Airway Function Tests

The most basic test of pulmonary function is the measurement of vital capacity (VC). This test simply measures the largest volume of air that can be moved into or out of the lungs. In the mid-1800s, a surgeon named Hutchinson developed a simple water-sealed spirometer that allowed measurement of what he named “vital capacity or vital breath” as he noted its relationship to survival. Hutchinson popularized the concept of using VC to assess lung function and named several other lung compartments that are still used today. He observed that VC was related to the standing height of the patient. He also developed tables to estimate the expected VC for a healthy patient. The VC was usually graphed on chart paper, which allowed subdivisions of the VC to be identified (see Chapter 2).

Forced vital capacity (FVC) is an enhancement of the simple VC test. During the 1930s, Barach observed that patients with asthma or emphysema exhaled more slowly than healthy patients. He noted that airflow out of the lungs was important in detecting obstruction of the airways. Barach used a rotating chart drum (kymograph) to display VC changes as a spirogram. He even evaluated the effects of bronchodilator medications, using the FVC traced as a spirogram.

In 1947, Tiffeneau described measuring the volume expired in the first second of a maximal exhalation in proportion to the maximal volume that could be inspired (FEV₁/IVC (inspiratory vital capacity)) as an index of airflow obstruction (i.e., the Tiffeneau index). Around 1950, Gaensler began using a microswitch in conjunction with a water-sealed spirometer to time FVC. He observed that healthy patients consistently exhaled approximately 80% of their FVC in 1 second, and almost all of the FVC in 3 seconds. He used the forced expired volume in the first second (FEV₁) to assess airway obstruction. In 1955, Leuallen and Fowler demonstrated a graphic method used to assess airflow. They measured airflow between the 25% and 75% points on a forced expiratory spirogram. This measure was described as the maximal midexpiratory flow rate (MMFR). This and similar measurements have been used to describe airflow from both healthy and airflow-obstructed patients. To standardize terminology, the MMFR is now referred to as the forced expiratory flow 25%-75% (FEF_25%-75%).

In addition to displaying FVC as a volume-time spirogram, it can also be represented by plotting airflow against volume. In the late 1950s, Hyatt and others began using the flow-volume display to assess airway function. The tracing was termed the maximal expiratory flow volume (MEFV) curve. By combining the forced expiration with an inspiratory maneuver, a closed loop can be displayed. This figure is called the flow-volume loop (see Chapter 2).

Peak expiratory flow (PEF) is measured using either a flow-sensing spirometer or a peak flow meter. In the 1960s, Wright and McKerrow popularized the use of peak flow to monitor asthmatic patients. Peak flow can be readily assessed from the flow-volume loop as well. Recently, portable peak flow meters that allow monitoring at home, as well as in the hospital or clinic, have been developed.

The FVC, FEV₁, and other flows, along with flow-volume loops, are all used to measure response to bronchodilator medications (see Chapter 2). Tests are performed before and after inhalation of a bronchodilator, and the percentage of change is calculated. The same tests may be used to assess airway response after a challenge to the airways. These tests are referred to as bronchial challenge or bronchial provocation tests. The challenge may be in the form of a nonspecific inhaled agent (e.g., methacholine) or a physical agent (e.g., exercise). In either case, airflow is assessed before and after the challenge. The percent change (normally a decrease) after the challenge is calculated (see Chapter 9).

Maximal voluntary ventilation (MVV) was described as early as 1941. Cournand and Richards originally called it the maximal breathing capacity (MBC). In the MVV test, the patient breathes rapidly and deeply for 12 to 15 seconds. The volume of air exchanged is expressed in liters per minute. The MVV gives an estimate of the peak ventilation available to meet physiologic demands.

Measurement of respiratory muscle strength is accomplished by assessing maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). This is done using either a pressure transducer or a simple aneroid manometer. MIP and MEP are important adjuncts to spirometry for monitoring respiratory muscle function in a variety of pulmonary and nonpulmonary diseases. Black and Hyatt developed the first device to assess these parameters and termed the device a “bugle” because the expiratory maneuver was similar to blowing into a bugle.

Airway resistance (Raw) measurements date back to the development of the body plethysmograph in the early 1950s. Comroe, DuBois, and others perfected a technique that provided estimates of alveolar pressure. The patient sits in an airtight box called a plethysmograph (see Chapter 11). The plethysmographic method allows the calculation of the pressure drop across the airways related to flow at the mouth (see Chapter 4). This technique originally required complicated monitoring and recording devices. Microprocessors have simplified the measurement of the required signals so that plethysmography is now widely used. The same equipment can also be used to rapidly and accurately measure thoracic gas volume (V_TG).

