OSA Phenotypes

You have been diagnosed with sleep apnea. You invested in a CPAP machine. You tried to use it night after night. But something is wrong.

The mask feels unbearable. You wake up gasping despite wearing it. Or perhaps you use it every single night, yet you still wake up exhausted, still struggle through afternoons, still feel like something is terribly off.

Your doctor checks your data. "Your AHI is under five," they say. "The machine is working. You just need to try harder."

And so you try harder. And fail again. And somewhere along the way, you begin to believe the problem is you.

But what if the problem is not you? What if the problem is that your treatment was never designed for your specific type of sleep apnea?

 

Sleep Apnea Is Not One Disease

For decades, we have treated Obstructive Sleep Apnea as a single condition. The Apnea-Hypopnea Index (AHI) became our guiding number. High AHI means severe disease. CPAP fixes it. End of story.

But here is what the AHI does not tell us. It tells us how often the airway collapses. It tells us nothing about why. And without understanding the why, we cannot reliably predict which treatment will work for which patient.

Two patients with an AHI of 30 can have completely different underlying physiology.

Patient A has a narrow airway but otherwise normal respiratory control. CPAP splints the airway open, and they sleep beautifully from night one.

Patient B has the same AHI but an unstable respiratory control system (high loop gain) and wakes at the slightest sensation (low arousal threshold). CPAP triggers central events and repeated awakenings. They struggle, feel worse, and eventually stop. Their chart reads "non-compliant."

But they are not non-compliant. They are simply the victim of a one-size-fits-all approach to a disease that is anything but one-size-fits-all.

This is where OSA phenotyping enters the conversation. Research over the past two decades has revealed that four distinct physiological disturbances, called phenotypes or endotypes, contribute to airway collapse during sleep. Most patients have a combination, but one is usually dominant. Identifying that dominant mechanism is the key to precision therapy.

The Four Phenotypes: Understanding Why Your Airway Collapses

1. Anatomical Collapsibility

What it is: Your airway is anatomically narrow due to obesity, crowded soft tissue, retrognathic jaw, or small maxilla. Under the negative pressure of inspiration, the airway simply collapses.

Who has it: Virtually every OSA patient has some degree of anatomical compromise. This is why PAP therapy remains the foundational treatment for almost everyone.

Treatment implications: CPAP or BiPAP works by pneumatically splinting the airway open. For patients with pure anatomical collapse, this is usually sufficient. Oral appliances that advance the jaw may also help. Surgical options targeting specific anatomical obstructions can be considered after appropriate evaluation.

2. Poor Pharyngeal Dilator Muscle Response

What it is: During wakefulness, your airway muscles work actively to keep the pharynx open. During sleep, these muscles normally relax, but in most people, they retain enough tone to maintain patency. In some patients, however, the muscles fail completely. The tongue and airway walls collapse because the muscles do not activate when they should.

Who has it: Patients who are not significantly overweight but have severe OSA. Those who collapse predominantly in REM sleep when muscle tone is lowest. Some post-menopausal women fall into this category.

Treatment implications: CPAP works by bypassing the muscle problem, but these patients are also ideal candidates for hypoglossal nerve stimulation. This implanted device activates the tongue muscles precisely when needed during sleep, mimicking the natural muscle response that is otherwise absent. No amount of CPAP pressure can replicate this physiological effect.

3. High Loop Gain

What it is: Loop gain refers to the stability of your ventilatory control system. Patients with high loop gain have an overly sensitive respiratory control centre. When CO₂ levels fluctuate slightly, their system overresponds, triggering an exaggerated breathing effort.

This overshoot drives CO₂ too low, causing a subsequent pause in breathing. The cycle repeats, creating oscillatory breathing patterns.

Think of it like a thermostat that is set too sensitively. The temperature dips slightly, the furnace kicks on too hard, the room overheats, the furnace shuts off, the room cools too much. Constant oscillation, never settling at the right temperature.

Who has it: Patients with heart failure, those on opioid medications, and some individuals with central sleep apnea components. But it can also occur in otherwise healthy OSA patients, explaining why they have residual events despite optimal CPAP pressure.

