Characterizing the Validity of Using VASES to Derive DIGEST-FEES Grades.

INTRODUCTION: Visual Analysis of Swallowing Efficiency and Safety (VASES) and Dynamic Imaging Grade of Swallowing Toxicity for Flexible Endoscopic Evaluation of Swallowing (DIGEST-FEES) are two complimentary methods for assessing swallowing during FEES. Whereas VASES is intended to facilitate trial-level ratings of pharyngeal residue, penetration, and aspiration, DIGEST-FEES is intended to facilitate protocol-level impairment grades of swallowing safety and efficiency. The aim of this study was to assess the validity of using VASES to derive DIGEST-FEES impairment grades. METHODS: DIGEST-FEES grades were blindly analyzed from 50 FEES - first using the original DIGEST-FEES grading method (n = 50) and then again using a VASES-derived DIGEST-FEES grading method (n = 50). Weighted Kappa (κw) and absolute agreement (%) were used to assess the relationship between the original DIGEST-FEES grades and VASES-derived DIGEST-FEES grades. Spearman's correlations assessed the relationship between VASES-derived DIGEST-FEES grades with measures of construct validity. RESULTS: Substantial agreement (κw = 0.76-0.83) was observed between the original and VASES-derived grading methods, with 60-62% of all DIGEST-FEES grades matching exactly, and 92-100% of DIGEST-FEES grades within one grade of each other. Furthermore, the strength of the relationships between VASES-derived DIGEST-FEES grades and measures of construct validity (r = 0.34-0.78) were similar to the strength of the relationships between original DIGEST-FEES grades and the same measures of construct validity (r = 0.34-0.83). CONCLUSION: Findings from this study demonstrate substantial agreement between original and VASES-derived DIGEST-FEES grades. Using VASES to derive DIGEST-FEES also appears to maintain the same level of construct validity established with the original DIGEST-FEES. Therefore, clinicians and researchers may consider using VASES to increase the transparency and standardization of DIGEST-FEES ratings. Future research should seek to replicate these findings and explore the simultaneous use of VASES and DIGEST-FEES in a greater sampling of raters and across other patient populations.

Dextromethorphan/quinidine for the treatment of bulbar impairment in amyotrophic lateral sclerosis.

OBJECTIVE: No efficacious treatments exist to improve or prolong bulbar functions of speech and swallowing in persons with amyotrophic lateral sclerosis (pALS). This study evaluated the short-term impact of dextromethorphan/quinidine (DMQ) treatment on speech and swallowing function in pALS. METHODS: This was a cohort trial conducted between August 2019 to August 2021 in pALS with a confirmed diagnosis of probable-definite ALS (El-Escorial Criteria-revisited) and bulbar impairment (ALS Functional Rating Scale score ≤ 10 and speaking rate ≤ 140 words per minute) who were DMQ naïve. Efficacy of DMQ was assessed via pre-post change in the ALS Functional Rating Scale-Revised bulbar subscale and validated speech and swallowing outcomes. Paired t-tests, Fisher's exact, and χ2 tests were conducted with alpha at 0.05. RESULTS: Twenty-eight pALS enrolled, and 24 participants completed the 28-day trial of DMQ. A significant increase in ALSFRS-R bulbar subscale score pre- (7.47 ± 1.98) to post- (8.39 ± 1.79) treatment was observed (mean difference: 0.92, 95% CI: 0.46-1.36, p < 0.001). Functional swallowing outcomes improved, with a reduction in unsafe (75% vs. 44%, p = 0.003) and inefficient swallowing (67% vs. 58%, p = 0.002); the relative speech event duration in a standard reading passage increased, indicating a greater duration of uninterrupted speech (mean difference: 0.33 s, 95% CI: 0.02-0.65, p = 0.035). No differences in diadochokinetic rate or speech intelligibility were observed (p > 0.05). INTERPRETATION: Results of this study provide preliminary evidence that DMQ pharmacologic intervention may have the potential to improve or maintain bulbar function in pALS.

Maximum Phonation Time as a Surrogate Marker for Airway Clearance Physiologic Capacity and Pulmonary Function in Individuals With Amyotrophic Lateral Sclerosis.

