- Email: [email protected]
A Trigger Reduction Approach to Treatment of Paradoxical Vocal Fold Motion Disorder in the Pediatric Population
ARTICLE IN PRESS
A Trigger Reduction Approach to Treatment of Paradoxical Vocal Fold Motion Disorder in the Pediatric Population *,†Craig Zalvan, *Erick Yuen, *Jan Geliebter, and *Raj Tiwari, *Valhalla, and ySleepy Hollow, New York Abstract: Objectives. Paradoxical vocal fold motion disorder (PVFMD), or induced laryngeal obstruction (ILO), is a clinical phenomenon characterized by inappropriate adduction of the true vocal folds during inspiration. The resultant episodes of acute respiratory distress marked by exercise-induced cough, inspiratory stridor, throat tightness, and shortness of breath are often misattributed to asthma despite normal pulmonary function testing results. Although the pathogenesis of the disease remains unclear, the etiology is likely multifactorial with an inflammatory, neurological, and psychiatric basis. Our trigger reduction approach, consisting of a plantbased, Mediterranean-style diet to treat laryngopharyngeal reflux and sinus toilet, aims to dampen the peripheral neuronal hyperexcitability of the laryngopharyngeal tissues that is hypothesized to contribute to this disorder. The primary objective of the present study was to assess for therapeutic efficacy by analyzing pre- and post-treatment subjective scores using four validated indices: Voice Handicap Index (VHI), Reflux Symptom Index (RSI), Dyspnea Index (DI), and Cough Severity Index (CSI). Methods. A retrospective chart review of all patients age ≤18 years seen by the senior author between 2012 and 2018 who reported laryngeal spasm (J35.5) as a presenting complaint with no underlying organic diagnosis that otherwise explained the symptom identified the study cohort. Patients were excluded if another cause of their laryngeal spasm was identified or their medical records were incomplete. Results. Of 80 patients, 24 met the criteria. The most frequent presenting symptom was exercise-induced dyspnea (79%). Of the four measured indices, only a change in DI (P = 0.024) met statistical significance. Of 24 patients, 18 (75%) demonstrated a reduction in DI following our treatment protocol. Using reduction in DI as a continuous variable to assess response, the patient cohort experienced a 4.62 (95% confidence interval [CI]: 0.65−8.6) mean point reduction. Using the eight-point reduction (improvement) in DI as an accepted clinical response to treatment, 8 of 24 patients (33%) experienced a clinically relevant response. Changes in CSI (P = 0.059), RSI (P = 0.27), and VHI (P = 0.25) did not meet statistical significance. Of 24 patients, 8 (33%), 11 (46%), and 7 (29%) demonstrated a reduction in CSI, RSI, and VHI following our trigger reduction protocol, respectively. The patient cohort experienced a mean point reduction of 1.8 (95% CI: 0.1 to 3.7), 1.3 (95% CI: 1.1 to 3.7), and 1.3 (95% CI: 1.0 to 3.6) in CSI, RSI, and VHI, respectively. Conclusions. Paradoxical vocal fold motion disorder is a multifactorial disease that poses diagnostic and therapeutic challenges. Early diagnosis and treatment are critical to ensure patient safety, satisfaction, and reduction in health care costs, as mistreatment with asthma pharmacotherapy, intubation, or tracheostomy may exacerbate their dyspnea and lead to preventable hospitalizations. Our results demonstrate that a trigger reduction approach consisting of a plant-based, Mediterranean-style diet and sinus toilet alone may not achieve a clinically meaningful response in the majority of patients. However, given their favorable safety profile, our therapeutic regimen, along with respiratory retraining therapy, may provide symptom relief for selected patients who would otherwise continue to suffer. Key Words: Paradoxical vocal fold motion disorder−Induced laryngeal obstruction−Vocal cord dysfunction −Asthma−Dyspnea.
INTRODUCTION Paradoxical vocal fold motion disorder (PVFMD) is characterized by inappropriate adduction of the true vocal folds during inspiration, and to some degree, on expiration. Many terms have been proposed to describe this disorder and efforts to standardize the nomenclature are ongoing. Accepted for publication August 15, 2019. Declarations of Interest: None. From the *Department of Otolaryngology, New York Medical College, School of Medicine, Valhalla, New York; and the yThe Institute for Voice and Swallowing Disorders, Sleepy Hollow, New York. Address correspondence and reprint requests to Craig Zalvan, 77 North Broadway, Suite 303, Sleepy Hollow, NY 10591. E-mail: [email protected] Journal of Voice, Vol. &&, No. &&, pp. &&−&& 0892-1997 © 2019 The Voice Foundation. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jvoice.2019.08.013
The term vocal cord dysfunction is often used to describe PVFMD but technically includes the broader category of laryngeal disturbances without acute upper airway obstruction.1 Induced laryngeal obstruction has recently been proposed as the new consensus term for this condition.2 Regardless of the nomenclature, these laryngeal spasms cause episodes of acute respiratory distress often marked by exercise-induced cough, inspiratory stridor, chest and throat tightness, and shortness of breath, mimicking the clinical presentation of asthma despite normal pulmonary function testing (PFT) results. Consequently, the diagnosis of PVFMD can be challenging to establish and is often only considered when initial corticosteroid and bronchodilator therapy for asthma have failed, usually after many months to years of symptoms.3,4 In some
ARTICLE IN PRESS 2 cases, the correct diagnosis may elude the clinician. To complicate the clinical picture, studies suggest that 30% of patients have coexisting PVFMD and asthma, making it unclear the proportion each entity is contributing to the varying symptoms.5 Once considered a disorder primarily of a psychiatric etiology, PVFMD is now recognized to have an inflammatory and a neurological basis with central influence from various degrees of anxiety-related disorders.6 Although observation of the paradoxical motion during inspiration by flexible laryngoscopy is suggestive, the intermittent episodes characteristic of the disorder can lead to false negative results.7 As laryngopharyngeal reflux (LPR) is cited across multiple studies as a common comorbidity, medical management directed at reducing laryngeal irritation is often recommended.4,7,8,9 Although treatment with proton pump inhibitors (PPI) has long been considered the gold standard, Zalvan et al has recommended a wholly dietary approach using alkaline water, a plant-based, Mediterranean-style diet, and standard reflux precautions prior to a trial of pharmacotherapy. The study concluded that a Mediterraneanstyle, plant-based approach was comparable, if not superior, to PPI therapy based on the effect of each treatment arm on Reflux Severity Index (RSI) scores. Due to the associated health care costs, side effect profile, and potential drug interactions with PPIs, treatment of LPR with a dietary approach first is warranted.10 PVFMD has been poorly studied in the pediatric population, which has been reported to account for 30% of patients diagnosed with the condition. Previous studies have noted that pediatric patients with PVFMD are often teenage girls who participate in regular organized sports, consistent with data recognizing exercise as a potential trigger for the condition. Investigators have also suggested that