Overview of pulmonary function testing in adults

INTRODUCTION — Evaluation of pulmonary function is important in many clinical situations, both when the patient has a history or symptoms suggestive of lung disease and when risk factors for lung disease are present, such as occupational exposure to agents with known lung toxicity [1].

The European Respiratory Society and the American Thoracic Society have published guidelines for the measurement and interpretation of pulmonary function tests (PFTs) [2-10].

An overview of pulmonary function testing will be presented here, summarizing the types of PFTs and their indications. Specific aspects of pulmonary function testing are discussed elsewhere. (See "Office spirometry" and "Selecting reference values for pulmonary function tests" and "Diffusing capacity for carbon monoxide" and "Pulmonary function testing in asthma" and "Bronchoprovocation testing" and "Overview of pulmonary function testing in children".)

ADVICE RELATED TO COVID-19 PANDEMIC — Spirometry and other pulmonary function test (PFT) maneuvers can promote coughing and aerosol generation and could lead to spread of coronavirus disease 2019 (COVID-19; SARS-CoV-2) by infected patients. It is difficult to screen patients for active COVID-19 infection, particularly those with underlying respiratory symptoms, and infected but asymptomatic patients can shed the virus. Thus, we agree with expert recommendations that spirometry and other PFTs be limited to patients in whom results are essential to immediate management decisions [11]. Use of nebulizers to administer bronchodilators or methacholine for testing should be avoided.

Measures to prevent spread of COVID-19 should include hand hygiene and personal protective equipment (PPE; gloves, gown, face mask and shield) for staff and anyone else in the testing space (eg, interpreters). N95 masks or powered air purifying respirators (PAPR) are preferred over surgical masks. Patients should be brought to a testing room using an approach that avoids queuing or grouping individuals in a waiting area.

PFT equipment should be fitted with single-use mouthpieces and disposable in-line bacterial and viral filters [12-14]. Enhanced cleaning of the testing area should be performed between patients. Performance of PFTs can generate aerosol particles, potentially carrying infectious virus, even when a filter is used [15]. Thus, it is preferred that negative pressure rooms with at least six air exchanges per hour be used. Recognizing that the time needed for optimal clearance of aerosol particles varies among laboratories, closure between patients is recommended for 20 minutes to 3 hours (depending on ventilation of the particular space) to enable clearance of respiratory aerosols [12-14]. A consensus statement has been published for reference [16].

PULMONARY FUNCTION TESTS — The major types of pulmonary function tests (PFTs) are spirometry, spirometry before and after a bronchodilator, lung volumes, and quantitation of diffusing capacity for carbon monoxide. Additional PFTs, such as measurement of maximal respiratory pressures, flow-volume loops, submaximal exercise testing, and bronchoprovocation challenge, are useful in specific clinical circumstances (table 1).

●Holding bronchodilator medications – In preparation for PFTs, bronchodilator medications are typically held so that bronchodilator response can be assessed after baseline spirometry. As examples, short-acting inhaled beta agonists (eg, albuterol, salbutamol) should not be used for four to six hours prior to testing [6]. The short-acting muscarinic antagonist ipratropium should be held for 12 hours. Long-acting beta agonist bronchodilators (eg, salmeterol, formoterol) should be held for 24 hours prior to testing. The ultra-long-acting beta agonists (eg, indacaterol, olodaterol, vilanterol) should be held for 36 hours, and the long-acting muscarinic antagonists (also called anticholinergic agents) glycopyrrolate (glycopyrronium), tiotropium, aclidinium, and umeclidinium should be held for 36 to 48 hours.

Spirometry — Spirometry, the most readily available and useful pulmonary function test, measures the volume of air exhaled at specific time points during a forceful and complete exhalation after a maximal inhalation [6]. The total exhaled volume, known as the forced vital capacity (FVC), the volume exhaled in the first second, known as the forced expiratory volume in one second (FEV₁), and their ratio (FEV₁/FVC) are the most important variables reported [17]. The test takes 10 to 15 minutes and carries minimal risk (eg, rarely syncope). The techniques for performing spirometry and interpretation of results are described separately. (See "Office spirometry" and "Flow-volume loops".)

Spirometry is a key diagnostic test for asthma and chronic obstructive pulmonary disease (COPD) when performed before and after bronchodilator and is useful to assess for asthma or other causes of airflow obstruction in the evaluation of chronic cough. It is also used to monitor a broad spectrum of respiratory diseases, including asthma, COPD, interstitial lung disease, and neuromuscular diseases affecting respiratory muscles.

The slow vital capacity (SVC) can be measured as the maximal amount of air exhaled in a relaxed expiration from full inspiration to residual volume; exhalation should be terminated after 15 seconds [6]. The SVC may be a useful measurement when the FVC is reduced and airway obstruction is present. Slow exhalation results in a lesser degree of airway narrowing, and the patient may produce a larger, even normal vital capacity. In contrast, the vital capacity with restrictive disease is reduced during both slow and fast maneuvers. Thus, if the slow or forced vital capacity is within the normal range, it is generally unnecessary to measure static lung volumes (residual volume and total lung capacity) [18].

