Video Foundational Pathobiological and Novel Therapeutic Advances in Non-Cystic Fibrosis Bronchiectasis (NCFBE) Play Pause Volume Quality 1080P 720P 576P Fullscreen Captions Transcript Chapters Slides Foundational Pathobiological and Novel Therapeutic Advances in Non-Cystic Fibrosis Bronchiectasis (NCFBE) Overview Good morning, I'm Francesca Blasi professor restroom medicine at the University of Milan and it's my pleasure to discuss with you the plateau biological and novel therapeutic advances in bronchi actresses. Um this is part of the C. M. A. Certified webinars and uh this is my my disclosures and uh first of all I want to give you the the first point is that wrong practices may be defined as a neglected disease. And I try to show you how the knowledge about bronchitis is has been improved in the last few years. We know very well that is bronchitis are an increasing clinical problem and the prevalence is increasing over the time and this is mainly due to the fact that people is looking for. And clearly we can say that bronchitis is are something that is uh difficult to understand because it's so heterogeneous and someone can say that is not a real disease. And in fact we can start from this one Is a nice paper published in the British medical journals some years ago in 1881 by $30 Williams that looked to Bronchi actresses and said that and he said that bronchitis can hardly be considered a disease is rather to be called as a result of disease. So we can start from this and try to understand how important number of characters is and if we can define brand characterizes as a disease of the like one of the point is even bronchitis research is a heterogeneous. This is a collection of data but I want to thank one of my coworkers andre Romania and peter Gorman. That looks to the different studies and look into the definition. The different studies used for brewing practices. And you can see there is the radiological definition, the clinical definition. And if 60 fibrosis has been excluded by the study in the study and how they excluded CF from the study because clearly bronchitis are one of the main feature of CF. But it's clearly when you look to practice as a disease, you should exclude CS and look into the radiological definition. You can see that in some study there is a red flag. So there is no reported definition for ideological disease and others are in yellow. The only cT or high resolution CT scan has been used and only few had a clear specific radiological criteria score has been used and the same is for clinical definition. You know, most of the study did not report any clinical definition or bring characters and there are studies on brand practices And the same is for 65 roses exclusion. Most of the studies use history. Uh recorded history, not any any test for CF has been performed. Only five studies used at least one test for excluding CF. So when you look to brand characters is how you can define brand characters as well. We have to use radiological appearance and clinical syndrome radiological appearance but some definition looking to run catalysis like cylindrical varicose cystic plus some additional features that can be used for defining bronchitis is in terms of radiological definition on the other side, we have a clinical syndrome related to carve spiritual production, recurrent infection and chronic bacterial colonization. But we have to define many things for the definition of grown characters is one of the point is that we have now a new definition are related to radiological and clinical diagnosis of bronchitis is in the in the adults. Uh the use for clinical trials is in the title, but at the end of the day you can use this also in your clinical practice has been published in the Lancet respiratory medicine. And the first statement is very important. There is a consensus between experts and brian cactuses is a chronic restaurant disease. So in this statement is clearly defined that bronchitis is a chronic respiratory disease that can be caused by multiple etiologies and and are associated with different conditions may be COPD, maybe severe asthma, whatever. And in some patients and its theological current cannot be identified. And we call this kind of breast cancers as Heidi apartheid. But certainly we need both clinical and radiological criteria to define from cactus. Right well, radiological significant drawn characters. What does it mean when most of us thinks that the main point is the relationship between the highway dia diameter and the diameter of the accompanying artery. But you can use different areas. You can use the luminaria, you can use the wall area and so you can have different interpretation of the so called radiological significant room characters. And another point is that this ratio can be affected by for example, vaso constriction. Uh So you can have a small artery related to vaso constriction. You can have our way delegation related to a bronchial world tinkering. And on the other side you can have in hypertension, vascular hypertension. You can have uh in increasing in the area of the of the of the vessels that is not related really to uh bronchitis. And clearly if you look to the relationship between age and bronco terror ratio, you can see that when you increase your age, you increase the ratio. So also age is important in interpreting the significant project. Is is in terms of radiological terms. And when you look to the city score for Bronchial, Pegasus Bridge one score. It is the bricks score. Have a look to bronchial dilation but can be absent. My moderate severe and it depends on the ratio with the diameter of the addition vessel. So this could be important. But when you go to for an external validation has been presented at the