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Idiopathic pulmonary fibrosis (IPF) is a devastating illness for which there is no known cause or cure. It creeps up on its victims and slowly robs them of their ability to breathe.
Although relatively rare, affecting about 50,000 people in the United States, IPF is on the rise. Recent studies show that the disease is 5 to 10 times more prevalent than previously thought, occurring more often among men than women.
IPF's insidious nature and similarities to other diseases marked by inflammation and scarring of the lungs make it one of the most difficult pulmonary diseases to diagnose and manage. This is complicated by a lack of awareness and understanding of the disease. Once diagnosed, patients typically have only a few years to live.
Fortunately, recent advances in the understanding of the cellular and molecular biology underlying fibrotic lung diseases including IPF are leading to more targeted interventions that could improve a patient's quality of life and survival. A better understanding of IPF's development may result in promising new approaches to treatment.
The purpose of this guide is to help increase awareness of IPF and to serve as a resource for journalists who are interested in the disease. Guidelines for diagnosis and management, current research and clinical studies are also included.
This guide was developed by the Coalition for Pulmonary Fibrosis, a national alliance of patients, physicians, medical professionals and organizations working toward advancing better diagnosis, understanding and treatment of pulmonary fibrosis. We hope you find the guide to be a valuable resource and encourage you to contact us if you are interested in pursuing coverage of IPF or would like to speak with physicians or patients. The guide is also accessible through the Coalition for Pulmonary Fibrosis Web site at www.coalitionforpf.org.
Sincerely,
Marvin I. Schwarz, MD
Chairman, CPF &
James C. Campbell Professor of Pulmonary Medicine
Head, Division of Pulmonary Sciences and Critical Care Medicine
University of Colorado Health Sciences Center (Denver, CO)
Definition and Characteristics of IPF
Idiopathic pulmonary fibrosis (IPF) is a chronic and generally fatal interstitial lung disorder. IPF is one of about 200 disorders called interstitial lung diseases (ILDs), so named because they involve inflammation and scarring of the interstitium or tissue layer between the air sacs (alveoli) of the lung and the blood vessels.
IPF is characterized by scarring that thickens and stiffens the interstitium, causing an irreversible loss of the tissues' ability to transport oxygen. Patients with IPF typically experience shortness of breath and a dry cough, which become progressively worse and debilitating.
Many ILDs have known causes such as exposure to asbestos or certain medications. However, the cause of IPF is unknown, hence the term idiopathic, which means "arising spontaneously from an obscure or unknown cause."
More specifically, IPF is defined as a specific form of chronic fibrosing interstitial pneumonia limited to the lung. A critical step in making a definitive diagnosis of IPF is the microscopic assessment of tissue obtained by a lung biopsy. Physicians look for specific changes in lung tissue that indicate a condition called usual interstitial pneumonia (UIP). The hallmark of UIP is alternating areas of normal tissue, interstitial inflammation, fibrosis and "honeycombing"-abnormal holes in the lungs. If present, UIP strongly points to a diagnosis of IPF (see Diagnosis).
 In 2000, the medical community issued an international consensus statement defining the diagnosis, evaluation, and management of patients with IPF. Prior to that, other diseases with similar symptoms were often called IPF, despite widely varying prognoses. This created confusion among patients and the medical community, and interfered with effective treatment.
Accurate diagnosis is critical because of the widely varying prognoses among other ILDs. In contrast to most other interstitial pneumonias, about two thirds of IPF patients die within five years.
Epidemiology
Determining precise numbers of people afflicted with IPF has been difficult until recently due to the lack of standard diagnostic criteria and terminology (see Terminology). However, an estimated 50,000 people in the United States have IPF with an estimated 15,000 new cases (five cases for every 100,000 people) expected each year.
Earlier estimates for IPF varied from three to six cases per 100,000 individuals. A more recent study of interstitial lung disease in Bernalillo County, N.M., showed the prevalence of IPF was 5 to 10 times higher than previously thought, with 20.2 cases per 100,000 men and 13.2 cases per 100,000 women.
 Males tend to present at a later state of disease progression than women, and typically present with more visible signs such as chest X-ray abnormalities and finger clubbing (enlargement of the fingertips). Women tend to present with more subjective complaints such as shortness of breath. Death rates for both men and women with IPF have increased over the past 10 years, with the mortality rate per 100,000 estimated to be 3.3 for males and 2.5 for women.
Patients are typically between 50 and 70 years old when diagnosed with IPF. Approximately two-thirds of patients with IPF are over the age of 60 at the time the disease arises, with the average age at diagnosis of 66 years.
Symptoms
IPF, as with other interstitial lung diseases, affects each person differently and at different rates. Typical early symptoms of IPF include shortness of breath (dyspnea) during periods of activity and a dry cough. Other possible symptoms include weight loss and fatigue. With later-stage IPF, enlargement or clubbing of the fingertips may develop.
As the disease progresses, dyspnea in some patients may occur at rest, making even normal activities such as walking, talking on the phone and eating difficult.
Virtually all IPF patients have an abnormal chest X-ray or high-resolution computed tomography (CT) scan. A "Velcro-like" crackling noise can be heard in their lungs when they breathe.
Terminology
IPF is known by a number of other names, causing confusion for patients and physicians alike. Other terms for idiopathic pulmonary fibrosis include:
- Cryptogenic fibrosing alveolitis
- Diffuse fibrosing alveolitis
- Hamman-Rich syndrome
- Interstitial diffuse pulmonary fibrosis
- Usual interstitial pneumonia
- Alveolocapillary block
With the publication of an International Consensus Statement in 2000 by the American Thoracic Society and the European Respiratory Society, in collaboration with the American College of Chest Physicians, it is hoped that use of the IPF label will become more universal.
Diagnosis
Until recently, there was no standard for the diagnosis of IPF. Consequently, other diseases involving inflammation and pulmonary fibrosis may have been called IPF if a cause could not be determined.
IPF is now recognized as a distinct clinical entity. In 2000, the American Thoracic Society and the European Respiratory Society, in collaboration with the American College of Chest Physicians, published an International Consensus Statement with a revised definition of IPF that also addresses its diagnosis and management (see Definition and Characteristics of IPF).
