Economic evaluation of telemonitoring as a follow-up approach for patients with obstructive sleep apnea syndrome starting treatment with continuous positive airway pressure.

Telemonitoring of obstructive sleep apnea patients is increasingly being adopted though its cost-effectiveness evidence base is scanty. This study investigated whether telemonitoring is a cost-effective strategy compared with the standard follow-up in patients with obstructive sleep apnea who are starting continuous positive airway pressure treatment. In total, 167 obstructive sleep apnea patients were randomised into telemonitoring (n = 79) or standard follow-up (n = 88), initiated continuous positive airway pressure treatment, and were followed up for 6 months. The frequencies of healthcare contacts, related costs (in USD 2021 prices), treatment effect and compliance were compared between the follow-up approaches using generalised linear models. The cost effectiveness analysis was conducted from a healthcare perspective and the results presented as cost per avoided extra clinic visit. Additionally, patient satisfaction between the two approaches was explored. The analysis showed no baseline differences. At follow-up, there was no significant difference in treatment compliance, and the mean residual apnea-hypoapnea index. There was no difference in total visits, adjusted incidence rate ratio 0.87 (0.72-1.06). Participants in the telemonitoring arm made eight times more telephone visits, 8.10 (5.04-13.84), and about 73% fewer physical healthcare visits 0.27 (0.20-0.36). This translated into significantly lower total costs for the telemonitoring approach compared with standard follow-up, -192 USD (-346 to -41). The form of follow-up seemed to have no impact on the extent of patient satisfaction. These results demonstrate the telemonitoring of patients with obstructive sleep apnea initiating continuous positive airway pressure treatment as a cost saving strategy and can be argued as a potential worthy investment.

Does obstructive sleep apnea increase the risk of cancer and cancer mortality in combined community-based cohorts?

Obstructive sleep apnea (OSA) has been linked to cancer in several clinical and community-based cohorts. The effect in community-based studies free of clinical referral bias needs to be replicated. In this observational prospective cohort study, we pooled data from three community-based prospective cohorts (Uppsala Sleep and Health in Men cohort [UMEN]; Sleep and health in women [SHE]; Men Androgen Inflammation Lifestyle Environment and Stress Cohort [MAILES]; nTotal = 1467). All cohorts had objective data on obstructive sleep apnea and registry linkage data on cancer and cancer mortality. Analyses for different obstructive sleep apnea measures (apnea-hypopnea index [AHI], oxygen desaturation index [ODI], and minimal saturation) as risk factors for cancer incidence (all cancers) were performed using Cox proportional hazards models (follow-up 5-16 years). We did not find an overall increased risk of cancer after adjustment for age, sex, and BMI (HRAHI [95% CI] = 1.00 [0.98; 1.01] and HRODI [95% CI] = 0.99 [0.97; 1.01]). Stratifying by daytime sleepiness did not influence the association. Cancer mortality was not significantly associated with obstructive sleep apnea. Taken together, we did not observe an overall increased risk of cancer or cancer mortality in relation to obstructive sleep apnea, however, our confidence limits remain wide for important diagnostic categories of sleep apnea severity. The relationship between obstructive sleep apnea and cancer needs further investigation in a comprehensive multi-cohort approach with greater statistical precision. For future studies we may need to find and then combine every community-based cohort study that can provide a definitive answer to the question on the risk of cancer from obstructive sleep apnea in the general population.

Development and performance of a sleep estimation algorithm using a single accelerometer placed on the thigh: an evaluation against polysomnography.

