ORCID Profile
0000-0003-3752-0328
Current Organisations
Helmholtz Zentrum München Deutsches Forschungszentrum für Umwelt und Gesundheit
,
Philipps University of Marburg
,
Brigham and Women's Hospital
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Publisher: American Physiological Society
Date: 15-12-2014
DOI: 10.1152/JAPPLPHYSIOL.00259.2014
Abstract: The human pharyngeal airway during sleep is conventionally modeled as a Starling resistor. However, inspiratory flow often decreases with increasing effort (negative effort dependence, NED) rather than remaining fixed as predicted by the Starling resistor model. In this study, we tested a major prediction of the Starling resistor model—that the resistance of the airway upstream from the site of collapse remains fixed during flow limitation. During flow limitation in 24 patients with sleep apnea, resistance at several points along the pharyngeal airway was measured using a pressure catheter with multiple sensors. Resistance between the nose and the site of collapse (the upstream segment) was measured before and after the onset of flow limitation to determine whether the upstream dimensions remained fixed (as predicted by the Starling resistor model) or narrowed (a violation of the Starling resistor model). The upstream resistance from early to mid inspiration increased considerably during flow limitation (by 35 ± 41 cmH 2 O·liter −1 ·s −1 , P 0.001). However, there was a wide range of variability between patients, and the increase in upstream resistance was strongly correlated with the amount of NED ( r = 0.75, P 0.001). Therefore, patients with little NED exhibited little upstream narrowing (consistent with the Starling model), and patients with large NED exhibited large upstream narrowing (inconsistent with the Starling model). These findings support the idea that there is not a single model of pharyngeal collapse, but rather that different mechanisms may dominate in different patients. These differences could potentially be exploited for treatment selection.
Publisher: American Physiological Society
Date: 11-2013
DOI: 10.1152/JAPPLPHYSIOL.00093.2013
Abstract: The mechanisms underlying not well-controlled (NWC) asthma remain poorly understood, but accumulating evidence points to peripheral airway dysfunction as a key contributor. The present study tests whether our recently described respiratory system reactance (Xrs) assessment of peripheral airway dysfunction reveals insight into poor asthma control. The aim of this study was to investigate the contribution of Xrs to asthma control. In 22 subjects with asthma, we measured Xrs (forced oscillation technique), spirometry, lung volumes, and ventilation heterogeneity (inert-gas washout), before and after bronchodilator administration. The relationship between Xrs and lung volume during a deflation maneuver yielded two parameters: the volume at which Xrs abruptly decreased (closing volume) and Xrs at this volume (Xrs crit ). Lowered (more negative) Xrs crit reflects reduced apparent lung compliance at high lung volumes due, for ex le, to heterogeneous airway narrowing and unresolved airway closure or near closure above the critical lung volume. Asthma control was assessed via the 6-point Asthma Control Questionnaire (ACQ6). NWC asthma was defined as ACQ6 1.0. In 10 NWC and 12 well-controlled subjects, ACQ6 was strongly associated with postbronchodilator (post-BD) Xrs crit ( R 2 = 0.43, P 0.001), independent of all measured variables, and was a strong predictor of NWC asthma (receiver operator characteristic area = 0.94, P 0.001). By contrast, Xrs measures at lower lung volumes were not associated with ACQ6. Xrs crit itself was significantly associated with measures of gas trapping and ventilation heterogeneity, thus confirming the link between Xrs and airway closure and heterogeneity. Residual airway dysfunction at high lung volumes assessed via Xrs crit is an independent contributor to asthma control.
Publisher: American Thoracic Society
Date: 15-11-2022
Publisher: Oxford University Press (OUP)
Date: 22-05-2017
DOI: 10.1093/SLEEP/ZSX094
Abstract: Upper airway surgery is often recommended to treat patients with obstructive sleep apnea (OSA) who cannot tolerate continuous positive airways pressure. However, the response to surgery is variable, potentially because it does not improve the nonanatomical factors (ie, loop gain [LG] and arousal threshold) causing OSA. Measuring these traits clinically might predict responses to surgery. Our primary objective was to test the value of LG and arousal threshold to predict surgical success defined as 50% reduction in apnea-hypopnea index (AHI) and AHI <10 events/hour post surgery. We retrospectively analyzed data from patients who underwent upper airway surgery for OSA (n = 46). Clinical estimates of LG and arousal threshold were calculated from routine polysomnographic recordings presurgery and postsurgery (median of 124 [91-170] days follow-up). Surgery reduced both the AHI (39.1 ± 4.2 vs. 26.5 ± 3.6 events/hour p < .005) and estimated arousal threshold (-14.8 [-22.9 to -10.2] vs. -9.4 [-14.5 to -6.0] cmH2O) but did not alter LG (0.45 ± 0.08 vs. 0.45 ± 0.12 p = .278). Responders to surgery had a lower baseline LG (0.38 ± 0.02 vs. 0.48 ± 0.01, p < .05) and were younger (31.0 [27.3-42.5] vs. 43.0 [33.0-55.3] years, p < .05) than nonresponders. Lower LG remained a significant predictor of surgical success after controlling for covariates (logistic regression p = .018 receiver operating characteristic area under curve = 0.80). Our study provides proof-of-principle that upper airway surgery most effectively resolves OSA in patients with lower LG. Predicting the failure of surgical treatment, consequent to less stable ventilatory control (elevated LG), can be achieved in the clinic and may facilitate avoidance of surgical failures.
Publisher: Oxford University Press (OUP)
Date: 10-12-2017
DOI: 10.1093/SLEEP/ZSW047
Publisher: Elsevier BV
Date: 06-2016
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JPEDS.2017.07.012
Abstract: To determine whether different modes of infant feeding are associated with childhood asthma, including differentiating between direct breastfeeding and expressed breast milk. We studied 3296 children in the Canadian Healthy Infant Longitudinal Development birth cohort. The primary exposure was infant feeding mode at 3 months, reported by mothers and categorized as direct breastfeeding only, breastfeeding with some expressed breast milk, breast milk and formula, or formula only. The primary outcome was asthma at 3 years of age, diagnosed by trained healthcare professionals. At 3 months of age, the distribution of feeding modes was 27% direct breastfeeding, 32% breastfeeding with some expressed breast milk, 26% breast milk and formula, and 15% formula only. At 3 years of age, 12% of children were diagnosed with possible or probable asthma. Compared with direct breastfeeding, any other mode of infant feeding was associated with an increased risk of asthma. These associations persisted after adjusting for maternal asthma, ethnicity, method of birth, infant sex, gestational age, and daycare attendance (some expressed breast milk: aOR, 1.64, 95% CI, 1.12-2.39 breast milk and formula, aOR, 1.73, 95% CI, 1.17-2.57 formula only: aOR, 2.14, 95% CI, 1.37-3.35). Results were similar after further adjustment for total breastfeeding duration and respiratory infections. Modes of infant feeding are associated with asthma development. Direct breastfeeding is most protective compared with formula feeding indirect breast milk confers intermediate protection. Policies that facilitate and promote direct breastfeeding could have impact on the primary prevention of asthma.
