Nematode ascarosides attenuate mammalian type 2 inflammatory responses.

Mounting evidence suggests that nematode infection can protect against disorders of immune dysregulation. Administration of live parasites or their excretory/secretory (ES) products has shown therapeutic effects across a wide range of animal models for immune disorders, including asthma. Human clinical trials of live parasite ingestion for the treatment of immune disorders have produced promising results, yet concerns persist regarding the ingestion of pathogenic organisms and the immunogenicity of protein components. Despite extensive efforts to define the active components of ES products, no small molecules with immune regulatory activity have been identified from nematodes. Here we show that an evolutionarily conserved family of nematode pheromones called ascarosides strongly modulates the pulmonary immune response and reduces asthma severity in mice. Screening the inhibitory effects of ascarosides produced by animal-parasitic nematodes on the development of asthma in an ovalbumin (OVA) murine model, we found that administration of nanogram quantities of ascr#7 prevented the development of lung eosinophilia, goblet cell metaplasia, and airway hyperreactivity. Ascr#7 suppressed the production of IL-33 from lung epithelial cells and reduced the number of memory-type pathogenic Th2 cells and ILC2s in the lung, both key drivers of the pathology of asthma. Our findings suggest that the mammalian immune system recognizes ascarosides as an evolutionarily conserved molecular signature of parasitic nematodes. The identification of a nematode-produced small molecule underlying the well-documented immunomodulatory effects of ES products may enable the development of treatment strategies for allergic diseases.

Expiratory central airway collapse during positive pressure ventilation: a case report.

BACKGROUND: Physiologic narrowing of the central airway occurs during expiration. Conditions in which this narrowing becomes excessive are referred to as expiratory central airway collapse. Expiratory central airway collapse is usually managed by applying positive pressure to the airways, which acts as a pneumatic stent. The particularity of the case reported here included the patient's left main bronchus being permeable during spontaneous breathing but collapsing during general anaesthesia, despite positive pressure ventilation and positive end-expiratory pressure. CASE PRESENTATION: We present the case of a 55-year-old man admitted for the placement of a ureteral JJ stent. Rapid desaturation occurred a few minutes after the onset of anaesthesia. After excluding the most common causes of desaturation, fibreoptic bronchoscopy was performed through the tracheal tube and revealed complete collapse of the left main bronchus. The collapse persisted despite the application of positive end-expiratory pressure and several recruitment manoeuvres. After recovery of spontaneous ventilation, the collapse was lifted, and saturation increased back to normal levels. No evidence of extrinsic compression was found on chest X-rays or computed tomography scans. CONCLUSION: Cases of unknown expiratory central airway collapse reported in the literature were usually managed with positive pressure ventilation. This approach has been unsuccessful in the case described herein. Our hypothesis is that mechanical bending of the left main bronchus occurred due to loss of the patient's natural position and thoracic muscle tone under general anaesthesia with neuromuscular blockade. When possible, spontaneous ventilation should be maintained in patients with known or suspected ECAC.

Comparison of three kinds of self-expandable metallic stents induced granulation tissue hyperplasia in the rabbit trachea.

To compare stent-induced granulation tissue hyperplasia of bare (SEMS), polyurethane-covered (PU-SEMS) and electrospun nanofibre-covered (EN-SEMS) self-expandable metallic stents in the rabbit trachea. Twenty-seven rabbits were randomly assigned to 3 groups that received SEMS, PU-SEMS or EN-SEMS. Computed tomography and sacrifice were performed as scheduled. Haematoxylin-eosin and Masson's trichrome staining protocols were performed for pathological analysis. The data for tracheal ventilation area ratio, qualitative histological scoring, number of epithelial layers, and thicknesses of papillary projection and submucosa were documented and statistically analysed. All stents were successfully placed under the guidance of fluoroscopy without complications. Post-stenting 3 and 7 days, computed tomography revealed that the fully expandable EN-SEMS was similar to the SEMS and PU-SEMS. The mean stented tissue score in the SEMS group was higher than those of both the PU-SEMS and EN-SEMS groups at 3 days post-stenting. The pathological findings suggested that there was no papillary projection formation 3 days after stent placement. The thickness of papillary projection in the SEMS group was significantly higher than those of the PU-SEMS and EN-SEMS groups at 7 days post-stenting. After stenting 4 weeks, the tracheal ventilation area ratio of SEMS, PU-SEMS and EN-SEMS was 0.214 ± 0.021, 0.453 ± 0.028 and 0.619 ± 0.033, respectively. There were significant between-group differences. In conclusion, the stent-induced granulation tissue formation in EN-SEMS is less severe than that of PU-SEMS and SEMS. EN-SEMS has smaller radial force, and the tracheal ventilation ratio after stent placement better than that of PU-SEMS.

