What are the examination findings, differential diagnoses, investigations, and management of interstitial lung disease (ILD)?

Interstitial Lung Disease: Clinical Examination, Differentials, Investigations, and Management

Examination Findings

General Appearance

• Observe for scalene muscle hypertrophy, which indicates increased work of breathing and is a specific finding in advanced ILD 1
• Look for digital clubbing, present in 25-50% of patients with idiopathic pulmonary fibrosis (IPF), though it may be absent in early disease 2, 1
• Assess for cyanosis, which appears in late-stage disease and indicates severe gas exchange impairment 2
• Note weight loss and signs of malaise, though fever is rare and suggests alternative diagnosis 2

Trachea

• Tracheal position is typically central in ILD, as this is a bilateral diffuse process 3
• Tracheal deviation would suggest alternative pathology such as pneumothorax or large pleural effusion 3

Palpation

• Assess for reduced chest expansion bilaterally due to restrictive physiology 3
• Palpate for signs of right ventricular heave in advanced disease with cor pulmonale 2
• Check for peripheral edema indicating right heart failure in late phases 2

Percussion

• Percussion typically reveals normal resonance in early ILD, as fibrosis does not significantly alter percussion notes 2
• Altered lung resonance may occur with extensive fibrosis or complications like pneumothorax 2

Auscultation

• Fine, dry, "Velcro-type" end-inspiratory crackles are the hallmark finding, detected in more than 80% of IPF patients 2, 4
• Crackles are most prevalent in lung bases initially, extending toward upper zones with disease progression 2, 4
• The presence of fine basilar crackles should prompt immediate HRCT evaluation, as they represent an early sign of ILD 4
• An accentuated pulmonic second sound may be heard in advanced disease with pulmonary hypertension 2

Differential Diagnoses

Primary ILD Categories

• Idiopathic pulmonary fibrosis (IPF): Most common progressive ILD, typically in patients >50 years, male smokers, with UIP pattern on HRCT 2, 1
• Connective tissue disease-associated ILD: Particularly rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease 2
• Hypersensitivity pneumonitis: Requires detailed environmental exposure history; causative antigens often not identified 5, 6
• Sarcoidosis: More common in young and middle-aged adults, granulomatous disease 2
• Drug-induced ILD: Comprehensive medication history essential, including over-the-counter and herbal supplements 6
• Occupational ILD: Detailed occupational exposure history critical 6

Important Mimics to Exclude

• Congestive heart failure: Also presents with fine basilar crackles but with different clinical context 4
• Chronic obstructive pulmonary disease: Different auscultatory findings and smoking history 7
• Bronchiectasis: Presents with coarse rather than fine crackles 4

Investigations

Initial Laboratory Testing

• Complete blood count with differential, C-reactive protein, serum creatinine, transaminases, gamma-glutamyltransferase, and alkaline phosphatases 3
• Autoimmune serologies including anti-nuclear antibodies, anti-citrullinated cyclic peptide antibodies, and rheumatoid factor 3
• Serum KL-6 and LDH are sensitive for ILD detection and activity monitoring 1

Pulmonary Function Tests

• Spirometry to identify restrictive pattern with decreased FVC 3
• Total lung capacity (TLC) measurement to confirm restriction 3
• Diffusion capacity (DLCO) to assess gas exchange impairment 3
• Serial PFTs at 3-6 month intervals initially, then annually if stable 3
• Baseline FVC <80% has only 47.5% sensitivity for detecting ILD, emphasizing need for imaging 2

Imaging

• High-resolution computed tomography (HRCT) is the gold standard and should be performed in all patients with suspected ILD 3
• HRCT has 95.7% sensitivity and 63.8% specificity for detecting ILD with ≥20% lung involvement 2
• HRCT patterns identify specific ILD types: usual interstitial pneumonia (UIP) with honeycombing and subpleural reticular opacity, or non-specific interstitial pneumonia (NSIP) 3, 1
• Chest radiography alone is insufficient; up to 10% of ILD patients have normal chest X-rays 2
• HRCT should include inspiratory prone images and supine end-expiratory imaging 2

