According to the National Institutes for Health (NIH), IPF is a condition in which over a period of time the lung tissue becomes thickened, stiff, and scarred. The development of the scar tissue is called fibrosis. As the lung tissue becomes scarred and thicker, the lungs lose their ability to transfer oxygen into the bloodstream. As a result, the brain and other organs don't get the oxygen they need. In some cases, doctors can determine the cause of the fibrosis, but in most cases, there is not a known cause. When there is no known etiology for the fibrosis (and certain pathologic criteria are met) the disease is called idiopathic pulmonary fibrosis or IPF. IPF affects approximately 200,000 Americans and an estimated 40,000 Americans pass away from IPF each year.
There are more than 100 related diseases of the lung known as interstitial lung diseases (ILD). ILD can also be referred to as usual interstitial pneumonia (UIP), or diffuse parencyhmal lung diseases (DPLD). These diseases can often have similar characteristics to IPF and most result in lung scarring. Further, IPF belongs to a subgroup of ILD called idiopathic interstitial pneumonias (IIP). IIP is further broken down into a number of pathological subtypes. The pathological pattern seen in IPF is referred to as usual interstitial pneumonia (UIP). There are a number of other subtypes of IIP. Two of the more common subtypes are nonspecific interstitial pneumonia (NSIP) and acute interstitial pneumonia (AIP).
Although this ‘alphabet’ soup is rather confusing and complicated, it is important for doctors to differentiate the cause and pattern of fibrotic disease, since standards of care and prognosis can vary. IPF is the most common of the all ILD and IIP. One recent study estimated thg prevalence of all interstitial lung diseases in the United States at about 500,000.
The origin (e.g. epidemiology) and development (e.g. pathogenesis) of IPF is still not completely understood. The current thinking is that there is an abnormal fibrotic and inflammatory response to microscopic injury which ultimately results in pathological scarring. There are also epidemiological and genetic factors that may contribute to the development of IPF, and as these are more clearly defined, the disease process should be better understood. Ultimately, this will lead to new pathways to treat the disease.
Epidemiological Factors: There are certain environmental or occupational exposures that seem to be prevalent in the medical histories of patients diagnosed with the disease, and as a result doctors may cite these exposures as contributing factors to a diagnosis of IPF. (If there is a clear causal relationship, which is uncommon, then the disease would no longer be considered IPF). These exposures may include the following:
Cigarette smoking Prolonged exposure to occupational or environmental contaminants or dusts (inorganic dusts such as asbestos, silica, beryllium and hard metal dusts; organic dusts such as such as bacteria and animal proteins) Viral or bacterial lung infections Certain medicines such as antibiotics (Nitrofurantoin, Sulfasalazine), antiarrythmics (Amiodarone, Propranolol), anticonvulsants (Phenytoin), chemotherapeutic agents (Methotrexate, Bleomycin, Oxaliplatin, Erbital) and therapeutic radiation. Acid reflux disease (GERD) In addition, IPF may be associated with upper respiratory infections such as pneumonia and tuberculosis. The specific connection between IPF and these diseases remains largely unknown.
Interstitial lung diseases (ILD) have also been associated with connective tissue diseases including rheumatoid arthritis, scleroderma, lupus, sarcoidosis.
Genetics and IPF: There is a growing body of clinical evidence suggesting that a gene or family of genes may predispose certain patients to IPF. In fact 10-15% of cases seem to be directly attributable to a genetic cause. Recent studies have found a mutation in the SP-C protein that exists in families with a history of more than 2 cases of IPF. Another recent study suggested that the presence of specific genes may predict which IPF patients will have a more severe, rapidly progressing form of the disease. Yet another recent study showed that shortened telomeres (which protect the fragile ends of chromosomes, and protect the end of the chromosome from deterioration) may be the cause of PF in certain patients as they grow older.