Publisher: American Thoracic Society
Date: 10-2010
Publisher: Elsevier BV
Date: 12-2008
DOI: 10.1016/J.RESP.2008.09.003
Abstract: Periodic breathing (PB) is an instability of the respiratory control system believed to be mediated principally by the peripheral chemoreceptors. We hypothesised that domperidone, a dopamine D(2)-receptor antagonist that increases carotid body sensitivity to O(2) and CO(2), would promote PB through an increase in the loop gain (LG) of the respiratory control system. Domperidone significantly increased controller gain for oxygen (p<0.05) and gave rise, following post-hyperventilation apnea, to an increased incidence of PB (14% vs. 86%), an increased PB epoch duration, and a decrease in duty ratio of PB (p<0.001) these changes are consistent with domperidone increasing LG. Although domperidone increased controller gain for CO(2) (p<0.05), the contribution of Pa(CO)(2) oscillations to the genesis of PB in the lamb remained small. We conclude that domperidone increases LG in the lamb via an increase in controller gain for oxygen. Our study demonstrates that a quantitative understanding of the factors that determine LG provides insight into the cause of PB.
Publisher: Wiley
Date: 21-12-2011
DOI: 10.1111/J.1440-1843.2011.02037.X
Abstract: Patients with OSA manifest different patterns of disease. However, this heterogeneity is more evident in patients with mild-moderate OSA than in those with severe disease and a high total AHI. We hypothesized that mild-moderate OSA can be categorized into discreet disease phenotypes, and the aim of this study was to comprehensively describe the pattern of OSA phenotypes through the use of cluster analysis techniques. The data for 1184 consecutive patients, collected over 24 months, was analysed. Patients with a total AHI of 5-30/h were categorized according to the sleep stage and position in which they were predominantly affected. This categorization was compared with one in which patients were grouped using a K-means clustering technique with log linear modelling and cross-tabulation. Patients with mild-moderate OSA can be categorized according to polysomnographic parameters. This clinical categorization was validated by comparison with a categorization in which patients were grouped by unsupervised K-means cluster analysis. The clinical groups identified were: (i) rapid eye movement (REM) predominant OSA, 44.6% (ii) non-REM predominant OSA, 18.9% (iii) supine predominant OSA, 61.9% and (iv) intermittent OSA, 12.4%. Patients categorized as having both REM and supine predominant OSA showed characteristics of both the REM predominant and supine predominant OSA groups. Patients with mild-moderate OSA show different polysomnographic phenotypes. This approach to categorization more appropriately reflects disease heterogeneity and the likely multiple pathophysiological processes involved in OSA.
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.EARLHUMDEV.2012.09.009
Abstract: Autonomic dysfunction, either sympathetic or parasympathetic, may explain the increased incidence of Sudden Infant Death Syndrome (SIDS) among preterm infants, as well as their subsequent heightened risk of hypertension in adulthood. As little is known about the development of autonomic function in preterm infants, we contrasted autonomic cardiovascular control across the first 6months after term-corrected age (CA) in preterm and term infants. Preterm (n=25) and age matched term infants (n=31) were studied at 2-4weeks, 2-3months and 5-6months CA using daytime polysomnography. Blood pressure and heart rate were measured during quiet (QS) and active (AS) sleep. Autonomic control was assessed using spectral indices of blood pressure and heart rate variability (BPV and HRV) in ranges of low frequency (LF, reflecting sympathetic+parasympathetic activity), high frequency (HF, respiratory-mediated changes+parasympathetic activity), and LF/HF ratio (sympatho-vagal balance). In preterm infants, HF HRV increased, LF/HF HRV decreased and LF BPV decreased with age (p<0.05) these changes were most evident in AS. Compared to term infants, preterm infants in QS exhibited lower LF, HF and total HRV at 5-6months higher HF BPV at all ages and lower LF BPV at 2-4weeks (p<0.05). With maturation, in preterm infants, parasympathetic modulation of the heart increases while sympathetic modulation of blood pressure decreases. Compared to term infants, preterm infants exhibit lesser parasympathetic modulation of the heart along with greater respiratory-mediated changes and lower sympathetic modulation of blood pressure. Impaired autonomic control in preterm infants may increase their risk of cardiovascular dysfunction later in life.
Publisher: Elsevier BV
Date: 07-2015
Publisher: European Respiratory Society (ERS)
Date: 09-2017
Publisher: Oxford University Press (OUP)
Date: 07-05-2019
Publisher: American Thoracic Society
Date: 25-10-2023
Publisher: American Physiological Society
Date: 11-2009
DOI: 10.1152/JAPPLPHYSIOL.00587.2009
Abstract: Limited evidence suggests that the ventilatory interaction between O 2 and CO 2 is additive after birth and becomes multiplicative with postnatal development. Such a switch may be linked to the propensity for periodic breathing (PB) in infancy. To test this idea, we characterized the maturation of the respiratory controller and its effect on breathing stability in ∼10-day-old lambs and 6-mo-old sheep. We measured 1) carotid body sensitivity via dynamic ventilatory responses to step changes in O 2 and CO 2 , 2) steady-state ventilatory sensitivity to CO 2 under hypoxic and hyperoxic conditions, 3) the dependence of the apneic threshold on arterial Po 2 , and 4) the effect of hypoxic or hypercapnic gas inhalation during induced PB. Stability of the system was assessed using surrogate measures of loop gain. Peripheral sensitivity to O 2 was higher in newborn than in older animals ( P 0.05), but peripheral CO 2 sensitivity was unchanged. Central CO 2 sensitivity was reduced with age, but the slopes of the ventilatory responses to CO 2 were the same in hypoxia and hyperoxia. Reduced arterial Po 2 caused a leftward shift in the apneic threshold at both ages. Inspiration of hypoxic gas during PB immediately halted PB, whereas hypercapnia stopped PB only after one or two further PB cycles. We conclude that the controller in the sheep remains additive over the first 6 mo of life. Our results also show that the loop gain of the respiratory control system is reduced with age, possibly as a result of a reduction of peripheral O 2 sensitivity.
