Specialized Test Regimens

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Chapter 10

Specialized Test Regimens

Diagnosis or evaluation of specific pulmonary disorders requires that appropriate tests be performed. Specialized test regimens, such as those described in the chapter, are often used to further define a specific condition. They may also involve a simple modification of the standard tests performed under special conditions. The clinical question asked regarding a patient might be whether he or she qualifies for disability or whether it is safe to undergo surgery. Spirometry, lung volumes, diffusing capacity (Dlco), or blood gas analysis may be required to answer these questions.

Specialized tests covered in this chapter include respiratory muscle strength, exhaled nitric oxide, impulse oscillometry, and metabolic measurements. Respiratory muscle strength measurements, such as maximal inspiratory pressure (MIP or PImax) and maximal expiratory pressure (MEP or PEmax), might assist in characterizing neuromuscular diseases. Measurement of exhaled nitric oxide (eNO) provides a sensitive and highly repeatable method for evaluating airway inflammation. It can be used to detect eosinophilic inflammation, which is common in asthma, and to evaluate response to treatments such as inhaled corticosteroids. Impulse oscillometry provides a unique way to evaluate airway function. It provides a measurement of airway resistance in spontaneously breathing subjects and can be used in conjunction with bronchodilator evaluation or bronchial challenge. Metabolic measurements are widely used to assess caloric needs and nutritional support in a variety of patients. The methods used are similar to those used in gas exchange measurements during exercise. Specialized calculations allow a precise description of the nutritional status of the patient.

Respiratory muscle strength testing

Description

Forced maneuvers during spirometry require the patient to give a maximal effort, as well as to have normal muscle function. Respiratory muscle strength is also critical in supporting adequate ventilation and airway protection (e.g., cough). Muscle function is best assessed by the measurement of maximal inspiratory and expiratory pressures. Maximal inspiratory pressure (MIP, also reported as PImax) is the lowest pressure developed during a forceful sustained inspiration against an occluded airway. It is usually measured at maximal expiration (near RV). It is recorded as a negative number in either cm H2O or mm Hg. Maximal expiratory pressure (MEP, also reported as PEmax) is the highest pressure that can be developed during a forceful sustained expiratory effort against an occluded airway. It is usually measured at maximal inspiration (near TLC) and reported as a positive number in either cm H2O or mm Hg. MIP and MEP are sometimes measured at the resting end-expiratory level (FRC); if so, this volume must be noted on the report.

Technique

The patient is connected to a valve, shutter apparatus, or the PF testing system with a mouthpiece (a flanged mouthpiece may facilitate testing in subjects with excessive muscle weakness) and noseclip in place. The mouthpiece can be placed in the mouth or the lips pressed against the mouthpiece opening, as would be done with a bugle, thus the early term for the procedure “bugles” (Figure 10-1). Regardless of the mouth-device interfaced used, there should be a tight fit so that the patient can exert maximal pressure. The airway is occluded by blocking a port in the valve or by closing a shutter. In either system, a small, fixed leak is introduced between the occlusion and the patient’s mouth. The leak may be a small opening such as a large-bore needle or created by the PFT system in their hardware. The leak eliminates pressures generated by the cheek muscles during the MEP maneuver by allowing a small amount of gas to escape the oral cavity. Likewise, the leak prevents glottic closure during the MIP maneuver. The incorporation of this small leak does not significantly change lung volume or the pressure measurement.

Pressure may be measured using a manometer, an aneroid-type gauge, or a pressure transducer. The pressure-monitoring device should be linear over its range. It should be able to record pressures from −200 to approximately +200 cm H2O. Pressure transducers are typically used in PF testing systems with the output incorporated into a data acquisition screen and algorithms used to calculate the sustained pressure. If a manometer or aneroid gauge is used, the technologist directly observes the pressure and records it. This type of monitoring is common in the hospital where measuring vital capacity and respiratory pressures are used to assess ventilatory adequacy (Figure 10-2). The technologist should record the plateau pressure that the patient can maintain for 1–2 seconds.

