The presence of inspiratory stridor, a characteristic symptom of VCD, occurs during exercise and most often spontaneously resolves within 2 to 5 min after exercise stops. The stridor associated with VCD is mistaken frequently for EIB and often leads to misdiagnosis (38) not only when it is self-reported but also when the symptoms are observed by the practitioner who may not be familiar with the unique symptomology. Unlike the typical wheeze of EIB, which originates in the chest region and predominates during exhalation, the stridor associated with VCD is pronounced most during inspiration and is accompanied by a feeling of throat tightness.
The precise pathophysiology that results in the VCD response has not been established firmly but probably involves multiple mechanisms. There are several studies that implicate gastroesophageal reflux disease (GERD) (26,32), laryngopharyngeal reflux, postnasal drip (7), irritant exposure (33), and psychological conditions (12,30). GERD has been found to be associated with asthma and the accompanying symptoms (32) as well as VCD, especially within the pediatric population (28). VCD has been observed in patients exposed to smoke, pollutant particulates, gas vapors as well as perfumes (4). These studies suggest that the upper airway may become sensitive to irritants and respond with a glottal closure reflex. VCD associated with exercise, especially in competitive sports, may be triggered by emotional stress but may not be exclusive of the above suspect triggers. In addition, the psychiatric disorders identified in association to VCD (13,21,30) may provide some insight to the relatively high comorbidity of VCD found with asthma and EIB. The higher levels of anxiety of these patients concerning their condition may provide a psychogenic stress that triggers VCD.
The true prevalence of EIB is difficult to ascertain because of the inconsistent definitions of EIB, patient populations, and the experimental conditions used in various studies. There is ample evidence that a diagnosis based on symptoms is unreliable. About half of the athletes who report symptoms will not have measurable falls in lung function and about half who report being symptom free will have significant falls in lung function after exercise (36). An exercise challenge is necessary to make the diagnosis; however, the conditions of the test are of paramount importance. Exercise intensity, ambient air allergen content and pollution, and medication use can alter the EIB response. Different studies have used varying cut-off criteria for a positive test. In addition, the water content of the inhalant is critical to the test response. In a study by Rundell et al. (36), 78% of 23 elite winter athletes who tested positive for EIB by a cold/dry air field run tested negative on a treadmill run at 95% of an estimated maximal heart rate in 60% RH and 21°C. Stensrud et al. (41) demonstrated that subjects with EIB exercising at room temperature and 95% RH had reduced bronchial hyperreactivity by half of that at room temperature and 40% RH; 12% versus 24% fall in a forced expiratory flow in 1 s (FEV1) (41). In another study by Castricum et al. (8) on 33 swimmers, 18 demonstrated EIB by dry air eucapnic voluntary hyperventilation (EVH), while only four tested positive by ambient air cycle ergometry.
Certain athlete populations appear to have a higher prevalence of EIB and BHR. This likely is due to the specific ventilatory demands in combination with environmental exposure to cold dry air and air pollutants during exercise. The wide range of prevalence values of EIB for different sports presented in Table 2 is indicative of the varied methodology employed to evaluate the athletes. Although this table is far from complete, and in spite of the inherent diagnostic flaws, it is quite clear that some athletic activities present a greater risk for EIB than others.
Like EIB, a lack of well-defined criteria for VCD diagnosis and the lack of awareness of VCD make the prevalence estimates difficult. Approximately 5% to 15% of patients referred for exercise dyspnea or EIB evaluation were reported to have solitary VCD (1,25,38). However, in one study, the incidence was as high as 27% (40). Another study evaluating military recruits found that 10% of 105 active duty patients had VCD (27). A retrospective analysis of 245 patients revealed 16 (6.5%) with suspected VCD, and these were confirmed through laryngoscopy in 4 (1.6%) (6). Pathologies were significantly more common in women than in men (63.8% vs 36.2%, respectively) (47).
EIB and VCD can both be present and responsible for exercise-induced symptoms in the same individual. Comorbidity of VCD with asthma or EIB is not well defined, but emerging data suggest that this may be a common occurrence. In fact, in a group of 370 elite winter athletes, Rundell and Spiering (38) found that 111 tested positive for EIB and 19 had pronounced inspiratory stridor consistent with VCD; of those 19, 10 (53%) tested positive for EIB; of note, the 9 VCD+/EIB− athletes were previously misdiagnosed as having EIB. Hanks et al. (16) evaluated 148 collegiate, middle school, high school, and recreational athletes who were referred to an asthma center for evaluation of respiratory complaints with exercise. Of these 148 athletes, 52% were diagnosed with EIB, 17% with asthma, and 70% with VCD, and 31% demonstrated coexistence of EIB and VCD.
