What is the appropriate work‑up and first‑line treatment for an adult presenting with progressive dyspnea, dry cough and possible crackles suggestive of interstitial lung disease?

Diagnostic Work-Up and First-Line Treatment for Suspected Interstitial Lung Disease

For an adult presenting with progressive dyspnea, dry cough, and possible crackles, immediately obtain high-resolution CT (HRCT) of the chest—not a standard chest X-ray—as conventional radiography misses up to 34% of ILD cases and may appear normal despite significant disease. 1, 2

Initial Clinical Assessment

Key Historical Elements to Elicit

• Occupational and environmental exposures (organic antigens for hypersensitivity pneumonitis, silica/asbestos for pneumoconiosis) as 47% of new-onset ILD may be hypersensitivity pneumonitis on detailed assessment 1, 2
• Complete medication history including over-the-counter drugs and supplements, as drug toxicity is a reversible cause 1, 2
• Symptoms suggesting connective tissue disease: joint pain/swelling, Raynaud's phenomenon, dry eyes/mouth, photosensitivity, muscle weakness 1
• Family history of ILD in first-degree relatives, as 30% have genetic predisposing factors 1
• Age and smoking history: IPF typically presents after age 60 in current or former smokers 1, 3

Physical Examination Findings

• Fine, dry "Velcro-type" inspiratory crackles are present in >80% of IPF cases, most prominent at lung bases 1, 3
• Digital clubbing occurs in 25-50% of IPF patients 1
• Absence of fever—fever suggests alternative diagnosis such as infection or hypersensitivity pneumonitis 1

Mandatory Diagnostic Testing

High-Resolution CT Chest (HRCT)

HRCT is the primary diagnostic tool and must be obtained immediately as it is 91% sensitive and 71% specific for ILD subtypes 1, 2, 4. The HRCT pattern determines the entire diagnostic pathway:

• UIP pattern (subpleural/basal predominant reticular abnormality, honeycombing, traction bronchiectasis without ground-glass): Diagnosis of IPF can be made without biopsy if other causes excluded 1, 2
• Probable UIP pattern: Requires multidisciplinary discussion and consideration of surgical lung biopsy 1, 2
• Indeterminate or alternative pattern: Requires multidisciplinary discussion and often surgical lung biopsy 1, 2

Laboratory Testing

Obtain the following to exclude alternative diagnoses 1:

• Complete blood count with differential 1
• Comprehensive metabolic panel including creatinine and transaminases 1
• Erythrocyte sedimentation rate and C-reactive protein 1
• Antinuclear antibodies (ANA) and rheumatoid factor: High titers (>1:160) suggest connective tissue disease rather than IPF 1
• Additional autoimmune serologies if CTD suspected: anti-CCP, anti-Scl-70, anti-Jo-1, anti-Ro/La 1

Pulmonary Function Testing

Obtain baseline spirometry, lung volumes (TLC), and diffusion capacity (DLCO) for prognostic information and monitoring 1, 4. A 5% decline in FVC over 12 months is associated with approximately 2-fold increase in mortality 4. These tests are essential for monitoring but not specific enough for diagnosis alone 1.

Multidisciplinary Discussion Requirement

All cases require multidisciplinary discussion integrating HRCT, clinical features, and histopathology (if obtained) among pulmonologists, radiologists, and pathologists with ILD expertise 1. This approach increases diagnostic accuracy and is especially critical for complex cases.

Surgical Lung Biopsy Decision Algorithm

• Do NOT perform biopsy if HRCT shows definite UIP pattern—diagnosis can be made confidently without biopsy when other causes excluded 1, 2
• Consider biopsy for probable UIP, indeterminate, or alternative HRCT patterns after multidisciplinary discussion, unless high surgical risk (severe hypoxemia, DLCO <25%, severe pulmonary hypertension) 1

First-Line Treatment Based on Diagnosis

For Idiopathic Pulmonary Fibrosis (IPF)

Initiate antifibrotic therapy with nintedanib or pirfenidone immediately upon diagnosis, which slows annual FVC decline by 44-57% 2, 4. Do NOT use systemic corticosteroids for IPF as they are associated with increased mortality 5.

For Hypersensitivity Pneumonitis

Immediate and complete avoidance of the causative exposure is the cornerstone of treatment 2. Identify and eliminate the specific antigen through detailed exposure history.

For Connective Tissue Disease-Associated ILD

Immunomodulatory therapy such as mycophenolate mofetil, rituximab, or tocilizumab may slow decline or improve FVC 4. Treatment should be coordinated with rheumatology.

Critical Pitfalls to Avoid

• Never rely on chest X-ray alone—it has unacceptably low sensitivity and may appear normal in significant disease 2
• Do not delay HRCT while pursuing empiric trials of antibiotics or bronchodilators 2
• Do not overlook occupational/environmental exposures—systematic questioning may identify reversible causes in a substantial proportion 2
• Do not attribute all cough to ILD—systematically evaluate for GERD, asthma, upper airway cough syndrome, and medication side effects (especially ACE inhibitors) before concluding cough is ILD-related 1, 5
• Do not perform surgical lung biopsy when HRCT shows definite UIP pattern and other causes are excluded 1, 2