Airflow and lung volume measurements can be used to differentiate obstructive from restrictive pulmonary disorders, to characterize severity, and to measure responses to therapy.
Tests include spirometry to measure inspiratory and expiratory air flow and lung volumes and sometimes flow-volume loop testing to define specific obstructive and restrictive abnormalities. In patients with obstructive abnormalities, spirometry is repeated after administration of inhaled short-acting bronchodilators to assess reversibility and response to treatment.
Measurements are typically reported as absolute flows and volumes and as percentages of predicted values using data derived from large populations of people presumed to have normal lung function. Variables used to predict normal values include age, sex, ethnicity, and height.
It is controversial whether to adjust for race and ethnicity when interpreting pulmonary function tests. There is increasing evidence that race and ethnicity do not accurately account for observed differences in measured pulmonary function, but rather reflect the effects of social and environmental factors, further contributing to health care disparities. Studies have shown that the use of race and ethnicity-based reference equations likely underestimate pulmonary disease severity (and thus result in undertreatment) in non-White individuals (1, 2). The American Thoracic Society (ATS) has recommended replacing previously used ethnicity or race-specific reference equations (3) with those derived from race-neutral reference equations such as those derived from the Global Lung Function Initiative (GLI) average equation (4, 5. The 2022 European Respiratory Society (ERS)/ATS has acknowledged that the use of race-neutral reference sets may result in changes in qualifications for specific treatments (eg, surgery, lung transplantation), which highlights the need for ongoing research to understand the potential impact on clinical decision-making and patient outcomes (6).
Airflow
Quantitative measures of inspiratory and expiratory flow are obtained by forced spirometry. Nose clips are used to occlude the nares.
In inspiratory flow and volume assessments, patients exhale as completely as possible, then forcibly inhale. The peak inspiratory volume is the maximum amount of air inhaled in one deep breath, and the inspiratory flow is the volume inspired per second.
In expiratory flow and volume assessments, patients inhale as deeply as possible, seal their lips around a mouthpiece, and exhale as forcefully and completely as possible into an apparatus that records the exhaled volume (forced vital capacity [FVC]) and the volume exhaled in the first second (the forced expiratory volume in 1 second [FEV1]—see figure Normal Spirogram).
These maneuvers provide several measures:
FVC: Maximal amount of air that the patient can forcibly exhale after taking a maximal inhalation
FEV1: Volume exhaled in the first second
Peak expiratory flow (PEF): Maximal speed of airflow as the patient exhales
FEV1 is the most reproducible flow parameter and is especially useful in diagnosing and monitoring patients with obstructive pulmonary disorders (eg, asthma, COPD [chronic obstructive pulmonary disease]).
FEV1 and FVC help differentiate obstructive and restrictive lung disorders. A normal FEV1 makes irreversible obstructive lung disease unlikely. A normal FVC makes restrictive disease unlikely. A decreased ratio of FEV1/FVC indicates obstruction. Repeat measurement of FEV1 and FVC with a short-acting bronchodilator in patients with evidence of obstruction on initial testing is useful in differentiating patients with reversible bronchospasm as occurs in asthma from those with fixed obstruction in COPD.
Some people have risk factors for COPD (eg, cigarette smoking, previous infection, occupational exposure, air pollution exposure) but do not demonstrate definite obstruction on pulmonary function testing. These people are said to have pre-COPD (7). Further studies are needed to characterize this population, but following spirometry values over time may be helpful identifying patients who are likely to develop COPD.
Normal Spirogram
FEF25–75% = forced expiratory flow during expiration of 25 to 75% of the FVC; FEV1 = forced expiratory volume in the first second of forced vital capacity maneuver; FVC = forced vital capacity (the maximum amount of air forcibly expired after maximum inspiration). |
The forced expiratory flow averaged over the time during which 25 to 75% of the FVC is exhaled may be a more sensitive marker of mild, small airway airflow limitation than the FEV1, but the reproducibility of this variable is poor.
The peak expiratory flow (PEF) is the peak flow occurring during exhalation. This variable is used primarily for home monitoring of patients with asthma and for determining diurnal variations in airflow. Asthma can be monitored by comparing PEF to one's own personal best.
Interpretation of these measures depends on good patient effort, which is often improved by coaching during the actual maneuver. Acceptable spirograms demonstrate
Good test initiation (eg, a quick and forceful onset of exhalation)
No coughing
Smooth curves
Absence of early termination of expiration (eg, minimum exhalation time of 6 seconds with no change in volume for the last 1 second)
Reproducible efforts agree within 5% or 100 mL with other efforts. Results not meeting these minimum acceptable criteria should be interpreted with caution.
Lung volume
Lung volumes are measured by determining functional residual capacity (FRC). FRC is the amount of air remaining in the lungs after normal exhalation. The total lung capacity (TLC) is the volume of gas that is contained in the lungs at the end of maximal inspiration. Knowing FRC allows the lungs to be divided into subvolumes that are either measured with spirometry or calculated (see figure Normal Lung Volumes). Normally the FRC represents about 40% of TLC.
