Nontuberculous Mycobacterial (NTM) Infections

Podcast Transcript

Raed Dweik:

Hello, and welcome to the Respiratory Inspirations podcast. I'm Raed Dweik, chairman of the Respiratory Institute at the Cleveland Clinic. This podcast series of short, digestible episodes is intended for patients and families, and covers topics related to respiratory health and disease. My colleagues and I will be interviewing experts about timely and timeless topics in the areas of pulmonary, critical illness, sleep, infectious disease and related disciplines. We will share with you information that will help you take better care of yourself and your loved ones. I hope you enjoy today's episode.

Hello everyone, and welcome to this episode of Respiratory Inspirations, I'm your host, Raed Dweik, chairman of the Respiratory Institute at Cleveland Clinic, and our topic for today is nontuberculous mycobacteria. And I have two special guests: Dr. Cyndee Miranda, who is an Infectious Disease Specialist and the leader of the Granuloma delta group in our Infectious Disease department. And Dr. Joe Khabbaza who's a Pulmonologist with a special interest in nontuberculous mycobacteria, the topic of our discussion today. Welcome, Joe and Cyndee.

Cyndee Miranda:

Thank you.

Joe Khabbaza:

Thank you.

Raed Dweik:

So, let's start with the very basics as for those who either never heard of it, or heard of it but don't know what it is. What is NTM or nontuberculous mycobacteria?

Cyndee Miranda:

NTM as it says, it's a type of bacteria. It is related to the more popular type of mycobacteria called mycobacterium tuberculosis. The difference however is that NTM, they are not contagious, they are generally not passed on from person-to-person, and these mycobacteria are typically in our environments. So they are in the soil, water, they could be in your municipal water supply and household plumbing actually. So, it's in the environment you generally acquire it through the environment, so that's inhalation of soil, or inhalation of aerosolized water that contains the mycobacteria.

Raed Dweik:

So, does anybody get it? Are we all at risk of that or is it only some people?

Cyndee Miranda:

You know, everyone is exposed to mycobacteria, nontuberculous mycobacteria but not everyone gets it. So again, there are certain types of patients that do get it, and these are usually those with chronic lung conditions such as what we call COPD.

Raed Dweik:

Chronic obstructive pulmonary disease or emphysema, yeah.

Cyndee Miranda:

Yeah. So, emphysema. Patients with underlying like let's say lung damage that they might have, you know, who have been diagnosed with what we call bronchiectasis where their airways are abnormal, can get these types of infections. Some patients with let's say weakened immune systems are at risk for these infections.

Raed Dweik:

Yeah. Joe, do you want to add to that? I know it's like, that's your thing.

Joe Khabbaza:

Yeah. So, we're all, I think the takeaway is that our whole globe is covered with NTM, this kind of family of bacterias. Think of them as kind of wimpy, slow growing bacterias that don't make people very sick, and we're all exposed to them all the time. And people with intact airways and normal lung function, we breathe them in, or swallow, or what have you and then we just cough. Our lungs naturally sweep up things that we breathe in and, and fluids we make. But in people where that process is impaired, sometimes those bacterias that we all come across end up drifting lower into the lungs and kind of setting up in the lower airways and slowly growing over time. And that mainly occurs in the people who have something wrong with their lungs and the way it clears that process. But so, we're all exposed to them, they're not dangerous alone in themselves but, you know, if not noticed and allowed to kind of sit in our airways for long periods of time, that's when some people can become symptomatic.

Raed Dweik:

I want to revisit one point that Cyndee mentioned is that these are not contagious, you don't catch it from another person. I just want to maybe, to elaborate on that a little bit because it is something you get from the environment, not from other people, unlike TB, tuberculosis which definitely is a highly infectious and dangerous disease, yeah.

Joe Khabbaza:

Right. Yeah. This is more pertinent to each individual's own immune system and the local way that their airways are functioning. So, there are very rare just in the, there's been like one or two cases in the cystic fibrosis world where maybe there has been a spread, but largely this is thought of a non-contagious illness that it's unique to the individual host that might have their own, you know, issues with their airway clearance and how their lungs work and not spread person-to-person.

Raed Dweik:

Yeah, that's great. And I know Cyndee, in prior conversation we talked about not only patients with lung disease, but certain individuals even without lung disease are susceptible to this, you know. Can you elaborate on that a little bit for our audience? Yeah.

