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Respiratory Function Testing in Infants and Preschool-Aged Children
PART 3 ASSESSMENT
12
CHAPTER
Respiratory Function Testing in Infants and Preschool-Aged Children Peter D. Sly and Wayne J. Morgan
TEACHING POINTS ● ● ● ●
Lung function testing is feasible in infants and preschoolaged children. Attention to detail in optimizing the measurement conditions is critical to producing reliable results. International efforts at producing standardized measurement techniques and reference values are continuing. Before introducing these techniques locally, labs should study healthy children to ensure that the available reference data are applicable to their population.
Measurement of lung function in adults and older children has become a routine part of the management of respiratory diseases. Pulmonary function tests provide objective evidence regarding the nature and control of respiratory diseases and the effect of therapy and provide opportunities to study the mechanisms by which diseases alter lung function. These objective assessments have been unavailable to those managing respiratory diseases in infants and younger children until relatively recently. Many advances have been made in the past decades, and now the techniques and equipment necessary to measure lung function in infants and young children are readily available. Measurements of lung function in preschool-aged children are being used clinically in many parts of the world. This chapter is not intended to be sufficiently detailed that the reader can learn to measure lung function in infants and young children from these pages. A joint task force from the American Thoracic Society and European Respiratory Society has produced numerous publications about how these tests should be performed. 1-9 The interested reader is referred to these publications for practical details of the various tests.
LUNG FUNCTION TESTING IN INFANTS Influence of Measurement Conditions on Lung Function A major requirement for most methods of measuring lung function in infants is to have the infant sleeping. This is necessary to effect reproducible results. However, infants cannot be relied on to sleep naturally on demand or to remain asleep long enough to allow pulmonary function to be measured.
Thus, the majority of infant lung function tests are performed with the infant sedated, most commonly with chloral hydrate or a similar sedative. Sedating infants for pulmonary function testing is considered safe, with no reported adverse effects despite many thousands of tests having been performed throughout the world. 10 However, a fall in arterial oxygen saturation has been reported in wheezy infants sedated for pulmonary function testing, 11 so continuous monitoring of oxygen saturation is considered mandatory in such infants. Standardization of measurement conditions must address both laboratory conditions and the infant’s state with respect to factors that influence the results of respiratory function tests, such as feeding, posture, and sleep state. 6 Measurement Techniques The techniques used to measure pulmonary function in infants can be conveniently grouped into four groups: measures of lung volume, measurements of ventilation inhomogeneity, measures of forced expiratory flow, and measures of compliance and resistance. Measures of Lung Volume Knowledge of lung volume can play an important role in the respiratory care of infants and young children and can assist in the interpretation of measurements of resistance, compliance, and forced expiratory flow. Two main techniques are used for measuring lung volumes in infants: body plethysmography and gas-dilution techniques. BODY PLETHYSMOGRAPHY In body plethysmography, the infant is placed inside a rigid, closed container (a plethysmograph) and makes respiratory efforts against an occlusion at the airway opening; the respiratory efforts rarefy and compress the thoracic gas (Fig. 12-1). Calculation of the amount of gas in the thorax during occluded breathing efforts is made by applying Boyle’s law. The assumptions underlying this technique are discussed more fully in Chapter 13. There are, however, a number of particular difficulties in applying these assumptions to measurements in infants. The success of the plethysmographic measurement of lung volume relies on the plethysmograph having an adequate frequency response over the range of frequencies used. In an adult plethysmograph, with a volume typically 50 to 100 times that of the adult’s intrathoracic volume, the fre-
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P A R T 3 ■ ASSESSMENT ∆Vbox
V
∆Vbox
V ∆Pbox
V ∆Vbox
Raw
Raw
Raw
∆PA
∆PA
∆PA
∆VL Volume-constant plethysmograph: measurement of the pressure change (differential manometer)
∆VL
∆VL
Volume-displacement plethysmograph: measurement of volume change by electronic integration of flow (pneumotachograph)
Volume-displacement plethysmograph: measurement of volume change by a wide-cylinder spirograph
Figure 12-1 Types of plethysmographs. Dotted lines indicate volume change by compression; solid lines indicate volume change by expansion of. thoracic gas (∆VL). ∆Vbox, Change in volume in plethysmograph; ∆Pbox, change in pressure in plethysmograph; V, gas flow; Raw, airway resistance; ∆PA, change in alveolar pressure; ∆VL, change in lung volume. (Redrawn from Tammeling GJ, Quanjer PH: Contours of Breathing. Burlington, Ontario, Canada, Boehringer Ingelheim Pharmaceuticals, 1985.)
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quency response is poor (<0.2 Hz) because of the thermal time constant of the box and the necessary presence of a slow leak to allow for gas expansion resulting from the heat generated by the subject. Adults and older children are asked to make occluded breathing efforts at a frequency of approximately 1 Hz. This is primarily to keep the glottic aperture open, aiding the transmission of alveolar pressure to the airway opening and minimizing the difference in airway resistance (Raw) between inspiration and expiration. 12 However, this technique ensures that the box is being operated at a frequency at which the frequency response is adequate and that gas compression within the box is essentially isothermal. The infant plethysmograph is considerably smaller than the adult, giving it a greater surface area–to-volume ratio. Thus, the mean distance over which heat diffusion must occur between any point inside the plethysmograph and its walls is greatly reduced. This in turn leads to a much reduced thermal time constant, 13 which adversely influences the frequency response of the plethysmograph in the frequency range usually encountered in infants. The thermal time constant of a 60-L plethysmograph, with metal walls, was reported to be 0.16 second. 13 Gas compression within this box was found to be polytropic (i.e., between isothermal and adiabatic) over a frequency range of 0.1 to 3 Hz. Infants, obviously, cannot be requested to breathe at a particular frequency, and the respiratory rate is likely to change during measurements, particularly those that involve giving the infant a bronchodilator or bronchial challenge agent. 13 Changes in the frequency of the occluded breathing efforts result in changes in the value of thoracic gas volume calculated simply because of the polytropic gas compression. An alternative to the “constant-volume” plethysmograph is the “flow plethysmograph” in which a pneumotachograph
measures gas flow between the plethysmograph and the exterior (see Fig. 12-1, center). The flow signal can be integrated to produce the volume change occurring in the box resulting from respiration (i.e., tidal volume). During occluded breathing efforts, this volume should equal the change in volume recorded in a constant-volume plethysmograph (see Chapter 13). In a flow plethysmograph, the gas displacement minimizes polytropic gas compression and eliminates thermal effects. If the resistance and inertance of the pneumotach are too high, the flow signal may be damped, introducing errors into the calculations of lung function. These errors can be improved by using a screen pneumotachograph fitted flush with the plethysmograph wall without any connecting tubing or by correcting for the resistance and inertance of the pneumotachograph. 14 Transmission of the changes in alveolar pressure to the airway opening during occluded breathing efforts occurs with a time constant dependent on the Raw and upper airway compliance. Infants have higher Raw and more compliant upper airways, both of which increase the time required to transmit alveolar pressure changes to the upper airway. This problem is magnified in conditions with increased Raw, such as wheezing illnesses. Under these conditions, the airway opening pressure may markedly underestimate alveolar pressure, resulting in overestimations of thoracic gas volume and thus limiting the accuracy and usefulness of this technique in infants with airway disease. Recent advances in technology and attention to detail in calculation of results have brought marked improvements in the accuracy of plethysmography in infants. 15 GAS-DILUTION TECHNIQUES The most common application of the gas-dilution technique is the helium-dilution technique. This technique is based on