Lung compliance is measured by passing a small balloon into the esophagus to measure pleural pressure. Intrapleural pressure can then be related to volume changes to estimate the distensibility of the lung (see Chapter 4). Other less invasive techniques are available but not widely used.

Lung Volume and Ventilation Tests

Measurement of lung volume dates back to the early 1800 s, well before Hutchinson’s development of spirometry. Various techniques have been used to estimate the volume of gas remaining in the lung after a complete exhalation. Davy used a hydrogen dilution technique to estimate residual air. This technique was later improved by Meneely and Kaltreider, using helium (He) instead of hydrogen. Around the same time, Darling, Cournand, and Richards began using oxygen breathing to wash nitrogen (N₂) out of the lungs. The collection and analysis of the volume of exhaled N₂ allowed the functional residual capacity (FRC) to be estimated. Using simple spirometry combined with FRC determinations allows total lung capacity (TLC) and residual volume (RV) to be calculated. The other commonly used method for measuring lung volumes uses the body plethysmograph to measure V_TG or FRC. Estimation of lung volumes from chest radiographs is possible but is not widely used. Lung volume can also be estimated from computerized tomography (CT) scans, but such measurements are seldom performed just for the purpose of measuring lung volume.

Closed-circuit (He dilution) and open-circuit (N₂ washout) techniques are both widely used to measure FRC. Besides determining lung volumes, each technique provides some limited information about the distribution of ventilation within the lungs. The pattern of N₂ washout can be displayed graphically. The time required for He to equilibrate during rebreathing provides a similar index of the evenness of ventilation. In the early 1950s and 1960s, Fowler developed a single-breath N₂-washout technique. This method plotted N₂ concentration in expired gas after a single breath of 100% oxygen. The single-breath N₂ washout also provides limited information about gas distribution in the lungs. It also allows estimates of the lung volume at which airway closure occurs when the patient exhales completely (see Chapter 4).

Measurement of resting ventilation requires only a simple gas-metering device and a means of collecting expired air. Portable computerized spirometers allow minute ventilation, tidal volume (V_T), and breathing rate to be readily measured in almost any setting. Determination of alveolar ventilation or dead space (wasted ventilation) requires measurement of arterial partial pressure of carbon dioxide (Paco₂) in addition to total ventilation. Alternately, the partial pressure of carbon dioxide (Pco₂) can be estimated from expired CO₂. The availability of blood gas analyzers and exhaled CO₂ analyzers makes these measurements routine.

Diffusing Capacity Tests

The basis for the modern single-breath diffusing capacity (Dlco) test was described by August and Marie Krogh in 1911. They showed that small but measurable differences existed between inspired and expired gas containing carbon monoxide (CO). This change could be related to the uptake of gas across the lung. Although they used the method to test a series of patients, they did not use the single-breath technique for clinical purposes. Around 1950, Forrester and others revisited the method. They developed it as a tool to measure the gas exchange capacity of the lung. About the same time, Filley and others were promoting other techniques, using CO to measure Dlco. Most of these techniques allowed patients to breathe normally, rather than hold their breath. These methods are called steady-state techniques. Each method has certain limitations. However, the single-breath technique is the most widely used and standardized in the United States and Europe (see Chapter 5).

Blood Gases and Gas Exchange Tests

Measurement of gases (O₂ and CO₂) in the blood began with volumetric methods used since the early 1900s. In 1957, Sanz introduced the glass electrode to measure pH of fluids potentiometrically. In 1958, Severinghaus added an outer jacket containing a bicarbonate buffer to the glass electrode. The electrode-buffer was separated from the blood being analyzed by a membrane that was permeable to CO₂. This allowed the pressure of CO₂ in the blood to be measured as a pH change in the electrode. In 1956, Leland Clark covered a platinum electrode with a polypropylene membrane. When a voltage was applied to the electrode, O₂ was reduced at the platinum cathode in proportion to its partial pressure. These three electrodes (pH, Pco₂, and partial pressure of oxygen [Po₂]) were the basic measurement device in blood gas analyzers for many years. Miniature electrodes gradually replaced the traditional electrodes. Today, blood gas analyzers use a variety of electrochemical techniques (see Blood Gas Analyzers, Chapter 11) to measure not only pH, Pco₂, and Po₂, but also the various fractions of Hb, such as O₂Hb and COHb. Similar methods to measure electrolytes (K⁺⁺, Na⁺⁺, Cl^–) are also included in many blood gas analyzer systems. Transcutaneous electrodes, using techniques similar to the classical blood gas electrodes, are available for the measurement of O₂ and CO₂ tensions (tcpO₂ and tcpCO₂).