U. S. Congress, the external validation is not always so good. So clearly if you look to be uh this data published in the last year, two years ago in restaurant medicine. You can see that the criteria for bronchitis. If you use an airway artery ratio higher than equal or higher than one, You have 89% of the patients. That can be classified. But if you look to other diameters in the Iowa diameter outer arm diameter, you can have very different results. So this is important. And so the the definition used in the paper in the Lancet Restaurant Medicine say that the first of all confirmation of the president of bronchitis is on, on cities can this should be based on a priority accepted definition and the definition is this one. So using different grading of the different diameter you can use, you can use lack of tampering of I ways, uh the visibility of highways in periphery and you can go downstream and clearly the most important grading is inner highway diameter artery ratio Higher or equal to 1.5. And the second one is older. Highway diameter artery ratio higher or equal to 1.5. The other point is that if you have a clinical trial central reading to confirm the presence of should be used because it clearly improved accuracy and clearly should consider in clinical trials. On the other side are the clinical status and ask him to the expert, what are the main symptoms you should record for defining bronchitis clinical status. And there are a number, you can see that calf and uh history of exacerbation, daily student production, daily production calf are clearly the main the main uh symptoms without recorded and taking account when you define the clinical status from cactus. And we uh define a couple of statements about this. The first one is, although there is a wide spectrum of silence, symptoms of bronchitis is the majority of patients who made the definition of clinical significant brown cactuses should have at least two of the following cough, most of the days, sputum production most of the day over weeks and free and history of exacerbation. But we know so that some patients with radiological bronchitis are symptomatic and this means that we the long term prognostic significant of this, a symptomatic radiological blanc characters is unknown. And so we clearly need a longitudinal studies look into this. This first statement is that underlying cause a condition associated with bronchitis is should be investigators investigated because we know very well that if you look to be possible underlying causes. You can find treatable traits for your patient and clearly the use of idea, partick or post infection broke. Yetis definition should be used with caution until you don't have. You can exclude other causes. The other point is that we know that broadcasters can be present in patients with chronic airway disease like COPD and severe asthma. And clearly this is another important thing to another important feature to think about because you can identify also in this case some treatable traits that can improve the the the life of our patient treating COPD or treating severe asthma. So when you look to be what happened if you look to be a problem of bronchitis is clearly you you can have different uh scenario. First of all you perform a cT scan in your patient, you can find evidence of bronchitis is at this point. You have to define if this bronchitis are important in terms of radiological evidence. If yes, then you have to look to symptoms, cough sputum production, history of exacerbation. If not, the patient has a radiological evidence of ground cactuses in the absence of the clinical significant disease. If there is symptoms, there are symptoms, yes, the patient has clinical significant brand characters is on the other point you have a clinical suspicion and bring characters is because the patient has at least two of the among calf, most day of the week sputum production history of exacerbation. Then you perform a city scan and if you find the presence of a ratio higher than equal to one than yes, the patient can have a significant clinical significance in ketosis and have a chronic. So the chronicle spiritual disease. If not, you have to look to other other causes. So you have to put together radiological significant brain ketosis and clinical significant disease. To make the diagnosis of bronchitis. And putting together one of the main point is the possibility to have a chronic material infection in your patient with some cactuses. So you have the diagnostic criteria. If you make the diagnosis, you can go for treatment and look to outcomes diagnostic criteria. Well you have to look to clinical feature disputing characteristics, the presence of inflammatory biomarkers. You you must use sputum culture and you have two plus cultural isolators for at least three months apart in one year to define chronic bacterial infection and the treatment will go to our way clearer. So physiotherapy treatment of exacerbation, a possible eradication or trial to eradicate the bacteria, particularly pseudomonas aeruginosa. You can use uh suppressive therapy with long term he nail antibiotic or long term macro views. And another step is the possibility to withdrawal withdrawal uh prenatal corticosteroids can that can be part of the problem of chronic bacterial infection. And the outcomes you look for is the reduction of bacterial load reduction of the number of exacerbations or acute infection, improve the quality of life and possibly to have an improvement in lung function or slowing the lung function decline. This could be the the the scenario for a clinical trial and in fact in the context of clinical significant banquette. Is this, we know that the we need the clinical definition of chronic bacterial infection. That