"Tuberculosis on the spot" - Discussion of a probable sternal tuberculosis from a late medieval cemetery from Hungary.

Investigations of non-adult remains are particularly suitable for finding epidemic periods in past populations. This study presents a probable unique example of osseous manifestation of tuberculosis on a child's skeletal remains from medieval Hungary. Between 2009 and 2011 the Field Service for Cultural Heritage excavated the exceptional cemetery of Perkáta - Nyúli-dulo in Hungary, with around 5000+ graves. The analysed skeleton (SNR 948) was located in the medieval (10-16th century) part of the cemetery. Besides the standard macroscopic pathological observation, we also performed radiographic analysis. The remains of the child (13-14 year-old) showed numerous skeletal lesions: the ribs have proliferative lesions (dense nodules) on the visceral surface of the shaft, lytic lesions with rounded edges occurred on the thoracic and lumbar vertebral bodies, and on the facies auricularis of the left ilium we can see pitting and new bone formation. What makes this pathological case exceptional is the significant change in the manubrium. It shows extensive osteolytic lesions, probably due to tuberculous osteomyelitis, which is a unique phenomenon in an archaeological context. This rare type of extra-spinal tuberculous osteomyelitis appears in less than 1% of cases with skeletal TB, and even less in case of children, according to modern medical literature. Although some cases of slight lesions on the manubrium have been described from an archaeological context, no such cases showing advanced lesions have been published so far. In the future, biomolecular analyses should be conducted as well, in order to confirm the presence of TB in this individual.

The prognostic role of ultrasound and magnetic resonance imaging in obstructive sleep apnoea based on lateral oropharyngeal wall obstruction.

PURPOSE: This study examined the prognostic value of the lateral pharyngeal wall (LPW)-based obstruction and obstructive sleep apnoea (OSA) prediction using ultrasound (US) and MRI (magnetic resonance imaging). METHODS: One hundred patients with and without OSA were enrolled, according to overnight polysomnography. The LPW thickness (LPWT) was measured using a Philips Ingenia 1.5 T MRI device, and US measurements were carried out at rest and during Müller's manoeuvre (MM) with a Samsung RS85 device. The obstruction was localised under drug-induced sleep endoscopy. RESULTS: Significantly greater LPWT using MRI was observed in the OSA group compared to the control group, while US results showed a significant difference only in the case of LPWT during MM on the left side. Obese patients presented significantly higher LPWT values. A significant correlation between BMI and LPWT was observed. Men presented significantly higher LPWT MRI values and left-sided LPWT using US compared to women. LPWT and AHI parameters were significantly correlated. The severity of LPW obstruction correlated with LPWT, while the LPW collapse significantly correlated with AHI. The severity of LPW collapse differed depending on the AHI values. Using US LPWT values and anthropometric parameters, a 93% effectiveness in OSA prognostication and 89% in LPWT-based obstruction were detected. MRI detected OSA in 90% and LPW-based obstruction in 84%. US successfully detected LPW-based collapse severity in 67%. CONCLUSION: US LPWT measurements were helpful in detecting OSA and LPWT-based obstruction. These examinations may be useful for surgical planning.

The Predictive Role of Subcutaneous Adipose Tissue in the Pathogenesis of Obstructive Sleep Apnoea.

INTRODUCTION: Our aim was to investigate the applicability of artificial intelligence in predicting obstructive sleep apnoea (OSA) and upper airway obstruction using ultrasound (US) measurements of subcutaneous adipose tissues (SAT) in the regions of the neck, chest and abdomen. METHODS: One hundred patients were divided into mild (32), moderately severe-severe (32) OSA and non-OSA (36), according to the results of the polysomnography. These patients were examined using anthropometric measurements and US of SAT and drug-induced sleep endoscopy. RESULTS: Using SAT US and anthropometric parameters, oropharyngeal obstruction could be predicted in 64% and tongue-based obstruction in 72%. In predicting oropharyngeal obstruction, BMI, abdominal and hip circumferences, submental SAT and SAT above the second intercostal space on the left were identified as essential parameters. Furthermore, tongue-based obstruction was predicted mainly by height, SAT measured 2 cm above the umbilicus and submental SAT. The OSA prediction was successful in 97% using the parameters mentioned above. Moreover, other parameters, such as US-based SAT, with SAT measured 2 cm above the umbilicus and both-sided SAT above the second intercostal spaces as the most important ones. DISCUSSION: Based on our results, several categories of OSA can be predicted using artificial intelligence with high precision by using SAT and anthropometric parameters.