Cyndee Miranda:

Yeah. So interestingly NTM lung disease can also occur in women with no obvious risk factors and in the medical world this is known as that Lady Windermere Syndrome, which you might have heard about. And these are typically post-menopausal women who are tall, they're slender, and they have certain like breastbone abnormalities such as pectus excavatum and scoliosis. So NTM lung disease can also occur in this group.

Raed Dweik:

So, if a patient or a family member wonders like somebody has a cough or symptoms, when should they suspect that they have NTM and maybe check with the doctor? Are there any particular symptoms or anything in mind?

Joe Khabbaza:

Well, I think, you know, chronic cough is a very common complaint and really, there are very common initial causes upfront to that and getting that initial workup... I think we're pretty good at working up and treating asthma and acid reflux, sinuses, and allergies, upper airway cough syndrome and even making sure they're not on an ACE inhibitor.

Raed Dweik:

ACE means one of the blood pressure medications. Some blood pressure medications can cause cough.

Joe Khabbaza:

Yes. Yeah. That family of blood pressure medications can cause a dry cough in people. Those are kind of the four first things we look at in somebody with chronic cough. And chronic is usually more than three weeks or a month you're thinking?

Yeah. I think generally we think about, I mean, I like to think in my head maybe at, at least two or three months.

Raed Dweik:

Two to three months. Okay.

Joe Khabbaza:

So, people who are coughing for a long period of time are the initial things where we look for, try to treat and work up. People who are not responding to those treatments or having workups that are suggesting anything is wrong in those areas, that's when my next thought is, could there be a slow-growing lung infection like NTM? I think what happens often is patients keep coughing despite the above workup, they end up in this kind of inhaler vortex where I think they just, more inhalers just keep getting added on and on without improvement in symptoms, and that to me is red flag as well that maybe there is an infection. And so that's when I'm, you know, very quick to think about.

Raed Dweik:

So, that's very helpful. From the vantage point of the patient to the family member, you know, how do they bring this up, the conversation with the doctor, family physician, or primary care? What should they tell them? How do they, kind of, have them raise index of suspicion?

Joe Khabbaza:

I mean, a cough that's worsening or not improving for, you know, at least three months despite having a workup, I mean, that's when they've got to ask and push for, for something more to be done. And I think generally that the next step would be a CAT scan of the lungs.

Raed Dweik:

Yeah.

Joe Khabbaza: So that is definitely part of my, you know, long-standing cough workup because that is the way we're gonna find out if there's something physically within the lungs driving this picture once we've ruled out asthma, reflux, sinus, allergy disease and reviewed their medication list.

Raed Dweik:

So Cyndee, back to you. So, what kind of testing do you do if somebody likes with these symptoms present to you, what do you do to evaluate them? What could a family or a patient expect when they present with these symptoms?

Cyndee Miranda:

Of course, as Joe said, you know, the CAT scan. Asking for a CAT scan of the chest, and that's what we usually do is get the CAT scan of the chest for these patients. The other thing to remember is to ask for also mycobacterial cultures.

Raed Dweik:

Sputum, yeah.

Cyndee Miranda:

Sputum culture which would test for bacteria, but sometimes they are not able to grow these mycobacteria that we're talking about. So, it takes another type of culture to grow these mycobacteria, it's generally what's called AFB sputum culture, which stands for Acid-Fast Bacilli, but that's a term that is used to test for mycobacteria. And that's one thing that we order for. We also of course, we look at your symptoms, we look at the culture, we would send that, your CAT scan of the chest to look inside your lungs. And then of course we also look at other blood work, you know, getting your count, looking at your liver and kidney function tests are also important, especially if we're thinking about treatment.

Raed Dweik:

Do you want to comment on that, Joe?

Joe Khabbaza:

Yeah. And that's a good point that a patient can advocate for themselves. Beyond the CT scan is if they are producing sputum, they should ask if that sputum can be tested. Because I think very often many of us and even in pulmonary, you know, don't check sputum cultures regularly even in people who produce sputum. So that is one way if you have a long-standing cough that is productive, asking if that can be cultured to look for bacteria and especially the mycobacteria.

Raed Dweik:

Yeah. And usually most of these are addressed by a primary care physician or family physician, but let's say if a patient wants to get specialist attention, here we have pulmonary doc, an ID doc, you know, which one should they start with? Start with you, Joe.