Accelerometers placed on the thigh provide accurate measures of daily physical activity types, postures and sedentary behaviours, over 24 h and across consecutive days. However, the ability to estimate sleep duration or quality from thigh-worn accelerometers is uncertain and has not been evaluated in comparison with the 'gold-standard' measurement of sleep polysomnography. This study aimed to develop an algorithm for sleep estimation using the raw data from a thigh-worn accelerometer and to evaluate it in comparison with polysomnography. The algorithm was developed and optimised on a dataset consisting of 23 single-night polysomnography recordings, collected in a laboratory, from 15 asymptomatic adults. This optimised algorithm was then applied to a separate evaluation dataset, in which, 71 adult males (mean [SD] age 57 [11] years, height 181 [6] cm, weight 82 [13] kg) wore ambulatory polysomnography equipment and a thigh-worn accelerometer, simultaneously, whilst sleeping at home. Compared with polysomnography, the algorithm had a sensitivity of 0.84 and a specificity of 0.55 when estimating sleep periods. Sleep intervals were underestimated by 21 min (130 min, Limits of Agreement Range [LoAR]). Total sleep time was underestimated by 32 min (233 min LoAR). Our results evaluate the performance of a new algorithm for estimating sleep and outline the limitations. Based on these results, we conclude that a single device can provide estimates of the sleep interval and total sleep time with sufficient accuracy for the measurement of daily physical activity, sedentary behaviour, and sleep, on a group level in free-living settings.

Rapid eye movement sleep apnea and carotid intima thickness in men and women: a SHE-MUSTACHE cohort study.

Rapid eye movement (REM) obstructive sleep apnea might be particularly harmful to the cardiovascular system. We aimed to investigate the association between sleep apnea during REM sleep and signs of atherosclerotic disease in the form of carotid intima thickness in a community-based sample of men and women and possible sex differences in this association. The association between sleep apnea during REM sleep and intima thickness was analysed cross-sectionally in women from the community-based "Sleep and Health in Women" (SHE) study (n = 253) and age- and body mass index (BMI)-matched men from the "Men in Uppsala; a Study of sleep, Apnea and Cardiometabolic Health" (MUSTACHE) study (n = 338). Confounders adjusted for were age, BMI, gender, alcohol, and smoking. All participants underwent a full-night polysomnography, high-resolution ultrasonography of the common carotid artery, anthropometric measurements, blood pressure measurements, and answered questionnaires. There was an association between sleep apnea during REM sleep and thicker carotid intima that remained after adjustment for confounding (adjusted ß = 0.008, p = 0.032). The intima was increased by 9.9% in the group with severe sleep apnea during REM sleep, and this association between severe sleep apnea during REM sleep and increased intima thickness remained after adjustment for confounders (adjusted ß = 0.043, p = 0.021). More women than men had severe sleep apnea during REM sleep; moreover, in sex-stratified analyses, the association between sleep apnea during REM sleep and intima thickness was found in women but not in men. We conclude that severe REM sleep apnea is independently associated with signs of atherosclerosis. When stratified by sex, the association is seen in women but not in men.

Relationship between sleep characteristics and markers of inflammation in Swedish women from the general population.

Systemic inflammation is thought to mediate the link between sleep and cardiovascular outcomes, but previous studies on sleep habits and inflammation markers have found inconsistent results. This study investigated the relationship between sleep characteristics and C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor α (TNFα). A representative sample of 319 Swedish women was randomly selected from the general population for in-home polysomnography, sleep questionnaire and blood samples. As variables were highly correlated, principal component analysis was used to reduce the number of original variables. Linear regression with log-transformation of the outcomes (lnCRP, lnIL-6 and lnTNFα) and quantile regression were fitted to estimate cross-sectional relationships. Multivariable linear regression models suggested a significant association of insomnia symptoms (self-reported) with higher lnCRP levels (ß = 0.11; 95% confidence interval [CI] = 0.02; 0.21), but not with lnIL-6 and lnTNFα. From quantile regression analysis we found that a high non-restorative index (subjective) and insomnia symptoms (self-reported) were associated with higher values of CRP, especially in the highest quantiles of the CRP distribution (90th percentile: ß = 0.71; 95% CI = 0.17; 1.24. ß = 1.23; 95% CI = 0.44; 2.02, respectively). Additionally, higher amounts of rapid eye movement (REM) sleep were associated with lower CRP values (90th percentile: ß = -0.80; 95% CI = -0.14; -1.46). In conclusion, sleep disturbances (self-reported), specifically difficulties maintaining sleep and early morning awakenings, but not sleep duration (neither subjective nor objective), were associated with higher CRP levels. No association was found with IL-6 or TNFα. Elevated REM sleep was associated with lower CRP levels. The results suggest that inflammation might be an intermediate mechanism linking sleep and health in women.

Sleep duration is associated with protein biomarkers for cardiometabolic health: A large-scale population study.

