Thank you so much for making it out at 8 a.m. on a Sunday morning, the first day of test. We're very honored to have you here. Today we are going to be talking about the diagnosis and management of non-cystic fibrosis bronchitis. So she's going to have to run after her presentation. that are specific to Dr. Keet, and then she is going to sprint Good morning, all. I'm from the University of Texas Health in San Antonio, and I have nothing to disclose for this talk. So for the next few minutes, I hope to provide you with a little bit of an overview, an introductory overview to bronchiectasis, as well as to leave you with some ideas about how to work up these patients and when to suspect bronchiectasis. So we'll get started. So I always think that medical history is interesting, so I just thought I would touch briefly on the history of bronchiectasis. Bronchiectasis has likely been around as long as human beings have had lungs that get infected by pathogens. But it was really only recognized first in the 1819 by Rene Lenac, who is the father of clinical auscultation. And he described in the literature a patient who had chronic coughs, sputum production, and hemoptysis. And it was a 72-year-old woman who unfortunately passed away, and then at autopsy was found to have findings of bronchiectasis. So this is a picture of Rene Lenac auscultating. And then later in the 1800s, Sir William Osler described the condition further, and before he actually died in 1919 of complications of severe pneumonia, and on his autopsy was found to have localized bronchiectasis. In the early 1900s, it was recognized that bronchiectasis had an association with tuberculosis infections, and there were limited therapies available. But really, beyond that, it wasn't particularly focused on and was considered to be really a rare phenomenon. As the 20th century went on, though, there were hallmark discoveries with regards to cystic fibrosis. And the focus of this talk is not cystic fibrosis, but really to make the point that in the 1930s, Dorothy Anderson described the findings of cystic fibrosis in the pancreases of children who had a similar clinical phenotype that caused early death. And there were discoveries of the CFTR gene and protein in the 1980s that led to the therapies that are available now for CF. But really, as the 20th century went along, non-CF bronchiectasis was kind of relegated to this entire big bucket of non-CF bronchiectasis versus CF bronchiectasis. And so while the 20th century, a lot of time and energy was focused on really deeply understanding molecular mechanisms in CF, that really has led to a complete transformation in the way these patients are cared for. Non-CF bronchiectasis still existed in this just general bucket of all the things that can cause it. But the good news is that this century, there's been a renowned interest in non-CF bronchiectasis. There's a lot of ongoing research. Researchers have gotten together and created large-scale registries that represent a lot of the world in different large data sets so that we can better understand the geographic variation of bronchiectasis. And publications have increased dramatically as we really are trying to better understand the deep core mechanisms that lead to bronchiectasis. And so that way we can better understand how to treat these patients. So a few important things to know about the epidemiology of bronchiectasis. The prevalence does seem to be increasing. Wide ranges are reported across the world depending on location, the age of people that are looked at, as well as different characteristics of the population that's surveyed. But there also has to be taken into account that a lot of these patients kind of fly under the radar. But now because CT is widely available throughout the world, more patients are being found on an incidental basis or because we have more advanced diagnostic imaging. It is more common in older individuals and slightly more common in women than men. There is significant geographic variation that we'll talk about. And there is definitely some overlap with our other known pulmonary diseases, asthma and COPD particularly. And the other important thing to know about these patients is that they cause significant burden to our healthcare communities. They use a lot of resources. When they're in the hospital, they use more antibiotics. Their hospital stays are longer than age-matched controls. They have more ER visits. And they use more steroids and bronchodilators as well. So it's important that we really understand this and get to hopefully where we are with CF therapies that are really revolutionizing the way we care for these patients. So a lot of work has been done over the last few years of understanding the pathophysiological mechanisms of bronchiectasis. And James Chalmers out of the UK has done a lot of work in collaboration with other researchers to better understand this mechanism and has this vicious cycle hypothesis in which structural lung disease happens to patients for a number of different reasons. How you enter this cycle varies. But it leads to this never-ending cycle of impaired mucociliary clearance, mucus plugging, chronic infection, chronic inflammation, and around and around and around the cycle you go until you get to advanced lung disease. So just to make sure everyone got their coffee this morning, here's a question. What is the most common cause of bronchiectasis worldwide? If y'all don't know, I think you guys need to go in the app to do the thing. This is probably a lot of people's first session of CHESS 2022. So if you go in the app under the session, I believe there should be a little audience room. So there is considerable overlap with COPD. Cystic fibrosis is also very common. But TB is not the most common cause of bronchiectasis in the United States and Europe. So these are all the potential etiologies that have so far been identified that lead to bronchiectasis. This is a long list. We're not obviously gonna read through all of it. But important to note that still, despite this long list, a significant number are what we call currently idiopathic, but really we just don't know, right? And I guess the question is, why does it matter? Does it matter if we can sort out why these people come to us, what their underlying disease is, or do we just need to know that they have bronchiectasis? And I think because as we get better with our targeted therapies and as we learn more about personalized medicine, it will be more and more important that