In a retrospective analysis of 59 patients with pulmonologist-diagnosed asthma who were referred for videolaryngostroboscopy analysis, 44 (∼75%) patients were identified with both asthma and VCD and 15 patients had asthma without concomitant VCD (31). The majority of patients referred for laryngostroboscopy testing had mild-to-moderate asthma (78%) and 72% had VCD. Interestingly, few patients with VCD had the “classic” symptoms of stridor or hoarseness. GERD and rhinitis were common in both VCD and non-VCD groups.
A descriptive study (50) examined 94 asthmatic patients and 40 control subjects by laryngoscopy and pulmonary function tests. The prevalence of VCD was 19% (n = 18) in the asthmatic group and 5% (n = 2) in the control group. No relationship was found between the presence of VCD, asthma attacks, and asthma severity. Laryngopharyngeal reflux and allergy were significantly more prevalent in the VCD group than in those without VCD. The most common symptoms in the VCD-positive patients were difficulty in breathing (88%), inspiratory stridor (66%), and a choking sensation (50%), and the most common symptoms in the VCD-negative asthmatic patients were cough (63%), dyspnea (55%), and wheezing (51%) (50).
It appears that both EIB and VCD are common disorders of the airways among the athlete population. VCD is misdiagnosed often as EIB and later perhaps refractory asthma when medications are ineffective. The existence of VCD among asthmatic patients and those experiencing EIB appears to be quite substantial, ranging from 19% to 75%.
Pulmonary function testing is of limited use in diagnosing VCD and differentiating it from asthma. In patients with persistent asthma, the characteristic finding is a reversible lower airway obstruction. There is a decrease in the ratio of FEV1 to the forced vital capacity and a decrease in FEV1. An increase in FEV1 of at least 12% is considered a positive bronchodilator response and indicates reversibility. However, the spirometry may be normal in both asthma and VCD. In addition, asthma and VCD often coexist, which further complicates the diagnosis (30,39).
The diagnosis of EIB should be made through standardized testing using spirometry. Current guidelines (American Thoracic Society (ATS), European Respiratory Society (ERS), and International Olympic Committee Medical Commission (IOC MC)) require a 10% or greater decrease in FEV1 in response to exercise or EVH for a diagnosis of EIB (37). In one study, there was no difference in postexercise FEV1 in elite athletes who developed inspiratory stridor (39). However, in some patients, the expiratory obstruction of VCD may mimic EIB. The time course of the obstruction in VCD and EIB usually differs. Obstruction due to VCD usually resolves quickly after cessation of exercise; in contrast, obstruction due to EIB usually develops during or immediately after exercise and may take up to 30 or more minutes to resolve depending on its severity.
Bronchoprovocation testing using methacholine, histamine, and inhaled dry powder mannitol are used to diagnose asthma. However, methacholine also has been shown to precipitate attacks of VCD (32). In addition, as asthma commonly exists with VCD, a positive response does not rule out VCD.
Examination of the flow-volume curve may yield some clues. The classic finding for VCD is the truncation of the inspiratory loop, which is consistent with the variable extrathoracic obstruction. However, the finding is neither sensitive nor specific (32,39,42). A postexercise midflow (forced expiratory flow (FEF) (50)/forced inspiratory flow (FIF) (50)) ratio >1.5 may correlate with the presence of VCD. In one study, the ratio was higher for those athletes with EIB who developed inspiratory stridor than for those who did not (38). Flow-volume curves obtained during exercise when the patient is symptomatic may be more helpful than those obtained postexercise, if symptoms have resolved. Neither radiologic nor laboratory studies are helpful in establishing the diagnosis of VCD.
The gold standard for diagnosis of VCD is direct fiberoptic laryngoscopy. The classic finding is paradoxical adduction of the vocal cords during inspiration and occasionally during expiration (9,30). However, evaluation should be performed during an acute episode. Normal findings when the patient is asymptomatic do not rule out VCD. Often, laryngoscopy is performed before and after exercise. However, laryngoscopy performed continuously during exercise has been described recently and is a powerful tool for assessing laryngeal function during exercise (46).
