Does Treatment of Paradoxical Vocal Fold Movement Disorder Decrease Asthma Medication Use?

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1 The Laryngoscope VC 2016 The American Laryngological, Rhinological and Otological Society, Inc. Does Treatment of Paradoxical Vocal Fold Movement Disorder Decrease Asthma Medication Use? Scott Kramer, MD; Brad desilva, MD; L. Arick Forrest, MD; Laura Matrka, MD Objectives/Hypothesis: To determine whether diagnosis and treatment of paradoxical vocal fold movement disorder (PVFMD) leads to decreased asthma medication use. Secondary objectives include determining initial rate of asthma medication use, characterizing symptom improvement, and correlating with pulmonary function testing (PFT). Study Design: Prospective observational study. Methods: Patients newly diagnosed with PVFMD at a single institution were recruited to participate. Medication questionnaires were completed at the initial visit, at the first return visit for therapy, and at 6 months. PFTs were reviewed when available. Results: Sixty-six patients were recruited; the study was closed early because findings reached significance. Fifty-six patients (85%) were taking asthma medication at presentation. Forty-four patients presented with PFTs, and two-thirds were normal. Forty-two patients completed follow-up questionnaires; 79% decreased asthma medication use (P <.001), and 82% reported symptom improvement. Seventy-seven percent of patients participated in therapy and 23% did not, with equal rates of decrease in asthma medication use between these groups. Outcomes did not vary based on PFT pattern (i.e., obstructive vs. nonobstructive, P 5.75). Conclusions: Diagnosis and treatment of PVFMD lead to a decline in asthma medication use. This decrease occurred alongside symptom improvement and irrespective of PFT findings. Use of asthma medication in this patient population is high, at 85%. Key Words: Paradoxical vocal fold movement, vocal cord dysfunction, asthma. Level of Evidence: 4. Laryngoscope, 127: , 2017 INTRODUCTION Paradoxic vocal fold movement disorder (PVFMD) is a disease characterized by intermittent episodes of dyspnea, cough, and stridor. This clinical constellation is nonspecific, and many patients with PVFMD are initially tested and treated for asthma before a proper diagnosis is reached. 1 3 Early diagnosis and treatment is critical, because undiagnosed PVFMD has been linked with very high healthcare costs, and efficacious therapy is available. 4,5 Asthma is one of the most common misdiagnoses, and patients referred to the otolaryngologist for PVFMD evaluation may already be taking asthma medication. 6 8 Patients with PVFMD who use asthma medications may in fact worsen their dyspnea, secondary to a vicious chemical-physiologic cycle. In this cycle, patients use asthma medication without significant From the James Care Voice and Swallowing Disorders Clinic, The Ohio State University, Wexner Medical Center, Columbus, Ohio, U.S.A. Editor s Note: This Manuscript was accepted for publication September 27, A portion of this research was presented at the American Broncho-Esophageal Association Annual Meeting, Las Vegas, Nevada, U.S.A., May 14, The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Laura Matrka, MD, Ohio State University, Wexner Medical Center, Eye and Ear Institute, Suite 4000, 915 Olentangy River Road, Columbus, OH laura.matrka@osumc.edu DOI: /lary effect on their dyspnea, and the inhaled medication causes laryngeal irritation that worsens their symptoms and prompts further inhaler usage, propagating the cycle. No studies have previously determined the effect of diagnosis and treatment of PVFMD on asthma medication use. It can be difficult to distinguish PVFMD from asthma; furthermore, asthma and PVFMD frequently coexist, with varying symptomatic contributions from each entity. 9 Patients who are referred for PVFMD evaluation by pulmonologists have often been told they have a degree of asthma, but with symptoms out of proportion to asthma alone. It can be unclear what proportion of their symptoms is due to asthma versus PVFMD. Some patients undergo pulmonary function testing (PFT) and are prescribed asthma medications, but are still not definitively given the diagnosis of asthma. The primary objective of this study was to determine if the treatment of PVFMD leads to decreased use of asthma medication. A secondary objective is to determine if diagnosis and education alone (absent the completion of any formal therapy) has any effect on medication use. Tertiary objectives are to determine 1) symptomatic response to diagnosis and treatment of PVFMD, 2) the percentage of patients presenting for PVFMD evaluation who are already using asthma medication, 3) any differences in the above outcomes based on PFT patterns. 1531

2 MATERIALS AND METHODS Study Design This is a prospective observational cohort study of 66 patients conducted at the JamesCare Voice and Swallowing Disorders Clinic at The Ohio State University, Wexner Medical Center from July 1, 2013 to July 1, Prior to beginning data collection, the Ohio State University Institutional Review Board approved the study protocol. Patients newly diagnosed with PVFMD ages 13 to 80 years were recruited to participate in a consecutive manner. Diagnosis of PVFMD was made based upon previously described guidelines. 10 All patients diagnosed with PVFMD underwent flexible transnasal laryngoscopy and demonstrated evidence of all of the following: 1) inappropriate Fig. 1. Initial medication questionnaire completed at the time of diagnosis. 1532