we understand the contributing factors to these patients in stage one disease. So who to consider evaluating for bronchiectasis? Well, there are patients like Renee Linek described way back in 1819. Patients that come with chronic cough, with purulent sputum, with hemoptysis, and particularly who have exacerbations of those symptoms periodically with worsening. There are also patients who have respiratory diseases underlying that are followed in the clinic but don't seem to be responding to the standard treatments and seem to be having these exacerbations. And also patients who have underlying diseases that we know are associated with bronchiectasis like rheumatologic disease, inflammatory bowel disease, immunodeficiency, people who have a history of infertility because that can clue you into a mechanism or sinus disease, and as well as people who have a family history of similar problems because there's a genetic component to this. So when you see this patient in the clinic and incidentally will find on a CT or someone is referred to you because they have findings of bronchiectasis, these are some of the radiographic features that are characteristic, particularly the signet ring sign or the bronchiole having an artery next to it that the bronchiole is larger than. So I tried to make a little picture of that up at the top. It looks like a ring for someone who's proposing. Or a lack of bronchiole tapering where you see the airways going all the way out to the periphery. And these are CTs of patients that I take care of who you can see some of these features in the lack of bronchiole tapering, dilated and thick airways filled with mucus, and then becoming more cystic changes. And sometimes these features on radiographic images can give us some clues as to what is the underlying etiology for bronchiectasis. So if patients have focal disease, it could be more related to an airway obstruction caused by a foreign body or a neoplasm or a focal stenosis. Whereas if they have more diffuse disease, it points to a more systemic disease. Also, predominance in upper versus middle versus lower lobes has some association with specific diseases. This is an x-ray of a patient that I follow who has a characteristic finding right here, which is called finger and glove, where those airways are impacted with mucus because of ABPA. So how to work these patients up. Well, there are some guidelines for this from ERS and recommend getting some basic labs on all patients who present the clinic with a suspicion of bronchiectasis, including a CBC, some immunoglobulin testing, as well as screening for ABPA. And then other testing based on clinical features. So whether they have features of cystic fibrosis, you know, the hallmark symptoms that we know of, of sinus disease, GI disease, as well as infertility. Or if they have other family history of alpha-1 antitrypsin deficiency, an autoimmune panel if they have joint pain or other systemic symptoms. And then considering ciliary biopsy for patients who might have that clinical spectrum. In our institution, we have a really lovely diagnostic algorithm created by Dr. Maselli, who's in the back of the room. And we use this as an order set for patients who present to clinic. So, and it really highlights all these features that we just talked about. So, for localized disease, a bronchoscopy to evaluate what is obstructing the airway if something is there. Versus if they have diffuse disease, then getting a sputum culture, the labs that I just mentioned, and PFTs to evaluate for coexisting conditions. And then, depending on other symptoms, or if you still haven't figured out a diagnosis, moving on to additional genetic testing, imaging, GI evaluations, and then considering additional microbiological assessment via bronchoscopy if necessary. These patients are frequently infected. That was part of the vicious cycle hypothesis. And the common pathogens that are seen are pseudomonas, staph, haemophilus, strep, MCAT, stenoshorphomonas, klebsiella, and E. coli. So, common bugs that we see in kind of healthcare-associated infections, and patients that are on frequent antibiotics who have this pressure to drive towards more resistant pathogens that are more and more difficult to treat. And particularly, pseudomonas, I want to point out, is associated as a marker of disease severity. So, when you have patients who have bronchiectasis who start culturing pseudomonas, important to pay attention because those patients will have a faster decline in their lung function, tend to have worse quality of life, and do have increased mortality. Of course, there are other pathogens you cannot mention, like NTM, which we know is particularly associated with bronchiectasis. Fungal infections, nocardia species. There's increasing awareness that viral infections may contribute particularly to exacerbations and lead to hospitalization. And then, as more and more research is done using 16S RNA sequencing technologies, understanding really more about the bugs that exist there. The airways are never sterile, but as these patients get more and more sick, the diversity within their airways decreases over time, and they become more predominantly infected with these multidrug-resistant gram-negative rods. So, in summary, bronchiectasis is increasingly prevalent and also increasingly recognized. So, it's important for all of us to have an understanding about this and have it something in our minds to be thinking of when patients come to us with chronic cough besides just COPD if they smoked or asthma if they haven't. There are a bunch of different things that can lead to bronchiectasis, but still, a large proportion of them are idiopathic, or it's never understood. The diagnosing can increase the therapeutic options, and as well, it helps us understand in registries so that we can contribute our data together to really come together to try to create better therapeutics for these patients. And a standard workup, as I suggested, includes really understanding the history and physical of patients to try to understand what other clinical syndromes they have, as well as some imaging, some labs, and then microbiological assessment. And as Gretchen mentioned, I have to run across to the conference center, so if anybody has any questions, I'd be happy to take them at this time. So, I see a lot of people who have focal bronchiectasis found incidental to a CT for some other reason, and maybe no history of prior infection, maybe yes, history, and then low risk for aspiration. That