laryngeal hypersensitivity contributes to the pathophysiology due to the high frequency of concurrent asthma and reflux symptoms in the cohort. Treatment with speech therapy and for comorbid conditions, including asthma, gastroesophageal reflux disease, and psychiatric disorders, has been demonstrated to offer an excellent prognosis for this patient population.7,8 However, due to the relative paucity of clinical data characterizing PVFMD and its treatment in pediatric patients compared to their adult counterparts, further studies are necessary to elucidate this disorder in the juvenile population. The primary objective of this study was to characterize the typical pediatric patient diagnosed with PVFMD and analyze the change, or lack thereof, in their subjective scores upon presentation and following treatment with our trigger reduction approach. We hypothesized that our approach would lead to improvement of symptoms as evidenced by a statistically significant reduction in all subjective scores. METHODS The New York Medical College institutional review board reviewed and approved the study prior to its initiation. A waiver of informed consent of study participants was
Journal of Voice, Vol. &&, No. &&, 2019
also granted because participant data were protected and deidentified. This is a retrospective chart review of all patients age ≤18 years seen by the senior author (C.H.Z.) between 2012 and 2018 who reported laryngeal spasm (ICD-10: J35.5) as a presenting complaint with no underlying organic diagnosis that otherwise explained the symptom. Patients who were ultimately diagnosed with PVFMD by the senior author by clinical history were included. Patients were excluded if another cause of their laryngeal spasm was identified or their medical records were incomplete. Patient demographics, etiology of the dyspnea, medications, allergies, past medical history, PFT results, and therapeutic measures such as trigger identification and reduction were reviewed for the final cohort. Response to treatment was gauged by a change in the following validated indices, each quantifying the severity of symptoms through a self-assessment questionnaire, from before and after this treatment protocol: The Voice Handicap Index (VHI) is a 10-item survey with responses rated on a scale of zero (never) to four (always) that determines the psychosocial effect of dysphonia on one’s life.11 The Reflux Symptom Index (RSI) is a 9-item survey with responses rated on a scale of zero (no problem) to five (severe problem) that assesses the severity of symptoms associated with LPR.12 The Dyspnea Index (DI) is a 10-item survey with responses rated on a scale of zero (never) to four (always) that quantifies the severity of symptoms in upper airway dyspnea.13 The Cough Severity Index (CSI) is a 10-item survey with responses rated on a scale of zero (never) to four (always) that quantifies the patients’ symptoms associated with upper airway chronic cough.14 Overall and point changes in VHI, RSI, DI, and CSI were reviewed at initial visit and at follow-up, ranging from 4.5 weeks to 24 weeks, for all patients included in the study. Patients were educated and advised on our nonsystemic pharmaceutical approach for management of PVFMD, which focuses on reduction of triggers of laryngeal spasm. Patient intervention consisted of a Mediterranean style, 90%−95% plant-based diet for treatment of LPR. The diet allowed for only three to four meals with 2−3 oz of any type of meat or dairy, alkaline water, and standard reflux precautions including significant reduction of coffee, tea, chocolate, soda, greasy or fried food, fatty food, spicy food, alcohol, or acidic foods, especially if any of these act as specific triggers. In addition, patients were counseled to make behavioral changes such as not lying down for 3 hours prior to sleep, smaller and more frequent meals, and head of bed elevation, as well as sinus toilet consisting of nasal saline irrigation and a nasal steroid/antihistamine combination. Patients are instructed to spray Simply Saline in each nostril for 3 seconds while sniffing inward forcefully until the saline enters the nasopharynx and is then expectorated. They are instructed to repeat this maneuver four to five times per
ARTICLE IN PRESS Craig Zalvan, et al
Trigger Reduction treatment with Paradoxical Vocal Fold Motion Disorder in Pediatric Population
day. Compliance was assessed with patient reporting fewer than three meals per week with 3−4 oz of any animal product. Changes in DI, VHI, CSI, and RSI were measured as continuous variables to assess response and statistical significance (P < 0.05) determined by the paired t test. Statistical analysis was performed using NCSS 12 (NCSS, Kaysville, UT). RESULTS Of 80 patients identified by ICD-10 analysis of the senior author’s electronic medical record, 24 met criteria to be included in the statistical analysis. Fifty-six patients were excluded due to incomplete medical records, including lack of pre- and post-treatment subjective data and prior pulmonology workup with PFTs, and deviation from treatment protocol. Demographics demonstrated a 79% female preponderance, consistent with prior studies reporting a higher prevalence of the disease among girls.7,8 The median patient age at initial consultation was 15 years, with a range of 10−17 years (Table 1). Of the 24 patients, 17 (70.8%) had previously been diagnosed with asthma, with a mean duration of pharmacological treatment of 2.8 years. The duration of treatment for asthma was not documented for one patient. Of the 17 patients, 3 (17.6%) had PFT findings consistent with asthma, eight (47.1%) had normal PFT
TABLE 1. Demographics and Characteristics of Our 24-Patient Cohort Demographics and Characteristics
results, five (29.4%) did not have testing documented, and one (5.9%) had flattening of the inspiratory loop. Within the 24-patient cohort, 13 (54.2%) reported allergies to medications, food, and/or environmental triggers. The most frequent presenting symptom was exerciseinduced dyspnea (79.2%), followed by inspiratory stridor (62.5%), cough (41.7%), throat clearing (29.2%), wheezing (25%), and chest discomfort (25%). At presentation, 6 (25%) patients reported symptoms lasting for less than 6 months. 9 (37.5%) and 5 (20.8%) patients had been symptomatic for 6−12 months and 1−2 years prior to initial consultation, respectively. Four (16.7%) patients experienced symptoms for more than 2 years before presenting for evaluation (Table 1). Of the four measured indices, only a change in DI (P = 0.024) met statistical significance. Of 24 patients, 18 (75%) demonstrated a reduction in DI following our trigger reduction protocol (Figure 1a). Using reduction in DI as a continuous variable to assess response, the patient cohort experienced a 4.62 (95% confidence interval [CI]: 0.65−8.6) mean point reduction (Table 2). Using the eight-point reduction (improvement) in DI as an accepted clinical response to treatment,15 8 of 24 patients (33%) experienced a clinically relevant response. In contrast, changes in CSI (P = 0.059), RSI (P = 0.27), and VHI (P = 0.25) did not meet statistical significance. Of 24 patients, 8 (33%), 11 (46%), and 7 (29%) demonstrated a reduction in CSI, RSI, and VHI following our trigger reduction protocol, respectively (Figure 1b−d). The patient cohort experienced a mean point reduction of 1.8 (95% CI: 0.1 to 3.7), 1.3 (95% CI: 1.1 to 3.7), and 1.3 (95% CI: 1.0 to 3.6) in CSI, RSI, and VHI, respectively (Table 2).
