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Because of miniaturization and advances in computer technology, microprocessor devices have become portable and automated with fewer moving parts. Pulmonary function testing is a valuable tool for evaluating the respiratory system, representing an important adjunct to the patient history, various lung imaging studies, and invasive testing such as bronchoscopy and open-lung biopsy.
Pulmonary function tests (PFTs) is a generic term used to indicate a battery of studies or maneuvers that may be performed using standardized equipment to measure lung function. Before a spirogram can be meaningfully interpreted, one needs to inspect the graphic data (the volume-time curve and the flow-volume loop) to ascertain whether the study meets certain well-defined acceptability and reproducibility standards.
Basic concepts of normal pulmonary physiology that are involved in pulmonary function testing include mechanics (airflows and lung volumes), the ventilation-perfusion interrelationship, diffusion and gas exchange, and respiratory muscle or bellows strength.
Forced inspiration is generally not flow limited and is a function of overall muscular effort. The mechanism for the maximal expiratory airflow limitation seen in normal airways results from the gradual drop in pressure inside the conducting airways from the alveoli to the mouth, creating a transmural pressure gradient with the pleural pressure. Pulmonary function studies use a variety of maneuvers to measure and record the properties of four lung components. Spirometry requires a voluntary maneuver in which a seated patient inhales maximally from tidal respiration to total lung capacity and then rapidly exhales to the fullest extent until no further volume is exhaled at residual volume3 (Figs.
Today, most clinical pulmonary function testing laboratories use a microprocessor-driven pneumotachometer to measure air flow directly and then to mathematically derive volume. A spirogram is a graphic representation of bulk air movement depicted as a volume-time tracing or as a flow-volume tracing. Adapted from American Thoracic Society: Single-breath carbon monoxide diffusing capacity (transfer factor). The FEV1 is the most widely used parameter to measure the mechanical properties of the lungs. FVC is a measure of lung volume and is usually reduced in diseases that cause the lungs to be smaller.
The volume-time tracing and flow-volume loop ascertain the technical adequacy of a maneuver and therefore the quality of the data (see Box 3) as well as identifying the anatomic location of airflow obstruction. The shape of the flow-volume loop can indicate the location of airflow limitation, such as the large upper airways or smaller distal airways (Fig.
A variety of parameters selectively reflect small airways.6 These include measures of flow from a spirogram, such as the maximal midexpiratory flow (MMEF) or forced expiratory flow at 25% to 75% vital capacity (FEF25-75). The closing volume from a single-breath N2 test and frequency-dependent dynamic lung compliance also can be used to detect small airways disease.
To define whether nonspecific airway hyperreactivity is a mechanism for atypical chest symptoms of unclear origin, inhalational challenge tests are often used in the pulmonary function laboratory.9-11 Methacholine and histamine are the agents most often used with this procedure, although other agents may also be useful. When the baseline spirogram is relatively normal, inhalational challenge may be performed by aerosolizing progressive concentrations of methacholine by a dosimeter. Bronchial hyperreactivity, as assessed by this inhalational challenge procedure, is very sensitive for the presence of active or current asthma.
Because spirometry is an expiratory maneuver, it measures exhaled volume or vital capacity but does not measure residual volume, functional residual capacity (resting lung volume), or total lung capacity.
Gas dilution techniques use either closed-circuit helium dilution or open-circuit nitrogen washout. Body plethysmography is an alterative method of measuring lung volume that takes advantage of the principle of Boyle's law, which states that the volume of gas at a constant temperature varies inversely with the pressure applied to it. After the FRC is measured by any of these techniques, measurement of lung subdivisions (inspiratory capacity, expiratory reserve volume, vital capacity) ensues, ideally while the patient is still on the mouthpiece. Understanding gas diffusion through the lungs requires recognizing the basics of the gas exchange interface and of the various forces at work by which oxygen and carbon dioxide move by molecular diffusion.
Because all lung volume is not exchanged, most gas exchange occurs as a function of diffusion independent of bulk flow. The clinical test diffusing capacity of the lung most commonly uses carbon monoxide as the tracer gas for measurement because of its high affinity for binding to the hemoglobin molecule. Diffusing capacity of the lung for carbon monoxide (DLCO) is the measure of carbon monoxide transfer. Overall, DLCO is expressed as the uptake of carbon monoxide in milliliters of gas at standard temperature and pressure, dry, per minute, and per millimeter of mercury driving pressure of carbon monoxide. The most widely used and standardized technique is the single-breath breath-holding technique.