Publisher: American Physiological Society
Date: 09-2012
DOI: 10.1152/JAPPLPHYSIOL.00091.2012
Abstract: The passive pharyngeal critical closing pressure (Pcrit) is measured using a series of pressure drops. However, pressure drops also lower end-expiratory lung volume (EELV), which independently affects Pcrit. We describe a technique to measure Pcrit at a constant EELV. Continuous positive airway pressure (CPAP)-treated obstructive sleep apnea (OSA) patients and controls were instrumented with an epiglottic catheter, magnetometers (to measure change in EELV), and nasal mask neumotachograph and slept supine on nasal CPAP. Pcrit was measured in standard fashion and using our novel “biphasic technique” in which expiratory pressure only was lowered for 1 min before the inspiratory pressure was dropped this allowed EELV to decrease to the drop level before performing the pressure drop. Seven OSA and three controls were studied. The biphasic technique successfully lowered EELV before the inspiratory pressure drop. Pcrit was similar between the standard and biphasic techniques (−0.4 ± 2.6 vs. −0.6 ± 2.3 cmH 2 O, respectively, P = 0.84). Interestingly, we noted three different patterns of flow limitation: 1) classic Starling resistor type: flow fixed and independent of downstream pressure 2) negative effort dependence within breaths: substantial decrease in flow, sometimes with complete collapse, as downstream pressure decreased and 3) and negative effort dependence across breaths: progressive reductions in peak flow as respiratory effort on successive breaths increased. Overall, EELV changes do not influence standard passive Pcrit measurements if breaths 3–5 of pressure drops are used. These results also highlight the importance of inspiratory collapse in OSA pathogenesis. The cause of negative effort dependence within and across breaths is not known and requires further study.
Publisher: Korean Society of Sleep Medicine
Date: 30-06-2023
Abstract: Patients with chronic rhinosinusitis (CRS) report improved sleep quality after dupilumab, an anti IL4/13 therapy. Concurrent CRS and obstructive sleep apnea (OSA) cases are not rare, and CRS seemingly raises nasal resistance. Thus, we hypothesized that improved sleep quality by dupilumab therapy in CRS patients might be due to lowered nasal resistance and subsequent improvement of unrecognized comorbid OSA. Patients with concurrent CRS and OSA were recruited. Nasal resistance was measured invasively with transnasal pressure and flow data collected during normal respiration in the supine position. Results from the first five participants did not support our hypothesis. Subjective and objective measures for CRS and nasal resistance values were improved with dupilumab therapy in CRS patients with nasal polyps. However, apnea severity and sleep-related subjective parameters did not change. In the patients with CRS without nasal polyps, no significant changes in either CRS or OSA-related measures were observed.
Publisher: Oxford University Press (OUP)
Date: 06-2015
DOI: 10.5665/SLEEP.4750
Publisher: Wiley
Date: 14-06-2010
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.RESP.2009.07.006
Abstract: Continous positive airway pressure (CPAP) is used to treat infant respiratory distress syndrome and apnea of prematurity, but its mode of action is not fully understood. We hypothesised that CPAP increases lung volume and stabilises respiratory control by decreasing loop gain (LG). Experimentally induced periodic breathing (PB) in the lamb was terminated early by CPAP in a dose-dependent manner, with a control epoch of 45.4+/-5.1s at zero CPAP falling to 32.9+/-5.4, 13.2+/-4.2 and 9.8+/-3.1s at 2.5, 5 and 10 cmH(2)O, respectively (p<0.001) corresponding duty ratios (duration of the ventilatory phase of PB ided by its cycle duration) increased from 0.50+/-0.02 to 0.62+/-0.05, 0.76+/-0.06 and 0.68+/-0.08, respectively (p<0.001). Since epoch duration and duty ratio are surrogate measures of LG, we conclude that CPAP ameliorates the effects of recurrent central apneas, and perhaps mixed and obstructive apneas, by decreasing LG via increases in lung volume.
Publisher: Elsevier BV
Date: 09-2014
Publisher: Elsevier BV
Date: 09-2017
Publisher: Oxford University Press (OUP)
Date: 02-2016
DOI: 10.5665/SLEEP.5440
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-01-2014
DOI: 10.5664/JCSM.3366
Publisher: American Academy of Pediatrics (AAP)
Date: 2012
Abstract: Impaired blood pressure (BP) control may underpin the increased incidence of the sudden infant death syndrome (SIDS) in preterm infants. This study aimed to examine the effects of preterm birth, postnatal age, and sleep state on BP control by measuring baroreflex sensitivity (BRS) across the first 6 months of term-corrected age (CA), when SIDS risk is greatest. Preterm (n = 25) and term (n = 31) infants were studied longitudinally at 2 to 4 weeks, 2 to 3 months, and 5 to 6 months CA using daytime polysomnography. BP was recorded during quiet (QS) and active (AS) sleep using a photoplethysmographic cuff placed around the infant’s wrist (Finometer [FMS, Finapres Medical Systems, Amsterdam, Netherlands]). BRS (milliseconds/mm Hg) was assessed in 1- to 2-minute epochs using cross-spectral analysis. In preterm infants, postnatal age had no significant effect on BRS within either QS or AS. This was in contrast to the maturational increase in QS observed in term infants. Compared with term infants, BRS of preterm infants was 38% higher at 2 to 4 weeks CA and 29% lower at 5 to 6 months CA during QS (P & .05). Comparing sleep states, BRS of preterm infants was 26% lower in QS compared with AS at 2 to 3 months CA (P & .05). Preterm birth impairs the normal maturational increase in BRS, resulting in a substantial reduction in BRS at 5 to 6 months CA during QS. Lower BRS during QS compared with AS at 2 to 3 months CA may place preterm infants at an increased risk for cardiovascular instability at this age of peak incidence of SIDS.
Publisher: European Respiratory Society (ERS)
Date: 02-2018
DOI: 10.1183/13993003.01419-2017
Abstract: In some in iduals with obstructive sleep apnoea (OSA), the palate prolapses into the velopharynx during expiration, limiting airflow through the nose or shunting it out of the mouth. We hypothesised that this phenomenon causes expiratory flow limitation (EFL) and is associated with inspiratory “isolated” palatal collapse. We also wanted to provide a robust noninvasive means to identify this mechanism of obstruction. Using natural sleep endoscopy, 1211 breaths from 22 OSA patients were scored as having or not having palatal prolapse. The patient-level site of collapse (tongue-related, isolated palate, pharyngeal lateral walls and epiglottis) was also characterised. EFL was quantified using expiratory resistance at maximal epiglottic pressure. A noninvasive EFL index (EFLI) was developed to detect the presence of palatal prolapse and EFL using the flow signal alone. In addition, the validity of using nasal pressure was assessed. A cut-off value of EFLI .8 detected the presence of palatal prolapse and EFL with an accuracy of % and 82%, respectively. The proportion of breaths with palatal prolapse predicted isolated inspiratory palatal collapse with 90% accuracy. This study demonstrates that expiratory palatal prolapse can be quantified noninvasively, is associated with EFL and predicts the presence of inspiratory isolated palatal collapse.
