Obstructive sleep apnea severity, circulating biomarkers, and cancer risk.

STUDY OBJECTIVES: To determine if obstructive sleep apnea (OSA) severity and/or biomarkers of inflammation/angiogenesis are associated with incident cancer in this clinical cohort. METHODS: Consenting adult patients at the University of British Columbia Hospital between 2003-2014 completed a questionnaire about their medical history and sleep habits prior to undergoing a polysomnogram (PSG). Blood samples were collected the morning after PSG and processed for biomarkers of inflammation and angiogenesis. The clinical, PSG, and biomarker data were linked to the British Columbia Cancer Registry to ascertain incident cancer diagnoses. Cox proportional hazard regression were used to assess the association between OSA severity and biomarker concentrations with cancer risk. RESULTS: A total of 1,990 patients were included in the analysis with a mean follow-up time of 12.8 years; 181 of them (9.1%) developed cancer after PSG. OSA severity was significantly associated with cancer risk after controlling for relevant covariates (hazard ratio (HR) = 1.08 per 10 events/h apnea-hypopnea index (AHI) increase, CI = 1.02-1.15, p=0.015). In an exploratory analysis, two biomarkers were significantly associated with an increased cancer risk after controlling for relevant covariates (HR per interquartile range (IQR) pg/mL increase of endostatin = 1.45, CI = 1.12-1.87, p=0.01 and HR for IQR pg/mL increase of VCAM-1 = 1.48, CI = 1.04-2.11, p=0.03, respectively). CONCLUSIONS: OSA severity was an independent risk factor for cancer. Furthermore, two circulating markers were significantly associated with cancer risk. If these preliminary findings can be reproduced in other cohorts, biomarkers could potentially be used to prognosticate OSA patients with respect to cancer risk.

Air pollution, weather and positive airway pressure treatment adherence in adults with sleep apnea: a retrospective community-based repeated-measures longitudinal study.

We assessed the relation between air pollution, weather, and adherence to positive airway pressure (PAP) therapy in a retrospective community-based repeated-measures study of adults with obstructive sleep apnea who purchased PAP devices from a registered provider between 2013 and 2017 (Ottawa, Ontario, Canada) and had at least one day of data. Daily PAP-derived data, air pollution, and weather databases were linked using postal code. The exposures were mean nocturnal (8:00 p.m. to 8:00 a.m.) (i) residential concentrations of nitrogen dioxide (NO2 ), fine particulate matter <=2.5 µm (PM2.5 ), ozone (O3 ), and Air Quality Health Index (AQHI), and (ii) temperature, relative humidity, and barometric pressure. Covariates in the main model were demographics, season, exposure year, and PAP therapy mode. We analysed 8148 adults (median age of 54 years and 61% men) and 2,071,588 days of data. Based on daily data, the median (interquartile range) daily PAP usage was 416 (323-487) min. Using mixed-effect regression analyses to incorporate daily data and clustering by individuals, we found a statistically significant decrease in adherence for increased levels of NO2 , PM2.5 , and AQHI. The largest effect was for NO2 : a decrease in daily PAP use while comparing the highest versus lowest quartiles (Qs) was 3.4 (95% confidence interval [CI] 2.8-3.9) min. Decreased PAP adherence was also associated with increased temperature (Q4 versus Q1: 2.6 [95% CI: 1.5-3.7] min) and decreased barometric pressure (Q1 versus Q4: 2.0 [95% CI 1.5-2.5] min). We observed modest but statistically significant acute effects of air pollution and weather on daily PAP adherence.

All Obstructive Sleep Apnea Events Are Not Created Equal: The Relationship Between Event-related Hypoxemia and Physiologic Response.

