The air within the lung at the end of a forced inspiration can be divided into four compartments or lung volumes (eFig. 14-1). The volume of air exhaled during normal quiet breathing is the Vt. The maximal volume of air inhaled above Vt is the inspiratory reserve volume (IRV), and the maximal air exhaled below Vt is the expiratory reserve volume (ERV). The residual volume (RV) is the amount of air remaining in the lungs after a maximal exhalation.
The combinations or sums of two or more lung volumes are termed capacities (eFig. 14-1). Vital capacity (VC) is the maximal amount of air that can be exhaled after a maximal inspiration. It is equal to the sum of IRV, Vt, and ERV. When measured on a forced expiration, it is called the forced vital capacity (FVC). When measured over an exhalation of at least 30 seconds, it is called the slow vital capacity (SVC). The VC is approximately 75% of the total lung capacity (TLC), and when the SVC is within the normal range, a significant restrictive disorder is unlikely. Normally, the values for SVC and FVC are very similar unless airway obstruction is present.
TLC is the volume of air in the lung after the maximal inspiration and is the sum of the four primary lung volumes (IRV, Vt, ERV, and RV). Its measurement is difficult because the amount of air remaining in the chest after maximal exhalation, RV, must be measured by indirect methods. The definition of restrictive lung disease is based on a reduction in TLC (i.e., an inability to get air into the lung or restriction to air movement on inhalation).
The functional residual capacity (FRC) is the volume of air remaining in the lungs at the end of a quiet expiration. It is the sum of RV and ERV. FRC is the normal resting position of the lung; it occurs when there is no contraction of either inspiratory or expiratory muscles and normally is 40% of TLC. Inspiratory capacity (IC) is the maximal volume of air that can be inhaled from the end of a quiet expiration and is the sum of Vt and IRV.
FVC, which represents the total amount of air that can be exhaled, can be expressed as a series of timed volumes. The forced expiratory volume in the first second of expiration (FEV1) is the volume of air exhaled during the first second of the FVC maneuver. Although FEV1 is a volume, it conveys information on obstruction because it is measured over a known time interval. FEV1 depends on the volume of air within the lung and the effort during exhalation; therefore, it can be diminished by a decrease in TLC or by a lack of effort. A more sensitive way to measure obstruction is to express FEV1 as a ratio of FVC. This ratio is independent of the patient’s size or TLC; therefore, FEV1/FVC is a specific measure of airway obstruction with or without restriction. Normally, this ratio is ≥75% (0.75), and any value <70% to 75% (<0.7 to 0.75) suggests obstruction.
Because flow is defined as the change in volume with time, forced expiratory flow (FEF) can be determined graphically by dividing the volume change by the time change. The FEF during 25% to 75% of FVC (FEF25–75%) represents the mean flow during the middle half of the FVC. FEF25–75%, formerly called the maximal midexpiratory flow, is reported frequently in the assessment of small airways. The 95% confidence limit is so wide that FEF25–75% has limited utility in the early diagnosis of small airways disease in an individual subject. The peak expiratory flow (PEF), also called maximum forced expiratory flow (FEFmax), is the maximum flow obtained during FVC. This measurement is used often in the outpatient management of asthma because it can be measured with inexpensive peak flow meters.
All lung volumes and flows are compared with normal values obtained from healthy subjects. There are significant ethnic and racial variations in normal values, and all PFTs should report that race/ethnic adjustment factors have been used. This is especially important in African American subjects who exhibit a greater proportion of their height in the waist-to-leg length. If not corrected for ethnicity, many subjects will appear to have restrictive lung functions. The 2005 American Thoracic Society–European Respiratory Society (ATS–ERS) guidelines for interpretation of PFT results recommend that, for spirometry in the United States, the National Health and Nutrition Examination Survey (NHANES) III reference be used for subjects aged 8 to 80 years and the Wang equation used in subjects younger than 8 years.2
Spirometry3 is the most widely available and useful PFT. It takes only 15 to 20 minutes, carries no risks, and provides information about obstructive and restrictive disease. Spirometry allows for measurement of all lung volumes and capacities except RV, FRC, and TLC; it also allows assessment of FEV1 and FEF25–75%. Spirometry measurements can be reported in two different formats—standard spirometry (eFig. 14-2) and the flow–volume loop (eFig. 14-3). In standard spirometry, the volumes are recorded on the vertical (y) axis and the time on the horizontal (x) axis. In flow–volume loops, volume is plotted on the horizontal (x) axis, and flow (derived from volume/time) is plotted on the vertical (y) axis. The shape of the flow–volume loop can be helpful in differentiating obstructive and restrictive defects and in diagnosing upper airway obstruction (eFig. 14-4). This curve gives a visual representation of obstruction because the expiratory descent becomes more concave with worsening obstruction.
