Pulmonary Function Testing Reference Values and Interpretations in Pediatric Training Programs

(1)

Pulmonary

Function

Testing

Reference

Values

and Interpretations

in Pediatric

Training

Programs

Edward

N. Pattishall,

MD, MPH

From the Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA

ABSTRACT.

A

questionnaire was sent to all pediatric

training programs to evaluate the use of pulmonary

func-tion reference standards and the interpretation of

pul-monary function test results. Responses were obtained

from 107 of 130 institutions, and 94 of these had

pulmo-nary function laboratories available. Of the 94, 60 used

one of three reference standards. The primary reason the

reference standards were chosen was either unknown or

because they came with the spirometer (24), were

rec-ommended by another person or were those used in that

person’s training (34), or were thought to be the best standards available or most applicable to the population

to be tested (31). To define abnormality, most used an 80% predicted cutoff for forced vital capacity, forced

expiratory volume in 1 second, and forced expiratory flow

at 25% to 75% vital capacity. For a change in an

individ-ual through time, most used a 10% change for forced vital

capacity, forced expiratory volume in 1 second, and forced

expiratory flow at 25% to 75% vital capacity. Thirteen

used statistical methods to define abnormal individuals

and none used statistical methods to define a significant

change over time. Although there are a few guidelines for

reference standards and interpretations of pulmonary

function tests, it appears that most laboratories are not using those guidelines and that further guidelines and education are needed. Pediatrics. 1990;85:768-773;

Res-piratory function tests, standards, reference standards.

The arrival of inexpensive, compact,

computer-ized pulmonary function testing equipment has

al-lowed pulmonary function testing to become

in-creasingly available for pediatric patients. However,

with the increased numbers and types of equipment

and methods used, pulmonary function testing has

become more complex. To address some of the

resulting confusion, various organizations have

Received for publication Mar 14, 1989; accepted Apr 21, 1989. Reprint requests to (E. N. P.) 8403 Sterling Bridge Rd, Chapel Hill, NC 27516.

published statements that recommend standardized

procedures to be used.’4 In general, these reports

emphasize quality control, recommend

standard-ized nomenclature, and describe methods to be used

for performing pulmonary function tests.

In contrast, a more standardized approach to the

interpretation of pulmonary function tests has

re-ceived less emphasis. There are numerous reference

standards available5’8; however, the only

recom-mendation of the latest American Thoracic Society

statement on the standardization of spirometry is

that the reference values for forced vital capacity

and the forced expiratory volume in 1 second come

from the same study.’ Some other reports have

given further suggestions, such as selecting

stand-ards from reports that use the recommended

meth-ods, provide race- and gender-specific equations,

and use large numbers of healthy individuals whose

study population most resembles the population to

be tested.2

In addition to which reference standards to use,

there is controversy as to what level of dysfunction

is considered abnormal and what constitutes a real

change through time in an individual. Some have

advocated the use of a specific percent predicted

value as a cutoff to indicate abnormality,’9 but

others favor statistical approaches such as using

the standard deviation of the reference population

to define abnormality.20’2’ For the changes in an

individual through time, some advocate the use of

a specific percent change, but others recommend

using each person’s own coefficient of variation to

calculate the change that would be statistically

significant.2”22

The purpose of this investigation was to discover

what reference standards are being used in pediatric

training programs and why those standards were

chosen. In addition, the definitions used to identify

abnormal individuals and to define changes over

(2)

METHODS

A confidential questionnaire was developed to obtain information about pulmonary function

test-ing performed at different institutions. The

ques-tionnaire included basic information, such as the

specialty of the person completing the

question-name, type of hospital, the availability of a

pulmo-nary function testing laboratory for children, the

number of tests performed on children, and the

number of full-time faculty and fellows in the

pul-monology and allergy divisions. The questionnaire

then requested information regarding the type of

equipment used and who administers the tests. For

forced vital capacity, forced expiratory volume in 1

second, peak expiratory flow rate, forced expiratory

flow at 25% to 75% vital capacity (FEF2S%75%),

maximum expiratory flow at 50% vital capacity,

maximum expiratory flow at 25% vital capacity,

total lung capacity, functional residual capacity),

and residual volume, the responder was asked what

reference standards were used and why. Finally,

responders were asked how they define a significant

difference from the normal standards and a

signif-icant change within one subject.