3 Fig. 2. The follow-up questionnaire shown is completed at first postdiagnosis visit and at 6 months. adduction of vocal folds during quiet respiration, breath holding, counting tasks, or after physical exertion or odor presentation as described by Forrest et al. 10 ; 2) full abduction at some point during the exam, ruling out paresis or paralysis; 3) no evidence of another cause of airway obstruction. If evidence of inappropriate movement was not observed at rest or with the provocative respiratory tasks, patients were challenged with either exercise or odor presentation, if either was noted as a symptom trigger for the patient. Exclusion criteria for study participation included: 1) systemic corticosteroid use for another disease besides asthma or chronic obstructive pulmonary disease, 2) evidence of other laryngeal pathology affecting vocal fold mobility, 3) previous treatment or diagnosis of PVFMD, and 4) inability to participate in laryngeal control therapy for cognitive reasons. Whether a patient was definitively diagnosed with asthma in addition to PVFMD did not affect eligibility, for reasons noted above. When available, PFT results were reviewed for evidence of an obstructive pattern; PFT results had no bearing on diagnosis or eligibility to participate. The study was initially designed to recruit 200 patients. However, due to the significance of results at an interval analysis time point, the decision was made to report results early and close the study. Data Collection Upon diagnosis and subsequent consent to participate in the study, patients completed a medication questionnaire (Fig. 1) examining their use of short-acting and long-acting b-agonists, inhaled or oral corticosteroids, inhaled corticosteroid/b-agonist combinations, leukotriene inhibitors, and inhaled anticholinergic medications. Patients were then educated on the features of PVFMD, using the video of their laryngoscopy to illustrate key aspects, and they were offered a course of laryngeal control therapy. Laryngeal control therapy was performed by a licensed speech language pathologist (SLP) with specialized training in the treatment of PVFMD. A second medication questionnaire (Fig. 2) was completed at the start of the first return visit for laryngeal control therapy to capture any effect from the initial visit and its associated education alone. The same follow-up questionnaire was completed at approximately 6 months following diagnosis, whether or not therapy had been completed. Patients were also questioned on subjective symptom improvement and the number of completed laryngeal control therapy sessions. PFT results were collected and tabulated when available. Diagnosis of obstructive airway disease was based on the forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and the pulmonologist s interpretation. 1533

4 Fig. 3. The asthma medication score decreases after diagnosis alone and after therapy, regardless of how much therapy is completed. Data included are only from time points with at least two responses. Partial therapy and Full therapy lines are closely overlapping. Statistical Analysis Patients were assigned a numerical score based on the frequency with which they used medications. The frequency intervals are detailed in Figures 2 and 3. Subjects were assigned values of 1, 2, 3, or 4 for each increasing frequency interval. For example, a patient using a short-acting b-agonist less than 2 days per week received one point, whereas a patient using the same medication more than two days per week received two points. Once numerical values were assigned, the values from each category were added together to form an aggregate score (asthma medication score). The asthma medication scores for each subject were compared at each time point for which data were available. Asthma medication scores were compared using the paired-samples t test or one-way analysis of variance. Nominal variables were compared using v 2 analysis. Data were analyzed using SPSS software (IBM, Armonk, NY). RESULTS Patient Characteristics Sixty-eight patients were identified as eligible to participate during the study period. Two were excluded because of chronic systemic corticosteroid use for diseases besides asthma or chronic obstructive pulmonary disease. Eighty-five percent were female, and the median age was 42 years. Forty-two patients completed follow-up questionnaires, 40 of whom completed questionnaires at least 6 months out from diagnosis (Table I). The remaining two completed follow-up questionnaires at the initial therapy visit but not thereafter. Seventy-two percent (18 of 25) of those completing a full course of therapy (two or more sessions, as determined by the therapist) demonstrated a decrease in asthma medication use, compared with 100% (five of five) of those completing a partial course; the decrease in medication use was significant, but the difference between the two groups was not. Nine patients completed no laryngeal control therapy, and eight of those (89%) showed decreased asthma medication use. The mean decrease in asthma medication score was 2.68 for patients completing a full therapy course, 2.60 for patients completing a partial therapy course, and 3.44 for patients completing no therapy (P 5.71; Fig. 3). The mean asthma medication score decreased from 4.62 to 3.29 after patients received a diagnosis alone, before any treatment (P 5.03). Asthma Medication Use at Presentation and Symptom Improvement Fifty-six patients (84.8%) were using asthma medication at the time of presentation. Fifty-four patients (82%) reported symptomatic improvement of their symptoms after diagnosis and/or treatment of their PVFMD. Ninety-two percent of patients completing a full therapy course reported improved symptoms, compared with 60% of patients completing a partial course and 66.7% of patients completing no therapy (P 5.09). Baseline asthma medication score was not significantly different between these groups. Diagnosis and Treatment of PVFMD Decreased Asthma Medication Use Overall, the mean asthma medication score decreased from 4.85 at diagnosis to 2.40 at last follow-up (P <.001) PFT Data Did Not Impact Asthma Medication Use or Symptoms Forty-four patients (66%) had PFT data available; 57% of these demonstrated no evidence of asthma,