The Ring-and-Sling complex - Does it "Ring" true?

BACKGROUND: The "Ring-and-Sling" complex (RSC) comprises congenital tracheal stenosis and an abnormal origin/course of the left pulmonary artery. Based on clinical and imaging studies, the luminal narrowing is assumed to be as a result of rings cartilage (forming an "O"). AIMS: This is a postmortem based study of tracheal histology in infants after an autopsy encounter of a case of RSC. SUBJECT AND METHODS: RSC was identified in an infant at autopsy. The tracheal histomorphology revealed the presence of cartilaginous plates (instead of rings) and fibro-elastotic proliferation at the site of trachealis muscle. These changes prompted a study on variations in the histology of the trachea (with no known anomaly) in 35 autopsied neonates and infants. The transverse sections of the trachea were taken at one or more levels (Level 1 - at the level of the thyroid, Level 2 - midway between the thyroid and the carina, and Level 3 - just above the carina. STATISTICAL ANALYSIS: Epi-info software (v1.4.3, CD, US). RESULTS: On histology, 83 sections showed the trachealis muscle on the posterior aspect. A single semicircular cartilage was identified in only 17 of the 83 sections studied (20.5%, 6 in level 1, 9 in level 2 and 2 in level 3). In the remaining 66 sections (79.5%), the cartilage was disposed as multiple plates, ranging in number from 2 to 10. No significant association was found between semicircular cartilage rings and age, sex, gestational age, and level of section (P < 0.05). However, 14 cases with sectioning at all three levels were taken into account; all levels showed more cartilaginous plates compared to single rings, which were more common at level 1 (P > 0.05). CONCLUSIONS: The "ring" in RSC and normal infantile tracheas show cartilage plates with intermittent semicircular cartilage rings. These findings may have surgical implications for tracheal anomalies and bode favorable surgical outcomes.

Oral Positive Expiratory Pressure Device for Excessive Dynamic Airway Collapse Caused by Emphysema.

Excessive dynamic airway collapse (EDAC) contributes to breathlessness and reduced quality of life in individuals with emphysema. We tested a novel, portable, oral positive expiratory pressure (o-PEP) device in a patient with emphysema and EDAC. MRI revealed expiratory tracheal narrowing to 80 mm2 that increased to 170 mm2 with the o-PEP device. After 2-weeks use of the o-PEP device for 33% to 66% of activities, breathlessness, quality of life, and exertional dyspnea improved compared with minimal clinically important differences (MCID): University of California-San Diego Shortness of Breath questionnaire score declined 69 to 42 (MCID, ≥5), St. George's Respiratory Questionnaire score decreased 71 to 27 (MCID, ≥4), and before and after the 6-minute walk test Borg score difference improved from Δ3 to Δ2 (MCID, ≥1). During the 6-minute walk test on room air without the use of the o-PEP device, oxyhemoglobin saturation declined 91% to 83%; whereas, with the o-PEP device, the nadir was 90%. Use of the o-PEP device reduced expiratory central airway collapse and improved dyspnea, quality of life, and exertional desaturation in a patient with EDAC and emphysema.

Association of Functional Outcomes in Tracheoesophageal Voicing With Intratracheal Pressures and Esophagram Findings.

