INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Infants with severe tracheomalacia have persistent wheezing and respiratory distress during tidal breathing, whereas infants with moderate tracheomalacia have intermittent wheezing that occurs with increased respiratory effort associated with activity. The more compliant airway in infants with tracheomalacia results in airway obstruction as a result of excessive dynamic airway narrowing during expiration. The degree of airway narrowing can be related to the expiratory effort associated with the increase in intrathoracic pressure during expiration. The diagnosis of tracheomalacia is established by bronchoscopic or fluoroscopic visualization of the airway narrowing (1).

Infants with severe tracheomalacia have been treated with continuous positive airway pressure (CPAP) to minimize their airway narrowing, and bronchoscopic visualization has documented less airway narrowing with CPAP (7). Measurements of flow-volume curves have also been used to assess the changes in airway obstruction with the application of CPAP to infants with tracheomalacia (11). The shapes of both the tidal breathing and the forced expiratory flow (FEF)-volume curves over the tidal volume (VT) range have been found to change from concave to convex with the application of CPAP, and there is an increase in the FEF at FRC. It has been suggested that the increase in airway pressure with CPAP "stents" the airway open and thus increases flow (13). However, both the measured flow and the shape of the flow-volume curve depend upon the lung volume at which they are measured. Expiratory flow is greater at higher lung volumes than at lower lung volumes. The previous assessments of the changes in flow with CPAP were limited to the VT range, and the potential effects of changes in lung volume and thus in flow were not considered. If CPAP increases lung volume at FRC, then the maximal flows at FRC will increase with CPAP as a result of the increase in the lung volume at which flow is measured. Therefore, in this study we measured full FEF-volume curves from near total lung capacity (TLC) to residual volume (RV), so that flows could be referenced to the same lung volume irrespective of the FRC at the different levels of CPAP.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Subjects

Pulmonary function testing was performed on six infants (3 to 10 mo of age) with moderate to severe tracheomalacia diagnosed by bronchoscopy. All infants exhibited at least 50% tracheal narrowing during bronchoscopy. These infants presented with clinical symptoms that varied from noisy breathing to wheezing and to respiratory distress, and four of the six infants required hospitalization for respiratory symptoms. One infant required a tracheostomy tube. Pulmonary function testing was also performed on five healthy infants (2 to 12 mo of age). The healthy infants had no history of lung disease or prematurity. The Indiana University Institutional Review Board approved the study, and informed consent was obtained from the infants' parents.

Pulmonary Function

Forced expiratory maneuvers from an increased lung volume were achieved with the rapid compression technique, as recently described by Feher and colleagaues (14). In this technique, forced expiration is initiated at a lung volume at which airway pressure is 30 cm H₂O (V₃₀), and which proceeds to RV. Delivering several inspiratory volumes to V₃₀ prior to forced expiration inhibits inspiratory effort during the forced expiratory maneuver. The circuit used to deliver the inspiratory breaths, measure FEFs, and apply CPAP is illustrated in Figure 1. A Sechrist Infant Ventilator (Model IV-100B; Anaheim, CA) was used to deliver an adjustable continuous flow of air through the inspiratory circuit, which contained a pressure-relief valve set at 30 cm H₂O. The expiratory portion of the circuit included an electronically controlled shutter valve in series with the CPAP valve of the Sechrist ventilator. Inspiratory and expiratory flows were measured with a pneumotachometer (Model 3700; Hans Rudolph, Kansas City, MO) attached to a differential pressure transducer (MP-45-871; Validyne, Northridge, CA). Inspiratory flow to the infant was produced by temporarily closing the expiratory valve and thus producing inflation of the respiratory system to an airway pressure of 30 cm H₂O. Opening the expiratory valve resulted in passive expiration to the preset level of CPAP. Following several inspiratory-expiratory cycles, the infant made no respiratory effort, forced expiration was initiated from V₃₀, and jacket pressure was sustained until flow declined to zero, which was defined as RV. The infant then resumed spontaneous respiration. Forced expiration was produced by rapidly increasing body-surface pressure with an inflatable jacket, as previously described for the rapid-compression technique (14). The jacket was wrapped loosely around the infant's chest and abdomen so that the jacket did not restrict lung inflation to V₃₀. Jacket-compression pressure was measured with a differential pressure transducer (MP-45-871; Validyne) referenced to the atmosphere. An electronic solenoid valve between the jacket and the pressure reservoir controlled inflation of the jacket. Pressure and flow signals were amplified and filtered above 50 Hz (CD19-A; Validyne), digitized at 100 samples per second (DT 3001; Data Translation, Marlboro, MA), displayed in real time on the computer monitor, and stored for subsequent analysis. The computer, via the digital to analog (D/A) board, controlled the valve in the expiratory circuit and the valve that connected the inflatable jacket to the pressure reservoir.

