Airway Protective Mechanisms Research Articles

The opioid buprenorphine differentially affects laryngeal and tracheal sensory receptors

The current study aims to determine mechanisms of impaired airway protection following opioid administration. Experiments were performed on N=10 anesthetized male Sprague Dawley rats. Bipolar fine wire electromyogram (EMG) wires were implanted in various muscles to evaluate breathing and swallowing. Swallows were evoked by activation of laryngeal touch receptors, tracheal mechanoreceptors, and tracheobronchial c-fibers as follows: A) Light laryngeal touch with a Von Frey filament; B) Rapid inflation of a balloon in the proximal trachea; C) Stimulation of the carina with thin polyethylene tubing. Trials were performed before and after buprenorphine administration (0.01 mg/kg IV). 2-Way ANOVA detected an effect of drug [F(1,16)=40.6, p<0.0001] and stimulus [F(2,19)=4.2, p=0.03] on swallow frequency. Post hoc comparisons showed that after buprenorphine administration, laryngeal touch evoked significantly more swallows (10±4) than tracheal distension (1±1, p=0.03) or carina stimulation (1±3, p=0.04), suggesting that laryngeal sensation is critical for airway protection following opioid administration. This has implications for prevention of aspiration pneumonia in populations that have an increased risk of reduced laryngeal sensation and are commonly treated with opioids (e.g., post-surgical, critically ill, and/or head and neck cancer patients). Research reported in this abstract was supported by NIH grants NS110169, HL155721, HL163008, HD110951, NS097781, OT20D001983, the Craig H. Neilsen Foundation Pilot Research Grant 546714, Kentucky Spinal Cord and Head Injury Research Trust, and the Commonwealth of Kentucky Challenge for Excellence. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Study on Subjective Aerodynamic Measurement among the Gujarati-speaking Healthy Adults in West Cost India

Abstract Introduction: The adequate respiratory functions are important for lifesaving like breathing, and communications such as vocalization in speech productions, and additionally, it supports for airway protective mechanisms by strengthening the protective cough. The maximum phonation duration (MPD) and maximum utterance of /s/, /Z/ and its ratio are the important aerodynamic parameters that indicate the respiratory functions and its impact on breathing, vocalization as well as protective mechanism. Aim: The aim of this study was to review and contrast the results of subjective aerodynamic assessments of maximum phonation time/duration and S/Z ratio in seconds among Gujarati-speaking healthy adult populations. Objective: The current study attempted to construct the normalization of MPD and S/Z Ratio for both males and females. Results: Mean MPD for males was greater than females, whereas s/z ratio for males and females was around 0.97 s. Conclusion: By developing normative statistics among Gujarati-speaking adult populations for both genders, it will be possible to utilize them as a reference for clinical diagnosis and for an intervention program for people with respiratory issues and other voice diseases.

Minimally Invasive Murine Laryngoscopy for Close-Up Imaging of Laryngeal Motion during Breathing and Swallowing.

The larynx is an essential organ in mammals with three primary functions - breathing, swallowing, and vocalizing. A wide range of disorders are known to impair laryngeal function, which results in difficultybreathing (dyspnea), swallowing impairment (dysphagia), and/or voice impairment (dysphonia). Dysphagia, in particular, can lead to aspiration pneumonia and associated morbidity, recurrent hospitalization, and early mortality. Despite these serious consequences, existing treatments for laryngeal dysfunction are largely aimed at surgical and behavioral interventions that unfortunately do not typically restore normal laryngeal function, thus highlighting the urgent need for innovative solutions. To bridge this gap, we have been developing an experimental endoscopic approach to investigate laryngeal dysfunction in murine (i.e., mouse and rat) models. However, endoscopy in rodents is quite challenging due to their small size relative to current endoscope technology, anatomical differences in the upper airway, and the necessity for anesthesia to optimally access the larynx. Here, we describe a novel transoral laryngoscopy approach that permits close-up, unobstructed video imaging of laryngeal motion in mice and rats. Critical steps in the protocol include precise anesthesia management (to prevent overdosing that abolishes swallowing and/or risks respiratory distress-related mortality) and micromanipulator control of the endoscope (for stable video recording of laryngeal motion by a single researcher for subsequent quantification). Importantly, the protocol can be performed over time in the same animals to study the impact of various pathological conditions specifically on laryngeal function. A novel advantage of this protocol is the ability to visualize airway protection during swallowing, which is not possible in humans due to epiglottic inversion over the laryngeal inlet that obstructs the glottis from view. Rodents therefore provide a unique opportunity to specifically investigate the mechanisms of normal versus pathological laryngeal airway protection for the ultimate purpose of discovering treatments to effectively restore normal laryngeal function.

