The CF and control populations were compared for age, weight, and height. Success in producing FVC, FEV₁, FEV_0.75, FEV_0.5, and FEF_25–75 was compared by age group, and by diagnosis. FET was plotted against age and height. Start of test was examined by plotting Vbe (as absolute, and as %FVC) against age. Repeatability was examined by calculating the difference between the two highest FEV_0.75 readings (ΔFEV_0.75), and between the two highest FVC readings (ΔFVC). Timed expired volumes as fractions of FVC (FEV_0.5/FVC, FEV_0.75/FVC, and FEV₁/FVC) were calculated. Vbe, Vbe/FVC, ΔFEV_0.75, ΔFVC, FEV_0.5/FVC, FEV_0.75/FVC, and FEV₁/FVC were all compared by age group and by diagnosis. Data obtained from healthy children were compared with published reference values.

Summary statistics are presented as mean and standard deviation (SD) if normally distributed, and as median and interquartile range (IQR) if nonnormally distributed. Proportions were compared by χ² test. t tests or Mann–Whitney tests were employed for comparison of two groups; Analysis of variance and post hoc analysis by Tukey's honestly significant difference (HSD) were used to compare three or more groups. When interaction between several factors was suspected this was investigated by multiple regression. z scores for FVC, FEV₁, and FEF_25–75 were calculated from reference equations derived from 184 healthy white preschool children tested in Indianapolis, Indiana (3). z scores for FVC, FEV_0.5, and FEV₁ were calculated from reference equations derived from 603 preschool children tested in Oslo, Norway (4). For all analyses a p value of 0.05 was regarded as significant.

Seven children were unwilling to attempt spirometry. The median number of spirometry maneuvers attempted by the remaining 72 children was 12 (range, 6–22). Success in producing a reportable FVC, FEV_0.5, FEV_0.75, FEV₁, and FEF_25–75 is presented in Table 2

There was no significant difference between the CF and control groups in success rate for any of the parameters. Children aged 2 to less than 4 years were significantly less likely to produce FEV_0.75 or FEV₁ than children aged 4 to less than 5 years or children aged 5 to less than 6 years. No other differences in success rates by age group were seen.

Ability to meet quality control criteria was assessed for the 59 children who produced acceptable results.

Values for back-extrapolated volume (Vbe) and Vbe/FVC are summarized in Table 3

FET, summarized by age group and diagnosis, is presented in Table 3. Twelve of the 59 children produced a FET less than 1 second. These results must be interpreted with caution.

For the majority of children FEV₁/FVC was greater than 90%, irrespective of age group or diagnosis. By contrast, for the majority of children FEV_0.5/FVC was less than 90%. In healthy children there was a significant negative relationship between FEV_0.5/FVC and height (r² = 0.22, p = 0.009) and between FEV_0.75/FVC and height (r² = 0.27, p = 0.008), but no relationship between FEV₁/FVC and height. There was no relationship between FEV/FVC parameters and height in the CF population.

Differences between the two highest values of FVC (ΔFVC) and FEV_0.75 (ΔFEV_0.75) are displayed in Table 3. The population median for all age groups was less than 4% for ΔFEV_0.75, and less than 5% for ΔFVC, with no significant difference for either parameter by age group. Twenty-four children (41%) had ΔFVC greater than 5%, of whom 5 (9%) had ΔFVC greater than 10%. Fifteen children (28%) had ΔFEV_0.75 greater than 5%, of whom 3 (6%) had ΔFEV_0.75 greater than 10%.

Figure 3

Additional results are presented in the online supplement. The online supplement includes traces that were excluded on visual inspection, traces from maneuvers that had high Vbe or Vbe/FVC, data on ethnic background, analysis of timed expired volumes as proportions of FVC by age and diagnosis, plots of ΔFEV_0.75 and ΔFVC against age, and plots of z scores for our healthy population (3, 4).