The Predictive Role of the Upper-Airway Adipose Tissue in the Pathogenesis of Obstructive Sleep Apnoea.

This study aimed to analyse the thickness of the adipose tissue (AT) around the upper airways with anthropometric parameters in the prediction and pathogenesis of OSA and obstruction of the upper airways using artificial intelligence. One hundred patients were enrolled in this prospective investigation, who were divided into control (non-OSA) and mild, moderately severe, and severe OSA according to polysomnography. All participants underwent drug-induced sleep endoscopy, anthropometric measurements, and neck MRI. The statistical analyses were based on artificial intelligence. The midsagittal SAT, the parapharyngeal fat, and the midsagittal tongue fat were significantly correlated with BMI; however, no correlation with AHI was observed. Upper-airway obstruction was correctly categorised in 80% in the case of the soft palate, including parapharyngeal AT, sex, and neck circumference parameters. Oropharyngeal obstruction was correctly predicted in 77% using BMI, parapharyngeal AT, and abdominal circumferences, while tongue-based obstruction was correctly predicted in 79% using BMI. OSA could be predicted with 99% precision using anthropometric parameters and AT values from the MRI. Age, neck circumference, midsagittal and parapharyngeal tongue fat values, and BMI were the most vital parameters in the prediction. Basic anthropometric parameters and AT values based on MRI are helpful in predicting OSA and obstruction location using artificial intelligence.

Analysis of the most important features of obstructive sleep apnoea / Az obstruktív alvási apnoe fobb jellemzoinek vizsgálata

Introduction and objective: Obstructive sleep apnoea results in metabolic and cardiovascular disorders due to inter- mittent hypoxia. The main aim of the present study was to analyze the most important features of obstructive sleep apnoea, using anthropometric measurements and blood tests. Material and method: In this prospective investigation, 100 patients (74 male and 26 female patients, mean age +/- SD years, 42.15 +/- 12.7) were enrolled. These patients were divided into control (n = 36) and obstructive sleep apnoea (n = 64) groups regarding the results of polysomnography. The examination of the patients consisted of detailed anamnestic data, anthropometric measurements, laboratory test and the use of apnoea questionnaires. Results: In the obstructive sleep apnoea group, significantly higher neck (p<0.015), hip and abdomen circumfer- ences and BMI values (p<0.000) were observed. Significantly higher ratio of male patients in the case of obstructive sleep apnoea was detected (p<0.000). In the control group, only the neck circumferences differed significantly be- tween the two genders (p<0.000), but in the obstructive sleep apnoea group the neck (p = 0.001) and abdominal circumferences (p = 0.028) have also differed. Hypertension (64% and 21%) and type 2 diabetes mellitus (6.4% and 0%) were more frequent in the obstructive sleep apnoea group, while cardiovascular disorders (1% and 2.7 %) and gastroesophageal reflux disease (4.71% and 5.42%) in the control group. BMI values were significantly positively cor- related with the neck, abdominal and hip circumferences, both in the control and obstructive sleep apnoea groups. Moreover, in the control group, a significant negative correlation between HDL-cholesterol and BMI, neck and abdominal circumferences was observed. Conclusion: Obesity, as one of the most important risk factors for obstructive sleep apnoea and the intermittent hypo- xia contribute to the development of comorbidities. The diagnosis and therapy of the comorbidities is of great im- portance due to their effects on the patients' quality of life.

Examination of the diaphragm in obstructive sleep apnea using ultrasound imaging.

PURPOSE: The aim of this study was to analyze the effect of obstructive sleep apnea (OSA) on the ultrasound (US) features of the diaphragm and to determine if diaphragmatic US may be a useful screening tool for patients with possible OSA. METHODS: Patients complaining of snoring were prospectively enrolled for overnight polygraphy using the ApneaLink Air device. Thickness and motion of the diaphragm during tidal and deep inspiration were measured. Logistic regression was used to assess parameters of the diaphragm associated with OSA. RESULTS: Of 100 patients, 64 were defined as having OSA. Thicknesses of the left and right hemidiaphragms were significantly different between OSA and control groups. Using a combination of diaphragmatic dimensions, diaphragm dilation, age, sex, and BMI, we developed an algorithm that predicted the presence of OSA with 91% sensitivity and 81% specificity. CONCLUSION: A combination of anthropometric measurements, demographic factors, and US imaging may be useful for screening patients for possible OSA. These findings need to be confirmed in larger sample sizes in different clinical settings.