Value
Sex, No. (%) Male 5 (20.8) Female 19 (79.2) Age, y, median (range) 15 (10−17) Baseline DI, No. (%) <10 4 (16.7) 11−20 9 (37.5) 21−30 9 (37.5) >30 2 (8.3) Mean (95% CI) of cohort 18.75 (15.4−22.1) Primary symptom, No. (%) Exercise-induced dyspnea 19 (79.2) Inspiratory stridor 15 (62.5) Cough 10 (41.7) Throat clearing 7 (29.2) Wheezing 6 (25) Chest discomfort 6 (25) Globus 5 (20.8) Throat tightness 5 (20.8) Waterbrash 5 (20.8) Symptom duration prior to presentation, No. (%) <6 mo 6 (25) 6−12 mo 9 (37.5) 1−2 y 5 (20.8) >2 y 4 (16.7) *Abbreviations: CI, confidence interval; DI, Dyspnea Index.
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DISCUSSION PVFMD is a recognized clinical phenomenon characterized by inappropriate inspiratory adduction of the vocal cords that poses diagnostic and therapeutic challenges. Early diagnosis and treatment are critical to ensure patient safety, satisfaction, and reduction in health care costs, as mistreatment with asthma pharmacotherapy, intubation, or tracheostomy may exacerbate their dyspnea and lead to preventable hospitalizations.3 The diagnosis of PVFMD in the pediatric population can be particularly challenging, as the disease is not well characterized in this group and the presentation of dyspnea in children can be multifactorial.16 Consistent with our patient demographics, the typical pediatric patient with PVFMD has been found to be a teenage girl who carries a diagnosis of asthma despite normal PFT findings, participates in organized sports, and reports attacks of stridor or wheezing with activity.7,8 Although exercise can trigger asthma in a person with a known history of asthma, the term “exercise-induced asthma” is a misnomer and likely represents PVFMD. Thus, patients and parents with children diagnosed with exercise-induced asthma, especially when long-standing and poorly responsive to therapy, should consider PVFMD as a potential diagnosis and seek treatment accordingly.
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FIGURE 1. (a) Pre- and posttreatment Dyspnea Index (DI) scores for our 24-patient cohort. (b) Pre- and posttreatment Cough Severity Index (CSI) scores for our 24-patient cohort. (c) Pre- and post-treatment Reflux Severity Index (RSI) scores for our 24-patient cohort. (d) Pre- and post-Voice Handicap Index (VHI) scores for our 24-patient cohort.
In this study, all patients diagnosed with PVFMD were advised to undergo our trigger reduction protocol, which consisted of nasal wash (nasal steroid/antihistamine spray and saline irrigation) and a plant-based diet approach for treatment of LPR. Multiple studies have documented the high prevalence of concurrent reflux symptoms in patients with PVFMD.4,7,8,9 In their pediatric cohort, Powell et al
found that 95% of their patients demonstrated posterior glottic changes on endoscopic examination typically seen in gastroesophageal reflux disease and therefore recommended empiric antireflux treatment.8 Smith et al, noting that 79% of their pediatric patients were previously treated for reflux, provided further evidence suggesting that laryngeal hypersensitivity contributes to the pathophysiology of PVFMD.7
ARTICLE IN PRESS Craig Zalvan, et al
Trigger Reduction treatment with Paradoxical Vocal Fold Motion Disorder in Pediatric Population
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FIGURE 1 Continued.
The peripheral neuronal hyperexcitability of the laryngopharyngeal tissues is mediated by a combination of peripheral and central sensitization through upregulation of a variety of receptors, including acid-sensing ion channels. These transmembrane ion channels are activated by a decrease in extracellular pH and upregulated in the peripheral and central nervous system with exposure to tissue inflammation, resulting in increased sensory neuronal sensitivity. Consequently,
stimuli at pathologically low thresholds trigger reflexive adduction of the vocal folds, producing the sensation of dyspnea that is characteristic of PVFMD. Irritants, dryness, and reflux are often cited culprits that sensitize mucosal afferents in the larynx thought to participate in the reflex involving vagal connections in the brainstem.6,9 As the combination of sinus toilet and dietary treatment for LPR has previously been demonstrated to reduce the symptoms of neurogenic
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TABLE 2. Change in Indices After Treatment DI Number patients Mean before treatment (95% CI) Mean after treatment (95% CI) Mean point reduction Paired t test
VHI
RSI
24 24 18.75 (95% CI; 15.4−22.1) 8.54 (95% CI; 1.2−8.4)
24 3.8 (95% CI; 1.0−6.7)
24 9.1 (95% CI; 5.6−12.6)
14.1 (95% CI; 11.5−16.8)
2.5 (95% CI; 0.2−4.8)
7.8 (95% CI; 5.0−10.7)
4.62 (95% CI; 0.65−8.6) P = 0.024
CSI
3.0 (95% CI; 0.4−5.7)
1.8 (95% CI; 0.1 to 3.7) 1.3 (95% CI; 1.0 to 3.6) 1.3 (95% CI; 1.1 to 3.7) P = 0.059 P = 0.25 P = 0.27
*Abbreviations: CI, confidence interval; CSI, Cough Severity Index; DI, Dyspnea Index; RSI, Reflux Symptom Index; VHI, Voice Handicap Index.
