Age Considerations for Children Performing Spirometry

Age considerations are a common concern that cannot be addressed until spirometry is attempted. Children as young as 3 years have the potential to perform the maneuver but with limitations. It has been suggested that at least 50% of children this age can perform pulmonary function tests (PFTs). Published data from several sources suggest that preschool children can perform technically repeatable forced vital capacity (FVC) maneuvers within 10%. Introducing spirometry to children at a young age often yields remarkable results within only a few training sessions. Figure 8-1 is a 5-year-old child performing spirometry for the first time. Note the child is standing, with noseclips in place, and mouthpiece fully in mouth.

Recommendations published from an ATS-ERS focus group on preschool lung function tests more clearly define acceptable and repeatable spirometry in this young age group. The most difficult part of spirometry for a very young child is to continue to exhale once the initial blast of air occurs. Small children do not understand how to sustain applied pressure to their chest and abdomen once they feel their lungs are empty. Additional guidelines from the ATS-ERS include the following:

Although it is desirable to have at least two repeatable maneuvers, even a single satisfactory trial provides important information. However, learning variability and lack of repeatability should be noted. Other testing modalities available in assessing very young children are discussed later in the chapter.

On average, by age 5 years, most children can perform spirometry with adequate technique and repeatability. Published guidelines from the ATS-ERS task force offer more realistic expectations for young children. There is not an age that all children, without exception, can perform technically acceptable spirometry. The ATS-ERS guidelines suggest that certain flow-volume curves may be “usable,” if not technically acceptable. Consider Figure 8-2, A. This is the first experience for this 5-year-old child in the pulmonary lab. On multiple attempts, her FEV₁ was repeatable with the best curve, as shown. Note, however, that exhalation is incomplete and expiratory time is very short (slightly over 1 second). Therefore, the FVC values are underestimated and the FEV₁/FVC is inaccurate. The curves, however, meet criteria for satisfactory start of test and are free of artifact for at least the first second. These classify as usable flow-volume loops, although not technically perfect.

As long as the patient blows for at least 1 second and that first second is free of artifact, the F-V loop and values may be used for interpretation. Caution is suggested in interpreting the FEV₁/FVC or any parameter, based on a full expiratory maneuver. It is certainly understood that this may not represent the child’s maximal effort; however, identifying that this young child’s FEV₁ is repeatable and within the normal range for her age is valuable information for the pulmonologist. The shape of the postbronchodilator flow-volume loop in Figure 8-2, B, is similar to the one in Figure 8-2, A, but larger. There is a proportional increase in both FVC and FEV₁, which suggests the child took a deeper breath before performing the FVC maneuver. Learning effect can be seen even during the first session of working with a young child and should definitely be considered when interpreting this study. Although a bronchodilator response should not be ruled out, it is likely that learning effect was responsible for most of the improvement. It should be emphasized that spirometry is an effort-dependent test that requires cooperation and attention from the child. Equally important is the experience and patience of a well-trained pulmonary function technologist. Children who are mentally delayed or not capable of following directions may not perform adequate spirometry at any age, regardless of the coach or technologist. Patients who are not feeling well or having chest pain, for example, may follow instructions but not perform maximally.

Ensuring Maximal Effort on the Part of the Child

First, gain the child’s confidence and do not rush into testing. Children are fearful that the testing will hurt. When possible, reassure the child by carrying on a conversation that is directed toward the child. As illustrated in Figure 8-3, try some “blowing” games with the very young child before approaching the PFT equipment. Use of a pinwheel is often very successful. It teaches the child the need to take a big breath and blow fast. Additionally, have the child try to continue to blow until the pinwheel stops turning. This important step reinforces a complete exhalation. Demonstrate the test and reassure the child that it is easy and fun. Pinwheels also make an excellent and inexpensive prize for the patient when testing is over. If a pinwheel is unavailable, the use of a tissue will substitute, although it is a bit harder. Demonstrate blowing the tissue as high, and keeping the tissue suspended for as long, as possible.

Once the child has practiced several times, move the child to the PFT machine and prepare for testing. When possible, the child should be standing and the technologist should be at eye level with the child. See Box 8-1 for a list of suggestions that will “break the ice” and get things going in a positive direction. The use of noseclips is recommended, depending on the age and cooperation of the child. The anatomy of the nasopharyngeal structures in younger children is such that the use of noseclips may not be necessary. If the child is willing to wear noseclips, encourage him or her to do so.

Many pulmonary function systems offer two mouthpiece techniques for performing spirometry: “closed” and “open” techniques. Each offers advantages and disadvantages. Attempt the technique with which laboratory personnel are most comfortable and consistent. For the closed technique, have the child stand with noseclips in place and the mouthpiece situated securely. Ask the patient to breathe tidally for several breaths. This offers the opportunity to observe the child and ensure that the seal around the mouthpiece is tight. It also gives the child a feeling of security that he or she will get plenty of air through the mouthpiece. The child should be reassured during tidal breathing that he or she is doing very well. If the spirometer permits real-time visualization of flow, the clinician may show the child that he or she is “drawing pictures” with his or her breathing. It is essential to gain the child’s confidence and offer praise whenever possible. It is very important to talk the child through the maneuver. Use simple words and phrases. For example, “Breathe in, breathe out,” “Take easy, little baby breaths,” or “One more little breath. Now take a giant breath in.” The technologist should be vocal and use hands and arms to demonstrate. The intonation of the voice should mimic the action, for example, “easy, gentle breaths” in a soft voice versus “big, fast, and long breath” in a louder tone. Sometimes having the child “race” with another technologist is helpful. Again the use of the pinwheel or tissue can reinforce what is expected of a very young patient while the test is actually going on.

If the child is having particular difficulty, changing the technique may lead to success. At times, tidal breathing may confuse the child. Have the patient get onto the mouthpiece, immediately take a maximal breath in and blast the air out. Alternately, use a different mouthpiece or try the open technique. The child may have a sensitive gag reflex or, for unclear reasons, become anxious with tidal breathing. With the open technique, the child should first be instructed to hold the mouthpiece close to his or her face, perhaps supported on the cheek. Next, open the mouth wide, take in the deepest breath possible, place the mouthpiece in the mouth, and immediately blow. The disadvantage of this technique is that air may be lost as the child tries to get the mouthpiece into his or her mouth and form a seal. To aid in a complete exhalation, the technologist can place his or her hands on the child’s belly. As the patient exhales, gently press on the stomach. This reinforces a smooth and continuous expiratory maneuver. Once the child is more comfortable performing spirometry, transition to a closed mouthpiece technique without any assistance from the technologist.

Importance of Effort

One of the biggest challenges with children is ensuring a maximal breath in before the forced expiration. The concept is simple: The more air in, the more air out. The technologist should strive to get the child to breathe in as deeply as possible and observe the child’s chest excursion. Movement of the shoulders upward without chest excursion is common and can fool the technologist into believing it is a maximal inspiratory capacity. This may also be a pitfall when comparing prebronchodilator and postbronchodilator spirometry. Figure 8-4 is also from a 5-year-old patient performing spirometry for the first time. The prebronchodilator spirometry (see Figure 8-4, A) appears to be normal and was repeatable. Postbronchodilators, both FVC and FEV₁, improve significantly (see Figure 8-4). The increase in FVC and FEV₁ is very symmetric, similar to the last example presented (see Figure 8-2, A). Learning effect cannot be ruled out. However, the shape of the F-V curve is very different with postbronchodilator spirometry. This is an example of a situation where the change in FEV_0.5 might be more helpful in assessing intrathoracic airflow obstruction than the change in FEV₁

The child is at a low lung volume when 1 second is reached (close to FVC) and the FEV₁ is not reflective of airflow changes that are occurring at mid-lung volumes. It is critically important to realize that all of the “action” has already taken place by the time 1 second has elapsed. Parameters such as FEV_0.5 or FEV_0.75 should be assessed in these young children, although standards and guidelines for interpretation are not available. Contrast Figure 8-4 with Figure 8-5, A and B. In this example of a 7-year-old child, both FVC and FEV₁ increase with postbronchodilator spirometry; however, the increase in FEV₁ is proportionately higher, which also increases the FEV₁/FVC ratio. Although learning may have some effect in this example, it is evident that mild intrathoracic airflow obstruction is completely reversed. Once a child has learned the technique and is capable of performing spirometry, the results are remarkably repeatable. The ATS-ERS guidelines now base repeatability of FVC and FEV₁ on lung volume. Because younger children have smaller lung volumes than adults, these revised guidelines pertain to the pediatric population as well as to older patients with severe lung disease.

Older children often are able to perform spirometry with an FVC and FEV₁ within 5%. However, for smaller children with even more reduced lung volume, the 100 mL criterion correlates with repeatability closer to 10%.

Once a maximal inspiration is accomplished, most young children do not have difficulty blowing out forcefully. As for adult spirometry, the technologist should minimize hesitation before the forced maneuver that may create a “time zero” or back-extrapolated volume error. Do not encourage a breath hold. Delayed exhalation can result in a poor peak flow measurement and falsely raise the FEV₁. Figure 8-6 demonstrates this volume extrapolation or time zero error.

Figure 8-6, A, is an acceptable FVC maneuver. Note how the delayed exhalation in Figure 8-6, B, can skew the curve to the right and falsely elevate timed parameters. Young children have a desire to please and, unless they are feeling unwell, will usually respond to the direction to “blast or burst the air out.”

Obtaining a maximal peak flow can actually be more difficult in an adolescent. Teenage children often can be reluctant to perform maximally unless strongly encouraged to do so. This may be due to chest pain, embarrassment, or fear that something is wrong with them. Occasionally, this poor effort may be related to typical teenage angst or attention-seeking motivation. A sensitive and perceptive technologist can often combine the right amount of compassion with the necessary verbal encouragement to obtain optimal results. Variability caused by effort alone may be especially important if the patient is performing serial measurements, as in a methacholine challenge. A change in treatment regimen or admission to the hospital is often based on spirometric changes; therefore, repeatability is critical.

Length of Exhalation for a Child During an FVC Maneuver

Long-established criteria from the ATS suggested that an FVC maneuver should last for at least 6 seconds or until there was a plateau in the volume-time curve. Young children often cannot meet these criteria. The 2005 ATS-ERS guidelines have added an age stipulation to the recommendations.

