INTRODUCTION

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Pulmonary function testing is an important tool in the diagnosis, assessment, and management of respiratory diseases in adults and older children. The ability to perform lung function testing on preschool children with the early onset of respiratory disease such as in cystic fibrosis would aid in the assessment and follow-up of individual patients. It would also permit evaluation of therapeutic interventions earlier in the course of the disease than is now possible. Many of the commonly used reference standards such as Polgar and Promadhat (1), Knudson and coworkers (2), and Hsu and coworkers (3) have few subjects of less than 115 cm standing height and do not include subjects of less than 110 cm in standing height and younger than 6 yr of age. In the compilation of normal data by Polgar and Promadhat, graphic comparisons of the results of 34 different published studies of vital capacity are made and summary plots are derived as a function of height, but all patients are taller than 110 cm (1). Quanjer (4) has recently compiled similar data from 45 reference populations, and these data are also limited to children above 110 cm in height and older than 5 yr of age.

Methods exist for testing lung function in infants using spirometric techniques in which the patient is passive and forced exhaled flows are generated from near total lung capacity (TLC) to residual volume (RV) by rapid chest compression (5). This technique is not applicable to preschool children because of size limitations and the need for the subject to be completely relaxed or asleep. Partial expiratory flow volume curves obtained in the tidal range of breathing have been used to assess pulmonary function of young children; however, this technique has not proved clinically useful (6, 7).

It has been thought that children in the preschool age group are unable to comply with the maneuvers necessary to produce consistent flow-volume curves. The expressed reasons for such difficulties include the following: the short attention span and low frustration tolerance of the younger child limit the number of good efforts that can be obtained; an inability to inspire consistently to TLC; and an inability to exhale completely and with consistent maximal effort to zero flow. The purpose of this study was to evaluate spirometric lung function in a group of normal preschool children between 3 and 6 yr of age.

	METHODS

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We recruited 307 healthy children from Indianapolis nursery schools and daycare centers after obtaining permission from respective directors to leave information for parents describing the study. The Institutional Review Board at the Indiana University Medical Center approved the study and written informed consent was obtained from each child's parent or legal guardian. The presence of underlying respiratory disease and environmental exposures were assessed with the questionnaire recommended by the Epidemiology Standardization Project, ATS-DLD-78-C, which was completed by a parent of each child. All subjects who were described by parents as being in "good health" were first identified. In addition, it was required that each subject's parents describe the child as being free of asthma, reactive airways disease, "chronic bronchitis," or any significant respiratory conditions.

Upon review of the health questionnaire, children were excluded from the study if any of the following applied:

1. Gestational birth age < 34 wk and birth weight < 5 lb.

2. The child had been hospitalized for any respiratory condition.

3. A physician had ever stated that the child had asthma, reactive airways disease, or if the child had taken antiasthma medications for symptoms on more than one occasion.

4. The child was diagnosed with congenital heart disease requiring surgery or medications for management.

5. There were positive responses concerning other serious chest problems, chest surgery, chronic productive cough, recurrent intractable wheezing, and shortness of breath.

Standing height was measured in duplicate with a standing straightedge ruler calibrated on site by confirming perpendicular alignment with the underlying hard floor. Weight was measured in duplicate with a portable scale. Spirometry was performed using the Cybermedic "Moose" (Cybermedic, Inc., Louisville, CO) or the Collins SurveyTach (Warren E. Collins, Inc., Braintree, MA). In testing most of the children they blew directly into the KOKO-MOE assembled filter (part #f 8510; PDS Instrumentation, Louisville, CO) or the Collins DCI disposable filter (Warren E. Collins Inc., Braintree, MA). In children with small mouths, we added a mouthpiece from an Assess low range peak flow meter with a diameter of 2 cm (Healthscan Products, Ceder Grove, NJ) attached externally with a rubber tubing end (part #022252; Warren E. Collins Inc.). Spirometric measurements included peak expiratory flow rate (PEFR), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁), and forced expiratory flow between 25% and 75% expired volume (FEF_25-75). Calibration was performed on site before each testing session and according to the manufacturer's instructions. In this equipment, expiratory flow at the mouth is measured using a pneumotachograph, and volume is derived from digital integration of flow. The flow-volume curve was monitored on the computer screen to ensure good effort. Results were corrected to BTPS.

