Video Diagnosis, Evaluation and Treatment of Bronchiectasis Play Pause Volume Quality 1080P 720P 576P Fullscreen Captions Transcript Chapters Slides Diagnosis, Evaluation and Treatment of Bronchiectasis Overview Hello and welcome to this webinar. On the diagnosis, evaluation and treatment of bronchial basis. I'm Mark McClusky, I'm a pulmonary physician at the University of Connecticut and I run a bronchial ethicists program there. This is a CMI certified webinar jointly provided by the University of Massachusetts Medical School and CMI Education Resources. And this was supported by an educational grant from Instead I have a few conflicts of interest to disclose. I've been a clinical trial investigator and consultant for instead and also a consultant to Beringer international biophysics and zambo bronchitis is characterized by recurrent chronic cough sputum production and acute infectious exacerbations in most patients. However, it's defined by permanently dilated airways visible on chest ct and an airway can be defined as dilated when its internal diameter is greater than that of the accompanying vessel. And in this ct scan where the cursor is you can see the classic signet ring sign with a small vessel in a very large airway. It's predominantly a disease of the elderly with also most cohorts demonstrating female predominance as much as 60-70%. We're certainly seeing more bronchi actresses now With prevalence increasing by an estimated 8% every year And a recent estimate was over 400,000 patients suffering from bronchial ethicist in the United States, which certainly means that it's no longer an orphan disease and this figure shows how it's predominantly a disease of the elderly, very few cases in younger patients. Let's talk about the pathogenesis of bronchial basis. I'd like to think of the factors as inciting factors which get the process going and then perpetuating factors which lead to ongoing disease and worsening impairment and the inciting factors are often related, two problems related to host defense against bacteria. And there are a variety of these because bronchitis is is a very heterogeneous condition. So some of them include abnormal mucus, such as in cystic fibrosis or in mutations of epithelial sodium channel, both of which can cause mucus that is thick, tenacious and difficult to clear, resulting in airway obstruction and a perfect milieu for the growth of bacteria. Even with normal mucus, there can be abnormal mucus clearance. Common examples being primary sillier dyskinesia or an atomic airway obstruction immunodeficiency is commonly seen with the most frequent being common variable immunodeficiency, at least for the adult population. We can see bronchi ethicists as a cycle of of acute or chronic airway infection with the resulting inflammatory insult. So patients can develop bronchi actresses after an acute infection such as pertussis, a severe pneumonia or more chronic infections such as non tuberculosis mycobacterium infection. We often see bronchi ethicists related to underlying autoimmune disease, some of the more common ones being show grins, we're inflammatory bowel disease and it's important to note that even after A complete work up, about 40% of cases remain idiopathic, that number has been coming down slowly over time as we identify more underlying causes but still a substantial percentage remain in the pacific. Now I alluded to some perpetuating factors which are related to ongoing airway inflammation and progressive damage due to the chronic airway a bacterial infection and there are numerous reasons for this. There are hosts arrived inflammatory mediators, some of which are listed here, but by no means all of them neutrophils. Syrian protease is neutral zone protein matrix, metallic protein ease and numerous markers of systemic inflammation are elevated in bronchi actresses, patients again pointing to the importance of inflammation and there are direct bacterial products including endo toxins exa toxins including pseudomonas at last days in some patients in biofilms and these factors result in mucus hyper secretion and impaired mucus clearance. Um in addition to other problems um and they contribute to progressive damage to the airways with resulting dilatation, worsening systemic symptoms, increasing frequency of exacerbations and ultimately impairment of pulmonary function. Many years ago, the vicious cycle to explain the pathogenesis of bronchi emphasis was proposed and indeed it is a cycle. Um It's hard to know where to start for some patients. Um but certainly in some it starts with avenue abnormal mucus clearance and others that maybe starting with bacterial infection colonization. But ultimately these lead to neutrophils derived inflammation, including from the last days is as we discussed and ultimately airway destruction and distortion, which leads to further abnormalities of mucus clearance, etcetera. More recently, Patrick flume and some colleagues decided that it was a little more