What causes lung scarring?

Causes of Lung Scarring

Lung scarring (pulmonary fibrosis) is primarily caused by occupational exposures, environmental toxins, medications, radiation, infections, and autoimmune conditions that trigger chronic inflammation leading to irreversible fibrotic changes in lung tissue. 1

Major Causes of Lung Scarring

Occupational and Environmental Exposures

• Inorganic dusts:

  • Asbestos: A well-established occupational carcinogen with strong association to lung scarring and cancer (>5-fold excess risk) 1
  • Silica: Associated with silicosis, which increases lung cancer mortality 2.4-fold 1
  • Coal, cement, manufactured vitreous fibers 1
  • Metal dusts, wood dust 2

• Organic dusts and chemicals:

  • Cotton dust (byssinosis), jute, hemp, flax, sisal 1
  • Various grains 1
  • Diesel exhaust particles 1

Radiation Exposure

• High-LET radiation: Radon, neutrons 1
• Low-LET radiation: X-rays, gamma rays 1
• Radiation therapy can cause radiation pneumonitis leading to fibrosis 2

Medications

• Nitrofurantoin: Can cause chronic pulmonary hypersensitivity reactions with diffuse interstitial pneumonitis or fibrosis, especially after continuous treatment for six months or longer 3
• Other drugs that can cause lung fibrosis include chemotherapeutic agents, amiodarone, and certain antibiotics 1

Inflammatory and Immune-Mediated Conditions

• Hypersensitivity pneumonitis: Caused by repeated inhalation of environmental antigens leading to bronchiolocentric fibrosis 1
• Autoimmune connective tissue diseases: Including rheumatoid arthritis, systemic sclerosis, polymyositis 1
• Chronic bronchitis: Long-term inflammation can lead to peribronchiolar fibrosis 1

Infections

• Various infections can cause scarring during the healing process 4
• Mycobacterial infections 1

Smoking

• Cigarette smoking causes inflammatory changes in airways 1
• Smoking-related interstitial fibrosis (airspace enlargement with fibrosis) 1
• Smoking increases risk for idiopathic pulmonary fibrosis 5

Idiopathic Causes

• Idiopathic pulmonary fibrosis (IPF): The most common form of idiopathic interstitial pneumonia with unknown cause 5
• Unclassifiable interstitial lung disease: Cases that don't fit established patterns 1

Pathophysiological Mechanisms

Inflammatory Process

1. Initial injury to lung epithelium by toxins, pathogens, or autoimmune processes 6
2. Inflammatory cell activation: Release of cytokines (IL-1, TNF-α, IL-8) and mediators 1
3. Chronic inflammation: Persistent inflammation leads to fibroblast activation 6
4. Fibroblast proliferation and resistance to apoptosis: Fibroblasts continue to produce collagen without normal cell death 2
5. Extracellular matrix deposition: Excessive collagen deposition (especially type III collagen in active scarring) 4
6. Tissue remodeling: Destruction of normal lung architecture 1

Toll-Like Receptor 4 (TLR4) Pathway

• TLR4 activation appears to be a key mediator in fibroblast apoptosis resistance, contributing to progressive scarring 2
• High mobility group box 1 (HMGB1) may act through TLR4 to interfere with wound resolution 2

Clinical Implications and Prevention

Prevention Strategies

• Workplace dust control measures should be implemented and enforced 7
• Cessation of exposure to causative agents is critical, though it may not stop progression once disease is established 7
• Smoke-free workplace and public place laws should be enacted in all communities 1

Monitoring and Management

• Regular monitoring for development of malignancies, especially in those with asbestos exposure 7
• High-Resolution Computed Tomography (HRCT) is superior to conventional radiography for detecting early parenchymal changes 7
• No prophylactic medication is available to prevent progression once exposure has occurred 7

Key Pitfalls in Diagnosis and Management

• Lung scarring may be misdiagnosed as other conditions (COPD, asthma) delaying proper treatment
• Failure to obtain detailed occupational history may miss crucial exposure information
• Continued exposure to causative agents can accelerate disease progression
• Lung scarring is often irreversible once established, making early identification and removal from exposure critical

Understanding the causes of lung scarring is essential for early intervention, as pulmonary fibrosis significantly impacts quality of life and mortality, with median survival of 2-5 years from diagnosis in idiopathic cases 5.