None of the children had any previous experience performing spirometry. In order to ensure the practicality of our methods in a clinical setting, the entire instruction and testing session for each child was strictly limited to 15 min, during which time children were instructed in the techniques of spirometry and performed at least three forced vital capacity maneuvers. A highly experienced children's pulmonary function technologist did the instruction for each child. At the time of testing, each child was given an explanation of the testing procedure individually and then tested using coaching techniques used in our pulmonary function laboratory in evaluating younger children:

1. Because all children learn differently, explanations were adjusted accordingly.

2. If the child appeared apprehensive, we established a nonthreatening environment by talking to him or her and gently exposing each to the procedure by blowing into party favors or whistles.

3. We began explaining the procedure by stating they needed to take a big breath and blow it into the tube (or mouthpiece) to make "a mountain" on the computer. Different techniques were used as needed so that each child understood what was being asked (e.g., phrases such as "blowing out birthday candles," "blowing party favors," "taking a big breath like sucking on a straw," and "blowing like the big bad wolf").

4. Once the general procedure was understood, specifics like "blowing all the air out" and "blowing the air out as hard as you can" were added.

5. The technician then demonstrated for the child the actual technique, blowing on the child's hand through the mouthpiece and instructing them at the same time to blow hard for one long breath without stopping.

6. The child was then asked to place the mouthpiece in his or her mouth and was coached to breathe at tidal volume and then to take a deep breath and blow out using the above-mentioned techniques, while maintaining a good seal between the lips and the mouthpiece.

7. All children were tested while standing and wearing nose clips.

8. We then had the child attempt a forced expiratory maneuver. Frequent practice and encouragement were given during the process. Some children learned how to "blow out fast" first (i.e., generate an adequate peak expiratory flow). After they had mastered this component of the forced vital capacity maneuver, we would then work on teaching the "blowing long" aspect of generating an adequate maximal expiratory flow-volume curve (i.e., exhaling completely and maximally to zero flow or residual volume). The child would be encouraged to blow on a tissue as if he or she "were the wind." Other children were encouraged to blow long until they heard a bell (e.g., on the Cybermedic spirometer) or until they "got a star" (e.g., on the Collins spirometer).

9. Usually the child was happy to keep trying but if he or she became scared or cried or seemed to be tired, the testing was stopped. The stopping point varied from child to child, and was determined by the pediatric technician's judgment as to how long to continue to attempt to obtain three technically acceptable efforts. No session lasted more than 15 min.

10. The respiratory therapist and the on-site physician (H.B.) assessed each effort to eliminate flow-volume curves that were clearly unacceptable. Data from each technically acceptable effort were stored. Maneuvers were repeated to obtain three acceptable curves but always within the 15-min time limit. The best effort curve for each subject was designated as the flow-volume curve with the largest sum of FEV₁ and FVC, assuming adequate technical effort.

Later, one investigator (H.E.), blinded as to name, age, height, and sex of the subject, reviewed all computer-derived individual flow-volume curves for technical acceptability. Flow volume curve efforts were deemed unacceptable and were deleted from the analysis file if

1. a peak flow could not be clearly determined;

2. the effort ended abruptly and there was a sharp drop or cessation in flow from a point where flow was > 25% of the peak expiratory flow;

3. the exhalation lasted for less than 1 s.

4. the child did not inhale above tidal volume breathing; or

5. variability with other generated flow-volume curves was evidently high.

In the case of peak flow we rejected curves if the top of the curve was rounded and there was no distinct peak or if there was more than one peak. These were categorized as technically inadequate for purposes of assessing what percentage of patients could perform adequate tests. Some families did not complete the respiratory health questionnaire satisfactorily at the time of testing. We attempted to contact these families again for completion and clarification. Only patients whose parents had fully completed the respiratory health questionnaire were included in the sample.

To evaluate the retest reliability of spirometric efforts of normal 3- to 6-yr-old children, 14 children performed spirometry on site twice within a 1-wk period.

