Pulmonary Function and Related Tests

Lori A. Wilken; Min J. Joo

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Cover Basic Skills in Interpreting Laboratory Data

Pulmonary Function and Related Tests

in Basic Skills in Interpreting Laboratory Data

Authors: Lori A. Wilken and Min J. Joo

DOI:: https://doi.org/10.37573/9781585286423.014

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OBJECTIVES

After completing this chapter, the reader should be able to

Identify common pulmonary function tests and list their purpose and limitations
Describe how pulmonary function tests are performed and discuss factors affecting the validity of the results
Interpret commonly used pulmonary function tests, given clinical information
Discuss how pulmonary function tests provide objective measurement to aid in the diagnosis of pulmonary diseases
Discuss how pulmonary function tests assist with monitoring efficacy and toxicity of various drug therapies

Pulmonary function tests (PFTs) provide objective and quantifiable measures of lung function and are useful in diagnosing, evaluating, and monitoring respiratory disease. Diagnosing and monitoring many pulmonary diseases, including diseases of gas exchange, often require measuring the flow or volume of air inhaled and exhaled by the patient. Spirometry, a test that measures the movement of air into and out of the lungs during various breathing maneuvers, is the most frequently used PFT. Clinicians use spirometry to aid in the diagnosis of respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Other tests of lung function include lung volume assessment, carbon monoxide diffusion capacity (DLCO), exercise testing, and bronchial provocation tests. Arterial blood gases (ABGs) can be measured with PFTs and are useful for assessing lung function. (Interpretation of arterial blood gases is discussed in Chapter 13.) This chapter discusses the mechanics and interpretation of PFTs.

ANATOMY AND PHYSIOLOGY OF LUNGS¹

The purpose of the lungs is to take oxygen from the atmosphere and exchange it for carbon dioxide in the blood. The movement of air in and out of the lungs is called ventilation; the movement of blood through the lungs is termed perfusion.

Air enters the body through the mouth and nose and travels through the pharynx to the trachea. The trachea splits into the left and right main stem bronchi, which deliver inspired air to the respective lungs. The left and right lungs are in the pleural cavity of the thorax. These two spongy, conical structures are the primary organs of respiration. The right lung has three lobes, whereas the left lung has only two lobes, thus leaving space for the heart. Within the lungs, the main bronchi continue to split successively into smaller bronchi, bronchioles, terminal bronchioles, and finally alveoli. In the alveoli, carbon dioxide is exchanged for oxygen across a thin membrane separating capillary blood from inspired air.

The thoracic cavity is separated from the abdominal cavity by the diaphragm. The diaphragm, a thin sheet of dome-shaped muscle, contracts and relaxes during breathing. The lungs are contained within the rib cage but rest on the diaphragm. Between the ribs are two sets of intercostal muscles, which attach to each upper and lower rib. During inhalation, the intercostal muscles and the diaphragm contract, which enlarges the thoracic cavity. This action generates a negative intrathoracic pressure, allowing air to rush in through the nose and mouth down into the pharynx, trachea, and lungs. During exhalation, these muscles relax, and a positive intrathoracic pressure causes air to be pushed out of the lungs. Normal expiration is a passive process that results from the natural recoil of the expanded lungs. However, in people with rapid or labored breathing or airflow limitation, the accessory muscles and abdominal muscles often must contract to help force air out of the lungs more quickly or completely.

The ability of the lungs to expand and contract to inhale and exhale air is affected by the compliance of the lungs, which is a measure of the ease of expansion of the lungs and thorax. Processes that result in scarring of lung tissue (eg, pulmonary fibrosis) can decrease compliance, thus decreasing the flow and volume of air moved by the lungs, and increase the work to breathe. The degree of ease in which air travels through the airways is known as resistance. The length and radius of the airways as well as the viscosity of the gas inhaled determine resistance. A patient with a high degree of airway resistance may not be able to take a full breath in or exhale fully (some air may become trapped in the lungs).

To have an adequate exchange of the gases, there must be a matching of ventilation (V) and perfusion (Q) at the alveolar level. An average V:Q ratio, determined by dividing total alveolar ventilation (4 L/min) by cardiac output (5 L/min), is 0.8. A mismatch of ventilation and perfusion may result from a shunt or dead space. A shunt occurs when there is flow of blood adjacent to alveoli that are not ventilated. This could be physiologic (eg, at rest, some alveoli are collapsed or partially opened but perfused) or pathologic when alveoli are filled with fluid (eg, heart failure) or cellular debris (eg, pneumonia) or are collapsed (eg, atelectasis). A shunt can also occur when airways are obstructed by mucus or collapse on exhalation (eg, COPD). In a shunt, blood moves from the venous circulation to the arterial circulation without being oxygenated.

Dead space occurs when there is ventilation of functional lung tissue without adjacent blood flow for gas exchange. Dead space can be physiologic (eg, the trachea) or pathologic because of airflow limitation of blood flow (eg, pulmonary embolism). The body uses a few mechanisms to normalize the V:Q ratio, such as hypoxic vasoconstriction and bronchoconstriction. When the V:Q ratio is low, hypoxic vasoconstriction leads to decreased perfusion to the hypoxic regions of the lungs, thus redirecting perfusion to functional areas of the lungs, which leads to an increase in the V:Q ratio. When the V:Q ratio is high, the bronchi constrict in areas that are not well perfused, which leads to a decrease in the amount of ventilation to areas that are not well perfused, a decrease in the amount of alveolar dead space, and a decrease in the V:Q ratio.

For the respiration process to be complete, gas diffusion must occur between the alveoli and the pulmonary capillaries. By the diffusion mechanism, gases equilibrate from areas of high concentration to areas of low concentration. Hemoglobin (Hgb) releases carbon dioxide and adsorbs oxygen as it diffuses through the alveolar walls. If these walls thicken, diffusion is hampered, potentially causing carbon dioxide retention, hypoxia, or both. Membrane formation with secondary thickening of the alveolar wall may result from an acute or chronic inflammatory process such as interstitial pneumonia and pulmonary fibrosis. The pulmonary diffusing capacity is also reduced in the presence of a V:Q mismatch, loss of lung surface areas (eg, emphysema, lung resection), or decrease in oxygen-carrying capacity (eg, anemia). The various PFTs can measure airflow in or out of the lungs, indicate how much air is in the lungs, and provide information on gas diffusion or specific changes in airway tone or reactivity.