Blood oximetry was developed during World War II to monitor the effects of exposure to high-altitude flight. During the 1960s, spectrophotometric analyzers that could measure the total hemoglobin (Hb), along with oxyhemoglobin (O₂Hb) and carboxyhemoglobin (COHb) levels, were perfected. Blood oximetry testing is commonly combined with blood gas analysis so that both can be accomplished with a single instrument. Pulse oximetry was developed in the 1970s as a result of efforts to monitor cardiac rate by using a light beam to sense pulsatile blood flow. It was quickly discovered that the pulse could be sensed, and changes in light absorption could also be used to estimate arterial oxygen saturation. Modern microprocessors have allowed pulse oximeters that are very small and portable, with some devices capable of measuring COHb in addition to O₂ saturation.

Capnography, or monitoring of exhaled carbon dioxide, was developed in conjunction with the infrared gas analyzer (see Chapter 11). This sensitive and rapidly responding analyzer allows exhaled CO₂ to be monitored continuously. Most critical care units, operating rooms, and emergency departments use some combination of blood gas analysis, pulse oximetry, and capnography for patient monitoring. Blood gas analysis is an integral part of routine pulmonary function testing because it is the definitive test of the basic functions of the lung.

Exhaled nitric oxide (eNO), although not a measure of blood gas or gas exchange, has emerged as an important parameter for assessing inflammatory changes in the lungs. Asthma, chronic obstructive pulmonary disease (COPD), and other pathologies characterized by inflammation of the airways or lung tissue, can be monitored by analyzing trace amounts of NO in exhaled gas.

Cardiopulmonary Exercise Tests

Exercise tests commonly use a treadmill or cycle ergometer to impose an external workload that stresses the cardiovascular and musculoskeletal systems. The simplest types of exercise tests are those in which the patient performs work and only noninvasive measurements are made. Such measurements include heart rate and rhythm monitoring using an electrocardiogram (ECG). Other simple, noninvasive measurements are blood pressure and respiratory rate monitoring. Analysis of exhaled gas is noninvasive, but the patient does have to breathe through a mouthpiece or mask. Ventilation and tidal volume (V_T) can be estimated by collecting the exhaled air. Analysis of expired gases permits oxygen consumption and CO₂ production to be measured. When invasive measures (blood gas analysis, arterial catheters, pulmonary artery catheters) are used, the entire range of physiologic variables that affect exercise can be monitored. Computerized exhaled gas analysis allows sophisticated measurements to be made rapidly while the patient continues to exercise (breath-by-breath gas analysis). Simple exercise tests, such as the 6-Minute Walk Test (6MWT), have become popular because the distance walked correlates well with more sophisticated exercise measurements and with clinical outcomes in a variety of diseases.

Metabolic Measurements

Measurement of energy expenditure and caloric requirements dates to the early 1900s. Basal metabolic rate (BMR) was measured by allowing subjects to rebreathe from a volume spirometer containing added oxygen. Plotting the rate at which oxygen was consumed derived an estimate of energy expenditure. Similar techniques are used today, except that oxygen consumption and carbon dioxide production are monitored using exhaled gas analysis. Resting energy expenditure (REE) has replaced BMR as the primary variable related to metabolic needs. Although BMR was used to detect disorders that affected metabolism, REE is used to manage critically ill patients whose caloric requirements may be difficult to estimate.

Spirometry

Spirometry is the pulmonary function test performed most often because it is indicated in many situations (see Box 1-2). Spirometry is often performed as a screening procedure. It may be the first test to indicate the presence of pulmonary disease. Spirometry is recommended as the “gold standard” for diagnosis of obstructive lung disease by the National Lung Health Education Program (NLHEP), the National Heart Lung and Blood Institute (NHLBI), the World Health Organization (WHO), and numerous other organizations concerned with the diagnosis of lung diseases. However, spirometry alone may not be sufficient to completely define the extent of disease, response to therapy, preoperative risk, or level of impairment. Spirometry must be performed correctly because of the serious impact its results can have on the patient’s life. It is one of the few tests that yields a false-positive response if performed poorly because low values are the result. These low results may lead to further testing, inappropriate diagnosis, treatment, and increased costs for the patient and the health care delivery system.

