What are the physiological changes and complications in a patient with a history of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) due to overlap syndrome?

Overlap Syndrome in OSA and COPD

Overlap syndrome refers to the coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) in the same patient, and these patients have significantly worse outcomes than those with either condition alone, including more profound nocturnal hypoxemia, increased cardiovascular complications, higher mortality, and greater risk of pulmonary hypertension. 1

Definition and Prevalence

Overlap syndrome is defined as the concurrent presence of COPD and OSA (typically with an apnea-hypopnea index ≥15/h) in the same individual. 1

Prevalence varies widely depending on the population studied:

• 1-3.6% in the general adult population 2
• 0.5% in patients with mild COPD 1
• 39% in U.S. veteran populations with milder COPD 1
• Up to 65-66% in pulmonary rehabilitation populations with moderate to severe COPD 1, 3, 2

The true prevalence in severe COPD remains uncertain due to limited data. 1

Physiological Changes in Overlap Syndrome

Nocturnal Gas Exchange Abnormalities

Patients with overlap syndrome experience more profound and prolonged nocturnal oxygen desaturations compared to those with either COPD or OSA alone. 1, 4, 2

• The combination creates worse nocturnal hypoxemia and hypercapnia than either disease in isolation 1, 4
• Desaturation episodes in COPD patients can originate from multiple mechanisms: upper airway obstruction, hypoventilation during REM sleep, ventilation/perfusion mismatches, and obesity 2
• Sleep efficiency is poor in approximately 45% of patients with moderate to severe COPD 3

Cardiovascular Pathophysiology

Overlap syndrome patients develop more cardiac arrhythmias than those with OSA or COPD alone. 1

• Daytime pulmonary hypertension is more likely to develop in overlap patients compared to those with just OSA or COPD 1
• OSA is a specific risk factor for pulmonary hypertension in COPD patients 2
• Evidence suggests systemic inflammation and oxidative stress in both conditions may interact to predispose patients to cardiovascular disease 4

Sleep Architecture Disturbances

Sleep disturbances are more severe in overlap syndrome than in either condition alone. 1

• Sleep quality may be worse in overlap patients compared to those with isolated OSA or COPD 2
• The severity of obstructive ventilatory impairment and hyperinflation (particularly the inspiratory capacity to total lung capacity ratio) correlates with the severity of sleep-related breathing disturbances 4

Clinical Complications and Outcomes

Mortality and Morbidity

Patients with overlap syndrome have a worse prognosis than patients with COPD or OSA alone. 1

• Early treatment with continuous positive airway pressure (CPAP) improves survival in overlap patients 5, 4
• CPAP therapy has demonstrated reductions in COPD exacerbations, hospitalizations, and healthcare costs 6
• Whether overlap syndrome increases mortality and morbidity risks compared to COPD or OSA alone requires further confirmation 2

Cardiovascular Complications

Cardiac arrhythmias are more frequent and severe in overlap syndrome. 1

• Atrial fibrillation is common and may precipitate acute respiratory decompensation 7
• Increased risk of myocardial damage, particularly during acute exacerbations 1
• Greater cardiovascular consequences than either condition in isolation 8

Pulmonary Complications

Overlap syndrome patients are at higher risk for:

• Daytime pulmonary hypertension 1
• Reduced hospitalization rates when treated with CPAP 4
• More severe hypoxemia requiring careful oxygen management 8

Clinical Recognition and Screening

When to Screen for OSA in COPD Patients

The American Thoracic Society suggests that patients with chronic stable hypercapnic COPD undergo screening for OSA before initiation of long-term noninvasive ventilation (NIV). 1

Screening tools available:

• STOP-BANG Questionnaire: Sensitivity 0.93, Specificity 0.35 (sensitive but not specific) 1
• Epworth Sleepiness Scale: Sensitivity 0.58, Specificity 0.60 (less sensitive and not specific) 1

Clinical Presentation Clues

Overlap syndrome should be suspected in COPD patients with:

• Excessive daytime sleepiness disproportionate to their COPD severity 1
• Witnessed apneas or loud snoring 1
• Morning headaches or unrefreshing sleep 1
• Hypercapnia out of proportion to their FEV1 1
• Pulmonary hypertension 1

Management Implications

Positive Airway Pressure Therapy

CPAP treatment is the cornerstone of therapy and significantly improves outcomes in overlap syndrome. 5, 4

• CPAP reduces mortality, hospitalizations, and pulmonary hypertension 4
• Survival of overlap patients treated with positive airway pressure is superior to those untreated 6
• PAP therapy addresses both sleep quality and disordered gas exchange 6

Noninvasive Ventilation Considerations

NIV may be beneficial in overlap syndrome patients with hypercapnic COPD. 1

• Desirable effects include possible reductions in mortality and hospital admissions, improved quality of life, reduced dyspnea, and improvements in functional capacity and blood gases 1
• Harms are generally minor and related to the interface (discomfort, skin breakdown, rash) 1
• Ongoing trials are evaluating CPAP versus NIV in overlap syndrome 1

Oxygen Therapy

Oxygen therapy must be carefully managed in overlap patients to avoid CO2 retention. 9, 8

• Maintain PaO2 >60 mmHg or SpO2 >90% without causing respiratory acidosis 9
• Careful oxygen administration is critical to prevent worsening hypercapnia 9

Common Pitfalls to Avoid

Do not assume all acute respiratory worsening in COPD patients represents COPD exacerbation alone - comorbid conditions including untreated OSA can contribute to symptoms. 7

Do not overlook OSA screening in COPD patients with:

• Hypercapnia disproportionate to their lung function 1
• Pulmonary hypertension 1
• Frequent hospitalizations despite optimal COPD management 6

Recognize that physical examination alone is unreliable for distinguishing overlap syndrome from COPD alone - objective sleep testing is required. 7

Be aware that most NIV trials in COPD excluded patients with OSA and/or high BMI, limiting the evidence base for this specific population. 1