Growth differentiation factor 15 protects the airway by inhibiting cell pyroptosis in obese asthmatic mice through the phosphoinositide 3-kinase/AKT pathway.

Obese asthma is a form of refractory asthma with inflammation as the underlying mechanism. The specific mechanism of action of anti-inflammatory growth differentiation factor 15 (GDF15) in obese asthma is unclear. The purpose of this study was to explore the effect of GDF15 on cell pyroptosis in obese asthma and to determine its mechanism of airway protection. Male C57BL6/J mice were fed with a high-fat diet, sensitized, and challenged with ovalbumin. Recombinant human (rh)GDF15 was administered 1h before the challenge. GDF15 treatment significantly reduced airway inflammatory cell infiltration, mucus hypersecretion and airway resistant, and decreased cell counts and inflammatory factors in bronchoalveolar lavage fluid. Serum inflammatory factors decreased, and the increased levels of NLR family pyrin domain containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and gasdermin-D (GSDMD-N) in obese asthmatic mice were inhibited. Furthermore, the suppressed phosphoinositide 3-kinase (PI3K)/AKT signal pathway was activated after rhGDF15 treatment. The same result was obtained by overexpression of GDF15 in human bronchial epithelial cells induced by lipopolysaccharide (LPS) in vitro, and the effect of GDF15 was reversed after the application of a PI3K pathway inhibitor. Thus, GDF15 could protect the airway by inhibiting cell pyroptosis in obese asthmatic mice through the PI3K/AKT signaling pathway.

Impact of early percutaneous dilatative tracheostomy in patients with subarachnoid hemorrhage on main cerebral, hemodynamic, and respiratory variables: A prospective observational study.

Patients with poor-grade subarachnoid hemorrhage (SAH) admitted to the intensive care unit (ICU) often require prolonged invasive mechanical ventilation due to prolonged time to obtain neurological recovery. Impairment of consciousness and airway protective mechanisms usually require tracheostomy during the ICU stay to facilitate weaning from sedation, promote neurological assessment, and reduce mechanical ventilation (MV) duration and associated complications. Percutaneous dilatational tracheostomy (PDT) is the technique of choice for performing a tracheostomy. However, it could be associated with particular risks in neurocritical care patients, potentially increasing the risk of secondary brain damage. We conducted a single-center, prospective, observational study aimed to assess PDT-associated variations in main cerebral, hemodynamic, and respiratory variables, the occurrence of tracheostomy-related complications, and their relationship with outcomes in adult patients with SAH admitted to the ICU of a neurosurgery/neurocritical care hub center after aneurysm control through clipping or coiling and undergoing early PDT. We observed a temporary increase in ICP during early PDT; this increase was statistically significant in patients presenting with higher therapy intensity level (TIL) at the time of the procedural. The episodes of intracranial hypertension were brief, and appeared mainly due to the activation of cerebral autoregulatory mechanisms in patients with impaired compensatory mechanisms and compliance. The low number of observed complications might be related to our organizational strategy, all based on a dedicated "tracheo-team" implementing both PDT following a strictly defined protocol and accurate follow-up.