means that you have an evidence of positive restaurant track cultures of the same microorganisms by standard microbiology on two or more occasions at least three months apart over one year. What you are in a stable state. And this is quite important because we know that chronic bacterial infection, particularly from some bugs pseudomonas aeruginosa for example are important in the in what happened in the in the in the natural history of the disease. So when you have a chronic infection you can or identification of the bark, you can look for an eradication trial. This is particularly important when you have the first pseudomonas infection and you can try to eradicate the back from the airways or and you can pass from eradication to the presence of intermittent intermittent pseudomonas infection till the chronic pseudomonas infection. And clearly you can use here eradication treatment but when you have a chronic pseudomonas infection, when you have to use suppressive therapy that can be inhaled antibiotic or micro light therapy or we will see other therapy. So if we think that eradication is possible. Well how we can define sustained cultural commercial and the group of experts decided to to give a pragmatic definition of sustaining cultural conversion. That is a negative respiratory tract culture for the target macro organized by standard microbiology on two or more consecutive occasions at least three months apart over one year and one point important. One important point is that the culture should be performed in a good lab as usual. It should be good labs. The other point is how to define exacerbation of broad characters and also in this case there is a consensus definition uh published some years ago and in the european respiratory journal and we define the definition of bronc practices as a parliament exacerbation mainly for clinical trials. But in any case you can use also in your clinical practice As a person with one character assist with the deterioration in three or more of the following key symptoms for at least 48 hours and again cough sputum, volume, volume or consistency, speed and power lines, breathlessness, fatigue or malaise and metamorphosis. And this is important. The fact that this determined a change in bronchitis treatment. So you need symptoms and you need to change the treatment because why is important because there is a phenotype that is a frequent exacerbate or this is a paper published by James charmer some years ago and he looked to the number of exacerbation along the year of the different natural history of the disease. And he found that if you have have a you are a frequent exacerbation in here for one. The probability to be a frequent exacerbation is actually better in year two or 3 is high. So certainly there is the possibility to identify patients with uh prone to exacerbation and probably are the most important uh patient to be followed. Look into epidemiology, we know that you know, we have different patients and different problems. We have scores that can help us to identify mild, moderate and severe patients using different scores. B. S. I. The bronchitis severity index is one of the possible scores. But clearly there is a clear correlation between the number of exacerbation and survival. The the kind of bacteria you can find in the highways and the score is also related to the survival of your patients. So our targets should be prevent exacerbation, control our way infection and try to optimize the functional status of our patient. So increasing the possibility to survive concerning the uh it's a logical uh nature of our of the product ketosis. It depends very much from the local data, europe is quite different from India for example, this is a paper looking to India data about bronchitis and you can see that tuberculosis is the first cause of bronchitis. If you look to what happened in europe, you have that idea politic from cactus as the first. So it it's clearly different situation, different environment and different epidemiology. So you have to know what happened in your country on the other side. The path of physiology is very clear. It's a mess. It's a clear mess. Uh there is a number of interaction in the highways related to our way dysfunction, inflammatory response, structural disease and infection that work all together and make this uh scenario. It is, it's not just a cycle is a is something more complex with an interaction between inflammation mainly related to Notre fille inflammation. But I will show you also there's an affiliate inflammation may be important. The chronic infection and bacterial virulence factors are also important lung destruction and and blankets are important. And clearly the what happened in the epithelial dysfunction. The mucus hyper secretion, considering dysfunction are all important and there is a clear interaction between all of these feature in project and certainly the Notre fille inflammation seems to be very important. If you look to the correlation between neutrophils illustrates activity and the disease activity is clearly the higher the neutrophils illustrates activity. The higher the activity of the disease, the presence of pseudomonas aeruginosa is important in terms of the severity of the disease. So clearly there is an interaction between the inflammation and infection leading to the severity of the disease. And indeed if you look to this nice uh slide uh taken from the paper of James charmers and ST shortly mall published in the Lancet Restaurant made this same some years ago that they put tried to put together everything so the underlying disorders radiology, microbiology the clinical phenotype. So the kind of inflammation, the response to intervention, the prognosis and the function and