For the MIP test, the patient is instructed to expire maximally. Monitoring expiratory flow or having the patient signal helps determine when maximal expiration has been achieved. Then the airway is occluded as described. The patient inspires maximally and maintains the inspiration for 1–2 seconds. The first portion of each maneuver is disregarded because it may include transient pressure changes that occur initially (Figure 10-3). The most negative value from at least three efforts that vary less than 20% is recorded.

MEP is recorded similarly. The patient inhales as much as possible, then exhales maximally against the occluded airway for 1–2 seconds. Longer efforts should be avoided as cardiac output can be reduced by the high thoracic pressures (e.g., Valsalva maneuvers) that are sometimes developed. MEP is usually larger than MIP in healthy patients. The pressure-monitoring device should be able to withstand the higher pressure without damage. The most positive value from at least three efforts that vary less than 20% is recorded. As for MIP, initial pressure transients during the MEP are disregarded. Both MIP and MEP require patient cooperation and effort. Low values may reflect a lack of understanding or insufficient effort. (Box 10-1)

Significance and Pathophysiology

MIP primarily measures inspiratory muscle strength. Healthy adults can generate inspiratory pressures greater than -50 cm H2O in women, and -75 cm H2O in men. Decreased MIP is seen in patients with neuromuscular disease or diseases involving the diaphragm, intercostals, or accessory muscles. MIP may also be decreased in patients with hyperinflation, as in emphysema where the diaphragm is flattened by the increased volume of trapped gas in the lungs. The intercostals and accessory muscles may also be compromised by injury to or diseases of the chest wall. Patients with chest wall or spinal deformities (e.g., kyphoscoliosis) may also have reduced inspiratory pressures. MIP is sometimes used to assess patient response to strength training of respiratory muscles. MIP is often used in the assessment of respiratory muscle function in patients who need ventilatory support.

MEP measures the pressure generated during maximal expiration. It depends on the function of the abdominal muscles and accessory muscles of respiration and the elastic recoil of the lungs and thorax. Healthy adults can generate MEP values greater than 80 cm H2O in women and greater than 100 cm H2O in men. MEP may be decreased in neuromuscular disorders, particularly those resulting in generalized muscle weakness. Another common disorder that results in the reduction of MEP is high cervical spine fracture. Damage to nerves controlling abdominal and accessory muscles of expiration can dramatically reduce MEP. However, MIP may be preserved in these patients.

Reduced MEP often accompanies increased RV, as seen in emphysema. A low MEP is associated with the inability to cough effectively. Inability to generate an adequate cough may complicate chronic bronchitis, cystic fibrosis, or other diseases that result in excessive mucus secretion.

Accurate measurement of MIP and MEP depends largely on patient effort. The technologist should carefully instruct the patient on how to do the maneuver. Low values may result if the patient fails to inhale or exhale completely before the airway is occluded. Some patients may show increased MIP or MEP with repeated efforts (training effect). Others may demonstrate decreasing pressures with repeated efforts (muscle fatigue). The best efforts should be reproducible within 20% or 10 cm H2O, whichever is greater. Widely varying pressures for either MIP or MEP should be assessed carefully before interpretation.

Sniff nasal inspiratory pressure (SNIP) has been proposed as an alternative or complementary test to MIP. The measurement is performed by occluding a nostril during a maximal sniff maneuver performed through the contralateral nostril from functional residual capacity or residual volume. In the contralateral nostril, a nasal olive with a central catheter is connected to a pressure transducer. Instrumentation can be sophisticated with computer incentive screens to simple hand-held devices (Figure 10-4). Measurement limitations include nasal obstruction or collapse during the maneuver. Several papers have compared the test method to sniff pressures measured using an esophageal catheter with good correlation in subjects with neuromuscular disease. A sniff nasal-inspiratory force less than 40 cm H2O has been shown to predict mortality in patients with amyotrophic lateral sclerosis (sensitivity 97%, specificity 79%).

Exhaled nitric oxide

Description

Measurement of exhaled nitric oxide (eNO) provides a simple and noninvasive method for assessing airway inflammation. It is particularly useful in diagnosing and monitoring lung diseases characterized by eosinophilic inflammation, such as asthma. The fraction of eNO in an exhaled breath (FeNO) can be measured with a sensitive chemiluminescent or electrochemical analyzer (see Chapter 13). FeNO is usually reported in parts per billion (ppb). Because the measurement is dependent on flow during exhalation, the flow (in liters per second) may be subscripted to the term (e.g., FeNO0.05 represents the FeNO measured at a flow of 0.05 L/sec). NO is also sometimes measured from the nasal cavities, including the sinuses, as a marker of nasal inflammation.