There is limited availability of genetic testing to identify genes that may contribute to IPF. In the absence of published findings, specifically identifying a gene or genes that are markers for IPF, patients should exercise great caution, and discuss with their physician, the benefits and risks of genetic testing.
Symptoms and diagnosis
Symptoms aren’t always present when the disease starts and may not be present until the disease has progressed. The main symptom is shortness of breath, also known as dyspnea. Many patients describe it as a feeling of “breathlessness.” Many individuals, especially older patients, often ignore the occasional difficulty with breathing, attributing it to just “getting older” or “being out of shape.” As the condition progresses and the damage to the lungs become more severe, breathlessness may occur with minor physical activity such as showering, getting dressed. Speaking on the phone and eating becomes more difficult and sometimes nearly impossible. Other common symptoms include:
Chronic dry, hacking cough Fatigue and weakness Discomfort in the chest Loss of appetite Rapid weight loss
Physicians will use a variety of diagnostic strategies to come to a diagnosis of IPF depending on the individual medical history and symptoms that patients present with. These usually include one or more of the following tests:
History and Physical Exam: The physician should take a detailed history to learn if there were any environmental, occupational, familial, or other medical conditions that could have contributed or predisposed a person to the diseases’ development. When listening to the lungs with a stethoscope, the physician may hear ‘crackles’ or Velcro-like sounds with the stethoscope. These are ‘opening’ sounds made by the small airways during inspiration. About 50% of patients with IPF may have “clubbing” of the fingertips. This is a widening of the fingertips due to a lack of oxygen in the blood. This is not specific to IPF and occurs in other lung disorders, heart disease, and can also be present from birth.
Chest X-Ray: A routine chest x-ray may be used as a screening test. However, 5-15% of patients with significant scarring will have a normal chest x-ray, and IPF cannot be diagnosed from chest x-ray alone.
High Resolution Computerized Tomography (HRCT): This test provides sharper and detailed image of your lungs to help a physician more clearly identify certain clinical patterns in your lung tissue that may indicate disease; in IPF, a radiologist may identify a “honeycombing” pattern that suggests lung scarring and damage to the air sacs, or “ground-glass opacity”, which refers to the hazy appearance of lung tissue that is most associated with inflammation.
Pulmonary Function Tests: These are breathing tests that measure the lungs’ ability to exchange oxygen and carbon dioxide properly. These tests are usually done in a hospital or clinical laboratory and consist of breathing into a spirometer, and are sometimes done in a “body box” which looks like a glass telephone booth. There are two important components to a Pulmonary Function Test: (1) Spirometry, which measure inspired and expired lung volumes and the rate at which this occurs, and diffusion capacity, or DLco, which measures the ability of oxygen to diffuse into the blood stream.
Pulse Oximeter: This is a screening test which indicates the amount of oxygen in the blood. A device is placed on the finger or earlobe. The oximeter transmits light at different wavelengths through small blood vessels. Normal ranges are 95-100% on room air. Pulse oximetry does not measure carbon dioxide levels so a blood gas level measurement may be necessary in some patients.
Arterial Blood Gas (ABG): A direct measurement of arterial pH, oxygen, and carbon dioxide through a direct arterial puncture. Arterial blood has recently been oxygenated by the lungs and thus indicates how much oxygen is available to the body. Venous blood has a lower oxygen concentration and indicates how much oxygen has been extracted.
Bronchoscopy: This involves an examination of the main airways of the lungs through the use of a small, flexible tube called a bronchoscope. Brochoscopy helps to evaluate lung problems or blockages and provides a means to sample tissue or fluids. Unfortunately, the lung tissue samples obtained through bronchoscopy are small and are usually inadequate for definitive diagnoses.
Bronchoalveolar lavage (BAL): BAL is done through the bronchoscope and is a way to remove a tiny sampling of cells from the lower respiratory tract. A small amount of saline is injected through the bronchoscope and when withdrawn removes a small sample of cells from the respiratory tract. Usually this is not helpful in making the diagnosis of IPF but may beneficial in other clinical situations.
