What is the protocol for work-up and management of a patient with suspected Interstitial Lung Disease (ILD)?

Protocol for Work-up and Management of Suspected Interstitial Lung Disease (ILD)

A multidisciplinary approach is the method of choice for ILD diagnosis and severity evaluation, integrating high-resolution computed tomography (HRCT), pulmonary function tests (PFTs), and symptom evaluation with pulmonary, rheumatology, and radiology expertise. 1

Initial Diagnostic Evaluation

Clinical Assessment

• Evaluate for respiratory symptoms such as dyspnea on exertion and non-productive cough, though these may be absent in up to 90% of early ILD cases 1
• Assess for finger clubbing, weight loss, and auscultate for fine crackles (Velcro-crackles), which have moderate sensitivity for early ILD detection 1
• Document detailed environmental and occupational exposure history to identify potential causes of hypersensitivity pneumonitis 1
• Evaluate for signs and symptoms of connective tissue diseases (CTDs) as they commonly associate with ILD 1

Laboratory Testing

• Complete blood count with differential, C-reactive protein, serum creatinine, transaminases, gamma-glutamyltransferase, and alkaline phosphatases 1
• Autoimmune serologies including:
  • Anti-nuclear antibodies, anti-citrullinated cyclic peptide antibodies, and rheumatoid factor 1
  • If clinical suspicion or positive ANA: anti-SSA/SSB (Sjögren's), anti-centromere/anti-topoisomerase-1 (systemic sclerosis), anti-synthetase antibodies, anti-thyroid antibodies 1
  • Consider creatine phosphokinase and serum protein electrophoresis 1
  • Anti-neutrophil cytoplasmic antibodies if vasculitis is suspected 1
  • Precipitin testing if hypersensitivity pneumonitis is suspected 1

Imaging Studies

• Chest radiography as initial screening, though it has limited sensitivity for early ILD 1
• HRCT is the gold standard for ILD diagnosis and should be performed in all patients with suspected ILD 1
• HRCT patterns help identify specific ILD types:
  • Usual interstitial pneumonia (UIP): reticulation, bronchiectasis, honeycombing (common in RA-ILD) 1
  • Non-specific interstitial pneumonia (NSIP): ground glass opacities with/without reticulations (common in other CTDs) 1

Pulmonary Function Tests

• Spirometry to identify restrictive pattern (decreased FVC) 1
• Total lung capacity (TLC) to confirm restriction 1
• Diffusion capacity (DLCO) to assess gas exchange impairment 1
• 6-minute walk test to evaluate exercise capacity and oxygen desaturation 1

Tissue Diagnosis

When to Consider Lung Biopsy

• When HRCT and clinical findings are insufficient for definitive diagnosis 1
• When histopathological data is needed to guide treatment decisions 1

Biopsy Options

• Transbronchial lung cryobiopsy (TBLC) is suggested as first-line biopsy method for patients who need histopathological confirmation 1
  • TBLC provides larger samples without crush artifacts compared to traditional transbronchial lung biopsy 1
  • TBLC has lower complication rates than surgical lung biopsy (SLB) 1
• Surgical lung biopsy (SLB) should be considered:
  • As an add-on test when TBLC is non-informative 1
  • When more definitive histopathological assessment is required 1
  • Note: SLB carries higher morbidity and mortality risk (approximately 2% in-hospital mortality for elective procedures) 1
• Bronchoalveolar lavage (BAL) for cellular analysis can provide diagnostic clues:
  • Lymphocyte count >25%: suggests granulomatous disease, cellular NSIP, drug reaction, or other specific conditions 1
  • Lymphocyte count >50%: suggests hypersensitivity pneumonitis 1
  • Neutrophil count >50%: supports acute lung injury or infection 1
  • Eosinophil count >25%: diagnostic of eosinophilic pneumonia 1

Multidisciplinary Discussion (MDD)

• MDD involving pulmonologists, radiologists, and pathologists is mandatory for optimal diagnostic yield 1
• MDD should integrate clinical, radiological, and pathological findings to establish a final diagnosis 1
• For complex cases, consider referral to specialized ILD centers with established MDT networks 1

Management of ILD

General Approach

• Treatment strategy depends on the specific ILD diagnosis and underlying cause 2, 3
• Address comorbidities and symptoms (dyspnea, cough, sleep disorders) 3
• Consider oxygen therapy for patients who desaturate below 88% on 6-minute walk test 4
• Structured exercise therapy to improve symptoms and functional capacity 4

Management of CTD-ILD

• For most CTD-ILD patients (except SSc-ILD), consider:
  • Mycophenolate, azathioprine, rituximab, or cyclophosphamide as first-line treatment options 1
  • Avoid glucocorticoids as first-line treatment in SSc-ILD (strong recommendation against) 1
• For SSc-ILD and mixed connective tissue disease-ILD:
  • Tocilizumab is conditionally recommended as first-line option 1
  • Nintedanib is conditionally recommended for SSc-ILD 1
• For idiopathic inflammatory myopathy-ILD:
  • JAK inhibitors and calcineurin inhibitors are conditionally recommended 1

Management of Progressive Pulmonary Fibrosis

• Monitor for disease progression using:
  • Symptom assessment 1, 2
  • Serial PFTs (a 5% decline in FVC over 12 months indicates worse prognosis) 4
  • Follow-up HRCT 2
• For progressive disease despite first-line treatment:
  • Consider adding nintedanib (conditionally recommended for most SARD-ILD) 1
  • Consider pirfenidone for RA-ILD progression 1
  • For SSc-ILD progression, consider referral for stem cell or lung transplantation 1

Follow-up and Monitoring

• Regular clinical assessment for symptoms progression 1
• Serial PFTs (spirometry and DLCO) at 3-6 month intervals initially, then annually if stable 1
• Follow-up HRCT based on clinical and PFT changes 1
• Progressive pulmonary fibrosis is defined by at least two of:
  1. Worsening respiratory symptoms
  2. Physiological evidence of progression on PFTs
  3. Radiological evidence of progression on chest CT 1

Common Pitfalls to Avoid

• Delaying diagnosis due to subtle or absent symptoms in early disease 1
• Failing to consider CTD in patients with ILD (perform thorough autoimmune evaluation) 1
• Overreliance on chest radiography, which has limited sensitivity for early ILD 1
• Initiating treatment without multidisciplinary discussion 1
• Using glucocorticoids as first-line treatment in SSc-ILD (strongly recommended against) 1