C H A P T E R 12 ■ Respiratory Function Testing in Infants and Preschool-Aged Children
the principle of gas equilibration between an unknown lung volume and a known volume containing helium as an indicator gas. Gas is mixed by ventilatory movements, and the lung volume is calculated from the change in helium concentration. Lung volume can also be measured using the nitrogenwashout technique. With this technique, the infant breathes from a reservoir of nitrogen-free gas, and the washout of nitrogen in the alveolar gas is measured with a rapidly responding nitrogen analyzer. The major problems with these techniques include the following: 1. Any leak in the circuit results in the final concentration of gas (especially helium) being artificially low, with the consequent overestimation of lung volume. For these tests, the infant breathes through a facemask, increasing the possibility of leaks, which may be difficult to detect. 2. Adequate time must be allowed for the helium to be distributed throughout the lung and for the final helium concentration to become stable. In the presence of small airways and in conditions with increased Raw, the time required for equilibration may be considerable. Long equilibration times may be impractical when testing infants. 3. Gas-dilution techniques measure the lung volume readily communicating with the airway opening, which may be substantially less than the total lung volume. The response to treatments, such as bronchodilators, can be difficult to interpret because a beneficial treatment effect may be measured as a decrease in lung volume if most airways are patent or as an increase in lung volume if the bronchodilator opens previously closed airways, resulting in an increased volume of lung in communication with the airway opening. Measurements of Ventilation Homogeneity The realizations that lung disease in infants with cystic fibrosis begins in the lung periphery and that measurements of forced expiration may not be sensitive enough to detect signs of early disease have led to an increase in interest in tests that measure ventilation distribution in infants. The multiple breath nitrogen washout technique has been used for decades in adults and has been investigated in infants. 16 Techniques using the inert gases SF6 and/or helium as a tracer gas are becoming increasingly popular. 17,18 The most common indices of lung function calculated from these multiple breath inert gas techniques are the functional residual capacity (FRC) and the lung clearance index (LCI). The measurements are performed as follows: ●
●
●
Tidal breathing is monitored and when a stable pattern with a stable end-expiratory level has been achieved the breathing circuit is switched to one containing the tracer gas (e.g., 4% SF6). The gas concentration is measured during tidal breathing until a stable plateau has been achieved. This phase is known as the wash-in phase. The breathing circuit is then switched to one without the tracer gas and gas concentration monitored until the concentration has dropped to 1/40 of the plateau concentration (the washout phase).
●
●
FRC is calculated from the cumulative expired tracer gas volume divided by the difference in end-tidal tracer gas concentration at the start of the washout and the end-tidal tracer gas concentration at the end of the washout. LCI is calculated as the number of lung volume turnovers (cumulative exhaled volume/FRC) required to lower tracer gas concentration to 1/40 of the starting concentration.
LCI is a useful measure of volume homogeneity and is essentially constant at 6 to 7 throughout childhood. 17 LCI also appears to be abnormal in children with cystic fibrosis and is more sensitive to the presence of early lung disease than standard spirometry. 17 Measures of Forced Expiratory Flow The primary method used to measure forced expiratory flows in infants has been the rapid thoracic compression (RTC) technique. The RTC technique produces forced expiratory flows by suddenly applying a pressure to the thorax and abdomen at the end of a tidal inspiration, using an inflatable thoracoabdominal jacket connected to a positive-pressure reservoir. Flow is measured at the mouth with an appropriately sized pneumotachograph attached to a mask sealed around the infant’s nose and mouth. 19 Flow is integrated to obtain volume, and a flow-volume curve is constructed. Before the RTC maneuver, a reproducible end-expiratory volume (FRC) is established from at least three tidal breaths. An RTC initiated at the end of inspiration then produces a partial expiratory flow-volume curve, with exhalation continuing to a volume below the previous FRC. RTC maneuvers are repeated at increasing jacket pressures until the pressure that produces the highest expiratory flows is determined. The maximum flow occurring at the previously established tidal . FRC (Vmax FRC) is reported. Use of the RTC has led to major advances in understanding the normal growth and development of the respiratory system and . of the development of respiratory diseases. For example, Vmax FRC shows an essentially linear increase with somatic growth and with lung volume throughout the first year of life. 20,21 Seidenberg and coworkers 22 demonstrated that lung function abnormalities persist for up to 3 months in the absence of clinical symptoms after an episode of acute viral bronchiolitis. However, the RTC technique has not proved to be the “panacea” it initially promised to be and has largely been replaced by the raised volume RTC (RVRTC), in which the infant’s lungs are inflated to a volume approaching total lung capacity before the forced expiration is initiated 9 (see later). The utility of measurements of forced expiration relies on expiratory flow limitation being achieved. Although this may be the case with the RTC technique in infants with airway obstruction, flow limitation is unlikely to be achieved in healthy infants. Furthermore, FRC is notoriously variable in infants, even over short periods, which leads to substantial . variability in the values of Vmax FRC (Fig. 12-2). Many studies have consistently failed to demonstrate a bronchodilator response after therapy with inhaled β-sympathomimetics; yet many clinical studies have shown that infants can benefit from the administration of inhaled bronchodilators. One possible reason for this discrepancy is that bronchodilators alter
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P A R T 3 ■ ASSESSMENT
Flow
Flow
FRCs occurring at higher lung volumes lead to larger values of VmaxFRC
Forced expiration
Bronchodilators move FRC Bronchoconstrictors move FRC
Vmax 2 Vmax 1
Expiration
Zero flow
Zero flow line Forced inspiration
Inspiration
End inspiration
FRC 2 FRC 1
Tidal breaths
FRC
Tidal volume
Volume
Volume
Tidal volume . Figure 12-2 Effect of variation of FRC on Vmax FRC as calculated from a partial expiratory flow-volume curve.
Figure 12-4
Flow-volume plot of the raised-volume RTC maneuver.
Measures of Resistance and Compliance FRC, possibly reducing hyperinflation. This would reduce the . Vmax FRC, masking the expected increase after bronchodilator treatment (see Fig. 12-2). In an attempt to overcome many of the problems with the RTC technique, Turner and colleagues 23,24 developed a technique in which the lungs were inflated to a preset pressure using a pump before the RTC. They reason that the use of a standard inflation pressure reduces the variability of the measurements produced. They then measure the volume forcibly exhaled in a given time, usually 0.75 second (Fig. 12-3). This technique is analogous to the 1-second forced expiratory volume (FEV1) that is routinely measured in older children and adults. In addition, because the forced expiration is induced from a higher lung volume, full forced expiratory flow-volume curves appear to be possible (Fig. 12-4). Other groups have used various methods to inflate the lungs and various inflation pressures have been used. The American Thoracic Society (ATS)–European Respiratory Society (ERS) Task Force has published standardized guidelines for the RVRTC, 9 and the interested reader is referred to that publication for further information.