RATIONALE: Obstructive sleep apnea (OSA) severity is typically assessed by the apnea-hypopnea index (AHI), a frequency-based metric that allocates equal weight to all respiratory events. However, more severe events may have a greater physiologic impact. OBJECTIVE: The purpose of this study was to determine whether the degree of event-related hypoxemia would be associated with the post-event physiologic response. METHODS: OSA patients (AHI>5/h) from the multi-center Canadian Sleep and Circadian Network cohort were studied. Using mixed-effect linear regression, we examined associations between event-related hypoxic burden (HBev) assessed by the area under the event-related oxygen saturation recording with heart rate changes (ΔHRev), vasoconstriction (vasoconstriction burden (VCBev) assessed with photoplethysmography), and electroencephalographic responses (power ratio before and after events). RESULTS: Polysomnography recordings from 658 patients (Median [IQR] age= 55.00 [45.00, 64.00] years, AHI= 27.15 [14.90, 64.05] event/h, 42% female) were included in the analyses. HBev was associated with an increase in all physiologic responses after controlling for age, sex, body mass index (BMI), sleep stage, total sleep time, and study centers; for example, one standard deviation (SD) increase in HBev was associated with a 0.21 [95% CI: 0.2, 0.22], 0.08 [0.08, 0.09] and 0.22 [0.21, 0.23] SD increase in ΔHRev, VCBev and Beta power ratio respectively). CONCLUSION: Increased event-related hypoxic burden was associated with greater responses across a broad range of physiologic signals. Future metrics that incorporate information about the variability of these physiologic responses may have promise in providing a more nuanced assessment of OSA severity.

Noninvasive Home Mechanical Ventilation for Stable Hypercapnic COPD: A Clinical Respiratory Review from Canadian Perspectives.

Acute short-term noninvasive ventilation (NIV) for hypercapnic respiratory failure in chronic obstructive pulmonary disease (COPD) has well-established benefits; however, the role of long-term home NIV remains controversial. In the past decade, studies utilizing aggressive NIV settings to maximally reduce carbon dioxide levels (PaCO2) have resulted in several positive clinical trials and led to updated guidelines on home NIV for stable hypercapnic COPD patients. This clinical respiratory review discusses the high-intensity NIV approach, summarizes recent key trials and guidelines pertaining to home NIV in COPD, and considers key clinical questions for future research and application in the Canadian context. With recent evidence and Canadian Thoracic Society (CTS) guidelines supporting the use of NIV in carefully selected COPD patients with persistent daytime hypercapnia, we believe it is time to reconsider our approach.

The association between sleep quality and obstructive sleep apnea with health-related quality of life in children with obesity.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and poor sleep quality are highly prevalent in children with obesity, but their individual associations with health-related quality of life (HRQOL) are unknown in this population. The primary objective was to describe the independent association of OSA and sleep quality with HRQOL in children with obesity. METHODS: This was a cross-sectional study of children with obesity at 2 tertiary care centers. Sleep quality and HRQOL were measured with the Pittsburgh Sleep Quality Index and Pediatric Quality of Life Inventory questionnaires, respectively. Multivariable regression models were created to evaluate associations between OSA and sleep quality with HRQOL. RESULTS: There were 98 children (median age 15.0 years, median body mass index z-score 3.8, 44% females). Among the study population, 49/98 (50%) children reported poor sleep quality, 41/98 (42%) children had OSA, and 52/98 (53%) children reported impaired HRQOL. Self-reported poor sleep quality was independently associated with reduced HRQOL, whereas the presence of OSA was not. Children with poor sleep quality had a reduced Pediatric Quality of Life Inventory score by 8.8 compared to children with good sleep quality (95% confidence interval, 2.6-14.9; P = .006), when adjusting for age, sex, body mass index z-score, attention-deficit/hyperactivity disorder, mood/anxiety disorder, and study site. CONCLUSIONS: In the current study of children with obesity, we found that HRQOL was more strongly associated with the self-reported experience of sleep than the presence of OSA. Clinicians should assess and optimize sleep quality as part of the evaluation for OSA in children with obesity. CITATION: Xiao L, Voutsas G, Ryan CM, Katz SL, Narang I. The association between sleep quality and obstructive sleep apnea with health-related quality of life in children with obesity. J Clin Sleep Med. 2023;19(11):1877-1883.

Role of precision medicine in obstructive sleep apnoea.