Standard spirometry. Curve 1 is for a normal subject with normal FEV1; curve 2 is for a patient with mild airway obstruction; curve 3 is for a patient with moderate airway obstruction; curve 4 is for a patient with severe airway obstruction. (BPTS, body temperature saturated with water vapor.)
Normal flow–volume loop. Flows are measured on the vertical (y) axis, and lung volumes are measured on the horizontal (x) axis. Forced vital capacity (FVC) can be read from the tracing as the maximal horizontal deflection. Instantaneous flow (V̇max) at any point in FVC also can be measured directly. (FEF50%, forced expiratory flow at 50% of forced vital capacity; PEF, peak expiratory flow; PIF, peak inspiratory flow; RV, residual volume; TLC, total lung capacity.)
A. Flow–volume loop depicting mild obstruction characterized by decreased flow at low lung volumes. B. Moderate airflow obstruction characterized by a more concave curve. C. Variable intrathoracic obstruction in which peak flow is decreased at higher lung volumes with normalization of curve at lower lung volumes. D. Restrictive lung disease with a curve that is decreased in width but with a normal shape. (RV, residual volume; TLC, total lung capacity.)
Spirometry measures three of the four basic lung volumes but cannot measure RV. RV must be measured to determine TLC. TLC should be measured anytime VC is reduced. In the setting of chronic obstructive pulmonary disease (COPD) and a low VC, measurement of TLC can help to determine the presence of a superimposed restrictive disorder. The four methods for measuring TLC are helium dilution, nitrogen washout, body plethysmography, and chest x-ray measurement (planimetry).4 The first two methods are called dilution techniques and only measure lung volumes in communication with the upper airway. In patients with airway obstruction who have trapped air, dilution techniques will underestimate the actual volume of the lungs. Planimetry measures the circumference of the lungs on the posteroanterior view and lateral views of a chest x-ray film and estimates the total lung volume.
Body plethysmography, or body box, is the most accurate technique for lung volume determinations. It measures all the air in the lungs, including trapped air. The principle of the measurement of the body box is Boyle’s gas law (P1V1 = P2V2): a volume of gas in a closed system varies inversely with the pressure applied to it. The changes in alveolar pressure are measured at the mouth, as well as pressure changes in the body box. The volume of the body box is known. Lung volumes can be determined measuring the changes in pressures caused by panting against a closed shutter. Measurement of lung volumes provides useful information about elastic recoil of the lungs. If elastic recoil is increased (as in interstitial lung disease), lung volumes (TLC) are reduced. When elastic recoil is reduced (as in emphysema), lung volumes are increased.
Carbon Monoxide Diffusing Capacity
The diffusing capacity of the lungs (Dl) is a measurement of the ability of a gas to diffuse across the alveolar–capillary membrane.5 Carbon monoxide is the usual test gas because normally it is not present in the lungs and is much more soluble in blood than in lung tissue. When the diffusing capacity is determined with carbon monoxide, the test is called the diffusing capacity of lung for carbon monoxide (Dlco). Because Dlco is directly related to alveolar volume (Va), it frequently is normalized to the value Dl/Va, which allows for its interpretation in the presence of abnormal lung volumes (e.g., after surgical lung resection).
The diffusing capacity will be reduced in all clinical situations where gas transfer from the alveoli to capillary blood is impaired. Common conditions that reduce Dlco include lung resection, emphysema (loss of functioning alveolar–capillary units), and interstitial lung disease (thickening of the alveolar–capillary membrane). Normal PFTs with reduced Dlco should suggest the possibility of pulmonary vascular disease (e.g., pulmonary embolus) but also can be seen with anemia, early interstitial lung disease, and mild Pneumocystis jiroveci pneumonia (PJP) infection in patients with acquired immune deficiency syndrome.
Obstructive lung disease implies a reduced capacity to get air through the conducting airways and out of the lungs. This reduction in airflow may be caused by a decrease in the diameter of the airways (bronchospasm), a loss of their integrity (bronchomalacia), or a reduction in elastic recoil (emphysema) with a resulting decrease in driving pressure. The most common diseases associated with obstructive pulmonary functions are asthma, emphysema, and chronic bronchitis; however, bronchiectasis, infiltration of the bronchial wall by tumor or granuloma, aspiration of a foreign body, and bronchiolitis also cause obstructive PFTs. The standard test used to evaluate airway obstruction is the forced expiratory spirogram.