Volume FRC End inspiration
Forced expiration
Forced inspiration FEV0.5
0.5
1
1.5
2
2.5
FEV1
3 Time
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Figure 12-3 Volume-time plot of the raised volume RTC maneuver. FEV0.5, 1/2-second forced expiratory volume; FEV1, 1-second forced expiratory volume.
A number of techniques are available for measuring resistance and compliance in spontaneously breathing infants. The most commonly used tests are occlusion tests, which invoke the Hering-Breuer reflex, and body plethysmography. Other possibilities include the use of forced oscillation techniques. Older techniques involving the measurement of esophageal pressure as an index of pleural pressure have largely fallen out of favor for use in spontaneously breathing infants and are not discussed here further. TECHNIQUES THAT INVOKE THE HERING-BREUER REFLEX Techniques invoking the Hering-Breuer reflex rely on the assumptions that this reflex, producing complete relaxation of both inspiratory and expiratory respiratory muscles, can be elicited during airway occlusion and that airway opening pressure comes into equilibrium with alveolar pressure during the occlusion. Occlusion techniques may involve multiple occlusions at different lung volumes or single occlusions at end-inspiration. Multiple-Breath Occlusion Technique
In the multiple-breath occlusion technique, pressure is measured at the mouth during brief airway occlusions performed on multiple breaths. Occlusions are performed at different volumes above FRC, and the individual measurements are plotted as volume versus pressure. The slope of the line of “best fit” is the compliance of the respiratory system (Fig. 12-5). In the single-breath occlusion technique, the airway is occluded at the end of inspiration, with the subsequent expiration occurring passively. A passive expiratory flow-volume curve is then constructed and a line fitted to the linear portion (Fig. 12-6). Compliance is calculated by dividing the total exhaled volume by the pressure at the airway opening recorded during the occlusion. The slope of the linear part of the passive flow-volume curve is equal to the reciprocal of the expiratory time constant (τrs). Resistance can be calculated by dividing the time constant by the compliance. The problem with these techniques is ensuring relaxation of the respiratory muscles after airway occlusion and equilibration of airway opening and alveolar pressures. Generally,
C H A P T E R 12 ■ Respiratory Function Testing in Infants and Preschool-Aged Children
Vocc
V1
V2
Volume
V3
FRC Time P1
Vol above FRC
Time
Pao
P2
Volume
FRC
Paoocc
P3 Time
Pao Time
Flow
Vocc (volume above FRC) V1
Crs = Slope =
V2
Vocc Pao
= Crs
Slope = 1 τrs
Total exhaled volume Paoocc
Rrs = τrs
Crs
Volume
V3 P3
P2
P1
Total exhaled volume
Pao
Figure 12-5 Calculation of compliance of the respiratory system using the multiple-breath occlusion technique. Vocc, volume at which occlusion is made; V, volume; P, pressure; Pao, pressure at the airway opening; Crs, compliance of the respiratory system.
Figure 12-6 Calculation of respiratory compliance (Crs) and resistance (Rrs) using the single-breath occlusion technique. Paoocc, airway opening pressure following occlusion; Pao, pressure at the airway opening; τrs, expiratory time constant.
the presence of a plateau in airway opening pressure indicates that both of these assumptions have been satisfied. The ERS/ ATS Task Force has recommended that occlusions should be held for a minimum of 400 milliseconds. 25 The length of the airway occlusion can influence the values of compliance calculated from the subsequent expiration, with compliance decreasing by 0.15 ml/cm H2O for each 0.1 second of occlusion time. 26 These data strongly argue for standardizing the length of occlusion and discarding data in which a plateau is not achieved. The ERS/ATS Task Force recommends that a plateau should be maintained for at least 100 miiliseconds. 25
infants, the forcing function is generally applied through a facemask and includes the impedance of the nose. When making measurements in infants, the clinician must take extreme care to prevent leaks around the facemask. An adaptation of the forced oscillation technique, using lower frequencies, has been developed for infants. 29 By applying the forcing function during a pause in breathing produced by invoking the Hering-Breuer reflex, reliable impedance data can be obtained from 0.5 to 20 Hz. The impedance spectra showed the same marked frequency dependence (Fig. 12-7) reported in paralyzed animals 30,31 and in adults studied either during voluntary muscle relaxation 32,33 or during mechanical ventilation with paralysis. 34 Fitting the constant phase model 31 to the respiratory system impedance (Zrs) allows partitioning into components representing the airway resistance (together with any Newtonian resistance in the chest wall) and the lung parenchyma, i.e.:
Low-frequency Forced Oscillation Technique
Forced oscillation techniques are described in detail in Chapter 13. These techniques have been used in infants, and impedance spectra have been measured above 4 Hz. 27,28 In
Zrs (cmH2O.s/L)
50
Real part = resistance
1
10
Parenchyma
Airway
0
-50
Imaginary part = reactance
-100
Frequency (Hz) Figure 12-7 Respiratory system impedance (Zrs) measured in an infant. The upper panel shows the resistive component and the lower panel the reactance plotted as a function of frequency.
