Validation of a single-use and reusable home sleep apnea test based on peripheral arterial tonometry compared to laboratory polysomnography for the diagnosis of obstructive sleep apnea.

STUDY OBJECTIVES: The objective of this study was to independently validate a disposable and a reusable home sleep apnea test (HSAT) recording on peripheral arterial tonometry, compared to laboratory polysomnography (PSG), for the diagnosis of obstructive sleep apnea (OSA). METHODS: 115 participants undergoing PSG for suspected OSA were recruited and fitted with the two study devices (NightOwl, Ectosense, Belgium). After exclusions were applied and device failures were removed, data from 100 participants were analyzed. HSAT-derived apnea-hypopnea index (AHI), OSA severity category, total sleep time, and oxygen desaturation index 3% were compared to PSG. RESULTS: Both study devices demonstrated satisfactory levels of agreement with minimal mean bias for determination of AHI and oxygen desaturation index 3% (disposable: AHI mean bias 2.04 events/h [95% limits of agreement -20.9 to 25.0], oxygen desaturation index 3% mean bias -0.21/h [-18.1 to 17.7]; reusable: AHI mean bias 2.91 events/h [-16.9 to 22.7], oxygen desaturation index 3% mean bias 0.77/h [-15.7 to 17.3]). Level of agreement diminished at higher AHI levels although misclassification for severe OSA occurred infrequently. Total sleep time level of agreement for the reusable HSAT was also satisfactory with minimal mean bias (4.18 minutes, -125.1 to 112.4), but the disposable HSAT was impacted by studies with high signal rejection (23.7 minutes, -132.7 to 180.1). Categorization of OSA severity demonstrated moderate agreement with laboratory PSG, with a kappa of 0.52 and 0.57 for the disposable and reusable HSATs respectively. CONCLUSIONS: The two HSAT devices were comparable and performed well compared to laboratory PSG for the diagnosis of OSA. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Identifier: ANZCTR12621000444886. CITATION: Lyne CJ, Hamilton GS, Turton ARE, et al. Validation of a single-use and reusable home sleep apnea test based on peripheral arterial tonometry compared to laboratory polysomnography for the diagnosis of obstructive sleep apnea. J Clin Sleep Med. 2023;19(8):1429-1435.

Examining the impact of multilevel upper airway surgery on the obstructive sleep apnoea endotypes and their utility in predicting surgical outcomes.

BACKGROUND AND OBJECTIVE: Upper airway surgery for obstructive sleep apnoea (OSA) is an alternative treatment for patients who are intolerant of continuous positive airway pressure (CPAP). However, upper airway surgery has variable treatment efficacy with no reliable predictors of response. While we now know that there are several endotypes contributing to OSA (i.e., upper airway collapsibility, airway muscle response/compensation, respiratory arousal threshold and loop gain), no study to date has examined: (i) how upper airway surgery affects all four OSA endotypes, (ii) whether knowledge of baseline OSA endotypes predicts response to surgery and (iii) whether there are any differences when OSA endotypes are measured using the CPAP dial-down or clinical polysomnographic (PSG) methods. METHODS: We prospectively studied 23 OSA patients before and ≥3 months after multilevel upper airway surgery. Participants underwent clinical and research PSG to measure OSA severity (apnoea-hypopnoea index [AHI]) and endotypes (measured in supine non-rapid eye movement [NREM]). Values are presented as mean ± SD or median (interquartile range). RESULTS: Surgery reduced the AHITotal (38.7 [23.4 to 79.2] vs. 22.0 [13.3 to 53.5] events/h; p = 0.009). There were no significant changes in OSA endotypes, however, large but variable improvements in collapsibility were observed (CPAP dial-down method: ∆1.9 ± 4.9 L/min, p = 0.09, n = 21; PSG method: ∆3.4 [-2.8 to 49.0]%Veupnoea , p = 0.06, n = 20). Improvement in collapsibility strongly correlated with improvement in AHI (%∆AHISupineNREM vs. ∆collapsibility: p < 0.005; R2  = 0.46-0.48). None of the baseline OSA endotypes predicted response to surgery. CONCLUSION: Surgery unpredictably alters upper airway collapsibility but does not alter the non-anatomical endotypes. There are no baseline predictors of response to surgery.

