What is the likely cause of persistent low‑90% oxygen saturations and daytime sleepiness in a 62‑year‑old woman with chronic bronchiolitis, lung nodules and mild obstructive sleep apnea well controlled on continuous positive airway pressure (CPAP) (apnea‑hypopnea index <2), and what are the appropriate next steps in management?

Likely Cause and Management of Persistent Hypoxemia in COPD-OSA Overlap

The most likely cause is chronic bronchiolitis-related parenchymal lung disease causing daytime and nocturnal hypoxemia, not inadequately treated OSA, since the AHI remains well-controlled at <2 on CPAP. 1, 2

Primary Diagnostic Consideration

This patient has COPD-OSA overlap syndrome with persistent hypoxemia despite optimal CPAP therapy. The return of morning headaches, excessive daytime sleepiness, and oxygen desaturations into the low 90s—both during CPAP use and during waking hours—strongly suggests that the underlying chronic bronchiolitis is causing chronic hypoxemia that CPAP alone cannot address. 1, 2

Key Clinical Points:

• Morning headaches in OSA are caused by nocturnal hypercapnia and cerebral vasodilation, not hypoxemia alone, so their recurrence despite an AHI <2 suggests CO₂ retention rather than inadequate airway patency. 1

• Daytime oxygen desaturations into the low 90s indicate significant parenchymal lung disease that extends beyond sleep-disordered breathing, consistent with her chronic bronchiolitis and lung nodules. 3, 2

• Patients with bronchiolitis obliterans have increased risk of nocturnal hypoxia that correlates with severity of lung disease, and this hypoxemia can persist even when obstructive events are controlled. 4

Immediate Next Steps

1. Verify CPAP Optimization Before Any Other Intervention

Before adding supplemental oxygen or making other changes, confirm that CPAP settings are truly optimal: 1, 5

• Download CPAP data to verify residual AHI, mask leak, and actual hours of use per night 5, 6
• Ensure CPAP pressure adequately eliminates all obstructive events, not just achieving an AHI <2 1
• Check for significant mask leak that could cause pseudo-control of AHI while allowing persistent hypoxemia 5

2. Obtain Arterial Blood Gas Analysis

Measure daytime arterial blood gases (ABG) while breathing room air to assess for hypoxemia and hypercapnia: 3, 1

• If PaO₂ <7.3 kPa (55 mmHg) with or without hypercapnia, long-term oxygen therapy (LTOT) is indicated 3
• If PaO₂ is 7.3-8.0 kPa (55-60 mmHg) with evidence of pulmonary hypertension, peripheral edema, or nocturnal hypoxemia, LTOT should be considered 3
• Measure PaCO₂ to determine if hypercapnia is present, which would explain morning headaches and suggest need for bilevel positive airway pressure (BiPAP) rather than CPAP 1, 2

3. Perform Pulmonary Function Testing

Obtain spirometry and lung volumes to quantify the severity of chronic bronchiolitis: 7, 4

• FEV₁, FVC, and FEF₂₅₋₇₅ correlate with nocturnal oxygen saturation in patients with bronchiolitis obliterans 4
• An FEV₁ <1.5 liters supports the need for LTOT if hypoxemia is present 3

4. Conduct In-Laboratory Polysomnography with CPAP

Perform overnight PSG while using her current CPAP settings to assess for: 1, 7

• Residual sleep-disordered breathing events that CPAP tracking may miss
• Nocturnal oxygen desaturation patterns and severity
• Evidence of REM-related desaturation that may require supplemental oxygen in addition to CPAP 7
• Presence of hypercapnia (via end-tidal CO₂ monitoring) 1

Treatment Algorithm Based on Findings

If Daytime Hypoxemia is Confirmed (PaO₂ <7.3 kPa or 55 mmHg):

Prescribe long-term oxygen therapy (LTOT) at 2-4 L/min for at least 15 hours daily, including during sleep: 3

• Critical: Supplemental oxygen must not be prescribed until positive airway pressure therapy is optimized, which you should verify first 1
• Both SpO₂ and PaCO₂ must be continuously monitored when oxygen is added to prevent unrecognized hypercapnic respiratory failure 1
• Recheck ABG with supplemental oxygen to ensure PaO₂ >8 kPa (60 mmHg) without unacceptable rise in PaCO₂ 3
• Clinical and physiological reassessment 4-8 weeks after initiating oxygen therapy is required 1

If Hypercapnia is Present (PaCO₂ elevated):

Consider switching from CPAP to high-intensity noninvasive ventilation (BiPAP) aiming to lower PaCO₂: 2

• In overlap syndrome patients with daytime hypercapnia, BiPAP may have additional benefits over CPAP alone 2
• This addresses the morning headaches caused by nocturnal CO₂ retention 1

If CPAP Settings Are Suboptimal:

Increase CPAP pressure or switch to auto-adjusting PAP (APAP) to eliminate all residual events: 3, 1, 5

• Even with AHI <2, significant mask leak or inadequate pressure can cause symptoms 5
• Address mask fit issues, skin irritation, or comfort problems that may reduce adherence 6

Common Pitfalls to Avoid

Do not add supplemental oxygen without first optimizing CPAP and measuring blood gases. Oxygen alone can prolong apneic episodes, mask hypoventilation on pulse oximetry, and worsen hypercapnia in overlap syndrome patients. 1

Do not assume the OSA is inadequately treated based solely on symptom recurrence. In overlap syndrome, symptoms may be driven by the underlying lung disease rather than residual sleep-disordered breathing. 7, 2

Do not prescribe LTOT based on Apple Watch oxygen readings alone. Consumer-grade pulse oximeters are not validated for medical decision-making; arterial blood gas analysis is the gold standard. 3

Monitoring and Follow-Up

• Six-monthly follow-up and reassessment is essential for patients on LTOT, ideally with home visits by a respiratory health worker 3
• Track CPAP adherence and efficacy through device downloads at each visit to ensure continued optimal treatment 5, 6
• Reassess symptoms using validated tools such as the Epworth Sleepiness Scale 5, 6
• Monitor for development of pulmonary hypertension, which is common in overlap syndrome and may require additional evaluation 3, 7, 2