What laboratory tests are used to evaluate interstitial lung disease?

Laboratory Evaluation of Interstitial Lung Disease

For patients with suspected ILD, perform an autoimmune panel including ANA, RF, anti-CCP, anti-Ro/SSA, anti-La/SSB, anti-Scl-70, anti-Jo-1, and other myositis antibodies, along with inflammatory markers (ESR, CRP), complete blood count, and comprehensive metabolic panel as initial screening tests. 1

Essential Serologic Testing

Autoimmune Panel

• Antinuclear antibody (ANA) with titer and pattern to screen for connective tissue disease-associated ILD 1
• Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies for rheumatoid arthritis-ILD, as RF positivity is a risk factor for ILD development 1
• Anti-Scl-70 (anti-topoisomerase) antibodies for systemic sclerosis-ILD, which carries high risk for pulmonary involvement 1
• Anti-Ro/SSA, anti-La/SSB, and anti-Ro52 antibodies for Sjögren syndrome-ILD, as these predict ILD risk 1
• Myositis-specific antibodies including anti-Jo-1 and other antisynthetase antibodies for inflammatory myopathy-ILD 1

Inflammatory Markers

• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) to assess disease activity and inflammation, as elevated levels are risk factors for CTD-ILD 1, 2
• ESR and CRP correlate with HRCT severity scores in ILD patients 3, 2

Hematologic Studies

• Complete blood count with differential to identify lymphopenia (risk factor for CTD-ILD) and eosinophilia (suggests eosinophilic pneumonia or drug reaction) 1, 3
• Lymphopenia specifically predicts ILD onset in primary Sjögren syndrome 3

Additional Laboratory Tests Based on Clinical Context

Serum Biomarkers

• Krebs von den Lungen-6 (KL-6) is elevated in IPF and ILD and may help distinguish disease subtypes 2
• Matrix metalloproteinase-1 (MMP-1) and MMP-7 are significantly elevated in both IPF and non-IPF ILD 2
• Galectin-3 and interleukin-6 (IL-6) show significant elevation in ILD patients compared to healthy controls 2

Metabolic and Oxidative Stress Markers

• Total oxidant status (TOS) and total antioxidant status (TAS) are significantly altered in IPF and ILD, reflecting oxidant-antioxidant imbalances 2
• Pyruvate kinase (PK) levels correlate with disease severity markers including visual semi-quantitative scores and 6-minute walk test results 2

Hypergammaglobulinemia

• Elevated immunoglobulin levels are a risk factor for Sjögren syndrome-associated ILD 1

Bronchoalveolar Lavage (BAL) Cellular Analysis

BAL with differential cell count should be performed when HRCT does not show a confident UIP pattern and the diagnosis remains uncertain after initial evaluation. 1

BAL Differential Cell Count Interpretation

• Lymphocytosis >25% suggests sarcoidosis, hypersensitivity pneumonitis, chronic beryllium disease, cellular NSIP, drug reaction, or lymphoid interstitial pneumonia 1
• Lymphocytosis >50% strongly suggests hypersensitivity pneumonitis or cellular NSIP 1
• Eosinophilia >25% is virtually diagnostic of acute or chronic eosinophilic pneumonia 1
• Neutrophilia >50% supports acute lung injury, aspiration pneumonia, or infection 1
• CD4/CD8 ratio >4 is highly specific for sarcoidosis when other inflammatory cells are not increased 1

BAL Technical Requirements

• Differential cell count must include macrophage, lymphocyte, neutrophil, eosinophil, and mast cell counts 1
• Remaining BAL fluid should be cultured for mycobacteria and fungi, and screened for malignant cells 1
• Cellular analysis should be performed within 1 hour if in saline or within 2-3 hours if in nutrient-supplemented media 1

Microbiological Testing

Infection Screening

• Mycobacterial cultures and fungal cultures from BAL fluid are essential because infections can masquerade as or coexist with ILD 1
• Microbiological studies should be performed routinely on BAL fluid in all suspected ILD cases 1

Beryllium Testing

• In vitro lymphocyte proliferation test to beryllium antigen on BAL fluid for suspected chronic beryllium disease 1

Common Pitfalls and Caveats

BAL Specimen Quality

• Presence of squamous epithelial cells indicates upper airway contamination and compromises diagnostic accuracy 1, 4
• Large numbers of bronchial epithelial cells suggest inadequate sampling of distal airspaces 1, 4
• Total retrieved BAL volume should be ≥30% of instilled volume; <10% recovery provides misleading cell differentials 1

Limitations of Laboratory Testing

• BAL cellular analysis alone cannot diagnose specific ILD types except in malignancies and rare ILDs; it must be interpreted with clinical and radiographic findings 1
• A normal BAL differential does not exclude microscopic lung abnormalities 1
• BAL has no firmly established prognostic value and cannot predict treatment response 1

Risk Stratification Considerations

• Laboratory abnormalities differ between CTD-ILD subtypes, requiring disease-specific interpretation 1
• Male sex, age ≥65 years, and smoking history are additional risk factors that should be considered alongside laboratory findings 1