chronic cough, presumably by addressing the heightened state of sensitivity of the laryngopharynx, we hypothesized that the same trigger reduction method could improve symptoms of PVFMD through similar mechanisms.17 No study to our knowledge has previously assessed the efficacy of our trigger reduction regimen, as previously outlined, for the management of PVFMD in the pediatric population, as gauged by a statistically significant reduction in VHI, RSI, DI, and CSI. The majority of our patients completed the self-administered questionnaires independently, whereas the younger subjects required assistance from their parents. In our study cohort, a statistically significant reduction in DI following our therapeutic approach was observed. Seventy-five percent of our patients demonstrated a reduction in DI while a third achieved a clinically relevant response following treatment. Given that a plethora of mechano- and chemoreceptors, endogenous and environmental stimuli, and neural reflex pathways have been implicated in the disease process,6,9,17 we were not surprised that our approach failed to achieve a clinically meaningful response in a higher proportion of patients. Our trigger reduction protocol attempts to modulate the laryngeal hypersensitivity by decreasing the stimulation peripherally, which we acknowledge does not address the other potential contributing factors of the disease. Despite our results, treatment with nasal steroid/antihistamine spray, saline irrigation, and a plant-based diet approach, in conjunction with respiratory retraining therapy, should be attempted for pediatric patients diagnosed with PVFMD given their favorable safety profile. In this patient population, the subjective sense of shortness of breath is often the primary complaint, usually presenting without a physical correlate (ie, normal pulse oximetry, blood gas values, chest radiographs, and PFTs).7 Given that 33% of our patients achieved symptomatic improvement, as measured by a statistically significant reduction in DI, initiation of our trigger reduction regimen may provide benefit to a subset of patients who would otherwise find no relief of their symptoms. The present study also assessed for improvement in a range of other self-reported symptoms that characterize PVFMD, including chest pain, throat clearing, cough, and voice changes, by analyzing changes in RSI, VHI, and CSI
following treatment. Collectively, these subjective scoring tools encompass a wide range of laryngopharyngeal sensory symptoms. Although a statistically significant reduction in these three validated indices was not observed after treatment, the results should not be interpreted as failure of our treatment approach to have any benefit on these domains. As dyspnea is often the most distressing complaint in this patient population, with cough, heart burn, and dysphonia being far less intrusive to daily activities, our therapeutic protocol sought to achieve a significant reduction in DI as the primary outcome. As illustrated in Figure 1b−d, the majority of patients who experienced no changes in CSI (13/13, 100%) or VHI (13/14, 93%) following trigger reduction had pre- and post-treatment scores of zero. Of the two patients who experienced no change in RSI after therapy, one had pre- and post-treatment scores of zero. These observations may explain why our trigger reduction protocol failed to achieve a statistically significant reduction in these three indices. These are several limitations to our study. First, due to its retrospective nature, although the trigger reduction protocol was standardized, the duration of therapy was not. Therefore, it is difficult to ascertain whether more patients did not achieve a clinically meaningful response due to lack of treatment efficacy or inadequate length of therapy. Second, although the four indices used in the study are validated tools to measure symptom severity, the literature is lacking with regards to their use in the pediatric population.
CONCLUSION PVFMD is a multifactorial disease that poses diagnostic and therapeutic challenges, necessitating a multipronged treatment approach. Due to the significant patient safety concerns and health care costs associated with mistreatment with asthma pharmacotherapy, PVFMD is a clinical entity that should not be overlooked. Although only a subset of our pediatric cohort achieved a clinically significant reduction in DI, a trigger reduction regimen that carries no associated health risks consisting of nasal wash and a plant-based, Mediterranean-style diet, along with respiratory retraining therapy, may improve symptoms for selected patients.
ARTICLE IN PRESS Craig Zalvan, et al
Trigger Reduction treatment with Paradoxical Vocal Fold Motion Disorder in Pediatric Population
REFERENCES 1. Denipah N, Dominguez CM, Kraai EP, et al. Acute management of paradoxical vocal fold motion (vocal cord dysfunction). Ann Emerg Med. 2017;69:18–23. 2. Johnston KL, Bradford H, Hodges H, et al. The Olin EILOBI breathing techniques: description and initial case series of novel respiratory retraining strategies for athletes with exercise-induced laryngeal obstruction. J Voice. 2018;32:698–704. 3. Kramer S, deSilva B, Forrest LA, et al. Does treatment of paradoxical vocal fold movement disorder decrease asthma medication use? Laryngoscope. 2017;127:1531–1537. 4. Marcinow AM, Thompson J, Forrest LA, et al. Irritant-induced paradoxical vocal fold motion disorder: diagnosis and management. Otolaryngol Head Neck Surg. 2015;153:996–1000. 5. Ye J, Nouraie M, Holguin F, et al. The ability of patient-symptom questionnaires to differentiate PVFMD from asthma. J Voice. 2017;31:382.e1–382.e8. 6. Cukier-Blaj S, Bewley A, Aviv JE, et al. Paradoxical vocal fold motion: a sensory-motor laryngeal disorder. Laryngoscope. 2008;118:367–370. 7. Smith B, Milstein C, Rolfes B, et al. Paradoxical vocal fold motion (PVFM) in pediatric otolaryngology. Am J Otolaryngol Head Neck Med Surg. 2017;2:230–232. 8. Powell DM, Karanfilov BI, Beechler KB, et al. Paradoxical vocal cord dysfunction in juveniles. Arch Otolaryngol Head Neck Surg. 2000;126: 29–34. 9. Forrest LA, Husein T, Husein O. Paradoxical vocal cord motion: classification and treatment. Laryngoscope. 2012;122:844–853.