It is important to make the diagnosis of VCD as misdiagnosis can result in the overuse of inappropriate and ineffective medications (30). Comorbid conditions such as gastroesophageal reflux, laryngopharyngeal reflux, and postnasal drip should be addressed (34). The diagnosis of gastroesophageal reflux and laryngopharyngeal reflux may be made on the basis of symptoms. Direct fiberoptic laryngoscopy may reveal supportive evidence of inflammation (20). The use of histamine-2 blockers or proton pump inhibitors should be considered in these patients. Postnasal drip from allergic or chronic rhinitis may cause laryngeal irritation. Assessment for specific allergies may be helpful in order to guide avoidance. Treatment with topical nasal or systemic anti-inflammatory or antihistamine medications may be indicated.
Control of concomitant asthma and EIB are important. In athletes with persistent asthma, daily treatment with inhaled corticosteroids will improve asthma symptoms, pulmonary function, and EIB (19,43). Short-acting inhaled b2-agonists given before exercise can prevent EIB; however, they should be used with caution since tolerance can occur when they are taken daily. This is seen most commonly when combination medications of inhaled corticosteroids and long-acting b2-agonists are used (3,29,35). Chronic use of b2-agonists also can increase the severity of EIB (15,18). Montelukast also can used to reduce EIB without inducing tolerance, and it can enhance the effect of the preexercise b2-agonists (10). Pretreatment with cromolyn sodium (sodium cromoglycate) and nedocromil can decrease EIB (49), but they are no longer readily available in the United States. This underscores the need to accurately diagnose VCD, which does not respond to any of these medications.
Specific pharmacologic treatment of VCD is rarely indicated. The use of anxiolytics, a mixture of helium and oxygen, and intralaryngeal botulinum toxin injection have been reported in the literature (14). In one study, an anticholinergic inhaler was used in order to prevent exercise-induced VCD (11). However, further studies are warranted before this becomes a standard of care.
Management of VCD should include assessment of contributing psychological issues such as anxiety, separation disorder, depression, posttraumatic stress disorder, and conversion disorders. Children and athletes with EIB have a lower incidence of severe psychiatric disorders than adults with spontaneous VCD (13,30,34). These patients have been described as coming from success-oriented backgrounds and were vulnerable to internal and/or external pressure not to fail. Social, academic, and athletic stressors should be examined. Assessment for more severe underlying psychiatric diseases also should be made. Counseling, psychotherapy, and stress management may help improve the response to stressors. Hypnosis and biofeedback have been utilized to treat VCD (2).
Speech and behavioral therapy are the cornerstones of therapy. Patient education and reassurance is important. The goal is to educate the patient to recognize the onset of a VCD attack and to use techniques to control it. Relaxed throat, diaphragmatic, and resistive breathing have been used to minimize the patients’ focus on the inspiratory phase of respiration, to coordinate thoracic and abdominal respiratory movement patterns, and to divert attention away from the larynx (30). Inspiratory muscle training has been shown to improve VCD (24). In one study of female athletes, 95% were able to control their symptoms 6 months after institution of a speech therapy program (45).
EIB and VCD are important causes of exercise-induced dyspnea. Their pathophysiological mechanisms are completely different. VCD is associated with paradoxical adduction of the vocal cords, while EIB is associated with bronchoconstriction of the lower airways and release of inflammatory mediators. VCD typically resolves as soon as the exercise stops, while EIB often peaks 5 to 15 min after cessation of exercise. VCD is associated often with inspiratory stridor, while the wheeze of EIB is usually expiratory in nature. EIB can be prevented, attenuated, or reversed by a bronchodilator, while a bronchodilator does not provide protection from exercise-related VCD. However, in practice, it is often very difficult to distinguish between the two entities. In addition, they often coexist in the same patient; 20% to 78% of patients with asthma have been reported to also have VCD. History alone cannot differentiate between EIB and VCD, and an appropriate challenge test for EIB accompanied by flexible laryngoscopy to observe the vocal cords during symptoms is often necessary for diagnosis. It is important for physicians and athletic trainers to be aware of the etiology, symptoms, diagnosis procedures, and treatment for both EIB and VCD.
There are no conflicts of interest or financial disclosures for Kenneth W. Rundell or Pnina Weis.
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