Statistical Methods

Multiple regression techniques were used to determine whether a significant relationship existed between the individual's measured best lung function parameters (PEFR, FVC, FEV₁, and FEF_25-75) and independent variables such as physical traits (height, weight, age, sex, and race) and health questionnaire items such as family asthma and environmental cigarette smoke exposure. To compare the rate of emptying of the lung during forced expiration for the preschool children and our previously reported results for infants and very young children (5), we calculated a rate constant: RC (s¹) = FEF_25-75/FVC. Intraclass correlation coefficients (ICC) were calculated to assess the overall reproducibility of pulmonary function parameters. In addition, the lung function parameters measured on two separate days in a subgroup of preschool children were compared using a paired t test.

	RESULTS

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We screened 307 healthy children aged 3-6 yr for this study. Of these, 259 children fully completed health assessment questionnaires and fulfilled inclusion criteria as normal. Of those entered as normal subjects, 82.6% (214 of 259 eligible subjects) were successful in generating technically acceptable flow- volume curves during their first testing session. For the 214 normal children who performed technically acceptable flow- volume curves, the age range was from 36 to 87 mo, and standing height ranged from 87 to 127 cm. There were 114 boys and 100 girls, and the ethnic distribution included 184 whites, 14 black, 7 Asian, and 9 other. Twenty-eight percent of the children had a positive history for daily environmental tobacco smoke exposure and 14% had a family member with asthma (Table 1). Because of known racial differences in spirometry for older children (3) and the small number of nonwhite children, we generated a regression model using only data from white children (n = 184) rather than the entire population tested.

The regression model with log-transformed parameters of pulmonary function and height had the best correlations and distribution of residuals. After accounting for height in the model, other physical traits and health questionnaire items did not contribute significantly to the following model:

(1)ln(pulmonary function parameter) =  +  × ln(Ht)

where  is the intercept,  is the slope from the regression analysis, and Ht is standing height in cm.

PEFR, FVC, FEV₁, and FEF_25-75 all increased with increasing height; correlation coefficients were 0.73, 0.93, 0.92, and 0.67, respectively. There was a significant decrease in the ratio FEV₁/FVC with increasing height; the mean predicted FEV₁/ FVC was 0.97 at 90 cm height and 0.89 at 125 cm height. Similarly the rate constant decreased with increasing height. The mean predicted RC (s¹) was 1.45 (s¹) at 90 cm height and 1.0 (s¹) at 125 cm height. Scatter plots of each pulmonary function parameter versus standing height, as well as the predicted regression values and the 95% confidence limits, are presented for the white children in Figures 1 and 2. The regression equations for these pulmonary function parameters are summarized in Table 2. Ninety-five percent of all subjects had three technically acceptable curves and the other 5% had only two technically acceptable curves. The reproducibility of the PEFR, FVC, FEV₁, and FEF_25-75 measurements obtained from each subject was expressed using the intraclass correlation coefficient (ICC). The ICC is an estimate of the correlation between two measurements from one subject. The very high values of ICC for these parameters (Table 2) indicate that our measurements are very reliable. The group mean coefficients of variation for replicate measurements of PEFR, FVC, FEV₁, and FEF_25-75 were 7.8%, 2.5%, 2.7%, and 8.3%, respectively. There was a small but significant effect of age upon variability with younger subjects having greater variability relative to their smaller absolute values of FVC and FEV₁.

View larger version (24K): [in this window] [in a new window]   Figure 1.   Individual data for lung function parameters versus standing height (cm). Included are the predicted regression values and the 95% confidence limits. (Top panel ) Forced vital capacity (FVC: L). (Middle panel ) Forced expiratory volume in 1 s (FEV1: L). (Bottom panel ) Forced expiratory flow between 25% and 75% expired FVC (FEF25-75: L/s).

View larger version (26K): [in this window] [in a new window]   Figure 2.   Individual data for peak expiratory flow rate (PEFR: L/s) and FEV1/ FVC versus standing height (cm). Included are the predicted regression values and the 95% confidence limits.

For the 14 preschool children who were retested within 1 wk, there was no significant change in FVC; however, there was a significant decrease in PEFR, FEV₁, and FEF_25-75 of 9%, 7%, and 14%, respectively (Table 3).

