Does OSA Increase Risk for Cancer?: A Large Historical Sleep Clinic Cohort Study.

BACKGROUND: The relationship between OSA and cancer is unclear. RESEARCH QUESTION: What is the association between OSA and cancer prevalence and incidence in a large Western Australian sleep clinic cohort (N = 20,289)? STUDY DESIGN AND METHODS: OSA severity was defined by apnea-hypopnea index (AHI) and nocturnal hypoxemia (duration and percentage at oxygen saturation < 90%) measured by in-laboratory polysomnogram. Measures of potential confounding included age, sex, BMI, smoking status, socioeconomic status, and BP. Outcomes were determined from the Western Australian cancer and death registries. Analyses were confined within periods using consistent AHI scoring criteria: January 1, 1989, to July 31, 2002 (American Sleep Disorders Association criteria), and August 1, 2002, to June 30, 2013 (Chicago criteria). We examined associations of AHI and nocturnal hypoxemia with cancer prevalence using logistic regression and cancer incidence using Cox regression analyses. RESULTS: Cancer prevalence at baseline was 329 of 10,561 in the American Sleep Disorders Association period and 633 of 9,728 in the Chicago period. Nocturnal hypoxemia but not AHI was independently associated with prevalent cancer following adjustment for participant age, sex, BMI, smoking status, socioeconomic status, and BP. Of those without prevalent cancer, cancer was diagnosed in 1,950 of 10,232 (American Sleep Disorders Association) and 623 of 9,095 (Chicago) participants over a median follow-up of 11.2 years. Compared with the reference category (no OSA, AHI < 5 events per hour), univariable models estimated higher hazard ratios for cancer incidence for mild (AHI 5-15 events per hour), moderate (AHI 15.1-30 events per hour), and severe (AHI > 30 events per hour) OSA. Multivariable analyses consistently revealed associations between age and, in some cases, sex, BMI, and smoking status, with cancer incidence. After adjusting for confounders, multivariable models showed no independent association between OSA severity and increased cancer incidence. INTERPRETATION: Nocturnal hypoxemia is independently associated with prevalent cancer. OSA severity is associated with incident cancer, although this association seems secondary to other risk factors for cancer development. OSA is not an independent risk factor for cancer incidence.

Society of Anesthesia and Sleep Medicine Position Paper on Patient Sleep During Hospitalization.

This article addresses the issue of patient sleep during hospitalization, which the Society of Anesthesia and Sleep Medicine believes merits wider consideration by health authorities than it has received to date. Adequate sleep is fundamental to health and well-being, and insufficiencies in its duration, quality, or timing have adverse effects that are acutely evident. These include cardiovascular dysfunction, impaired ventilatory function, cognitive impairment, increased pain perception, psychomotor disturbance (including increased fall risk), psychological disturbance (including anxiety and depression), metabolic dysfunction (including increased insulin resistance and catabolic propensity), and immune dysfunction and proinflammatory effects (increasing infection risk and pain generation). All these changes negatively impact health status and are counterproductive to recovery from illness and operation. Hospitalization challenges sleep in a variety of ways. These challenges include environmental factors such as noise, bright light, and overnight awakenings for observations, interventions, and transfers; physiological factors such as pain, dyspnea, bowel or urinary dysfunction, or discomfort from therapeutic devices; psychological factors such as stress and anxiety; care-related factors including medications or medication withdrawal; and preexisting sleep disorders that may not be recognized or adequately managed. Many of these challenges appear readily addressable. The key to doing so is to give sleep greater priority, with attention directed at ensuring that patients' sleep needs are recognized and met, both within the hospital and beyond. Requirements include staff education, creation of protocols to enhance the prospect of sleep needs being addressed, and improvement in hospital design to mitigate environmental disturbances. Hospitals and health care providers have a duty to provide, to the greatest extent possible, appropriate preconditions for healing. Accumulating evidence suggests that these preconditions include adequate patient sleep duration and quality. The Society of Anesthesia and Sleep Medicine calls for systematic changes in the approach of hospital leadership and staff to this issue. Measures required include incorporation of optimization of patient sleep into the objectives of perioperative and general patient care guidelines. These steps should be complemented by further research into the impact of hospitalization on sleep, the effects of poor sleep on health outcomes after hospitalization, and assessment of interventions to improve it.