Lung Volumes

Lung volume determination usually includes the VC and its subdivisions, along with the FRC. From these two basic measurements, TLC and other lung volumes can be calculated (see Chapter 4). Lung volumes are almost always measured in conjunction with spirometry, although the indications for them are distinct (see Box 1-3). The most common reason for measuring lung volumes is to identify restrictive lung disease. A reduced VC (or FVC) measured with spirometry may suggest restriction, particularly if airflow is normal. Measurement of FRC and determination of TLC are necessary to confirm restriction because a low FVC can be caused by either restriction or obstruction. If TLC is reduced below the 5th percentile of the predicted value, restriction is present. The severity of the restrictive process is determined by the extent of reduction of the TLC. TLC and its components can be determined by several methods. For patients with obstructive lung diseases (COPD, asthma), lung volumes measured by body plethysmography may be indicated (see Chapter 4) because multiple-breath or single-breath dilution techniques may underestimate TLC. In obstructive lung disease, lung volumes are necessary to determine whether air trapping or hyperinflation is present. The degree of hyperinflation, measured by indices such as the IC/TLC ratio, correlates with increased mortality in patients who have COPD.

Diffusing Capacity

Diffusing capacity is measured by having the patient inhale a low concentration of CO and a tracer gas to determine gas exchange within the lungs (Dlco). Several methods of evaluating the uptake of CO from the lungs are available, but the single-breath technique (Dlcosb) is most commonly used. This method is also called the breath-hold technique because CO transfer is measured during 10 seconds of breath holding. Dlco is usually measured in conjunction with spirometry and lung volumes. Although many pulmonary and cardiovascular diseases reduce Dlco (see Box 1-4), it may be abnormally increased in some cases (see Chapter 5). Dlco testing is commonly used to monitor diseases caused by dust (pneumoconioses). These are conditions in which lung tissue is infiltrated by substances such as silica or asbestos that disrupt the normal structure of the gas exchange units. Dlco testing is also used to evaluate pulmonary involvement in systemic diseases such as rheumatoid arthritis. Dlco measurements are often included in the evaluation of patients with obstructive lung disease, particularly in emphysema. Dlco tests may be indicated to monitor changes in lung function (i.e., gas exchange) induced by drugs used to treat cardiac arrhythmias, as well as changes caused by chemotherapy and radiation therapy for lung cancer.

Blood Gases

Blood gas analysis is often done in conjunction with pulmonary function studies. Blood is drawn from a peripheral artery without being exposed to air (i.e., anaerobically). The radial artery is often used for a single arterial puncture or indwelling catheter. Blood gas analysis includes the measurement of pH, along with Pco₂ and Po₂. Other calculated parameters (HCO3−, base excess, etc.) are often included in the standard blood gas report. The same specimen may be used for blood oximetry to measure total Hb, oxyhemoglobin saturation (O₂Hb), carboxyhemoglobin (COHb), and methemoglobin (MetHb).

Blood gas analysis is the ideal measure of pulmonary function because it assesses the two primary functions of the lung (oxygenation and CO₂ removal). Evaluation of many pulmonary disorders may include blood gas analysis. Specific indications for blood gas analysis are listed in Box 1-5. Blood gas analysis is most commonly used to determine the need for supplemental oxygen and to manage patients who require ventilatory support. Some pulmonary function measurements require blood gas analysis as an integral part of the test (i.e., shunt or dead space studies). Blood gas analysis is invasive; noninvasive measurements of oxygenation or gas exchange are often preferred since they are safer or less costly. Many noninvasive techniques (e.g., pulse oximetry, transcutaneous monitoring, and capnography) rely on a blood gas analysis to verify their validity (see Chapter 6).

Exercise Tests

Physical exercise stresses the heart, lungs, and the pulmonary and peripheral circulatory systems. Exercise testing allows simultaneous evaluation of the cellular, cardiovascular, and ventilatory systems. Cardiopulmonary exercise tests can be used to determine the level of fitness or extent of dysfunction. Appropriately designed tests can determine the role of cardiac or pulmonary involvement. COPD, interstitial lung disease, pulmonary vascular disease, and exercise-induced bronchospasm are respiratory disorders that often require exercise evaluation. Understanding the physiologic basis for the patient’s inability to exercise is an important aspect in prescribing effective therapy (i.e., cardiac or pulmonary rehabilitation). Exercise testing may also be required for the determination of disability. Box 1-6 lists specific indications for exercise tests.

Equipment used to measure oxygen consumption and CO₂ production during exercise can also measure resting metabolic rates. This allows estimates of caloric needs in patients who are critically ill. Indications for performing studies of REE are detailed in Chapter 9.