CLINICAL USE OF PULMONARY FUNCTION TESTING

Pulmonary function tests are useful in many clinical situations.² They aid in the diagnostic differentiation of various pulmonary diseases. PFT results are divided into two types of pulmonary abnormalities: obstructive and restrictive lung diseases. Obstructive diseases (eg, asthma and COPD) decrease the flow rate of air (liters/minute) out of the lungs but have less impact on the total volume of air per breath. In restrictive diseases (eg, kyphosis or sarcoidosis), the lungs are limited in the amount of air they can contain. Restrictive diseases usually decrease the total volume of air per breath in a similar ratio to the flow rate of air. Table 14-1 summarizes common pulmonary disease states with PFT results.

TABLE 14-1.

Pulmonary Disease States and Common PFT Results

PULMONARY ABNORMALITY	PATHOPHYSIOLOGY	DISEASE STATE EXAMPLES	COMMON PFT RESULTS
PULMONARY ABNORMALITY	PATHOPHYSIOLOGY	DISEASE STATE EXAMPLES	FEV₁/FVC	FEV₁	FVC	RV	TLC
Obstructive lung disease, chronic	Fixed airflow limitation	Asthma with fixed airflow limitation, COPD, cystic fibrosis, bronchiectasis	Decreased	Decreased	Normal or decreased	Normal or increased	Normal or increased
Obstructive lung disease, reversible and stable	Reversible (eg, bronchoconstriction)	Asthma	Normal	Normal	Normal	Normal	Normal
Restrictive lung disease	Parenchymal infiltration or fibrosis	Idiopathic pulmonary fibrosis and other idiopathic interstitial pneumonias, drug induced, secondary to autoimmune diseases, sarcoidosis	Normal or increased	Decreased	Decreased	Decreased	Decreased
	Extrathoracic compression	Kyphosis, morbid obesity, ascites, chest wall deformities, pregnancy	Normal or increased	Decreased	Decreased	Decreased	Decreased
	Neuromuscular causes	Guillain-Barré syndrome, myasthenia gravis, muscular dystrophy, amyotrophic lateral sclerosis	Normal or increased	Decreased	Decreased	Decreased	Decreased
Mixed obstructive and restrictive	Combinations of restrictive and obstructive processes	Both restrictive and obstructive diseases	Decreased	Decreased	Decreased	Increased, normal, or decreased	Decreased

FEV₁ = forced expiratory volume in 1 second; FVC = forced vital capacity; RV= residual volume; TLC = total lung capacity

In addition, serial PFTs allow tracking of the progression of pulmonary diseases and the need for or response to various treatments. They also help to establish a baseline of respiratory function before surgical, medical, or radiation therapy. Subsequent serial measurements then aid in the detection and tracking of changes in lung function caused by these therapies. Similarly, serial PFTs can be used to evaluate the risk of lung damage from exposure to environmental or occupational hazards. Table 14-2 summarizes the selected uses of PFTs.

TABLE 14-2.

Selected Uses of PFTs

Diagnosis

Evaluate signs and symptoms of respiratory disease

Screen at-risk individuals for pulmonary disease

Evaluation

Assess the health status before initiating physical activity or rehabilitation

Determine preoperative risk of having pulmonary-related issues during surgery

Monitoring

Describe the course of lung function from a respiratory disease

Monitor respiratory changes for occupational or environmental exposure to toxins

Assess therapeutic drug effectiveness (eg, inhaled corticosteroids or bronchodilators for asthma)

Monitor adverse drug effects on pulmonary function (eg, amiodarone)

PULMONARY FUNCTION TESTS AND MEASUREMENTS

Pulmonary function tests use equations based on an individual’s age, height, sex, and race (when available) to calculate reference values from the population. The reference values most commonly used for spirometry is the National Health and Nutrition Examination Survey III and, more recently, the Global Lung Function Initiative (GLI)-2012.³ The individual’s measurement is then compared with the calculated reference values and the lower limit of normal (LLN). The LLN value is set at the fifth percentile, indicating that if the measured value is less than the lower fifth percentile of a normal population, then it is considered reduced and may be associated with disease. Using both the reference measurement and the LLN helps decrease overdiagnosing by removing bias from age seen in fixed value cutoffs.³

Spirometry

Spirometry is a PFT that helps detect airflow limitation that can be manifested in asthma or COPD. Spirometry measures the flow of air in volume per time. The physical forces of the airflow and the total amount of air inhaled and exhaled are converted by transducers to electrical signals, which are displayed on a computer screen.

During this maneuver, a volume-time curve—a plot of the volume exhaled against time—and a flow-volume curve or flow-volume loop—a diagram with flow (liters/second) on the vertical axis and volume on the horizontal axis (liters)—are generated as the report (Figure 14-1). After the data are generated, the patient’s spirometry results are compared with the reference values. The flow-volume curve is visually useful for diagnosing airflow limitation. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy suggests suspecting COPD in patients >40 years old with symptoms and/or risk factors and recommends spirometry to definitively diagnose COPD.⁵ Once diagnosed with COPD, spirometry, in conjunction with symptoms and history of exacerbations, can be used to monitor disease state severity.⁵ When asthma is suspected, spirometry can be used to assess for airflow variation and is recommended at the time of diagnosis, 3 to 6 months after starting treatment, at least every 1 to 2 years, and as needed to assess ongoing risk of exacerbations.⁶

Spirometry Measurements

Spirometry routinely assesses forced vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), and FEV₁/FVC.

