What is the diagnostic approach for a patient with suspected asthma-Chronic Obstructive Pulmonary Disease (COPD) overlap?

Diagnosing Asthma-COPD Overlap

Diagnose asthma-COPD overlap when a patient over 40 years old with significant smoking history (≥10 pack-years) demonstrates persistent airflow obstruction (post-bronchodilator FEV1/FVC <0.70) combined with substantial bronchodilator reversibility (≥12% and ≥200 mL improvement in FEV1) or has documented asthma history plus features of COPD. 1, 2, 3

Diagnostic Algorithm

Step 1: Confirm Chronic Airflow Limitation

• Perform spirometry showing post-bronchodilator FEV1/FVC ratio <0.70 in a patient ≥35-40 years old with smoking or biomass exposure history 4, 3
• This persistent obstruction distinguishes overlap from pure asthma, which typically shows complete reversibility 5, 2

Step 2: Identify Features of Both Diseases

Major criteria (Spanish consensus requires 2 major OR 1 major + 2 minor criteria): 4, 3

• Significant bronchodilator response: FEV1 improvement ≥15% and ≥400 mL (or ≥12% and ≥200 mL by some definitions) 4, 3, 6
• Sputum eosinophilia ≥3% on induced sputum analysis 4, 1
• Documented history of asthma before age 40 4, 6

Minor criteria: 4

• Elevated total IgE levels 4
• History of atopy (allergic rhinitis, eczema, food allergies) 4
• Positive bronchodilator response ≥12% and ≥200 mL on two or more separate occasions 4

Step 3: Additional Supportive Testing

Blood eosinophilia: 3

• Peripheral blood eosinophils ≥300 cells/μL supports the diagnosis 3
• This marker indicates potential responsiveness to inhaled corticosteroids 1, 3

FeNO measurement: 1

• Elevated fractional exhaled nitric oxide suggests asthmatic inflammation 1
• Particularly useful when sputum analysis is unavailable 1

Bronchial hyperresponsiveness testing: 5

• Methacholine challenge showing PC20 <2 mg/mL confirms asthma component 5
• Peak flow variability >15% over 2 weeks also supports asthma features 5

Key Clinical Features to Assess

History elements favoring overlap: 4

• Childhood or early adult asthma that persisted into middle age with subsequent smoking exposure 4
• Variable symptoms: Wheezing and chest tightness that vary between days and throughout single days (asthma feature) 4
• Progressive dyspnea: Worsening breathlessness over time despite variable symptoms (COPD feature) 4
• Nocturnal symptoms: Paroxysmal dyspnea, cough, and wheeze worse at night and early morning 4
• Atopic history: Allergies, sinusitis, nasal polyps 4

Physical examination: 4

• Physical signs are rarely diagnostic but assess for hyperinflation and airflow limitation 4
• Signs typically only appear when lung function is significantly impaired 4

Critical Diagnostic Pitfalls

Avoid misdiagnosing asthma with airway remodeling as overlap: 6

• Patients with long-standing asthma can develop fixed obstruction from remodeling alone 6
• Lack of significant smoking exposure (typically <10 pack-years) should exclude overlap diagnosis 6
• In patients without documented asthma before age 40, require FEV1 improvement >400 mL to diagnose overlap 6

Don't rely on fixed ratio alone in younger or older patients: 4

• FEV1/FVC <0.70 may overdiagnose COPD in elderly patients 4
• May underdiagnose in adults younger than 45 years 4

Distinguish from pure COPD: 5, 2

• Pure COPD shows minimal reversibility (<10% predicted improvement or <12% and <200 mL change) 5
• COPD patients lack significant atopic history and childhood respiratory symptoms 5

Prognostic Implications

Overlap carries worse outcomes than either disease alone: 1, 7

• Highest mortality risk (HR 1.45) compared to COPD alone (HR 1.28) or asthma alone (HR 1.04) 1, 7
• More severe respiratory symptoms and lower quality of life 1
• Increased risk of exacerbations and hospitalizations 1
• These patients require ICS-based therapy rather than LAMA monotherapy 1