Sleep problems and short sleep duration have been linked to adverse health effects, such as cardiovascular disease and diabetes, but the mechanisms are not fully understood. Finding biomarkers could explain mechanistic pathways and help in understanding relationships between sleep and cardiometabolic health. The aim was to assess if sleep duration and sleep quality affect the cardiometabolic-related protein profile. In total, 242 proteins related to cardiometabolic health were measured in 2,430 plasma samples (male:female ratio 1:1, aged 45-75 years) from the population-based EpiHealth cohort, using a proximity extension assay. The association of self-reported sleep duration and sleep quality with each of the 242 proteins (primary outcome) was assessed with linear regression modelling, adjusting for confounders, and corrected for multiple testing using the false discovery rate (5%). Potential effect modification of age and sex was also tested using an interaction term. We identified U-shaped associations between sleep duration and the plasma levels of the proteins follistatin (more prominent in younger individuals), matrix metallopeptidase 9 (men only), urokinase receptor, adrenomedullin and kidney injury molecule, all previously known to be related to cardiovascular risk. There was no relationship between sleep quality and any of the proteins, after adjustment for confounders. These results give new leads to investigate the potential mechanistic pathways between sleep and cardiometabolic health.

Association between proteomics and obstructive sleep apnea phenotypes in a community-based cohort of women.

Proteomic-based technologies offer new opportunities to identify proteins that might reflect the cardiometabolic stress caused by different aspects of sleep-disordered breathing. We aimed to investigate whether severe obstructive sleep apnea and severe obstructive sleep apnea during rapid eye movement sleep are associated with changed levels of inflammatory and cardiac disease-related proteins in a population-based cohort of women. In the community-based "Sleep and Health in Women" (SHE) cohort study, 400 women underwent polysomnography, anthropometric measurements and blood sampling. Two proteomic assays (Olink Proseek® Inflammation panel and Olink Proseek® Cardiovascular II panel), each measuring 92 proteins, were analysed in a subsample of 253 women. p-Values were adjusted for multiple testing, with false discovery rate set at 10%. In unadjusted models, 57 proteins were associated with apnea-hypopnea index, 56 proteins with oxygen desaturation index and 64 proteins with rapid eye movement-apnea-hypopnea index. After adjustment for age, body mass index and plate, there were no significant associations between apnea-hypopnea index or oxygen desaturation index and any of the proteins. Severe obstructive sleep apnea during rapid eye movement sleep (rapid eye movement-apnea-hypopnea index ≥ 30) was associated with decreased levels of two anti-inflammatory proteins; Sirt2 (q-value .016) and LAP-TGF-ß1 (q-value .016). There was also a negative association between rapid eye movement-apnea-hypopnea index of ≥ 30 and Axin1 (q-value .095), a protein thought to facilitate TGF-ß-signalling. We conclude that severe obstructive sleep apnea during rapid eye movement sleep is associated with low levels of Sirt2, LAP-TGF-ß1 and Axin1, anti-inflammatory proteins involved in metabolic regulation and in the atherosclerotic process. For obstructive sleep apnea based on a whole night, the associations with cardiac and inflammatory proteins are weaker, and explained to a large extent by age and body mass index.

Short sleep-poor sleep? A polysomnographic study in a large population-based sample of women.

There is a lack of studies on the association between total sleep time (TST) and other polysomnographical parameters. A key question is whether a short sleep is an expression of habitual short sleep, or whether it reflects temporary impairment. The purpose of the present study was to investigate the association between TST and amount of sleep stages and sleep continuity measures, in a large population-based sample of women (n = 385), sleeping at home in a normal daily life setting. The results show that sleep efficiency, N1 (min), N2 (min), REM (min), REM% and proportion of long sleep segments, increased with increasing TST, whereas the number of awakenings/hr, the number of arousals/hr, N1% and REM intensity decreased. In addition, longer sleep was more associated with TST being perceived as of "usual" duration and with better subjective sleep quality. TST was not associated with habitual reported sleep duration. It was concluded that short TST of a recorded sleep in a real-life context may be an indicator of poor objective sleep quality for that particular sleep episode. Because individuals clearly perceived this reduction, it appears that self-reports of poor sleep quality often may be seen as indicators of poor sleep quality. It is also concluded that PSG-recorded sleep duration does not reflect habitual reported sleep duration in the present real-life context.