Importance: Tracheoesophageal voice prosthesis (TEP) is a commonly used device for alaryngeal voicing following total laryngectomy. Variability in TEP voice and speech production may be reflected in differences in intratracheal pressures. Objective: To examine the association between intratracheal manometric pressure (IMP), speech function, and proximal esophageal abnormalities in patients with TEP. Design, Setting, and Participants: This retrospective cohort study was conducted at a single academic institution and included all patients with a history of total laryngectomy and TEP who completed a radiographic esophagram and intratracheal manometry between September 9, 2019, and December 4, 2019. Main Outcomes and Measures: Intratracheal manometric pressures during sustained phonation, conversational speech, and maximum loudness tasks were obtained for 22 patients. Pressure metrics, phonation duration time, and fluency of speech production were compared between patients with dysphagia with those without swallowing complaints. The association between pressure and speech metrics was also assessed. Results: Of 22 patients, 17 (77.2%) were men, 5 (22.7%) were women, and the mean (SD) age was 66.6 (8.8) years. The mean (SD) sustained phonation duration time was 9.3 (5.2) seconds, and the mean (SD) IMP during sustained phonation was 50.5 (21.4) cm H20. The IMPs during sustained phonation were strongly correlated with conversational speech (r = 0.712; 95% CI, 0.384-1.039) and moderately correlated with maximum loudness tasks (r = 0.524; 95% CI, 0.127-0.921). The IMPs during conversational speech were moderately correlated with maximum loudness task (r = 0.538; 95% CI, 0.145-0.931). Increased IMP during sustained phonation was moderately correlated with decreased sustained phonation duration time (r = -0.450; 95% CI, -0.867 to -0.034) and conversational speech was moderately correlated with decreased sustained phonation duration time (r = -0.524; 95% CI, -0.921 to -0.127). Patients with subjective swallowing complaints and proximal esophagus abnormalities had a shorter maximum phonation time (mean [SD], 7.08 [5.03] seconds) compared with patients without subjective dysphagic complaints (mean [SD], 11.95 [4.40] seconds), with a large effect size (Cohen d = 1.031; 95% CI, 0.141-1.92). All patients with nonfluent TEP speech production had structural abnormalities of the proximal esophagus. No difference in pressure or speech metrics was observed for primary closure vs reconstructive flap type. Conclusions and Relevance: This cohort study found that increased IMP and abnormalities of the proximal esophagus were associated with worse TEP speech quality. Evaluation of the esophagus should be considered in patients who are experiencing difficulties with TEP voicing. Further investigation of intratracheal manometry as a biofeedback tool to improve TEP voicing is needed.

Lipoxin A4 inhibits ovalbumin-induced airway inflammation and airway remodeling in a mouse model of asthma.

Asthma is a chronic respiratory disease, which is characterized by airway inflammation, remodeling and airway hyperresponsiveness. Airway remodeling is caused by long-term inflammation of the airways. Lipoxin A4 (LXA4) is a natural eicosanoid with powerful anti-inflammatory properties, and has been shown to serve a critical role in orchestrating pulmonary inflammation and airway hyper-responsiveness in asthmatic mice. However, its effect on airway remodeling is unknown. Female BALB/c mice were used to establish a mouse model of asthma which were sensitized and challenged by ovalbumin (OVA). LXA4 was intranasally administrated prior to the challenge. The results of our study indicated that LXA4 suppressed the OVA-induced inflammatory cell infiltration and T helper type 2 (Th2) cytokines secretion in the mouse model of asthma. Characteristics of airway remodeling, such as thickening of the bronchial wall and smooth muscle, overdeposition of collagen, and overexpression of α-smooth muscle actin (α-SMA) and collagen-I were reversed by LXA4. Furthermore, LXA4 suppressed the aberrant activation of the signal transducer and activator of transcription 3 (STAT3) pathway in the lung tissues of asthmatic mice. In conclusion, these findings demonstrated that LXA4 alleviated allergic airway inflammation and remodeling in asthmatic mice, which may be related to the inhibition of STAT3 pathway.

Effect of swirling flow and particle-release pattern on drug delivery to human tracheobronchial airways.

The present study aims to investigate the effect of swirling flow on particle deposition in a realistic human airway. A computational fluid dynamic (CFD) model was utilized for the simulation of oral inhalation and particle transport patterns, considering the k-ω turbulence model. Lagrangian particle tracking was used to track the particles' trajectories. A normal breathing condition (30 L/min) was applied, and two-micron particles were injected into the mouth, considering swirling flow to the oral inhalation airflow. Different cases were considered for releasing the particles, which evaluated the impacts of various parameters on the deposition efficiency (DE), including the swirl intensity, injection location and pattern of the particle. The work's novelty is applying several injection locations and diameters simultaneously. The results show that the swirling flow enhances the particle deposition efficiency (20-40%) versus no-swirl flow, especially in the mouth. However, releasing particles inside the mouth, or injecting them randomly with a smaller injection diameter (dinj) reduced DE in swirling flow condition, about 50 to 80%. Injecting particles inside the mouth can decrease DE by about 20%, and releasing particles with smaller dinj leads to 50% less DE in swirling flow. In conclusion, it is indicated that the airflow condition is an important parameter for a reliable drug delivery, and it is more beneficial to keep the inflow uniform and avoid swirling flow.