Surgical Lung Biopsy: Surgical lung biopsy is the most revealing diagnostic tool in the evaluation of patients suspected of having idiopathic pulmonary fibrosis and is considered the “gold standard.” Since there are many diseases that mimic IPF, and since there can be significant differences in the treatment and prognosis, it is important to get a correct diagnosis. A lung biopsy in conjunction with the HRCT can also help determine how far the disease has progressed. Usually the biopsy can be obtained minimally invasively with video assisted thoracoscopic surgery (VATS). VATS is usually well tolerated, but it may not be recommended for all individuals.
Exercise testing: Typically performed with a six-minute walk test (6MWT), exercise testing is used to measure how well the lungs respond to exertion. The methods used for exercise testing vary from hospital to hospital, but usually include the use of a stationary bike or treadmill. Blood pressure, EKG and oxygen saturation levels (recorded by an electronic device placed on the ear or finger) are monitored during exercise.
There is a lack of newly published data to demonstrate an accurate estimate for the incidence of pulmonary fibrosis in the United States. The most recent estimates indicate that approximately 128,000 Americans have IPF, although there are published estimates that suggest the number is as high as 200,000. Varying terminology and lack of standard diagnostic criteria have complicated the accrual of accurate data.
More importantly, it is anticipated that the number of individuals diagnosed with IPF will continue to increase. This will be a result of people living longer, and an improved clinical understanding of IPF which will lead to earlier and more accurate diagnosis.
The lack of clinical understanding of IPF remains a concern in the medical community. Limited awareness of the epidemiology (causes) and pathogenesis (disease progression) has made misdiagnosis of IPF a common problem. In fact, a recent study showed that more than 50% of IPF patients may be initially misdiagnosed. Further complicating the difficulty in diagnosis is the fact that there are more than 100 different types of interstitial lung diseases (ILD), and it has not been until recent times that the American Thoracic Society (ATS) recognized IPF by its specific clinical and pathological characteristics. At times, progress was slowed by an incorrect understanding of the pathophysiology, inability to perform adequate clinical trials, and a failure to communicate and collaborate within the research community.
IPF has no strong demographic profile; it is found in equal proportions in urban and rural environments. A history of smoking has been associated with an increased risk of IPF, and a variety of published studies show that, on average, two thirds of those with IPF have a history of smoking.
IPF affects more men than women and most commonly occurs between the fifth and seventh decades. The median age at time of diagnosis is approximately 63 years old according to a variety of published studies; however, IPF has been diagnosed from early adulthood into the late eighties.
Treatment and prevention
The clinical course of idiopathic pulmonary fibrosis (IPF) is highly variable and unknown, and as a result strategies to treat IPF are highly individualized, based upon the specific patients’ medical history and other conditions (comorbitities). While there are currently no effective treatments or a cure for IPF, there are a variety of therapeutic options to help patients manage their condition and maintain their quality of life and activities of daily living (ADL’s).
Since there are currently no FDA approved therapies to treat IPF, many patients choose to participate in clinical trials. New, experimental therapies are tested for their effectiveness through clinical trials. It is very important that patients discuss this possibility of participating in a clinical trial with their physician upon diagnosis. It is through clinical trials that a cure for the disease will be found. Please visit the Research section of this Web page to learn more about active clinical trials in the United States.
Typical standards of care may include prescription therapies, supplemental oxygen, pulmonary rehabilitation, and lung transplantation. Lung transplantation remains the most viable course of treatment to extend the lives of those with IPF, and this option should be discussed with your physician as soon as you are diagnosed.