Airway Protection in Children With Dysphagia: A Preliminary Study

Purpose : The physiology and pathophysiology of pediatric swallowing are challenging due to anatomical differences. There are only a few videofluoroscopic case studies examining the relationship between physiologic events and aspiration in infants, especially, airway protection mechanisms using temporal measurements. This study examined the airway protection mechanisms using two temporal measurements: the initiation and duration of laryngeal closure between two groups of children who were referred for dysphagia evaluation.BRMethods : Twelve children (8 younger and 4 older children) were patriciate in the study. Initiation of laryngeal closure (ILC) and laryngeal closure duration (LCD) were measured using videofluoroscopic swallowing examinations (VFSEs) with a 100-ms timer for bottle-fed or 2mL thin liquids and/or puree boluses. Two-way analysis of variance (ANOVA) was used at a significance level of p.05.BRResults : Younger children showed longer LCD than older children. There was no significant difference in ILC between younger and older children with dysphagia. The puree had longer ILC and shorter LCD than the thin liquid bolus.BRConclusions : The longer duration of laryngeal closure in younger children may indicate that their anatomical structure is more prone to better protect their airways than older children. Longer ILC and shorter LCD were observed in both children groups who presented penetration or aspiration. These pathophysiological phenomena should be observed closely as indicators of the higher risk of dysphagia. Bolus modification such as thickened liquid may help the children to keep from aspiration.

Voluntary Cough Testing as a Clinical Indicator of Airway Protection in Cervical Spinal Cord Injury.

Voluntary cough testing (VCT) may be useful for determining aspiration risk in neurogenic dysphagia; however, has yet to be investigated in traumatic cervical spinal cord injury (tCSCI). The study explored if VCT may elucidate swallowing safety and kinematics related to airway protection in tCSCI survivors. Ten inpatients, 13-73 days post-tCSCI (7 incomplete injuries), completed VCT and a modified barium swallowing study that was analyzed via the Penetration Aspiration Scale (PAS) and norm-referenced measures of swallowing events related to airway protection. Spearman rho correlations explored relations among cough airflow, median PAS, and airway protection. Mann-Whitney U tests explored group differences based on clinical airway invasion (PAS > 2) and receiver operating characteristic statistics probed the sensitivity/specificity of VCT measures. Safe (PAS > 2) and unsafe swallowers differed by cough volume acceleration (CVA) for the total sample and by inspiratory duration for incomplete injuries (p= 0.03, r> 0.7). A cut-off value of 24.8 L/s for CVA predicted airway invasion (AUC= 0.917, p= 0.03) with sensitivity=100%/specificity=75%. CVA correlated with delayed laryngeal vestibule closure during swallowing for both the total sample and for incomplete injuries (rs > 0.6, p< 0.05). Blunted peak flow and prolonged cough phases were associated with disordered laryngeal kinematics and prolonged bolus transit during swallowing (p< 0.05). Reduced CVA, blunted peak flow, and prolonged cough phases reflected PAS and disrupted mechanisms of airway protection in tCSCI survivors, demonstrating promise for VCT as a clinical assessment for post-tCSCI dysphagia. 3 Laryngoscope, 133:1434-1441, 2023.

Submental transcutaneous electrical stimulation can impact the timing of laryngeal vestibule closure.

BackgroundLaryngeal vestibule closure (LVC) is one of the critical airway protection mechanisms during swallowing. LVC timing impairments during swallowing are among the common causes of airway invasion in patients with dysphagia.ObjectivesTo understand whether using submental transcutaneous electrical stimulation (TES) with varying pulse durations can impact the LVC reaction time (LVCrt) and LVC duration (LVCd) measures in healthy adults.MethodsTwenty‐six healthy adults underwent three TES conditions while receiving three trials of 10 ml pureed: no TES, TES with short pulse duration (300 μs) and TES with long pulse durations(700 μs). Two pairs of electrodes were placed diagonally on the submental area. For each active TES condition, the stimulation was increased up to the participant's self‐identified maximum tolerance. Each swallow trial was recorded using videofluoroscopic swallowing study. All data were extracted and analysed offline using VideoPad Video Editor program.ResultsSubmental TES reduced LVCrt during swallowing [F (2, 46) = 7.234, p < .007, ηp2 = .239] but had no significant impact on LVCd [F (2, 50) = .1.118, p < .335, ηp2 = .043]. Furthermore, pulse duration had no distinguished impact on any LVC timing measures.ConclusionTranscutaneous electrical stimulation may benefit patients with dysphagia who suffer from delayed LVC during swallowing. Future studies should seek whether the same physiologic effect can be observed in patients with dysphagia.