Visual inspection of the flow–volume curve and the volume–time curve is a mandatory first step for quality control of spirometry. Some of the faults that require results to be excluded are self-evident: these include cough or glottic closure, double expiration (seen as a double peak on the flow–volume curve), or failure to produce an adequate peak flow. Previous studies of spirometry in this age group have used similar criteria for accepting or discarding loops (3–5).

Evaluation of end-of-test by visual inspection is more difficult. In older children and adults the volume–time trace asymptotes to horizontal toward the end of expiration (1). In preschool children, particularly the youngest, this asymptote is frequently not seen, even in children who appear to have produced a complete expiration (Figure 1). The abrupt cessation of expiration in very young children complicates assessment of end-of-test, as curves such as that shown in Figure 1 should not be excluded inappropriately. Eigen and colleagues (from the Indianapolis group) have suggested excluding curves when expiratory flow abruptly ceases from a point greater than 25% of peak flow (3); Marostica and colleagues (also from the Indianapolis group) have proposed excluding curves when expiratory flow abruptly ceases from a point greater than 10% of peak flow (9); while Vilozni and colleagues have suggested excluding curves when cessation occurs abruptly from a flow of 300 ml · second^–1 or more (5). All suggestions have merit, particularly if consensus could be reached, but many spirometry software systems do not provide such information automatically. Our current study design, in which all curves are inspected by at least two experienced researchers, and “borderline” curves by at least three, is not possible in daily practice. We therefore suggest that manufacturers should modify software so that information on change in rate of lung emptying toward the end of expiration is easily available, with automatic identification and display of critical cutoff points as suggested above. In those curves where incomplete expiration is identified, timed expired volumes and peak flows may still be reportable (13), even though FVC and forced expiratory flows cannot be reported from such maneuvers.

ATS guidelines recommend that start of test be assessed quantitatively by calculating the Vbe, and that this volume should be no greater than 5% of FVC, or an absolute volume of 150 ml, whichever is the greater (1). ERS criteria use 5% of FVC, or absolute volume of 100 ml as the cutoff (2). Although the majority of school-age children can achieve the 5% criterion (11), this does not appear to be the case among preschool children. In our study only 16 (27%) children produced a Vbe/FVC of less than 5%, suggesting that this cutoff is too strict, whereas a cutoff of 150 ml is too high to be of any value in a preschool population. In Figure 2B we have marked the four children who produced a Vbe greater than 80 ml; all these children had Vbe/FVC less than 12.5%.

All the curves included in this analysis had been passed visually as showing acceptable rise to peak flow. After reinspection of curves with high Vbe or Vbe/FVC, we concluded that our initial visual inspection had included and excluded curves correctly. We therefore suggest that expirations with Vbe greater than 80 ml or Vbe/FVC greater than 12.5% should be visually reinspected to ensure acceptable rise to peak flow, but should not necessarily be excluded.

ATS criteria recommend that expiration continue until there is a clear plateau on the volume–time trace, and that FET should be at least 6 seconds, or that there should be no volume change for 1 second. Although these ATS recommendations state that a shorter exhalation time is acceptable in children they do not specify what this time should be. ERS criteria do not quantify duration of expiration for quality control. A previous study has demonstrated that a 6-second forced expiration is impossible even for school-age children to achieve (11), and we intended to examine this in our preschool population. Unfortunately, the FET results obtained from the Jaeger system were found to be unreliable.

