IDIOPATHIC PULMONARY FIBROSIS

I. Pathophysiology

1. Etiology unknown
2. Thickening of alveolar walls
3. Mononuclear infiltrate in alveolar space

II. Clinical features

1. Tends to be progressive with mean 5y survival rate about 50%
2. Usual onset 40-70yo
3. 1/3 of pts have an autoimmune condition
4. Nonproductive cough and dyspnea
5. Px shows bilateral basilar crackles and clubbed fingernails
6. CXR typically shows diffuse reticular markings, predominantly in lower lobes; up to 16% of pts may have normal CXR
7. CT shows linear opacities and honeycombing with areas of ground-glass attenuation
8. PFT's show evidence of restrictive disease with low FVC and impaired gas exchange

III. Dx

1. Occupational and environmental hx to
2. CT can help confirm the dx
3. Transbronchial lung bx and bronchoalveolar lavage can help r/o other dx's e.g. sarcoidosis, hypersensitivity pneumonitis, cryptogenic organizing pneumonia, and malignancy

IV. Tx

1. Steroids--only 10-15% of pts will improve. Predictors of response:
   1. Ground-glass attenuation on CT
   2. Young age
   3. Female gender
   4. Active inflammation on lung bx
2. Interferon-gamma-1b + prednisolone 7.5mg QD ass'd with sig. greater increase in total lung capacity and PaO2c/w prednisolone alone in a 12mo randomized study of 18 pts with IPF not responsive to high-dose steroid tx (NEJM 341:1264, 1999--JW)
3. In a study in 155 pts with idiopathic pulmonary fibrosis randomized to acetylcysteine 600mg TID vs. placebo (acetylcysteine is a precursor of glutathione, which is an antioxidant that is depleted in lungs of pts with IPF), all of whom also received prednisone + azathioprine, after 12mos, the acetylcysteine group had sig. less decline in mean vital capacity and DLCO but there was no sig. diff. in mortality rates (NEJM 353:2229, 2005--JW)
4. Other agents used: azathioprine, cyclophosphamide, other cytotoxic drugs
5. Lung transplantation

Source: AFP summary of Lancet 350:651, 1997