Obstructive sleep apnoea is a substantial clinical and public health problem because it contributes to harmful effects on quality of life, daytime symptoms, road traffic incidents, and cardiometabolic disease. Increasingly, obstructive sleep apnoea is recognised as a heterogeneous disease, and patients have varied susceptibility to long term complications and different responses to treatment. This narrative review summarises the current knowledge of precision medicine in obstructive sleep apnoea, particularly the role of symptom clusters, polysomnogram phenotypes, physiological endotypes, and circulating biomarkers in defining subtypes. In the near future, the prognostic accuracy of these measures in predicting long term complications in obstructive sleep apnoea will likely be improved, together with better matching of treatments to disease subtypes.

Causes, Consequences, and Treatments of Sleep and Circadian Disruption in the ICU: An Official American Thoracic Society Research Statement.

Background: Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non-ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD. Methods: We convened a multidisciplinary group with relevant expertise to participate in an American Thoracic Society Workshop. Workshop objectives included identifying ICU SCD subtopics of interest, key knowledge gaps, and research priorities. Members attended remote sessions from March to November 2021. Recorded presentations were prepared and viewed by members before Workshop sessions. Workshop discussion focused on key gaps and related research priorities. The priorities listed herein were selected on the basis of rank as established by a series of anonymous surveys. Results: We identified the following research priorities: establish an ICU SCD definition, further develop rigorous and feasible ICU SCD measures, test associations between ICU SCD domains and outcomes, promote the inclusion of mechanistic and patient-centered outcomes within large clinical studies, leverage implementation science strategies to maximize intervention fidelity and sustainability, and collaborate among investigators to harmonize methods and promote multisite investigation. Conclusions: ICU SCD is a complex and compelling potential target for improving ICU outcomes. Given the influence on all other research priorities, further development of rigorous, feasible ICU SCD measurement is a key next step in advancing the field.

Moving toward Equitable Care for Sleep Apnea in the United States: Positive Airway Pressure Adherence Thresholds: An Official American Thoracic Society Policy Statement.

Background: Positive airway pressure (PAP) is a highly effective treatment for obstructive sleep apnea (OSA), but adherence limits its efficacy. In addition, coverage of PAP by CMS (Centers for Medicare & Medicaid Services) and other insurers in the United States depends on adherence. This leaves many beneficiaries without PAP, disproportionally impacting non-white and low socioeconomic position patients with OSA and exacerbating sleep health disparities. Methods: An inter-professional, multidisciplinary, international committee with various stakeholders was formed. Three working groups (the historical policy origins, impact of current policy, and international PAP coverage models) met and performed literature reviews and discussions. Using surveys and an iterative discussion-based consensus process, the policy statement recommendations were created. Results: In this position paper, we advocate for policy change to CMS PAP coverage requirements to reduce inequities and align with patient-centered goals. We specifically call for eradicating repeat polysomnography, eliminating the 4-hour rule, and focusing on patient-oriented outcomes such as improved sleepiness and sleep quality. Conclusions: Modifications to the current policies for PAP insurance coverage could improve health disparities.

Contribution of obstructive sleep apnea to disrupted sleep in a large clinical cohort of patients with suspected obstructive sleep apnea.

STUDY OBJECTIVES: The response of sleep depth to CPAP in patients with OSA is unpredictable. The odds-ratio-product (ORP) is a continuous index of sleep depth and wake propensity that distinguishes different sleep depths within sleep stages, and different levels of vigilance during stage wake. When expressed as fractions of time spent in different ORP deciles, nine distinctive patterns are found. Only three of these are associated with OSA. We sought to determine whether sleep depth improves on CPAP exclusively in patients with these three ORP patterns. METHODS: ORP was measured during the diagnostic and therapeutic components of 576 split-night polysomnographic (PSG) studies. ORP architecture in the diagnostic section was classified into one of the nine possible ORP patterns and the changes in sleep architecture were determined on CPAP for each of these patterns. ORP architecture was similarly determined in the first half of 760 full-night diagnostic PSG studies and the changes in the second half were measured to control for differences in sleep architecture between the early and late portions of sleep time in the absence of CPAP. RESULTS: Frequency of the three ORP patterns increased progressively with the apnea-hypopnea index. Sleep depth improved significantly on CPAP only in the three ORP patterns associated with OSA. Changes in CPAP in the other six patterns, or in full diagnostic PSG studies, were insignificant or paradoxical. CONCLUSIONS: ORP architecture types can identify patients in whom OSA adversely affects sleep and whose sleep is expected to improve on CPAP therapy.