Joe Khabbaza:

Well, well, yeah, because, you know, pulmonary disease is generally what makes you susceptible to developing NTM. So having the pulmonary side fully worked up and then also get a diagnosis of their suspicion, that's gonna make it a lot smoother ride for the patient, but also once they do see an infectious disease specialist because it's nice to have a diagnosis to give Dr Miranda when you see her, versus her having to work up and test the lungs. So, I think chronic cough, especially productive cough, shortness of breath, what have you, if it's not responding seeing a lung doctor first to help try to get that diagnosis, I think will be a lot smoother and easier for once they do see an infectious disease doctor to help treat it.

Raed Dweik:

So that's what the lung doctor says. What does the ID doctor say? Do you agree with him, Cyndee?

Cyndee Miranda:

Yes. I do agree and in fact we do have some patients that come to us from the primary care physician and what's surprising to me sometimes is they have no involvement at all with a pulmonologist, or a lung doctor. So, I recognize the importance of partnering with a pulmonologist, and so generally I do refer them to one of our pulmonologists to partner with me in helping care for these patients.

Joe Khabbaza:

Yeah. It's a true team effort and I think patients can run into problems in regions where ID or pulmonary view it as just the other specialty's issue. It's actually both of our issues and we both bring lot to the table at helping kind of have successful treatment long-term. So, I think it's not a just pulmonary or just ID issue, it's both. And so having both expertise I think will really benefit patients in the long run.

Raed Dweik:

Yeah. I like that approach. I think that's what allowed us to be very successful here at the Cleveland Clinic is approaching this as a team instead of liking just pointing, you know, in different directions. So, now the patient came, they saw the consultant and then they were identified that they have nontuberculous mycobacteria, or NTM, how do we treat? Cyndee, I'll start with you.

Cyndee Miranda:

So, treatment, and Joe will talk to you about this later, there is an important component and that's why I refer my patients to the pulmonologist as the airway clearance which becomes important, which I'll let Joe talk about more. But the treatment involves multiple medications actually, more than one, is what we use to treat these nontuberculous mycobacterial infections and they're typically given for a long period, for a long period of time. So most commonly for the most common NTM infection, which is MAC, which you'll hear about a lot or Mycobacterium avium complex, and we refer to that as MAC, for short, which I think a lot of our patients are familiar with. Typically, it's treated with three drugs, and the names of these drugs are azithromycin, ethambutol, and rifampin. These are the main drugs that we use to treat MAC and there are of course side effects associated with these drugs.

For example, for ethambutol, one of the things that we are careful about is the patient's vision. So, we monitor your vision while you're on ethambutol. Rifampin can cause orange urine. So that's something that we discuss with our patients. And azithromycin can sometimes affect your hearing. Again, not all of these things are going to happen, but it's good to be mindful of these side effects and we do closely monitor our patients for these side effects while on treatment.

Raed Dweik:

Yeah. So, Joe, you may follow up on that. These kinds of unusual maybe side effects, vision, urine, and you know, and hearing make people wonder, is the treatment really worse than the disease? And I think there's a misconception out there about that. Can you maybe help us clarify that?

Joe Khabbaza:

Yeah. So, anyone who has NTM or MAC certainly has read out there or has been told by providers that treatment's worse than disease and they should sit back and not treat it. But I think the reality is that for some people, the disease is worse than, that treatment and those are kind of important discussions to be had, because if you are in that category of high risk of progression, which would be certain changes on the CAT scan, high amount of bacteria on the sputum, or if you have a low body weight. I mean, those are categories where we know if we put you in this observing boat there is a high risk of progression of the lung disease. And, you know, what I found which was really new to me, because I also kind of came out of training thinking treatment was worse than the disease for most, is that most patients do tolerate treatment. So, it can sound scary thinking, or like you're going to very likely do poorly.

And one of my very first ever MAC patients that I diagnosed, I still remember vividly uncontrolled COPD, recurrent exacerbations. Then we started sending cultures and they, they all were growing MAC and I, you know, I'd urged him to get and consider to be treated. You know, he's an older man, and one of his only hobbies is not just reading. So even though the risk of ethambutol affecting his vision is small, most people don't get that more serious side effect. He did not want to take even that small risk of affecting one of the few remaining things he gets enjoyment from, so he decided to defer treatment. So watchful waiting was appropriate for him because of his values, and he would rather tolerate the symptoms of his disease than potentially take on a side effect, though small. So, I think it's important to have these discussions and to understand your doctors, to understand what each route might entail, you know.

