INTRODUCTION — Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers [1]. Numerous other terms have been used to describe this ILO, including paradoxical vocal fold motion, laryngeal dyskinesia, vocal cord dysfunction (VCD), and periodic occurrence of laryngeal obstruction [1,2].
While clinical observations of this phenomenon were described by Dunglison in 1842, reports began to appear with increasing frequency in the 1970s and 1980s with the greater availability of laryngoscopy [3,4]. In 2015, the European Respiratory Society (ERS), European Laryngological Society (ELS), and the American College of Chest Physicians (ACCP) published a revised nomenclature and defined the term "inducible laryngeal obstruction" [2].
This topic will review the presentation, diagnosis, and treatment of ILO. Other causes of episodic dyspnea and exercise-induced laryngeal obstruction are discussed separately. (See "Evaluation of wheezing illnesses other than asthma in adults" and "Asthma in adolescents and adults: Evaluation and diagnosis" and "Assessment of stridor in children" and "Evaluation of wheezing in infants and children" and "Exercise-induced laryngeal obstruction".)
DEFINITIONS
Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing in the larynx in response to external triggers [1,2]. It is an umbrella term that includes exercise-induced laryngeal obstruction (EILO). Normally, the vocal folds abduct (move apart) during inspiration and slightly adduct (move towards each other) during expiration, coughing, and speech. During a symptomatic episode of ILO, paradoxical vocal fold adduction can be seen during inspiration, expiration, or both (figure 1) [3,5,6]. As the false vocal folds and supraglottic tissue may also dynamically constrict the airway, the term ILO is preferred to the more narrow description paradoxical vocal fold motion.
Exercise-induced laryngeal obstruction (EILO) refers to narrowing of the laryngeal airway at the glottic (vocal folds) or supraglottic (above the glottis) level during exercise. (See "Exercise-induced laryngeal obstruction".)
INDUCERS OF ILO — An inducer or trigger of ILO can be isolated or multifactorial. The most common inducers are exercise, irritants, and emotional stress [1]. Sometimes, ILO is idiopathic and no specific inciting agent can be clearly identified [2,7].
Asthma — While ILO is often misdiagnosed as asthma, it can be seen concomitantly with asthma [8,9]. Bronchoconstriction, such as during histamine inhalation challenge, appears to induce or be commensal with laryngeal obstruction in occasional patients [1,10-12].
Exercise — Exercise-induced laryngeal obstruction (EILO) refers to ILO that occurs during exercise and is discussed separately. (See "Exercise-induced laryngeal obstruction".)
Postextubation — ILO can occur shortly after extubation of patients who have been intubated for surgery or respiratory failure and presents with dyspnea and stridor. The use of flexible laryngoscopy in the immediate postextubation period allows differentiation between ILO and laryngospasm. Laryngospasm is usually an acute brief episode of sustained vocal fold adduction, often seen on emergence from general anesthesia [13-16]. (See "Overview of the management of postoperative pulmonary complications", section on 'Acute upper airway obstruction'.)
Inhaled irritants — Patients sometimes attribute ILO to inhalational exposure to a variety of irritants (eg, cigarette smoke, ammonia, soldering fumes, cleaning chemicals, aerosolized machining fluids, and construction dust) [1,5].
Laryngopharyngeal reflux — Reflux of gastric contents to the larynx and pharynx, also known as laryngopharyngeal reflux (LPR), is associated with ILO. However, it is unclear whether there is a causal relationship between LPR and ILO [17]. (See "Laryngopharyngeal reflux".)
Neurologic injury — ILO has been demonstrated in patients after thyroid and cervical spine surgery and in one patient after a polycranial neuropathy from herpes simplex. In this setting, the presumed etiology is recurrent laryngeal nerve aberrant reinnervation or synkinesis (involuntary contraction of a muscle caused by voluntary contraction of another muscle) [18].
Psychosocial disorders and stress — ILO has been associated with a variety of psychosocial disorders. In a prospective cohort of 45 patients, 18 patients were found to have conversion disorder, and 11 patients were found to have no psychopathology [19]. In a series of military personnel with ILO, 52 percent reported symptoms related to high stress and anxiety [20]. (See "Conversion disorder in adults: Clinical features, assessment, and comorbidity".)