Targeted Genome Sequencing Identifies Multiple Rare Variants in Caveolin-1 Associated with Obstructive Sleep Apnea.

Rationale: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. There is strong clinical and epidemiologic evidence supporting the importance of genetic factors influencing OSA but limited data implicating specific genes. Objectives: To search for rare variants contributing to OSA severity. Methods: Leveraging high-depth genomic sequencing data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and imputed genotype data from multiple population-based studies, we performed linkage analysis in the CFS (Cleveland Family Study), followed by multistage gene-based association analyses in independent cohorts for apnea-hypopnea index (AHI) in a total of 7,708 individuals of European ancestry. Measurements and Main Results: Linkage analysis in the CFS identified a suggestive linkage peak on chromosome 7q31 (LOD = 2.31). Gene-based analysis identified 21 noncoding rare variants in CAV1 (Caveolin-1) associated with lower AHI after accounting for multiple comparisons (P = 7.4 × 10-8). These noncoding variants together significantly contributed to the linkage evidence (P < 10-3). Follow-up analysis revealed significant associations between these variants and increased CAV1 expression, and increased CAV1 expression in peripheral monocytes was associated with lower AHI (P = 0.024) and higher minimum overnight oxygen saturation (P = 0.007). Conclusions: Rare variants in CAV1, a membrane-scaffolding protein essential in multiple cellular and metabolic functions, are associated with higher CAV1 gene expression and lower OSA severity, suggesting a novel target for modulating OSA severity.

Continuous positive airway pressure and adverse cardiovascular events in obstructive sleep apnea: are participants of randomized trials representative of sleep clinic patients?

STUDY OBJECTIVES: Randomized controlled trials (RCTs) have shown no reduction in adverse cardiovascular (CV) events in patients randomized to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA). This study examined whether randomized study populations were representative of OSA patients attending a sleep clinic. METHODS: Sleep clinic patients were 3,965 consecutive adults diagnosed with OSA by in-laboratory polysomnography from 2006 to 2010 at a tertiary hospital sleep clinic. Characteristics of these patients were compared with participants of five recent RCTs examining the effect of CPAP on adverse CV events in OSA. The percentage of patients with severe (apnea-hypopnea index, [AHI] ≥ 30 events/h) or any OSA (AHI ≥ 5 events/h) who met the eligibility criteria of each RCT was determined, and those criteria that excluded the most patients identified. RESULTS: Compared to RCT participants, sleep clinic OSA patients were younger, sleepier, more likely to be female and less likely to have established CV disease. The percentage of patients with severe or any OSA who met the RCT eligibility criteria ranged from 1.2% to 20.9% and 0.8% to 21.9%, respectively. The eligibility criteria that excluded most patients were preexisting CV disease, symptoms of excessive sleepiness, nocturnal hypoxemia and co-morbidities. CONCLUSIONS: A minority of sleep clinic patients diagnosed with OSA meet the eligibility criteria of RCTs of CPAP on adverse CV events in OSA. OSA populations in these RCTs differ considerably from typical sleep clinic OSA patients. This suggests that the findings of such OSA treatment-related RCTs are not generalizable to sleep clinic OSA patients.Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA (RICCADSA) trial, https://clinicaltrials.gov/ct2/show/NCT00519597, ClinicalTrials.gov number, NCT00519597.Usefulness of Nasal Continuous Positive Airway Pressure (CPAP) Treatment in Patients with a First Ever Stroke and Sleep Apnea Syndrome, https://clinicaltrials.gov/ct2/show/NCT00202501, ClinicalTrials.gov number, NCT00202501.Effect of Continuous Positive Airway Pressure (CPAP) on Hypertension and Cardiovascular Morbidity-Mortality in Patients with Sleep Apnea and no Daytime Sleepiness, https://clinicaltrials.gov/ct2/show/NCT00127348, ClinicalTrials.gov number, NCT00127348.Continuous Positive Airway Pressure (CPAP) in Patients with Acute Coronary Syndrome and Obstructive Sleep Apnea (OSA) (ISAACC), https://clinicaltrials.gov/ct2/show/NCT01335087, ClinicalTrials.gov number, NCT01335087.

