Effects of low-frequency repetitive transcranial magnetic stimulation in adductor laryngeal dystonia: a safety, feasibility, and pilot study.

PURPOSE: The effects of neuromodulation are virtually unexplored in adductor laryngeal dystonia (AdLD), a disorder characterized by involuntary contraction of intrinsic laryngeal muscles. Recent findings indicated that intracortical inhibition is reduced in people with AdLD. Low-frequency repetitive transcranial magnetic stimulation (rTMS) induces prolonged intracortical inhibition, but the effects in AdLD are unexplored. This pilot and feasibility study aimed to examine the safety, feasibility, and effects of a single session 1 Hz rTMS over the laryngeal motor cortex (LMC) in people with AdLD and healthy individuals. METHODS: The stimulation location was individualized and determined through TMS-evoked responses in the thyroarytenoid muscles using fine-wire electrodes. 1200 pulses of 1 Hz rTMS were delivered to the left LMC in two groups: Control (n = 6) and AdLD (n = 7). Tolerance, adverse effects, intracortical inhibition, and voice recordings were collected immediately before and after rTMS. Voice quality was assessed with acoustic-based and auditory-perceptual measures. RESULTS: All participants tolerated the procedures, with no unexpected adverse events or worsening of symptoms. No significant effects on intracortical inhibition were observed. In the AdLD group, there was a large-effect size after rTMS in vocal perturbation measures and a small-effect size in decreased phonatory breaks. CONCLUSIONS: One rTMS session over the LMC is safe and feasible, and demonstrated trends of beneficial effects on voice quality and phonatory function in AdLD. These preliminary findings support further investigation to assess clinical benefits in a future randomized sham-controlled trial. CLINICALTRIALS.GOV: NCT02957942, registered on November 8, 2016.

Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes.

Reduced upper airway muscle activity during sleep is a key contributor to obstructive sleep apnea pathogenesis. Hypoglossal nerve stimulation activates upper airway dilator muscles, including the genioglossus, and has the potential to reduce obstructive sleep apnea severity. The objective of this study was to examine the safety, feasibility and efficacy of a novel hypoglossal nerve stimulation system (HGNS; Apnex Medical, St Paul, MN, USA) in treating obstructive sleep apnea at 12 months following implantation. Thirty-one subjects (35% female, age 52.4 ± 9.4 years) with moderate to severe obstructive sleep apnea and unable to tolerate positive airway pressure underwent surgical implantation and activation of the hypoglossal nerve stimulation system in a prospective single-arm interventional trial. Primary outcomes were changes in obstructive sleep apnea severity (apnea-hypopnea index, from in-laboratory polysomnogram) and sleep-related quality of life [Functional Outcomes of Sleep Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 ± 16% of nights for 5.4 ± 1.4 h per night. There was a significant improvement (P < 0.001) from baseline to 12 months in apnea-hypopnea index (45.4 ± 17.5 to 25.3 ± 20.6 events h(-1) ) and Functional Outcomes of Sleep Questionnaire score (14.2 ± 2.0 to 17.0 ± 2.4), as well as other polysomnogram and symptom measures. Outcomes were stable compared with 6 months following implantation. Three serious device-related adverse events occurred: an infection requiring device removal; and two stimulation lead cuff dislodgements requiring replacement. There were no significant adverse events with onset later than 6 months following implantation. Hypoglossal nerve stimulation demonstrated favourable safety, feasibility and efficacy.

Effects of an 11-week vibro-tactile stimulation treatment on voice symptoms in laryngeal dystonia.