complex than a cycle. And they proposed the vicious vortex model, which includes some of the same issues, but this model points to the complexity of it, because of all the interconnected issues here. And I believe this is a morph accurate representation of what's going on. So let's have a clinical case to to put everything in context. And this is a patient that I've been seeing for For over a decade. He was a 69 year old male who was self referred with a long history of bronchi ethicists. When I evaluate him, his sputum grew staph aureus and might go back to your maybe. Um um he never grows the Mac again, so we don't have to deal with that potential complexity. He was next seen two years later. This is his cat scan which again shows bronchi ethicists and dilated airways but not not hardly severe. Certainly many patients look much worse than this on ct scanning. By the time I saw him that next time his sputum production had increased, he grows methicillin sensitive staphylococcus and pseudomonas on multiple cultures. Over the next year, he's using a positive exploratory pressure vibrate, torrey device, handheld device for airway clearance twice a day he's a very adherent patient but nonetheless, he's having About three exacerbations a year characterized by increased sputum but without systemic complaints, luckily each time he responds well to leave a flock system. He started on inhale to permission because of his frequency of exacerbations and his chronic cough which really was impairing his quality of life. Um he comes back and tells me that it was life changing his sputum production completely. Rem it's And then promptly his creatinine increases from 0.9 to 1.4. Which is not supposed to happen with inhaled antibiotics but unfortunately occasionally can. Um We switched him to inhaled as tree and mm. Um And within several days he develops a diffused popular rash. So we have to stop that now. About eight years later, his lung function has declined. He's got more exertion of dystonia when he goes on the treadmill. His cough is more productive and persistent with increased impairment of his quality of life. So what are the important issues that we're seeing with this patient? And he's he's quite typical. There's nothing unusual about him other than perhaps his uh reaction to these inhaled antibiotics. Um Quality of life impaired, right? He's got daily coffin sputum, luckily he's not having systemic symptoms. He's not losing weight, having fevers or sweats, but that is seen in some patients he's having exacerbations and a higher frequency is associated with worse overall outcomes. Perhaps due to increased damage that's caused during these exacerbations. He's got loss of lung function, which is causing his dystonia. And this really highlights the unmet needs and treatment both um efficacy and toxicity as well as treatment burden. Um If you have patients who are doing airway clearance twice a day and inhaled antibiotic twice a day, hyper tonic sailing twice a day, which we'll discuss. We're talking about a lot of time and many patients don't have time for that. And it's important to note that there are no pharmacological therapies That are FADA approved for the treatment of bronchitis is zero. Everything we do is off label, which speaks to the lack of high quality data supporting highly efficacious treatments. Otherwise we would likely have something that's FDA approved. So I'd like to talk a little bit about how I evaluate a patient. Um, de novo who comes in with bronchial basis and one of the things that is important to do is to assess for underlying causes for which there are specific treatments. We don't want to miss an underlying cause, which we can directly address. These include common variable immunodeficiency for which we routinely check quantitative immunoglobulin levels. α one Anti trips and deficiency, which is not very common, but certainly shows up. I've diagnosed a handful of patients with alpha one anti trips and efficiency as a cause of their bronchi actresses and of course it's a very cheap, easy blood test. We don't want to miss cystic fibrosis, which everyone knows. Um, but it's important to understand that milder variants can present an advanced age, often with mild disease. And I've diagnosed Several individuals in their 60s and 70s that had unsuspected cystic fibrosis and we can do that with a mutation screen or sweat chloride. Um although it's important to know that it's very difficult to get a mutation screen on a Medicare aged patient. Um It's the most insurances will not approve it. So we often do a sweat chloride instead. We certainly don't want to miss non tuberculosis michael bacterial infection. So every patient will get micro bacterial cultures both on presentation and then at least yearly for um surveillance. Allergic broncho pulmonary tuberculosis is another cause of bronchi ethicists. Most patients do not need specific testing but if you have a patient who has high I. G. Levels hemophilia um severe asthma then these patients should be tested for A. B. P. A. And the opposite of course is most of these patients don't have asthma um and don't have hi I. G. Levels and therefore you don't need to do the specific aspergillus sorry allergies. And then for some of the slightly less common causes you want to test patients with suggestive findings. So do an autoimmune panel for patients who have suggestion of autoimmune disease. Um Look for primary biliary dyskinesia in patients who present who have um disease since childhood and in an adult practice like mine. Um It will be fairly unusual to diagnose primary salary dyskinesia. Although it does happen most patients are diagnosed at younger age And again approximately 40% will remain idiopathic. Despite this type of evaluation every patient initially gets cultured for bacteria. Mycobacterium and fungus. And at least yearly um surveillance for bacteria. And micro bacteria generally don't need to keep repeating that for fungal cultures And we want to determine the severity. How severe is there cough? How frequent is it? How much sputum are they bringing up? What color is it? How does it impact their quality of life? We want to know the frequency of exacerbations and we want to know baseline pulmonary function. Why is that important? Well the severity of disease can be quantified and it is a predictor for important outcomes. Um There's the bronchi ethicists severity index and then there's a frequent exacerbate or phenotype and you can see that the severity index correlates with frequency of exacerbations, hospitalization and mortality. Um Obviously important outcomes. Some of the factors that contribute to both. The bronchi exorcist severity index and the frequent exacerbate or phenotype includes frequency of exacerbations which is probably pretty obvious but the historical frequency of exacerbations predicts future frequency once a frequent exacerbate er generally um always a frequent exacerbated and other predictors include bacterial infection with with pathogens as opposed to patients who cough up only normal flora. 51 radiologic severity disease and coexisting COPD. There are other factors but these are some of the most important ones. So I've shown a few HR cts. It is the study of choice. Um We don't do bronchi grams anymore luckily. Um It's also one of the markers of severity, basically the extent of disease. How many lobes are involved as well as the character of the bronchi actresses. How severe is the dilatation, how much mucus plugging there is etcetera. And there are also some clues regarding ideology that can be gleaned from the higher ed. C. T. So one of the most important one is um clues for non tuberculosis mycobacterium infection. The most common of which of course is mycobacterium avian complex. So patients with this infection often have prominent right middle lobe or lingual er involvement. Um prominent tree and bud modularity, cafeteria diseases highly suggestive and practice excavatum. So these are two different patients who have MAC as the cause of the bronchial basis. When I quiz my fellows on what's the cause of this patient's bronchi ethicist. They intently scour the lungs uh on this image and this image and and they don't find anything. And then every once in a while one of the fellows is smart enough to look at the skeleton um the bones and see the severe practice and get the answer. So there are clues both within and outside the lungs. This patient was actually missed bye for many years. Her MAC disease I think because this cavity was not picked up on as a cavity it was probably considered part of the cystic bronchi exorcist this is all bronchitis is here but this is much thicker walls you can see and this was this was mycobacterium avian complex. Um And this this woman was quite sick, losing weight and here's a nodule that will ultimately become a cavity if this patient isn't treated aggressively. Other potential clues are common in emphysema and a patient with alpha one anti trips and deficiency. But it's important to note that the lack of emphysema does not rule out anti trips in alpha one anti trips and efficiency. There is a phenotype of patients with this genetic condition who will present with bronchi exorcist that can be quite severe and without emphysema. Um And I've seen this twice. Cystic fibrosis will predominantly have upper lobe disease which is otherwise fairly unusual in bronchi ethicists and allergic broncho pulmonary tuberculosis, which is what this patient has. Has characteristically has central bronchial ethicists. And you can see this patients central airways are quite dilated, but then you go out to the periphery and there's really nothing going on. So this is A. B. P. A. And sometimes you can also see prominent mucus plugging with very high density mucus. So the hands field units your radiologist or you can measure that. Um And you'll find that it's much higher density than normal. We'll move on to treatment. Now I think one of