Whole-genome association analyses of sleep-disordered breathing phenotypes in the NHLBI TOPMed program.

BACKGROUND: Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing. METHODS: The study sample was comprised of 7988 individuals of diverse ancestry. Common-variant and pathway analyses included an additional 13,257 individuals. We examined five complementary traits describing different aspects of sleep-disordered breathing: the apnea-hypopnea index, average oxyhemoglobin desaturation per event, average and minimum oxyhemoglobin saturation across the sleep episode, and the percentage of sleep with oxyhemoglobin saturation < 90%. We adjusted for age, sex, BMI, study, and family structure using MMSKAT and EMMAX mixed linear model approaches. Additional bioinformatics analyses were performed with MetaXcan, GIGSEA, and ReMap. RESULTS: We identified a multi-ethnic set-based rare-variant association (p = 3.48 × 10-8) on chromosome X with ARMCX3. Additional rare-variant associations include ARMCX3-AS1, MRPS33, and C16orf90. Novel common-variant loci were identified in the NRG1 and SLC45A2 regions, and previously associated loci in the IL18RAP and ATP2B4 regions were associated with novel phenotypes. Transcription factor binding site enrichment identified associations with genes implicated with respiratory and craniofacial traits. Additional analyses identified significantly associated pathways. CONCLUSIONS: We have identified the first gene-based rare-variant associations with objectively measured sleep-disordered breathing traits. Our results increase the understanding of the genetic architecture of sleep-disordered breathing and highlight associations in genes that modulate lung development, inflammation, respiratory rhythmogenesis, and HIF1A-mediated hypoxic response.

Prevalence and patterns of multimorbidity in Australian baby boomers: the Busselton healthy ageing study.

BACKGROUND AND OBJECTIVE: Chronic medical conditions accumulate within individuals with age. However, knowledge concerning the trends, patterns and determinants of multimorbidity remains limited. This study assessed the prevalence and patterns of multimorbidity using extensive individual phenotyping in a general population of Australian middle-aged adults. METHODS: Participants (n = 5029, 55% female), born between 1946 and 1964 and attending the cross-sectional phase of the Busselton Healthy Ageing Study (BHAS) between 2010 and 2015, were studied. Prevalence of 21 chronic conditions was estimated using clinical measurement, validated instrument scores and/or self-reported doctor-diagnosis. Non-random patterns of multimorbidity were explored using observed/expected (O/E) prevalence ratios and latent class analysis (LCA). Variables associated with numbers of conditions and class of multimorbidity were investigated. RESULTS: The individual prevalence of 21 chronic conditions ranged from 2 to 54% and multimorbidity was common with 73% of the cohort having 2 or more chronic conditions. (mean ± SD 2.75 ± 1.84, median = 2.00, range 0-13). The prevalence of multimorbidity increased with age, obesity, physical inactivity, tobacco smoking and family history of asthma, diabetes, myocardial infarct or cancer. There were 13 pairs and 27 triplets of conditions identified with a prevalence > 1.5% and O/E > 1.5. Of the triplets, arthritis (> 50%), bowel disease (> 33%) and depression-anxiety (> 33%) were observed most commonly. LCA modelling identified 4 statistically and clinically distinct classes of multimorbidity labelled as: 1) "Healthy" (70%) with average of 1.95 conditions; 2) "Respiratory and Atopy" (11%, 3.65 conditions); 3) "Non-cardiometabolic" (14%, 4.77 conditions), and 4) "Cardiometabolic" (5%, 6.32 conditions). Predictors of multimorbidity class membership differed between classes and differed from predictors of number of co-occurring conditions. CONCLUSION: Multimorbidity is common among middle-aged adults from a general population. Some conditions associated with ageing such as arthritis, bowel disease and depression-anxiety co-occur in clinically distinct patterns and at higher prevalence than expected by chance. These findings may inform further studies into shared biological and environmental causes of co-occurring conditions of ageing. Recognition of distinct patterns of multimorbidity may aid in a holistic approach to care management in individuals presenting with multiple chronic conditions, while also guiding health resource allocation in ageing populations.