standard evaluation in an asymptomatic person with incidental bronchiectasis, do you still apply that algorithm, or do you just note it as an incidental finding? I still apply it because it would be a shame to miss something that could be there. You might not see an obstruction from imaging, and if you missed an endobronchial tumor or something like that. Any other questions? You know, I never give up a chance to ask a question, so would you make a comment on the role of surgery in bronchiectasis? Again, as a small student, I was taught when it's focal, that especially if it's causing a lot of symptoms or recurrent pneumonia, that's good, but if there's bronchiectasis in the same lobe, resecting a lobe will actually make the residual bronchiectasis worse. So I'm interested in your thoughts. Yeah, I think, so my experience mostly on the CF side with surgical management, and we have had a couple of patients who were absolutely desperate because they had recurrent hemoptysis that was massive. But surgery is never something to be taken lightly with these patients. They frequently will have exacerbations, and you might not be able to, there might be areas of bronchiectasis that you don't recognize because they're not as pronounced than that area, in which case, at the time of surgery, they can't do airway clearance, those areas get worse, and it leads to this kind of cycle of worsening. So something to be taken, I think, very seriously. Thank you. Thank you all. Thank you so much. That's great. All right, I'll be professional and actually put on the jacket. Okay, so thank you guys so much for coming again. The next talk is on airway clearance, which I know gets everyone all hot and bothered on a Sunday morning. I'm Dr. Gretchen Winter from the University of Alabama at Birmingham, and I have nothing to disclose, except that I am probably not gonna be able to live tweet my own session, so if any of you guys are on Twitter, go for it. Okay, so today, we're just gonna share with you guys an overview of how to optimize airway clearance for your patients. Why are we talking about airway clearance at all? Because mucociliary clearance is actually impaired in bronchiectasis, and clinically... Go ahead. Oh, sorry. Clinically, more than 70% of patients with bronchiectasis actually have daily sputum production. All published guidelines for the diagnosis of the management of bronchiectasis promote airway clearance as a standard treatment, but only 56% of patients in the U.S. with bronchiectasis are actually prescribed non-pharmacologic measures to improve their bronchial hygiene. So, airway clearance actually relies on two overriding physiological principles. The first is that you have to have a mechanism to allow air to move behind the obstruction and ventilate those distal regions, and the second is modulation of the expiratory airflow in order to propel those secretions proximally and up in the airway. Now, those two things require a peak expiratory flow rate that has to be higher than the peak inspiratory flow rate, and the peak expiratory flow rate has to be at least 30 to 60 liters per minute in order to break those adhesive bonds that are generated between the mucous layer and the airway epithelial surface. So then, what is the purpose of airway clearance? To prevent that stasis of the mucous that leads to the mucous plugging, the airflow obstruction, the progressive lung damage, and that vicious cycle that Dr. Kee was just talking about. So, the short-term goal is obviously to provide more effective sputum clearance and then improve ventilation and breathlessness and chronic cough, and then longer-term goals include things like preventing further airway damage, reducing the number of pulmonary exacerbations and hospitalizations, and improving their health-related quality of life. So, what are the benefits of airway clearance? Various studies of various airway clearance techniques have shown benefits in a number of things. Increasing sputum volume, decreasing exacerbations, improving exercise capacity, reducing breathlessness, and improving health-related quality of life. So, what are the actual recommendations? The guidelines say, for all patients who have a chronic productive cough or a difficulty expectorating sputum, or who have evidence of mucous plugging on their CT, they should be taught an airway clearance technique, just a technique, it doesn't say which ones have to be done, to be done at least one to two times a day. Additionally, individuals with a non-productive cough should still be taught airway clearance techniques to use during exacerbations, during pulmonary infections to help prevent an exacerbation, and to minimize any irritating non-productive cough symptoms that they might have. And finally, airway clearance techniques should be taught by a trained respiratory therapist. On that point, if you do come up to the microphone and ask me how to show you guys autogenic drainage, I'm gonna fake diarrhea and run out of here, because I am not an RT. So then, the next question is, how often should airway clearance be recommended? Well, unfortunately, evidence for the frequency and duration of airway clearance techniques is not clear in non-CF bronchiectasis. So the frequency of how often you do these, and for how long, should really be specific to each individual patient's needs. I have patients who really don't have a lot of sputum production, whose FEV1 is 90%, and they have minimal symptoms, who really only do it when they get sick. And I have patients who have chronic symptoms every day, frequent exacerbations, who do these things four times a day. So it really just depends on their own exacerbation frequency, mucus production, and symptoms. Now, guidelines do recommend doing one to two times a day for about 20 to 30 minutes, and then doing them more often during exacerbations. And if a patient does call in and say that they're sick, they're having increased symptoms, before my clinical coordinator even sends me the message, the first thing she tells the person on the phone is increase your airway clearance. Hydrate, increase your airway clearance, Dr. Winter will call you back. So that is the first step in any exacerbation. So, let's discuss a quick case here. We have a 64-year-old female, who has a history of high blood pressure, dyslipidemia, and anxiety, who presents with two years of productive cough, and a CT showing bilateral lower lobe bronchiectasis and mucus plugging. So which of the following treatments would not be recommended? Go