Post-bronchodilator — Performance of spirometry before and after bronchodilator is used to determine the degree of bronchodilator responsiveness. Administration of albuterol by metered-dose inhaler (MDI) is indicated if baseline spirometry demonstrates airway obstruction or if one suspects asthma or COPD. Albuterol or an equivalent short-acting beta agonist is administered by MDI with a spacer or chamber device (picture 1); proper MDI technique is important to prevent false negative results [6]. Bronchodilator may also be administered by nebulizer according to standard local practice. Spirometry should be repeated 10 to 15 minutes after administration of a bronchodilator. (See "The use of inhaler devices in adults".)

The European Respiratory Society/American Thoracic Society(ERS/ATS) interpretation standards recommend that a significant bronchodilator response be defined by a greater than or equal to increase in FEV₁ or FVC by 10 percent of their respective predicted values [3]. This is in contrast to the prior definition of an increase in the FEV₁ or FVC of more than 12 percent and greater than 0.2 L [2]. This new definition is thought to be more accurate in terms of avoiding age and size bias [19], is based on the upper limit of normal from worldwide data [20], and is also associated with the important clinical outcome of mortality [19].

In patients with asthma, bronchodilator administration often results in improvement, and in some patients with asthma, post-bronchodilator testing may improve to normal spirometry values. Among patients with COPD, administration of bronchodilator sometimes leads to a significant change in FEV₁ or FVC [21], but reversal to normal spirometry makes COPD less likely [22]. Bronchodilators may also lead to improvement in flow in the small airways and a reduction in air trapping. While criteria for assessment of reduced air trapping have not been formalized, an increase in inspiratory capacity (IC) and a decrease in functional residual capacity (FRC) are thought to reflect this response. (See 'Lung volumes' below.)

Sometimes, patients will note subjective improvements in their breathing after bronchodilator inhalation, but without associated changes in FVC or FEV₁ [23]. It is thought that increased airflow within the tidal volume range, but not during deep inhalation, may account for this discrepancy. Deep inhalations may be associated with airway narrowing, which may offset the measured bronchodilator response. Thus, the lack of an acute bronchodilator response on spirometry should not preclude a therapeutic trial of bronchodilators and/or inhaled glucocorticoids, with reassessment of clinical status and change in FEV₁ at the end of that time [2].

Flow-volume loop — Flow-volume loops, which include forced inspiratory and expiratory maneuvers, are always useful but especially whenever stridor is heard over the neck and when evaluating unexplained dyspnea. Airway obstruction located in the pharynx, larynx, or trachea (upper airways) is usually impossible to detect from standard expiratory FVC maneuvers. Reproducible forced inspiratory vital capacity (FIVC) maneuvers may detect variable extrathoracic upper airway obstruction [24], as can be seen with vocal fold paralysis or dysfunction, which causes a characteristic limitation of flow (plateau) during forced inhalation but little if any obstruction during exhalation (figure 1). (See "Flow-volume loops" and "Inducible laryngeal obstruction (paradoxical vocal fold motion)", section on 'Pulmonary function tests'.)

Less commonly, a fixed upper airway obstruction (UAO) (eg, tracheal stenosis) causes flow limitation during both forced inhalation and forced exhalation maneuvers (figure 1). However, the flow-volume loop is not sensitive for detecting a fixed UAO, since the tracheal lumen is often reduced to less than 1 cm before a plateau is recognized. Poor technique or effort can mimic the flow-volume loop shapes of upper airway obstruction but are usually excluded when three or more maneuvers are seen to be repeatable.

Bronchoprovocation challenge — Spirometry is used to assess the airway hyperresponsiveness to a variety of bronchoprovocation challenges, such as methacholine, mannitol, exercise, and isocapnic hyperpnea. Bronchoprovocation challenge is discussed separately. (See "Bronchoprovocation testing".)

Supine and sitting spirometry — To evaluate respiratory muscle weakness, spirometry can be obtained with the patient supine and sitting. Diaphragmatic weakness is suggested by a decrease in the supine vital capacity (VC) >10 percent. Unilateral diaphragmatic paralysis is usually associated with a decrease in VC of 15 to 25 percent; bilateral diaphragmatic paralysis can be associated with a decrease in supine VC approaching 50 percent. (See "Diagnostic evaluation of adults with bilateral diaphragm paralysis", section on 'Pulmonary function tests' and "Diagnosis and management of nontraumatic unilateral diaphragmatic paralysis (complete or partial) in adults", section on 'Pulmonary function testing'.)

Lung volumes — Measurement of lung volumes is important when spirometry shows a decreased forced vital capacity. Body plethysmography is the gold standard for measurement of lung volumes, particularly in the setting of airflow obstruction [5], although lung volumes can be overestimated in the situation of severe airflow obstruction [25]. Alternative methods include helium dilution, nitrogen washout, and measurements based on chest imaging. Helium dilution and nitrogen washout may underestimate lung volume in patients with moderate to severe COPD because they do not access under- or nonventilated areas.