5 TABLE I. Follow-up Data. Asthma Medication Score Symptoms (%) Baseline After Diagnosis 6 Months P Value Improved Unchanged P Value Therapy completed None (n 5 9) 6 NA Partial, 1 session (n 5 5) 4.6 NA* Complete, 2 or more (n 5 25) PFT result No obstructive pattern (n 5 25) Obstructive disease (n 5 19) Total < *Data are shown only from time points with at least two responses. NA 5 not available; PFT 5 pulmonary function testing. whereas 43% had some degree of obstructive pulmonary disease. The mean decrease in asthma medication score did not differ between patients with PFT evidence of asthma versus those without (3.08 vs. 2.76, P 5.75). The proportion of patients with PFT evidence of obstructive disease did not differ between the various therapy groups (P 5.24). In addition, the proportion of patients experiencing improvement or resolution of their symptoms did not differ based on PFT results (0.83 vs. 0.71, P 5.30). DISCUSSION PVFMD accounts for a large proportion of patients with unexplained dyspnea. Undiagnosed PVFMD has been associated with high healthcare costs. 3,7,11 Patients use emergency room services for their complaints and occasionally are intubated for respiratory distress. 12 Many patients with unexplained dyspnea are initially diagnosed with asthma, and only after a trial of asthmadirected medications are they referred for evaluation of PVFMD. To our knowledge, no studies have previously examined the effect of diagnosis and treatment of PVFMD on asthma medication use. We hypothesized that diagnosing and treating patients with this disorder would lead to a decrease in their use of asthma medication. The data collected support this hypothesis. Diagnosis and treatment of PVFMD reduced asthma medication use significantly. The distinction between diagnosis and treatment is emphasized. The first follow-up questionnaire was intentionally administered before treatment began to examine the effect of diagnosis alone. Results indicate that diagnosis of PVFMD, even before any therapy, prompted decreased use in asthma medication. This effect may be related to the education that patients receive upon diagnosis; they are shown examples of normal vocal fold movement during respiration followed by their own laryngoscopic video with evidence of constriction during respiration. They are also shown how their vocal fold abduction improved while using basic laryngeal control therapy techniques performed during the exam. In other words, patients finally received an explanation for their symptoms, along with tangible evidence of why their asthma medication may not have been helping. Medication use decreased even while symptoms improved. Eighty-two percent of patients experienced symptomatic improvement after diagnosis and/or treatment of PVFMD. Treatment consisted of laryngeal control therapy performed by a licensed SLP with additional training in management of PVFMD. This rate of improvement is consistent with previous reports that have demonstrated the efficacy of laryngeal control therapy. 4,13 It should be noted that both patients undergoing any treatment and those who did not reported improved symptoms (87% vs. 66%, P 5.17). At the initial diagnostic visit, patients are educated on the basics of rescue breathing techniques; some find this to be sufficient for controlling their symptoms. Thus, they seek no further therapy even when it is recommended. It is possible that those with less severe symptoms or with vocal fold constriction more rapidly responsive to the basic laryngeal control therapy techniques self-selected themselves out of the treatment group. This effect has been described in the management of other disorders. 14 Interestingly, there was no significant difference in the proportion of patients who decreased asthma medication use after partial versus complete therapy, or the degree to which they decreased. The same was true when comparing those who completed no therapy and those who completed any therapy. In other words, patients appeared to decrease their asthma medication use upfront, shortly after their initial visit and education session. This can again be explained by an education effect, meaning that an understanding of the disease process impacted patients decision to use asthma medications. This should not be interpreted to mean that therapy was not helpful; many patients reported further symptomatic improvement with therapy sessions, even after an initial decrease in use of asthma medication. The lack of difference in rates of decreased medication use again raises the question of whether patients who did not complete a full therapy course had less severe symptoms initially, similar to the effect noted above. Sixty percent of all study patients, in fact, reported significantly improved symptoms after only one therapy 1535