Positive association and future perspectives of mitochondrial DNA copy number and telomere length - a pilot twin study.

INTRODUCTION: Recent experimental and population studies have highlighted the existence of telomere-mitochondria interplay. Besides studies revealing the molecular mechanisms underlying the associations of telomere defects and mitochondrial functions, investigations of mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) in healthy and disease phenotypes have likewise begun, with the aim of gaining more insights about their relationship in humans. MATERIAL AND METHODS: A total of 142 asymptomatic adult twins, comprising 96 monozygotic (MZ) and 46 dizygotic (DZ) twins (mean age: 50.54 ±15.43 years), members of the Hungarian Twin Registry, were included in the analysis. Applying the qPCR standard curve method, we investigated the relationship of mtDNA copy number, telomere length and clinical data, besides assessing co-twin similarities of MZ and DZ twins for their mtDNAcn and TL measures. RESULTS: We found that twins were similar in their intraclass correlation coefficients irrespective of zygosity, suggesting a possibly more important role of common (shared) environmental factors compared to non-shared (unique) environmental and to a smaller degree also individual genetic influences. We confirmed a significant positive association between mtDNAcn and TL (r = 0.28, p < 0.01) in age- and sex-corrected analysis. Following bivariate estimates and correction with significant predictors, the independent positive associations were further verified. CONCLUSIONS: Our results extend the until now modest number of studies investigating mtDNAcn and TL simultaneously in humans. In addition, we are the first to examine the relationship between mtDNAcn and telomere length in MZ and DZ twin subjects.

Lumbar spine abnormalities in patients with obstructive sleep apnoea.

Previous studies suggested cervical spondylosis as a risk factor for development of obstructive sleep apnoea (OSA). We aimed to assess lumbar disc degeneration in patients with OSA and correlate the findings with symptoms and disease severity. Twenty-seven patients with OSA and 29 non-OSA controls underwent sleep studies and lumbar magnetic resonance imaging (MRI), and completed the Epworth Sleepiness Scale and the 24-item Roland-Morris Disability Questionnaire (RMDQ) questionnaires. Plasma klotho was determined with enzyme-linked immunosorbent assay. Patients with OSA had higher number of disc bulges (4.6 ± 3.7 vs. 1.7 ± 2.5, p < 0.01) and anterior spondylophytes (2.7 ± 4.2 vs. 0.8 ± 2.1, p < 0.01), increased disc degeneration (total Pfirrmann score 16.7 ± 4.7 vs. 13.2 ± 4.1, p < 0.01) and vertebral fatty degeneration (7.8 ± 4.7 vs. 3.8 ± 3.7, p < 0.01). There was no difference in the RMDQ score (0/0-3.5/ vs. 0/0-1/, p > 0.05). Markers of OSA severity, including the oxygen desaturation index and percentage of total sleep time spent with saturation < 90% as well as plasma levels of klotho were correlated with the number of disc bulges and anterior spondylophytes (all p < 0.05). OSA is associated with lumbar spondylosis. Our study highlights the importance of lumbar imaging in patients with OSA reporting lower back pain.

Circulating Survivin Protein Levels in Lung Cancer Patients Treated With Platinum-Based Chemotherapy.

