Improved Breath Phase and Continuous Adventitious Sound Detection in Lung and Tracheal Sound Using Mixed Set Training and Domain Adaptation

Previously, we established a lung sound database, HF_Lung_V2 and proposed convolutional bidirectional gated recurrent unit (CNN-BiGRU) models with adequate ability for inhalation, exhalation, continuous adventitious sound (CAS), and discontinuous adventitious sound detection in the lung sound. In this study, we proceeded to build a tracheal sound database, HF_Tracheal_V1, containing 11107 of 15-second tracheal sound recordings, 23087 inhalation labels, 16728 exhalation labels, and 6874 CAS labels. The tracheal sound in HF_Tracheal_V1 and the lung sound in HF_Lung_V2 were either combined or used alone to train the CNN-BiGRU models for respective lung and tracheal sound analysis. Different training strategies were investigated and compared: (1) using full training (training from scratch) to train the lung sound models using lung sound alone and train the tracheal sound models using tracheal sound alone, (2) using a mixed set that contains both the lung and tracheal sound to train the models, and (3) using domain adaptation that finetuned the pre-trained lung sound models with the tracheal sound data and vice versa. Results showed that the models trained only by lung sound performed poorly in the tracheal sound analysis and vice versa. However, the mixed set training and domain adaptation can improve the performance of exhalation and CAS detection in the lung sound, and inhalation, exhalation, and CAS detection in the tracheal sound compared to positive controls (lung models trained only by lung sound and vice versa). Especially, a model derived from the mixed set training prevails in the situation of killing two birds with one stone.Comment: To be submitted, 31 pages, 6 figures, 5 table

Orthodontic risk factors for obstructive sleep apnea in childhood: a pilot study (ORFOS Project)

Background: Orthodontic risk factors have mainly been discussed as consequences of, rather than as a reason for obstructive sleep apnea (OSA) in childhood. Although they have gained importance concerning OSA treatment options, they scarcely attract attention in screening or diagnosis. The ORFOS pilot study aims to test feasibility of an OSA screening method in the setting of an orthodontic clinic in order to confirm known risk factors and identify new orthodontic conspicuous parameters. In the long term, we plan to establish a nationwide pediatric OSA screening to see if the identified OSA risk factors are transferable to the ethnic background of Germany, with the objective to define OSA risk profiles. Methods: The study comprised 162 minor orthodontic patients between 6 and 16 years of age (median 13 years). To evaluate a comprehensive medical (sleep) history, 6 questionnaires were applied and a non-invasive, self-developed ear-nose and throat (ENT) examination was performed. Orthodontic parameters covering clinical history, intra- and extraoral examination, dental and cephalometric analysis were recorded. Using the PSQ, we divided the study sample into a sleep disordered breathing/OSA (42 children) and an unaffected control group (120 children). We tested the feasibility of examination and screening methods, as well as performed a statistical group comparison. Results: Of 188 children approached, 167 (88,8 %) participated with a drop-out rate of 0 %, 5 met exclusion criteria. Concerning time factor of our study model, probands and their parents had to consider approximately 20 minutes for questionnaires and the ENT examination in addition to their routine orthodontic appointment. 7 variables showed a missing n rate greater than 10 % concerning clinical history, 3 in ENT examination (missing data rate over 5 %). The group comparison revealed 8 intergroup differences (p < 0.1) in both, orthodontic clinical history plus examination, and dental cast models: The test group "snorers" had less often sucking habits (9.5 %) than controls "non-snorers" (24.2 %, risk ratio (RR) = 0.39). Concerning lip configuration, a lower median of lip configuration lower third of 15 mm/ 67 % was detected in the test group by contrast with a median of 18 mm/ 69 % in the reference group. Another difference was seen in asymmetries of the face: "snorers" were over three times less likely to display asymmetries of the mandible to the right (n = 2, 4.9 %) than "non-snorers" (n = 21, 17.8 %, RR = 0.28). An asymmetry of the mandible to the left was less common in "snorers", too (n = 4, 9.8 % versus (vs.) n = 15, 12.7 %, RR = 0.77). The median overbite in "snorers" (4 mm) was relevantly larger than in "non-snorers" (3 mm). A frontal crossbite was diagnosed half as frequently in "snorers" (9.8 %) than in "non-snorers" (23.7 %, RR = 0.41). An edge-to-edge occlusion was seen in 33.3 % of the test and in 24.6 % of the reference group (RR = 1.35). A lateral open bite was less frequent in "snorers" (7.5 %) compared to "non-snorers" (18.6 %, RR = 0.40). Relevant differences were also found in the transversal width maxilla anterior (median of 19.5 mm in "snorers" and 18 mm in "non-snorers") and posterior (median of 28.5 mm vs. 24 mm). Also the transversal width mandible anterior differed between the groups: a median of 31.5 mm in "snorers" and 18 mm in "non-snorers". The transversal width of the posterior mandible was increased in the test group (41 mm vs. 25 mm). Conclusion: The tested OSA screening and examination methods demonstrated practicability in the setting of an orthodontic practice regarding acceptance, adherence and feasibility. The PSQ serves as a suitable screening tool. ORFOS could not clearly identify orthodontic risk factors for OSA in childhood. We found differences relating to edge-to-edge bite, frontal facial asymmetries, overbite, crossbite, transversal widths, sucking habits and open bite between potential pediatric OSA patients and controls