Measurements of total lung capacity (TLC) using the chest radiograph or high-resolution computed tomography (HRCT) correlate within 15 percent of those obtained by body plethysmography [5,26]. Since the TLC is equivalent to the amount of air seen in the lungs on a chest radiograph taken at maximal inspiration, it is important that the subject inhales maximally as the image is created.

Common lung volume measurements include vital capacity, total lung capacity, functional residual capacity, and residual volume. By convention, the term capacity is used for compartments composed of two or more volumes. The relationships among the lung volumes and capacities are shown in the figure (figure 2) and listed below:

●Vital capacity (VC): maximum volume exhaled after maximum inspiration; can be measured during forced exhalation (FVC) or slow exhalation (SVC)

●Functional residual capacity (FRC): volume of air remaining in chest at the end of a tidal volume breath

●Residual volume (RV): volume of air remaining in chest after maximal exhalation

●Expiratory reserve volume (ERV): volume of air exhaled from end-tidal volume (FRC) to point of maximal exhalation (RV), so RV plus ERV = FRC

●Inspiratory capacity (IC): maximum inspiration from end-tidal volume (FRC) to total lung capacity

●Inspiratory reserve volume (IRV): volume of air inhaled during tidal breathing from end-inhalation to total lung capacity

●Total lung capacity (TLC): volume of air in lungs at end of maximal inspiration (usually calculated by RV plus VC or FRC plus IC)

A schema for the interpretation of PFT results is provided in the algorithm (algorithm 1) [3]. TLC is the key lung volume for determining restriction, defined as a TLC value less than the 5^th percentile of the predicted normal range (z-score <-1.645; roughly and imperfectly approximated by values less than 80 percent of predicted); a reduced VC alone is not sufficient evidence of restriction because it can be caused by air trapping due to severe obstruction, neuromuscular weakness, or suboptimal effort [2].

Air trapping is indicated when the RV or RV/TLC is increased (>upper limit of normal [ULN]); hyperinflation is indicated when the FRC and/or TLC are increased (>ULN). Thus, in the setting of COPD with obstruction on spirometry and a low vital capacity, measurement of lung volumes can help determine if there is a superimposed restrictive disorder or if VC is decreased due to air trapping or hyperinflation.

The combination of an FEV₁/FVC and TLC both less than the fifth percentile lower limit of normal (LLN) is considered a mixed defect [3]. The combination of a normal FEV₁/FVC and a normal TLC and a low FEV₁ or FVC is considered the nonspecific pattern [27]. The pattern in which the FVC is disproportionately reduced relative to TLC has been described as the complex restrictive pattern [28].

Maximal respiratory pressures — Measurement of maximal inspiratory and expiratory pressures is indicated whenever there is an unexplained decrease in vital capacity or respiratory muscle weakness is suspected clinically. Maximal inspiratory pressure (MIP), measured near RV, is the maximal pressure that can be produced by the patient trying to inhale through a blocked mouthpiece after a full exhalation. Maximal expiratory pressure (MEP) is the maximal pressure measured during forced expiration (with cheeks bulging) through a blocked mouthpiece after a nearly full inhalation to TLC. Repeated measurements of MIP and MEP are useful in following the course of patients with neuromuscular disorders. The slow vital capacity may also be followed, but it is less specific and usually less sensitive. (See "Tests of respiratory muscle strength".)

Maximal inspiratory and expiratory pressures are easily measured using a simple mechanical pressure gauge connected to a mouthpiece. MIP measures the ability of the diaphragm and the other respiratory muscles to generate inspiratory force, reflected by a negative airway pressure. The average MIP and MEP for adult men are -100 and +170 cm H₂O, respectively, while the corresponding values for adult women are approximately -70 and +110 cm H₂O, respectively [29,30]. The LLN range is approximately two-thirds of these values. (See "Tests of respiratory muscle strength", section on 'Interpretation (PImax, PEmax, SNIP)'.)

Diffusing capacity — Measurement of the single-breath diffusing capacity for carbon monoxide (DLCO; also known as transfer factor or TLCO) is quick, safe, and useful in the evaluation of restrictive and obstructive lung disease, as well as pulmonary vascular disease. The technique and interpretation are discussed separately [3,7,31]. (See "Diffusing capacity for carbon monoxide", section on 'Methodology'.)

Interpretation of abnormal DLCO values differs based on any underlying concomitant pulmonary process (table 2). In the setting of restrictive disease, the diffusing capacity helps distinguish between intrinsic lung disease, in which DLCO is usually reduced, and other causes of restriction due to reduced lung volume, in which DLCO is often normal. In the setting of obstructive disease, the DLCO helps distinguish between emphysema, in which it is usually reduced, and other causes of chronic airway obstruction, like asthma or chronic bronchitis, where it is usually normal. The DLCO is also used in the assessment of pulmonary vascular disease (eg, thromboembolic disease, pulmonary hypertension), which typically causes a reduction in DLCO in the absence of significant restriction or obstruction. (See 'Pulmonary vascular disease' below and "Diffusing capacity for carbon monoxide".)

