How do you differentiate between asthma and chronic obstructive pulmonary disease (COPD) in adults, particularly those with a history of smoking or respiratory symptoms?

Differentiating Asthma from COPD

The most reliable way to differentiate asthma from COPD is through post-bronchodilator spirometry showing FEV1/FVC <0.70 with minimal reversibility (<12% and <200 mL improvement) for COPD versus significant reversibility (≥12% and ≥200 mL) for asthma, combined with key clinical features including smoking history, age of onset, and pattern of symptoms. 1, 2

Spirometric Differentiation

Post-bronchodilator spirometry is the definitive diagnostic test that must be performed in all suspected cases. 3, 1

• COPD diagnosis requires: FEV1/FVC <0.70 after bronchodilator with minimal reversibility defined as <10% predicted improvement or <12% and <200 mL absolute change 1, 2
• Asthma diagnosis requires: Significant reversibility with >10% predicted improvement or ≥12% and ≥200 mL improvement, or peak flow variability >15% over 2 weeks 1, 4
• Adding spirometry to clinical history increases diagnostic accuracy from 84% to 89% (AUC), while more advanced testing provides no additional benefit in primary care 5

Clinical History Features That Favor COPD

Heavy smoking history is the single most important distinguishing feature. 3

• Smoking exposure: ≥10 pack-years or significant occupational/environmental exposures 1, 2
• Age of onset: Typically >40 years, rarely presents before this age 3, 2
• Symptom pattern: Gradual, progressive worsening over years rather than episodic variation 1, 2
• Dyspnea characteristics: Persistent breathlessness that develops gradually and eventually limits daily activities, present on exertion initially and at rest in advanced disease 3, 6
• Cough pattern: Chronic productive cough, often worse in morning, with persistent sputum production 3
• Disease progression: FEV1 decline of approximately 70 mL per year with 10-year survival of about 30% in community surveys 3, 2

Clinical History Features That Favor Asthma

Atopy and marked treatment response are the hallmarks distinguishing asthma. 3, 2

• Personal history: Atopy, allergic conditions (rhinitis, eczema), or family history of asthma 3, 1
• Age of onset: Can begin at any age, often in childhood or adolescence 1, 2
• Symptom pattern: Variable, episodic symptoms with symptom-free intervals; paroxysmal dyspnea and nocturnal symptoms 1, 6
• Cough characteristics: Often dry cough, mainly at night, frequently associated with allergies 6
• Treatment response: Marked improvement with bronchodilators or glucocorticosteroids 3, 2

Additional Diagnostic Features

Several ancillary findings help when spirometry and history are equivocal. 3

Favoring COPD:

• Evidence of emphysema on chest imaging 3, 2
• Decreased diffusing capacity (DLCO) 3, 2
• Chronic hypoxemia in advanced disease 3
• Minimal airway hyperresponsiveness 3
• Weight loss and anorexia in severe disease 3

Favoring Asthma:

• Elevated FeNO (fraction of exhaled nitric oxide) 4
• Sputum eosinophilia ≥3% 4
• Marked airway hyperresponsiveness on bronchial challenge testing (PC20 <2 mg/mL) 4
• Normal diffusing capacity 3

The Overlap Syndrome (ACOS)

Approximately 20% of patients have features of both conditions, creating diagnostic complexity. 2, 4

Diagnostic Criteria for ACOS:

• Post-bronchodilator FEV1/FVC <0.70 (persistent airflow limitation) AND 4
• Significant bronchodilator reversibility (≥12% and ≥200 mL) despite fixed obstruction 4
• Age >40 years with smoking history but also features of asthma (atopy, eosinophilia) 2, 4

Clinical Significance:

• ACOS patients have the highest mortality risk (HR 1.45) compared to asthma alone (HR 1.04) or COPD alone (HR 1.28) 2
• More severe respiratory symptoms, lower quality of life, and increased exacerbations compared to COPD alone 4
• Require ICS/LABA combination therapy as first-line treatment, with LAMA addition if symptoms persist 1, 4

Common Diagnostic Pitfalls

Several clinical scenarios create diagnostic confusion that must be recognized. 3, 2

• Older asthmatics with smoking history: May develop irreversible airflow limitation, making differentiation from COPD impossible in some cases 3
• COPD with bronchodilator response: Up to 50% of COPD patients show some bronchodilator response, which does not exclude COPD diagnosis 7
• Unhelpful features: Presence or absence of cough, sputum, wheeze, partial bronchodilator response, or family history of chest disease do not reliably differentiate between the conditions 3
• Eosinophilic COPD: Approximately 20-30% of COPD patients have elevated eosinophils and may respond better to ICS therapy 2

Practical Diagnostic Algorithm

Follow this stepwise approach for systematic differentiation: 1, 4

1. Obtain detailed smoking history: Calculate pack-years and assess occupational exposures 3, 1
2. Assess age of symptom onset: <40 years favors asthma; >40 years with smoking favors COPD 1, 2
3. Characterize symptom pattern: Episodic/variable favors asthma; progressive/persistent favors COPD 1, 2
4. Perform pre- and post-bronchodilator spirometry: This is mandatory and non-negotiable 3, 1
5. Assess reversibility: <12% and <200 mL = COPD; ≥12% and ≥200 mL = asthma or ACOS 1, 4
6. If overlap features present: Consider ACOS diagnosis and treat with ICS/LABA combination 1, 4
7. Consider additional testing only if diagnosis remains unclear: FeNO, sputum eosinophils, or DLCO 4

Inflammatory Patterns

Understanding the underlying inflammation helps guide treatment decisions. 2

• COPD: Predominantly neutrophilic inflammation with increased neutrophils, macrophages, and CD8+ T lymphocytes; elevated IL-1β, IL-6, and TNF-α 2
• Asthma: Predominantly eosinophilic inflammation with CD4+ T lymphocytes and elevated Th2 cytokines 2
• Heterogeneity exists: Both diseases can show mixed inflammatory patterns, with eosinophilia in 20-30% of COPD and neutrophilia in severe asthma 2, 7