What is the differential diagnosis for an elderly male with a history of sandblasting and creosote exposure, presenting with acute hypoxemia, shortness of breath (SOB), and expiratory wheeze associated with environmental fog, and having a soft tissue mass in the upper mediastinum and supraclavicular nodes, with elevated C-reactive protein (CRP) and airway thickening?

Differential Diagnosis for Elderly Male with Occupational Dust Exposure and Recurrent Fog-Associated Wheezing

The most likely diagnosis is occupational asthma (OA) with underlying mixed-dust pneumoconiosis from sandblasting (silica) and creosote exposure, complicated by reactive lymphadenopathy from chronic inflammatory lung disease. 1, 2

Primary Diagnostic Considerations

1. Occupational Asthma (Most Likely)

• The recurrent fog-associated wheezing episodes that resolve spontaneously or with medication strongly suggest OA, which is now the most common chronic occupational lung disease and accounts for approximately 10% of all adult-onset asthma cases. 1
• Sandblasting creates respirable silica particles that cause both sensitizer-induced and irritant-induced airway disease. 1
• The pattern of symptoms improving away from environmental triggers (fog as an irritant) and recurring with exposure is characteristic of OA. 1
• Expiratory wheeze with airway thickening but no endobronchial lesions supports reversible airway obstruction rather than fixed structural disease. 1
• The elevated CRP (17.7) without leukocytosis indicates chronic inflammatory airway disease rather than acute infection. 1

2. Mixed-Dust Pneumoconiosis (Underlying Chronic Process)

• Sandblasting exposure creates mixed dust exposures to silica, while creosote work involves polycyclic aromatic hydrocarbons and other chemical irritants—this combination produces heterogeneous pulmonary structural changes. 3, 4
• The airway thickening on imaging reflects chronic inflammatory and fibrotic changes from cumulative dust exposure. 1, 5
• Mixed-dust pneumoconiosis is frequently misdiagnosed as idiopathic pulmonary fibrosis when detailed occupational history is not obtained. 3
• These exposures require 15+ years latency before clinical manifestation, consistent with this patient's longstanding symptoms. 2

3. Reactive Mediastinal and Supraclavicular Lymphadenopathy

• The 2.5 cm mediastinal mass and 1.2 cm supraclavicular nodes with preserved fatty hila are most consistent with reactive lymphadenopathy from chronic pneumoconiosis rather than malignancy. 1, 5
• Silicosis and mixed-dust pneumoconiosis commonly cause hilar and mediastinal lymph node enlargement as part of the inflammatory response. 1, 6
• The preserved fatty hila strongly argue against malignancy. 1

Critical Differential Diagnoses to Exclude

4. Silicosis with Mycobacterial Infection Risk

• Sandblasting is a classic high-risk occupation for silicosis, which increases tuberculosis risk 2.8 to 39-fold depending on severity. 6
• The mediastinal lymphadenopathy and elevated CRP warrant exclusion of mycobacterial infection (TB or atypical mycobacteria). 6
• Obtain sputum cultures for acid-fast bacilli and fungal organisms, as silica-exposed workers have increased risk for both mycobacterial and fungal infections. 6

5. Asbestosis (Less Likely but Consider)

• While sandblasting is the primary exposure, construction workers often have concurrent asbestos exposure from working near insulation, cement, or other asbestos-containing materials. 2
• However, asbestosis typically shows irregular opacities in lower lung fields with pleural plaques, not the airway thickening described here. 1, 2
• The absence of pleural plaques makes pure asbestosis less likely. 1, 2

6. Hypersensitivity Pneumonitis (Consider)

• Chronic hypersensitivity pneumonitis can present with NSIP pattern and small airway abnormalities. 7
• However, the occupational exposures to inorganic dusts (silica, creosote) rather than organic antigens make this less likely. 7

7. Lung Malignancy (Must Exclude)

• Silica exposure increases lung cancer risk, and creosote contains carcinogenic polycyclic aromatic hydrocarbons. 2, 8
• The mediastinal mass requires tissue diagnosis to definitively exclude malignancy despite benign imaging features. 1
• Smoking history (if present) would further increase malignancy risk. 1

Diagnostic Algorithm

Step 1: Confirm Asthma and Work-Relationship

• Perform spirometry with bronchodilator testing within 24 hours of symptoms to document reversible airflow obstruction. 1
• If spirometry is normal, perform methacholine or histamine challenge testing to identify airway hyperresponsiveness. 1
• Obtain serial peak expiratory flow measurements (4 times daily in triplicate) for 2-4 weeks, recording at work and away from work. 1

Step 2: Detailed Occupational History

• Document specific sandblasting duration, intensity, and protective equipment use—even several months of heavy exposure in confined spaces can cause disease. 2
• Identify all creosote exposure details including duration and concurrent chemical exposures. 1, 2
• Assess for "bystander" exposures to asbestos or other dusts from coworkers. 2
• Focus on exposures from 15+ years ago, not recent work, as pneumoconiosis requires prolonged latency. 2

Step 3: Exclude Infection

• Obtain sputum for acid-fast bacilli smear and culture (3 samples). 6
• Obtain sputum for fungal culture. 6
• Consider tuberculin skin test or interferon-gamma release assay. 6

Step 4: Tissue Diagnosis of Mediastinal Mass

• Perform endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of mediastinal and supraclavicular nodes to exclude malignancy and identify granulomatous disease. 1, 5
• If EBUS-TBNA is non-diagnostic, consider transbronchial lung cryobiopsy to assess for pneumoconiosis pattern. 7, 5

Step 5: Advanced Imaging

• High-resolution CT chest to characterize interstitial changes, nodular opacities, and distribution pattern. 1, 5, 4
• Look for upper lobe predominance (suggests silicosis), lower lobe irregular opacities (suggests asbestosis), or mixed patterns. 1, 3

Step 6: Laboratory Evaluation

• Complete blood count with differential (already done—no leukocytosis). 1
• Autoimmune serologies (ANA, RF, anti-CCP) to exclude connective tissue disease-associated ILD. 7
• Serum ACE and calcium to exclude sarcoidosis. 1

Common Pitfalls to Avoid

• Don't dismiss short intense exposures—several months to 1 year of heavy sandblasting in confined spaces can cause pneumoconiosis. 2
• Don't overlook bystander exposure—workers not directly handling dusts but working nearby can develop disease. 2
• Don't rely on job title alone—"construction worker" or "industrial worker" requires detailed exposure assessment. 2
• Don't assume the mediastinal mass is benign without tissue diagnosis—silica exposure increases lung cancer risk. 2, 8
• Don't forget to test for mycobacterial infection—silicosis increases TB risk up to 39-fold. 6
• Don't perform pulmonary function testing more than 24 hours after workplace exposure—airway hyperresponsiveness may normalize with longer periods away from exposure. 1
• Don't diagnose idiopathic pulmonary fibrosis without excluding mixed-dust pneumoconiosis through detailed occupational history. 3

Management Implications

• Remove patient from further dust exposure immediately—continued exposure accelerates disease progression. 1, 8
• Treat OA with inhaled bronchodilators and corticosteroids as needed for symptom control. 1, 9
• Monitor for progressive massive fibrosis and declining lung function with serial spirometry. 1, 6
• Screen for lung cancer with annual low-dose CT given high-risk occupational exposures. 2, 8
• Consider disability evaluation and workers' compensation claim. 6