Background: Laryngeal dystonia is a task-specific focal dystonia of laryngeal muscles that impairs speech and voice production. At present, there is no cure for LD. The most common therapeutic option for patients with LD involves Botulinum neurotoxin injections. Objective: Provide empirical evidence that non-invasive vibro-tactile stimulation (VTS) of the skin over the voice box can provide symptom relief to those affected by LD. Methods: Single-group 11-week randomized controlled trial with a crossover between two dosages (20 min of VTS once or 3 times per week) self-administered in-home in two 4-week blocks. Acute effects of VTS on voice and speech were assessed in-lab at weeks 1, 6 and 11. Participants were randomized to receive either 40 Hz or 100 Hz VTS. Main outcome measures: Primary: smoothed cepstral peak prominence (CPPS) of the voice signal to quantify voice and speech abnormalities, and perceived speech effort (PSE) ranked by participants as a measure of voice effort (scale 1-10). Secondary: number of voice breaks during continuous speech, the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) inventory as a measure of overall disease severity and the Voice Handicap Index 30-item self report. Results: Thirty-nine people with a confirmed diagnosis of adductor-type LD (mean [SD] age, 60.3 [11.3] years; 18 women and 21 men) completed the study. A single application of VTS improved voice quality (median CPPS increase: 0.41 dB, 95% CI [0.20, 0.61]) and/or reduced voice effort (PSE) by at least 30% in up to 57% of participants across the three study visits. Effects lasted from less than 30 min to several days. There was no effect of dosage and no evidence that the acute therapeutic effects of VTS increased or decreased longitudinally over the 11-week study period. Both 100 and 40 Hz VTS induced measurable improvements in voice quality and speech effort. VTS induced an additional benefit to those receiving Botulinum toxin. Participants, not receiving Botulinum treatment also responded to VTS. Conclusion: This study provides the first systematic empirical evidence that the prolonged use of laryngeal VTS can induce repeatable acute improvements in voice quality and reductions of voice effort in LD. Clinical trial registration: ClinicalTrials.gov ID: NCT03746509.

Transcranial magnetic stimulation and functional magnet resonance imaging evaluation of adductor spasmodic dysphonia during phonation.

BACKGROUND: Reduced intracortical inhibition is a neurophysiologic finding in focal dystonia that suggests a broader problem of impaired cortical excitability within the brain. A robust understanding of the neurophysiology in dystonia is essential to elucidate the pathophysiology of the disorder and develop new treatments. The cortical silent period (cSP) is a reliable, non-invasive method to measure intracortical inhibition in the primary motor cortex associated with a muscle of interest. In adductor spasmodic dysphonia (AdSD), cSP of the laryngeal motor cortex (LMC) which directly corresponds to the affected musculature, the thyroarytenoid (TA), has not been examined. OBJECTIVE: This work evaluated the cSP of the LMC and the relationship between cSP and functional magnetic resonance imaging (fMRI) blood-oxygen-level dependent (BOLD) activation in people with AdSD (n = 12) compared to healthy controls (CTL, n = 14). RESULTS: Shortened LMC cSP were observed bilaterally in people with AdSD vs CTL (F(1, 99) = 19.5226, p < 0.0001), with a large effect size (η2 = 0.1834). Between-group fMRI analysis revealed greater activation in bilateral LMC in the AdSD > CTL contrast as compared to CTL > AdSD contrast. Correlation analysis showed that people with AdSD have positive correlation of left LMC BOLD activation and the cSP. Further, the right LMC cSP lacks either positive or negative associations with BOLD activation. CTL individuals displayed both positive and negative correlations between cSP and BOLD activation in the left LMC. In CTL, the LMC cSP and BOLD activation showed exclusively negative correlations in both hemispheres. CONCLUSION: In AdSD, the cortical activation during phonation may not be efficiently or effectively associated with inhibitory processes, leading to muscular dysfunction. These findings may give insight into the maladaptive cortical control during phonation in people with AdSD.

Evaluation of the Cortical Silent Period of the Laryngeal Motor Cortex in Healthy Individuals.

Objective: This work aimed to evaluate the cortical silent period (cSP) of the laryngeal motor cortex (LMC) using the bilateral thyroarytenoid (TA) muscles with transcranial magnetic stimulation (TMS). Methods: In 11 healthy participants, fine-wire electromyography (EMG) was used to record bilateral TA muscle responses to single pulse TMS delivered to the LMC in both hemispheres. Peripheral responses to stimulation over the mastoid, where the vagus nerve exits the skull, were collected to verify the central origin of the cortical stimulation responses by comparing the latencies. Results: The cSP duration ranged from 41.7 to 66.4 ms. The peripherally evoked motor-evoked potential (MEP) peak occurred 5-9 ms earlier than the cortical responses (for both sides of TAs: p < 0.0001) with no silent period. The right TA MEP latencies were earlier than the left TA responses for both peripheral and cortical measures (p ≤ 0.0001). Conclusion: These findings demonstrate the feasibility of measuring cSP of LMC based on intrinsic laryngeal muscles responses during vocalization in healthy volunteers. Significance: The technique could be used to study the pathophysiology of neurological disorders that affect TA muscles, such as spasmodic dysphonia. Further, the methodology has application to other muscles of the head and neck not accessible using surface electrodes.

Effect of recurrent laryngeal nerve section on the laryngeal muscles of adult rabbits.

OBJECTIVE: To examine the effect of recurrent laryngeal nerve section on myonuclear addition and myofiber remodeling in adult rabbit laryngeal muscles. STUDY DESIGN AND SETTING: Unilateral section of the recurrent laryngeal nerve was performed on adult rabbits. Rabbits were labeled with bromodeoxyuridine, euthanized, and the laryngeal muscles were examined for bromodeoxyuridine (brdU) and neonatal myosin heavy chain (MyHC) expression. RESULTS: One week after nerve section, brdU-positive myonuclei were significantly increased on the denervated and contralateral sides. Neonatal MyHC expression significantly increased. By 24 weeks, the upregulation of myonuclear addition returned to control levels. CONCLUSION: Laryngeal muscle denervation results in significant upregulation of myonuclear addition. Denervation also resulted in a significant upregulation of neonatal MyHC expression. SIGNIFICANCE: Laryngeal muscles can be successfully reinnervated after long periods of denervation. This significant and maintained increase in myonuclear addition may contribute to the ability of laryngeal muscles to survive for extended periods following interruption of the recurrent laryngeal nerve.

Combined endoscopic medial and external lateral orbital decompression for progressive thyroid eye disease.

OBJECTIVE: To compare the efficacy of endoscopic medial and lateral orbital wall surgery to 3-wall decompression in patients with thyroid eye disease. STUDY DESIGN AND SETTING: A retrospective study of patients with thyroid eye disease with severe proptosis, exposure keratitis, or compressive optic neuropathy was conducted. RESULTS: Mean reduction in proptosis was 4.37 mm in the 2-wall approach and 4.59 mm in the 3-wall group. Seventy-five percent of patients in the 2-wall group demonstrated improved visual acuity; 50% improved after 3-wall decompression. Vertical palpebral fissure height decreased by an average of 2.50 mm in the 2-wall group and by 2.03 mm in the 3-wall group. New onset diplopia was 11.8% and 12.5%, respectively. CONCLUSIONS: Improvement in the degree of proptosis, visual acuity, and palpebral fissure height was seen in the majority of our patients and compared favorably to our results with 3-wall orbital decompression.

Myonuclear addition to uninjured laryngeal myofibers in adult rabbits.

OBJECTIVES: In normal mature limb skeletal muscle, satellite cells are quiescent and myonuclei do not divide after formation of their associated myofibers in the absence of injury. The possibility of myonuclear addition in uninjured laryngeal myofibers of adult rabbits was investigated in an immunohistochemical pilot study. METHODS: Bromodeoxyuridine (brdU), a marker for cell division, was administered by intraperitoneal injection over a 12-hour period in rabbits. The number of brdU-positive myonuclei per myofiber was determined on cross sections through the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles. RESULTS: In the TA muscle, 0.13% +/- 0.03% (mean +/- SEM) of the myofibers counted had a brdU-positive nucleus. In the PCA muscle, 0.13% +/- 0.01% of the myofibers counted had a brdU-positive nucleus. Approximately 0.2% and 0.3% of the myofibers of the TA and PCA muscles, respectively, had brdU-positive satellite cells associated with them. Tibialis anterior and pectoralis major muscle controls were negative for brdU-positive myonuclei. CONCLUSIONS: These data support the possibility of continuous remodeling in uninjured adult laryngeal myofibers and accentuate the distinct nature of laryngeal muscle relative to limb skeletal muscle in the rabbit model.

The clinical utility of vocal dosimetry for assessing voice rest.