GRADING PHYSIOLOGIC IMPAIRMENT — ERS/ATS interpretation standards emphasize that PFTs can only assess physiologic diagnoses and not clinical ones. Similarly, the severity of lung disease cannot be determined by PFTs, only the degree of physiologic impairment. Physiologic impairment should preferably be assessed based on z-score, instead of percent predicted, because this scale helps avoid age, sex, and height bias and is closely associated with important clinical outcomes [32,33].

FEV₁ is the primary measure used to grade the physiologic severity of obstructive or mixed obstructive-restrictive processes (algorithm 2). We prefer to use TLC z-score to grade severity of restriction; however, FEV₁ may be used as an alternative to grade previously confirmed restriction if lung volumes or z-scores are not available [2]. When using z-scores, physiologic impairment severity (by FEV₁, TLC, or DLCO) is graded as follows:

•Abnormally elevated – Z-score >1.645

•Normal – Z-score of -1.645 to 1.645

-In the setting of established obstruction (a reduced FEV₁/FVC), an FEV₁ in the normal range still indicates a mild obstructive deficit.

•Mildly impaired – Z-score of -1.65 to -2.5

•Moderately impaired – Z-score of -2.5 to -4

•Severely impaired – Z-score <-4

A grading approach using percent of predicted normal values can be used as a nonpreferred alternative when z-scores are not available (algorithm 2 and table 3).

OTHER TESTING

Submaximal exercise testing — Submaximal exercise testing is often conducted in the pulmonary function laboratory and does not require the resources needed for a maximal cardiopulmonary exercise test [4,34]. Three commonly used submaximal tests are the six-minute walk test, the incremental shuttle walk test, and the endurance shuttle walk test. Cardiopulmonary exercise testing is discussed separately. (See "Cardiopulmonary exercise testing in cardiovascular disease".)

Six-minute walk test — The six-minute walk test (6MWT) is a good index of physical function and therapeutic response in patients with chronic lung disease, such as COPD, pulmonary fibrosis, or pulmonary arterial hypertension [4,34-37]. The test should be performed according to standard methods (table 4) [4], including a practice walk to orient the patient to the procedure. During a 6MWT, healthy subjects can typically walk 400 to 700 m [35,38]. In addition to total distance walked, the magnitude of desaturation and timing of heart rate recovery have been associated with clinical outcomes.

Studies to understand meaningful changes in six-minute walk distances have been conducted in several disease states. While there is some variability based on methods and study population, the available evidence suggests an improvement of approximately 30 m in distance walked is the minimally important difference (MID) [36,39-46]. While pulse oxygen saturation and heart rate are recorded before and after the test, the 6MWT is not designed to be an oxygen titration study, and a separate study should be performed to determine supplemental oxygen needs.

Incremental shuttle walk test — The incremental shuttle walk test (ISWT) is a 12-level test in which the subject walks at a progressively increasing speed for 12 minutes over a 10-meter course, where each 10 m trip between cones is a "shuttle" [47-50]. Heart rate can be monitored by pulse oximetry or telemetry [50]. The walking speed increases every minute from an initial 0.5 m/sec to 2.37 m/sec at level 12. The test is stopped when the subject is limited by dyspnea or heart rate (>85 percent predicted maximum), is unable to maintain the required speed, or completes the 12 levels. The primary outcome is the distance covered, which is calculated from the number of completed shuttles.

The distance walked in the ISWT depends on factors such as age, body mass index, FEV₁, quadriceps strength, and activity status, but reliable predictive equations for normal values have not been developed [49]. As a rough estimate, healthy men were able to achieve the following ISWT distances: age 40 to 49 years, 824 m; 50 to 59 years, 788 m; 60 to 69 years, 699 m; and 70 years and older, 633 m [49,51].

The validity of the ISWT was assessed in a systematic review, which found that the ISWT distance correlated with peak oxygen uptake in subjects with COPD or cardiac disease (r values ranged from 0.67 to 0.95) [47]. In addition, the ISWT distance walked was responsive to pulmonary rehabilitation and bronchodilator administration. The minimal clinically important distance in the ISWT in patients with COPD was 48 meters.

The ISWT is sometimes used as a screening test in the preoperative assessment of patients for lung resection for lung cancer. An ISWT distance greater than 400 meters has been associated with a maximum oxygen uptake (VO₂ max) ≥15 mL/kg per minute [52], indicating sufficient pulmonary reserve to tolerate lung resection surgery. (See "Preoperative physiologic pulmonary evaluation for lung resection", section on 'Integrated cardiopulmonary exercise testing'.)