Normal Lung Volumes
ERV = expiratory reserve volume; FRC = functional residual capacity; IC = inspiratory capacity; IRV = inspiratory reserve volume; RV = residual volume; TLC = total lung capacity; VC = vital capacity; VT= tidal volume. FRC = RV + ERV; IC = VT + IRV; VC = VT+ IRV + ERV. |
FRC is measured using gas dilution techniques or a plethysmograph (which is more accurate in patients who have airflow limitation and trapped gas).
Gas dilution techniques include
Nitrogen washout
Helium equilibration
With nitrogen washout, the patient exhales to FRC and then breathes from a spirometer containing 100% oxygen. The test ends when the exhaled nitrogen concentration is zero. The collected volume of exhaled nitrogen is equal to 81% of the initial FRC.
With helium equilibration, the patient exhales to FRC and then is connected to a closed system containing known volumes of helium and oxygen. Helium concentration is measured until it is the same on inhalation and exhalation, indicating it has equilibrated with the volume of gas in the lungs, which can then be estimated from the change in helium concentration that has occurred.
Both of these techniques may underestimate FRC because they measure only the lung volume that communicates with the airways. In patients with severe airflow limitation, a considerable volume of trapped gas may communicate very poorly or not at all.
Body plethysmography uses Boyle’s law (P1V1 = P2V2, where P is pressure and V is volume) to measure the compressible gas volume within the thorax. Body plethysmography is more accurate than gas dilution techniques. While sitting in an airtight box, the patient tries to inhale against a closed mouthpiece from FRC. As the chest wall expands, the pressure in the closed box rises. Knowing the pre-inspiratory box volume and the pressure in the box before and after the inspiratory effort allows for calculation of the change in box volume, which must equal the change in lung volume.
Flow-volume loop
In contrast to the spirogram, which displays airflow (in L) over time (in seconds), the flow-volume loop displays airflow (in L/second) as it relates to lung volume (in L) during maximal inspiration from complete exhalation (residual volume [RV]) and during maximum expiration from complete inhalation (TLC). The principal advantage of the flow-volume loop is that it can show whether airflow is appropriate for a particular lung volume. For example, airflow is normally slower at low lung volumes because elastic recoil is lower at lower lung volumes. Patients with pulmonary fibrosis have low lung volumes and their airflow appears to be decreased if measured alone. However, when airflow is presented as a function of lung volume, it becomes apparent that airflow is actually higher than normal (as a result of the increased elastic recoil characteristic of fibrotic lungs).
Flow-volume loops require that absolute lung volumes be measured. Unfortunately, many laboratories simply plot airflow against the FVC; the flow-FVC loop does not have an inspiratory limb and therefore does not provide as much information.
General references
1. Baugh AD, Shiboski S, Hansel NN, et al. Reconsidering the Utility of Race-Specific Lung Function Prediction Equations [published correction appears in Am J Respir Crit Care Med 2022 Jul 15;206(2):230]. Am J Respir Crit Care Med 2022;205(7):819-829. doi:10.1164/rccm.202105-1246OC
2. Ekström M, Mannino D. Research race-specific reference values and lung function impairment, breathlessness and prognosis: Analysis of NHANES 2007-2012 [published correction appears in Respir Res 2023 Feb 3;24(1):41]. Respir Res 2022;23(1):271. Published 2022 Oct 1. doi:10.1186/s12931-022-02194-4
3. Bhakta NR, Bime C, Kaminsky DA, et al. Race and Ethnicity in Pulmonary Function Test Interpretation: An Official American Thoracic Society Statement. Am J Respir Crit Care Med 2023;207(8):978-995. doi:10.1164/rccm.202302-0310ST
4. Quanjer PH, Stanojevic S, Cole TJ, et al. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J 2012;40(6):1324-1343. doi:10.1183/09031936.00080312
5. Bowerman C, Bhakta NR, Brazzale D, et al. A Race-neutral Approach to the Interpretation of Lung Function Measurements. Am J Respir Crit Care Med 2023;207(6):768-774. doi:10.1164/rccm.202205-0963OC
6. Stanojevic S, Kaminsky DA, Miller MR, et al. ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J 2022;60(1):2101499. Published 2022 Jul 13. doi:10.1183/13993003.01499-2021
7. Han MK, Agusti A, Celli BR, et al. From GOLD 0 to Pre-COPD. Am J Respir Crit Care Med 2021;203(4):414-423. doi:10.1164/rccm.202008-3328PP
Patterns of Abnormalities
Most common respiratory disorders can be categorized as obstructive or restrictive on the basis of airflow and lung volumes (see table Characteristic Physiologic Changes Associated With Pulmonary Disorders).