Machine learning model for predicting the optimal depth of tracheal tube insertion in pediatric patients: A retrospective cohort study.

OBJECTIVE: To construct a prediction model for optimal tracheal tube depth in pediatric patients using machine learning. METHODS: Pediatric patients aged <7 years who received post-operative ventilation after undergoing surgery between January 2015 and December 2018 were investigated in this retrospective study. The optimal location of the tracheal tube was defined as the median of the distance between the upper margin of the first thoracic(T1) vertebral body and the lower margin of the third thoracic(T3) vertebral body. We applied four machine learning models: random forest, elastic net, support vector machine, and artificial neural network and compared their prediction accuracy to three formula-based methods, which were based on age, height, and tracheal tube internal diameter(ID). RESULTS: For each method, the percentage with optimal tracheal tube depth predictions in the test set was calculated as follows: 79.0 (95% confidence interval [CI], 73.5 to 83.6) for random forest, 77.4 (95% CI, 71.8 to 82.2; P = 0.719) for elastic net, 77.0 (95% CI, 71.4 to 81.8; P = 0.486) for support vector machine, 76.6 (95% CI, 71.0 to 81.5; P = 1.0) for artificial neural network, 66.9 (95% CI, 60.9 to 72.5; P < 0.001) for the age-based formula, 58.5 (95% CI, 52.3 to 64.4; P< 0.001) for the tube ID-based formula, and 44.4 (95% CI, 38.3 to 50.6; P < 0.001) for the height-based formula. CONCLUSIONS: In this study, the machine learning models predicted the optimal tracheal tube tip location for pediatric patients more accurately than the formula-based methods. Machine learning models using biometric variables may help clinicians make decisions regarding optimal tracheal tube depth in pediatric patients.

Computational Fluid Dynamic Modeling Reveals Nonlinear Airway Stress during Trachea Development.

Normative trachea dimensions and aerodynamic information during development was collected to establish clinical benchmarks and showed that airway development seems to outpace respiratory demands. Infants and toddlers' trachea exhibit higher aerodynamic stress that significantly decreases by teenage years. This implies large airway pathology in younger children may have a more substantial clinical impact.

Distinct modulation of tracheal and laryngopharyngeal cough via superior laryngeal nerve in cat.

Unilateral and bilateral cooling and bilateral transsection of the superior laryngeal nerve (SLN) were employed to modulate mechanically induced tracheobronchial (TB) and laryngopharyngeal (LPh) cough in 12 anesthetized cats. There was little effect of SLN block or cut on TB. Bilateral SLN cooling reduced the number of LPh (<50 %, p < 0.05), amplitudes of diaphragm EMG activity (<55 %, p < 0.05), and cough expiratory efforts (<40 %, p < 0.01) during LPh. Effects after unilateral SLN cooling were less pronounced. Temporal analysis of LPh showed only shortening of diaphragm and abdominal muscles burst overlap in the inspiratory-expiratory transition after unilateral SLN cooling. Bilateral cooling reduced both expiratory phase and total cough cycle duration. There was no significant difference in the average effects of cooling left or right SLN on LPh or TB as well as no differences in contralateral and ipsilateral diaphragm and abdominal EMG amplitudes. Our results show that reduced afferent drive in the SLN markedly attenuates LPh with virtually no effect on TB.

Assessment of Extensive Airway Obstruction Using Point-by-Point Lateral Pressure Measurements during Bronchoscopy.