The questionnaires were distributed to all 130

members of the Association of Medical School

Pe-diatnic Department Chairmen, Inc, who were from

institutions in the United States. The only

excep-tion was when a department had a pediatric

pul-monary fellowship training program,23 in which

case the questionnaire was mailed directly to the

training program director. The chairman or director

was asked to have the questionnaire completed by

the physician responsible for the pulmonary

func-tion laboratory and returned in a self-addressed,

stamped envelope.

The questionnaire was sent repeatedly until a

response was obtained or for a maximum of three

times. The responses were entered into a

microcom-puter database program (RBASE for DOS,

Micro-rim, Inc) and tabulated.

RESULTS

Responses to one of the three mailings of the

questionnaire were obtained from 107 (82%) of the

130 institutions. There were 62 responses from the

first mailing, 31 from the second, and 14 from the

third. Most responders were pediatric

pulmonolo-gists (59), but others included allergists (14),

pul-monary function technicians (5), chairmen (6),

in-tensivists (3), neonatologists (3), general

pediatni-cians (2), physiologists (2), a biomedical engineer,

an adult pulmonologist, and a hematology-oncology

subspecialist. The remaining 10 did not list their

specialty. There were 38 free-standing children’s

hospitals. There were no pediatric pulmonologists

associated with 23 institutions, no allergists in 29,

and neither in 10.

A pulmonary function laboratory was available

in 94 of the institutions, and over 41 600 tests per

year were performed at these institutions. Of the

94 laboratories, 51 were pediatric laboratories, 41

were combined adult/pediatric laboratories, and in

2 the type of laboratory used was unknown.

Of the 94 pulmonary function laboratories, the

type of spirometer used most often was either a

pneumotachograph (33) or dry sealed spirometer

(27). Others used a water-sealed spirometer (14),

wedge or bellows spirometer (7), or a combination

of any type (10). In three the type of spinometer

was unknown. For lung volumes, methods used

routinely included body plethysmography (43),

he-hum dilution or nitrogen washout (28), or both (13).

Lung volumes were not measured in five

labonato-nies, and the method used was unknown in five.

The person primarily responsible for administering

tests was almost always a trained pulmonary

func-tion technician (52) or a respiratory therapist (29).

In other institutions testing was primarily

per-formed by a nurse (7), physician (1), a combination

of these persons (2), or was unknown (3).

Nine of the responders did not know the

refer-ence standards used for any of the parameters of

lung function. In the remaining 85 institutions that

listed reference standards used, most used those

from Polgar and Promadhat,5 Weng and Levison,6

or Knudson et al7’8 (Table 1). For lung volumes,

most used the method of Polgar and Promadhat5 or

Weng and Levison.6

The reasons the standards used were chosen are

shown in Table 2. About one fourth of the

re-sponders either did not know the reference standard

used (9) or simply used whatever standard came

with the machine (16). In one third, the reference

standards were recommended by another person

(17) or were those used in the responder’s training

(17). In another third, the standards were chosen

according to their applicability to that laboratory,

the population being tested, or were thought to be

the best standards available (31). Two of these

institutions used standards derived from their own

laboratories. In the remaining 4, no answer was

given.

Eighty-three laboratories answered questions

re-garding the definition of abnormality. Sixty-seven

of these used a percent predicted difference from

the reference standard to define an abnormal result

(Table 3). There was surprising agreement among

laboratories, with 80% predicted used as the most

common cutoff for forced vital capacity, forced

(3)

TABLE 2.

Primary Reason for Use of Reference Stand- TABLE 4. Percent Change Used to Indicate a

Signifi-cant Change in an Individual Through Time

Midpoint Forced Forced Forced

Percent Vital Expiratory Expiratory Change Capacity Volume at 1 Flow at

Second 25% to

75% Vital

Capacity

5 6 4 1

10 35 34 17

15 22 23 16

20 5 9 12

25 1 10

30 3

35 3

>35 1

No Answer 1 7

from baseline (Table 4), 6 used a trend through

time with no definite cutoff, 4 used a change of 1

standard deviation ofthe individual or the reference

standards, while the remaining 3 used subjective

deterioration, or the cutoff depended on the clinical

situation. A 10% change was the most common

answer for all parameters, although a 15% change

was also common. There was again less agreement

for the percent change needed in the FEF25%.75%

taken to indicate a real change in an individual.

DISCUSSION

Based on the results of this survey, it appears

that more investigation and education are needed

to guide the interpretation of pulmonary function

testing in children. There have been only a few

recommendations to date, and most of those are

not being used. For example, greater accuracy can

be obtained by using gender- and race-specific

equa-tions.2 Of the three most widely used reference

although there was less agreement for the

FEF25%75%. Of the 83 persons that defined

abnor-mal values, 13 used a difference greater than 2

standard deviations from the reference standard to

indicate abnormality, although six of these also

used a specific percent predicted cutoff. Three used

other undefined means to define abnormality.