A CASE OF RETAINED ORAL CARE SPONGE IN THE BRONCHUS CAUSING PNEUMONIA IN CHRONICALLY VENTILATED PATIENT

TOPIC: Lung Pathology TYPE: Medical Student/Resident Case Reports INTRODUCTION: Aspiration of foreign bodies is not uncommon and mostly accidental with the highest prevalence in young children [1]. Occurrence in adults is rare and usually as a result of diminished consciousness, sedation, trauma, and neuromuscular disorders. We present a case of a 70 year old patient receiving chronic mechanical ventilation who had multiple episodes of hypoxia due to a dislodged oral care sponge. CASE PRESENTATION: A 70 year-old bedbound male with chronic mechanical ventilation (via tracheostomy?) after traumatic brain injury, and recurrent pneumonia was admitted for pneumonia. On admission, respiratory cultures grew Carbapenem resistant Acinetobacter Bumanii and Pseudomonas Aeruginosa with negative urinalysis and blood cultures. Chest radiograph showed bilateral lower lobe opacities. He was treated with vancomycin, polymyxin B, and meropenem. However, his FiO2 fluctuated between 40% and 60% and despite being on antibiotics he was persistently febrile. He continued to have copious secretions requiring frequent suctioning without any new infiltrates on repeat chest radiograph. A Computer tomography (CT) of the chest was performed which showed a tubular structure extending from the right main bronchus to the bronchus intermedius (Image 1). Bronchoscopy was done and the object was found to be the head of an oral care sponge. After foreign body removal his respiratory status improved and fevers resolved. DISCUSSION: Oral care in mechanically ventilated patients has been studied extensively and there are many guidelines recommend to minimize ventilator associated pneumonia. Extreme care must be taken by providers as defective products or aggressive technique can result in fragments being dislodged into the oral cavity and can result in aspiration especially in patients with chronic tracheostomy. In patients with tracheostomy, diminished airway protective mechanisms and a deflated balloon can result in an increased risk of foreign body aspiration. Aspiration of a foreign body is a significant cause of morbidity as it can cause asphyxiation or trauma to the airway resulting in pneumothorax, bleeding, and infections [2]. In patients with diminished consciousness the signs of foreign body aspirations can be subtle such a mild cough, fevers, frequent infections, or increasing oxygen and they may not be able to provide a proper history. CONCLUSIONS: This case highlights the need for vigilance regarding potential complications from providing oral care in the elderly who have diminished ability to protect their airway. REFERENCE #1: 1. Ding G et al., Tracheobronchial foreign body aspiration in children: A retrospective single-center cross-sectional study. Medicine (Baltimore). 2020 May 29;99(22):e20480. REFERENCE #2: 2. Aissaoui, N. H. Salem, and A. Chadly, "Unusual foreign body aspiration as a cause of asphyxia in adults: an autopsy case report," The American Journal of Forensic Medicine and Pathology, vol. 33, no. 3, pp. 284–285, 2012. DISCLOSURES: No relevant relationships by Kabu Chawla, source=Web Response No relevant relationships by Varun tej Gonuguntla, source=Web Response Speaker/Speaker's Bureau relationship with pfizer Please note: $1001 - $5000 by Yizhak Kupfer, source=Admin input, value=Consulting fee No relevant relationships by Sharad Oli, source=Web Response No relevant relationships by kiran para, source=Web Response No relevant relationships by Ankur Sinha, source=Web Response