I think we used to just tell patients what route to take but I think it’s very important to know, have an understanding of what treatment would entail or what waiting would entail, and what kind of monitoring will be done if you're in that watchful waiting category. But I think the disease can be quite bad for people who are not treated. It is so important to know your options.

Raed Dweik:

Yeah. So, what I'm hearing from you is that definitely the medications have side effects, but you have to weigh up the disease itself is serious and progression of the disease needs to be taken into account, you know when making treatment decisions. Lot of patients would ask, is there anything else I can do other than taking drugs? And they, you know, I think Doctor Miranda mentioned something about airway clearance. Can you elaborate on that a little bit?

Joe Khabbaza:

Yes. And that's always what I think the first treatment for NTM lung disease and the first thing I talk about and educate with patients before I ever reach for an antibiotic. So, you know, patients who have some changes in their airways or lungs that make it hard to clear out mucus and infection, you know, we need to artificially help the lung in coughing that stuff up. And that's what we refer to as an airway clearance regimen. These are different treatments that are not antibiotics, that are physically going to help you cough up and remove these mycobacteria from your lungs and that is the first treatment. And studies have shown that most of the studies in NYM are small, but studies have shown that people with mild disease can clear their culture just by doing a good airway clearance regimen. So it is important to understand that there are non-medicinal things, non-antibiotic approaches that you can take as a patient to increase the odds of clearing the infection without antibiotics, but also increasing the odds that antibiotics are successful if you do start treatment, because getting rid of that mucus and bacteria from your airways is so important.

You know, we could probably spend a whole other hour talking about airway clearance and bronchiectasis, but it really centers around breathing treatments that help make your sputum less dry and more wet and doing maneuvers that help you cough up that sputum as it gradually becomes more moveable.

Raed Dweik:

Yeah. It looks like something practical that patients can do. Back to you Cyndee, you know, how do I know like if, whether we go the watchful waiting approach or we go the drug treatment approach, whether I'm getting better or worse, you know? How can you monitor my symptoms? How do I know as a patient or as a family member taking care of a patient whether they're getting better or not?

Cyndee Miranda:

So first of all, there are certain patients that need to be started right away on treatment and if you have what's called cavitary form of the disease. You have cavities in your lungs which will be seen on X-ray or a CAT scan of the chest, you need to start treatment right away. Other things that increase your risk like, if you have low weight or something to do with your cultures, the burden of the mycobacteria in your lungs might make us want to treat. So, once you're on treatment, like I said, because the drugs have multifold side effects, you know, other things I forgot to mention like GI symptoms. What they mean is nausea, vomiting, or diarrhea, those are some things that can happen. I do stay in close communication with my patients because that is key to helping manage these side effects because there are maneuvers that we can do as physicians to help you tolerate the drugs better. So, it's important to talk to your physicians about it.

So, what we monitor as you're on treatment is we monitor, the most important is how you're feeling, so your symptoms are getting better. You may not get better right away but we expect you to at least over time feel that there is an improvement in your respiratory symptoms.

Yes. And then the other thing of course is we talked about cultures earlier, and that's really important to determine how long you're going to be on treatment. So, we do check your sputum cultures while you're on treatment and when you've cleared the mycobacteria from the sputum, meaning we don't find it anymore in your sputum, then usually we treat for a year after we say you've cleared the mycobacteria. So that's why we monitor your sputum cultures. And of course, we also monitor your CAT scan of the chest to make sure that there is improvement, or it hasn't progressed, or gotten worse. So those are the things we look at. And then of course we also monitor your blood count, liver tests, kidney functions tests, EKG during the course of your treatment.

Raed Dweik:

Maybe something I should have asked at the beginning, but I think maybe for the benefit of our audience is if you know for example you have lung disease, you're at risk of this, is there anything you can do to protect yourself from even getting it in the first place, Joe? Like is there anything people can do day-to-day to avoid exposure, avoid getting it?