ILO patients with a previous psychological history are prone to symptoms of depression and anxiety. Several studies have reported an association of ILO with a history of prior psychiatric illness, including depression, personality disorders, posttraumatic stress disorder, or a history of childhood sexual abuse [19,21-24]. In a case-control study comparing adolescents with ILO (called vocal fold dysfunction) to those with asthma, ILO patients had higher levels of anxiety and more frequent diagnoses of generalized anxiety disorder and separation anxiety [25].
CLINICAL PRESENTATION — Most studies note a female predominance, but ILO is well-documented in males [7,26]. ILO affects most all ages, occurring in the pediatric population and in adults [6,27].
The predominant complaint is dyspnea; patients may also report throat tightness, a choking sensation, dysphonia, cough, gastroesophageal reflux, or dysphagia [26,28,29]. When exercise is the inducer, the onset of respiratory symptoms is typically during maximal exercise [1,30]. For other inducers the temporal relationship with exposure is less well-established.
Stridor (noisy breathing) may be noted on inspiration, expiration, or both [31]. Stridulous sounds are usually loudest over the anterior neck and less audible through the chest wall. Patients may report these sounds as “wheezing”. Typically, albuterol has minimal to no beneficial effect. (See "Asthma in adolescents and adults: Evaluation and diagnosis", section on 'Bronchodilator response'.)
Some patients with ILO experience dysphonia during or between attacks [32]. On examination, this is often associated with supraglottic hyperfunction (eg, muscle tension dysphonia on examination, excessive false vocal fold adduction, and anterior-superior laryngeal compression during phonation). (See "Hoarseness in adults".)
EVALUATION — ILO should be suspected in patients with intermittent dyspnea, particularly in association with throat tightness, hoarseness, and/or stridor. A high index of suspicion is needed as ILO is sometimes misdiagnosed as asthma.
Pulmonary function tests — Patients who report intermittent symptoms isolated to exercise should undergo pulmonary function tests (PFTs) with spirometry pre and post bronchodilator to evaluate for asthma.
There is no evidence to suggest that ILO can be confirmed or excluded by PFTs alone [26]. Historically, flattening of the inspiratory loop of the flow-volume curve has been associated with extrathoracic airway obstruction from ILO (figure 2) [33]. However, there are many causes of a blunted inspiratory flow-volume curve, including inadequate instruction, suboptimal effort, inability to perform the procedure, and other respiratory conditions [1]. (See "Flow-volume loops".)
Surrogate or substitute inducers — Surrogate inducers (eg, methacholine, histamine, mannitol) have been used for provocation challenges with a focus on the inspiratory flow volume loop or with concomitant laryngoscopy [1]. However, results are mixed [12,34], and it is unclear how well a surrogate or substitute inducer recreates the findings of a symptomatic episode that occurs outside of the testing environment [1,35].
Laryngoscopy — Flexible laryngoscopy is essential to the diagnosis of ILO. The procedure should be performed by an experienced laryngoscopist who can direct the patient to perform tasks such as sniffing and phonation to correctly assess vocal fold motion. The location of any obstruction should be described, whether supraglottic (eg, arytenoid region, epiglottis, false vocal folds), true vocal folds, or a combination [2].
During the baseline laryngeal examination, when the patient is asymptomatic, the true vocal folds abduct (open) during inspiration and partially adduct (close) during expiration (figure 1). Full brisk abduction can be induced by sniffing. Adduction of the true vocal folds occurs with phonation, coughing, throat clearing, swallowing, and during a Valsalva maneuver. Partial adduction (approximately 10 to 40 percent) is normal during expiration. It is also normal to see vocal fold adduction for 0.2 seconds following the end of the inspiratory phase just prior to a cough [36].
The diagnosis of inspiratory ILO is made when laryngoscopy reveals abnormal adduction of the membranous true vocal folds (figure 1) [3,37]. There may also be adduction or bunching of the false vocal folds [3,37,38].
Visualization of the larynx using a flexible laryngoscope is imperative to confirm a patent supraglottis, glottic aperture, and subglottis and exclude other static and dynamic causes of upper airway obstruction. (See 'Differential diagnosis' below.)
