Can a person have both Interstitial Lung Disease (ILD) and emphysema at the same time?

Can a Person Have Both ILD and Emphysema Simultaneously?

Yes, a person can absolutely have both interstitial lung disease (ILD) and emphysema at the same time—this is a well-recognized clinical syndrome called Combined Pulmonary Fibrosis and Emphysema (CPFE). 1

Understanding CPFE as a Distinct Syndrome

CPFE is formally recognized as a syndrome by the American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association, characterized by the coexistence of upper-lobe emphysema and lower-lobe pulmonary fibrosis. 2 This is not merely coincidental overlap but represents a distinct clinical entity with:

• Shared pathogenetic pathways between the two disease processes 2
• Unique clustering patterns that distinguish it from either disease alone 2
• Specific prognostic implications including increased mortality risk 2

Epidemiology and Prevalence

CPFE is surprisingly common among patients with fibrotic ILD:

• Among patients with idiopathic pulmonary fibrosis (IPF), 39% have concurrent emphysema (CPFE-IPF) 3
• Among patients with other fibrotic ILDs, 36.3% have concurrent emphysema (CPFE-fILD) 3
• Prevalence ranges from 71-100 per 100,000 in veteran populations 3
• Annual incidence ranges from 16-39 per 100,000 3

Clinical Presentation: The Diagnostic Challenge

CPFE presents a unique diagnostic challenge because emphysema and fibrosis counterbalance each other on standard testing, creating deceivingly normal-appearing results despite severe disease. 4

Key Clinical Features:

• Severe exertional dyspnea disproportionate to spirometry findings 2
• Predominantly male patients with significant smoking history 2, 3
• Preserved or near-normal lung volumes on spirometry (emphysema increases volumes, fibrosis decreases them) 1, 2
• Severely impaired diffusing capacity (DLCO) despite normal spirometry 2, 3
• Profound exertional hypoxemia 2
• Lower BMI compared to ILD alone 3

Radiologic Recognition

High-resolution CT (HRCT) is essential for diagnosis and will show the characteristic pattern of upper-lobe emphysema with lower-lobe fibrosis. 1

HRCT Patterns in Smokers with ILD:

Multiple patterns may coexist including:

• Langerhans cell histiocytosis 1
• Respiratory bronchiolitis 1
• Desquamative interstitial pneumonia 1
• Pulmonary fibrosis (UIP or NSIP patterns) 1
• Emphysema 1

Critical Diagnostic Pitfall

The most dangerous pitfall is attributing preserved lung volumes to mild disease severity when CPFE is actually present. 1

• You must actively search for emphysema on every HRCT performed for ILD diagnosis 1
• Preserved FVC in the setting of severe dyspnea and low DLCO should raise immediate suspicion for CPFE 1
• Monitoring FVC alone does not allow accurate assessment of disease progression in CPFE 1

Prognostic Implications and Complications

CPFE carries a dismal prognosis with significantly increased risk of life-threatening complications compared to either disease alone. 2

Major Complications:

• Pulmonary hypertension is particularly frequent and represents the main predictor of mortality 1, 2
• Increased risk of lung cancer 5, 2
• Higher risk of acute exacerbations 6
• Increased overall mortality in unadjusted analyses 3

After adjustment for age, sex, and BMI, CPFE mortality is similar to ILD without emphysema (HR 1.13 for CPFE-IPF vs IPF alone, 95% CI 0.96-1.33). 3 However, the absolute mortality burden remains high due to the severe baseline disease.

Management Approach

Essential Initial Steps:

• Immediate smoking cessation is mandatory 1
• Screen for pulmonary hypertension given the high prevalence and prognostic significance 1
• Assess for airflow obstruction and prescribe inhaled bronchodilators if present 1
• Evaluate oxygen requirements, as these patients often need supplemental oxygen 1

Treatment Considerations:

No specific data support unique pharmacologic management of CPFE versus ILD alone. 1 Treatment decisions must be individualized considering:

• Antifibrotic therapy (pirfenidone or nintedanib) should be considered based on the fibrotic component 1
• The absence of evidence for benefit in CPFE specifically 1
• The difficulty evaluating disease evolution due to minimal FVC changes 1
• Potential side effects of therapy 1

Monitoring Strategy:

• FVC and DLCO monitoring does not allow accurate prognosis assessment 1
• Serial HRCT imaging is more useful for tracking progression 1
• Regular assessment for pulmonary hypertension development 1
• Long-term oxygen therapy is frequently indicated 1

Recognition Across ILD Subtypes

CPFE is not limited to IPF—it occurs across a wide variety of interstitial lung diseases including:

• Connective tissue disease-associated ILD 4
• Hypersensitivity pneumonitis 4
• Other fibrotic ILDs 4, 3

This broad occurrence emphasizes that clinicians must actively look for emphysema in all patients with fibrotic ILD, regardless of the underlying ILD subtype.