Because children have lung volumes that are significantly smaller than adult lung volumes, their lungs may completely empty in only 2 or 3 seconds. When a child feels empty, the natural instinct is take a breath back in. With instruction, practice, and maturing, the child can learn to continue the expiration; however, this may not be possible on the first several visits to the lab. This does not invalidate the FVC maneuvers but requires that the testing be evaluated carefully. Figure 8-7, A, represents three prebronchodilator flow-volume (F-V) loops superimposed over each other. Although this young child does not meet the end-of-test criteria, the FEV₁ and shape of the F-V loop are remarkably repeatable. Postbronchodilator (see Figure 8-7, B) F-V loops are significantly improved and repeatable. The current ATS-ERS guidelines more realistically represent what can be expected of a younger child.

Children who are severely obstructed, like their adult counterparts, may have the ability to exhale for an extended time. Figure 8-8 shows the F-V loop and volume-time tracing of a 10-year-old girl with cystic fibrosis. This child is able to sustain expiration for 15 seconds. However, the additional volume measured in this prolonged expiration is small and may exhaust the child performing the test. She approaches a flow plateau at approximately 7–8 seconds, and the maneuver can be terminated at this point. The spirometry is certainly still valid for interpretation if terminated before zero flow occurs. Many decisions regarding acceptability of PFT results require good judgment from the technologist and careful interpretation from the physician.

Reliability of FEF_25%–75% in Children

Historically, FEF_25%–75% has been used to evaluate flow from the “small airways”. More precisely, the FEF_25%–75% should be considered a measurement of flow at lower lung volumes, not merely flow from medium-sized and smaller airways. As in adults, the variability of the FEF_25%–75% is greater than that of the FVC and FEV₁. Because children may be even less repeatable at baseline, the reliability of this measurement in pediatric testing may be questionable. In addition, if the child does not fully exhale to RV, FEF_25%–75% may be artificially elevated because of reduced vital capacity. If it is reported, the FEF_25%–75% in a pediatric subject should be interpreted with caution, especially in a very young child. A substantially greater change postbronchodilator is needed before a change can be considered significant. Refer back to Figure 8-4, A and B. Although the exhalation times do not meet the revised 3-second guideline for a child younger than age 10 years, it does appear that this patient exhaled to a volume plateau. The change in shape of the F-V loop, as well as the change in FEF_25%–75% of 65%, is certainly suggestive of a reversal of intrathoracic airflow obstruction. An FEF_25%–75% that improves by more than 35%–45% after a bronchodilator may be indicative of airway reactivity, but again caution is advised when considering this parameter. Repeatability of the FEF_25%–75% is more reliable in older children and teenagers. As previously noted, FEF_25%–75% can be reduced for several reasons that are not always related to peripheral airway disease. Refer to Figure 8-9. This F-V loop is from a 17-year-old patient who had tracheal stenosis after a prolonged intubation as a young child. The FEF_25%–75% of this curve is severely reduced, as is the FEV₁. The reduction is not caused by peripheral airway obstruction but by a large central (tracheal) airway obstruction.

Parameters of Inspiratory Forced Flow Helpful in Pediatrics

Spirometry yields a variety of expiratory and inspiratory flows, including FEF_25%, FEF_50%, FEF_75%, FEF_85%, FIF_50%, and the FEF_50%/FIF_50% ratio. Each of these parameters relates to flow at a particular lung volume and may have some benefit for particular instances. These flows, like the FEF_25%–75%, are less repeatable than the FEV₁ and FVC and do not have any reference values. The FEF_50%/FIF_50% ratio may be helpful in identifying intrathoracic versus extrathoracic airflow obstruction (see Chapter 2). Unlike the expiratory limb of the F-V loop, the inspiratory limb has not been well characterized in pediatric subjects. There are several reasons for this; however, the most important are energy expenditure and effort dependence. Expiration from TLC is far more repeatable because of the elastic recoil of the lung. The FEF_50% occurs in the portion of the expiratory limb that is considered effort independent. The inspiratory limb, conversely, is effort dependent and energy dependent for the entire maneuver. Therefore, optimal patient effort is vital for analyzing the inspiratory loop. A great deal of important information can be obtained from an appropriately performed maneuver. Too often, the inspiratory limb is ignored. When teaching children how to perform spirometry, certainly the emphasis is on expiration. Once it is mastered, attention should be paid to the inspiratory maneuver as well.

The aperture, or opening, through the vocal cords is approximately the same at both 50% of expiratory vital capacity and 50% of inspiratory vital capacity. Therefore, the FEF_50%/FIF_50% ratio should not be greater than 1.0. A ratio greater than 1.0 suggests an extrathoracic obstruction; however, this relationship has not been closely studied or reported in pediatric patients. Conversely, an FEF_50%/FIF_50% ratio of less than 1.0 may be normal or may represent significant intrathoracic obstruction. In addition, a ratio close to normal is possible if significant obstruction is seen on both inspiration and expiration (fixed obstruction), yielding a ratio of 1.0. Figure 8-9 demonstrates the effect of tracheal stenosis in a 17-year-old patient on the shape of the flow-volume loop, and the resulting FEF_50%/FIF_50% ratio. This underlies the importance of correlating the F-V loop with the child’s clinical picture and symptoms.

Figure 8-10 shows examples of F-V loops with differing FEF_50%/FIF_50% ratios and the shape of the loops represented by those ratios. Although FEF_50%/FIF_50% may not always discriminate between intrathoracic and extrathoracic airflow obstruction, the importance of extrathoracic obstruction should not be underestimated. Laryngeal webs, subglottic stenosis, tracheal malacia, and other lesions of the laryngeal-tracheal airway are important causes of upper airway obstruction in the pediatric population. In addition, the vocal cords represent a major “choke point” to airflow. The cords may have a structural abnormality, such as nodules or granulomas, or may become edematous, as in croup. The recurrent laryngeal nerve may be damaged, resulting in inappropriate movement or paralyzed cords. These conditions are generally easy to diagnose with direct visualization of the vocal cords. Vocal cord dysfunction (VCD) may also be responsible for poor abduction (opening) of the vocal cords during inspiration.

Role of Vocal Cord Dysfunction

Vocal cord dysfunction has become increasingly recognized as a reason for shortness of breath, in addition to throat and sternal chest pain, often mimicking asthma. Adolescents who are competitive athletes or are exceptionally goal oriented and children who have stress-related disorders are at highest risk. Unfortunately, vocal cord dysfunction is highly variable and may be detectable only when the patient is stressed in a manner that provokes the condition. The term vocal cord dysfunction (VCD) has sparked controversy among pediatric pulmonologists. Perhaps the term is not the most important consideration, but rather understanding that the vocal cords and larynx are very complex structures. There are likely many scenarios, some consciously controlled and others unconsciously controlled, that lead to the malfunction or inappropriate movement of the vocal cords. In very severe forms, “clipping,” or truncation, of the inspiratory loop with a completely normal expiratory loop is the classic presentation (see Figure 8-10, E). The child may or may not sound very stridorous during inspiration. The patient may try to speak while inspiring in short, gasping sentences. More common is a completely normal-appearing child with normal expiratory loops but highly variable inspiratory loops. Some inspiratory loops may be normal (FEF_50%/FIF_50%<1.0); however, many are often abnormal with an FEF_50%/FIF_50% greater than 1.0.

Vocal cord dysfunction is an example of a disorder in which the variability in the patient’s inspiratory loop is the hallmark of the dysfunction (Figure 8-11, A). These are the baseline loops from one patient, a 15-year-old teenager. Note how different all of the inspiratory loops look. Some have a triangular-shape appearance, some with the more classic flat, truncated appearance, and others have multiple inflection points. The inspiratory volume may be limited, giving a short, gasping type of inspiratory loop. A more normal inspiratory loop may appear among many abnormal loops (Figure 8-11, A, Trial 4). This is very important to capture when possible. It indicates that the child is capable of performing normal inspiratory loops, and the problem is likely more dynamic in nature, that is, a vocal cord malfunction. If there is a structural upper airway abnormality, the inspiratory loops should all look abnormal and very similar in shape. Structural obstructions are usually more fixed in nature with expiratory clipping also present. Refer again to an example of fixed airflow obstruction, as seen in Figure 8-10.

Bronchoprovocation testing can sometimes provoke vocal cord dysfunction; however, conclusive evidence of inappropriate movement of the vocal cords should be visualized through a laryngoscope, ideally during an episode. Because laryngoscopy may not be practical or available, a series of well-performed F-V loops may be helpful in making this presumptive diagnosis. It should be noted that VCD, on the milder side of the spectrum, is primarily a diagnosis of exclusion, and the absence of inspiratory clipping on F-V loops does not rule out the diagnosis. It is important to emphasize that effort, technique, and learning play a major role in the shape of inspiratory loops. In young children, it may require several sessions, on different days, with abnormal inspiratory loops consistently obtained before the diagnosis of vocal cord dysfunction can be suggested.

Under certain circumstances, very unusual inspiratory loops can be seen in multiple trials that are not effort- or technique-related. Consider Figure 8-11, B. These loops were obtained in a patient with excessive secretions and laryngospasm. Flow-volume loops are rarely diagnostic as a single test but certainly can suggest and support other diagnoses that are being considered.

VCD Combined with Intrathoracic Airflow Obstruction

To further complicate matters, vocal cord dysfunction is often seen in children with asthma. The relationship between these two disorders is not fully understood. There is certainly some similarity in symptoms, primarily shortness of breath, chest pain, and/or throat pain. However, some children who experience both asthma and vocal cord dysfunction can actually distinguish between the two disorders. Refer to Figure 8-12, A. These loops are from a known asthmatic child experiencing symptoms of shortness of breath and chest pain. The expiratory loops show very mild (if any) airflow obstruction. However, the inspiratory flow loops are variable and abnormal, as described in the earlier section. Vice versa, in Figure 8-12, B, note the characteristic “scoopy” appearance of severe expiratory airflow obstruction. This is accompanied by a normal appearing inspiratory loop. Note that the relationship of FEF₅₀/FIF₅₀ is skewed when the expiratory loop is not normal. The FEF₅₀/FIF₅₀ ratio discussed earlier is no longer valid in the face of intrathoracic obstruction. This ratio also does not hold true when the inspiratory loops are not complete, full loops or very irregular in shape.

