Vocal cord dysfunction (VCD) is the intermittent, abnormal adduction of the vocal cords during respiration resulting in variable upper airway obstruction. The variable airway obstruction classically affects the inspiratory phase of respiration but the expiratory phase can be affected as well. VCD frequently co-exists with asthma and complicates effective care and management when not recognized as a separate entity. Common symptoms of VCD include intermittent shortness of breath, wheezing, stridor, or cough, which may be interpreted as worsening asthma control given their nonspecific nature and can lead to unnecessary increases in asthma therapy. The gold standard for the diagnosis of VCD is by direct observation of the vocal cords with videolaryngostroboscopy (VLS). The variable nature of VCD can limit the diagnostic value of VLS and other direct observational approaches if symptoms are not present at the time of the study. Therefore, provocation techniques may be used to trigger symptoms during testing. Laryngeal control taught by a speech therapist is the primary treatment modality. Diagnosis and treatment of VCD as a comorbid condition of asthma requires a high index of suspicion on the part of the clinician and a multidisciplinary team approach for effective management.
The prevalence of VCD is unknown as there are no large, prospective, population-based studies examining its prevalence. Small clinical studies report increased frequency among females and those with uncontrolled gastroesophageal reflux disease (GERD), allergic rhinitis, and obesity [1,2•,3,4••,5••,6•]. VCD also frequently co-exists with asthma [2•,3,4••,5••,6•,7]. One study of 96 asthma and 40 control patients revealed 19% of the asthmatics, representing all levels of severity, had VCD compared to 5% of the controls based on direct laryngoscopy [6•].
Parsons et al. [4••] reported a significant co-existence of asthma and VCD and also showed that VCD occurs across the spectrum of asthma severity including mild-to-moderate asthmatics. Of the 59 consecutive asthma patients suspected of VCD referred for testing, 44 (75%) were diagnosed with VCD. The majority of patients (75%) had mild-to-moderate asthma, and only 25% were classified as severe persistent asthma per NIH guidelines [4••]. It is not clear why asthmatics have an increased susceptibility to VCD but several theories have emerged from small clinical studies.
The specific pathogenesis of VCD is unknown. Clinicians suggest psychogenic, neurogenic, or laryngeal hyper-responsiveness as possible underlying causes of VCD [7–10]. Early nomenclature implied that psychopathology was the primary underlying cause of VCD . However, a growing body of literature dispels psychopathology as the only primary underlying cause of VCD, and it is more likely a trigger of VCD in some patients. Husein et al.  performed psychological testing on 45 adults newly diagnosed with VCD and found 18 with classic conversion disorder, 13 with elevated scores for hypochondriasis and hysteria, and 11 with no identified psychopathology. VCD has also been associated with depression, anxiety, posttraumatic stress disorder, history of sexual abuse and stress [3,4••,11,12,13•]. In patients with underlying psychopathology, developing a treatment plan to include psychotherapy or appropriate medications in addition to laryngeal control techniques is associated with improved treatment outcomes [8,11,12,13•,14].
Neurogenic causes of VCD are rare but have been associated with brainstem compression or central or peripheral injury to the lower cranial nerves . Obtaining a history of surgical or traumatic injuries to the head and neck and performing a modified neurological assessment of cranial nerves IX–XI may help identify those with neurogenic pathology.
The concept of a hyper-responsive larynx, similar to the hyper-responsive airway in asthma, has been the focus of recent studies and may help explain the high prevalence of VCD seen in asthmatics. The larynx is highly innervated with sensory and motor nerve fibers which are thought to become hyperexcitable by intrinsic or extrinsic stimuli resulting in hyperfunctional glottic movement, cough and other laryngeal sensations [6•,7,10]. Symptoms are similar to asthma and it can be difficult to differentiate the two processes which may also co-exist in the same patient. Intrinsic irritants include GERD, laryngopharyngeal reflux (LPR), post nasal drip (PND), chronic cough, laryngeal dryness, exercise, and respiratory infections [1,7,15]. Extrinsic factors include any inhaled agent such as medications (beta-agonists, inhaled corticosteroids, etc.), fumes, allergens or particulate matter [15,16••,17,18•]. Providers have a growing awareness of the importance of treating common comorbid conditions such as GERD or PND; however, the asthmatic patients with VCD triggered by their inhalers may be under-recognized. Inhaled corticosteroids have been associated with laryngeal dryness, irritation and fungal infections, all of which could serve as triggers for VCD [16••]. Using the least amount of inhaled steroids to control asthma or changing the delivery of the medication may be of benefit in these patients [16••].
