Elevation of CD40/CD40L Inflammatory Pathway Molecules in Carotid Plaques from Moderate-and-Severe Obstructive Sleep Apnea Patients.

A chronic inflammatory process characteristic of obstructive sleep apnea promotes vascular endothelial dysfunction and atherogenesis. This process can lead to destabilization and rupture of cardiovascular plaques, which clinically manifests as an acute coronary syndrome or stroke. The aim of this study was to investigate the inflammatory pathway leading to plaque destabilization in non-to-mild and moderate-to-severe groups of OSA patients. This prospective study involved enrollment of patients scheduled for endarterectomy. A sleep study was performed prior to surgery. Immunohistochemistry was performed on atherosclerotic plaques from carotid arteries obtained during standard open endarterectomy to determine levels of CD40, CD40L receptors, MCP-1, and MMP-9. The 46 patients included 14 controls, 13 with mild, 11 with moderate, and 8 with severe OSA. Increased expression of CD40, CD40L receptors, MCP-1, and MMP-9 were found to be proportionate with OSA severity. However, significant differences among groups were observed only for MCP-1 (p = 0.014). Increased expression of inflammatory markers (CD40, CD40L, MCP-1, MMP-9) is associated with increasing OSA severity. This suggests the CD40-CD4-L inflammatory pathway may contribute to plaque instability and rupture in OSA patients.

The effect of in-lab polysomnography and home sleep polygraphy on sleep position.

PURPOSE: Little is known regarding the influence of in-laboratory polysomnography (PSG) equipment on sleep position, especially on the prevalence of supine positioning, which in many cases may lead to a more severe sleep apnea diagnosis. The aim of this study was to assess the percentage of supine sleep during an in-laboratory PSG compared to that seen during a home sleep apnea test (HSAT). METHODS: This was a retrospective cohort study comparing in-laboratory PSG and HSAT using a peripheral arterial tone (PAT) technology device. RESULTS: Of 445 PSG and 416 HSAT studies analyzed, there was no significant difference in the proportion of supine sleep time between PSG (44%) and HSAT (45%, p = 0.53). Analysis of the differences in sleep position (supine versus non-supine), analyzed by sex, BMI (≥ 30 kg/m2 versus < 30 kg/m2), and age (≥ 60 years versus < 60 years), was significant only for women, who had more supine sleep during HSAT at 61 ± 24% than during PSG at 45 ± 26% (p < 0.001). CONCLUSION: Overall there was no difference in the percentage of supine sleep when comparing in-laboratory PSG to HSAT. However, women had more supine sleep with HSAT than with PSG.

TLRs and RAGE are elevated in carotid plaques from patients with moderate-to-severe obstructive sleep apnea syndrome.

BACKGROUND: There is growing evidence that obstructive sleep apnea (OSA) promotes vascular endothelial dysfunction and atherogenesis. Pathways that mediate this pathology may include Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) which play a significant role in proinflammatory processes. The aim of this study was to measure the expression of the above-mentioned receptors in relation to OSA severity in carotid plaques obtained during open endarterectomy. METHODS: This prospective study included patients with a sleep study prior to surgery and a plaque specimen obtained during standard open endarterectomy. Immunohistochemistry of TLR2, TLR4, TLR7, TLR9, RAGE, HMGB1, and NF-κB was performed on atherosclerotic plaques from carotid arteries of patients with and without OSA. RESULTS: There were 46 patients (22 women, mean age 73.2 ± 1.3 years): 14 control patients, 13 with mild, 11 with moderate, and 8 with severe OSA. The expression of all TLRs and RAGE increased proportionately with increasing OSA severity. The largest differences between patients with severe OSA and no OSA were found for TLR2 (2.88 ± 0.35 vs. 1.27 ± 0.47, p < 0.001), TLR4 (2.88 ± 0.35 vs. 1.64 ± 0.5, p < 0.001), TLR9 (2.38 ± 0.52 vs. 1.45 ± 0.52, p < 0.01), and RAGE (2.5 ± 0.53 vs. 1.82 ± 0.6, p < 0.05). CONCLUSION: TLR2, TLR4, TLR9, and RAGE expression was significantly increased in carotid plaques of patients with moderate-to-severe OSA when compared with control patients with no OSA and those with mild OSA. TLR and RAGE-mediated pathways may play a significant role in OSA-dependent atherogenesis.