For significant changes in an individual through

time, 70 laboratories used a specific percent change

TABLE 1. Reference Standards Used by the 94 Institutions With a Pulmonary Function

Laboratory Available for Pediatr ic Patients

Reference FVC* FEV, PEFR FEF25%75% MEF00 MEF25 TLC FRC RV

Polgar and Promadhat5 32 31 38 29 2 2 39 38 35

Weng and Levison6 12 13 13 14 20 21 22

Knudson et al7’8 16 15 4 17 32 30 1 1 1

Hsuetal9 7 7 10 8

Dickman et al’#{176} 5 5 2 6

Zapletal et al’2 3 3 5 15 16 6 6 5

Othert 3 3 3 2 9 10 5 5 5

Combination$ 7 8 3 6 2 2 3 1 2

Standards not known 9 9 14 ii 16 15 16 17 19

Not performed 2 1 18 19 4 5 5

t Includes no more than two using standards from the following references: DeMuth et

al,” Warwick,’3 Schoenberg et al,’4 Murray and Cook,’5 Needham et al,16 Cook and

Hamann,’7 Morris et al,’8 or unpublished data.

:1:

Different standards used depending on race, gender, or age.

* Abbreviations: FVC, forced vital capacity; FEy,, forced expiratory volume in 1 second;

PEFR, peak expiratory flow rate; FEF25%75%, forced expiratory flow at 25% to 75% vital

capacity; MEF00, maximum expiratory flow at 50% vital capacity; MEF25, maximum

expiratory flow at 25% vital capacity; TLC, total lung capacity; FRC, functional residual capacity; RV, residual volume.

ard

Reason Number

Applicability or best available 31

Recommended by another person 17

Standard used in responder’s training 17

Came with the machine used 16

Don’t know why they were chosen 9

No answer given 4

TABLE 3. Percent Predicted of Reference Standard

Used as a Cutoff Between Normal and Abnormal Lung

Function

Midpoint

Pr:dicd

P ulmonary Function Parameter

Forced Vital

Forced Expiratory Volume in 1

Forced Expiratory Flow at 25% to

Capacity Second 75% Vital

Capacity

90 2 2

85 3 3

80 59 55 24

75 4 6 9

70 1 5

65 9

60 9

<60 3

(4)

standards for spirometry, one has neither gender

nor race-specific equations 6 and the others have

gender specific equations only.5’7’8 The standards

from Knudson et al7’8 were derived from a white

population only and may not be applicable to other

races.

Another example of a guideline not being used is

the recommendation to use reference values from

investigations using similar techniques.2”8’22 Of the

16 laboratories that used the reference standards of

Knudson et al7’8 for forced vital capacity, 14 used

the standards from their report in 1976. As they

described in a later report,7 the reference values

were derived using specific measurement

tech-niques to apply to their population for a

longitudi-nal study and were never intended to be used by

others for other populations using other techniques.

Similarly, 31 of the 59 laboratories that used the

reference standards of Polgar and Promadhat5 or

Weng and Levison6 for total lung capacity used

body plethysmography, even though both of these

reference standards were derived from studies using

gas dilution.

Because in most instances the few

recommenda-tions are not being followed, the most common

responses in this investigation should not be

con-strued to indicate the best reference standards or

the best indicators of abnormality.

One set of predicted equations used by all would

be helpful to standardize the interpretation of

pul-monary function tests, because different equations

give widely varied results. For example, using the

prediction equations from Knudson et a17 and Weng

and Levison,6 an average 14-year-old white female

with a height of 160 cm and a forced vital capacity

of 2.8 L would have a percent predicted of 90% and

79%, respectively. Persons of different races and

more extreme values may have even more disparate

results. Thus, it is difficult to compare

interpreta-tions based on percent predicted values from

labo-ratonies that use different standards. However, no

single pulmonary function reference standard was

used by a majority of laboratories.

On the other hand, one reference standard may

not be applicable to all populations. The reference

standard used should be derived using similar

tech-niques and from a population similar to that being

tested. Thus, standards would be as different as the

populations that are to be tested.

