What is Idiopathic Pulmonary Fibrosis (IPF)?

Idiopathic Pulmonary Fibrosis: Overview

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown cause that occurs primarily in older adults (typically 60-70 years), is limited to the lungs, and is characterized by the histopathological pattern of usual interstitial pneumonia (UIP). 1, 2

Definition and Core Characteristics

IPF represents a specific form of interstitial lung disease distinguished by:

• Histopathological hallmark: The UIP pattern shows heterogeneous fibrosis with scarring and honeycomb changes alternating with less affected or normal lung tissue 2
• Age predilection: Predominantly affects patients in their sixth and seventh decades; patients younger than 50 years are rare 2
• Unknown etiology: Despite extensive research, the underlying cause remains unidentified 1, 2

Risk Factors and Pathogenesis

The disease develops through an aberrant reparative response to repetitive alveolar epithelial injury in genetically susceptible aging individuals 3. Key risk factors include:

• Male gender (74% of patients are male) 2, 4
• Cigarette smoking history (65% are current or former smokers) 2, 4
• Gastroesophageal reflux disease 2
• Genetic predisposition (approximately 30% have genetic factors increasing risk) 2
• Possible viral infections (Epstein-Barr virus, hepatitis C) 2

Clinical Presentation

The typical patient presents with:

• Progressive exertional dyspnea with insidious onset 2
• Dry, nonproductive cough that is often refractory to antitussive medications 2
• Bibasilar inspiratory "Velcro" crackles on auscultation (present in >80% of patients) 2
• Digital clubbing (present in <50% of cases) 2

Critical pitfall: Symptoms are nonspecific and most patients present several years after initial radiographic changes occur, leading to delayed diagnosis 5

Diagnostic Criteria

Definitive diagnosis requires three 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: HRCT findings typical of UIP pattern 2

High-Resolution CT Features

The UIP pattern on HRCT demonstrates 2:

• Bibasilar reticular abnormalities with minimal ground glass opacities
• Honeycombing with or without traction bronchiectasis
• Predominantly peripheral and basal distribution

Approximately 93% of IPF patients meet criteria for definite IPF on HRCT 4

Baseline Pulmonary Function

At diagnosis, typical findings include 4:

• Mean percent predicted FVC: 72%
• Mean percent predicted DLCO: 46%
• Eligibility for clinical trials typically requires FVC ≥50% and DLCO ≥30-35%

Disease Progression and Monitoring

IPF is characterized by progressive worsening of dyspnea and lung function with uniformly poor prognosis. 2

Prognosis

• Median survival: 2-4 years after diagnosis without treatment 2, 5
• Primary cause of death: Respiratory failure (approximately 40% of deaths) 2
• Increased cancer risk: 10-15% of patients develop bronchogenic carcinoma 2

Monitoring Parameters

Patients should be evaluated every 3-6 months or sooner as clinically indicated 1. Disease progression is defined by at least one of the following 1:

• Progressive dyspnea (objectively assessed with validated tools)
• FVC decline: Absolute decrease of ≥10% predicted (or 5-10% sustained decline may also indicate progression)
• DLCO decline: Absolute decrease of ≥15% predicted
• Radiological progression: Increased fibrosis on HRCT
• Acute exacerbation
• Death from respiratory failure

Important caveat: Isolated changes <5% in FVC and <10% in DLCO should be interpreted with caution as they may overlap with test variability 1

Treatment Approach

Antifibrotic Therapy

Two FDA-approved antifibrotic medications slow disease progression: 1, 4

• Pirfenidone: Administered at 2,403 mg/day (three times daily with food) reduces decline in FVC and may improve progression-free survival 4, 3
• Nintedanib: Also slows physiological progression 1, 3

Both medications demonstrated statistically significant reductions in FVC decline in clinical trials, with pirfenidone showing a mean treatment difference of 193 mL at Week 52 compared to placebo 4

Non-Pharmacological Management

Oxygen supplementation is strongly recommended for hypoxemic patients (desaturation <88% during 6-minute walk test) 1, 2

Pulmonary rehabilitation is recommended to improve exercise capacity and quality of life 1, 2

Comorbidity Management

Evaluate and treat 1:

• Pulmonary hypertension
• Gastroesophageal reflux (though antacid medication and antireflux surgery received conditional recommendations against in the 2022 update) 1
• Obstructive sleep apnea
• Lung cancer surveillance

Palliative Care

Symptom control focuses on 1:

• Cough management: Limited data suggest corticosteroids and thalidomide may be beneficial 1
• Dyspnea management: Chronic opioids may be used with careful monitoring for side effects 1
• Advanced directives: Should be discussed in the ambulatory setting, particularly for patients with severe physiologic impairment 1

Lung Transplantation

Lung transplantation is the only intervention shown to improve survival and should be considered for patients with progressive deterioration 2. Patients at increased risk of mortality should be evaluated and listed for transplantation at the time of diagnosis 1

Acute Exacerbations

Corticosteroids are an appropriate treatment option for acute exacerbations (weak recommendation) 1. Mechanical ventilation is not recommended for the majority of patients with respiratory failure due to disease progression (weak recommendation against) 1

Clinical Trial Enrollment

All patients should be made aware of available clinical trials for possible enrollment at all stages of disease 1