Flow-volume loops

INTRODUCTION — Spirometry, which includes measurement of forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC), is the most readily available and most useful pulmonary function test. The flow-volume loop is a plot of inspiratory and expiratory flow (on the Y-axis) against volume (on the X-axis) during the performance of maximally forced inspiratory and expiratory maneuvers.

Changes in the contour of the loop can aid in the diagnosis and localization of airway obstruction [1]. Characteristic flow-volume loop patterns are also often found in certain forms of restrictive disease, although flow-volume studies are not considered primary diagnostic aids in the evaluation of these disorders.

An overview of flow-volume loops will be presented here. General reviews of pulmonary function testing in adults and children and performance of spirometry are provided separately.

●(See "Office spirometry".)

●(See "Overview of pulmonary function testing in adults".)

●(See "Overview of pulmonary function testing in children".)

●(See "Pulmonary function testing in asthma".)

NORMAL FLOW-VOLUME LOOP — The flow-volume loop is a plot of inspiratory and expiratory flow (on the Y-axis) against volume (on the X-axis) during the performance of maximally forced inspiratory and expiratory maneuvers (figure 1). The patient is instructed to take a full inspiration (to total lung capacity), exhale forcefully and completely into the mouthpiece (to residual volume [RV]), and then inspire forcefully and fully back to total lung capacity. Typically, a flow-volume loop needs to be requested specifically, as an order for "spirometry" frequently yields just the expiratory portion. (See "Overview of pulmonary function testing in adults", section on 'Flow-volume loop'.)

The normal expiratory portion of the flow-volume curve is characterized by a rapid rise to the peak flow rate, followed by a nearly linear fall in flow as the patient exhales toward RV (figure 1). The inspiratory curve, in contrast, is a relatively symmetrical, saddle-shaped curve. The flow rate at the midpoint of vital capacity (between total lung capacity and residual volume), known as the forced expiratory flow-50 (FEF₅₀), is normally slightly less than the flow rate at the midpoint of inspiration, known as the forced inspiratory flow-50 (FIF₅₀). Thus, the ratio FEF₅₀/FIF₅₀ is normally <1.

CLINICAL USE OF FLOW-VOLUME LOOP — The utility of flow-volume loops for detection of obstructing lesions of the upper airway was first reported by Miller and Hyatt, who described three distinct patterns: variable extrathoracic obstruction; variable intrathoracic obstruction; and fixed obstruction (figure 1 and figure 2 and figure 3) [2]. When evaluating patients with dyspnea or noisy breathing, the contour of the flow-volume loop can provide additional information about the location of airway constriction, beyond that provided by the numeric values for forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) [3]. However, the sensitivity is low for mild obstruction and interpretation can be hampered by overlapping diseases (eg, chronic obstructive pulmonary disease [COPD] and tracheal stenosis). Furthermore, airway lesions at the thoracic inlet can move between the intrathoracic and extrathoracic compartments (see 'Variable obstruction at the thoracic inlet' below). Thus, positive and negative findings should be confirmed with imaging and/or direct visualization.

The area under the expiratory flow-volume curve (AEX) is a method for differentiating between patterns of ventilatory impairment. (See 'Area under the expiratory flow-volume curve' below.)

Identification of upper airway lesions — The flow-volume loop test is simple and readily available, whenever an upper airway lesion is suspected (figure 1 and figure 2 and figure 3) [4]. For the purposes of this discussion, the upper airway is defined as that portion of the airway extending from the mouth to the mainstem bronchi. The upper airway is divided into intra- and extrathoracic components by the thoracic inlet, which projects 1 to 3 cm above the suprasternal notch on the anterior chest at the level of the first thoracic vertebra.

