Idiopathic Pulmonary Fibrosis Signs And Symptoms

Idiopathic%20pulmonary%20fibrosis Signs and Symptoms

Signs and Symptoms

The most common type of idiopathic interstitial pneumonia (IIP)
The most common interstitial lung disease among referrals & 2nd most common diagnosis or frequent disease for lung transplantation

A specific form of chronic, progressive fibrosing interstitial pneumonia that occurs spontaneously & is limited to the lungs, associated with a pattern of usual interstitial pneumonia (UIP) both on high-resolution computed tomography (HRCT) or lung biopsy
Also known as cryptogenic fibrosing alveolitis (CFA)

Exposure to agents like smoke, environmental pollutants & dust, viral infections, gastroesophageal reflux disease (GERD) & chronic aspiration may lead to initial alveolar epithelial damage especially in susceptible hosts
Familial pulmonary fibrosis (FPF)
- Account for <5% of the total number of patients with idiopathic pulmonary fibrosis
- May affect ≥2 family members of the same primary biological family
- May be caused by a genetic mutation in serum surfactant protein C or A2 (SFTPA2)
- Also associated with the gene encoding mucin 5B (MUC5B) & mutant human telomerase RNA

Respiratory viruses
- Common cause of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF)

Exertional dyspnea
Nonproductive cough
Finger clubbing
Bilateral inspiratory crackles
Systemic symptoms (arthralgia, fatigue, low-grade fever, myalgia, weight loss)
Exertional dyspnea & nonproductive cough are the 2 most common presenting symptoms in patients with idiopathic pulmonary fibrosis
- Dyspnea is the most prominent symptom

Symptoms are nonspecific as it may present in patients with cardiac & pulmonary disease
Approximately 5% of the patients are asymptomatic
- Asymptomatic patients develop their symptoms approximately 1000 days after the diagnosis of idiopathic pulmonary fibrosis on routine chest radiograph & usual interstitial pneumonia on lung biopsy

It would take about 1-2 years (median duration of symptoms) before a diagnosis of idiopathic pulmonary fibrosis is established

Cigarette smoking
Environmental exposure to metal dust (brass, lead, steel) & wood dust
Occupational exposure (farming, livestock, salon waste, stone cutting/polishing, vegetable dust)
Infections (Epstein-Barr virus, Hepatitis C, cytomegalovirus)
Gastroesophageal reflux disease via microaspiration
Familial pulmonary fibrosis
- Further studies are needed to prove the association of the genetic polymorphisms for cytokines, enzymes, profibrotic molecules, coagulation pathway genes, surfactant protein-A & -B, immunomodulatory genes, & matrix metalloproteinase & idiopathic pulmonary fibrosis

Histopathology

Characteristic histopathologic features of usual interstitial pneumonia include:
- Presence of abnormal proliferation of mesenchymal cells
- Varying degrees of fibrosis
- Overproduction & disorganized disposition of collagen & extracellular matrix
- Honeycomb cysts

The histological hallmark of usual interstitial pneumonia is the presence of a subepithelial fibroblast foci
Inflammation, aberrant fibroblast & epithelial cell function, or abnormal epithelial-mesenchymal interactions with little or without an inflammatory component may play a role in the development of fibrosis in idiopathic pulmonary fibrosis
The initiation & perpetuation of a fibrotic response, which is considered a trigger for the development of idiopathic pulmonary fibrosis, will depend on:
- Genetic factors
- Environmental triggers
- Imbalance of oxidants & anti-oxidants
- Imbalance of Th1 & Th2 cell-derived cytokines

Marked proliferation of type II epithelial cells & loss of type 1 epithelial cells may be present
Serum concentrations of lung surfactant proteins SP-A & SP-D, & Kerbs von Lungren 6 antigen (KL-6) are increased in patients with idiopathic pulmonary fibrosis
- A change in the concentration of KL-6 may be used as a marker for the activity of the disease

Abnormalities of the alveolar epithelium cells (AECs) causing altered reepithelization in idiopathic pulmonary fibrosis patients include loss of type 1 epithelial cells, proliferation of type 2 epithelial cells, & impaired regenerative capacity of the epithelium
- On electron microscopy, the space between the alveolar epithelium & capillary endothelium is where the resident mesenchymal cells are located

Excess collagen deposition within the extracellular matrix that may be due to decreased collagenolytic activity prevents re-expansion of collapse lung tissue
Recurring lung tissue injury & TNF-alpha gene polymorphisms have been linked to excessive collagen synthesis
Cytokines & growth factors that stimulates fibroblast proliferation & matrix synthesis include resident epithelial cells, endothelial cells & fibroblasts located within the lungs
TNF-α may be increased in patients with idiopathic pulmonary fibrosis but its role in idiopathic pulmonary fibrosis is not clear
Overexpressed molecules from a lung tissue or blood sample include:
- Fibrotic cytokines
- Matrix metalloprotein (MMP-7 & MMP-1)
- Surfactant protein A1
- Cyclin A2 (CCNA2)
- Alpha-defensins

Genetic Factors