OBJECTIVES/HYPOTHESIS: Voice rest is frequently recommended following surgical disruption of vocal fold epithelium, but patients report variable adherence to voice rest recommendations. The objective of this study was to assess the clinical utility of an ambulatory vocal dosimeter for measuring adherence to voice rest recommendations. STUDY DESIGN: Outcomes research. METHODS: Part 1: To determine the utility of the dosimeter in nonclinical use, the relationship between self-reported voice use and dosimeter measurements was examined in normal subjects (n = 11) who prospectively logged voice use while wearing the dosimeter. Part 2: To determine clinical utility of the dosimeter, patients undergoing vocal fold surgery for which postoperative voice rest was recommended (n = 11) wore a dosimeter for 2 days prior to and 2 days after surgery. Phonation percent and sound level were compared at baseline and during voice rest. RESULTS: The dosimeter performed as hypothesized with both normal subjects and patients. A moderate correlation (r = 0.62) was noted between self-reported voice use and dosimeter measurements in normal subjects. In patients on voice rest, a statistically and clinically significant decrease was observed in measured voice use, both in phonation time (P = .002) and intensity of phonation (P = .004). CONCLUSIONS: Ambulatory vocal dosimetry may have clinical utility for assessing adherence to voice rest recommendations. This information will be useful for the design of future studies on voice rest.

Reanimation of the paralyzed human larynx with an implantable electrical stimulation device.

OBJECTIVES/HYPOTHESIS: Electrical stimulation of the posterior cricoarytenoid muscle, when paced with inspiration, offers a physiological approach to restore ventilation in bilateral laryngeal paralysis without any of the disadvantages associated with conventional treatment. STUDY DESIGN: A prospective study of six patients. METHODS: The patients were successfully implanted with an Itrel II stimulator (Medtronic, Inc). In postoperative sessions, stimulated vocal fold abduction, patient ventilation, and voice were assessed and compared with preoperative values. RESULTS: The optimum stimulus paradigm was a 1- to 2-second train of 1-millisecond pulses delivered at a frequency of 30 to 40 Hz and amplitude of 2 to 7 V. Posterior cricoarytenoid stimulation produced a large dynamic abduction (3.5-7 mm) in three patients and moderate abduction (3 mm) in a fourth patient. The fifth patient showed a large but delayed response of 4 mm to stimulation with some lateralization of the vocal fold. In the sixth patient, stimulated abduction was noted on device implantation but was lost postoperatively. All five patients with stimulated abduction postoperatively met the ventilatory criteria for decannulation, and three patients subsequently had decannulation. Long-term stimulation of the posterior cricoarytenoid muscle had no appreciable effect on voice quality. CONCLUSIONS: Electrical stimulation of the posterior cricoarytenoid muscle shows potential as an improved therapy for bilateral vocal fold paralysis.

The relationship between cepstral peak prominence and selected parameters of dysphonia.

Traditional measures of dysphonia vary in their reliability and in their correlations with perceptions of grade. Measurements of cepstral peak prominence (CPP) have been shown to correlate well with perceptions of breathiness. Because it is a measure of periodicity, CPP should also predict roughness. The ability of CPP and other acoustic measures to predict overall dysphonia and the subcategories of breathiness and roughness in pathological voice samples is explored. Preoperative and postoperative speech samples from 19 patients with unilateral recurrent laryngeal nerve paralysis who underwent operative intervention were analyzed by trained listeners and by measures of smoothed CPP (CPPS), noise-to-harmonic ratio (NHR), amplitude perturbation quotient (APQ), relative average perturbation (RAP), and smoothed pitch perturbation quotient (sPPQ). The data were analyzed with bivariate Pearson correlation statistics. Grade of dysphonia and breathiness ratings correlated better with measurements of CPPS than with the other measures. CPPS from samples of connected speech (CPPS-s) best predicted overall dysphonia. None of the measures were useful in predicting roughness.

Complications from office sclerotherapy for epistaxis due to hereditary hemorrhagic telangiectasia (HHT or Osler-Weber-Rendu).

BACKGROUND: The aim of this study was to identify and evaluate adverse clinical outcomes following office-based sclerotherapy using sodium tetradecyl sulfate (STS) for epistaxis due to hereditary hemorrhagic telangiectasias (HHT or Osler-Weber-Rendu). METHODS: A retrospective chart review of 36 adult patients treated with STS sclerotherapy for severe and/or recurrent epistaxis due to HHT was performed. RESULTS: A total of 153 separate treatment sessions were analyzed. Each patient underwent an average of 4.3 sessions with an average of 7 intralesional injections per session. Bleeding during the procedure was experienced by 8 patients with a maximum reported blood loss of 200 mL in 1 patient, but less than 50 mL in all others. Seven patients reported some postinjection pain, which included nasal, cheek, and eye pain. Nasal congestion, sneezing, and vasovagal responses were each noted to occur 2 times. No complications of postprocedural visual loss, deep venous thrombosis/pulmonary embolus, transient ischemic attack (TIA)/stroke, or anaphylaxis were encountered. CONCLUSION: Conventional therapies used in the management of HHT-related epistaxis, such as laser coagulation, septodermoplasty, selective arterial embolization, and Young's occlusion each have specific associated complications, including worsened epistaxis, septal perforation, foul odor, nasal crusting, and compromised nasal breathing. STS is a safe office-based treatment option for HHT-mediated epistaxis that is associated with exceedingly few of the aforementioned serious sequelae.