Changes of vitamin D levels and bone turnover markers after CPAP therapy: a randomized sham-controlled trial.

The aim was to investigate whether continuous positive airway pressure treatment could modulate serum vitamin D (25-hydroxyvitamin D) and bone turnover markers (collagen-type 1 cross-linked C-telopeptide, osteocalcin and N-terminal propeptide of type 1 collagen) in secondary analysis from a randomized controlled trial. Sixty-five continuous positive airway pressure-naïve male patients with obstructive sleep apnea (age = 49 ± 12 years, apnea-hypopnea index = 39.9 ± 17.7 events h-1 , body mass index = 31.3 ± 5.2 kg m-2 ) were randomized to receive either real (n = 34) or sham (n = 31) continuous positive airway pressure for 12 weeks. At 12 weeks, all participants received real continuous positive airway pressure for an additional 12 weeks. After 12 weeks of continuous positive airway pressure (real versus sham), there were no between-group differences for any of the main outcomes [Δ25-hydroxyvitamin D: -0.80 ± 5.28 ng mL-1 (mean ± SE) versus 3.08 ± 3.66 ng mL-1 , P = 0.42; Δcollagen-type 1 cross-linked C-telopeptide: 0.011 ± 0.014 ng mL-1 versus -0.004 ± 0.009 ng mL-1 , P = 0.48; Δosteocalcin: 1.13 ± 1.12 ng mL-1 versus 0.46 ± 0.75 ng mL-1 , P = 0.80; ΔN-terminal propeptide of type 1 collagen: 2.07 ± 3.05 µg L-1 versus -1.05 ± 2.13 µg L-1 , P = 0.48]. There were no further differences in subgroup analyses (continuous positive airway pressure-compliant patients, patients with severe obstructive sleep apnea or sleepy patients). However, after 24 weeks irrespective of initial randomization, vitamin D increased in patients with severe obstructive sleep apnea (9.56 ± 5.51 ng mL-1 , P = 0.045) and in sleepy patients (14.0 ± 4.69 ng mL-1 , P = 0.007). Also, there was a significant increase in osteocalcin at 24 weeks (3.27 ± 1.06 ng mL-1 , P = 0.01) in compliant patients. We conclude that 12 weeks of continuous positive airway pressure did not modulate vitamin D or modulate any of the bone turnover markers compared with sham. However, it is plausible that continuous positive airway pressure may have late beneficial effects on vitamin D levels and bone turnover markers in selected groups of patients with obstructive sleep apnea.

An educational intervention to improve hand hygiene compliance in Vietnam.

BACKGROUND: Hand hygiene compliance is the basis of infection control programs. In developing countries models to improve hand hygiene compliance to reduce healthcare acquired infections are required. The aim of this study was to determine hand hygiene compliance following an educational program in an obstetric and gynecological hospital in Vietnam. METHODS: Health care workers from neonatal intensive care, delivery suite and a surgical ward from Hung Vuong Hospital, Ho Chi Minh City, Vietnam undertook a 4-h educational program targeting hand hygiene. Compliance was monitored monthly for six months following the intervention. Hand hygiene knowledge was assessed at baseline and after six months of the study. RESULTS: There were 7124 opportunities over 370 hand hygiene recording sessions with 1531 opportunities at baseline and 1620 at 6 months following the intervention. Hand hygiene compliance increased significantly from baseline across all sites (43.6% [95% Confidence interval CI: 41.1-46.1] to 63% [95% CI: 60.6-65.3]; p < 0.0001). Health care worker hand hygiene compliance increased significantly after intervention (p < 0.0001). There were significant improvements in knowledge scores from baseline to 2 months post educational intervention with mean difference standard deviations (SD): 1.5 (2.5); p < 0.001). CONCLUSIONS: A simple educational model was implemented in a Vietnamese hospital that revealed good hand hygiene compliance for an extended period of time. Hand hygiene knowledge increased during the intervention. This hand hygiene model could be used in developing countries were resources are limited.

Age affects sleep microstructure more than sleep macrostructure.