Forced Vital Capacity

The FVC is the total volume of air, measured in liters, forcefully and rapidly exhaled in one breath (from maximum inhalation to end of forced expiration). End of forced expiration is achieved when there is less than a 0.025 L change in volume for at least 1 second, or the forced expiratory time has reached 15 seconds, or the FVC is within 0.150 L of another FVC measurement if the patient is older than 6 years of age. When the full inhalation-exhalation procedure is repeated slowly—instead of forcefully and rapidly—it is called the slow vital capacity (SVC). This value is the maximum amount of air exhaled after a full and complete inhalation. In patients with normal airway function, FVC and SVC are usually similar and constitute the vital capacity. In patients with diseases such as COPD, the FVC may be lower than the SVC due to collapse of narrowed or floppy airways during forced expiration. Because of this, some interpretive strategies recommend using the FEV₁/SVC ratio to determine the presence of airflow limitation, especially for pronounced airflow limitation.⁵

Forced Expiratory Volume in One Second

The full, forced inhalation-exhalation procedure was already described as the FVC. During this maneuver, the computer can discern the amount of air exhaled at specific time intervals of the FVC. By convention, FEV_0.5, FEV_0.75, FEV₁, FEV₃, and FEV₆ are the amounts of air exhaled after one-half, three-fourths, 1, 3, and 6 seconds, respectively. Usually, a patient’s value is described in liters and as a percentage of a predicted value based on reference values adjusted for age, height, sex, and race. Of these measurements, FEV₁ has the most clinical relevance, primarily as an indicator of airway function. A value ≥80% of the predicted normal value or greater than the LLN is considered normal. Normal values can be seen in patients with asthma when the disease is mild or well controlled. FEV₁ is an important value for predicting clinical outcomes, such as mortality, hospitalizations, and lung transplantation.⁵ For children aged 6 years and younger, FEV_0.75 is used instead of FEV₁ if the maximal volume expired by time is less than 1 second.⁴

Forced Expiratory Volume in One Second/Forced Vital Capacity

The ratio of FEV₁ to the FVC is used to estimate the presence and amount of airflow limitation in the airways. This ratio indicates the amount of air mobilized in 1 second as a percentage of the total amount of movable air. Normal, healthy individuals can exhale approximately 50% of their FVC in the first one-half second, about 80% in 1 second, and about 98% in 3 seconds. Patients with obstructive disease usually show a decreased ratio, and the actual percentage reduction varies with the severity of airflow limitation. In COPD, the GOLD strategy defines persistent airflow limitation as a postbronchodilator FEV₁/FVC ratio <0.70.⁵ Table 14-3 summarizes the definition of airflow limitation severity for COPD. Minicase 1 discusses how spirometry is used to diagnose COPD.

TABLE 14-3.

Severity of Airflow Limitation for COPD with the Postbronchodilator FEV₁/FVC <0.7

GOLD GRADE	SEVERITY	POSTBRONCHODILATOR FEV₁ (% PREDICTED)
1	Mild	≥80
2	Moderate	50–79
3	Severe	30–49
4	Very severe	<30

Refer to the Global Initiative for Chronic Obstructive Lung Disease (GOLDCOPD) 2022 Report⁴ for more information.

Spirometry can also show airflow variability necessary for the diagnosis of asthma. However, frequency of asthma symptoms, quick-relief medication use, and level of medications required to control symptoms are also necessary to assess asthma severity.

Generally, the FEV₁/FVC is normal (or high) in patients with restrictive diseases. In mild restriction, the FVC alone may be decreased, resulting in a high ratio. Often in restrictive lung disease, both the FVC and FEV₁ are similarly reduced compared with predicted values resulting in a normal ratio. It is important to note that this pattern is consistent with a restrictive pattern on spirometry, but lung volumes are needed to confirm restriction.

Flow-Volume Curves

Figure 14-2 shows several flow-volume curves in which the expiratory flow is plotted against the exhaled volume. As explained earlier, these curves are graphic representations of inspiration and expiration. The shape of the curve can indicate both the type of disease and the severity of airflow limitation. Obstructive changes result in decreased airflow, revealing a characteristic concave appearance. Restrictive changes result in a shape similar to that of a healthy individual, but the size is considerably smaller. The flow-volume loop also reveals mixed obstructive and restrictive disease by a combination of the two patterns.

Standardization of Spirometry Measurements

Spirometry is performed by having a person breathe into a tube (mouthpiece) connected to a machine (spirometer) that measures the amount and flow of inhaled and exhaled air. Prior to performing spirometry, relative contraindications such as recent brain, eye, or sinus surgery are assessed.⁴ Spirometry results depend greatly on the completeness and speed of the patient’s inhalation and exhalation, so the importance of completely filling and emptying the lungs of air during the test is emphasized. During spirometry, nose clips are worn to minimize air loss through the nose. The patient is seated comfortably without leaning or slumping, and any restrictive clothing (such as ties or tight belts) is loosened or removed. The patient is coached to take a full deep breath in and then blast the air out as quickly and forcefully as possible and to keep blowing the air out, while maintaining an upright posture, until all the air is exhaled. The patient is then instructed to inspire with maximal effort until completely full. This maneuver can be repeated up to eight times in adults if needed to meet testing standards.

MINICASE 1

Using Spirometry to Diagnose Asthma and COPD

Debra T. is a 56-year-old woman who reports chronic cough and shortness of breath when walking up a few stairs. She has been admitted several times each year for COPD exacerbations and pneumonia. She has a 40 pack-year-history of tobacco use. She is allergic to dust mites and dogs and has had a history of asthma since childhood. Today, on exam, she is wheezing and has nasal congestion.

QUESTION: How do the results from this patient’s spirometry test support the diagnosis of asthma and COPD?

DISCUSSION: A postbronchodilator measurement for FEV₁/FVC <0.70 is consistent with COPD using the GOLD criteria⁴ in the right clinical setting. She has a postbronchodilator FEV₁/FVC of <0.70 at 0.643 consistent with a diagnosis of COPD. A postbronchodilator FEV₁ of 65.69% of her predicted is considered moderate airflow limitation or GOLD Grade 2 COPD.