the most important concepts is that it is not one size fits all. I one of my trainees was presenting some research some of our research once and and someone sort of challenged him because the cohort were presenting everyone's getting different types of treatment. They said you don't have a protocol and yes some of our treatments protocol. Ized but it doesn't make sense to give a patient who's virtually asymptomatic who has bronchi ethicist the same treatment As someone who has four exacerbations a year ends up in the hospital has chronic pseudomonas. Again it's a very heterogeneous condition. Uh there's significant burden to some of our treatments so you don't want to give everybody the same treatment. And very often we add them in a stepwise fashion as needed. So for just about every patient airway clearance has to start what we do for the patient. It is a mainstay of treatment. We think it's very important but I have to admit that there is very little high quality evidence for airway clearance in bronchial texas. But we've all seen many patients who have improved greatly from a symptom standpoint with airway clearance alone, we think it's because airway clearance promotes removal of secretions and the bacteria and inflammatory mediators that the secretions contain. It also prevents mucus plugging and electrolysis and um used to be done holy with non device modalities, chest percussion with postural drainage, automatic drainage, active cycle of breathing. These techniques are still used by some patients. Um But very often we try to help them along with devices most commonly we use the handheld vibrate, Torrey positive expository pressure devices. The positive pressure prevents airway collapsed during exploratory maneuvers and the vibration that uh that these devices caused during exhalation result in changes in shear forces due to alterations in airflow velocity and those changes help promote detachment of mucus and their advantages that they are inexpensive and they're relatively easy to use for most patients for patients who don't do well on those types of devices. We generally will will switch over to a high frequency chest wall oscillation vest um or start them at that if if they're already fairly advanced disadvantages are that they're more expensive And there's increased treatment burden. It's just more time to strap one of these on, turn it on and use it for 20 minutes. Um Studies have shown increased mucus production compared to handheld devices associated with with these types of devices. But not yet do we have we don't yet have any evidence of improved outcomes but it's not to say that we have great studies that show the outcomes aren't improved. We just don't have great studies yet. Then there are airway clearance modalities that are pharmacologic most commonly is hyper tonic sailing which presents an osmotic load to the airway to draw water into the airway and increase hydration and therefore make the mucus easier to clear. It's very commonly used. Some patients end up loving it. Some patients hate it. Um It is very soft, you can cause irritation or nausea. Um and so it really becomes patient preference. Again, we have limited evidence of benefit with high quality data but again, some patients do very well in it. Then there are mutual itics. There's really only one that we have strong evidence that it's um you politic, but it's very important to know that Germany's alpha DNA. In contrast to cystic fibrosis resulted in worsened outcomes in a large, well done randomized controlled trial. So it is generally contraindicated in bronchi actresses, patients will frequently use mew, mew chemist and in europe similar agents. There is limited evidence, there's certainly no evidence of harm. I don't recommend these agents in general, but if the patients using them and and feels they're doing well with them, I certainly don't discourage them back to inflammation. As I mentioned before in most patients information is driving symptoms and disease progression. It's predominantly neutral filic information generally in response to chronic bacterial infection. However, there is an important and substantial minority of patients who seem to have uh a scientific information which can be identified by the assassin ophelia in the blood very often. Um we generally don't test um in the airways unless it's part of a clinical trial or other type of study. And um these patients often seem to have more bronco spasm. Not surprisingly, And there is an ongoing trial of an aisle five inhibitor targeting the eosinophilic inflammation because of these, these findings, many patients who come to us are on inhaled corticosteroids, even though there's no significant evidence of asthma or airway hyper reactivity and we try to avoid them unless there is evidence of hyper reactivity because they're associated with increased risk of developing non tuberculosis. Mycobacterium infection which do developing a substantial uh percentage of patients with