It is well known that the quantity and quality of physiological sleep changes across age. However, so far the effect of age on sleep microstructure has been mostly addressed in small samples. The current study examines the effect of age on several measures of sleep macro- and microstructure in 211 women (22-71 years old) of the 'Sleep and Health in Women' study for whom ambulatory polysomnography was registered. Older age was associated with significantly lower fast spindle (effect size f2  = 0.32) and K-complex density (f2  = 0.19) during N2 sleep, as well as slow-wave activity (log) in N3 sleep (f2  = 0.21). Moreover, total sleep time (f2  = 0.10), N3 sleep (min) (f2  = 0.10), rapid eye movement sleep (min) (f2  = 0.11) and sigma (log) (f2  = 0.05) and slow-wave activity (log) during non-rapid eye movement sleep (f2  = 0.09) were reduced, and N1 sleep (f2  = 0.03) was increased in older age. No significant effects of age were observed on slow spindle density, rapid eye movement density and beta power (log) during non-rapid eye movement sleep. In conclusion, effect sizes indicate that traditional sleep stage scoring may underestimate age-related changes in sleep.

The relation between polysomnography and subjective sleep and its dependence on age - poor sleep may become good sleep.

Women complain more about sleep than men, but polysomnography (PSG) seems to suggest worse sleep in men. This raises the question of how women (or men) perceive objective (PSG) sleep. The present study sought to investigate the relation between morning subjective sleep quality and PSG variables in older and younger women. A representative sample of 251 women was analysed in age groups above and below 51.5 years (median). PSG was recorded at home during one night. Perceived poor sleep was related to short total sleep time (TST), long wake within total sleep time (WTSP), low sleep efficiency and a high number of awakenings. The older women showed lower TST and sleep efficiency and higher WTSP for a rating of good sleep than did the younger women. For these PSG variables the values for good sleep in the older group were similar to the values for poor sleep in the young group. It was concluded that women perceive different levels of sleep duration, sleep efficiency and wake after sleep onset relatively well, but that older women adjust their objective criteria for good sleep downwards. It was also concluded that age is an important factor in the relation between subjective and objective sleep.

Impact of nasal obstruction on sleep quality: a community-based study of women.

The aim of the study was to analyse the impact of self-reported nasal obstruction on sleep quality in women. A community-based sample of 400 women underwent a full night of polysomnography. Airway diseases, allergies and sleep-related symptoms were assessed by questionnaires. Women with subjective nasal obstruction were subdivided into three groups: persistent nasal obstruction (PNO, n = 46), hay fever (n = 88) and nasal obstruction at night (NON, n = 30). Sleep problems and related daytime symptoms were most prevalent among women with NON. After adjusting for age, BMI, smoking and asthma, NON was an independent predictor of 'Difficulties inducing sleep due to nasal obstruction' [adjusted odds ratio (95 % CI): 89.5 (27.0-296.7)], 'Snoring' [4.2 (1.7-10.2)], 'Sweating at night' [2.6 (1.1-6.1)], 'Difficulties maintaining sleep' [2.7 (1.2-6.2)], and 'Waking up hastily gasping for breath' [32.2 (8.7-119.1)]. 'Dry mouth on awakening' [7.7 (3.2-18.4)], 'Waking up unrefreshed' [2.7 (1.2-6.0)], 'Excessive daytime sleepiness' [2.6 (1.1-6.0)], and 'Daytime nasal obstruction' [12.2 (4.8-31.2)] were also associated with NON. Persistent nasal obstruction and hay fever were both associated with some reported sleep problems due to an overlap with NON. When women with NON were excluded, only 'Daytime nasal obstruction' was still significantly associated with PNO, while hay fever was associated with 'Daytime nasal obstruction' and 'Waking up hastily gasping for breath'. There were no significant differences in objectively measured sleep variables between any of the three subgroups and the study cohort. Self-reported nasal obstruction at night in women has a significant effect on several subjective day- and nighttime symptoms, but it does not appear to affect objectively measured sleep quality.

What do women mean by poor sleep? A large population-based sample with polysomnographical indicators, inflammation, fatigue, depression, and anxiety.