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10. Zalvan CH, Hu S, Greenberg B, et al. A comparison of alkaline water and mediterranean diet vs proton pump inhibition for treatment of laryngopharyngeal reflux. JAMA Otolaryngol Head Neck Surg. 2017;143:1023–1029. https://doi.org/10.1001/jamaoto.2017. 1454. 11. Rosen CA, Lee AS, Osborne J, et al. Development and validation of the voice handicap index-10. Laryngoscope. 2004;114:1549–1556. 12. Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the reflux symptom index (RSI). J Voice. 2002;16:274–277. 13. Gartner-Schmidt JL, Shembel AC, Zullo TG, et al. Development and validation of the Dyspnea Index (DI): a severity index for upper airway-related dyspnea. J Voice. 2014;28:775–782. https://doi.org/10. 1016/j.jvoice.2013.12.017. Epub 2014 Oct 12. 14. Shembel AC, Rosen CA, Zullo TG, et al. Development and validation of the cough severity index: a severity index for chronic cough related to the upper airway. Laryngoscope. 2013;123:1931–1936. https://doi. org/10.1002/lary.23916. Epub 2013 Jun 4. 15. De Guzman V, Ballif CL, Maurer R, et al. Validation of the dyspnea index in adolescents with exercise-induced paradoxical vocal fold motion. JAMA Otolaryngol Head Neck Surg. 2014;140:823–828. https://doi.org/10.1001/jamaoto.2014.1405. 16. Hseu A, Sandler M, Ericson D, et al. Paradoxical vocal fold motion in children presenting with exercise induced dyspnea. Int J Pediatr Otorhinolaryngol. 2016;90:165–169. 17. Zalvan C, Berzofsky C, Tiwari R, et al. Trigger reduction prior to systemic drugs for neurogenic chronic cough. Laryngoscope. 2019;129:198– 202. https://doi.org/10.1002/lary.27459.
A Trigger Reduction Approach to Treatment of Paradoxical Vocal Fold Motion Disorder in the Pediatric Population *,†Craig Zalvan, *Erick Yuen, *Jan Geliebter, and *Raj Tiwari, *Valhalla, and ySleepy Hollow, New York Abstract: Objectives. Paradoxical vocal fold motion disorder (PVFMD), or induced laryngeal obstruction (ILO), is a clinical phenomenon characterized by inappropriate adduction of the true vocal folds during inspiration. The resultant episodes of acute respiratory distress marked by exercise-induced cough, inspiratory stridor, throat tightness, and shortness of breath are often misattributed to asthma despite normal pulmonary function testing results. Although the pathogenesis of the disease remains unclear, the etiology is likely multifactorial with an inflammatory, neurological, and psychiatric basis. Our trigger reduction approach, consisting of a plantbased, Mediterranean-style diet to treat laryngopharyngeal reflux and sinus toilet, aims to dampen the peripheral neuronal hyperexcitability of the laryngopharyngeal tissues that is hypothesized to contribute to this disorder. The primary objective of the present study was to assess for therapeutic efficacy by analyzing pre- and post-treatment subjective scores using four validated indices: Voice Handicap Index (VHI), Reflux Symptom Index (RSI), Dyspnea Index (DI), and Cough Severity Index (CSI). Methods. A retrospective chart review of all patients age ≤18 years seen by the senior author between 2012 and 2018 who reported laryngeal spasm (J35.5) as a presenting complaint with no underlying organic diagnosis that otherwise explained the symptom identified the study cohort. Patients were excluded if another cause of their laryngeal spasm was identified or their medical records were incomplete. Results. Of 80 patients, 24 met the criteria. The most frequent presenting symptom was exercise-induced dyspnea (79%). Of the four measured indices, only a change in DI (P = 0.024) met statistical significance. Of 24 patients, 18 (75%) demonstrated a reduction in DI following our treatment protocol. Using reduction in DI as a continuous variable to assess response, the patient cohort experienced a 4.62 (95% confidence interval [CI]: 0.65−8.6) mean point reduction. Using the eight-point reduction (improvement) in DI as an accepted clinical response to treatment, 8 of 24 patients (33%) experienced a clinically relevant response. Changes in CSI (P = 0.059), RSI (P = 0.27), and VHI (P = 0.25) did not meet statistical significance. Of 24 patients, 8 (33%), 11 (46%), and 7 (29%) demonstrated a reduction in CSI, RSI, and VHI following our trigger reduction protocol, respectively. The patient cohort experienced a mean point reduction of 1.8 (95% CI: 0.1 to 3.7), 1.3 (95% CI: 1.1 to 3.7), and 1.3 (95% CI: 1.0 to 3.6) in CSI, RSI, and VHI, respectively. Conclusions. Paradoxical vocal fold motion disorder is a multifactorial disease that poses diagnostic and therapeutic challenges. Early diagnosis and treatment are critical to ensure patient safety, satisfaction, and reduction in health care costs, as mistreatment with asthma pharmacotherapy, intubation, or tracheostomy may exacerbate their dyspnea and lead to preventable hospitalizations. Our results demonstrate that a trigger reduction approach consisting of a plant-based, Mediterranean-style diet and sinus toilet alone may not achieve a clinically meaningful response in the majority of patients. However, given their favorable safety profile, our therapeutic regimen, along with respiratory retraining therapy, may provide symptom relief for selected patients who would otherwise continue to suffer. Key Words: Paradoxical vocal fold motion disorder−Induced laryngeal obstruction−Vocal cord dysfunction −Asthma−Dyspnea.