It appears that there is a spectrum of phenotypes among people with VCD with varying underlying mechanisms of disease. Thus optimal therapy often requires a multidisciplinary team to formulate individualized treatment plans. In addition to treatment of any comorbidities that can serve as a trigger, treatment of VCD is directed toward elimination of any identified irritant, providing rescue breathing techniques, and suppressive techniques for related throat symptoms. Obviously, recognition of VCD is a necessary first step.
VCD can masquerade or co-exist with asthma and may be difficult to discern due to overlapping symptoms. Diagnosis of VCD based on symptoms alone is inaccurate. Parsons et al. [4••] found that ‘classic’ symptoms of VCD such as hoarseness and stridor occur overall infrequently in patients with both VCD and asthma and do not distinguish asthmatics with VCD from those without VCD. In fact, patients with both VCD and asthma present with nonspecific symptoms of dyspnea, cough, and wheezing which can complicate assessment of asthma control [4••]. Important historical points that may raise suspicion of underlying VCD are if the patient's symptoms are out of proportion to objective measures or there is an inadequate or lack of response to standard asthma rescue therapy [1,11,13•]. Additionally, in our experience, many patients will describe exposure to scents, fumes or smoke as causing ‘their throat to close’ and often relate hearing an audible ‘wheeze’ which may in fact be stridor. Some patients also note the symptoms often resolve quickly with just relaxing or stopping an activity, which is atypical for asthma. Providers who obtain a careful history regarding symptoms, triggers, and medication response while maintaining a high index of suspicion for VCD increase the likelihood of identifying those patients with VCD and related comorbid conditions.
Patients with VCD and asthma report increases in nonspecific symptoms and worse asthma control as measured by the Asthma Therapy Assessment Questionnaire (ATAQ) [4••]. It is unclear whether these patients truly have more poorly controlled asthma or whether the increase in the ATAQ scores in patients with more severe asthma is due to the presence of VCD. Nonetheless, the failure to identify and treat VCD in patients with asthma may result in exposure to unnecessary medications, increased healthcare utilization and impaired quality of life.
Spirometry is commonly used to diagnose or guide therapy in asthma but is not a reliable diagnostic tool for VCD [13•]. A flattened or truncated flow volume loop has been described as a possible indicator of variable extrathoracic airway obstruction but is an insensitive and nonspecific indicator of VCD [6•,19••]. Sterner et al. [19••] reviewed 2662 pulmonary function tests (PFTs) and found 123 patients or 4.6% with abnormal inspiratory loops. Those with one out of three abnormal inspiratory loops generally had poor effort. In patients with two or more abnormal loops during testing, 20% (16 patients) underwent upper airway assessment revealing VCD (six), reflux disease (four), or obstructive lung disease (three) [19••]. In a cross-sectional study of 226 patients who had undergone laryngoscopy, three pulmonologists, blinded to all clinical information, were asked to predict VCD by reviewing flow volume loops only [5••]. All three pulmonologists rated 37 with normal loops of whom 14 were diagnosed with VCD. Similarly, in 18 patients with loops highly suggestive of VCD only five were diagnosed with VCD [5••]. The second arm of the study attempted to determine clinical or spirometric predictors of VCD but found no correlation [5••].
In a small prospective study of 20 patients, Holmes et al. [20•] explored a noninvasive diagnostic technique using high resolution dynamic volume computerized tomography (CT) of the larynx and found reductions in luminal area of the vocal cords could be measured during the inspiratory and expiratory cycles. Although use of CT holds promise, one would anticipate limitations similar to those encountered during direct visualization due to the intermittent nature of VCD.
Direct observation of the vocal cords is considered the gold standard for the diagnosis of VCD. It is also useful for ruling out other laryngeal abnormalities which may be contributing to symptoms [21•]. VLS is commonly used and has the advantage of recording the cord movement for diagnostic interpretation, patient education, and treatment biofeedback [21•]. A number of provocation techniques are used to induce symptoms during testing including breathing techniques (rapid deep breathing, panting, sniffing, coughing, various speaking tasks); exercise (stationary bike, treadmill, stair climbing, or sprinting); or scent or fume exposure (perfume, scented candles, nontoxic cleaners) [4••,5••,6•,13•,21•,22,23]. Ideally, the provocation techniques used are tailored to the patient based on triggers identified in the history. If provocation fails to elicit VCD in the lab but suspicion is high for the presence of VCD, the patient may require retesting. Alternatively, an empiric trial of speech therapy may be implemented. Highly trained athletes may not experience symptoms during short periods of exercise, thereby requiring distance running or similar cardiovascular activity immediately prior to the appointment to elicit symptoms. Future studies are needed to generate more evidence-based guidelines for the most effective diagnostic techniques.