Joe Khabbaza:

Yeah. I think that's the big question because it's everywhere in our environment. So how do you avoid something that's in water and soil, and that's what all of us are exposed to wherever we live? You know, I think there have been times where patients had been advised to make big lifestyle changes and don't shower anymore, and to avoid gardening and, and, you know, other things in the outdoors or the, but I think we've kind of found that major lifestyle changes sometimes, you know, patients still can get reinfected or infected with these major lifestyle changes because the source can be anywhere, you know. So, I've kind of taken a step back and I, you know, I think if there's things that are easy to do when you're like, if you're gardening just have this, dampen the soil so less can get aerosolized. If a mask is not too bothersome outside to you, that's fine too. I mean, that'll decrease the risk.

But I think what's different from a patient who's been identified to have NTM lung disease versus someone who's yet to be diagnosed is that they will be on an airway clearance regimen, of some kind for the future. So whatever exposure they have after the diagnosis, it's gonna be less, it's gonna have less chance to settle in their lower lungs because they're doing airway clearance. So, anything that's exposed is more likely to come out. So, I don't really recommend big lifestyle changes because people who have really changed their lives tremendously still gotten infected or generally reinfected. Generally, people we've identified before, so because of that airway clearance emphasis where, you know, if something ends up in your airways it's less likely gonna hang out there because you're mobilizing things regularly with airway clearance.

So that's kind of how I approach. I don't really make big, unless there's an obvious exposure source and that's in a less common setting like a hot tub lung setting, which is kind of off topic a little bit.

Raed Dweik:

Anything else to add to that?

Cyndee Miranda:

No. I think Joe is right. I think there's environmental risks everywhere. There are little things that you can do, for example, like with Joe said is just wetting the soil so that it doesn't aerosolize. Typically heating up your water to greater than 130 degrees Fahrenheit is, is one thing they've talked about, wearing a dust mask. But again, it's not 100 percent, you know, it's not a guarantee that you won't get the NTM infection.

Joe Khabbaza:

And I think something we didn't actually talk about too much was that, you know, acid reflux is something that can increase the odds of developing pulmonary NTM. So thought as we would drink or eat something that has an NTM on it and then if we're aspiring into the airways that's a route that it can get down. So, I think being vigilant about, you know, reflux symptoms are important. So having that index of suspicion, whether that's present and that's a slightly different topic. But even if we're ingesting or drinking our water supply is all NTM. If we're not aspirating, it's not going to get into our lungs.

Raed Dweik:

Basically, treat reflux if you have it basically what you're suggesting. That's great. Well thank you both, it's been really very informative. I'm trying to maybe share a few takeaways with our audience today. One is when to suspect nontuberculous mycobacterial infection. If you have a chronic cough, meaning lasting more than two to three months with or without treatment, especially if it's productive although it can be non-productive obviously. You may not always have sputum but usually you do. And then sputum testing is really the first step, sometimes with or without the CAT scan but, you know, finding the mycobacteria in the sputum is how you make the diagnosis. And you both made an important point about treatment is that it really is a shared decision between the patient and the physician because there are side effects with the medications, but also there are downsides to not treating because the disease can progress. So, it really having to weigh the risks and benefits of both watchful waiting, which can have its own problems, but also treatment which has its own side effects.

Any other thoughts to add to this?

Cyndee Miranda:

For the patients, you know, what I would like for them to make sure that they know is when somebody tells them they have an NTM infection it's very important to ask, what kind of NTM do I have? And, and the doctors can tell you that because it matters what that NTM is as far as how important it is and whether we need to treat it. And then to ask for cultures, not just a sputum culture but if you ask your doctors for mycobacterial culture, they'll know what that means and that's being proactive in your care.

Raed Dweik:

All right. I’ll let that be the last word. Thank you both for joining me today. And thank you to our audience for listening to this podcast. I'm your host Raed Dweik, chairman of the Respiratory Institute at the Cleveland Clinic, and my guests today were Dr. Cyndee Miranda from Infectious Disease who leads our delta group focusing on Granuloma, and Dr. Joe Khabbaza our pulmonologist with a specific interest in nontuberculous mycobacteria which was the topic of our conversation today. Thank you and have a great day.

Thank you for listening to this episode of the Respiratory Inspirations podcast. For more stories and information from the Cleveland Clinic Respiratory Institute you can follow me on Twitter @RaedDweikMD.