Quantification of the Swallowing Mechanism Through Muscle Synergy Analysis.

Decreased swallowing function increases the risk of choking and aspiration pneumonia. Videofluoroscopy and computed tomography allow for detailed observation of the swallowing movements but have radiation risks. Therefore, we developed a method using surface electromyography (sEMG) to noninvasively assess swallowing function without radiation exposure. A 44-channel flexible sEMG sensor was used to measure the sEMG signals of the hyoid muscles during swallowing in 14 healthy young adult and 14 elderly subjects. Muscle synergy analysis was performed to extract the muscle synergies from the sEMG signals, and the three synergies were extracted from the hyoid muscle activities during the swallowing experiments. The experimental results showed that the three synergies represent the oral, early pharyngeal, and late pharyngeal swallowing phases and that swallowing strength is tuned by the strength of the muscle activities, whereas swallowing volume is controlled by adjusting muscle activation timing. In addition, the timing of the swallowing reflex is slower in elderly individuals. The results confirm that the proposed approach successfully quantifies swallowing function from sEMG signals, mapping the signals to the swallowing phases.

Jaw-Opening Force as a Useful Index for Dysphagia: A Cross-Sectional and Multi-Institutional Study.

INTRODUCTION: Jaw-opening force (JOF) can be a potential screening tool for dysphagia. However, confounding variables such as comorbidities or physical and oral functions that are associated with the physiology of swallowing have not previously been examined. Adjusting for these variables could reveal the relationship between JOF and dysphagia and indicate whether JOF is an independent factor associated with dysphagia. We therefore aimed to assess the efficacy of using JOF for dysphagia screening in this multi-institutional study. METHODS: Community-dwelling older adults over the age of 65 years (N = 403) who visited the university dental hospitals and participated in health surveys (mean age ± standard deviation, 77.1 ± 7.0 years; range, 65-96 years) between November 2018 and January 2020 were included in this study. The JOFs of all participants were measured. The measured JOF was compared with the presence of dysphagia, which was defined using the Functional Oral Intake Scale and the Eating Assessment Tool-10. RESULTS: Multiple logistic regression analysis revealed that the presence of dysphagia was independently associated with JOF, calf circumference, and dependence after adjusting for age and sex. DISCUSSION/CONCLUSION: Decreased JOF can be a risk factor for dysphagia in older adults.

Fractionation of Regenerated Silk Fibroin and Characterization of the Fractions.

The molecular weight (MW) of regenerated silk fibroin (RSF) decreases during degumming and dissolving processes. Although MW and the MW distribution generally affect polymer material processability and properties, few reports have described studies examining the influences of MW and the distribution on silk fibroin (SF) material. To prepare different MW SF fractions, the appropriate conditions for fractionation of RSF by ammonium sulfate (AS) precipitation process were investigated. The MW and the distribution of each fraction were found using gel permeation chromatography (GPC) and SDS-polyacrylamide electrophoresis (SDS-PAGE). After films of the fractionated SFs formed, the secondary structure, surface properties, and cell proliferation of films were evaluated. Nanofiber nonwoven mats and 3D porous sponges were fabricated using the fractionated SF aqueous solution. Then, their structures and mechanical properties were analyzed. The results showed AS precipitation using a dialysis membrane at low temperature to be a suitable fractionation method for RSF. Moreover, MW affects the nanofiber and sponge morphology and mechanical properties, although no influence of MW was observed on the secondary structure or crystallinity of the fabricated materials.

Food intake and oral health status of inpatients with dysphagia in acute care settings.

Adequate oral status and functional assessments are important for dysphagia rehabilitation in acute care inpatient settings, especially to establish individualised oral intake. However, the association between food intake levels and oral function has not been elucidated in acute care inpatients. This cross-sectional study clarified the association between oral intake levels and the oral status/function of patients with dysphagia admitted to acute care settings. Admitted patients aged ≥40 years (n = 459; men: 288; mean age: 70.8 ± 12.0) examined at the Department of Dysphagia Rehabilitation at the Iwate Medical University Hospital from April 2007 to March 2014 were included. The oral health status was evaluated by the tongue coating, oral dryness severity, plaque control, posterior occlusal support and a repetitive saliva swallowing test (RSST). Dysphagia severity was determined from the Dysphagia Severity Scale. Oral intake levels were evaluated using the Functional Oral Intake Scale (FOIS) at the time of the initial dental examination (FOIS-I), and they were re-evaluated after the revision of levels according to the participants' general condition and oral health status (FOIS-R). Divergence between FOIS-I and FOIS-R was noted in >40% patients. Multiple regression analysis showed significant associations between FOIS-R and consciousness level, activities of daily living, tongue coating, RSST and posterior occlusal support. Patients with dysphagia in acute care settings require detailed assessments of their oral status and function, including swallowing, to determine the most suitable feeding methods and dental interventions to improve oral intake levels.