INTRODUCTION Paradoxical vocal fold motion disorder (PVFMD) is characterized by inappropriate adduction of the true vocal folds during inspiration, and to some degree, on expiration. Many terms have been proposed to describe this disorder and efforts to standardize the nomenclature are ongoing. Accepted for publication August 15, 2019. Declarations of Interest: None. From the *Department of Otolaryngology, New York Medical College, School of Medicine, Valhalla, New York; and the yThe Institute for Voice and Swallowing Disorders, Sleepy Hollow, New York. Address correspondence and reprint requests to Craig Zalvan, 77 North Broadway, Suite 303, Sleepy Hollow, NY 10591. E-mail: [email protected] Journal of Voice, Vol. &&, No. &&, pp. &&−&& 0892-1997 © 2019 The Voice Foundation. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jvoice.2019.08.013
The term vocal cord dysfunction is often used to describe PVFMD but technically includes the broader category of laryngeal disturbances without acute upper airway obstruction.1 Induced laryngeal obstruction has recently been proposed as the new consensus term for this condition.2 Regardless of the nomenclature, these laryngeal spasms cause episodes of acute respiratory distress often marked by exercise-induced cough, inspiratory stridor, chest and throat tightness, and shortness of breath, mimicking the clinical presentation of asthma despite normal pulmonary function testing (PFT) results. Consequently, the diagnosis of PVFMD can be challenging to establish and is often only considered when initial corticosteroid and bronchodilator therapy for asthma have failed, usually after many months to years of symptoms.3,4 In some
ARTICLE IN PRESS 2 cases, the correct diagnosis may elude the clinician. To complicate the clinical picture, studies suggest that 30% of patients have coexisting PVFMD and asthma, making it unclear the proportion each entity is contributing to the varying symptoms.5 Once considered a disorder primarily of a psychiatric etiology, PVFMD is now recognized to have an inflammatory and a neurological basis with central influence from various degrees of anxiety-related disorders.6 Although observation of the paradoxical motion during inspiration by flexible laryngoscopy is suggestive, the intermittent episodes characteristic of the disorder can lead to false negative results.7 As laryngopharyngeal reflux (LPR) is cited across multiple studies as a common comorbidity, medical management directed at reducing laryngeal irritation is often recommended.4,7,8,9 Although treatment with proton pump inhibitors (PPI) has long been considered the gold standard, Zalvan et al has recommended a wholly dietary approach using alkaline water, a plant-based, Mediterranean-style diet, and standard reflux precautions prior to a trial of pharmacotherapy. The study concluded that a Mediterraneanstyle, plant-based approach was comparable, if not superior, to PPI therapy based on the effect of each treatment arm on Reflux Severity Index (RSI) scores. Due to the associated health care costs, side effect profile, and potential drug interactions with PPIs, treatment of LPR with a dietary approach first is warranted.10 PVFMD has been poorly studied in the pediatric population, which has been reported to account for 30% of patients diagnosed with the condition. Previous studies have noted that pediatric patients with PVFMD are often teenage girls who participate in regular organized sports, consistent with data recognizing exercise as a potential trigger for the condition. Investigators have also suggested that laryngeal hypersensitivity contributes to the pathophysiology due to the high frequency of concurrent asthma and reflux symptoms in the cohort. Treatment with speech therapy and for comorbid conditions, including asthma, gastroesophageal reflux disease, and psychiatric disorders, has been demonstrated to offer an excellent prognosis for this patient population.7,8 However, due to the relative paucity of clinical data characterizing PVFMD and its treatment in pediatric patients compared to their adult counterparts, further studies are necessary to elucidate this disorder in the juvenile population. The primary objective of this study was to characterize the typical pediatric patient diagnosed with PVFMD and analyze the change, or lack thereof, in their subjective scores upon presentation and following treatment with our trigger reduction approach. We hypothesized that our approach would lead to improvement of symptoms as evidenced by a statistically significant reduction in all subjective scores. METHODS The New York Medical College institutional review board reviewed and approved the study prior to its initiation. A waiver of informed consent of study participants was
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also granted because participant data were protected and deidentified. This is a retrospective chart review of all patients age ≤18 years seen by the senior author (C.H.Z.) between 2012 and 2018 who reported laryngeal spasm (ICD-10: J35.5) as a presenting complaint with no underlying organic diagnosis that otherwise explained the symptom. Patients who were ultimately diagnosed with PVFMD by the senior author by clinical history were included. Patients were excluded if another cause of their laryngeal spasm was identified or their medical records were incomplete. Patient demographics, etiology of the dyspnea, medications, allergies, past medical history, PFT results, and therapeutic measures such as trigger identification and reduction were reviewed for the final cohort. Response to treatment was gauged by a change in the following validated indices, each quantifying the severity of symptoms through a self-assessment questionnaire, from before and after this treatment protocol: The Voice Handicap Index (VHI) is a 10-item survey with responses rated on a scale of zero (never) to four (always) that determines the psychosocial effect of dysphonia on one’s life.11 The Reflux Symptom Index (RSI) is a 9-item survey with responses rated on a scale of zero (no problem) to five (severe problem) that assesses the severity of symptoms associated with LPR.12 The Dyspnea Index (DI) is a 10-item survey with responses rated on a scale of zero (never) to four (always) that quantifies the severity of symptoms in upper airway dyspnea.13 The Cough Severity Index (CSI) is a 10-item survey with responses rated on a scale of zero (never) to four (always) that quantifies the patients’ symptoms associated with upper airway chronic cough.14 Overall and point changes in VHI, RSI, DI, and CSI were reviewed at initial visit and at follow-up, ranging from 4.5 weeks to 24 weeks, for all patients included in the study. Patients were educated and advised on our nonsystemic pharmaceutical approach for management of PVFMD, which focuses on reduction of triggers of laryngeal spasm. Patient intervention consisted of a Mediterranean style, 90%−95% plant-based diet for treatment of LPR. The diet allowed for only three to four meals with 2−3 oz of any type of meat or dairy, alkaline water, and standard reflux precautions including significant reduction of coffee, tea, chocolate, soda, greasy or fried food, fatty food, spicy food, alcohol, or acidic foods, especially if any of these act as specific triggers. In addition, patients were counseled to make behavioral changes such as not lying down for 3 hours prior to sleep, smaller and more frequent meals, and head of bed elevation, as well as sinus toilet consisting of nasal saline irrigation and a nasal steroid/antihistamine combination. Patients are instructed to spray Simply Saline in each nostril for 3 seconds while sniffing inward forcefully until the saline enters the nasopharynx and is then expectorated. They are instructed to repeat this maneuver four to five times per