In a retrospective review of 2662 flow-volume loops, 123 (4.6 percent) had abnormalities of the inspiratory flow-volume curve (consisting of truncation, flattening or absent loop) [5]. Further evaluation of 21 (17 percent) of the identified inspiratory abnormalities led to a specific etiology in 11 (52 percent), including vocal cord dysfunction, vocal fold paralysis, and other conditions. In this study, abnormalities were detected more often among patients with more than one abnormal inspiratory curve in a pulmonary function testing session, suggesting that functional and anatomic assessment is particularly useful when more than one flow-volume curve attempt is abnormal. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults".)

Limitations — The flow-volume loop is an insensitive test for upper airway obstruction, as lesions must narrow the tracheal lumen to less than 8 mm (a reduction of the tracheal area by at least 80 percent) before abnormalities can be detected (figure 4) and some types of obstruction only become apparent with provocation (eg, noxious stimuli, exercise) [2,6,7]. Depending on the degree of suspicion, absence of an abnormality in a patient with exertional dyspnea should be further evaluated with direct visualization (eg, imaging, laryngoscopy, flexible bronchoscopy) and/or cardiopulmonary exercise testing, which may be combined with sequential flow-volume loops or direct visualization during exercise. (See 'Exercise flow-volume loops' below.)

The most common cause of an abnormal inspiratory loop is submaximal patient performance either due to lack of effort or insufficient coaching [7]. Evidence demonstrating the insensitivity of flow-volume loops for detecting upper airway obstruction in various settings includes the following:

●Upper airway obstruction – In a study of 475 flow-volume loops, the aggregate sensitivity of several quantitative and visual criteria for upper airway obstruction was 69.4 percent and the areas of the receiver operating curves for all the individual criteria were low (ie, receiver-operating-characteristic [ROC] <0.522) [8].

●Inducible laryngeal obstruction – In a study of 226 patients who underwent laryngoscopy, the accuracy of flow-volume loops for detecting inducible laryngeal obstruction (also called paradoxical vocal fold motion or vocal fold dysfunction) was evaluated [9]. Assessment of flow-volume loops by a pulmonologist had low predictive value (ROC <0.68), leading to the conclusion that a normal flow-volume loop should not preempt laryngoscopy when vocal fold dysfunction is suspected. Another study found that patients with inducible laryngeal obstruction (ILO, also called paradoxical vocal fold dysfunction [PVFM]) and subglottic stenosis could be differentiated by specific measurements derived from the flow-volume loop, with peak expiratory flow (PEF) being higher and FEV₁/PEF being lower in patients with ILO [10]. (See "Inducible laryngeal obstruction (paradoxical vocal fold motion)", section on 'Evaluation'.)

●Tracheobronchomalacia – In an evaluation of 76 flow-volume loops in subjects with symptomatic tracheobronchomalacia, 13 (17 percent) had no flow-volume loop abnormalities [11]. (See "Tracheomalacia in adults: Clinical features and diagnostic evaluation", section on 'Diagnostic criteria'.)

[12,13]

ABNORMAL EXPIRATORY LOOP — Abnormalities in the contour of the expiratory flow-volume loop depend in part on the size and location of the airway that is narrowed. Patterns include diffuse truncation of the expiratory curve in intrathoracic tracheal narrowing, a biphasic pattern in tracheomalacia, a concave upward curve in diffuse lower airways disease (eg, asthma, chronic obstructive pulmonary disease [COPD]), a narrow curve in restrictive disease, and a "saw-tooth" irregularity in neuromuscular disease. (See 'Saw-tooth pattern' below.)

Variable intrathoracic obstruction — This pattern, also known as dynamic or non-fixed intrathoracic obstruction, demonstrates truncation (flattening) of the envelope of the maximal expiratory curve, due to expiratory flow limitation (figure 1). The pleural pressure surrounding the intrathoracic trachea is negative relative to the intratracheal pressure during inspiration, thereby producing no restraint to inspiratory airflow. In contrast, flow limitation is encountered during forced expiration, when the pleural pressure becomes positive relative to airway pressure, and the effect of any obstructive lesion in this region is accentuated (figure 2).