bronchiolitis is over time. And these this type of infection again most commonly MAC is often difficult to treat and associated with significant morbidity. So we don't want to do things that don't help the patients and are associated with risk. That's in contrast to chronic low dose macro light therapy. Macro slides in addition to their antimicrobial effect have direct anti inflammatory and immuno module Torrey effects on the host. And several well done multi center R. C. T. S. Have demonstrated benefit from macro leads in reducing frequency of exacerbation or time to exacerbation with chronic low dose use most commonly azithromycin and erythromycin or what's used. And certainly in the US it's most commonly azithromycin and this is a meta analysis demonstrating the immaculate effect on the ST George's respiratory questionnaire. So a quality of life questionnaire where um a drop is associated with improved outcomes and you can see a statistically significant improvement on in quality of life. Only one of the studies individually showed that, but with the meta analysis you can see a very strong signal um In addition the primary endpoint for most of these studies was the effect on exacerbation rates. And you can see also again um a strong um diminishment of the frequency of exacerbations. So macro leads certainly are the one treatment where we have high quality evidence in bronchial basis and therefore the frequency with which they are being used in bronchitis patients is steadily increasing. So based on these data. Um macro leads are recommended in the european respiratory society guidelines For patients with greater than two exacerbations per year. Um It's important to note however, that even in patients who don't have frequent exacerbations who may have severe daily symptoms, macro leads maybe a benefit. And many of us have had patients who have had very very nice responses in terms of their quality of life uh to chronic macro light therapy unrelated to to their exacerbations. Um The dose most frequently used is 250 Three times weekly or 503 times weekly. Um And perhaps a very important thing I can tell you is that although The guidelines generally have recommended 500 mg three times a week, patients Do very well quite often on 250 Milligrams three times a week. And the frequency of side effects that we can see with the higher dose um is much lower. Patients tolerate this low dose three times a week. Very, very well. Another thing that has to be stressed is that it's imperative. Absolutely imperative to rule out non tuberculosis mycobacterium infection before you start chronic low dose mackerel right there. Otherwise there's a risk of inducing macro died resistant michael back to maybe um complex disease which is almost impossible to cure. Uh and is is associated with a very high risk of mortality. So you've got to make sure the patient doesn't have MAC before you start this therapy. And at the bottom of the slide I have the exact wording for macro light therapy from the E. R. S. Guidelines. They suggest long term treatment for adults with bronchitis is not infected with pseudomonas. And then for patients infected with pseudomonas um they recommend it if they're not doing well despite taking an inhaled antibiotic. So one of the prime um bad actors in neutrophils inflammation is neutrophils last days. And in this figure you can see that the levels correlate with disease severity as measured by mortality. So patients with the lowest levels of neutrophils last days had the lowest mortality, highest levels the highest mortality. But the levels also correlate with the severity index. The presence of bacterial exacerbation. I'm sorry bacterial colonization, frequency of exacerbation, lung function, loss, hospitalization, all the bad outcomes. Carly with neutrophils, Alaska's levels. The other thing neutrophils last days does which which isn't helpful is that it stimulates the mucus secretion directly from the goblet cells. So again perpetuating the problems. Um So it seems to be a natural target. Uh for bronchi actresses patients, Brent's academy is a small molecule inhibitor of dependable pep. Today's one otherwise known as Catholics and see and what this enzyme does is it cleaves. And in terminal di peptide from the probe um uh Syrian proteus is before they're released before the white cells are released from the bone marrow. So with this inhibitor of DPP one um there are no active um neutrophils are the last days is released or at least there are decreased amount of them depending upon the dousing of the inhibitor. So basically we do not get active neutrophils. Syrian protein cases in the presence of this drug. And this is one ah graph showing changes in neutrophils last days in the study where this is the baseline placebo, you see no decline, 10 mg and then 25 mg, market declines and then showing that it's temporary back to normal. After the study is over. This study was um randomized double blind placebo controlled study looking at