Pulmonary function testing provides an effective way of testing upper airway obstruction

Upper-airway obstruction (UAO) can occur as an acute disorder or on a chronic basis. The acute causes of airway obstruction are usually life threatening and need immediate medical and surgical management. Upper-airway compromise of a sub-acute or chronic variety can progress (with respiratory difficulty for days or months) before patients seek medical attention. At this juncture, appropriate recognition of the problem is crucial in order to avoid delay in the institution of measures that relieve the obstruction. Pulmonary-function (PF) testing can help significantly by showing the site of airway obstruction, thereby leading to the use of appropriate investigative strategies that can uncover the nature of the obstruction.

Case Report
A 49-year-old female presented in March 1999 with increasing dyspnea on exertion over the preceding 6 months. Dyspnea was associated with inspiratory stridor at maximal exertion and wheezing for the previous 3 months. The patient’s activity was considerably limited because of her dyspnea, and she had stopped exercising at her gym 2 months earlier. She also complained of a dry, intermittent cough that had lasted a few weeks. She was seen by a local primary care practitioner at the onset of symptoms and given escalating doses of bronchodilators, but there was no improvement.

The patient had no history of smoking. She worked as a seamstress. She did have a history of endotracheal intubation, which she had undergone for brief periods on two occasions for surgeries performed under general anesthesia. Examination findings were unremarkable, with normal breath sounds on chest auscultation and no audible stridor over the trachea. Spirometry results were normal (Table 1), with a mild reduction in peak expiratory flow rate (PEFR) and a moderate reduction in maximal voluntary ventilation (MVV). The following spirometric values were seen (values in parantheses indicate % of predicted values).

A flow-volume loop showed flattening of the inspiratory limb (Figure 1a), with a midpoint maximal expiratory to inspiratory flow (MEF50%:MIF50%) value of 1.2. The patient subsequently underwent a fiberoptic bronchoscopy that showed a subglottic stenosis of 5 to 6 mm (Figure 1b).

Figure 1a. Flow-volume loop showing a plateau in the inspiratory limb.	Figure 1b. Bronchoscopic view of the proximal trachea showing a 5-mm to 6-mm subglottic stenosis.

Anatomy and dynamics of the upper airway
Anatomically, the upper airway extends from the mouth to the main carina. It is further subdivided into extrathoracic and intrathoracic portions. Compared to the huge cross-sectional area of the bronchioles (around 180 cm2), the cross-sectional area of the airway at the level of the trachea is only 2.5 cm2. Multiple anatomic constrictions in the upper airway favor the lodging of foreign bodies, as well as having a tendency to reduce the airway lumen significantly following disease.¹ Although the upper airways can be construed to be relatively rigid conducting passages, changes in airway diameter occur during the normal respiratory cycle. During inspiration, the intrathoracic airways expand along with the expanding lungs. In contrast, the extrathoracic airways diminish in caliber during inspiration due to their intraluminal pressure being lower than the atmospheric pressure. The reverse happens during expiration.

Flow in large airways is turbulent (due to high airflow rates) under normal conditions. Turbulent flow increases when there is a smaller tube radius; this usually happens if obstructing lesions are present in the upper airway. Due to smaller airway dimensions and turbulent flows, the upper airways are responsible for the majority of airway resistance seen under normal conditions. This resistance is partially dependent on the density of the flowing gas medium, which explains the salutary effects that breathing low-density gas mixtures of helium and oxygen has on patients with acute UAO.²

Causes and clinical presentation
Unlike acute UAO that is apparent on clinical assessment, chronic UAO tends to be diagnosed as asthma or chronic obstructive pulmonary disease (COPD).³ Dyspnea is the usual presenting symptom, with patients developing gradual complaints without any hypoxemia or hypercapnia at rest.⁴ Usually, patients compensate by reducing their physical activities. The condition is often brought to light following an acute upper-respiratory infection that significantly worsens the obstruction.⁴ Worsening of dyspnea following recumbency may also result.³ Typically, exertional dyspnea occurs in UAO when the airway diameter is reduced to about 8 mm; resting dyspnea occurs at a diameter of 5 mm, at which point stridor also occurs.⁵ Voice changes reflect the laryngeal localization of the obstruction. Hypoxemia upon exercise has been reported in a series of seven patients secondary to alveolar hypoventilation.⁶ Exertional hypoxemia in a patient with a normal diffusion capacity is reflective of alveolar hypoventilation that calls for further workup for appropriate etiologies, one of which is UAO.⁷

