How should I diagnose and manage a middle‑aged to elderly patient with progressive dyspnea, dry cough, and reduced exercise tolerance due to pulmonary fibrosis?

Diagnosis and Management of Pulmonary Fibrosis

Diagnostic Approach

Begin with high-resolution computed tomography (HRCT) as the gold standard to confirm interstitial lung disease and characterize the fibrosis pattern, specifically looking for subpleural and basal predominant reticulation, honeycombing, traction bronchiectasis, and absence of ground-glass opacity or centrilobular micronodules. 1, 2

Essential Clinical Features to Identify

• Progressive exertional dyspnea combined with dry cough are the hallmark presenting symptoms 1
• Bibasilar inspiratory crackles (velcro crackles) are constant and appear early in the disease 1
• Finger clubbing is present in less than 50% of cases 1
• The disease primarily occurs between 60-70 years of age, with slight male predominance 1

Exclude Alternative Diagnoses

Before diagnosing idiopathic pulmonary fibrosis (IPF), you must systematically exclude other causes of interstitial lung disease through detailed exposure history and autoimmune screening. 1

• Obtain comprehensive environmental and occupational exposure history to identify hypersensitivity pneumonitis, which accounts for 47% of patients initially thought to have ILD of unknown cause 3
• Screen for connective tissue diseases with antinuclear antibodies, rheumatoid factor, anti-CCP antibodies, myositis panel, and anti-topoisomerase antibodies 2, 3
• Investigate pharmaceutical agents, inhaled organic antigens, mineral particles (silica, asbestos), and cancer as potential causes 1

HRCT Pattern Classification

If HRCT shows a definite UIP pattern (subpleural/basal reticulation with honeycombing), do NOT perform surgical lung biopsy—the diagnosis can be made confidently with clinical and radiographic features alone. 1, 3

• For probable UIP, indeterminate for UIP, or alternative diagnosis patterns on HRCT, consider surgical lung biopsy only if the patient is not at high surgical risk 1
• Avoid biopsy if DLCO is less than 25% after correction for hematocrit, severe hypoxemia at rest is present, or severe pulmonary hypertension exists 1, 3

Multidisciplinary Discussion Requirement

• All cases should undergo multidisciplinary discussion involving pulmonologists, radiologists, and pathologists experienced in ILD to integrate clinical, radiological, and pathological features 1, 3

Initial Functional Assessment

Obtain baseline pulmonary function tests within the first evaluation, specifically measuring forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), which are mandatory for all patients being evaluated for pulmonary fibrosis. 2, 4

• Perform 6-minute walk test with continuous oxygen saturation monitoring, as oxygen saturation ≤88% at end of test predicts worse prognosis and increased mortality risk 2, 4
• Assess dyspnea severity systematically, as progressive worsening indicates disease progression regardless of pulmonary function test results 4

Disease Severity Stratification

Use the GAP (Gender, Age, Physiology) score to provide validated survival estimates at 1,2, and 3 years based on age, sex, FVC, and DLCO. 4

High-Risk Features Requiring Aggressive Management

• UIP pattern on HRCT 2
• FVC less than 70% predicted or greater than 20% disease extent on HRCT 2
• Honeycombing on HRCT, which is associated with increased mortality risk 4
• DLCO ≤35-40% predicted at baseline 4
• Echocardiographic signs of pulmonary hypertension 4

Pharmacological Management

Initiate antifibrotic therapy with either pirfenidone or nintedanib immediately upon diagnosis in patients with mild-to-moderate disease (FVC ≥50% predicted, DLCO ≥30-35% predicted). 2

Pirfenidone Dosing and Evidence

• Administer pirfenidone 2,403 mg/day (801 mg three times daily with food) 5
• In clinical trials, pirfenidone reduced mean decline in FVC by 193 mL compared to placebo at Week 52 5
• For all categorical declines in lung function, the proportion of patients declining was lower on pirfenidone than placebo 5
• Monitor for gastrointestinal adverse effects including nausea, diarrhea, and anorexia, which are the most common side effects 6, 7

Treatments to Avoid

Do NOT initiate triple therapy with prednisone, azathioprine, and N-acetylcysteine in patients with definite IPF. 3

• Do NOT use antacid medication for the purpose of improving respiratory outcomes in IPF, though it may be appropriate for GERD symptoms 3

Monitoring Strategy for Disease Progression

Repeat pulmonary function tests every 3-6 months to detect progression, defined as ≥10% decline in FVC or ≥15% decline in DLCO over 6 months. 2, 4, 3

• FVC decline ≥10% (absolute or relative value) over 6 months indicates disease progression and predicts increased mortality 4
• DLCO decline ≥15% (absolute or relative value) over 6 months signals worsening disease 4
• A decline of ≥50 meters in 6-minute walk test distance over 6 months indicates disease progression 4
• Perform annual HRCT if clinical suspicion of worsening or risk of lung cancer exists 2

Supportive Care Measures

Prescribe long-term oxygen therapy for patients with severe hypoxemia at rest. 2

• Initiate pulmonary rehabilitation program for patients with significant exercise limitation, including exercise training, psychosocial support, and education 2
• Address smoking cessation immediately, as smoking is a major risk factor for disease progression 2

Lung Transplantation Considerations

Provide information about lung transplantation early in the disease course, as transplantation improves survival in advanced disease. 2

• Refer patients at increased risk of mortality at diagnosis to transplant centers 2
• Consider referral when FVC declines below 50-60% predicted or DLCO falls below 30-40% predicted 2

Special Considerations for Elderly Patients

• IPF predominantly affects elderly patients with median age at diagnosis of 66 years, and incidence increases with age 6
• Exercise caution with antifibrotic medications in elderly patients due to polypharmacy concerns and potential drug-drug interactions 7
• Balance the benefits of therapy against potential toxicities, particularly gastrointestinal symptoms that may lead to anorexia and weight loss in frail elderly patients 6, 7
• Implement timely supportive and palliative measures, with individualized counseling to guide decision-making and enhance quality of life 7