Delayed diagnosis of Swyer-James-MacLeod syndrome.

Swyer-James-MacLeod Syndrome is a rare obliterative lung disease typically caused by childhood infection resulting in arrested pulmonary development. Imaging findings include unilateral hyperlucency on chest x-ray, and hyperlucency, hypovascularity and expiratory gas trapping on computed tomography. Recognition of abnormal imaging can lead to earlier diagnosis and institution of appropriate management.

Inter-night variability of in-home, overnight pulse oximetry screening in an asymptomatic older adult population.

PURPOSE: Obstructive sleep apnoea (OSA) is common, yet often undiagnosed. Self-administered, overnight pulse oximetry (OPO) could screen for OSA in asymptomatic, older populations. However, the inter-night variability of OPO in an asymptomatic, older population is unknown. We determined the inter-night variability of home OPO parameters in an older population and correlated with sleep questionnaires. METHODS: Participants > 50 years without a diagnosis of OSA undertook home OPO for three consecutive nights and completed two sleep questionnaires (STOP-BANG (SBQ) and Epworth Sleepiness Score (ESS)). Analysis was performed with linear mixed models and Spearman's correlation coefficient. RESULTS: There was no difference in oxygen desaturation index (ODI), MeanSpO2, MinimumSpO2, and time spent with SpO2 < 90% (T90) across two or three nights (P ≥ 0.282). However, the variability of all parameters across nights increased with the magnitude of departure from normal values (P ≤ 0.002). All OPO parameters were associated with age (P ≤ 0.034) and body mass index (P ≤ 0.049). There was a weak correlation between three OPO parameters and SBQ (absolute ρ = 0.22 to 0.32; P ≤ 0.021), but not ESS (P ≥ 0.254). CONCLUSION: Inter-night variability of home OPO was minimal when values were near-normal in an older population. However, as values depart from normal, the inter-night variability increases, indicating the need for multiple night recordings. Low correlation to sleep questionnaires suggest the need for more robust OSA questionnaires in an asymptomatic population.

Role of sleep-disordered breathing in age-related macular degeneration.

AIMS: To examine the association between obstructive sleep apnoea (OSA) and age-related macular degeneration (AMD), and the subphenotype of AMD with reticular pseudodrusen (RPD). METHODS: Case-control study with 351 participants (211 AMD and 140 controls) using the Epworth Sleepiness Scale (ESS) and the STOP-BANG Questionnaire (SBQ) validated sleep questionnaires. Participant risk of having moderate-to-severe OSA was determined using a binary risk scale based on the ESS and SBQ combined and an ordinal risk scale based on the SBQ. A prior diagnosis of OSA and whether receiving assisted breathing treatment was also ascertained. Retinal imaging allowed AMD and RPD determination. RESULTS: Higher risk of moderate-to-severe OSA according to the binary and ordinal scales was not associated with the presence of AMD (p≥0.519) nor AMD with RPD (p≥0.551). Per point increase in ESS or SBQ questionnaire score was also not associated with AMD nor AMD with RPD (p≥0.252). However, being on assisted breathing treatment for diagnosed OSA was significantly associated with a higher likelihood of having AMD with RPD, but not all AMD, (OR 3.70; p=0.042 and OR 2.70; p=0.149, respectively), when compared with those without diagnosed OSA on treatment. CONCLUSIONS: Formally diagnosed OSA undergoing treatment, increased the likelihood of having AMD with RPD, but not overall AMD compared with those who were not undergoing treatment. Risk-based OSA questionnaires showed no difference in risk for all AMD or AMD with RPD. Future research, using formal sleep studies could further explore the potential role of nocturnal hypoxia in AMD.

Insomnia Symptoms and Biomarkers of Alzheimer's Disease in the Community.