ahead and open up your little app there. A positive expiratory pressure device, or PEP device, inhaled Dornase Alpha, or Pulmozyme, hypertonic saline, otherwise known as 3% sodium chloride, or inhaled albuterol. All right, perfect, and 89% of you guys got it right. The correct answer for what not to do here is Doronase Alpha. We'll actually come back to that in a minute. So airway clearance techniques consist of breathing techniques, as well as positive expiratory pressure devices, as well as postural positioning and manual techniques. Now, breathing techniques include things like active cycle of breathing and autogenic drainage. Positive expiratory pressure, or PEP devices, are things that modify your expiratory flow. And examples of those include aerobicas, flutter valves, acapella. My little anecdote, my favorite thing here, when I was a fellow, I got a call one Sunday from a man who was a post-lung transplant patient. And he was speaking so slow that by the time he finished his sentence, I couldn't remember the beginning of the sentence. And after a few minutes, I have no idea what this man wants. And he finally hands the phone to a pharmacist, very confused pharmacist, who goes, can you please help me? This man keeps asking me for pickles. And we, at the Cleveland Clinic at the time, called the acapella a pickle. And so we were able to sort that out. But still, to this day, my favorite call that I've ever received. So of note, positive expiratory pressure devices do appear to have similar effects on health-related quality of life, symptoms of breathlessness, sputum expectoration, and lung volumes compared to other airway clearance techniques. So the British Thoracic Society recommends starting with active cycle of breathing or a PEP device and considering gravity-associated positioning and huff coughing as well. They also recommend autogenic drainage, high-frequency chest wall oscillation, and intrapulmonary percussive inhalation as alternatives when needed. So we'll get into this a little later. But I start with a PEP device and have my RTs train them on how to use them because it's just part of what they do. It's part of their triple therapy. I don't have to rely on them to make sure that they're doing all their techniques so well with active cycle of breathing and stuff. And then I add some of these more advanced things like IPV and VEST later if they continue to have problems. Now, we do not have evidence on whether manual techniques like chest clapping and shaking provide additional benefit in secretion clearance over these breathing techniques alone. So let's talk about other medications. Oh, one thing I do want to add on the prior slide. The most important thing in choosing your airway clearance is your patient, not what you have in clinic, not what's easy for you, not what your RTs prefer. It's what your patient can do and will do. If they hate the flutter, don't give them a flutter. If they'd rather do autogenic drainage or have someone clap on their chest or whatever the patient is willing to do and be most compliant with is what you should start them on. And in addition to that, whenever possible, try to prescribe something that can be done independently so that they don't rely on another person to do it for them. So now let's talk about an overview of adjunctive medications that can be used. So mucolytic and hyperosmolar agents can alter the mucus viscosity and thus enhance the mucociliary clearance. And long-term mucoactive treatment is recommended for adults with bronchiectasis who have difficulty expectorating their sputum and that they have poor quality of life. So what medications do we add? Well, the British Thoracic Society and me recommend the use of hypertonic saline. A study of isotonic versus 6% hypertonic saline actually showed similar exacerbation rates, improvements in quality of life, increases in FEV1, and reduction of sputum colonization in both the isotonic and the 6% groups. So whatever you use is whatever works for the patient. I normally start with 3% sodium chloride. And if they continue to be symptomatic but are tolerating that fine, I attempt to increase to 7%. And if they're doing great on the 3%, I leave them on that. And if they can't tolerate the 3%, I also try isotonic inhaled saline. One thing that I will mention when you're prescribing this, the first time I do it, I do it in clinic. I actually do a dose of albuterol and then hypertonic saline three or 7% in clinic before I prescribe it. It will never be covered by insurance for any of your non-CF patients unless they just have the world's best plan somehow. And before they drop $30 or $40 in a month's supply, I wanna make sure that they're gonna be able to tolerate it. So try that in clinic first. And then I also warn patients of a couple things. First of all, it's gonna make you cough. Can't tell you the number of times people come back and they say, well, I didn't take it because it made me cough. Like, we want you to cough. That's kind of the whole point of the medication. It should not make you cough all day. You should cough while you're doing it for a few minutes after, but it is good to cough while you're doing it. The other thing I warn them is that when you first start it, you might get a sore throat. That's normal. Typically, it goes away after a few days. So if you get a mild sore throat, just keep with it, your body will adjust. If you get a wicked sore throat, stop the medicine, wait till it goes away, try again. If the wicked sore throat comes back, call me and let me know. But I've only had like one patient who had the wicked, wicked sore throat and it didn't come back again. But a lot of patients will have a sore throat at first and they just get used to it after three, four days and it goes away. So when nebulizing hypertonic saline, it is recommended to pre-treat with a bronchodilator in patients with bronchial hyper-reactivity. But let's be real, hypertonic saline will induce bronchospasm in like everyone, so I pre-medicate everyone with a bronchodilator. I generally prescribe a Saba in most patients in order to increase the tolerability of these medications and to optimize the pulmonary deposition in those diseased areas of the lung. I start with albuterol. If they don't tolerate that due to tachycardia and stuff, based on anecdotal stories, I do leave albuterol. If they still don't tolerate that, I do half a vial and leave albuterol. If they still don't tolerate that, then I pre-medicate with ipratropium. Of note, I only