Treatment implications: More CPAP pressure will not fix high loop gain. It may even worsen central events. These patients may need:

• ASV (Adaptive Servo-Ventilation) which provides dynamic support that stabilises breathing without overshooting
• Supplemental oxygen to dampen chemosensitivity
• Acetazolamide to mildly acidify the blood and stabilise ventilatory drive
• EERS (Enhanced Expiratory Rebreathing Space) — an intervention where an extra length of tubing is added between the mask and the exhalation port, allowing the patient to rebreathe a small amount of CO₂, which stabilises the respiratory drive

4. Low Arousal Threshold

What it is: Some patients wake up at the slightest airway narrowing. They do not obstruct long enough to desaturate significantly, so their AHI may look modest. But their sleep is shattered by repeated micro-arousals, sometimes hundreds per night, that prevent them from entering or sustaining deep restorative sleep.

Who has it: Younger patients, those with insomnia comorbid with OSA, and individuals who are generally "light sleepers." Women with OSA are more likely to have this phenotype than men.

Treatment implications: For these patients, pushing CPAP pressure higher is counterproductive. It only creates more arousal stimuli. The goal is to raise the arousal threshold, allowing the airway to narrow slightly without triggering a full awakening. Options include:

• Sedative agents like trazodone or zolpidem to increase the threshold for arousal
• Lower pressures with EPR (Expiratory Pressure Relief) to make exhalation more comfortable

Non-PAP options like oral appliances which may cause fewer arousals than positive pressure.

The Promise of Precision Sleep Medicine

Imagine a world where your sleep apnea treatment is designed specifically for your unique physiology. Where the days of trial-and-error, of mask after mask, of being labelled "non-compliant," are behind you.

This is not science fiction. This is the direction sleep medicine is moving, and at JCS Lung and Sleep Centre, we are already practising it.

When a patient comes to us struggling with CPAP, we do not simply tell them to try harder. We ask different questions.

• Could high loop gain explain why they have residual events despite optimal pressure?
• Could low arousal threshold explain why they wake up repeatedly despite adequate support?
• Could poor muscle responsiveness make them a candidate for hypoglossal nerve stimulation?
• Could a DISE (Drug-Induced Sleep Endoscopy) reveal a pattern of collapse that surgery could address?

We look beyond the AHI. We look at the patient beneath the numbers.

The Diagnostic Gap: Why Standard Testing Falls Short

Here is the honest truth. Our diagnostic tools have not fully caught up with our understanding.

A standard in-lab polysomnogram, while comprehensive, does not directly measure these phenotypes. We can infer loop gain from breathing patterns. We can suspect low arousal threshold from frequent EEG arousals without significant desaturation. But we cannot definitively quantify these traits in routine clinical practice.

And home sleep tests? They are grossly inadequate for this level of precision. They confirm that the airway collapses. They measure oxygen desaturation. They reveal nothing about why the collapse occurs.

This is why experience matters. This is why a centre with three decades of clinical depth can see patterns that automated reports miss. This is why the conversation between patient and physician remains irreplaceable.

At JCS, we combine state-of-the-art diagnostics with the clinical wisdom that comes from reading thousands of sleep studies and following thousands of patients through their treatment journeys. We may not have a single test that spits out a phenotype score, but we have something equally valuable: the ability to see the whole picture.

Your Path to Personalised Sleep Care

If you have struggled with CPAP, if you are using it every night but still feel exhausted, if you have been labelled "non-compliant" without anyone asking why, we want to hear from you.

You may not be the problem. The problem may be that your unique physiology was never fully understood.

Here is what you can do:

1. Schedule a Comprehensive Sleep Phenotype Consultation
   We will review your history, your previous sleep studies, your treatment journey, and your current challenges. We will look for clues that point to your dominant phenotype.
2. Undergo Targeted Evaluation
   Depending on your presentation, we may recommend:

• A full in-lab PSG with detailed phenotyping analysis
• A review of your CPAP data for patterns suggesting loop gain or arousal issues
• A DISE procedure if surgical options are being considered
• A trial of alternative or adjunctive therapies

3. Receive a Personalised Treatment Plan
   Based on your phenotype, we will recommend the therapy most likely to succeed. Not the therapy that works for everyone, but the therapy that works for you.
4. The JCS DifferenceFor over three decades, JCS Lung and Sleep Centre has been at the forefront of sleep medicine in India. From establishing the country's first sleep laboratory in 1992 to training over 500 physicians through our advanced sleep medicine course, we have built our reputation on one principle: look deeper.We do not accept "non-compliant" as a final diagnosis. We do not believe in one-size-fits-all treatment. We believe in understanding the patient beneath the numbers and designing therapy that fits their unique physiology.

   If your CPAP therapy is failing, the problem may not be you. It may be time to find a centre that looks beyond the AHI.