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P A R T 3 ■ ASSESSMENT
Zrs = Raw + jωIaw + (G − jH)/ωα where Raw and Iaw are the frequency-independent resistance and inertance of the airways (see earlier); G and H are the coefficients for tissue damping and elastance, respectively; j is the imaginary unit, and ω is the angular frequency. The frequency dependence of the respiratory tissues is governed by the coefficient α, which can be expressed as α = (2/p)arctan (H/G). As shown schematically in Figure 12-7, Zrs in the lower frequency range (<4 to 6 Hz in infants) is dominated by the mechanical properties of the pulmonary parenchyma, whereas those at higher frequencies are dominated by the mechanical properties of the conducting airways. Interrupter Technqiue
Respiratory system resistance can also be measured in infants using the interrupter technique. The use of this technique is far more common in preschool-aged children, and the reader is directed to that section for a description of the technique. The major difference in infants is that the measurement is made through a facemask, which adds a compliant compartment (the gas in the facemask) in front of the respiratory system. This can decrease the accuracy of the measurements, especially in the presence of airway obstruction. Body Plethysmography Body plethysmography is commonly used to measure Raw in adults and older children but has been modified for infants by the inclusion of a rebreathing bag containing heated, humidified, oxygen-enriched gas at body temperature, pressure, and saturation. This sophisticated technique requires a large amount of expertise and training but can produce simultaneous measurements of lung volume and Raw. The ATSERS Task Force expended a great deal of time developing standardized techniques and has worked with industry to ensure that reliable equipment is commercially available. The interested reader is directed to the task force publications 6,15 for further information. Measures of Tidal Breathing Parameters Inductance plethysmography is a noninvasive technique that can be used for measuring tidal breathing in infants. The
inductance plethysmograph consists of a pair of wire bands that are usually embedded into an elastic material encircling the chest wall and abdomen. The wires are arranged in a sinusoidal fashion and are excited by an oscillator to produce impedance proportional to the area enclosed within the band. By calibrating the impedance signal with known volume changes, it is possible to calculate changes in the crosssectional areas of the thoracic and abdominal cavities in terms of changes in lung volume. However, the calibration is notoriously unstable and extremely sensitive to changes in body posture. A new generation of respiratory inductance plethysmographs was introduced in the mid-1980s. These devices produce an automatic qualitative calibration during the initial period of operation. Subsequent measurements of tidal breathing excursion are related to that measured during this initial period. 35 The shape of the tidal breathing flow-volume curve can be influenced by airway function. Martinez and coworkers 36 reported that the time to peak tidal expiratory flow (Tptef) expressed as a percentage of total expiratory time (TE) (Fig. 12-8) (referred to by them as Tme/Te) was low in infants who subsequently developed wheezing lower respiratory illnesses. Martinez and coworkers 36 used a pneumotachograph and facemask in sedated infants to measure Tptef/TE. Stick and associates 37 demonstrated that Tptef/TE could be successfully measured using an uncalibrated respiratory inductance plethysmograph during quiet sleep in infants. The precise physiologic interpretation of Tptef/TE is unclear. In adults, Tptef/TE is correlated with airway conductance, lower values occurring with subjects with airway obstruction and low airway conductance. 38 This can be conceptualized by comparing the normally rounded shape of the expiratory limb of the flow-volume loop seen during tidal breathing (see Fig. 12-8, left), at which Tptef/TE approximates 0.5 with the peaked shape of the expiratory limb of a forced expiratory flow-volume curve (see Fig. 12-8, right), at which Tptef/TE approaches 0.15 to 0.2. For a given level of respiratory drive, as airways become more obstructed the tidal flow-volume curve becomes more like that normally seen during forced expiration, and Tptef/TE decreases. Martinez and coworkers 36 interpreted a low premorbid value of Tptef/TE as being indicative of smaller than usual airways, making the infants more likely to develop wheezing illnesses with the usual respiratory tract viral infections. However, the flow-volume
Time
PEF
PEF Expiratory flow
Tptef
Tptef Te
Te Normal Tptef/Te = 0.45
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Abnormal Tptef/Te = 0.15
Figure 12-8 Calculation of the ratio of time to Tptef/TE from tidal expiratory flow and time recordings. PEF, peak expiratory flow.
C H A P T E R 12 ■ Respiratory Function Testing in Infants and Preschool-Aged Children
curve represents an “integrated” output from the respiratory system, and factors other than airway conductance are likely to influence the expiratory flow pattern. Tptef/TE is also influenced by respiratory rate, becoming lower as respiratory rate increases and becoming lower in the prone than the lateral or supine sleeping positions. 39,40 Thus, it is not possible to assign precise physiologic meaning to Tptef/TE.
LUNG FUNCTION TESTING IN PRESCHOOL-AGED CHILDREN Children under the age of 7 to 8 years are frequently unable to perform the standard lung function tests used in older children and adults. Evaluating lung function in young children is important not only for clinical reasons but also due to the considerable growth and development of the respiratory system that occur, with associated changes in lung mechanics. 41 Children commonly present with recurrent cough and wheeze during this period. Many of these children will lose their symptoms as they grow, yet others will continue to have asthma that persists into adult life. 42 The treatment implications of these two clinical patterns are different, and we are currently hampered by a lack of objective assessments to help distinguish between these two patterns. In addition, children recovering from chronic neonatal lung disease and children afflicted with cystic fibrosis are prone to recurrent or persistent respiratory symptoms. Objective assessments of pulmonary function in these children would be expected to improve clinical management. The preschool-aged group presents a number of special challenges. Children in this age group are not able to voluntarily perform many of the physiological maneuvers required for the pulmonary function tests used in older children and adults. They have a short attention span and are easily distracted. Due to these issues, the children need to be engaged and encouraged by the operator to participate in the test. A child-friendly laboratory is essential for success, and staff must be prepared to adjust to the child’s schedule. A number of pulmonary function tests have been attempted in conscious children within the preschool-aged group. These . include standard spirometry, 43-50 VmaxFRC, 51-53 forced oscillation, 54-60 interrupter resistance, 55,58,59,61-67 specific airway resistance measured in a plethysmograph, 58,59,68 FRC using gas dilution techniques, 53,66,69 and measurements of gas mixing indices. 17,18 Commercial equipment is available for most of these tests, although not specifically designed for preschoolaged children. Equipment dead space, resistance, and software programs designed for adults, not young children, may introduce unpredictable errors into the measurements, and no systematic research on these factors has been conducted.
The emotional developmental stage of the preschool-aged child will be an important determinant of the child’s success at performing pulmonary function tests. This influence will be greatest in tests requiring more active cooperation from the child. For example, young children frequently have difficulties in performing the forced expiratory maneuvers required for spirometry. They can either blow “hard” or “long,” but frequently cannot blow both “hard and long.” 44 Measurements that can be made during tidal breathing, such as with forced oscillation, the interrupter technique, and gas washout techniques, may be more suitable for the child unable to accurately perform spirometry. The physiological developmental stage of the respiratory system must also be considered in determining which outcome variables are applicable to this age group. For example, recent studies have demonstrated that the ratio of FEV1 to forced vital capacity in healthy 5- to 6-year-old children is approximately 90% to 95%, 43,46,49,50 implying that young children essentially empty their lungs within 1 second. The physiological and clinical utility of FEV1 comes from its location on the effort-independent (flow-limited) part of the maximal forced expiratory flow-volume (MEFV) curve (see Chapters 7 and 13). The flow-limited portion of the MEFV curve extends down to lung volumes as low as 85% to 90% of exhaled vital capacity in adults. The ability to maintain flow-limitation at low lung volumes depends largely on the ability of the chest wall muscles to maintain sufficient driving pressure to exceed that needed to ensure flow-limitation. It is highly unlikely that children in the preschool-aged group will have the chest wall muscle strength to maintain flow-limitation to lung volumes as low as 90% exhaled vital capacity. While this concept is not new, 70 the use of variables such as FEV0.75 or FEV0.5 has not yet been adopted into clinical practice and most commercial equipment does not report such variables. The most appropriate lung function test for use in the preschool-aged group will depend on the purpose for measuring lung function. The interrupter technique is easily implemented and is suitable for use in epidemiological studies, particularly those involving measurements in the field. However, it may be more suited for studies reporting group mean data than for studies reporting individual data. Measurements capable of reflecting changes in the lung parenchyma, such as gas washout techniques and potentially forced oscillation, are likely to be more suitable for detecting early lung disease in a condition such as cystic fibrosis, which is known to start in the peripheral airways. The clinical and research roles for measuring bronchodilator responses and for provocation testing still need to be evaluated.
SUGGESTED READING Beydon N, Davis SD, Lombardi E, et al: An Official American Thoracic Society/European Respiratory Society Statement: Pulmo-
nary function testing in preschool children. Am J Respir Crit Care Med 175:1304-1345, 2007.