A number of causes can account for a chronic reduction in upper-airway diameter, the commonest being the hypertrophy of tonsils and adenoids, vocal cord paralysis, airway stenosis following tracheostomy or prolonged intubation, and neoplastic disease.³ In adults, the most commonly encountered cause is tracheal stricture following prolonged intubation or tracheostomy (as reflected in its occurrence in as many as 10% of survivors of adult respiratory distress syndrome).⁸ The pathogenetic mechanism involves ischemic injury to the tracheal mucosa from the endotracheal tube cuff; the incidence of this complication has been reduced significantly since the adoption of low-pressure, high-volume tube cuffs.⁷ Predisposing factors for tracheal and laryngeal stenosis include extended trans-laryngeal intubation, secondary tracheostomy, severe laryngeal injury upon extubation, and female gender.⁸ Other important causes of obstruction in adults include extraluminal compression by a goiter; relapsing polychondritis, with its characteristic tendency to destroy cartilaginous structures; and functional vocal-cord dysfunction (or episodic laryngeal dyskinesia) occurring secondary to paradoxical inspiratory and/or expiratory closure of the vocal cords. The latter condition is characterized by mild to severe asthma-like attacks with stridor, hypoxemia, and wheezing. It is usually seen in young females with previous psychiatric illnesses, and these patients report many previous hospital admissions for asthma.⁹ Rarely, UAO can be seen due to abnormalities in tracheal compliance, such as tracheomalacia due to extreme tracheal collapsibility during inspiration.

Spirometry and Flow-Volume Loops
Conventional spirometric techniques measure a number of parameters that shed light on pulmonary volume and flow characteristics during the inspiratory and expiratory stages of breathing. Although forced inspiratory and expiratory maneuvers are effort dependent, they provide more information on flow-resistive characteristics than tidal maneuvers do. In their classic paper on the obstructing lesions of the larynx and trachea, Miller and Hyatt¹⁰ made spirometric measurements in normal subjects breathing through fixed external resistances. Among the various parameters measured, MVV and PEFR were found to be most sensitive for mild to moderate degrees of UAO.¹⁰ Forced expiratory volume in 1 second (FEV1), the spirometric parameter that is used for identifying lower airway narrowing in COPD and asthma, was found to be least sensitive.¹⁰ More important, this work indicated that the contour of the flow-volume loop became abnormal earlier than other spirometric measurements did in these patients.¹¹

Figure 2. Normal appearance of a flow-volume loop.

A flow-volume loop is generated by having the patient inhale deeply to total lung capacity (TLC), forcefully exhale until the lungs have been emptied to residual volume (RV), and rapidly inhale to reach TLC. Flow is plotted on the Y axis and the volume on the X axis; a typical loop is shown in Figure 2. The upper portion of the curve reflects the expiratory portion of the forced vital capacity (FVC) maneuver and is also referred to as the maximal expiratory flow-volume (MEFV) curve. Unlike the flow in the inspiratory portion, the flow during the maximal expiratory maneuver diminishes at the end of the MEFV curve due to shrinking lung volumes. This happens because a decreasing lung volume causes a corresponding decrease in the lung’s elastic recoil forces, which keep the airways open during exhalation.¹² This fact has important implications for the flow-volume contour in patients with COPD, where small-airway narrowing secondary to loss of elastic recoil leads to a coved appearance in the terminal portion of the MEFV curve.¹³

Figure 3. Flow-volume patterns in upper-airway obstruction. The dotted lines represent the midpoints of the maximal expiratory and inspiratory flows. a. Fixed upper-airway obstruction (intrathoracic or extrathoracic). b. Variable extrathoracic obstruction. c. Variable intrathoracic obstruction.

Miller and Hyatt defined three classic patterns of flow-volume loop contours in patients with UAO, depending on the location of the obstruction and depending on whether the obstruction was fixed or variable.^10,11 Fixed lesions are characterized by lack of changes in caliber during inhalation or exhalation and produce a constant degree of airflow limitation during the entire respiratory cycle. A fixed lesion may be extrathoracic or intrathoracic. Its presence results in similar flattening of both the inspiratory and expiratory portions of the flow-volume loop (Figure 3a). Its causes include postintubation strictures, goiters, and tracheal tumors.⁵ Variable lesions are characterized by changes in airway lesion caliber during breathing. Depending on their location (intrathoracic or extrathoracic), they tend to behave differently during inhalation and exhalation. Airway lesions located above the thoracic inlet are not affected directly by changing thoracic pressures during the respiratory cycle. Instead, during inspiration, there is acceleration of airflow from the atmosphere toward the lungs, and the intraluminal pressure decreases with respect to the atmospheric pressure due to a Bernoulli effect. This effect is exaggerated in the presence of an extrathoracic obstructing lesion, resulting in the limitation of inspiratory flow seen as a flattening in the inspiratory limb of the flow-volume loop (Figure 3b). During expiration, the air is forced out of the lungs through a narrowed (but potentially expandable) extrathoracic airway. Therefore, the maximal expiratory flow-volume curve is usually normal. Causes of variable extrathoracic lesions include glottic strictures, tumors, and vocal-cord paralysis.⁵