ARTICLE IN PRESS Craig Zalvan, et al
Trigger Reduction treatment with Paradoxical Vocal Fold Motion Disorder in Pediatric Population
day. Compliance was assessed with patient reporting fewer than three meals per week with 3−4 oz of any animal product. Changes in DI, VHI, CSI, and RSI were measured as continuous variables to assess response and statistical significance (P < 0.05) determined by the paired t test. Statistical analysis was performed using NCSS 12 (NCSS, Kaysville, UT). RESULTS Of 80 patients identified by ICD-10 analysis of the senior author’s electronic medical record, 24 met criteria to be included in the statistical analysis. Fifty-six patients were excluded due to incomplete medical records, including lack of pre- and post-treatment subjective data and prior pulmonology workup with PFTs, and deviation from treatment protocol. Demographics demonstrated a 79% female preponderance, consistent with prior studies reporting a higher prevalence of the disease among girls.7,8 The median patient age at initial consultation was 15 years, with a range of 10−17 years (Table 1). Of the 24 patients, 17 (70.8%) had previously been diagnosed with asthma, with a mean duration of pharmacological treatment of 2.8 years. The duration of treatment for asthma was not documented for one patient. Of the 17 patients, 3 (17.6%) had PFT findings consistent with asthma, eight (47.1%) had normal PFT
TABLE 1. Demographics and Characteristics of Our 24-Patient Cohort Demographics and Characteristics
results, five (29.4%) did not have testing documented, and one (5.9%) had flattening of the inspiratory loop. Within the 24-patient cohort, 13 (54.2%) reported allergies to medications, food, and/or environmental triggers. The most frequent presenting symptom was exerciseinduced dyspnea (79.2%), followed by inspiratory stridor (62.5%), cough (41.7%), throat clearing (29.2%), wheezing (25%), and chest discomfort (25%). At presentation, 6 (25%) patients reported symptoms lasting for less than 6 months. 9 (37.5%) and 5 (20.8%) patients had been symptomatic for 6−12 months and 1−2 years prior to initial consultation, respectively. Four (16.7%) patients experienced symptoms for more than 2 years before presenting for evaluation (Table 1). Of the four measured indices, only a change in DI (P = 0.024) met statistical significance. Of 24 patients, 18 (75%) demonstrated a reduction in DI following our trigger reduction protocol (Figure 1a). Using reduction in DI as a continuous variable to assess response, the patient cohort experienced a 4.62 (95% confidence interval [CI]: 0.65−8.6) mean point reduction (Table 2). Using the eight-point reduction (improvement) in DI as an accepted clinical response to treatment,15 8 of 24 patients (33%) experienced a clinically relevant response. In contrast, changes in CSI (P = 0.059), RSI (P = 0.27), and VHI (P = 0.25) did not meet statistical significance. Of 24 patients, 8 (33%), 11 (46%), and 7 (29%) demonstrated a reduction in CSI, RSI, and VHI following our trigger reduction protocol, respectively (Figure 1b−d). The patient cohort experienced a mean point reduction of 1.8 (95% CI: 0.1 to 3.7), 1.3 (95% CI: 1.1 to 3.7), and 1.3 (95% CI: 1.0 to 3.6) in CSI, RSI, and VHI, respectively (Table 2).
Value
Sex, No. (%) Male 5 (20.8) Female 19 (79.2) Age, y, median (range) 15 (10−17) Baseline DI, No. (%) <10 4 (16.7) 11−20 9 (37.5) 21−30 9 (37.5) >30 2 (8.3) Mean (95% CI) of cohort 18.75 (15.4−22.1) Primary symptom, No. (%) Exercise-induced dyspnea 19 (79.2) Inspiratory stridor 15 (62.5) Cough 10 (41.7) Throat clearing 7 (29.2) Wheezing 6 (25) Chest discomfort 6 (25) Globus 5 (20.8) Throat tightness 5 (20.8) Waterbrash 5 (20.8) Symptom duration prior to presentation, No. (%) <6 mo 6 (25) 6−12 mo 9 (37.5) 1−2 y 5 (20.8) >2 y 4 (16.7) *Abbreviations: CI, confidence interval; DI, Dyspnea Index.
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DISCUSSION PVFMD is a recognized clinical phenomenon characterized by inappropriate inspiratory adduction of the vocal cords that poses diagnostic and therapeutic challenges. Early diagnosis and treatment are critical to ensure patient safety, satisfaction, and reduction in health care costs, as mistreatment with asthma pharmacotherapy, intubation, or tracheostomy may exacerbate their dyspnea and lead to preventable hospitalizations.3 The diagnosis of PVFMD in the pediatric population can be particularly challenging, as the disease is not well characterized in this group and the presentation of dyspnea in children can be multifactorial.16 Consistent with our patient demographics, the typical pediatric patient with PVFMD has been found to be a teenage girl who carries a diagnosis of asthma despite normal PFT findings, participates in organized sports, and reports attacks of stridor or wheezing with activity.7,8 Although exercise can trigger asthma in a person with a known history of asthma, the term “exercise-induced asthma” is a misnomer and likely represents PVFMD. Thus, patients and parents with children diagnosed with exercise-induced asthma, especially when long-standing and poorly responsive to therapy, should consider PVFMD as a potential diagnosis and seek treatment accordingly.
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FIGURE 1. (a) Pre- and posttreatment Dyspnea Index (DI) scores for our 24-patient cohort. (b) Pre- and posttreatment Cough Severity Index (CSI) scores for our 24-patient cohort. (c) Pre- and post-treatment Reflux Severity Index (RSI) scores for our 24-patient cohort. (d) Pre- and post-Voice Handicap Index (VHI) scores for our 24-patient cohort.
In this study, all patients diagnosed with PVFMD were advised to undergo our trigger reduction protocol, which consisted of nasal wash (nasal steroid/antihistamine spray and saline irrigation) and a plant-based diet approach for treatment of LPR. Multiple studies have documented the high prevalence of concurrent reflux symptoms in patients with PVFMD.4,7,8,9 In their pediatric cohort, Powell et al
found that 95% of their patients demonstrated posterior glottic changes on endoscopic examination typically seen in gastroesophageal reflux disease and therefore recommended empiric antireflux treatment.8 Smith et al, noting that 79% of their pediatric patients were previously treated for reflux, provided further evidence suggesting that laryngeal hypersensitivity contributes to the pathophysiology of PVFMD.7
ARTICLE IN PRESS Craig Zalvan, et al
Trigger Reduction treatment with Paradoxical Vocal Fold Motion Disorder in Pediatric Population
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FIGURE 1 Continued.