The most common treatment approach for the reduction or elimination of symptoms, involves laryngeal control maneuvers taught by speech-language pathologists [8,13•,22,24,25]. Laryngeal control is a behavioral intervention that requires active patient participation. Speech-language pathologists assist patients in assimilating specific breathing techniques for adduction of the vocal cords. Patients may be rather suspect when offered a referral to a speech pathologist for treatment of VCD as few conditions with physically debilitating symptoms are managed without the use of pharmaceuticals. Patients with symptoms of VCD but a negative VLS test may also benefit from laryngeal control. Unfortunately, studies evaluating the effectiveness of laryngeal control are rare. Speyer  performed a systematic review of 47 studies evaluating the effectiveness of voice therapy for a broad range of laryngeal and voice pathology. He reported insufficient evidence for voice therapy in the literature due to the diversity of diagnoses, variety of voice therapy techniques and lack of standardization in assessment tools . Sullivan et al.  studied the effect of laryngeal control in 20 adolescent female athletes with VCD and found 95% were able to control symptoms of VCD with laryngeal control for up to 6 months after treatment. Murry et al.  reported subjective symptom improvement in cough and VCD in all 20 patients aged 18–87, treated with speech therapy and medical management for LPR.
Case reports and small studies support the effectiveness of laryngeal control but have limitations when attempting to generalize to large cohorts with varying comorbid conditions. Despite these limitations it appears laryngeal control is currently the most efficacious treatment of VCD. The techniques can be learned in as few as two or three sessions and have no direct or indirect consequences or side-effects of treatment. Van Leer and Connor [26•] evaluated patient perceptions of voice therapy adherence and reported three common themes: patients enrolled in voice therapy thought it was ‘hard’ due to the attention, awareness and compliance required for success; motivation and being actively engaged were necessary for improvement; the therapist they were paired with played an important role in keeping them motivated to learn the techniques and change behavior.
Adjunctive therapy includes biofeedback techniques using VLS to assist the patient in developing specific laryngeal techniques and psychotherapy for those with comorbid psychopathology [8,11,12,14,21•]. A validated Vocal Disability Coping Questionnaire is available to assist providers in assessing patient coping skills and identifying those with dysphonia who may require assistance in coping and adaptation . In extreme cases of respiratory compromise due to movement disorders of the larynx, botulinum toxin type A has been injected into the vocal folds for temporary relief of symptoms [21•].
VCD commonly affects the inspiratory cycle and patients experience an array of breathing symptoms, yet spirometry and peak flow measurements are rarely affected [10,17]. Therefore, spirometry remains an effective tool for assessing asthma control and medication response in those with asthma and VCD. In those with asthma symptoms out of proportion to spirometry, VCD should be suspected as the underlying cause. Additionally, incorporating a peak flow meter for home use in combination with an asthma action plan can help patients learn to distinguish symptoms of VCD from asthma. For patients with VCD and asthma, laryngeal control techniques should be included on the asthma action plan to initiate at the start of breathing symptoms. The techniques can be used in combination with standard asthma therapy during exacerbations. A ‘refresher’ session with a speech-language pathologist may be necessary if techniques are forgotten or effectiveness wanes.
Evaluating patients presenting to an emergency department (ED) or urgent care setting in acute respiratory distress can be challenging to discern VCD from asthma. Jain et al.  found that 10.4% of 48 patients presenting to the ED for presumed acute asthma exacerbations had upper airway dysfunction as evidenced by adduction of the anterior two-thirds of the vocal cords. Peters et al.  explored markers of inflammation as potential differentiating factors between VCD and asthma and reported that asthmatics (n = 77) presenting to an ED with acute asthma symptoms had more sinus pathology on computed tomography (CT) scan, elevated eNO, IgE, and eosinophils compared to 13 patients presenting to the ED with similar symptoms who only had VCD. It may be that these factors could be used to help distinguish acute attacks due to asthma versus VCD in allergic asthmatics; however, it does not appear to be useful for patients with both asthma and VCD and it is unclear whether similar findings would be present in nonallergic, non-IgE driven asthmatics. In a smaller study involving 17 adolescent patients presenting to an ED in acute respiratory distress, those with nonasthma were identified based on the presence of therapy resistant wheezing, near normal FEV1 on spirometry and pulse oximeter readings greater than 97% . Studies of patients presenting to the ED in acute respiratory distress have limitations as the environment is not amenable to withholding pharmacologic therapy until a battery of diagnostic testing can be performed.
There has been increased awareness in recent years of identifying VCD as a comorbid condition affecting the management of asthma. Clearly, the current state of the literature is inadequate for both defining and treating this prevalent entity. Future studies are needed to identify the specific pathogenesis of VCD and establish standard protocols for diagnostic evaluation and treatment.
J.G.M. and C.B. have no conflicts to report. J.P. serves as a consultant for Teva, Inc.
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 52).
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