BACKGROUND: Insomnia is one of the most common sleep disorders yet its relationship to the biology of Alzheimer's disease remains equivocal. OBJECTIVE: We investigated the cross-sectional relationship between insomnia symptom severity and cerebrospinal fluid (CSF) concentrations of Alzheimer's disease biomarkers in a cognitively unimpaired middle-aged community sample. METHODS: A total of 63 participants from the Healthy Brain Project (age = 59±7 years; 67% women) completed a lumbar puncture and two weeks of actigraphy to measure two of insomnia's core features: difficulty initiating sleep (prolonged sleep onset latency) and difficulty maintaining sleep (wake after sleep onset [WASO] and number of awakenings). Additionally, the Insomnia Severity Index (ISI) was completed by 58 participants. Linear and Tobit regression were used to estimate the associations between each insomnia variable and CSF Aß42, phosphorylated tau 181 (p-tau181), total-tau, and neurofilament light chain protein (NfL), adjusting for age, sex, and APOEɛ4 genotype. RESULTS: Higher ISI score was associated with greater average levels of CSF Aß42 (per point: 30.7 pg/mL, 95% CI: 4.17-57.3, p = 0.023), as was higher WASO (per 10 min: 136 pg/mL, 95% CI: 48-223, p = 0.002) and more awakenings (per 5:123 pg/mL, 95% CI = 55-192, p < 0.001). Difficulty initiating sleep was not associated with CSF Aß42, nor were insomnia features associated with p-tau181, total-tau, or NfL levels. CONCLUSION: Insomnia symptoms were associated with higher CSF Aß42 levels in this relatively young, cognitively unimpaired sample. These findings may reflect increased amyloid production due to acute sleep disruption.

The treatment of sleep dysfunction to improve cognitive function: A meta-analysis of randomized controlled trials.

OBJECTIVE: This meta-analysis of randomized controlled trials (RCTs) evaluates if treating sleep disturbances improves cognitive function over at least 12 weeks. METHODS: Multiple data sources were searched until November 1, 2021. RCTs were included if they examined the effect of an intervention (behavioral or medical) on sleep and cognition in an adult sample with sleep disturbances and had an intervention duration and follow-up of at least 12 weeks. Two independent reviewers located 3784 studies; 16 satisfied the inclusion criteria. Primary outcomes included the broad cognitive domains of visual processing, short-term memory, long-term storage and retrieval, processing speed, and reaction time. RESULTS: Most trials were conducted in participants with obstructive sleep apnea (OSA; N = 13); the most studied intervention was continuous positive airway pressure (CPAP; N = 10). All RCTs were 12 months in duration or less. The estimates of mean pooled effects were not indicative of significant treatment effect for any primary outcome. Although the interventions reduced daytime sleepiness (Hedge's g, 0.51; 95% confidence interval, 0.29-0.74; p < 0.01), this did not lead to cognitive enhancement. CONCLUSIONS: Overall, there was insufficient evidence to suggest that treating sleep dysfunction can improve cognition. Further studies with longer follow-up duration and supporting biomarkers are needed.

Effects of hyperventilation length on muscle sympathetic nerve activity in healthy humans simulating periodic breathing.

Background: Periodic breathing (PB) is a cyclical breathing pattern composed of alternating periods of hyperventilation (hyperpnea, HP) and central apnea (CA). Differences in PB phenotypes mainly reside in HP length. Given that respiration modulates muscle sympathetic nerve activity (MSNA), which decreases during HP and increases during CA, the net effects of PB on MSNA may critically depend on HP length. Objectives: We hypothesized that PB with shorter periods of HP is associated with increased MSNA and decreased heart rate variability. Methods: 10 healthy participants underwent microelectrode recordings of MSNA from the common peroneal nerve along with non-invasive recording of HRV, blood pressure and respiration. Following a 10-min period of tidal breathing, participants were asked to simulate PB for 3 min following a computed respiratory waveform that emulated two PB patterns, comprising a constant CA of 20 s duration and HP of two different lengths: short (20 s) vs long (40 s). Results: Compared to (3 min of) normal breathing, simulated PB with short HP resulted in a marked increase in mean and maximum MSNA amplitude (from 3.2 ± 0.8 to 3.4 ± 0.8 µV, p = 0.04; from 3.8 ± 0.9 to 4.3 ± 1.1 µV, p = 0.04, respectively). This was paralleled by an increase in LF/HF ratio of heart rate variability (from 0.9 ± 0.5 to 2.0 ± 1.3; p = 0.04). In contrast, MSNA response to simulated PB with long HP did not change as compared to normal breathing. Single CA events consistently resulted in markedly increased MSNA (all p < 0.01) when compared to the preceding HPs, while periods of HP, regardless of duration, decreased MSNA (p < 0.05) when compared to normal breathing. Conclusion: Overall, the net effects of PB in healthy subjects over time on MSNA are dependent on the relative duration of HP: increased sympathetic outflow is seen during PB with a short but not with a long period of HP.

