IDIOPATHIC PULMONARY FIBROSIS

BASICS in IPF

CLASSIFICATION OF INTERSTITIAL LUNG DISEASE OR DIFFUSE PARENCHYMAL LUNG DISEASE

Classification of interstitial lung disease(ILD) or diffuse parenchymal lung disease(DPLD)

IIP: Idiopathic interstitial pneumonia LAM: Lymphangioleiomyomatosis HX: histiocytosis X

•Account for about 15% of the respiratory disease in general practice and comprise of a very wide spectrum of pathologies, presentations and outcomes• Diffuse lung diseases such as emphysema or chronic obstructive lung disease (COPD), bronchiolitis, and pulmonary hypertension are excluded from this classification

Am J Respir Crit Care Med 2002; 165:277–304.

ILDs or DPLDs

Acute and chronic lung disorders with variable degrees of pulmonary inflammation and fibrosis are collectively referred to as ILDs or DPLDs They may have known causes (e.g., collagen vascular disease, environmental or drug-related) or an unknown cause (idiopathic)

IDIOPATHIC INTERSTITIAL PNEUMONIA (IIPS)Idiopathic indicates unknown cause and interstitial pneumonia refers to involvement of the lung parenchyma by varying combinations of fibrosis and inflammation, in contrast to airspace disease typically seen in bacterial pneumonia. The interstitium includes the space between the epithelial and endothelial basement membranes and it is the primary site of injury in the IIPs

What is idiopathic pulmonary fibrosis (IPF) ?

IPF is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause, occurring primarily in older adults, limited to the lungs, and associated with the histopathologic and/or radiologic pattern of usual interstitial pneumonia (UIP)

It requires the exclusion of other forms of interstitial pneumonia, including other IIPs and ILD associated with environmental exposure, medication or systemic disease

Most frequent of the IIPs, associated with the worst prognosis

Am J Respir Crit Care Med 2002; 165:277–304. Am J Respir Crit Care Med 2011; 183: 788–824.Ind J Chest All Sc 2004; 46: 23-26.

IPF accounts for around 45% of all patients having ILD in India

IDIOPATHIC PULMONARY FIBROSIS: NATURAL HISTORY , RISK FACTORS AND PATHOGENESIS

Epidemiology of IPF

Progressive and fatal lung disease Median survival is 2-5 years Insidious decline in lung function Considered a ‘rare disease’ Affects around 100,000 Americans IPF accounts for around 45% of all patients having ILD in India Incidence and prevalence of IPF increases with age, and that

the disease is more common in men than women

Eur Respir J 2007; 30: 835-839Allergy 2010; 65: 537-553

Eur Respir Mon 2009;46: 357-374Ind J Chest All Sc 2004; 46: 23-26.

Natural history of IPF

Unpredictable with a progressive decline in pulmonary function until eventual death from respiratory failure or comorbidity

Majority show a slow, gradual progression over many years (‘‘Slow progression’’)

Some patients remain stable (‘‘Stable’’), while others have an accelerated decline

Some patients may experience episodes of acute respiratory worsening (‘‘Rapid progression’’)

Minority of patients may experience unpredictable acute worsening or exacerbation of their disease (lightning bolt in fig.), either from a secondary complication such as pneumonia, or for unrecognized reasons which may be fatal

Fig. Natural history of IPFAm J Respir Crit Care Med 2011; 183:788–824.

Risk factors

Genetic Factors

Familial IPF (fIPF): This is reported in less than 5% of the total IPF patients

Cigarette Smoking Environmental Exposures: Significantly increased risk observed

after exposure to metal dusts (brass, lead and steel) and wood dust (pine), farming, raising birds, hair dressing, stone cutting/polishing, and exposure to livestock and to vegetable dust/animal dust

Microbial Agents: Epstein-Barr virus, cytomegalovirus, human herpes virus (HHV-7, and HHV-8).

Gastroesophageal Reflux Disease (GERD) Other risk factors: E.g., diabetes mellitus.

Am J Respir Crit Care Med 2011; 183:788–824.

Pathogenesis of IPF

Inflammation causes fibrosis

Noninflammatory (multiple hit) hypothesis: fibrosis results from epithelial injury and abnormal wound healing in the absence of chronic inflammation

Vascular remodeling

Clin Chest Med. 2004;25:749-758Clin Chest Med. 2004;25: 621-636Am J Respir Cell Mol Biol. 2003;29(3 suppl):S67-S69.

Multiple Hypotheses

Eur Respir J 2007; 30:835–839.

Pathogenesis of IPFNoninflammatory (multiple hit) hypothesis in IPF

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