Therapeutic Options: For some patients depending on their diagnosis and biopsy, medication will stabilize their disease and some patients may benefit from their continuing usage. While there remains no consistent standard of care in the IPF community, the following medications are commonly prescribed in an attempt to treat your symptoms:
Corticosteroids: (Prednisone) Prednisone is used for suppressing the immune system and inflammation. It mimics the action of cortisol which is produced by the adrenal glands. Depending on the dose, prolonged therapy can cause the adrenal glands to stop producing its own cortisol. For this reason when prednisone is discontinued, it may be necessary to gradually lower or taper the dose to allow time for the adrenal glands to recover. Since Prednisone suppresses the immune system, it can potentially increase the frequency and severity of infections. Prednisone has many side effects including sugar intolerance (can worsen diabetes), weight gain, swelling, depression, anxiety, fatigue, and peptic ulcer (to name just a few). Individuals receiving prolonged treatment or higher doses need to be carefully monitored.
Cyclophosphamide (Cytoxan): Cytoxan is an anticancer drug and is used for its immune suppression properties. Cytoxan is frequently given in conjunction with Prednisone or may be given alone. While it is usually taken daily by mouth, in some instances it may also be administered intravenously, usually monthly for six months.
Azathioprine (Imuran): Although there have been some successful reports in a small number of individuals, its effectiveness has not been confirmed in a randomized clinical trial to-date.
N-acetylcysteine (NAC): NAC is a naturally occurring antioxidant. It can be taken orally and theoretically could prevent some of the oxidative injury that precedes fibroproliferation. A small non-randomized study demonstrated some improvement in lung function in patients with IPF. There are number of ongoing studies investigating the efficacy of NAC in combination with other drugs.
As with any medicine for any condition, patients should discuss specific treatment options directly with their physician to determine the best approach for your case.
Supplemental Oxygen Therapy: All the body’s functions depend upon delivery of a steady supply of oxygen. Because IPF inhibits an adequate transfer of oxygen into the blood stream, some patients may require supplemental oxygen. This helps to reduce breathlessness, enabling the patient to be more active. Some may need oxygen therapy all the time while others may only need it during sleep and exercise. By testing the saturation level of oxygen in your blood, your physician can tell if you require supplemental oxygen. If your doctor has prescribed oxygen, use it. Many patients are fearful that they will become “addicted” to oxygen. This just is not true.
Pulmonary Rehabilitation: Pulmonary rehabilitation has become the standard of care for people with chronic lung disease, and recent studies have demonstrated improvements in both exercise capacity and health-related quality of life in patients with IPF. (12). The goal of pulmonary rehab is to restore the patient’s ability to function without extreme breathlessness. These programs offer a variety of services and can be inpatient, outpatient or home/community based. The programs are “multidisciplinary,” meaning that the team includes nurses, respiratory therapists, physical therapists, social workers, dieticians, etc. The range of services includes: exercise training; breathing exercises and retraining; anxiety, stress and depression management; and nutritional counseling, to name a few. Another recent study recommended that pulmonary rehabilitation be considered as a standard of care for those with ILDs like IPF because of its potential to improve functional status and dyspnea. (13)
Lung Transplantation: IPF is now the leading indication for lung transplantation in most large centers. In 2009, at the Cleveland Clinic, University of Pittsburgh Medical Center, and number of other large transplant centers, over 50% of the lung transplants performed were for IPF. Transplantation can improve both longevity and the quality of life in properly selected patients who have no other significant health problems. Previously it was uncommon for individuals over the age of 70 to receive transplants, however as surgical techniques and outcomes have improved; more individuals over 70 are receiving transplants, and many medical centers have updated their age requirements to now include those over the age of 70.
Until recently, because of long pre-transplant wait times, early referrals were essential so that patients could begin accruing time on the transplant waiting list. Fortunately with a new lung allocation system (LAS) used by the United Network for Organ Sharing, or UNOS (www.unos.org), candidates are evaluated based on the severity of their disease, and as a result wait times for those with IPF have been dramatically reduced. Similarly, in many institutions, the one-year survival rate is over 90%. Transplantation is not without risk, and patients should discuss all the possible complications with their physician.