Sleep-disordered breathing was associated with lower health-related quality of life and cognitive function in a cross-sectional study of older adults.

BACKGROUND AND OBJECTIVE: The clinical significance of sleep-disordered breathing (SDB) in older age is uncertain. This study determined the prevalence and associations of SDB with mood, daytime sleepiness, quality of life (QOL) and cognition in a relatively healthy older Australian cohort. METHODS: A cross-sectional analysis was conducted from the Study of Neurocognitive Outcomes, Radiological and retinal Effects of Aspirin in Sleep Apnoea. Participants completed an unattended limited channel sleep study to measure the oxygen desaturation index (ODI) to define mild (ODI 5-15) and moderate/severe (ODI ≥ 15) SDB, the Centre for Epidemiological Studies Scale, the Epworth Sleepiness Scale, the 12-item Short-Form for QOL and neuropsychological tests. RESULTS: Of the 1399 participants (mean age 74.0 years), 36% (273 of 753) of men and 25% (164 of 646) of women had moderate/severe SDB. SDB was associated with lower physical health-related QOL (mild SDB: beta coefficient [ß] -2.5, 95% CI -3.6 to -1.3, p < 0.001; moderate/severe SDB: ß -1.8, 95% CI -3.0 to -0.6, p = 0.005) and with lower global composite cognition (mild SDB: ß -0.1, 95% CI -0.2 to 0.0, p = 0.022; moderate/severe SDB: ß -0.1, 95% CI -0.2 to 0.0, p = 0.032) compared to no SDB. SDB was not associated with daytime sleepiness nor depression. CONCLUSION: SDB was associated with lower physical health-related quality of life and cognitive function. Given the high prevalence of SDB in older age, assessing QOL and cognition may better delineate subgroups requiring further management, and provide useful treatment target measures for this age group.

A case of extreme carboxyhaemoglominemia due to vaping.

Acute carbon monoxide (CO) poisoning is known to cause neurological, metabolic and cardiorespiratory sequalae. However, data on chronic CO exposure are scant, particularly in the context of vaping, which recent literature suggests may be a greater source of CO than tobacco cigarette smoking. During a series of admissions at the time of vaping, our patient repeatedly presented with significant CO poisoning and developed pulmonary arterial hypertension with resultant high-output right heart failure. On each occasion, our patient's levels of carboxyhaemoglobin were both higher and took longer to resolve than 12 smokers who underwent arterial blood gas testing at two time points. Our observation may reveal an association between vaping, chronic carboxyhaemoglobinemia and the development of cardiorespiratory disease. Thus, further studies into the safety of vaping and chronic CO exposure are urged.

Cough syncope as a cause of motor vehicle crash: fatal distraction?

Coughing is a rare cause of syncope that can contribute to motor vehicle crashes. The precise pathophysiological mechanisms responsible for the syncope are unclear. We report six occasions in which motor vehicle drivers have been involved in serious crashes and cough syncope was cited as the cause. In each occasion, an alternative cause leading to the crash could be identified. Cough as a cause of syncope should be a diagnosis of exclusion and used with great caution as a medico-legal defence. A suggested criterion for confirmation of cough syncope is recommended.

Sleep apnoea and heart failure.