use ipratropium as a pre-medication for hypertonic saline. Most of these patients will come to you guys with a diagnosis of COPD or asthma just because no one else knew what to diagnose them with before they got their appropriate diagnosis. And a lot of them will be on ICS, LABA, LAMAs, Duonebs, et cetera. If you look at the pathophysiology of LAMAs and SAMAs, theoretically, they can increase the viscosity of your secretions, which is really not ideal in someone who you're trying to actually break up the viscosity. So I do not prescribe ipratropium and actually regularly take people off of Duonebs and LAMAs when they come to me. But the only time I will use ipratropium is as a pre-medication for hypertonic saline in a patient who cannot tolerate albuterol or leave albuterol, or for patients who also have significant concomitants, non-bronchiectatic COPD. So let's go on to other medications. A study looking at high versus low-dose inhaled mannitol did not show a reduction in exacerbation rates, but there was improvement in the time to the first exacerbation and improved St. George respiratory questionnaire scores. However, it did not show convincing benefit, so mannitol is not routinely used and inhaled mannitol is actually not available in the US, so there we go. Now, there are no well-designed studies of inhaled acetylcysteine in non-CF bronchiectasis, and there's no clear benefit in CF bronchiectasis. However, a few years ago, oral NAC was found to be effective at reducing exacerbations in a small trial. So for patients who just have a lot of sputum and a lot of trouble expectorating it, I will sometimes recommend starting oral NAC in addition to the airway clearance. Now, coming back to our patients, one study of inhaled Dornase Alpha actually showed more frequent pulmonary exacerbations and a greater FEV1 decline. Thus, the European Respiratory Society recommends not offering recombinant human DNAs to patients with non-CF bronchiectasis. However, there are select patients that may benefit anecdotally, especially those with really thick, tenacious sputum that I will sometimes consider it for, but just in the general population of non-CF bronchiectasis, it's a no-go. Now, there was a study in CHESS that compared LAVA-ICS to ICS alone, and the group that received LAVA had a significant improvement in their symptoms and an improvement in their health-related quality of life. However, there was no change in their PFTs or microbiologic data or exacerbation rates. So both the ERS and the BTS suggest not routinely offering LAVAs, but suggest considering their use in patients with significant breathlessness on individual basis. And additionally, the use of bronchodilators, ICS, LAMAs, et cetera, should be considered for people who have coexisting asthma or non-bronchiectatic COPD and should follow the guidelines for those diseases. So the biggest take-home point here is that secretion clearance is key in the management of these patients. And I recommend starting most patients to boil all this down on triple therapy. So albuterol, hypertonic saline, and a PEP device. And this is my recommended order of airway clearance. I want you to start with the albuterol to open up your airways and make sure we get that medicine nice deep into your airways. And this is how I describe it to the patients. I write it all out for them. I have RT go over it with them again. But if you explain why you're doing this, it helps. Then we do the hypertonic saline. And that helps get down into those lungs and really break up that mucus and helps you cough it up. And then the PEP device. I do not initially start with vest therapy, but if you do add it on later, the vest can be used during the hypertonic saline and it should be done with an aggressive airway clearance protocol. Now after the completion of the albuterol and the hypertonic saline, I do recommend the use of a PEP device like Arabica, Flutter Evolve, Acapella, as well as Huff Coffee. And if your patient is on inhaled antibiotics, which the incomparable Dr. Dazenbrook will talk about next, or any other inhaled medications like inhaled corticosteroids or lavas, those should be done last. And the reason is you want those medications to stay in the lung. So you wanna do all your coughing and mucus expectoration first and then deposit those medicines that you want to actually stay in there to have time to work. As far as nebulizers go, I personally recommend the Parivias Pro Compressor with a Parisprint nebulizer. This machine is faster than most nebulizers. There are a couple of other really good ones on the market now. So that minimizes the time that your patients spend doing airway clearance, which is actually a huge thing to them. And this machine is also a little bit more hardy so it can handle some of the tougher medications like hypertonic saline and inhaled antibiotics. If the patient's insurance won't cover it because they already have a nebulizer, it's only around 60 to $70 and can be purchased individually on just nebulizers.com. I also, as mentioned here, prefer not to use masks in patients who are able because you minimize the medication that's lost if you use a mouthpiece. So exercise is very important for airway clearance and I actually prescribe it to all of my patients and it goes on their medication list. Pulmonary rehab has been shown to lead to improvements in exercise tolerance, symptoms, walking distances and health-related quality of life. And it should be offered to all patients who have breathlessness affecting their activities of daily life or those with impaired exercise capacity. Now whether or not they are a candidate for pulmonary rehab, I suggest prescribing 150 minutes of exercise a week. So whatever exercise the patient likes, I advocate they do. They can switch it up every day. For some people, this is running. For some people, this is walking to the mailbox. You can lift weights. You can jump on a trampoline. You can bike. You can dance it out to Taylor Swift in your living room. It can be different every day. The most important thing is that you're breathing deeply and that you're doing it regularly. And invariably, people ask me, well, how hard do I have to be working? How do I know? And my answer is, if you can talk in full sentences, you're probably not working hard enough. So whatever it takes to get you a little bit breathless to where you're really taking those deep breaths, that's what I want you doing and I want you doing it regularly. And then of course, yoga and core