Non-Repeatability in the Expiratory Maneuver

The ATS-ERS recommendations emphasize the importance of repeatability of the FVC and FEV₁. In some instances, patients cannot reproduce these parameters, and effort is not the reason. Figure 8-13 shows an example of such an instance. If only a single (best) F-V loop (Trial 1) were reported to the physician, the interpretation would state that this patient has mild to moderate intrathoracic airflow obstruction. However, the next two successive maneuvers performed by this 15-year-old asthmatic are also illustrated (Figure 8-11, A, Trials 2 and 3). These successive trials reveal progressively significant drops in FEV₁ and FEV₁/FVC, which are not repeatable with Trial 1. This pattern is an extremely important clue to the hyperreactivity of the patient’s airway. Simply performing repeated forced maneuvers may cause an asthmatic to become suddenly more obstructed and vulnerable to further bronchospasm. In such an instance, the technologist should stop testing the patient and administer a bronchodilator. If the patient’s report included only his or her best prebronchodilator and postbronchodilator spirometry, it would completely omit this important information and might prevent necessary changes in his or her asthma medication regimen.

An interesting but opposite phenomenon may be seen in the spirometry of a mild asthmatic patient. Deep inspirations may cause progressive bronchodilation with improving FEV₁ and FEV₁/FVC. This is a beneficial compensatory mechanism and is likely similar to the asthmatic athlete who is able to “run through” his or her asthma with bronchodilation during exercise. After exercise, tidal volumes decrease, airway temperature changes, and bronchoconstriction may be provoked.

Airway Malacia

Unusual flow-volume curves may be very helpful in providing clues to the location of fixed or variable obstruction. One scenario common in pediatrics is tracheal and/or bronchial malacia. Malacia refers to an airway (or more than one airway) that is soft and pliable because of a lack of supportive connective or cartilaginous tissue. Depending on the location (intrathoracic, extrathoracic, or both), these airways may collapse during inspiration or be compressed during exhalation. Tracheal or bronchomalacia in infants may produce significant stridor and “noisy breathing,” especially when the baby is excited or crying. With time and growth, the airways stiffen and are less prone to collapse.

For older children, airway malacia may produce some bizarre-shaped F-V curves. Refer to Figure 8-14. These F-V loops are from a 12-year-old child with a malaciac left main stem bronchus. Trial 1 represents a forced exhalation that is normal in shape. Trial 2 is from the same patient during the same testing session. Notice the rapid drop in flow rate, followed by a “flattening” or shelf-like appearance in the curve. Blowing harder caused critical compression at the malaciac segment and resulted in a sudden decrease in flow rate, or flow transient. Note the reduction in FEV₁, as well as FEF_25%–75%, from Trial 1 to Trial 2. This represents another example of the inadequacy of looking solely at one or two parameters instead of considering the entire picture. The shape of the curve in Trial 2 is characteristic of two lungs emptying at different time constants. One lung empties normally during forced exhalation, whereas the other lung takes considerably longer to empty because of the central intrathoracic obstruction present. Obtaining repeatable and acceptable F-V loops in the face of airway malacia can be challenging. Although not always successful, taking extra time with the child to try different breathing techniques or different mouthpieces may result in a more normal expiratory loop.

Inhalation Challenges

The most common type of inhalation challenge performed is the methacholine challenge. The child inhales methacholine chloride in succeedingly higher doses of medication. One popular dosing regimen involves a ten dose schedule beginning at a low dose (0.031 mg/mL), doubling each successive dose to a maximal dose of 16 mg/mL. A second recommended regimen with five levels of dosing starts at 0.0625 mg/mL and increases to 16 mg/mL. The drug can be administered either with a dosimeter that delivers a very specific dose with each breath or via the 2-minute tidal breathing method. Details of these two methods are discussed in Chapter 9 and both methods are generally considered to be equivocal. The 1999 ATS Guidelines provide specific recommendations for choosing the appropriate method, dosing regimens for methacholine chloride and modifications as necessary, and many other considerations for labs undertaking bronchoprovocation studies. As mentioned earlier, it is necessary to establish a consistent and repeatable spirometric flow-volume loop at baseline before the administration of the methacholine. Obtaining not only repeatable expiratory loops, but also maximal inspiratory loops, can be very helpful in considering possible vocal cord dysfunction. Serial spirometry is obtained at approximately 30-60 seconds after the administration of methacholine and again at 90 seconds. Because the half life of methacholine chloride is very short, further spirometry trials may not reflect the action of the methacholine. However, caution is advised if the child’s spirometry worsens with repeated blows, and a third trial of spirometry may be warranted. Additionally, if symptoms such as cough, wheezing, or shortness of breath begin during trials, bronchoconstriction may also be worsening, and this child should not be given an increased dose of methacholine until his or her spirometry stabilizes. A drop of 20% or more in the FEV₁ is considered the stopping point for the challenge. Most often, the computer software is able to calculate the provocative concentration that would produce a fall in FEV₁ of exactly 20% (PC₂₀), Laboratories that use dosimeters often report the provocative dose (PD₂₀), or the dose of methacholine that correlates with an exact drop of 20% in FEV₁. Pediatric patients should always be given a bronchodilator, such as albuterol, to reverse any possible bronchospasm that has occurred from the administration of the methacholine. This is true even if the challenge is considered negative. The bronchodilator may produce a significant response in FEV₁ above the child’s baseline spirometry, and that information may be relevant to the physician.

Methacholine chloride has also been shown to provoke vocal cord dysfunction. It is not known whether the medication itself causes the vocal cords to behave abnormally, or if the child experiences enough stress performing the multiple trials to unmask the vocal cord dysfunction. Examination of the flow-volume loops throughout the entire challenge can be very helpful in identifying flow abnormalities in both the inspiratory and expiratory loops. Refer to the previous discussion of flow-volume loops. An important point worth repeating: One of the hallmarks of vocal cord dysfunction is the variability in the clipping or truncation of the inspiratory loops. Because the child is required to perform multiple trials, it is possible to examine many flow-volume loops.

Most recently, the use of mannitol as a provocative inhalational agent has been proposed by many pulmonary laboratories. The advantage of mannitol over methacholine chloride is the method of delivery and the cost of medication. Mannitol can be delivered as a dry powder inhalant; therefore nebulization of medication is unnecessary. The mannitol capsules are much cheaper to produce and do not require the pharmacy making dilutions on a regular basis. An added bonus is that the sensitivity and specificity are very similar to methacholine. A disadvantage of mannitol is the dosing regimen that has been proposed. The number of doses currently recommended is eight, plus a placebo baseline. For young children, use of a dry powder inhaler may be difficult. The number of spirometry trials and the time necessary to do the testing are also extended, therefore limiting the use of mannitol challenges in the pediatric laboratory.

Pulmonary Exercise Stress Testing

Pulmonary function laboratories are asked to perform exercise stress tests for two main reasons: (1) to provoke bronchoreactivity and (2) to assess level of fitness. Protocols for exercise are as varied as protocols for inhalation challenges. The protocol used is often geared toward answering a specific question, such as, “Does this child have exercise-induced bronchospasm or asthma (EIB or EIA)?” An example of a protocol to evoke EIB includes pre-exercise spirometry as the first step. ECG leads are placed on the chest for heart rate assessment, and pulse oximetry is used to follow oxygen saturation. The patient performs a “free run” on a treadmill, with noseclips in place, but without a mouthpiece. Jogging on a treadmill is the most “asthmagenic” exercise because it mimics natural exercise and uses many muscle groups. This protocol also permits the technologist to watch and listen to the child without a mouthpiece in place. Evaluation of hyperventilation and/or stridorous respirations can be made. Several of the symptoms manifested (i.e., intense shortness of breath and sternal chest pain) should also be noted. The speed and elevation of the treadmill are increased every minute to increase the patient’s heart rate to approximately 85% of the maximal HR and sustained at this level for 6-8 minutes. This equates to a HR of 170-180 for at least 6 minutes. The entire exercise study should take no more than 8-10 minutes and should end abruptly without a cool-down period. Following exercise, the airways cool rapidly, and it is felt that the rapid change in temperature and/or humidity causes an inflammatory response that further elicits a bronchospasm. Post-exercise spirometry is performed every 3-5 minutes until 20-30 minutes after exercise. Laboratories differ as to the parameter and percent decrease needed to signify EIB. A decrease in the FEV₁ of 15%, often associated with a decreased FEV₁/FVC, is considered diagnostic of EIB. Some laboratories consider a drop of 10% or greater in the FEV₁ as a significant decrease. Maximal bronchoconstriction most often occurs 6-12 minutes after exercise. Cough, desaturation, and worsening shortness of breath usually accompany changes in pulmonary function. Researchers now question whether repeated exposure in cold weather sports, ice rinks, chlorinated pools, and high pollution climates causes chronic airway inflammation and eventual remodeling of the airways. This may be particularly relevant in elite endurance athletes, as well as in children whose lungs are still growing and developing. Clinicians should be mindful, however, of effort-related problems after exercise. A proportionate decrease in flows and volumes immediately after exercise is suspect for poor patient effort or technique-related problems.

Other possible causes should be considered for poor performance during exercise or with post-exercise spirometry. Obesity in children has become epidemic in our society. Many pediatric pulmonary laboratories see a high proportion of overweight, poorly conditioned children. Parents question why their child cannot exercise or participate in the sports activities of other children. It’s a difficult and delicate topic that should be addressed by the child’s physician. To complicate the issue, obesity goes hand-in-hand with asthma. The comorbidity of these two conditions can cause a vicious cycle difficult to break. Therefore, it should not be assumed, by any clinician, that an obese child is poorly conditioned just because of his or her weight. Asthma may also be playing a major role. Performing exercise stress tests on these children should be undertaken with care and thoughtful preparation.

Vocal cord dysfunction should, once again, be considered a possible culprit responsible for the shortness of breath and sternal chest pain that children experience with exercise. Often performing a pulmonary or submaximal exercise test will produce enough stress for the child to evoke his or her symptoms. Inspiratory stridor may be audible with more severe VCD. Children who exhibit VCD tend to recover very quickly after the stress of exercise. Inspiratory loops may appear completely normal shortly after exercise. This does not exclude the diagnosis of VCD. However, persistently abnormal and variable inspiratory flow loops may persist and strongly suggest a component of VCD. Neither VCD nor exercise-induced bronchospasm is mutually exclusive. Although each diagnosis may occur without the other, it is common to have a child with both asthma and VCD. It is important to understand that pulmonary function testing does not always distinguish the role that VCD plays in the child’s symptomatology. Clinical correlation by an experienced technologist and physician is key to correctly diagnosing true exercise-induced asthma versus VCD, exercise-induced hyperventilation, technique-related problems, or comorbid conditions.

