What is the next step in managing a patient with a 3-month history of chronic cough, pulmonary function tests (PFTs) showing hyperinflation with reduced diffusing capacity of the lungs for carbon monoxide (DLCO) at 70% of normal, normal 6-minute walk (6MW) test, and elevated immunoglobulin G (IgG) antibodies to Cladosporium and Phoma species, with normal lab tests except for elevated IgG and reactive IgE (Immunoglobulin E) levels?

Hypersensitivity Pneumonitis Evaluation with High-Resolution CT Chest

The next step is to obtain a high-resolution CT (HRCT) chest to evaluate for hypersensitivity pneumonitis (HP), given the elevated IgG antibodies to Cladosporium and Phoma species combined with reduced DLCO and hyperinflation on PFT. 1

Clinical Reasoning for Hypersensitivity Pneumonitis

The clinical presentation strongly suggests HP based on several key features:

• Chronic cough for 3 months is a common presenting symptom of HP, along with dyspnea 1
• Elevated specific IgG antibodies to fungal antigens (Cladosporium and Phoma species) support the diagnosis, as demonstration of specific serum IgG antibodies to the suspected agent further supports HP diagnosis 1
• Reduced DLCO (70%) is characteristic of HP, as pulmonary function tests show reduced diffusing capacity especially on exercise 1
• Hyperinflation pattern can occur in chronic HP with bronchiolitis, where chronic airflow limitation may predominate 1

Why HRCT is the Critical Next Step

HRCT chest is essential for distinguishing chronic HP from other interstitial lung diseases and should be performed before proceeding with invasive testing: 1

• Ground-glass appearance on HRCT is helpful in distinguishing chronic HP from idiopathic pulmonary fibrosis 1
• CT is indicated when clinical suspicion of underlying pulmonary disease exists, particularly with abnormal PFTs and positive fungal antibodies 1
• The ACR Appropriateness Criteria recommend chest CT for chronic cough when interstitial lung disease is suspected, especially with reduced DLCO 1

Environmental and Exposure History

While obtaining imaging, conduct a detailed exposure assessment:

• Indoor fungal contamination including contaminated humidifiers, vaporizers, hot tubs, and swimming pool areas 1
• Home environment for water damage, visible mold, or areas generating fungal bioaerosol exposures 1
• Occupational exposures to organic dusts or contaminated environments 1
• Temporal relationship between symptoms and specific environments—suspicion increases if respiratory findings are intermittent in relation to exposures and clear up after a few days away 1

Differential Diagnosis Considerations

The elevated fungal IgG antibodies raise two primary considerations:

Hypersensitivity Pneumonitis (Most Likely)

• Multiple fungal species (Cladosporium and Phoma) can cause HP through hypersensitivity response to inhaled environmental high-molecular-weight antigens 1
• The combination of reduced DLCO, hyperinflation, and positive fungal antibodies fits the HP pattern 1

Allergic Bronchopulmonary Mycosis (Less Likely)

• While Cladosporium can cause allergic bronchopulmonary fungosis 2, this typically presents with:
  • Asthma as the underlying condition 3, 4
  • Central bronchiectasis on imaging 5, 2
  • Markedly elevated total IgE (often >1000 IU/mL) 3, 4
  • Blood eosinophilia 5, 2
• The absence of these features makes ABPM less likely in this case

Subsequent Diagnostic Steps After HRCT

If HRCT shows findings consistent with HP:

• Bronchoalveolar lavage (BAL) may be considered, as BAL findings of predominant lymphocytosis support HP diagnosis 1
• Lung biopsy may be needed if diagnosis remains uncertain, as findings of giant cell granulomas raise suspicion of HP 1
• Specific inhalation challenge may occasionally be needed for medico-legal purposes to confirm diagnosis, especially if radiographic findings are nonspecific 1

Critical Management Principle

Early identification and removal from further exposure are key components of treatment for HP, making environmental assessment and HRCT imaging urgent priorities. 1

Common Pitfalls to Avoid

• Do not delay imaging while pursuing empiric treatment for common causes of chronic cough, as the reduced DLCO and positive fungal antibodies indicate likely parenchymal lung disease 1
• Do not assume normal 6-minute walk test excludes significant disease, as DLCO impairment may be more apparent on exercise testing 1
• Do not interpret positive fungal IgG antibodies as definitive diagnosis without imaging correlation, as standardization of antigen extracts can be difficult 1