 satisfactory FVC’s and 39 subjects performed 3 FVC’s. In all there were 49 subjects in this group and they are designated as the Patient Group. Although the setting of the testing was different and the care taken with each subject to assure proper performance was much greater in the laboratory it was deemed valid to compare the performance of the 2 groups if it could be demonstrated that the results obtained in the field were no more variable than those obtained in careful TABLE 1.
COMPARISONOF THE VARIANCEOF DATAIN THIS STUDYWITH TWO OTHERSTUDIES (The maximal midexpiratory flow in normal males) Decade mean age
Number of subjects
MMF mean (k1.S.D.) coeff. of var.
3 27.2
24.3
10
64
5.50
4.68 (1.10) 24%
(1.42) 26%
4.38 (1 .Ol) 23%
5.27 (1.02) 19%
4 34.5
23
38
44.7 j44.4
19
33
5.21 (1.07) 21%
14
20
4.80 (1.05) 22%
34.3
6 54.3
53.5
The forced vital capacity in normal males Correlation coefficient Standard error of the estimate 0.63 0.64 0.58 0.57 In each column the number to the left is from another study, to the right from data obtained during a field study by this laboratory. For the MMF the data is that of LEUALLENand FOWLER [12], and for the Forced Vital Capacity from KORY, et al. [3]. Note the similarity in these tests of scatter. S.D.: Standard Deviation. Coeff. of var. : Coefficient of variation.
The Expiratory Flow Rate in Patients with Chronic Pulmonary Disease
213
studies. Comparison for the vital capacity was made with the results obtained by KORY etal[3] and for a measure of flow rate, the maximal midexpiratory flow (MMF), with those of LEUALLEN and FOWLER. [12] Table 1 illustrates this comparison and demonstrates that the field study used here gave results with no greater variance than that of the laboratories cited above. For the purpose of comparing reproducibility, 49 of the original 155 field study subjects were matched for age against the 49 laboratory subjects. This was done to assure against bias due to age since there was a slight indication that with increasing age there was decreasing reproducibility. [l] In both groups of 49 subjects, the first effort for 1 of 6 measures of flow rate was plotted against the second effort and the correlation coefficient determined. The flow rates measured were the peak flow rate (PFR), the first second volume (FEVl), the volume of the first second divided by the FVC X 100 (per cent FEV& the flow rate at the point when 50 per cent of the FVC had been expelled (50 per cent FR), the flow rate when 75 per cent of the FVC had been expelled (75 per cent FR), and the MMF. In the patient group the maximum expiratory flow rate (MEFR) was also measured. The per cent variability between the first and second effort for each flow rate was determined by the formula: (I El---E2 I/ElSEa/2) X 100 where El= the first effort and ES= the second effort. This formula gives the mean percentage difference for the 49 subjects and was applied to each measure of flow rate. The standard deviation around the mean is not reported since the lower limit is set by zero and the data is skewed. For the 39 subjects who performed 3 FVC’s the mean per cent variation between the first two efforts was computed as well as the mean per cent variation of the largest and smallest value for three efforts. Correlation coefficients for EI : ES were also calculated. At the lower flow rates, MMF, 50 per cent FR and 75 per cent FR there was a tendency of the data to crowd toward the lower values. This crowding was obviated by the use of the logarithms of the observed values. However, the correlation coefficients so obtained did not differ substantially from those obtained with the observed values. Flow rates obtained during the same FVC (the largest obtained were used; if 2 FCV’s were identical the second was used) were plotted against each other and the correlation coefficient determined. If the plot did not meet the requirements for linear regression the data was replotted using semilogarithmic or log-logarithmic coordinates. The correlation coefficient was determined in each case where the graphic plot justified such a determination.
laboratory
RESULTS
Table 2 lists the correlation coefficients and the mean percentage differences between 2 efforts for both groups as well as the mean percentage difference for the 39 subjects in the Patient Group who made 3 efforts. The FVC is included for comparison even though the maximum variance was artificially limited to 10 per cent in the Normal Group. Table 2 contains, what at first glance may appear to be a paradox, that is, that the correlation coefficients for the Patient Group tend to be better than the Normal Group while the per cent variation tends to be worse. Figure 1 is an attempt to clarify
BRUCE3.SOBOL and CWL
214
0
0
ov 0
’
. 10
EMJFRGU
ra0.75
Mean % va49 r = 0.75 Mean96 Vac=lO
20
30
40
50
60
,
70
FIG. I.