Diagnosis of IPF is a "diagnosis of exclusion." In other words, other known causes of interstitial lung disease—such as environmental and occupational factors, legal and illegal drug use, arthritis, etc.—must first be ruled out. To exclude these other diseases that could mimic IPF, physicians must take a complete patient history, perform a thorough physical examination, assess pulmonary function, and examine chest X-rays and high-resolution computed tomographic images. Lung biopsy, with or without bronchoalveolar lavage (a "lung washing" technique used for the examination of cells and proteins from inside the lung), is frequently required to rule out alternative diagnoses.
For IPF to be diagnosed correctly, the guidelines provide major diagnostic criteria-all four of which must be present-and four minor criteria, three of which when present increase the likelihood that the patient has IPF (see Table below). The guidelines emphasize the need for a surgical lung biopsy because it provides the best evidence for distinguishing UIP from other forms of interstitial pneumonia. UIP is the pathological hallmark essential to the diagnosis of IPF.
The diagnosis of IPF requires a high index of suspicion and a thorough and exhaustive history in order to rule out other diseases whose symptoms may mimic IPF.
Criteria for a Diagnosis of Idiopathic Pulmonary Fibrosis
Major Criteria
- Exclusion of other known causes of interstitial lung disease
- Abnormal pulmonary function studies that include evidence of restriction and impaired gas exchange
- Specific abnormalities on high-resolution computed tomography scans
- Lung biopsy specimen or bronchoalveolar lavage fluid showing no features to support an alternative diagnosis
Minor Criteria
- More than 50 years old
- Insidious onset of unexplained dyspnea on exertion
- Duration of illness greater than three months
- "Velcro" crackling sound heard in lungs during breathing
Potential Risk Factors
Although there is no known cause of IPF, the following risk factors for the disease have been identified:
- Cigarette smoking
- Occupational exposure to wood or metal dust
- Other family members with pulmonary fibrosis
Hereditary factors may contribute to the risk of developing IPF. Familial pulmonary fibrosis (FPF) is a form of pulmonary fibrosis that appears to run in families rather than occurring randomly. A study underway at Duke University Medical Center is seeking to find the cause of FPF. Specifically, it will attempt to determine if certain genes are associated with the development of pulmonary fibrosis.
Disease Progression and Patient Prognosis
Many patients, particularly in the early stages of the disease, can continue to go about their normal activities. Some respond to anti-inflammatory treatment (corticosteroids), and their loss of lung capacity may be slowed.
Physicians often recommend that patients follow the usual measures for maintaining health such as eating a healthy diet, maintaining proper weight, exercising regularly and getting enough rest. Patients who are smokers are advised to quit smoking.
Although the prognosis for IPF patients remains poor, a variety of factors can help physicians determine the risk of disease progression and effectiveness of treatment. For example, there is a clear relationship between age and prognosis. The median survival of a 70-year-old diagnosed with IPF is less than two years while that of a 50-year-old patient is more than five years.
Factors Indicating a Poorer Prognosis
- Male gender, although recent information indicates the effect may be small
- More severe dyspnea (shortness of breath)
- Certain features of a patient's X-ray or high-resolution computed tomographic scan, or the presence of "honeycombing"
- Oxygen-deficient blood (hypoxemia) at rest at the time of presentation
- Various abnormalities in the bronchoalveolar lavage fluid
Treatment and Management
There are currently no effective treatments to extend patients' lives, nor is there a cure for IPF. The rarity of the disease, the difficulty of diagnosis, and the mystery surrounding its cause have been significant obstacles in developing an effective therapy.
Treatment for the disease is based on the concept that inflammation in the lung leads to fibrosis. Patients typically are treated with anti-inflammatory drugs, including corticosteroids and cytotoxic agents (e.g. azathioprine and cyclophosphamide). This approach has remained essentially unchanged for the past 30 years despite the fact that it has demonstrated little impact on long-term patient survival. In addition, it can be difficult for physicians to objectively determine the effectiveness of ongoing treatments.
Some patients may need supplemental oxygen to help reduce breathlessness and allow the patient to be more active. Lung transplantation is recommended for consideration for patients with severe functional impairment, dependency on oxygen and continued, rapid deterioration despite optimal medical management if they meet transplantation criteria established by the United Network for Organ Sharing. Successful transplantation frequently alleviates the requirement for supplemental oxygen. It may also increase lung capacity and reverse pulmonary hypertension and other conditions. However, only about half of patients survive more than five years after transplantation.
Pathogenesis
Whatever IPF's cause, it is known that the disease results from a normal tissue repair process gone awry. Normally, inflammation is the body's response to injury, followed by rapid restoration of healthy tissue.
With IPF, inflammation is chronic, and tissue repair is uncontrolled and exaggerated. An imbalance of "cytokines" —biologically active proteins in the body-appears to contribute to pulmonary fibrosis, and current research focuses on trying to regulate cytokines and thereby limit collagen accumulation and scarring. Both of these processes reduce elasticity of the lungs and impair their ability to transfer oxygen to the bloodstream.
Clinical Trials/Research
Researchers are developing and testing a variety of new ways to treat IPF. These approaches target the various steps in the
disease process. Therapies under investigation include:
- Antifibrotic or antifibrogenic agents (such as interferon and certain blood-pressure-lowering medications) to suppress the
scarring process
- Antioxidants (such as N-acetylcysteine and glutathione) to prevent damage to lung tissue
- Monoclonal antibodies to inhibit "bad" cytokines (protein growth factors that activate inflammation)
A promising new approach to treatment involves the cytokine interferon gamma-1b. An advanced clinical trial was recently
completed by InterMune, Inc. (www.intermune.com) to confirm interferon
gamma-1b's effectiveness in slowing or reversing the scarring associated with IPF and in potentially improving lung function
and patient survival. The randomized, double-blind, placebo-controlled Phase III study of 200 micrograms of interferon gamma-1b
administered subcutaneously three times per week was conducted in 330 IPF patients at 58 centers in the United States, Europe and
South Africa. The results continued to support a potential survival benefit for IPF patients. For more information on this trial,
please click here.
