What is idiopathic pulmonary fibrosis (IPF)?

What is Idiopathic Pulmonary Fibrosis?

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown cause that occurs primarily in older adults and is characterized by the radiological and histopathological pattern of usual interstitial pneumonia (UIP), leading to progressive worsening of dyspnea and lung function with a poor prognosis. 1

Core Definition and Pathophysiology

IPF is a specific disease entity limited to the lungs, distinguished by its characteristic UIP pattern showing heterogeneous areas of fibrosis with scarring and honeycomb changes alternating with less affected or normal lung tissue 2. The disease represents an aberrant reparative response to repetitive alveolar epithelial injury in genetically susceptible aging individuals 3. The underlying cause remains unknown, though sustained alveolar epithelial micro-injury and activation trigger disordered repair mechanisms 4.

Epidemiology and Risk Factors

• Age: IPF occurs predominantly in the sixth and seventh decades of life, with patients younger than 50 years being rare 2
• Gender: Male predominance is observed 2
• Smoking: History of cigarette smoking increases risk 2
• Genetic factors: Approximately 30% of patients have genetic predisposition 2
• Other associations: Gastroesophageal reflux and possible viral infections (Epstein-Barr virus, hepatitis C) are linked to disease development 2

Clinical Presentation

The disease manifests with:

• Dyspnea: Insidious onset of progressive exertional breathlessness 2
• Cough: Dry, nonproductive cough refractory to antitussive agents 2
• Physical examination: Bibasilar inspiratory "Velcro" crackles present in >80% of patients 2
• Digital clubbing: Present in <50% of cases 2

Diagnostic Requirements

Diagnosis requires three essential components 2:

1. Exclusion of other causes: Rule out drug toxicities, environmental exposures, and connective tissue diseases 2
2. Abnormal pulmonary function: Restriction and/or impaired gas exchange 2
3. Characteristic imaging: High-resolution CT (HRCT) showing UIP pattern with bibasilar reticular abnormalities, honeycombing with or without traction bronchiectasis, and predominantly peripheral and basal distribution 2

The UIP pattern on HRCT is bilateral, peripheral, and basally distributed with reticular changes, traction bronchiectasis, and subpleural cystic airspaces 3. Lung biopsy may be required when imaging is inconclusive 3.

Disease Course and Prognosis

IPF carries a grave prognosis with median survival of 2-4 years after diagnosis without treatment 2. The disease is characterized by progressive worsening of dyspnea and lung function 2. Respiratory failure accounts for approximately 40% of deaths 2. Additionally, patients face a 10-15% increased risk of developing bronchogenic carcinoma 2.

Management Framework

The 2022 ATS/ERS/JRS/ALAT guidelines outline a comprehensive management pathway 1:

Pharmacological Treatment

• Antifibrotic therapy: Nintedanib and pirfenidone slow disease progression 1
• These medications can improve quality of life and attenuate symptoms but do not cure the disease 5

Non-Pharmacological Interventions

• Oxygen supplementation: For hypoxemic patients 1
• Pulmonary rehabilitation: Improves quality of life and functional level 1, 6

Comorbidity Management

Evaluate and treat 1:

• Pulmonary hypertension
• Gastroesophageal reflux
• Obstructive sleep apnea
• Lung cancer

Palliative Care

Symptom management for cough, dyspnea, and anxiety should be integrated throughout the disease course 1. Advanced directives must be discussed in the ambulatory setting 1.

Lung Transplantation

Patients at increased risk of mortality should be referred for lung transplantation evaluation at the time of diagnosis 1. This is the only intervention shown to improve survival 2.

Monitoring Disease Progression

Patients should be evaluated every 3-6 months or more frequently for disease progression 1. Progression is defined by 1:

• Progressive dyspnea (objectively assessed)
• Sustained decline in FVC ≥10% predicted or DLCO ≥15% predicted
• Radiological progression of fibrosis on HRCT
• Acute exacerbations

A critical pitfall: Isolated changes <5% in FVC and <10% in DLCO should be interpreted with caution as they may overlap with test variability 1.

Key Clinical Considerations

Mechanical ventilation is not recommended for the majority of patients with respiratory failure due to disease progression 1. Acute exacerbations may be treated with corticosteroids 1. Patients should be made aware of available clinical trials for possible enrollment at all stages of disease 1.