View larger version (52K): [in this window] [in a new window]   Figure 1.   Equipment for measuring FEFs at different levels of CPAP. A Sechrist ventilator was used to deliver a constant flow of air to the inspiratory side of the circuit and to adjust the level of CPAP in the expiratory side of the circuit. Occluding the expiratory valve resulted in the respiratory system being inflated to an airway pressure of 30 cm H2O, which was set by a popoff valve on the inspiratory side of the circuit. Increasing body-surface pressure with an inflatable jacket wrapped around the infant's chest and abdomen produced forced expiration when the expiratory valve was opened. The jacket was inflated from a 50-gallon reservoir.

Protocol

Infants received 75 mg/kg of chloral hydrate orally, and when asleep were placed in a supine position. The face mask attached to the circuit used to measure FEFs was placed over the infant's nose and mouth. Therapeutic putty was used between the mask and the face to prevent leaks during inflation of the respiratory system. Forced expiratory maneuvers were initially obtained at a CPAP of 0 cm H₂O. Jacket-compression pressures were increased in the range between 20 and 120 cm H₂O until maximal flows were obtained over the lower half of the FVC curve. The forced expiratory maneuvers were repeated with the infant breathing on the circuit with CPAP levels of 4 and 8 cm H₂O. For each level of CPAP, the jacket pressure was adjusted to obtain the maximal flows over the lower portion of the FVC curve.

Data Analysis

FRC was defined as the end-expiratory lung volume at each level of CPAP (FRC₀, FRC₄, FRC₈). Inspiratory capacity (IC) was defined as the lung volume between FRC and V₃₀ (Figure 2). Multiple inflations were performed prior to the forced expiratory maneuver, and IC was measured during the last inflation prior to the forced maneuver. RV was defined as the lung volume at the completion of forced expiration. FVC was defined as the lung volume between V₃₀ and RV (Figure 2). For each subject, FEF-volume curves recorded at CPAP levels of 0, 4, and 8 cm H₂O were overlaid with lung volumes matched at V₃₀. FVC, IC, flow at 50% of expired vital capacity (VC) (₅₀), flow at 75% of expired VC (₇₅), and flow at FRC (FRC) were measured. Differences among measurements at CPAP levels of 0, 4, and 8 cm H₂O were analyzed with Friedman's repeated measures analysis of variance on ranks. If there was a statistically significant difference, the results at each level of CPAP were compared through the Student-Newman- Keuls method. A value of p < 0.05 was considered statistically significant. A nonpaired t test was used to compare the age, length, FVC, ₅₀, and ₇₅ values without CPAP of healthy infants and infants with tracheomalacia.

View larger version (13K): [in this window] [in a new window]   Figure 2.   Schematic illustration of volumes and flows measured during flow-volume maneuver. IC is the volume of inflation from FRC to a respiratory system volume at an airway pressure of 30 cm H2O (  V30). FVC is the volume from V30 to RV. 50 and 75 are the FEFs at 50% and 75% of the expired FVC, respectively.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

There were no significant differences in age or body length for the infants with tracheomalacia and the healthy control infants (Table 1). Baseline pulmonary function assessed without CPAP indicated that the infants with tracheomalacia had moderate airway obstruction as compared with the healthy control infants. The group means for FEFs at 50% and 75% of the expired volume (₅₀, ₇₅) were significantly lower for the infants with tracheomalacia than for the control infants; however, there was no difference between the two groups for the percent predicted FEVs (FVC).