friends Academy in patients with bronchial illnesses and patients with frequent exacerbations. So, patients enrolled in this study had to have had at least two exacerbations during the prior year and the primary outcome was the proportion of patients Um with no exacerbation. And you can see that with both the 10 and 25 mg dose there was a market improvement in the percentage of patients who had no exacerbations. More patients exacerbated that were on placebo and this was highly statistically significant. And I would venture to say clinically significant. So in this slide we see a forest plot. Looking at the characteristics of the patients included in the study. And you can see that the improvements in exacerbation rate, we're not for any specific type of patient. The improvements were seen in all ages. Um it didn't depend upon how frequently they had had exacerbations prior to enrollment. It was identical for whether or not they were on my acolytes, which was something of significant interest would would the benefit of this potential benefit of this drug B present Even if the patient was already on metabolized and it certainly seems as if it was pseudomonas. Yes or no didn't affect it interestingly, the the level of neutrophils last days didn't seem to correlate much other markers of severity. Didn't predict improvement. It was a fairly widespread population that was improved. Moving on to antibiotics which are the mainstay of treatment for acute exacerbations and generally we treat for the likely pathogen based upon the ongoing serial sputum surveillance, which as I mentioned, we do minimum of once a year. The most common pathogens. We see our h flu about 30 Pseudomonas in 25-30%. Depending upon which cohort Staph aureus up to 10 And standard trophy mon is approximately 5%. It's also important to realize that about 50% of exacerbations related to respiratory viruses and it's the usual suspects the same respiratory viruses we see causing pneumonia or or upper respiratory infections. Um No, just because you isolate arrest or a virus in a patient who is having an exacerbation doesn't mean that that viral infection hasn't caused one of the bacterias that they're colonized with two um contribute to the exacerbation. So it doesn't actually mean that they don't need antibiotics but it's important to know that um there's a potential that as we learn more and do more viral testing that maybe we can spare some of these patients antibiotics with their exacerbations. Unfortunately for pseudomonas fluoroquinolones are the only oral option. So patients may need I. V. Therapy if they're intolerant of fluoroquinolones or resistant or of course if it's a severe exacerbation, luckily the vast majority of exacerbations are treated as an outpatient with oral therapy in the United States. We also use antibiotics commonly to prevent infection and and diminished the amount of inflammation most commonly used for patients with chronic pseudomonas infection and frequent exacerbations but sometimes other gram negatives or even um MRSA will prompt the need for and held antibiotics long term and how Bank of Meissen can be used for M. R. S. A. In the US through a quirk of history. We used them intermittently 28 days on 28 days off. This may not be the best way to treat it. The logic would dictate that every month allowing the bacteria to come back may not be the best thing to do but uh it would be difficult currently to get an insurance company to pay for continuous antibiotics long term. Um Because that's not the standard in europe they often use continuous inhaled antibiotics. Um Despite the fact that none of these are FDA approved, our accumulated experience is that that this type of treatment is effective. Uh for some patients um And patients do report improvement. Um There was a very nice randomized but open label trial of inhaled gentamicin Back about 11 years ago that showed nice benefit. Um Farmer companies became more interested in this patient population. Uh And this type of treatment after that study and numerous studies followed pharma companies sponsored clinical trials which failed to hit their primary outcome which was generally quality of life or frequency of exacerbations. Um We're some of these were dropped due to less than promising results so we still don't have FDA approval for inhale to permission as trans am Callison dry powder ciprofloxacin inhale by personal super flux. Again, non FDA approved. However the first three are available and are very often used off label. And I often use gentamicin off label which seems to be as effective as to promise in may have less um incidents of cough and bronchial spasm and perhaps most importantly unfortunately is that it may be easier to get because it's cheaper. Um You hate for price to be what dictates therapy but that's the world we live in. And I have not had a lot of pushback or really high copays with inhale gentamicin as opposed to inhale to bring medicine or as tree and m which are