Treating insomnia symptoms with medicinal cannabis: a randomized, crossover trial of the efficacy of a cannabinoid medicine compared with placebo.

STUDY OBJECTIVES: This randomized, double-blind, placebo-controlled, crossover study was conducted to evaluate the safety and efficacy of 2 weeks of nightly sublingual cannabinoid extract (ZTL-101) in treating chronic insomnia (symptoms ≥3 months). METHODS: Co-primary study endpoints were safety of the medication based on adverse event reporting and global insomnia symptoms (Insomnia Severity Index [ISI]). Secondary endpoints included: self-reported (sleep diary), actigraphy-derived, and polysomnography measurements of sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST), sleep efficiency (SE); and self-reported assessments of sleep quality (sSQ) and feeling rested upon waking. Adjusted mean differences between placebo and ZTL-101 were calculated. RESULTS: Twenty-three of 24 randomized participants (n = 20 female, mean age 53 ± 9 years) completed the protocol. No serious adverse events were reported. Forty mild, nonserious, adverse events were reported (36 during ZTL-101) with all but one resolving overnight or soon after waking. Compared to placebo, ZTL-101 decreased ISI (-5.07 units [95% CI: -7.28 to -2.86]; p = 0.0001) and self-reported SOL (-8.45 min [95% CI: -16.33 to -0.57]; p = 0.04) and increased self-reported TST (64.6 min [95% CI: 41.70 to 87.46]; p < 0.0001), sSQ (0.74 units [95% CI: 0.51 to 0.97]; p < 0.0001), and feeling of being rested on waking (0.51 units [95% CI: 0.24 to 0.78]; p = 0.0007). ZTL-101 also decreased actigraphy-derived WASO (-10.2 min [95% CI: -16.2 to -4.2]; p = 0.002), and increased actigraphy-derived TST (33.4 min [95% CI: 23.07 to 43.76]; p < 0.001) and SE (2.9% [95% CI: 2.0 to 3.8]; p = 0.005). CONCLUSIONS: Two weeks of nightly sublingual administration of a cannabinoid extract (ZTL-101) is well tolerated and improves insomnia symptoms and sleep quality in individuals with chronic insomnia symptoms. CLINICAL TRIAL: ANZCTR; anzctr.org.au; ACTRN12618000078257.

Sleep Loss in the Hospitalized Patient and Its Influence on Recovery From Illness and Operation.

Adequate sleep is essential to health and well-being. Adverse effects of sleep loss are evident acutely and are cumulative in their effect. These include impairment of cognition, psychomotor function, and mood, as well as cardiovascular, metabolic, and immune dysfunction including proinflammatory effects and increased catabolic propensity. Such effects are counterproductive to recovery from illness and operation, yet hospitalization challenges sleep through the anxieties, discomforts, and sleep environmental challenges faced by patients, the inadequate attention given to the needs of patients with preexisting sleep disorders, and the lack of priority these issues receive from hospital staff and their leaders. Mitigation of the adverse effects of noise, light, uncomfortable bedding, intrusive observations, anxiety, and pain together with attention to specific sleep needs and monitoring of sleep quality are steps that would help address the issue and potentially improve patient outcomes.

Increasing Walking Speed to Achieve a Pre-training Endurance Shuttle Walk Time of 5-10 min May Improve Test Responsiveness in People With Chronic Obstructive Pulmonary Disease.