The process of evaluating reference standards

was performed in about one third of the

laborato-ries. Two thirds either didn’t know the standard,

used whatever was provided with the machine, used

a standard recommended by another person, or

used standards used in their training. While these

standards may have been appropriate, the process

of evaluating different standards was not

per-formed. In the third that had evaluated standards,

most chose the standard because it was determined

to be the best available at the time, not because it

applied to the population to be tested. In most

instances, the equations were the summary

equa-tions provided by Polgar and Promadhat.5 On the

other hand, a few laboratories went to great lengths

to evaluate reference standards, and some even

produced standards derived from their own

labo-ratory or compared results from their laboratory to

the reference standard used.

For the definition of abnormal values, most

lab-oratories used the conventional rule of thumb of

less than 80% of predicted as being abnormal. The

use of a percent predicted cutoff rather than a

percentile or 95% confidence interval continues to

be debated’921; however, most recent textbooks

nec-ommend using statistical methods, such as

confi-dence intervals or percentiles from the reference

standards, rather than the 80% predicted

cu-toff.’8’24’25 For the most commonly used reference

standard for spirometry,5 confidence intervals are

not available because summary equations of

flu-merous studies are used. Although the use of a

percent predicted cutoff may not be as

inappro-pniate in children as in adults due to increased

variability with increased height

(heteroscedastic-ity), at the very least, a lower percent predicted

cutoff less than 80% should be used due to the

increased variability of FEF2S%75%. Weng and

Levison6 and Hsu et al9 reported standard

devia-tions of 32.9% and 24% to 30% for the FEF25%75%,

respectively, compared to 6.2% and 13% to 17% for

forced vital capacity. Thus, a cutoff of 60%

pre-dicted would be more justifiable than 80% predicted

for FEF25%.75%. Better yet, the standard deviations

from the equation utilized should be used to

deter-mine the lower limits of normal for each person.

In an individual through time, a 10% to 15%

change indicated a significant change to most

lab-oratories. Again, the increased variability of

FEF2S%.75% caused a wider range reported to indicate

real change; however, the most common answer

was still 10% to 15%. As with the definition of

abnormality at one time, the increased variability

of FEF25%.75% should be recognized and the change

required should be larger. No laboratories used

statistical approaches, such as using the

individ-ual’s own coefficient of variation to calculate the

change required to define a change from baseline.

IMPLICATIONS

AND

RECOMMENDATIONS

In the past, pulmonary function standardization

(5)

clear that in the future, further evaluation and

recommendations for interpretation of pulmonary

function testing are needed. This study evaluated

standards and interpretations used by laboratories

in academic institutions which often provide

guid-ance to practicing pediatricians. It appears that the

few recommendations published are not being used

by these academic institutions. If pulmonary

func-tion testing is to be used in office practice,

pedia-tnicians will need guidance with easily applied

methods of interpretation to complement the

standardized methods that have already been

pub-lished. Specifically, better prediction equations are

needed for different genders, races, and ages,

espe-cially the adolescent age group. For spirometry,

only one reference’4 provides gender, race, and

age-specific equations for children and adolescents and

includes variability for determining the normal

range. Other equations which include variability

are also available 6.8,9; however, only one of these9

provides race and gender specific equations.

In addition to better prediction equations, further

evaluation of theoretical and practical definitions

of abnormality are needed. Use of the 95% percent

normal range to identify abnormality is preferable

to a specific percent predicted cutoff. There is still

disagreement whether other methods, such as the

percentile method2’ or normalizing persons to a

single value,’9 are superior to using the 95% normal

range. With the availability of computerized

equip-ment, more complicated equations and calculation

of normal ranges are much more practical than in

the past.

Until further recommendations are made, there

are some reasonable suggestions. Reference

stand-ards should be chosen from a study using the same

techniques that will be used and from a study using

a healthy population similar to the population being

tested. This requires examining the few reports

available for the methods used and the population

characteristics, such as age range as well as gender

and race composition. After a reference standard is

chosen, a small number of healthy children should

be tested occasionally to examine for systematic

differences. To determine abnormality, studies that

specify the standard deviation are preferable so that

the 95% normal limits can be determined. If

equa-tions must be chosen in which the vaniablity is

unknown, then fixed percent predicted cutoffs of

80%, 80%, and 60% are reasonable for forced vital

capacity, forced expiratory volume in 1 second, and

FEF25%.75%, respectively.20

Thus, until better equations are available,

per-sons responsible for pulmonary function testing

need to examine the studies available and

deter-mine the best reference values for their purpose. In

addition, different methods used to determine

ab-normality should be considered and applied

con-sistently.