PURPOSE: The increased use of telehealth practices has created a critical need for home-based surrogate markers for prognostic respiratory indicators of disease progression in persons with amyotrophic lateral sclerosis (pALS). Given that phonation relies on the respiratory subsystem of speech production, we aimed to examine the relationships between maximum phonation time (MPT), forced vital capacity, and peak cough flow and to determine the discriminant ability of MPT to detect forced vital capacity and peak cough flow impairments in pALS. METHOD: MPT, peak cough flow, forced vital capacity, and ALS Functional Rating Scale scores were obtained from 62 pALS (El-Escorial Revised) every 3 months as part of a longitudinal natural history study. Pearson's correlations, linear regressions, and receiver operator characteristic curve analyses with the area under the curve (AUC), sensitivity, specificity, and likelihood ratios were calculated. RESULTS: The mean age of pALS was 63.14 ± 10.95 years, 49% were female, and 43% had bulbar onset. MPT predicted forced vital capacity, F(1, 225) = 117.96, p < .0001, and peak cough flow, F(1, 217) = 98.79, p < .0001. A significant interaction was noted between MPT and ALS Functional Rating Scale-Revised respiratory subscore for forced vital capacity, F(1, 222) = 6.7, p = .010, and peak cough flow, F(1, 215) = 4.37, p = .034. The discriminant ability of MPT was excellent for peak cough flow (AUC = 0.88) and acceptable for forced vital capacity (AUC = 0.78). CONCLUSIONS: MPT is a simple clinical test that can be measured via telehealth and represents a potential surrogate marker for important respiratory and airway clearance indices. Further larger studies are required to validate these findings with remote data collection. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.22186408.

Predictors of Peak Expiratory Cough Flow in Individuals with Amyotrophic Lateral Sclerosis.

Dystussia is prevalent in individuals with amyotrophic lateral sclerosis (ALS), leading to a diminished physiologic capacity to effectively defend the airway. We aimed to identify predictors of peak expiratory cough flow rate in individuals with ALS. One hundred and thirty-four individuals with a confirmed diagnosis of ALS (El-Escorial criteria revised) completed the ALS Functional Rating Scale-Revised (ALSFRS-R) and underwent pulmonary function and cough spirometry testing. Pearson's correlation coefficients and hierarchical multiple regression modeling were conducted to determine predictors of voluntary cough peak expiratory flow rate (p < 0.05). The full model including age, bulbar disease, cough spirometry metrics, and respiratory parameters had a marginal R2 = 0.635, F (7, 126) = 30.241, p < 0.0005, adjusted R2 = 0.61. Maximum expiratory pressure, compression phase, and vital capacity did not contribute and were therefore removed (p < 0.05). The most parsimonious predictive model included age, bulbar disease, peak inspiratory flow rate and duration, peak expiratory rise time, and inspiratory pressure generation with a marginal R2 = 0.543. Although expiratory pressure generation has historically served as the therapeutic target to improve dystussia in ALS, the current dataset highlighted that the inability to quickly and forcefully inspire during the inspiratory phase of voluntary cough places patients at a mechanical disadvantage to generate subsequent high-velocity expiratory airflow to clear the airway. Thus, therapeutic training programs that include both inspiratory and expiratory strength targets may optimize airway clearance capacity in this challenging patient population.

Discriminant Ability of the Eating Assessment Tool-10 to Detect Swallowing Safety and Efficiency Impairments.