PURPOSE: The endurance shuttle walk test (ESWT) was used to evaluate ground-based walking training in chronic obstructive pulmonary disease. During pre-training testing, those who walked 5-10 min on the first ESWT with minimal symptoms performed additional ESWTs at increasing speeds until they were at least moderately symptomatic and terminated the test between 5 and 10 min. This report compares participant characteristics and test responsiveness with participants grouped according to whether or not faster walking speeds were selected for the ESWT during pre-training testing. METHODS: We conducted a retrospective analysis of data collected in the intervention group during a randomized controlled trial. The intervention was supervised ground-based walking training, performed two to three times/wk, for 8-10 wk. Prior to and immediately following completion of training, participants completed the 6-min walk test (6MWT), incremental shuttle walk test (ISWT), and ESWT. RESULTS: Data were available on 77 participants (70 ± 9 yr, forced expiratory volume in the first second of expiration [FEV1] 43 ± 15 % predicted). For those whom a faster speed was selected during the pre-training ESWTs were characterized by milder dyspnea and leg fatigue on completion of the baseline 6MWT and ISWT (P < .05 for all). On training completion, the change in ESWT was greater in those for whom a faster speed was selected (376 ± 344 sec vs 176 ± 274 sec; P = .017). CONCLUSIONS: Participants who report modest symptoms on completion of the pre-training 6MWT or ISWT may achieve a long pre-training ESWT time. In this situation, repeating the pre-training ESWT at a faster walking speed to achieve an exercise time between 5 and 10 min with moderate symptoms may be advantageous.

The prevalence of common sleep disorders in young adults: a descriptive population-based study.

Sleep disorders in adults are associated with adverse health effects including reduced quality of life and increased mortality. However, there is little information on sleep disorders in young adults. A cross-sectional observational study was undertaken in 1,227 young adults participating in the Western Australian Pregnancy (Raine) Study (2012-2014) to describe the prevalence of common sleep disorders. In-laboratory polysomnography (PSG) and validated survey methods were used, including the Epworth Sleepiness Scale, Pittsburgh Sleep Symptom Questionnaire-Insomnia, and International Restless Legs Syndrome Study Group criteria. A total of 1,146 participants completed a core questionnaire, 1,051 completed a sleep-focused questionnaire and 935 had analyzable PSG data. Participants had a mean age of 22.2 years and female to male ratio of 1.1 to 1. The respective sleep disorder prevalences in females and males were: obstructive sleep apnea (OSA) (apnea-hypopnea index [AHI]: ≥5 events/hour) 14.9% (95% CI: 11.8-18.5) and 26.9% (95% CI: 22.9-31.2); chronic insomnia, 19.3% (95% CI: 16.7-23.9) and 10.6% (95% CI: 8.3-13.9); restless legs syndrome, 3.8% (95% CI: 2.4-5.6) and 1.9% (95% CI: 0.9-3.4); and abnormal periodic leg movements during sleep (>5 movements/hour), 8.6% (95% CI: 6.3-11.5) and 9.6% (95% CI: 7.1-12.7). There were statistically significant differences in prevalence between sexes for OSA and insomnia, which persisted after adjustment for body mass index and education. In those with complete data on all sleep-related assessments (n = 836), at least one sleep disorder was present in 41.0% of females and 42.3% of males. Sleep disorders are very common in young adults. Health practitioners should be aware of these high prevalences, as early identification and treatment can improve quality of life and may reduce later morbidity and mortality.

Comparison of Collapsibility of the Human Upper Airway During Anesthesia and During Sleep.

BACKGROUND: The propensities for the upper airway to collapse during anesthesia and sleep are related, although much of our understanding of this relationship has been inferred from clinical observation and indirect measures such as the apnea-hypopnea index. The aim of this study was to use an identical, rigorous, direct measure of upper airway collapsibility (critical closing pressure of the upper airway) under both conditions to allow the magnitude of upper airway collapsibility in each state to be precisely compared. METHODS: Ten subjects (8 men and 2 women; mean ± SD: age, 40.4 ± 12.1 years; body mass index, 28.5 ± 4.0 kg/m) were studied. Critical closing pressure of the upper airway was measured in each subject on separate days during (1) propofol anesthesia and (2) sleep. RESULTS: Critical closing pressure of the upper airway measurements were obtained in all 10 subjects during nonrapid eye movement sleep and, in 4 of these 10 subjects, also during rapid eye movement sleep. Critical closing pressure of the upper airway during anesthesia was linearly related to critical closing pressure of the upper airway during nonrapid eye movement sleep (r = 0.64 [95% CI, 0.02-0.91]; n = 10; P = .046) with a similar tendency in rapid eye movement sleep (r = 0.80 [95% CI, -0.70 to 0.99]; n = 4; P = .200). However, critical closing pressure of the upper airway during anesthesia was systematically greater (indicating increased collapsibility) than during nonrapid eye movement sleep (2.1 ± 2.2 vs -2.0 ± 3.2 cm H2O, respectively, n = 10; within-subject mean difference, 4.1 cm H2O [95% CI, 2.32-5.87]; P < .001) with a similar tendency during rapid eye movement sleep (1.6 ± 2.4 vs -1.9 ± 4.3 cm H2O, respectively, n = 4; unadjusted difference, 3.5 cm H2O [95% CI, -0.95 to 7.96]; P = .087). CONCLUSIONS: These results demonstrate that the magnitude of upper airway collapsibility during anesthesia and sleep is directly related. However, the upper airway is systematically more collapsible during anesthesia than sleep, suggesting greater vulnerability to upper airway obstruction in the anesthetized state.