Heart failure and sleep disordered breathing (SDB) are two common conditions that frequently overlap and have been studied extensively in the past three decades. Obstructive sleep apnoea (OSA) may result in myocardial damage due to intermittent hypoxia that leads to increased sympathetic activity and transmural pressures, low-grade vascular inflammation, and oxidative stress. On the other hand, central sleep apnoea and Cheyne-Stokes respiration (CSA-CSR) occurs in heart failure, irrespective of ejection fraction, either reduced (HFrEF), preserved (HFpEF) or mildly reduced (HFmrEF). The pathophysiology of CSA-CSR relies on several mechanisms leading to hyperventilation, breathing cessation and periodic breathing. Pharyngeal collapse may result at least in part from fluid accumulation in the neck, owing to daytime fluid retention and overnight rostral fluid shift from the legs. Although both OSA and CSA-CSR occur in heart failure, the symptoms are less suggestive than in typical (non-heart failure-related) OSA. Overnight monitoring is mandatory for a proper diagnosis, with accurate measurement and scoring of central and obstructive events, since the management will be different depending on whether the sleep apnoea in heart failure is predominantly OSA or CSA-CSR. SDB in heart failure is associated with worse prognosis, including higher mortality, than in patients with heart failure but without SDB. However, there is currently no evidence that treating SDB improves clinically important outcomes in patients with heart failure, such as cardiovascular morbidity and mortality.

Exercise oscillatory ventilation during autonomic blockade in young athletes and healthy controls.

PURPOSE: Exercise oscillatory ventilation (EOV) is a form of periodic breathing that is associated with a poor prognosis in heart failure patients, but little is known about EOV in other populations. We sought to provide insights into the phenomenon of EOV after it was observed in young healthy subjects, including athletes, after the administration of dual autonomic blockade (DAB). METHODS: From 29 participants who completed cardiopulmonary exercise testing (CPET) with and without DAB (0.04 mg/kg atropine and 0.2 mg/kg metoprolol), 5 subjects developed EOV (age = 29 ± 5 years; 3/5 were athletes) according to American Heart Association criteria. For each case, we identified 2 non-EOV healthy controls (age = 34.2 ± 8.3; 7/10 were athletes) that were subsequently age- and sex-matched. RESULTS: No participants had EOV during exercise without DAB. The 5 participants (4 male, 1 female) who demonstrated EOV with DAB had lower mean tidal volume (1.7 ± 0.5 L/min vs. 1.8 ± 0.5 L/min; p = 0.04) compared to participants in the non-EOV group and a decrease in peak tidal volume (2.9 ± 0.6 L/min to 2.2 ± 0.7 L/min; p = 0.004) with DAB. There were few other differences in CPET measures between EOV and non-EOV participants, although the PETCO2 tended to be higher in the EOV group (p = 0.07). CONCLUSION: EOV can be elucidated in young healthy subjects, including athletes, during cardiopulmonary exercise testing, suggesting that it may not be an ominous sign in all populations.

Sleep-Disordered Breathing and Nocturnal Hypoxemia in Precapillary Pulmonary Hypertension: Prevalence, Pathophysiological Determinants, and Clinical Consequences.

BACKGROUND AND OBJECTIVE: The clinical relevance and interrelation of sleep-disordered breathing and nocturnal hypoxemia in patients with precapillary pulmonary hypertension (PH) is not fully understood. METHODS: Seventy-one patients with PH (age 63 ± 15 years, 41% male) and 35 matched controls were enrolled. Patients with PH underwent clinical examination with assessment of sleep quality, daytime sleepiness, 6-minute walk distance (6MWD), overnight cardiorespiratory polygraphy, lung function, hypercapnic ventilatory response (HCVR; by rebreathing technique), amino-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and cardiac MRI (n = 34). RESULTS: Prevalence of obstructive sleep apnea (OSA) was 68% in patients with PH (34% mild, apnea-hypopnea index [AHI] ≥5 to <15/h; 34% moderate to severe, AHI ≥15/h) versus 5% in controls (p < 0.01). Only 1 patient with PH showed predominant central sleep apnea (CSA). Nocturnal hypoxemia (mean oxygen saturation [SpO2] <90%) was present in 48% of patients with PH, independent of the presence of OSA. There were no significant differences in mean nocturnal SpO2, self-reported sleep quality, 6MWD, HCVR, and lung and cardiac function between patients with moderate to severe OSA and those with mild or no OSA (all p > 0.05). Right ventricular (RV) end-diastolic (r = -0.39; p = 0.03) and end-systolic (r = -0.36; p = 0.04) volumes were inversely correlated with mean nocturnal SpO2 but not with measures of OSA severity or daytime clinical variables. CONCLUSION: OSA, but not CSA, is highly prevalent in patients with PH, and OSA severity is not associated with nighttime SpO2, clinical and functional status. Nocturnal hypoxemia is a frequent finding and (in contrast to OSA) relates to structural RV remodeling in PH.