The survivin protein contributes to the development and progression of tumors. Protein expression and mRNA levels correlate with clinicopathological parameters and survival of cancer patients. Our purpose was to evaluate whether circulating survivin levels have any diagnostic or predictive value in lung cancer. 118 patients with advanced stage lung cancer participated in our study. 53 suffered from adenocarcinoma (ADC), 33 from squamous cell carcinoma (SqCC), and 32 from small cell lung cancer (SCLC). We also enrolled 21 control subjects. Blood samples were collected before and after two cycles of chemotherapy. We measured survivin concentrations with ELISA. Non-parametric tests were used for analysis. We did not find significant difference in survivin levels between patients and control subjects (17.19/0-829.74/vs. 49.13/0-165.92/pg/ml; p = 0.07). We found lower survivin concentrations in patients with SqCC (0/0-171.24/pg/ml) than in those with ADC (24.94/0-626.46 pg/ml) and SCLC (45.51/0-829.74/pg/ml) (ADC vs. SqCC p < 0.0001, ADC vs. SCLC p = 0.0405, SqCC vs. SCLC p < 0.0001). Survivin levels were higher in stage IV patients than in patients without distant metastases (p = 0.0061), and concentrations were progressively higher with increasing number of metastatic organ sites (p = 0.04). We observed a decrease in survivin levels in ADC patients after platinum plus pemetrexed chemotherapy (26.22/0-626.46/pg/ml before vs. 0/0-114.36/pg/ml after; p = 0.01). Neither progression-free nor overall survival correlated with survivin levels at baseline. Our data imply that survivin may be involved in the development of metastases and it might be used as a biomarker of disease progression. However, circulating survivin concentrations do not predict survival of patients with lung cancer.

Triglyceride-Glucose Index in Non-Diabetic, Non-Obese Patients with Obstructive Sleep Apnoea.

Obstructive sleep apnoea (OSA) is associated with increased insulin resistance. Triglyceride-glucose index (TyG) is a simple marker of insulin resistance; however, it has been investigated only by two studies in OSA. The aim of this study was to evaluate TyG in non-diabetic, non-obese patients with OSA. A total of 132 patients with OSA and 49 non-OSA control subjects were included. Following a diagnostic sleep test, fasting blood was taken for the analysis of the lipid profile and glucose concentrations. TyG was calculated as ln(triglyceride [mg/dL] × glucose [mg/dL]/2). Comparison analyses between OSA and control groups were adjusted for age, gender, body mass index (BMI) and smoking. TyG was higher in men (p < 0.01) and in ever-smokers (p = 0.02) and it was related to BMI (ρ = 0.33), cigarette pack-years (ρ = 0.17), apnoea-hypopnoea index (ρ = 0.38), oxygen desaturation index (ρ = 0.40), percentage of total sleep time spent with oxygen saturation below 90% (ρ = 0.34), and minimal oxygen saturation (ρ = -0.29; all p < 0.05). TyG values were significantly higher in OSA (p = 0.02) following adjustment for covariates. OSA is independently associated with higher TyG values which are related to disease severity in non-obese, non-diabetic subjects. However, the value of TyG in clinical practice should be evaluated in follow-up studies in patients with OSA.

The Role of Soluble Low-Density Lipoprotein Receptor-Related Protein-1 in Obstructive Sleep Apnoea.

Intermittent hypoxia in obstructive sleep apnoea (OSA) is related to inflammation and metabolic abnormalities. Soluble low-density lipoprotein receptor-related protein-1 (sLRP-1) is involved in anti-inflammatory and metabolic processes. However, its ligand, calreticulin (CALR) promotes pro-inflammatory responses and apoptosis. Our aim was to analyse the levels of these biomarkers in OSA. We recruited 46 patients with OSA and 30 control subjects. Inpatient sleep study was performed and fasting plasma samples were collected. Triglyceride glucose index (TyG) and atherogenic index of plasma (AIP) were calculated. Plasma sLRP-1 levels were significantly lower in the OSA group compared to the controls (1.67 (0.90-2.11) mg/L vs. 1.99 (1.53-3.51) mg/L; p = 0.04) after adjustment for age, gender, BMI and lipid profile. Plasma sLRP-1 concentrations were inversely related to age (r = -0.29), BMI (r = -0.35), cigarette pack years (r = -0.31), LDL-C (r = -0.34) and triglyceride levels (r = -0.27), TyG (r = -0.37) and AIP (r = -0.27) as well as to the oxygen desaturation index (ODI, r = -0.24; all p < 0.05). BMI (p = 0.01) and ODI (p = 0.04) were independent predictors for low sLRP-1 levels. CALR did not differ significantly between the two groups (0.23 (0.17-0.34) ng/mL vs. 0.24 (0.20-0.36) ng/mL p = 0.76). We detected lower sLRP-1 levels in subjects with OSA which could contribute to metabolic abnormalities associated with this disease.

