What is the treatment for lung disease caused by exposure to moldy corn, presenting with tree in bud nodularity?

Treatment of Lung Disease Caused by Moldy Corn Exposure with Tree-in-Bud Nodularity

For patients with lung disease caused by exposure to moldy corn presenting with tree-in-bud nodularity, treatment should focus on a macrolide-based antimicrobial regimen (clarithromycin 1,000 mg/day or azithromycin 250-500 mg/day) combined with ethambutol (15-25 mg/kg/day) and a rifamycin (rifampin 600 mg/day or rifabutin 150-300 mg/day) for at least 12 months. 1

Diagnostic Considerations

Before initiating treatment, confirm the diagnosis through:

• High-resolution CT scan to document the tree-in-bud pattern and evaluate for bronchiectasis
• Sputum cultures for mycobacteria, particularly Mycobacterium avium complex (MAC)
• Bronchoscopy with bronchoalveolar lavage (BAL) for microbiological identification
• Fungal biomarkers such as Aspergillus galactomannan if fungal etiology is suspected
• Transbronchial biopsy to identify granulomatous inflammation if diagnosis remains unclear

The tree-in-bud pattern on CT is characterized by centrilobular nodules and branching linear opacities that resemble a budding tree. This pattern reflects inflammatory changes including bronchiolitis and is commonly associated with MAC infection, particularly in the setting of exposure to environmental sources 1.

Treatment Algorithm

1. For MAC Infection (Most Likely Etiology)

MAC infection is the most probable cause of tree-in-bud nodularity in the setting of moldy corn exposure, particularly if the pattern involves the middle lobe or lingula. Treatment should follow these guidelines:

• First-line therapy: Three-drug regimen consisting of:

  • Macrolide: Clarithromycin 1,000 mg daily or azithromycin 500 mg three times weekly
  • Ethambutol: 25 mg/kg three times weekly
  • Rifampin: 600 mg three times weekly 1

• For severe disease or fibrocavitary presentation:

  • Daily regimen of clarithromycin (500-1,000 mg) or azithromycin (250 mg)
  • Rifampin (600 mg) or rifabutin (150-300 mg)
  • Ethambutol (15 mg/kg)
  • Consider adding amikacin or streptomycin early in therapy 1

• Duration: Continue treatment until sputum cultures are negative for at least 12 months 1

2. For Aspergillus or Other Fungal Infection

If diagnostic workup suggests fungal etiology (particularly Aspergillus species, which commonly contaminate corn):

• For hypersensitivity pneumonitis due to fungal exposure:

  • Remove from exposure source
  • Corticosteroids for acute/subacute presentation (prednisone 0.5-1 mg/kg/day with gradual taper)
  • Environmental remediation to prevent reexposure 2, 3

• For invasive fungal infection:

  • Voriconazole or a lipid formulation of amphotericin B for severe disease
  • For less severe disease, oral azole therapy (voriconazole, itraconazole, or posaconazole) 1

Monitoring Treatment Response

• Clinical assessment every 4-8 weeks during initial therapy
• Sputum cultures monthly until conversion to negative, then every 2-3 months
• Chest imaging (CT scan) at 3-6 month intervals to assess radiographic improvement
• Monitor for medication side effects:
  • Visual acuity and color discrimination tests for ethambutol toxicity
  • Liver function tests for rifampin and macrolide toxicity
  • Audiometry if aminoglycosides are used

Management of Treatment Failure

If clinical or radiographic deterioration occurs despite appropriate therapy:

1. Reassess antimicrobial susceptibility
2. Consider increasing macrolide dosage
3. Add parenteral aminoglycoside (amikacin) for refractory cases
4. Consider surgical resection for localized disease that fails to respond to medical therapy 1

Supportive Measures

• Airway clearance techniques to improve mucus clearance
• Bronchodilators if bronchospasm is present
• Nutritional support
• Pulmonary rehabilitation for patients with significant functional impairment

Prevention

• Avoid further exposure to moldy corn and other potential sources of mycobacteria or fungi
• Use of N95 respirators when exposure to agricultural dusts is unavoidable
• Environmental remediation of water damage and mold in living/working spaces
• Regular monitoring of high-risk individuals with occupational exposure 1

Special Considerations

The tree-in-bud pattern is not pathognomonic for any single disease but is most commonly associated with infectious bronchiolitis. While MAC infection is the most likely diagnosis in this clinical scenario, the differential diagnosis includes other mycobacteria, bacteria, fungi, and non-infectious causes 4, 5. The random small airways pattern with alternating areas of normal lung and regions of small airways disease is highly specific (0.92) for MAC infection 5.

Treatment should be initiated promptly upon diagnosis to prevent progression to irreversible bronchiectasis and lung damage. The regimen may need adjustment based on culture results and clinical response.