Sleep is a complex amalgam of physiological and behavioural processes. ^[2]

Why does this matter? Sleep is not simply "the brain turning off." It is an actively regulated state with distinct EEG patterns, hormonal surges, memory consolidation, and — critically for this lecture — changes in respiratory control.

Why REM muscle atonia matters: If you didn't have atonia during REM, you'd physically act out your dreams (this is exactly what happens in REM Sleep Behaviour Disorder, common in Parkinson's/Lewy body dementia). For OSA, the atonia extends to upper airway dilator muscles → making REM the most vulnerable period for airway collapse.

NREM stages 1 & 2 = light sleep; Stage 3 (& 4) = slow wave sleep / deep sleep. REM sleep = about 20–25% of total sleep time. NREM and REM cycles = about 90–110 minutes each cycle. ^[2]

Pattern: You cycle through NREM → REM roughly 4–5 times per night. Deep sleep (N3) predominates in the first third of the night; REM predominates in the last third. This is why OSA-related desaturation is often worst in the early morning hours (more REM).

Reading the slide's hypnogram: Time runs left to right and sleep depth runs downward from wakefulness through NREM to REM. Early cycles descend into long blocks of slow-wave sleep; later cycles contain little deep sleep but progressively longer REM periods. The thin upward excursions are brief awakenings/arousals, while the body-movement marks cluster around stage transitions. This picture is more useful than memorising percentages: normal sleep has an organised, repeating architecture, whereas recurrent respiratory arousals fragment it.

Age, prior sleep history, circadian rhythms, drug ingestion, pathological states. ^[2]

With advance in age: decrease in total sleep time, deep sleep, and REM sleep; increase in Wake After Sleep Onset (WASO). ^[2]

Clinical correlation: Elderly patients naturally have more fragmented sleep, less deep sleep, and more awakenings. This makes them more susceptible to daytime fatigue and also makes it harder to distinguish "normal ageing sleep" from pathological sleep disorders.

Control of breathing involves: respiratory centres, chemical/mechanical/CNS information, respiratory muscles (upper airway muscles, diaphragm, intercostal muscles). ^[2]

During wakefulness, breathing is maintained by:

1. Chemical drive (chemoreceptors sensing CO₂, O₂, pH)
2. Behavioural/cortical drive (talking, voluntary hyperventilation)
3. Wakefulness drive (reticular activating system keeping respiratory neurons active)

Compared to wakefulness, sleep causes a decrease in minute ventilation (tidal volume × respiratory rate). NREM sleep — decrease in tidal volume and ventilation. REM sleep — breathing pattern unstable and variable in amplitude and frequency, with further decrease in ventilation. ^[2]

Contributors to decreased ventilation in sleep: ^[2]

• Decreased muscle contraction from intercostal muscles
• Recumbency with decrease in functional residual capacity (FRC)
• Decreased chemosensitivity to O₂ and CO₂ with decreased ventilatory response to hypoxia and hypercarbia
• Decreased arousal response

First-principles explanation:

• When you lie down, abdominal contents push the diaphragm cephalad → FRC drops → lung bases close → V/Q mismatch worsens.
• During sleep, the "wakefulness drive" to breathe is withdrawn. You rely almost entirely on chemical/automatic drive. If your automatic drive is impaired (central apnoea) or your airway collapses (obstructive apnoea), there is no cortical backup.
• Chemoreceptor sensitivity is blunted during sleep → you tolerate higher CO₂ and lower O₂ before arousing.

In healthy people, during sleep: slight decrease in blood oxygen tension but no decrease in oxygen saturation (Note: Oxygen-Hb dissociation curve); mild increase in blood CO₂ tension but still normal. ^[2]

The flat portion of the O₂-Hb dissociation curve protects healthy people: a small PaO₂ fall usually produces little or no clinically important change in SpO₂. “No decrease” is a teaching simplification rather than an absolute physiological rule.

In diseased states (e.g. COPD, morbid obesity): pre-existing impaired blood gas exchange (e.g. low baseline oxygenation) would worsen during sleep, and further worsens during REM sleep. ^[2]

With abnormal lungs, physiologic breathing changes during sleep may lead to derangement in blood gas exchange (e.g. worse oxygenation during REM sleep in COPD). ^[2]

Some diseases are more prone to manifest during sleep (may not only be attributed to sleep/wake state per se — may be due to associated changes in posture, temperature, or circadian function):

• Asthma symptoms typically worse at night
• Aspiration occurs in elderly
• Airway secretions accumulate overnight
• Post-nasal drip with cough on lying down
• Pain or medications may disturb sleep ^[2]

