Treating Rare Lung Diseases with Patrick Flume, M.D

A lingering cough, fatigue and fever that does not improve with antibiotics can all be symptoms of a rare lung disease caused by a common bacteria called mycobacteria. Dr. Patrick Flume, a pulmonologist and director of the Adult Cystic Fibrosis Center at MUSC Health, is an expert on this condition called nontuberculous mycobacterial lung disease, or NTM disease. In this episode, he explains why some people are at risk of developing it and the specialized care offered to these patients at MUSC Health.

“Early on in our clinic, the referrals that we would get typically were people with established disease who just weren't getting better or having complications related to their infection. But now, I think that there's greater awareness that clinicians are looking for it. Radiologists are starting to call features on the CT scans that look like NTM. I think we're finding that patients are being at least suspected of having NTM a lot earlier than in the past, which is a good thing. ”

-- Patrick Flume, M.D.

Topics Covered In This Show

• Mycobacteria, the bacteria that causes NTM disease, is a group of organisms that live in the water and soil. Flume says everyone is at risk of being exposed to this bacteria.
• Patients who tend to develop NTM disease from the bacteria include patients with bronchiectasis or abnormal airways, cystic fibrosis (CF), COPD, and the immunocompromised. Women who are post-menopausal are more at risk for NTM disease as well, he says.
• For those at risk, Flume suggests avoiding exposure to mycobacteria by limiting the aerosolization of this bacteria by taking baths instead of showers, since the bacteria tends to live on shower heads. For those who garden, wetting the soil before tending or wearing a mask is recommended.
• In general, he says mycobacteria prefer wet environments, with an abundance of warm water.
• When it comes to treatment, Flume says sometimes a year-long course of antibiotics will eradicate the infection, but doctors take a cautious approach to treatment because the correct course is not always clear.
• Patients suffering from a persistent cough and fatigue for long periods of time are being scanned for NTM more often now than before. A coordinated team of clinicians and practitioners at MUSC Health help NTM patients navigate their treatment, which can be very specific from patient to patient.
• People with a persistent cough that’s not getting better through standard therapies can be tested for NTM through CT scans and sputum culture tests.
• Flume’s work with NTM started with his work on cystic fibrosis (CF). Patients with CF suffer from chronic airway infections, caused by a multitude of bacteria including mycobacteria.
• Flume partnered with a colleague working in infectious diseases to establish a clinic to see patients who may have NTM disease. The clinic has a steady number of patients, which is increasing.
• Treatments for patients with CF have come a long way, and patients with CF can expect to live a full life with the correct treatment, he says.
• There are few treatment options for people suffering from rare lung diseases. MUSC Health offers treatment options for patients suffering from rare diseases, and they use an effective multidisciplinary approach for treatment.
• Flume was recently named the Associate Vice President for Clinical Research and the Office of the Vice President for Research at MUSC Health. He oversees clinical research initiatives to ensure their quality. There are hundreds of active clinical trials at MUSC Health.
• The state legislature has passed a provision for the establishment of a rare disease advisory council, which will hopefully provide more resources for those suffering from rare lung disease.

Read The Show Transcript Below

Erin Spain: [00:00:03] Welcome to Advance with MUSC Health. I'm your host, Erin Spain. This show's mission is to help you find ways to preserve and optimize your health and get the care you need to live well. A lingering cough, fatigue and fever that does not improve with antibiotics can all be symptoms of a rare lung disease caused by a common bacteria. Dr. Patrick Flume, a pulmonologist and director of the Adult Cystic Fibrosis Center, MUSC Health, is an expert on this condition called nontuberculous mycobacterial lung disease, or NTM disease and is here to explain why some people are at risk of developing it and specialized care offered to patients at MUSC Health. He's also going to share some more information about an upcoming initiative to address all rare diseases in patients who come to MUSC Health. Welcome to the show.

Patrick Flume: [00:00:57] Thank you very much. I'm happy to be here.

Erin Spain: [00:00:59] As I mentioned, NTM disease is caused by exposure to specific bacterial germs known as mycobacteria. Describe this condition to me. When do people most commonly come in contact with this bacteria?

Patrick Flume: [00:01:13] Mycobacteria is a group of organisms. There are many members in this family. The one that people probably have the most knowledge of is tuberculosis. But there are a lot of other cousins, if you will, in that family and that's why we call them non-tuberculous mycobacteria or NTM, because that's a mouthful. So these bugs are everywhere. They're in the water, they're in the soil. We're all being exposed to them. But it's only some of us who will develop infections or complications related to these mycobacteria.

Erin Spain: [00:01:44] So who are the people that are most likely to become ill after contact?