BACKGROUND: The positioning of the stent at the flow-limiting segment is crucial for patients with extensive airway obstruction to relieve dyspnea. However, CT and flow-volume curves cannot detect the area of maximal obstruction. OBJECTIVES: The aim of this study is to physiologically evaluate extensive airway obstruction during interventional bronchoscopy. METHODS: We prospectively measured point-by-point lateral airway pressure (Plat) at multiple points from the lower lobe bronchus to the upper trachea using a double-lumen catheter in 5 patients. The site of maximal obstruction was evaluated continuously to measure point-by-point Plat at multiple points when the airway catheter was withdrawn from the lower lobe bronchus to the upper trachea. RESULTS: Remarkable pressure differences occurred at the site of maximal obstruction assessed by point-by-point Plat measurements. After initial stenting in 1 case, migration of the maximal obstruction to a nonstented segment of the weakened airway was seen with extensive stenosis from the trachea to the bronchi. In the second case, in addition to radiological analysis, point-by-point Plat measurements could identify the location of the maximal obstruction which contributed to dyspnea. CONCLUSIONS: Point-by-point Plat measurement could be used to detect the site of maximal obstruction physiologically. Furthermore, Plat measurement could assess the need for additional procedures in real time in patients with extensive airway obstruction.

Common pathogenesis for sirenomelia, OEIS complex, limb-body wall defect, and other malformations of caudal structures.

Decades of clinical, pathological, and epidemiological study and the recent application of advanced microarray and gene sequencing technologies have led to an understanding of the causes and pathogenesis of most recognized patterns of malformation. Still, there remain a number of patterns of malformation whose pathogenesis has not been established. Six such patterns of malformation are sirenomelia, VACTERL association, OEIS complex, limb-body wall defect (LBWD), urorectal septum malformation (URSM) sequence, and MURCS association, all of which predominantly affect caudal structures. On the basis of the overlap of the component malformations, the co-occurrence in individual fetuses, and the findings on fetal examination, a common pathogenesis is proposed for these patterns of malformation. The presence of a single artery in the umbilical cord provides a visible clue to the pathogenesis of all cases of sirenomelia and 30%-50% of cases of VACTERL association, OEIS complex, URSM sequence, and LBWD. The single artery is formed by a coalescence of arteries that supply the yolk sac, arises from the descending aorta high in the abdominal cavity, and redirects blood flow from the developing caudal structures of the embryo to the placenta. This phenomenon during embryogenesis is termed vitelline vascular steal.

Intratracheal parathyroid gland: an unexpected diagnosis.

Ectopic or supernumerary parathyroid tissue has been generally described in the literature in cases found during workup for parathyroid adenoma. We present two unique cases of intratracheal parathyroid gland, a rare occurrence that has not yet been described in the literature. In both cases, the masses were found incidentally and showed no clinical or laboratory evidence of hyperparathyroidism. In both cases, surveillance was chosen as the method of treatment. We present this case series to increase awareness of this potential diagnosis.

Effects of upper airway obstruction or hypoxia on gastroesophageal reflux in newborn lambs.

BACKGROUND: Although it is commonly accepted that upper airway obstruction (UAO) increases gastroesophageal reflux (GER), the link is poorly understood and insufficiently documented. In addition, while hypoxia is often encountered in infants with UAO, its consequences on GER are virtually unknown. The two aims of the present study were to characterize the effects of (1) UAO and (2) hypoxia on GER. METHODS: Seventeen lambs underwent polysomnographic and esophageal impedance/pH-metry monitoring during UAO vs. a control condition (6 h, ten lambs) or 10% hypoxia vs. normoxic condition (3 h, seven other lambs). RESULTS: Moderate-to-severe UAO was maintained throughout monitoring (inspiratory tracheal pressure of -13 (-15, -12) cm H2O vs. -1 (-1, -1) cm H2O in control condition, p = 0.005). While the number of GERs increased with UAO (2 (1, 4) vs. 0 (0, 3) in the control condition, p = 0.03), the increase was less than anticipated and inconsistent among the lambs. Also, sustained 10% hypoxia did not alter the number of GERs (2 (1, 3) vs. 0 (0, 5) in the control condition, p = 0.9). CONCLUSIONS: The presence of an UAO for 6 h mildly increased the number of GERs, whereas hypoxia for 3 h had no significant effect. IMPACT: The effect of upper airway obstruction and hypoxia on gastroesophageal reflux is poorly documented in the neonatal period. A moderate-to-severe upper airway obstruction for 6 h results in a mild, inconsistent increase in the number of gastroesophageal refluxes. Overall, a hypoxia of 10% for 3 h had no significant impact on gastroesophageal reflux. The prescription of an antireflux medication in infants with upper airway obstruction must not be systematic but rely on objective signs of a pathologic gastroesophageal reflux.