The indication for a maximal cardiopulmonary exercise test is to evaluate how well the respiratory and cardiovascular systems work together. The clinical question asked is often whether the child has normal exercise tolerance. If not, is the child limited by the lungs (ventilator limitation), the heart (cardiovascular limitation), or both? Maximal tests are performed with a full 12-lead ECG, pulse oximetry, and a mouthpiece in place to measure ventilation, oxygen consumption, and carbon dioxide production (see Chapter 7 for a detailed discussion of indications, protocols, analysis, etc.). Use of an ergometer versus a treadmill may be a laboratory preference. Maximal oxygen consumption is usually slightly higher on a treadmill. The advantage of an ergometer, however, is that the child’s upper body is relatively still while the legs cycle. This decreases movement of the head and leaks around the mouthpiece. Pulse oximetry is often problematic during exercise because of movement of the arms and fingers. With cycle ergometry, however, less whole body motion produces less artifact. Alternatively, an oximeter probe placed above the eyebrow may yield more stable readings. The disadvantages of cycle ergometry in children are (1) modifying the equipment to fit the child, (2) keeping the child cycling consistently, and (3) obtaining true maximal oxygen consumption. Children may simply stop cycling when they feel fatigued. Unless a plateau in oxygen consumption (o₂) can be identified, the highest level reached is termed peak oxygen consumption.

Eucapnic Voluntary Hyperventilation

As discussed previously, one reason for performing an exercise stress test is to potentially provoke bronchospasm via temperature and humidity changes associated with rapid change of respiratory rate. An alternative method of induced hyperventilation can be accomplished voluntarily if carbon dioxide levels can be controlled during the rapid breathing. This procedure is known as eucapnic voluntary hyperventilation (EVH). Different setups are possible (see Chapter 9), but essentially the system must provide a high flow or reservoir of dry air and a means to control carbon dioxide in the normal physiologic range. Refer to Figure 8-16 as an example of a setup available to perform EVH challenges. For this particular setup, the subject breathes a dry mixture of air (or oxygen) and carbon dioxide, 95% O₂/5% CO₂, for example. The higher F_IO₂ may not be needed; however, it does safeguard against induced hypoxia during the challenge. Also, subfreezing cold air may be incorporated into an EVH setup, if desired. An end-tidal CO₂ monitor is necessary to indirectly measure Paco₂. The flow of gas from the tank’s flow meter, along with a “slow bleed” from a reservoir bag, can be used to titrate the flow needed by the patient during the challenge. Before the actual hyperventilation challenge, the patient performs baseline spirometry and usually a maximal voluntary ventilation (MVV) maneuver. During the hyperventilation phase of the challenge, the patient is asked to breathe rapidly to a target level (approximately 60%-70% of his MVV) for 6 minutes. Spirometry is then repeated every 3-5 minutes after the hyperventilation. Figure 8-17 depicts types of graphs that may be obtained during the hyperventilation phase, and the trending of FEV₁ pre- and post-hyperventilation. This patient’s data and trending graph did not indicate any change in FEV₁ after hyperventilation. The mechanism of potential induced bronchospasm is very similar to that provoked from exercise. The advantage of the EVH procedure is that it does not involve the time, equipment, and personnel needed to perform an exercise stress test. The disadvantage is that hyperventilation is voluntary, and the stimulus has an indirect effect. Asking a child to breathe at a rate and depth approaching his MVV for 6 minutes can be a challenge. EVH may be an attractive alternative for performing an exercise challenge on a child who cannot, or will not, exercise to a significant degree. However, many pulmonary labs perform EVH challenges only on motivated young adults or dedicated athletes who have negative exercise bronchoprovocation studies.

First Step

The first step in performing plethysmography in the pediatric population is getting the child into the body box. This is usually not a major obstacle. In many cases, the child has been to the pulmonary function laboratory on previous occasions and is familiar with the environment and personnel. The child often asks, “What’s that?” This becomes an opportunity to appeal to the child’s imagination. A body box, in a child’s eye, can be a spaceship or Cinderella’s coach. Sometimes the child sits in the body box only on the first or second visit, but ultimately this is a valuable experience. It may be possible to have the parent also sit in the body box and perform some testing until the child feels comfortable alone. The instructions should be kept simple and be demonstrated to the child. In many instances, the child will perform adequately without the need to modify instructions. Too many instructions can lead to confusion. A fitted mouthpiece and noseclips are required for testing in the body box. Some technologists suggest supporting the cheeks during the test. It may be preferable not to hold the cheeks. This may cause the child to raise his or her shoulders and not breathe at a true resting level. The child should sit up straight with hands relaxed in the lap. The instructions can be modified if the child pouches his or her cheeks, producing open loops rather than closed loops during panting. The door should be opened periodically to let the child rest and converse with the technologist or parent. Children requiring O₂ should also be given a break between trials to replace their cannula or mask until their oxygenation is back to baseline.

Important Plethysmographic Parameters

The tests performed and parameters examined depend on the reason for performing the study and on the ability of the child. In very young children, obtaining a stable resting level and reproducible FRC may be all that can be accomplished. Once spirometry is mastered, the child can quickly learn to perform a full IC and VC in the body box. In a clinical setting, a skilled technologist and user-friendly software allow data to be edited as necessary to provide TLC, FRC, RV, and RV/TLC. It is important that the technologist understand when and how to average data versus deleting data and when to accept the “best test” data. This is especially true with pediatric patients who may not reproduce the entire maneuver with each trial.

Although spirometry is the first test performed in many patients, spirometry alone may not accurately predict lung volumes in children. Figure 8-17 demonstrates case presentations of obstructive and restrictive lung disease, as well as a mixed presentation. Note that predicted values, as well as the lower limit of normal (LLN), are presented. In some reference sets, the LLN is not available and is indicated with asterisks (**).

The case in Figure 8-17, A, is a 15-year-old white boy with advanced cystic fibrosis. Severe obstruction is evident in the spirometry data. Both FEV₁ and FEV₁/FVC are reduced, consistent with an obstructive disorder. Lung volume measurements confirm the severity of obstruction and air trapping. Although the TLC is within normal limits, FRC, RV, and RV/TLC are significantly elevated. Compare these findings with the spirometry and lung volumes in Figure 8-17, B. This case is a 13-year-old white girl with scoliosis. Her pulmonary function results represent a restrictive defect. FVC and FEV₁ are reduced in a symmetric pattern; however, the ratio is normal. Restrictive disorders often present with a normal or elevated FEV₁/FVC. The lung volume measurements are also consistent with a pure restrictive defect, showing reduced volumes (TLC, FRC, RV, ERV) and a normal RV/TLC.

Many pediatric and adult diseases do not present as a purely obstructive or restrictive process but as a combination of obstruction and restriction. Refer to Figure 8-17, C. This 10-year-old African-American girl has systemic scleroderma. The FVC and FEV₁ are severely reduced. Her flow-volume loop has a very restrictive appearance, with a disproportionately high peak flow and increased FEV₁/FVC. A closer look at her lung volumes, however, reveals not only a moderate restrictive defect, but also an elevated RV and RV/TLC. Some elements of this pulmonary function study point to a restrictive component, whereas others are consistent with obstruction. This pattern is the hallmark of a mixed obstructive and restrictive disorder. Scleroderma is a generalized disease that can cause shrinkage of any of the connective tissues in the body. When the lungs are affected, the disease initially presents as a restrictive disorder, but severe end-stage disease results in a “honeycomb lung” with obstruction in distal airways and air trapping.

Are lung volumes necessary? The cases in Figure 8-17, A and B, are straightforward presentations in which spirometry alone is very representative of the child’s disease process. The lung volumes merely confirm the degree of airflow obstruction (see Figure 8-17, A) and lung restriction (see Figure 8-17, B). Mixed obstructive and restrictive disorders (Figure 8-17, C) definitely require lung volume determination to better define the child’s lung mechanics. It is not uncommon in the pediatric population to observe a seemingly restrictive spirometric pattern with a proportional reduction in percent predicted FVC and FEV₁. However, subsequent lung volumes may identify a completely normal TLC, with an elevated RV/TLC. What appears to be a restrictive pattern on spirometry is, indeed, an obstructive disorder once lung volumes are examined. The relatively smaller size of the intrathoracic airways in the pediatric population leads to early obstruction in the peripheral airways. This may be compounded with mucus secretions in the airways or bronchoconstriction of these airways. With a forced expiration, distal airways are squeezed and occlude, resulting in significant air trapping.

Role of Measurement of Airway Resistance

Depending on the equipment and software being used, measurement of airway resistance during plethysmography may be an option. Airway resistance (Raw) is measured while having the patient pant before closing a shutter or valve to obtain the thoracic gas volume (V_TG). Patients, including children, have a tendency to pant at an elevated lung volume. In other words, they do not return to the resting expiratory level with every pant, and progressively increase their chest volume. If V_TG is measured at the very end of the maneuver, it will be artificially elevated. Although this is not the patient’s true FRC, the application software makes a correction and reports separate values for V_TG and FRC. Raw should always be reported and interpreted at the lung volume at which it was measured (i.e., using V_TG to calculate specific airway resistance and specific conductance). Except in trained patients, Raw tends to be less reproducible than other pulmonary function parameters. Measurement of Raw may complicate and prolong the test and may not be necessary for routine testing. However, Raw can be significantly increased in patients with extrathoracic obstruction, central airway intrathoracic obstruction, and diffuse peripheral obstruction. Many laboratories find the measurement of Raw, specific airway resistance (sRaw), and specific conductance (sGaw) helpful during methacholine challenges. Because the variability of these measurements is greater, a greater change is required to meet clinical significance. Whereas a decrease of 20% in FEV₁ is considered a positive response to methacholine, a corresponding increase of 35%–40% in Raw is required. The measurement of Raw may be a more sensitive test and may identify changes in airflow earlier in the challenge.