Patrick Flume: [00:01:48] So there are a variety of infections that can occur, and I'll separate those, what we call pulmonary infections, so infections of the lung. And then there are, of course, extra pulmonary infections like in the skin or joints or, you know, there had to be a break in the skin and there is exposure and the infection started. So there are people who are at greater risk for development of pulmonary infections. These are people who have conditions like bronchiectasis or the airways are abnormal. They're dilated. They don't have effective clearance mechanisms. And so when we introduce bacteria into our lower airways - and we do this all the time - these are subjects in whom these bacteria are able to persist. These are opportunists. They find a way to survive and then multiply in those lower airways. So people who have bronchiectasis, there's a very long list of reasons why they have it, including cystic fibrosis. People who have COPD, so tobacco related lung disease, will be at greater risk. People who are immunocompromised, they have autoimmune disease or immune deficiencies, they become at greater risk of developing infections. And then there is a group of persons that we identify. They tend to be women post-menopausal. Then they tend to have these persistent infections in the front part of their chest. We're not quite sure exactly the mechanism by which they are have greater vulnerability, but that is sort of a subgroup of the people that we see.

Erin Spain: [00:03:18] So for folks who are at risk, how can they protect themselves from being exposed to this bacteria?

Patrick Flume: [00:03:25] This is the challenge because if we go hunting for where that infection may have originated and there are plenty of studies that have done this, like going into the home and culturing the sinks and the showerheads. And what do they find? They find mycobacteria. Now, was that the source? Well, maybe, maybe not. But that certainly is a place of exposure. But one of the things that you learned when you were very young is you start turning over rocks and stumps looking for bugs. And what do you find? You find bugs. So it's not surprising that we find these bacteria. So there are some who have suggested that some ways of trying to reduce one's risk might be to try and avoid aerosolization of materials that would have mycobacteria. So there are some people who would advocate that people take baths rather than showers or people who love gardening either to stop or perhaps a better suggestion is to wet the soil. So it's not so dusty that that might stay more compact or to wear a mask while doing those kinds of activities. Now, I will tell you that these are suggestions that some people have made, but there's no evidence that they actually significantly reduce that risk.

Erin Spain: [00:04:34] And the reason is because these bacteria, they love these warm places like warm water. Isn't that right?

Patrick Flume: [00:04:41] They love the water. And if you look at maps of where there are greater incidences of NTM infections, they tend to be in coastal regions. So that's why South Carolina, we have a great deal of disease.

Erin Spain: [00:04:53] So what are the typical course of treatments or care?

Patrick Flume: [00:04:57] Well, the decision about treatment ultimately comes down to: what's the evidence that that bug is causing the problems that we see in the patient? And if none, what is the chance that it's going to become a problem? Now, unfortunately for the latter question, we don't really have the testing that would give us a hint of who's going to get progressive disease and who is not. They're clearly people who have NTM infections where it's going to be worse, that they're going to have persistent symptoms. Those symptoms range from respiratory symptoms like cough and sputum production or constitutional symptoms like fevers and sweats and fatigue, kind of like having the flu all the time. So it's a real quality of life issue. But others can have destruction of the lung that if you look at the imaging, you see destructive changes. So in those patients, clearly intervention is warranted. If we feel compelled to recommend treatment, it really depends upon which species we're talking about. And as I said, there are a lot of cousins in this family. The most common when we see is called mycobacterium avium complex. That's a mouthful. So we call it MAC. And then mycobacterium abscesses is another frequent organism that we see. And each of those would have very different treatment strategies. But in general, we're talking about multiple antibiotics for long periods of time, more than a year. With that, in a proportion of patients, we will eradicate the infection. But in some people we can't get rid of the infection. It doesn't mean we can't make them better, but the infection will persist. And that's why we want to make sure what are we trying to make better with treatment? Because if a person isn't having any symptoms, we found MAC in their lung and nothing is changing over time, it's hard to know that antibiotics would have made anything better. So that's why we take a very cautious approach to trying to understand what are the problems and what needs to be made better.

Erin Spain: [00:06:50] What is it like for these patients who've really had a run around in other places with getting diagnosed? What's it like for them to come to your clinic, get a diagnosis and get treatment?

Patrick Flume: [00:07:00] So there's a number of challenges that these patients have lived through, but there is change evolving. And what I mean by that is in the past it was kind of typical that these patients would be suffering with symptoms of usually cough and fatigue for long periods of time before a diagnosis was ever made, sometimes years before someone eventually looked and found NTM. And early on in our clinic, the referrals that we would get typically were people with established disease who just weren't getting better or having complications related to their infection. But now I think that there's greater awareness that clinicians are looking for it. Radiologists are starting to call features on the CT scans that look like NTM. I think we're finding that patients are being at least suspected of having NTM a lot earlier than in the past, which is a good thing. When these patients come to our clinic, obviously when they hear terms like bronchiectasis and mycobacteria, these are foreign words. And of course, they've done the worst thing they could do, and that was get on Google and start reading about things. So they oftentimes come in as if they feel like they've had a diagnosis of cancer. But one of the advantages that we have is because we have the ability to devote more time, and our clinic consists of not just the clinicians, which includes pulmonary infectious diseases. We have a nurse practitioner, but also we have nurse coordinators. We have pharmacists, psychologists, respiratory therapists all present in the clinic to be able to look at the other needs that the patients have to make sure that they get a better understanding of what we're talking about and really what's more specific to their particular needs. Because the other part of this is not everybody needs to be treated, but we need to understand why they have it and then decide what needs to be done about it.

