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Am. J. Respir. Crit. Care Med., Volume 161, Number 3, March 2000, 713-717

Flow Limitation in Infants Assessed by Negative Expiratory Pressure

MARCUS H. JONES, STEPHANIE D. DAVIS, JEFFREY A. KISLING, JOHN M. HOWARD, ROBERT CASTILE, and ROBERT S. TEPPER

Riley Children's Hospital, Indianapolis, Indiana; and Columbus Children's Hospital, Columbus, Ohio


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Forced expiratory flows by the rapid compression technique are often used to assess airway function in infants; however, it remains unclear as to whether flow limitation (FL) is achieved. Studies in adults have used negative expiratory pressure (NEP) at the airway opening as a noninvasive technique to assess whether FL is achieved. An increase in flow with NEP indicates that FL has not been achieved, whereas no increase in flow with NEP indicates FL has been achieved. In the adult studies, the change in flow was assessed by visual inspection of the flow-volume curve. We evaluated whether NEP could be used to assess FL during forced expiration in infants. In addition, we quantified the change in flow secondary to NEP. We applied -5 cm H2O NEP to four infants during forced expiratory maneuvers. The step increase in flow with NEP was always less than 5% at high jacket compression pressures and consistent with FL. For one subject, FL was also confirmed from isovolume pressure flow-curves measured with an esophageal catheter. We conclude that NEP can be used in infants to assess FL during forced expiratory maneuvers by the rapid compression technique. Jones MH, Davis SD, Kisling JA, Howard JM, Castile R, Tepper RS. Flow limitation in infants assessed by negative expiratory pressure.

    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Forced expiratory maneuvers by the rapid compression technique have been used to assess airway function in sleeping infants (1). Although significant insights into airway function have been gained using this methodology, it has been unclear whether flow limitation (FL) is routinely achieved in this age group (1, 7). When FL is achieved, flow reflects the airway function of the intrathoracic airways. It is the achievement of FL that has made forced expiratory maneuvers so reproducible and clinically useful in older children and adults.

During forced expiration by the rapid compression technique, the transpulmonary pressure (Ptp) developed depends upon the jacket pressure (Pj) applied to the body surface, the pressure transmitted across the chest wall, and whether the infant inspires during the maneuver. Increasing Pj may result in no further increases in Ptp secondary to chest wall reflexes and inspiratory effort by the infant. The Ptp required to achieve FL may not be achieved with increasing Pj; however, the flow-volume curves may be reproducible and suggest FL, as there was no increase in flow with increasing Pj.

Recently, it was demonstrated that FL can be achieved in normal healthy infants when several large inspiratory breaths prior to the forced expiratory maneuver inhibit inspiration (2). In that study, FL was determined from isovolume pressure- flow curves with changes in pleural pressure assessed from changes in esophageal pressure. Measurements of esophageal pressure in infants are difficult and time-consuming, and infants may arouse during placement of the esophageal catheter and thus result in no measurements being obtained. Currently, it is assumed that FL is achieved during routine testing when an increase in Pj does not produce further increases in flow.

A noninvasive technique to assess FL has been developed in adults (8). Transient application of negative expiratory pressure (NEP) to the airway opening during forced expiration transiently increases the driving pressure for expiratory flow. An increase in flow with the application of NEP indicates that FL had not been achieved, whereas no increase in flow indicates that FL had been achieved. The potential advantage of the NEP technique is not only its noninvasiveness but also the possibility that FL can be assessed with a single forced expiratory maneuver. In previous studies in adults, an increase in flow with NEP was evaluated visually; however, this analysis is subjective. The purpose of our study was to determine whether the NEP technique could be adapted to assess FL during forced expiratory maneuvers in infants and to quantify the assessment of FL with the NEP technique.

    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Subjects

Five infants between 1.5 and 20 mo of age were evaluated in the infant pulmonary function laboratory. The Institutional Review Board approved this study, and informed consent was obtained from the subjects' parents.