Will the extraction of COVID-19 from wastewater help flatten the curve?

With the potentially fatal effect of COVID-19 and its devastating impact on economies worldwide, some environmental scientist has suggested the use of waste from household sewage to trace the movement of SARS-CoV-2, within a given country. However, this approach is not without challenges where developing countries lack proper and adequate hygiene and sanitation, resulting in widespread defecation. Limited scientific research has been done to determine how many times a recently infected person can defecate and the quantification of SARS-CoV-2 found in a single expel. On the other hand, there is no detailed research to specify where the heavy viral load of SARS-CoV-2 can be found in human excreta. In this paper, we present some obstacles that this approach could face in the absence of an intense lockdown in developing nations such as sub-Saharan countries. To achieve this, we identify some research needs that will strengthen our understanding of the transmission, occurrence, and persistence of SARS-CoV-2 in sewage and wastewater, including the life-span that depends on temperature. A methodology to follow in the process of identifying a hotspot on a small scale using some mathematical distributions, including the normal distribution, log-normal distribution, and the most complex one known as Blancmange function, was presented with some examples. Our investigation showed that this method might have some challenges, especially in developing countries (sub-Sahara countries) where open latrine usage is very high. Some recommendations we suggested to ensure the efficiency of such a method on a small scale. However, in general, it is essential to note the extraction/detection method will not help more than the testing method used all over the world to trace SARS-CoV-2 -19 in humans.

Assessing the Physiologic Endotypes Responsible for REM- and NREM-Based OSA.

BACKGROUND: Patients with OSA can have the majority of their respiratory events in rapid eye movement (REM) sleep or in non-rapid eye movement (NREM) sleep. No previous studies have linked the different physiologic conditions in REM and NREM sleep to the common polysomnographic patterns seen in everyday clinical practice, namely REM predominant OSA (REMOSA) and NREM predominant OSA (NREMOSA). RESEARCH QUESTION: (1) How does OSA physiologic condition change with sleep stage in patients with NREMOSA and REMOSA? (2) Do patients with NREMOSA and REMOSA have different underlying OSA pathophysiologic conditions? STUDY DESIGN AND METHODS: We recruited patients with three polysomnographic patterns. (1) REMOSA: twice as many respiratory events in REM sleep, (2) NREMOSA: twice as many events in NREM sleep, and (3) uniform OSA: equal number of events in NREM/REM sleep. We deployed a noninvasive phenotyping method to determine OSA endotype traits (Vpassive, Vactive, loop gain, arousal threshold) in NREM sleep, REM sleep, and total night sleep in each group of patients (NREMOSA, REMOSA, uniform OSA). RESULTS: Patients with NREMOSA have significantly worse ventilatory control stability in NREM sleep compared with REM sleep (loop gain, 0.546 [0.456,0.717] in NREM vs 0.365 [0.238,0.459] in REM sleep; P = .0026). Patients with REMOSA displayed a significantly more collapsible airway (ie, lower Vpassive) in REM compared with NREM sleep (98.4 [97.3,99.2] %Veupnea in NREM vs 95.9 [86.4,98.9] %Veupnea in REM sleep; P < .0001). The major between-group difference across the whole night was a significantly higher loop gain in the NREMOSA group (0.561 [0.429,0.675]) compared with the REMOSA group (0.459 [0.388,0.539]; P = .0033). INTERPRETATION: This study is the first to link long-recognized polysomnographic patterns of OSA to underlying physiologic differences. Patients with NREMOSA have a higher loop gain in NREM sleep; patients with REMOSA have a worsening of Vpassive in REM sleep.

A randomized controlled trial of oxygen therapy for patients who do not respond to upper airway surgery for obstructive sleep apnea.