Frequency of signs and symptoms in children with foreign body aspiration: A retrospective study in Iran

Foreign body aspiration is still one of the most important diagnostic and therapeutic items for physicians. The mortality rate and prevalence of diseases caused by foreign bodies are higher in children due to the relatively narrow airway and immature protective mechanisms. Considering the high prevalence of foreign body aspiration in children, as well as the possible complications, we decided to investigate the frequency distribution of signs and symptoms in children with foreign body aspiration. This retrospective cross-sectional study was performed on the files of 50 children with foreign body aspiration who referred to Khatam Al-Anbia Hospital in Zahedan, Iran from 2016 to 2018. The files were entered into the study by the census method, based on inclusion and exclusion criteria. Finally, demographic factors (age and sex), as well as the type of aspirated object, signs, and symptoms, were examined. The files of 50 children with a foreign body aspiration were reviewed. Among the patients, 27 (54%) were boys and 23 (46%) were girls. The highest frequency was between 1 and 2 years, with 36%. The most common symptom in these patients was cough and respiratory distress with a frequency of 72% and the most common clinical findings were unilateral wheezing with 50% and decreased unilateral respiratory sounds with 18%. Also, the most common types of foreign objects were nuts with a frequency of 44% and supari with 38%. Also, unilateral wheezing had a significant relationship with the type of aspirated foreign body (P = 0.01). Children between the ages of one and two years are more likely to have foreign body aspiration, and in children with symptoms of cough and respiratory distress, as well as clinical findings of unilateral wheezing and decreased unilateral respiratory sounds, foreign body aspiration should be suspected.

Neural Mechanisms of Swallowing and Airway Protection During Swallowing

Neural Mechanisms of Swallowing and Airway Protection During Swallowing

An Oral Whole-Cell Killed Nontypeable Haemophilus influenzae Immunotherapeutic For The Prevention Of Acute Exacerbations Of Chronic Airway Disease.

In subjects with chronic bronchitis, protection against acute bronchitis following oral administration of a whole-cell killed nontypeable Haemophilus influenzae (NTHi) preparation was demonstrated in the mid-1980s. Subsequently, studies aiming to validate clinical efficacy of this oral treatment were complicated by a number of factors, including the modification of clinical definitions, the implications of which were not recognized at that time. The objective of this review is to integrate our pre-clinical and clinical research in this field conducted over the past 30 years to demonstrate the evolution of the idea of communication between mucosal surfaces through the common mucosal immune system and the development of an effective oral NTHi immunotherapy. Our earliest studies recruited subjects with chronic sputum production and high levels of culture-positive sputum for Gram-negative bacteria but by 2000, the clinical diagnostic focus had switched from “chronic bronchitis” to “chronic obstructive pulmonary disease” (COPD), which was functionally defined using spirometry. This change led to variable clinical trial results, confirming the importance of chronic sputum production and culture-positive sputum. Additional conditioning factors such as patient age and gender were influential in study populations with low culture-positive sputum production. Through this period, studies in human and in rodent models provided new insights into airway protection mechanisms and the pathogenesis of airway inflammation. Key findings were the importance of a dysbiosis within the airway microbiome, and the critical role of an interdependence between the bronchus and the gut, with a Peyer’s patch-dependent extra-bronchus “loop” controlling the composition of the bronchus microbiome. Within this context, intercurrent virus infections initiate a microbiome-dependant hypersensitivity reaction involving Peyer’s patch-derived Th17 cells. We conclude that whole-cell killed NTHi immunotherapy has consistent and significant benefits when examined in the context of changing clinical disease definitions, age and gender, and has the potential to change the natural history of chronic airway disease.

Swallow and Aspiration in Chronic Obstructive Pulmonary Disease.