Circulating levels of clusterin and complement factor H in patients with obstructive sleep apnea.

Aim: Obstructive sleep apnea (OSA) activates the complement system; however, the levels of membrane attack complex (MAC) are unaltered suggesting regulatory mechanisms. Our aim was to investigate complement factor H (CFH) and clusterin, two important complement regulators in OSA. Materials & methods: We analyzed clusterin and CFH levels in plasma of 86 patients with OSA and 33 control subjects. Results: There was no difference in CFH levels between patients (1099.4/784.6-1570.5/µg/ml) and controls (1051.4/652.0-1615.1/µg/ml, p = 0.72). Clusterin levels were higher in patients with OSA (309.7/217.2-763.2/µg/ml vs 276.1/131.0-424.3/µg/ml, p = 0.048) with a trend for a positive correlation with disease severity (p = 0.073). Conclusion: Increase in clusterin levels may be protective in OSA by blocking the MAC formation.

Atherogenic Index of Plasma in Obstructive Sleep Apnoea.

BACKGROUND: Dyslipidaemia is well recognised in obstructive sleep apnoea (OSA) and could contribute to the development of cardiovascular disease (CVD). Atherogenic index of plasma (AIP) predicts cardiovascular morbidity and mortality better than the individual lipid levels. The aim of this study was to investigate the AIP in patients with OSA in relation with disease severity. METHODS: Four hundred sixty-one patients with OSA and 99 controls participated in this study. AIP was assessed in the morning following a diagnostic sleep study. The association between lipid values and OSA were adjusted for age, gender, and body mass index. RESULTS: Patients with OSA had higher AIP and triglyceride, and lower high-density lipoprotein cholesterol (HDL-C) levels (all p < 0.05). AIP significantly correlated with the Epworth Sleepiness Scale score (ρ = 0.19), the apnoea-hypopnoea index (ρ = 0.40) and oxygen desaturation index (ρ = 0.43, all p < 0.05). However, there was no relationship between the AIP and markers of sleep quality such as total sleep time, sleep period time, sleep efficiency, arousal index or percentage of REM sleep (all p > 0.05). AIP was not a better predictor for self-reported cardiovascular disease or diabetes than HDL-C. CONCLUSIONS: AIP is elevated in OSA and is related to disease severity. However, it does not seem to have an additional clinical value compared to HDL-C.

Characteristics of Hungarian patients with obstructive sleep apnoea / Obstruktív alvási apnoéban szenvedo betegek jellemzoi hazai beteganyagon.