Turbulent flow and a Venturi effect may result in a further drop in airway pressure, adding to airway narrowing and flow limitation.

The FEF₅₀/FIF₅₀ ratio is reduced, with an average value of 0.32 (figure 1) [14]. This pattern may occur with tracheomalacia of the intrathoracic airway, bronchogenic cysts, or with tracheal lesions, which are often malignant [14,15]. An early expiratory notch has been described in a patient with a glomus tumor of the trachea [16]. In the case of a goiter, intrathoracic obstruction may only become evident if spirometry is performed with arm elevation (known as Pemberton sign) [17]. This may be true of other causes of intrathoracic obstruction as well.

Intrathoracic tracheobronchomalacia — A variety of flow-volume patterns have been described with intrathoracic tracheobronchomalacia: biphasic with a sharp narrow peak followed by a flat tail, a notched expiratory loop, and an oscillatory contour (figure 5) [11]. The peak expiratory flow rate is typically lower than normal. (See "Tracheomalacia in adults: Clinical features and diagnostic evaluation", section on 'Pulmonary function tests and flow volume loop'.)

Mainstem bronchial obstruction — Several abnormalities in the expiratory flow-volume loop have been described in patients with unilateral mainstem bronchial obstruction. Total functional obstruction of a mainstem bronchus results in an apparent restrictive ventilatory pattern of the expiratory curve, reflecting the loss of function of the affected side (figure 6) [18].

On the other hand, a partially occluded bronchus may result in a mixed obstructive and restrictive pattern. This would presumably result from initial normal emptying of the unaffected side, followed by slow emptying of the affected side. The net effect is an increasing upward concavity at lower lung volumes, as occurs with asthma or emphysema [18]. However, these patterns may be masked in patients with underlying emphysema [19].

Other patterns that may be seen with differential emptying include:

●An end-inspiratory tail (figure 7) [20,21]

●A biphasic spirogram, with an initial normal curvature of the expiratory loop and a "straight line" appearance at end-expiration (figure 7) [20]

●A flattening or plateau of the initial portion of the expiratory flow curve [22]

●A combination of the above with early slow decrease in expiratory flow followed by a "straight (horizontal) line" at end-expiration [23].

Lower airway obstruction — A frequently recognized abnormality in the flow-volume loop is the concave upward, or "scooped-out" or "coved," pattern encountered in asthma, COPD, bronchiectasis, and bronchiolitis (figure 1). Concavity of the expiratory portion of the flow-volume loop may be an early marker of peripheral airway obstruction and is seen in about a quarter of smokers with normal spirometry [24]. Maximal expiratory flow rates during the latter two-thirds of an expiratory maneuver are largely effort independent (ie, flow cannot be accelerated by increased expiratory effort), and vary directly with the elastic recoil of the lung and inversely with the airway resistance upstream of the equal pressure point.

Two changes are present in emphysema that will reduce flow rate during this phase of respiration: the elastic recoil of the lung is decreased due to loss of lung parenchyma; and airway resistance is increased due to secretions, bronchospasm, or narrowing of small airways.

The concave upward appearance of the flow-volume loop in obstructive lung disease probably results from the following two factors:

●Compression of the major central airway with a precipitous decline in flows. This process is often referred to as negative effort-dependence and results in excessive airway compression and premature airway closure. This may be more prominent in patients with emphysema, and is due to loss of airway support from the tethering effect of the surrounding parenchyma.

●A disproportionate decrease in flow later in expiration. Specifically, the heterogeneity of lung disease results in the more rapid and earlier emptying of areas with higher elastic recoil or lower airway resistance, compared with the slower emptying of more diseased areas.

Narrow expiratory loop in restrictive disease — The flow-volume loop has a recognizable pattern in restrictive lung or chest wall diseases that are associated with increased elastic recoil of the respiratory system. The characteristic pattern, which is seen most frequently with interstitial lung disease, is a decrease in vital capacity, with supernormal expiratory flows when corrected for lung volume. The resulting shape of the flow-volume curve is a tall, "witch's hat" appearance with a steep descending limb (figure 8). (See "Overview of pulmonary function testing in adults", section on 'Restrictive ventilatory defect'.)