Publisher: Wiley
Date: 03-09-2014
Publisher: American Thoracic Society
Date: 15-10-2014
Publisher: Public Library of Science (PLoS)
Date: 04-12-2009
Publisher: Oxford University Press (OUP)
Date: 08-2013
DOI: 10.5665/SLEEP.2862
Publisher: Frontiers Media SA
Date: 21-12-2017
Publisher: American Physiological Society
Date: 05-2012
DOI: 10.1152/JAPPLPHYSIOL.01259.2011
Abstract: Airway distensibility appears to be unaffected by airway smooth muscle (ASM) tone, despite the influence of ASM tone on the airway diameter-pressure relationship. This discrepancy may be because the greatest effect of ASM tone on airway diameter-pressure behavior occurs at low transpulmonary pressures, i.e., low lung volumes, which has not been investigated. Our study aimed to determine the contribution of ASM tone to airway distensibility, as assessed via the forced oscillation technique (FOT), across all lung volumes with a specific focus on low lung volumes. We also investigated the accompanying influence of ASM tone on peripheral airway closure and heterogeneity inferred from the reactance versus lung volume relationship. Respiratory system conductance and reactance were measured using FOT across the entire lung volume range in 22 asthma subjects and 19 healthy controls before and after bronchodilator. Airway distensibility (slope of conductance vs. lung volume) was calculated at residual volume (RV), functional residual capacity (FRC), and total lung capacity. At baseline, airway distensibility was significantly lower in subjects with asthma at all lung volumes. After bronchodilator, distensibility significantly increased at RV (64.8%, P 0.001) and at FRC (61.8%, P 0.01) in subjects with asthma but not in control subjects. The increased distensibility at RV and FRC in asthma were not associated with the accompanying changes in the reactance versus lung volume relationship. Our findings demonstrate that, at low lung volumes, ASM tone reduces airway distensibility in adults with asthma, independent of changes in airway closure and heterogeneity.
Publisher: American Thoracic Society
Date: 08-2023
Publisher: Oxford University Press (OUP)
Date: 20-03-2018
DOI: 10.1093/SLEEP/ZSY040
Publisher: Springer Science and Business Media LLC
Date: 09-2007
Publisher: European Respiratory Society (ERS)
Date: 16-10-2014
DOI: 10.1183/09031936.00062914
Abstract: Elevated loop gain, consequent to hypersensitive ventilatory control, is a primary nonanatomical cause of obstructive sleep apnoea (OSA) but it is not possible to quantify this in the clinic. Here we provide a novel method to estimate loop gain in OSA patients using routine clinical polysomnography alone. We use the concept that spontaneous ventilatory fluctuations due to apnoeas/hypopnoeas (disturbance) result in opposing changes in ventilatory drive (response) as determined by loop gain (response/disturbance). Fitting a simple ventilatory control model (including chemical and arousal contributions to ventilatory drive) to the ventilatory pattern of OSA reveals the underlying loop gain. Following mathematical-model validation, we critically tested our method in patients with OSA by comparison with a standard (continuous positive airway pressure (CPAP) drop method), and by assessing its ability to detect the known reduction in loop gain with oxygen and acetazolamide. Our method quantified loop gain from baseline polysomnography (correlation versus CPAP-estimated loop gain: n=28 r=0.63, p .001), detected the known reduction in loop gain with oxygen (n=11 mean± sem change in loop gain (ΔLG) −0.23±0.08, p=0.02) and acetazolamide (n=11 ΔLG −0.20±0.06, p=0.005), and predicted the OSA response to loop gain-lowering therapy. We validated a means to quantify the ventilatory control contribution to OSA pathogenesis using clinical polysomnography, enabling identification of likely responders to therapies targeting ventilatory control.
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-05-2018
DOI: 10.5664/JCSM.7112
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-11-2013
DOI: 10.5664/JCSM.3158
Publisher: American Thoracic Society
Date: 10-2016
Publisher: Wiley
Date: 13-02-2012
Publisher: Oxford University Press (OUP)
Date: 07-2014
DOI: 10.5665/SLEEP.3844
Publisher: Hindawi Limited
Date: 15-06-2023
DOI: 10.1155/2023/8787132
Abstract: Obstructive sleep apnea (OSA) pathologically stresses the cardiovascular system. Apneic events cause significant oscillatory surges in nocturnal blood pressure (BP). Trajectories of these surges vary widely. This variability challenges the quantification, characterization, and mathematical modeling of BP surge dynamics. We present a method of aggregating trajectories of apnea-induced BP surges using a s le-by-s le averaging of continuously recorded BP. We applied the method to recordings of overnight BP (average total sleep time: 4.77 ± 1.64 h) for 10 OSA patients (mean AHI: 63.5 events/h range: 18.3-105.4). We studied surges in blood pressure due to obstructive respiratory events separated from other such events by at least 30 s (274 total events). These events increased systolic (SBP) and diastolic (DBP) BP by 19 ± 7.1 mmHg (14.8%) and 11 ± 5.6 mmHg (15.5%), respectively, relative to mean values during wakefulness. Further, aggregated SBP and DBP peaks occurred on average 9 s and 9.5 s after apnea events, respectively. Interestingly, the litude of the SBP and DBP peaks varied across sleep stages, with mean peak ranging from 128.8 ± 12.4 to 166.1 ± 15.5 mmHg for SBP and from 63.1 ± 8.2 to 84.2 ± 9.4 mmHg for DBP. The aggregation method provides a high level of granularity in quantifying BP oscillations from OSA events and may be useful in modeling autonomic nervous system responses to OSA-induced stresses.
Publisher: American Thoracic Society
Date: 11-2016
Publisher: Wiley
Date: 16-03-2017
DOI: 10.1111/RESP.13022
Abstract: Ethnic differences in obstructive sleep apnoea (OSA) phenotype may not be limited to obesity and craniofacial factors. The aims of the study were to (i) compare the proportion of Caucasians and Chinese patients with a low respiratory arousal threshold (ArTH) and (ii) explore the influence of anatomical compromise on ArTH. Interethnic comparison was conducted between cohorts of Caucasian and Chinese patients from specialist sleep disorder clinics. Polysomnography and craniofacial photography were performed. A low respiratory ArTH was determined by an ArTH score of 2 or above (one point for each: apnoea-hypopnoea index (AHI) < 30/h, nadir oxygen saturation (SaO A total of 348 subjects (163 Caucasians and 185 Chinese) were analysed. There was a significantly lower proportion of Chinese patients with moderate-severe OSA (AHI ≥ 15) who had a low ArTH (28.4% vs 48.8%, P = 0.004). This difference remained significant among those with severe OSA (AHI ≥ 30) (2.6% vs 17.1%, P = 0.02). The proportion of moderate-severe OSA Caucasians with a low ArTH was significantly less in those with severe anatomical compromise (36.6% vs 61.0%, P = 0.03), whereas there was no difference in Chinese patients (25.5% vs 31.5%, P = 0.49). Compared to Caucasians with severe OSA, a low respiratory ArTh appears to be a less common pathophysiological mechanism in Chinese patients. Caucasians with less severe anatomical compromise exhibit evidence of a lower ArTh, an association which is absent in Chinese patients. Our data suggest that OSA mechanisms may vary across racial groups.