Obstructive disorders
Obstructive disorders are characterized by a reduction in airflow, particularly the FEV1 and the FEV1 expressed as a percentage of the FVC (FEV1/FVC). The degree of reduction in FEV1 compared with predicted values determines the degree of the obstructive defect. Obstructive defects are caused by
Increased resistance to airflow due to abnormalities within the airway lumen (eg, tumors, secretions, mucosal thickening)
Changes in the wall of the airway (eg, contraction of smooth muscle, edema)
Decreased elastic recoil (eg, the parenchymal destruction that occurs in emphysema)
With decreased airflow, expiratory times are longer than usual, and air may become trapped in the lungs due to incomplete emptying, thereby increasing lung volumes (eg, TLC, RV).
The most common examples of obstructive disorders are COPD, asthma, and bronchiectasis.
The ERS and ATS have updated their guidelines on interpretation of pulmonary function tests in grading severity of obstructive lung disease (see table Severity of Lung Impairment) (1). These guidelines recommend expressing all measurements, including spirometry, lung volumes, and diffusing capacity of the lungs for carbon monoxide (DLCO), as z-scores rather than as percentages of predicted values to grade severity. A z-score less than -1.645 indicates that the value is less than 5th percentile of predicted based on healthy matched controls. In judging response to bronchodilators, the guidelines now recommend the use of percent change relative to an individual's predicted value (instead of baseline value) and they recommend using improvement of FEV1 and/or FVC ≥ 10% as the criterion for airway hyperresponsiveness.
Restrictive disorders
Restrictive disorders are characterized by a reduction in lung volume, specifically a TLC less than the lower limit of normal (a z-score less than -1.65, corresponding to less than the fifth percentile of predicted based on healthy matched controls). However, in early restrictive disease, the TLC can be normal (as a result of strong inspiratory effort) and the only abnormality might be a reduction in RV. The decrease in TLC determines the severity of restriction. The decrease in lung volumes causes a decrease in airflow (reduced FEV1). However, airflow relative to lung volume is increased, so the FEV1/FVC ratio is normal or increased.
Restrictive defects are caused by the following:
Loss in lung volume (eg, lobectomy)
Abnormalities of structures surrounding the lung (eg, pleural disorder, kyphosis, obesity)
Weakness of the inspiratory muscles of respiration (eg, neuromuscular disorders)
Abnormalities of the lung parenchyma (eg, pulmonary fibrosis)
The feature common to all is a decrease in the compliance of the lungs, the chest wall, or both.
Patterns of abnormalities references
1. Stanojevic S, Kaminsky DA, Miller MR, et al. ERS/ATS technical standard on interpretive strategies for routine lung function tests. Eur Respir J 2022;60(1):2101499. Published 2022 Jul 13. doi:10.1183/13993003.01499-2021
2. Coates AL, Wanger J, Cockcroft DW, et alEur Respir J 2017;49(5):1601526. Published 2017 May 1. doi:10.1183/13993003.01526-2016
3. Parsons JP, Hallstrand TS, Mastronarde JG, et al. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med 2013;187(9):1016-1027. doi:10.1164/rccm.201303-0437ST
Bronchoprovocation Challenge
Some patients with asthma can have normal pulmonary function and normal spirometric parameters between exacerbations. When suspicion of asthma remains high despite normal spirometry results, bronchprovocation challenge testingacetylcholine that is a nonspecific bronchial irritant, is indicated to detect or exclude bronchoconstriction. In a methacholine challenge test, spirometric parameters are measured at baseline and after inhalation of increasing doses of methacholine. The dose of methacholine that causes a 20% drop in FEV1 is called the PD20. Laboratories have different definitions of airway hyperreactivity, but in general, patients showing at least a 20% drop in FEV1 from baseline (PD20) when the delivered dose of inhaled methacholine is < 25 mcg is considered diagnostic of increased bronchial reactivity, whereas a PD20 > 400 mcg excludes the diagnosis. PD20 values between 25 and 400 mcg are inconclusive (1).
Exercise testing≥ 10 to 15% after exercise (2).
EVH may also be used to diagnose exercised-induced asthma. EVH involves hyperventilation of a gas mixture of 5% carbon dioxide and 21% oxygen at 85% of maximum voluntary ventilation for 6 minutes. FEV1 is then measured at specified intervals after the test. As with other bronchial provocation tests, the drop in FEV1 that is diagnostic of exercise-induced bronchospasm varies by laboratory.
Cold-induced hyperreactivity can be assessed with a similar test in which the patient hyperventilates for 3 to 6 minutes with the gas mixture cooled to between -10° C and -20° C. This test requires specialized cooling equipment that may not be available in many testing laboratories.
Bronchprovocation challenge references
1. Coates AL, Wanger J, Cockcroft DW, et alEur Respir J 2017;49(5):1601526. Published 2017 May 1. doi:10.1183/13993003.01526-2016
2. Parsons JP, Hallstrand TS, Mastronarde JG, et al. An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction. Am J Respir Crit Care Med 2013;187(9):1016-1027. doi:10.1164/rccm.201303-0437ST