physiological consequences the underlying disorders. We no idea. Patrick, post effective related to immunodeficiency. ABP are the NTM infection COPD severe asthma alpha one and trips and efficiency I. B. D. And all look to be radiology that can be different in the different disease. Micro biology can be different and pseudomonas aeruginosa. NTM are the the main pageant in terms of severity and but you have also patient with culture, culture negative and usually have milder disease but in any case you can have also patient with culture negative, highly inflamed may become frequent exacerbate er Notre filic inflammation is clearly in the main inflammation you can record in in bronchitis and it was on the field is there. And I'll show you some data later. But this is important because when you have a vagina filic inflammation you can have a response to steroids. You can have a response to biological drugs if you have a natural filic inflammation. Uh the antibiotics are important but I'll show you. But now we have also anti inflammatory drugs that can act on Notre filic inflammation that can change the natural history of the disease. And clearly the the presence of pseudo monastery regional is particularly severe pseudomonas infection are correlated with an increased mortality. Severe exacerbation are related to increased mortality. So these are clearly a complex disease. But each of these points needs more research. If you look to the patient you can look to inflammatory phenotype. Ng you know, I think there are two main inflammatory phenotype since one is that as I said before, neutral field and neutrophils Estates and the other point is there was in the fields concerning neutrophils, neutrophils ella status. We know that when you increase the the inflammatory response to neutrophils and particularly the levels of neutrophils illustrates the survival of the patient is related with the level of neutrophils illustrates. So the higher inflammation with Notre fields. The below is the survival. The target for neutrophils information, antibiotics. Uh maybe in any corticosteroids may not be the right response to neutral feel inflammation, but we have and assure you novel anti inflammatory treatments for neutrophils inflammation that seems to work very well on the other side you have a voice in the fields. And you you can see in this this paper we published some years ago looking to the Uh presence of Arizona field and you can see that about 20% of Bronchi anticipation has an ozone field inflammation. So in this kind of patient hidden stairs could be one of the of the possible treatment and biologicals can work. And indeed, if you look to negative fill inflammation, microlight seems to be one of the possible treatment Michael and are clearly drugs that can modulate the immune response in in our patients can have some effect on pseudomonas aeruginosa in terms of reduction of the activity of pseudomonas aeruginosa. Even if macro lights are not active as antibiotic in against episode of monastery region Osa, but can act on the different uh feature of response to the Monastery regionals inflammation. And what is the data showed that macro light can really increase the survival, reduce the exacerbation with a with a response to macro light with a reduction of about 50% of exacerbation and improved in quality of life. So clearly this is an important uh target for for mackerel. I treat. The other important point is working on neutral field extra several transformation and reducing the inflammation related to neutrophils metastasis, we have a inhibitor of DPP one. Uh and this is a activator of protest cases in in in the neutral field. Uh The executive can act blocking within irreversible way the activation uh in the blood marrow. The of the protest is in the neutral fields. And indeed at the end of the day you have a peripheral blood neutral field. But this disarmed of the without the possibility to express the neutral field, other states and other protests. So at the end of the day uh this inactivation is seems to be very important. This is a recently published paper on in New England Journal of Medicine of a Phase two trial of a DPP one inhibitor. And what happened is that But both doses are used in the in this trial reducing clearly reducing a significant manner. The number of exacerbation impatient with bronchitis. It is quite interesting because it's not an antibiotic, it's just an anti inflammatory looking. Working on neutral field and this lead to a reduction in exacerbation. We know that DPP one doesn't imply a reduction in the activity as a immune system of the immune system and the response to buy neutral field to bacteria is still there. But the response in terms of neutrophils ella stasis is blocked and this led to a reduction in exacerbation and indeed there is an invasion of neutrophils Estates in protein. It is free and paid apps in G. Uh So uh there is a real suppression of inflammation in the highways of the patient treated with DPP one inhibitor. And what is important is that all the patients that were treated with consecutive, which is a low level of neutrophils real estate uh have a clearly prolonged time to first exacerbation. And this seems to a very important data because the reduction of inflammation, Notre fille inflammation has an important impact in the natural history of the disease and potentially very important. On the other part side there is the it was on the field counts and exacerbation. This paper has been just published by schumacher in the Blue journal. And what happened is that if you have a high level of blood Arizona field count, you have a lower a higher number of exacerbation. And this is seems to be very important because the risk ratio is more than three times if you have you're gonna feel higher than 300 cells. Microlight. So uh it was an affair seems to be again important. 