Endurance shuttle walk test — In the endurance shuttle walk test (ESWT), the subject walks at a constant speed between cones that are 10 meters apart [53]. The subject's speed is selected to be approximately 85 percent of the maximal capacity measured from the ISWT, so an ISWT is needed before the first ESWT [54]. During the ESWT, a pre-recorded audio signal is used to communicate the target speed to the subject. Subjects walk until they are too breathless, too tired, or no longer able to maintain the pace. Generally, the test is stopped at 20 minutes, if the subject is still walking at that time. The primary measure is total time walked with a minimal important difference of 65 seconds or 85 meters following bronchodilation.

Pulse oxygen saturation — Assessment of oxygen saturation can be used to identify a gas transfer defect and to titrate the amount of oxygen needed to maintain adequate oxygenation. (See "Pulse oximetry" and "Long-term supplemental oxygen therapy".)

A clear consensus has not been reached about what value for resting oximetry differentiates normal and abnormal. At sea level, values for pulse oxygen saturation (SpO₂) ≤95 percent are considered abnormal, although a decrease to 96 percent in a patient who has a previous value of 100 percent could be abnormal. Exertional decreases in SpO₂ ≥5 percentage points are also considered abnormal. A value of SpO₂ ≤88 percent is generally an indication for supplemental oxygen, although the benefits of supplemental oxygen in patients with normal resting saturations and exertional decreases to ≤88 percent are unclear [55]. Confirmation of abnormal values with arterial blood gas (ABG) measurements may be indicated.

Arterial blood gases — ABGs are a helpful adjunct to pulmonary function testing in selected patients. The primary role of measuring ABGs in stable outpatients is to confirm hypercapnia when it is suspected on the basis of clinical history (eg, respiratory muscle weakness, advanced COPD), an elevated serum bicarbonate level, and/or chronic hypoxemia. ABGs also provide a more accurate assessment of the severity of gas exchange impairment in patients who have low normal pulse oxygen saturation (eg, <92 percent) [56]. (See "Arterial blood gases" and "Venous blood gases and other alternatives to arterial blood gases" and "Simple and mixed acid-base disorders".)

CLINICAL USE OF PULMONARY FUNCTION TESTS — Pulmonary function testing is useful for evaluation of a variety of forms of lung disease or for assessing the presence of disease in a patient with known risk factors, such as certain rheumatic diseases and occupational exposure to agents with known lung toxicity. The American Thoracic Society advises using a standard report format to improve communication and understanding of test results (figure 3) [17].

Indications — Indications for pulmonary function tests (PFTs) include (table 1):

●Evaluation of symptoms such as chronic persistent cough, wheezing, dyspnea, and exertional cough or chest pain

●Objective assessment of bronchodilator therapy

●Evaluation of effects of exposure to dusts or chemicals at work

●Risk evaluation of patients prior to thoracic or upper abdominal surgery

●Objective assessment of respiratory impairment

●Monitoring disease course and response to therapy

Chronic dyspnea — Many lung diseases begin slowly and insidiously and finally manifest themselves with the nonspecific symptom of dyspnea on exertion. PFTs are an essential part of the workup of such patients. In the outpatient setting, in which several days to weeks are available to make the diagnosis, a cost efficient method of ordering PFTs is to start with spirometry before and after a bronchodilator and then order further tests in a stepwise fashion to refine the diagnosis (algorithm 3). (See "Approach to the patient with dyspnea".)

When a diagnosis is needed within a day or two, a full set of PFTs may be ordered, often including spirometry before and after (pre- and post-) bronchodilator therapy, static lung volumes, and diffusing capacity. If the cause of dyspnea on exertion remains uncertain after these tests have been performed, cardiopulmonary exercise testing should be considered.

Asthma — Spirometry before and after a bronchodilator is indicated during the initial workup of patients suspected of having asthma (algorithm 3). Spirometry is also indicated during most follow-up office visits to provide an objective measure of asthma control [57]. (See 'Spirometry' above and "Asthma in adolescents and adults: Evaluation and diagnosis" and "Pulmonary function testing in asthma".)

Cough or chest tightness with exercise or exposure to cold air, dusts, or fumes suggests bronchial hyperresponsiveness (BHR). However, BHR may not be detected by pre- and post-bronchodilator spirometry if the patient is asymptomatic at the time of evaluation. Commonly, the patient is asked to return for retesting when symptoms occur; however, this delays the diagnosis and may be impractical. Inhalation challenge testing can increase or decrease the pretest probability of asthma in less than an hour. (See "Bronchoprovocation testing" and "Exercise-induced bronchoconstriction".)

An alternative to inhalation challenge testing for the detection of airway hyperreactivity is measurement of airway lability for two weeks in the patient's own environment, using ambulatory monitoring of peak flow. Children with asthma (not controlled by medication) typically demonstrate peak flow lability (amplitude/mean) in excess of 30 percent, while adults with active asthma have peak expiratory flow (PEF) lability greater than 20 percent. (See "Peak expiratory flow monitoring in asthma".)

