What is the best course of treatment for a patient with Interstitial Lung Disease (ILD) and fungal sensitization with normal Pulmonary Function Test (PFT) results?

Management of ILD with Fungal Sensitization and Normal PFTs

For a patient with ILD and fungal sensitization but normal PFTs, continue regular monitoring with PFTs every 3-12 months and HRCT when clinically indicated, while treating any symptomatic cough or dyspnea according to standard protocols, but defer immunosuppressive or antifibrotic therapy until evidence of disease progression emerges. 1

Monitoring Strategy

The presence of normal PFTs indicates mild or early-stage disease that warrants surveillance rather than immediate pharmacologic intervention. 1

Pulmonary Function Testing Schedule

• Perform complete PFTs (spirometry, lung volumes, and DLCO) every 3-12 months for the first year, then less frequently once stability is confirmed 1
• The specific interval depends on the underlying systemic autoimmune rheumatic disease (SARD): every 3-6 months for idiopathic inflammatory myopathy-ILD (IIM-ILD) and systemic sclerosis-ILD (SSc-ILD), versus every 3-12 months for rheumatoid arthritis-ILD (RA-ILD), Sjögren disease-ILD (SjD-ILD), and mixed connective tissue disease-ILD (MCTD-ILD) 1

Imaging Surveillance

• HRCT chest should be performed when clinically indicated rather than on a routine schedule 1
• Clinical indicators for repeat HRCT include: new or worsening respiratory symptoms, decline in PFT parameters, or increased oxygen requirements 1, 2
• HRCT has 95.7% sensitivity for detecting ILD with ≥20% lung involvement, making it superior to PFTs alone for early disease detection 1, 2

Additional Monitoring

• Assess for ambulatory desaturation every 3-12 months 1
• Evaluate respiratory symptoms (dyspnea on exertion, cough) at each clinical visit 1, 2
• Do not routinely use chest radiography, 6-minute walk distance, or bronchoscopy for monitoring 1

Addressing Fungal Sensitization

The fungal sensitization component requires careful consideration but does not automatically mandate antifungal therapy in the absence of active infection. 3

Evaluation for Active Infection

• Review for clinical signs of fungal infection: fever, productive cough, hemoptysis, or constitutional symptoms 3, 4
• Consider bronchoscopy with bronchoalveolar lavage (BAL) only if there is clinical suspicion for active infection, particularly in patients on immunosuppression 1
• Fungal cultures and galactomannan testing may be warranted if infection is suspected 3, 4

Management Approach

• Fungal sensitization without active infection does not require antifungal treatment 3
• If concurrent infection is identified, treat according to pathogen-specific protocols while monitoring for ILD progression 3, 4
• Aminoglycosides and carbapenems are preferred for bacterial co-infections when present 4

Symptom Management

Even with normal PFTs, symptomatic patients require systematic evaluation and treatment of cough or dyspnea. 1, 5

Cough Evaluation and Treatment

• First, assess for and treat alternative causes of cough before attributing it to ILD: gastroesophageal reflux disease (GERD), asthma or eosinophilic bronchitis, upper airway cough syndrome, and medication side effects 1, 5
• For IPF patients with chronic cough and negative GERD workup, do not prescribe proton pump inhibitors 1, 5
• For pulmonary sarcoidosis, do not routinely prescribe inhaled corticosteroids for chronic cough, as three trials showed no benefit 1, 5
• For refractory ILD-associated cough, initiate gabapentin or multimodality speech pathology therapy as first-line treatment 1, 5

Dyspnea Management

• Exclude cardiac disease, asthma, and postnasal drainage before attributing dyspnea solely to ILD 2
• Structured exercise therapy reduces symptoms and improves 6-minute walk test distance 6
• Oxygen therapy is indicated only if desaturation below 88% occurs on 6-minute walk test 6

When to Initiate Disease-Modifying Therapy

Defer immunosuppressive or antifibrotic therapy until evidence of disease progression emerges, as normal PFTs indicate insufficient disease severity to warrant treatment risks. 1, 2, 7

Criteria for Disease Progression

Progressive pulmonary fibrosis is defined by at least two of the following over 12 months: 2

• Worsening respiratory symptoms (increased dyspnea, cough, or functional limitation)
• Physiological progression: ≥5% decline in FVC or ≥10% decline in DLCO
• Radiological progression on HRCT: increased extent of fibrosis, new ground-glass opacities, or traction bronchiectasis

Treatment Initiation Thresholds

• FVC <80% predicted or DLCO <70% predicted suggests moderate disease warranting consideration of therapy 1
• FVC <60% predicted or DLCO <40% predicted indicates severe disease requiring treatment 1
• Shortness of breath at rest (NYHA class III-IV) warrants treatment regardless of PFT values 1

Important Caveats

Risk Stratification

• Patients with high-titer anti-CCP or rheumatoid factor (RA-ILD), Scl-70 positivity or early diffuse cutaneous disease (SSc-ILD), or anti-MDA-5/anti-synthetase antibodies (IIM-ILD) are at increased risk for progression and require closer monitoring 1
• These high-risk patients may warrant PFTs every 3-6 months rather than every 3-12 months 1

Pitfalls to Avoid

• Do not attribute all respiratory symptoms to ILD without excluding common comorbidities 2, 5
• Baseline FVC <80% has only 47.5% sensitivity for detecting ILD, so normal PFTs do not exclude early disease 2
• Up to 10% of ILD patients have normal chest radiographs, making HRCT essential for diagnosis 2
• Avoid initiating systemic corticosteroids for stable ILD with normal PFTs, as they increase mortality in IPF and lack evidence in other ILDs without active inflammation 1, 7, 5

Multidisciplinary Approach

• Optimal management requires integration of pulmonology, rheumatology, and radiology expertise through multidisciplinary discussion 2
• This is particularly important when deciding whether radiographic findings represent true ILD progression versus transient changes 2