Erin Spain: [00:08:45] Patients who are listening, who may suspect that they or a loved one could have symptoms of this disease, how can they advocate for themselves and get the care that they need?

Patrick Flume: [00:08:55] So the first aspect of that is obviously the level of suspicion. Not everyone that coughs is going to have NTM lung disease. There's still other issues like asthma and so forth. But when things persist and they're not getting better with more standard front line therapies, then it should really raise that level of suspicion. And the two most important things, one is imaging and a high resolution CT scan of the chest is really the best way for us to assess what the lung looks like. And there are some distinctive features that would be suspicious for NTM. And the other is to get cultures. And ideally a sputum culture may be all that's needed to send for testing, specifically for regular bacteria, but also mycobacterium in those persons who really were suspicious of it, but they cannot produce a good sputum sample, there are some in which going down into the lungs with a bronchoscopy is necessary to try to see if they have the infection.

Erin Spain: [00:09:52] Now, you've made it a point to study this disease and treat people with it. Tell me about when you first decided to really focus on diagnosing and treating patients here in South Carolina.

Patrick Flume: [00:10:03] So we established our NTM clinic a little more than a decade ago, but we're really where it stemmed from was my work in cystic fibrosis. So I came to Charleston in 1993 to establish the Adult CF center. So persons with CF, they have bronchiectasis, they have chronic airway infections, and they have a multitude of different bacteria that we see. But one that has become of increasing concern are the mycobacteria. And so in our adult population, about 10 to 15% will eventually have mycobacteria found in their sputum cultures. Because of my work in CF, it seemed natural that I was beginning to get a lot of patients referred to me who had bronchiectasis for other reasons. And so as I began to evaluate these patients and identifying many of those that had mycobacteria, what became clear to me was that the way that these patients were being managed out in the community was a little bit chaotic. And I felt like we needed to have a much more organizational structure. So I partnered up with a colleague from Infectious Diseases to establish the clinic. Back then we started, we thought we do a half day every month. That program has exploded to the point where we now have four providers in our NTM program. We see at least four new referrals every week, looking probably to actually add another day of clinic to be able to meet the needs of these patients. So it really was a natural extension of of the work that we do, which is really related to persistent airways infection.

Erin Spain: [00:11:30] Cystic fibrosis is something that's usually diagnosed in childhood, yet you're an expert for treating adults with cystic fibrosis. Tell me about that.

Patrick Flume: [00:11:39] Well, in my time doing CF, which is really over the last 30 plus years, we have seen remarkable changes in the CF story is probably one of the most amazing health stories today. When I started in cystic fibrosis care, the median age of survival was really in the mid-twenties. That meant that half the people weren't going to survive past that time. Now, if you have a child born with CF, I would tell you to expect a full life for that child. So in the beginning, all of our therapies were targeting the consequences of this genetic disease that this gene codes for a very specific protein. And because it's not there, it doesn't work right, it led to all these complications related to chronic infection and the like. And so we developed a lot of therapies over time that targeted things like treating infection or helping clear stuff out of the lungs, treating their nutrition and survival was marching along. There was great hopes that we would solve this problem and cure it with gene therapy once we had discovered the gene. We're not there yet. But what we learned was that we can use drugs to actually improve the basic defect. And so depending upon what the gene mutation is, there might not be enough protein, might not be any protein, or the protein is made, but it doesn't work right. And so depending upon that, we have these cocktails of medications that can actually increase the quantity and the effectiveness of that protein. So it's not a cure, but it's treating the basic defect. And this has had an amazing change. I mean, I want you to imagine that you've had a lifetime of coughing, producing sputum, and now you don't cough anymore that your lung function went up 10 or 20%. The frequency of being in the hospital went from one or two times a year to now I have hardly anybody in the hospital. Nutrition has continued to improve, so it's been a dramatic change in the therapies available for these folks. The work that we do there developing these drugs initially started with adults. And so obviously we want to treat younger and younger. If you have a child born with CF, you want us to get a therapy as soon as that can be done. So that work is ongoing to prove that these drugs are effective and safe in the very young. Even though we have these therapies available for the majority of people with CF, it's not the entirety. And so there's 10 to 15% of people that don't have the right gene mutations. There are another 10 to 15% that might have problems with the medications. So we're still trying to develop a treatment strategy that would be just as effective for the rest of them. [00:14:09][149.9]

Erin Spain: [00:14:09] What would you say to patients who their loved one is experiencing a rare lung disease or condition? Why should they consider coming to MUSC health?