The anti-asthmatic potential of flavonol kaempferol in an experimental model of allergic airway inflammation.

Flavonol kaempferol possesses a broad spectrum of potent pharmacological activities that seem to be effective in the modulation of allergic respiratory diseases. In our study, an experimental animal model of ovalbumin (OVA)-induced allergic airway inflammation in guinea pigs was used to determine the anti-asthmatic potential of kaempferol. The parameters of specific airway resistance (sRaw) and cough reflex response were evaluated in vivo. In vitro, an assessment of tracheal smooth muscle (TSM) contractility and analyses of inflammatory cytokines (IL-4, IL-5, IL-13, GM-CSF, IFN-γ), transforming growth factor (TGF-ß1), immune cells count and ciliary beating frequency (CBF) were performed. Both single (6, 20 mg/kg b. w. p. o.) and long-term administered doses of kaempferol (20 mg/kg b. w. p. o., 21 days) suppressed sRaw provoked by histamine in conscious animals. The administration of kaempferol for 21 days attenuated histamine-induced TSM contractility in vitro and ameliorated the progression of chronic airway inflammation by decreasing the levels of IL-5, IL-13, GM-CSF, eosinophil count in bronchoalveolar lavage (BAL) fluid and TGF-ß1 protein level in lung tissue. Kaempferol also eliminated the alterations in cough reflex sensitivity invoked by OVA-sensitization, but it did not affect CBF. The results demonstrate that flavonol kaempferol can modulate allergic airway inflammation and associated asthma features (AHR, aberrant stimulation of cough reflex).

CPAP protects against hyperoxia-induced increase in airway reactivity in neonatal mice.

BACKGROUND: Oxygen and continuous positive airway pressure (CPAP) are primary modes of respiratory support for preterm infants. Animal models, however, have demonstrated adverse unintended effects of hyperoxia and CPAP on lung development. We investigate the effects of combined neonatal hyperoxia and CPAP exposure on airway function and morphology in mice. METHODS: Newborn mice were exposed to hyperoxia (40% O2) 24 h/day for 7 consecutive days with or without daily (3 h/day) concomitant CPAP. Two weeks after CPAP and/or hyperoxia treatment ended, lungs were assessed for airway (AW) hyperreactivity and morphology. RESULTS: CPAP and hyperoxia exposure alone increased airway reactivity compared to untreated control mice. CPAP-induced airway hyperreactivity was associated with epithelial and smooth muscle proliferation. In contrast, combined CPAP and hyperoxia treatment no longer resulted in increased airway reactivity, which was associated with normalization of smooth muscle and epithelial proliferation to values similar to untreated mice. CONCLUSIONS: Our data suggest that the combination of CPAP and hyperoxia decreases the adverse consequences on airway remodeling of either intervention alone. The complex interaction between mechanical stretch (via CPAP) and hyperoxia exposure on development of immature airways has implications for the pathophysiology of airway disease in former preterm infants receiving non-invasive respiratory support. IMPACT: CPAP and mild hyperoxia exposure alone increase airway reactivity in the neonatal mouse model. In contrast, combined CPAP and hyperoxia no longer induce airway hyperreactivity. Combined CPAP and hyperoxia normalize smooth muscle and epithelial proliferation to control values. Interaction between CPAP-induced stretch and mild hyperoxia exposure on immature airways has important implications for airway pathophysiology in former preterm infants.

Home Sleep Testing to Direct Upper Airway Stimulation Therapy Optimization for Sleep Apnea.