STUDY OBJECTIVES: We aimed to determine whether patients diagnosed with obstructive sleep apnea (OSA) who fail to respond to upper airway surgery may be successfully treated with supplemental oxygen and whether we could identify baseline physiologic endotypes (ie, collapsibility, loop gain, arousal threshold, and muscle compensation) that predict response to oxygen therapy. METHODS: We conducted a single night, randomized double-blinded cross over trial in which patients with OSA who failed to respond to upper airway surgery were treated on separate nights with oxygen therapy (4 L/min) or placebo (medical air). Effect of oxygen/air on OSA on key polysomnography outcomes were assessed: apnea-hypopnea index (AHI), AHI without desaturation (ie, flow-based AHI), arousal index, and morning blood pressure. OSA endotypes were estimated from the polysomnography signals to determine whether baseline OSA physiology could be used to predict response to oxygen therapy. RESULTS: There was a statistically significant reduction in AHI and flow-based AHI on oxygen vs placebo (flow-based AHI: 42.4 ± 21.5 vs 30.5 ± 17.1 events/h, P = .008). Arousal index was also reduced on oxygen vs placebo (41.1 ± 19.5 vs 33.0 ± 15.3 events/h, P = .006). There was no significant difference in morning blood pressure between oxygen and placebo. Although 7 of 20 individuals experienced a 50% reduction or greater in flow-based AHI on oxygen (responders), there was no difference in the baseline OSA endotypes (or clinical characteristics) between responders and nonresponders. CONCLUSIONS: Our findings demonstrate that a proportion of patients who fail to respond to upper airway surgery for OSA respond acutely to treatment with supplemental oxygen. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; Name: Oxygen therapy for treating patients with residual obstructive sleep apnea following upper airway surgery; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373566; Identifier: ACTRN12617001361392.

Effect of Hypopnea Scoring Criteria on Noninvasive Assessment of Loop Gain and Surgical Outcome Prediction.

Rationale: Unstable ventilatory control (high loop gain) is a causal factor in the development of obstructive sleep apnea. Methods for quantifying loop gain using polysomnography have been developed that predict favorable responses to upper airway surgery. However, this method is reliant on respiratory event scoring and hence may be affected by hypopnea scoring criteria.Objectives: To determine to what extent differences in hypopnea scoring influence loop gain measurement.Methods: We performed a retrospective analysis of 46 polysomnograms before and after upper airway surgery. Polysomnograms were rescored according to three different American Academy of Sleep Medicine hypopnea definitions (2007Alternative, 2012Recommended, and 2012Acceptable criteria). Loop gain and apnea-hypopnea indexes (AHIs) were compared between criteria using linear regression and Bland-Altman limits of agreement (LOA). Responders to surgery were classified by a 50% or greater reduction in AHI and AHIpostsurgery less than 10 events per hour. Responders were determined separately for each American Academy of Sleep Medicine criterion. Receiver operating characteristic curve analysis predicting surgical outcome was performed for each loop gain measurement derived from each criterion.Results: A near-perfect agreement was found between loop gains derived using the 2007Alternative and 2012Recommended criteria (r2 = 0.99; bias = -0.003; LOA, -0.016 to 0.010). Greater variability was found for 2012Acceptable compared to the 2007Alternative (r2 = 0.70; bias = -0.015; LOA, -0.099 to 0.070) and 2012Recommended (r2 = 0.69; bias = +0.018; LOA, -0.068 to 0.104) criteria. Both 2007Alternative and 2012Recommended loop gains significantly predicted surgical response with similar areas under the curve (AUCs; 2007Alternative AUC = 0.86 [95% confidence interval (CI), 0.75-0.97]; 2012Recommended AUC = 0.84 [95% CI, 0.71-0.97]). 2012Acceptable loop gains were a poor predictor of surgical response (AUC = 0.62 [95% CI, 0.43-0.80]).Conclusions: Loop gain measured noninvasively by polysomnography can be influenced by respiratory event scoring. We recommend caution when using the 2012Acceptable criteria with this method, because such findings may not be directly generalizable to other loop gain values derived from other scoring criteria.