The peripheral neuronal hyperexcitability of the laryngopharyngeal tissues is mediated by a combination of peripheral and central sensitization through upregulation of a variety of receptors, including acid-sensing ion channels. These transmembrane ion channels are activated by a decrease in extracellular pH and upregulated in the peripheral and central nervous system with exposure to tissue inflammation, resulting in increased sensory neuronal sensitivity. Consequently,
stimuli at pathologically low thresholds trigger reflexive adduction of the vocal folds, producing the sensation of dyspnea that is characteristic of PVFMD. Irritants, dryness, and reflux are often cited culprits that sensitize mucosal afferents in the larynx thought to participate in the reflex involving vagal connections in the brainstem.6,9 As the combination of sinus toilet and dietary treatment for LPR has previously been demonstrated to reduce the symptoms of neurogenic
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TABLE 2. Change in Indices After Treatment DI Number patients Mean before treatment (95% CI) Mean after treatment (95% CI) Mean point reduction Paired t test
VHI
RSI
24 24 18.75 (95% CI; 15.4−22.1) 8.54 (95% CI; 1.2−8.4)
24 3.8 (95% CI; 1.0−6.7)
24 9.1 (95% CI; 5.6−12.6)
14.1 (95% CI; 11.5−16.8)
2.5 (95% CI; 0.2−4.8)
7.8 (95% CI; 5.0−10.7)
4.62 (95% CI; 0.65−8.6) P = 0.024
CSI
3.0 (95% CI; 0.4−5.7)
1.8 (95% CI; 0.1 to 3.7) 1.3 (95% CI; 1.0 to 3.6) 1.3 (95% CI; 1.1 to 3.7) P = 0.059 P = 0.25 P = 0.27
*Abbreviations: CI, confidence interval; CSI, Cough Severity Index; DI, Dyspnea Index; RSI, Reflux Symptom Index; VHI, Voice Handicap Index.
chronic cough, presumably by addressing the heightened state of sensitivity of the laryngopharynx, we hypothesized that the same trigger reduction method could improve symptoms of PVFMD through similar mechanisms.17 No study to our knowledge has previously assessed the efficacy of our trigger reduction regimen, as previously outlined, for the management of PVFMD in the pediatric population, as gauged by a statistically significant reduction in VHI, RSI, DI, and CSI. The majority of our patients completed the self-administered questionnaires independently, whereas the younger subjects required assistance from their parents. In our study cohort, a statistically significant reduction in DI following our therapeutic approach was observed. Seventy-five percent of our patients demonstrated a reduction in DI while a third achieved a clinically relevant response following treatment. Given that a plethora of mechano- and chemoreceptors, endogenous and environmental stimuli, and neural reflex pathways have been implicated in the disease process,6,9,17 we were not surprised that our approach failed to achieve a clinically meaningful response in a higher proportion of patients. Our trigger reduction protocol attempts to modulate the laryngeal hypersensitivity by decreasing the stimulation peripherally, which we acknowledge does not address the other potential contributing factors of the disease. Despite our results, treatment with nasal steroid/antihistamine spray, saline irrigation, and a plant-based diet approach, in conjunction with respiratory retraining therapy, should be attempted for pediatric patients diagnosed with PVFMD given their favorable safety profile. In this patient population, the subjective sense of shortness of breath is often the primary complaint, usually presenting without a physical correlate (ie, normal pulse oximetry, blood gas values, chest radiographs, and PFTs).7 Given that 33% of our patients achieved symptomatic improvement, as measured by a statistically significant reduction in DI, initiation of our trigger reduction regimen may provide benefit to a subset of patients who would otherwise find no relief of their symptoms. The present study also assessed for improvement in a range of other self-reported symptoms that characterize PVFMD, including chest pain, throat clearing, cough, and voice changes, by analyzing changes in RSI, VHI, and CSI
following treatment. Collectively, these subjective scoring tools encompass a wide range of laryngopharyngeal sensory symptoms. Although a statistically significant reduction in these three validated indices was not observed after treatment, the results should not be interpreted as failure of our treatment approach to have any benefit on these domains. As dyspnea is often the most distressing complaint in this patient population, with cough, heart burn, and dysphonia being far less intrusive to daily activities, our therapeutic protocol sought to achieve a significant reduction in DI as the primary outcome. As illustrated in Figure 1b−d, the majority of patients who experienced no changes in CSI (13/13, 100%) or VHI (13/14, 93%) following trigger reduction had pre- and post-treatment scores of zero. Of the two patients who experienced no change in RSI after therapy, one had pre- and post-treatment scores of zero. These observations may explain why our trigger reduction protocol failed to achieve a statistically significant reduction in these three indices. These are several limitations to our study. First, due to its retrospective nature, although the trigger reduction protocol was standardized, the duration of therapy was not. Therefore, it is difficult to ascertain whether more patients did not achieve a clinically meaningful response due to lack of treatment efficacy or inadequate length of therapy. Second, although the four indices used in the study are validated tools to measure symptom severity, the literature is lacking with regards to their use in the pediatric population.
CONCLUSION PVFMD is a multifactorial disease that poses diagnostic and therapeutic challenges, necessitating a multipronged treatment approach. Due to the significant patient safety concerns and health care costs associated with mistreatment with asthma pharmacotherapy, PVFMD is a clinical entity that should not be overlooked. Although only a subset of our pediatric cohort achieved a clinically significant reduction in DI, a trigger reduction regimen that carries no associated health risks consisting of nasal wash and a plant-based, Mediterranean-style diet, along with respiratory retraining therapy, may improve symptoms for selected patients.
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Trigger Reduction treatment with Paradoxical Vocal Fold Motion Disorder in Pediatric Population
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