OBJECTIVES/HYPOTHESIS: Quick, sensitive dysphagia screening tools are necessary to identify high-risk patients for further evaluation in busy multidisciplinary amyotrophic lateral sclerosis (ALS) clinics. We examined the relationship between self-perceived dysphagia using the validated Eating Assessment Tool-10 (EAT-10) and videofluoroscopic analysis of swallowing safety and efficiency. STUDY DESIGN: Prospective, observational, longitudinal study. METHODS: Individuals with ALS completed the EAT-10 and a videofluoroscopic swallowing study. Duplicate, independent, blinded analyses of the validated Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale were performed to index swallowing safety and efficiency (mild dysphagia: DIGEST ≥ 1, moderate dysphagia: DIGEST ≥ 2). A between-groups analysis of variance with Games-Howell test for post-hoc pairwise comparisons was performed to examine EAT-10 scores across dysphagia severity levels. Receiver operator characteristic curve analysis, area under the curve (AUC), sensitivity, specificity, positive-negative predictive values (PPV, NPV), and odds ratios (OR) were derived. RESULTS: Four hundred and thirty five paired EAT-10 and DIGEST scores were analyzed. Mean EAT-10 score was 8.48 (95% confidence interval [CI]: 7.63-9.33). Individuals with dysphagia demonstrated higher EAT-10 scores (mild: 4.1 vs. 11.3, moderate: 6.0 vs. 17.5, P < .001). Mean EAT-10 scores increased across DIGEST levels (D0: 4.1, D1: 7.9, D2: 15.1, D3: 20.4, D4: 39.0). For mild dysphagia, an EAT-10 cut score of 3 was optimal: AUC 0.74 (95% CI: 0.69-0.78; sensitivity: 77%; specificity: 53%; PPV: 71%; NPV: 60%; OR: 3.5). An EAT-10 cut score of 7 optimized detection of moderate dysphagia: AUC 0.83 (95% CI: 0.78-0.87; sensitivity: 81%; specificity: 66%; PPV: 39%; NPV: 93%; OR: 8.1). CONCLUSION: The EAT-10 is an easy-to-administer dysphagia screening tool with good discriminant ability for use in ALS clinics. LEVEL OF EVIDENCE: 2 Laryngoscope, 132:2319-2326, 2022.

Discriminant ability of the 3-ounce water swallow test to detect aspiration in amyotrophic lateral sclerosis.

BACKGROUND: Given the need for quick and accurate dysphagia screening tools to optimize referral workflows and resource utilization in fast-paced multidisciplinary amyotrophic lateral sclerosis (ALS) clinics, we evaluated the discriminant ability of the 3 oz. water swallow test (WST) to detect aspiration in individuals with ALS. METHODS: A total of 212 paired 3 oz. WST (index test) and standardized videofluoroscopic swallow studies (reference test) were completed in individuals with a confirmed diagnosis of ALS. Blinded raters analyzed swallowing safety using the validated penetration-aspiration scale (PAS; non-aspirator: PAS < 6; aspirator: PAS ≥ 6). Receiver operating characteristic curve analysis, area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated. KEY RESULTS: Index test: 78 (36.8%) WSTs were scored as a fail and 134 (63.2%) as a pass. REFERENCE TEST: Aspiration was confirmed in 67 (31.6%) reference tests with 145 (68.4%) reference tests verified as having no aspiration. Sensitivity and specificity of the 3 oz. WST to detect radiographically confirmed aspiration was 55.2% and 71.7%, respectively (AUC: 0.635, PPV: 47.4%, NPV: 77.6%). CONCLUSIONS & INFERENCES: In this dataset, the 3 oz. WST did not demonstrate adequate sensitivity or specificity to detect aspiration in people with ALS as a stand-alone dysphagia screening tool.

Adaptation and Validation of the Dynamic Imaging Grade of Swallowing Toxicity for Flexible Endoscopic Evaluation of Swallowing: DIGEST-FEES.

