IDIOPATHIC PULMONARY FIBROSIS (IPF)
Mita Sanghavi Goel, M.D.
February 21, 2003
Overview
 Originally a term used to describe many types of interstitial lung disease, the term IPF is now
reserved only for those patients with histopathology consistent with usual interstitial pneumonitis
(UIP).
 As a result of confusing terminology, however, the reported prevalence of IPF has varied from 36/100,000 to 13-20/100,000, with an incidence of approximately 7-10/100,000 annually.
 Male predominance, with onset of symptoms between ages 40-70 (mean age at diagnosis of 66).
Definition
In the presence of surgical biopsy,
 Exclusion of other known causes of interstitial lung disease, including drug toxicities,
environmental exposures, collagen vascular disease
 Abnormal PFTs with evidence of restriction (decreased VC) and/or impaired gas exchange
(increased A-a gradient) with rest or exercise, or decreased DLCO.
 Abnormal cxr or high res CT
In the absence of surgical biopsy, must have all the major and 3 of the minor criteria,
 Major criteria
o Exclusion of other known causes of interstitial lung disease
o PFTs with evidence of restriction, and impaired gas exchange
o Bibasilar reticular abnormalities with minimal ground glass opacities on high res CT
o Transbronchial lung bx or BAL show no evidence of alternate diagnosis
 Minor criteria
o Age>50 years
o Insidious onset of otherwise unexplained dysnea on exertion
o Duration of illness =< 3 months
o Bibasilar dry, inspiratory crackles.
Pathogenesis
Original Theory
 Unidentified insultchronic inflammation injuryfibrosis
 Led to the use of corticosteroids and cytotoxic agents to interrupt the inflammatory cascade.
New Theory
 Unidentified insultrepeated lung injuryaberrant wound healingfibrosis
 The aberrant wound healing may result from Th2-type > Th1-type of immune response to tissue
injury.
 ?involvement of genetic susceptibility, environmental insults (tobacco), latent viral infections
(EBV, herpesvirus family)
Clinical Presentation
 Most present with insidious onset of exertional dyspnea and non-productive cough.
 Associated symptoms such as low-grade fevers and myalgias may be present.
 Physical exam generally reveals fine bibasilar inspiratory (“Velcro”) crackles and clubbing. Findings
consistent with collagen vascular disease, such as rash, arthritis, or myositis, generally indicate an
alternative diagnosis.
Diagnosis
Labs
 Overall, not very helpful
 May have signs of systemic inflammation (elevated ESR and CRP)
 Nonspecific elevations in ANA, RF (approx. 30% of patients)
 May have mild anemia initially
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Pulmonary Function Testing
 Parenchymal restrictive ventilatory defect
 Decreased total lung capacity
 Decreased functional residual capacity
 Decreased residual volume because of decreased lung compliance
 Decreased DLCO
Imaging
 CXR typically shows bilateral reticular opacities most prominent in the lower lobes and the
periphery progressing to cystic dilation of distal airspacesperipheral honeycombing
 High resolution CT scan may show patchy peripheral reticular abnormalities, irregular septal
thickening, traction bronchiectasis, and subpleural honeycombing. (May be around 80% specific
with experienced clinicians).
 No clear role for gallium scanning, which was previously used for evaluation.
Biopsy
 Gold standard of diagnosis
 Requires large amount of tissue for proper diagnosis; therefore, patients must have thoracotomy
or VATS to obtain tissue.
 Hallmark findings are:
o Fibrotic zones with associated honeycombing alternating with zones of normal tissue
o Some areas of chronic lung injury (scarring and honeycoming) as well as regions of acute
injury, with foci of actively proliferating fibroblasts and myofibroblasts
o In summary, geographically and temporally heterogeneous parenchymal fibrosis with a
background of mild inflammation.
Treatment
Antiinflammatory Therapy
 Corticosteroids: Early studies showed a 10-40% response rate; however these studies included
other idiopathic interstitial pneumonias. Steroids do not appear to stabilize or improve true IPF.
As a result, their use and dosing in the treatment of IPF is very controversial. Many practitioners
still prescribe a course of prednisone (3-6 months) and monitor for response.
 Cytotoxic agents: No clear evidence supporting their use, but a 3-6 month trial period of various
agents (cytoxan) may be reasonable.
Antifibrotic Therapy
 Colchicine: Suppresses the release of fibroblast growth factors by macrophages, but clinical
studies do not demonstrate a benefit over placebo.
 Penicillamine: Like colchicine, there does not appear to be a benefit over placebo to
penicillamine, which inhibits collagen cross-linking.
 Pirfenidone: Blocks in vitro growth factor stimulated collagen synthesis, extracellular matrix
secretion, and fibroblast proliferation. Small studies show stabilization of disease, but no larger
trial data available. This agent is not available for clinical use in the U.S.
 Relaxin: Decreases collagen production by fibroblasts and favors collagen matrix breakdown.
Shown to improve PFTs in patients with systemic sclerosis.
 Suramin: Inhibits the effect of many profibrotic growth factors and may be studied for IPF in the
future.
 Endothelin Inhibitor: Found in association with fibroblast foci in lung biopsies. In animal models
inhibition of endothelin-1 prevents pulmonary scarring after lung injury.
 Angiotensin II Inhibitor: Given the fibroblast mitogenic effects of angiotensin II, an inhibitor will
likely be evaluated for use with IPF in the near future.
Immune Modulator Therapy
 Interferon gamma-1b: A Th1 cytokine, interferon gamma may suppress established Th2-type
responses. In one small clinical trial, treatment resulted in small improvements of lung volumes,
gas exchange, and symptoms. The major side effect is an influenza like effect.
Lung Transplantation
 Many patients show improvement after a single-lung transplant
 IPF patients are given 3 month bonus when added to a transplant list.
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