Her FEV₁ increased by more than 12% and 200 mL, which are the criteria for a positive bronchodilator test. Patients with asthma and COPD can have a positive bronchodilator test, but patients with asthma usually have a more extreme response. In addition, her clinical picture substantiates a diagnosis of both asthma and COPD: significant smoking history and shortness of breath on exertion are common with COPD, whereas allergies are associated more with asthma. Many patients, like Debra T., have both asthma and COPD that can be detected with PFTs and need to be treated appropriately.

PREBRONCHODILATOR				POSTBRONCHODILATOR
PFT	LLN	MEASURED	% PREDICTED	MEASURED	% PREDICTED	% CHANGE
FVC (L)	2.07	1.70	66	2.13	82.48	+24.97
FEV₁ (L)	1.59	1.15	55.18	1.37	65.69	19.04
FEV₁/FVC	0.696	0.676		0.643

Like most medical tests, spirometry has seen changes over the years in equipment, computer support, and recommendations for standardization. In an effort to maximize the usefulness of spirometry results, the American Thoracic Society (ATS), in conjunction with the European Respiratory Society (ERS), developed standardizations of spirometry testing.³^,⁴ These recommendations are intended to decrease the variability of spirometry testing by improving the performance of the test. The recommendations cover equipment, quality control, the training and education of people conducting the test, and the training of patients performing the test. The recommendations also provide criteria for acceptability and usability of the patient’s spirometry efforts and guidelines on interpreting the spirometry test results. For acceptability and usability of both the FEV₁ and FVC results, three criteria must be met. The first criterion is the back-extrapolated volume (BEV), which must be ≤5% of the FVC or 0.100 L, whichever is greater. BEV is the volume of gas exhaled before the start of forced expiration. The BEV would be too high if a patient leaked out air before maximal exhalation. Spirometers show the BEV calculation. The second criterion is the measurement must have no evidence of a faulty zero-flow setting, or airflow through the mouthpiece sensor before the start of the test. Newer spirometers use technology to detect this error and alert the user. The last criterion is there must be no glottic closure in the first second of expiration. Glottic closure appears like a flat line on the volume-time graph and shows a stop in airflow. Because the results of spirometry depend on the patient’s effort, at least three acceptable efforts are obtained with a goal of having the two highest measurements of FVC and FEV₁ vary ≤0.150 L if the patient’s age is >6 years and FVC and FEV₁ vary ≤0.100 L or 10% of the highest value, whichever is greater for patients 6 years of age and younger.⁴

Bronchodilator Responsiveness Test

One of many tests that may be useful in the diagnostic workup of asthma is spirometry with bronchodilator responsiveness to assess airflow variability. Before the testing day, the patient is asked to hold short-acting β₂-agonists (SABA) for at least 4 hours; twice daily long-acting β₂-agonists (LABA) for at least 12 hours and once-daily LABA for at least 24 hours; and ultra-LABA for 36 hours and long-acting muscarinic antagonists for 48 hours.⁴ Spirometry is performed at baseline and then again 15 to 30 minutes after the administration of an inhaled SABA. A positive bronchodilator response is defined as an improvement of the postbronchodilator FEV₁ and FVC by at least 12% and 200 mL from the prebronchodilator measurement.⁷ The Global Initiative for Asthma defines airway reversibility in adults as an increase in FEV₁ of at least 12% and 200 mL from the prebronchodilator measurement, with more confidence of a positive test with an increase in FEV₁ of at least 15% and 400 mL from baseline. For children, an increase of at least 12% of predicted for the FEV₁ is considered positive.⁶ Minicase 1 illustrates how spirometry is used to confirm COPD and how the bronchodilator reversibility study is useful for diagnosing asthma.

Peak Expiratory Flow

The peak expiratory flow (PEF) is measured with a simple, inexpensive hand-held peak flow meter that can be used at a patient’s home, in the clinician’s office, or in the emergency department. Because PEF measures airflow through the upper airway over a shorter time and readings can vary depending on the patient’s efforts and meter type, it is not the preferred test to detect airflow limitation.

When spirometry is not available, PEF can be used to help diagnose asthma by assessing diurnal variability.⁶^,⁸ Diurnal variability is indicative of asthma when the diurnal variability is >10% after 1 to 2 weeks in adults and >13% for children.⁶ One can calculate diurnal variability by dividing [day’s highest PEF minus day’s lowest PEF] by the mean of these two values and then averaging these daily variability results over 1 week.⁹ Twice-daily PEF is measured in the morning before using inhalers and in the afternoon or evening. Variability decreases after about 3 months of use an inhaled corticosteroid.

Peak flow meters are designed for both pediatric and adult patients with PEFR between 60 and 400 L/min for children and between 60 and 850 L/min for adults. PEFR is measured by having a patient perform the following steps:

Stand up.
Move the indicator on the peak flow meter to the end nearest the mouthpiece.
Hold the meter and avoid blocking the movement of the indicator and the holes on the end of the meter.
Take a deep breath in and then seal the mouth around the mouthpiece.
Blow out into the meter as hard and as fast as possible without coughing into the meter (like blowing out candles on a cake).
Examine the indicator on the meter to identify the number corresponding to the peak flow measurement.
Repeat the test two more times (remembering to move the indicator to the base of the meter each time).
Record the highest value of the three measurements in a diary (readings in the morning and afternoon are ideal).

To establish a patient’s personal best peak flow rate, measure the peak flow rate over a 2-week period when asthma symptoms and treatment are stable. The highest value over the 2-week period is the personal best. Using the individual patient’s personal best peak flow instead of predicted peak flow values is considered best practice. Asthma patients typically have lower peak flow readings than the healthy population, and using predicted values may result in overtreatment.

Using PEF for long-term monitoring is helpful for patients who have sudden asthma exacerbations or severe asthma. Improved asthma outcomes have been seen in asthma action plans, including personal best PEF. PEF is also helpful for identifying environmental and occupational asthma triggers along with differentiating between asthma and anxiety symptoms.⁶

MINICASE 2

Six-Minute Walk Test

Charles O. is a 65-year-old man diagnosed with World Health Organization group 1 pulmonary arterial hypertension after completing a right-heart catheterization. He reports a persistent and progressive dyspnea on exertion with walking from room to room in his home with use of oxygen via nasal cannula at 6 L/min with exertion only. His medications were changed 6 months ago because he was experiencing side effects.