Techniques

FeNO can be measured either on-line or off-line. The methods for each type of collection differ slightly in adults and children. On-line measurements sample exhaled gas continuously at the mouth; off-line measurements collect exhaled air in a sampling device for later analysis.

On-Line FeNO in Adults

Before measuring FeNO, patients should refrain from smoking, eating, or drinking (except water) for at least 1 hour before testing. Measurement of eNO should be performed before other tests such as spirometry, methacholine challenge, or exercise testing. Any recent infections, as well as the current medication regimen, should be recorded at the time of testing.

Because NO is produced in the airways (and in the alveoli), it is important that the patient inhale NO-free gas. This is accomplished by having the subject inspire through an NO scrubber. The ambient NO level should be recorded as well. The patient should be instructed to exhale to RV, then insert the mouthpiece and inspire over a 2- to 3-second interval to TLC. A noseclip is not used; this lessens the possibility that the much higher nasal NO will accumulate and contaminate the lower airway sample.

Without breath holding, the patient then exhales slowly and evenly while exhaled gas is sampled continuously. To prevent contamination of the exhalate with nasal NO, the patient exhales against an expiratory resistance while receiving feedback to maintain a positive pressure at the mouth. This positive pressure (usually about +5 cm H2O) causes the velum in the posterior pharynx to close, preventing nasal NO from entering the air stream. The fractional concentration of NO in the exhaled gas varies inversely with the flow. To standardize on-line measurements, an exhaled flow of 0.05 L/sec (i.e., 50 mL/sec) ±10% is recommended. This flow allows dead space gas to be exhaled and a plateau in NO to be observed in about 10 seconds in adults (Figure 10-5). The correct flow can be maintained by using a pressure-sensitive flow controller and providing visual feedback to the subject. Current commercially available instrumentation (Chapter 11 uses visual incentives to assure standardized flow/pressure and will mark a maneuver as not meeting acceptability criteria if flow/pressure is not maintained).

FeNO is measured from the plateau of the single-breath exhalation profile (see Figure 10-5). The plateau phase may slope up or down slightly. The exhalation should last long enough to establish this plateau (>6 seconds for adults and children older than 12 years, >4 seconds for children ages 12 years and younger). Two points should be chosen on the plateau that represent a 3-second interval (about 0.15 L) in which the FeNO varies less than 10%. The FeNO is the mean concentration over this 3-second interval. For FeNO values of 10 ppb or less, variability of 1 ppb NO may be used in place of the 10% criteria. A minimum of 30 seconds should elapse between repeated measurements with the subject breathing air (off the NO sampling circuit).

At least two acceptable measurements of FeNO that agree within 10% of each other should be averaged for the final report value. Three acceptable measurements should be averaged if FeNO is measured at multiple flow rates.

Off-Line FeNO in Adults

Off-line measurements of NO allow the gas to be collected away from the analyzer, making more efficient use of the analyzer. Potential problems with off-line measurements include contamination with gas from the upper airway, errors caused by storing the sample, and lack of feedback to the patient regarding technique during gas collection.

The patient inhales through an NO scrubber or from a reservoir with NO-free gas. After inhaling to TLC, the patient exhales his or her VC into an appropriate sampling device without breath holding. Expiratory resistance (+5 cm H2O) is added just as is done for on-line measurements to minimize contamination by nasal NO. Flow is usually controlled by monitoring the back-pressure in the system; flows of 0.35 L/sec ±10% are recommended to allow the VC to be collected in a reasonable interval. The sample is collected in a balloon made of polyester (Mylar) or a similar material that is impermeable to NO and large enough to accommodate the adult’s VC. Off-line samples should be analyzed within 12 hours. Exhaled nitric oxide can be performed in children able to perform the single breath maneuver and is described in Chapter 8.

