Chapter 8
Pediatric Pulmonary Function Testing
1. State how the combined American Thoracic Society-European Respiratory Society (ATS-ERS) task force guidelines relate to pulmonary function testing and, specifically, spirometry in children.
2. Suggest techniques for approaching young children, gaining their confidence, and ensuring maximal effort.
3. Identify common technique and/or effort-related errors during FVC maneuvers and the resultant effect on reliability of testing.
4. Discuss the potential importance of examining both the expiratory and inspiratory loops during spirometry.
5. State the most common pharmaceutical agent used for bronchoprovocation testing and the steps involved in performing this challenge in children.
6. State limitations and considerations for equipment as they relate to testing in children for the measurement of lung volumes and diffusion capacity.
7. State the physiologic and testing effects that sedation may produce in infants.
8. Identify various passive techniques to evaluate pulmonary function in infants, toddlers, and preschool children.
9. State the components of lung volume measurements that can be obtained in well-sedated infants and the equipment necessary to make those measurements.
10. State considerations that are important when establishing a normative or reference set for pediatric patients.
1. According to ATS-ERS recommendations, state the difference in a usable versus an acceptable FVC maneuver in a young child.
2. Discuss a scenario when the FEV0.5 may be a valuable parameter evaluating bronchodilator response during spirometry in very young children.
3. Explain the limitations of the FEF25%-75% in a very young child performing spirometry.
4. Compare the appearance of the flow-volume loop in variable intrathoracic versus extrathoracic obstruction and fixed patterns of obstruction, and provide examples of pediatric disorders associated with each.
5. State the difference between direct and indirect methods of bronchoprovocation, and give examples of each.
6. Discuss problems associated with the delivery of pharmaceutical agents in pediatric patients, and state advantages and disadvantages of each.
7. Discuss how exercise stress testing protocols can be of benefit in evaluating both airway hyperresponsiveness and pediatric cardiovascular problems.
8. Explain the purpose of the eucapnic voluntary hyperventilation (EVH) challenge.
9. Discuss the added benefit of performing lung volume measurements in pediatric patients to differentiate obstructive and restrictive components of disease.
10. Identify potential problems in obtaining diffusion capacity measurements in children and relate the effect of potential errors to resultant data.
11. Discuss the role of passive mechanics in evaluating infants and toddlers.
12. Compare and contrast an adult plethysmograph to an infant plethysmograph.
13. State the purpose of performing the raised volume technique when measuring lung volumes in infants.
14. Define the components that comprise respiratory impedance (Z), and state how airway reactivity can be evaluated using these measurements.
15. Explain why the use of the 95% confidence interval and/or Z score are superior methods of evaluating pediatric patient data rather than using standard percent predicted reference values.
Spirometry
Spirometry, by far, is the most common type of pulmonary function test performed in the pediatric population. Understanding how to teach children to perform this test well will help ensure that the physician will use and interpret this tool to treat his or her patient. The basics of spirometry apply to both pediatrics and adults (see Chapter 2). The same principles for testing and equipment are used. The indications for testing are similar, although disease processes in pediatrics often differ. The anatomy and physiology of the respiratory system change significantly from the infant to the young child and to the older adolescent. As for adults, the primary goals of spirometry are the following:
1. To identify the presence of an obstructive defect or a restrictive pattern of flow
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.
1. Identify premature termination of the maneuver by comparing the flow at termination to that of peak flow. If cessation of flow occurs at greater than 10% of peak flow, the vital capacity and forced expiratory flows should not be reported. FEV0.5 or FEV1 may still be reportable. Because vital capacity may be completely exhaled by 1 second, examining exhaled volumes closer to peak flow (e.g., FEV0.5) may provide more accurate information regarding intrathoracic airflow obstruction.
2. As with current recommendations, the highest FVC and FEV1 (or FEV0.5) should be reported and the selection of “best” curve, based on the sum of FVC and FEV0.5.
3. Additionally, a close look at extrapolated volume is recommended. Because children have smaller lung volume, extrapolated volume during spirometry may exceed the 5% (or 50 mL) criteria currently stated in ATS-ERS guidelines. In very young children, an expiratory curve with an extrapolated volume as high as 80 mL or 12.5% (whichever is greater) may be acceptable and should be reexamined.