Dynamic loop gain increases upon adopting the supine body position during sleep in patients with obstructive sleep apnoea.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea (OSA) is typically worse in the supine versus lateral sleeping position. One potential factor driving this observation is a decrease in lung volume in the supine position which is expected by theory to increase a key OSA pathogenic factor: dynamic ventilatory control instability (i.e. loop gain). We aimed to quantify dynamic loop gain in OSA patients in the lateral and supine positions, and to explore the relationship between change in dynamic loop gain and change in lung volume with position. METHODS: Data from 20 patients enrolled in previous studies on the effect of body position on OSA pathogenesis were retrospectively analysed. Dynamic loop gain was calculated from routinely collected polysomnographic signals using a previously validated mathematical model. Lung volumes were measured in the awake state with a nitrogen washout technique. RESULTS: Dynamic loop gain was significantly higher in the supine than in the lateral position (0.77 ± 0.15 vs 0.68 ± 0.14, P = 0.012). Supine functional residual capacity (FRC) was significantly lower than lateral FRC (81.0 ± 15.4% vs 87.3 ± 18.4% of the seated FRC, P = 0.021). The reduced FRC we observed on moving to the supine position was predicted by theory to increase loop gain by 10.2 (0.6, 17.1)%, a value similar to the observed increase of 8.4 (-1.5, 31.0)%. CONCLUSION: Dynamic loop gain increased by a small but statistically significant amount when moving from the lateral to supine position and this may, in part, contribute to the worsening of OSA in the supine sleeping position.

Loop Gain Predicts the Response to Upper Airway Surgery in Patients With Obstructive Sleep Apnea.

Study Objectives: 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. Methods: 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). Results: 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). Conclusions: 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.

Oxygen Desaturation Index Differs Significantly Between Types of Sleep Software.

STUDY OBJECTIVES: The aim of this study was to compare the oxygen desaturation index (ODI) generated by two different sleep software systems. METHODS: Participants undergoing diagnostic polysomnography for suspected obstructive sleep apnea underwent simultaneous oximetry recording using the ResMed ApneaLink Plus device (AL) and Compumedics Profusion PSG3 system (Comp). The ODI was calculated by the algorithms in the respective software of each system. To determine if differences were due to algorithm or recording devices, the Comp software was also used to generate ODI values using oximetry data from the AL. RESULTS: In 106 participants, there was good correlation but poor agreement in the ODI generated by the two systems. AL ODI values tended to be higher than Comp ODI values, but with significant variability. For ODI4%, bias was 4.4 events/h (95% limits of agreement -5.8 to 14.6 events/h). There was excellent correlation and agreement when the same oximetry raw data was analyzed by both systems. For ODI4%, bias was 0.03 events/h (95% limits of agreement -2.7 to 2.8 events/h). Similar results were evident when the ODI3% was used. CONCLUSIONS: There is a clinically significant difference in ODI values generated by the two systems, likely due to device signal processing, rather than difference in ODI calculation algorithms.

Control theory prediction of resolved Cheyne-Stokes respiration in heart failure.

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 >1), 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 (LGtherapy), 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 LGtherapy predicts CSR persistence (LGtherapy >1) versus resolution (LGtherapy <1).As predicted, when LGtherapy >1.0, CSR continued during therapy in 23 out of 25 (92%) trials. A borderline loop gain zone (0.8

Oronasal Masks Require a Higher Pressure than Nasal and Nasal Pillow Masks for the Treatment of Obstructive Sleep Apnea.

STUDY OBJECTIVES: Oronasal masks are frequently used for continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). The aim of this study was to (1) determine if CPAP requirements are higher for oronasal masks compared to nasal mask interfaces and (2) assess whether polysomnography and patient characteristics differed among mask preference groups. METHODS: Retrospective analysis of all CPAP implementation polysomnograms between July 2013 and June 2014. Prescribed CPAP level, polysomnography results and patient data were compared according to mask type (n = 358). RESULTS: Oronasal masks were used in 46%, nasal masks in 35% and nasal pillow masks in 19%. There was no difference according to mask type for baseline apnea-hypopnea index (AHI), body mass index (BMI), waist or neck circumference. CPAP level was higher for oronasal masks, 12 (10-15.5) cm H2O compared to nasal pillow masks, 11 (8-12.5) cm H2O and nasal masks, 10 (8-12) cm H2O, p < 0.0001 (Median [interquartile range]). Oronasal mask type, AHI, age, and BMI were independent predictors of a higher CPAP pressure (p < 0.0005, adjusted R(2) = 0.26.). For patients with CPAP ≥ 15 cm H2O, there was an odds ratio of 4.5 (95% CI 2.5-8.0) for having an oronasal compared to a nasal or nasal pillow mask. Residual median AHI was higher for oronasal masks (11.3 events/h) than for nasal masks (6.4 events/h) and nasal pillows (6.7 events/h), p < 0.001. CONCLUSIONS: Compared to nasal mask types, oronasal masks are associated with higher CPAP pressures (particularly pressures ≥ 15 cm H2O) and a higher residual AHI. Further evaluation with a randomized control trial is required to definitively establish the effect of mask type on pressure requirements. COMMENTARY: A commentary on this article appears in this issue on page 1209.