Microvascular alterations and Corpora Amylacea progression in the post-mortem hippocampus of patients with obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is a sleep disorder that involves frequent episodes of breathing cessation or significant decreases in airflow during sleep, leading to periods of blood oxygen desaturation. These episodes of intermittent hypoxia (IH) followed by reoxygenation are thought to induce oxidative stress and neuroinflammation. Patients with severe OSA exhibit neuropsychological deficits and impaired memory. Continuous positive airway pressure (CPAP) is the standard treatment for OSA patients, but not all cognitive symptoms can be reversed by this procedure, suggesting that severe OSA may permanently injure the brain. The CA1 region of the hippocampus is one of the first regions of the brain to suffer hypoxic injury. This vulnerability is supported by imaging studies showing that the volume of the hippocampus is reduced in people with severe OSA. Since it is not known why some parts of the hippocampus are selectively vulnerable to hypoxia, an investigation of the microvessels in these regions could provide new insights. The first aim of the present study was to investigate the effects of OSA severity, regular CPAP use and advanced age on angiogenesis and microvascular remodelling in different regions of the hippocampus (Chapter 3). It was hypothesised that there would be significantly increased microvascular alterations in the high OSA group (oxygen desaturation index: ODI &amp;ge; 20 events/h sleep) compared to the low OSA group (ODI &amp;lt; 20 events/h sleep). The hypothesis was tested by measuring capillaries that had been immunostained by either CD34, VWF, Claudin 5, GluT-1 or Collagen IV, in the fimbria, CA4, CA1, subiculum and collateral sulcus regions. Analyses were conducted on formalin-fixed, paraffin-embedded hippocampal tissues obtained at autopsy from 30 OSA patients. The results showed that angiogenesis did not occur in OSA; instead moderate-severe OSA was associated with a 10 - 25% increase in the mean diameters of capillaries in the fimbria and CA4 regions, suggesting that microvascular remodelling occurred in response to IH in OSA. These changes were not reversed by CPAP treatment. The lack of adaptive microvascular changes in the CA1 region might be a factor in the selective vulnerability of this region to hypoxia. The second aim was to systematically investigate the presence of morphological abnormalities in the microvessels of the hippocampus of OSA patients (Chapter 4). It was hypothesised that if microvascular abnormalities are caused by oxidative stress, they would be more prevalent in the high OSA group and advanced age group, while regular CPAP users would display fewer abnormalities. The results showed there were increased numbers of abnormal microvessels in the high OSA group in the CA1 region, but not in other parts of the hippocampus. It is speculated that increased numbers of abnormal microvessels in the CA1 region enhances its vulnerability to hypoxic injury and causes permanent degenerative changes that limit the ability of CPAP to reverse memory impairments. Corpora amylacea (CoA) are often regarded as correlates of the ageing process, and their numbers have been reported to increase steadily after the age of 50. Despite the fact that CoA were first identified in the central nervous system (CNS) over a century ago, little is known about their spatial distribution in the hippocampus of aged OSA patients. The third aim was to determine the distribution and progression pattern of CoA in the hippocampus, and to assess how the density and size of CoA change with advancing age (Chapter 5). It was hypothesised that CoA would be concentrated in periventricular and subpial regions, and that their density and size would increase with age. The results revealed that while the size of CoA increases with age, the packing density does not. A distinct distribution pattern of CoA was observed by low-magnification scanning photomicrographs that began at the fimbria and then progressively spread along the pial surface of the hippocampal formation to more distant regions. This progression pattern did not correlate with age. This spatiotemporal sequence has not been reported previously, and the reasons for this pattern of spread are unknown. The fourth aim of the present study was to investigate factors that may be associated with CoA formation (Chapter 6). Since CoA contain oxidised lipids and proteins, it has been speculated that they are markers of oxidative stress or the consequence of neurodegenerative processes. It was hypothesised that increased OSA severity would be associated with larger and more numerous CoA. The results confirmed that OSA severity was significantly correlated with the spatiotemporal distribution of CoA, as well as increased CoA density. However, as these correlations did not diminish with regular CPAP use, a role for hypoxia or oxidative stress was not supported. Furthermore, CoA were rarely observed in the CA1 region, despite this region being thought to experience the highest levels of hypoxia and oxidative stress. The data also failed to support neurodegeneration as a cause of CoA, as no correlations were found between CoA burden (distribution, density or size), and the burden of Amyloid &amp;szlig; (A&amp;szlig;) plaques, Tau+ neurofibrillary tangles, neuropil loss or demyelination. This study advances our understanding of regional differences in the capacity of the hippocampal microvasculature to remodel in response to increasing severity of OSA and to ageing, and offers a new explanation for the selective vulnerability of the CA1 to hypoxia. This study also advances our understanding of the factors that contribute to the formation of CoA, showing that OSA severity is correlated with the spatial extent and numbers of CoA in the hippocampus, while patient age is correlated with their size. In contrast, oxidative stress and neurodegeneration now appear unlikely to contribute to the formation of CoA in the human hippocampus. It is recommended that larger studies be conducted, that include patients without OSA, so that the present findings can be confirmed and extended