Pulmonary Medicine

Pulmonary Function Testing

General description of procedure, equipment, technique

Pulmonary function testing refers to a battery of routinely performed lung function tests that include spirometry, lung volumes, and diffusing capacity.

Spirometry is one of the most commonly ordered tests of pulmonary function. The word "spirometry," is derived from the Latin, spiro, meaning "to breathe," and the Greek, metron, meaning "to measure." Spirometry, which can be performed either in specialized pulmonary function laboratories or in physicians' offices, measures airflow during forceful exhalation. Results are used primarily in distinguishing obstructive from restrictive lung diseases and in quantifying the degree of lung dysfunction.

Lung volume testing measures individual components of lung volumes, rather than airflow (Figure 1). One of three basic techniques--nitrogen helium dilution, or body plethysmography--may be used to measure lung volumes. Assessment begins with the measurement of functional residual capacity (FRC), which is the end-expiratory or resting lung volume. Once the FRC is known, expiratory reserve volume (ERV), vital capacity (VC), and inspiratory capacity (IC) are determined, and total lung capacity (TLC) and residual volume (RV) are calculated.

Figure 1.

Lung volume components. Vital Capacity (VC), Inspiratory Reserve Volume (IRV), Tidal Volume (Vt), Expiratory Reserve Volume (ERV), Reserve Volume (RV), Inspiratory Capacity (IC), Functional Residual Capacity (FRC) and Total Lung Capacity (TLC). The TLC and RV are calculated from the other measured components.

Diffusing capacity (DLCO) provides information on the efficiency of gas transfer from alveolar air into the bloodstream. The transfer is affected by a multitude of factors, including alveolar membrane thickness, surface area for gas exchange, and red blood cell uptake of the tracer gas (carbon monoxide, CO) used in the test. Additional determinants include hemoglobin concentration, hemoglobin affinity for CO, and red blood cell flow through the lung. Consequently, DLCO should be viewed as parameter that is affected by many pathological processes.

The combination of spirometry, lung volumes, and DLCO may be useful in the diagnosis of lung disorders and in assessing their severity over time and their response to treatment. The routine battery of pulmonary function tests described here may be supplemented with more specialized tests of lung function when clinically indicated. (See "Specialized Tests of Pulmonary Function.")

Indications and patient selection

Common indications for pulmonary function testing include:

  • Evaluation of respiratory complaints, such as cough and dyspnea

  • Assessment and monitoring of disease severity and progression

  • Monitoring for drug toxicity and efficacy

  • Pre-operative assessment

  • Evaluation of the effects of occupational or hazardous exposures

  • Participation in epidemiologic surveys

Because spirometry requires active patient participation, the patient must be cooperative and able to follow requests of the pulmonary technician. Because of stringent test performance criteria, many ill patients may not be able to complete the tests adequately. While lung volume testing is less dependent on maximal patient effort than is spirometry, the patient must be cooperative and be able to follow comparatively complex commands. In addition, assessment of lung volumes and DLCO necessitates that patients be off supplemental oxygen; hence, those with significant hypoxemia at rest may not be able to complete the testing. In addition, patients with very small lung volumes may not be able to perform DLCO testing because a fixed volume of the initial exhalation is discarded. With a small lung volume and a fixed-volume discard, insufficient lung volume may be left with which to make a reliable measurement.

Contraindications

There are few absolute contraindications to pulmonary function testing, but several conditions should raise the level of caution in conducting the tests that may adversely affect results. Pain, nausea, subjective discomfort, or altered mental status is likely to lead to unreliable results. American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines suggest that spirometry be terminated if sequential maneuvers demonstrate a 20 percent or greater decrease in either the forced expiratory volume in one second (FEV1) or forced vital capacity (FVC).

Although there is a theoretical concern about transmission of infection to patients, including immunocompromised patients, maintenance of proper hygiene and proper handling of equipment minimize the risk.

Details of how the procedure is performed

Spirometry

Spirometry testing is performed with the patient seated or standing. The patient should wear comfortable, non-restrictive clothing and avoid vigorous exercise or ingestion of a large meal just prior to the test. Inhaled bronchodilators and other pulmonary-related medications are held or continued at the discretion of the clinician ordering the test. Age, height, weight, gender, and race/ethnicity should be recorded to allow for calculation of reference values.