Bilateral hypoglossal nerve stimulation for treatment of adult obstructive sleep apnoea.

BACKGROUND AND AIM: Hypoglossal nerve stimulation (HNS) decreases obstructive sleep apnoea (OSA) severity via genioglossus muscle activation and decreased upper airway collapsibility. This study assessed the safety and effectiveness at 6 months post-implantation of a novel device delivering bilateral HNS via a small implanted electrode activated by a unit worn externally, to treat OSA: the Genio™ system. METHODS: This prospective, open-label, non-randomised, single-arm treatment study was conducted at eight centres in three countries (Australia, France and the UK). Primary outcomes were incidence of device-related serious adverse events and change in the apnoea-hypopnoea index (AHI). The secondary outcome was the change in the 4% oxygen desaturation index (ODI). Additional outcomes included measures of sleepiness, quality of life, snoring and device use. This trial was registered with ClinicalTrials.gov, number NCT03048604. RESULTS: 22 out of 27 implanted participants (63% male, aged 55.9±12.0 years, body mass index (BMI) 27.4±3.0 kg·m-2) completed the protocol. At 6 months BMI was unchanged (p=0.85); AHI decreased from 23.7±12.2 to 12.9±10.1 events·h-1, a mean change of 10.8 events·h-1 (p<0.001); and ODI decreased from 19.1±11.2 to 9.8±6.9 events·h-1, a mean change of 9.3 events·h-1 (p<0.001). Daytime sleepiness (Epworth Sleepiness Scale; p=0.01) and sleep-related quality of life (Functional Outcomes of Sleep Questionnaire-10; p=0.02) both improved significantly. The number of bed partners reporting loud, very intense snoring, or leaving the bedroom due to participant snoring decreased from 96% to 35%. 91% of participants reported device use >5 days per week, and 77% reported use for >5 h per night. No device-related serious adverse events occurred during the 6-month post-implantation period. CONCLUSIONS: Bilateral HNS using the Genio™ system reduces OSA severity and improves quality of life without device-related complications. The results are comparable with previously published HNS systems despite minimal implanted components and a simple stimulation algorithm.

Sequencing Analysis at 8p23 Identifies Multiple Rare Variants in DLC1 Associated with Sleep-Related Oxyhemoglobin Saturation Level.

Average arterial oxyhemoglobin saturation during sleep (AvSpO2S) is a clinically relevant measure of physiological stress associated with sleep-disordered breathing, and this measure predicts incident cardiovascular disease and mortality. Using high-depth whole-genome sequencing data from the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) project and focusing on genes with linkage evidence on chromosome 8p23,1,2 we observed that six coding and 51 noncoding variants in a gene that encodes the GTPase-activating protein (DLC1) are significantly associated with AvSpO2S and replicated in independent subjects. The combined DLC1 association evidence of discovery and replication cohorts reaches genome-wide significance in European Americans (p = 7.9 × 10-7). A risk score for these variants, built on an independent dataset, explains 0.97% of the AvSpO2S variation and contributes to the linkage evidence. The 51 noncoding variants are enriched in regulatory features in a human lung fibroblast cell line and contribute to DLC1 expression variation. Mendelian randomization analysis using these variants indicates a significant causal effect of DLC1 expression in fibroblasts on AvSpO2S. Multiple sources of information, including genetic variants, gene expression, and methylation, consistently suggest that DLC1 is a gene associated with AvSpO2S.

