The Coalition for Pulmonary Fibrosis (CPF) has issued the first-ever treatment guidelines for idiopathic pulmonary fibrosis (IPF) based on medical evidence. The guidelines, developed with Cerner Health Insights, were published in the October 2005 issue of the Journal of Sarcoidosis, Vasculitis, & Diffuse Lung Diseases.

An expert panel evaluated existing literature on IPF to produce two basic treatment findings: Anti-inflammatory agents are never appropriate as single agents, and all patients should be referred as early as possible in the course of their disease for lung transplantation. Patients should also be referred for enrollment in a clinical trial. Other treatments, including steroids plus cytotoxics, interferon, and interferon plus steroids, were found to be appropriate for some patients, but not for most.

Lynn Martin

The Food & Drug Administration has not approved any drugs for the treatment of IPF. "There are not any recommended treatments for IPF, as evidenced by the referral to clinical trials for most patients," said pharmacist Lynn Martin, associate director of evidence-based medicine for Cerner Health Insights. "There is no evidence to support any specific treatment because the randomized clinical trials have not been done yet."

IPF is a progressive lung disorder characterized by progressive inflammation and fibrosis of the interstitium, the tissue layer between the alveoli and the circulatory system. Scarring of the interstitial tissues reduces the transport of oxygen, producing dyspnea and other symptoms. About two-thirds of IPF patients die within five years of diagnosis.

CPF president Mark Shreve estimated that about 50,000 Americans have IPF, with 15,000 new cases diagnosed annually. Diagnosis is extremely difficult, he said. IPF is defined largely by the exclusion of other known causes of interstitial lung disease. X-ray or high-resolution computed tomographic images and lung biopsy are usually required to rule out alternative diagnoses.

Not surprisingly, Shreve said, at least 50% of IPF patients have been misdiagnosed during the course of their disease. "Assuming patients are correctly diagnosed, there are several treatment strategies that vary greatly across the country," he said. "There's really no standard of care."

IPF is the most common of about 200 different interstitial lung diseases (ILDs). Some ILDs can be attributed to exposure to asbestos or medications, but IPF has no known causes. It appears to be associated with smoking and exposure to wood or metal dust and may have a genetic component. The condition did not even have consistent diagnostic criteria until 2000. The American Thoracic Society and the European Respiratory Society issued a consensus statement on the diagnosis, evaluation, and management of the disease.

IPF is still known by several terms, which can be confusing to both clinicians and patients. Common confounding terms include cryptogenic fibrosing alveolitis, diffuse fibrosing alveolitis, interstitial diffuse pulmonary fibrosis, and alveolocapillary block.

Nirav Shah

Treatment strategies are just as diverse. Because IPF has an inflammatory element, many clinicians start with anti-inflammatory agents, typically corticosteroids. When steroids fail to halt the progression of the disease, cytotoxic agents such as azathioprine or cyclophosphamide are often added. Some clinicians add antifibrotic agents such as colchicine or D-penicillamine. Interferon gamma-1b (Actimmune, InterMune) has also been used in an attempt to block the cytokine cascade leading to further inflammation. Several randomized prospective clinical trials are under way with gamma-1b, but results are not expected for some time.

The therapeutic logic seems sound for all of these approaches, but there is no evidence that any of the conventional treatments have any effect on progression or long-term survival. The only firm conclusion the expert panel was able to reach is that steroids alone do not work. "There is no evidence at all that steroids work as a single agent," said lead author Nirav Shah, M.D., MPH, assistant professor of medicine at New York University School of Medicine.

The overall prognosis of IPF remains poor, although patients in the earlier stages may see slowed progression of their disease with steroids plus cytotoxics. Azathioprine is generally preferred to cyclophosphamide because of comparative side-effect profiles.

The guidelines will be on the CPF Web site, www.coalitionforpf.org, during the first quarter of 2006.