The FVC maneuver has three phases: inhalation, the initial “blast” phase of exhalation, and completion of exhalation (Figure 2). The patient is instructed to inhale maximally and then to exhale immediately by “blasting” the breath out. The patient is coached to continue exhalation until airflow is no longer recorded and a minimum of six seconds has elapsed since initiation of the test. Application of a nose clip or manual occlusion of the nostrils is recommended.

Figure 2.

Technique for performing forced exhalation maneuver. The subject starts with tidal breathing and, when ready, inhales maximally and rapidly. Forced exhalation begins with a “blast” and continues until plateau is seen on the volume-time curve or the patient is unable to continue.

ATS/ERS guidelines have determined specific criteria for the start and end of the test. Since much of the test interpretation relies on the exhaled volume during the first second (FEV1), a valid "time zero" is crucial for accurate measurement; patient hesitation or a slow start may lead to inaccuracy. The test's end is determined as the point at which the patient can no longer exhale or when the patient stops exhalation because of discomfort. There should be no change in volume for at least one second, evident as a plateau in the volume-time curve, and exhalation should last at least six seconds for patients ten years old or older.

ATS/ERS have outlined criteria for test acceptability (Table 1), including a satisfactory start and end of the test. The subject must understand the instructions and perform with maximal effort, including maximal inhalation and smooth exhalation, without interruptions from cough or Valsalva maneuver (glottic closure). For an adequate test, the subject should perform at least three acceptable maneuvers. Although some circumstances warrant more maneuvers, eight consecutive attempts are a practical upper limit for most subjects. In addition to three acceptable maneuvers, at least two of these efforts must be repeatable; results are repeatable when there is a difference of no more than 0.15L between the largest and next-largest FVC and between the largest and next-largest FEV1. In patients who have an FVC of 1L or less, a difference of 0.10L or less is used. The largest values for both FEV1 and FVC, whether or not they are from the same attempt, are reported as the test result.

Table 1.

Acceptability criteria (adapted from Miller et al)

The response to inhaled bronchodilators may be assessed by repeating the FVC maneuver following drug administration. According to ATS/ERS guidelines, four puffs of any acute bronchodilator (e.g., Albuterol or Ipratropium) may be administered by metered dose inhaler (MDI), or an equivalent dose may be delivered via a nebulizer. The study is repeated after fifteen minutes. Once again, three acceptable maneuvers, with at least two repeatable measurements, are obtained, and the highest FVC and FEV1 are reported.

Spirometry is associated with many potential sources of error and variability, so scrupulous care must be exercised in its performance. Factors related to equipment, the environment, and the operators play roles. Quality control, regular maintenance, and equipment calibration help eliminate errors attributable to faulty equipment. Patient coaching through explanation, demonstration of the technique, and enthusiastic encouragement while the patient is performing the maneuver are essential to obtaining accurate results. Training workshops in coaching technique are especially important for staff that conduct testing in primary care practices, as such workshops increase the percentage of tests that meet ATS/ERS criteria for acceptability and repeatability.

Lung Volumes

Two of the three techniques used to measure lung volumes--helium dilution and nitrogen washout--are based on the principle of conservation of mass: [initial gas concentration] x [initial volume of the system] = [final gas concentration] x [final volume of the system]

In the helium dilution method, a known volume and concentration of helium are added to the patient's respiratory system. Helium, which is inert and is not absorbed significantly from the lungs, is diluted in proportion to the lung volume to which it is added. The final concentration of helium is then measured and the conservation of mass equation solved for the initial volume of the system, which is FRC.

The nitrogen washout method is based on the fact that nitrogen is present in the air we breathe. The patient is given 100 percent oxygen to breathe, and the expired gas, which contains nitrogen in the lung at the beginning of the test, is collected. When no more nitrogen is noted in the expirate, the volume of air expired and the entire amount of nitrogen in that volume are measured. The amount of nitrogen in ambient air is assumed to be relatively constant. With three of the four components of the conservation of mass equation in hand, the initial volume of the system (FRC) can be calculated.

Body plethymography (also known as the "body box" method) for determining lung volumes is based on Boyle’s law, which dictates that the product of the pressure and volume of a gas is constant at a constant temperature. The patient is placed in an air-tight box that incorporates a pressure transducer and a pneumotachograph to measure airflow. At the end of quiet expiration, a shutter on the pneumotach is closed, and the patient is asked to pant against the closed circuit. Pressure changes at the mouth (which, in a closed system, equals alveolar pressure) and in the box are measured. Based upon measurements of changes in pressure and volume, the initial lung volume (FRC) can be calculated.