Hypothetical relationships between the correlation coeEcient and the mean per cent variation. The heavy black line indicates the regression line for all points. Light solid lines indicate the variance for 0 and l . Broken lines indicate the variance for x . The variance for 0 and l is the same, 5, while for x it is 10. The correlation coefficient for 0 and e are the same while the per cent variation is much Larger for 0. This is due to the fact that the absolute values for 0 are small and for Olarge, while the variance is the same for both. On the other hand the variance for x is twice that for 0, 10, giving a poorer correlation coefhcient, but since the absolute values of the numbers are larger the average per cent variation is smaller.
this. It is a representation of severa hypothetical relationships illustrating the type of divergence which is possible between the correlation coefficient and the mean per cent variation. Figure 2 demonstrates graphically the type of scatter and correlation which is presented in Table 2. These two flow rates were chosen merely to demonstrate one of the more reproducible and one of the least reproducible flow rates. Also quite evident from these graphs is that there is no tendency for the second effort to produce a higher Aow rate than the first, either in the Normal or Patient Group. As a matter of fact there was no tendency for a third effort to be superior to the first 2 in those subjects with 3 FVC’s. For example there were only 9 subjects in the Patient Group whose third effort was superior to the first 2 for the PFR and MMF (not the same 9 subjects) out of 39. This does not suggest a learning factor with repeated efforts even in those exposed to the spirogram for the first time-the Normal Group.
The Expiratory TABLE 2.
215
Flow Rate in Patients with Chronic Pulmonary Disease
CORRELATION COEFRCIENTS AND PER CENT VARIATION BETWEENSEQUENTIAL EFFORTS FOR
SEVENMEASURES OF FLOWBATE
Av. % diff.
r FVC PFR 50% FR 75% FR MMF FEVl % FEVr MEFR
0.98 0.79 0.81 0.87 0.81 0.96 0.82 -
39 Patients
49 Patients
49 Normals
3.3 17.5 18.1 17.3 17.1 4.6 4.9 -
r
0.97 0.93 0.98 0.92 0.96 0.99 0.97 0.96
Av. % diff. 6.1 12.8 16.7 25.7 17.3 6.1 7.7 12.8
2 Efforts Av. % diff.
3 Efforts Av. % diff.
6.9 13.1 17.5 25.8 18.0 6.2 8.1 12.5
9.7 18.2 23.9 34.3 24.2 9.9 12.8 20.5
The number at the top of each column indicates the number of subjects. r=Correlation coefficient. Av. % DifI. = Average per cent difference. Definitions of flow rate abbreviations given in text. MEFR was not measured on the normal subjects. Note the improvement in correlation between sequential efforts of the patients as against normal subjects. Note the worsening per cent difference. between efforts when 3 rather than 2 efforts are compared.
Table 2 illustrates a point that has been previously made on a different set of subjects, [l] namely that there is nothing to choose from in terms of reproducibility between the early-PFR, mid-50 per cent FR, or later-75 per cent FR of the expiratory effort. In the Patient Group there is a tendency for the reproducilibity to get worse toward the terminal portion of the effort. Table 3 demonstrates the dramatic improvement in correlation between flow rates obtained during a single expiratory effort when one is dealing with subjects with TABLE 3.
CORRELATIONCOEFFICIENTSOF VARIOUS FLGW MEASUREMENTS OBTAINEDDURING THE PERFORMANCE OF A SINGLEFORCEDVITALCAPAClTY PFR
MMF
50%
75%
MEFR
FEV,
‘XFEV, 0.31
I
75%
-
-
-
E
MEFR
N
FEV,
0.88
0.95
0.96
-
T
%FEVr
0.80
0.91
0.89
-
-
PFR
N
MEFR
A
The correlations for the various pairs of flow rates are obtained by relating the flow rate listed across the top with a flow rate on the left for subjects with pulmonary disease, or a flow rate on the right for normal subjects. Values above the diagonal line, therefore, represent correlations for normal subjects while those below for patients with pulmonary disease. Underlined numbers indicate linear correlations, others are logarithmic-logarithmic. *These correlations taken from KORY et al [3], the other correlations on normals are taken from this laboratory[ll]-the entire group of 155 subjects. The slash indicates correlations which are not available while the horizontal line indicates relationships which would not permit the use of a correlation coe5cient. see text. Note the marked improvement in correlation between various measures of flow rate when these determinations are made on pulmonary patients.