Survey studies indicate that reports of disturbed sleep are prevalent and may be prospectively linked to several major diseases. However, it is not clear what self-reported disturbed sleep represents, since the link with objective sleep measures (polysomnography; PSG) seems very weak. The purpose of the present study was to try to investigate what combination of variables (PSG, inflammation, fatigue, anxiety, depression) that would characterize those who complain of disturbed sleep. This has never been done before. Participants were 319 women in a population-based sample, who gave ratings of sleep quality, fatigue, depression, and anxiety, then had their sleep recorded at home, and had blood drawn the following morning for analysis of immune parameters. Correlations and hierarchical multivariable regression analyses were applied to the data. For ratings of difficulties initiating sleep, the associations in the final step were ß = .22, (p < .001) for fatigue, ß = 0.22 (p < .001) for anxiety, and ß = 0.17 (p < .01) for sleep latency, with R2 = 0.14. The rating of repeated awakenings was associated with fatigue (ß = 0.35, p < .001) and C-reactive protein (CRP) (ß = 0.12, p < .05), with R2 = 0.19. The rating of early morning awakenings was associated with fatigue (ß = 0.31, p < .001), total sleep time (TST) (ß = -0.20, p < .01), and CRP (ß = 0.15, p < .05), with R2 = 0.17. Interleukin-6 and Tumour Necrosis Factor were not associated with ratings of sleep problems. The results indicate that subjective fatigue, rather than objective sleep variables, is central in the perception of poor sleep, together with CRP.

Effects of telemonitoring follow-up, side effects, and other factors on CPAP adherence.

STUDY OBJECTIVES: This study aimed to investigate the effect of telemonitoring compared with standard clinic visits on adherence to continuous positive airway pressure (CPAP) treatment after 6 months. In addition, the impact of other factors including CPAP side effects on treatment adherence were assessed. METHODS: Consecutive patients (n = 217) who were prescribed CPAP treatment for obstructive sleep apnea were randomized to either telemonitoring or standard-care follow-up. All patients were followed up 6 months after treatment started. Clinical/anthropometric variables, socioeconomical and lifestyle factors, psychological distress, daily function, and personality traits along with CPAP side effects were assessed. Differences between groups were analyzed using 2-sample t-test, chi-square test, or Fisher's exact test. Regression modeling was used to explore associations between dependent and independent variables. RESULTS: There were no differences in CPAP adherence between telemonitoring and standard-care groups after 6 months (53.2% vs 48.7%; P = .54). CPAP side effects such as dry throat (odds ratio = 2.17; 95% confidence interval = 1.25-3.70), increased awakenings (2.50; 1.31-4.76), and exhaling problems (3.70; 1.25-10.1) were independently associated with low CPAP adherence, although these associations were weakened when adding smoking to the model. No other baseline or follow-up factors were associated with CPAP adherence at 6 months. CONCLUSIONS: We could not show that telemonitoring follow-up improved adherence levels. Dry throat, increased awakenings, exhaling problems, and smoking had negative effects on CPAP adherence. Preventing side effects and assessing smoking status is therefore of importance when wanting to improve CPAP adherence. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Benefits of Telemedicine in CPAP Treatment; URL: https://clinicaltrials.gov/ct2/show/NCT03202602; Identifier: NCT03202602. CITATION: Delijaj F, Lindberg E, Johnsson L, Kristiansson P, Tegelmo T, Theorell-Haglöw J. Effects of telemonitoring follow-up, side effects, and other factors on CPAP adherence. J Clin Sleep Med. 2023;19(10):1785-1795.

Breathlessness and exercise performance to predict mortality in long-term oxygen therapy - The population-based DISCOVERY study.