The helium dilution method, the nitrogen washout method, and the body plethymography method each have advantages and disadvantages. The two techniques that are based on gas equilibration may underestimate lung volumes in patients with advanced airways obstruction because equilibration may take a long time. Plethysmography is fast and allows for repetitive measurements in quickly assessing the reproducibility of results, and the results do not vary with the severity of underlying airway obstruction. However, since plethysmography measurements are based on all gas in the chest, large bullae or hiatal hernias may be included in lung volume estimates. Furthermore, plethysmographs are expensive, and some patients cannot tolerate plethysmography because of their body size, skeletal abnormalities, or claustrophobia.

Diffusing Capacity

Diffusing capacity (DLCO) is most commonly measured using the single-breath technique. The patient takes a full inspiration of a gas mixture containing 0.3 percent carbon monoxide and 10 percent helium (the dilution of which provides an index of lung or "alveolar" volume). After a ten-second breath-hold, the patient exhales. The first portion of the exhaled breath, which is composed of dead-space ventilation, is discarded, and the next liter is collected and analyzed. The difference between the original and final concentrations of carbon monoxide is assumed to represent the gas transported across the lung alveolar surface and to reflect the diffusion capacity.

Interpretation of results

Interpreting pulmonary function test results is a multi-step process of assessing the adequacy of the study, comparing the results to an appropriate reference standard, defining the pattern of abnormality, determining the degree of abnormality, assessing response to bronchodilators, and evaluating changes in measurements over time (Figure 3).

Figure 3.

AIS/ERS Algorithm for Interpreting PFTs

Spirometry and Lung Volumes

Assuming the test is adequate, the use of appropriate reference standards is critical. ATS/ERS recommend using NHANES III in the United States as the spirometry reference standard. Each laboratory should ensure that the race/ethnicity of the subjects tested is represented in the reference population. Furthermore, because reference values often derive from populations with few members at the extremes of age and size, use of appropriate standards for the elderly, the very young, the very small, and the very tall can be problematic. Finally, geographic considerations, such as urban versus suburban populations or high-altitude versus low-altitude dwelling, may significantly impact the comparability of reference populations.

The most recent (2005) ATS/ERS guidelines recommend an interpretation algorithm that differs from prior schemes (Figure 4). The most notable changes are the use of a lower limit of normal (LLN) based on normal value distributions, rather than a fixed cutoff of percent predicted, and the use of vital capacity (VC), rather than forced vital capacity (FVC), as the denominator of the term, FEV1/VC, to determine the presence of obstruction. The use of LLN is believed to do a better job of incorporating age-related changes in spirometry, while the use of VC is thought to be more sensitive in diagnosing obstruction. LLN is defined as the fifth percentile of the normal population for a particular age, height, gender, and race. VC is defined as the largest of the measurements of FVC, slow vital capacity (SVC), and the forced inspiratory vital capacity (FIVC).

Figure 4.

Steps for Interpreting PFTs.

Alternately, the method espoused by the Global Initiative on Obstructive Lung Disease (GOLD) for the diagnosis of obstruction is based on a fixed cut-off of 0.70 for the post-bronchodilator FEV1/FVC. Both approaches have limitations, the most important among them being that spirometry values must be interpreted in clinical context.

Once the nature of the abnormality has been defined (typically as obstructive or restrictive), its severity is determined. According to ATS/ERS guidelines, the level of severity is defined by the reduction in percent of predict FEV1 for both obstruction and restriction. Obstruction is considered bronchodilator-responsive if, following the administration of bronchodilator, there is an increase of at least 12 percent in FEV1 or FEV and an absolute increment of at least 200cc.

Serial pulmonary function testing over time has demonstrated significant variation in spirometry, both in normals and in patients with pulmonary disease. The variability is due to the complex requirements of the tests, variations of the disease state in individuals (e.g., diurnal variation), and the inherent error of the machines employed in an effort-dependent test. Therefore, defining "significant change" in results is challenging.

In this regard, a conservative approach, which is supported by ATS/ERS guidelines, is to consider a significant a change of at least 15 percent and 200cc. However, the clinician must consider the clinical context. For instance, a change of 10 percent over two months following a hospitalization for pneumonia is likely to be important, even though the change falls short of the 15 percent mark.

