What is the diagnosis and management approach for a patient with interstitial lung disease (ILD) presenting with interstitial markings on chest X-ray (CXR)?

Interstitial Markings on Chest X-Ray: Diagnosis and Management

When interstitial markings are identified on chest X-ray, you must immediately obtain a high-resolution CT (HRCT) scan, as chest radiography has only 62% sensitivity for detecting interstitial lung disease and up to 10% of ILD patients have normal chest X-rays. 1, 2

Critical First Step: Obtain HRCT Immediately

• Chest X-ray alone is insufficient and should never be relied upon for definitive diagnosis of interstitial lung disease, with sensitivity of only 62% and specificity of 90% compared to HRCT 2
• HRCT has 95.7% sensitivity and 63.8% specificity for detecting ILD with ≥20% lung involvement and is the gold standard for diagnosis 1
• HRCT should include inspiratory prone images and supine end-expiratory imaging 1

Distinguish Between ILA and ILD on HRCT

Once HRCT is obtained, classify findings as either Interstitial Lung Abnormalities (ILA) or Interstitial Lung Disease (ILD) based on the 2025 American Thoracic Society criteria:

ILA Definition (Less Severe)

• Nondependent bilateral parenchymal abnormalities including ground-glass or reticular abnormalities, lung distortion, traction bronchiectasis, and/or honeycombing involving ≤5% of a lung zone 3
• Three subtypes exist: non-subpleural ILA, subpleural nonfibrotic ILA, and fibrotic ILA 3

ILD Definition (More Severe - Requires Treatment)

ILD is diagnosed when any one of the following criteria is met 3:

Imaging criteria:

• Fibrotic abnormalities (honeycombing and/or reticulation with traction bronchiectasis) involving >5% of total lung volume 3
• Progressive fibrotic abnormality on serial chest CT 3
• Presence of major fibrotic ILD pattern (UIP/probable UIP, fibrotic hypersensitivity pneumonitis, or fibrotic NSIP) 3

Clinical criteria (in presence of ILA on imaging):

• Respiratory symptoms (cough or dyspnea) without clear alternative explanation 3
• Abnormal pulmonary function tests: reduced FVC, TLC, or DLCO 3

Mandatory Initial Workup for All Patients

1. Baseline Symptom Assessment

• Inquire specifically about cough and dyspnea on exertion, even if patient appears asymptomatic 3, 1
• Note that 37.1% of ILA patients have dyspnea on exertion versus 18.4% without ILA, but up to 90% of early ILD cases may be asymptomatic 3, 1
• Chronic cough occurs in 30.5% of ILA patients versus 13.9% without ILA 3, 1
• Auscultate for fine, dry "Velcro-type" end-inspiratory crackles, present in >80% of IPF patients 1

2. Baseline Pulmonary Function Tests

• Measure FVC, TLC, and DLCO to establish baseline for future comparison and identify early ILD 3, 1
• DLCO <80% has 83.6% sensitivity and 45.8% specificity for detecting ILD 4
• Baseline FVC <80% has only 47.5% sensitivity, emphasizing need for DLCO measurement 1
• The combination of reduced DLCO, chest X-ray, and HRCT yields 95.2% sensitivity and 77.4% specificity 4

3. Risk Factor Assessment

Screen for connective tissue diseases (25% of ILD cases): 1, 5

• Obtain autoimmune serologies: anti-nuclear antibodies, anti-citrullinated cyclic peptide antibodies, rheumatoid factor 1
• CTDs associated with ILD include rheumatoid arthritis, systemic sclerosis, polymyositis, dermatomyositis, Sjögren's disease 1

Document exposure history:

• Smoking history (8% of smokers undergoing lung cancer screening have ILA/ILD) 3, 1
• Family history of pulmonary fibrosis (24-26% of first-degree relatives have ILA/ILD) 3, 1
• Occupational and environmental exposures including mold and air pollution 1

Management Algorithm Based on Classification

If Diagnosed as ILA (Not Yet ILD)

Monitoring strategy based on progression risk: 6

High-risk features requiring proactive serial monitoring:

• Fibrotic ILA subtype (traction bronchiectasis/honeycombing) 3
• Subpleural distribution 3
• Presence of symptoms (cough, dyspnea) 3
• Reduced DLCO 3
• High-risk exposures (smoking, CTD, family history) 3

Monitoring protocol for high-risk ILA:

• Repeat PFTs at 3-6 month intervals initially, then annually if stable 1
• Follow-up HRCT based on clinical and PFT changes 1
• Approximately 10% of ILA patients progress to ILD annually 3, 1
• Over 50% experience radiologic progression over 5 years with associated clinical worsening 3, 1

If Diagnosed as ILD (Meets Criteria Above)

Treatment depends on underlying etiology:

For Idiopathic Pulmonary Fibrosis (IPF): 7, 5

• Initiate antifibrotic therapy with nintedanib or pirfenidone, which slows annual FVC decline by 44-57% 5
• Pirfenidone 2,403 mg/day reduces mean FVC decline from -428 mL to -235 mL at 52 weeks (mean treatment difference 193 mL) 7

For Connective Tissue Disease-ILD: 1, 5

• First-line options: mycophenolate, azathioprine, rituximab, or cyclophosphamide 1
• Avoid glucocorticoids as first-line treatment in systemic sclerosis-ILD (strong recommendation against) 1
• Tocilizumab is conditionally recommended for SSc-ILD and mixed CTD-ILD 1
• Nintedanib is conditionally recommended for SSc-ILD 1

For Smoking-Related ILD:

• Smoking cessation is the single most effective intervention and must be first-line therapy 8
• Combine pharmacotherapy (nicotine replacement, varenicline, or bupropion) with behavioral support 8

Supportive care for all ILD patients: 1, 5

• Structured exercise therapy reduces symptoms and improves 6-minute walk distance 5
• Supplemental oxygen for patients who desaturate below 88% on 6-minute walk test 5
• Influenza and pneumococcal vaccinations 8
• Consider lung transplant referral for progressive disease (median survival 5.2-6.7 years post-transplant versus <2 years without transplant in advanced ILD) 1, 5

Critical Pitfalls to Avoid

• Never dismiss interstitial markings on chest X-ray as clinically insignificant, even in asymptomatic patients, as ILAs are associated with 66% increased mortality risk 3, 1
• Do not attribute cough and dyspnea solely to ILD without excluding cardiac disease, asthma, and postnasal drainage 1
• Never delay obtaining HRCT when chest X-ray shows interstitial markings, as 10% of ILD patients have normal chest X-rays 1
• Avoid delaying smoking cessation intervention while focusing solely on pharmacologic treatments 8
• Do not fail to establish baseline PFTs, as patients with radiologically progressive ILA experience 64-ml annual FVC decline versus 35-ml in those without progression 3, 1