Description

• Interstitial lung diseases (ILDs) represent a diverse group of chronic progressive lung diseases associated with alveolar inflammation and/or potentially irreversible pulmonary fibrosis.
• >200 individual diseases may present with similar characteristics, making ILD difficult to classify.
• A classification scheme proposed by the American Thoracic Society and European Respiratory Society includes these subtypes:
  • Known causes (environmental, occupational, or drug-associated disease)
  • Systemic disorders (e.g., sarcoidosis, Wegener granulomatosis, collagen vascular disease)
  • Rare lung diseases (e.g., pulmonary histiocytosis, lymphangioleiomyomatosis)
  • Idiopathic interstitial pneumonias (IIPs)
• Based on clinical, radiologic, and histologic features, IIPs are further subclassified into the following diagnoses:
  • Idiopathic pulmonary fibrosis (IPF), characterized by progressive dyspnea, cough, restrictive lung disease, and a specific histopathologic pattern
  • IIPs other than IPF (including nonspecific interstitial pneumonia [NSIP], respiratory bronchiolitis-associated ILD [RBILD], acute interstitial pneumonia [AIP], cryptogenic organizing pneumonia [COP], etc.)
• Classification of IIPs and relationships between the subtypes continue to be areas of clinical controversy.

Pediatric Considerations
ILD in infants and children represents a heterogeneous group of respiratory disorders that are mostly chronic and associated with high morbidity and mortality. As with adults, diseases result from a variety of processes involving genetic factors and inflammatory or fibrotic responses (1). Some diseases result from developmental disorders and growth abnormalities in infancy (1). Classification can center around whether disease is primarily a pulmonary process or if symptoms occur as a result of a systemic disorder.

Epidemiology

• Due to lack of consistency in disease presentation and definition, epidemiologic data are not well defined. Exact incidence has been difficult to determine because of differences in case definitions and procedures used in diagnosis.
• Ranges cited for incidence of IPF: 4.6–10.7/100,000 (2)
• According to the National Heart, Lung, and Blood Institute, ~50,000 new cases of IPF are diagnosed each year in the US.

• Exact prevalence has been difficult to determine because of differences in case definitions and procedures used in diagnosis.
• Ranges cited for prevalence of IPF: 2–29 cases/100,000 in the general population (2)

Risk Factors

• Environmental or occupational exposure to inorganic or organic dusts
• 66–75% of patients with ILD have a history of smoking.
• Due to diversity of diseases, age is not a reliable predictor of pathology:
  • Most patients with connective tissue disease-related pathology and inherited subtypes present between ages 20 and 40.
  • Median age of patients with IPF is 66 years. Studies of clinical predictors of survival including age, ethnicity, and smoking status have been inconsistent (3).

Genetics
Some studies suggest that some subtypes of ILD may be associated with specific predisposing genes and environmental exposures; however, the role of genetic factors is unknown at this time.

General Prevention

Avoiding environmental/occupational exposure to organic or inorganic dust and smoking cessation may reduce incidence or improve clinical course in patients with established ILD.

Pathophysiology

• Alveolar inflammation may progress into irreversible fibrosis.
• Varying degrees of ventilatory dysfunction occur among the ILD subtypes.
• ILD associated with collagen vascular disease and systemic connective disorders can manifest involvement of skin, joints, muscular, and ocular systems.

Etiology

Some types of ILD are associated with specific exposures:

• Medications (amiodarone, antibiotics [especially nitrofurantoin], chemotherapy agents, gold, illicit drugs)
• Inorganic dusts (silicates, asbestos, talc, mica, coal dust, graphite)
• Organic dusts (moldy hay, inhalation of fungi, bacteria, animal proteins)
• Metals (tin, aluminum, cobalt, iron, barium)
• Gases, fumes, vapors, aerosols

Commonly Associated Conditions

Many systemic disorders and primary diseases are associated with ILD. A partial list includes:

• Collagen vascular disease
• Sarcoidosis
• Amyloidosis
• Goodpasture syndrome
• Churg-Strauss syndrome
• Wegener granulomatosis