6 session. Of course, even if symptom severity was initially less for this subgroup, they did not have less pathologic PFT results; the incidence of an obstructive pattern on PFT was the same (P 5.24). Finally, it is possible that poor compliance explains the lack of difference among these groups; many of those participating in therapy may have been noncompliant with the daily laryngeal control exercises outside of therapy appointments, and therefore gained little additional benefit beyond that of the education and instruction given at the initial visit. Eighty-five percent of patients referred to us were being treated with asthma medication, 43% of those with PFT performed had an obstructive pattern, and the majority was female. These characteristics are comparable with other series of PVFMD patients. 3,4 The median age of 42 years is also on par with the subjects of the aforementioned studies (42.6 and 45, respectively). Although PVFMD has been described specifically in young athletic persons, it is clearly not restricted to this demographic. Although many patients had previously undergone PFT, our subjects were not initially stratified based on PFT results or a preexisting diagnosis of asthma. There are several reasons for this. First of all, a diagnosis of asthma does not exclude the possibility of PVFMD. Suggestive PFT results, and even a positive methacholine challenge test, cannot rule out PVFMD. Additionally, some patients referred by a pulmonologist have PFT suggestive of obstructive disease but do not have a clear diagnosis of asthma. They may have symptoms incompletely controlled by inhaled b-agonists, or their symptom severity is out of proportion to PFT findings. Additionally, patients with asthma undergoing PFT who are already controlled on proper medication may have nondiagnostic results. The authors felt that if a referring pulmonologist was not able to give a definitive diagnosis of asthma based on the available information, it would be inappropriate for us to do so. Thus, PFT data do not impact patient eligibility. Results were compared between the group of patients with obstructive pattern on PFT and those without an obstructive pattern, but it should be clear that this is not the same as a comparison between patients with coexisting asthma and those without. PFT results did not impact asthma medication use. In other words, both patients with PFT evidence of obstruction and those without evidence of obstruction significantly decreased their asthma medication scores. Study Limitations A potential point of bias is that compliance with home therapy exercises was not measured. Another is the relatively low rate of patients completing follow-up questionnaires (64%). There are several possible reasons for this. Importantly, speech therapy (and particularly laryngeal control therapy) is not covered by certain insurance carriers. Patients may become lost to followup if they seek less expensive care elsewhere or determine that laryngeal control therapy is not worth the cost at all. Symptom severity or resolution may also lead to the choice not to follow up. Thus, the true rate of symptomatic improvement may be under- or overreported by this study. However, by reaching out to all patients at the 6-month point, whether they had been lost to follow-up or not, we attempted to avoid this bias. Implications and Future Directions This study highlights the importance of diagnosing and treating PVFMD. Patients properly diagnosed and treated use less asthma medication and have improved symptoms, avoiding the hassle, cost, and side effects of taking superfluous medication. Although we do not specifically counsel patients regarding asthma medication use, results of this study have led many in our practice to routinely recommend that the patient revisit his or her asthma medication regimen with the pulmonologist once symptoms are improving. Future directions include an expansion of this study to our pediatric population, which is currently underway. Other studies might include a cost-analysis of diagnosis and treatment of PVFMD versus the cost of a missed diagnosis; the cost of the initial visit, flexible laryngoscopy procedure, and speech therapy is likely much less than the cost of inappropriate medication usage, missed work, emergency service utilization, and multiple medical visits. Further research might focus on PVFMD in patients with chronic obstructive pulmonary disease, laryngopharyngeal reflux, or allergic rhinitis and their use of disease-specific medication. We encourage otolaryngology and nonotolaryngology practitioners to have a high suspicion for this disorder in patients with otherwise unexplained dyspnea. CONCLUSION Diagnosis and treatment of PVFMD leads to a decline in use of asthma medication. This decrease in medication use occurs even as symptoms improve. Decreased use of asthma medications is seen immediately after the initial diagnostic visit for many patients, typically with further decrease in medication use and symptomatic improvement as therapy proceeds. This is the first study, prospective or otherwise, to demonstrate a decrease in asthma medication use with diagnosis and treatment of PVFMD. Future endeavors should examine the overall expense of misdiagnosed PVFMD, including the cost of asthma medication and emergency care, and compare this with the cost of diagnosing and treating PVFMD. BIBLIOGRAPHY 1. Seear M, Wensley D, West N. How accurate is the diagnosis of exercise induced asthma among Vancouver schoolchildren? 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