Publisher: Elsevier BV
Date: 05-2023
Publisher: Wiley
Date: 23-12-2014
DOI: 10.1111/RESP.12216
Publisher: Oxford University Press (OUP)
Date: 31-01-2017
DOI: 10.1093/SLEEP/ZSX005
Publisher: American Thoracic Society
Date: 05-2018
Publisher: Oxford University Press (OUP)
Date: 23-07-2017
DOI: 10.1093/SLEEP/ZSX128
Publisher: BMJ
Date: 21-01-2022
DOI: 10.1136/THORAXJNL-2021-217756
Abstract: In the classic model of obstructive sleep apnoea (OSA), respiratory events occur with sleep-related dilator muscle hypotonia, precipitating increased neural ventilatory ‘drive’. By contrast, a drive-dependent model has been proposed, whereby falling drive promotes dilator muscle hypotonia to precipitate respiratory events. Here we determine the extent to which the classic versus drive-dependent models of OSA are best supported by direct physiological measurements. In 50 OSA patients (5–91 events/hour), we recorded ventilation (‘flow’, oronasal mask and pneumotach) and ventilatory drive (calibrated intraoesophageal diaphragm electromyography, EMG) overnight. Flow and drive during events were ensemble averaged patients were classified as drive dependent if flow fell/rose simultaneously with drive. Overnight effects of lower drive on flow, genioglossus muscle activity (EMGgg) and event risk were quantified (mixed models). On average, ventilatory drive fell (rather than rose) during events (−20 (−42 to 3)% baseline , median (IQR)) and was strongly correlated with flow (R=0.78 (0.24 to 0.94)). Most patients (30/50, 60%) were classified as exhibiting drive-dependent event pathophysiology. Lower drive during sleep was associated with lower flow (−17 (−20 to –14)%/drive) and EMGgg (−3.5 (−3.8 to –3.3)% max /drive) and greater event risk (OR: 2.2 (1.8 to 2.5) per drive reduction of 100% eupnoea ) associations were concentrated in patients with drive-dependent OSA (ie, flow: −37 (−40 to –34)%/drive, OR: 6.8 (5.3 to 8.7)). Oesophageal pressure—without tidal volume correction—falsely suggested rising drive during events ( classic model). In contrast to the prevailing view, patients with OSA predominantly exhibit drive-dependent event pathophysiology, whereby flow is lowest at nadir drive, and lower drive raises event risk. Preventing ventilatory drive decline is therefore considered a target for OSA intervention.
Publisher: Oxford University Press (OUP)
Date: 06-2011
DOI: 10.5665/SLEEP.1036
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-09-2017
DOI: 10.5664/JCSM.6716
Publisher: American Physiological Society
Date: 15-04-2014
DOI: 10.1152/JAPPLPHYSIOL.00853.2013
Abstract: The upper airway is often modeled as a classical Starling resistor, featuring a constant inspiratory airflow, or plateau, over a range of downstream pressures. However, airflow tracings from clinical sleep studies often show an initial peak before the plateau. To conform to the Starling model, the initial peak must be of small magnitude or dismissed as a transient. We developed a method to simulate fast or slow inspirations through the human upper airway, to test the hypothesis that this initial peak is a transient. Eight subjects [4 obstructive sleep apnea (OSA), 4 controls] slept in an “iron lung” and wore a nasal mask connected to a continuous/bilevel positive airway pressure machine. Downstream pressure was measured using an epiglottic catheter. During non-rapid eye movement (NREM) sleep, subjects were hyperventilated to produce a central apnea, then extrathoracic pressure was decreased slowly (∼2–4 s) or abruptly ( .5 s) to lower downstream pressure and create inspiratory airflow. Pressure-flow curves were constructed for flow-limited breaths, and slow vs. fast reductions in downstream pressure were compared. All subjects exhibited an initial peak and then a decrease in flow with more negative pressures, demonstrating negative effort dependence (NED). The rate of change in downstream pressure did not affect the peak to plateau airflow ratio: %NED 22 ± 13% (slow) vs. 20 ± 5% (fast), P = not significant. We conclude that the initial peak in inspiratory airflow is not a transient but rather a distinct mechanical property of the upper airway. In contrast to the classical Starling resistor model, the upper airway exhibits marked NED in some subjects.
Publisher: Wiley
Date: 31-10-2016
DOI: 10.1111/RESP.12927
Publisher: American Thoracic Society
Date: 12-2016
Publisher: American Thoracic Society
Date: 15-01-2017
Publisher: Oxford University Press (OUP)
Date: 10-12-2017
DOI: 10.1093/SLEEP/ZSW005
Publisher: Oxford University Press (OUP)
Date: 13-04-2017
DOI: 10.1093/SLEEP/ZSX056
Publisher: Wiley
Date: 06-07-2018
DOI: 10.1113/JP276206
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.JSMC.2015.10.003
Abstract: Congestive heart failure (CHF) is among the most common causes of admission to hospitals in the United States, especially in those over age 65. Few data exist regarding the prevalence CHF of Cheyne-Stokes respiration (CSR) owing to congestive heart failure in the intensive care unit (ICU). Nevertheless, CSR is expected to be highly prevalent among those with CHF. Treatment should focus on the underlying mechanisms by which CHF increases loop gain and promotes unstable breathing. Few data are available to determine prevalence of CSR in the ICU, or how CSR might affect clinical management and weaning from mechanical ventilation.
Publisher: American Thoracic Society
Date: 15-06-2017
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.RESP.2010.04.003
Abstract: Preterm infants have a reduced pulmonary diffusing capacity that has been invoked to explain rapid arterial O(2)-desaturation during apnea, despite little evidence to support this view. We explored the role of diffusion limitation on O(2)-desaturation during apnea by developing a mathematical model of gas exchange in which O(2) dynamically loads the blood traversing the pulmonary capillary. While normal diffusing capacity DL((O(2)) had negligible impact on apneic desaturation, reduced DL((O(2)) advanced the onset of desaturation during apnea. Unexpectedly, despite considerable diffusion limitation, its influence on O(2)-desaturation disappeared within 15s, because its impact in slowing alveolar O(2) depletion maintained a higher driving pressure for diffusion. In contrast, reduced DL((O(2)) substantially slowed reoxygenation following apnea. Our findings do not support the hypothesis that reduced DL((O(2)) explains the rapid apneic desaturation observed in preterm infants. Instead, the signature of reduced DL((O(2)) is a prolonged hypoxemia following apnea, potentially causing a persistence of hypoxic conditions when heart rate and cardiac workload reach a peak.