ALKBH overexpression in head and neck cancer: potential target for novel anticancer therapy.

The nine identified human homologues of E. coli AlkB 2-oxoglutarate (2OG) and Fe(II)-dependent dioxygenase, ALKBH1-8 and FTO, display different substrate specificities and diverse biological functions. Here we discovered the combined overexpression of members of the ALKBH family in head and neck squamous cell carcinomas (HNSCC). We found direct correlation of ALKBH3 and FTO expression with primary HNSCC tumor size. We observed unidentified thus far cytoplasmic localization of ALKBH2 and 5 in HNSCC, suggesting abnormal role(s) of ALKBH proteins in cancer. Further, high expression of ALKBHs was observed not only in HNSCC, but also in several cancerous cell lines and silencing ALKBH expression in HeLa cancer cells resulted in dramatically decreased survival. Considering the discovered impact of high expression of ALKBH proteins on HNSCC development, we screened for ALKBH blockers among newly synthetized anthraquinone derivatives and demonstrated their potential to support standard anticancer therapy.

RAGE and TLRs as Key Targets for Antiatherosclerotic Therapy.

Receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs) are the key factors indicating a danger to the organism. They recognize the microbial origin pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs). The primary response induced by PAMPs or DAMPs is inflammation. Excessive stimulation of the innate immune system occurs in arterial wall with the participation of effector cells. Persistent adaptive responses can also cause tissue damage and disease. However, inflammation mediated by the molecules innate responses is an important way in which the adaptive immune system protects us from infection. The specific detection of PAMPs and DAMPs by host receptors drives a cascade of signaling that converges at nuclear factor-κB (NF-κB) and interferon regulatory factors (IRFs) and induces the secretion of proinflammatory cytokines, type I interferon (IFN), and chemokines, which promote direct killing of the pathogen. Therefore, signaling of these receptors' pathways also appear to present new avenue for the modulation of inflammatory responses and to serve as potential novel therapeutic targets for antiatherosclerotic therapy.

Functional identification of abductor and adductor branches for laryngeal transplantation.

PURPOSE: This is a feasibility study of functional identification of the abductor and adductor recurrent laryngeal nerve branches, which could be used in the donor's larynx for functional laryngeal transplantation. METHODS: The study was performed on swine (n = 3) and human (n = 4) models of a donor larynx. The recurrent laryngeal nerve and its branches were found. Using stimulator, abductor and adductor branches were identified, and glottis closing and opening were captured with an endoscope. RESULTS: The result was positive if two ENT specialists noticed at least one adduction and one abduction movement in the same subject. It was obtained in three out of three swine and three out of four humans. CONCLUSIONS: This study shows a way of reinnervation of a transplanted larynx which might result in a functional organ. It describes the first step of the procedure: functional identification of the abductor and adductor branches of the recurrent laryngeal nerve in the donor before the larynx is excised for transplantation.

Obstructive sleep apnea in patients scheduled for endarterectomy - preliminary study.

Introduction The association between obstructive sleep apnea and atherosclerosis is confirmed for long time, but the pathomechanism is still not known. The aim of this study was to investigate the prevalence of OSA in patients scheduled for endarterectomy and the influence of this procedure on the sleep study parameters and sleepiness. Materials and methods 46 patients scheduled for open carotid endarterectomy were enrolled in the study. Sleep study and Epworth Sleepiness Scale (ESS) was performed preoperatively. In 11 out of 46 patients, sleep study was performed both before and after the surgery. Results The mean age of the group was 69,9 years (± 8,6), 21 patients (45,7%) were female. For 46 patients mean pAHI, ODI, pRDI and %snoring were 16,2 (± SD=15,2), 10,4 (± SD=12,2) and 18,9 (± SD=14,9), respectively. Normal pAHI was noticed in 14 patients (30%), while mild (pAHI 5-15), moderate (pAHI 15-30) and severe (pAHI>30) OSA was observed in 13 (38%), 11 (24%) and 8 (18%) subjects, respectively. The mean ESS score for 27 out of 46 patients was 6,3 (± SD=5,6). The postoperative results of sleep study in 11 patients showed no significant change. Conclusions This study revealed the prevalence of moderate to severe OSA in 42% of patients scheduled for endarterectomy, while no excessive daytime sleepiness was observed in this group. The results of the study show that patients with carotid atherosclerosis should undergo sleep diagnosis in order to rule out obstructive sleep apnea.