A forced inspiratory maneuver performed as part of a flow-volume loop may be useful in detecting inducible laryngeal obstruction, also known as vocal fold (or cord) dysfunction or paradoxical vocal fold motion, in patients with a presentation suggestive of asthma who do not respond appropriately to asthma therapy. (See "Evaluation of wheezing illnesses other than asthma in adults" and "Inducible laryngeal obstruction (paradoxical vocal fold motion)".)

Chronic obstructive pulmonary disease — Spirometry before and after an inhaled bronchodilator administration is the best method to detect or confirm airways obstruction in smokers with respiratory symptoms (algorithm 3) [58,59].

In patients with chronic obstructive pulmonary disease (COPD), the forced expiratory volume in one second/forced vital capacity (FEV₁/FVC) ratio and the FEV₁ are decreased. Repeating spirometry after bronchodilator enables assessment of irreversible airflow limitation, which is needed for the diagnosis of COPD. Traditionally, values below 70 percent for the FEV₁/FVC ratio and below 80 percent predicted for the FEV₁ were used to define airflow obstruction. However, several studies suggest that use of fixed thresholds leads to misclassification, particularly in older adults where COPD can be falsely diagnosed [60,61]. Using the fifth percentile lower limit of normal (LLN), or equivalently a z-score <­1.645, instead of a fixed value avoids this misdiagnosis of COPD in older adults, although some argue that the fixed ratio of 0.7 has more clinical relevance [62]. The value for the post-bronchodilator FEV₁ is used to assess COPD severity. (See 'Post-bronchodilator' above and "Office spirometry", section on 'Ratio of FEV1/FVC' and "Chronic obstructive pulmonary disease: Diagnosis and staging", section on 'Diagnosis' and "Chronic obstructive pulmonary disease: Diagnosis and staging", section on 'Assessment of severity and staging'.)

The FEV₁/FVC ratio is typically the value reported and used to assess the presence of airflow obstruction, although FEV₁/slow vital capacity (FEV1/SVC) can also be used and may be more sensitive in detecting airflow obstruction [3].

The gold standard for measurement of total lung capacity (TLC), particularly in the setting of significant airflow obstruction, is body plethysmography. Other methods, such as helium dilution and nitrogen washout, may underestimate the TLC in patients with moderate to severe COPD. As noted above, lung volume measurement may identify air trapping or hyperinflation caused by airflow limitation. A concomitant restrictive ventilatory defect is detected in less than 10 percent of patients with a reduced FVC [63]. (See "Chronic obstructive pulmonary disease: Diagnosis and staging".)

Once the diagnosis of COPD is established, the course and response to therapy may be followed by observing changes in the FEV₁, as was done in the multicenter Lung Health Study [64]. Continued smoking in a patient with airways obstruction often results in an abnormally rapid decline in FEV₁ (90 to 150 mL/year). On the other hand, smoking cessation often results in an increase in FEV₁ during the first year, followed by a nearly normal rate of FEV₁ decline (20 to 30 mL/year) [65]. Both a low FEV₁ and chronic mucus hypersecretion are predictors of hospitalization due to COPD [66].

Once the airways obstruction due to COPD has become very severe, with an FEV₁ z-score of <-4, changes from visit to visit are usually within the error of the measurement (0.2 L). In this circumstance, measurements of pulse oxygen saturation (SpO₂) during exercise and distance walked during six minutes may be more clinically meaningful for evaluating disease progression or therapeutic response than are changes in spirometry values [4,67].

Measurement of the diffusing capacity for carbon monoxide (DLCO) helps to distinguish between emphysema and other causes of chronic airway obstruction and has been shown to improve assessment of patients with COPD [68]. As an example, emphysema lowers the DLCO, obstructive chronic bronchitis does not affect the DLCO, and asthma sometimes increases the DLCO. Changes in the DLCO in patients with established, smoking-related COPD are probably not clinically useful during follow-up visits, unless dyspnea suddenly worsens without an obvious cause. (See "Diffusing capacity for carbon monoxide".)

Upper airway obstruction — Intrathoracic upper airway obstruction can be either fixed (eg, due to an airway stricture or goiter) or variable (eg, tracheomalacia, tracheal tumors). Fixed intrathoracic obstruction is associated with reduced airflow during expiration and inspiration with flattening of both limbs on the flow-volume loop (figure 1). Variable intrathoracic obstruction is associated with flow limitation during forced expiration, but not during inhalation. (See "Flow-volume loops".)

Extrathoracic upper airway obstruction can also be fixed or variable. When fixed, the pattern looks like fixed intrathoracic upper airway obstruction and flow is limited during inspiration and expiration. When variable, the inspiratory portion of the loop shows flow limitation and flattening (figure 1). (See "Flow-volume loops", section on 'Abnormal inspiratory loop'.)