strengthening may also have benefits in flexibility and core stabilization, helping with your ability to expectorate sputum. So I encourage those as well. So what are some next steps? If a patient is on triple therapy and then on their return visit, they report continued difficulty expectorating sputum, you can consider adding best therapy at this point. When I have a patient who's in the hospital, I often add IPV with their nebulized medications and occasionally they'll be like, wow, this was a game changer. Can I get one of these for home? And for patients who really benefit from that, sometimes I'll even arrange home IPV. Airway clearance should be increased during exacerbations. You can consider adding manual techniques, especially during exacerbations to enhance your sputum clearance. You can also consider intermittent noninvasive ventilation to offload the work of breathing so that patients are able to more actively participate later in their airway clearance sessions. And if you wanna learn more about that, come to our CF session in a couple of days. And in the event of severe or new hemoptysis, I recommend holding airway clearance until the hemoptysis has resolved. And then I add the components back in one at a time, one per day, watching to see if they develop recurrence of that hemoptysis. So 24 hours after bleeding has stopped, you start the albuterol. Another 24 hours, add your hypertonic saline. Another 24 hours, add your PEP device back in. So what are our take home points? Airway clearance is the standard of treatment for patients with non-CF bronchiectasis. There are multiple benefits of airway clearance, including increased sputum volume, decreased exacerbations, improved exercise capacity, and improved quality of life. All patients should be prescribed airway clearance that is taught by a respiratory therapist, not me. And patients with mucus plugging, chronic productive cough, or difficulty expectorating sputum should be prescribed airway clearance techniques at least daily. Airway clearance techniques include breathing techniques, PEP devices, postural drainage, and manual techniques. And consider adding a short-acting bronchodilator followed by hypertonic saline in your airway clearance regimens, not ipratropium. So here are a whole bunch of different references. And I will take questions at the end. But next up, we have my mentor, who I have been told not to refer to as my old mentor, but my former mentor, Dr. Elliot Dazenbrook from the Cleveland Clinic, who's gonna be talking on initiation of long-term antibiotics. All right. Thank you very much, Dr. Winner. So that was masterful. That was very, very impressive. I worked with, I'm going to say Gretchen, sorry Dr. Winner, Gretchen when she was a fellow in her early stages of her bronchiectasis and CF career and to see where you're at now is very impressive. That was fantastic. I feel like with my partner, Dr. Kabaza, who's also here, listening to him now talk about NTM with people as well, trainees and our colleagues is really impressive. So thank you for inviting me to talk today. And so I'm going to kind of talk about this next step in the treatment of patients with bronchiectasis, right? And anti-inflammatory therapy and inhaled antibiotics and when do we introduce these for our patients, okay? And so this talk, I will refer to some randomized control trials, systematic reviews, the international guidelines, but what I want to share with all of you is that a lot of this is going to be what I actually do in my clinic, right? How do you incorporate these into your process during clinic with the limitations of being in a pulmonary clinic in the United States, right? And so a couple of my approaches are going to be different than what is actually in the guidelines. I'll highlight that is in my rationale for why I do that. But hopefully you'll find that this is a helpful talk as you think about how you approach the treatment of these patients in your own clinic. So for a disclosure, I do work with INSMED. I'm an unbranded speaker for them. I also participate in advisory boards and I'm going to refer to the Brenso-Catib phase two data in my talk today. So at the first visit, if you kind of think about this in terms of how you approach your patients, the first visit I really focus on the fundamentals, right? And so any of my patients that are inclined, sports inclined, I will give this analogy to them. I say we have to do the fundamentals right. Even LeBron James, who is the second greatest basketball player in the history of the world, he shoots 100 free throws every single day. He works on his form every single day. And so in bronchiectasis, your treatment, exercise and airway clearance that Dr. Winter just highlighted for us why that is so important is an anti-inflammatory therapy, inhaled antibiotics, the time that they take, the expense, the side effects are not going to be as effective until you've started exercise and airway clearance. So that has to be first, and so we spend a lot of time talking about that at our first visit. Like Dr. Winter said, get your patients into pulmonary rehab. Most of these patients will qualify for pulmonary rehab. If they don't, the exercise program as she highlighted is absolutely key. I feel like in addition to the benefits of airway clearance, it gives patients some ownership over their disease when they're exercising regularly. It's something they come back and talk to me about and they're proud. Like you told me to do 150 minutes of exercise a week. Dr. Daszak, I'm doing 107, you know, and they're very proud of themselves for doing that. Fatigue is a huge issue with bronchiectasis patients that isn't really recognized. I feel like the exercise really helps with that fatigue. And so this is a big part of what we talk about and recommend. And then finally, since I'm talking about anti-inflammatory therapies, please stop the inhaled corticosteroids, okay? These are not COPD patients. It's, you know, stop treating these bronchiectasis patients like COPD. And so there is a subset of bronchiectasis patients that have asthma overlap, they have underlying inflammatory bowel disease, you know, ABPA, rheumatologic disorders. So maybe 20 to 25% of bronchiectasis patients actually require an inhaled corticosteroid. But the downside to the inhaled corticosteroid in patients with bronchiectasis is that it causes local issues with immune dysregulation and predisposes them to exacerbations, right? And so we really want to try and wean those off. And I make