20% of the patient with bronchitis is has a high level of Arizona fields. And looking to be the the data is clearly that patient with the uh with it was a new field inflammation respond to in their states. So we have a some some interesting data on this. On the other side. This is a paper from my group looking to th t to high end the type and response to biological treatments in patient rebrand characters is what we found is that if the patient has 82 response in terms of high number of Arizona field and oral Fenno, then the the use of biological drugs leads to a clear reduction in the number of exacerbations of this patient. And this data has been confirmed. Also by this data from this paper from the group of beers welt in Germany Look into the uh not only the number of exacerbation, but also in this case you have a reduction and exacerbation but you have also an improvement in F- 51. An improvement in this player scores an improvement in quality of life and also a reduction in the production of rasputin. So uh in when you have a T. two high end the type you can use apparently with a good um affect the biological drugs. Another important point for bronchitis are the use of inhaled antibiotics. Uh The rationale for use of an antibiotic is that in this patient you have microorganisms, you have a chronic infection. You have acute infection with exacerbation related to impaired Mukasi, larry clearance, impair innate and adaptive immune response are related to uh the high level of inflammation mainly related to neutrophils, as I said before. Uh clearly this patient can have a possibility to to have a good response to any antibiotics in term of both acute exacerbation and chronic inflammation chronic infection. Uh Clearly in L. A. Tibetan has potential advantages related to the the fact that the the nail antibiotic go directly to the target at the site of infection can reach very high concentration. There are several fold higher than the M. I. C. Of the of the park. You can reduce the side effects of the systemic side effects of drugs angular early, you can increase the local side effects mainly broncho constriction and in some cases the the the the expense and the cost can be high. Why we are discussing about inhale antibiotics in bronchiolitis is first of all, there is no license treatments of for bronchitis for nail antibiotics. And if you look at this, the european respiratory society guidelines for the management of Edinburgh cactuses. There are at least two points related to initial antibiotic for absurd. A monastery generosa and initially antibiotic for other bucks. And you can see that recommendation in these guidelines are weak and the quality is low or moderate and most of the RCT failed to meet the primary endpoint in terms of use of an antibiotic in brown catharsis. So the the problem is that research priority in brancato's newspaper published in the year J some years ago, four of the research priorities in bronchial diseases are related with the use of an antibiotic. The first one is when and how and duration should pseudomonas aeruginosa be eradicated and the the use of intravenous or a nail nebulizer antibiotics. The 2nd 1. the indication and of the optimal antibiotic therapy. The oral versus intravenous versus nl antibiotic And when we have to use long term suppressive antibiotic therapy mainly with a nail antibiotics or oral microlight. And what are the indication? The oral versus inhale antibiotics? So there there's a lot of open questions and the challenges that most of our patients present to democracy, chronic infection uh mainly in the southern part of europe. And the other point is that most of our patients are classified as severe patients. So the understanding of the role of antibiotic and the non antibiotic is very important. Another point is that the most solid phenotype in bronchitis is related to survival is the presence of pseudomonas aeruginosa chronic infection and two or more exacerbation period Where the survival rate is the lower one. So clearly the presence of chronic infection seems to be very important in terms of survival of our patients. And what are the guidelines indication? If you have more than three examples, at least three exacerbation career you have to optimize our clearance treating the possible underlying causes like you know in you know deficit and if you have certain monastery originals infection, the indication by the guidelines is to use long term in jail antibiotic treatment taking account. There is no license treatment for an antibiotic in bronchitis and if you have a lack of response or intolerance mint you can go to microlight treatment if you have a non standard monetary originals infection, you can use micro light treatment and if you don't have a good response, you can go to inhale antibiotic treatment or using combined or any nail antibiotic treated. These are weak recommendation with low quality of evidence, you know? And on the other side, if you look to the what the pickle question response and the guidelines suggest that is the new is isolation of pseudomonas aeruginosa should be offered eradication and uh the if you have you don't have certain monetary regionalism and you have another bug. The indication is not too offering eradication but this is still under discussion. And for chronic pseudomonas aeruginosa is important to have long term antibiotic treatment uh maybe mainly email antibiotic and when you don't have pseudomonas Originals around uh then the oral prophylaxis is contraindicated or so. And if you look to the data, what are the data about chronic pseudomonas infection? We know that high Bs i having