by Keyword: Upper airway

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da Palma, R. K., Farré, R., Montserrat, J. M., Gorbenko Del Blanco, D., Egea, G., de Oliveira, L. V. F., Navajas, D., Almendros, I., (2015). Increased upper airway collapsibility in a mouse model of Marfan syndrome Respiratory Physiology & Neurobiology , 207, 58-60

Marfan syndrome (MFS) is a genetic disorder caused by mutations in the FBN1 gene that codifies for fibrilin-1. MFS affects elastic fiber formation and the resulting connective tissue shows abnormal tissue laxity and organization. Although an increased prevalence of obstructive sleep apnea among patients with MFS has been described, the potential effects of this genetic disease on the collapsible properties of the upper airway are unknown. The aim of this study was to assess the collapsible properties of the upper airway in a mouse model of MFS Fbn1(C1039G/+) that is representative of most of the clinical manifestations observed in human patients. The upper airway in wild-type and Marfan mice was cannulated and its critical pressure (Pcrit) was measured in vivo by increasing the negative pressure through a controlled pressure source. Pcrit values from MFS mice were higher (less negative) compared to wild-type mice (-3.1±0.9cmH2O vs. -7.8±2.0cm H2O) suggesting that MFS increases the upper airway collapsibility, which could in turn explain the higher prevalence of OSA in MFS patients.

Keywords: Marfan syndrome, Obstructive sleep apnea, Upper airway collapsibility

Carreras, Alba, Wang, Yang, Gozal, David, Montserrat, Josep M., Navajas, Daniel, Farre, Ramon, (2011). Non-invasive system for applying airway obstructions to model obstructive sleep apnea in mice Respiratory Physiology & Neurobiology , 175, (1), 164-168

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstructions during sleep. The most common animal model of OSA is based on subjecting rodents to intermittent hypoxic exposures and does not mimic important OSA features, such as recurrent hypercapnia and increased inspiratory efforts. To circumvent some of these issues, a novel murine model involving non-invasive application of recurrent airway obstructions was developed. An electronically controlled airbag system is placed in front of the mouse's snout, whereby inflating the airbag leads to obstructed breathing and spontaneous breathing occurs with the airbag deflated. The device was tested on 29 anesthetized mice by measuring inspiratory effort and arterial oxygen saturation (SaO(2)). Application of recurrent obstructive apneas (6s each, 120/h) for 6h resulted in SaO(2) oscillations to values reaching 84.4 +/- 2.5% nadir, with swings mimicking OSA patients. This novel system, capable of applying controlled recurrent airway obstructions in mice, is an easy-to-use tool for investigating pertinent aspects of OSA.

Keywords: Animal model, Upper airway Obstruction, Mouse model, Non-invasive system, Model sleep apnea, Respiratory disease

Morgenstern, C., Schwaibold, M., Randerath, W. J., Bolz, A., Jané, R., (2009). Assessment of changes in upper airway obstruction by automatic identification of inspiratory flow limitation during sleep IEEE Transactions on Biomedical Engineering , 56, (8), 2006-2015

New techniques for automatic invasive and noninvasive identification of inspiratory flow limitation (IFL) are presented. Data were collected from 11 patients with full nocturnal polysomnography and gold-standard esophageal pressure (Pes) measurement. A total of 38,782 breaths were extracted and automatically analyzed. An exponential model is proposed to reproduce the relationship between Pes and airflow of an inspiration and achieve an objective assessment of changes in upper airway obstruction. The characterization performance of the model is appraised with three evaluation parameters: mean-squared error when estimating resistance at peak pressure, coefficient of determination, and assessment of IFL episodes. The model's results are compared to the two best-performing models in the literature. The obtained gold-standard IFL annotations were then employed to train, test, and validate a new noninvasive automatic IFL classification system. Discriminant analysis, support vector machines, and Adaboost algorithms were employed to objectively classify breaths noninvasively with features extracted from the time and frequency domains of the breaths' flowpatterns. The results indicated that the exponential model characterizes IFL and subtle relative changes in upper airway obstruction with the highest accuracy and objectivity. The new noninvasive automatic classification system also succeeded in identifying IFL episodes, achieving a sensitivity of 0.87 and a specificity of 0.85.

