INTERSTITIAL PULMONARY FIBROSIS. By: Dr.Bidhi Chand. Junior Resident Pulmonary Medicine. INTERSTITIAL PULMONARY FIBROSIS ATS Definition
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Junior Resident Pulmonary Medicine
Interstitial Pulmonary Fibrosis is defined as a specific form of chronic fibrosing interstitial pneumonia of unknown causes, limited to the lungs and associated with a histologic pattern of usual interstitial pneumonia (UIP).
Growth factors and other
products of epithelial
Recurrent pulmonary injury
endothelial injury and apoptosis
TGF-b = transforming growth factor-beta
PDGF = platelet derived growth factor
IGF-1 = insulin-like growth factor-1
Loss of basement membrane
Failure of re-epithelialization/ re-endothelialization
Release of profibrotic growth factors (TGF-b, PDGF, IGF-1)
Progressive fibrosis with loss of lung architecture
PA chest radiograph shows medium to coarse reticular
B: CT scan shows multiple small cysts (honeycombing) involving predominantly the subpleural peripheral regions of lung. Traction bronchiectasis, another sign of end-stage lung fibrosis.
Classic idiopathic pulmonary fibrosis in 70-year-old man. High-resolution CT shows bilateral subpleural reticulation, traction bronchiectasis (curved arrow), and honeycombing (straight arrows).
Not helpful in making a diagnosis of IPF as limited Lung tissue is obtained. But can exclude by identifying an alternative specific diagnosis.
By open or video assisted thoracoscopic methods – gold standard for diagnosis of IPF. Large piece of Lung parenchyma is required, optimally from several sites.
Mason: Murray & Nadel's Textbook of Respiratory Medicine, 4th ed.
Idiopathic Pulmonary Fibrosis, Gross and Huninghake, NEJM, 2001.
Interstitial lung disease can lead to series of life-threatening complications, including :-
Unlike systemic high Blood Pressure, this condition affects only the artries in Lungs. It begins when scar tissue retricts the smaller blood vessels, limiting blood flow in Lungs. This in turn raises pressure within the Pulmonary arteries. Pulmonary hypertension is a serious illness that becomes progressively worse.
Right sided heart failure (cor-pulmonale) : This is serious condition occur when heart’s lower chamber (right ventricle) : which is less muscular than the left- has to pump harder than usual to move blood through obstructed pulmonary arteries Eventually the right ventricle fails from the extra strain.
Although the course of idiopathic pulmonary fibrosis varies greatly from person to person, the disease usually develops slowly, sometimes over years.
The early stages are marked by alveolitis, an inflammation of the air sacs called alveoli, in the lungs. The job of the air sacs is to allow the transfer of O2 from Lungs into the blood and elimination of CO2 from Lungs and out of the body.
As IPF progresses, the alveoli become damaged and scarred, the stiffening of the lungs, makes breathing difficult and bring on a feeling of breathlessness, especially during activities that require extra effort.
In addition, scarring of the alveoli reduces the ability of lungs to transfer oxygen. The resulting lack of O2 in to the blood (hypoxemia) may cause increase in the blood vessels of the lungs, a situation known as pulmonary hypertension. The high blood pressure in the lungs then puts a strain on right ventricle the lower right side of the heart, which pumps the oxygen – poor blood into the lungs.
Azothioprine : is a medicine that effects the immune system. Because it can cause serious side effects, it may be prescribed with corticosteroids – is associated with improvement and enhanced survival in some patient.
Cyclophosphamide : High dose IV administered every 2-4 weeks (500-1800mg) – tried in open trial result were un-impressive. A recent study suggested that combined corticosteroid and cyclophosphamide therapy has no impact on the survival of patient with IPF.
Interferon gamma : inhibits proliferation of lung fibroblasts in dose dependent manner and a reduce protein synthesis in fibroblasts.
- In an open randomized study with 18 patients who had not respondendto glucocorticoidsand other immunosupressive agents – 200mg interferon gamma 1b , 3 times/wk for 12 month along with predinsolone resulted in improvement in TLC and partial pressure of O2.
Subsequent studies dampened hopes, when Honore et al reported 4 cases of IPF who developed irreversible respiratory failure following treatment with Interferon Gamma.
A larged well controlled multinational clinical trial programme has been demonstrated the effectiveness and safety of pirfenidone in the treatment of IPF. Study present in American Thoracic Society International Conference, Tronoto. Daily consumption of pirfenidonecan slow down the progression of IPF by improving the lung capacity. Study conducted on 275 patient by Takashi Ogura in Japanese patients with mild-moderate IPF patient was randomly divided into three groups were administered 1800mg/ day (High dose) or 1200mg/day (low dose) of pirfenidone or placebo for 52 weeks.
Then vital capacity assessed at week 52, the researchers found that the loss of vital capacity in high dose regimen group was significantly lower when compared with the low dose regime and with the placebo group.
The rate of deterioration IPF was reduced in patients taking pirfenidone. The drug was relatively well tolerated. The only side effect of the drug to be noticed was photosensitivity, which as mild severity.
The aim of the pulmonary rehabilitation is not only to improve daily functioning, but also to help people with interstitial lung disease to live fully satisfying life. Pulmonary rehabilitation program focus on:
Physical exercise, to improve your endurance.
Breathing techniques that improve lung efficiency.
Lung transplantation is a treatment option for selected patients with advanced disease refractory to medical therapy. Lung transplant improves long term survival. Survival rates worldwide after single lung transplantation are approximately :
74% at 1 year
58% at 3 years
47% at 5 years
and 42% at 10 years
The prognosis variable and depends on the specific diagnosis and severity. Some disease are insidious in onset and gradual progression, while other disease are acute in onset but responsive to therapy. Idiopathic pulmonary fibrosis is progressive illness, producing increasingly severe symptoms, and generally has a poor prognosis.
Mortality data for 3 year and 5 year mortality rate are approximately 50% and 80% respectively. Although IPF occurs in older patients with co-morbid diseases, most patients with IPF die as direct consequence of the Lung fibrosis. However, some patients with IPF remain stable for a number of years. The median survival rate of biopsy – proven IPF is less than three years. Most will die as a result of respiratory failure, but other will develop infections secondary to steroid therapy or right heart failure.
The accuracy and timeliness of IPF diagnosis must be improved in order to improve treatment opportunities and outcomes.
However, there is often a long delay before a diagnosis is made and today the diagnosis is too often insufficiently secure or accurate.CONCLUSION
The guidelines (exclusion of alternate diagnosis, optimal interpretation of CT, combination CT and histopathological evaluation with a multidisciplinary discussion implying a pulmonologist, a radiologist and a pathologist expert on ILD) have to be strictly applied.issues need to be addressed