What is the appropriate diagnostic workup and initial treatment for an adult presenting with new‑onset interstitial pneumonia characterized by progressive dyspnea, non‑productive cough, and fine inspiratory crackles?

Diagnostic Workup and Initial Treatment for New-Onset Interstitial Pneumonia

For an adult presenting with progressive dyspnea, non-productive cough, and fine inspiratory crackles, immediately obtain high-resolution CT (HRCT) to characterize the pattern of lung involvement, as this single test determines whether you can make a definitive diagnosis or need tissue biopsy. 1

Initial Clinical Assessment

Key clinical features to document:

• Age and smoking history: IPF typically presents in the sixth-seventh decade; DIP and RBILD occur in current/former smokers 1
• Symptom duration: Acute onset (days-weeks) suggests acute interstitial pneumonia; subacute (<3 months) suggests cryptogenic organizing pneumonia; chronic (months-years) suggests IPF or NSIP 1
• Occupational/environmental exposures: Organic antigens (hypersensitivity pneumonitis), mineral particles (pneumoconiosis), drugs 1
• Systemic symptoms: Joint pain, muscle weakness, Raynaud's phenomenon, dry eyes/mouth suggest connective tissue disease; fever/weight loss uncommon in IPF but may occur in organizing pneumonia 1, 2
• Physical examination: Fine "Velcro" crackles in >80% of IPF cases, most prominent at lung bases; clubbing in 25-50%; absence of fever (fever suggests alternative diagnosis) 1, 2

Essential Laboratory Workup

Order these tests to exclude secondary causes:

• Autoantibody panel: ANA, rheumatoid factor, anti-CCP, anti-Scl-70, anti-Jo-1, anti-Ro/La 1
  • Titers >1:160 suggest connective tissue disease rather than idiopathic disease 1
• Serum precipitins if exposure history suggests hypersensitivity pneumonitis 1
• Complete blood count, comprehensive metabolic panel, LDH (nonspecific but may be elevated) 1

Do NOT order serum MMP-7, SPD, CCL-18, or KL-6 for distinguishing IPF from other ILDs 1

High-Resolution CT: The Critical Decision Point

HRCT patterns determine your next diagnostic step:

Pattern 1: Definite UIP Pattern on HRCT

• Features: Subpleural/basal predominant reticular abnormality, honeycombing, traction bronchiectasis, absence of features inconsistent with UIP 1
• Action: In patients >50 years without alternative cause, this IS the diagnosis of IPF—do NOT perform surgical lung biopsy, transbronchial biopsy, cryobiopsy, or BAL 1
• Treatment: Initiate antifibrotic therapy (pirfenidone or nintedanib); do NOT use corticosteroids 3, 4

Pattern 2: Probable UIP, Indeterminate, or Alternative Pattern

• Action: Proceed to surgical lung biopsy to obtain definitive histopathologic diagnosis 1
• Consider BAL cellular analysis before biopsy (conditional recommendation) 1
  • Lymphocyte count >25% suggests sarcoidosis, hypersensitivity pneumonitis, or NSIP 1
  • Eosinophils >25% suggest eosinophilic pneumonia or drug reaction 1
  • Smoking-related macrophages suggest DIP/RBILD 1

Pattern 3: Ground-Glass Opacities with Subpleural Sparing

• Suggests NSIP: Bilateral symmetric ground-glass opacities, lower zone predominance, minimal honeycombing 1, 5
• Action: Surgical lung biopsy to confirm temporally uniform inflammation/fibrosis 1, 5

Pattern 4: Patchy Consolidation, Often Migratory

• Suggests cryptogenic organizing pneumonia: Subpleural/peribronchial distribution, reversed halo sign 1
• Action: May proceed with empiric corticosteroid trial if clinical presentation strongly supports diagnosis 1, 3

Treatment Based on Histopathologic Diagnosis

If Biopsy Shows UIP Pattern (IPF)

Do NOT use corticosteroids—they provide no survival benefit and may cause harm 3

• First-line: Pirfenidone or nintedanib (reduce FVC decline by 44-57% annually) 3, 4
• Supportive care: Pulmonary rehabilitation, oxygen for hypoxemia (SpO2 <88% on 6-minute walk test), lung transplant referral if progressive 3, 4
• Prognosis: Mean survival ~3 years without treatment 6

If Biopsy Shows NSIP Pattern

Corticosteroids are first-line therapy with favorable prognosis 1, 3

• Initial regimen: Prednisone 0.5-1 mg/kg/day 3
• Taper: Over 2-4 months based on response 3
• Add cyclophosphamide if inadequate response to corticosteroids alone 3
• Prognosis: 15-20% mortality at 5 years with treatment (vs. ~70% for UIP) 1
• Monitoring: Serial PFTs, HRCT, clinical symptoms every 3-6 months 3

If Biopsy Shows Organizing Pneumonia Pattern

Corticosteroids are highly effective 1, 3

• Dose: Prednisone 0.5 mg/kg/day initially 3
• Expected response: Clinical improvement within 3 days 3
• Duration: Taper over >1 month for grade 2 severity, >2 months for grade 3-4 3
• Prognosis: Majority recover completely, but relapses common 1

If DIP or RBILD Pattern

Smoking cessation is essential 1

• Add corticosteroids if symptoms persist after smoking cessation 1
• Prognosis: Substantially better than IPF; 70% 10-year survival for DIP 1

Critical Pitfalls to Avoid

Do NOT treat presumed IPF with corticosteroids without tissue diagnosis—if the patient actually has UIP/IPF, corticosteroids cause harm without benefit 3

Do NOT delay surgical lung biopsy in patients with indeterminate HRCT patterns—accurate histopathologic subtyping is essential because treatment differs dramatically (corticosteroids for NSIP vs. antifibrotics for UIP) 3

Do NOT assume all interstitial pneumonias are idiopathic—thoroughly exclude connective tissue disease, drug toxicity, and hypersensitivity pneumonitis, as these require different management 1

Do NOT perform lung biopsy if HRCT shows definite UIP pattern in appropriate clinical context—this is sufficient for IPF diagnosis 1

Multidisciplinary Discussion

Convene pulmonologist, radiologist, and pathologist to review clinical, radiographic, and histopathologic data together for consensus diagnosis—this improves diagnostic accuracy 1, 7