Clinical Trials
Clinical trials are being conducted to better understand how pulmonary fibrosis develops and to advance the treatment of IPF. In a
clinical trial, healthcare providers use a new treatment for patients to determine if it is safe and effective. These studies
investigate the effectiveness of vaccines, new drugs, or new ways of using known treatments. A new drug, for example, might be
tested to see if patients live longer than they would without the drug. Not all patients in a clinical trial will receive the new
treatment-often these studies compare patients given the new treatment with patients given a placebo (sugar pill) or standard
treatment. For more information on clinical trials, click here, or ask your physician.
Please note that you do not necessarily need to live in the same city as the principal investigator (the person managing the clinical
trial) in order to participate. Active clinical trials include:
PHASE III CLINICAL TRIALS
- Actimmune (Manufactured by InterMune, Inc.): A randomized double-blind, placebo controlled Phase III trial designed to evaluate the safety and efficacy of Actimmune (interferon gamma-1b) in IPF patients with mild-to-moderate impairment in lung function; the primary endpoint of the trial is survival time. The trial will enroll 600 patients at approximately 70 centers in the United States, Europe and Canada. Patients will be randomized at a ratio of 2:1 to receive either 200 micrograms of interferon gamma-1b three times a week or placebo, respectively. Each patient enrolled will be followed for at least 24 months. For inclusion/exclusion criteria, please click here. For further information, please
visit www.inspiretrial.com, or call 415-466-2200.
PHASE II CLINICAL TRIALS
- Enbrel (etanercept) - Manufactured by Wyeth: A Phase II, Double-Blind, Parallel, Placebo-Controlled, Randomized Study of the Efficacy and Safety of (Enbrel) Etanercept in Patients with IPF. Enbrel is a recombinant human tumor necrosis factor alpha soluble receptor that blocks TNFalpha binding to cell surface receptors and initiation of intracellular signaling. Inhibiting TNF by Enbrel could potentially lead to therapeutic benefit in this disease. The primary endpoint of the trial is to evaluate the safety and efficacy of Enbrel in patients with IPF; the secondary objective is to evaluate quality of life and pharmacokinetics. Approximately 100 subjects at 20 to 25 sites will participate in the trial. Duration is about 80 weeks. Enbrel is given subcutaneously (shot) two times per week Please note that as of 12/31/04 this clinical trial is fully enrolled.
- Gleevec (imatinib mesylate) - Manufactured by Novartis: A phase II, randomized, double blind, placebo-controlled study of the clinical effects of Gleevec (imatinib mesylate) administered orally to patients with idiopathic pulmonary fibrosis (IPF). The primary endpoint is progression of IPF as defined as a greater than 10% decline in the forced vital capacity or death. Study subjects with IPF will be treated initially with Gleevec (imatinib mesylate) 600 mg orally once per day versus placebo for a period of up to 2 years. Sponsor: Novartis, Inc. (www.novartis.com) Patients will be randomized into the trial using an IVR (Interactive Voice Randomization) system. One Hundred patients will be enrolled into the trial in total (50 active drug and 50 placebo). The study population consists of male and female outpatients with IPF ages 20 to 79. Pregnant or breast feeding subjects are not permitted in the trial. For more information on this clinical trial, please contact Chodie Gabor, RN at Tulane University egabor@tulane.edu or 504-585-6966) or
Kathy Mieras, RN at the Mayo Clinic ( mieras.kathleen@mayo.edu or 507-284-9187).
For patient eligibility information, please click here.
- Ventavis (iloprost) - Manufactured by CoTherix, Inc (www.cotherix.com): A Phase II, double-blind, placebo-controlled clinical trial with a primary objective of determining the safety of Ventavis (iloprost) Inhalation Solution in patients with pulmonary hypertension (PH) associated with mild or moderate idiopathic pulmonary fibrosis (IPF). The study will also assess other clinically relevant measures including, the six-minute walk test, NYHA class change and hemodyamic parameters. The study will be conducted in approximately 50 patients at 15 sites in the United States. Ventavis was approved by the Food and Drug Administration in December 2004 for the treatment of pulmonary arterial hypertension (PAH) (World Health Organization Group I) in patients with NYHA Class III or IV symptoms. For additional information, including inclusion/exclusion criteria and clinical trial sites in the United States, please visit www.cotherix.com or call 650-808-6500. Source: CoTherix, Inc. (www.cotherix.com)
PHASE I CLINICAL TRIALS
- GC1008 - Manufactured by Genzyme Corp/Cambridge Antibody Technologies A Phase I clinical trial investigating the safety of GC1008, a fully human monoclonal antibody that neutralizes transforming growth factor beta (TGFb). The trial is currently enrolling patients at several medical centers in the United States. Further information about this clinical trial, including a list of enrolling centers and inclusion and exclusion criteria, may be found at http://www.clinicaltrials.gov/ct/show/NCT00125385
Additionally, the National Institutes of Health (NIH) offers an informative web page for those interested in identifying clinical trials for patients with Rheumatoid Arthritis, Hermansky-Pudlak Syndrome, or pulmonary hypertension where associated pulmonary fibrosis also exists. For further information please visit www.clinicaltrials.gov, and enter 'pulmonary fibrosis' in the "Search Clinical Trials"
Investigational Research
Several ongoing patient-oriented research programs are examining pulmonary fibrosis development and expression. Again, you do
not necessarily need to live in the same city as the principal investigator in order to participate in these programs. Some of
the active research programs include:
- National Health, Lung & Blood Institute Investigational
Research
National Institutes of Health (NIH) Clinical Research Studies: The NIH is currently screening and enrolling pulmonary fibrosis patients in three clinical research studies at the NIH Clinical Center in Bethesda, MD. Patients must be pre-screened to determine if they are eligible to participate in each study. To learn more, please follow the links provided below:
- Texas Tech University Medical Center: Interferon Alpha as a Treatment for IPF : Principal Investigators: Lorenz O. Lutherer,
M.D. Ph.D. and Cynthia A. Jumper, M.D.: Sponsor: State of Texas: A pilot study involving 20 patients to investigate Interferon Alpha as a
Treatment for IPF. The study is taking place at the TUMC Internal Medicine clinics in Amarillo, El Paso, Lubbock, and Odessa. Enrollment
began January 1, 2002. Patients are required to be under the care of , or referred to, a pulmonologist at one of the clinics noted. Please
contact your physician if you are interested in participating in this trial.