Purpose While flexible endoscopic evaluation of swallowing (FEES) is a common clinical procedure used in the head and neck cancer (HNC) population, extant outcome measures for FEES such as bolus-level penetration-aspiration and residue scores are not well suited as global patient-level endpoint measures of dysphagia severity in cooperative group trials or clinical outcomes research. The Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) was initially developed and validated for use during videofluoroscopic evaluations as a way to grade safety, efficiency, and overall pharyngeal swallowing impairment. The purpose of this study was to adapt and validate DIGEST for use with FEES. Method A modified Delphi exercise was conducted for content validation, expert consensus, adaptation, and operationalization of DIGEST-FEES. Three blinded, expert raters then evaluated 100 de-identified post-HNC treatment FEES examinations. Intra- and interrater reliability were tested with quadratic weighted kappa. Criterion validity against the MD Anderson Dysphagia Inventory, Functional Oral Intake Scale, Secretion Severity Scale, and Yale Residue Rating Scale was assessed with Spearman correlation coefficients. Results Interrater reliability was almost perfect for overall DIGEST-FEES grade (κw = 0.83) and safety grade (κw = 0.86) and substantial for efficiency grade (κw = 0.74). Intrarater reliability was excellent for all raters (0.9-0.91). Overall DIGEST-FEES grade correlated with MD Anderson Dysphagia Inventory (r = -.43, p < .0001), Functional Oral Intake Scale (r = -.43, p < .0001), Secretion Severity Scale (r = .47, p < .0001), Yale Vallecular Residue (r = .73, p < .0001), and Yale Pyriform Sinus Residue (r = .65, p < .0001). Conclusion DIGEST-FEES is a valid and reliable scale to describe the severity of pharyngeal dysphagia in patients with HNC. Supplemental Material https://doi.org/10.23641/asha.14642787.

Reflexive Airway Sensorimotor Responses in Individuals with Amyotrophic Lateral Sclerosis.

BACKGROUND: Progressive motor denervation in amyotrophic lateral sclerosis (ALS) leads to reduced expiratory cough flow and diminished airway clearance physiologic capacity. Although ALS is thought to primarily impact motor systems, preliminary data from our laboratory suggest degradation of afferent pathways that regulate reflexive cough responses to radiographically confirmed aspiration. We, therefore, aimed to delineate both sensory and motor responses to a tussigenic airway irritant in individuals with ALS compared to healthy controls. METHODS: Thirty-two individuals with ALS and 34 healthy age and gender-matched controls completed reflex cough testing. Capsaicin stimuli (0, 50, 100, 150, 200 µM) were presented in a randomized three-block design and motor (cough spirometry metrics) and sensory (patient-rated urge to cough, UtC) ratings collected. ALS patients underwent videofluoroscopy with penetration-aspiration ratings completed. Descriptives, Mann-Whitney U, and mixed models ANOVAs were performed. RESULTS: Sensory: Individuals with ALS demonstrated greater UtC sensitivity slopes (i.e., increased stimulus sensitivity) vs. healthy controls (p = 0.036). Within the ALS group, however, silent aspirators (PAS = 8) demonstrated blunted UtC sensitivity slopes compared to ALS patients who did not (PAS ≤ 7, p = 0.0001). Motor: Compared to healthy controls, ALS individuals demonstrated reduced peak expiratory flow rates (p = 0.004), longer peak expiratory rise time (p = 0.017), and lower cough volume acceleration (p = 0.000). CONCLUSIONS: ALS individuals demonstrated increased sensitivity to an upper airway irritant; however, they demonstrated slower and weaker expiratory cough motor output compared to healthy controls. In ALS silent aspirators, blunted sensorimotor responses were observed, suggesting that sensory degradation may occur at the final or most severe stage of bulbar disease progression.

Differences in voluntary and reflexive cough strength in individuals with amyotrophic lateral sclerosis and healthy adults.

INTRODUCTION: Dystussia impacts the ability to protect the airway. Voluntary cough provides a metric of airway defense but differs from the reflexive response to aspiration during swallowing. Therefore, we evaluated relationships between voluntary and reflexive cough among individuals with amyotrophic lateral sclerosis (ALS) and a healthy cohort. METHODS: Twenty-eight individuals with ALS and 26 healthy individuals completed voluntary and reflexive cough testing. Descriptive statistics, reliability, and paired t tests were conducted to evaluate differences in cough volume acceleration (CVA) and peak expiratory flow rate (PEFR) in voluntary vs reflexive cough. RESULTS: Compared with reflexive cough, voluntary CVA and PEFR were greater in individuals with ALS [t(27) = 4.83, P < .001 and t(27) = 8.69, P < .001] and the healthy cohort [t(21) = 5.91, P < .001 and t(21) = 12.26, P < .001], respectively. DISCUSSION: These findings hold important implications for the use and interpretation of voluntary peak cough flow during clinical swallowing evaluations.