Test 1.

Baseline

	SpO₂ (%)	HEART RATE (beats/min)	BLOOD PRESSURE (mm Hg)	SUPPLEMENTAL OXYGEN (L/min)
Baseline on room air	89	69	100/69	Room air
Baseline on supplemental oxygen
Minute 1	90	96		Room air
Minute 2	86	104		Room air
Minute 3	83 85	109 112		2 L/min O₂ NC 4 L/min O₂ NC
Minute 4	89	114		6 L/min O₂ NC
Minute 5	89	115		6 L/min O₂ NC
Minute 6	90	115	104/69	6 L/min O₂ NC
Recovery 2nd minute	89	65	106/75	Room air

Distance walked	274.3 m
Number of rests	0

Borg scale self-rate	Pretest	Posttest
Dyspnea	2	5
Fatigue	2	5

NC = nasal cannula.

Test 2.

6 Months Later

	SATURATION (%)	HEART RATE (beats/min)	BLOOD PRESSURE (mm Hg)	SUPPLEMENTAL OXYGEN (L/min)
Baseline on room air	90	81	109/78	Room air
Baseline on supplemental oxygen
Minute 1	91	88		Room air
Minute 2	88	103		Room air
Minute 3	86	113		3 L/min O₂ NC
Minute 4	88	115		4 L/min O₂ NC
Minute 5	90	116		6 L/min O₂ NC
Minute 6	90	118	108/81	6 L/min O₂ NC
Recovery 2nd minute	90	70	112/79	Room air

Distance walked	320 m
Number of rests	0

Borg scale self-rate	Pretest	Posttest
Dyspnea	2	3
Fatigue	2	4

NC = nasal cannula.

QUESTION: Do the results from this patient’s 6-month 6MWT show an improvement in distance walked after his medications were changed?

DISCUSSION: According to the first 6MWT, the patient walked 274.3 meters. He required 6 L/min of oxygen with exercise. The patient’s distance walked was 48% of the LLN. The patient became tachycardic with exertion, which improved after a 2-minute recovery period. The results of the second 6MWT show the patient walked for 320 m with no rests. The patient required 6 L/min supplemental oxygen with exertion. Comparing his 6MWT after starting the new medication regimen, the patient’s 6-minute walk distance improved by 45.7 m and his oxygen requirement remained unchanged. A distance greater than a 30-m walk is considered clinically important.²⁰ The patient has improved with the medication change.

Body Plethysmography

Body plethysmography is a method used to obtain lung volume measures. Lung volume tests indicate the amount of gas contained in the lungs at the various stages of inflation. The lung volumes and capacities may be obtained by several methods, including body plethysmography, gas dilution, and imaging techniques.¹⁰ Different methods can have small but significant effects on the values reported. Gas dilution methods only measure ventilated areas, whereas body plethysmography measures both ventilated and nonventilated areas. Therefore, body plethysmography values may be larger in patients with nonventilated or poorly ventilated lung areas. Computed tomography (CT) and magnetic resonance imaging can estimate lung volumes with additional detail of the lung tissue. Because body plethysmography is the most used method, this technique is discussed in more detail.

In body plethysmography, a patient sits in an airtight box and is told to inhale and exhale to functional residual capacity (FRC), or the volume of gas remaining at the end of a normal breath. Inside, a mouthpiece contains a pressure transducer. This is done to measure the change in pressure within the box during respiration. It senses the intrathoracic pressure generated when the patient rapidly and forcefully puffs against the closed mouthpiece. These data are then placed into the equation for Boyle’s law:

P_{1} \times V_{1} = P_{2} \times V_{2}

where P₁ is pressure inside the box in which the patient is seated (atmospheric pressure), V₁ is volume of the box, P₂ is intrathoracic pressure generated by the patient, and V₂ is the calculated volume of the box at the end of chest expansion. The difference between this V₂ and the initial volume of the box is the change in the volume of the box which is the same as the change in the volume in the chest. Because temperature (T₁ and T₂) is constant throughout testing, it is not included in the calculations.

Using this change in volume in Boyle’s law again, this test provides a measure of the FRC. Once the FRC is determined, the other lung volumes and capacities can be calculated based on this FRC and volumes obtained in static spirometry. After these data are generated, the patient’s plethysmography results are usually compared with references from a presumed normal population. This comparison necessitates the generation of predicted values for that patient if he or she were completely normal and healthy. Through complex mathematical formulas, sitting and standing height, age, sex, race, barometric pressure, and altitude are factored in to give predicted values for the pulmonary functions being assessed. The patient’s results are compared with the percentage of predicted values based on the results of these calculations.

Lung Volumes and Lung Capacities

Lung volumes include tidal volume (TV), inspiratory reserve volume (IRV), expiratory reserve volume (ERV), and residual volume (RV). These four volumes in various combinations make up lung capacities, which include inspiratory capacity, FRC, SVC, and total lung capacity (TLC).

Tidal Volume, Functional Residual Capacity, Expiratory Reserve Volume, and Residual Volume

The tidal volume is the amount of air inhaled and exhaled at rest in a normal breath. It is usually a small proportion of the lung volume and is infrequently used as a measure of respiratory disease. The IRV is the volume measured from the “top” of the TV (ie, initial point of normal exhalation) to the maximal inspiration. During exhalation, the ERV is the volume from the “bottom” of the TV (ie, initial point of normal inhalation) to maximal expiration. The RV is the volume of air left in the lungs at the end of forced expiration to the bottom of ERV. Without the RV, the lungs would collapse like deflated balloons. In diseases characterized by airflow limitation that trap air in the lungs (eg, COPD), the RV increases and the patient is less able to mobilize trapped air out of the lung. These four lung volumes are depicted in Figure 14-3.

