INTRODUCTION

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Although forced expiratory maneuvers are routinely used to assess the lung function of adults and older children, there is relatively little use of this measurement in children younger than 6 yr of age, except for measurements of infants who are evaluated while sleeping (1). In adults, forced expiratory maneuvers can be very reproducible because flow limitation is achieved, that is, increasing effort or transpulmonary pressure does not produce an increase in flow (4). In young children, forced maneuvers may be less reproducible than in adults because the shorter attention span of the younger child limits the number of good efforts that can be obtained and subjects may not achieve flow limitation on multiple efforts. Cooperative subjects between 3 and 5 yr of age can be instructed to perform forced expiratory maneuvers; however, it has not yet been demonstrated that flow limitation is achieved in this age group. If a single best flow-volume curve achieves flow limitation, then a single curve may be adequate to define the subject's pulmonary function.

In adults, flow limitation is usually assessed using an esophageal catheter to estimate transpulmonary pressure during forced expiration (4). This technique to assess flow limitation would not be well tolerated in children 3 to 5 yr of age. Recently, a noninvasive technique has been used to demonstrate flow limitation in adults (5, 6). The application of negative expiratory pressure (NEP) at the airway opening during the forced maneuver will increase the driving pressure for flow. If flow increases with the application of NEP, then flow limitation was not present; however, if there is no increase in flow with NEP then flow limitation was achieved. This noninvasive methodology for assessing whether maximal flows are obtained during a forced maneuver has potential to improve our ability to assess pulmonary function in young children.

The aim of our study was to extend the use of NEP as a tool for demonstrating the occurrence of flow limitation in an age group that has been difficult to determine whether maximal flows are obtained. In addition, we propose a method to quantify the effect of NEP upon flow.

	METHODS

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Subjects

We evaluated 10 subjects between 3 and 5 yr of age (four male, six female), who had no previous experience in performing pulmonary function tests. All subjects were healthy at the time of evaluation.

Methodology

Forced expiratory maneuvers. The pediatric pulmonary function technician in our laboratory instructed the children on the performance of forced expiratory maneuvers and performed the testing. Forced expiratory maneuvers were measured while the children were standing and wearing noseclips. Testing was repeated until either maximal effort was obtained or the child was no longer cooperative. We also asked the more cooperative children to perform submaximal expiratory maneuvers.

Negative expiratory pressure. During the forced expiratory maneuver, negative pressure at the airway opening was generated with a circular Venturi device (Aeromech Devices, ON, Canada) described by Volta and coworkers (5). The Venturi device was attached downstream of the pneumotachometer (Figure 1). In this study, we used two methods to apply NEP: (1) long manually controlled NEP pulse and (2) short computer-controlled pulse. In the first six subjects, a manually operated switch opened the solenoid and a subatmospheric pressure of 10 cm H₂O was applied to the airway opening early in the forced expiratory maneuver. NEP was then maintained until the forced expiratory maneuver was completed (long pulse method). In these subjects flow-volume curves were obtained using Medical Graphics no. 1070 pulmonary function equipment (MediGraphics, St. Paul, MN). For the last four subjects, a short pulse was applied during the forced maneuver. The Venturi device was set to produce an airway pressure of 5 cm H₂O. We developed software that enabled us to measure the forced expiratory flow and mouth pressure and control the time delay between the beginning of the forced maneuver and the onset of the NEP pulse. In addition, we could set the duration of the NEP pulse. For these subjects we set the delay so that NEP was triggered after approximately 50% of the vital capacity was expired, and the duration of the pulse was 500 ms (short pulse method).

View larger version (35K): [in this window] [in a new window]   Figure 1.   Negative expiratory pressure (NEP) was applied with a Venturi orifice attached downstream of the pneumotachometer. The Venturi orifice was activated during the forced maneuver either manually or by the computer.

	RESULTS

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The application of NEP was well tolerated by the subjects. The median and range for the number of forced maneuvers performed by the 10 subjects was 15 (9 to 26).

Long Pulse Method

The effect of NEP on forced expiratory flow was visually assessed in these six patients. In Figure 2, the best flow-volume curves obtained during baseline and with the application of NEP with the long pulse method are illustrated for the six children studied. The NEP curves demonstrate a flow transient at the onset of NEP. Because NEP was removed after completion of the forced maneuver, a transient in the opposite direction is not seen in the flow-volume curve. For all subjects there appears to be no step increase in flow with the application of NEP, a finding consistent with flow limitation. In addition, the flow-volume curves with and without NEP appear to overlay by visual inspection.

View larger version (17K): [in this window] [in a new window]   Figure 2.   Forced maneuvers in six children. For each subject the best baseline curve is overlaid with the best NEP curve (long pulse method). There is no significant increase in flow or volume with NEP, thus suggesting that maximal flows were generated in these maneuvers.