Standard spirometry and flow–volume loop measurements include many variables; however, according to ATS guidelines, the diagnosis of obstructive and restrictive ventilatory defects should be made using the basic measurements of spirometry.2,3 A reduction in FEV1 (with normal FVC) establishes the diagnosis of obstruction. When both FEV1 and FVC are reduced, FEV1 cannot be used to assess airway obstruction because such patients may have either obstruction or restriction. In restrictive lung disease, the patient has an inability to get air into the lung, which results in a reduction of all expiratory volumes (FEV1, FVC, and SVC). In obstructed patients, a better measurement is the ratio FEV1/FVC. Patients with restrictive lung disease have reduced FEV1 and reduced FVC, but FEV1/FVC remains normal. Although a normal FEV1/FVC ratio is >70% to 75% (>0.7 to 0.75), the ratio is age dependent, and slightly lower values may be normal in older patients. Younger children have increased lung elastic recoil and may have higher ratios. Children with asthma should have a FEV1/FVC ≥85% (≥0.85). According to the 2007 National Asthma Education and Prevention Program, any value below this value should be considered a sign of obstruction, even if the FEV1 and FVC are within the normal range. Caution should be used in interpreting obstruction when FEV1/FVC is below normal, but both FEV1 and FVC are within the normal range, because this pattern can be seen with healthy, athletic subjects as well as subjects with mild asthma. Clinical judgment and response to bronchodilator challenge are often required to separate out these two groups. In children, the improvement in FEV1 often is the only way to document mild-to-moderate obstructive lung disease.
In screening spirometry performed in office practice, forced expiratory volume in 6 seconds (FEV6) can be used in place of FVC. FEV6 is a more reproducible number when obtained by less skilled personnel. The measurement of FEF25–75% also is abnormal in patients with obstructive airways disease. In general, this test has so much variability that it adds little to the measurement of FEV1 and FEV1/FVC.
Although there is no standardization for interpretation of severity of obstruction, most pulmonary laboratories state that FEV1/FVC <70% (<0.70) of the predicted value is diagnostic for obstruction, and the degree of obstruction then is based on the percent predicted of FEV1. FEV1 between 70% and 100% of the predicted value is mild obstruction, 60% and 69% of the predicted value is moderate obstruction, and <50% of the predicted value is severe obstruction. In patients with obstruction, a dose of a bronchodilator (e.g., albuterol or isoproterenol) by metered-dose inhaler is given during the initial examination. An increase in FEV1 of >12% and >0.2 L suggests an acute bronchodilator response.2,3 Because bronchodilator responsiveness is variable over time, the lack of an acute bronchodilator response should not preclude a 6- to 8-week trial of bronchodilators and/or corticosteroids.
Although all patients with obstructive lung disease of any etiology will have reduced flow rates on forced exhalation, the pattern on PFTs may be helpful in differentiating among the various etiologies (eTable 14-1). Asthma is characterized by variable obstruction that often improves or resolves with appropriate therapy. Because asthma is an inflammatory disorder of the airways (predominantly large airways), Dlco is normal. Most patients with acute asthma have a bronchodilator response >15% to 20%; however, this response is also seen in 20% of patients with COPD. These patients are said to have asthmatic bronchitis. Chronic bronchitis may be limited to the airways, but the vast majority of patients with chronic bronchitis and airway obstruction have a mixture of bronchitis and emphysema and have a reduction in Dlco. Therefore, Dlco is the best PFT for separating asthma from COPD.
eTable 14-1 Specific Patterns of Pulmonary Function in Patients with Chronic Obstructive Pulmonary Disease |Favorite Table|Download (.pdf)
eTable 14-1 Specific Patterns of Pulmonary Function in Patients with Chronic Obstructive Pulmonary Disease
|Increased airway resistance||++++||++++||+|
|Response to bronchodilators||++++||+b||−b|
After the diagnosis of obstructive airways disease is established, the course and response to therapy are best followed by serial spirometry. The multicenter Lung Health Study demonstrated an abnormally rapid decline (90 to 150 mL/y) in patients with COPD who continue to smoke.6 Smoking cessation often resulted in an increase in FEV1 during the first year and a near-normal rate of decline (30 to 50 mL/y) in subsequent years.