How should I evaluate and manage a patient with suspected interstitial lung disease?

Evaluation and Management of Suspected Interstitial Lung Disease

All patients with suspected ILD require high-resolution CT (HRCT) as the diagnostic gold standard, baseline pulmonary function testing (spirometry, TLC, and DLCO), and symptom assessment through multidisciplinary evaluation integrating pulmonology, radiology, and when applicable, rheumatology expertise. 1, 2

Initial Clinical Assessment

Symptom Evaluation

• Assess for dyspnea on exertion and non-productive cough, though recognize that up to 90% of early ILD cases may be asymptomatic 2, 3
• Document the presence and severity of cough (present in 30.5% of ILD patients) and dyspnea (37.1% of cases), as baseline dyspnea associates with increased mortality 1, 2
• Evaluate for fatigue, weight loss, and reduced exercise tolerance 1, 2
• Do not dismiss findings in asymptomatic patients—ILD carries 66% increased mortality risk regardless of symptoms 2

Physical Examination

• Auscultate for fine, dry, "Velcro-type" end-inspiratory crackles, detected in >80% of IPF patients and most prevalent in lung bases initially 2, 3
• Examine for digital clubbing (present in 25-50% of IPF cases) 2
• Check for cyanosis in advanced disease and peripheral edema indicating right heart failure 2
• Assess for signs of pulmonary hypertension: accentuated pulmonic second sound, right ventricular heave 2

Exposure and Risk Factor Assessment

• Document comprehensive environmental and occupational exposure history (mold, air pollution, vapors, gases, dusts, fumes), as these interact with genetic susceptibility 2, 4
• Obtain detailed smoking history—approximately 8% of smokers undergoing lung cancer screening have ILD 2
• Elicit family history of pulmonary fibrosis, as 15-30% of first-degree relatives of affected patients show interstitial abnormalities 2

Diagnostic Workup

Laboratory Testing

• Obtain autoimmune serologies including anti-nuclear antibodies, anti-citrullinated cyclic peptide antibodies, rheumatoid factor, anti-topoisomerase (Scl-70), anti-MDA5, and anti-synthetase antibodies 1, 2
• Complete blood count with differential, C-reactive protein, serum creatinine, transaminases, gamma-glutamyltransferase, and alkaline phosphatases 2
• CTD-associated ILD accounts for 25% of all ILD cases, making autoimmune screening essential 3, 5

Imaging

• HRCT is mandatory for all suspected ILD patients with 95.7% sensitivity and 63.8% specificity for detecting ILD with ≥20% lung involvement 2
• HRCT should include inspiratory prone images and supine end-expiratory imaging 2
• Chest radiography alone is insufficient—up to 10% of ILD patients have normal chest X-rays 2
• HRCT patterns identify specific subtypes: usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), and others 2, 3

Pulmonary Function Testing

• Measure FVC, TLC, and DLCO at baseline—any value below the lower limit of normal attributed to ILD upgrades diagnosis from interstitial lung abnormality (ILA) to ILD 1, 2, 4
• Baseline FVC <80% has only 47.5% sensitivity for detecting ILD, emphasizing imaging necessity 2
• A 5% FVC decline over 12 months associates with approximately 2-fold increased mortality 3, 5

Additional Testing

• Perform 6-minute walk test with oxygen saturation monitoring to evaluate exercise capacity and detect desaturation indicating gas exchange impairment 2, 3
• Obtain echocardiography routinely to identify pulmonary hypertension and structural cardiac abnormalities—up to 85% of end-stage fibrotic ILD patients develop pulmonary hypertension 2, 5