Nasal Nitric Oxide

Although various methods of sampling nasal NO have been described, the recommended method uses transnasal airflow in series. In this technique, air is aspirated into one naris and out the opposite side, where NO is sampled. The subject exhales against a resistance of approximately 10 cm H2O, while air is aspirated at a constant flow rate. As for measurement of FeNO from the lower airways, exhalation against resistance closes the velum in the posterior pharynx to prevent contamination of the sample. Airflow of 0.25–3.0 L/min is used for nasal NO measurements. Flows in this range allow a plateau in the NO signal within 20–30 seconds in most adults. The flow used for NO analysis, along with the transnasal flow, should be recorded (Figure 10-6).

Significance and Pathophysiology

Normal values for FeNO depend largely on the flow at which gas is sampled during analysis. At a standardized flow of 0.05 L/sec (50 mL/sec), healthy adults show FeNO values of 10–30 ppb, whereas in children the values are slightly lower (5–15 ppb). FeNO actually increases with increasing age in children. The upper limit of normal in adults isapproximately 35 ppb (25 ppb in children) when FeNO is measured using standardized methods and flows (50 mL/sec). FeNO appears to be related to airway size; thus, it tends to be slightly higher in males than in females.

Exhaled NO appears to correlate most closely with eosinophilic inflammation in the airways. Because this type of inflammation is characteristic of bronchial asthma, measurement of FeNO can be viewed as a surrogate for measuring eosinophils in induced sputum samples, bronchoalveolar lavage, or bronchial biopsy in patients who have asthma. These correlations persist when inflammation is treated, making FeNO an excellent tool for monitoring therapy.

Some studies have indicated a correlation between FeNO and bronchial hyperresponsiveness, as measured by the PC20 from methacholine or histamine challenge. However, many studies show little or no correlation between eNO and hyperresponsiveness. These conflicting findings may result because eosinophilic inflammation is characteristic mainly in atopic individuals. Responsiveness to methacholine appears to correlate with FEV1, whereas increased FeNO correlates with other markers of inflammation.

Although pulmonary function tests (including bronchial challenge) are considered a standard method for diagnosing and assessing asthma, there appears to be little correlation between these measures and airway inflammation. In general, most tests of lung function do not correlate with levels of eNO. Changes in NO during periods of exacerbation tend to occur more rapidly than changes in pulmonary function indices (e.g., FEV1). Spirometry and bronchial challenge tests can reduce the level of eNO, so that if both procedures are to be performed on a patient, FeNO should be measured first.

FeNO is reduced by corticosteroids’ effects on airway inflammation. Numerous well-designed studies have demonstrated that steroid therapy, including inhaled corticosteroids, can be monitored and evaluated using FeNO as a marker of inflammation. FeNO does not appear to be reduced by either short-acting or long-acting β-agonists, either alone or in combination with inhaled corticosteroids. FeNO may also be reduced in some patients treated with leukotriene modifiers.

Because of the correlation between FeNO and airway inflammation and the known anti-inflammatory effects of inhaled corticosteroids, eNO has several potential uses in asthma diagnosis and management. FeNO can be used as a simple diagnostic screening tool to differentiate asthma from other conditions (such as chronic cough). Exhaled NO compares favorably with bronchial challenge tests (methacholine, exercise) in terms of sensitivity and specificity in detecting asthma. Patients who have an elevated NO level typically respond to corticosteroid therapy. FeNO is therefore a good tool to evaluate response to anti-inflammatory therapy. Failure of FeNO to decrease with steroid treatment suggests that the patient may be unresponsive to standard therapy or that the patient may be noncompliant with the recommended treatment. Some studies have suggested that the dosage of inhaled corticosteroids can be optimized with FeNO to guide therapy.

Patients who have COPD often show normal levels of FeNO. However, some studies have shown increased NO in patients with COPD. These differences may be related to the presence or absence of eosinophilic inflammation in COPD patients. Many COPD patients respond poorly to inhaled corticosteroids; measurement of FeNO may provide an indicator as to whether eosinophilic inflammation is present and whether the patient may respond to steroid therapy. FeNO may also be increased in pulmonary diseases that are characterized by inflammatory changes such as chronic bronchitis, chronic cough, sarcoidosis, pneumonia, alveolitis, bronchiolitis obliterans syndrome (BOS), and bronchiectasis.