Measurement of muscle strength can be an important parameter in the pediatric population. Children have a variety of congenital and acquired neuromuscular disorders and thoracic deformities that reduce the strength of the diaphragm and intercostal muscles. Examples of neuromuscular diseases include, but are not limited to, muscular dystrophies, spinal muscle atrophy, meningomyeloceles, Guillain-Barré syndrome, myasthenia gravis, trauma-related paralysis, and steroid-induced myopathies. Thoracic deformities include scoliosis, kyphoscoliosis, pectus excavatum or carinatum, and undefined congenital syndrome abnormalities. Measuring maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) may help (1) identify the degree of weakness and (2) follow the progression of the specific disorder. See Chapter 10 for a discussion of the technique for performing MIP and MEP. This test can be scary for children. The patient and parent should be gently warned that the measurement of the MIP might be uncomfortable and cause the child to cry. For this reason, this test should be performed after all other measurements are made. In children, it may be necessary to attach a mask and one-way valve to the pressure manometer and apply the mask snugly to the child’s face. It may also be necessary to hold the mask in place until the child becomes “air hungry” and feels a need to gasp for air. It is understandable why this test is so unpopular with children. A similar measurement of spontaneous inspiratory strength may be made while a child is undergoing mechanical ventilation, and this parameter is often referred to as the negative inspiratory force (NIF). Although the measurement of inspiratory strength may ultimately be involuntary, the expiratory strength measurement (MEP) is completely effort-dependent. The child cannot be forced to push as hard as possible unless he or she chooses to do so. For this reason, MEP results should be viewed cautiously. Although predicted values are available for MIP and MEP, a single measurement in time may be difficult to interpret. Rather, trending serial measurements often provides information that is more useful once the child is accustomed to the test.

Performance of Pulmonary Function Testing in Infants and Toddlers

Newborn babies, older infants, and young toddlers are not capable of following the directions needed to perform conscious PFTs. Placing a mask on an infant is usually not tolerated and results in a screaming baby. Even a child who permits a mask over his or her nose and mouth invariably changes his or her breathing pattern (i.e., volume and frequency of breathing). Only premature babies and young newborns will tolerate a mask while sleeping. In these specific and rare instances, it may be possible to assess passive tidal breathing mechanics. More sophisticated PFTs that measure lung volumes and forced flows require the infant to be in a quiet sleep, fully relaxed, and spontaneously breathing. To accomplish this state of sleep and cooperation, the child must be sedated.

Purpose of Pulmonary Function Tests for Infants and Toddlers

Infant and toddler PFTs provide important data regarding growth of the lungs, identification of airflow obstruction, progression of a disease state, and response to therapeutic interventions. Infant PFTs require a significant time commitment and competent and patient technologists. Sedation carries some risk, and testing should not be viewed as routine. Commercially available equipment typically uses the most technically advanced flow sensors and analyzers and may be expensive for a pulmonary laboratory to purchase. Before pursuing this type of testing, the laboratory should thoroughly evaluate its expectations, goals, and resources available to perform quality testing.

Sedation as an Important Consideration

Sedation of infants and toddlers is a common practice in pediatric hospitals because many procedures require a calm, motionless child. Procedures and protocols for sedation of children that follow The Joint Commission (TJC) guidelines are usually established by the hospital anesthesia department. It is essential that established procedures be closely observed for the protection of the child, the pulmonary laboratory, and the hospital. The sedating agent chosen, the personnel needed, and the required recovery time all depend on the extent of testing needed and patient history. A straightforward test in an uncomplicated infant can be safely performed by minimal personnel with the use of an oral sedating agent, such as chloral hydrate. At the other end of the spectrum may be an infant with an unstable airway, severe pulmonary compromise, or other organ complications. This scenario may warrant an anesthesiologist and sedation nurse, in addition to the technologist(s) performing the study.

Chloral hydrate is a relatively safe and easy sedating medication to administer, although several other IV agents are available with the current armamentarium of drugs. The advantages of chloral hydrate are that it is administered orally and may not require all the resources of a “sedation team.” However, sedation of infants has become a highly regulated and supervised service of the anesthesia department. Many hospitals now require that any sedation, including chloral hydrate, be given by sedation certified physicians, nurses, or nurse anesthetists. Chloral hydrate, arguably once classified as a ‘conscious sedating agent’ is now considered to produce unconscious sedation in the higher dosing range. A dose of 75–100 mg/kg of chloral hydrate is usually required to provide a sedation time long enough to complete the study. An important action of chloral hydrate is that it generally maintains the infant’s normal respiratory pattern, even with the dose suggested above. This is not the case for most IV sedation agents. Additionally, predicted reference sets for infant pulmonary function tests have almost exclusively been obtained using chloral hydrate as the sedation agent. If a child sleeps well during this type of sedation and for ample time, he or she arouses easily by the end of the study. An unfortunate disadvantage of chloral hydrate is that a large quantity of a very unpleasant medicine must be swallowed. Oral dose sedation may cause vomiting, crying, and upset stomachs. Nevertheless, chloral hydrate works very well in the majority of cases.

Intravenous (IV) narcotics such as pentobarbital or secobarbital need to administered and monitored by a sedation nurse or nurse anesthetist. The advantage of IV medications is that IV access is available if needed, and the medication can be titrated to the child’s need. Additional options include ketamine and propofol. Both of these drugs require a physician and possibly an anesthesiologist or specially trained hospitalist to administer. The rapid onset of action and quick recovery make these attractive sedating agents but also require close monitoring for apnea. Regardless of the agent chosen, safety is the primary concern. The child must be closely monitored throughout the entire procedure, including recovery, and written documentation of the sedation procedure placed in the patient’s record. A fully stocked crash cart should be nearby, and a resuscitation bag and mask should be on the patient’s bed. Loss of a patent airway is always possible with any sedating agent. It is also extremely important to remember that sleep induced with sedation is not natural sleep. Changes in respiratory pattern, depth of respiration, and breathing rate should be noted. Interpretation of any test of respiratory mechanics should be made with the level of sedation in mind.

When Children Are Too Old for Infant-Style Testing and Too Young for Standard Testing

Once toddlers reach ages 2½–3 years, changes are occurring that make it more difficult to perform the infant-style PFTs. The most obvious is that the child may “outgrow” the size of the plethysmograph. Chloral hydrate sedation may no longer be an option, therefore requiring general anesthesia. IV sedatives (narcotics, ketamine, propofol) carry more risks, and the expense increases with additional personnel required to deliver more complicated sedations. The risk to benefit ratio may tip in the direction that the benefits of the test no longer outweigh the risks and cost of sedation. Physiologic changes are also occurring as the infant grows through the toddler and preschool years. The child’s chest wall becomes more rigid, and the Hering-Breuer reflex disappears. This makes several of the techniques discussed in the following sections available only to infants and small toddlers but unavailable to children in the 3-year-old to 5-year-old range. Very young children also may be able to tolerate simple passive mechanics without the need for sedation. Earlier in the chapter, spirometric measurements in young children were discussed. The following sections discuss several other available techniques to measure pulmonary mechanics. Some may be performed on any patient from infancy through adulthood, and some are developed specifically for infants, toddlers, and preschool children.

Lung Volume Measurement

As with measurement of lung volumes in adults, the lung volume compartments in the infant can be measured by several techniques, including gas dilution and whole-body plethysmography. Until recently, body plethysmography in infants was performed almost exclusively by infant pulmonary research laboratories. Only a few manufacturers produce commercially available body boxes for infants (Figure 8-18). Whole-body plethysmography in an infant presents a unique set of challenges. The theory and technical aspects of measuring V_TG, previously discussed in Chapter 3, are essentially the same for adults and infants but with several additional caveats. The sedated infant is placed in a supine position with nose and mouth surrounded by a tight-fitting mask with a small dead space volume. Rapidly moving valves may make airway occlusions at end-inspiration or end-expiration for determination of V_TG and Raw. The infant does not pant. However, tidal breaths may be shallow; therefore, the pressure transducers and flow sensors must be critically precise and accurate. In addition, the infant body box is relatively small, and temperature changes can drastically alter these measurements. Therefore, the temperature in the box must be controlled and the air vented. Signal-to-noise ratios are particularly critical in an infant plethysmograph. Although the child is motionless, safety features must permit rapid access to the box and the baby. The breathing apparatus should be easily removable, in case the child is in distress or vomits. The advantage of plethysmography in infants is that it accurately measures V_TG, and thus FRC may be determined. Because the infant is not capable of performing a voluntary maximal inspiration or expiration, residual volume and TLC cannot be obtained in the traditional manner. However, if the infant pulmonary function system is capable of performing raised volumes and forced thoracic compressions, then a full set of fractional lung volumes can be estimated. A forced squeeze from TLC provides a volume close to a vital capacity measurement and can be used to calculate ERV, RV, TLC, FRC/TLC, and RV/TLC.

Optional methods of determining lung volumes are available for infants, as well as for toddlers and young children. These include gas equilibration techniques such as helium dilution, nitrogen washout, and SF₆ (sulfur hexafluoride) washin/washout techniques. Although technically easy to perform, gas equilibration techniques have several disadvantages applicable to both infants and young children. Infants will still require sedation; however, children ages 3–4 years may tolerate sitting in a chair with a mouthpiece/noseclips or facemask applied. Distractions to the awake child, such as television, reading by parent, or videos, are often necessary to obtain a quality test. Fussing and movement lead to leaks in the systems and may falsely elevate FRC values. When possible and practical, facemasks should be sealed with therapeutic putty. Dead space from the mask and valve switching apparatus should be taken into consideration. Adequate inspiratory flow with an appropriate inspired O₂ concentration should be available to the patient. Children with intrathoracic airflow obstruction may have poor ventilation distal to obstructed airways, causing an incomplete washout or equilibration and falsely low FRC values. The smaller the child, the smaller the radius of the airways, and superimposed obstruction from secretions or bronchospasm will further narrow the airway.

The effect of sedation in infants may compound the problem and inhibit the natural sigh mechanism, resulting in atelectasis, hypoventilation, or hypoxemia. Monitoring end-tidal CO₂ is helpful in this regard. Infants do have an incredible ability to adjust their FRC, depending on their clinical status. Babies may respond to hypoxia by dynamically elevating their FRC to create a PEEP-like effect (dynamic FRC). Grunting is a clinical sign that an infant may be hypoxic. In this situation, further sedation and supplemental O₂ tend to relax a child. It is possible to see consecutive FRC measurements decrease as the infant falls into a deeper sedation and static lung volume decreases to a resting FRC. Nevertheless, the measurement of FRC is an important parameter in pulmonary function testing. The preceding clinical scenarios should, however, be taken into account. The normal FRC range for an infant is between 15 and 25 mL/kg of weight and 2 and 3 mL/cm of length. FRC serves as a reference lung volume when analyzing flows or compliance. When a parameter is referenced to a lung volume such as FRC, it is termed specific (e.g., specific flow at FRC, specific compliance, or specific resistance).