Inspiratory Capacity, Functional Residual Capacity, Slow Vital Capacity, and Total Lung Capacity

The inspiratory capacity is the volume measured from the point of the TV at which inhalation normally begins to maximal inspiration, and it is a summation of TV and IRV. The functional residual capacity is the sum of the ERV and RV, and it is the volume of gas remaining in the lungs at the end of the TV. It also may be defined as a balance point between chest wall forces that increase volume and lung parenchymal forces that decrease volume. An increased FRC represents hyperinflation of the lungs and usually indicates airflow limitation. The FRC may be decreased in diseases that affect many alveoli (eg, pneumonia) or by restrictive changes, especially those due to fibrotic pulmonary tissue changes. The SVC is the volume of air that is exhaled as much as possible after inhaling as much as possible. It is a summation of the IRV, TV, and ERV and is described in more detail in the Spirometry Measurements section. The total lung capacity is the summation of all four lung volumes (IRV + TV + ERV + RV). It is the total amount of gas contained in the lungs at maximal inhalation. Restrictive lung disease is defined as a TLC below the 5th percentile of normal predicted value with a normal FEV1/VC ratio.⁷

Diffusion Capacity Tests

Tests of gas exchange measure the ability of gases to cross (diffuse) the alveolar-capillary membrane and are useful in assessing interstitial lung disease.¹¹ Typically, these tests measure the per-minute transfer of a gas, usually carbon monoxide (CO), from the alveoli to the blood. CO is used because it is a gas that is not normally present in the lung, has a high affinity for Hgb in red blood cells, and is easily delivered and measured. The diffusion capacity may be lessened after losses in the surface area of the alveoli or thickening of the alveolar-capillary membrane. Membrane thickening may be due to infiltration of inflammatory cells or fibrotic changes. These test results can be confounded by a loss of diffusion capacity due to poor ventilation, which may be related to closed or partially closed airways (as with airflow limitation) or to a ventilation-perfusion mismatch (as with pulmonary emboli or pulmonary hypertension). The diffusion capacity of the lungs to CO can be measured by either a single-breath test or steady-state test.

In the single-breath test, the patient deeply inhales—to vital capacity—a mixture of 0.3% CO, a tracer gas such as 10% helium or 0.3% methane, and balanced air. After holding his or her breath for 10 seconds, the patient exhales fully, and the concentrations of CO and helium are measured during the end of expiration (ie, alveolar flow). These concentrations are compared with the inspired concentrations to determine the amount diffusing across the alveolar membrane. The mean value for CO is about 25 to 30 mL/min/mm Hg.

A normal DLCO using a cutoff of the percent predicted has not been standardized but 70% to 75% if often utilized. A normal DLCO is also considered when greater than the LLN for the patient. Diffusion capacity is decreased in diseases that cause alveolar fibrotic changes. Changes may be idiopathic, such as those seen with sarcoidosis or environmental or occupational disease (asbestosis and silicosis), or be induced by drugs (eg, nitrofurantoin, amiodarone, and bleomycin).¹²^,¹³ Anything that alters Hgb, decreases the red blood cell Hgb concentration, or changes diffusion across the red blood cell membrane may alter the DLCO. The DLCO also reflects the pulmonary capillary blood volume. An increase in this volume (pulmonary edema or asthma) may increase the DLCO. Minicase 3 describes how PFTs are used to diagnose restrictive airway disease.

Specialized Tests

Bronchial Challenge Tests

Bronchial challenge tests (BCTs) are used to (1) aid in the diagnosis of asthma when the more common tests (symptom history, spirometry with reversibility) cannot confirm or reject the diagnosis, (2) evaluate the effects of drug therapy on airway hyperreactivity, and (3) evaluate potential drug effectiveness. A BCT measures the reactivity of the airways to known concentrations of agents that induce airway narrowing. Negative BCTs are useful in excluding the diagnosis of asthma more than confirming the diagnosis when a test is positive. Using this technique in research, the magnitude and duration of the effect of different drugs on the airways may be compared. BCTs are often referred to as challenges because the airways are challenged with increasing doses of methacholine, a synthetic derivative of acetylcholine, in a protocolized manner to determine whether there is a drop in the FEV₁. A decrease in the FEV₁ of 20% at specified doses is considered a positive test result.¹⁴ The ERS has published guidelines for methacholine challenge testing to enhance the safety, accuracy, and validity of the test.¹⁴

MINICASE 3

Using Pulmonary Function Tests to Evaluate a Patient with Interstitial Lung Disease

Jacob K. is a 59-year-old man who presents to the medicine clinic with reports of progressive dyspnea on exertion and minimal dry cough for the past 3 months. He has a history of rheumatoid arthritis and was started on methotrexate 4 months ago. CT of the chest shows diffuse ground glass opacities consistent with active inflammation and some minimal fibrosis at the bases. He had a PFT performed over a year ago that was completely normal. A repeat PFT is ordered and includes spirometry, lung volumes, and diffusion capacity. His PFT reveals the following results and the flow-volume curve in Figure 14-2 labeled “Restriction.”

QUESTION: How are these PFTs useful in the diagnosis, evaluation, and management of this patient?

DISCUSSION: Looking at his PFT in the following table, the FVC is 56% of predicted (reduced), the FEV₁ is 60% of predicted (reduced), and the FEV₁/FVC ratio is 0.85 (normal). This is consistent with a restrictive pattern. A TLC is 54% of predicted (reduced), verifying a restrictive pulmonary defect, and the DLCO is 50% of predicted (normal range is ≥70–75% of predicted). These findings are helpful in the diagnosis of interstitial lung disease in the setting of abnormal results on CT scan and change from previous normal spirometry. The severity of restriction can also be determined by the amount of decrease in TLC.⁶

PREBRONCHODILATOR			POSTBRONCHODILATOR
PFT	LLN	MEASURED	% PREDICTED	MEASURED	% CHANGE
FVC (L)	4.09	3.03	56	3.11	+2
FEV₁ (L)	3.10	2.48	60	2.65	+6
FEV₁/FVC		0.82		0.85	+3
SVC (L)	4.09	3.06	57
TLC (L)	6.54	4.36	54
RV (L)	1.71	1.30	51
DLCO (mL/min/mm Hg)	22.06	15.99	50

He is diagnosed with methotrexate-induced lung disease. The methotrexate is discontinued, and he is treated with prednisone. After 3 months of therapy, a repeat PFT is performed. The FVC is 75% of predicted, the FEV₁ is 72% of predicted, and the FEV₁/FVC ratio is 0.80. The TLC has increased to 65%, and the DLCO has increased to 60% of predicted. The repeat PFT shows that he is improved. He reports improvement in his symptoms. The follow-up PFT is used to help evaluate the response to discontinuing the offending medication and establish a new pulmonary function status.