Association of clinically significant obstructive sleep apnoea with risks of contracting COVID-19 and serious COVID-19 complications: a retrospective population-based study of health administrative data.

RATIONALE/OBJECTIVES: Despite plausible pathophysiological mechanisms, more research is needed to confirm the relationship between obstructive sleep apnoea (OSA) and the risk of COVID-19 infection or COVID-19-related serious complications. METHODS: We conducted a retrospective population-based cohort study using provincial health administrative data (Ontario, Canada). Adults with physician-diagnosed OSA who received positive airway pressure therapy in the 5 years prepandemic (OSA group) were propensity score matched by baseline characteristics to individuals in the general population at low risk of OSA (non-OSA group) using inverse probability of treatment weighting. Weighted HRs of (1) a positive COVID-19 test and (2) COVID-19-related emergency department (ED) visits, hospitalisations, intensive care unit (ICU) admissions and mortality, within 12 months of pandemic onset, were compared between groups. We also evaluated the impact of comorbid cardiometabolic or chronic airways disease. RESULTS: We identified and matched 324 029 individuals in the OSA group to 4 588 200 individuals in the non-OSA group. Compared with the non-OSA group, those in the OSA group were at a greater hazard of testing positive for COVID-19 (HR=1.17, 95% CI 1.13 to 1.21), having a COVID-19-related ED visit (HR=1.62, 95% CI 1.51 to 1.73), hospitalisation (HR=1.50, 95% CI 1.37 to 1.65) or ICU admission (HR=1.53, 95% CI 1.27 to 1.84). COVID-19-related 30-day mortality was not different (HR=0.98, 95% CI 0.82 to 1.16).We found that for the OSA group, comorbid airways disease but not cardiometabolic conditions increased the hazards of COVID-19-related outcomes, including mortality. CONCLUSION: In this large population-based study, we demonstrated that a recent diagnosis of OSA requiring treatment was associated with an increased hazard of testing positive for COVID-19 and serious COVID-19-related complications, particularly in those with co-existing chronic airways disease.

Association of alternative polysomnographic features with patient outcomes in obstructive sleep apnea: a systematic review.

STUDY OBJECTIVES: Polysomnograms (PSGs) collect a plethora of physiologic signals across the night. However, few of these PSG data are incorporated into standard reports, and hence, ultimately, under-utilized in clinical decision making. Recently, there has been substantial interest regarding novel alternative PSG metrics that may help to predict obstructive sleep apnea (OSA)-related outcomes better than standard PSG metrics such as the apnea-hypopnea index. We systematically review the recent literature for studies that examined the use of alternative PSG metrics in the context of OSA and their association with health outcomes. METHODS: We systematically searched EMBASE, MEDLINE, and the Cochrane Database of Systematic Reviews for studies published between 2000 and 2022 for those that reported alternative metrics derived from PSG in adults and related them to OSA-related outcomes. RESULTS: Of the 186 initial studies identified by the original search, data from 31 studies were ultimately included in the final analysis. Numerous metrics were identified that were significantly related to a broad range of outcomes. We categorized the outcomes into 2 main subgroups: (1) cardiovascular/metabolic outcomes and mortality and (2) cognitive function- and vigilance-related outcomes. Four general categories of alternative metrics were identified based on signals analyzed: autonomic/hemodynamic metrics, electroencephalographic metrics, oximetric metrics, and respiratory event-related metrics. CONCLUSIONS: We have summarized the current landscape of literature for alternative PSG metrics relating to risk prediction in OSA. Although promising, further prospective observational studies are needed to verify findings from other cohorts, and to assess the clinical utility of these metrics. CITATION: Hajipour M, Baumann B, Azarbarzin A, et al. Association of alternative polysomnographic features with patient outcomes in obstructive sleep apnea: a systematic review. J Clin Sleep Med. 2023;19(2):225-242.