Click Decoration of Bombyx mori Silk Fibroin for Cell Adhesion Control.

Silk fibroin produced by the domesticated silkworm, Bombyx mori, has been studied widely as a substrate for tissue engineering applications because of its mechanical robustness and biocompatibility. However, it is often difficult to precisely tune silk fibroin's biological properties due to the lack of easy, reliable, and versatile methodologies for decorating it with functional molecules such as those of drugs, polymers, peptides, and enzymes necessary for specific applications. In this study we applied an azido-functionalized silk fibroin, AzidoSilk, produced by a state-of-the-art biotechnology, genetic code expansion, to produce silk fibroin decorated with cell-repellent polyethylene glycol (PEG) chains for controlling the cell adhesion property of silk fibroin film. Azido groups can act as selective handles for chemical reactions such as a strain-promoted azido-alkyne cycloaddition (SPAAC), known as a click chemistry reaction. We found that azido groups in AzidoSilk film were selectively decorated with PEG chains using SPAAC. The PEG-decorated film demonstrated decreased cell adhesion depending on the lengths of the PEG chains. Azido groups in AzidoSilk can be decomposed by UV irradiation. By partially decomposing azido groups in AzidoSilk film in a spatially controlled manner using photomasks, cells could be spatially arranged on the film. These results indicated that SPAAC could be an easy, reliable, and versatile methodology to produce silk fibroin substrates having adequate biological properties.

Higher Gene Expression Related to Wound Healing by Fibroblasts on Silk Fibroin Biomaterial than on Collagen.

Silk fibroin (SF), which offers the benefits of biosafety, biocompatibility, and mechanical strength, has potential for use as a good biomedical material, especially in the tissue engineering field. This study investigated the use of SF biomaterials as a wound dressing compared to commercially available collagen materials. After human fibroblasts (WI-38) were cultured on both films and sponges, their cell motilities and gene expressions related to wound repair and tissue reconstruction were evaluated. Compared to the collagen film (Col film), the SF film induced higher cell motility; higher expressions of genes were observed on the SF film. Extracellular matrix production-related genes were up-regulated in WI-38 fibroblasts cultured on the SF sponges. These results suggest that SF-based biomaterials can accelerate wound healing and tissue reconstruction. They can be useful biomaterials for functional wound dressings.

Porous Silk Fibroin/Cellulose Hydrogels for Bone Tissue Engineering via a Novel Combined Process Based on Sequential Regeneration and Porogen Leaching.

Scaffolds used for bone tissue engineering need to have a variety of features to accommodate bone cells. The scaffold should mimic natural bone, it should have appropriate mechanical strength, support cell differentiation to the osteogenic lineage, and offer adequate porosity to allow vascularization and bone in-growth. In this work, we aim at developing a new process to fabricate such materials by creating a porous composite material made of silk fibroin and cellulose as a suitable scaffold of bone tissue engineering. Silk fibroin and cellulose are both dissolved together in N,N-dimethylacetamide/LiCl and molded to a porous structure using NaCl powder. The hydrogels are prepared by a sequential regeneration process: cellulose is solidified by water vapor treatment, while the remaining silk fibroin in the hydrogel is insolubilized by methanol, which leads to a cellulose framework structure embedded in a silk fibroin matrix. Finally, the hydrogels are soaked in water to dissolve the NaCl for making a porous structure. The cellulose composition results in improving the mechanical properties for the hydrogels in comparison to the silk fibroin control material. The pore size and porosity are estimated at around 350 µm and 70%, respectively. The hydrogels support the differentiation of MC3T3 cells to osteoblasts and are expected to be a good scaffold for bone tissue engineering.

Supplementary cryoprotective effect of carboxylated ε-poly-l-lysine during vitrification of rat pancreatic islets.