Forced Expiratory Flows

Forced expiratory maneuvers from elevated lung volumes were performed using the rapid thoracic compression technique as described by Feher and colleagues (2). Forced expiratory flows were initiated from a lung volume at which the airway pressure was equal to 30 cm H2O (V30) and proceeded to residual volume (RV). The forced expired volume between V30 and RV was defined as the forced vital capacity (FVC). The circuit used to deliver inspiratory breaths and to measure the forced expiration is illustrated in Figure 1. The inspiratory circuit contained an adjustable continuous flow of air and a pressure relief valve set at 30 cm H2O, which limited inflation of the respiratory system when the expiratory valve was occluded. Forced expiration was initiated at this elevated lung volume by rapidly inflating the jacket, which was wrapped around the infant's chest and abdomen. An electronic solenoid valve between the jacket and the pressure reservoir controlled jacket inflation, and jacket pressure was monitored with a differential pressure transducer (Validyne MP-45-871; Validyne, Northridge, CA) referenced to atmospheric pressure. A pneumotachometer (Model 3700; Hans Rudolph, Kansas City, MO) and differential pressure transducer (Validyne MP-45-871) were used to measure the inspiratory and expiratory flow. The analog signals of flow and pressure are amplified and filtered above 50 Hz (Validyne CD 19-A) and digitized at 100 samples per second (D/A board Data Translation, DT 3001). Volume was obtained by digital integration of the flow signal, and the signals are displayed on the computer monitor in real time and stored for subsequent analysis.


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Figure 1.   The circuit used to deliver inspiratory breaths and to measure the forced expiration. The inspiratory circuit contained an adjustable continuous flow of air and a pressure pop-off valve set at 30 cm H2O, which limited inflation of the respiratory system, when the expiratory portion of the 3-way valve was occluded. During forced expiration, the computer could activate the negative pressure controller so that the venturi orifice produced -5 cm H2O pressure in the face mask.

For the forced expiratory maneuvers using negative expiratory pressure at the airway opening, a circular venturi device (Aeromech Devices, Almonte, ON, Canada) was attached downstream from the pneumotachometer (Figure 1). The NEP device was set to generate -5 cm H2O. The computer controlled the onset and the duration of NEP after the start of forced expiration.

In one subject, esophageal pressure was measured with a microtip catheter (MTC P5FC Catheter; Dräger, Lübeck, The Netherlands) to demonstrate that the application of NEP during the forced expiratory maneuver increases the transpulmonary pressure. The catheter was placed in the lower third of the esophagus and the occlusion test was used to document that the esophageal catheter was properly functioning in the measurement of the changes in pleural pressure (9). The magnitude of the changes in airway and esophageal pressures were the same during inspiratory efforts with the airway occluded.

Protocol

The subjects were sleeping in the supine position after receiving 75 mg/kg of chloral hydrate orally. After several inflations to inhibit respiratory effort, forced expiratory maneuvers were obtained at increasing Pj between 30 and 100 cm H2O until maximal flows over the lower 50% of the FVC were attained. After obtaining the maximal flow-volume curve, forced expiratory maneuvers were repeated with the application of NEP. The computer triggered NEP at approximately 50% of the FVC for a duration of 200 ms.

Analysis

The effect of NEP on the flow-volume curve was analyzed using a method that we have recently described (10). NEP produced a flow transient when applied and removed during the forced expiratory maneuver. Three segments of the flow-volume curve were isolated for analysis (Figure 2): (1) flow points prior to the NEP segment (closed circles), (2) flow points during NEP, excluding the flow transients (open circles), and (3) flow points just after the NEP segment (closed circles). The digital points of the flow-volume curve before and after the NEP segment were modeled with a fourth-order quadratic equation. This regression equation yielded predicted values of flow over the NEP segment (crosses). The differences between the actual flows during NEP (open circles) and the predicted flows from the regression equation (crosses) were expressed as a mean percent difference from the predicted flows as follows:
Δ<IT>flow%</IT>=<FR><NU>1</NU><DE><IT>n</IT></DE></FR><LIM><OP>∑</OP><LL><IT>i</IT>=1</LL><UL><IT>n</IT></UL></LIM><FENCE><FR><NU><IT>flow</IT><SUB><IT>i</IT></SUB>(<IT>actual</IT>)−<IT>flow</IT><SUB><IT>i</IT></SUB>(<IT>predicted</IT>)</NU><DE><IT>flow</IT><SUB><IT>i</IT></SUB>(<IT>predicted</IT>)</DE></FR></FENCE>×100


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Figure 2.   Method of analysis to assess the percent change in flow with the application of negative expiratory pressure (NEP) during forced expiration. Three segments of the flow-volume curve were isolated for analysis: (1) flow points prior to the NEP segment (closed circles), (2) flow points during NEP (open circles), excluding the flow transients, and (3) flow points just after the NEP segment (closed circles). The digital points of the flow-volume curve before and after the NEP segment were modeled with a fourth-order quadratic equation. This regression equation yielded predicted values of flow over the NEP segment (crosses). The differences between the actual flows during NEP (open circles) and the predicted flows from the regression equation (crosses) were expressed as a mean percent difference from the predicted flows (Equation 1, see text).

    RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The changes in mouth pressure, transpulmonary pressure, and expiratory flow versus expired volume during forced expiration with the application of NEP for a 3.5-mo-old infant are illustrated in Figure 3. The onset of NEP produced a step decrease in mouth pressure and a simultaneous step increase in transpulmonary pressure of approximately 5 cm H2O. For this same subject, flow-volume curves obtained at two different jacket pressures (Pj) are presented in Figure 4. At the lower Pj (34 cm H2O), there is a visual step increase in flow with the application of NEP. Our NEP analysis yields a Delta flow% = 9.4%. At the higher Pj (76 cm H2O) there was no visual increase in flow during NEP, and our analysis yielded a Delta flow% = -1.8%. The change in flow during NEP at the higher Pj is consistent with flow limitation.


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Figure 3.   Tracing of mouth pressure, transpulmonary pressure, and flow versus expired volume during a forced expiration in a normal infant (age: 15 wk; length: 65 cm). During the application of negative expiratory pressure (NEP), at approximately 50% expired volume, there is a step decrease in mouth pressure and a step increase in transpulmonary pressure, demonstrating that NEP increases the driving pressure for flow during the forced expiratory maneuver. At the onset and offset of NEP, there is a flow transient; however, there is no visual step increase in flow with the step increase in transpulmonary pressure.


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Figure 4.   Flow-volume curves at two different jacket compression pressures (Pj). (Left panel   ) Pj = 30 cm H2O; (right panel ) Pj = 76 cm H2O, for the same subject as in Figure 3. For each flow-volume curve, three segments were isolated for analysis: (1) flow points prior to the NEP segment (closed circles), (2) flow points during NEP (open circles), excluding the flow transients, and (3) flow points just after the NEP segment (closed circles). The digital points of the flow-volume curve before and after the NEP segment were modeled with a fourth-order quadratic equation. This regression equation yielded predicted values of flow over the NEP segment (crosses). The differences between the actual flows during NEP (open circles) and the predicted flows from the regression equation (crosses) were expressed as a mean percent difference from the predicted flows (Equation 1, see text). NEP produced a mean percentage increase in flow (Delta flow %) of 9.4% at the lower Pj and -1.8% at the higher Pj.

Forced expiratory flow-volume curves with and without the application of NEP are illustrated for the five subjects in Figure 5. For each subject, the flow-volume curves with and without NEP are visually the same over at least the lower 50% of the FVC and there is no step increase in flow with the application of NEP. These findings are consistent with flow limitation during the forced expiratory maneuvers. Analyzing only the NEP flow-volume curves, the Delta flow% calculated using Equation 1 was +1.6%, -1.4%, +4.7%, +3.0%, and -8%, respectively.


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Figure 5.   Comparison of flow-volume curves with and without NEP for five infants. The solid lines are the flow- volume curves obtained without NEP. The dashed lines are the flow-volume curves obtained with NEP, and the transients indicate the beginning and the end of the application of NEP. Over at least the lower 50% of the forced vital capacity, the flow-volume curves with and without NEP are the same for all of the subjects, and there are no step increases in flow with the application of NEP.

    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Forced expiration by the rapid compression technique is a widely used methodology for assessing airway function in infants. The primary limitation of this methodology in infants has been the uncertainty as to whether FL is achieved, particularly in the absence of airway obstruction. Although IVPF curves indicate that FL can be achieved in normal infants, multiple maneuvers are required to construct IVPF curves, even if an esophageal catheter is not used (2). NEP offers a simple noninvasive technique to assess whether FL is achieved within a single maneuver. We have illustrated that the application of NEP does increase Ptp during forced expiration by the rapid compression technique in the infant. In contrast to previous studies in adults that used visual inspection to assess FL, we have quantified the change in flow during the application of NEP (8, 11). We have proposed that an increase in flow of less than 5% is consistent with flow limitation. This value appears reasonable as it approaches the accuracy of the flow measurement. In addition, at transpulmonary pressures below the value required to produce flow limitation, a change in Ptp of 5 cm H2O generally produces greater increases of flow than 5%, judging by the slopes of the IVPF curves (2). Ideally, one might establish criteria by comparing NEP with another method, such as IVPF curves. However, IVPF curves probably have a greater variability related to the use of multiple flow-volume curves secondary to FVC differences between maneuvers and variations in esophageal pressure, and there are no accepted criteria as to when a plateau is achieved in an IVPF curve.