	DISCUSSION

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Our study found that the majority of 3- to 5-yr-old preschool children, who were naïve to pulmonary function testing, could be taught to perform reproducible spirometry within 15 min. In this age group, the pulmonary function parameters were highly correlated with standing height, and the intratesting variability and the intersubject variability are similar to those reported for older subjects. These findings suggest that spirometry can be used for the assessment of pulmonary function in this age group and that the regression equations generated from the data we obtained from 184 healthy preschool white children can be used as reference values for comparable populations.

Of the 214 normal preschool children whom we evaluated, 95% produced three technically acceptable forced expiratory maneuvers with FVC within 10%, and there was no significant difference in FVC for the subgroup of preschool children evaluated on two different days. There was a small but statistically significant decrease in PEFR, FEV₁, and FEF_25-75 for the subgroup of preschool children evaluated twice within the same week. We retested this group to determine if there was a learning effect, which would have shown an increase on the subsequent testing and which did not occur. The changes in the parameters may reflect a small decrease in maximal effort on the follow-up testing. We have recently demonstrated that preschool children can achieve flow limitation during forced expiration (8). In this current study, the shapes of the flow-volume curves for each subject were visually very reproducible and the reproducibility of the pulmonary function parameters in these preschool children was similar to that reported for older children (9). In addition, in the region where height for the subjects in this study overlaps that for older children from previous studies, the predicted values for FVC and FEV₁ are in good agreement with those of Polgar and Promadhat (1) and of Knudson and coworkers (2) (Figures 3A and 3B), whereas the values for PEFR and FEF_25-75 were higher in our subjects. The slopes of the regression equations of the log-transformed parameters are also similar for our preschool children and for older children (4). These findings are all consistent with the achievement of maximal flow-volume curves for the preschool children evaluated in this study. We were forced to use two different spirometers in order to test patients at the convenience of the preschool staffs and families. Both units met the ATS criteria for accuracy and reproducibility, and were calibrated on site prior to each session. While this may have added a small amount of variability to our data, we would expect that these normative data would be used to compare young children tested on a variety of equipment and so we feel it does not reduce the usefulness of the data generated.

View larger version (13K): [in this window] [in a new window]   View larger version (14K): [in this window] [in a new window]   Figure 3.   Shows a comparison of regression equations from this study with those of Polgar (1) and of Knudson (2); (A) FVC versus standing height and (B) FEV1 versus standing height.

We did not find sex differences in the spirometric parameters for the normal white preschool children in this study. This finding is consistent with our recent evaluation of forced expiratory maneuvers in infants and very young children where there was no sex difference in FVC, FEV_0.5, or FEF_25-75; however, we did find lower forced expiratory flows at low lung volumes (FEF₇₅) in the infant boys compared with infant girls (4). Sex differences in lung volume and forced expiratory flows at higher lung volumes, which are present in older children, may not be present in preschool children or the differences may be too small to detect with the number of subjects evaluated in our study.

In our recent assessment of forced expiratory flows in infants and very young children, we found that the rate of lung emptying was fastest in the neonates (RC = 7.4 s¹ at 50 cm and rapidly declined during the first 2 yr of life (5, 10). This finding was consistent with a more rapid increase in lung volume than airway caliber, which has been referred to as dysanaptic growth of the airways and the lung parenchyma. Among our preschool children, we also found that RC declined with increasing height although the magnitude of the decline in RC with growth was greater for the infants and toddlers than for the preschool children. In addition the RC values in our older infants and toddlers were similar to RC values for the youngest preschool children. These findings suggest that lung volume is still growing faster than airway caliber in preschool children, although the most rapid rate of lung parenchymal growth relative to airway caliber occurred in the first year of life.

In conclusion, reproducible spirometry can be obtained in the majority of preschool children. The relationship between spirometric pulmonary function and height in this age group is consistent with the relationships reported in older children as well as in infants and very young children. The values reported in this study for preschool children can be used as reference values for similar populations. In this age group spirometry has the potential to improve our assessment and our management of pulmonary disease, and there is a potential to use forced expiratory maneuvers to assess pulmonary function from infancy to adulthood.