Association of breathing patterns and quality of life in patients with nasal obstruction.

INTRODUCTION: In the general population, nasal obstruction is a common complaint. However, an objective evaluation of nasal obstruction is difficult. Nose examination, computed tomography (CT), acoustic rhinometry, and anterior rhinomanometry do not accurately reflect the discomfort reported by patients with nasal obstruction. In patients with nasal obstruction, this study evaluated nasal breathing with a unique device for continuous nasal-oral spirometry - a nasal-oral flow analyzer (NOFA); moreover, quality of life was compared between patients with normal nasal breathing on NOFA and of those with impaired nasal breathing on NOFA. METHODS: Of 181 adult patients admitted to an ENT department due to nasal obstruction that were enrolled in the study, 97 (53.6%) completed all per-protocol assessments, including the SF-36 questionnaire and 3-hour, continuous nasal-oral spirometry with NOFA. Based on the presence of normal nasal breathing defined as ≥95% of nasal flow, the 97 patients were divided into those with normal nasal breathing (n=31) and impaired nasal breathing (n=66). RESULTS: Patients with normal nasal breathing differed from those with impaired nasal breathing with respect to all SF-36 subscales (physical functioning, p=0.004; role-physical, p=0.009; bodily pain, p<0.001; general health, p=0.007; vitality, p=0.002; social functioning, p=0.008; mental health, p=0.009; physical component summary, p<0.001; mental component summary, p=0.02), except for the role-emotional subscale (p=0.1). CONCLUSIONS: Among patients with symptoms of nasal obstruction, compared to patients with normal nasal breathing, those with impaired nasal breathing had significantly lower quality of life in the physical and mental domains. Further research needs to determine whether NOFA can be used to diagnose nasal obstruction.

Prevalence of upper respiratory tract infections in habitually snoring and mouth breathing children.

OBJECTIVES: The aim of the study was to investigate the prevalence of upper respiratory tract infections (URI) - as indicated by rhinosinusitis (RS), ear infections (EI), and antibiotic consumption - in a general pediatric population and evaluate the relationship between these conditions and habitual snoring and mouth breathing during sleep. METHODS: A population-based cross-sectional study was performed in three medium-sized Polish cities from 2011 to 2015. RESULTS: 4837/6963 questionnaires (69.5%) were completed, returned and analyzed. Mean age of studied group was 7.07 ±â€¯0.72 and 7.14 ±â€¯0.73 in girls and boys, respectively. Habitual mouth breathing during sleep (MB) was reported in 907 (18.7%) children and habitual snoring (HS) in 290 (6.0%). 230/290 (79.3%) of children with HS were also MB. Both HS and MB were more prevalent in boys than in girls (p = 0.027 and p < 0.0001, respectively) and neither was associated with BMI (p = 0.11 and p = 0.07, respectively). Habitual snoring and habitual mouth breathing were highly associated with more frequent bouts of rhinosinusitis, ear infections, and antibiotic use (p < 0.0001 for each parameter). CONCLUSIONS: Higher rates of rhinosinusitis, ear infections, and antibiotic consumption were similarly associated with HS and MB. MB is over three times more prevalent in the pediatric population relative to HS, therefore it might be considered as a risk factor for URI and may be included in history of URI.

Detecting Breathing and Snoring Episodes Using a Wireless Tracheal Sensor-A Feasibility Study.

OBJECTIVE: Sleep-disordered breathing is both a clinical and a social problem. This implies the need for convenient solutions to simplify screening and diagnosis. The aim of the study was to investigate the sensitivity and specificity of a novel wireless system in detecting breathing and snoring episodes during sleep. METHODS: A wireless acoustic sensor was elaborated and implemented. Segmentation (based on spectral thresholding and heuristics) and classification of all breathing episodes during recording were implemented through a mobile application. The system was evaluated on 1520 manually labeled episodes registered from 40 real-world, whole-night recordings of 16 generally healthy subjects. RESULTS: The differentiation between normal breathing and snoring had 88.8% accuracy. As the system is intended for screening, high specificity of 95% is reported. CONCLUSION: The system is a compromise between nonmedical phone applications and medical sleep studies. The presented approach enables the study to be repetitive, personal, and inexpensive. It has additional value in the form of well-recorded data which are reliable and comparable. SIGNIFICANCE: The system opens unexplored possibilities in sleep monitoring and study enabling a multinight recording strategy involving the collection and analysis of abundant data from thousands of people.