- Duke University Medical Center: Genetic factors that may underlie pulmonary fibrosis: Principal Investigator: David Schwartz,
MD, MPH; Sponsor: National Institutes of Health: Co-investigators; M. Steele, M.Wahidi, M. Speer, K. Brown, M. Schwarz, J. Loyd: The study
will attempt to determine if certain genes are associated with the development of pulmonary fibrosis. Family members of people with pulmonary
fibrosis are screened with a questionnaire, chest X-ray and a breathing test to determine if they currently have fibrosis. Everyone is then divided
up into those with fibrosis and those without. A sample of DNA is isolated from a blood specimen. Alternatively, DNA can be obtained from cheek cells
which are obtained with a swab, like a Q-tip, rubbed on the inside of the cheek. Then the DNA from those with fibrosis is compared with the DNA
from those without fibrosis to see if there are any significant differences. Any family with more than one person who has been diagnosed with
pulmonary fibrosis of unknown cause that would be interested in participating in this study is encouraged to contact us toll-free at 877-587-4411
or 919-668-0380.
- Vanderbilt University Medical Center: James E. Loyd, M.D., Professor of Allergy, Pulmonology & Critical Care Medicine at Vanderbilt
University Medical Center is collaborating with David Schwartz, MD (Duke University Medical Center, Durham, N.C.) and Kevin Brown, MD
(National Jewish Medical Center, Denver, CO) to investigate possible genetic factors that could cause IPF. If you live in the Tennessee area
and believe that your family has more than one patient with IPF, please contact Dr. Loyd toll free at (888) 898-1550 to learn more. There is
ongoing recruitment for this study.
- Mechanisms of pulmonary fibrosis and factors that influence prognosis and predict survival in interstitial lung disease (ILD) patients:
National Institutes of Health-sponsored Specialized Centers of Research in diffuse lung disease: National Jewish Medical and Research Center, Denver, CO; University of Michigan, Ann Arbor, MI; and Boston University
Medical Center. This study is no longer accepting patients because patient accrual is complete.
- University of Alabama at Birmingham- Kirklin Clinic: Reactive Nitrogen Species and Glutathione in Lung Biopsy Sections,
Bronchoalveolar Lavage Fluid and Serum Correlate With Disease Activity and Response to Therapy in Patients With Idiopathic Pulmonary
Fibrosis. Investigators will measure nitrite and glutathione, which are markers of inflammation and oxidant stress, in sections of
lung biopsies and fluid obtained from lung washings and serum of patients with idiopathic pulmonary fibrosis. Investigators propose
that these variables predict disease activity and/or response to therapy. Any patient with IPF that undergo bronchoscopy with
bronchoalveolar lavage or lung biopsy (transbronchial or VATS). Fluid and biopsy specimens not utilized for clinical purposes will be saved
and subsequently analyzed. A sample of venous blood is obtained at the same time. For further information, please email ipf@uab.edu
- IFEGENIA: An international study of N-Acetylcysteine (NAC) in IPF patients. Investigators: M. Demedts, J. Behr, U. Costabel, B. Wallaert,
J. Van den Bosch, P.N.R. Dekhuijzen, H.M. Jansen, W. MacNee, R. Buhl, M. Thomeer, L. Licciardello, I. Lankhorst, A. Ardia. Sponsor:
Zambon Group. A prospective double blind placebo-controlled study evaluating up to 150 patients. The trial will investigate the impact of
1800 mg/ daily NAC added to prednisone (0.5 mg/kg/day) and azathioprine (2 mg/kg/day) on VC and DLCO (primary endpoints) and CRP score,
HRCT- score, survival, and health status (secondary endpoints).
- University of Pittsburgh Medical Center:
Identifying new targets for drug therapy and diagnostic microarrays in IPF using genomics technologies: This study carried out the
Simmons Center for Interstitial lung disease aims to identify new disease markers and new targets for therapeutic intervention by applying
advanced genomic, proteomic and bioinformatic methods. We aim to identify all of the genes expressed in the blood or lung of an affected
patient and then determine which could serve as diagnostic markers and which could serve as targets for development of new drugs for IPF.
(Principal Investigator: Naftali Kaminski MD, Co-Investigators: Kevin Gibson, MD James Dauber, MD, Moises Selman MD, Augustine Choi, MD,
Rajiv Dhir, MD, Sam Yousem, Nir Friedman PhD, MD, Hiran Fernando, MD, and James Luketich, MD.)
Exploring the Disease Impact of Idiopathic Pulmonary Fibrosis. The purpose of this study is to describe the prevalence of anxiety,
depression, and sleep disturbances in patients with IPF, and examine relationships between these variables and disease severity, time since
diagnosis, health-related quality of life, and social support. We aim to evaluate for these psychosocial variables and plan to test
interventions to increase quality of life (Principal Investigator: Leslie Hoffman, RN, PhD, Co-Investigators: Kathleen Lindell, MSN, RN,
Kimberly A. Morris, PhD, Fred Tasota, RN, MSN, James Dauber, MD, & Naftali Kaminski, MD)..
- University of Washington Medical Center: Medical treatment for depression in chronic non-reversible pulmonary diseases,
including IPF: Investigators: Soo Borson MD; Julie Fields BA - Neuropsychology; Beth Zuhr - Program Coordinator. A study of an approved
antidepressant medication in patients with chronic non-reversible pulmonary diseases including IPF, emphysema, chronic bronchitis, and COPD.