M/45, chronic smoker and social drinker. Manager, sedentary lifestyle. c/o feeling fatigued for about 2 years. Further enquiry: actually feels sleepy during "boring" work or difficult to concentrate after lunch (but only rarely dozes off because he was at work). Wife: he would doze off easily on buses or while watching TV. Drives private car on weekends, has "never dozed off" at the wheels, but needs to keep himself awake by loud music if driving longer distances. Has heavy snoring for many years. Weight gain of about 5 kg in past few years. No other constitutional symptoms. Recent health check: BP "borderline" high. ^[2]

Body habitus — BMI, waist, neck; craniofacial and oropharyngeal features including tonsils; blood pressure and pulse. ^[2]

Sleep apnoea — recurrent episodes of cessation of breathing during sleep. Obstructive — episodic functional occlusion of upper airways due to complete or partial closure of the upper airways. Termination of apnoeas — cerebral arousals (microarousals) with opening of upper airway and thus resumption of airflow. ^[2]

First-principles pathophysiology: During sleep, pharyngeal dilator muscles (especially genioglossus) lose tone. In a predisposed individual (obesity, narrow airway anatomy), the negative intraluminal pressure generated during inspiration exceeds the ability of these muscles to keep the airway open → airway collapses → airflow stops (apnoea) or is reduced (hypopnoea) → O₂ falls, CO₂ rises → chemoreceptors eventually trigger a microarousal → muscle tone briefly returns → airway reopens with a gasp/snore → patient falls back asleep → cycle repeats.

What the airway drawings show: In normal sleep, a patent column remains behind the soft palate and tongue. In OSA, the tongue/soft-palate complex falls posteriorly into an already narrow pharynx. Inspiratory suction then favours further collapse rather than airflow. The obstruction is therefore dynamic and sleep-dependent—a normal-looking awake airway does not exclude OSA—and it may occur at retropalatal, retroglossal, or multiple levels.

Sleep itself is associated with decreased muscle tone. In those predisposed to more collapsible upper airway muscles → Obstructive sleep apnoea. ^[2]

Apnoea — cessation of breathing. Event lasts > 10 seconds. ^[2]

For current adult scoring, a respiratory event must last at least 10 seconds. The lecture's shorthand “hypopnoea = partial closure” conveys the mechanism but not the scoring rule: a hypopnoea requires a qualifying fall in airflow plus an associated oxygen desaturation and/or EEG arousal under the scoring rule in use. Different hypopnoea rules can therefore produce different AHIs in the same recording.

Hence the term Apnoea-Hypopnoea Index (AHI) — numbers of apnoeas and hypopnoeas per sleep hour. OSA is the commonest type of sleep apnoea in the general population. ^[2]

AHI uses measured sleep time, which requires EEG. Most home tests lack EEG and instead report a respiratory-event index (REI) per hour of monitoring/recording time; because wake time may be included in the denominator, HSAT can underestimate severity.

One person may have a mixed pattern with both obstructive and central apnoeic events (different from the term "mixed apnoea" which refers to one apnoeic event). ^[2]

Classification for diagnosis and severity of OSA (Adults): ^[2]

• No OSA: AHI < 5 events/sleep hour
• Mild: 5 to < 15
• Moderate: 15 to < 30
• Severe: 30 and above

Normal adult AHI is < 5 events/sleep hour. ^[2]

Level 1: Full-lead (usually 16 channels) overnight polysomnogram (PSG), supervised in-laboratory — GOLD STANDARD Level 2: Unattended polysomnogram Level 3: Home study with fewer leads (no EEG) — HSAT (Home Sleep Apnoea Test) Level 4: 1–2 leads (esp. sleep oximetry) for screening and monitoring ^[2]

Reading the obstructive PSG and oximetry traces

The multi-channel example is a pattern-recognition slide:

1. Airflow becomes markedly reduced or absent, while the thoracic and abdominal belts continue to oscillate: respiratory effort is present against an obstructed airway.
2. The belts may move out of phase (thoracoabdominal paradox) as inspiratory effort increases.
3. Oxygen saturation falls after a short physiological lag, then recovers after airflow resumes. Repeated events create the regular “saw-tooth” desaturation–reoxygenation pattern on overnight oximetry.
4. A brief EEG arousal, burst of snoring, and heart-rate acceleration often accompany airway reopening. Repetition explains both sleep fragmentation and cyclical bradycardia–tachycardia.

The decisive comparison is with central apnoea: obstructive apnoea has effort without airflow; central apnoea has neither airflow nor effort.

Emerging technologies:

Devices not requiring many leads, providing multiple signals, may be used at home, may be disposable. Sleep "wearables" (watches/rings) — not yet ready for diagnosis. ^[2]

This table is directly from the lecture and is extremely high-yield:

Snoring; Excessive daytime sleepiness (some just c/o being tired); Witnessed apnoeas; Nocturnal choking; Restless sleep; Unrefreshing sleep, morning headache; Irritability, intellectual deterioration, poor concentration; Decreased libido; Enuresis / nocturia. ^[2]

Why morning headache? CO₂ retention during sleep → cerebral vasodilation → headache on waking. It typically resolves within 30 minutes of waking.