Endoscopic cold incision, balloon dilation, mitomycin C application, and steroid injection for adult laryngotracheal stenosis.

OBJECTIVES/HYPOTHESIS: To describe the presentation, stenosis characteristics, etiological differences, and outcomes of adult laryngotracheal stenosis treated with endoscopic cold incision, balloon dilation, topical mitomycin C application, and steroid injection. STUDY DESIGN: Retrospective chart review. METHODS: Demographic and clinical data were extracted for patients treated between March 2000 and December 2010. Prolonged intubation and idiopathic patient data were utilized for comparative analysis. RESULTS: Eighty patients (65 females; 15 males; 220 procedures; 2.9 years mean follow-up) presented with dyspnea (81%) and/or exercise intolerance (40%). Most commonly, etiologies were idiopathic (53 of 80; 66%) or prolonged intubation (14 of 80; 18%). Mean procedures per patient and interval between procedures were 2.8 procedures and 405 days, respectively. Mean stenosis length and distance from the caudal phonating edge of the true vocal folds were 9 mm and 19 mm. Complication, tracheotomy, and open-procedure rates were 1.8%, 1.4%, and 10.0%, respectively. Patients with more than two procedures demonstrated a mean 4-mm reduction in stenosis length and a 2-mm cephalad progression of stenosis over time. More caudal stenoses required more frequent procedures. Procedures were less frequent as more procedures were performed. Stenosis characteristics, interval between procedures, and total procedures were similar between idiopathic patients with or without intubation histories, but different between idiopathic and prolonged intubation patients. CONCLUSIONS: This procedure was shown to be a viable option in adult laryngotracheal stenosis. Repeat dilation was likely, but was performed without adversely affecting stenosis characteristics. Stenoses farther from the vocal folds required procedures more frequently. Idiopathic patients with a history of brief, elective intubation had stenosis characteristics and responses to therapy similar to idiopathic patients without an intubation history. Both idiopathic groups together demonstrated stenosis characteristics and responses to therapy dissimilar to patients with a history of prolonged intubation.

Hypoglossal nerve stimulation and airway changes under fluoroscopy.

OBJECTIVE: To characterize the changes in the anteroposterior dimensions of both the retropalatal and retrolingual airway spaces of the pharynx and hyoid bone position during hypoglossal nerve stimulation under general anesthesia in subjects with obstructive sleep apnea. STUDY DESIGN: Cross-sectional. SETTING: Academic center. SUBJECTS AND METHODS: Cross-table fluoroscopic images obtained during hypoglossal nerve stimulation were studied in 26 subjects enrolled in the Apnex Medical Hypoglossal Nerve Stimulation (HGNS) system feasibility trials. Changes in the anteroposterior dimensions (2-dimensional) of the retropalatal and retrolingual airway spaces and hyoid bone position were recorded. Measurements were estimated in millimeters and standardized to each subject's C3 vertebral height. Opening of the pharyngeal airspace was examined relative to body mass index. RESULTS: During hypoglossal nerve stimulation, all subjects demonstrated anterior displacement of the tongue base on fluoroscopy. The average retrolingual airway opening was 0.71 ± 0.23 C3 vertebral body heights (9 ± 3 mm). Opening of the retropalatal airway with stimulation occurred in 65% (15/23) of subjects. When present, the average opening was 0.42 ± 0.14 vertebral heights (5 ± 3 mm). Anterior displacement of the hyoid occurred in 92% (23/25) of subjects. Retrolingual airway opening was independent of baseline body mass index. CONCLUSION: Unilateral hypoglossal nerve stimulation results in anterior tongue base displacement and an increase in the anterior-posterior retrolingual airway dimensions of the pharynx, independent of body mass index. Opening of the retropalatal airway occurred in a majority of subjects and had a trend toward correlation with body mass index.

Treating obstructive sleep apnea with hypoglossal nerve stimulation.