Evaluation of the role of lung volume and airway size and shape in supine-predominant obstructive sleep apnoea patients.

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Effect of Body Position on Physiological Factors that Contribute to Obstructive Sleep Apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) resolves in lateral sleep in 20% of patients. However, the effect of lateral positioning on factors contributing to OSA has not been studied. We aimed to measure the effect of lateral positioning on the key pathophysiological contributors to OSA including lung volume, passive airway anatomy/collapsibility, the ability of the airway to stiffen and dilate, ventilatory control instability (loop gain), and arousal threshold. DESIGN: Non-randomized single arm observational study. SETTING: Sleep laboratory. PATIENTS/PARTICIPANTS: 20 (15M, 5F) continuous positive airway pressure (CPAP)-treated severe OSA patients. INTERVENTIONS: Supine vs. lateral position. MEASUREMENTS: CPAP dial-downs performed during sleep to measure: (i) Veupnea: asleep ventilatory requirement, (ii) passive V0: ventilation off CPAP when airway dilator muscles are quiescent, (iii) Varousal: ventilation at which respiratory arousals occur, (iv) active V0: ventilation off CPAP when airway dilator muscles are activated during sleep, (v) loop gain: the ratio of the ventilatory drive response to a disturbance in ventilation, (vi) arousal threshold: level of ventilatory drive which leads to arousal, (vii) upper airway gain (UAG): ability of airway muscles to restore ventilation in response to increases in ventilatory drive, and (viii) pharyngeal critical closing pressure (Pcrit). Awake functional residual capacity (FRC) was also recorded. RESULTS: Lateral positioning significantly increased passive V0 (0.33 ± 0.76L/min vs. 3.56 ± 2.94L/min, P < 0.001), active V0 (1.10 ± 1.97L/min vs. 4.71 ± 3.08L/min, P < 0.001), and FRC (1.31 ± 0.56 L vs. 1.42 ± 0.62 L, P = 0.046), and significantly decreased Pcrit (2.02 ± 2.55 cm H2O vs. -1.92 ± 3.87 cm H2O, P < 0.001). Loop gain, arousal threshold, Varousal, and UAG were not significantly altered. CONCLUSIONS: Lateral positioning significantly improves passive airway anatomy/collapsibility (passive V0, pharyngeal critical closing pressure), the ability of the airway to stiffen and dilate (active V0), and the awake functional residual capacity without improving loop gain or arousal threshold.

Energy expenditure in obstructive sleep apnea: validation of a multiple physiological sensor for determination of sleep and wake.

PURPOSE: Obstructive sleep apnea (OSA) may be associated with increased energy expenditure (EE) during sleep. As actigraphy is inaccurate at estimating EE from body movement counts alone, we aimed to compare a multiple physiological sensor with polysomnography for determination of sleep and wake, and to test the hypothesis that OSA is associated with increased EE during sleep. METHODS: We studied 50 adults referred for routine overnight polysomnography. In addition to polysomnography, the SenseWear Pro3 Armband(TM) (Bodymedia Inc.) was placed on the upper right arm. Epoch-by-epoch agreement rate between the measures of sleep versus wake was calculated. Linear regression analyses were performed for EE against apnea-hypopnea index (AHI), 3% oxygen desaturation index (ODI), body mass index (BMI), waist-hip ratio (WHR), gender, age, and average heart rate during sleep. RESULTS: The epoch-by-epoch agreement rate was high (79.9 ± 1.6%) and the ability of the SenseWear to estimate sleep was very good (sensitivity, 88.7 ± 1.5%). However, it was less accurate in determining wake (specificity 49.9 ± 3.6%). Sleep EE was associated with AHI, 3% ODI, BMI, WHR, and male gender (p < 0.001 for all). Stepwise multiple linear regression however revealed that BMI, male gender, age, and average heart rate during sleep were independent predictors of EE (Model R (2) = 0.78). CONCLUSIONS: The SenseWear armband provides a reasonable estimation of sleep but a poor estimation of wake. Furthermore, in a selected population of OSA patients, increasing OSA severity is associated with increased EE during sleep, although primarily through an association with increased BMI. However, as our data are not adjusted for fat-free mass and the SenseWear has yet to be validated for EE in OSA patients, these data should be interpreted with caution.