Shift working and cardiovascular health.

Adequate sleep is an important component of cardiovascular health. Due to circadian misalignment and irregular shifts, inadequate sleep is common in shift workers. Adverse consequences include daytime sleepiness, decreased cognitive performance, increased sympathetic tone, inflammation, impaired glucose tolerance, and altered leptin and ghrelin levels. When circadian adjustment has not occurred, daytime sleepers often experience decreased sleep duration and increased wakefulness during displaced sleep; additionally, skipping sleep is common in shift workers, further contributing to sleep deprivation. Habitual decreased sleep duration and physiological changes contribute to obesity, diabetes, hypertension, and increased cardiovascular disease risk in shift workers. Shift workers with obstructive sleep apnea (OSA), the most common sleep-related breathing disorder, can experience more frequent sleep disruptions than non-shift workers with OSA. Furthermore, shift work-induced circadian misalignment may potentiate cardiometabolic risk in OSA patients through autonomic nervous system dysfunction and other mechanisms.

The rs579459 ABO gene polymorphism and risk of incident cardiovascular events in obstructive sleep apnea: a pilot study.

PURPOSE: We have previously shown that the TT genotype (rs579459 location of the ABO gene) is significantly associated with circulating levels of e-selectin in patients with suspected obstructive sleep apnea (OSA). We hypothesized that this genotype would be associated with incident cardiovascular disease (CVD). METHODS: Patients with suspected OSA who had a full diagnostic polysomnogram from 2003 to 2011 were recruited; CV events occurring within 8 years of polysomnography were identified by linkage to provincial health databases. Cox proportional hazards models were used to evaluate the incidence of first CV events as a function of the rs579459 genotype. RESULTS: In this targeted study, 408 patients were studied, and 39 incident events were identified. A larger proportion of patients with the TT genotype had an event (31/247; 12.6%) than the CT and CC genotypes (8/161; 5.0%); in univariate analysis, the TT genotype was significantly associated with CV events (HR = 2.53; 95% CI = 1.16-5.51, p = 0.02). After adjustment for age, AHI, sex, smoking, diabetes, statin use, and BMI, the TT genotype remained a significant predictor (HR = 2.35; 95% CI = 1.02-5.42, p = 0.046). No events were found in patients with an absence of both OSA and the TT genotype (N = 30). The effect of the SNP was partially (16.2%) mediated by e-selectin levels. CONCLUSION: This is the first study to examine genetic variants as a risk factor for incident CVD in the context of OSA. Although these results are preliminary and in need of replication, it suggests that genetic markers may become useful in helping to guide precision clinical care.

Patient-reported Differences in Obstructive Sleep Apnea Care between Jurisdictions with and without Government Funding for Continuous Positive Airway Pressure.

Rationale: Funding for obstructive sleep apnea (OSA) treatment may impact how patients access care, wait times, and costs of care. Objectives: The aim of this study was to compare differences in diagnosis and treatment of OSA between Canadian jurisdictions with and without public funding for continuous positive airway pressure (CPAP). Methods: We administered an anonymous internet survey to Canadian adults reporting a physician diagnosis of OSA. Responses were categorized on the basis of whether the respondent's province provided full or partial funding for CPAP therapy for all patients. We assessed wait times for diagnosis and treatment, patient-borne costs, and model of care delivery compared between jurisdictions with and without universal CPAP funding. Results: We received 600 responses representing all Canadian provinces and territories. The median (interquartile range) age was 59 (49-66) years; 57% were male, and 21% were from rural settings. Patients living in provinces without public CPAP funding (n = 419) were more likely to be diagnosed using home sleep apnea testing (69% vs. 20%; P = 0.00019). Wait times were similar after adjustment for demographics, disease characteristics, and model of care. Although patient-borne costs of care were similar between jurisdictions, patients from regions without CPAP funding reported that cost had a greater influence on the choice of therapy. Sleep specialists were more commonly involved in OSA care in regions with CPAP funding. There was no difference in the current use of therapy between jurisdictions with and without public funding. Conclusions: This survey study demonstrates that public funding for CPAP therapy impacts how Canadians access OSA care but is not associated with differences in wait times or costs. Future research is required to determine the impact of different funding models for OSA care on clinical outcomes.