Variable intrathoracic constrictions expand during inspiration, causing an increase in airway lumen and resulting in a normal-appearing inspiratory limb of the flow-volume loop. During expiration, compression by increasing pleural pressures leads to a decrease in the size of the airway lumen at the site of intrathoracic obstruction, producing a flattening of the expiratory limb of the flow-volume loop (Figure 3c). Causes of variable intrathoracic lesions include malignant tumors and tracheomalacia.⁵

Miller and Hyatt¹⁰ described another ratio, MEF50%:MIF50%, based on maximal flows in inspiration and expiration during the flow-volume–loop maneuver. Under normal circumstances, the flows generated during the forced inspiratory maneuver are effort dependent, but during expiration, the maximal flows generated remain effort independent during the majority (nearly 70% to 80%) of the maximal expiratory flow maneuver.⁵ Due to this, the flow during the middle of inspiration measured at 50% of the FVC (FIF50% or MIF50%) is usually greater than the maximal expiratory flow at 50% of FVC (FEF50% or MEF50%). A MEF50%:MIF50% ratio is, therefore, usually less than 1. In variable extrathoracic lesions, the ratio is increased (usually greater than 1), while in variable intrathoracic lesions, the ratio is diminished (0.2 or less).¹³ In fixed obstructions (intrathoracic or extrathoracic), the ratio is expected to be close to 1, although three of six patients with fixed lesions had ratios of 1.5 or more in one study.¹⁴ This was believed to be due to the response of normal tracheal segments between the lesion and thoracic outlet to negative intraluminal pressures that tended to close the airway during inspiration.¹⁴

Since expiratory flow rates are significantly reduced in patients with COPD and emphysema, the effort-independent portions of the flow-volume loop have a flattened or coved appearance in these patients. Concomitant upper-airway lesions in these patients may be missed due to lack of demonstrable plateaus in the expiratory portion of the flow-volume loop.¹⁵ Therefore, the absence of plateaus suggestive of UAO on flow-volume loops in patients with COPD does not rule out this problem. The FEV1:FEV0.5 ratio has been proposed as a useful parameter for separation of the functional abnormalities seen in COPD from those of UAO.¹⁶ When the FEV0.5 is less than 60% of the FEV1, a diagnosis of UAO is suggested. Other ratios based on the effort dependence or independence of expiratory flow parameters—namely FEV1:forced expiratory flow, midexpiratory phase; PEFR:MEF50%; and FEV1:PEFR—have been proposed, but the visual inspection of the flow-volume loop remains the single most effective detection method.^5,13 Four values derived from the spirogram and the flow-volume loop have been suggested as being useful in aiding clinicians in the recognition of UAO (Table 2).¹⁷

The syndrome of obstructive sleep apnea (OSA) causes intermittent nocturnal hypopharyngeal obstruction and is probably the commonest form of UAO.5 Flow volume curves in these patients may have the sawtooth sign, which consists of regular oscillations in the forced expiratory or inspiratory flow-volume tracing.¹⁸ Though this finding was initially believed to be characteristic of the upper-airway narrowing seen in OSA patients, it has also been reported in patients with neuromuscular diseases, Parkinson disease, and episodic laryngeal dyskinesia.⁷

Alterations in the contour of the flow-volume loop can occur when there are changes in posture, as shown by Meysman and Vincken.¹⁹ They also measured spirometric indices and flow-volume loop contours in normal subjects in three recumbent postures. Based on decreases in all measured spirometric values seen in normal subjects following recumbency, they have suggested that obtaining flow-volume loops in different postures may increase the sensitivity of this method in detecting an upper-airway lesion.¹⁹ Recently, Melissant et al²⁰ performed exercise testing in normal volunteers breathing through fixed external resistances and found marked influences on the exercise capacity that could be attributed to hypoventilation secondary to increases in airway resistance.

Radiographic and Endoscopic evaluation
With the advent of spiral CT, multiplanar reconstruction of the upper airway in a longitudinal plane became possible. It can demonstrate the extent of tracheal and main-bronchial stenosis with a high degree of sensitivity and specificity.³ Fiber-optic bronchoscopy is usually the final step in the investigative paradigm for UAO, demonstrating definitively the extent, nature, and severity of obstruction (and also helping the clinician diagnose conditions, such as tracheomalacia, that may be missed using noninvasive imaging techniques).