This study was designed to investigate whether cryosurvival of rat pancreatic islets can be improved by carboxylated ε-poly-l-lysine (CPLL). Islets isolated from Wistar × Brown-Norway F1 rats (101-200 µm in diameter) were cryopreserved in three vitrification solutions containing ethylene glycol (EG; 30%, v/v) and CPLL (0%, 10%, or 20%, v/v) by Cryotop® protocol (10 islets per device). The post-warm survival rate of the islets vitrified in the presence of 20% CPLL (74%), assessed by FDA/PI double staining, was higher than those in 0% and 10% CPLL (65% and 66%, respectively). Decreased EG concentrations (10% and 20%) in the presence of 20% CPLL resulted in impaired post-warm islet survival rates (50% and 64%, respectively). Value of stimulus index (SI) for 20 mM/3 mM glucose-stimulated insulin secretion was 4.1 in islets vitrified-warmed in the presence of 30% EG and 20% CPLL, which was comparable with those in fresh control islets and vitrified islets in 30% EG alone (4.1 and 4.4, respectively). A large number of islets (50 islets per device) could be cryopreserved in the presence of 30% EG and 20% CPLL by using nylon mesh as the device, without considerable loss of post-warm survival (68%) and SI value (3.7). In conclusion, supplementation of antifreeze 20% CPLL was effective in improving the post-warm survival of isolated rat pancreatic islets when vitrification solution containing 30% EG was used.

Wearing complete dentures is associated with changes in the three-dimensional shape of the oropharynx in edentulous older people that affect swallowing.

OBJECTIVE: To investigate the effects of wearing complete dentures on pharyngeal shape for swallowing in edentulous older people. BACKGROUND: In the absence of complete dentures, edentulous older people often lose the occlusal support necessary to position the mandible, which leads to an anterosuperior shift of the mandible during swallowing. This may result in pharyngeal shape changes effecting swallowing function in older people. However, the details of this phenomenon are currently unclear. MATERIALS AND METHODS: Participants were 17 older edentulous volunteers. Cone-beam computed tomography imaging was performed with the participant in the seated position and wearing (i) both maxillary and mandibular dentures, (ii) maxillary dentures only and (iii) no dentures. During imaging, participants were instructed to keep their mouth closed to the mandibular position determined in advance during swallowing for each denture-wearing condition. The volume, height and average cross-sectional area of the velopharynx and oropharynx were measured, and the positions of the epiglottis and mandible were recorded. RESULTS: While the vertical height of the oral cavity and pharynx significantly decreased, the volume and average cross-sectional area of the oropharynx significantly increased when dentures were not worn (p < 0.01). The absence of dentures caused an anterosuperior shift of the mandible when swallowing and drew the epiglottis forward, resulting in expansion of the oropharynx where the tongue base forms the anterior wall. CONCLUSION: The absence of dentures results in anatomical changes in oropharyngeal shape that may exacerbate the pharyngeal expansion caused by ageing and reduce the swallowing reserve.

Immobilization of Arg-Gly-Asp peptides on silk fibroin via Gly-Ala-Gly-Ala-Gly-Ser sequences.

A simple method by which the functional peptide of Gly-Arg-Gly-Asp-Ser (GRGDS) is immobilized on the surface of silk fibroin (SF) films via Gly-Ala-Gly-Ala-Gly-Ser (GAGAGS) sequences is proposed. GAGAGS, a repeating amino acid sequence in the crystal region of Bombyx mori SF, performs a key role in interacting with and immobilizing SF molecules. Immobilization by this proposed method involves no chemical reaction, thereby preserving the original properties of the SF molecule. The density of GRGDS peptides existing on SF film was found to be higher in the GAGAGS-bound type than in the non-GAGAGS-bound type. Furthermore, results showed that the amount of immobilized (GAGAGS)GRGDS peptide increased as the ß-sheet crystallization was promoted in the SF film. Fibroblasts, which adhered to the surface of the SF film, showed more extensibility because of the (GAGAGS)GRGDS immobilization, which suggests that the cell adhesion activity of RGD is functioning effectively.

Electrospun composite nanofibers of deoxyribonucleic acid and polylactic acid for skincare applications.

The development of useful biomaterials has resulted in significant advances in various fields of science and technology. The demand for new biomaterial designs and manufacturing techniques continues to grow, with the goal of building a sustainable society. In this study, two types of DNA-cationic surfactant complexes were synthesized using commercially available deoxyribonucleic acid from herring sperm DNA (hsDNA, <50 bp) and deoxyribonucleic acid from salmon testes DNA (stDNA, ~2000 bp). The DNA-surfactant complexes were blended with a polylactic acid (PLA) biopolymer and electrospun to obtain nanofibers, and then copper nanoparticles were synthesized on nanofibrous webs. Scanning electron microscopic images showed that all nanofibers possessed uniform morphology. Interestingly, different diameters were observed depending on the base pairs in the DNA complex. Transmission electron microscopy showed uniform growth of copper nanoparticles on the nanofibers. Fourier-transform infrared spectroscopy spectra confirmed the uniform blending of both types of DNA complexes in PLA. Both stDNA- and hsDNA-derived nanofibers showed greater biocompatibility than native PLA nanofibers. Furthermore, they exerted significant antibacterial activity in the presence of copper nanoparticles. This study demonstrates that DNA is a potentially useful material to generate electrospun nanofibrous webs for use in biomedical sciences and technologies.