216
BRUCEJ. SOBOLand CECIL EMIRGIL
PFR
FEV,
NORMALS
NORMALS
. .
13
.
r.0.79
i
.
.
a.
11 -
45
rz0.96
. .
.
9. 9-
.
.*
8"
s*
a*
.
41)
l
.
.
.*,r . ..
.:
%
+
l
: J-
0.
.*
. 9
.
*
7-
s-
l
. .
. .
1
I
I
I
1
3
I
5
I
,
,
,
7
9
,
,
Ii
,
.
’ ij
PATIENTS
PATIENTS
I1 -
. .
r : 0.93
4D .
r :0.99
. 0.
9-
.
.
a0
.
.
7-
l
. i
?
5-
01
0
SECOND FIG. 2.
The relationship
,
, 1.0
I
,
,
2.0
, 31)
,
(
4.0
EFFORT
of the first to second effort for two flow rates in normals and patients.
PFR: Peak flow rate FEV, : 1 Second forced expiratory volume Note the lack of any impressive tendency for the second effort to be superior to the first.
pulmonary disease as against normals. This has also been observed recently in the Veterans Administration Cooperative Study [8] in which they point out that the correlation between FEVl and MEFR went from 0.17 in normals to 0.89 in subjects with obstructive pulmonary disease. Also pointed out by this group was the excellent
The Expiratory Flow Rate in Patients with Chronic Pulmonary Disease
217
correlation between FEVl and other measures of expiratory flow rate. In this study FEVl had the best correlation with the other measures of flow rate as well. DISCUSSION
that in a group of subjects, a majority of whom have obstructive pulmonary disease, the correlation of one measure of expiratory flow rate with another is far superior to that observed with normal subjects. [2,4] However, it is also equally apparent that in terms of the reproducibility of flow rates with sequential expiratory efforts, there is little to choose from between the Normal Group and the Patient Group. Naturally, since the flow rates of the Normal Group are higher, the absolute variation between the 2 efforts will be larger. However, when one is attempting to follow the course of a disease or assess the value of therapy it is usually the per cent change which is of concern. Furthermore, one must bear in mind that the data presented here are the average per cent changes for each flow rate in each group. Obviously, the more severely impaired the individual is the larger his per cent difference will be since the variance along the regression lines of the data presented here is fairly constant, Fig. 2. For example, the average per cent difference between paired efforts in the Patient Group for the MMF was 17.3 per cent. However, some patients had an MMF that ranged between 0.1 to 0.2 for the two efforts, a change of 100 per cent (67 per cent by the formula used here). In other words, if one is interested in assessing the benefits of therapy on individual patients one is forced to follow long term trends rather than establishing arbitrary criteria of improvement. It is interesting to note that there was no tendency for the second or third effort to produce a higher flow rate than the first. This is not the same as saying that many efforts are not more likely to produce a higher flow rate than a single effort. What it does imply is that the likelihood of getting the highest flow rate on the first effort is entirely random and that perhaps the benefits of training and familiarity with the spirogram have been over-emphasized in the past. Whether random or not, however, it is certainly evident that the more efforts the subject makes the more likely one is to find a higher variance between the largest and smallest effort. And the variance is discouragingly high. Why one measure of flow rate should be less variable than another remains a matter of speculation. However, there are inherent in the methods of measuring flow rates certain factors which would incline one to suspect that one measure might be superior to another. For example, certain measures of flow rate are dependent not only on the force of the expiratory effort but on the volume expired as well. These are represented by the MMF, the 50 per cent FR and the 75 per cent FR as well as all portions of the timed vital capacity, such as the per cent FEVl. Under such circumstances one would expect more variability, since both a change in effort and a change in the duration of the effort would vary the value obtained. On the other hand the PFR, which is not dependent on the volume expired, is extremely sensitive to varying effort and one might expect considerable variation from this fact alone. The FEVl and the MEFR are not dependent on the volume expired and are therefore free from the requirement of an adequate terminal effort. They would also appear to have the advantage that they are in a sense “averages”, the FEVl an average of volume and the MEFR an average of time. One would suspect that this might tend to “smooth out” variations in the point in time in which the maximum effort occurs. The fact that they correlate so well It is quite apparent