Bronchial challenge testing begins by measuring baseline spirometry parameters to ensure it is safe to conduct the test. A BCT should not be performed if the FEV₁ is <60% of predicted.¹⁴ Most BCTs then begin with nebulization of a solution of phosphate buffered saline. This both serves as a placebo to assess the airway effect of nebulization and establishes baseline airway function from which the amount of pulmonary function to be reduced is calculated. After each dose, spirometry efforts are performed based on ATS/ERS criteria. The challenge data are then summarized into a single number, the provocative dose causing a 20% fall in forced expiratory volume in 1 second (PD₂₀/mcg).

For methacholine, a PD₂₀FEV₁ of <6 mcg indicates severe airway hyperresponsiveness (AHR), 6–25 mcg indicates moderate AHR, 25–100 mcg indicates mild AHR, 100–400 mcg suggests borderline AHR, and >400 mcg is a normal AHR test and excludes asthma. During a BCT, patients may experience transient respiratory symptoms such as cough, shortness of breath, wheezing, and chest tightness. An inhaled, SABA or short-acting muscarinic antagonist may be administered to alleviate symptoms and quicken the return of the FEV₁ to the baseline value. Because BCTs can elicit severe, life-threatening bronchospasm, trained personnel and medications to treat severe bronchospasm should be on hand in the testing area.

Exercise Challenge Test

The exercise challenge test is used to confirm or rule out exercise-induced bronchospasm (EIB) and to evaluate the effectiveness of medications used to treat or prevent EIB, which occurs usually in patients with normal PFTs who become symptomatic with exercise. The etiology of EIB is thought to be related to the cooling and drying of the airways caused by rapid breathing during exercise.

Exercise tests are usually done with a motor-driven treadmill (with adjustable speed and grade) or an electromagnetically braked cycle ergometer. Heart rate should be monitored throughout the test, nose clips should be worn, and the room air should be dry and cool to promote water loss from the airways during the exercise test. In most patients, symptoms are effectively blocked by use of an inhaled bronchodilator immediately before beginning exercise or other exertion causing the problem. After obtaining baseline spirometry, the exercise test is started at a low speed that is gradually increased over 2 to 4 minutes until the heart rate is 80% to 90% of the predicted maximum or the work rate is at 100%. The duration of the exercise is age and tolerance dependent. Children <12 years generally take 6 minutes, while older children and adults take 8 minutes to complete the test. After the exercise is completed, the patient does serial spirometry at 5-minute intervals for 20 to 30 minutes. FEV₁ is the primary outcome variable. A 10% or more decrease in FEV₁ from baseline is generally accepted as an abnormal response, although some clinicians feel a 15% decrease is more diagnostic of EIB.¹⁵

Six-Minute Walk Test

The six-minute walk test (6MWT) is a test used to measure the distance a patient can walk on a flat, hard surface in 6 minutes.¹⁶ The results of the test are used to determine if a patient requires continuous oxygen at home. The results have also been correlated to a patient’s quality of life and abilities to complete daily activities. The results of the 6MWT also help predict morbidity and mortality for patients with congestive heart failure, COPD, and primary pulmonary hypertension.¹⁷^–¹⁹ Pulmonary hypertension studies use this test to monitor the efficacy of interventions with medications.²⁰ Minicase 2 is an example of how a 6MWT is used to monitor a patient with pulmonary hypertension.

While performing the 6MWT, the patient is educated that the goal of the test is to walk as far as possible in 6 minutes, allowing the patient to select the intensity of exercise. Stopping and resting is allowed during the test. Reference equations for healthy adults have been published; however, large variations in the predicted values exist.²¹ The minimal important difference for the 6MWT is 30 meters for adults with chronic respiratory disease.²¹ Continuous pulse oximetry is recommended to capture the lowest arterial oxygen saturation (SpO₂). The lowest SpO₂ is a marker for prognosis and disease severity. The test is discontinued if the SpO₂ decreases to <80%. Heart rate measurements and heart rate recovery are recorded during the test. Poorer outcomes have been associated with reduced heart rate recovery in the first minute after the test. Use of the Borg scale to document dyspnea and fatigue before and after the 6MWT has good reliability when determining exercise limitations in patients with chronic respiratory disease. Practice tests, younger age, taller height, less weight, male sex, longer corridor length, and encouragement all improve test results. Unstable angina and myocardial infarction in the past 3 to 5 days and syncope and arterial oxygen saturation by pulse oximetry ≤85% are all contraindications for performing the 6MWT.²² In practice, the 6MWT is also used to assess the amount of oxygen needed with exertion. Patients with mild-to-moderate pulmonary disease may have normal oxygen saturation at rest but poor saturation with exertion. An oxygen saturation of ≤88% indicates the need for supplemental oxygen.

Carbon Monoxide Breath Test

Carbon monoxide is a poisonous gas emitted from anything burning, including cigarette smoke. As discussed in the Diffusion Capacity Tests section, CO binds more readily to Hgb than oxygen, causing increased fatigue and shortness of breath. With a simple breath test by a handheld CO meter, the patient can see how much CO is in the body (parts per million [ppm]) and in the blood (% COHgb). In clinical studies, a result of ≤10 ppm often defines a nonsmoker; however, in clinical practice, depending on the meter used, the level is usually lower. A Cochrane Review found no significant increase in smoking abstinence rates with CO measurements.²³

Testing exhaled CO is a simple breath test in which the patient holds his or her breath for 15 seconds and then exhales into a meter. The meter is able to indicate how much CO is in the patient’s lungs and estimate how much is attached to Hgb in the patient’s blood. The test is an objective value in which patients can visually see the effects of inhaling smoke when higher values of CO are detected. After 8 to 12 hours without smoking, CO levels become undetectable.