Acute hypoxia elicits lasting reductions in the sympathetic action potential transduction of arterial blood pressure in males.

Post-hypoxia sympathoexcitation does not elicit corresponding changes in vascular tone, suggesting diminished sympathetic signalling. Blunted sympathetic transduction following acute hypoxia, however, has not been confirmed and the effects of hypoxia on the sympathetic transduction of mean arterial pressure (MAP) as a function of action potential (AP) activity is unknown. We hypothesized that MAP changes would be blunted during acute hypoxia but restored in recovery and asynchronous APs would elicit smaller MAP changes than synchronous APs. Seven healthy males (age: 24 (3) years; BMI: 25 (3) kg/m2 ) underwent 20 min isocapnic hypoxia (PET O2 : 47 (2) mmHg) and 30 min recovery. Multi-unit microneurography (muscle sympathetic nerve activity; MSNA) and continuous wavelet transform with matched mother wavelet was used to detect sympathetic APs during baseline, hypoxia, early (first 7 min) and late (last 7 min) recovery. AP groups were classified as synchronous APs, asynchronous APs (occurring outside an MSNA burst) and no AP activity. Sympathetic transduction of MAP was quantified using signal-averaging, with ΔMAP tracked following AP group cardiac cycles. Following synchronous APs, ΔMAP was reduced in hypoxia (+1.8 (0.9) mmHg) and early recovery (+1.5 (0.7) mmHg) compared with baseline (+3.1 (2.2) mmHg). AP group-by-condition interactions show that at rest asynchronous APs attenuate MAP reductions compared with no AP activity (-0.4 (1.1) vs. -2.2 (1.2) mmHg, respectively), with no difference between AP groups in hypoxia, early or late recovery. Sympathetic transduction of MAP is blunted in hypoxia and early recovery. At rest, asynchronous sympathetic APs contribute to neural regulation of MAP by attenuating nadir pressure responses. KEY POINTS: Acute isocapnic hypoxia elicits lasting sympathoexcitation that does not correspond to parallel changes in vascular tone, suggesting blunted sympathetic transduction. Signal-averaging techniques track the magnitude and temporal cardiovascular responses following integrated muscle sympathetic nerve activity (MSNA) burst and non-burst cardiac cycles. However, this does not fully characterize the effects of sympathetic action potential (AP) activity on blood pressure control. We show that hypoxia blunts the sympathetic transduction of mean arterial pressure (MAP) following synchronous APs that form integrated MSNA bursts and that sympathetic transduction of MAP remains attenuated into early recovery. At rest, asynchronous APs attenuate the reduction in MAP compared with cardiac cycles following no AP activity, thus asynchronous sympathetic APs appear to contribute to the neural regulation of blood pressure. The results advance our understanding of sympathetic transduction of arterial pressure during and following exposure to acute isocapnic hypoxia in humans.

National strategy on the integration of sleep and circadian rhythms into public health research and policies: Report from the Canadian Sleep and Circadian Network.

Scientists in sleep and circadian rhythms, public health experts, healthcare providers, partners, and stakeholders convened in 2020 for a 2-day meeting organized by the Canadian Sleep and Circadian Network to develop a national strategy for integrating sleep and circadian rhythms into public health and policies in Canada. The objective of this paper is to present the national strategy that emerged from this meeting of 60 participants from across Canada. The meeting focused on 4 key target priorities: (1) atypical working schedules, (2) sleep and circadian rhythms of children and adolescents, (3) insomnia, and (4) impact of sleep apnea on health. Following constructive discussions, it was decided that the following 4 strategic objectives should be prioritized to accelerate the integration of sleep and circadian rhythms into public health policies in Canada: (1) increase public health sleep and circadian rhythm research, (2) increase public health education and knowledge mobilization on sleep, (3) inform and support public health sleep interventions and policies, and (4) promote sleep health training. Participants recommended that research and public health efforts address needs along the continuum of sleep health. The committee noted that strategies and interventions could differ across contexts, settings, sectors, and jurisdictions. The national strategy also identified high-priority research questions in public health and recommended mechanisms to build research capacity, providing a path forward for the integration of sleep and circadian rhythms into public health research and policies.