Összefoglaló. Bevezetés és célkituzés: Az obstruktív alvási apnoe (OSA) a felnott lakosság jelentos részét érinto betegség, mely ismert rizikófaktora a cardiovascularis és metabolicus betegségeknek és a korai halálozásnak. Mindazonáltal kevés magyarországi adat áll rendelkezésre az OSA-ban szenvedo betegek demográfiai és klinikai jellemzoirol, így vizsgálatunk célja ennek bemutatása volt. Módszer: Retrospektív vizsgálatunkban a Semmelweis Egyetem Pulmonológiai Klinikájának Alváslaboratóriumában kivizsgált 394 személy (58 [46-66] év, 73% férfi, testtömegindex [BMI] = 32,5 [29,2-37,5]) adatait elemeztük, akik kitöltötték az Epworth Álmosság Skálát, poliszomnográfiás vizsgálaton estek át; felvettük az anamnézist, és 255 esetben reggeli éhomi vérvétel történt. Eredmények: 282 esetben igazolódott OSA. Ebben a csoportban magasabb volt a férfiak aránya (66 vs. 35%), magasabb volt az életkor (59 [48-66] vs. 47 [39-60] év) és a BMI (32,11 [27,78-37,18] vs. 25,29 [22,04-29,03] kg/m2), magasabbak voltak a C-reaktív protein értékek (3,0 [1,71-5,34] mg/l vs. 1,71 [0,91-3,31] mg/l), illetve a betegek gyakrabban szenvedtek társbetegségekben a kontrollcsoporthoz képest (magas vérnyomás 74% vs. 39%, cukorbetegség 24% vs. 11%, dyslipidaemia 46% vs. 30%, szív- és érrendszeri betegség 22% vs. 5%, szívritmuszavar 27% vs. 16%; minden p<0,05). Bár az OSA valószínusége progresszívan nott az életkorral és az Epworth Álmosság Skála emelkedésével, a trendekben szignifikáns különbségeket észleltünk a férfiak és a nok között (mindketto p<0,05). Ezzel szemben az OSA valószínuségének BMI-függése nemektol független volt (p = 0,94). Következtetés: Az OSA valószínusége progresszívan emelkedik a kor, a BMI és a nappali aluszékonyság függvényében, ugyanakkor ezt befolyásolja a nem is. Közleményünk rámutat a társbetegségek szurésének fontosságára is az OSA különbözo súlyossági fokaiban. Orv Hetil. 2020; 161(50): 2117-2123. INTRODUCTION AND OBJECTIVE: Obstructive sleep apnoea (OSA) is a common disease which is a known risk factor for cardiovascular and metabolic disease and mortality as well. However, the demographic and clinical characteristics of Hungarian patients with OSA are less known. The aim of this study was to describe them. METHOD: We analysed the data of 394 subjects (58 [46-66] years, 73% male, body mass index [BMI] = 32.5 [29.2-37.5]) who attended the Sleep Laboratory of the Department of Pulmonology at Semmelweis University. The volunteers filled out the Epworth Sleepiness Scale, we performed a polysomnography and took medical history. In 255 subjects, fasting blood samples were collected. RESULTS: OSA was diagnosed in 282 cases. This group had higher proportion of males (66 vs. 35%) and comorbidities (hypertension 74% vs. 39%, diabetes 24% vs. 11%, dyslipidaemia 46% vs. 30%, cardiovascular diseases 22% vs. 5%, arrhythmia 27% vs. 16%), the patients were older (59 [48-66] vs. 47 [39-60] years) and had higher BMI (32.11 [27.78-37.18] vs. 25.29 [22.04-29.03] kg/m2) and C-reactive protein levels (3.0 [1.71-5.34] mg/l vs. 1.71 [0.91-3.31] mg/l, all p<0.05). There was a significant relationship between the propensity of OSA along increasing age, BMI and Epworth Sleepiness Scale; however, the relationship depended on gender for age and Epworth Sleepiness Scale (both p<0.05). CONCLUSION: The propensity of OSA increases with age, BMI and symptoms burden and it is affected by the gender. Our study highlights the importance of screening comorbidities in different severity grades of OSA. Orv Hetil. 2020; 161(50): 2117-2123.

The Burden of Associated Comorbidities in Patients with Obstructive Sleep Apnea-Regional Differences in Two Central-Eastern European Sleep Centers.

BACKGROUND: Obstructive sleep apnea (OSA) is usually associated with cardiovascular and cerebrovascular disease, metabolic syndrome and depression. Data on relevant OSA-associated comorbidities in Central-European populations are scarce. The aim of this study was to compare the prevalence of comorbidities in two OSA cohorts from Hungary and Romania. METHODS: Data from 588 (282 from Hungary, 306 from Romania) untreated patients with OSA were retrospectively analyzed. The prevalence rates of hypertension, diabetes, dyslipidemia, allergic rhinitis, asthma, chronic obstructive pulmonary disease (COPD), osteoporosis, cerebrovascular and cardiovascular disease, arrhythmia and depression were compared between the two populations following adjustment for demographics, body mass index, smoking history, comorbidities and sleep parameters. RESULTS: The prevalence rates of hypertension, arrhythmia, cerebrovascular and cardiovascular disease, diabetes and COPD in the whole study population were directly related to the severity of OSA. We found an inverse correlation between the prevalence of osteoporosis and OSA severity (all p < 0.05). Following adjustment, the prevalence of dyslipidemia was higher in the Hungarian cohort, whilst the prevalence of asthma, cardiovascular and cerebrovascular diseases was higher in the Romanian cohort (all p < 0.05). CONCLUSIONS: There was no difference in the prevalence rate of most comorbidities in patients with OSA from the two cohorts, except for dyslipidemia, asthma, cardiovascular and cerebrovascular disease.

The role of hyaluronic acid and hyaluronidase-1 in obstructive sleep apnoea.