If you are between 60 and 80 years of age, live in the Seattle area, have a chronic non-reversible pulmonary disease or IPF, and think you may
be suffering from depression, please call 206-790-8514 to learn more about the study. This study is currently accepting patients in the
Seattle area only.
- University of Washington Medical Center; Seattle VA Hospital; Harborview Medical Center: Mood, memory and thinking in the brain of
patients with chronic non-reversible pulmonary diseases, including IPF: Investigators: Soo Borson, MD: A study of mood, memory and thinking
in the brain of patients with chronic non-reversible pulmonary diseases including IPF, emphysema, chronic bronchitis, and COPD. Study will
involve lung function testing and blood testing, tests of memory and problem-solving, and a brain scan. No medications will be used in this
study. If you are between 55 and 80 years of age, live in the Seattle area, have a chronic non-reversible pulmonary disease or IPF, or are
married to someone with one of these conditions, please call 206-685-9453 to learn more about the study. This study is currently accepting
patients in the Seattle area only.
- Minocycline Treatment in Patients with Idiopathic Pulmonary Fibrosis - a Pilot Study (Investigator: Eric Kleerup, M.D and David Zisman, M.D.; Sponsor: UCLA SCOR on the Pathobiology of Pulmonary Fibrosis)
A randomized, double-blind, placebo-controlled study to determine the efficacy and safety of minocycline in patients with Idiopathic Pulmonary Fibrosis (IPF). Minocycline could prevent the overgrowth of small blood vessels (angiogenesis) and delay the progression of idiopathic pulmonary fibrosis (IPF). Randomization will be 1:1 active-to-placebo ratio. Duration of study will be 48 weeks. The INSPIRE Trial: A Study of Interferon gamma-1b for Idiopathic Pulmonary Fibrosis (IPF) (Investigator: David Zisman, M.D; Sponsor: InterMune Pharmaceuticals)
A phase 3, randomized, double-blind, placebo-controlled trial to determine the efficacy and safety of 200 µg of recombinant Interferon gamma-1b administered by subcutaneous (SC) injection, compared with placebo, in patients with IPF. Interferon gamma-1b may improve survival in patients with mild to moderate IPF. Randomization will be 2:1 active-to-placebo ratio. Duration of study will be 2 years active drug or placebo (rescue therapy will be permitted for patients who meet predefined criteria). Efficacy and safety of oral bosentan in patients with Idiopathic Pulmonary Fibrosis (Investigator: David Zisman, M.D; Sponsor: Actelion Pharmaceuticals)
Endothelin-1 (ET-1) is expressed in a variety of pulmonary pathological conditions including pulmonary vascular disease and pulmonary fibrosis. Bosentan (an oral dual ET-1 receptor antagonist) could delay the progression of idiopathic pulmonary fibrosis (IPF), a condition for which no established treatment is available. The present trial investigates a possible use of bosentan, which is currently approved for the treatment of symptoms of pulmonary arterial hypertension (PAH) to a new category of patients suffering from IPF. A Safety and Efficacy Study of Sirolimus in Patients with Idiopathic Pulmonary Fibrosis – a Pilot Study (Investigator: David Zisman, M.D; Sponsor: UCLA SCOR on the Pathobiology of Pulmonary Fibrosis)
The objective of this study is to determine the safety and efficacy of sirolimus compared to placebo on pulmonary function and resting gas exchange in patients with idiopathic pulmonary fibrosis (IPF). Sirolimus could prevent the overgrowth of small blood vessels (angiogenesis) and delay the progression of idiopathic pulmonary fibrosis (IPF). We believe that this drug will result in stabilization or improvement in pulmonary function and/or resting gas exchange over 48 weeks as compared with placebo. The study was designed as a randomized, double-blind, placebo-controlled study of 32 patients. Eligible patients are randomly assigned, in a 1:1 ratio, to receive either sirolimus or placebo daily for 12 months. Sildenafil Treatment in Patients with Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension- a Pilot Study (Investigator: David Zisman, M.D; Sponsor: UCLA SCOR on the Pathobiology of Pulmonary Fibrosis)
The objective of this study is to demonstrate that a single dose of sildenafil improves exercise capacity in patients with idiopathic pulmonary fibrosis (IPF) and pulmonary hypertension. We believe that this drug will result in an increase in distance walked in subjects with IPF and pulmonary hypertension as compared with placebo. This study was designed as a placebo-controlled study of sildenafil and its effect on distance walked, shortness of breath, and blood oxygenation. Eligible patients will be randomly assigned, in a 1:1 ratio, to receive either sildenafil or placebo.
- Tufts University School of Medicine, Boston, MA: Investigator: Regina Day, PhD: Sponsor; American
Lung Association (ALA) Research Grant: Pulmonary fibrosis, or scarring of the lungs, affects some 100,000 people in the U.S.,
but the process by which it develops is not well understood. Previous studies have shown that an agent called bleomycin can induce
fibrosis and that the level of a substance called Protein Tumor Growth Factor Beta 1 (TGF-beta 1) is increased in the lungs of people
and laboratory animals with pulmonary fibrosis. Scientists believe that the increase in TGF-beta 1 is a key step in the development of
pulmonary fibrosis, but are not sure how bleomycin causes it to increase. This research is aimed at identifying the precise changes in
protein activities that occur when cells are treated with bleomycin and gaining a greater understanding of the events leading to increased
TGF-beta 1 production. This knowledge may make it possible to identify treatment approaches that would reduce the levels of TGF-beta 1 and
slow down or stop the deadly progression of pulmonary fibrosis.
- University of Virginia School of Medicine: : Investigator: Richard I. Enelow, MD: Sponsor; American Lung Association (ALA)
Investigator Award: Immune system cells called T lymphocytes infiltrate the lungs in a number of serious lung diseases that are notoriously
difficult to treat, such as sarcoidosis, hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis. The aim of this project is to
understand the mechanisms by which the body's own T cells injure the lungs, particularly a specific type of lung cell called the alveolar
epithelial cell. The researchers are seeking to unravel the chain of events that leads to the amplification of the normal immune processes
by which the body defends itself against foreign invaders. A precise understanding of how this happens might make it possible to interrupt
the sequence of events, halting the undesirable inflammatory cascade without impairing normal immune system responses to viruses or other
agents that cause disease. This would offer new treatment options for several serious lung diseases.