more than three exacerbation and having chronic pseudomonas infection from the clinical perspectives are the main point for having the worst clinical outcome. And uh from the research perspective we know that drugs works. But if you looked at this randomized clinical trial using Nl colistin impatient with bronchitis and chronic pseudomonas infection the time to first exacerbation doesn't meet the range point. The study doesn't mean the end point. But if you look to be patient with In adherence higher than 80%, then this study is successful. So it's not just to give antibiotics but to give antibiotics for having a good adherence from our patients. So these open another another possible question for uh understanding the the role of the nail antibiotic. And these are the other studies with the result with the two phase three studies evaluating the treatment with poor McQueen in uh bronchitis is unfortunately this study also the study failed to reach the to to touch the the endpoint. And so at the end of the day uh the problem is ah to find out the evidence for the use of an antibiotic. Uh if you look to this radio, there is a an effect in terms of reduction of bacterial load that may be important in terms of reduction of inflammation in the highways. Uh there is a significant effect on exacerbation, but as usual the studies are quite quite different And if you look to this meta analysis looking to 16 trials again, there is a an effect in terms of reduction of exacerbation, but there is an I eat originality of the of the studies, so it's quite difficult to to have a good evidence of the use of an antibiotic from catalysts. However, now we have to two new studies. The first one is my best study That has been published in the E. R. J. in 2021 and this is a quite interesting study with a double blind within treatment arm with three quarts using different dosages of of uh of the drug and uh the using also different way to give the dog with an on off or continuous treatment with minimal trouble missy. And the result is that look into with bacterial load. Uh This is a clear effect of the higher dose and continuous treatment compared to lower dose and on off treatment. So apparently the use of a continuous treatment with the antibiotic we're using high does the effect on bacterial load is better than the other. The other possibility. And look at this study that was unfortunately terminated because of administrative problem because the drug was sell by by the by the company to another company. So the study was stopped. But in any case the miniature of the patients are quite similar to what we expect to have inpatient within catalysis. Uh The same as for pulmonary function. One third used microlight bronchodilator was using most of the patients in and steroids was used in about 12% of the patients. The main Bs. I score was what we expected to have a moderate severe patient And the number of pullman exacerbation was higher than three in about 1/3 of the patient. Unfortunately this study, a significant proportion of our patient was lost to follow up and draw apart from the study about more than one third of the start of the patient due mainly due to adverse event. And at the end of the day, what happened is that any of the three dose of uh delta promising reduced to the Monastery regionals bacterial load with an effect that was higher in in the in the higher dose and the continuous treatment. And obviously as we didn't reach the number of patient plant, we don't have a obvious trend in the improvement of clinical endpoints. But now we have another study. It is the promised one Phase 3 trial that is another study using uh colistin is a 12 month multinational randomized double blind placebo controlled study using colistin using a device with his inept that delivers drugs on inspiration. Uh and uh during the first phase of inspiration. And it's important because the there is a recording of what the patient did. So this is important in terms of measuring adherence of the picture. The key includes inclusion criteria. Was a city confirmed diagnosis. Brown ketosis and the number of exacerbation to a more requiring antibiotics. Documented history of pseudomonas infection with a positive between Calvin for absurd monastery regionals during the screening period In the 51 higher than 25 and no no change no measures changing the primary treatment. And what happened is that the reduction in pulmonary exacerbation rate comparing treatment with placebo was highly significant. The severe exacerbation race was highly significant for in in compared to placebo the time of the survival retirement of first exacerbation again was clearly superior in in the the drug was spirit of placebo with a very very highly significant results and the same. It was for the change in central's questionnaire. So the quality of life And it is important that we touch the the mean significant difference of four point it was less than 4.6. So the it was really a significant effect on quality of life. And also the material Lord was clearly reduced by the by the drug compared to placebo. So and this was not paid with adverse events at the end of the day, there's no real difference between uh colistin and placebo treatment. And this was quite good compared to what happened with Deborah mice. At the end of the day, there was a 39 reduction in pulmonary exacerbation. 