DLCO

Many pathologic conditions are associated with changes in DLCO [Table 2]. Since DLCO is affected by the lung surface area available for gas diffusion, any condition that reduces the number of functioning alveolar units lowers the DLCO. Examples include prior lobectomy, cystic lung disease, pulmonary consolidation, atelectasis, pulmonary fibrosis, and alveolar filling processes (e.g., pulmonary edema).

Table 2.

Conditions Associated with Alterations in Diffusing Capacity

Incomplete expansion of alveoli secondary to muscle weakness or chest wall abnormalities, and uneven distribution of the inspired helium and CO gas mixture used in the test as a result of airway obstruction also reduces DLCO. Changes in pulmonary blood flow may reduce the surface area available for gas exchange. Therefore, loss of the pulmonary microvasculature, as seen in emphysema or pulmonary fibrosis, or changes in blood volume, may affect DLCO. In addition, increased membrane thickness, like that which occurs in interstitial lung disease or pulmonary edema may also reduce DLCO.

An elevated DLCO is usually associated with circumstances in which more hemoglobin-binding sites for CO available; such circumstances include the presence of polycythemia, alveolar hemorrhage, and increased pulmonary blood flow. Obesity and asthma have also been associated with elevations in DLCO.

Although abnormalities in DLCO occur most often in conjunction with impairments in pulmonary mechanics, they may also occur in isolation. If the patient does not have anemia or an elevated carboxyhemoglobin level, an isolated reduction in DLCO suggests loss of the pulmonary capillary bed from pulmonary vascular disease (e.g., pulmonary emboli or pulmonary hypertension) or an early parenchymal lung disease that has not yet affected lung volumes or spirometry.

Measurement of DLCO is particularly useful in assessing patients at risk for desaturation with exercise, who would benefit from additional testing. The test may also be useful in making distinctions within a pathophysiologic group of disorders. For example, obstruction associated with a reduced DLCO is more likely to be due to COPD than to asthma.

DLCO has more inherent variability over time than other pulmonary function tests do. Several well-established causes of fluctuations in DLCO, other than changes in lung function, include increased depth of inspiration during the test, exercise, changes in altitude, and changes in hemoglobin concentration. Elevations in carboxyhemoglobin reduce DLCO by limiting the available CO-binding sites and by increasing the "back pressure" for CO diffusion. Measured values for DLCO in heavy smokers or those exposed to heavy exhaust may be spuriously low because of elevated CO levels. A conservative approach to interpreting serial measurements of DLCO over time is to consider significant a change of at least 10percent and 3 units.

In addition to encompassing single, numerical measurements of flow, such as FEV1 or FVC, contemporary spirometry measurements yield graphic depictions of flow over time. These flow-volume loops provide additional insight into both test quality and the underlying disease process (Figure 5). In addition to evaluating rates of flow, flow-volume loops should be inspected as part of interpreting the pulmonary function test.

Figure 5.

Idealized flow volume loops Top panel: (A) Normal flow volume loop, (B) flow volume loop demonstrating obstruction, (C) Flow volume loop typically seen in restriction Lower panel (A) Normal flow volume loop (B) flow volume loop seen in variable intra-thoracic obstruction (C) flow volume loop seen in variable extrathoracic obstruction (D) flow volume loop of fixed central obstruction.

Performance characteristics of the procedure

Spirometric results from multiple studies reveal an association with mortality from both respiratory and non-respiratory causes. A longitudinal survey from the 1970s of more than fifteen thousand adults in Scotland demonstrated that relative FEV1 correlated with all-cause mortality, as well as with death from ischemic heart disease, cerebrovascular disease, lung cancer, and respiratory disease, when controlled for age, smoking history, blood pressure, body mass index (BMI), cholesterol, social class, and respiratory symptoms. Thus, significant correlations were also present in lifelong non-smokers and in individuals who had no respiratory symptoms.

Other studies have shown that FEV1 predicts respiratory or overall mortality; whether this finding reflects an association or causality remains unclear. Based on these results, some experts recommend routine screening for airflow obstruction.

Since spirometric results do not significantly increase smoking cessation rates, the United States Preventive Services Task Force (USPSTF) does not recommend spirometry for COPD screening.

Outcomes (applies only to therapeutic procedures)

Not applicable.

Alternative and/or additional procedures to consider

For some patients, cardiopulmonary exercise testing (CPET may provide additional diagnostic information in the evaluation of dyspnea.

Complications and their management

Complications of pulmonary function testing are rare.

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