brand name. So what do the guidelines say about inhaled antibiotics? Again the er S guidelines they recommend um inhaled antibiotics but they again limited to patients with greater than two exacerbations per year. And many many of us think that the target population should be somewhat broader. And they say we suggest long term treatment with inhaled antibiotics for patients with bronchial illnesses and chronic pseudomonas. Um They also suggested for patients not infected with pseudomonas in whom oral antibiotic prophylaxis is contraindicated, not tolerated were ineffective. And you can see that these recommendations are not strong recommendations are conditional with either moderate or low quality of evidence. Again reflecting um the positivity of high quality evidence we have for so many issues in Brownsville texas. So why are there no FDA approved pharmacologic treatments? Um We we've we've theorized about this is it the wrong patients or the wrong drugs being studied? And that's what it turned out to be with D. N. A. S. Works for cf not for bronchitis. Um Are the wrong outcomes being studied in which patients should we study quality of life in which patients should exacerbations be the the primary outcome are the right drugs being given the wrong way and Intermittent inhaled antibiotics 28 days on 20 days off is a potential example of this. And the other question is the wrong sub population of bronchitis patients being studied as as I've said a few times it's a very heterogeneous disease. It's entirely possible that that therapies that have failed for sort of all comers with bronchitis is would be very effective for a more narrow population. And here's an example. So as I mentioned before, inhaled as training um was studied in Phase three trials and uh failed to meet the end point. It was a negative clinical trial. Despite the fact that as you can see on the left this is the number of colony forming units of bacteria. It was effective, it killed bacteria and then of course they came back. Um But if you took the patients, so this was sort of an individual patient analysis if you took the patients in that study who had a high bacterial load to start with. So not only did they have pseudomonas but they had a lot of it. Then you see that among these patients it was highly effective in preventing exacerbations, the primary endpoint. But in patients who didn't have much bacteria in their airways, as you can imagine, it was less effective. So this brings us to a recently completed trial that was presented in abstract form on inhale dry powder calista method or calista patients. It was a nice large study. Almost 400 patients double blind RCT for patients who are pseudomonas infected. And they showed a very significant and clinically significant decrease in exacerbation rate from about one per year down to almost a half a year. Um Relative risk .61 quality of life measured by the ST George's restaurant questionnaire also improved. Um Unlike inhaled immediately decides which I mentioned can cause cough and uh bronco spasm adverse events like these were quite rare. The potentially the reason why this was successful. While some of the other studies I mentioned to you were not it was in this study the antibiotic was given continuously. There was no 28 day on 28 day off schedule. Pseudomonas pseudomonas. I think I've convinced you I hope I've convinced you as a bad actor you don't want pseudomonas. It's associated with worse outcomes. So there's a potential benefit of attempting to eradicate it when you first see it. Which is another reason to do surveillance cultures. Oops I'm sorry. Um Certainly eradication is standard of care and cystic fibrosis for bronchi ethicists. We have less evidence but um more recently there is a guideline recommendation that it should be attempted when pseudomonas is newly isolated. Um There's not a lot of strong evidence. It's mostly observational studies and and a small randomized controlled trial. But um it's it's recommended again. Um It's usually done with an oral and I. V. Antibiotic for 2 to 3 weeks With a concurrent inhaled antibiotic for up to three months. And the studies um Show about a 40- 50% 1 year eradication rate. Um And eradication is associated with lower exacerbation rates. So there is some evidence that that this is a um something that's reasonable to try for a patient who has newly isolated pseudomonas. So in summary bronchi ethicists uh is increasing. We see more and more patients with it. Um the symptoms and the disease progression are driven by neutrophils inflammation in the majority of patients. I think there's no debate that there's a large unmet need for symptom control prevention of exacerbations and prevention of disease progression treatments targeting specific aspects of inflammation, including neutrophils last days and eosinophilic inflammation are being studied and we're optimistic. So, stay tuned. Thank you very much for your attention. Published February 9, 2022 Created by