Duration of expiration determines which time-limited volumes are reportable. If FET is less than 1 second, then FEV₁ cannot be reported from that expiration. Success in producing FEV₁ was dependent on age in this study, with only 41% of children younger than 4 years able to produce a FEV₁, compared with 80% of those more than 5 years of age. There was no difference in the success rates between the healthy and CF groups. Previous researchers have reported similar findings. Eigen and coworkers reported results only from children who were able to expire for at least 1 second, but still recorded a creditable success rate of 83% in a slightly older population than ours (mean [SD] age, 5.0 [0.9] years) (3). Crenesse and coworkers reported results in 473 children aged 3 to 5 years. Seventy-five percent (355) were able to produce at least 1 acceptable forced expiratory maneuver. Of these, only 75% of children 3 to less than 4 years old, 73% of children 4 to less than 5 years old, and 87% of children 5 to less than 6 years old were able to produce an FET of greater than 1 second (10). Nystad and colleagues reported results from 630 children aged 3–6 years, and found that 10% were unable to expire for 1 second (4). It is therefore recommended that spirometry software should calculate FEV_0.5 and FEV_0.75, and that all laboratories should analyze and report both these parameters in addition to FEV₁ for children aged under 6 years, to allow comparison with others of similar age. For many 2- to 4-year-old children, only the shorter timed volumes will be reportable. The Jaeger software currently allows timed expiratory volumes to be reported incorrectly. Operators should ensure that their own software does not contain similar errors. Any timed volume that is reported as equal to FVC should be considered potentially erroneous.

Even when an FEV₁ is attainable, the clinical value of this parameter in this age group is questionable. Compared with older children and adults, infants and preschool children have large airways relative to their lung volume, and therefore empty their lungs more rapidly. As a result, the FEV₁/FVC ratio is more than 90% in the majority of preschool children, including those aged 5 to 6 years, and regardless of whether these children have lung disease. Reporting of FEV_0.4 or FEV_0.5 in infants is now accepted (13), and assessment of FEV_0.5 or FEV_0.75 may be more clinically relevant than FEV₁ in the preschool age group. Further investigation of the discriminative ability of different spirometric parameters is beyond the scope of the present study, but is an important area for future research.

ATS criteria recommend that the difference between the two highest values of FVC and FEV₁ should ideally be less than 200 ml, whereas ERS criteria stipulate that such differences should be less than 100 ml, or 5% of the best effort, whichever is the greater. In the present study, the repeatability of FVC and FEV_0.75 were assessed. All but five children had ΔFVC less than 100 ml, and all had a ΔFEV_0.75 less than 100 ml. However, as FVC and FEV_0.75 are much lower in this age group, use of absolute values as measures of repeatability may not be appropriate. Arets and colleagues (11) have previously reported that 88% of school-age children can produce a second FVC within 5% of their highest, and 87% can produce a second FEV₁ within 5% of their highest. In comparison, only 59% of our population were able to produce a second FVC and 72% a second FEV_0.75 within 5% of their highest. However, for both parameters, almost all were able to produce a second effort within 10% of their highest. These figures are similar to those previously reported by Nystad and colleagues (4). We therefore suggest that either an absolute value of 100 ml, or 10% of best effort, would be achievable repeatability targets for FVC and FEV_0.75 in this age group. We echo the ATS recommendation for adults that failure to meet repeatability criteria does not necessarily invalidate the maneuver (11).

To test whether results in our healthy children were similar to those reported by other groups we plotted our data alongside those previously reported by Eigen and colleagues, and also calculated z scores from published reference equations. The population measured in the current study had a higher proportion of nonwhite children (11 of 29 successful children, or 38%) than that reported by Eigen and colleagues (30 of 214, or 14%) (3). This may explain why concordance between the two populations is better for white children only than when data from children of all ethnic groups are combined. From data presented in Figure 3 and Table 4, it appears that nonwhite children have lower FVC and lower timed expired volumes than white children of the same height. Small numbers and the heterogeneity of our nonwhite population prevent further conclusions being drawn from the data currently available. However, this phenomenon warrants further investigation.

Ethnic group was not specified by the Oslo group, but Oslo has a very small nonwhite population. We therefore calculated summary statistics for our entire healthy population and separately for our healthy white children. z scores for our control population should be zero, with a standard deviation of 1, for all parameters, provided that our equipment and methodology are similar to that used by previous groups, and that our control population is similar to those from whom the reference equations were derived (14). For our white population, this was true for FEV_0.5 z scores calculated from Oslo data, for FVC and FEF_25–75 z scores calculated from Indianapolis data, and arguably true for FEV₁ z scores calculated from Indianapolis data. Our FVC and FEV₁ results did not fit the reference equations reported by the Oslo group.