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.
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 FEV0.5 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 FEV0.5 or FEV0.75 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.
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.”
Length of Exhalation for a Child During an FVC Maneuver
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 FEF25%–75% in Children
Historically, FEF25%–75% has been used to evaluate flow from the “small airways”. More precisely, the FEF25%–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 FEF25%–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, FEF25%–75% may be artificially elevated because of reduced vital capacity. If it is reported, the FEF25%–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 FEF25%–75% of 65%, is certainly suggestive of a reversal of intrathoracic airflow obstruction. An FEF25%–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 FEF25%–75% is more reliable in older children and teenagers. As previously noted, FEF25%–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 FEF25%–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 FEF25%, FEF50%, FEF75%, FEF85%, FIF50%, and the FEF50%/FIF50% 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 FEF25%–75%, are less repeatable than the FEV1 and FVC and do not have any reference values. The FEF50%/FIF50% 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 FEF50% 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 FEF50%/FIF50% 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 FEF50%/FIF50% 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 FEF50%/FIF50% 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 FEF50%/FIF50% ratios and the shape of the loops represented by those ratios. Although FEF50%/FIF50% 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 (FEF50%/FIF50%<1.0); however, many are often abnormal with an FEF50%/FIF50% 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.
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.
Airway Malacia
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 FEF25%–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.
Bronchoprovocation challenges
Traditionally, methacholine chloride has been considered to be the “gold standard” for bronchoprovocation testing. If a conclusive answer is not obtained, the physician may then choose to rechallenge the patient with a stimulus that has a different mode of action. For example, a common complaint in adolescents is shortness of breath and chest pain with exercise. The specific question posed by the physician might be: Does this child have exercise-induced asthma? If symptoms present only while the child is exercising, the logical provocation study to perform first would be an exercise stress test. Most pediatric laboratories will admit, however, that only a small percentage of children exercised actually exhibit exercise-induced asthma. This type of provocation study is very specific but not very sensitive. Recall that exercise is an indirect method of provoking bronchospasm and may be influenced by the type of exercise performed (running vs. swimming vs. gymnastics, for example). The environment may contribute to the provocation. Is the child running outdoors during allergy season? Is the child swimming in a chlorinated indoor pool? Do the temperature of the air and humidity affect the response, such as cold ice rinks versus hot, humid football fields. It is not unusual for a child with intermittent or mild persistent asthma to test negative during an exercise challenge in a controlled laboratory environment. The next step might then be a methacholine challenge, a direct stimulus, which is less specific than exercise, but much more sensitive for eliciting bronchospasm. The child with a negative exercise challenge may well have a positive methacholine challenge, although likely positive in the mild or borderline range. Should the physician skip the exercise challenge and move directly to a methacholine challenge? This decision is up to the physician and is dependent on the question he or she is asking. There is neither a right or wrong answer nor a right or wrong challenge to perform. Recently, alternative provocation agents, such as EVH and mannitol, have been investigated. Specific protocols for each type of challenge should be established by the pulmonary laboratory and approved by the medical director. Whichever provocation agent is used, it is very important that the child be capable of performing serial spirometry at specific time intervals in a repeatable manner. Challenges can be time intensive. The child should be continually monitored for signs of fatigue or waning effort. Because children can become fatigued or easily distracted with prolonged testing, abbreviated protocols have been published. In some pediatric laboratories, challenges on very young children who cannot perform spirometry are obtained. Techniques for monitoring airway resistance and reactance, such as impulse oscillometry (IOS), have been successfully used in 3-year-old children and older who cannot perform spirometry adequately. See Figure 8-15 and the IOS discussion to follow later in the chapter. Laboratories that do not have this type of equipment can also perform challenges in the ages 3-5 range by closely monitoring breath sounds, oxygen saturation, respiratory rate, and symptoms. Physicians must be immediately available when challenging very young children. Challenges in pediatric patients are not recommended in any facility unfamiliar or inexperienced with children. A fully stocked emergency cart is also essential. Patient safety and well-being are always the number-one priority.
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.