- University of Minnesota Medical School: Investigator: Imad Y. Haddad, MD: Sponsor; American Lung Association (ALA) Investigator Award:
Many individuals who undergo bone marrow transplantation subsequently develop a severe lung injury called Idiopathic Pneumonia Syndrome or IPS.
This problem is dubbed "idiopathic" because its cause is unknown. The researchers hope to gain insight into new treatment strategies for limiting
lung inflammation and injury after bone marrow transplantation by studying the role that substances known as oxidants play in this process.
Transplantation, radiation treatment, and chemotherapy all generate large amounts of oxidants in the lungs. The oxidants damage tissue,
contribute to lung dysfunction, and hinder the normal processes by which lungs repair themselves. This project is using a model of lung
transplantation in laboratory animals to explore how oxidants are formed and how they damage the lungs. The investigators will then study the
effects of supplementing the lungs with anti-oxidants to see whether this can prevent lung injury and inflammation.
- Johns Hopkins University School of Medicine: Investigator: Maureen Horton, MD: Sponsor; American Lung Association (ALA) Research Grant:
Scarring of the lungs is the end result of chronic, unremitting inflammation and a major cause of death due to lung disease. In many cases,
neither the initial cause of the inflammatory process or the precise factors that drive the chronic response are known, and most people with
this condition die of respiratory failure within five years regardless of treatment. The aim of this research is to elucidate the molecular
mechanisms that cause pulmonary fibrosis, which could point the way to improved treatment strategies. The investigators are studying a
substance called hyaluronan that induces the expression of chemokines, chemical messengers that are important mediators of chronic inflammation
and fibrosis. Another substance, interferon-g, regulates the expression of chemokines. The researchers hypothesize that hyaluronan plays an
active role in the inflammatory response and the nature of the response that is modulated by regulatory substances such as interferon-g. Understanding
precisely how this takes place could make it possible to intervene and prevent or halt fibrosis.
- Ohio State University: Investigator: Clay Braden Marsh, MD: Sponsor; American Lung Association (ALA) Investigator Award: Pulmonary
fibrosis, or scarring of the lungs, is a devastating and progressive disease that occurs when cells called macrophages accumulate in the lungs.
Macrophages are derivatives of circulating blood cells, and need specific substances called growth factors in order to mature. The body's normal
mechanisms preventing this are apparently circumvented in pulmonary fibrosis, but the mechanism stimulating the macrophages to survive remains unknown.
This project is focusing on understanding how a protein called SHP-1 works to suppress the accumulation of macrophages in the lungs of
laboratory animals. The knowledge gained by these studies at the molecular level will be useful in creating safe and effective treatment for people
with pulmonary fibrosis of unknown origin.
- The Johns Hopkins University School of Medicine: Investigator: Albert Polito, MD: Sponsor; American Lung Association (ALA) Research
Scholar Award: Idiopathic Pulmonary Fibrosis (IPF) is a deadly disease of unknown cause that usually affects middle-aged people, who see a
doctor because they feel increasingly breathless. The disease causes scarring and stiffening of the lungs, impairing their ability to deliver
oxygen to the bloodstream. It is treated with steroids and other drugs that suppress the immune system, but only a small percentage of patients
show any response to treatment. Most people with IPF become progressively worse and also experience significant side effects from their medication,
surviving an average of three to five years. Lung function tests are usually used to study the progress of the disease and the response to treatment,
but they do not always reflect how the patient feels. For example, the test may show no change in lung function, but the patient is experiencing
increasing difficulty performing daily chores. This project is developing a questionnaire for patients and will report on their sense of how their
health and quality of life are being affected. This will help physicians understand the impact of the disease and its treatment and be useful in
evaluating new treatments for IPF.
- University of Rochester School of Medicine and Dentistry: Investigator: Patricia Sime, MBChB: Sponsor; American Lung Association (ALA)
Research Scholar Award: Lung scarring can be due to a number of causes, including inhaling silica, coal, or asbestos dusts, radiation therapy
for lung cancer, rheumatoid arthritis, asthma, and idiopathic pulmonary fibrosis (lung scarring of unknown cause). The air spaces in the lungs
become filled with scar tissue, and the result is breathlessness and possibly lung failure and death. There is no effective treatment, and the
mechanisms that bring about this condition are poorly understood. One common theme, however, is that a protein called Transforming Growth Factor
Beta (TGFb) is typically elevated in fibrotic lungs. When placed directly in the lung, this molecule causes fibrosis similar to that, which occurs
after inhaling silica dust. This project is examining the role of TGFb in silica-induced lung fibrosis and seeking ways to block its function. Gene
therapy techniques are being used to introduce inhibitor molecules called decorin and latency-associated peptide directly into the lungs of
laboratory animals to block the action of TGFb and thus prevent fibrosis. This approach may offer a novel treatment for people with silicosis
and other disorders involving lung fibrosis.
- University of Miami, Jackson Memorial Medical Center: Investigator: Marilyn K. Glassberg, M.D., Sharon Elliot, Ph.D., Michael Karl, M.D.
Cigarette smoke-induced pulmonary fibrosis. Investigators interested in developing a spontaneous model of early IPF. Based on epidemiological
data indicating that cigarette smoke is a major risk factor for the development of IPF, this group of investigators propose that cigarette smoke
alters the extracellular matrix and leads to indolent, yet progressive pulmonary fibrosis. These studies will define the role of key proteins in
the extracellular matrix and will lead to the development of new therapies in the treatment of IPF.