If possible, tracheoscopy is performed during flexible laryngoscopy to exclude causes of central airway obstruction that might have a similar presentation. Otherwise, the central airway should be evaluated by another method, such as flexible bronchoscopy or high resolution computed tomography (HRCT) with reconstruction. (See "Clinical presentation, diagnostic evaluation, and management of central airway obstruction in adults" and "Tracheomalacia and tracheobronchomalacia in adults".)
Continuous laryngoscopy during exercise — For patients with symptoms limited to exercise and suspected EILO, exercise testing with continuous laryngoscopy is considered the test of choice. (See "Exercise-induced laryngeal obstruction", section on 'Continuous laryngoscopy during exercise'.)
Imaging — Imaging is predominantly used to exclude other causes of dyspnea. If examination of the trachea is not possible during laryngoscopy, Computed tomography (CT) of the upper airways can be used to exclude subglottic stenosis, tracheal and extratracheal (eg, thyroid) masses, or excessive dynamic airway collapse. (See "Evaluation of wheezing illnesses other than asthma in adults", section on 'Imaging' and "Tracheomalacia and tracheobronchomalacia in adults".)
DIAGNOSIS — Laryngoscopy when the patient is symptomatic is the gold standard for the diagnosis of ILO. As noted, the characteristic feature on laryngoscopy is abnormal adduction of the membranous true vocal folds, which may be accompanied by adduction or bunching of the false vocal folds (figure 1) [3,37]. Laryngoscopy is typically normal between episodes. (See 'Laryngoscopy' above.)
DIFFERENTIAL DIAGNOSIS — In patients suspected of having ILO, a thorough evaluation for asthma and other causes of upper airway obstruction is essential [39].
●Asthma – Features that support a diagnosis of asthma with or without ILO include fully reversible airflow limitation on spirometry and a clear symptomatic response to asthma therapy. On laryngoscopy, some patients with asthma have expiratory vocal fold adduction that is thought to be a form of intrinsic positive expiratory pressure [2]. Generally, this resolves when asthma is well-controlled. (See "Asthma in adolescents and adults: Evaluation and diagnosis" and "Asthma in children younger than 12 years: Initial evaluation and diagnosis".)
●Laryngospasm – Patients with laryngospasm describe the abrupt onset of complete airway obstruction (the sensation of choking) and aphonia. Laryngospasm may be triggered by laryngopharyngeal reflux, and it sometimes awakens the patient from sleep. Laryngospasm can be seen in the setting of a viral upper respiratory infection with severe coughing or following extubation after general anesthesia or mechanical ventilation [40]. (See "Laryngopharyngeal reflux".)
●Laryngeal angioedema – Laryngeal angioedema can be caused by anaphylaxis, angiotensin converting enzyme inhibitor therapy, and C1 inhibitor deficiency. Extralaryngeal angioedema (eg, lips, tongue) may be a clue to the diagnosis, if present. (See "An overview of angioedema: Pathogenesis and causes".)
●Vocal fold motion abnormalities – Vocal fold motion abnormalities such as bilateral vocal fold paresis from central or peripheral causes, such as motor neuron disease, brainstem compression, neuropathy or iatrogenic injury of the vagus or recurrent laryngeal nerves, or adductor laryngeal breathing dystonia [41]. (See "Etiology, clinical features, and diagnostic evaluation of dystonia", section on 'Laryngeal dystonia'.)
●Laryngeal or tracheal stenosis – Laryngeal or tracheal stenosis or narrowing (eg, supraglottic, glottic, or tracheal scar or neoplasms) can cause upper airway obstruction and requires careful visualization of the airway for exclusion. (See "Clinical presentation, diagnostic evaluation, and management of central airway obstruction in adults".)
●Excessive dynamic airway collapse – Excessive dynamic airway collapse, such as prolapse of supraglottic tissue, laryngomalacia, or tracheomalacia, can mimic ILO or coexist with it [31,42]. Exercise-induced laryngomalacia can be differentiated from exercise-induced laryngeal obstruction (EILO) upon exercise testing with laryngoscopy that shows redundant tissue rather than abnormal vocal fold motion [42]. (See "Evaluation of wheezing illnesses other than asthma in adults", section on 'Extrathoracic upper airway causes of wheeze' and "Exercise-induced laryngeal obstruction", section on 'Laryngeal findings' and "Tracheomalacia and tracheobronchomalacia in adults".)
