What is the approach to diagnosing and managing interstitial lung disease?

Approach to Diagnosing and Managing Interstitial Lung Disease

The diagnosis of ILD requires a multidisciplinary discussion (MDD) integrating high-resolution CT (HRCT), pulmonary function tests, and clinical assessment, with HRCT serving as the gold standard imaging modality and transbronchial cryobiopsy as the preferred biopsy method when histopathology is needed. 1, 2

Initial Diagnostic Evaluation

Clinical Assessment

• Evaluate for dyspnea on exertion and non-productive cough, though recognize that up to 90% of early ILD cases may be asymptomatic 2, 3
• Auscultate for fine inspiratory "Velcro" crackles, which are present in >80% of IPF patients and have moderate sensitivity for early ILD detection 2, 3
• Examine for digital clubbing (present in 25-50% of IPF cases), cyanosis in advanced disease, and signs of right heart failure including peripheral edema and right ventricular heave 2
• Document comprehensive environmental and occupational exposure history to identify potential hypersensitivity pneumonitis triggers including mold, water damage, and poor ventilation 2, 4
• Screen systematically for connective tissue disease (CTD) features, as CTD accounts for 25% of ILD cases and includes rheumatoid arthritis, systemic sclerosis, inflammatory myositis, and Sjögren syndrome 2, 3

Laboratory Testing

• Order complete blood count, C-reactive protein, serum creatinine, and liver function tests as baseline assessment 2
• Test autoimmune serologies including anti-nuclear antibodies, anti-citrullinated cyclic peptide antibodies, and rheumatoid factor to identify underlying CTD 2
• Consider disease-specific biomarkers such as anti-topoisomerase (Scl-70) which predict disease activity and guide additional testing 3

Imaging

• Obtain HRCT as the gold standard for ILD diagnosis with 95.7% sensitivity and 63.8% specificity for detecting ILD with ≥20% lung involvement 2, 3
• Include inspiratory prone images and supine end-expiratory imaging in the HRCT protocol 2
• Identify specific radiological patterns: usual interstitial pneumonia (UIP) shows reticulation, bronchiectasis, and honeycombing (common in RA-ILD); non-specific interstitial pneumonia (NSIP) shows ground glass opacities with or without reticulations (common in most other CTD-ILDs) 1, 2
• Recognize that chest radiography alone is insufficient, as up to 10% of ILD patients have normal chest X-rays 2

Pulmonary Function Testing

• Perform spirometry to identify restrictive pattern with decreased FVC, though baseline FVC <80% has only 47.5% sensitivity for detecting ILD 2
• Measure total lung capacity (TLC) to confirm restriction 2
• Test diffusion capacity (DLCO) to assess gas exchange impairment, which is typically reduced in ILD 2, 3
• Conduct 6-minute walk test with pulse oximetry to evaluate exercise capacity and detect oxygen desaturation indicating gas exchange impairment 2, 3

Tissue Diagnosis When Needed

Indications for Biopsy

• Pursue lung biopsy when HRCT and clinical findings are insufficient for definitive diagnosis 2
• Recognize that many typical cases can be diagnosed without biopsy through classical HRCT patterns, environmental antigen identification, or positive serological testing 1

Biopsy Method Selection

• Use transbronchial lung cryobiopsy (TBLC) as first-line biopsy method when histopathological confirmation is needed 2
• TBLC provides larger samples without crush artifacts compared to traditional transbronchial forceps biopsy and has lower complication rates than video-assisted thoracoscopic surgery (VATS) 2
• Be aware that TBLC yields less tissue than VATS, resulting in higher unclassifiable rates (17.2% vs 1.3%), but offers decreased morbidity 1
• Reserve VATS biopsy for cases where TBLC is inadequate or contraindicated, recognizing that VATS has 2.1% 30-day mortality versus 4.3% for open lung biopsy 5
• Perform bronchoalveolar lavage (BAL) for cellular analysis, as lymphocyte count >25% suggests granulomatous disease or cellular NSIP 2

Optimizing Biopsy Yield

• Use preoperative radiological data to target biopsy sites and increase likelihood of obtaining informative tissue 1
• Ensure proper histological processing techniques to maximize evaluable tissue 1

Multidisciplinary Discussion Framework

MDD Structure

• Conduct mandatory multidisciplinary discussion involving pulmonologists, radiologists, and pathologists to integrate clinical, radiological, and pathological findings 1, 2, 3
• Classify diagnostic certainty into four tiers: confident diagnosis (>90% certainty), provisional diagnosis with high confidence (70-90%), provisional diagnosis with low confidence (50-70%), and unclassifiable ILD (<50% certainty) 1

Common Pitfall

• Avoid premature classification as "unclassifiable ILD" without proper multidisciplinary evaluation, as approximately half of pathologically unclassifiable cases can be categorized after MDD incorporating clinical and radiological data 1

