Idiopathic Pulmonary Fibrosis: A discussion with Dr. Albert Rizzo

Background
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown etiology. The annual incidence of IPF in the United States was estimated at 6.8 to 8.8 per 100,000 population using narrow case definitions and 16.3 to 17.4 per 100,000 population using broad case definitions. In Europe, the annual incidence ranged between 0.22 and 7.4 per 100,000 population. IPF prevalence and incidence increase with age, are higher among males, and appear to be on the increase in recent years.

MDLinx editors recently interviewed Albert A. Rizzo, MD, section chief of pulmonary and critical care medicine at Christiana Care Health System, Newark, DE, regarding the latest diagnosis and treatment of idiopathic pulmonary fibrosis.

MDLinx: Can you describe in brief what idiopathic pulmonary fibrosis is?
Dr. Rizzo: It is one of the interstitial lung diseases. It is rare but it is the most common of that group of diseases. It is basically a type of abnormal fibrosing process in the texture of the lung tissue. We feel it is probably triggered by some combination of exposures, genetics, infections that lead to an abnormal healing or wound repair process in the lung, which leads to the fibrosis and the thickening of the lung tissue. The fact that it is idiopathic means that we are not really sure why it exists in certain individuals.

MDLinx: For these patients, what are the symptoms and can you talk a bit about survival?
Dr. Rizzo: The symptoms early on tend to be a mild, dry cough. It may then be associated with shortness of breath especially with exertion. And those may be the only symptoms that gradually progress to the point where patients seek some advice from a pulmonary physician. It can sometimes be a long time before it is diagnosed because if the symptoms are mild, not much is done in the way of investigative studies that might include a chest X-ray or a CAT scan of the chest. It is usually a study such as that that is a tip off that an interstitial process is present and diagnosis may sometimes take months to years to be made after the patient first has some symptoms, again depending on the severity of the symptoms and how quickly they are to seek advice from their physician. Once it is diagnosed, the numbers vary but on average the survival from time of diagnosis is about 3.8 years. Unfortunately, the survival is only a little bit better than that of lung cancer. It is a disease that often changes life expectancy and varies from individual to individual but across the board that 3.8 years is the average.

MDLinx: What are some of the symptoms, signs, or tests that clearly distinguish it from other similar diseases?
Dr. Rizzo: The main symptoms are often cough and shortness of breath; and then depending on how severe they are and how much the complaint is brought to the physician; they may do early on a chest X-ray or a CAT scan of the chest. Those are the two tests that would be the best way to start being suspicious that a patient has idiopathic pulmonary fibrosis. The chest X-ray or CAT scan would be abnormal and once that suspicion is substantiated then there are other blood tests and breathing tests that are done to help confirm the abnormality that is often present with regard to the abnormal lung function. The blood tests are often done to make sure that this is not a process related to another condition. The most common differentiating diagnosis between idiopathic pulmonary fibrosis and other conditions are those that involve what are called collagen vascular diseases or autoimmune diseases such as rheumatoid arthritis or lupus. They can look exactly like, or very close to, pulmonary fibrosis but they are treated differently because of the fact that these are other entities and not idiopathic pulmonary fibrosis. When we talk about treatments; that is where the distinguishing feature is.

MDLinx: What are the traditional treatments for IPF?
Dr. Rizzo: Prior to last year, there were no specific treatments that were thought to be tried and true. Supporting the patient with oxygen when they needed it, and there were medications that helped with the cough that were often the main symptomatic treatments we would give. We had no medication that we thought would do anything to the process itself. About a year ago, two medications were approved by the FDA that, for the first time, did show an impact with regard to slowing down the abnormal fibrosis in the lungs and hopefully by slowing down the decline of lung function is going to improve the individual survival.

MDLinx: What is the mechanism of action for these agents?
Dr. Rizzo: We don’t know exactly how these two new drugs work in idiopathic pulmonary fibrosis. In fact, we are not sure of the exact mechanism that causes idiopathic pulmonary fibrosis. We believe the combination of an abnormal healing process in the cells that are normally responsible for healing let’s say from an anomaly or something like that would be abnormal in the way that they repair the lungs. That could be based on underlying inflammatory components in the lungs, possibly infections that might have been in the lungs, and certain genetic predispositions. Since we don’t know the exact process of how idiopathic pulmonary fibrosis starts, it is hard to say how these medications actually work, although we do know that they slow down the abnormal pulmonary fibrosis process.

MDLinx: Can you describe these new drugs and how they work?
Dr. Rizzo: The first drug is called pirfenidone and it has been approved outside the United States for a few years longer than it has been approved here so experience world-wide is a little bit more available. Nintedanib was approved about a year ago as well and also works in slowing down the progression of the disease. Both of these drugs are oral medications. The doses that are given and the number of pills that are taken are different and that can be an issue when deciding which drug to give to a patient. They both work to slow down the fibrosis process and decrease the decline in lung function and therefore, hopefully improve the lung function for whatever time that the individual has left so it doesn’t decline too rapidly.

MDLinx: How effective were these drugs shown to be?
Dr. Rizzo: The studies were designed to show forced vital capacity and by measuring that over the course of time on patients who took the medications vs those who were given the placebo, it showed that the decline in forced vital capacity could be slowed. About one third of the patients who were on medication vs those on placebo did not have as rapid a decline as those on placebo. It really was a matter of looking at this breathing test number to see if it could be kept from declining over a 52-week timeframe; that was the timeframe for most of these studies. Effectiveness is hard to state other than showing the slowing of the decline in function as each individual has a lot of variability as to the rate of progression of disease.

MDLinx: What are the side effects found with these drugs?
Dr. Rizzo: The side effects were a little bit different between the two drugs. Both of them had side effects that were mainly related to the gastrointestinal tract including nausea and diarrhea and maybe some indigestion and dyspepsia. Some of that can be improved by taking the medications with meals. The other side effect that is a little bit more common with pirfenidone was photosensitivity or the development of a rash or skin eruptions especially in sun-exposed areas.

MDLinx: Knowing that these treatments are not cures, are there other studies being proposed for other treatments that could be more effective?
Dr. Rizzo: There are studies that are certainly going to look at whether there is a benefit to using both of these drugs. Sometimes that can mean more side effects but if there is more benefit then it may be a worthwhile option. So those studies are going to be looked at. There are still a lot of studies looking at the actual cause of pulmonary fibrosis with the hope that a better target for new medications will be identified that will slow down what might be the fibroblast which is the cell possibly involved or the macrophage. There are multiple cells in the lungs that could be looked at as the offending agent in causing the fibrosis. If we can find the specific cell or chemical that we can target then that medication has yet to be developed and is being looked for. If we can not only slow down the process of fibrosis but ideally even reverse it that would be the ultimate treatment.

Dr. Albert Rizzo, MD, is a pulmonologist in Newark, Delaware and is affiliated with Christiana Care Hospital. He received his medical degree from Jefferson Medical College and has been in practice for 37 years.