Hemoglobin concentration is a very important measurement in interpreting reductions in DLCO. Diseases such as interstitial pulmonary fibrosis or any interstitial lung disease can make the DLCO abnormal long before spirometry or volume abnormalities are present.
On the other end of the spectrum, alveolar hemorrhage or congested capillary beds can actually increase the DLCO.
The measurement of exhaled nitric oxide as a reflection of airway inflammation is gaining rapid acceptance as a pulmonary function test.
These guidelines include the selection of equipment, important technical considerations for variability, and standardization between laboratories for the maneuver.
Race plays an important role in determining normal lung function; it has been recognized that persons of different races for any given height and age have proportionately different lung volumes. Over time, the NHANES III reference equations will likely become the standard in most pulmonary function testing laboratories around the country.7 The methodologies and the sample size are most robust for this dataset, as well as being representative of the American population. As previously discussed, spirometry is the most widely used screening test of lung function or pulmonary function studies. In a simplistic way, respiratory disease can be classified as obstructive or restrictive processes.
Once the technical adequacy of the spirogram has been established, the next step is to classify whether the study is normal or has an obstructive pattern, a restrictive pattern, or a mixed obstructive and restrictive pattern. Once the presence of airflow obstruction is established, then a typical approach in the laboratory is to administer two puffs of inhaled albuterol and repeat the spirogram after 15 minutes to establish bronchodilator responsiveness. Because the FVC is not a reliable measure of total lung capacity, spirometry can only suggest a restrictive process and, in general, should be followed up by lung volume measurement.
The test is most reliably interpreted as showing restrictive abnormality on the basis of total lung capacity. Diffusing capacity is a pulmonary function test that is commonly performed to help further characterize abnormalities in spirometry or lung volume measurements. Lung function testing helps us to understand the physiologic working of the lungs and chest mechanics.
Pulmonary function testing is the primary method used to diagnose, stage, and monitor various pulmonary diseases. Lung function testing requires operators to follow published guidelines for administering and interpreting tests. Crapo RO, Casaburi R, Coates AL, et al: Guidelines for methacholine and exercise challenge testing, 1999. Enright PL, Kronmal RA, Higgins M, et al: Spirometry reference values for women and men 65 to 85 years of age. Testing equipment, patient maneuvers, and testing techniques have become widely standardized throughout the world through the efforts of professional societies. Insight into underlying pathophysiology can often be gained by comparing the measured values for pulmonary function tests obtained on a patient at any particular point with normative values derived from population studies. PFTs can include simple screening spirometry, formal lung volume measurement, diffusing capacity for carbon monoxide, and arterial blood gases. Tests that fail to meet these standards can provide useful information about minimum levels of lung function, but, in general, they should be interpreted cautiously.

Ventilation is the process of generating the forces necessary to move the appropriate volumes of air from the atmosphere to the alveoli to meet the metabolic needs of the body under a variety of conditions. In contrast, a variety of factors affect expiratory flow, including the overall driving pressure, airway diameter, overall distensibility of the lungs and chest wall, dynamic airway collapse (from a flow-limiting segment), and muscular effort.
This can cause dynamic airway compression and narrowing or closure of airways that have lost elastic recoil support from the lung parenchyma. These include the airways (large and small), lung parenchyma (alveoli, interstitium), pulmonary vasculature, and the bellows-pump mechanism. It generally should be the clinician's first option, with other studies being reserved for specific indications.
Values generated from a simple spirogram provide important graphic and numeric data regarding the mechanical properties of the lungs, including airflow (forced expiratory volume in 1 second [FEV1] along with other timed volumes) and exhaled lung volume (FVC or SVC). The American Thoracic Society standardization guidelines for acceptability and reproducibility criteria are shown in Box 3.4 A well-trained pulmonary function technician usually coaches the patient through the session until the demonstrated reproducibility of key parameters suggests the results represent the best possible measure of lung function at that time.
In normal persons, the FEV1 accounts for the greatest part of the exhaled volume from a spirometric maneuver and reflects mechanical properties of the large and the medium-sized airways.