Patrick Flume: [00:14:19] In general, people who have rare conditions, there are far fewer options available to them in terms of people with the expertise in that specific condition. And obviously there might be limited options in terms of therapeutics. Some of those conditions will have active research, even to the point of clinical trials where therapies are being tested. And so people need to know what's available to them, where there's access for that. And more than likely, those are going to be happening at academic centers. We are fortunate in that we have a number of clinicians, not just in the pulmonary space, but at MUSC Health in general, who do focus on rare diseases. We have the ability to identify the clinical needs and address them. Typically, we will have the team's support to be able to address the other needs, whether they be social or psychosocial. And I can't tell you enough how important it is to work within those multidisciplinary teams because each of these fields bring that expertise to be able to communicate with the patients. And then with the advent of telemedicine, the pandemic being the accelerant, we've taken advantage of that to try and make sure that these patients get the information that they need.

Erin Spain: [00:15:34] You were recently named the Associate Vice President for Clinical Research and the Office of the Vice President for Research at MUSC Health. Tell me about your new role.

Patrick Flume: [00:15:42] My work consists through these years of clinical work and as we talked about in the fields of CF and bronchiectasis and NTM lung disease and my research was really all clinical research and whether that was studies that I had developed or that we brought here as clinical trials, developing therapies for our patients. And so I had developed an expertise in just the conduct of clinical trials in my role in the office of the Vice President for research as oversight of the institutional research offices, to be able to provide that infrastructure to assure that not only is research done the right way, but that we can do it efficiently. You know, we need to be able to bring a good product to the patients that we serve and bring the right trials. But we have to be successful at it and to make it work for those clinicians, you know, in the clinical space were very busy. And so we need to have efficient systems running to be able to make that work. And so my job is to identify those hurdles to the successful conduct of clinical research and try to find solutions to them.

Erin Spain: [00:16:45] How many clinical trials are typically taking place at MUSC Health?

Patrick Flume: [00:16:49] The short answer to that is hundreds. I can tell you in my own group we have a number of physicians in the pulmonary division who are conducting research. So my work in CF, NTM, and bronchiectasis, but we have others that are in the pulmonary hypertension, pulmonary fibrosis, the intensive care unit and then we took on a lot of the COVID research doing the vaccine trials and the ICU trials. And so we have a staff of about 30 research staff, research coordinators that manage these trials, and our own group has about 50 to 60 trials ongoing at any time. You know, we looking to grow that as we find trials that we think are important for the people that we take care of. We don't do research just for the sake of doing research. We're doing studies that we believe have an opportunity of making a difference for people.

Erin Spain: [00:17:38] Is there anything else you want to add or mention about rare lung diseases? What's taking place at MUSC Health?

Patrick Flume: [00:17:44] So the other recent activity in the space for rare diseases is the state legislature passed a proviso for the establishment of a rare disease advisory council. This is something that's cropping up in pretty much every state and essentially to create a body that would advise Congress about the needs and the resources and to make it available to people with rare diseases. That task was charged to happen at MUSC. I was asked to lead that council and so we have put together that group. It is representative of major stakeholders but also other parts of the state. It is not just an MUSC entity. And so that literally is in its infancy in terms of building out the resources. And so there will be more to come. But the expectation I have of this group, based on what the proviso had written, was that we would offer recommendations to the state legislature about where we think opportunities exist or deficiencies and gaps really need to be filled.

Erin Spain: [00:18:43] This has to be great news for families and patients who don't have a lot of answers for rare diseases right now.

Patrick Flume: [00:18:49] And really, one of the first things we're trying to build out is the website that can identify as many resources that exist already. I don't need to reinvent the wheel if others have already created great places and resources for people, and then we can begin to work on identifying where the gaps are. [00:19:05][16.3]

Erin Spain: [00:19:05] What do you do to optimize your health and live well?

Patrick Flume: [00:19:08] I do a couple of things that I try to keep trying to improve upon. My exercise: I make sure I get my steps in. My dogs are always anxious to help me be better at that, and I can't say enough for getting a good night's sleep. And then finally I cut the caffeine one cup in the morning and no more after that.

Erin Spain: [00:19:28] Thank you so much for coming on the show and explaining the work you're doing with other rare diseases.

Patrick Flume: [00:19:33] Thank you very much.

Erin Spain: [00:19:39] For more information on this podcast, check out advance.muschealth.org.