Generation of novel cationic antimicrobial peptides from natural non-antimicrobial sequences by acid-amide substitution.

BACKGROUND: Cationic antimicrobial peptides (CAMPs) are well recognized to be promising as novel antimicrobial and antitumor agents. To obtain novel skeletons of CAMPs, we propose a simple strategy using acid-amide substitution (i.e. Glu→Gln, Asp→Asn) to confer net positive charge to natural non-antimicrobial sequences that have structures distinct from known CAMPs. The potential of this strategy was verified by a trial study. METHODS: The pro-regions of nematode cecropin P1-P3 (P1P-P3P) were selected as parent sequences. P1P-P3P and their acid-amide-substituted mutants (NP1P-NP3P) were chemically synthesized. Bactericidal and membrane-disruptive activities of these peptides were evaluated. Conformational changes were estimated from far-ultraviolet circular dichroism (CD) spectra. RESULTS: NP1P-NP3P acquired potent bactericidal activities via membrane-disruption although P1P-P3P were not antimicrobial. Far-ultraviolet CD spectra of NP1P-NP3P were similar to those of their parent peptides P1P-P3P, suggesting that NP1P-NP3P acquire microbicidal activity without remarkable conformational changes. NP1P-NP3P killed bacteria in almost parallel fashion with their membrane-disruptive activities, suggesting that the mode of action of those peptides was membrane-disruption. Interestingly, membrane-disruptive activity of NP1P-NP3P were highly diversified against acidic liposomes, indicating that the acid-amide-substituted nematode cecropin pro-region was expected to be a unique and promising skeleton for novel synthetic CAMPs with diversified membrane-discriminative properties. CONCLUSIONS: The acid-amide substitution successfully generated some novel CAMPs in our trial study. These novel CAMPs were derived from natural non-antimicrobial sequences, and their sequences were completely distinct from any categories of known CAMPs, suggesting that such mutated natural sequences could be a promising source of novel skeletons of CAMPs.

Fabrication of Poly(Ethylene-glycol 1,4-Cyclohexane Dimethylene-Isosorbide-Terephthalate) Electrospun Nanofiber Mats for Potential Infiltration of Fibroblast Cells.

Recently, bio-based electrospun nanofiber mats (ENMs) have gained substantial attention for preparing polymer-based biomaterials intended for use in cell culture. Herein, we prepared poly(ethylene-glycol 1,4-Cyclohexane dimethylene-isosorbide-terephthalate) (PEICT) ENMs using the electrospinning technique. Cell adhesion and cell viability of PEICT ENMs were checked by fibroblast cell culture. Field emission electron microscope (FE-SEM) image showed a randomly interconnected fiber network, smooth morphology, and cell adhesion on PEICT ENM. Fibroblasts were cultured in an adopted cell culturing environment on the surface of PEICT ENMs to confirm their biocompatibility and cell viability. Additionally, the chemical structure of PEICT ENM was checked under Fourier-transform infrared (FTIR) spectroscopy and the results were supported by -ray photoelectron (XPS) spectroscopy. The water contact angle (WCA) test showed the hydrophobic behavior of PEICT ENMs in parallel to good fibroblast cell adhesion. Hence, the results confirmed that PEICT ENMs can be potentially utilized as a biomaterial.

All-in-One Silk Fibroin Sponge as the Vitrification Cryodevice of Rat Pancreatic Islets and the VEGF-Embedded Scaffold for Subrenal Transplantation.