Publisher: Wiley
Date: 13-04-2017
DOI: 10.1111/RESP.13044
Publisher: Elsevier BV
Date: 06-2010
DOI: 10.1016/J.JTBI.2010.03.041
Abstract: Ventilation-perfusion (V/Q) mismatch is a prominent feature of preterm infants and adults with lung disease. V/Q mismatch is known to cause arterial hypoxemia under steady-state conditions, and has been proposed as the cause of rapid arterial oxygen desaturation during apnea. However, there is little evidence to support a role for V/Q mismatch in the dynamic changes in arterial oxygenation that occur during apnea. Using a mathematical model, we quantified the effect of V/Q mismatch on the rate of desaturation during apnea to ascertain whether it could lead to rates of up to 10%s(-1) as observed in preterm infants. We used a lung-body model for the preterm infant that incorporated 50 parallel alveolar-capillary units that were ventilated and perfused with the severity of V/Q mismatch (sigma) defined conventionally according to sigma=S.D. of the distribution of V/Q ratios. Average desaturation rate 10s from apnea onset was strongly elevated with worsening V/Q mismatch as a result of an earlier desaturation of low V/Q units compared with high V/Q units. However, V/Q mismatch had little impact after apnea onset, with peak desaturation rate only substantially increased if mismatching caused a lowered resting arterial O(2) saturation. In conclusion, V/Q mismatch causes a more immediate onset of desaturation during apnea, and therefore places preterm infants and adults with lung disease at risk of hypoxemic dips. However, V/Q mismatch does not accelerate desaturation rate beyond apnea onset and cannot, therefore, explain the rapid desaturation observed during recurrent apnea in preterm infants.
Publisher: American Thoracic Society
Date: 02-08-2023
Publisher: Oxford University Press (OUP)
Date: 09-11-2018
DOI: 10.1093/SLEEP/ZSX183
Publisher: American Thoracic Society
Date: 11-2011
Publisher: Elsevier BV
Date: 07-2015
Publisher: American Physiological Society
Date: 08-2015
DOI: 10.1152/JAPPLPHYSIOL.01105.2014
Abstract: Systemic maternal inflammation is implicated in preterm birth and bronchopulmonary dysplasia (BPD) and may induce morbidities including reduced pulmonary function, sleep-disordered breathing, and cardiovascular disorders. Here we test the hypothesis that antenatal maternal inflammation per se causes altered alveolar development and increased chemoreflex sensitivity that persists beyond infancy. Pregnant C57BL/6 mice were administered lipopolysaccharide (LPS) (150 μg/kg ip) to induce maternal inflammation or saline (SHAM) at embryonic day 16 (randomized). Pups were weighed daily. On days 7, 28, and 60 (D07, D28, and D60), unrestrained wholebody plethysmography quantified ventilation and chemoreflex responses to hypoxia (10%), hypercapnia (7%), and asphyxia (hypoxic hypercapnia). Lungs were harvested to quantify alveolar number, size, and septal thickness. LPS pups had reduced baseline ventilation per unit bodyweight (∼40%, P 0.001) vs. SHAM. LPS increased ventilatory responses to hypoxia (D07: 66% vs. 28% increase in ventilation P 0.001) hypercapnia (170% vs. 88% P 0.001), and asphyxia (249% vs. 154% P 0.001) hypersensitive hypoxic responsiveness persisted until D60 ( P 0.001). LPS also increased apnea frequency ( P 0.01). LPS caused thicker alveolar septae (D07, P 0.001), diminished alveolar number (D28, P 0.001) vs. SHAM, but effects were minimal by D60. Pups delivered from mothers exposed to antenatal inflammation exhibit deficits in lung structure and hypersensitive responses to respiratory stimuli that persist beyond the newborn period. Antenatal inflammation may contribute to impaired gas exchange and unstable breathing in newborn infants and adversely affect long-term health.
Publisher: Elsevier BV
Date: 12-2018
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.RESP.2012.06.003
Abstract: Any general model of respiratory control must explain a puzzling array of breathing patterns that are observed during the course of a lifetime. Particular challenges are to understand why periodic breathing is rarely seen in the first few days after birth, reaches a peak at 2-4 weeks postnatal age, and disappears by 6 months, why it is prevalent in preterm infants, and why it reappears in adults at altitude or with heart failure. In this review we use the concept of loop gain to obtain quantitative insight into the genesis of unstable breathing patterns with a particular focus on how changes in carotid body function could underlie the age-related dependence of periodic breathing.
Publisher: Springer Science and Business Media LLC
Date: 13-05-2022
DOI: 10.1007/S11325-022-02634-X
Abstract: Preliminary studies have shown a significant decrease in severity of obstructive sleep apnea (OSA) with the use of a combination of atomoxetine and oxybutynin, with patients having moderate pharyngeal collapsibility during sleep more likely to respond. This study evaluated the efficacy and safety of AD036 (atomoxetine 80 mg and oxybutynin 5 mg) in the treatment of OSA. This trial was a phase 2, randomized, placebo-controlled crossover study comparing AD036, atomoxetine 80 mg alone, and placebo during three home sleep studies, each separated by about 1 week. The trial included patients with OSA and moderate pharyngeal collapsibility as defined by a higher proportion of hypopneas to apneas and mild oxygen desaturation. Of 62 patients who were randomized, 60 were included in efficacy analyses. The apnea–hypopnea index (AHI) from a median (interquartile range) of 14.2 (5.4 to 22.3) events/h on placebo to 6.2 (2.8 to 13.6) with AD036 and 4.8 (1.4 to 11.6) with atomoxetine alone ( p .0001). Both drugs also decreased the oxygen desaturation index (ODI) and the hypoxic burden ( p .0001). AD036, but not atomoxetine alone, reduced the respiratory arousal index and improved ventilation at the respiratory arousal threshold (greater V active ). There was a trend for total sleep time to be decreased more with atomoxetine alone than with AD036. The most common adverse event was insomnia (12% with AD036, 18% with atomoxetine). AD036 significantly improved OSA severity in patients with moderate pharyngeal collapsibility. Atomoxetine may account for the majority of improvement in OSA severity, while the addition of oxybutynin may mitigate the disruptive effect of atomoxetine on sleep and further improve ventilation. Clinical trial registered with www.clinicaltrials.gov (NCT04445688).