Phenotypes of patients with mild to moderate obstructive sleep apnoea as confirmed by cluster analysis.

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Loop gain as a means to predict a positive airway pressure suppression of Cheyne-Stokes respiration in patients with heart failure.

RATIONALE: Patients with heart failure (HF) and Cheyne-Stokes respiration or periodic breathing (PB) often demonstrate improved cardiac function when treatment with continuous positive airway pressure (CPAP) resolves PB. Unfortunately, CPAP is successful in only 50% of patients, and no known factor predicts responders to treatment. Because PB manifests from a hypersensitive ventilatory feedback loop (elevated loop gain [LG]), we hypothesized that PB persists on CPAP when LG far exceeds the critical threshold for stable ventilation (LG = 1). OBJECTIVES: To derive, validate, and test the clinical utility of a mathematically precise method that quantifies LG from the cyclic pattern of PB, where LG = 2π/(2πDR - sin2πDR) and DR (i.e., duty ratio) = (ventilatory duration)/(cycle duration) of PB. METHODS: After validation in a mathematical model of HF, we tested whether our estimate of LG changes with CPAP (n = 6) and inspired oxygen (n = 5) as predicted by theory in an animal model of PB. As a first test in patients with HF (n = 14), we examined whether LG predicts the first-night CPAP suppression of PB. MEASUREMENTS AND MAIN RESULTS: In lambs, as predicted by theory, LG fell as lung volume increased with CPAP (slope = 0.9 ± 0.1; R(2) = 0.82; P < 0.001) and as inspired-arterial PO(2) difference declined (slope = 1.05 ± 0.12; R(2) = 0.75; P < 0.001). In patients with HF, LG was markedly greater in 8 CPAP nonresponders versus 6 responders (1.29 ± 0.04 versus 1.10 ± 0.01; P < 0.001); LG predicted CPAP suppression of PB in 13/14 patients. CONCLUSIONS: Our novel LG estimate enables quantification of the severity of ventilatory instability underlying PB, making possible a priori selection of patients whose PB is immediately treatable with CPAP therapy.

Laryngeal penetration and aspiration in individuals with stable COPD.

BACKGROUND AND OBJECTIVE: Swallowing is closely coordinated with breathing but in COPD altered synchronization may predispose patients to a breach of the upper airway protective mechanisms. However, aspiration during swallow has never been shown in COPD. We examined penetration of liquid material into the airway of patients with COPD and correlated it with breathing-swallow patterns. METHODS: A case-control study was performed. Patients with COPD (n = 16) were matched with normal control subjects (n = 15). Sub-mandibular videofluoroscopy was carried out during swallow of graduated volumes of barium to detect penetration (contrast enters the airway and may contact vocal folds) and aspiration (contrast passes glottis). Respiration was monitored simultaneously to gauge synchronization. Hospitalization and mortality were assessed after 36 months. RESULTS: Penetration/aspiration scores were higher in patients with COPD (3.3 ± 0.7 vs 1.6 ± 0.4 in healthy controls, P = 0.03; mean ± SE). Penetration with aspiration was observed in 4/16 patients with COPD versus 1/15 controls (P = 0.07). Penetration with or without aspiration was found in 6/16 patients (P = 0.04). Inspiration-swallow-expiration patterns were favoured in individuals with COPD (P = 0.02). Penetration/aspiration was associated with higher respiratory rates (P = 0.01), reduced hyoid elevation (P = 0.04), post-swallow larynx penetration (P = 0.05) and oxygen desaturation (P = 0.01). There was a trend for the penetration/aspiration group to have an adverse outcome. CONCLUSIONS: Upper airway protective mechanisms may be flawed in COPD, possibly through reduced coordination of breathing with swallowing. This abnormality may contribute to COPD morbidity in a subgroup of patients.