What are the diagnostic criteria for Combined Pulmonary Fibrosis and Emphysema (CPFE)?

Diagnostic Criteria for Combined Pulmonary Fibrosis and Emphysema (CPFE)

Combined Pulmonary Fibrosis and Emphysema (CPFE) is diagnosed based on high-resolution computed tomography (HRCT) findings showing the coexistence of upper lobe emphysema and lower lobe fibrosis.1

Clinical Characteristics

• CPFE typically presents in older patients (sixth and seventh decades), with a male predominance and a significant history of cigarette smoking 1
• Common symptoms include exertional dyspnea and cough, which may be insidious in onset 1, 2
• Physical examination may reveal bibasilar inspiratory crackles and digital clubbing 1
• CPFE is frequently complicated by pulmonary hypertension, acute exacerbations, and lung cancer, contributing to poor prognosis 2

Radiological Criteria

• HRCT is essential for diagnosis and should be performed with:

  • Thinnest collimation, shortest rotation time, and highest pitch to ensure motion-free images 1
  • Volumetric acquisition in supine position at sustained end-inspiration 1
  • Second acquisition in supine position at sustained end-expiration 1

• Key HRCT findings include:

  • Upper lobe predominant emphysema 3, 2
  • Lower lobe predominant pulmonary fibrosis with reticular abnormalities 3, 2
  • Possible honeycombing and traction bronchiectasis in fibrotic areas 1
  • Subpleural and basal distribution of fibrotic changes 1

Pulmonary Function Test Characteristics

• Distinctive pulmonary function profile showing:
  • Relatively preserved lung volumes (FVC and TLC) compared to isolated pulmonary fibrosis 3, 4
  • Preserved FEV1/FVC ratio despite the presence of emphysema 3
  • Severely reduced diffusing capacity for carbon monoxide (DLCO) 3, 4
  • Increased oxygen requirements despite preserved spirometric values 4

Diagnostic Algorithm

1. Initial Assessment:

   • Identify risk factors: older age, male sex, significant smoking history 1, 2
   • Evaluate symptoms: exertional dyspnea, cough 1
   • Physical examination: bibasilar crackles, digital clubbing 1

2. Imaging:

   • Perform HRCT with proper technique (as described above) 1
   • Confirm coexistence of upper lobe emphysema and lower lobe fibrosis 3, 2

3. Pulmonary Function Testing:

   • Document preserved or mildly impaired FVC and TLC 3
   • Confirm preserved FEV1/FVC ratio 3
   • Measure DLCO (typically severely reduced) 3, 4

4. Exclusion of Alternative Diagnoses:

   • Rule out other causes of interstitial lung disease such as:
     • Drug toxicities and environmental exposures 1
     • Connective tissue diseases (evaluate for high-titer autoantibodies) 1

5. Multidisciplinary Discussion:

   • Involve pulmonologists, radiologists, and pathologists experienced in interstitial lung diseases 1
   • Consider referral to specialized centers for complex cases 1

Biomarkers and Monitoring

• Serum biomarkers may help assess the degree of fibrosis in CPFE:

  • KL-6 and surfactant protein D (SP-D) levels correlate with the extent of fibrotic lesions 5
  • The combined product of KL-6 and SP-D shows strong correlation with vital capacity and total lung capacity 5

• Monitoring should include:

  • Regular assessment of symptoms, particularly worsening dyspnea 1
  • Serial pulmonary function tests (FVC, DLCO) 1
  • Evaluation for pulmonary hypertension with echocardiography 1, 2
  • Surveillance for lung cancer development 2, 6

Clinical Pitfalls and Caveats

• CPFE may be underdiagnosed due to the paradoxically preserved lung volumes despite significant disease 3
• The preserved FEV1/FVC ratio may lead to underestimation of the emphysema component 3
• Severe reduction in DLCO may be the only significant functional abnormality in early disease 3, 4
• Patients with CPFE have worse prognosis compared to those with isolated pulmonary fibrosis or emphysema 2, 6
• CPFE patients are at increased risk for pulmonary hypertension, which further worsens prognosis 2