Keywords: Esophageal pressure, Exponential model, Inspiratory flow limitation, Noninvasive, Classification, Upper airway obstruction

Almendros, I., Carreras, A., Ramirez, J., Montserrat, J. M., Navajas, D., Farre, R., (2008). Upper airway collapse and reopening induce inflammation in a sleep apnoea model European Respiratory Journal , 32, (2), 399-404

The upper airway of obstructive sleep apnoea patients is subjected to recurrent negative pressure swings promoting its collapse and reopening. The aim of the present study was to ascertain whether this mechanical stress induces upper airway inflammation in a rat model. The upper airway of Sprague-Dawley rats was subjected to a periodic pattern of recurrent negative (-40 cmH2O, 1 s) and positive (4 cmH2O, 2 s) pressures inducing collapse and reopening for 5 h. Rats that were instrumented but not subjected to negative pressure swings were used as controls. The gene expression of the pro-inflammatory biomarkers macrophage inflammatory protein (MIP)-2, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and P-selectin in the soft palate and larynx tissues was assessed by real-time PCR. A marked overexpression of MIP-2, TNF-alpha, IL-1beta and P-selectin (approximately 40-, 24-, 47- and 7-fold greater than controls, respectively) was observed in the larynx tissue; similar results were found in the soft palate tissue (approximately 14-, 7-, 35- and 11-fold greater than controls, respectively). Recurrent upper airway collapse and reopening mimicking those experienced by obstructive sleep apnoea patients triggered an early local inflammatory process. These results could explain the inflammation observed in the upper airway of obstructive sleep apnoea patients.

Keywords: Airway collapse, Airway reopening, Inflammation, Negative pressure, Obstructive sleep apnoea, Upper airway

Farre, R., Montserrat, J. M., Navajas, D., (2008). Assessment of upper airway mechanics during sleep Respiratory Physiology & Neurobiology , 163, (1-3), 74-81

Obstructive sleep apnea, which is the most prevalent sleep breathing disorder, is characterized by recurrent episodes of upper airway collapse and reopening. However, the mechanical properties of the upper airway are not directly measured in routine polysomnography because only qualitative sensors (thermistors for flow and thoraco-abdominal bands for pressure) are used. This review focuses on two techniques that quantify upper airway obstruction during sleep. A Starling model of collapsible conduit allows us to interpret the mechanics of the upper airway by means of two parameters: the critical pressure (Pcrit) and the upstream resistance (Rup). A simple technique to measure Pcrit and Rup involves the application of different levels of continuous positive airway pressure (CPAP) during sleep. The forced oscillation technique is another non-invasive procedure for quantifying upper airway impedance during the breathing cycle in sleep studies. The latest developments in these two methods allow them to be easily applied on a routine basis in order to more fully characterize upper airway mechanics in patients with sleep breathing disorders.

Keywords: Obstructive sleep apnea, Upper airway, Airway resistance, Critical pressure, Respiratory impedance

Morgenstern, C., Jané, R., Schwaibold, M., Randerath, W., (2008). Automatic classification of inspiratory flow limitation assessed non-invasively during sleep IEEE Engineering in Medicine and Biology Society Conference Proceedings 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (ed. IEEE), IEEE (Vancouver, Canada) 1-8, 1132-1135

Detection of inspiratory flow limitation (IFL) is being recognized of increasing importance in order to diagnose pathologies related to sleep disordered breathing. Currently, IFL is usually identified with the help of invasive esophageal pressure measurement, still considered the gold-standard reference to assess respiratory effort. But the invasiveness of esophageal pressure measurement and its impact on sleep discourages its use in clinical routine. In this study, a new non-invasive automatic system is proposed for objective IFL classification. First, an automatic annotation system for IFL based on pressure/flow relationship was developed. Then, classifiers (Support Vector Machines and adaboost classifiers) were trained with these gold-standard references in order to objectively classify breaths non-invasively, solely based on the breaths' flow contours. The new non-invasive automatic classification system seems to be promising, as it achieved a sensitivity of 0.92 and a specificity of 0.89, outperforming prior classification results obtained by human experts.

Keywords: Upper airway-resistance

Solà, J., Jané, R., Fiz, J. A., Morera, J., (2008). Formant frequencies of normal breath sounds of snorers may indicate the risk of obstructive sleep apnea syndrome IEEE Engineering in Medicine and Biology Society Conference Proceedings 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (ed. IEEE), IEEE (Vancouver, Canada) 1-8, 3500-3503

Several differences between the airway of normal subjects and those with OSAS are well known. The characteristics of the upper airway may be indirectly studied through the formant frequencies of breathing sounds. In this work we analyze the formants of inspiration and exhalation sounds in snoring subjects with and without OSAS. Formant frequencies of inspiration and exhalation appear in the same bands as snores. Formant F1 is significantly lower in inspiration episodes of OSAS patients (p=0.008) with a decreasing tendency as the AHI increases (r=0.705). In addition, this formant has a significantly higher variability SF1 in pathological subjects, for both inspiration (p=0.022) and exhalation (p=0.038) episodes, as was previously found in snores. A higher variability of formant frequencies seems to be an indicator of the presence of OSAS. The proposed technique could allow the identification of OSAS patients from normal breathing alone.

Keywords: Upper airway