Short Pulse Method

Two flow-volume curves obtained with a short NEP pulse were obtained from the same child performing submaximal and maximal efforts (Figure 3). In both maneuvers, NEP was applied at approximately 50% expired volume. Simultaneous with the application NEP there is a flow transient, which appears as a spike in the flow tracing. When NEP is removed there is also a flow transient, but in the opposite direction. We quantified the change in flow during the short NEP pulse that was not associated with the flow transients. Excluding the flow transient, we compared the measured flow during the pulse to the predicted flow during the pulse. The predicted flow points were obtained by fitting a fourth-order equation to the flow points before and after the NEP pulse, as illustrated in Figure 3. The difference between the measured and the predicted flow points were averaged and expressed as the %flow. A step increase in flow with the application of a short NEP pulse as demonstrated in Figure 3, left panel. There was a %flow = 22.7%, which is consistent with a submaximal effort. In contrast, Figure 3, right panel, illustrates that during this forced maneuver a short NEP pulse was not able to increase flow, and %flow = 2.7%, which is consistent with flow limitation.

View larger version (14K): [in this window] [in a new window]   View larger version (11K): [in this window] [in a new window]   Figure 3.   Flow-volume curves with NEP illustrating submaximal (left) and maximal (right) efforts in the same child. The analysis with a quadratic equation of the flow points before and after NEP (black dots) provide the predicted flow for that segment (crosses). The resulting predicted flow was compared to the measured flow (open circles). The average difference between the observed and predicted flow points during NEP was expressed as a percentage of the predicted flow. The curve of the left panel demonstrates a step increase in flow with the application of NEP (Flow% = 22.7), while there is not a step increase in flow in the curve of the right panel (Flow% = 2.7).

The short NEP pulse during forced maneuvers for three additional children is displayed in Figure 4. The NEP did not produce a significant increase in flow in these subjects, with values for %flow of 6.6% (left panel ), 1.1% (right panel ), and 2.8% (lower left panel ).

View larger version (13K): [in this window] [in a new window]   View larger version (11K): [in this window] [in a new window]   View larger version (13K): [in this window] [in a new window]   Figure 4.   Flow-volume curves obtained with the application of short pulses of NEP for three additional children. The NEP did not produce a significant increase in flow in these subjects, with values for %flow of 6.6% (upper left panel ), 1.1% (right panel ), and 2.8% (lower left panel ).

In order to assess whether the application of NEP altered the calculated parameters from the flow-volume curves, we compared the values of FVC, FEV₁, and FEF_25-75 from the best baseline and NEP curves for the 10 subjects. Using a paired t test, there were no significant differences in FVC or FEF_25-75 (Table 1). Although, FEV₁ was statistically higher with NEP than at baseline, the mean increase was less than 2%. When the subgroup with the short NEP pulse was analyzed, there was no effect of NEP; however, the long pulse NEP subgroup had a statistically significant increase in FEV₁ (p < 0.05).

	DISCUSSION

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The young children we evaluated were able to achieve flow limitation during the forced expiratory maneuver when assessed by the application of NEP. This technique was well tolerated by the children, and it did not present significant technical difficulties. In some tests, we found evidence of a leak, which was suggested by a rightward shift in the flow-volume curve with an increase in flow and FVC. This leak was corrected by instructing the children how to obtain a better seal with their lips around the mouthpiece, thus avoiding air from being drawn from the atmosphere through the lips and then through the pneumotachometer.

In the application of the NEP methodology to adults (5), the investigators used pressures from of 5 to 20 cm H₂O. We chose the range between 5 and 10 cm H₂O to produce an obvious flow spike marking the application of NEP, and this increase in transpulmonary pressure should produce an increase in flow in submaximal efforts. The flow transients at the onset of NEP most likely result from the displacement of volume from the upper airways. In the study of adult subjects (5), there was a small but statistically significant decrease in FVC measured with NEP when compared with measurements without NEP; however, there was no significant difference for the other pulmonary function parameters. When we applied NEP in the children, we found no difference in FVC or FEF_25-75; however, there was a statistically significant increase in FEV₁ with NEP, which was associated with the long NEP pulse. Although there was a statistically significant increase in FEV₁, the mean increase of less than 2% would not be clinically significant. The difference associated with the long pulse may be secondary to the more negative value for NEP for the long versus the short pulse (10 versus 5 cm H₂O) and the presence of only the positive flow transient.

We initially applied NEP manually as a long sustained pulse since it was difficult to control manually the timing required for a short pulse. The long pulse visually gave the impression that a step increase in flow was not observed, a finding that would be consistent with flow limitation. The long pulse had the disadvantage as to difficulty in quantifying the change in flow, and that a sustained application of NEP until residual volume may result in more frequent leaks near the end of the maneuver. However, a potential advantage of a long NEP pulse may be to assist some children to achieve flow limitation or to sustain expiratory effort until residual volume is reached. The fact that the baseline and NEP curves were the same indicates that our subjects had achieved flow limitation during baseline measurements. However, if these subjects cannot reproduce this single best curve, it would be unclear as to whether they had achieved flow limitation without the application of NEP. In this age group with limited attention span and cooperation, it is important to minimize the number of maneuvers requested, particularly if an intervention such as a bronchodilator is to be assessed. We subsequently applied the short NEP pulse with timing controlled by the computer. The change in flow during NEP was readily quantified by our proposed method of comparing the measured flow to the predicted flow.

In conclusion, the application of NEP to young children is well tolerated. This methodology demonstrates that children between 3 and 5 yr of age can achieve flow limitation during forced expiratory maneuvers. Additional studies are required to assess the usefulness of NEP for routine assessment of airway function in this age group.