BACKGROUND: Patients with chronic respiratory failure treated with long-term oxygen therapy (LTOT) often have severe breathlessness, impaired exercise performance, and high but variable mortality that is difficult to predict. We aimed to evaluate breathlessness and exercise performance upon starting LTOT as predictors of overall and short-term mortality. METHODS: This was a longitudinal, population-based study of patients who initiated LTOT between 2015 and 2018 in Sweden. Breathlessness was measured using the Dyspnea Exertion Scale, and exercise performance using the 30s-Sit-To-Stand test. Associations with overall and three-month mortality were analyzed using Cox-regression. Subgroup analyses were performed for patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) respectively. The predictive capacity of models was assessed using a C-statistic. RESULTS: A total of 441 patients (57.6% female, aged 75.4 ± 8.3 years) were analyzed, of whom 141 (32%) died during a median follow-up of 260 (IQR 75-460) days. Both breathlessness and exercise performance were independently associated with overall mortality in the crude models, but only exercise performance remained independently associated with overall mortality when models were adjusted for other predictors, when short-term mortality was analyzed, or when breathlessness and exercise capacity were analyzed concurrently. The multivariable model including exercise performance but not breathlessness provided a relatively high predictive capacity for overall mortality, C-statistic 0.756 (95% CI 0.702-0.810). Similar results were seen in the COPD and ILD subgroups. CONCLUSION: Exercise performance as measured by the 30s-STS may be useful to identify patients with higher mortality on LTOT for optimized management and follow-up.

National Knowledge-Driven Management of Obstructive Sleep Apnea-The Swedish Approach.

INTRODUCTION: This paper describes the development of "Swedish Guidelines for OSA treatment" and the underlying managed care process. The Apnea Hypopnea Index (AHI) is traditionally used as a single parameter for obstructive sleep apnea (OSA) severity classification, although poorly associated with symptomatology and outcome. We instead implement a novel matrix for shared treatment decisions based on available evidence. METHODS: A national expert group including medical and dental specialists, nurses, and patient representatives developed the knowledge-driven management model. A Delphi round was performed amongst experts from all Swedish regions (N = 24). Evidence reflecting treatment effects was extracted from systematic reviews, meta-analyses, and randomized clinical trials. RESULTS: The treatment decision in the process includes a matrix with five categories from a "very weak"" to "very strong" indication to treat, and it includes factors with potential influence on outcome, including (A) OSA-related symptoms, (B) cardiometabolic comorbidities, (C) frequency of respiratory events, and (D) age. OSA-related symptoms indicate a strong incitement to treat, whereas the absence of symptoms, age above 65 years, and no or well-controlled comorbidities indicate a weak treatment indication, irrespective of AHI. CONCLUSIONS: The novel treatment matrix is based on the effects of treatments rather than the actual frequency of respiratory events during sleep. A nationwide implementation of this matrix is ongoing, and the outcome is monitored in a prospective evaluation by means of the Swedish Sleep Apnea Registry (SESAR).

Cardiovascular disease-linked plasma proteins are mainly associated with lung volume.

Background: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. Methods: We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort. Results: Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity. Conclusions: Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.

OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study.

BACKGROUND: OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism. RESEARCH QUESTION: Does OSA in adults associate with the composition and functional potential of the human gut microbiota? STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register. RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Finally, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively. INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.

Total sleep time, sleep efficiency, and next day subjective sleepiness in a large group of women.

The relationship between sleep duration and sleepiness has seen much research, but no data are available on the association between polysomnographically (PSG) determined total sleep time (TST) (or other PSG variables) and subjective sleepiness during the subsequent day in individuals in their habitual life situation. The purpose of the present study was to study the association between TST and sleep efficiency (SE) (and other PSG variables) and next-day sleepiness at 7 times of the day. A large population-based group of women (N = 400) participated. Daytime sleepiness was measured with the Karolinska Sleepiness Scale (KSS). The association was studied through analysis of variance (ANOVA), as well as regression analyses. For SE there was a significant difference in sleepiness across groups with >90%, 80%-89.99%, and <80% SE (F = 7.2, p < .001, eta2 = 0.04), with lowest sleepiness in the first group. In contrast, TST groups of <6 h, 6-6.99 h, and ≥7 h did not differ significantly. In addition, a pronounced U-shape (eta2 > 0.45) was seen for both analyses, with maximum sleepiness at bedtime (≈ 7.5 KSS units). A multiple regression analysis, including all PSG variables (adjusted for age and BMI), showed that SE was a significant predictor (ß = 0.16, p < .05) of mean sleepiness, even after depression, anxiety, and subjective sleep duration were entered, but this was eliminated by subjective sleep quality. It was concluded that high SE is modestly associated with lower next-day sleepiness in women in a real-life context, but that TST is not.