REFERENCES The references for this chapter can be found at www.pedrespmedtext.com.
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12
CHAPTER
Respiratory Function Testing in Infants and Preschool-Aged Children Peter D. Sly and Wayne J. Morgan
TEACHING POINTS ● ● ● ●
Lung function testing is feasible in infants and preschoolaged children. Attention to detail in optimizing the measurement conditions is critical to producing reliable results. International efforts at producing standardized measurement techniques and reference values are continuing. Before introducing these techniques locally, labs should study healthy children to ensure that the available reference data are applicable to their population.
Measurement of lung function in adults and older children has become a routine part of the management of respiratory diseases. Pulmonary function tests provide objective evidence regarding the nature and control of respiratory diseases and the effect of therapy and provide opportunities to study the mechanisms by which diseases alter lung function. These objective assessments have been unavailable to those managing respiratory diseases in infants and younger children until relatively recently. Many advances have been made in the past decades, and now the techniques and equipment necessary to measure lung function in infants and young children are readily available. Measurements of lung function in preschool-aged children are being used clinically in many parts of the world. This chapter is not intended to be sufficiently detailed that the reader can learn to measure lung function in infants and young children from these pages. A joint task force from the American Thoracic Society and European Respiratory Society has produced numerous publications about how these tests should be performed. 1-9 The interested reader is referred to these publications for practical details of the various tests.
LUNG FUNCTION TESTING IN INFANTS Influence of Measurement Conditions on Lung Function A major requirement for most methods of measuring lung function in infants is to have the infant sleeping. This is necessary to effect reproducible results. However, infants cannot be relied on to sleep naturally on demand or to remain asleep long enough to allow pulmonary function to be measured.
Thus, the majority of infant lung function tests are performed with the infant sedated, most commonly with chloral hydrate or a similar sedative. Sedating infants for pulmonary function testing is considered safe, with no reported adverse effects despite many thousands of tests having been performed throughout the world. 10 However, a fall in arterial oxygen saturation has been reported in wheezy infants sedated for pulmonary function testing, 11 so continuous monitoring of oxygen saturation is considered mandatory in such infants. Standardization of measurement conditions must address both laboratory conditions and the infant’s state with respect to factors that influence the results of respiratory function tests, such as feeding, posture, and sleep state. 6 Measurement Techniques The techniques used to measure pulmonary function in infants can be conveniently grouped into four groups: measures of lung volume, measurements of ventilation inhomogeneity, measures of forced expiratory flow, and measures of compliance and resistance. Measures of Lung Volume Knowledge of lung volume can play an important role in the respiratory care of infants and young children and can assist in the interpretation of measurements of resistance, compliance, and forced expiratory flow. Two main techniques are used for measuring lung volumes in infants: body plethysmography and gas-dilution techniques. BODY PLETHYSMOGRAPHY In body plethysmography, the infant is placed inside a rigid, closed container (a plethysmograph) and makes respiratory efforts against an occlusion at the airway opening; the respiratory efforts rarefy and compress the thoracic gas (Fig. 12-1). Calculation of the amount of gas in the thorax during occluded breathing efforts is made by applying Boyle’s law. The assumptions underlying this technique are discussed more fully in Chapter 13. There are, however, a number of particular difficulties in applying these assumptions to measurements in infants. The success of the plethysmographic measurement of lung volume relies on the plethysmograph having an adequate frequency response over the range of frequencies used. In an adult plethysmograph, with a volume typically 50 to 100 times that of the adult’s intrathoracic volume, the fre-
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P A R T 3 ■ ASSESSMENT ∆Vbox
V
∆Vbox
V ∆Pbox
V ∆Vbox
Raw
Raw
Raw
∆PA
∆PA
∆PA
∆VL Volume-constant plethysmograph: measurement of the pressure change (differential manometer)
∆VL
∆VL
Volume-displacement plethysmograph: measurement of volume change by electronic integration of flow (pneumotachograph)
Volume-displacement plethysmograph: measurement of volume change by a wide-cylinder spirograph
Figure 12-1 Types of plethysmographs. Dotted lines indicate volume change by compression; solid lines indicate volume change by expansion of. thoracic gas (∆VL). ∆Vbox, Change in volume in plethysmograph; ∆Pbox, change in pressure in plethysmograph; V, gas flow; Raw, airway resistance; ∆PA, change in alveolar pressure; ∆VL, change in lung volume. (Redrawn from Tammeling GJ, Quanjer PH: Contours of Breathing. Burlington, Ontario, Canada, Boehringer Ingelheim Pharmaceuticals, 1985.)
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quency response is poor (<0.2 Hz) because of the thermal time constant of the box and the necessary presence of a slow leak to allow for gas expansion resulting from the heat generated by the subject. Adults and older children are asked to make occluded breathing efforts at a frequency of approximately 1 Hz. This is primarily to keep the glottic aperture open, aiding the transmission of alveolar pressure to the airway opening and minimizing the difference in airway resistance (Raw) between inspiration and expiration. 12 However, this technique ensures that the box is being operated at a frequency at which the frequency response is adequate and that gas compression within the box is essentially isothermal. The infant plethysmograph is considerably smaller than the adult, giving it a greater surface area–to-volume ratio. Thus, the mean distance over which heat diffusion must occur between any point inside the plethysmograph and its walls is greatly reduced. This in turn leads to a much reduced thermal time constant, 13 which adversely influences the frequency response of the plethysmograph in the frequency range usually encountered in infants. The thermal time constant of a 60-L plethysmograph, with metal walls, was reported to be 0.16 second. 13 Gas compression within this box was found to be polytropic (i.e., between isothermal and adiabatic) over a frequency range of 0.1 to 3 Hz. Infants, obviously, cannot be requested to breathe at a particular frequency, and the respiratory rate is likely to change during measurements, particularly those that involve giving the infant a bronchodilator or bronchial challenge agent. 13 Changes in the frequency of the occluded breathing efforts result in changes in the value of thoracic gas volume calculated simply because of the polytropic gas compression. An alternative to the “constant-volume” plethysmograph is the “flow plethysmograph” in which a pneumotachograph
measures gas flow between the plethysmograph and the exterior (see Fig. 12-1, center). The flow signal can be integrated to produce the volume change occurring in the box resulting from respiration (i.e., tidal volume). During occluded breathing efforts, this volume should equal the change in volume recorded in a constant-volume plethysmograph (see Chapter 13). In a flow plethysmograph, the gas displacement minimizes polytropic gas compression and eliminates thermal effects. If the resistance and inertance of the pneumotach are too high, the flow signal may be damped, introducing errors into the calculations of lung function. These errors can be improved by using a screen pneumotachograph fitted flush with the plethysmograph wall without any connecting tubing or by correcting for the resistance and inertance of the pneumotachograph. 14 Transmission of the changes in alveolar pressure to the airway opening during occluded breathing efforts occurs with a time constant dependent on the Raw and upper airway compliance. Infants have higher Raw and more compliant upper airways, both of which increase the time required to transmit alveolar pressure changes to the upper airway. This problem is magnified in conditions with increased Raw, such as wheezing illnesses. Under these conditions, the airway opening pressure may markedly underestimate alveolar pressure, resulting in overestimations of thoracic gas volume and thus limiting the accuracy and usefulness of this technique in infants with airway disease. Recent advances in technology and attention to detail in calculation of results have brought marked improvements in the accuracy of plethysmography in infants. 15 GAS-DILUTION TECHNIQUES The most common application of the gas-dilution technique is the helium-dilution technique. This technique is based on