University of Califonia - San Francisco:
UCSF is currently enrolling patients in:
BUILD1; Bosentan Use in Interstitial Lung Disease: A double-blind, randomized, placebo-controlled,
multicenter study to assess the safety, efficacy, and tolerability of bosentan in patients with
idiopathic pulmonary fibrosis (Sponsor: Actelion); Primary Investigator: Jeffrey A Golden, MD
GIPF-007: A Randomized, Double-Blind, Placebo-Controlled Phase III Study of the Safety and Efficacy
of Interferon-y-1b in Patients with Idiopathic Pulmonary Fibrosis (INSPIRE)
Sponsor: InterMune Primary Investigator: Paul J Wolters, MD; Coordinator: Michele DesMarais,
415 353 2060 (phone) 415 353 2674 (fax)
The location for both trials is:
UCSF
400 Parnassus Avenue, Room A580
San Francisco CA 94143-0359
Please contact Michele DesMarais at 415-353-2060 for further information on either trial.
In addition, our transplant program is available to IPF patients. (Age eligibility
determinations are made on a case by case basis.)
Our physicians see IPF patients in our Interstitial Lung Disease Clinic on Friday mornings (400
Parnassus Ave, 5th Floor Chest Clinic). This clinic includes the practices of Doctors:
- Ken Fang, MD
- Michelle Freemer, MD
- Jeffrey A. Golden, MD
- Laura Koth, MD
- Talmadge King, MD
- Nadia Tchao, MD
- Paul J Wolters, MD
Appointments for this clinic can be made by calling 415 353 2961.
Patients visits are most productive when they are able to bring the following items with them to their
appointment (or make them available to the clinic in advance):
- Clinical records - clinic visits and hospitalizations
- Referring physician information - telephone and fax numbers, and mailing address
- Chest X-rays - current and past films to enable comparisons
- Chest CT scans - current and prior studies to enable comparisons (if possible we would prefer
copies of radiographs on film or CD so that we can retain)
- Laboratory studies - all blood tests, serologies, microbiologic cultures
- Pulmonary function tests - all current and prior results of PFTs and spirometry
- Bronchoscopy reports - results of bronchoalveolar lavage (BAL) and biopsies
- Lung biopsy tissues slides and report: if possible we would prefer that the pathology
department send several slides that we can retain)
- Echocardiograms - all reports
- Ventilation-Perfusion (V/Q) scans - original films and reports
Resources
A number of nonprofit health care associations and patient advocacy groups provide information on IPF and other chronic lung diseases, and support resources for patients and their families.
Current CPF Offerings
To order free copies of any of these publications, click here.
You must have Adobe® Acrobat® ReaderTM to download these files. For a free copy of
Adobe Acrobat, click here.
Web Sites
Medical Associations/Societies
American Association of Cardiovascular and Pulmonary Rehabilitation
www.aacvpr.org
American College of Chest Physicians
www.chestnet.org
American Thoracic Society (ATS)
www.thoracic.org
Government Agencies
National Heart, Lung, and Blood Institute (NHLBI)
www.nhlbi.nih.gov
National Institutes of Health (Medline)
www.nlm.nih.gov/medlineplus/pulmonaryfibrosis.html (pulmonary fibrosis information)
National Library of Medicine
www.nlm.nih.gov/medlineplus/druginformation.html (drug information)
Clinical Study Results - Voluntary database of clinical trial results
www.clinicalstudyresults.org
Food and Drug Administration (FDA)
www.fda.gov
Research and Education Institutions
Centerwatch - www.centerwatch.com - An international listing of clinical research trials, and physicians and medical centers performing clinical research
University of Alabama at Birmingham
http://www.health.uab.edu/ (search for "IPF")
Univ. Colorado Health Sciences Center- Dept. of Pulmonary & Critical Care Medicine
http://www.coloradopulmonarycriticalcare.org/
Duke University
www.fpf.duke.edu
Emory Center for the Treatment and Study of Interstitial Lung Disease
http://www.emoryhealthcare.org/departments/lung/index.html
Inova Fairfax Hospital
www.inova.org/inovapublic.srt/ifh/index.jsp
University of Iowa (Virtual Hospital)
www.vh.org/adult/patient/internalmedicine/interstitiallung/index.html
Univ. of Miami Medical Center Dept. of Pulmonary & Critical Care Medicine
http://www.med.miami.edu/med/pulmonarymed/
National Jewish Medical and Research Center
www.njc.org/diseases/dt10.html
University of Pennsylvania Medical Center- Lung Center
http://www.uphs.upenn.edu/lungctr/
University of Pittsburgh Medical Center
http://ipf.upmc.com
UC-San Francisco/San Francisco General Hospital
http://www.ucsf.edu
Univ. of Washington Dept. of Pulmonary & Critical Care Medicine
http://depts.washington.edu/pulmcc/
University of Minnesota Center for Advanced Lung Disease
http://www.cald.umn.edu/
Patient Education and Support Organizations
American Lung Association
www.lungusa.org/diseases/pulmfibrosis.html
American Lung Association of California
www.californialung.org
Breathin' Easy
http://www.oxygen4travel.com/
Chronic Lung Disease Forum
www.cheshire-med.com/programs/pulrehab/forum/cldforum.html
Dynamics in Healthcare (IPF section)
www.epler.com
Huff 'n Puff Online Lung Disease Forum
http://www.huff-n-puff.net/newforum/
MDLinx.com
http://www.pulmonologylinx.com
Needy Meds.com
www.needymeds.com
The Pulmonary Paper
www.pulmonarypaper.org
Young Lung Online Support
Online Support: www.geocities.com/younglungz
Email Group: www.topica.com/lists/younglung
Other lung health organizations also have chapters and groups that support patients with IPF. Click here to request information on support services that may be available for IPF patients in your community, or call us at (888) 222-8541.
Resources for Patient Assistance RX Programs and Discount Card Programs
BenefitsCheckUp
www.benefitsCheckUp.org
Free, online screening tool to more than 240 RX saving programs.
Volunteers in Health Care:
(877) 844-8442
Guide to Patient Assistance Programs.
NeedyMeds:
www.needymeds.com
Directory of Patient Assistance Programs
Pharmaceutical Research and Manufacturers of America (PhRMA):
www.Phrma.org
Directory of Patient Assistance Programs
RxHope:
www.rxhope.org
Information and application forms for Patient Assistance Programs.