BACKGROUND: Reduced upper airway muscle activity during sleep is fundamental to obstructive sleep apnea (OSA) pathogenesis. Hypoglossal nerve stimulation (HGNS) counteracts this problem, with potential to reduce OSA severity. STUDY OBJECTIVES: To examine safety and efficacy of a novel HGNS system (HGNS, Apnex Medical, Inc.) in treating OSA. PARTICIPANTS: Twenty-one patients, 67% male, age (mean ± SD) 53.6 ± 9.2 years, with moderate to severe OSA and unable to tolerate continuous positive airway pressure (CPAP). DESIGN: Each participant underwent surgical implantation of the HGNS system in a prospective single-arm interventional trial. OSA severity was defined by apnea-hypopnea index (AHI) during in-laboratory polysomnography (PSG) at baseline and 3 and 6 months post-implant. Therapy compliance was assessed by nightly hours of use. Symptoms were assessed using the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Calgary Sleep Apnea Quality of Life Index (SAQLI), and the Beck Depression Inventory (BDI). RESULTS: HGNS was used on 89% ± 15% of nights (n = 21). On these nights, it was used for 5.8 ± 1.6 h per night. Nineteen of 21 participants had baseline and 6-month PSGs. There was a significant improvement (all P < 0.05) from baseline to 6 months in: AHI (43.1 ± 17.5 to 19.5 ± 16.7), ESS (12.1 ± 4.7 to 8.1 ± 4.4), FOSQ (14.4 ± 2.0 to 16.7 ± 2.2), SAQLI (3.2 ± 1.0 to 4.9 ± 1.3), and BDI (15.8 ± 9.0 to 9.7 ± 7.6). Two serious device-related adverse events occurred: an infection requiring device removal and a stimulation lead cuff dislodgement requiring replacement. CONCLUSIONS: HGNS demonstrated favorable safety, efficacy, and compliance. Participants experienced a significant decrease in OSA severity and OSA-associated symptoms. CLINICAL TRIAL INFORMATION: NAME: Australian Clinical Study of the Apnex Medical HGNS System to Treat Obstructive Sleep Apnea. REGISTRATION NUMBER: NCT01186926. URL: http://clinicaltrials.gov/ct2/show/NCT01186926.

The laryngeal chemoreflex: an evaluation of the normoxic response.

OBJECTIVES: The laryngeal chemoreflex is a reflexive central apnea, bradycardia, and cardiovascular collapse that occurs in young, maturing mammals in response to exposure of the laryngeal mucosa to acidic and/or organic stimuli. The severity of the laryngeal chemoreflex varies within a species from one animal to another, and in some animals, the response can be fatal. This study seeks to identify those factors that contribute to fatal laryngeal chemoreflex responses when the larynx is stimulated under normoxic conditions, and to define how the normoxic response differs from the hypoxic laryngeal chemoreflex response. STUDY DESIGN: This is a prospective study evaluating the response to laryngeal stimulation of 80 newborn piglets. METHODS: The laryngeal chemoreflex response was elicited from 67 piglets under normoxic conditions. The data were collected from a combination of three separate experimental protocols, each of which included inducing the laryngeal chemoreflex under normoxic conditions as the first step. The physiologic response was recorded with a combination of arterial blood gas, pulse oximetry, blood pressure, and continuous cardiac monitoring. RESULTS: Resumption of respirations occurred when the pCO(2) rose by a mean of 8.34 (Standard Deviation [SD] = 4.8) mmHg, regardless of response severity (ANOVA, P > .05). Moderate (requiring supplemental O(2) for recovery) and profound (fatal) responders had a significantly higher prestimulation pCO(2) (95% confidence interval [CI] 39.8-44.8 mmHg and 40.5-46.4 mmHg, respectively) than did mild (recovery without assistance) responders (95% CI 36.8-40.8 mmHg, ANOVA, P < .05). Baseline pH was statistically significantly different as a function of response severity (95% CI profound: 7.29-7.37, moderate: 7.33-7.38, and mild 7.36-7.39, P < .05). CONCLUSIONS: Accumulation of arterial CO(2) is associated with resumption of respirations during the normoxic laryngeal chemoreflex. The combination of an elevated prestimulation pCO(2) and a low prestimulation pH predicts a profound laryngeal chemoreflex response under normoxic conditions.