patients, you know, show me that they benefit from the inhaled steroid to continue that, unless they clearly have an asthma phenotype. Another thing I'll point out with these patients, often they're put on inhaled corticosteroids because when you auscultate their lungs, they have wheezing. Well, dilated floppy airways and bronchiectasis are going to wheeze. And like we all learned early on in our training careers, all that wheezes is not asthma. So really make sure that this patient has an asthma overlap or an inflammatory bowel disease. And the last thing I'll say is that if you look at the US bronchiectasis registry, this always shocks me, 50 to 60% of patients are on inhaled corticosteroids, right? And these are centers of excellence that are submitting data to this registry. So anyway, enough on my dislike of inhaled corticosteroids. So my daughter helped me with this slide. So I like to say chronic macrolides are underutilized. So if you think about that for a second. Yes, so that's my ode to you, Dr. Winter. I tried to get one joke in there. So hopefully you will remember that. I think that's one of the most important points of this talk today, is that we don't use chronic macrolides enough. So I use 250 milligrams of azithromycin once daily. I write a script out, dispense 90, three refills. I tell the patient, we're gonna do this for six months, and then we are going to reassess. This is a daily therapy. 250 once daily is equivalent to 500 milligrams three times a week in terms of efficacy. So either one is fine. I personally do 250 milligrams once daily to decrease the number of phone calls that I get from my patients. Just anecdotally, the GI side effects are less at 250 once daily compared to the 500 three times a week. But if you do that as part of your process, that is fine as well. For tolerability reasons, azithromycin is preferred over clorithro and erythromycin in my practice. Why do we use macrolides? Why do we use daily azithromycin? So here's a picture of a neutrophil and pseudomonas. So when we think about the pathophysiology of bronchiectasis, right, it's a disease that's characterized by neutrophilic inflammation. When we think about our approach to treatment, everybody thinks about the infection, right? Most or some people think about the airway obstruction and how we're gonna target that with airway clearance that Dr. Winter just talked about. But I feel like a lot of us don't concentrate on the airway inflammation part, right? Or your treatment for the airway inflammation is inhaled corticosteroids, right? But neutrophilic inflammation is what characterizes bronchiectasis. And so azithromycin, which obviously is an antibiotic, has these other non-antibiotic properties and it's hypothesized that azithromycin impairs neutrophil chemotaxis. So it's gonna inhibit the movement of neutrophils in the airway. And that's what translates into the clinical benefit for your patients when they take the azithromycin. Decreased pulmonary exacerbations, improvement in their day-to-day symptoms that bother them so much with their coughing and sputum production. The picture below the neutrophils is a flagellated pseudomonas so that's probably an acute infection. But I care about pseudomonas for lots of reasons in bronchiectasis that were highlighted earlier. But primarily because it is a potent stimulus, pseudomonas is a potent stimulus of neutrophilic inflammation. So you've already got neutrophilic inflammation in bronchiectasis, whatever the cause is, and then you put pseudomonas on top and it really takes it to the next level. So in my personal practice, when I have patients that continue to be symptomatic, exacerbate, when I see them at visit two, visit three, despite airway clearance, right, I've initiated that, they've improved, but they're still not to where they wanna be. This is my next step in terms of treatment. And so if you look at the international guidelines, they'll actually recommend inhaled antibiotics in this specific situation. Well in the US, and this is a conversation I have with my patients, shared decision making, here's the downside to inhaled antibiotics. They take 40 to 50 minutes a day to nebulize, they are very difficult to access through insurance, they are very expensive in terms of cost to the patient, in contrast to azithromycin, which is a pill that you take once a day, it works great for this neutrophilic inflammation, the cost to the patient is fairly low, and the treatment burden is pretty minimal. So this is usually my next step for those specific reasons. Now, it's not the easiest thing in the world, so this is a physician on the phone with the insurance company, right? Like fighting for a prior auth, we all love those, and probably have a whole session just on that. And so I have created a dot phrase that my assistant has now. So you can have someone in your office, whoever gets the prior auth, just reply back with, I have prescribed daily azithromycin as a chronic therapy for bronchiectasis, it is supported in international guidelines and three randomized control trials, please approve this medication. If you would like me to send you the articles, I'm happy to do that. And so, and I have about a 99% success rate with that. So what do I think about when I prescribe chronic daily azithromycin? So the first picture there is a sputum cup, right? So at the first visit, I get sputum on every single patient that I see with the diagnosis of bronchiectasis, right? So I know we get bacteria, which is important, right? This is another point that we haven't really highlighted yet today. If you see patients with bronchiectasis in your clinic, in your practice, you have to have a process to get sputum for these patients. So you have to have sputum cups in your clinic, you have to have them in the PFT lab, oh, you're seeing Dr. Dasmerk, you're coughing stuff up, here's a, he wants the sputum, let's go ahead and get that. So you have to have a process to do that. So I know that they do not have MAC detected, at least at their first visit, you don't want macrolide monotherapy in patients that you're gonna be prescribing this. Number two, a lot of the patients have pseudomonas, they're gonna flare, you're gonna be giving them levofloxacin, you're gonna be giving them ciprofloxacin. I hold the azithro for the QT reasons primarily if they're going to be on both at the same time. Third, I screen all my patients at every visit. Do you have tinnitus? Yes, no, how severe is it? If someone has moderate or severe tinnitus, I