Islet transplantation is a promising option for the clinical treatment of insulin-dependent diabetes, but a reliable islet cryopreservation/transplantation protocol should be established to overcome the donor shortage. The current study reports that a silk fibroin (SF) sponge disk can be used as a cryodevice for vitrification of large quantity pancreatic islets and the scaffold for subsequent subrenal transplantation in a rat model. The marginal islet mass (550 islet equivalents [IEQs]) on an SF sponge disk was vitrified-warmed and transplanted beneath the kidney capsule of a streptozotocin-induced diabetic rat with or without vascular endothelial growth factor (VEGF). Subrenal transplantation (no scaffold) of 550 IEQ fresh islets and post-warm islets vitrified on a nylon mesh device resulted in achieving euglycemia of recipient rats at 60% and 0%, respectively. Transplantation of 550 IEQ islets vitrified-warmed on an SF sponge disk failed to achieve euglycemia of recipient rats (0%), but the VEGF inclusion in the SF sponge disk contributed to acquiring the euglycemic recipients (33%). All cured recipient rats regained hyperglycemia after nephrectomy, and the histopathologic analysis exhibited a well-developing blood vessel network into the islet engrafts. Thus, an SF sponge disc was successively available as the cryodevice for islet vitrification, the transporter of the angiogenic VEGF, and the scaffold for subrenal transplantation in the rat model.

An enhancer peptide for membrane-disrupting antimicrobial peptides.

BACKGROUND: NP4P is a synthetic peptide derived from a natural, non-antimicrobial peptide fragment (pro-region of nematode cecropin P4) by substitution of all acidic amino acid residues with amides (i.e., Glu --> Gln, and Asp --> Asn). RESULTS: In the presence of NP4P, some membrane-disrupting antimicrobial peptides (ASABF-alpha, polymyxin B, and nisin) killed microbes at lower concentration (e.g., 10 times lower minimum bactericidal concentration for ASABF-alpha against Staphylococcus aureus), whereas NP4P itself was not bactericidal and did not interfere with bacterial growth at

Drawing-induced changes in morphology and mechanical properties of hornet silk gel films.

Complete amino acid sequences of the four major proteins (Vssilk 1-4) of silk (hornet silk) obtained from yellow hornet ( Vespa simillima , Vespinae, Vespidae) cocoons have been determined. The native structure of the hornet silk (HS), in which Vssilk 1-4 have an alpha-helix domain with coiled-coil alpha-helices and a beta-sheet domain, is restored when hornet silk gel films (HSGFs) are formed by pressing and drying HS hydrogel. Necking occurs when dry HSGFs are drawn; however, wet HSGFs can be uniaxially drawn with a draw ratio (DR) of 2. Drawing helps obtain high-performance films with a maximum tensile strength and tensile modulus of 170 MPa and 5.5 GPa, respectively. Drawing-induced changes in the orientation and conformation of the coiled-coil structure are investigated.

Silk fibroin sheet multilayer suitable for vitrification of in vitro-matured bovine oocytes.

Minimum volume cooling (MVC) procedure has been successfully applied to vitrify mammalian oocytes, but high skill of capillary pipetting is required to load the oocytes on a cryodevice with a minimal volume (<1 µL) of vitrification solution (VS). Here we report a novel cryodevice for bovine oocyte vitrification, silk fibroin (SF) sheet multilayer, of which spontaneous absorption property can eliminate pipette operation for removal of excess VS. Based on physical stability and scanning electron microscopic observation, the SF sheet prepared from 1.5% (wt/vol) fibroin solution was selected and layered around a polypropylene strip (0.1-mm thickness, 0.7-mm width, 10-mm depth). Ten denuded bovine mature oocytes were loaded onto the SF sheet multilayer with 2-3 µL of the VS, and then cooled rapidly by plunging into liquid nitrogen. Nylon mesh (NM) device with square opening 37-µm length of a side and commercially available Cryotop® (CT) device were used as controls, and the minimization of VS volume was performed by paper towel absorption and capillary aspiration, respectively. In SF, NM and CT groups, post-warming oocyte recovery rates were 99.5, 99.1 and 100%, and the morphological survival rates were 99.7, 94.5 and 99.0%, respectively. Subsequent IVF and 8-days IVC resulted in comparable blastocyst yields among the three groups (25.5, 25.0 and 26.1% in SF, NM and CT groups, respectively). These results suggest that SF sheet multilayer is a useful cryodevice for bovine matured oocytes in MVC vitrification because VS volume surrounding the oocytes can be easily minimized through its absorption property.

Transplantation of rat pancreatic islets vitrified-warmed on the nylon mesh device and the silk fibroin sponge disc.