In summary, UAO represents an important but remediable condition that is often overlooked in patients with respiratory disorders. A considerable proportion of UAO seen in clinical practice occurs due to iatrogenic causes, with postintubation tracheal and glottic strictures accounting for the majority. PF testing, especially flow-volume–loop measurement, remains the most effective way of detecting UAO. Flattening of the inspiratory and/or expiratory limbs during flow-volume–loop measurements should alert the RCP and clinician to the possibility of UAO. That, in turn, should initiate further testing and management aimed at relieving the obstruction.

Krishna M. Sundar, MD, is senior fellow in the Division of Respiratory, Critical Care, and Occupational Pulmonary Medicine, Department of Medicine, University of Utah, Salt Lake City. Richard E. Kanner, MD, is director of the Pulmonary Function Laboratory.

References
1. Jacobson S. Upper airway obstruction. Emerg Med Clin North Am. 1989;7:205-217.
2. Smith SW, Biros M. Relief of imminent respiratory failure from upper airway obstruction by use of helium-oxygen: a case series and brief review. Acad Emerg Med. 1999;6:953-956.
3. Fraser GM. Upper airway obstruction. In: Fraser RD, Muller NL, Colman N, Paré PD, eds. Diagnosis of Diseases of the Chest. 4th ed. Philadelphia: WB Saunders; 1999:III:2021-2053.
4. Courey MS. Airway obstruction: the problem and its causes. Otolaryngol Clin North Am. 1995;28:673-684.
5. Braman SS, Gaissert HA. Upper airway obstruction. In: Fishman AP, Elias JA, Fishman JA, et al, eds. Fishman’s Pulmonary Diseases and Disorders. 3rd ed. New York: McGraw-Hill; 1998:783-801.
6. Al-Bazzaz F, Grillo H, Kazemi H. Response to exercise in upper airway obstruction. Am Rev Respir Dis. 1975;111:631.
7. Aboussouan LS, Stoller JK. Diagnosis and management of upper airway obstruction. Clin Chest Med. 1994;1:35-53.
8. Elliott CG, Rasmusson BY, Crapo RO. Upper airway obstruction following adult respiratory distress syndrome : an analysis of 30 survivors. Chest. 1988;94:526-530.
9. Goldman J, Muers M. Vocal cord dysfunction and wheezing. Thorax. 1991;46:401-404.
10. Miller RD, Hyatt RE. Obstructing lesions of the larynx and trachea: clinical and physiologic characteristics. Mayo Clin Proc. 1969;44:145-161.
11. Miller RD, Hyatt RE. Evaluation of obstructing lesions of the trachea and larynx by flow-volume loops. Am Rev Respir Dis. 1973;108:475-481.
12. Mead J, Turner JM, Macklem PT, Little JB. Significance of the relationship between lung recoil and maximum expiratory flow. J Appl Physiol. 1967;22:95-108.
13. Lunn WW, Sheller JR. Flow volume loops in the evaluation of upper airway obstruction. Otolaryngol Clin North Am. 1995;28:721-729.
14. Gamsu G, Borson DB, Webb WR, Cunnigham JH. Structure and function in tracheal stenosis. Am Rev Respir Dis. 1980;121:519-531.
15. Gelb AF, Tashkin DP, Epstein JD, Farishter R, Zamel N. Diagnosis and Nd-YAG laser treatment of unsuspected malignant tracheal obstruction. Chest. 1988;94:767-771.
16. Rotman HH, Liss HP, Weg JG. Diagnosis of upper airway obstruction by pulmonary function testing. Chest. 1975;68:796-799.
17. Acres JA, Kryger MH. Clinical significance of pulmonary function tests: upper airway obstruction. Chest. 1981;80:207-211.
18. Krieger J, Weitzenblum E, Vandevenne A, Stierle J-L, Kurtz D. Flow-volume curve abnormalities and obstructive sleep apnea syndrome. Chest. 1985;87:163-167.
19. Meysman M, Vincken W. Effect of body posture on spirometric values and upper airway obstruction indices derived from the flow-volume loop in young nonobese subjects. Chest. 1998;114:1042-1047.
20. Melissant CF, Lammers J-WJ, Demedts M. Relationship between external resistances, lung function changes and maximal exercise capacity. Eur Respir J. 1998;11:1369-1375.

Acknowledgements
The authors thank Michael Skokan, MD, for providing the case summary and figures 1a and 1b and Sandy Lowe for expert secretarial assistance.