Many studies have examined the passive tidal loops of infants and have attempted to differentiate normal tidal loops from loops associated with airflow obstruction. Fewer studies have concentrated on passive mechanics in preschool-aged children. Several parameters have been suggested to examine intrathoracic airflow obstruction during tidal breathing, such as t_TPEF/t_E (ratio of time to reach tidal peak flow to total expiratory time) and V_PTEF/V_E. Even recording simple measures such as tidal volume, respiratory rate, and minute ventilation may have some benefit. Passive loops are highly variable, however, and the degree of variability may differ for different age groups. They are especially subject to changes in upper airway tone, as may be seen with sedation, or with laryngeal or diaphragmatic braking. As mentioned previously, infants can adduct their vocal cords (grunt) during exhalation to create a physiologic PEEP. Likewise, they have the ability to modulate their diaphragms and intercostal muscles in an attempt to dynamically elevate their FRC and improve oxygenation. Therefore, the shape of tidal loops and the parameters used to describe the shape may change from minute to minute. To assure repeatability of measures, it is advisable to express these parameters as a mean of at least 10 consecutive breaths, or at least 30 seconds of tidal breathing. The coefficient of variation should also be reported. Baseline passive measurements may then be compared to like parameters following any desired intervention (bronchodilator, for example). As with standard pulmonary function testing, passive tidal loops are not maximal maneuvers. Therefore, efforts have concentrated on techniques to identify flow limitation and quantify forced flows measurements.

Passive Compliance, Resistance, and Time Constants

The chest wall of the infant is extremely compliant, unlike that of an adult. It does not contribute significantly to the compliance of the total respiratory system. Measuring pulmonary mechanics in the infant takes advantage of this very important difference. Noninvasive measures of respiratory system compliance, therefore, directly reflect the child’s lung compliance. In simplest terms, compliance is defined as change in volume divided by change in pressure (C=ΔV/ΔP) (see Chapter 2). In a quiet, relaxed baby (usually sedated), these parameters can be measured easily. The method is referred to as the passive occlusion technique. Rapid occlusion of the airway may occur once (single occlusion) at the end of a tidal breath, or with multiple occlusions at different lung volumes. Young infants will hold their breath when their airway is occluded. This phenomenon is known as the Hering-Breuer reflex and is present in children until approximately 1 year of age. During a single-breath occlusion and breath hold, alveolar pressure equalizes and can be measured by a pressure transducer at the airway opening (mouth). Once the occlusion valve opens, the child can passively exhale, and the exhaled volume can be measured by a flow sensor. The two components of respiratory system compliance (Crs), change in pressure and change in volume, are obtained. Respiratory system resistance (Rrs) can be easily calculated from the same maneuver. Resistance is defined as change in driving pressure divided by flow (R=ΔP/). With the maneuver described, the driving pressure is the plateau pressure (alveolar pressure) measured at the airway opening developed during the occlusion. Flow is the peak flow (discounting pneumotach artifact) measured from the passive exhalation. Refer to Figure 8-19. The graphs on the left side of the page represent passive exhalation after occlusion. The graphs on the right depict the increase in airway opening pressure to plateau (alveolar) pressure during occlusion. A normal passive exhalation after occlusion in an infant without any lung disease is shown in Figure 8-19, A.

The slope of the curve is linear as the baby exhales to a relaxed FRC. Children with airflow obstruction do not empty their lungs at a constant rate. The expiration may be forced with paradoxical movement of the diaphragm and belly. The accuracy of compliance and airway resistance measurements made under these conditions is poor. The exhaled curve may end abruptly with the child at an elevated FRC or may appear “scooped out” or curvilinear, as in Figure 8-19, B. The lungs do not empty homogeneously or uniformly and therefore have multiple time constants. One time constant represents the amount of time to expire approximately 2/3 of the tidal volume. Time constant (TRS or τ) is easily calculated as compliance times resistance (Trs=Crs×Rrs). Because respiratory system compliance is dependent on the lung volume at which it is measured, it may be important to “correct” the measured parameter by the infant’s FRC. As mentioned earlier, dividing the raw or actual compliance by the FRC yields specific compliance.

PF Tip 8-11

Diameter of the airway is an important determinant of flow. Inflammation or secretions in the airways of a young child can cause significant intrathoracic obstruction and profound clinical symptoms.

Single-breath passive measurement of compliance is not feasible in the toddler and older age groups. The chest wall develops more rigidity as the child ages and becomes an increasingly important factor in the overall measure of respiratory system compliance. Additionally, loss of the Hering-Breuer reflex makes equilibration of pressure from the alveolus to the mouth more difficult to achieve.

Compliance in infants can also be determined by other methods, including insertion of an esophageal catheter or by weighted spirometry. Although inserting an esophageal catheter into an infant is usually not difficult, it is invasive, and the exact placement of the catheter may affect measurements. In addition, the distortion of pleural pressure in children with airflow obstruction causes associated artifactual changes, yielding inaccurate compliance values. Under ideal circumstances, when accurate pleural pressures are measured, total respiratory system compliance can be subdivided into the chest wall and lung compliance components.

Children undergoing intubation and ventilation represent an additional challenge when assessing pulmonary mechanics. Several of the parameters discussed can also be obtained in babies on ventilators; however, several technical and mechanical problems must be considered. The endotracheal tube represents a resistor and can limit flow and alter pressure readings at the airway opening. Endotracheal tubes in infants are generally uncuffed, and leaks around the tubes are common. Secretions in the endotracheal tube and water condensation in the tubing easily clog pneumotachometers. Ventilators offer a variety of operational modes, such as pressure or volume control, intermittent mandatory ventilation (IMV) or synchronized IMV (SIMV), and pressure support. Depending on the mode chosen, auxiliary flow through the ventilator circuit will result in inaccurate flow measurements at the child’s airway. Children on ventilators are often sedated, and passive mechanics are dependent on the sleep state. For all of the reasons stated, pulmonary mechanics on children undergoing ventilation should be done only by experienced technologists who are familiar with the child and the ventilator. In addition, measurements made under artificial conditions (e.g., ventilator, PEEP) do not necessarily reflect the infant’s own lung mechanics when not ventilated.

Thoracoabdominal Motion Analysis

One of the main disadvantages of all of the measurements discussed in the preceding sections is that they involve the use of a mask or mouthpiece. Unfortunately, the presence of any foreign body in the airway is invasive and can alter breathing, especially passive tidal breathing. An advantage to this next technique is that it does not use any device at the mouth and can be truly considered noninvasive. Although the following techniques are not commonly performed in many clinical pediatric pulmonary function laboratories, they are central to the measurements made in a sleep laboratory. Observing the motion of the respiratory system can also provide valuable qualitative and quantitative assessment of pulmonary and chest wall mechanics and are worthy of discussion. Recall the basic mechanics of breathing and the coordination of the diaphragm and respiratory muscles during the passive breathing cycle. During inspiration, the diaphragm contracts and flattens, which causes the abdomen to rise. Simultaneously, the intercostal muscles contract, pulling the ribs upward and forward. During passive expiration, the diaphragm and intercostal muscles relax, and the abdomen and chest fall. This synchronous movement of the abdomen and rib cage can be easily monitored by placing an expandable strain gauge or band around both the abdomen and the chest wall (rib cage). These devices differ as to how they are made and the method by which they make measurements. Although the devices differ, the principle is similar. This technique is not generally limited by size or age; therefore, it can apply to infants, toddlers, older children, and even adults. The length of the strain gauges or bands is appropriate for the size of the patient. A popular example of this method is known as respiratory inductive plethysmography (RIP). The band is elasticized and has coiled wire sewn through the band in a sinusoidal pattern. A very low-voltage alternating current is passed through the coils. As each band expands (as with inspiration), the coils are stretched, which alters the cross-sectional area of the bands and changes the inductance of the coiled wire. A positive voltage signal (upward deflection) can be visualized on the monitoring device for both the abdominal component and rib cage component (Figure 8-20, A). The change in the cross-sectional area is proportional to the expansion of the band, and therefore the depth of the inspiratory maneuver. As passive exhalation occurs, the bands relax, and the voltage signal drops (downward deflection), with the pattern producing a sinusoidal respiratory tracing. The movements of the rib cage (RC) and the abdomen (AB) are monitored simultaneously. Both components independently contribute to lung volume, and the sum of the two signals determines tidal volume (V_T).

The tidal volume is maximized when the rib cage and abdomen move in synchrony, or are “in phase” with one another. The phase shift, Φ or phi, describes the asynchrony (or lack of synchrony) of the sinusoidal relationship between these two independent components. Both qualitative and quantitative information can be obtained from these tracings. A phase shift equal to 0 degrees denotes perfect synchrony. Figure 8-20, A, is representative of normal, quiet breathing. The movement of the rib cage and abdomen are in complete unison or synchrony. The child’s resultant tidal volume is the sum of the components of rib cage and abdominal movements. Figure 8-20, B, represents a child with paradoxical breathing. Note that the rib cage tracing is moving in the opposite direction of the abdomen. The abdominal and rib cage components are out of phase with one another. If observing this child, one would see the abdomen appear to sink while the chest was rising. This is the extreme end of asynchrony; however, there are endless variations in the movements of the rib cage and abdomen between complete synchrony and asynchrony. The phase shift will increase from 0 degrees to a maximum of 180 degrees with complete paradoxical breathing. Refer to Figure 8-19, C. Notice the difference in the shape of the tracing of the abdominal component. There are asynchronous movements of the rib cage and abdomen in this child.