Restrictive ventilatory defect — The many disorders that cause reduction of lung volumes (restriction) may be divided into three groups:

●Intrinsic lung diseases, which cause inflammation or scarring of the lung tissue (interstitial lung disease) or fill the airspaces with exudate or debris (acute pneumonitis)

●Extrinsic disorders, such as disorders of the chest wall or the pleura, which mechanically compress the lungs or limit their expansion

●Neuromuscular disorders, which decrease the ability of the respiratory muscles to inflate and deflate the lungs

The history, physical examination, and chest radiograph are usually helpful in distinguishing among these disorders. Spirometry can be useful in detecting restriction of lung volumes, meaning a reduced FEV₁ and/or FVC with a normal or increased FEV₁/FVC ratio. Evaluation of lung volumes and diffusing capacity are helpful in confirming the presence of restriction and assessing severity of impaired gas exchange (algorithm 1). However, patients with mild interstitial lung disease (ILD) may have normal values for FVC and TLC [69].

In ILD, the DLCO is decreased by diffuse alveolar capillary damage, and the measured alveolar volume (VA) is low due to the loss of aerated alveoli. The DLCO divided by alveolar volume (DLCO/VA, also known as KCO) is typically reduced to a lesser extent than the DLCO, as ILD is typically inhomogeneous with some diversion of blood flow from more diseased units to those that are less affected [31,70]. By comparison, in patients with restrictive physiology due to incomplete lung expansion (eg, neuromuscular disease or kyphoscoliosis), the DLCO is less decreased, and the reduction in DLCO is proportionately less than the reduction in VA, so the ratio DLCO/VA is actually increased. (See "Diffusing capacity for carbon monoxide", section on 'Relationship between DLCO and KCO (DLCO/VA)'.)

Changes in the FVC and DLCO are also useful for following the course of or response to therapy in patients with interstitial lung disease. Measurement of SpO₂ during a six-minute walk test (6MWT) is also useful in this setting, since SpO₂ often falls during mild exercise in patients with interstitial lung disease and responds to successful therapeutic interventions [71]. (See 'Six-minute walk test' above and "Approach to the adult with interstitial lung disease: Diagnostic testing".)

Pulmonary vascular disease — In pulmonary vascular disease (eg, thromboembolic disease or pulmonary arterial hypertension) not due to COPD or ILD, the DLCO is typically reduced due to impairment of gas exchange at the alveolar-capillary interface. Testing for desaturation with exercise oximetry can provide additional evidence of pulmonary vascular disease. (See "Diffusing capacity for carbon monoxide", section on 'Interpretation'.)

Preoperative testing — Spirometry is useful for determining the risk of postoperative pulmonary complications in certain high-risk situations, including patients known to have COPD or asthma, current smokers, and those scheduled for thoracic or upper abdominal surgery [72]. The degree of airways obstruction predicts the risk of postoperative pulmonary complications, such as atelectasis, pneumonia, and the need for prolonged mechanical ventilation. If spirometry demonstrates moderate to severe obstruction and the surgery can be delayed, a prophylactic program of pulmonary hygiene, including smoking cessation, inhaled bronchodilators or glucocorticoids, and possibly antibiotics for bronchitis, will reduce the risk. However, the results of spirometry alone should not be used to deny surgery. Combining the results of spirometry with radioisotope or CT lung scans is also useful for predicting the remaining lung function following a lobectomy or pneumonectomy. (See "Evaluation of perioperative pulmonary risk", section on 'Preoperative risk assessment' and "Preoperative physiologic pulmonary evaluation for lung resection".)

Evaluation of patients being considered for lung resection begins with spirometry and DLCO. If either of these tests is ≤80 percent of predicted, further testing is generally needed to calculate predicted postoperative lung function. A number of studies indicate that the maximum oxygen uptake (absolute value, or as a percent of predicted), determined by cardiopulmonary exercise testing, is better than spirometry for predicting postsurgical complications [73], but the cost:benefit ratio is unknown. (See "Preoperative physiologic pulmonary evaluation for lung resection".)

Respiratory impairment and disability assessment — Most schemes for evaluation of respiratory impairment use spirometry and DLCO, but the results in studies performed at rest are only a rough indication of an individual's ability to perform a given job. It is ideal to measure maximal oxygen consumption (VO₂ max), but cardiopulmonary exercise testing is often not available to the primary care physicians who perform "disability" testing, or the expense is not reimbursed. (See "Evaluation of pulmonary disability".)

The American Medical Association provides guidelines for the classification of respiratory impairment based upon the results of clinical evaluation, spirometry, DLCO, and cardiopulmonary exercise testing, if available. These guidelines are described separately. (See "Evaluation of pulmonary disability", section on 'Calculating the permanent impairment rating'.)

The Social Security Administration, Department of Veterans' Affairs in the United States, and United States Department of Labor have slightly different criteria for assessment of disability. (See "Evaluation of pulmonary disability" and "Evaluation of pulmonary disability", section on 'Other systems'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pulmonary function testing".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Breathing tests (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Overview – Pulmonary function testing is indicated for evaluation of respiratory symptoms (eg, cough, wheezing, dyspnea, chest pain), response to bronchodilator therapy, effect of workplace exposure to dust or chemicals, and pulmonary disability (algorithm 3). It can also be used to assess severity and progression of lung diseases, such as asthma, chronic obstructive lung disease, and various restrictive diseases. (See 'Introduction' above.)

