What is the difference in treatment approach between emphysema and airway dominance in Chronic Obstructive Pulmonary Disease (COPD)?

Emphysema vs Airway Dominance in COPD: Clinical Distinctions and Treatment Implications

COPD encompasses two distinct pathophysiologic components—emphysema (parenchymal destruction) and airway disease (bronchial/bronchiolar inflammation and obstruction)—and distinguishing between these phenotypes is critical because they respond differently to treatment, particularly regarding inhaled corticosteroids and bronchodilator selection. 1

Pathophysiologic Differences

Emphysema-Dominant Disease

• Emphysema is defined as permanent destructive enlargement of airspaces distal to the terminal bronchioles without obvious fibrosis 2, 1
• Results in loss of lung elastic recoil and destruction of alveolar attachments to airway walls, causing airways to collapse during expiration 2, 1
• Two major patterns exist: centriacinar emphysema (destruction of respiratory bronchioles and central acinus with intact surrounding alveoli) and panacinar emphysema (destruction of entire acinus) 2, 1
• Emphysema is the predominant lesion causing airflow obstruction in severe COPD 3

Airway-Dominant Disease

• Characterized by chronic bronchitis, small airway inflammation, increased airway wall thickness, mucus hypersecretion, and fibrosis 1
• Mucus gland thickness relates to sputum production but not to loss of respiratory function 2
• Small airway abnormalities play a greater role in mild to moderate COPD, while emphysema dominates in severe disease 1
• Airway eosinophilia is associated with measurable bronchodilator response to β-agonists and relatively less emphysema for any degree of airflow limitation 2

Diagnostic Differentiation

Clinical Features

Emphysema-dominant patients typically present with:

• Higher lung volumes (hyperinflation) 4
• Lower diffusing capacity (DLCO) due to alveolar destruction 2, 4
• Lower PaO2 and PaCO2 4
• Higher hemoglobin and blood leukocyte counts 4
• Less prominent cough and sputum production 2

Airway-dominant patients typically present with:

• Chronic productive cough (chronic bronchitis defined as expectoration on most days for ≥3 months/year for ≥2 successive years) 1
• More severe air trapping (higher RV and RV/TLC ratio) 5
• Thicker airway walls on quantitative CT (higher WA% and Pi10) 5
• More frequent acute exacerbations 5
• Bronchiectasis and/or bronchial wall thickening more common on imaging 5

Imaging Assessment

• High-resolution CT (HRCT) with quantitative analysis is the gold standard for phenotyping 2, 4
• Emphysema index (percentage of lung below -910 Hounsfield units) quantifies parenchymal destruction 5, 6
• Airway wall thickness measurements (WA%, Pi10) quantify airway disease 5, 4
• Standardized quantitative CT using phantom-based calibration reduces scanner variability and improves phenotype reliability 4
• Visual assessment combined with quantitative measures identifies four phenotypes: emphysema-dominant, airway-dominant, mixed, and mild disease 4

Functional Testing

• DLCO is helpful in distinguishing emphysema (reduced) from pure airway disease (relatively preserved), though its value in planning treatment is less clear 2
• Static lung volume measurement documents hyperinflation degree 2
• Bronchodilator reversibility (≥12% and ≥200 mL improvement in FEV1) suggests airway-dominant disease or asthma-COPD overlap 7

Treatment Approach Differences

Emphysema-Dominant COPD

Start with long-acting muscarinic antagonists (LAMAs) as first-line therapy 7

• LAMAs are preferred because they reduce hyperinflation and improve exercise tolerance in emphysema-dominant disease
• Add long-acting beta-agonists (LABAs) if symptoms persist despite LAMA monotherapy 7
• Inhaled corticosteroids (ICS) should NOT be routinely added unless frequent exacerbations occur or features of asthma overlap exist 7
• Smoking cessation is essential as it is the only intervention that slows emphysema progression 1

Airway-Dominant COPD

Consider ICS/LABA combination therapy earlier in the treatment algorithm 7, 5

• Airway-dominant patients show marked reduction in residual volume (RV) with 3 months of ICS/LABA treatment (-531 mL in lower-lobe dominant emphysema with airway involvement vs -86 mL in upper-lobe dominant) 5
• The presence of airway eosinophilia predicts better bronchodilator response to β-agonists 2
• Patients with bronchiectasis/bronchial wall thickening on CT experience more frequent exacerbations and may benefit from ICS 5
• Add LAMA (triple therapy) if symptoms persist on ICS/LABA 7

Asthma-COPD Overlap (Mixed Phenotype)

ICS must be included as part of the treatment regimen from the outset 7

• Diagnosed when post-bronchodilator FEV1/FVC <0.70 with significant reversibility (≥12% and ≥200 mL) 7
• Start with ICS/LABA combination, then add LAMA if symptoms persist 7
• These patients have more severe symptoms, lower quality of life, and increased exacerbation risk compared to COPD alone 7

Common Pitfalls and Caveats

Do not assume all COPD patients have emphysema: 25 of 209 patients (12%) with spirometry-confirmed COPD had no radiological evidence of emphysema 6

Do not use ICS indiscriminately in emphysema-dominant COPD: The pathological data show that inflammatory cells in airways provide rationale for anti-inflammatory treatment only in some cases 2, specifically those with airway eosinophilia or frequent exacerbations

Lower-lobe dominant emphysema is a distinct phenotype: These patients have more prominent airway involvement, more frequent exacerbations, and better response to ICS/LABA compared to upper-lobe dominant emphysema 5

Recognize that emphysema severity increases with GOLD stage: Mean emphysema index progresses from 7.4% (GOLD I) to 17.0% (GOLD II) to 24.2% (GOLD III) to 33.9% (GOLD IV), with 7.8% increase per GOLD stage 6

Functional small airways disease (fSAD) on parametric response mapping identifies patients at risk for rapid emphysema progression, even in those with normal spirometry 8