Research Priorities for Patients with Heart Failure and Central Sleep Apnea. An Official American Thoracic Society Research Statement.

Background: Central sleep apnea (CSA) is common among patients with heart failure and has been strongly linked to adverse outcomes. However, progress toward improving outcomes for such patients has been limited. The purpose of this official statement from the American Thoracic Society is to identify key areas to prioritize for future research regarding CSA in heart failure.Methods: An international multidisciplinary group with expertise in sleep medicine, pulmonary medicine, heart failure, clinical research, and health outcomes was convened. The group met at the American Thoracic Society 2019 International Conference to determine research priority areas. A statement summarizing the findings of the group was subsequently authored using input from all members.Results: The workgroup identified 11 specific research priorities in several key areas: 1) control of breathing and pathophysiology leading to CSA, 2) variability across individuals and over time, 3) techniques to examine CSA pathogenesis and outcomes, 4) impact of device and pharmacological treatment, and 5) implementing CSA treatment for all individualsConclusions: Advancing care for patients with CSA in the context of heart failure will require progress in the arenas of translational (basic through clinical), epidemiological, and patient-centered outcome research. Given the increasing prevalence of heart failure and its associated substantial burden to individuals, society, and the healthcare system, targeted research to improve knowledge of CSA pathogenesis and treatment is a priority.

Depression scores improve with continuous positive airway pressure in specialized sleep clinics: real-world data.

STUDY OBJECTIVES: To assess changes in Hospital Anxiety and Depression Scale (HADS) scores after continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea. METHODS: Consecutive patients attending the Alfred Health sleep clinic, diagnosed with obstructive sleep apnea, and prescribed CPAP were recruited. The primary outcome was a change in the HADS depression (HADS-D) and anxiety (HADS-A) subscales from the time of diagnosis to follow-up. Secondary analysis compared high (> 4 hours) and low (< 4 hours) CPAP adherence groups and change in depression cases, defined by HADS-D ≥ 8, and anxiety cases, defined by HADS-A ≥ 11. RESULTS: We included 108 participants in the final analysis. Adherence groups were well matched in baseline mood, sleepiness, and apnea variables. Overall age (mean ± standard deviation) was 56.1 ± 12.8 years, and there was a median (interquartile ratio) apnea-hypopnea-index of 42.7 (27.5-58.1) or median (interquartile ratio) oxygen-desaturation-index of 43.0 (26.0-74.0). The median duration of CPAP therapy was 1.3 years. The HADS-D decreased after CPAP by -1.4 (adjusted 95% confidence interval, -2.1 to -0.6; P = .001). Patients with high-CPAP adherence (n = 84) had a tendency towards a greater reduction in HADS-D (-1.5) compared with those with low-CPAP adherence (n = 24; -0.3; adjusted P = .19). Depression cases (HADS-D ≥ 8) decreased by 13.1% in the high-CPAP-adherence group (P = .03) and increased by 4.1% in the low-CPAP-adherence group (P = .71). The HADS-A decreased after CPAP by -1.8 (adjusted 95% confidence interval, -1.8 to -0.4; P = .004). There was no significant difference between adherence groups or anxiety cases (HADS-A > 11). CONCLUSIONS: Specialized obstructive sleep apnea treatment with CPAP reduces depression scores, with a trend toward greater reduction in those with high CPAP adherence.