The major types of pulmonary function tests (PFTs) include spirometry, spirometry before and after bronchodilator, lung volumes, and diffusing capacity (table 1). Other PFTs include flow-volume loops (which record forced inspiratory and expiratory flow rates), measurements of maximal respiratory pressures, and the six-minute walk test. (See 'Pulmonary function tests' above.)

●Spirometry – Forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) are the primary measurements obtained by spirometry (algorithm 1). Their ratio (FEV₁/FVC) is important for distinguishing obstructive airways disease and restrictive disease. A reduced ratio suggests obstructive airway disease. A reduced FVC in combination with a normal or increased ratio suggests restrictive disease, if accompanied by reduced lung volumes. (See 'Spirometry' above.)

●Flow-volume loops – Flow-volume loops with maximal inspiratory and expiratory data can identify upper airway obstruction, which can be undetectable with standard expiratory measurements. A characteristic limitation of flow (ie, a plateau) during forced inhalation suggests variable extrathoracic obstruction, while limitation of flow during forced exhalation suggests variable intrathoracic obstruction (figure 1). Fixed upper airway obstruction causes flow limitation during both forced inhalation and forced exhalation. (See "Flow-volume loops".)

●Bronchodilator response – When airflow limitation is noted on spirometry or when obstructive disease is suspected, the test is repeated after inhaled bronchodilator to detect bronchodilator responsiveness. An increase in the FEV₁ or FVC of more than 10 percent of their respective predicted values suggests bronchodilator responsiveness; full return to normal values for FEV₁ and FEV₁/FVC suggests asthma. Partial improvement is consistent with asthma, COPD, or bronchiolitis. The lack of a bronchodilator response should not preclude a therapeutic trial of bronchodilators and/or inhaled glucocorticoids. (See 'Post-bronchodilator' above.)

●Lung volumes – Measurement of lung volumes complements spirometry (algorithm 1). Common measurements include total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV) (figure 2). Decreased lung volumes suggest restrictive disease if accompanied by a normal or increased FEV₁/FVC ratio. Increased lung volumes suggest static hyperinflation due to obstructive airways disease if accompanied by decreased FEV₁/FVC ratio. Coexisting restriction and obstruction can be identified when the TLC and FEV₁/FVC ratio are reduced. (See 'Lung volumes' above.)

●Tests of muscle strength – Measurement of maximal inspiratory and expiratory pressures detects respiratory muscle weakness. Maximal inspiratory pressure (MIP) is the maximal pressure that can be produced by the patient trying to inhale through a blocked mouthpiece. Maximal expiratory pressure (MEP) is the maximal pressure measured during forced expiration through a blocked mouthpiece after a full inhalation. (See 'Maximal respiratory pressures' above and "Tests of respiratory muscle strength".)

●Diffusing capacity of the lung for carbon monoxide (DLCO) – Measurement of DLCO assesses gas exchange. A decreased DLCO accompanied by restrictive disease suggests intrinsic lung disease, whereas a normal DLCO accompanied by restrictive disease suggests a nonpulmonary cause of restriction. A decreased DLCO accompanied by obstructive airways disease suggests emphysema. A reduced DLCO with normal lung volumes suggests possible pulmonary vascular disease (table 2). (See 'Diffusing capacity' above and "Diffusing capacity for carbon monoxide".)

●Grading physiologic impairment – Physiologic impairment should preferably be assessed based on z-score, instead of percent predicted value, because this scale helps avoid age, sex, and height bias and is closely associated with important clinical outcomes. FEV₁ is the primary measure used to grade the physiologic severity of obstructive or mixed obstructive-restrictive processes (algorithm 2). We prefer to use TLC z-score to grade severity of restriction; however, FEV₁ may be used as an alternative to grade previously confirmed restriction if lung volumes or z-scores are not available.

●Submaximal exercise tests – Submaximal exercise testing can help in the evaluation of dyspnea and exercise intolerance. Three commonly used tests are the six-minute walk test (6MWT), the incremental shuttle walk test, and the endurance shuttle walk test. The 6MWT provides information about the distance walked and exertional desaturation when combined with pulse oximetry (table 4). (See 'Submaximal exercise testing' above.)

●Pulse oxygen saturation (SpO₂) – Assessment of SpO₂ at rest or with exertion can be used to identify a gas exchange defect and to titrate the amount of oxygen needed to maintain adequate oxygenation. A clear consensus has not been reached about the value for resting oximetry that differentiates normal and abnormal. At sea level, values for SpO₂ ≤95 percent are generally considered abnormal, although a decrease to 96 percent in a patient who has a previous value of 100 percent could be abnormal. Exertional decreases in SpO₂ ≥5 percentage points are also considered abnormal. (See 'Pulse oxygen saturation' above and "Pulse oximetry".)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Paul Enright, MD, who contributed to earlier versions of this topic review.