TREATMENT — Various treatment strategies have been used for ILO, although none have been studied in a controlled fashion. The treatment of ILO can sometimes be guided by medical management of associated inducers when present [7]. If the inducer is not known, treatments are empiric rather than evidence-based. (See 'Inducers of ILO' above.)
The management of exercise-induced laryngeal obstruction is described separately. (See "Exercise-induced laryngeal obstruction", section on 'Treatment'.)
Acute management — Acute management strategies that may be useful include:
●Reassurance and supportive care until the episode spontaneously resolves. Asking patients to pant can sometimes abort an episode; panting activates the posterior cricoarytenoid muscle causing abduction of the true vocal folds [43].
●Inhaled bronchodilators are not useful for ILO but may be useful for patients with concomitant asthma.
●Use of continuous positive airway pressure [37,44]. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)
●While rarely used, inhalation of a helium-oxygen mixture (heliox) has been reported to be helpful [3,45,46]. In a small series, patients experienced an improvement in symptoms, including anxiety, with heliox inhalation during acute episodes [45]. (See "Physiology and clinical use of heliox".)
●Endotracheal intubation or tracheostomy is not needed for ILO [44].
Long-term prevention — Long-term prevention strategies employ a multidisciplinary approach of minimizing laryngeal irritation and treatment by a speech-language pathologist (SLP) [27,47]. When ILO coexists with asthma, medications for asthma should be continued during treatment for ILO and coordinated with the treating asthma specialist.
Avoidance of airway irritants — Based on clinical experience, efforts should be made to identify inducers (eg, perfume, cleaning chemicals, dust, smoke, laryngopharyngeal reflux) and mitigate further exposure, when possible [1,48]. (See 'Inducers of ILO' above and "Laryngopharyngeal reflux".)
Speech-behavioral therapy — The SLP may assist with the diagnosis during the acute management stage, provide treatment during longer-term management, and coordinate communication of patient care when multiple health care providers are involved.
The SLP's role includes:
●Behavioral speech/voice therapy to address vocal use issues, perilaryngeal tension, and respiratory retraining
●Supporting and educating patients who are prescribed medical treatment of any underlying reflux-associated vocal fold lesions and/or allergies
●Education of family members, school personnel, and coaches in the case of adolescent athletes, as appropriate (see "Exercise-induced laryngeal obstruction")
A typical SLP therapy plan is designed to help the patient regain laryngeal control. Strategies often include:
●Respiratory retraining, focusing on rescue breathing for use during an episode, rhythmic low abdominal breathing to help with prevention, coordination of timing between respiration, and phonation
●Whole-body relaxation techniques
●Relaxation techniques for the extrinsic laryngeal muscles, neck, shoulders, and thoracic area
●Vocal hygiene
●Phonatory retraining when appropriate to eliminate vocally abusive and tension-causing behaviors
Success has been reported with speech/voice therapy that uses breathing, voice, and neck relaxation exercises to abort the onset of ILO episodes [3,27,37,49-58]. In a series of five adults with ILO, all patients improved with respiratory retraining, after failure of proton pump therapy for laryngopharyngeal reflux [59]. Techniques, such as focusing attention away from the larynx (eg, nasal breathing, diaphragmatic breathing) and inspiration, using abdominal muscles for breathing, and relaxing the neck muscles [3,48].
SLPs who are trained in the use of videolaryngoscopy may employ this tool for biofeedback during a therapy session, so the patient can observe the result of measures to control breathing.
Preliminary data suggest that a newly developed Vocal Cord Dysfunction Questionnaire (VCDQ) may be useful in monitoring responses to speech-language therapy in patients with a confirmed ILO diagnosis [60].
The role of speech therapy in the management of exercise-induced laryngeal obstruction (EILO) is discussed in greater detail separately. (See "Exercise-induced laryngeal obstruction", section on 'Treatment'.)