Swallowing is a complex biomechanical process that is synchronized with breathing to protect the airway. In chronic obstructive pulmonary disease (COPD) altered upper airway protective mechanisms coupled to ventilatory adaptations may lead to laryngeal penetration during swallow that can be followed by pulmonary aspiration. To date investigations have reported a spectrum of swallow and breathing dysfunction in COPD ranging from mild (laryngeal penetration) to severe abnormality (pulmonary aspiration). However, the prevalence of penetration and aspiration in COPD is uncertain and important aspects such as a role in recurrent lung infections and repeated exacerbations are not understood. Current evidence indicates that aspiration during swallow occurs in up to 25% of individuals with COPD. Factors putatively associated with aspiration include increased respiratory rate, reduced laryngeal elevation during swallow, post-swallow pharyngeal residue and inspiration-swallow patterns. Timely identification of indi...

Pathophysiology of Oropharyngeal Dysphagia Assessed by Videofluoroscopy in Patients with Dementia Taking Antipsychotics

ObjectivesThe objective of this study was to assess the pathophysiology of oropharyngeal dysphagia (OD) in patients with dementia, specifically in those taking antipsychotics (APs). DesignA cross-sectional study was performed from January 2011 to May 2017 in a general hospital. Setting and ParticipantsWe included 114 patients with dementia, of which 39 (34.2%) were taking APs (82.5 ± 7.8 years, Barthel Index 52.28 ± 30.42) and 29 patients without dementia (82.4 ± 6.7 years, Barthel Index 77.71 ± 24.7) and OD confirmed by a videofluoroscopy. MeasuresDemographical and clinical factors as well as swallowing function of patients with dementia with OD were compared with older patients without dementia with OD. We also compared patients with dementia taking and not taking APs. Impaired efficacy during videofluoroscopy was defined as the presence of oral and/or pharyngeal residue, and impaired safety (unsafe swallow) was defined as aspiration or penetration. Receiver operating characteristic curves were drawn for laryngeal vestibule closure (LVC) time to predict unsafe swallow. Results87.7% of patients with dementia presented impaired efficacy of swallow and 74.6% impaired safety [penetration-aspiration scale (PAS) 3.94 ± 1.94]. 86.2% of patients without dementia presented impaired efficacy and 44.8% impaired safety (PAS 2.21 ± 1.92). Time to LVC was significantly delayed in patients with dementia taking APs in comparison with patients without dementia (LVC 0.377 ± 0.093 vs 0.305 ± 0.026, P = .003). In contrast, there were no differences in the PAS and LVC time in patients with dementia taking and not taking APs (PAS 3.96 ± 0.26 vs 3.88 ± 0.22, LVC 0.398 ± 0.117 vs 0.376 ± 0.115, NS). LVC time ≥0.340 seconds predicted unsafe swallow in patients with dementia with an accuracy of 0.71. Conclusions/ImplicationsPatients with dementia presented high prevalence and severity of videofluoroscopy signs of impaired efficacy and safety of swallow and a more severe impairment in airway protection mechanisms (higher PAS and LVC delay). Clinical practice should implement specific protocols to prevent OD and its complications in these patients. AP treatment did not significantly worsen swallowing impairments.

Epiglottic kinematics alterations and risk of laryngeal penetration-aspiration

Epiglottic retroflexion seems to be an important mechanism of airway protection during swallowing. Although epiglottic dysfunction has been correlated with aspiration, the kinematics alterations underlying this condition remain unclear. Two distinct movements of epiglottic inversion were described in videofluoroscopic swallowing studies (VFSS). The first epiglottic movement brings the epiglottis to a horizontal position and the second consists of its full inversion. Retrospective cohort study of 28 patients with post-stroke dysphagia admitted to our institution in 2017. Based on VFSS images, and in regard with the epiglottic mobility, two groups were assigned for comparison: one group with complete epiglottic inversion and other with partial inversion. Other parameters of VFSS were also compared. Of the 28 patients in the study, 68% were male (19) and 32% female (9); 28.6% of the patients had hemorrhagic stroke, 67.9% ischemic, and 3.5% ischemic stroke with hemorrhagic transformation. We found significant statistical correlation between epiglottic mechanics alterations and risk of laryngeal penetration (Fisher's exact-test; P = 0.036). Regarding other evaluated parameters, only the absence of the cough reflex was shown to statistically correlate with the risk of laryngeal penetration (Pearson's Chi 2 ; P = 0.007). The results suggest that epiglottis movement is an important mechanism to avoid penetration-aspiration. The absence of cough reflex in patients with laryngeal penetration (silent aspiration) emphasizes the importance of the VFSS. We are also of the opinion that this result may be related to the pre selection of patients with suspected silent aspiration. Further studies are needed to better understand the influence of these epiglottic movement alterations in the swallowing process.