A Cross-Sectional, Quantitative Videofluoroscopic Analysis of Swallowing Physiology and Function in Individuals With Amyotrophic Lateral Sclerosis.

Purpose To date, research characterizing swallowing changes in individuals with amyotrophic lateral sclerosis (ALS) has primarily relied on subjective descriptions. Thus, the degree to which swallowing physiology is altered in ALS, and relationships between such alterations and swallow safety and/or efficiency are not well characterized. This study provides a quantitative representation of swallow physiology, safety, and efficiency in a sample of individuals with ALS, to estimate the degree of difference in comparison to published healthy reference data and identify parameters that pose risk to swallow safety and efficiency. Secondary analyses explored the therapeutic effect of thickened liquids on swallowing safety and efficiency. Method Nineteen adults with a diagnosis of probable-definite ALS (El-Escorial Criteria-Revised) underwent a videofluoroscopic swallowing study, involving up to 15 sips of barium liquid (20% w/v), ranging in thickness from thin to extremely thick. Blinded frame-by-frame videofluoroscopy analysis yielded the following measures: Penetration-Aspiration Scale, number of swallows per bolus, amount of pharyngeal residue, degree of laryngeal vestibule closure (LVC), time-to-LVC, duration of LVC (LVCdur), pharyngeal area at maximum constriction, diameter of upper esophageal sphincter opening, and duration of UES opening (UESOdur). Measures of swallow physiology obtained from thin liquid trials were compared against published healthy reference data using unpaired t tests, chi-squared tests, and Cohen's d effect sizes (adjusted p < .008). Preliminary relationships between parameters of swallowing physiology, safety, and efficiency were explored using nonparametric Cochrane's Q, Friedman's test, and generalized estimating equations (p < .05). Results Compared to healthy reference data, this sample of individuals with ALS displayed a higher proportion of swallows with partial or incomplete LVC (24% vs. < 1%), increased time-to-LVC (d = 1.09), reduced UESwidth (d = 0.59), enlarged pharyngeal area at maximum constriction, prolonged LVCdur (d = 0.64), and prolonged UESOdur (d = 1.34). Unsafe swallowing (i.e., PAS ≥ 3) occurred more frequently when LVC was partial/incomplete or time-to-LVC was prolonged. Pharyngeal residue was associated with larger pharyngeal areas at maximum constriction. Unsafe swallowing occurred less frequently with extremely thick liquids, compared to thin liquids. No significant differences in pharyngeal residue were observed based on liquid thickness. Conclusions Quantitative videofluoroscopic measurements revealed moderate-to-large differences in swallow physiology between this sample of individuals with ALS and healthy reference data. Increased time-to-LVC, noncomplete LVC, and enlarged pharyngeal area at maximum constriction were associated with impaired swallow safety or efficiency. Thickened liquids may mitigate the risk of acute episodes of aspiration in individuals with ALS. Further work is needed to corroborate these preliminary findings and explore how swallowing profiles evolve throughout disease progression.

Characteristics of impaired voluntary cough function in individuals with amyotrophic lateral sclerosis.

OBJECTIVE: Although cough impairment (dystussia) is common in individuals with amyotrophic lateral sclerosis (ALS) and contributes to a reduced physiologic capacity to defend the airway, characteristics of dystussia have not yet been delineated. Therefore, we aimed to compare voluntary cough spirometry airflow patterns between individuals with ALS and healthy age and gender-matched controls. METHODS: Thirty-two individuals with a diagnosis of probable-definite ALS (El-Escorial Criterion) and 29 healthy age and gender-matched controls underwent voluntary cough spirometry testing. Two blinded raters derived six objective voluntary cough airflow measures including: peak inspiratory phase duration, peak inspiratory flow rate, compression phase duration, peak expiratory rise time, peak expiratory flow rate, and cough volume acceleration. Independent samples t-tests with Cohen's d effect sizes were performed between Healthy versus ALS groups for cough metrics (alpha =0.05). RESULTS: ALS individuals demonstrated prolonged inspiratory phase and expiratory phase rise time durations, reduced inspiratory and expiratory flow rates, and lower cough volume acceleration during voluntary cough production compared with healthy controls (p < 0.05). No differences in compression phase duration were observed (p > 0.05). CONCLUSIONS: This study compared characteristics of voluntary cough airflow patterns of individuals with ALS to healthy-matched controls. Findings identified impairments in both inspiratory and expiratory voluntary cough airflow, resulting in slower, weaker, and thus less effectiveness voluntary cough production in ALS individuals. These data afford insight into the impaired physiology underlying inadequate airway clearance and secretion management in individuals with ALS.