Normal variant "knee pattern" — In contrast to the concave inflection commonly noted in patients with obstructive lung disease, the "knee" pattern is a normal variant representing a convex inflection in the expiratory portion of a flow-volume loop (figure 9). The prevalence of this finding on post-bronchodilator loops is 70 percent at age 18, and decreases by age 38 to 58 percent in women and 41 percent in men [25]. The convexity in the expiratory flow has been attributed to a proximal flow-limiting (choke point) section of the bronchial tree that moves distally with age due to loss of parenchymal elastic recoil [25].

ABNORMAL INSPIRATORY LOOP

Variable extrathoracic obstruction — The flow-volume loop pattern associated with dynamic (non-fixed) extrathoracic obstruction (eg, vocal fold paralysis, extrathoracic tracheomalacia, polychondritis, mobile tumors) is characterized by truncation of the envelope of the maximal inspiratory curve (figure 1). During thoracic expansion with inspiration, the combination of atmospheric extraluminal pressure and negative (subatmospheric) intraluminal pressure results in decreased luminal size of the extrathoracic portion of the upper airway, thus accentuating the effect of any obstructive lesion in this region (figure 3).

Turbulent flow and a Venturi effect also contribute to the drop in intratracheal pressure, producing further narrowing and flow limitation. In addition, the ratio of expiratory to inspiratory flow at 50 percent vital capacity (FEF₅₀/FIF₅₀) is elevated, with an average value of 2.2 (normal ratio <1) (figure 1) [14]. Diseases that exhibit this pattern include structural or functional vocal fold abnormalities, laryngomalacia, and tracheomalacia of the extrathoracic trachea. (See "Inducible laryngeal obstruction (paradoxical vocal fold motion)".)

Extrathoracic tracheomalacia is associated with flattening of the inspiratory curve and an increase in the FEF₅₀/FIF₅₀ to 1.4 to 1.8 [26]. (See "Tracheomalacia in adults: Clinical features and diagnostic evaluation".)

ABNORMAL INSPIRATORY AND EXPIRATORY LOOPS

Fixed upper airway obstruction — Firm tracheal lesions (eg, tracheal stenosis) can limit the modulating effect of transmural pressures on airway luminal diameter with the result that flow is limited during both inspiration and expiration, causing flattening of both limbs of the flow-volume loop. An FEF₅₀/FIF₅₀ ratio close to 1 (average 0.9) has been observed as a characteristic of fixed upper or central airway obstruction (figure 1) [14].

Dynamic narrowing of airway segments adjacent to the obstructive lesion may skew this ratio depending upon its location. One report, for example, evaluated patients with rigid thoracic lesions [26]:

●A ratio greater than 1.3 was noted in three of six patients with rigid extrathoracic lesions. Cinefluoroscopy suggested that the greater inspiratory limitation resulted from dynamic compression of the normal extrathoracic trachea between the stenotic segment and the thoracic inlet (ie, caudal to the stenosis).

●A ratio below 0.5 was seen in one patient with a rigid intrathoracic lesion. Cinefluoroscopy confirmed that the greater expiratory limitation was due to dynamic narrowing of the normal intrathoracic trachea between the stenotic segment and the thoracic inlet (ie, cephalad to the stenosis).

●A ratio of 1 would be expected for fixed lesions at the thoracic inlet or with a noncompliant trachea [26]. Examples of fixed upper airway obstruction include tracheal stenosis (as from prolonged intubation) or a goiter compressing the trachea.

Of note, severe chronic obstructive pulmonary disease (COPD) with a marked decrease in flow rates can obscure the expected truncation of the flow-volume loop or produce a mixed pattern with an early narrow peak on expiration, overall reduced expiratory flow without a clear plateau, and reduced inspiratory flow, also without a plateau [26].