Older Age Reduces Upper Esophageal Sphincter and Esophageal Body Responses to Simulated Slow and Ultraslow Reflux Events and Post-Reflux Residue

It is not clear how age affects airway protective mechanisms. We investigated the effects of aging on upper esophageal sphincter (UES) and esophageal body pressure responses to slow and ultraslow simulated reflux events and post-reflux residue. We performed a prospective study of 11 elderly (74 ± 9 years old) and 11 young (28 ± 7 years old) healthy volunteers. Participants were placed in a supine position and evaluated by concurrent high-resolution impedance manometry and an esophageal infusion technique. Potential conditions of gastroesophageal reflux were simulated, via infusion of 0.1 N HCl and saline. UES and esophageal pressure responses were measured during the following: slow infusion (1 mL/s) for 60 seconds, 60 seconds of postinfusion dwell period, ultraslow infusion (0.05 mL/s) for 60 seconds, and 60 seconds of a postinfusion dwell period. All infusions were repeated 3 times. We used the UES high-pressure zone contractile integral (UES-CI) to determine responses of the UES. Young and elderly subjects each had a significant increase in the UES-CI during slow infusions and during entire passive dwell intervals compared with baseline (P < .01, both groups). Ultraslow infusions were associated with a significant increase in UES-CI in only the young group, in the late infusion period, and into the dwell interval (P < .01). During the slow infusions and their associated dwell periods, young subjects had a higher frequency of secondary peristalsis than elderly subjects (P<.05). There was more secondary peristalsis during activeinfusions than dwell intervals. Secondary peristalsis was scarce during ultraslow infusions in both groups. UES and esophageal body pressure responses to low-volume ultraslow reflux and associated post-reflux residue are reduced in elderly individuals. This deterioration could have negative effects on airway protection for people in this age group.

Spatiotemporal organization of cilia drives multiscale mucus swirls in model human bronchial epithelium

Mucociliary clearance is a biomechanical mechanism of airway protection. It consists of the active transport along the bronchial tree of the mucus, a fluid propelled by the coordinated beating of a myriad of cilia on the epithelial surface of the respiratory tract. The physics of mucus transport is poorly understood because it involves complex phenomena such as long-range hydrodynamic interactions, active collective ciliary motion, and the complex rheology of mucus. We propose a quantitative physical analysis of the ciliary activity and mucus transport on a large panel of human bronchial cultures from control subjects, patients with asthma and chronic obstructive pulmonary disease obtained from endobronchial biopsies. Here we report on the existence of multiple ciliary domains with sizes ranging from the tens of a micron to the centimeter, where ciliary beats present a circular orientational order. These domains are associated with circular mucus flow patterns, whose size scales with the average cilia density. In these domains, we find that the radial increase of the ciliated cell density coupled with the increase in the orientational order of ciliary beats result in a net local force proportional to the mucus velocity. We propose a phenomenological physical model that supports our results.

Videofluoroscopic assessment of the pathophysiology of chronic poststroke oropharyngeal dysphagia.