OBJECTIVES/HYPOTHESIS: Selective upper airway stimulation (sUAS) is a well-established treatment option for obstructive sleep apnea (OSA). This study aimed to determine if there are benefits in performing a home sleep test (HST) to evaluate postoperative sUAS effectiveness after patient acclimatization compared to the generally used polysomnography (PSG) titration, as measured by long-term follow-up outcomes. STUDY DESIGN: Retrospective comparative cohort analysis. METHODS: We conducted an analysis of consecutive patients at our center who had completed a 6-month follow-up (month 6 [M6]) and recorded data from M6, month 12 (M12), and month 24 (M24). After device activation, we performed an HST with the patient's stimulation settings, and measured the apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), and device usage. These values were compared to patients who had undergone PSG-based device titration. RESULTS: Baseline values of the initial 131 patients show high ESS and moderate OSA. At the 2-month time point of the HST, nearly half of the patients (46.2%) reached an AHI ≤15/hr, and approximately a fifth (19.2%) reached <5/hr. The PSG and HST groups differed in median ESS at M24, but no other differences were observed for ESS at M6 and M12. Both groups showed similar AHI, oxygen desaturation, and usage hours per week. CONCLUSIONS: Adjusting therapy by using the HST technique after device activation and acclimatization has clinical and economic advantages. These advantages are contingent on several conditions being met when deviating from the standard device protocol, including precise communication with the referring sleep medicine physicians, especially their role in helping with long-term follow-up. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1375-E1379, 2021.

The preventive and therapeutic effects of AAV1-KLF4-shRNA in cigarette smoke-induced pulmonary hypertension.

We found previously that KLF4 expression was up-regulated in cultured rat and human pulmonary artery smooth muscle cells (PASMCs) exposed to cigarette smoke (CS) extract and in pulmonary artery from rats with pulmonary hypertension induced by CS. Here, we aim to investigate whether CS-induced pulmonary hypertension (PH) is prevented and ameliorated by targeted pulmonary vascular gene knockdown of KLF4 via adeno-associated virus 1 (AAV1)-KLF4-shRNA in vivo in rat model. The preventive and therapeutic effects were observed according to the different time-point of AAV1-KLF4-shRNA intratracheal administration. We tested haemodynamic measurements of systemic and pulmonary circulations and observed the degree of pulmonary vascular remodelling. In the preventive experiment, KLF4 expression and some pulmonary circulation hemodynamic measurements such as right ventricular systolic pressure (RVSP), mean right ventricular pressure (mRVP), peak RV pressure rate of rise (dP/dt max) and right ventricle (RV) contractility index were increased significantly in the CS-induced PH model. While in the prevention group (AAV1-KLF4-shRNA group), RVSP, mRVP, dP/dt max and RV contractility index which are associated with systolic function of right ventricle decreased and the degree of pulmonary vascular remodelling relieved. In the therapeutic experiment, we observed a similar trend. Our findings emphasize the feasibility of sustained pulmonary vascular KLF4 gene knockdown using intratracheal delivery of AAV1 in an animal model of cigarette smoke-induced PH and determined gene transfer of KLF4-shRNA could prevent and ameliorate the progression of PH.

Evaluation of regenerated tracheal cilia function on a collagen-conjugated scaffold in a canine model.

OBJECTIVES: It is unclear whether the movement and function of the regenerated cilia on collagen-conjugated artificial trachea are the same as those of normal cilia. This study assessed the ciliary beat frequency (CBF) and ciliary transport functions (CTFs) of regenerated cilia in a canine model. METHODS: A tracheal defect introduced into the anterior portion of the cervical trachea of an adult beagle dog was covered with a collagen-conjugated prosthesis. Two months later, the trachea was harvested along the long axis, both from normal and regenerated regions. The cilia were stained with isothiocyanate-conjugated wheat germ agglutinin, and their movement was monitored with a high-speed camera to analyse CBF and CTF. Four samples each were obtained from the regenerated and normal regions for CBF analysis and 7 samples each were obtained for CTF analysis. RESULTS: The wheat germ agglutinin-stained cells showed well-regulated beats in both the regenerated and normal regions of the trachea. Mean CBF in the regenerated and normal regions did not differ significantly (7.11 ± 0.41 vs 7.14 ± 1.09 Hz; P = 981). By contrast, CTF was significantly lower in the regenerated region than in the normal region (30.0 ± 6.62 vs 7.43 ± 0.58 µm/s; P = 0.005). CONCLUSIONS: Mean CBF in the regenerated and normal regions did not differ significantly at 2 months. The CTF in the regenerated region recovered partially but remained lower than those in the normal region. Methods are needed to improve the CTF of regenerated cilia.