REFERENCES

1. Gardner RM, Hankinson JL, Clausen JL, et a!. Standardi-zation of spirometry - 1987 update. Am Rev Respir Dis.

1987;136:1285-1298

2. Taussig LM, Chernick V, Wood R, et al. Standardization of lung function testing in children. Proceedings and recom-mendations of the GAP conference committee, Cystic Fi-brosis Foundation. J Pediatr. 1980;97:668-676

3. Zame! N, Altose MD, Speir WA Jr. Statement on spirome-try: A report of the section on respiratory pathophysiology of the American College of Chest Physicians. J Asthma. 1983; 20:307-311

4. Permutt 5, Chester E, Anderson W, et al. Office spirometry in clinical practice. Statement of the American College of Chest Physician’s committee on clinic and office pulmonary function testing. Chest. 1978;74:298

5. Polgar G, Promadhat V. Pulmonary Function Testing in Children: Techniques and Standards. Philadelphia: WB Saunders Co; 1971

6. Weng T, Levison H. Standards of pulmonary function in children. Am Rev Respir Dis. 1969;99:879-894

7. Knudson RJ, Lebowitz MD, Holberg CJ, et al. Changes in the normal maximal expiratory flow-volume curve with growth and aging. Am Rev Respir Dis. 1983;127:725-734 8. Knudson RI, Slatin RC, Lebowitz MD, et al. The maximal

expiratory flow- volume curve. Normal standards, variabi!-ity, and effects of age. Am Rev Respir Dis. 1976;113:587 9. Hsu KHK, Jenkins DE, Hsi BP. Ventilatory functions of

normal children and young adults: Mexican-American, white, and black. Part I. Spirometry. J Peidatr.

1979;95:14-23

10. Dickman ML, Schmidt CD, Gardner RM. Spirometric standards for normal children and adolescents (ages 5 years through 18 years). Am Rev Respir Dis. 1971;104:680-687 11. Demuth GR, Howatt WF, Hill BM The growth of lung

function. Pediatrics. 1965;35:159

12. Zapletal A, Motoyama EK, Van De Woestijne KP, et a!. Maximum expiratory flow-volume curves and airway con-ductance in children and adolescents. J Appl Physiol. 1969;26:308-316

13. Warwick WJ. Pulmonary function in healthy Minnesota children. Minn Med. 1977;6:435-440

14. Schoenberg JB, Beck GJ, Bouhuys A. Growth and decay of pulmonary function in healthy blacks and whites. Respir Physiol. 1987;33:367-393

15. Murray AB, Cook CD. Measurement ofpeak expiratory flow rates in 200 normal children from 4.5 to 18.5 years of age. J

Pediatr. 1963;62:186-189

16. Needham CD, Rogan MC, McDonald I. Normal standards for lung volumes, intrapulmonary gas mixing, and maximal breathing capacity. Thorax. 1954;9:313

17. Cook CD, Hamann JF. Relation of lung volumes to height in healthy persons between the ages of 5 and 38 years. J Pediatr. 1961;59:710-714

18. Morris AH, Kanner RE, Crapo RO, Gardner RM, eds. Clin-ical Pulmonary Function Testing. A Manual of Uniform Laboratory Procedures. 2nd ed. Salt Lake City, UT:Intermountain Thoracic Society; 1984:21-27

19. Sobol BJ, Sobol PG. Per cent of predicted as the limit of normal in pulmonary function testing: a statistically valid approach. Thorax. 1979;34:1-3

20. Pennock BE, Rogers RM, McCaffree DR. Changes in meas-ured spirometric indices. What is significant? Chest.

1981;80:97-99

21. Buist AS. Evaluation of lung function: concepts of normal-ity. Curr Pulmonol. 1982;4:141-165

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variability and per cent change for significance of spirometry 24. Dawson A. Spirometry. In: Wilson AF, ed. Pulmonary Func-in normal subjects and in patients with cystic fibrosis. Am tion Testing Indications and Interpretations. A Project of the

Rev Respir Dis. 1980;122:859-866 California Thoraclc Society. Orlando, FL: Grune & Stratton;

23. Training programs in respiratory disease and training pro- 1985:23-25

grams in pediatric respiratory disease, 1987 editions. Amer- 25. Miller A. Prediction equations and ‘normal values’ for pul-ican Thoracic Society/American Lung Association, New monary function tests. In Miller A, ed. Pulmonary Function York. Am Rev Respir Dis. 1987;136:497-523 Tests. Orlando, FL: Grune & Stratton; 1987:127-131

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(7)

1990;85;768

Pediatrics

Edward N. Pattishall

Training Programs