Biological functions of hyaluronic acid (HA) depend on its molecular size. High-molecular weight HA (HMW-HA) is an important component of the endothelial wall and has anti-inflammatory and antioxidant properties. Under inflammation or hypoxia, HMW-HA is degraded by hyaluronidases, such as HYAL-1 resulting in pro-inflammatory low-molecular weight fragments. Obstructive sleep apnoea (OSA) is characterised by intermittent hypoxia and systemic inflammation. Our aim was to evaluate circulating HMW-HA and HYAL-1 in OSA. We recruited 68 patients with OSA and 40 control volunteers. After full-night sleep study blood samples were taken for HMW-HA and HYAL-1 measurements. HYAL-1 levels were significantly higher in patients with OSA compared to controls (0.59/0.31-0.88/ng/mL vs. 0.31/0.31-0.58/ng/mL; p = 0.005) after adjustment for gender, age, BMI and smoking. There was a trend for reduced HMW-HA concentrations in OSA (31.63/18.11-59.25/ng/mL vs. 46.83/25.41-89.95/ng/mL; p = 0.068). Significant correlation was detected between circulating HMW-HA and apnoea-hypopnoea-index (r = - 0.195, p = 0.043), HYAL-1 and apnoea-hypopnoea-index (r = 0.30, p < 0.01) as well as oxygen desaturation index (r = 0.26, p < 0.01). Our results suggest that chronic hypoxia is associated with increased plasma HYAL-1 concentration and accelerated HMW-HA degradation. Altered hyaluronan metabolism may be involved in the inflammatory cascade potentially leading to endothelial dysfunction in OSA.

Validation of the Hungarian version of the SRI Questionnaire.

BACKGROUND: Home mechanical ventilation is a reliable treatment for patients suffering from chronic respiratory failure, improving survival and quality of life. Prevalence has been increasing worldwide as a result of evolving technical possibilities, telemedicine and improving national guidelines. Projects to establish a national guideline and registry for patients treated with home mechanical ventilation are currently under way in Hungary and our aim was to validate a quality of life questionnaire suited for evaluation and follow up in this specific patient group. The Severe Respiratory Insufficiency Questionnaire (SRI) is a quality of life tool designed to evaluate patients receiving home mechanical ventilation and has been validated both in patient groups receiving invasive and noninvasive ventilation. METHODS: The Hungarian version of the SRI was created using the translation-backtranslation method, which was then tested for validity, viability and reliability in a cohort involving patients from three centers, receiving long-term home mechanical ventilation for chronic respiratory failure through an invasive or noninvasive interface. Patient data was collected (demographic data, lung function test, arterial blood gas, ventilation settings) and quality of life was measured with the previously validated SF-36 and newly created Hungarian SRI Questionnaires at two time points. RESULTS: One hundred four patients receiving home mechanical ventilation were enrolled. The time to complete the SRI Questionnaire was 8.6 (±3.1) minutes, 69.2% questionnaires were self-administered. Exploratory factor analysis explained 73.8% of the variance of the questionnaire, but resulted in 13 scales. We found correlations between the SRI subscale scores to corresponding scales of the previously validated general quality of life survey SF-36. The Cronbach alpha coefficient was 0.928 for the Summary Scale of the SRI Questionnaire, proving high internal consistency. Reproducibility was high for most scales, resulting in a high overall correlation for the summary score (0.877, p < 0.001). CONCLUSIONS: The Hungarian version of the SRI Questionnaire is a viable, valid, reliable and reproduceable quality of life tool applicable for patients treated with home mechanical ventilation.

Circulating Soluble Urokinase-Type Plasminogen Activator Receptor in Obstructive Sleep Apnoea.