Tissue Diagnosis When Needed

• Consider transbronchial lung cryobiopsy (TBLC) as first-line biopsy method when HRCT and clinical findings are insufficient for definitive diagnosis 2
• TBLC provides larger samples without crush artifacts and has lower complication rates than surgical lung biopsy 2
• Bronchoalveolar lavage (BAL) provides diagnostic clues: lymphocyte count >25% suggests granulomatous disease or cellular NSIP; >50% strongly indicates hypersensitivity pneumonitis; eosinophils >25% virtually diagnoses eosinophilic pneumonia; CD4+/CD8- ratio >4 is highly specific for sarcoidosis 2
• Surgical lung biopsy should be considered in rapidly progressive cases or when TBLC yields nondiagnostic results 2

Multidisciplinary Discussion

Multidisciplinary discussion (MDD) involving pulmonologists, radiologists, and pathologists is mandatory for optimal diagnostic yield, integrating clinical, radiological, and pathological findings to establish final diagnosis 2, 3, 6

Management Strategy

CTD-Associated ILD

• For most CTD-ILD patients (except SSc-ILD), initiate mycophenolate mofetil, azathioprine, rituximab, or cyclophosphamide as first-line treatment 2, 3
• Avoid glucocorticoids as first-line treatment in SSc-ILD (strong recommendation against) 2
• Tocilizumab is conditionally recommended as first-line option for SSc-ILD and mixed connective tissue disease-ILD 2, 3
• Nintedanib is conditionally recommended for SSc-ILD 2
• JAK inhibitors and calcineurin inhibitors are conditionally recommended for idiopathic inflammatory myopathy-ILD 2

Idiopathic Pulmonary Fibrosis Pattern

• Initiate antifibrotic therapy with nintedanib or pirfenidone, as these agents slow annual FVC decline by 44-57% 4, 3, 5
• Do not use immunosuppressive therapy for IPF—it is ineffective and potentially harmful 4

Risk Reduction Interventions

• Counsel on smoking cessation using combined pharmacotherapy (nicotine replacement, varenicline, or bupropion) and behavioral support—this is the single most effective intervention to slow progression 2
• Remove or remediate identified environmental, occupational, or medication triggers 2
• Ensure age-appropriate vaccinations (influenza and pneumococcal) to reduce respiratory infection risk 2

Supportive Care

• Structured exercise therapy reduces symptoms and improves 6-minute walk test distance in patients with dyspnea 3, 5
• Oxygen therapy improves quality of life in patients who desaturate below 88% on 6-minute walk test 5
• Inhaled treprostinil improves walking distance and respiratory symptoms in patients with pulmonary hypertension 5
• Consider lung transplant for end-stage ILD—median survival is 5.2-6.7 years post-transplant versus <2 years without transplant 5

Follow-Up and Monitoring

Serial Assessment Schedule

• Perform serial PFTs (spirometry and DLCO) every 3-6 months during the first year, then annually if stable 2, 3
• Ambulatory desaturation testing every 3-12 months for monitoring 2
• Repeat HRCT in 2-3 years after baseline to assess radiologic progression 2, 4

High-Risk Features Requiring Earlier Monitoring

• In patients with high-risk features, perform HRCT at 12 months: definite fibrosis on CT, subpleural fibrotic pattern, extensive radiographic abnormalities, abnormal PFTs, family history of fibrosis, older age, or smoking history 2, 4
• More than 50% of patients with ILAs experience radiologic progression over 5 years, with approximately 10% progressing to clinically significant ILD annually 2

Progressive Disease Criteria

• Progressive pulmonary fibrosis is defined by at least two of: worsening respiratory symptoms, physiological evidence of progression on PFTs, and radiological evidence of progression on chest CT 2
• Patients with radiologically progressive ILAs experience 64-ml annual FVC decline versus 35-ml in those without progression 2

Critical Pitfalls to Avoid

• Do not attribute cough and dyspnea solely to ILD without excluding cardiac disease, asthma, and postnasal drainage 2
• Do not rely on chest radiography alone—HRCT is essential even with normal X-rays 2
• Do not dismiss asymptomatic patients with imaging findings—they still carry increased mortality risk 2
• For patients with anti-MDA5 and anti-synthetase antibodies, urgent assessment and baseline HRCT referral are necessary due to rapidly progressive disease risk 1