218
BRUCBJ. SOBOLand CECIL EMIRGIL
with each other, r =O. 98 would tend to support this view although certainly not substantiate it. Although the reasons for the superiority of one measure of flow-rate over another are speculative, it is evident from the data presented here that the FEVl is superior to the other measures of flow rate, in that it has the smallest per cent variation for both normals and patients and it correlates best with the other measures of flow rate. This latter may be discounted to some extent since it is not important that a good measure of airway resistant ecorrelate well with a poorer one. If one accepts this then there is little to choose from between the FEVl and the per cent FEVL Furthermore, previous work has shown that they correlate equally well with airway conductance/ unit lung volume (CA/V). (13). Between the two the per cent FEVl has the advantage of more widespread use with a more or less universally accepted lower range of normal. In contradistinction to this the FEVl is less widely used and the normal values will vary with the subject’s vital capacity. In conclusion some statistical observations seem pertinent. In the first place one must be cautious of slavish adherence to the correlation coefficient in choosing a test which will provide the most useful information. As pointed out in Fig. 1 a simple correlation coefficient can be misleading. In choosing any test of ventilatory function one might do well to choose that test which provides the least variability regard1 ess of the correlation coefficient. In the second place, because of the easy access to computers which exists today, there is a temptation to skip the arduous business of graphically plotting the data prior to any statistical analysis. Under such circumstances one can mathematically develop correlation coefficients which have no valid meaning. In the work presented here, Table 3, 6 correlations in the Patient Group have not been included because the linear, semilogarithmic and the log-logarithmic plots did not permit the use of the correlation coefficient, and only 3 out of the 15 correlations developed were linear on linear coordinates. If the data had not been graphed 21 correlation coefficients could have been presented only 3 of which would have been legitimate, the other 18 would have been invalid by reasons of curvilinearity, poor dispersion or inconstant variance. Acknowle&ements-The authors acknowledge with gratitude the help of ALEIERTAVARBLZ in the preparation of this manuscript. This work was supported by a Grant from the State of New York Department of Health. REFERENCES 1. 2. 3. 4. 5. 6. 7.
SOBOL,B. J. and &IIRGIL C.: Subject effort and the expiratory
flow rate. Am. Rev. resp. Dis. 89,402-408,1964. SOUL, B. J.: Assessment of ventilatory abnormality in the asymptomatic subject-an exercise in futility. Thorax, 31,445-449, 1966. KORY, R. C., CALLAHAN,R. Q., BORENH. G. and SYNER.J. C. : The veterans administrationarmy cooperative study of pulmonary function I. Am. J. Med. 30,243-258, 1961. SOBOL, B. J. and EMIRGIL. C.: The expiratory flow rate in normal subjects. Rev. AlZergy (accepted for publication). Boaaows, B., STRAUSSR. H. and NIDEN. A. H.: Chronic obstructive lung disease III. Am. Rev. resp. Dis. 91, 861-868, 1965. FAIRBAIRN,A. S., FLETCHER,C. M. TINKER C. M. and WOOD. C. H.: A comparison of spirometric and peak expiratory flow measurements in men with and without chronic bronchitis. Thorax 17,16&174, 1962. IIALLEIT, W. Y. and MARTIN.C. J. : Obstructive pulmonary disease testing in hospital patients. Am, Rev. resp. Dis. 86, 686-696, 1962.
The Expiratory Flow Rate in Patients with Chronic Pulmonary Disease 8. 9. 10. 11. 12. 13.
219
RENZET~,A. D., McCLEMENT .I. H. and Lrrr. B. D.: The veterans administration cooperative study of pulmonary function III. Am. J. Med. 41,115-129,1966. Rrrcmx, B.: A comparison of forced expiratory volume and peak flow in clinical practice. Lancer 2,271-273, 1962. ROSENBLAIT, G., ALKALAY, I., MCCANNP. D. and Smr~. M. : The correlation of peak flow rate with maximal expiratory flow rate, one second forced expiratory volume, and maximal breathing capacity. Am. Rev. resp. Dis. 87, 589-591, 1963. SHEPHARD, R. J.: Some observations on peak expiratory flow. Thorax 17, 39-48, 1962. LEU.ULZ.N, E. C and FOWLER,W. S.: Maximal midexpiratory flow. Am. Rev. Tuberc. pulm. Dis. 72,783-800, 1955. Sono~, B. J. and E~GIL, C.: Airway resistance as measured by body plethysmograph versus measurements of expiratory flow rate. Am. Rev. resp. Dis. 96, 275-283, 1967.