Such processes are generally termed restrictive and can include disorders of the lung parenchyma, such as pulmonary fibrosis, or of the bellows, including kyphoscoliosis, neuromuscular disease, and pleural effusion. The volume-time tracing is most useful in assessing whether the end-of-test criteria have been met, whereas the flow-volume loop is most valuable in evaluating the start-of-test criteria. The FEF25-75 is the slope of the spirogram between the 25th and the 75th percentiles of an FVC maneuver.
It is believed that small airways dysfunction can precede and exist separately in the setting of a normal FEV1 and FVC.
Methacholine is considered safe, can be used in outpatient clinics, and has no systemic side effects. This is typically performed as a five-stage procedure with five different increasing concentrations. Vital capacity is a simple measure of lung volume that is usually reduced in restrictive disorders; however, reduction in the vital capacity measured during spirometry should prompt measurement of lung volumes to confirm the presence or absence of a true restrictive ventilatory disorder. Gas dilution techniques are based on a simple principle, are widely used, and provide a good measurement of all air in the lungs that communicates with the airways.
They are based on the inhalation of a known concentration and volume of an inert tracer gas, such as helium, followed by equilibration of 7 to 10 minutes in the closed-circuit helium dilution technique. The primary advantage of body plethysmography is that it can measure the total volume of air in the chest, including gas trapped in bullae. From these volumes and capacities, the residual volume and total lung capacity can be calculated. The role of ventilation is to reset concentration of the bulk flow of gas with the ambient air and to provide a constant gradient for oxygen and carbon dioxide.
This property allows a better measurement of pure diffusion, such that the movement of the carbon monoxide in essence only depends on the properties of the diffusion barrier and the amount of hemoglobin.
In Europe, it is often called the transfer factor of carbon monoxide, which describes the process more accurately. In this technique, a subject inhales a known volume of test gas that usually contains 10% helium, 0.3% carbon monoxide, 21% oxygen, and the remainder nitrogen. Because the hemoglobin present in the alveolar capillaries serves as a carbon monoxide sink such that oxygen and carbon monoxide are removed from dissolved gases, the concentration gradient from alveolar to arterial blood remains relatively constant in favor of dissolved gas flow toward the arterial circulation. Low DLCO is not only an abnormality of restrictive interstitial lung disease but also can occur in the presence of emphysema.
Hemoglobin trapped in proximity to alveolar gas will absorb carbon monoxide despite the actual severe limitation of gas exchange and oxygen delivery. Over the years, many regression equations have been generated by several investigators using different methodologies to study a variety of populations.7,15,17 The recommendation is for clinical laboratories to choose a published reference standard that is most similar to the typical patient population at a given institution as well as the testing methods used. Obese patients might have abnormal spirometry (decrease in FVC) based on the diaphragm's ability to displace the intra-abdominal fat. Specifically, based on anthropometric differences, the lung function for African Americans is systematically lower compared with whites.6 The American Thoracic Society recommends a 12% correction for African Americans for FEV1, FVC, and total lung capacity. Obstructive disorders, such as emphysema or asthma, are characterized by airflow limitation, have increased lung volumes with air trapping, and have normal or increased compliance (based on pressure volume profile). Lack of bronchodilator response certainly does not exclude asthma, and the result needs to be used in the context of a patient's clinical history. The DLCO has greater degrees of variability between laboratories and requires some level of expertise to perform reliably. Our proposed approach to the interpretation of diffusing capacity is shown in Figures 10 and 11. This official statement of the American Thoracic Society was adopted by the ATS Board of Directors, July 1999.
Effects of increasing carboxyhemoglobin on the single breath carbon monoxide diffusing capacity. Pulmonary function characteristics of patients with different patterns of methacholine airway hyperresponsiveness. The interpretive strategy usually involves establishing a pattern of abnormality (obstructive, restrictive, or mixed), grading the severity of the abnormality, and assessing trends over time. Simply, the contraction of the diaphragm and other inspiratory muscles expands the thorax, generating negative pressure in the pleural space.
The overall driving pressure is the pressure head at the alveolus, or PALV, which is the difference between pleural pressure (PPL) and negative transpulmonary pressure (PTP). Most patients can easily perform spirometry when coached by an appropriately trained technician or other health care provider.
The maneuver may be performed in a forceful manner to generate a forced vital capacity (FVC) or in a more relaxed manner to generate a slow vital capacity (SVC).
The measurement is typically expressed in liters for volumes or in liters per second for flows and is corrected for body temperature and pressure of gas that is saturated with water vapor.