Extraluminal tracheal obstruction — Extraluminal intrathoracic airway obstruction can cause a pattern of fixed airway obstruction or an atypical pattern of extrathoracic obstruction. As an example, one series described the flow-volume loops of patients with bulky mediastinal adenopathy due to Hodgkin lymphoma [27]. None of these patients had evidence of extrathoracic airway involvement on computed tomographic studies. Fourteen of 25 patients (56 percent) had abnormal flow-volume loops; the abnormalities consisted of flattening of both limbs of the flow-volume loop (seven patients) or flattening of the inspiratory loop only (seven patients) (figure 1). While the former pattern is consistent with a fixed airway obstruction, the latter is unexpected in intrathoracic disease. Moreover, the FEF (50 percent)/FIF (50 percent) was unexpectedly elevated in all, including those with a fixed pattern of obstruction, which is more typical of extrathoracic obstruction. It is possible that the bulky mediastinal adenopathy resulted in external splinting of the airway, which may have prevented the usual dynamic changes (figure 2), limiting both the narrowing of the intrathoracic airway in expiration and the widening of the airway in inspiration [27].

Variable obstruction at the thoracic inlet — This form of upper airway obstruction may result in a double hump (also called twin hump) of the expiratory curve as the narrowing moves from an intrathoracic to a relative extrathoracic location toward the end of expiration (figure 10) [14,26,28]. Inspiratory slowing is often present in addition [26]. Interestingly, repeated flow-volume loops may show first an intrathoracic and then an extrathoracic location, as the lesion moves within the chest with neck flexion and outside the thoracic inlet with neck extension (figure 11) [28].

Examples of such lesions include low post-tracheostomy scars or strictures that may be located at or above the suprasternal notch [14,28]. A similar double hump pattern in the contour of the expiratory curve has been described in a patient with vocal cord dysfunction characterized by initial adduction and subsequent abduction of the vocal cords in mid-expiration [29].

Saw-tooth pattern — A so-called "saw-tooth" pattern has been described that consists of small, rapid oscillations in flow during both expiration and inspiration (figure 12) [30,31]. Detecting the saw-tooth pattern is subjective and artifacts in the resonance frequency of the recording equipment can have a similar appearance [32,33].

Conditions associated with a saw-tooth pattern on the flow-volume loop include neuromuscular diseases [34], Parkinson disease [35], laryngeal dyskinesia [36], pedunculated tumors of the upper airway [37], tracheobronchomalacia [11,38], upper airway burns [39], and obstructive sleep apnea (OSA) [30-32]. The saw-tooth pattern has also been described in 31 percent of snorers without sleep apnea and in 10 percent of normal individuals [39,40]. Among 401 patients referred for evaluation of snoring, the sensitivity and specificity of the saw-tooth pattern for OSA were 11 and 94 percent, respectively [40].

Another feature of flow-volume loops sometimes seen in patients with OSA is an increased ratio of FEF₅₀/FIF₅₀. Normally, the FEF₅₀/FIF₅₀ is ≤1, but in patients with sleep apnea, it is often >1. When this criterion was examined in a group of 405 patients referred for evaluation of OSA, the sensitivity and specificity were 12 and 86 percent, respectively [32].

EXERCISE FLOW-VOLUME LOOPS — Patients with inducible laryngeal obstruction (paradoxical vocal fold motion) often have symptoms during exercise, but not at rest, or following exposure to a noxious stimulus. Sometimes, flow-volume loops performed after induction of symptoms by exercise or noxious stimuli can identify flow limitation during inspiration, expiration, or both [41], including the development of a cigar-shaped, tall, narrow loop [42]. However, the correlation of pre- and post-exercise flow-volume loops with findings on direct visualization is poor [43-45]. As an example, in a series of 100 patients, findings on continuous laryngoscopy during exercise testing did not correlate with the pre- and post-exercise shape of the flow-volume loop or the ratio of expiratory to inspiratory flow at 50 percent vital capacity (FEF₅₀/FIF₅₀) [43]. Nonetheless, if direct visualization during or immediately after exercise is not available, flow-volume loop data may be helpful. (See "Exercise-induced laryngeal obstruction", section on 'Continuous laryngoscopy during exercise'.)