C H A P T E R 12 ■ Respiratory Function Testing in Infants and Preschool-Aged Children
the principle of gas equilibration between an unknown lung volume and a known volume containing helium as an indicator gas. Gas is mixed by ventilatory movements, and the lung volume is calculated from the change in helium concentration. Lung volume can also be measured using the nitrogenwashout technique. With this technique, the infant breathes from a reservoir of nitrogen-free gas, and the washout of nitrogen in the alveolar gas is measured with a rapidly responding nitrogen analyzer. The major problems with these techniques include the following: 1. Any leak in the circuit results in the final concentration of gas (especially helium) being artificially low, with the consequent overestimation of lung volume. For these tests, the infant breathes through a facemask, increasing the possibility of leaks, which may be difficult to detect. 2. Adequate time must be allowed for the helium to be distributed throughout the lung and for the final helium concentration to become stable. In the presence of small airways and in conditions with increased Raw, the time required for equilibration may be considerable. Long equilibration times may be impractical when testing infants. 3. Gas-dilution techniques measure the lung volume readily communicating with the airway opening, which may be substantially less than the total lung volume. The response to treatments, such as bronchodilators, can be difficult to interpret because a beneficial treatment effect may be measured as a decrease in lung volume if most airways are patent or as an increase in lung volume if the bronchodilator opens previously closed airways, resulting in an increased volume of lung in communication with the airway opening. Measurements of Ventilation Homogeneity The realizations that lung disease in infants with cystic fibrosis begins in the lung periphery and that measurements of forced expiration may not be sensitive enough to detect signs of early disease have led to an increase in interest in tests that measure ventilation distribution in infants. The multiple breath nitrogen washout technique has been used for decades in adults and has been investigated in infants. 16 Techniques using the inert gases SF6 and/or helium as a tracer gas are becoming increasingly popular. 17,18 The most common indices of lung function calculated from these multiple breath inert gas techniques are the functional residual capacity (FRC) and the lung clearance index (LCI). The measurements are performed as follows: ●
●
●
Tidal breathing is monitored and when a stable pattern with a stable end-expiratory level has been achieved the breathing circuit is switched to one containing the tracer gas (e.g., 4% SF6). The gas concentration is measured during tidal breathing until a stable plateau has been achieved. This phase is known as the wash-in phase. The breathing circuit is then switched to one without the tracer gas and gas concentration monitored until the concentration has dropped to 1/40 of the plateau concentration (the washout phase).
●
●
FRC is calculated from the cumulative expired tracer gas volume divided by the difference in end-tidal tracer gas concentration at the start of the washout and the end-tidal tracer gas concentration at the end of the washout. LCI is calculated as the number of lung volume turnovers (cumulative exhaled volume/FRC) required to lower tracer gas concentration to 1/40 of the starting concentration.
LCI is a useful measure of volume homogeneity and is essentially constant at 6 to 7 throughout childhood. 17 LCI also appears to be abnormal in children with cystic fibrosis and is more sensitive to the presence of early lung disease than standard spirometry. 17 Measures of Forced Expiratory Flow The primary method used to measure forced expiratory flows in infants has been the rapid thoracic compression (RTC) technique. The RTC technique produces forced expiratory flows by suddenly applying a pressure to the thorax and abdomen at the end of a tidal inspiration, using an inflatable thoracoabdominal jacket connected to a positive-pressure reservoir. Flow is measured at the mouth with an appropriately sized pneumotachograph attached to a mask sealed around the infant’s nose and mouth. 19 Flow is integrated to obtain volume, and a flow-volume curve is constructed. Before the RTC maneuver, a reproducible end-expiratory volume (FRC) is established from at least three tidal breaths. An RTC initiated at the end of inspiration then produces a partial expiratory flow-volume curve, with exhalation continuing to a volume below the previous FRC. RTC maneuvers are repeated at increasing jacket pressures until the pressure that produces the highest expiratory flows is determined. The maximum flow occurring at the previously established tidal . FRC (Vmax FRC) is reported. Use of the RTC has led to major advances in understanding the normal growth and development of the respiratory system and . of the development of respiratory diseases. For example, Vmax FRC shows an essentially linear increase with somatic growth and with lung volume throughout the first year of life. 20,21 Seidenberg and coworkers 22 demonstrated that lung function abnormalities persist for up to 3 months in the absence of clinical symptoms after an episode of acute viral bronchiolitis. However, the RTC technique has not proved to be the “panacea” it initially promised to be and has largely been replaced by the raised volume RTC (RVRTC), in which the infant’s lungs are inflated to a volume approaching total lung capacity before the forced expiration is initiated 9 (see later). The utility of measurements of forced expiration relies on expiratory flow limitation being achieved. Although this may be the case with the RTC technique in infants with airway obstruction, flow limitation is unlikely to be achieved in healthy infants. Furthermore, FRC is notoriously variable in infants, even over short periods, which leads to substantial . variability in the values of Vmax FRC (Fig. 12-2). Many studies have consistently failed to demonstrate a bronchodilator response after therapy with inhaled β-sympathomimetics; yet many clinical studies have shown that infants can benefit from the administration of inhaled bronchodilators. One possible reason for this discrepancy is that bronchodilators alter
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P A R T 3 ■ ASSESSMENT
Flow
Flow
FRCs occurring at higher lung volumes lead to larger values of VmaxFRC
Forced expiration
Bronchodilators move FRC Bronchoconstrictors move FRC
Vmax 2 Vmax 1
Expiration
Zero flow
Zero flow line Forced inspiration
Inspiration
End inspiration
FRC 2 FRC 1
Tidal breaths
FRC
Tidal volume
Volume
Volume
Tidal volume . Figure 12-2 Effect of variation of FRC on Vmax FRC as calculated from a partial expiratory flow-volume curve.
Figure 12-4
Flow-volume plot of the raised-volume RTC maneuver.
Measures of Resistance and Compliance FRC, possibly reducing hyperinflation. This would reduce the . Vmax FRC, masking the expected increase after bronchodilator treatment (see Fig. 12-2). In an attempt to overcome many of the problems with the RTC technique, Turner and colleagues 23,24 developed a technique in which the lungs were inflated to a preset pressure using a pump before the RTC. They reason that the use of a standard inflation pressure reduces the variability of the measurements produced. They then measure the volume forcibly exhaled in a given time, usually 0.75 second (Fig. 12-3). This technique is analogous to the 1-second forced expiratory volume (FEV1) that is routinely measured in older children and adults. In addition, because the forced expiration is induced from a higher lung volume, full forced expiratory flow-volume curves appear to be possible (Fig. 12-4). Other groups have used various methods to inflate the lungs and various inflation pressures have been used. The American Thoracic Society (ATS)–European Respiratory Society (ERS) Task Force has published standardized guidelines for the RVRTC, 9 and the interested reader is referred to that publication for further information.