FeNO is typically decreased in smokers, even though smoking causes airway inflammation. The physiologic explanation for the reduction in NO levels in smokers is unclear. Cigarette smoking may decrease the production of NO by epithelial cells lining the airways. Exhaled NO levels are also usually lower than normal in patients who have cystic fibrosis (CF). As in the case of smokers, it is not clear whether the reduced levels in CF are a result of decreased production or increased metabolism of NO in the lungs.

Nasal NO levels are typically much higher than eNO. Values from 100 ppb up to more than 1000 ppb have been reported. Most of the nasal NO appears to be produced by the epithelial cells in the paranasal sinuses. Patients with allergic rhinitis show elevated levels of NO that appear to be responsive to nasal corticosteroids. One disease in which nasal NO measurements may be particularly useful is primary ciliary dyskinesia (PCD). Patients who have PCD have much lower levels of nasal NO (Interpretive Strategies Box 10-1).

Forced oscillation technique

One way to measure the mechanical properties of the respiratory system is to apply an oscillating flow of gas to the system and measure the resulting pressure response. This method is commonly called the forced oscillation technique (FOT). When the forced oscillations are applied at the mouth and the resulting pressure oscillations are measured at the mouth, the output is known as input impedance. When the oscillations are applied around the body in a closed body plethysmograph, and resulting pressures are measured at the mouth, the output is known as transfer impedance.

Impedance of the respiratory system (Zrs) represents the net force that must be overcome to move gas in and out of the respiratory system (upper airway, lungs, and chest wall). Applying oscillatory flow is appropriate because that is how we breathe, in a regular in-and-out fashion. Imagine the lungs modeled as a stiff pipe (the airways) with a balloon on the end (the alveoli). The pressure required to push gas down the pipe and into the balloon must overcome three basic forces: the resistance (R) of the pipe, the elastance (E), or stiffness, of the balloon, and the inertia (I) of the gas itself (Figure 10-7). Stated mathematically, the pressure necessary to move gas down the pipe and into the balloon is as follows:

< ?xml:namespace prefix = "mml" />Pressure=R(VY)+E(V)+I(VYY)

image

where:

V= volume

VY= flow

VYY= acceleration

This is known as the equation of motion for the system. Impedance depends not only on these three variables, R, E and I, but also on the frequency of the oscillation. At low frequencies, I is negligible, R is less important, and E is dominant. At higher frequencies, R and I become more important. Frequency is also important because the lung tissues have viscoelastic mechanical properties that change with the frequency of motion.

To measure Z, one could apply flow at various single frequencies and measure the resulting pressures generated at each frequency. Alternatively, one could apply a flow signal consisting of many different frequencies at once and then use a mathematical function known as the fast Fourier transform (FFT) to break down the output into unique sine waves, each of its own frequency. Despite involving complex mathematics with real and imaginary numbers, computers have made this method quick and accurate, and it has become the technique most commonly used (Figure 10-8, A).

Traditional devices use loudspeakers pulsating at different, predetermined frequencies to generate the broadband flow signals (Figure 10-9, A). One commercially available device (Figure 10-9, B) generates the broadband flow signal by an electronically controlled deflection of an internal speaker to create an impulse of flow containing many frequencies, although the frequencies analyzed range from 5–35 Hz. For all devices, the flow signal can be applied during quiet spontaneous breathing and thus requires little subject effort or cooperation. Once performed, the output is recorded in two parts: the part of Z that is in phase with the flow signal, which represents the real part of the Z and is due to flow resistive properties of the respiratory system, R, and the part that is out of phase with the flow signal, called the reactance (X), which represents the imaginary part of Z, and encompasses E and I. These real and imaginary parts are plotted against frequency, as shown in Figure 10-8, B.

In most clinical applications, the FOT is used to measure R. Because the technique is noninvasive, fast, and easy, it can be applied in many situations where other methods of measuring R are difficult or cumbersome. These situations include use in pediatric patients or others who cannot perform the panting maneuvers to measure Raw by the body box technique. However, as with Raw measured in the body box, the maneuver does require some degree of subject cooperation, including cheek holding to reduce the effect of facial noise in the signal (Figure 10-10). The R derived from the FOT has been shown to be sensitive to bronchoconstriction and bronchodilatation and thus can be used to assess airway hyperresponsiveness. An important disadvantage of the technique is that, unless an esophageal balloon is placed to measure transpulmonary pressure, the R measured is not of the lungs alone but of the entire respiratory system, thus including the upper airway and chest wall. The upper airway, in particular, can markedly influence the measurement because of its high compliance and the propensity for glottic interference.