Publisher: American Thoracic Society
Date: 15-05-2018
Publisher: American Physiological Society
Date: 04-2013
DOI: 10.1152/JAPPLPHYSIOL.00747.2012
Abstract: We previously published a method for measuring several physiological traits causing obstructive sleep apnea (OSA). The method, however, had a relatively low success rate (76%) and required mathematical modeling, potentially limiting its application. This paper presents a substantial revision of that technique. To make the measurements, continuous positive airway pressure (CPAP) was manipulated during sleep to quantify 1) eupneic ventilatory demand, 2) the level of ventilation at which arousals begin to occur, 3) ventilation off CPAP (nasal pressure = 0 cmH 2 O) when the pharyngeal muscles are activated during sleep, and 4) ventilation off CPAP when the pharyngeal muscles are relatively passive. These traits could be determined in all 13 participants (100% success rate). There was substantial intersubject variability in the reduction in ventilation that in iduals could tolerate before having arousals (difference between ventilations #1 and #2 ranged from 0.7 to 2.9 liters/min) and in the amount of ventilatory compensation that in iduals could generate (difference between ventilations #3 and #4 ranged from −0.5 to 5.5 liters/min). Importantly, the measurements accurately reflected clinical metrics the difference between ventilations #2 and #3, a measure of the gap that must be overcome to achieve stable breathing during sleep, correlated with the apnea-hypopnea index ( r = 0.9, P 0.001). An additional procedure was added to the technique to measure loop gain (sensitivity of the ventilatory control system), which allowed arousal threshold and upper airway gain (response of the upper airway to increasing ventilatory drive) to be quantified as well. Of note, the traits were generally repeatable when measured on a second night in 5 in iduals. This technique is a relatively simple way of defining mechanisms underlying OSA and could potentially be used in a clinical setting to in idualize therapy.
Publisher: Wiley
Date: 04-05-2015
DOI: 10.1111/RESP.12549
Abstract: This study aimed to evaluate the involvement of airway cross-sectional area and shape, and functional residual capacity (FRC), in the genesis of obstructive sleep apnoea (OSA) in patients with supine-predominant OSA. Three groups were recruited: (i) supine OSA, defined as a supine apnoea-hyponoea index (AHI) at least twice that of the non-supine AHI (ii) rapid eye movement (REM) OSA, defined as REM AHI at least twice the non-REM AHI and also selected to have supine AHI less than twice that of the non-supine AHI (i.e. to be non-positional) and (iii) no OSA, defined as an AHI less than five events per hour. The groups were matched for age, gender and body mass index. Patients underwent four-dimensional computed tomography scanning of the upper airway in the supine and lateral decubitus positions. FRC was measured in the seated, supine and lateral decubitus positions. Patients with supine OSA demonstrated a significant decrease in FRC of 340 mL (P = 0.026) when moving from the lateral to supine position compared to controls with no OSA, and REM OSA patients. We found no differences between groups in upper airway size and shape. However, all groups showed a significant change in airway shape with the velopharyngeal airway adopting a more elliptoid shape (with the long axis laterally oriented), with reduced anteroposterior diameter in the supine position. A fall in FRC when moving lateral to supine in supine OSA patients may be an important triggering factor in the generation of OSA in this patient group.
Publisher: Elsevier BV
Date: 11-2013
Publisher: European Respiratory Society (ERS)
Date: 09-2016
DOI: 10.1183/13993003.00615-2016
Abstract: Cheyne–Stokes respiration (CSR) foretells deleterious outcomes in patients with heart failure. Currently, the size of therapeutic intervention is not guided by the patient's underlying pathophysiology. In theory, the intervention needed to resolve CSR, as a control system instability (loop gain ), can be predicted knowing the baseline loop gain and how much it falls with therapy. In 12 patients with heart failure, we administered an inspiratory carbon dioxide fraction of 1–3% during CSR (n=95 interventions) as a means to reduce loop gain. We estimated the loop gain on therapy (LG therapy ), using the baseline loop gain (using hyperpnoea length/cycle length) and its expected reduction (18% per 1% inspired carbon dioxide), and tested the specific hypothesis that LG therapy predicts CSR persistence (LG therapy ) versus resolution (LG therapy ). As predicted, when LG therapy .0, CSR continued during therapy in 23 out of 25 (92%) trials. A borderline loop gain zone (0.8 LG therapy ) yielded an unpredictable outcome, while LG therapy .8 consistently yielded CSR resolution (37 out of 37 trials). A threshold of LG therapy =0.9 determined outcome in 76 out of 95 (80%) trials. We establish proof-of-concept that control theory provides predictive insight into CSR resolution in heart failure. Thus, we now have a means to calculate the size of interventions needed to ameliorate CSR on a patient-by-patient basis.
Publisher: American Thoracic Society
Date: 15-06-2021
Publisher: American Thoracic Society
Date: 09-2015
Publisher: European Respiratory Society (ERS)
Date: 06-10-2016
DOI: 10.1183/13993003.00823-2016
Abstract: We recently demonstrated that desipramine reduces the sleep-related loss of upper airway dilator muscle activity and reduces pharyngeal collapsibility in healthy humans without obstructive sleep apnoea (OSA). The aim of the present physiological study was to determine the effects of desipramine on upper airway collapsibility and apnoea–hypopnea index (AHI) in OSA patients. A placebo-controlled, double-blind, randomised crossover trial in 14 OSA patients was performed. Participants received treatment or placebo in randomised order before sleep. Pharyngeal collapsibility (critical collapsing pressure of the upper airway ( P crit )) and ventilation under both passive ( V′ 0,passive ) and active ( V′ 0,active ) upper airway muscle conditions were evaluated with continuous positive airway pressure (CPAP) manipulation. AHI was quantified off CPAP. Desipramine reduced active P crit (median (interquartile range) −5.2 (4.3) cmH 2 O on desipramine versus −1.9 (2.7) cmH 2 O on placebo p=0.049) but not passive P crit (−2.2 (3.4) versus −0.7 (2.1) cmH 2 O p=0.135). A greater reduction in AHI occurred in those with minimal muscle compensation (defined as V′ 0,active − V′ 0,passive ) on placebo (r=0.71, p=0.009). The reduction in AHI was driven by the improvement in muscle compensation (r=0.72, p=0.009). In OSA patients, noradrenergic stimulation with desipramine improves pharyngeal collapsibility and may be an effective treatment in patients with minimal upper airway muscle compensation.