However, a reduction in FVC is not always due to reduced total volumes and can occur in the setting of large lungs hyperinflated due to severe airflow obstruction and air trapping, as in emphysema.
The technique of back-extrapolation of the start of the test to establish a zero time point on the volume-time tracing has been carefully defined and provides a uniform start point for timed measurements. With common obstructive airflow disorders, such as asthma or emphysema, the disease generally affects the expiratory limb and can reduce the effort-dependent peak expiratory flow as well as subsequent airflows that are independent of effort. Normal values and lower limits of normal for the FEF25-75% have been published.7 Care must be taken to use the statistically defined lower limit of normal and avoid assessing this parameter using the percentage of predicted normal value because the lower limit of normal falls significantly with age. The hypothesis is that smokers might have isolated small airways dysfunction and that there is an obligatory passage through a silent period during which only sensitive tests are impaired. However, this test may be falsely positive in a variety of conditions, including chronic obstructive pulmonary disease, parenchymal respiratory disorders, congestive heart failure, recent upper respiratory tract infection, and allergic rhinitis. A limitation of this technique is that it does not measure air in noncommunicating bullae, and therefore it can underestimate total lung capacity, especially in patients with severe emphysema. The final exhaled helium concentration is diluted in proportion to the unknown volume of air in the patient's chest (residual volume).
DLCO is a measure of the interaction of alveolar surface area, alveolar capillary perfusion, the physical properties of the alveolar capillary interface, capillary volume, hemoglobin concentration, and the reaction rate of carbon monoxide and hemoglobin.
The most commonly used standards are those of Morris and colleagues,19 Crapo and colleagues,20 Knudson and colleagues,21 and the National Health and Nutrition Examination Survey (NHANES III).7 These reference standards are based on a cohort of normal subjects of similar age, height, and race, with normal being defined as persons without a history of smoking or disease that can affect lung function.
Supplemental studies may be conducted as needed, such as a formal lung volume measurement, diffusing capacity, methacholine provocation test, or cardiopulmonary exercise studies.
In contrast, restrictive disorders such as pulmonary fibrosis are characterized by reduced lung volumes and an increase in overall stiffness of the lungs (with reduced compliance) (Fig.

In general, the measured values are compared with the lower limits of normal predicted values from one of the published studies. When spirometry suggests a restrictive process or when the abnormalities seen on the spirogram do not adequately explain a patient's clinical history, then formal measurements of lung volume are helpful. A pattern of diffusing capacity reduced proportionate to airflow obstruction (a proportionate reduction in FEV1 and DLCO) is typical for emphysema.
Survey at institutions with respiratory disease training programs in the United States and Canada.
Practicing clinicians must become familiar with pulmonary function testing because it is often used in clinical medicine for evaluating respiratory symptoms such as dyspnea and cough, for stratifying preoperative risk, and for diagnosing common diseases such as asthma and chronic obstructive pulmonary disease. One component of pleural pressure, known as transpulmonary pressure, causes a flow of air into the airways and lungs (inspiration). The test can be administered in the ambulatory setting, physician's office, emergency department, or inpatient setting. In normal persons, the inspiratory vital capacity, the expiratory SVC, and expiratory FVC are essentially equal.
Data from a spirogram provide important clues to help distinguish obstructive pulmonary disorders that typically reduce airflow, such as asthma and emphysema, from restrictive disorders that typically reduce total lung volumes, including pulmonary fibrosis and neuromuscular disease. In this setting, the FVC is decreased due to reduced airflow, air trapping, and increased residual volume, a phenomenon referred to as pseudorestriction. It corrects for delayed or hesitant starts that might otherwise be mistaken for a falsely reduced FEV1.
However, there is a greater coefficient of variation for these tests of small airways function.
When there is a 20% reduction in the FEV1, the test is terminated and is considered positive for airway hyperreactivity. Usually, the patient is connected at the end-tidal position of the spirometer; therefore, the lung volume measured is FRC.
Drawbacks include the complexity of the equipment as well as the need for a patient to sit in a small enclosed space. The patient exhales to wash out a conservative overestimate of mechanical and anatomic dead space. Because the level of hemoglobin present in the blood and diffusing capacity are directly related, a correction for anemic patients (DLCOc) is used to further delineate whether a DLCO is decreased due to anemia or due to parenchymal or interface limitation. Additionally, the loss of alveolar surface area, the pathologic lesion of emphysema, is not proportionate to volume. Airflow obstruction exists, by definition, when the ratio of FEV1 to FVC is below the lower limits of normal.
