What is the appropriate management for an adult patient with worsening interstitial markings and ground-glass opacities on CT (computed tomography) chest scan, with no specified underlying medical history?

Management of Worsening Interstitial Markings and Ground-Glass Opacities on CT Chest

Refer the patient to a pulmonology department experienced in interstitial lung diseases (ILDs) or an expert center for multidisciplinary evaluation, as the diagnosis requires integration of clinical assessment, CT features, pulmonary function tests, and potentially pathological findings to guide appropriate treatment and assess prognosis. 1

Immediate Diagnostic Priorities

Clinical Context Assessment

• Determine symptom duration to categorize as acute (<4 weeks), persistent (4-8 weeks), or chronic (>8 weeks), as this fundamentally alters the differential diagnosis 2, 3
• Obtain detailed exposure history including:
  • Occupational exposures (asbestos, hard metals containing tungsten/cobalt, organic antigens) 4, 5, 6
  • Medication history, particularly molecular targeting agents (EGFR-TKIs, mTOR inhibitors), immune checkpoint inhibitors, and other pneumotoxic drugs 5
  • Smoking history (current or former smokers suggest DIP or RBILD) 5
• Screen for systemic disease with autoantibody panels (ANA >1:160, rheumatoid factor) to identify connective tissue disease-related ILD 5
• Exclude COVID-19 with RT-PCR testing, especially if symptoms are acute and bilateral peripheral ground-glass opacities are present 1, 2

Critical CT Pattern Analysis

Distribution pattern is the most important radiographic feature for narrowing the differential diagnosis 5, 2:

• Peripheral and basal predominance suggests idiopathic pulmonary fibrosis (IPF), asbestosis, or connective tissue disease-related ILD 4, 5
• Upper and mid-lung predominance indicates hypersensitivity pneumonitis or sarcoidosis 5
• Diffuse bilateral symmetric pattern suggests nonspecific interstitial pneumonia (NSIP) or drug-related pneumonitis 5

Associated findings that refine diagnosis 1, 5, 2:

• Honeycombing with traction bronchiectasis: strongly suggests IPF (usual interstitial pneumonia pattern) 1, 5
• Ground-glass opacity >30% without honeycombing: consider NSIP, desquamative interstitial pneumonitis, or hypersensitivity pneumonitis rather than IPF 5, 2
• Pleural plaques: pathognomonic for asbestos exposure 4, 5
• Centrilobular nodules: characteristic of hypersensitivity pneumonitis or RBILD 5
• "Crazy paving" pattern (ground-glass with superimposed septal thickening): suggests COVID-19, Pneumocystis jirovecii, or organizing pneumonia 2, 7

Prognostic Assessment for Suspected IPF

If the pattern suggests IPF, assess prognosis immediately using 1:

• Severity of dyspnea
• Pulmonary function tests (FVC and DLCO)
• Oxygen saturation at end of 6-minute walk test
• Extent of honeycombing on HRCT
• Signs of pulmonary hypertension on echocardiography
• GAP score (gender, age, physiology) for 1-, 2-, and 3-year survival estimates 1

Worsening disease indicators requiring urgent intervention include 1:

• ≥5% absolute or 10% relative decrease in FVC over 6 months
• ≥15% decrease in DLCO over 6 months

• 50 m decrease in 6-minute walk distance

• Progressive fibrosis on HRCT

Diagnostic Algorithm Based on Symptom Duration

Acute Presentation (<4 weeks)

• Prioritize infectious etiologies: obtain RT-PCR for COVID-19 and other respiratory viruses 1, 2
• In immunocompromised patients: consider Pneumocystis jirovecii pneumonia, especially with diffuse bilateral ground-glass and peripheral preservation 2
• Supportive care while awaiting microbiologic results 7

Persistent Ground-Glass (4-8 weeks)

• Perform high-resolution CT with thin slices to better characterize the pattern 2
• Consider bronchoscopy with bronchoalveolar lavage for microbiology and cytology if ground-glass persists without diagnosis 2
• Re-evaluate medication history for temporal relationship between drug exposure and symptom onset 5

Chronic Presentation (>8 weeks)

• Detailed environmental/occupational exposure history for hypersensitivity pneumonitis 5, 2
• Autoantibody evaluation for connective tissue diseases 5, 2
• Surgical lung biopsy when CT pattern and clinical history do not allow definitive diagnosis 1, 2

Multidisciplinary Discussion Requirements

Complex cases require multidisciplinary discussion involving 1:

• Pulmonologist experienced in ILDs
• Radiologist experienced in thoracic imaging
• Pathologist experienced in interstitial pneumonias (if biopsy obtained)
• Clinical context integration

This discussion should ideally occur at a reference center or competence center for rare lung diseases 1.

Critical Pitfalls to Avoid

• Do not assume normal chest X-ray excludes significant disease: plain radiographs have limited sensitivity, with 15-20% of histopathologically confirmed cases showing no radiographic evidence 4
• Do not initiate triple therapy (prednisone, azathioprine, N-acetylcysteine) in patients with definite IPF diagnosis 1
• Do not delay referral: early specialist evaluation improves diagnostic accuracy and allows timely prognostic assessment 1
• Do not overlook drug-induced pneumonitis: improvement with drug cessation supports this diagnosis 5
• Ground-glass without traction bronchiectasis may be reversible, but traction bronchiectasis with ground-glass always indicates fibrosis 5