Publisher: American Thoracic Society
Date: 12-2014
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-03-2012
Abstract: High-grade gliomas of the CNS are characterized by poor treatment response and prognosis for long-term survival. The Children's Oncology Group (COG) L991 study investigated the neuropsychological, behavioral, and quality of life (QoL) outcomes after treatment on the Children's Cancer Group (CCG) trial for high-grade gliomas (CCG-945). Fifty-four patients (29 males, 25 females) with a median age of 8.8 years at diagnosis (range, 0.2 to 19.5 years) were enrolled at 25 institutions in North America, representing 81% of available survivors median length of follow-up was 15.1 years (range, 9.5 to 19.2 years), and median age at study evaluation was 23.6 years (range, 11.3 to 36 years). Standardized tests of neuropsychological functioning and QoL were performed. Descriptive statistics summarized principal findings, and one-way analysis of variance identified potential predictors of outcomes. With an average follow-up time of 15 years, survivors demonstrated intellectual functioning within the low-average range. Executive functioning and verbal memory were between the low-average and borderline ranges. In contrast, visual memory and psychomotor processing speed were between the borderline and impaired ranges, respectively. Approximately 75% of patient reported overall QoL within or above normal limits for both physical and psychosocial domains. Nonhemispheric tumor location (midline or cerebellum), female sex, and younger age at treatment emerged as independent risk factors. These results serve as a benchmark for comparison with future pediatric high-grade glioma studies, in addition to identifying at-risk cohorts that warrant further research and proactive interventions to minimize late effects while striving to ensure survival.
Publisher: Elsevier BV
Date: 07-2014
Publisher: Wiley
Date: 20-07-2017
DOI: 10.1111/RESP.13108
Publisher: American Thoracic Society
Date: 03-2013
Publisher: Elsevier BV
Date: 11-2017
Publisher: Springer Science and Business Media LLC
Date: 24-06-2016
Publisher: American Physiological Society
Date: 07-2011
DOI: 10.1152/JAPPLPHYSIOL.01358.2010
Abstract: Cyclic ventilatory instabilities are widely attributed to an increase in the sensitivity or loop gain of the chemoreflex feedback loop controlling ventilation. A major limitation in the conventional characterization of this feedback loop is the need for labor-intensive methodologies. To overcome this limitation, we developed a method based on trivariate autoregressive modeling using ventilation, end-tidal Pco 2 and Po 2 this method provides for estimation of the overall “loop gain” of the respiratory control system and its components, chemoreflex gain and plant gain. Our method was applied to recordings of spontaneous breathing in 15 anesthetized, tracheostomized, newborn lambs before and after administration of domperidone (a dopamine D 2 -receptor antagonist that increases carotid body sensitivity). We quantified the known increase in hypoxic ventilatory sensitivity in response to domperidone controller gain for O 2 increased from 0.06 (0.03, 0.09) l·min −1 ·mmHg −1 to 0.09 (0.08, 0.13) l·min −1 ·mmHg −1 median (interquartile-range). We also report that domperidone increased the loop gain of the control system more than twofold [0.14 (0.12, 0.22) to 0.40 (0.15, 0.57)]. We observed no significant changes in CO 2 controller gain, or plant gains for O 2 and CO 2 . Furthermore, our estimate of the cycle duration of periodic breathing compared favorably with that observed experimentally [measured: 7.5 (7.2, 9.1) vs. predicted: 7.9 (7.0, 9.2) breaths]. Our results demonstrate that model-based analysis of spontaneous breathing can 1) characterize the dynamics of the respiratory control system, and 2) provide a simple tool for elucidating an in idual's propensity for ventilatory instability, in turn allowing potential therapies to be directed at the underlying mechanisms.
Publisher: European Respiratory Society (ERS)
Date: 10-2020
DOI: 10.1183/23120541.00123-2020
Abstract: A workshop entitled “Stem Cells, Cell Therapies and Bioengineering in Lung Biology and Diseases” was hosted by the University of Vermont Larner College of Medicine in collaboration with the National Heart, Lung and Blood Institute, the Alpha-1 Foundation, the Cystic Fibrosis Foundation, the International Society for Cell and Gene Therapy and the Pulmonary Fibrosis Foundation. The event was held from July 15 to 18, 2019 at the University of Vermont, Burlington, Vermont. The objectives of the conference were to review and discuss the current status of the following active areas of research: 1) technological advancements in the analysis and visualisation of lung stem and progenitor cells 2) evaluation of lung stem and progenitor cells in the context of their interactions with the niche 3) progress toward the application and delivery of stem and progenitor cells for the treatment of lung diseases such as cystic fibrosis 4) progress in induced pluripotent stem cell models and application for disease modelling and 5) the emerging roles of cell therapy and extracellular vesicles in immunomodulation of the lung. This selection of topics represents some of the most dynamic research areas in which incredible progress continues to be made. The workshop also included active discussion on the regulation and commercialisation of regenerative medicine products and concluded with an open discussion to set priorities and recommendations for future research directions in basic and translation lung biology.
Publisher: Oxford University Press (OUP)
Date: 02-2013
DOI: 10.5665/SLEEP.2390
Publisher: American Physiological Society
Date: 15-03-2012
DOI: 10.1152/JAPPLPHYSIOL.00372.2011
Abstract: We describe a method to determine the phase III slope for the purpose of calculating indexes of ventilation heterogeneity, S acin and S cond , from the multiple breath nitrogen washout test (MBNW). Our automated method applies a recursive, segmented linear regression technique to each breath of the MBNW test and determines the best point of transition, or breakpoint, between each phase of the washout. A s le set of 50 MBNW tests (controls, asthma, and COPD) was used to establish the conditions in which the phase III slope obtained from the automated technique best matched that obtained by two manual interpreters. We then applied our technique to a test set of 30 subjects (with an even number of subjects in each of the above groups) and compared these results against the manual analysis of a third independent manual interpreter. Indexes of ventilation heterogeneity were determined using both methods and compared. The phase III slopes determined by the automatic technique best matched the manual interpreter when the phase III slope was calculated from the phase II-III transition point plus the addition of 50% of the phase II volume to the end of the expiration. Calculation of the indexes S acin and S cond showed no overall difference between analysis methods in either S acin ( P = 0.14) or S cond ( P = 0.59) when the set threshold was applied to our automated analysis. Our analysis method provides an alternate means for rapid quantification of the MBNW test, removing operator dependence without alteration in either S acin or S cond .
Publisher: American Thoracic Society
Date: 07-04-2017
Publisher: Oxford University Press (OUP)
Date: 02-2012
DOI: 10.5665/SLEEP.1616
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.RESP.2017.06.006
Abstract: Short pauses or "transition-periods" at the end of expiration and prior to subsequent inspiration are commonly observed during sleep in humans. However, the role of transition periods in regulating ventilation during physiological challenges such as partial airway obstruction (PAO) has not been investigated. Twenty-nine obstructive sleep apnea patients and eight controls underwent overnight polysomnography with an epiglottic catheter. Sustained-PAO segments (increased epiglottic pressure over ≥5 breaths without increased peak inspiratory flow) and unobstructed reference segments were manually scored during apnea-free non-REM sleep. Nasal pressure data was computationally segmented into inspiratory (T
Publisher: American Thoracic Society
Date: 2014
Location: Germany
No related grants have been discovered for Scott Sands.