People With COPD Who Respond to Ground-Based Walking Training Are Characterized by Lower Pre-training Exercise Capacity and Better Lung Function and Have Greater Progression in Walking Training Distance.

PURPOSE: To investigate the characteristics that distinguish responders from nonresponders to ground-based walking training (GBWT) in people with chronic obstructive pulmonary disease (COPD). METHODS: An analysis was undertaken of data collected during a trial of GBWT in people with COPD. Responders to GBWT were defined in 2 ways: (1) improved time on the endurance shuttle walk test of ≥190 sec (criterion A); or (2) improved ability to walk, perceived by the participant to be at least "moderate" (criterion B). Differences in participant characteristics, pre-training exercise capacity, health-related quality of life, and the improvement in the distance walked during the training program were examined between responders and nonresponders. RESULTS: Of the 95 participants randomized to GBWT (age 69 ± 8 yr, forced expiratory volume in 1 sec [FEV1] % predicted = 43% ± 15%), data were available for analysis on 78 and 73 patients by criterion A and criterion B, respectively. According to criterion A, 32 (41%) participants were responders. The odds of being a responder increased with increasing FEV1 % predicted (OR = 1.2; 95% CI, 1.0-1.5, for every 5% increase) and increased with decreasing pre-training incremental shuttle walk distance (OR = 1.4; 95% CI, 1.0-1.8, for every 50-m decrement). According to criterion B, 42 (58%) participants were responders. There were no differences in characteristics or pre-training measures between the responders and nonresponders. For both criteria, responders demonstrated greater change in the distance walked during the training program (P < .05). CONCLUSION: Responders to GBWT had lower pre-training exercise capacity, had better lung function, and demonstrated greater change in the distance walked during the training program.

Upper Airway Collapsibility during Dexmedetomidine and Propofol Sedation in Healthy Volunteers: A Nonblinded Randomized Crossover Study.

BACKGROUND: Dexmedetomidine is a sedative promoted as having minimal impact on ventilatory drive or upper airway muscle activity. However, a trial recently demonstrated impaired ventilatory drive and induction of apneas in sedated volunteers. The present study measured upper airway collapsibility during dexmedetomidine sedation and related it to propofol. METHODS: Twelve volunteers (seven female) entered this nonblinded, randomized crossover study. Upper airway collapsibility (pharyngeal critical pressure) was measured during low and moderate infusion rates of propofol or dexmedetomidine. A bolus dose was followed by low (0.5 µg · kg · h or 42 µg · kg · min) and moderate (1.5 µg · kg · h or 83 µg · kg · min) rates of infusion of dexmedetomidine and propofol, respectively. RESULTS: Complete data sets were obtained from nine volunteers (median age [range], 46 [23 to 66] yr; body mass index, 25.4 [20.3 to 32.4] kg/m). The Bispectral Index score at time of pharyngeal critical pressure measurements was 74 ± 10 and 65 ± 13 (mean difference, 9; 95% CI, 3 to 16; P = 0.011) during low infusion rates versus 57 ± 16 and 39 ± 12 (mean difference, 18; 95% CI, 8 to 28; P = 0.003) during moderate infusion rates of dexmedetomidine and propofol, respectively. A difference in pharyngeal critical pressure during sedation with dexmedetomidine or propofol could not be shown at either the low or moderate infusion rate. Median (interquartile range) pharyngeal critical pressure was -2.0 (less than -15 to 2.3) and 0.9 (less than -15 to 1.5) cm H2O (mean difference, 0.9; 95% CI, -4.7 to 3.1) during low infusion rates (P = 0. 595) versus 0.3 (-9.2 to 1.4) and -0.6 (-7.7 to 1.3) cm H2O (mean difference, 0.0; 95% CI, -2.1 to 2.1; P = 0.980) during moderate infusion of dexmedetomidine and propofol, respectively. A strong linear relationship between pharyngeal critical pressure during dexmedetomidine and propofol sedation was evident at low (r = 0.82; P = 0.007) and moderate (r = 0.90; P < 0.001) infusion rates. CONCLUSIONS: These observations suggest that dexmedetomidine sedation does not inherently protect against upper airway obstruction.