Why nocturia/enuresis? Increased intrathoracic pressure swings during obstructed breathing → increased atrial natriuretic peptide (ANP) release → increased urine production. Nocturia in a middle-aged man should prompt consideration of OSA (not just prostatic disease).

OSA may occur in all age groups. Hong Kong community-based study of middle-aged subjects: OSA (AHI > 5 + EDS) estimated at least 4% of men and 2% of women. Much higher if only AHI is used — up to half of middle-aged men may have AHI > 5. Very high global burden. Prevalence expected to rise with increasing obesity trends. Pathogenesis is multifactorial — lean subjects can still have OSA. ^[2]

Sleepiness does not correlate very well with the AHI — may miss asymptomatic OSA subjects. ^[2]

100% have anatomical compromise of variable magnitude (related to obesity or craniofacial factors or both). 36% have poor muscle responsiveness. 36% have unstable respiratory control (high loop gain). 37% have low arousal threshold. ^[2]

What is "loop gain"? This is a control systems concept. High loop gain means the ventilatory response to a perturbation (e.g. a brief apnoea) is excessive — you overshoot with hyperventilation, which then drives CO₂ too low, which then causes another central pause → perpetuating the cycle. This is more important in central apnoea but contributes to some OSA phenotypes.

What is "low arousal threshold"? Some patients wake up too easily from even minor respiratory events. Paradoxically, this fragments sleep and prevents them from reaching deeper sleep stages where muscle tone might stabilize.

Clinical implication: Not every OSA patient is purely an "anatomy problem." This explains why weight loss alone doesn't cure all OSA, and why some non-obese patients have OSA (craniofacial anatomy, high loop gain, low arousal threshold).

Controlled for confounding factors, untreated severe OSA have a much higher incidence of fatal or non-fatal cardiovascular events, while OSA treated with CPAP have a much lower incidence (Marin et al., Lancet 2005, 10-year follow-up). ^[2]

In the slide's two cumulative-incidence plots, the untreated severe-OSA curve separates progressively from controls, snorers, mild–moderate OSA, and CPAP-treated OSA for both fatal and non-fatal events. This is an important observational signal, but allocation to CPAP was not random; residual confounding and “healthy adherer” effects remain possible.

The lecture presents four major RCTs. The key message:

ITT analyses: CPAP did NOT show statistically significant reduction in CVD events in any of the four major RCTs (CERCAS, RICCADSA, SAVE, ISAACC). BUT in CPAP-adherent subgroup analyses: three of four trials (CERCAS, RICCADSA, SAVE) showed statistically significant benefit. ^[2]

How to interpret the apparent discrepancy: These trials largely enrolled non-sleepy patients (ESS roughly 5–7), and average CPAP exposure was only about 3–4 hours/night, so limited nightly use is one plausible reason for a diluted effect. However, adherent-subgroup analyses break randomisation: people who use CPAP consistently may differ in many other health behaviours. They show a benefit signal, not proof that CPAP prevents cardiovascular events when used for a particular number of hours.

Exam interpretation: There is a strong observational association but no convincing intention-to-treat RCT evidence that CPAP reduces hard cardiovascular endpoints in the populations studied. Do not turn a post-hoc adherence association into a causal treatment claim.

RCT evidence for improvement: EDS, health-related quality of life, blood pressure control in hypertension, intermediary outcomes (e.g. endothelial function). ^[2]

Weight reduction/control — a "must" advice for those who are overweight/obese. Sleep hygiene — e.g. adequate sleep hours (most people need 7–8 hours), otherwise may still be sleepy despite adequately treating OSA. ^[2]

Correlation between AHI and BMI, though obesity only accounts for 60% of AHI variance (younger adults). Reduction in body weight can improve OSA AND directly benefit obesity-related cardiometabolic diseases. CPAP treatment per se does NOT reduce body weight. ^[2]

Management of obesity: lifestyle behavioural modification, anti-obesity medications, bariatric surgery. ^[2]

Indications of treatment: based on both degree of AHI severity AND symptoms, and other concurrent risk factors. ^[2]

Do not use AHI as the only treatment switch. Current AASM guidance strongly recommends PAP for adults with OSA and excessive sleepiness, and conditionally supports it for impaired sleep-related quality of life or comorbid hypertension. AHI severity, hypoxaemic burden, driving/occupational risk, symptoms, comorbidities, anatomy, patient preference, and ability to use the treatment all matter. ^[10]

Residual high degree of sleepiness after OSA treatment: Check treatment adherence (e.g. some only use CPAP for 2 hours out of 7 hours sleep). Look for other concurrent causes of EDS (e.g. sleep deprivation, insufficient sleep). ^[2]