Impact of expiratory strength training in amyotrophic lateral sclerosis: Results of a randomized, sham-controlled trial.

INTRODUCTION: The purpose of this study was to determine the impact of an in-home expiratory muscle strength training (EMST) program on pulmonary, swallow, and cough function in individuals with amyotrophic lateral sclerosis (ALS). METHODS: EMST was tested in a prospective, single-center, double-blind, randomized, controlled trial of 48 ALS individuals who completed 8 weeks of either active EMST (n = 24) or sham EMST (n = 24). The primary outcome to assess treatment efficacy was change in maximum expiratory pressure (MEP). Secondary outcomes included: cough spirometry; swallowing; forced vital capacity; and scoring on the ALS Functional Rating Scale-Revised. RESULTS: Treatment was well tolerated with 96% of patients completing the protocol. Significant differences in group change scores were noted for MEP and Dynamic Imaging Grade of Swallowing Toxicity scores (P < 0.02). No differences were noted for other secondary measures. DISCUSSION: This respiratory training program was well-tolerated and led to improvements in respiratory and bulbar function in ALS. Muscle Nerve 59:40-46, 2019.

Combined respiratory training in an individual with C9orf72 amyotrophic lateral sclerosis.

This case study examined the impact of a respiratory strength training program targeting inspiratory and expiratory musculature in an individual with C9orf72 amyotrophic lateral sclerosis (ALS). The individual tolerated 24 months of respiratory training completed at home, 50 repetitions per day, and 5 days per week. Significant increases in maximum inspiratory pressure (from 71 to 134 centimeters of water), maximum expiratory pressure (from 108 to 197 centimeters of water) and peak cough flow (from 331 to 655 Liters per minute) were noted and forced vital capacity remained unchanged. A moderate intensity respiratory strength training program applied early in the disease progression improved function in this C9orf72 ALS individual.

Reduced pharyngeal constriction is associated with impaired swallowing efficiency in Amyotrophic Lateral Sclerosis (ALS).

BACKGROUND: Swallowing inefficiency is a prevalent but understudied problem in individuals with Amyotrophic Lateral Sclerosis (ALS). Although reduced pharyngeal constriction has been identified as a mechanism contributing to swallowing inefficiency following stroke, this relationship has not been empirically tested in the ALS population. This study sought to characterize profiles of swallowing efficiency in a sample of ALS patients and investigate relationships between pharyngeal constriction and swallowing efficiency. METHODS: Twenty-six adults with ALS underwent videofluoroscopic swallowing studies, involving 3 mL-thin, 20 mL-thin, and 3 mL-pudding boluses. Full-length recordings were segmented into bolus clips and randomized for analysis. We recorded the total number of swallows per bolus and obtained normalized pixel-based measures of pharyngeal constriction area and post-swallow residue in the vallecular and pyriform sinuses. Linear mixed models with Spearman's correlations were used to determine relationships between pharyngeal constriction and swallowing efficiency, with added factors of bolus volume and thickness. KEY RESULTS: Individuals with ALS demonstrated reduced pharyngeal constriction and increased vallecular and pyriform sinus residue, compared to norms. Reduced pharyngeal constriction had a significant effect on the presence of vallecular and pyriform sinus residue as well as the number of swallows per bolus. Increased bolus thickness was associated with increased vallecular residue, while increased bolus volume was associated with reduced pharyngeal constriction. Results were significant at P < 0.05. CONCLUSIONS & INFERENCES: Our results suggest that reduced pharyngeal constriction is a significant physiological parameter related to swallow inefficiency in ALS. Future work is needed to corroborate these preliminary results and investigate factors to mitigate such impairments.