Flow-volume curves obtained at CPAP levels of 0, 4, and 8 cm H₂O are illustrated in Figure 3 for a healthy control infant and for an infant with tracheomalacia. For both infants, the FEF-volume curves at the different levels of CPAP are matched at V₃₀. The three curves for each subject are very similar with respect to the forced expired volume, and for the flows at 50% and 75% of the expired volume. Increasing CPAP from 0 to 4 to 8 cm H₂O produced an increase in the end-expiratory lung volume (FRC) and a decrease in IC.

View larger version (24K): [in this window] [in a new window]   Figure 3.   Flow-volume curves obtained at CPAP levels of 0, 4, and 8 cm H2O in (A) a healthy control infant, and (B) an infant with tracheomalacia. For both infants, the three FEF-volume curves at the different levels of CPAP are matched at V30. The three curves for each subject are similar with respect to the FEVs and the flows at 50% and 75% of expiratory volume. Increasing CPAP from 0 to 4 to 8 cm H2O produced a progressive increase in FRC and in the flows at FRC.

For both the infants with tracheomalacia and the healthy control infants, IC decreased significantly with each increase in CPAP, and there were no significant changes in FVC (Table 2). For both groups of infants, flow at FRC increased; however, there were no significant changes in the flows at 50% and 75% of expired volume at the three different levels of CPAP.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

The application of CPAP significantly increased maximal expiratory flow at FRC in healthy infants and infants with tracheomalacia. This increase in flow at FRC was secondary to the increase in lung volume with CPAP, since maximal expiratory flows measured at the different levels of CPAP were not different when compared at the same lung volumes. Because there was no significant change in the FEF-volume curve over the lower half of lung volume, our findings indicate that the primary effect of CPAP on maximal flows at FRC in infants with tracheomalacia is related to the increase in lung volume with CPAP.

In this study we measured maximal expiratory flow-volume curves from a lung volume near TLC to RV. Using the methodology employed in this study, we have previously demonstrated that flow limitation is achieved over the lower half of lung volume in healthy infants (14). In order to compare flows at the same lung volume, we matched the flow-volume curves at V₃₀. This lung volume is a constant-volume reference, as evidenced by values of FVC that were reproducible to within 5% during baseline measurements, and which also did not change with CPAP.

At any given lung volume, maximal expiratory flow depends upon the cross-sectional area of the airway and the compliance of the airway (15). Larger, stiffer airways will have greater flow than smaller, more compliant airways. An increase in lung volume with CPAP will increase transmural airway pressure, giving the airway a greater cross-sectional area and relating to a different portion of the pressure-area curve, which may result in either a more or less compliant airway. The increased lung volume could be associated with a net increase, decrease, or no change in flow, depending on the relative changes in airway cross-sectional area and airway-wall compliance. Because we obtained the same maximal flows at the same lung volumes with and without CPAP, it appears that CPAP merely increased the lung volume, and that the airways maintained the same pressure-area characteristics with or without CPAP. The previous report of a change in the shape of the partial flow-volume curve from concave to convex, and an increase in flow at FRC with CPAP, is consistent with a shift in the partial flow-volume curve to a higher lung volume (13). These infants had severe tracheomalacia and peripheral airway disease, which most likely would produce a full flow-volume curve that would be concave at lower lung volumes. Because partial flow-volume curves are obtained only over the range of VT, increasing CPAP would increase the absolute lung volume at which flow is measured and shift the measurement to a lung volume above the concave segment of the flow-volume curve.

One of the infants with tracheomalacia (Subject 2) was diagnosed with cystic fibrosis (CF) 1 yr after being evaluated in this study. This infant did not have respiratory symptoms of CF at the time of the study, and his results did not differ from those for the five other infants with tracheomalacia. In addition, the previous reports of the effects of CPAP on partial flow-volume curves included infants with tracheomalacia who also had bronchopulmonary dysplasia. These infants with tracheomalacia and peripheral airway disease also showed the same changes in partial flow-volume curves with CPAP as did those infants who had only tracheomalacia.

In conclusion, the application of CPAP to infants produces an increase in maximal expiratory flow at FRC as a result of the increase in lung volume with CPAP. The optimal level of CPAP in infants with severe tracheomalacia may be related to increasing the lung volume to a level at which the infant is not flow-limited during tidal breathing, without also significantly increasing the work of breathing through a decrease in pulmonary compliance at increased lung volumes.