Concordance Analysis of the Pressure Chamber and Tubomanometer According to Estève for the Determination of Eustachian Tube Opening Pressure.

INTRODUCTION: For the diagnosis of Eustachian tube dysfunction (ETD), clinical procedures such as tympanometry, micro-otoscopy, and maneuvers according to Toynbee and Valsalva only allow an indirect assessment for the moment. With a prevalence of up to 5%, the selection of patients with ETD and its subtypes is clinically relevant. Dynamic methods of Eustachian tube function assessment include a hypo/hyperbaric pressure chamber and Estève's tubomanometer (TMM). One method of assessing ETD is the evaluation of Eustachian tube opening pressure (ETOP). MATERIAL AND METHODS: We performed a concordance analysis between pressure chamber and TMM to determine ETOP. For this purpose, we analyzed the measurements of both methods from 28 healthy subjects using Bland-Altman plots, regression according to Passing-Bablok and Lin's concordance correlations coefficient. The maximum tolerated clinical deviation of measured values was set at 10%. RESULTS: A maximum of 53 measurements of ETOP between pressure chamber and TMM were compared. Mean ETOP for TMM was 28.7 hPa, passive opening was 32 hPa, Toynbee maneuver was 28.4 hPa, and Valsalva maneuver was 54.6 hPa. Concordance analysis revealed following results: passive opening versus TMM: Bland-Altman mean difference 3.3 hPa, limits of agreement ±31.8 hPa; Passing-Bablok regression y = 0.67 x + 9.36; Lin's rccc = 0.18. Toynbee versus TMM: Bland-Altman mean difference 0.7 hPa, limits of agreement ±35.8 hPa; Passing-Bablok regression y = 0.47x + 14.03; Lin's rccc = 0.14. Valsalva versus TMM: Bland-Altman mean difference 24.2 hPa, limits of agreement ±117.5 hPa; Passing-Bablok regression y = 0.17x + 25.12; Lin's rccc = 0.18. CONCLUSION: Estève's tubomanometer and pressure chamber measurements of ETOP are not concordant. The two methods cannot be interchanged without reservation.

The lncRNA MRPL20-AS1 is associated with severe OSAS and downregulated upon hypoxic injury of endothelial cells.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is the most common sleep disorder in humans. Although OSAS is clearly related to arterial hypertension, coronary artery disease, and heart failure, it remains unknown through which pathomechanisms OSAS influences cardiovascular health. Recent research has pinpointed long non-coding RNAs (lncRNA) as important molecular mediators of various cardiovascular pathologies. In this study, we have identified the lncRNA MRPL20-AS1 to be affected by OSAS in patients as well as by hypoxia in vitro. METHODS AND RESULTS: A transcriptomic analysis was performed on peripheral blood from four patients with severe OSAS taken after one night of polygraphic assessment. We found that three lncRNAs were significantly dysregulated, of which MRPL20-AS1 was the most significant. In a larger cohort of 22 OSAS patients, MRPL20-AS1 was inversely correlated with the apnea-hypopnea index (AHI). This indicates that OSAS patients with higher AHI levels and therefore more severe OSAS had lower levels of MRPL20-AS1 in the blood. The results were recapitulated in vitro by subjecting endothelial cells to hypoxia. In these experiments, hypoxia led to a significant downregulation of MRPL20-AS1 in endothelial cells. CONCLUSION: MRPL20-AS1 may serve as a useful tool to identify patients suffering from severe OSAS and further research should be done to evaluate the therapeutic potential of MRPL20-AS1 as a target to counteract the cardiovascular effects of OSAS.

Analysis of nocturnal, hypoxia-induced miRNAs in sleep apnea patients.

INTRODUCTION: Obstructive sleep apnea syndrome (OSAS) is associated with an increased cardiovascular risk. The underlying mechanisms are largely unclear. MicroRNAs (miRNAs) are RNAs circulating in the blood that can be released into the bloodstream during hypoxia. In the present study, we investigate if OSAS-induced hypoxia results in a release of miRNAs that may mediate OSAS-associated cardiovascular damage. METHODS: Blood was sampled from 23 OSAS patients before and after a polygraphically monitored night. Total circulating RNA was isolated from the plasma and quantified using real-time qPCR. Using a Taqman miRNA array, the levels of 384 different miRNAs were compared between evening and morning after polysomnography. The most highly upregulated miRNA (miRNA-505) and four additionally upregulated miRNAs (miRNA-127, miRNA-133a, miRNA-145, and miRNA-181a) were then quantified in a bigger patient cohort individually. RESULTS: Apnea/Hypopnea-Index (AHI) was evaluated and averaged at 26 per hour on nocturnal polygraphy. In an initial miRNA array, a total of 4 miRNAs were significantly regulated. A significant increase of miRNA-145 was observed in the larger patient cohort. No significant changes in concentration were detected for miRNA-127, miRNA-133a, miRNA-181a, and miRNA-505 in this larger cohort. CONCLUSION: OSAS results in the nocturnal release of miRNAs into the bloodstream. Our collected data may indicate a hypoxia-induced release of miRNAs into the bloodstream of OSAS-patients. In vitro experiments are needed to confirm the secretion of these miRNAs under hypoxia and evaluate the effect on the cardio vasculature.

Shortened up-dosing with sublingual immunotherapy drops containing tree allergens is well tolerated and elicits dose-dependent clinical effects during the first pollen season.

BACKGROUND: This study compared a rapid home-based up-dosing schedule for sublingual immunotherapy (SLIT) drops containing tree pollen allergens with two previously established schedules. Furthermore, the clinical effect of the SLIT was investigated with respect to patients' first pollen season under treatment. METHODS: In this open-label, prospective, patient-preference, non-interventional study, local and systemic reactions were compared between three up-dosing groups using a SLIT formulation containing birch, alder, and hazel pollen extracts (ORALVAC® Compact Bäume). Clinical improvement after patients' first season under treatment was analysed using symptom scores, ARIA classification, symptom control, and the use of symptomatic medication and was compared with data from the previous, pre-treatment pollen season. As the real-life study design allowed no placebo group, the late-treated patients (co-seasonal) served as a control, and crowd-sourced symptom data from persons with hay fever were used from a free web-based online diary. RESULTS: In 33 study centres in Germany and Austria, 164 patients were included. The treatment was well tolerated, without difference between the groups during the up-dosing phase. At the end of the assessment, 96.1% rated the tolerability of the treatment as good or very good. Local reactions were mostly mild in severity and no serious adverse events occurred. Symptom scores decreased from the 2016 pollen season to the 2017 pollen season. As for the ARIA classification, 79.0% of patients had persistent, moderate-to-severe rhinitis before treatment, but only 18.6% had the same classification after treatment. In all, 62.4% of patients achieved symptom control, and 34.3% of patients required no symptomatic medication after treatment. The rhinoconjunctivitis score was 34.4% lower for pre-seasonal treatment initiation than for the control group. Crowd-sourced symptom load indices showed that the 2016 season caused slightly more symptoms; however, it is assumed that this difference of 0.3-0.5 (score range 0-10) was of less clinical relevance. CONCLUSION: The treatment administered using the rapid home-based up-dosing schedule was safe and well tolerated. Symptom relief and reduction in medication use were observed during the first pollen season with SLIT. TRIAL REGISTRATION NUMBER: NCT03097432 (clinicaltrials.gov).