Background and Objectives: Obstructive sleep apnoea (OSA) is associated with heightened systemic inflammation and a hypercoagulation state. Soluble urokinase-type plasminogen activator receptor (suPAR) plays a role in fibrinolysis and systemic inflammation. However, suPAR has not been investigated in OSA. Materials and Methods: A total of 53 patients with OSA and 15 control volunteers participated in the study. Medical history was taken and in-hospital sleep studies were performed. Plasma suPAR levels were determined by ELISA. Results: There was no difference in plasma suPAR values between patients with OSA (2.198 ± 0.675 ng/mL) and control subjects (2.088 ± 0.976 ng/mL, p = 0.62). Neither was there any difference when patients with OSA were divided into mild (2.134 ± 0.799 ng/mL), moderate (2.274 ± 0.597 ng/mL) and severe groups (2.128 ± 0.744 ng/mL, p = 0.84). There was no significant correlation between plasma suPAR and indices of OSA severity, blood results or comorbidities, such as hypertension, diabetes, dyslipidaemia or cardiovascular disease. Plasma suPAR levels were higher in women when all subjects were analysed together (2.487 ± 0.683 vs. 1.895 ± 0.692 ng/mL, p < 0.01), and also separately in controls (2.539 ± 0.956 vs. 1.411 ± 0.534 ng/mL, p = 0.02) and patients (2.467 ± 0.568 vs. 1.991 ± 0.686 ng/mL, p < 0.01). Conclusions: Our results suggest that suPAR does not play a significant role in the pathophysiology of OSA. The significant gender difference needs to be considered when conducting studies on circulating suPAR.

Obstructive sleep apnea and hypertriglyceridaemia share common genetic background: Results of a twin study.

Obstructive sleep apnea is associated with an increased risk of hypertension, diabetes and dyslipidaemia. Both obstructive sleep apnea and its comorbidities are at least partly heritable, suggesting a common genetic background. Our aim was to analyse the heritability of the relationship between obstructive sleep apnea and its comorbidities using a twin study. Forty-seven monozygotic and 22 dizygotic adult twin pairs recruited from the Hungarian Twin Registry (mean age 51 ± 15 years) attended an overnight diagnostic sleep study. A medical history was taken, blood pressure was measured, and blood samples were taken for fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and lipoprotein (a). To evaluate the heritability of obstructive sleep apnea and its comorbidities bivariate analysis was performed with an adjustment for age, gender, body mass index (BMI) and smoking after false discovery rate correction and following exclusion of patients on lipid-lowering and antidiabetic medications. There was a significant correlation between indices of obstructive sleep apnea severity, such as the apnea-hypopnea index, oxygen desaturation index and percentage of sleep time spent with oxygen saturation below 90%, as well as blood pressure, serum triglyceride, lipoprotein (a) and glucose levels (all p < .05). The bivariate analysis revealed a common genetic background for the correlations between serum triglyceride and the oxygen desaturation index (r = .63, p = .03), as well as percentage of sleep time spent with oxygen saturation below 90% (r = .58, p = .03). None of the other correlations were significantly genetically or environmentally determined. This twin study demonstrates that the co-occurrence of obstructive sleep apnea with hypertriglyceridaemia has a genetic influence and heritable factors play an important role in the pathogenesis of dyslipidaemia in obstructive sleep apnea.

Decreased Levels of Anti-Aging Klotho in Obstructive Sleep Apnea.

The klotho protein is secreted primarily by the kidneys. It is responsible for phosphate homeostasis and has an anti-aging, anti-inflammatory, and anti-oxidative stress role. Obstructive sleep apnea (OSA) is associated with an enhanced systemic inflammation and oxidative stress, but mechanisms that regulate these processes are poorly understood. The aim of the study was to investigate the plasma levels of klotho in OSA. Twenty-one previously untreated patients with OSA (56 ± 13 years, 12 males) and 41 non-OSA control volunteers (48 ± 16 years, 8 males) participated in the study. Medical history has been taken; participants filled out the Epworth Sleepiness Scale. C-reactive protein and renal function, glucose and lipid profile measurements were performed in sera; klotho was determined in citrate-treated plasma samples. Levels of plasma klotho were decreased in OSA (519.1 ± 164.9 pg/mL) versus controls (700.8 ± 431.4 pg/mL, p = 0.02). Reduced klotho concentrations were associated with markers of overnight hypoxemia determined with O2 desaturation index (r = -0.31, p = 0.01), percentage of sleep time spent with saturation <90% (r = -0.41, p < 0.01), and minimal saturation during sleep (r = 0.33, p = 0.01). Interestingly, there was no relationship with apnea-hypopnea index, total sleep time, or arousal index (all p > 0.05). Significant association was also found between low plasma klotho levels and the presence of hypertension (p < 0.05). Our results suggest that chronic intermittent hypoxia reduces the levels of klotho in OSA, which may contribute to the development of hypertension. Decreased klotho levels may play a role in enhanced systemic inflammation in OSA and may be a future target for drug development.