won't prescribe it. Someone, if I say, do you have any issues with hearing? And they say, what? Then I send them for a hearing test just to get a baseline and follow that while they're on long-term azithromycin. And then finally, an EKG, I like to get a baseline, just know where their QT is. If it's kind of greater than 450, then we kind of have a conversation about the risk benefits and then I'll repeat it two to four weeks after to make sure that it's not growing out of control. So I mentioned earlier the phase two study of brentsicatum. And one thing that I think was underappreciated about this trial that hasn't been talked about is that this concept that addressing and treating, this kind of proved the concept that addressing and treating neutrophilic inflammation will result in improved clinical outcomes in humans, right? And so to me, I thought that this is a very important point in the treatment of bronchiectasis and kind of the pathophysiology. But in that phase two study, it was shown to be safe at about a 40% reduction in pulmonary exacerbations. So again, I think we're gonna be hearing more about neutrophilic inflammation and how we approach that in the future. And the phase three study right now is ongoing. And so I look forward to those results. So that's my approach for chronic macrolide therapy that is underutilized in our patients. And the next step in terms of treatment, so exercise and airway clearance, chronic macrolide therapy, patients that are still symptomatic, this is where I start to think about the inhaled antibiotics in these patients. So the guidelines will talk about three or more pulmonary exacerbations in the last 12 months. But this paper, I thought, was particularly influential to me in how I think about the use of inhaled antibiotics because the literature is rife with failed inhaled antibiotic studies and non-CF bronchiectasis. So we could probably have a whole day talking about why that is. But this was Dr. Flum and colleagues' experience at their own center. And really what they looked at was patients that were on what I would call maximal therapy or ideal therapy. They're doing their exercise, they're doing their airway clearance, and maybe they're on a macrolide and they continue to exacerbate. So frequent exacerbators, they have pseudomonas, and they're kind of getting optimal therapy. And that group of patients that continue to exacerbate, that's who they introduce the inhaled antibiotics in. And what you see is the shift from the number of exacerbations being two or three per year, shifting over after treatment to zero or one. So to me, I found that to be fairly convincing and consistent with my clinical experience about the use of inhaled antibiotics in those specific patients. So a lot of challenges about prescribing inhaled antibiotics in the United States. You definitely, this is bronchiectasis, master's level, basically because I think it's almost impossible to do on a regular basis without a team to kind of help you out. And so the first go-to is inhaled tobramycin, 300 milligrams, twice a day. This is, if it is on formulary, this is usually the one that is on. It also comes as a powder formulation. I try to avoid it in women of childbearing age who are trying to get pregnant. People that already have tinnitus or hearing loss all tend to try and go to the next level. Inhaled as Trianam. Again, failed studies, specifically in bronchiectasis, methodologic issues, but I will try and get access to this for my patients. In Medicare, it's next to impossible. Private insurance, occasionally you'll be able to get access, maybe through a patient program. But again, very expensive and can be quite a barrier. Inhaled colistin, they use a ton of in Europe. I think this is great, especially if patients have stenotrophomonas or acromobacter. I'll use a lot of inhaled colistin. I also use it in pseudomonas. And lately, I've been using more inhaled Ceftaz because it's once a day. So especially in my Medicare patients, I can, again, having these conversations with them, I can get 14 vials of Ceftaz. It's by far the cheapest for Medicare patients. And I say, let's do a two week trial. Let's kind of see how you do. We'll do two weeks on, two weeks off. And then we can make a decision if the cost to you is worth it to continue this therapy. So these are kind of some of the different doses and the inhaled antibiotics that I'll consider for my patients. As Gretchen alluded to earlier, the order of the inhaled medications is extremely important. The people do not, or it's not intuitive to our patients. So I'll tell them, I don't want you to spend $1,000 on your TOBY and then do hypertonic saline right after it and cough, it's like coughing dollar bills all over your kitchen table. So please don't do that. And then same thing with no masks. That was great. And so, and then if they are an inhaled corticosteroid, it doesn't matter if the steroid or the antibiotic are last, but those can be interchanged. And then the Pari ProNeb Max, I also do the same recommendation for my patients. If they go to CVS, Walmart, Walgreens, whatever, the nebulizer that they give them will burn out after about three weeks of inhaled antibiotics and hypertonic saline, or it'll take them an hour to nebulize, so I also recommend that they get it from a local website. Just don't go through your insurance. It'll take forever to get reimbursed. So in conclusion, again, as you're kind of thinking about a stepwise approach to how you manage your patients with bronchiectasis, do the fundamentals first. If they continue to be symptomatic, I really think that us focusing on not just the infection, not just the airway clearance, but also how are we gonna attack the inflammation, and azithromycin or macrolide therapy is a great way to do that. But at that same point, if they also have pseudomonas, it's not unreasonable to do inhaled antibiotics instead of the macrolide at that point if you're able to get access to that. I think that that's also a reasonable approach, but I do start personally with the macrolide in most of our patients, and it can be very helpful for our patients in treating them. So I'd be happy to take any questions, anybody that disagrees with anything that I said or has an alternative viewpoint, happy to discuss that as well. So thank you.

non-cystic fibrosis bronchiectasis

diagnosis

management

early diagnosis

treatment

airway clearance techniques

chronic macrolide therapy

pulmonary exacerbations

personalized treatment plans