Volume FRC End inspiration
Forced expiration
Forced inspiration FEV0.5
0.5
1
1.5
2
2.5
FEV1
3 Time
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Figure 12-3 Volume-time plot of the raised volume RTC maneuver. FEV0.5, 1/2-second forced expiratory volume; FEV1, 1-second forced expiratory volume.
A number of techniques are available for measuring resistance and compliance in spontaneously breathing infants. The most commonly used tests are occlusion tests, which invoke the Hering-Breuer reflex, and body plethysmography. Other possibilities include the use of forced oscillation techniques. Older techniques involving the measurement of esophageal pressure as an index of pleural pressure have largely fallen out of favor for use in spontaneously breathing infants and are not discussed here further. TECHNIQUES THAT INVOKE THE HERING-BREUER REFLEX Techniques invoking the Hering-Breuer reflex rely on the assumptions that this reflex, producing complete relaxation of both inspiratory and expiratory respiratory muscles, can be elicited during airway occlusion and that airway opening pressure comes into equilibrium with alveolar pressure during the occlusion. Occlusion techniques may involve multiple occlusions at different lung volumes or single occlusions at end-inspiration. Multiple-Breath Occlusion Technique
In the multiple-breath occlusion technique, pressure is measured at the mouth during brief airway occlusions performed on multiple breaths. Occlusions are performed at different volumes above FRC, and the individual measurements are plotted as volume versus pressure. The slope of the line of “best fit” is the compliance of the respiratory system (Fig. 12-5). In the single-breath occlusion technique, the airway is occluded at the end of inspiration, with the subsequent expiration occurring passively. A passive expiratory flow-volume curve is then constructed and a line fitted to the linear portion (Fig. 12-6). Compliance is calculated by dividing the total exhaled volume by the pressure at the airway opening recorded during the occlusion. The slope of the linear part of the passive flow-volume curve is equal to the reciprocal of the expiratory time constant (τrs). Resistance can be calculated by dividing the time constant by the compliance. The problem with these techniques is ensuring relaxation of the respiratory muscles after airway occlusion and equilibration of airway opening and alveolar pressures. Generally,
C H A P T E R 12 ■ Respiratory Function Testing in Infants and Preschool-Aged Children
Vocc
V1
V2
Volume
V3
FRC Time P1
Vol above FRC
Time
Pao
P2
Volume
FRC
Paoocc
P3 Time
Pao Time
Flow
Vocc (volume above FRC) V1
Crs = Slope =
V2
Vocc Pao
= Crs
Slope = 1 τrs
Total exhaled volume Paoocc
Rrs = τrs
Crs
Volume
V3 P3
P2
P1
Total exhaled volume
Pao
Figure 12-5 Calculation of compliance of the respiratory system using the multiple-breath occlusion technique. Vocc, volume at which occlusion is made; V, volume; P, pressure; Pao, pressure at the airway opening; Crs, compliance of the respiratory system.
Figure 12-6 Calculation of respiratory compliance (Crs) and resistance (Rrs) using the single-breath occlusion technique. Paoocc, airway opening pressure following occlusion; Pao, pressure at the airway opening; τrs, expiratory time constant.
the presence of a plateau in airway opening pressure indicates that both of these assumptions have been satisfied. The ERS/ ATS Task Force has recommended that occlusions should be held for a minimum of 400 milliseconds. 25 The length of the airway occlusion can influence the values of compliance calculated from the subsequent expiration, with compliance decreasing by 0.15 ml/cm H2O for each 0.1 second of occlusion time. 26 These data strongly argue for standardizing the length of occlusion and discarding data in which a plateau is not achieved. The ERS/ATS Task Force recommends that a plateau should be maintained for at least 100 miiliseconds. 25
infants, the forcing function is generally applied through a facemask and includes the impedance of the nose. When making measurements in infants, the clinician must take extreme care to prevent leaks around the facemask. An adaptation of the forced oscillation technique, using lower frequencies, has been developed for infants. 29 By applying the forcing function during a pause in breathing produced by invoking the Hering-Breuer reflex, reliable impedance data can be obtained from 0.5 to 20 Hz. The impedance spectra showed the same marked frequency dependence (Fig. 12-7) reported in paralyzed animals 30,31 and in adults studied either during voluntary muscle relaxation 32,33 or during mechanical ventilation with paralysis. 34 Fitting the constant phase model 31 to the respiratory system impedance (Zrs) allows partitioning into components representing the airway resistance (together with any Newtonian resistance in the chest wall) and the lung parenchyma, i.e.:
Low-frequency Forced Oscillation Technique
Forced oscillation techniques are described in detail in Chapter 13. These techniques have been used in infants, and impedance spectra have been measured above 4 Hz. 27,28 In
Zrs (cmH2O.s/L)
50
Real part = resistance
1
10
Parenchyma
Airway
0
-50
Imaginary part = reactance
-100
Frequency (Hz) Figure 12-7 Respiratory system impedance (Zrs) measured in an infant. The upper panel shows the resistive component and the lower panel the reactance plotted as a function of frequency.