In conclusion, NEP can be applied to forced expiratory maneuvers by the rapid compression technique in infants and the method can be used to identify the occurrence of flow limitation. Use of this technique in infants has the potential advantage of decreasing the number of maneuvers performed to determine whether flow limitation has been achieved.

    Footnotes

Correspondence and requests for reprints should be addressed to Robert S. Tepper, M.D., Ph.D., Department of Pediatrics, Indiana University Medical Center, James Whitcomb Riley Hospital for Children, Rm. 2750, 702 Barnhill Drive, Indianapolis, IN 46202. E-mail: RTEPPER{at}iupui.edu

(Received in original form July 28, 1998 and in revised form August 2, 1999).

Acknowledgments: Supported by Grant HL-54062 from the National Institutes of Health and by the Cystic Fibrosis Foundation.
    References
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

1. American Thoracic Society/European Respiratory Society Committee. 1995. Respiratory function measurements in infants: measurement conditions. Am. J. Respir. Crit. Care Med. 151: 2058-2064 [Medline].

2. Feher, A., R. Castile, J. Kisling, C. Angelicchio, D. Filbrun, R. Flucke, and R. Tepper. 1996. Flow limitation in normal infants: a new method for forced expiratory maneuvers from raised lung volumes. J. Appl. Physiol. 80: 2019-2025 [Abstract/Free Full Text].

3. Tepper, R. S.. 1987. Airway reactivity in infants: a positive response to methacholine and metaproterenol. J. Appl. Physiol. 62: 1155-1159 [Abstract/Free Full Text].

4. Tepper, R. S., H. Eigen, J. Brown, and R. Hurwitz. 1989. Use of maximal expiratory flows to evaluate central airways obstruction in infants. Pediatr. Pulmonol. 6: 272-274 [Medline].

5. Tepper, R. S., and T. Reister. 1993. Forced expiratory flows and lung volumes in normal infants. Pediatr. Pulmonol. 15: 357-361 [Medline].

6. Turner, D. J., S. M. Stick, K. L. Lesouef, P. D. Sly, and P. N. Lesouef. 1995. A new technique to generate and assess forced expiration from raised lung volume in infants. Am. J. Respir. Crit. Care Med. 151: 1441-1450 [Abstract].

7. England, S.. 1998. Current techniques for assessing pulmonary function in the newborn and infant: advantages and limitations. Pediatr. Pulmonol. 4: 48-53 .

8. Volta, C. A., Y. Ploysongsang, L. Eltayara, J. Sulc, and J. Milic-Emili. 1996. A simple method to monitor performance of forced vital capacity. J. Appl. Physiol. 80: 693-698 [Abstract/Free Full Text].

9. Coates, A., and J. Stocks. 1991. Esophageal pressure manometry in human infants. Pediatr. Pulmonol. 11: 350-360 [Medline].

10. Jones, M. H., S. D. Davis, D. Grant, K. Christoph, J. Kisling, and R. S. Tepper. 1999. Forced expiratory maneuvers in very young children: assessment of flow limitation. Am. J. Respir. Crit. Care Med. 159: 791-795 [Abstract/Free Full Text].

11. Eltayara, L., M. R. Becklake, C. A. Volta, and J. Milic-Emili. 1996. Relationship between chronic dyspnea and expiratory flow limitation in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 154: 1726-1734 [Abstract].

12. Koulouris, N. G., P. Valta, A. Lavoie, C. Corbeil, M. Chasse, J. Braidy, and J. Milic-Emili. 1995. A simple method to detect expiratory flow limitation during spontaneous breathing. Eur. Respir. J. 8: 306-313 [Abstract].

13. Koulouris, N. G., I. Dimopoulou, P. Valta, R. Finkelstein, M. G. Cosio, and J. Milic-Emili. 1997. Detection of expiratory flow limitation during exercise in COPD patients. J. Appl. Physiol. 82: 723-731 [Abstract/Free Full Text].





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