Health Resources and Services:
(888) ASH-HRSA (888) 275-4722
Referral source for community health centers that may offer RX assistance.
Local Area Agencies on Aging:
www.eldercare.gov or (800) 677-1116.
Provides assistance to patients 65 and older.
Finding a Doctor
American Medical Association (AMA Physician Select)
www.ama-assn.org
Lung Transplant Information and Support
Second Wind Lung Transplant Association
www.2ndwind.org
United Network for Organ Sharing (UNOS)
www.unos.org
Caregiver Support Organizations
Caregiving.com
www.caregiving.com
Well Spouse Foundation
www.wellspouse.org
Inova Fairfax Hospital
http://www.inova.org/inovapublic.srt/transplant/index.jsp
End-of-Life Support Organizations
Aging With Dignity
www.agingwithdignity.org
American Hospice and Palliative Care Organization
www.nhpo.org
Patient Assistance for Medical Air Transportation
National Patient Travel Center
www.patienttravel.org - or 800-296-1217
Nonprofit organization assisting financially-needy patients with financial assistance to travel for specialized medical evaluations, diagnosis or treatment that may require medical air transportation. 24-hour toll free 800-296-1217.
Glossary
- Alveoli
- Very small air sacs found in the lungs. Click here to see how the alveolar tissue changes with IPF.
- Antifibrotic/antifibrogenic agents
- Experimental medications used to suppress the scarring process associated with IPF.
- Antioxidants
- Experimental medications that may prevent or reverse lung tissue damage caused by IPF.
- Azathioprine
- A medication commonly prescribed for IPF patients that can suppress the activity of the immune system and reduce inflammation.
- Bronchoalveolar lavage (BAL)
- A diagnostic technique in which fluid is instilled into the lungs and removed for examination.
- Clubbing
- A buildup of tissue in the fingertips (or sometimes the toes). Clubbing is a sign of advanced IPF. Click here to see what clubbing looks like.
- Collagen
- Proteins found in tendons, bones, and connective tissue. Scar tissue found in the lungs of patients with IPF also contains collagen.
- Computed tomography (CT or CAT scan) or high-resolution computed tomography (HRCT)
- A type of x-ray for which a computer is used to construct a three-dimensional image from a series of cross-sectional images. The procedure generates multiple pictures of your lungs in layers (slices) from the top (at your shoulders) to the bottom (just above your waist). This test requires that you lie on a table while the pictures are taken, holding your breath and letting it out as instructed.
- Corticosteroids
- Medications used to suppress the activity of the immune system and reduce inflammation. The most commonly prescribed corticosteroid is prednisone.
- Cyclophosphamide
- A medication commonly prescribed for IPF patients that can suppress the activity of the immune system and reduce inflammation.
- Cytokines
- Molecules produced by the immune system. A cytokine imbalance may be the cause of IPF.
- Dyspnea
- Shortness of breath or labored breathing, usually associated with physical exertion.
- Epidemiology
- The incidence, distribution, and control of a disease in a population.
- Etiology
- The cause(s) of a disease.
- Familial
- Tending to occur in more members of a family than would be expected by chance alone.
- Fibrosis
- An abnormal scarring of body tissue.
- Histopathology
- Tissue changes (e.g., scarring of the lungs) that accompany a disease and are recognized by microscopic examination.
- Hypertension
- High blood pressure.
- Hypoxemia
- A lack of oxygen in the blood.
- Hypoxia
- A lack of oxygen in the tissues of the body.
- Idiopathic
- Arising spontaneously or from an obscure or unknown cause.
- Idiopathic pulmonary fibrosis (IPF)
- A disease characterized by progressive scarring (fibrosis) and deterioration of the lungs.
- Interferon gamma-1b
- A regulatory cytokine that has antifibrotic and
antifibrogenic effects and may regulate macrophage, fibroblast, and mast
cell function; inhibit a variety of neutrophil-derived cytokines; and modify
the balance of Th1 and Th2 cells in the lung.
- Interstitial lung disease (ILD)
- A general term for the approximately 200 disorders characterized by inflammation and scarring (fibrosis) of the lungs' interstitium. IPF is an example of an interstitial lung disease.
- Interstitium
- The tissue layers between the lungs' air sacs (alveoli) and blood vessels.
- Lung biopsy
- A procedure in which a tissue sample is obtained through a flexible tube or by means of a small surgical incision between the ribs.
- Lung transplant
- Replacement of a lung or lungs with donor organ(s).
- Monoclonal antibodies
- Experimental medications for the treatment of IPF. They may inhibit "bad" cytokines.
- Pathogenesis
- The mode of origin or development of a disease.
- Pathology
- The abnormalities that characterize a particular disease.
- Phase I trial
- The first phase of drug testing in humans. It usually involves 20 to 100 subjects and focuses on safety.
- Phase II trial
- The second phase of drug testing in humans. It involves up to several hundred patients, lasts as long as two years, and focuses on safety and effectiveness.
- Phase III trial
- The third phase of drug testing in humans. It involves several hundred to several thousand patients, often lasts several years, and focuses on safety, dosage, and effectiveness.
- Prednisone
- The most commonly prescribed therapy for IPF. Prednisone is a corticosteroid that can suppress the activity of the immune system and reduce inflammation.
- Prognosis
- The prospect for survival and recovery from a disease.
- Pulmonary
- Having to do with the lungs.
- Pulmonary embolism
- A blood clot in the lungs.
- Pulmonary fibrosis
- Thickening and scarring of the lungs, specifically the pulmonary interstitium.
- Pulmonary hypertension
- High blood pressure in the lungs.
- Usual interstitial pneumonia (UIP)
- A condition indicated by specific changes in the lung tissue. Finding UIP in a lung biopsy strongly points to a diagnosis of IPF (although other criteria must be met).
Consultants:
Talmadge E. King Jr., MD
Member, Board of Directors
Chairman, Scientific Advisory Committee
Coalition for Pulmonary Fibrosis
Teresa Barnes
Member, Board of Directors
Coalition for Pulmonary Fibrosis
References Used to Create the coalitionforprf.org Web Site
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