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P A R T 3 ■ ASSESSMENT
Zrs = Raw + jωIaw + (G − jH)/ωα where Raw and Iaw are the frequency-independent resistance and inertance of the airways (see earlier); G and H are the coefficients for tissue damping and elastance, respectively; j is the imaginary unit, and ω is the angular frequency. The frequency dependence of the respiratory tissues is governed by the coefficient α, which can be expressed as α = (2/p)arctan (H/G). As shown schematically in Figure 12-7, Zrs in the lower frequency range (<4 to 6 Hz in infants) is dominated by the mechanical properties of the pulmonary parenchyma, whereas those at higher frequencies are dominated by the mechanical properties of the conducting airways. Interrupter Technqiue
Respiratory system resistance can also be measured in infants using the interrupter technique. The use of this technique is far more common in preschool-aged children, and the reader is directed to that section for a description of the technique. The major difference in infants is that the measurement is made through a facemask, which adds a compliant compartment (the gas in the facemask) in front of the respiratory system. This can decrease the accuracy of the measurements, especially in the presence of airway obstruction. Body Plethysmography Body plethysmography is commonly used to measure Raw in adults and older children but has been modified for infants by the inclusion of a rebreathing bag containing heated, humidified, oxygen-enriched gas at body temperature, pressure, and saturation. This sophisticated technique requires a large amount of expertise and training but can produce simultaneous measurements of lung volume and Raw. The ATSERS Task Force expended a great deal of time developing standardized techniques and has worked with industry to ensure that reliable equipment is commercially available. The interested reader is directed to the task force publications 6,15 for further information. Measures of Tidal Breathing Parameters Inductance plethysmography is a noninvasive technique that can be used for measuring tidal breathing in infants. The
inductance plethysmograph consists of a pair of wire bands that are usually embedded into an elastic material encircling the chest wall and abdomen. The wires are arranged in a sinusoidal fashion and are excited by an oscillator to produce impedance proportional to the area enclosed within the band. By calibrating the impedance signal with known volume changes, it is possible to calculate changes in the crosssectional areas of the thoracic and abdominal cavities in terms of changes in lung volume. However, the calibration is notoriously unstable and extremely sensitive to changes in body posture. A new generation of respiratory inductance plethysmographs was introduced in the mid-1980s. These devices produce an automatic qualitative calibration during the initial period of operation. Subsequent measurements of tidal breathing excursion are related to that measured during this initial period. 35 The shape of the tidal breathing flow-volume curve can be influenced by airway function. Martinez and coworkers 36 reported that the time to peak tidal expiratory flow (Tptef) expressed as a percentage of total expiratory time (TE) (Fig. 12-8) (referred to by them as Tme/Te) was low in infants who subsequently developed wheezing lower respiratory illnesses. Martinez and coworkers 36 used a pneumotachograph and facemask in sedated infants to measure Tptef/TE. Stick and associates 37 demonstrated that Tptef/TE could be successfully measured using an uncalibrated respiratory inductance plethysmograph during quiet sleep in infants. The precise physiologic interpretation of Tptef/TE is unclear. In adults, Tptef/TE is correlated with airway conductance, lower values occurring with subjects with airway obstruction and low airway conductance. 38 This can be conceptualized by comparing the normally rounded shape of the expiratory limb of the flow-volume loop seen during tidal breathing (see Fig. 12-8, left), at which Tptef/TE approximates 0.5 with the peaked shape of the expiratory limb of a forced expiratory flow-volume curve (see Fig. 12-8, right), at which Tptef/TE approaches 0.15 to 0.2. For a given level of respiratory drive, as airways become more obstructed the tidal flow-volume curve becomes more like that normally seen during forced expiration, and Tptef/TE decreases. Martinez and coworkers 36 interpreted a low premorbid value of Tptef/TE as being indicative of smaller than usual airways, making the infants more likely to develop wheezing illnesses with the usual respiratory tract viral infections. However, the flow-volume
Time
PEF
PEF Expiratory flow
Tptef
Tptef Te
Te Normal Tptef/Te = 0.45
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Abnormal Tptef/Te = 0.15
Figure 12-8 Calculation of the ratio of time to Tptef/TE from tidal expiratory flow and time recordings. PEF, peak expiratory flow.
C H A P T E R 12 ■ Respiratory Function Testing in Infants and Preschool-Aged Children
curve represents an “integrated” output from the respiratory system, and factors other than airway conductance are likely to influence the expiratory flow pattern. Tptef/TE is also influenced by respiratory rate, becoming lower as respiratory rate increases and becoming lower in the prone than the lateral or supine sleeping positions. 39,40 Thus, it is not possible to assign precise physiologic meaning to Tptef/TE.
LUNG FUNCTION TESTING IN PRESCHOOL-AGED CHILDREN Children under the age of 7 to 8 years are frequently unable to perform the standard lung function tests used in older children and adults. Evaluating lung function in young children is important not only for clinical reasons but also due to the considerable growth and development of the respiratory system that occur, with associated changes in lung mechanics. 41 Children commonly present with recurrent cough and wheeze during this period. Many of these children will lose their symptoms as they grow, yet others will continue to have asthma that persists into adult life. 42 The treatment implications of these two clinical patterns are different, and we are currently hampered by a lack of objective assessments to help distinguish between these two patterns. In addition, children recovering from chronic neonatal lung disease and children afflicted with cystic fibrosis are prone to recurrent or persistent respiratory symptoms. Objective assessments of pulmonary function in these children would be expected to improve clinical management. The preschool-aged group presents a number of special challenges. Children in this age group are not able to voluntarily perform many of the physiological maneuvers required for the pulmonary function tests used in older children and adults. They have a short attention span and are easily distracted. Due to these issues, the children need to be engaged and encouraged by the operator to participate in the test. A child-friendly laboratory is essential for success, and staff must be prepared to adjust to the child’s schedule. A number of pulmonary function tests have been attempted in conscious children within the preschool-aged group. These . include standard spirometry, 43-50 VmaxFRC, 51-53 forced oscillation, 54-60 interrupter resistance, 55,58,59,61-67 specific airway resistance measured in a plethysmograph, 58,59,68 FRC using gas dilution techniques, 53,66,69 and measurements of gas mixing indices. 17,18 Commercial equipment is available for most of these tests, although not specifically designed for preschoolaged children. Equipment dead space, resistance, and software programs designed for adults, not young children, may introduce unpredictable errors into the measurements, and no systematic research on these factors has been conducted.
The emotional developmental stage of the preschool-aged child will be an important determinant of the child’s success at performing pulmonary function tests. This influence will be greatest in tests requiring more active cooperation from the child. For example, young children frequently have difficulties in performing the forced expiratory maneuvers required for spirometry. They can either blow “hard” or “long,” but frequently cannot blow both “hard and long.” 44 Measurements that can be made during tidal breathing, such as with forced oscillation, the interrupter technique, and gas washout techniques, may be more suitable for the child unable to accurately perform spirometry. The physiological developmental stage of the respiratory system must also be considered in determining which outcome variables are applicable to this age group. For example, recent studies have demonstrated that the ratio of FEV1 to forced vital capacity in healthy 5- to 6-year-old children is approximately 90% to 95%, 43,46,49,50 implying that young children essentially empty their lungs within 1 second. The physiological and clinical utility of FEV1 comes from its location on the effort-independent (flow-limited) part of the maximal forced expiratory flow-volume (MEFV) curve (see Chapters 7 and 13). The flow-limited portion of the MEFV curve extends down to lung volumes as low as 85% to 90% of exhaled vital capacity in adults. The ability to maintain flow-limitation at low lung volumes depends largely on the ability of the chest wall muscles to maintain sufficient driving pressure to exceed that needed to ensure flow-limitation. It is highly unlikely that children in the preschool-aged group will have the chest wall muscle strength to maintain flow-limitation to lung volumes as low as 90% exhaled vital capacity. While this concept is not new, 70 the use of variables such as FEV0.75 or FEV0.5 has not yet been adopted into clinical practice and most commercial equipment does not report such variables. The most appropriate lung function test for use in the preschool-aged group will depend on the purpose for measuring lung function. The interrupter technique is easily implemented and is suitable for use in epidemiological studies, particularly those involving measurements in the field. However, it may be more suited for studies reporting group mean data than for studies reporting individual data. Measurements capable of reflecting changes in the lung parenchyma, such as gas washout techniques and potentially forced oscillation, are likely to be more suitable for detecting early lung disease in a condition such as cystic fibrosis, which is known to start in the peripheral airways. The clinical and research roles for measuring bronchodilator responses and for provocation testing still need to be evaluated.
SUGGESTED READING Beydon N, Davis SD, Lombardi E, et al: An Official American Thoracic Society/European Respiratory Society Statement: Pulmo-
nary function testing in preschool children. Am J Respir Crit Care Med 175:1304-1345, 2007.
REFERENCES The references for this chapter can be found at www.pedrespmedtext.com.
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