Obstructive sleep apnea and cancer: effects of intermittent hypoxia?

Obstructive sleep apnea (OSA) is a common disorder characterized by pauses in regular breathing. Apneic episodes lead to recurrent hypoxemia-reoxygenation cycles with concomitant cellular intermittent hypoxia. Studies suggest that intermittent hypoxia in OSA may influence tumorigenesis. This review presents recent articles on the potential role of OSA in cancer development. Relevant research has focused on: molecular pathways mediating the influence of intermittent hypoxia on tumor physiology, animal and epidemiological human studies linking OSA and cancer. Current data relating OSA to risk of neoplastic disease remain scarce, but recent studies reveal the potential for a strong relation. More work is, therefore, needed on the impact of OSA on many cancer-related aspects. Results may offer enlightenment for improved cancer diagnosis and treatment.

Long-term parental satisfaction with adenotonsillectomy: a population study.

OBJECTIVE: This study reports the presence of sleep-disordered breathing (SDB) symptoms among first graders. We evaluated the severity of symptoms and parental satisfaction in children who had undergone adenotonsillectomy (T&A) compared to children who never had T&A. METHODS: A population-based, cross-sectional study was conducted. Parent-reported questionnaire data including age, weight, height, BMI, history of T&A, and SDB symptoms (snoring intensity, observed dyspneas, mouth breathing during sleep) were analyzed. RESULTS: Of 3580 eligible children, 2504 (69.9 %) returned questionnaires. Two hundred fifty-nine (10.3 %) children had a history of T&A. Within this group, 76 % of parents were still satisfied with their child's outcome after surgery. The satisfaction rate decreased from 88.9 % in those who had surgery within 1 year to 71.3 % in those who had surgery ≥3 years prior. The mean values of intensity for all analyzed SDB symptoms on a five-point scale were significantly higher for children who had ever undergone T&A when compared to those who never underwent surgery [e.g., snoring (2.11 vs 1.87; P = 0.0004), dyspneas (1.64 vs 1.22; P < 0.0001), and mouth breathing during sleep (2.95 vs 2.58; P < 0.0001)]. For those who had undergone T&A, 24 % of caregivers were not satisfied with the surgical outcome and the symptom intensity was highest (snoring = 3.16, dyspneas = 2.20, and mouth breathing = 4.23) for these children. CONCLUSIONS: The mean SDB symptom intensity was significantly higher in children who had undergone T&A when compared to those who had not. The elevated symptom intensity in those children whose caregivers were not satisfied after T&A suggests possible SDB recurrence and need for further evaluation.

Recurrent laryngeal edema imitating angioedema caused by dislocated screw after anterior spine surgery.

The anterior cervical spine surgery is a common procedure to stabilize vertebrae damaged by various diseases. The plates and screws are usually used in the spine fixation. This kind of instrumentation may detach from the bones which is a rare but well-known complication. A 77-year-old male presented to the otorhinolaryngology department with throat pain, choking, and dysphagia. At first the angioedema was diagnosed and he was treated conservatively. The endoscopy revealed laryngeal edema, being more defined on the right side with right vocal fold paresis. CT scans showed the stabilizing plate with two screws attached tightly and the back-out of the third screw toward soft tissue of the neck. In the meantime, his condition deteriorated and he needed tracheotomy. In few days the surgical removal of the dislocated screw was performed successfully. Although two-month follow-up reported no obstruction of the larynx, the vocal folds paresis with gradual functional improvement was observed. Long-term complication of anterior spine surgery sometimes may suggest laryngeal angioedema at first. If the conservative treatment is ineffective and there is a history of anterior spine surgery, the clinicians should consider the displacement of the plate or screws in differential diagnosis.