Obstructive Airway Diseases

An obstructive airway disease is one in which airflow into or out of the lungs is reduced. This simple definition includes a variety of pathologic conditions. Some of these conditions are closely related regarding how they cause airway obstruction. For example, mucus hypersecretion is a component of chronic bronchitis, asthma, and cystic fibrosis (CF), although their causes are distinct.

Chronic Obstructive Pulmonary Disease

The term COPD is often used to describe long-standing airway obstruction caused by emphysema, chronic bronchitis, or asthma. These three conditions may be present alone or in combination (Figure 1-2). Bronchiectasis is sometimes considered a component of COPD. COPD is characterized by dyspnea at rest or with exertion, often accompanied by a productive cough. Delineation of the type of obstruction depends on the history, physical examination, and pulmonary function studies. Unfortunately, the term COPD is used to describe the clinical findings of dyspnea or cough without attention to the actual cause. This may lead to inappropriate therapy. Other similar terms include chronic obstructive lung disease (COLD) and chronic airway obstruction (CAO).

Emphysema

Emphysema means “air trapping” and is defined morphologically. The air spaces distal to the terminal bronchioles are abnormally increased in size. The walls of the alveoli undergo destructive changes. This destruction results in the overinflation of lung units. If the process mainly involves the respiratory bronchioles, the emphysema is termed centrilobular. If the alveoli are also involved, the term panlobular emphysema is used to describe the pattern. These distinctions require the examination of lung tissue either by biopsy or at postmortem. Because this is often impractical, emphysema is suspected when there is airway obstruction with air trapping. Physical assessment, chest x-ray or CT studies, and pulmonary function studies are the primary diagnostic tools. Spirometry (FVC, FEV₁, and FEV₁/FVC) is used to determine the presence and extent of obstruction. Lung volumes (TLC, RV, IC, and RV/TLC) define the pattern of air trapping or hyperinflation caused by emphysema. Dlco and blood gas analyses are useful in tracking the degree of gas exchange abnormality in emphysema. Exercise testing may be necessary if the emphysema patient is suspected of oxygen desaturation with exertion or to plan pulmonary rehabilitation.

Emphysema is caused primarily by cigarette smoking. Repeated inflammation of the respiratory bronchioles results in tissue destruction. As the disease advances, more and more alveolar walls are destroyed. Loss of elastic tissue results in airway collapse, air trapping, and hyperinflation. Some emphysema is caused by the absence of a protective enzyme, α₁-antitrypsin. The lack of this enzyme is caused by a genetic defect. The enzyme α₁-antitrypsin inhibits proteases in the blood from attacking healthy tissue. Deficiency of α₁-antitrypsin causes the gradual destruction of alveolar walls, resulting in panlobular emphysema. Chronic exposure to environmental pollutants can also contribute to the development of emphysema. The natural aging of the lung also causes some changes that resemble the disease entity. The natural decline of elastic recoil in the lung reduces maximal airflow and increases lung volume as people age. Surgical removal of lung tissue sometimes causes the remaining lung to overinflate.

The main symptom of emphysema is breathlessness, either at rest or with exertion. Hypoxemia may contribute to this dyspnea, particularly in advanced emphysema. However, the destruction of alveolar walls also causes loss of the capillary bed. Ventilation-perfusion matching may be relatively well preserved in patients with emphysema. As a result, oxygen levels may be only slightly decreased, particularly at rest. This type of patient is sometimes called the “pink puffer.” As the disease advances, the loss of alveolar surface causes a decreased ability to oxygenate mixed venous blood. Dlco is reduced. The patient becomes increasingly breathless, particularly with exertion. Muscle wasting seems to be common in emphysema, and patients are often below their ideal body weight. As noted, symptoms of chronic bronchitis and asthma may be present as well.

The chest x-ray film of a patient with emphysema shows flattened diaphragms and increased air spaces. The lung fields appear hyperlucent (dark) with little vascularity. The heart appears to be hanging from the great vessels (Figure 1-3). Computerized tomography (CT) scans, especially spiral CT scans, show a three-dimensional picture of enlarged air spaces and loss of supporting tissue. CT scans also delineate whether the emphysematous changes are localized or spread throughout the lungs.

The physical appearance of the chest confirms what is shown radiographically. The chest wall is immobile with the shoulders elevated. The diameter of the chest is increased in the anterior-posterior aspect (so-called barrel chest). There is little diaphragmatic excursion during inspiration. Intercostal retractions may be prominent. Accessory muscles (neck and shoulders) are used to lift the chest wall. Breath sounds are distant or absent. Patients may need to support the arms and shoulders to catch their breath. Breathing is often done through pursed lips in an attempt to alleviate the sensation of dyspnea (Figure 1-4).

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