We report the adaptability of rat islets vitrified-warmed on nylon mesh (NM) device or silk fibroin (SF) sponge disc for the normalization of the blood glucose level in rat models of diabetes. One-hundred rat islets were cryopreserved according to a minimum volume cooling protocol on an NM device or a solid surface vitrification protocol on an SF sponge disc. The recovery rate (97.1% vs. 93.8%), the viability (77.9% vs. 74.4%), and the stimulation index (4.7 vs. 4.2) in glucose-stimulated insulin secretion (GSIS) assay of the post-warm islets were comparable between the NM vitrification and the SF vitrification groups. The viability and the stimulation index of the fresh control islets were identified to be 97.5% and 6.5, respectively. Eight hundred islets from the NM or the SF vitrification group or the fresh control group were transplanted beneath the kidney capsule of a streptozotocin-induced diabetic rat (blood glucose level > 350 mg/dl). Within 3 weeks after transplantation, the acquisition of euglycemia (< 200 mg/dl) was observed in recipient rats (80.0-83.3%). An intraperitoneal glucose tolerance test on Day-30 and Day-60 showed similar 2-h responses to the glucose uptake of cured rats among the compared groups. Moreover, the successful engraftment of transplants was confirmed by the Day-70 nephrectomy through the subsequent diabetes reversal and histological evaluation. Thus, large quantities of rat islets vitrified-warmed on an NM device or an SF sponge disc were proven to be fully functional both in vitro and in vivo, due to the GSIS and syngeneic transplantation, respectively.

Manuka honey incorporated cellulose acetate nanofibrous mats: Fabrication and in vitro evaluation as a potential wound dressing.

Wound dressings are the primary barrier between the wound surface and the outer environment. Here we report the fabrication of cellulose acetate (CA)-Manuka honey (MH) composite nanofibrous mats as a biocompatible and antimicrobial wound dressing. CA mats with different quantities of MH were developed by electrospinning. The ATR-FTIR spectra confirm the inclusion of MH in the composite CA-MH nanofibrous mats. The fibers were continuous and bead-free with acceptable mechanical properties. The fiber diameter increased with an increase in MH content. Inclusion of MH in the electrospun composite CA-MH nanofibrous mats shows high efficacy to prevent bacterial growth on the wound surface. The MH loaded CA nanofiber mats showed good antioxidant abilities, while the ability to free radicalize the DPPH was dependent upon the factors of MH content in the fiber and the time of immersion in the DPPH solution. Besides, the nanofibrous mat's high porosity (85-90%) and WVTR values of 2600 to 1950 g/m2/day, suitable for wound breathability and the mats show high cytocompatibility to NIH 3T3 cell line in in vitro testing, proving to be effective for promoting wound healing.

Efficacy of nasal high flow therapy on the coordination between breathing and swallowing of saliva during daytime nap in chronic obstructive pulmonary disease patients: A single center, randomized crossover controlled study.

BACKGROUND: There are some clinical reports on dysphagia in patients with chronic obstructive pulmonary disease (COPD); however, its pathophysiology remains largely unknown.Changes in respiratory function occur in patients with COPD causing a decrease in tidal volume and an increase in respiratory rate (tachypnea). In addition, it leads to lack of coordination between respiration and swallowing.A new treatment called nasal high flow (NHF) has been introduced for patients with COPD, replacing the traditional non-invasive ventilation (NIV) procedure. The NHF therapy involves inhalation of high flow of humidified air, which reduces respiratory effort in patients with COPD. Furthermore, NHF therapy facilitates swallowing of saliva even during respiratory management. A recent clinical study reported that high-flow nasal cannula oxygen therapy for 6 weeks improved the health-related quality of life and reduced hypercapnia in patients with stable COPD. Taken together, NHF therapy is gaining attention in the clinical management of patients with COPD.Therefore, in this study, we aim to examine the efficacy of NHF therapy on the coordination between breathing and swallowing of saliva during daytime nap in patients with COPD. METHODS/DESIGN: This open-label, investigator-initiated, single center study will evaluate the efficacy of NHF therapy on the coordination between breathing and swallowing of saliva during the daytime nap in COPD patients with forced expiratory volume in 1 second (FEV1%) of <70% during treatment at the Nagasaki University Hospital Respiratory Rehabilitation Center. Evaluations will be performed during the 90 to 180 minute "daytime nap" in the measurement room of the hospital. The primary endpoint will be the rate of appearance of the expiratory phase after swallowing of saliva and the frequency of swallowing during the measurement period. DISCUSSION: The purpose of this study is to obtain evidence regarding the utility of NHF as a potential therapeutic device for COPD patients to prevent aspiration of saliva during the sleep stage of daytime nap. The utility will be assessed by comparing the decrease in incidence rates of the expiratory phase after swallowing of saliva in the NHF device group and the control group, wherein this device was not used.