In this study we tested children in the seated position whenever possible, and asked them to wear nose clips. Very young children may rebel against such instructions and we believe in such cases that these criteria should be relaxed if this is the only means of obtaining results. ATS guidelines suggest that subjects can be tested either seated or standing, but that this should be reported with the data (1). A report from school-age children who were tested with and without nose clips found no systematic effect on FEV₁ or FVC (15).

Incentive software can be distracting for older children (16), but in our population we found it helpful. We used the Jaeger incentive program (which is routinely available with Jaeger spirometry software) for all children. Vilozni and colleagues have reported that only 2% of 3- to 6-year-old children are able to produce an FEV₁ with the Jaeger incentive software, as compared with 49% of children who could produce an FEV₁ with their own SpiroGame incentive software (5). We note that in Vilozni's study only the Jaeger “Candle” incentive (which encourages rapid expiration) was used, and that, unlike in our study, the investigators did not move on to alternative incentives that encourage prolongation of expiration. We believe this methodologic difference explains the marked discrepancy between our results (in a younger population) and those previously reported by Vilozni's group.

On a related matter, children in the current study performed a maximum of 22 expiratory maneuvers, rather than the 8 recommended by the ATS (1). The reason for this is that many younger children initially produced incomplete expirations, particularly when using the “Candle” incentive. The Jaeger system does not allow easy recording of repeated maneuvers, and does not allow borderline or excluded traces to be stored for later reanalysis. Overcoming these hurdles required considerable effort on our part, including the use of custom-written software, and we consider this a strength of our study.

The most notable weakness of our study is that children were tested toward the end of a 2-hour laboratory visit. It is likely that some children were fatigued by the time they performed spirometry, and success rates may have been adversely affected. It is unlikely that other parameters would have been influenced by this methodologic issue. By contrast, one factor that may have increased our success rate was our use of a specially adapted preschool laboratory, with data collection performed by trained operators. This setup is not always available in the clinical setting.

There is now no doubt that spirometry in preschool children is feasible. Although some failure is inevitable, results can be obtained in 70 to 80% of these subjects. It remains to be proven whether measures obtained at this age are sensitive enough to influence clinical or research practice, but we suggest that establishing standards for quality control in the preschool age group, similar to those established for infant lung function testing (17), is now essential. The ATS and ERS have formed a working party to address this issue, and it is hoped that the data presented here will contribute to their effort. From our data we would suggest the following:

1. All curves must be visually inspected, but this process could be speeded and facilitated by modifications to software.

2. Start of test can be quantitatively assessed as in adults, but results greater than 80 ml for Vbe or 12.5% for Vbe/FVC should be indications for visual reinspection of the flow–volume trace, rather than automatic exclusion.

3. FEV_t should be reported only if FET for that expiration is greater than t.

4. In all preschool children both FEV_0.75 and FEV_0.5 should be reported in addition to FEV₁.

5. Repeatability can be assessed as for adults, but criteria of 100 ml and 10% of best effort for ΔFVC and ΔFEV_t may be more appropriate than the criteria applied to adults.

In addition to these recommendations, we caution users that current spirometry software may result in erroneous reporting of FET and timed expired volumes. We have contacted manufacturers with requests to amend software to allow quantitative assessment of end-of-test, and to allow recording and reanalysis of multiple maneuvers, including those initially assessed as inadequate or borderline. These software amendments should allow data to be excluded from reports or summaries, while still being retained on databases to allow future reanalysis.

Before incorporating such recommendations into guidelines it will be necessary for other groups to assess these criteria in their own populations. Given the portability of spirometry equipment, these criteria should ideally be tested in both specialized laboratories and in general clinics or health centers. Accurate application and interpretation of spirometric assessment in the preschool age group has considerable potential benefit, both for clinical practice and research. This benefit justifies the effort required for standardization.