Phase shift, Φ, can also be represented on an X-Y recorder. The figures produced, known as Lissajous figures or Konno-Mead loops, graphically plot abdominal movement on the x-axis, and rib cage movement on the y-axis. The arrows on the figures represent the direction of movement of the rib cage and abdomen during the respiratory cycle. Refer back to the tracing in Figure 8-20, A. Perfect synchrony would produce a loop that appears to be a straight line oriented as depicted (Φ = 0°). Figure 8-20, B, is representative of a Konno-Mead loop that demonstrates paradoxical breathing. The phase shift for this loop is 153 degrees, approaching the maximum of 180 degrees. The tracing in Figure 8-20, C, represents an interesting Konno-Mead loop, as one can imagine from the asynchronous movements of the rib cage and abdomen. Notice that the figure is vertical and forms a figure eight. Unfortunately, Konno-Mead loops often form figure-eight patterns, which cannot be assigned a quantitative phi value. There is also significant variation in the shape of Konno-Mead loops and phi values in patients with normal and abnormal breathing patterns. The limitations of quantifying these loops make it impractical for clinical testing in a pulmonary function laboratory. Nevertheless, there is a wealth of physiologic information in these measurements, and they are a valuable tool in illustrating the relationship of rib cage movement to abdominal movement.

An important advantage to respiratory inductance plethysmography is that it is possible to calibrate the movement of the bands in quiet breathing to a flow signal from a pneumotachometer placed over the patient’s mouth. This enables quantitative measurement of tidal volumes or minute ventilation over an extended period. The calibration period is very short, and the pneumotach is removed after the calibration period.

Impulse oscillometry (IOS) is also referred to as the forced oscillation technique (FOT). See Chapter 10 for a detailed description. A miniature loudspeaker is placed proximal to the device’s flow sensor and produces forced oscillations of flow with a range of frequencies into the airway. They are sensed as popping pulsations as the child breathes tidally. The pressure oscillations generated by the sound waves are of two types: (1) those in phase with airflow, termed resistance (Rrs), and (2) those out of phase with airflow, termed reactance (Xrs). The reactance component is complex and relates to delays of pressure change caused by elastic components of the respiratory system, as well as inertia. The interaction of resistance and reactance constitutes respiratory impedance (Zrs), or Zrs=Rrs+Xrs.

The advantage of IOS is that it requires passive tidal breathing only. The patient is asked to breathe on a mouthpiece for approximately 30–60 seconds; however, only 15–20 seconds of stable data are required. Although it is often stated that IOS is a relatively easy test to perform, even for a small child, this is not necessarily the case. The child must sit still with a mouthpiece in his or her mouth and noseclips in place. The patient’s cheeks and floor of the mouth are supported by the technician’s (or parent’s) hands to prevent oscillations of the mouth. Gagging, swallowing, or coughing will interfere with accurate measurements. The tongue cannot move around or obstruct the mouthpiece. This can be a challenge in a 2-year-old or 3-year-old child, even for technicians experienced working with children. Often, several visits to the laboratory for practice are necessary to obtain repeatability in these very young children. Three to five trials should be collected with a mean and coefficient of variation reported. IOS should be performed before any spirometric maneuvers because the forced expirations may produce airway hyperreactivity. Several minutes should also be given between trials to allow the child to relax.

Refer to Figure 8-21 for an example of the types of graphs that IOS measurements produce. Notice there is a graph for resistance (Rrs) measurements and reactance (Xrs) measurements. In both graphs, however, the x-axis is labeled as Hz representing the multifrequency band of forced oscillations being emitted by the loudspeaker. Note in Figure 8-20 that the resistance in this 12-year-old child’s lung is higher at lower frequencies and falls as the frequency of oscillations increases. This phenomenon is known as frequency dependence and is a characteristic pattern for a child this age. In an adult, however, this would not be normal but more characteristic of peripheral airflow obstruction, as seen in a smoker. Caution is needed, however, in viewing resistance measurements at very low frequencies (e.g., 5 Hz) in children because of other confounding factors, such as the effect of the cardiac impulse on these measurements. Reactance measurements are even less understood. Researchers are interested in the area of the curve that is formed by the reactance curve at 5 Hz and where it crosses “zero” reactance. The triangular region highlighted in the figure is known as AX. The larger the area of this region, the more abnormal the measurement, which may be related to airflow limitation. The point (Hz) that the reactance curve crosses the zero line is known as the resonant frequency of the lung (F_res). Because reactance as this point equals zero, only resistive forces are active and contributing to impedance. The resonant frequency (F_res) depicted in Figure 8-21 is approximately 18 Hz.

Reference values for impulse oscillometry have been collected in European children, and several ongoing studies in the United States are collecting data for additional predictive purposes. The clinical significance of IOS is yet unclear. Some researchers think that it will not provide any additional information, especially regarding peripheral airflow obstruction, for children who can be trained to do spirometry. However, there may be several scenarios in which IOS is beneficial. It may be helpful for any child who cannot perform spirometry or has a significant degree of central airway malacia. Forced flows, as with spirometry, cause compression and collapse in malacic airways, whereas IOS is a passive, tidal breathing maneuver. Patients may be able to serve as their own controls and perform this procedure serially at every clinic visit. Some laboratories have performed methacholine challenges with changes in IOS parameters as the endpoint. The sensitivity of this test may be greater than that of the FEV₁, especially with methacholine challenges, although its variability is somewhat greater.

Figure 8-22 shows the results from a 5-year-old child performing IOS. She was unable to perform spirometry during a clinic visit to the pediatric pulmonologist. The child was very symptomatic with cough, but her pediatrician had never heard any wheezing in her lungs. Note on the data chart that the resistance and reactance measurements prebronchodilator all appear normal as a percent of predicted. Let’s introduce a new term: coherence. The terms CO5 and CO10 represent the coherence of the measurements at 5 and 10 Hz. Coherence is a measure of how technically acceptable the measurements are, with a perfect coherence of 1.0. The closer the coherence is to 1.0, the more technically accurate the measurements. In very young children, however, a CO5 of 0.6 or higher is considered acceptable because of the child’s small chest size and the interference of cardiac impulse. Postbronchodilator, note the resistance measurements of R5, R10, and R20 all dropped in the range of 28%-33%. Because of the variability of this test, it is necessary to see a percent change this high to interpret the results as a significant response to the bronchodilator. The 32% increase in reactance at 5 Hz (X5) along with the 64% decrease in AX and 42% decrease in resonant frequency (F_res) all correlate with a decrease in resistance and a significant response to the bronchodilator. The first set of diagrams (see Figure 8-22) again illustrates how resistance and reactance are graphed at the various frequencies or Hertz. Observe the change in both graphs after the bronchodilator is administered. The postbronchodilator curve for reactance (red) drops vertically or downward indicating a drop in airway resistance. The postbronchodilator curve for reactance moves to the left and upward. The two diagrams at the bottom of Figure 8-22 are a second method of graphing IOS measurements. The axes are reversed with frequency (Hz) on the vertical axis, and both resistance and reactance graphed on the x axis. The line on the left side of the zero point is represented by reactance (X), and the line on the right side of zero is resistance (R). The graph is shaded between the two lines and has the appearance of a tree trunk. The higher the resistance and more negative the reactance, the wider the tree trunk. Notice postbronchodilator that the lines move closer to one another and to the zero point. The width of the tree trunk decreases as resistance falls and reactance increases (becomes less negative) postbronchodilator.

Flow is related to the volume of air in the chest during the forced exhalation. Stated simply, the larger the volume, the faster the flow. The advantage and reason for the repeatability of spirometry is that it is performed from TLC with every maneuver. As discussed earlier, with training sessions and reasonable patient effort, exhaled flows and volumes are repeatable in young children. However, if the child does not understand or cannot inhale to TLC, significant variability in flows and volumes will be observed. This is a common obstacle in the youngest of children. Traditional spirometric measurements (FVC, FEV₁, PEFR) may not be repeatable. These forced flows are not without merit, however. It is possible to relate these flows to a lung volume that the child can reproduce. This can be accomplished if the child is able to breathe quietly and relax for several breaths. More important, if he or she returns to a stable resting level with each exhalation, then this relaxed resting level represents the child’s FRC. It is not necessary to measure FRC; rather, it represents a reference point (static lung volume) to which flow can then be related. After several tidal breaths, the child is asked to take a slightly deeper breath in and blow out as hard and long as possible. It does not matter how deep the breath is, but the forced exhalation has to extend beyond the FRC point from the previous tidal breaths. Once the FRC point is identified, the flow corresponding to that point is then recorded. Because FRC is approximately 40% of TLC, flows at this relatively low lung volume correspond to flows such as FEF_25%–75%, FEF_50%, and FEF_75% seen in standard spirometry. These flow rates are only as repeatable as the resting level FRC. The technique may be of value in a cooperative child when assessing response to bronchodilator therapy or performing a methacholine challenge, for example. If the child’s tidal loops are highly variable, a stable FRC cannot be identified. The corresponding flow at FRC will not be reproducible in such instances. An additional confounding factor is the lack of predicted values for partial forced flows in the toddler age range. Because of the variability in testing, the trend has been to begin training in very young children (age 3 years) to do full FVC maneuvers from TLC or traditional spirometry.

From a historic perspective, the technique of performing partial forced F-V curves was the first attempt at obtaining forced flows in infants and dates back to the late 1970s and the work of several notable respiratory physiologists. This technique is increasingly being replaced by measuring maximal forced flows from a raised lung volume close to TLC. The principle of the partial forced flows is similar to that described previously, but the infant must be sedated for complete relaxation. The child’s chest is mechanically squeezed (or “hugged”) by an inflatable jacket that surrounds the chest or a bladder placed over the chest and upper abdominal region. The technique is referred to as rapid thoracoabdominal compression (RTC). The flows that are generated are maximal flows from within tidal range (partial forced expiratory flow). They are measured by a flow sensor (usually a pneumotachometer) attached to a mask placed on the infant’s face. The lung volume that can be identified and referenced is the FRC. This is the resting level that the child passively exhales to with each tidal breath. Once the FRC point is identified on the y-axis (volume), a line can be drawn upward to intersect the F-V loop. The flow at this point is referred to as the flow at FRC or maxFRC. Figure 8-23 identifies these points.

