Human tear fluid modulates the Pseudomonas aeruginosa transcriptome to alter antibiotic susceptibility.

PURPOSE: Previously, we showed that tear fluid protects corneal epithelial cells against Pseudomonas aeruginosa without suppressing bacterial viability. Here, we studied how tear fluid affects bacterial gene expression. METHODS: RNA-sequencing was used to study the P. aeruginosa transcriptome after tear fluid exposure (5 h, 37 oC). Outcomes were further investigated by biochemical and physiological perturbations to tear fluid and tear-like fluid (TLF) and assessment of bacterial viability following tear/TLF pretreatment and antibiotic exposure. RESULTS: Tear fluid deregulated ~180 P. aeruginosa genes ≥8 fold versus PBS including downregulating lasI, rhlI, qscR (quorum sensing/virulence), oprH, phoP, phoQ (antimicrobial resistance) and arnBCADTEF (polymyxin B resistance). Upregulated genes included algF (biofilm formation) and hemO (iron acquisition). qPCR confirmed tear down-regulation of oprH, phoP and phoQ. Tear fluid pre-treatment increased P. aeruginosa resistance to meropenem ~5-fold (4 µg/ml), but enhanced polymyxin B susceptibility ~180-fold (1 µg/ml), the latter activity reduced by dilution in PBS. Media containing a subset of tear components (TLF) also sensitized bacteria to polymyxin B, but only ~22.5-fold, correlating with TLF/tear fluid Ca2+ and Mg2+ concentrations. Accordingly, phoQ mutants were not sensitized by TLF or tear fluid. Superior activity of tear fluid versus TLF against wild-type P. aeruginosa was heat resistant but proteinase K sensitive. CONCLUSION: P. aeruginosa responds to human tear fluid by upregulating genes associated with bacterial survival and adaptation. Meanwhile, tear fluid down-regulates multiple virulence-associated genes. Tears also utilize divalent cations and heat resistant/proteinase K sensitive component(s) to enhance P. aeruginosa sensitivity to polymyxin B.

Effects of Submental Surface Electrical Stimulation on Swallowing Kinematics in Healthy Adults: An Error-Based Learning Paradigm.

Purpose: Hyoid bone and laryngeal approximation aid airway protection (laryngeal vestibule closure) while moving toward their peak superior and anterior positions during swallowing. Submental surface electrical stimulation (SES) is a therapeutic technique that targets the muscles that move the hyoid bone during swallowing. It is unknown whether submental SES only increases peak hyoid bone swallowing positions but not peak laryngeal swallowing positions, which could require faster or greater laryngeal movement to achieve adequate laryngeal vestibule closure. Method: We examined the effects of submental SES on hyo-laryngeal kinematics in 30 healthy adults who swallowed 50 times using an error-based learning paradigm. Results: Submental SES did not alter any hyo-laryngeal swallowing kinematic. However, submental SES significantly changed the starting position of the hyoid bone just prior to the swallow onset (more anterior; p = .003). On average, submental SES immediately prior to swallow onset can position the hyoid approximately 20% closer to its peak swallowing point. Conclusions: These findings indicate that electrical stimulation of the agonists for hyoid movement might not alter swallowing outcomes tested in this study. However, submental SES could have clinical utility by minimizing swallowing impairments related to reduced hyoid swallowing range of motion in individuals with dysphagia.

The evaluation of bulbar dysfunction in amyotrophic lateral sclerosis: survey of clinical practice patterns in the United States.

OBJECTIVE: Speech and swallowing impairments are highly prevalent in individuals with amyotrophic lateral sclerosis (ALS) and contribute to reduced quality of life, malnutrition, aspiration, pneumonia and death. Established practice parameters for bulbar dysfunction in ALS do not currently exist. The aim of this study was to identify current practice patterns for the evaluation of speech and swallowing function within participating Northeast ALS clinics in the United States. METHODS AND RESULTS: A 15-item survey was emailed to all registered NEALS centres. Thirty-eight sites completed the survey. The majority (92%) offered Speech-Language Pathology, augmentative and alternative communication (71%), and dietician (92%) health care services. The ALS Functional Rating Scale-Revised and body weight represented the only parameters routinely collected in greater then 90% of responding sites. Referral for modified barium swallow study was routinely utilised in only 27% of sites and the use of percutaneous gastrostomy tubes in ALS patient care was found to vary considerably. CONCLUSIONS: This survey reveals significant variability and inconsistency in the management of bulbar dysfunction in ALS across NEALS sites. We conclude that a great need exists for the development of bulbar practice guidelines in ALS clinical care to accurately detect and monitor bulbar dysfunction.

Respiratory training in an individual with amyotrophic lateral sclerosis.

We examined the impact of expiratory muscle strength training on maximum expiratory pressure, cough spirometry, and disease progression in a 71-year-old male with amyotrophic lateral sclerosis. Maximum expiratory pressure declined 9% over an 8-week sham training period, but subsequently improved by 102% following 8 weeks of expiratory muscle strength training. Improvements in cough spirometry and mitigated disease progression were also observed post expiratory muscle strength training. Improvements in maximum expiratory pressures were maintained 6 months following expiratory muscle strength training and were 79% higher than baseline data obtained 301 days prior. In this spinal-onset amyotrophic lateral sclerosis patient, respiratory training improved subglottic air pressure generation and sequential cough generation.

Defining Swallowing-Related Quality of Life Profiles in Individuals with Amyotrophic Lateral Sclerosis.