Screening in High-Risk Populations

Smokers Undergoing Lung Cancer Screening

• Systematically assess and document presence or absence of interstitial lung abnormalities (ILAs)/ILD in all smokers undergoing chest CT for lung cancer screening 1
• Recognize that 8% of screened smokers have ILAs/ILD, and these individuals have 66% increased risk of death and 60% increased risk of dyspnea on exertion 1, 2

Connective Tissue Disease Patients

• Obtain baseline chest HRCT to screen for ILAs/ILD in adults with CTDs associated with increased ILD risk, including systemic sclerosis, rheumatoid arthritis, inflammatory myositis, mixed CTD, and Sjögren syndrome 1
• For rheumatoid arthritis patients, use validated risk scores incorporating age at RA onset, DAS28-ESR disease activity scores, and sex to identify high-risk individuals requiring screening 1

First-Degree Relatives of IPF Patients

• Consider screening first-degree relatives of patients with familial pulmonary fibrosis or idiopathic pulmonary fibrosis, as 24-26% have ILAs/ILD on chest CT 1, 2

Management Approach

CTD-Associated ILD Treatment

• For most CTD-ILD patients (except SSc-ILD), use mycophenolate mofetil, azathioprine, rituximab, or cyclophosphamide as first-line immunosuppressive therapy 2, 3
• Initiate mycophenolate mofetil at 500-1000mg twice daily, titrating to 1500mg twice daily as tolerated for moderate-severe or symptomatic disease 4
• For SSc-ILD specifically, consider tocilizumab as first-line option and avoid glucocorticoids as first-line monotherapy 2
• Add nintedanib for SSc-ILD as conditionally recommended antifibrotic therapy 2
• For idiopathic inflammatory myopathy-ILD, consider JAK inhibitors and calcineurin inhibitors 2

Progressive Pulmonary Fibrosis

• Add antifibrotic therapy (nintedanib or pirfenidone) for patients with progressive pulmonary fibrosis, defined by at least two of: worsening respiratory symptoms, physiological progression on PFTs, and radiological progression on chest CT 2, 3, 4
• Recognize that antifibrotic therapy slows annual FVC decline by 44-57% in progressive disease 3
• For idiopathic pulmonary fibrosis, pirfenidone 2,403 mg/day reduces FVC decline (mean treatment difference 193 mL at Week 52) compared to placebo 6

Hypersensitivity Pneumonitis Management

• Implement immediate environmental remediation combined with immunosuppressive therapy if chronic hypersensitivity pneumonitis is suspected based on CT scarring/fibrosis and elevated IgG antibodies to fungal species 4
• Do not delay treatment while pursuing complete diagnostic workup, as early immunosuppression prevents irreversible fibrosis 4
• Avoid high-dose corticosteroids as monotherapy long-term, as this increases mortality without addressing underlying pathophysiology 4

Supportive Care

• Provide structured exercise therapy, oxygen therapy as needed, and consider inhaled treprostinil to improve symptoms and quality of life 3

Follow-Up and Monitoring Strategy

Initial Intensive Monitoring

• Perform pulmonary function tests (spirometry and DLCO) every 3 months for the first year after diagnosis or treatment initiation 2, 4
• Obtain repeat HRCT at 6-12 months to assess treatment response and identify progression 4
• Conduct 6-minute walk test with pulse oximetry and monitor for worsening dyspnea, cough, and signs of cor pulmonale every 3-12 months 1, 4

Long-Term Monitoring

• Continue PFTs every 6 months if stable, then annually once disease stability is established 2
• Obtain follow-up HRCT based on clinical and PFT changes rather than routine scheduled intervals 2
• Recognize that 5% FVC decline over 12 months is associated with approximately 2-fold increased mortality 3

Prognostic Indicators

• Monitor for radiologic progression, as >50% of patients with ILAs experience progression over 5 years with associated clinical worsening 1
• Approximately 10% of patients with ILAs progress to clinically significant ILD annually 1, 2
• Progressive ILAs are associated with accelerated FVC decline (64 mL/year vs 35 mL/year in those without ILAs) 1

Critical Pitfalls to Avoid

• Do not dismiss bilateral lower lobe interstitial changes as clinically insignificant even in asymptomatic patients, as ILAs are associated with increased mortality and progression risk regardless of symptoms 2
• Do not attribute cough and dyspnea solely to ILD without excluding cardiac disease, asthma, and postnasal drainage 2
• Do not rely on symptom assessment alone for ILD detection, as 90% of HRCT-confirmed ILD patients may not report dyspnea or cough 3
• Do not use chest radiography as the sole imaging modality, as it misses up to 10% of ILD cases 2