Pulmonary fibrosis

Introduction

Pulmonary fibrosis is a chronic and progressive lung disease characterized by scarring of lung tissue, which impairs gas exchange and reduces lung compliance. It can lead to significant respiratory compromise, reduced quality of life, and increased mortality. Understanding its causes, pathophysiology, and clinical management is essential for timely diagnosis and effective treatment.

Definition and Classification

Definition

Pulmonary fibrosis refers to the formation of excessive fibrous connective tissue in the lungs, resulting in thickened alveolar walls, impaired oxygen diffusion, and reduced lung elasticity. The scarring process is usually irreversible and progressively affects respiratory function.

Classification

Pulmonary fibrosis can be classified into several categories based on etiology and clinical characteristics:

• Idiopathic Pulmonary Fibrosis (IPF): the most common form of interstitial lung disease with unknown cause, typically occurring in adults over 50 years.
• Secondary Pulmonary Fibrosis: develops as a consequence of known conditions such as connective tissue diseases, chronic infections, or environmental exposures.
• Familial and Genetic Forms: rare hereditary forms caused by mutations in genes related to surfactant production or telomerase function.

Etiology

Pulmonary fibrosis can arise from multiple causes, including idiopathic, environmental, drug-induced, autoimmune, infectious, and genetic factors. Identifying the underlying cause is essential for targeted management and prognosis.

• Idiopathic causes: most cases of pulmonary fibrosis, especially idiopathic pulmonary fibrosis, have no identifiable trigger.
• Environmental exposures:
  • Occupational exposures such as asbestos, silica, and coal dust
  • Environmental pollutants including smoke, fumes, and chemical irritants
• Medications and drugs: certain chemotherapeutic agents, amiodarone, and nitrofurantoin can induce lung fibrosis.
• Connective tissue and autoimmune diseases: systemic sclerosis, rheumatoid arthritis, and lupus can lead to secondary pulmonary fibrosis.
• Infections: chronic viral, bacterial, or fungal infections may contribute to fibrotic changes.
• Genetic predisposition: familial pulmonary fibrosis due to mutations in surfactant proteins or telomerase genes.

Pathophysiology

Pulmonary fibrosis develops through complex interactions between alveolar epithelial injury, fibroblast activation, and abnormal repair mechanisms, resulting in irreversible scarring of lung tissue.

• Alveolar epithelial injury and abnormal repair: repeated injury to alveolar cells triggers aberrant healing responses instead of normal regeneration.
• Fibroblast activation and extracellular matrix deposition: activated fibroblasts and myofibroblasts produce excessive collagen and other matrix proteins, thickening alveolar walls.
• Inflammation and cytokine involvement: inflammatory cells release cytokines and growth factors such as TGF-β, promoting fibrogenesis.
• Vascular remodeling and hypoxia: fibrosis alters pulmonary vasculature, leading to reduced perfusion and ventilation-perfusion mismatch, causing hypoxemia.

Clinical Features

Symptoms

Patients with pulmonary fibrosis often present with progressive respiratory symptoms that develop over months to years.

• Dyspnea: progressive shortness of breath, initially on exertion and later at rest
• Chronic dry cough: persistent non-productive cough that worsens over time
• Fatigue and weight loss: systemic effects of chronic hypoxia and reduced lung function

Signs

Physical examination may reveal characteristic findings suggestive of pulmonary fibrosis.

• Clubbing of fingers: enlargement of distal phalanges due to chronic hypoxia
• Velcro crackles: fine inspiratory crackles heard at the lung bases on auscultation
• Cyanosis: bluish discoloration of lips and fingertips in advanced disease

Diagnostic Evaluation

Diagnosis of pulmonary fibrosis involves a combination of clinical assessment, imaging, functional testing, and, in some cases, tissue sampling.

• History and physical examination: assessment of symptoms, exposure history, comorbidities, and familial risk
• Imaging studies:
  • Chest X-ray: may show reticular or nodular patterns, reduced lung volumes
  • High-resolution CT (HRCT): provides detailed visualization of fibrotic changes, honeycombing, and traction bronchiectasis
• Pulmonary function tests: demonstrate restrictive pattern with reduced lung volumes and impaired diffusion capacity (DLCO)
• Laboratory investigations: autoimmune panels, inflammatory markers, and other tests to identify secondary causes
• Lung biopsy and histopathology: considered in unclear cases to confirm diagnosis and differentiate subtypes
• Bronchoscopy and bronchoalveolar lavage: can assist in excluding infections or other interstitial lung diseases

Differential Diagnosis

Pulmonary fibrosis must be distinguished from other respiratory and systemic conditions that produce similar clinical and radiological features. Accurate differentiation is essential for appropriate management.

• Other interstitial lung diseases: nonspecific interstitial pneumonia, hypersensitivity pneumonitis, sarcoidosis
• Chronic obstructive pulmonary disease (COPD): may coexist with fibrosis or mimic restrictive symptoms in advanced disease
• Heart failure-related pulmonary congestion: pulmonary edema can produce reticular patterns on imaging and dyspnea
• Connective tissue disease-related lung involvement: systemic sclerosis, rheumatoid arthritis, lupus, and mixed connective tissue disease

Management and Treatment

The management of pulmonary fibrosis involves pharmacological therapy, supportive measures, and in selected cases, surgical intervention. Treatment aims to slow disease progression, relieve symptoms, and improve quality of life.

• Pharmacological therapy:
  • Antifibrotic agents such as pirfenidone and nintedanib to reduce progression in idiopathic pulmonary fibrosis
  • Immunosuppressive drugs in select secondary forms associated with autoimmune disease
  • Corticosteroids for inflammatory components or acute exacerbations
• Oxygen therapy: supplemental oxygen for hypoxemia and to improve exercise tolerance
• Pulmonary rehabilitation: exercise training, education, and breathing techniques to enhance functional capacity
• Lung transplantation: considered in advanced disease with progressive respiratory failure
• Supportive care: management of comorbidities, vaccination, and palliative measures for symptom relief

Prognosis

The prognosis of pulmonary fibrosis varies depending on the etiology, disease severity, and response to therapy. Idiopathic pulmonary fibrosis generally has a poorer prognosis compared to secondary forms.

• Disease progression and survival rates: median survival for idiopathic pulmonary fibrosis is approximately 3 to 5 years after diagnosis
• Factors affecting prognosis: age, baseline lung function, extent of fibrosis on imaging, comorbidities, and acute exacerbations
• Complications and comorbidities: pulmonary hypertension, respiratory failure, infection, and increased risk of lung cancer

Prevention and Future Directions

Preventive strategies and ongoing research are focused on reducing risk factors, early detection, and developing novel therapies to improve outcomes in pulmonary fibrosis.

• Risk factor modification and occupational safety: minimizing exposure to dust, asbestos, silica, and other environmental toxins
• Early detection strategies: screening high-risk populations and monitoring patients with autoimmune diseases or genetic predisposition
• Ongoing research and emerging therapies: new antifibrotic drugs, stem cell therapy, gene-targeted treatments, and personalized medicine approaches under clinical investigation

References

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