Fractional Exhaled Nitric Oxide

Measurement of exhaled concentrations of nitric oxide is a noninvasive biomarker test of airway inflammation for both diagnosing and monitoring eosinophilic airway inflammation.²⁴ Various handheld devices using the patient’s breath are available that include an electrochemical sensor to determine the exhaled nitric oxide concentration. Fractional exhaled nitric oxide (FENO) results of >50 parts per billion (ppb) in adults and >35 ppb in children younger than 12 years indicate eosinophilic inflammation with a high likelihood to respond to corticosteroids and certain add-on biologic asthma treatments.²⁵^,²⁶ As a monitoring test, FENO results are best interpreted as changes from baseline for each patient rather than using population normal readings. FENO measurements have many confounding factors, including smoking history, age, and sex. The test should be used in context with the patient history and as a tool with other diagnostic and monitoring tests.

SUMMARY

This chapter discusses the importance of pulmonary function testing as it relates to the diagnosis, treatment, and monitoring of respiratory disease states. After a review of the anatomy and physiology of the lungs, the mechanics of obtaining PFTs were emphasized. By understanding these mechanics, a clinician can better understand the interpretation of PFTs, use findings from different PFTs to help differentiate among diagnoses, and assist in making optimal therapeutic recommendations. PFT results are not interpreted in isolation but need to be assessed within the context of the other findings from the medical history and from other laboratory or clinical test results. Clearly, PFTs are an important tool to aid the clinician in decision-making.

LEARNING POINTS

1. What is a PFT?

ANSWER: A PFT is any test used to assess the function of the lungs (eg, spirometry, body plethysmography, 6MWT). The component of the PFT to be ordered is determined by the information needed. For example, spirometry is performed to reveal the presence of obstructive lung disease. Lung volumes determine the presence of restrictive lung disease, and the diffusion capacity test ascertains the adequacy of gas exchange.

2. Why is spirometry an important test in the diagnosis of COPD?

ANSWER: In COPD, postbronchodilator spirometry is necessary to determine the presence of persistent airflow limitation and the degree of disease severity. In the absence of COPD, other causes of symptoms should be considered. Physical exam and history alone are often not adequate to detect airflow limitation. Therefore, an objective test with spirometry is needed to confirm a clinical suspicion.

3. Does a significant bronchodilator response on spirometry testing differentiate asthma from COPD?

ANSWER: Traditionally, reversibility after bronchodilator use was considered a criterion to differentiate asthma and COPD. However, evidence has shown that a significant bronchodilator response is common in COPD as well, and this assessment is no longer used to differentiate between asthma and COPD. It is still a useful test when used in conjunction with a clinical history (eg, risk factors for COPD, presentation of shortness of breath, evidence of atopy), physical exam, and other PFTs to support a clinical suspicion of asthma and/or COPD.

4. How is restrictive lung disease diagnosed?

ANSWER: It is important to note that spirometry only can provide evidence consistent with restrictive disease, such as a decrease in FEV₁ and FVC with a normal or elevated FEV₁/FVC ratio. However, restriction is a decrease in lung volume as defined by a decrease in the TLC, which is obtained by lung volume tests, such as body plethysmography. Test results are needed to diagnose restrictive lung disease.

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Table of Contents

Pulmonary Function and Related Tests

OBJECTIVES

ANATOMY AND PHYSIOLOGY OF LUNGS1

CLINICAL USE OF PULMONARY FUNCTION TESTING

Pulmonary Disease States and Common PFT Results

Selected Uses of PFTs

PULMONARY FUNCTION TESTS AND MEASUREMENTS

Spirometry

Spirometry Measurements

Forced Vital Capacity

Forced Expiratory Volume in One Second

Forced Expiratory Volume in One Second/Forced Vital Capacity

Severity of Airflow Limitation for COPD with the Postbronchodilator FEV1/FVC <0.7

Flow-Volume Curves

Standardization of Spirometry Measurements

Using Spirometry to Diagnose Asthma and COPD

Bronchodilator Responsiveness Test

Peak Expiratory Flow

Six-Minute Walk Test

Baseline

6 Months Later

Body Plethysmography

Lung Volumes and Lung Capacities

Tidal Volume, Functional Residual Capacity, Expiratory Reserve Volume, and Residual Volume

Lung volumes and capacities. Representation of various lung compartments based on a typical spirogram. Refer to Pellegrino et al6 for more information.

Lung volumes and capacities. Representation of various lung compartments based on a typical spirogram. Refer to Pellegrino et al6 for more information.

Lung volumes and capacities. Representation of various lung compartments based on a typical spirogram. Refer to Pellegrino et al6 for more information.

Inspiratory Capacity, Functional Residual Capacity, Slow Vital Capacity, and Total Lung Capacity

Diffusion Capacity Tests

Specialized Tests

Bronchial Challenge Tests

Using Pulmonary Function Tests to Evaluate a Patient with Interstitial Lung Disease

Exercise Challenge Test

Six-Minute Walk Test

Carbon Monoxide Breath Test

Fractional Exhaled Nitric Oxide

SUMMARY

LEARNING POINTS

REFERENCES

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Lung volumes and capacities. Representation of various lung compartments based on a typical spirogram. Refer to Pellegrino et al6 for more information.

ANATOMY AND PHYSIOLOGY OF LUNGS¹

Severity of Airflow Limitation for COPD with the Postbronchodilator FEV₁/FVC <0.7

Lung volumes and capacities. Representation of various lung compartments based on a typical spirogram. Refer to Pellegrino et al⁶ for more information.

Lung volumes and capacities. Representation of various lung compartments based on a typical spirogram. Refer to Pellegrino et al⁶ for more information.

Lung volumes and capacities. Representation of various lung compartments based on a typical spirogram. Refer to Pellegrino et al⁶ for more information.

Lung volumes and capacities. Representation of various lung compartments based on a typical spirogram. Refer to Pellegrino et al⁶ for more information.