It is important that several tidal loops are observed before the hugging maneuver to ensure that the infant returns with each breath to a stable resting level, or FRC. The RTCs are done at progressively higher pressures until maximal flow at FRC from the child is attained. The pressures are generated from a large air reservoir connected to the hugging bag. The pressure within the hugging bag usually does not exceed 100 cmH₂O. A significantly lower pressure is transmitted across the chest wall to the lung tissue. With progressively higher hugging pressures, flow at FRC increases until flow limitation is reached. At this point, higher hugging pressures do not yield higher flows, and flow at FRC may in fact decrease. Reaching flow limitation while doing these maneuvers is an important concept and is somewhat controversial. Because infants grow (length and weight) at such different rates and because males differ from females, the question often arises of whether flow limitation is achieved with partial forced flows. This question is especially difficult in infants with normal lung function. The problem is complicated when trying to identify normal flows for any particular child. Several infant research centers have published a collaborative study combining data from healthy infants, but technique-related differences still exist. It is recommended that PFT laboratories performing infant studies test a group of infants without respiratory difficulties to confirm that the normal values obtained concur with published reference norms. Although this type of comparison is desirable, some hospital internal review boards may not permit the sedation of infants for the collection of normative data. Another method of standardizing flow is to compare maximal flow at FRC with the actual FRC measured. This parameter is known as the specific flow at FRC (SmaxFRC or maxFRC/FRC) As discussed earlier, FRC serves as a static measured reference volume. Because flow increases with higher volumes, a fixed relationship or constant value, independent of age or height, can be determined for flow at that volume. This constant value is termed specific flow, and normal specific flow should equal or exceed 1.20.

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V·maxFRCFRC

Figure 8-23 shows a partial forced expiratory flow-volume curve from an infant. A rapid thoracoabdominal compression was performed after a tidal inspiration. Parameters measured include a maxFRC of 440 mL/sec and an SmaxFRC of 1.63. The specific flow at FRC was obtained by dividing the child’s max FRC of 440 mL/sec by a previously measured FRC of 270 mL (from nitrogen washout).

Forced Flows from Raised Lung Volume

Success in standardization of spirometry has been dependent on the patient inspiring to total lung capacity (TLC) before performing a maximal expiration. This is the key to standardization in infants as well. Techniques have been developed to raise the volume of the infant’s lungs before a rapid thoracoabdominal compression (RVRTC). This may be accomplished by stacking inspirations or by a method known as the raised volume technique. For this maneuver, a bias flow of air is provided to the child during inspiration. The exhalation port is simultaneously occluded, raising the intrathoracic pressure and volume in the child’s lungs. A pressure of +30 cm H₂O is required to inflate the infant’s lung to near TLC. Once inflated, the child is then permitted to passively exhale. After several cycles of inflation and deflation, the child’s Pco₂ decreases, relaxing the child further. The final inflation is then followed by a forced compression from the inflatable jacket. The maneuver is repeated at an increasingly higher jacket pressure until expired volume and flows maximize at mid-lung volumes. The advantage of this method compared with partial forced flows is that the expired volume is nearly an FVC measurement. The traditional FEV₁ is not measured because the infant reaches residual volume before 1 second of exhalation occurs. However, the volume expired in 0.5 seconds or 0.75 seconds can be calculated and is analogous to the FEV₁ in standard spirometry. Figure 8-24 shows several F-V curves obtained after rapid thoracic compressions (from raised lung volume) superimposed. Progressively higher squeeze pressures do not yield higher flows or volumes, indicating that flow limitation has been met. In addition, a partial F-V curve (from a lower lung volume) is superimposed on the diagram. The F-V curve in this example is from a child with normal lung function. Compare this to the F-V loop pictured in Figure 8-25. This infant PFT report is representative of a 1-year-old child with cystic fibrosis and mild intrathoracic airflow obstruction.

Note that the report resembles that of a standard PFT for an older child, except that the FEV₁ is replaced with the FEV_0.5%. Although the FVC, FEV_0.5, and FEV_0.5%/FVC are within normal percent predicted range, the flows from lower lung volumes (i.e., FEF_75% and FEF_85%) are reduced. TLC and FRC are within percent predicted values. The RV and RV/TLC are mildly elevated, consistent with mild air trapping. Also note that the values for forced flows may be represented as a “Z” score. This is a statistical method comparing test results to normative data that is growing in popularity in the pediatric pulmonary function world and is now recommended by the ATS-ERS focus group for infants and preschool children. It is thought that Z scores more accurately reflect normative data in pediatrics because of varying growth rates for age and sex differences. Refer to Evolve site (http://evolve.elsevier.com/Mottram/Ruppel/) for a discussion of means, standard deviation, and confidence ranges. One standard deviation equals “1” Z score. Two (+/–) standard deviations from the mean, in a positive or negative direction, is generally considered to be within the limits of normal, or the 95% confidence range. This would be represented by a Z score of +/–2.0. Refer again to Figure 8-25, and notice that the parameters that have normal percent predicted values also have Z scores close to zero. The FEF_75% and FEF_85%, however, have reduced percent predicted values, and their Z scores are greater than –2.0, both indicative of values outside of the normal range.

PF Tip 8-13

Normative data may be viewed in a variety of statistical methods. “Z” scores are an alternative method of viewing standard deviation from the mean. A Z score of ±2.0 approximates two standard deviations from the mean, otherwise referred to as the 95% confidence range.

Variability in Reference Sets and Predicted Values for Pediatrics

Accurate interpretation of pediatric pulmonary function tests rely on accurate and consistent normative data. Pediatric “predicted” or reference sets are now quite numerous; however, many are outdated, being 30-50 years old. Others are flawed, either in how data was collected or the number of children participating in the study. Careful consideration is warranted when choosing an appropriate normative set. It is always best to select a reference set that most closely represents the population being tested. Questions to consider include the following:

The number of patients studied is critically important to the value of the reference set. Older reference sets, often named for an author or primary investigator (e.g., Polgar/Promadhat, Knudson, Hsu) are still used, especially in PFT labs that do not specialize in pediatric testing. Many of these older reference sets, developed between the 1960s and 1980s, were based on a relatively small number (several hundred) of children. Each child was tested once only, and, therefore, the sample is termed cross-sectional. Repeat studies were not performed on the same children as they aged and grew. By 2000, population studies on many thousands of school children for spirometry had been completed. In addition, some studies were longitudinal by design. Longitudinal means that repeated measurements were made on the same children as they grew. The power of the regression equations generated from these population studies is far greater than those of preceding decades. The ATS-ERS guidelines recommended that, in the United States, the reference set of NHANES III (National Health and Nutrition Evaluation Survey III) be used for patients ages 8-80 years. This spirometry norm set separates three ethnic groups, that is Caucasian, African-American, and Mexican American, with male and female datasets for each (hence 6 subsets). For laboratories specializing in pediatrics, the Wang-Dockery reference set is appropriate for patients ages 6-18. However, for those over 18 years old, a different norm set must be chosen, causing a “gap” or transition period between adolescence and adulthood. Additionally, normative data for children ages 3-6 years is available from several different authors. Since the ATS-ERS guidelines were released, even newer and more comprehensive spirometry reference sets have been published.

Further problems arise when trying to combine “older” predicted values for lung volumes and Dlco with newer, updated spirometric reference sets. Many commercial pulmonary function systems permit the user to “mix and match” regression equations and build their own reference set. Caution must be exercised when doing this. It is important that the laboratory personnel know whether their reference set is a standard (unaltered) set or whether it is compiled from available reference sets. It is also advisable that the reference sets be identified on the final pulmonary function reports. Pulmonary function data shared between hospitals and physicians should be referenced to the same norm set to avoid confusion.

Biologic variability for physiologic measurements, including pulmonary function, is critically dependent on the populations’ sex, age, race, and body dimensions. Many older reference sets did not always distinguish between Caucasian and non-Caucasian participants. Often a “constant” correction factor was applied for race corrections, such as African-Americans (see Chapter 13). In addition, the ages of children tested were often in the range of 8 to 18 years. There is tremendous growth during these years, but at different rates, depending on sex and pubertal changes. Attempting to apply a simple regression for each parameter tested (FVC, FEV₁, etc.), based on one independent variable (usually height), may be misleading. Although the distribution of pulmonary function values may follow the normal Gaussian (bell-shaped) curve (see Chapter 13), there is increasing disparity at both ends of the age range. Further error is introduced if these regression equations are extrapolated to ages younger than actually tested (e.g., down to 6 years). The Wang and Dockery reference set was the first widely accepted pediatric norm set that examined races separately and used both age and height as independent variables.

As recently as 2009, European, Canadian, and American respiratory physiologists, physicians, and technologists joined efforts to form an organization known as the Global Lung Initiative (GLI). The goal of this dedicated group of individuals is to establish a seamless “All Ages” reference set for numerous ethnic groups that spans ages 3-80 years and incorporates spirometry, plethysmography, and Dlco measurements. This is an ambitious undertaking, but the advantages are many. Initial publications from researchers active in this group have used sophisticated mathematical modeling to demonstrate the validity of combining data from the large NHANES III reference set with other European- and Canadian-generated norm sets that included younger children (starting at age 3). Therefore, it is now possible to use one reference set for spirometry from ages 3 to 80 for the Caucasian race. It is now the industry’s job to take this research and make it commercially available for software download to their respective pulmonary function systems. Other ethnic groups will be added as data sets are collected from around the world. Additionally, the work of the GLI will continue by adding lung volume determination and diffusion capacity normative data to this expanding global reference set.

Reporting of pulmonary function results is also undergoing transition. Traditionally, PFT parameters have included the patient’s actual value, a predicted value, and the percent of predicted. However, the use of “percent predicted” only to define abnormal parameters has been shown to lead to erroneous conclusions. The ATS-ERS suggests using the upper and lower limits of normal to compare test data to reference data, or the 95% confidence range. Percentiles and Z scores are becoming more popular as alternative methods of reporting data. As the number of “normal” children tested increases, the significance of the CV (coefficient of variation) between subjects has been increasingly appreciated. It is vital to understand the importance of using the CV to establish a lower limit of normal (LLN). “Abnormal” cannot be clearly defined until the limits of “normal” are identified. This is essential in relating pulmonary function data to respiratory disease in children (see Chapter 13).

Measurement technique can also significantly alter physiologic data. Lung volumes measured via gas dilution versus those measured by body plethysmography are one example. Dlco is measured by the collection of exhaled gas versus continuous analysis of exhaled gas. In pediatrics, even simple differences in performing tests may affect results. Examples include the use of noseclips versus no noseclips, or standing versus sitting while performing testing. Consistency is the key, although there may be no absolutes in the correct methodology for a particular test. The technologist should be aware of the methods used in his or her laboratory as compared with those of the reference sets used.