Functional Assessment

• 6-minute walk test to evaluate exercise capacity and oxygen desaturation 3
• Ambulatory desaturation testing every 3-12 months for monitoring 2

Tissue Diagnosis

• Transbronchial lung cryobiopsy (TBLC) is suggested as first-line biopsy method when HRCT and clinical findings are insufficient 3
• TBLC provides larger samples without crush artifacts and has lower complication rates than surgical lung biopsy 3
• Bronchoalveolar lavage with lymphocyte count >25% suggests granulomatous disease or cellular NSIP 3
• Multidisciplinary discussion involving pulmonologists, radiologists, and pathologists is mandatory for optimal diagnostic yield 3

Tests NOT Recommended

• Baseline telomere length measurement is not recommended 2
• MUC5B testing is not recommended for routine evaluation 2
• Routine histopathological sampling is not recommended unless meeting specific ILD criteria 2

Management

General Approach

• A multidisciplinary approach integrating HRCT, PFTs, and symptom evaluation with pulmonary, rheumatology, and radiology expertise is the method of choice 3
• Document detailed environmental and occupational exposure history to identify treatable causes 3

Specific Pharmacologic Management

Connective Tissue Disease-Associated ILD

• For most CTD-ILD patients (except SSc-ILD), consider mycophenolate, azathioprine, rituximab, or cyclophosphamide as first-line options 3
• Avoid glucocorticoids as first-line treatment in SSc-ILD (strong recommendation against) 3
• Tocilizumab is conditionally recommended as first-line for SSc-ILD and MCTD-ILD 3
• Nintedanib is conditionally recommended for SSc-ILD 3
• JAK inhibitors and calcineurin inhibitors are conditionally recommended for idiopathic inflammatory myopathy-ILD 3

Idiopathic Pulmonary Fibrosis

• Pirfenidone 2,403 mg/day demonstrated statistically significant reduction in FVC decline (mean treatment difference 193 mL at Week 52) and slows disease progression 8
• Nintedanib is an alternative anti-fibrotic agent that slows FVC decline and prevents acute exacerbations 1
• Both anti-fibrotic drugs can slow FVC decline and prevent acute exacerbations 1

Hypersensitivity Pneumonitis

• When antigen is identified or suspected, immediate avoidance is the first action 5
• If antigen avoidance does not improve symptoms, introduce prednisolone 5

Sarcoidosis

• Most patients do not require treatment for lung involvement 5
• Anti-inflammatory drugs or immunosuppressants for progressive pulmonary disease 5
• Steroid treatment is mandatory for critical extrapulmonary involvement including cardiac, neurogenic, and ocular sarcoidosis 5

Monitoring for Disease Progression

• Regular clinical assessment for symptom progression including dyspnea and cough 3
• Serial PFTs at 3-6 month intervals initially, then annually if stable 3
• Follow-up HRCT based on clinical and PFT changes 3
• Progressive pulmonary fibrosis is defined by at least two of: worsening respiratory symptoms, physiological progression on PFTs, and radiological progression on chest CT 3
• Ambulatory desaturation testing every 3-12 months 2

Prognostic Factors

• Reduced baseline FVC together with higher age are significant predictors for progression 9
• Acute exacerbations and respiratory hospitalizations are associated with significantly shorter survival (median 7.3 vs 19.6 years) 9
• Higher GAP indices predict shorter survival time 9
• Baseline dyspnea is associated with increased mortality in ILD patients 2

Advanced Disease Management

• Lung transplantation should be considered for refractory progressive disease 7
• For patients with progressive disease and contraindications to transplantation, palliative care measures should be implemented 7

Common Pitfalls

• Do not rely on symptom assessment alone; 90% of patients with RA-ILD confirmed on HRCT did not have dyspnea or cough 4
• Do not assume normal chest X-ray excludes ILD; up to 10% of ILD patients have normal radiographs 2
• Do not attribute cough and dyspnea solely to ILD without excluding cardiac disease, asthma, and postnasal drainage 2
• Do not delay HRCT when fine crackles are detected on examination 4
• Fever is rare in ILD and suggests alternative diagnosis or infection 2