Idiopathic pulmonary fibrosis (IPF)


Chronic, progressive disease characterized by the aberrant accumulation of fibrotic tissue in the lungs parenchyma, associated with significant morbidity and poor prognosis.

  • M/C and M/lethal type of idiopathic interstitial pneumonia (IIP) (55% of IIPs)

Classification

Interstitial lung disease (ILD):

Interstitial lung disease (ILD), sometimes called diffused parenchymal diseases is a group of diseases characterized by a combination of chronic inflammation within the lung, consisting of an accumulation of chronic inflammatory cells (predominantly lymphocytes and macrophages) and increased levels of numerous pro-inflammatory cytokines, chemokines, and cell surface molecules; and varying degrees of lung fibrosis.

Idiopathic interstitial pneumonia (IIP):

Chronic, progressive fibrosing interstitial pneumonia characterized by idiopathic origin, occurrence primarily in older adults, exclusively pulmonary involvement and pattern of Usual Interstitial Pneumonia (UIP) proven by histopathology and/or radiology

American Thoracic Society/European Respiratory Society (ATS/ERS) 2002 consensus classification statement:

Histopathologic classification separating the IIPs into seven clinicopathologic entities (in order of relative frequency)
  • Idiopathic pulmonary fibrosis (IPF) (47-64%)
  • Nonspecific interstitial pneumonia (NSIP) (14-36%)
  • Respiratory bronchiolitis ILD(10-17%)
  • Cryptogenic organizing pneumonia (4-12%)
  • Acute interstitial pneumonia (AIP) (< 2%)
  • Lymphoid interstitial pneumonia (LIP) (< 2%)

Aetiology

Risk factors:

Recurrent injury to the alveolar epithelium triggers a cascade of signaling by the immune system leading to fibrosis
  • Exposure to tobacco smoke, metal, wood, dust
  • Gastroesophageal reflux (GERD)
Schematic classification of interstitial lung diseases according to aetiology. The finding of histological usual interstitial pneumonitis in a patient with an idiopathic interstitial pneumonia leads to the specific diagnosis of idiopathic pulmonary fibrosis. | NSIP = non-specific interstitial pneumonitis. | Mikolasch, T. A., Garthwaite, H. S., & Porter, J. C. (2017). Update in diagnosis and management of interstitial lung disease . Clinical medicine (London, England), 17(2), 146–153. https://doi.org/10.7861/clinmedicine.17-2-146

Pathophysiology

Schematic view of idiopathic pulmonary fibrosis (IPF) pathogenesis. Genetic and epigenetic phenomenon contribute to the development of an inherently dysfunctional epithelium. This epithelium is susceptible to recurrent micro-injury from environmental exposures (such as cigarette smoke (CS), inhaled dusts, infection, and gastro-oesophageal reflux (GOR)). The inability of the dysfunctional epithelium to regenerate following repetitive injury is a significant juncture in the propagation of IPF. Damage to the epithelium, disrupts the basement membrane and thus the alveolar capillary barrier. Capillary leakage of proteins (including fibrin and fibronectin) into the interstitial and alveolar spaces occurs, with activation of the coagulation cascade and abnormal vascular remodelling as part of the ongoing attempted repair process. Activated epithelial and endothelial cells create a milieu whereby aberrant epithelial–mesenchymal crosstalk, alongside fibrocyte/fibroblast recruitment, migration, proliferation, and differentiation, flourishes. Transforming growth factor β1 (TGFβ1), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor (FGF) are some of the pro-fibrotic mediators implicated in these processes. Collections of active fibroblasts and myofibroblasts form fibrotic foci (FF), considered to be at the leading edge of extracellular matrix (ECM) deposition, with progressive lung remodelling and architectural distortion. | AEC I/II: alveolar epithelial type I/II cell; UPR: unfolded protein response; EMT: epithelial–mesenchymal transition; UPR: unfolded protein response. | Barratt, S. L., Creamer, A., Hayton, C., & Chaudhuri, N. (2018). Idiopathic Pulmonary Fibrosis (IPF): An Overview. Journal of clinical medicine, 7(8), 201. https://doi.org/10.3390/jcm7080201

Clinical features

  • Progressive dyspnea (esp on exertion)
  • Nonproductive cough
  • Clubbing (advanced cases)

Complications

  • Pulmonary hypertension
  • Thromboembolic disease
  • Adverse effects of medications 
  • Superimposed lung infections
  • Acute coronary syndrome
  • Hypoxic respiratory failure

Diagnosis

Pulmonary function test (PFT):

Pulmonary function tests every 3 to 6 months should be performed based on symptoms and the disease’s progression.
  • Decreased lung volumes: ↓ FVC, ↓ TLC, and ↓ FRC
  • FVC1/FVC: N/↑ (> 0.7)
  • Decreased diffusion capacity: ↓ DLCO

Computed tomography (CT) scan:

  • Usual interstitial pneumonia (UIP) pattern:
    • Peripheral distribution of bilateral fibrosis, more pronounced at the bases
    • Honeycombing and loss of architecture
  • Ground glass opacity (atypical finding)
Typical Usual Interstitial Pneumonia pattern on high resolution computed scan sections showing upper, middle and lower lung regions from left to right. Black arrows indicate subpleural honeycombing; white arrow indicates traction bronchiectasis | Sgalla, G., Iovene, B., Calvello, M., Ori, M., Varone, F., & Richeldi, L. (2018). Idiopathic pulmonary fibrosis: pathogenesis and management. Respiratory research, 19(1), 32. https://doi.org/10.1186/s12931-018-0730-2

Lung biopsy:

If there is diagnostic uncertainty
  • Presence of foci of fibroblasts
  • Evidence of honeycombing and or disruption of lung architecture
  • Patchy involvement of the lung by fibrosis
  • Absence of other features suggesting an alternative diagnosis

Management

Supportive measures:

  • Tobacco cessation
  • Oxygen supplementation
  • Control of gastroesophageal reflux (GERD) with proton pump inhibitors
  • Influenza and pneumococcal vaccination recommended

Anti-fibrotic drugs:

Slow the disease progression but not significantly impact mortality
  • Pirfenidone
  • Nintedanib (tyrosine kinase inhibitors)

Lung transplant for severe disease:

Recommended early in the course of the disease, especially in a patient with a progressive decline in lung function

Leave a Reply

%d bloggers like this: