Why is serum Angiotensin-Converting Enzyme (ACE) a good test for Interstitial Lung Disease (ILD)?

Serum ACE is NOT a Good Test for Interstitial Lung Disease (ILD)

Serum Angiotensin-Converting Enzyme (ACE) is not recommended as a screening or diagnostic test for interstitial lung disease (ILD) in general, as it lacks sensitivity and specificity for most forms of ILD. Current guidelines from the American College of Rheumatology (ACR) and American College of Chest Physicians (CHEST) do not include serum ACE in their recommended screening or monitoring protocols for ILD 1.

Why Serum ACE is Not Useful for General ILD Diagnosis

Limited Diagnostic Value

• Serum ACE is primarily elevated in sarcoidosis, not in other forms of ILD
• The 2023 ACR/CHEST guidelines make no mention of serum ACE as a recommended test for ILD screening or monitoring 1
• The guidelines specifically recommend against several tests but focus on HRCT and PFTs as the primary diagnostic tools 1

Preferred Diagnostic Approach for ILD

1. High-Resolution CT (HRCT): Considered the gold standard for ILD diagnosis

   • Sensitivity of 95.7% for early ILD detection 2
   • Recommended as primary screening tool by ACR/CHEST 1

2. Pulmonary Function Tests (PFTs):

   • Including spirometry, lung volumes, and DLCO
   • Recommended for both screening and monitoring 1
   • Less sensitive than HRCT (47.5% for FVC <80%) but useful for monitoring 2

When Serum ACE Is Actually Useful

Serum ACE is primarily valuable in the specific context of sarcoidosis:

1. Sarcoidosis Diagnosis:

   • Elevated in approximately 60-80% of patients with active sarcoidosis 3
   • Sensitivity of 58.1% overall, rising to 92.1% in clinically active sarcoidosis 3
   • Specificity of 83.8% for sarcoidosis 3

2. Disease Activity Monitoring:

   • Useful for monitoring disease activity in sarcoidosis 4, 5
   • Complete remission is accompanied by normalization of ACE levels 4
   • Correlates with clinical activity longitudinally 3

3. European Position Paper on Rhinosinusitis and Nasal Polyps (2020):

   • Recognizes serum ACE as a useful tool for sarcoidosis diagnosis and disease activity evaluation 1
   • "Elevated serum levels of ACE, IL-2R, and lysozyme are usually associated with more aggressive disease and multiple-organ involvement" 1

Limitations of Serum ACE Testing

• Poor Specificity: False positives occur in:

  • Military tuberculosis (38.9%) 3
  • Silicosis (48%) 3
  • Gaucher's disease (100%) 3

• Variable Sensitivity:

  • Only 58.1% overall for sarcoidosis 3
  • 7.9% of patients with active sarcoidosis have normal levels 3

• No Correlation with ILD Pattern:

  • No correlation between ACE levels and radiological stages of sarcoidosis 4
  • No evidence supporting its use in non-sarcoid ILD

Current Guideline Recommendations for ILD Diagnosis

The 2023 ACR/CHEST guidelines for ILD screening and monitoring in systemic autoimmune rheumatic diseases recommend:

1. For initial screening:

   • HRCT and PFTs over history and physical examination alone 1
   • Against chest radiography, 6-minute walk test, ambulatory desaturation testing, bronchoscopy, and surgical lung biopsy 1

2. For monitoring:

   • PFTs every 3-6 months in the first year for high-risk patients (systemic sclerosis, inflammatory myopathies) 1, 2
   • PFTs every 3-12 months for moderate-risk patients (RA, Sjögren's) 1, 2
   • HRCT as needed based on symptoms or PFT changes 1

Alternative Biomarkers for ILD

Other biomarkers may have greater utility than serum ACE for certain ILDs:

• Serum lysozyme: More frequently elevated (80%) than ACE (40%) in sarcoidosis patients and correlates better with clinical measurements 6
• BAL lymphocyte counts: Better predictor of radiographic response to corticosteroids in sarcoidosis 6
• Autoantibodies: Essential for diagnosing connective tissue disease-associated ILD 2

Conclusion

Serum ACE is not a good test for general ILD diagnosis or screening. It has limited utility restricted primarily to sarcoidosis diagnosis and monitoring. Current guidelines recommend HRCT and PFTs as the primary tools for ILD screening and monitoring, with no role for serum ACE in the general approach to ILD.