Preoperative pulmonary function testing

Preoperative pulmonary function testing is one of several means available to clinicians to evaluate surgical candidates at risk for developing respiratory complications. Preoperative testing, in conjunction with history and physical examination, ECG, and chest x-ray examination, may be indicated for any of the following reasons:

The need for preoperative pulmonary function testing is controversial. Some studies show increased odds of postoperative complications related to low FEV1, hypoxemia, low Dlco, hypercarbia, or low imageo2. Other studies show little relationship between pulmonary function and postoperative risk, especially for general surgical and cardiovascular operations. Many investigations, both prospective and retrospective, have identified that the risk of postoperative pulmonary complications is highest in thoracic procedures, followed by upper and lower abdominal procedures. Postoperative pulmonary complications may occur in as many as 25%–50% of major surgical procedures. Patients who have pulmonary disease are at higher risk in proportion to the degree of their pulmonary impairment. Specific tests, such as spirometry or Dlco, seem to be most useful in candidates for lung resection or esophagectomy. Preoperative testing is also indicated for patients undergoing surgical procedures designed to alter lung function, such as lung volume reduction surgery or correction of scoliosis.

Preoperative pulmonary function testing may be indicated in patients who have the following:

Preoperative testing may also be indicated in patients who are obese (more than 30% above ideal body weight), advanced in age (usually more than 70 years of age), have a history of respiratory infections, or who are markedly debilitated or malnourished.

In surgical candidates, the primary purpose of pulmonary function testing is to reveal preexisting pulmonary impairment. VC may decrease more than 50% from the preoperative value in thoracic or upper abdominal procedures. This places individuals with compromised function at risk of having atelectasis and pneumonia. Postoperative decreases in FRC and increases in closing volume (CV) may lead to ventilation-perfusion image/imageabnormalities and hypoxemia. Abnormal ventilatory function related to the central control of respiration or to the ventilatory muscles may also play a role in postoperative complications.

Certain tests of pulmonary function appear to be better predictors of postoperative complications. These tests should be used both for risk evaluation and to assist in planning the perioperative care of the individual.

Perfusion and image/imageScans

Lung scans are particularly useful in estimating the remaining lung function in patients who are likely to require removal of all or part of a lung. Split-function scans are performed. These allow partitioning of lungs into right and left halves, or into multiple lung regions. Although ventilation-perfusion scans give the best estimate of overall function, simple perfusion scans yield similar information. Lung scan data, in the form of regional function percentages, are used in combination with simple spirometric indices to calculate the patient’s postoperative capacity. An example follows:

Postoperative FEV1=Preoperative FEV1× %Perfusion to unaffected regions

image

This calculation is termed the predicted postoperative FEV1, or ppo-FEV1.

Patients whose postoperative FEV1 is less than 800 mL are typically not considered surgical candidates. Resection of any lung parenchyma resulting in an FEV1 less than 800 mL would leave the patient more severely impaired. One exception to this general guideline occurs in patients referred for lung volume reduction surgery (LVRS). These candidates are usually end-stage COPD patients, often with FEV1 values less than 800 mL and significant air trapping. Removal of poorly ventilated lung tissue often results in an improvement in spirometry, with significant increases in both FVC and FEV1.

Pulmonary Artery Occlusion Pressure

In some candidates for pneumonectomy, the development of postoperative pulmonary hypertension may be a limiting factor. To estimate the effect of redirecting the entire right ventricular output to the remaining lung, a catheter is inserted into the pulmonary artery of the affected lung and blood flow occluded by means of a balloon. The resulting pulmonary artery pressure increase in the remaining lung is then measured. A pressure increasing to less than 35 mm Hg is usually considered consistent with acceptable postoperative pressures. The effect of redirected blood flow on oxygenation may also be a consideration. This can also be examined during occlusion to estimate postoperative Pao2.

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