Although it is known that dysphagia contributes to significant malnutrition, pneumonia, and mortality in amyotrophic lateral sclerosis (ALS), it remains unclear how swallowing impairment impacts quality of life in this vulnerable patient population. The aim of the current study was to (1) delineate swallow-related quality of life (SR-QOL) profiles in individuals with ALS and (2) evaluate relationships between SR-QOL, degree of swallowing impairment, and ALS global disease progression. Eighty-one ALS patients underwent a standardized videofluoroscopic swallow study and completed the swallowing quality of life (SWAL-QOL) instrument and ALS functional rating scale-revised (ALSFRS-R). Penetration Aspiration Scale (PAS) scores were derived by a blinded rater. Correlation analyses and a between groups ANOVA (safe vs. penetrators vs. aspirators) were performed. Mean SWAL-QOL score for this cohort was 75.94 indicating a moderate degree of SR-QOL impairment with fatigue, eating duration, and communication representing the most affected domains. Correlations were revealed between the SWAL-QOL and (1) PAS (r = -0.39, p < 0.001) and (2) ALSFRS-R (r = 0.23, p < 0.05). Mean (SD) SWAL-QOL scores for safe versus penetrator versus aspirator groups were 81.2 (2.3) versus 77 (3.4) versus 58.7 (5.9), respectively, with a main effect observed [F(2,78) = 9.71, p < 0.001]. Post hoc testing revealed lower SWAL-QOL scores for aspirators versus safe swallowers (p < 0.001) and aspirators versus penetrators (p < 0.001). Overall, SR-QOL was moderately reduced in this cohort of ALS patients and profoundly impacted in ALS aspirators and individuals with advanced disease. These findings highlight the importance of early multidisciplinary intervention to not only avoid malnutrition, weight loss, and pulmonary sequelae but also the associated reduced QOL seen in these individuals.

Voluntary Cough Airflow Differentiates Safe Versus Unsafe Swallowing in Amyotrophic Lateral Sclerosis.

Dysphagia and aspiration are prevalent in amyotrophic lateral sclerosis (ALS) and contribute to malnutrition, aspiration pneumonia, and death. Early detection of at risk individuals is critical to ensure maintenance of safe oral intake and optimal pulmonary function. We therefore aimed to determine the discriminant ability of voluntary cough airflow measures in detecting penetration/aspiration status in ALS patients. Seventy individuals with ALS (El-Escorial criteria) completed voluntary cough spirometry testing and underwent a standardized videofluoroscopic swallowing evaluation (VFSE). A rater blinded to aspiration status derived six objective measures of voluntary cough airflow and evaluated airway safety using the penetration-aspiration scale (PAS). A between groups ANOVA (safe vs. unsafe swallowers) was conducted and sensitivity, specificity, area under the curve (AUC) and likelihood ratios were calculated. VFSE analysis revealed 24 penetrator/aspirators (PAS ≥3) and 46 non-penetrator/aspirators (PAS ≤2). Cough volume acceleration (CVA), peak expiratory flow rise time (PEFRT), and peak expiratory flow rate (PEFR) were significantly different between airway safety groups (p < 0.05) and demonstrated significant discriminant ability to detect the presence of penetration/aspiration with AUC values of: 0.85, 0.81, and 0.78, respectively. CVA <45.28 L/s/s, PEFR <3.97 L/s, and PEFRT >76 ms had sensitivities of 91.3, 82.6, and 73.9 %, respectively, and specificities of 82.2, 73.9, and 78.3 % for identifying ALS penetrator/aspirators. Voluntary cough airflow measures identified ALS patients at risk for penetration/aspiration and may be a valuable screening tool with high clinical utility.

Impact of expiratory strength training in amyotrophic lateral sclerosis.

INTRODUCTION: We evaluated the feasibility and impact of expiratory muscle strength training (EMST) on respiratory and bulbar function in persons with amyotrophic lateral sclerosis (ALS). METHODS: Twenty-five ALS patients participated in this delayed intervention open-label clinical trial. Following a lead-in period, patients completed a 5-week EMST protocol. Outcome measures included: maximum expiratory pressure (MEP); physiologic measures of swallow and cough; and penetration-aspiration scale (PAS) scores. RESULTS: Of participants who entered the active phase of the study (n = 15), EMST was well tolerated and led to significant increases in MEPs and maximum hyoid displacement during swallowing post-EMST (P < 0.05). No significant differences were observed for PAS scores or cough spirometry measures. CONCLUSIONS: EMST was feasible and well tolerated in this small cohort of ALS patients and led to improvements in expiratory force-generating pressures and swallow kinematics. Further investigation is warranted to confirm these preliminary findings. Muscle Nerve 54: 48-53, 2016.

To Cough or Not to Cough? Examining the Potential Utility of Cough Testing in the Clinical Evaluation of Swallowing.

PURPOSE: The clinical swallowing evaluation (CSE) represents a critical component of a comprehensive assessment of deglutition. Although universally utilized across clinical settings, the CSE demonstrates limitations in its ability to accurately identify all individuals with dysphagia. There exists a need to improve assessment and screening techniques to improve health outcomes, treatment recommendations and ultimately mortality in individuals at risk for dysphagia. The following narrative review provides a summary of currently used validated CSE's and examines the potential role of cough testing and screening in the CSE. RECENT FINDINGS: Recent evidence highlights a relationship between objective physiologic measurements of both voluntarily and reflexively induced cough and swallowing safety status across several patient populations. Although more research is needed across a wider range of patient populations to validate these findings; emerging data supports the consideration of inclusion of cough testing during the CSE as an index of airway defense mechanisms and capabilities in individuals at risk for aspiration. SUMMARY: The sensorimotor processes of cough and swallowing share common neuroanatomical and functional substrates. Inclusion of voluntarily or reflexively induced cough testing in the CSE may aide in the identification of dysphagia and reduced airway protection capabilities.