What is the appropriate diagnostic workup and initial management for an adult with suspected interstitial lung disease?

Diagnostic Workup and Initial Management for Suspected Interstitial Lung Disease

For an adult with suspected interstitial lung disease, obtain high-resolution CT (HRCT) of the chest as the primary diagnostic tool, complete pulmonary function testing including DLCO, and perform an autoimmune panel to screen for connective tissue disease—these three components form the foundation of your initial workup. 1, 2

Initial Clinical Assessment

History and Physical Examination

• Listen for "velcro" crackles on lung auscultation, which strongly suggest lung fibrosis and mandate further investigation 2, 3
• Assess for dyspnea on exertion (the most common presenting symptom) and chronic cough (present in approximately 30% of patients) 4
• Obtain a detailed occupational history including specific job tasks, duration of exposure, use of respiratory protection, and review of workplace safety data sheets—this is likely the single most important factor for achieving optimal outcomes 5, 6
• Document environmental exposures: farming, bird handling, metal-working fluids, beryllium, asbestos, diisocyanates, and moldy hay 5
• Review all medications for potential drug-induced ILD 6
• Assess for smoking history (both active and passive exposure) 6

Risk Factor Identification

• Screen for connective tissue disease manifestations: skin thickening, sclerodactyly, rashes, joint inflammation, Raynaud phenomenon, and abnormal nail-fold capillaries 3
• Document family history of pulmonary fibrosis in first-degree relatives 2
• Note demographic risk factors: male sex, older age, African-American ethnicity 3

Imaging Studies

High-Resolution CT Protocol

• Acquire volumetric HRCT on full inspiration with 1.5 mm slice thickness 2
• Obtain additional acquisitions in ventral decubitus and on expiration (1 mm slice thickness, 20 mm intervals) at baseline 2
• HRCT is approximately 91% sensitive and 71% specific for diagnosing ILD subtypes 4
• Plain chest radiography misses up to 34% of cases and should not be relied upon 5

Pattern Recognition on HRCT

Look for these specific findings 2:

• Ground-glass opacities
• Reticular abnormalities
• Traction bronchiectasis (indicates fibrosis)
• Honeycombing (indicates advanced fibrosis)
• Distribution pattern: subpleural and basal predominance suggests usual interstitial pneumonia (UIP) 1

Classification of Patterns

• UIP pattern: Honeycombing with or without traction bronchiectasis, subpleural and basal predominant, heterogeneous distribution 1
• Probable UIP pattern: Reticular pattern with traction bronchiectasis but no honeycombing 1
• Nonspecific interstitial pneumonia (NSIP): Most common in systemic sclerosis, inflammatory myopathies, and Sjögren syndrome 3
• Indeterminate patterns: Require additional diagnostic procedures 1

Pulmonary Function Testing

Obtain complete testing including 2:

• Forced vital capacity (FVC): A 5% decline over 12 months is associated with approximately 2-fold increase in mortality 4
• Total lung capacity (TLC): Demonstrates restrictive physiology 2
• Diffusing capacity for carbon monoxide (DLCO): Often the earliest physiologic abnormality in ILD and critical for early diagnosis 1, 2, 3

Important caveat: Pulmonary function tests do not have a role in the differential diagnosis of ILD—they provide prognostic information but cannot distinguish between subtypes 2

Laboratory Testing

Autoimmune Panel (Mandatory for All Patients)

The American Thoracic Society and European Respiratory Society recommend performing an autoimmune panel in every patient with interstitial pneumonia, as nearly 20% of ILDs are associated with connective tissue diseases and pulmonary manifestations can be the first sign 3

Include these tests 3:

• Antinuclear antibodies (ANA) by immunofluorescence: Positive ANA >1/320 increases likelihood of CTD diagnosis (OR=14.4)
• Rheumatoid factor (RF): Particularly important for RA-ILD
• Anti-cyclic citrullinated peptide (anti-CCP): High specificity for RA-ILD
• Myositis-specific antibodies: For suspected inflammatory myopathy
• C-reactive protein (CRP): Elevated levels suggest active inflammation

Additional Testing Based on Clinical Suspicion

• Disease-specific biomarkers as indicated by clinical presentation 2
• Do not routinely order MUC5B testing or telomere length measurement even in patients with family history of pulmonary fibrosis 2

Additional Diagnostic Procedures

Bronchoalveolar Lavage (BAL)

• Reserve for cases where the first diagnostic impression is inconclusive 2
• Consider when infection or lung toxicity is suspected 2

Lung Biopsy

• Consider when diagnosis remains uncertain after non-invasive testing 2
• Needed when specific histopathologic patterns must be identified for treatment decisions 1, 2
• Diagnostic confidence may need downgrading if using transbronchial lung cryobiopsy due to smaller sample size and greater sampling error compared to surgical lung biopsy 1

Multidisciplinary Discussion

Integrate findings from clinical, radiological, and when available, pathological evaluations in a multidisciplinary team discussion 2, 3. This collaboration is essential for accurate diagnosis and optimal management 1.

Classify the pattern as 2:

• Usual interstitial pneumonia (UIP)
• Nonspecific interstitial pneumonia (NSIP)
• Hypersensitivity pneumonitis (HP)
• Other patterns specific to underlying conditions

Initial Management Approach

For Idiopathic Pulmonary Fibrosis Pattern

• Initiate antifibrotic therapy with nintedanib or pirfenidone, which slow annual FVC decline by 44-57% 5, 4

For Connective Tissue Disease-Associated ILD

• Immunomodulatory therapy such as tocilizumab, rituximab, or mycophenolate mofetil may slow decline or improve FVC at 12-month follow-up 4

For Hypersensitivity Pneumonitis

• Immediate and complete avoidance of the causative exposure is the cornerstone of treatment 5

Supportive Care for All Patients

• Structured exercise therapy reduces symptoms and improves 6-minute walk test distance 4
• Supplemental oxygen for patients who desaturate below 88% on 6-minute walk test—this reduces symptoms and improves quality of life 4

Monitoring and Follow-Up

• Serial pulmonary function tests to assess disease progression 2
• For patients with connective tissue disease and stable pulmonary function, repeat chest HRCT within 12-24 months from baseline 2
• For stable disease without high-risk features, repeat HRCT in 2-3 years 5
• For high-risk features, repeat HRCT in 12 months 5

Special Populations

Connective Tissue Disease Patients

• Baseline chest CT scan is suggested to screen for interstitial lung abnormalities 2
• Systemic sclerosis: ILD occurs in approximately 50% of patients 3
• Rheumatoid arthritis: Significant ILD prevalence, particularly with UIP pattern 3

Family History of Pulmonary Fibrosis

• For adults ≥50 years with a first-degree relative with familial pulmonary fibrosis, chest CT screening is recommended 2

Critical Pitfalls to Avoid

• Do not fail to distinguish between interstitial lung abnormalities (ILAs) and established ILD—ILAs may not require immediate treatment but need monitoring 2
• Do not overlook connective tissue disease in patients presenting with interstitial changes—perform the autoimmune panel on every patient 3
• Do not rely solely on pulmonary function tests for diagnosis—they provide prognostic but not diagnostic information 2
• Do not delay referral to a multidisciplinary team with ILD expertise—this leads to misdiagnosis and inappropriate treatment 2, 3
• Do not miss occupational exposures—many patients are unaware of relevant exposures, so proactively query specific job tasks 5
• Irreversible lung function loss can occur asymptomatically—early detection is essential for informed treatment decisions and improved prognosis 3