Handouts and internet resources are often helpful for supervisors (in the case of adults) and parents/caregivers, school personnel, and coaches (in the case of children and adolescents), so they will understand the challenges of someone with a diagnosis of ILO or EILO. Patients (or their parents/caregivers) may request that the SLP communicate with other care providers regarding strategies for coping with an episode or to report progress or reasonable expectations for a return to activity.
Psychotherapy — For patients with psychosocial inducers of ILO, psychotherapy may be a part of the comprehensive treatment plan in combination with speech therapy, although this has not been formally studied [1]. Therapy may help patients identify psychosocial inducers/triggers and gain control of emotional responses to stress.
Botulinum toxin for refractory laryngeal dyspnea — Preliminary data suggest a potential role for botulinum toxin in the management of refractory ILO [1]. Botulinum toxin has been injected into the larynx to treat laryngeal dyspnea, caused by bilateral vocal fold hypomobility, laryngeal dystonia, and ILO. Botulinum toxin is used in combination with speech therapy and psychotherapy, or as a stand-alone treatment [61,62].
In a series of 13 patients with ILO that was refractory to medical management and respiratory retraining with an SLP, 11 of 13 (84.6 percent) patients experienced improvement of dyspnea [62]. In this study, the average dose of botulinum toxin was 2.55 units per vocal fold, and the average number of injections was 3.85. Further study is needed to confirm benefit and clarify optimal dosing. (See "Treatment of dystonia in children and adults", section on 'Focal dystonia'.)
Side effects of botulinum toxin injection in the larynx can include voice change, increased difficulty breathing, and aspiration when swallowing [61].
ADDITIONAL RESOURCES
American Academy of Asthma Allergy and Immunology
American Thoracic Society: Patient Information
American Thoracic Society Vocal Cord Dysfunction
National Jewish Health
National Jewish Health Vocal Cord Dysfunction
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Inducible laryngeal obstruction (ILO) (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Inducible laryngeal obstruction (ILO) describes an inappropriate, transient, reversible narrowing of the larynx in response to external triggers. (See 'Introduction' above.)
●ILO may be triggered or may occur spontaneously. (See 'Inducers of ILO' above and "Exercise-induced laryngeal obstruction".)
●ILO is often mistaken for asthma because it is episodic, it may be brought on by exertion, and the stridor may sound similar to wheezing. Some patients have both asthma and ILO. In asthma, however, the wheezing is typically expiratory. (See 'Clinical presentation' above.)
●Between episodes, when patients are asymptomatic, spirometry is often normal. Flow-volume curves may show flattening of the inspiratory loop consistent with extrathoracic airway obstruction, but this finding is variable and not specific for ILO (figure 2). (See 'Pulmonary function tests' above.)
●The diagnosis is confirmed by flexible laryngoscopy during an episode by visualization of abnormal adduction of the vocal folds and exclusion of other causes of glottic and subglottic obstruction. In some patients, the glottic aperture may be obliterated during inspiration except for a posterior diamond-shaped passage (figure 1). (See 'Evaluation' above.)
●The differential diagnosis of ILO includes asthma, angioedema, laryngospasm, vocal fold motion abnormalities, laryngotracheal stenosis, and excessive dynamic airway collapse (eg, laryngomalacia, tracheomalacia). (See 'Differential diagnosis' above.)
●In patients with an acute episode of ILO, we suggest initially using a combination of reassurance and panting maneuvers (Grade 2C). If this is not effective, continuous positive airway pressure may be helpful; inhalation of a helium-oxygen mixture might be another alternative based on anecdotal reports. (See 'Treatment' above.)
●In patients with recurrent ILO, we suggest a long-term management strategy that combines speech and behavioral therapy, and also avoidance of perceived laryngeal irritants (Grade 2C). When ILO coexists with asthma, medications for asthma should be continued. (See 'Treatment' above.)
●The treatment of exercise-induced laryngeal obstruction (EILO) includes speech-behavioral therapy and sometimes biofeedback using therapeutic laryngoscopy during exercise. (See 'Speech-behavioral therapy' above and "Exercise-induced laryngeal obstruction", section on 'Treatment'.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Jo Shapiro, MD, who contributed to an earlier version of this topic review.
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