Oropharyngeal dysphagia (OD) is a major complaint following stroke, associated with poor clinical outcome and high mortality rates. We aimed at characterizing the kinematics of swallow response associated with unsafe swallowing in chronic poststroke patients with OD. Consecutive poststroke patients with a positive volume-viscosity swallow test for OD 3months following stroke were studied by videofluoroscopy (VFS). Demographical and clinical factors and kinematics of swallow response were compared between those poststroke patients with safe swallow (penetration-aspiration scale, PAS≤2) and those with unsafe swallow (PAS≥3). Receiver operating characteristic (ROC) curves were drawn for laryngeal vestibule closure (LVC) time which predicts unsafe swallow. We studied 73 poststroke patients (76.7±9.3years, 53.4% male) by VFS (60.4% with impaired safety, PAS=4.47±1.44, and 95.9% with impaired efficacy of swallow). Poststroke patients with unsafe swallow presented a poorer functional (Rankin 2.2±1.6 vs 1.2±1.0, P<.012) and nutritional status (MNA-sf≤11, 34.2% vs 7.4%, P<.05) than poststroke patients with safe swallow. Poststroke patients with unsafe swallow presented a significant delay in LVC time (406.4±99.5ms vs 318.9±80.4ms; P<.05) and weaker tongue bolus propulsion forces (0.771±0.450mJ vs 1.638±3.212mJ; P=.043). LVC time ≥340ms predicts unsafe swallow in chronic poststroke patients with a diagnostic accuracy of 0.78. Impaired safety of swallow in chronic poststroke patients is caused by specific impairments in swallow response including delayed timing of airway protection mechanisms and weak tongue propulsion forces. Treatments aiming to restore swallowing function in poststroke patients with OD should be targeted to improve these critical biomechanical events.

Translational Aspects of the Human Respiratory Virome.

Despite the dominant role of community-acquired respiratory viruses as etiological agents of disease, there has been little focus to date on the translation of rapidly developing diagnostic modalities, such as next-generation sequencing techniques in the examination of lower respiratory tract samples. When applied, these techniques should inform strategies to both understand the nexus between health and disease states of the respiratory virome, and drive a paradigm shift in how the practicing pulmonologist views the conceptual framework of respiratory infections. The lower respiratory tract was once thought to be a sanctuary site from microbiological colonization owing to the efficacy of upper airway-protective mechanisms and the host mucosal barrier function of the lower airways, combined with both innate and adaptive immune responses. As a small number of recent studies confirm, this is a naive vision of the lung, the viral component of which parallels recent revelations from respiratory microbiome studies. Hence, it is now timely to revise our thinking regarding the constituents, diversity, and changing nature of the respiratory virome in health and disease. One area worthy of focus is the interface between community-acquired respiratory viruses and the respiratory virome to better understand the dynamics in acute infection, as well as the factors that may lead to viral persistence and chronic disease. Given recent advances in metagenomics, the tools are now at hand to accomplish these goals.

Swallowing Disorders in Severe Brain Injury in the Arousal Phase.

The objective of this study was to determine the clinical characteristics of swallowing disorders in severe brain injury in the arousal phase after coma. Between December 1, 2013 and June 30, 2014, eleven patients with severe acquired brain injury who were admitted to rehabilitation center (Male 81.8%; 40.7±14.6years) were included in the study. Evaluation of swallowing included a functional examination, clinical functional swallowing test, and naso-endoscopic swallowing test. All patients had swallowing disorders at admission. The first functional swallowing test showed oral (77.8%) and pharyngeal (66.7%) food bolus transport disorders; and alterations in airway protection mechanisms (80%). Swallowing test under endoscopic control showed a disorder in swallowing coordination in 55.6% of patients tested. Seven (63.6%) patients resumed oral feeding within an average of 6weeks after admission to rehabilitation center and 14weeks after acquired brain injury. Six (85.7%) of these seven patients continued to require modified solid and liquid textures. Swallowing disorders are a major concern in severe brain injury in the arousal phase. Early bedside assessment of swallowing is essential for detection of swallowing disorders to propose appropriate medical rehabilitation care to these patients in a state of altered consciousness.