Garun S. Hamilton

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.

Obstructive sleep apnoea and cardiovascular disease

Abstract

Abnormal vocal cord function in difficult-to-treat asthma.

RATIONALE Upper airway dysfunction may complicate asthma but has been largely ignored as an etiological factor. Diagnosis using endoscopic evaluation of vocal cord function is difficult to quantify, with limited clinical application. OBJECTIVES A novel imaging technique, dynamic 320-slice computerized tomography (CT), was used to examine laryngeal behavior in healthy individuals and individuals with asthma. METHODS Vocal cord movement was imaged using 320-slice CT larynx. Healthy volunteers were studied to develop and validate an analysis algorithm for quantification of normal vocal cord function. Further studies were then conducted in 46 patients with difficult-to-treat asthma. MEASUREMENTS AND MAIN RESULTS Vocal cord movement was quantified over the breathing cycle by CT using the ratio of vocal cord diameter to tracheal diameter. Normal limits were calculated, validated, and applied to evaluate difficult-to-treat asthma. Vocal cord movement was abnormal with excessive narrowing in 23 of 46 (50%) patients with asthma and severe in 9 (19%) patients (abnormal > 50% of inspiration or expiration time). Imaging also revealed that laryngeal dysfunction characterized the movement abnormality rather than isolated vocal cord dysfunction. CONCLUSIONS Noninvasive quantification of laryngeal movement was achieved using CT larynx. Significant numbers of patients with difficult-to-treat asthma had excessive narrowing of the vocal cords. This new approach has identified frequent upper airway dysfunction in asthma with potential implications for disease control and treatment.

Supine position related obstructive sleep apnea in adults: pathogenesis and treatment.

The most striking feature of obstructive respiratory events is that they are at their most severe and frequent in the supine sleeping position: indeed, more than half of all obstructive sleep apnea (OSA) patients can be classified as supine related OSA. Existing evidence points to supine related OSA being attributable to unfavorable airway geometry, reduced lung volume, and an inability of airway dilator muscles to adequately compensate as the airway collapses. The role of arousal threshold and ventilatory control instability in the supine position has however yet to be defined. Crucially, few physiological studies have examined patients in the lateral and supine positions, so there is little information to elucidate how breathing stability is affected by sleep posture. The mechanisms of supine related OSA can be overcome by the use of continuous positive airway pressure. There are conflicting data on the utility of oral appliances, while the effectiveness of weight loss and nasal expiratory resistance remains unclear. Avoidance of the supine posture is efficacious, but long term compliance data and well powered randomized controlled trials are lacking. The treatment of supine related OSA remains largely ignored in major clinical guidelines. Supine OSA is the dominant phenotype of the OSA syndrome. This review explains why the supine position so favors upper airway collapse and presents the available data on the management of patients with supine related OSA.

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

PurposeObstructive 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.MethodsWe studied 50 adults referred for routine overnight polysomnography. In addition to polysomnography, the SenseWear Pro3 ArmbandTM (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.ResultsThe 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 R2 = 0.78).ConclusionsThe 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.

The reciprocal interaction between obesity and obstructive sleep apnoea

Obesity is a significant risk factor in the pathogenesis of obstructive sleep apnoea (OSA) altering airway anatomy and collapsibility, and respiratory control. The association between obesity and OSA has led to an increasing focus on the role of weight loss as a potential treatment for OSA. To date, most discussion of obesity and OSA assumes a one-way cause and effect relationship, with obesity contributing to the pathogenesis of OSA. However, OSA itself may contribute to the development of obesity. OSA has a potential role in the development and reinforcement of obesity via changes to energy expenditure during sleep and wake periods, dietary habits, the neurohormonal mechanisms that control satiety and hunger, and sleep duration arising from fragmented sleep. Thus, there is emerging evidence that OSA itself feeds back into a complex mechanism that leads either to the development or reinforcement of the obese state. Whilst current evidence does not confirm that treatment of OSA directly influences weight loss, it does suggest that the potential role OSA plays in obesity and weight loss deserves further research.

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.

Weight loss from lifestyle interventions and severity of sleep apnoea: A systematic review and meta-analysis

BACKGROUND Excess body weight is a risk factor for obstructive sleep apnoea (OSA). The aim of the systematic review was to establish whether weight loss via lifestyle interventions such as diet and exercise are useful in the treatment of OSA. METHODS A literature search was conducted between 1980 and February 2012. Systematic reviews and randomised controlled trials (RCTs) with participants who had OSA, were overweight or obese, and who had undergone lifestyle interventions with the aim of improving sleep apnoea were included. Meta analyses were conducted for a subset of RCTs with appropriate data. RESULTS Two systematic reviews and eight RCTs were included. Meta-analyses were conducted for four RCTs comparing intensive lifestyle interventions to a control. The overall weighted mean differences for weight change, change in apnoea -hypopnoea index (AHI) and change in oxygen desaturation index of ≥4% were as follows: -13.76 kg (95% confidence interval (CI) -19.21, --8.32), -16.09 (95% CI -25.64, -6.54) and -14.18 (95% CI -24.23, -4.13), respectively. Although high heterogeneity within the meta analyses, all studies favoured the interventions. Long-term follow-up data from three RCTs suggest that improvements in weight and AHI are maintained for up to 60 months. CONCLUSIONS Intensive lifestyle interventions are effective in the treatment of OSA, resulting in significant weight loss and a reduction in sleep apnoea severity. Weight loss via intensive lifestyle interventions could be encouraged as a treatment for mild to moderate OSA.

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.

Diagnosis of vocal cord dysfunction in asthma with high resolution dynamic volume computerized tomography of the larynx

Background and objective:  Vocal cord dysfunction (VCD) often masquerades as asthma and reports have suggested that up to 30% of patients with asthma may have coexistent VCD. Diagnosis of VCD is difficult, in part because it involves laryngoscopy which has practical constraints, and there is need for rapid non‐invasive diagnosis. High speed 320‐slice volume CT demonstrates laryngeal function during inspiration and expiration and may be useful in suspected VCD.