Box 7 summarizes the American Thoracic Society's criteria for grading the severity of lung function abnormalities. A DLCO is reduced proportionately to a reduction in total lung capacity in the context of restrictive abnormalities suggests a parenchymal process such as pulmonary fibrosis. Automated spirometry systems usually have built-in software that can generate a preliminary interpretation, especially for spirometry; however, algorithms for other pulmonary function studies are not as well established and necessitate appropriate clinical correlation and physician oversight. When the transpulmonary and alveolar pressures equilibrate, airflow stops, the inspiratory muscles relax, and the lungs and chest wall elastic recoil raise pleural pressure, forcing air out of the lungs (expiration). However, in patients with obstructive small airways disease, the expiratory SVC is generally higher than the FVC. Standards for acceptability define limits for the degree of hesitation that can still yield an acceptable FEV1 (see Box 3).
In contrast, several unusual anatomic disorders that narrow the large airways can produce a variety of patterns of truncation or flattening of either one limb of the loop (variable upper airway obstruction) or both limbs of the loop (fixed upper airway obstruction). In addition, because these measures are vitally influenced by lung volumes, they cannot be interpreted separately without volume correction. The provocative concentration dosage level of the inhalational agent required to produce a 20% reduction in the FEV1 is labeled PC20FEV1. In the nitrogen-washout technique, the patient breathes 100% oxygen, and all the nitrogen in the lungs is washed out. Thus, one can understand that other obstructive entities that predominantly affect the airways can have similar spirometry, but a low DLCO implies a loss of alveolar surface area consistent with emphysema. Patients are asked to inspire to total lung capacity and then exhale into an analyzer using a steady, controlled exhaled flow rate. It is also often adequate for rotated obstructive lung disease, such as emphysema or asthma.
Total lung capacity can be particularly helpful when a patient has severe airflow obstruction and has a reduction in FVC.
An isolated or disproportionate reduction in diffusing capacity along with either normal or fairly well preserved mechanics suggests predominantly a pulmonary vascular process such as primary pulmonary hypertension or thromboembolic disease.
It can be used for diagnosing and monitoring respiratory symptoms and disease, for preoperative risk stratification, and as a tool in epidemiologic and other research studies. This difference might, however, be due partly to the difficulty in maintaining a maximum expiratory effort for an extended time period without experiencing dizziness or lightheadedness. Therefore, FVC is not a reliable indicator of total lung capacity or restriction, especially in the setting of airflow obstruction. The loss of elastic recoil characteristic of emphysema results in airflow limitation during the maximal forced exhalation that may be grossly underestimated if the patient applies less than maximal expiratory force. If the drop in FEV1 is less than 20% after five stages of this procedure, the challenge test is considered negative for airway hyperreactivity.
DLCO is calculated from the total volume of the lung, breath-hold time, and the initial and final alveolar concentrations of carbon monoxide. In this case, a normal or increased total lung capacity excludes an associated restrictive process, and the reduction in FVC is actually a pseudorestriction. The difference in nitrogen volume at the initial concentration and at the final exhaled concentration allows a calculation of intrathoracic volume, usually FRC.
From the FRC, the patient pants with an open glottis against a closed shutter to produce changes in the box pressure proportionate to the volume of air in the chest.
The exhaled helium concentration is used to calculate a single-breath estimate of total lung capacity and the initial alveolar concentration of carbon monoxide.
Some forms of interstitial lung disease can have components of restrictive physiologies, such as low lung volume and clear evidence of decreased diffusion but also can have airway flow limitation.
The time to peak flow appears to have excellent usefulness in identifying such efforts in this population (time to peak flow will be greater than 120 msec when effort is submaximal), but it is not yet a recommended acceptability criterion (Fig.
The volume measured by this technique is referred to as thoracic gas volume (TGV) and represents the lung volume at which the shutter was closed, typically FRC. The driving pressure is assumed to be the calculated initial alveolar pressure of carbon monoxide. Sarcoidosis and Wegener's granulomatosis can produce an endobronchial component of airway webs or strictures, limiting flow before overt volume loss, and sufficient interstitial granulomatous inflammation to reduce the DLCO. The calculated DLCO is a product of the patient's single-breath estimate of total lung capacity multiplied by the rate of carbon monoxide uptake during the 10-second breath hold.

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