Air Pollution and the Effectiveness of Positive Airway Pressure Therapy in Individuals With Sleep Apnea: A Retrospective Community-Based Repeated-Measures Longitudinal Study.

BACKGROUND: Ambient air pollution may affect the severity of untreated OSA, but it is unknown whether air pollution adversely impacts the effectiveness of positive airway pressure (PAP) therapy. RESEARCH QUESTION: Do short-term changes in outdoor air pollution adversely impact adults with OSA using PAP therapy? STUDY DESIGN AND METHODS: We conducted a retrospective community-based repeated-measures longitudinal study of adults with OSA who purchased a PAP device from a registered equipment provider between 2013 and 2017 (Ontario, Canada) and had data on the daily device-derived residual apnea-hypopnea index (AHIFlow). We linked daily PAP-derived data to air pollution databases using postal codes. The primary exposures were mean nocturnal (8 pm to 8 am) residential concentrations of ozone, fine particulate matter, nitrogen dioxide, carbon monoxide, sulfur dioxide, and the Air Quality Health Index (AQHI). Potential confounders considered were demographics, season and year of exposure, initial OSA severity, other PAP parameters, and climate-related variables. RESULTS: Eight thousand one hundred forty-eight adults were analyzed with a median of 89 days (interquartile range [IQR], 29-302 days) of observation during which PAP was used for ≥ 4 h. The median daily AHIFlow was 1.2/h (IQR, 0.5-2.5/h). In mixed multivariate regression analyses, an increase in air pollution was associated with a statistically significant increase in AHIFlow for most statistical models. The largest effect was for the AQHI: an increase in AHIFlow while comparing highest vs lowest quartiles was 0.07/h (95% CI, 0.05-0.10/h). INTERPRETATION: We demonstrated a modest but statistically significant increase in residual respiratory events during PAP therapy associated with an increase in air pollution concentrations.

The Link between Obstructive Sleep Apnea and Neurocognitive Impairment: An Official American Thoracic Society Workshop Report.

There is emerging evidence that obstructive sleep apnea (OSA) is a risk factor for preclinical Alzheimer's disease (AD). An American Thoracic Society workshop was convened that included clinicians, basic scientists, and epidemiologists with expertise in OSA, cognition, and dementia, with the overall objectives of summarizing the state of knowledge in the field, identifying important research gaps, and identifying potential directions for future research. Although currently available cognitive screening tests may allow for identification of cognitive impairment in patients with OSA, they should be interpreted with caution. Neuroimaging in OSA can provide surrogate measures of disease chronicity, but it has methodological limitations. Most data on the impact of OSA treatment on cognition are for continuous positive airway pressure (CPAP), with limited data for other treatments. The cognitive domains improving with CPAP show considerable heterogeneity across studies. OSA can negatively influence risk, manifestations, and possibly progression of AD and other forms of dementia. Sleep-dependent memory tasks need greater incorporation into OSA testing, with better delineation of sleep fragmentation versus intermittent hypoxia effects. Plasma biomarkers may prove to be sensitive, feasible, and scalable biomarkers for use in clinical trials. There is strong biological plausibility, but insufficient data, to prove bidirectional causality of the associations between OSA and aging pathology. Engaging, recruiting, and retaining diverse populations in health care and research may help to decrease racial and ethnic disparities in OSA and AD. Key recommendations from the workshop include research aimed at underlying mechanisms; longer-term longitudinal studies with objective assessment of OSA, sensitive cognitive markers, and sleep-dependent cognitive tasks; and pragmatic study designs for interventional studies that control for other factors that may impact cognitive outcomes and use novel biomarkers.