Patients with COPD who develop excessive concavity of the expiratory loop during exercise have been shown to be more likely to develop dynamic hyperinflation [46].

FUTURE DIRECTIONS

Area under the expiratory flow-volume curve — The area under the expiratory portion of the flow-volume curve (AEX) can help discriminate among physiologic patterns of pulmonary function derangement and is available as part of the software of some spirometry equipment manufacturers. Alternatively, the AUC can be estimated using the measured forced vital capacity and instantaneous expiratory flow measures at various specified fractions of the vital capacity [12,13]. The AUC, which is progressively reduced from normal in restrictive, obstructive, and mixed ventilatory impairments, can sometimes differentiate between these various ventilatory patterns, particularly when a neural network trains the modeling. The net effect may be to obviate the need to obtain lung volume measurements [12]. In one study, the presence of emphysema in a patient with the COPD-bronchiectasis overlap could be ascertained by a low area under the expiratory flow-volume curve when referenced to the predicted reference curve [47]. Broader availability of that measure and normative data are needed before widespread application of this technique [48].

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".)

SUMMARY AND RECOMMENDATIONS

●Definition – The flow-volume loop is a plot of expiratory and inspiratory flow (on the Y-axis) against volume (on the X-axis) during the performance of maximal forced expiratory and inspiratory maneuvers between total lung capacity and residual volume (figure 1). (See 'Normal flow-volume loop' above.)

●Significance – The contour of the flow-volume loop provides additional information about the location of airway constriction, beyond that provided by the numeric values for forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC). (See 'Introduction' above.)

●Isolated abnormal expiratory loop

•Obstructive lower airway disease – Patients with airflow limitation due to asthma or chronic obstructive pulmonary disease (COPD) often have a concave upward pattern, sometimes called "scooped-out" or "coved," on the expiratory portion of the flow-volume loop (figure 1). (See 'Lower airway obstruction' above.)

•Restrictive interstitial disease – The characteristic flow-volume loop pattern of restrictive disease (seen most frequently with interstitial lung disease) is a decrease in vital capacity combined with supernormal expiratory flows when corrected for lung volume. The resulting shape of the flow-volume curve is a tall, "witch's hat" appearance with a steep descending limb (figure 8). (See 'Narrow expiratory loop in restrictive disease' above.)

●Abnormal inspiratory loop

•Contour analysis – The contour of the flow-volume loop (inspiratory and expiratory) is particularly useful for defining whether an obstructing lesion of the upper airway is intrathoracic or extrathoracic and also whether it is fixed (eg, tracheal stenosis, goiter, tumor) (figure 1) or dynamic (eg, structural and functional vocal cord abnormalities, laryngomalacia, extrathoracic tracheomalacia) (figure 3 and figure 2). (See 'Abnormal inspiratory loop' above.)

•Limitations – The flow-volume loop is an insensitive test for upper airway obstruction, as lesions must narrow the tracheal lumen to less than 8 mm (a reduction of the tracheal area by at least 80 percent) before abnormalities can be detected (figure 4). (See 'Limitations' above.)

•Reproducibility and further work-up – An abnormal inspiratory flow-volume loop should prompt a clinical assessment and review of all the flow-volume loops of the current and previous sessions. In general, abnormalities of the upper airway need radiographic and/or direct visualization for confirmation. (See 'Limitations' above.)

●Investigational uses – The area under the expiratory flow volume curve (AEX) may differentiate patterns of ventilatory impairment. Broader availability of that measure and normative data are needed for more widespread application of this technique. (See 'Clinical use of flow-volume loop' above.)