59 reduction in severe pulmonary exacerbation. There is a problem prolongation of time to first exacerbation, prolongation tied to first severe exacerbation and improving in quality of life. We felt any increase in Sudan monetary, regionals are resistant to colistin. Everybody is not really safety concerns. So this is a quite interesting paper results. And so at the end of the day when you have a frequent exacerbations exacerbate or you have to uh clinic, go for airway clearance physiotherapy using maybe I platonic salon or eyewear clearance devices. You can use Mac relied and look into treatable traits, particularly you know if you have a bacterial load and ultra feel inflammation you can use you have using affiliate inflammation. You can use any steroids. So now we have many different possible intervention in our patient and this is related to the need to understand it better. The broad cactuses and clearly the genetic cause is important. And there are a number of studies looking to the uh screening of genetic uh underlying disease for for the patient. And the other point is my last point is about microbiome. Uh Usually we look to a single kingdom macrobiotic looking to bacteria, virus fungi. But the in the highways we have bacteria, we have viruses, we have fungi. So at the end of the day it's important to put all together and this is has been published in the in natural medicine. Last april look into the putting together bacteria, fungi, viruses and and and and trying to understand the work, how they work together to to give us the problem of bronchitis and trying to identify the patient who had high risk. Look into all the boxes that are present in the highways. So the interactive home is one of the main points. And we know that if you look to the different relationship between bacteria, fungus and virus, you can identify patients with a higher risk, particularly, you know, diversity is important. But the interaction between bacteria and other bugs are important. And in fact if you can look to the different core networks that are clearly important in defining the the role of bacteria. The single bacteria in the highways. Uh and clearly the interaction during the exacerbation are important but also are important. The difference that are present in the low exacerbation exacerbate hours and the higher exacerbate hours. And pseudomonas is not the only thing to think about because when you have a less negative interaction and you can change the interaction between the different players in the highways. This may be important and this may explain why we are treating our patient with an exacerbation I think. So the monetary regionals in the airways and we treat the patient with a drug that is not active against pseudomonas aeruginosa as a better lacked. Um non active example pseudomonas. And you resolve the the exacerbation because probably we act on this interaction with different bacteria. So at the end of the day, this kind of approach can give us some more information about why do Sudo Monastery Gino's a a positive patients respond to macro clearly there is a an anti inflammatory effect on microlight, but microlight can also act as an antibiotic working on what is around the Monastery regionals. Uh and clearly as I said before, why do antimicrobial to which an organism detected as a resistant work in practice? And this could be the activity of the of the antibiotic in the other on other bacteria. And the other point is that maybe this is another important piece of the puzzle to understand the role of bacteria in the airways. So clearly uh micro bionics is important but we had to to think about the interaction between bacteria, fungi and and the presence of virus because with different interaction may be important in controlling inflammation controlling the number of exacerbation and the and so the our impact the impact of our treatment may be very different in this kind of patient. So in conclusion of my presentation I want to just to underline some highlights some some of the of the main point I assured you. First of all it's clearly that branch campuses are in a heterogeneous disease. Uh the clinical estrogen itty is is present and we try to look to this to visit their virginity. Trying to understand how to manage visitor virginity and we have different consensus and guidelines look into exacerbation definition, disease definition and try to to give some advice on better clinical care. Clearly physiotherapy is one of the main intervention we had to do to in all of our patients the use of inhaled antibiotics and microlight. I show you some results and some indication for the use of inhaled antibiotic and macro light. We had to assess the patient risk, try to identify the more severe patient and the patient's at high risk for exacerbation. And clearly this is important for the follow up of the patient. It is important to participate to registry, sharing the data and try to put together the knowledge uh in uh for research and uh embark of european blanketed. The registry is one of the possibility and I really invite you to look to have a look to the website of Embark and if you are treating patients with bronchitis is please join us in Embark on the other side there is a biological heterogeneity we discussed with different in terms of inflammation. We have different ender types. We can look to different biomarkers and clearly try to link the understanding of inflammation to clinical data. Try to identify uh the the role of our treatment trying to have a precision medicine, understanding how the drug drug works, sharing the data again and clearly looking, trying to have translational research in the trials. And the most important thing is try to facilitate research using bio bank joining Emburgh Enbridge. And clearly international collaboration are important on the other side we know that the we are developing new drugs, new therapies and try to identify new targets. I show you how important can be controlling neutrophils inflammation using DPP one in innovators that the dark drugs seems to work very well on the other side, it is important to use final antibiotic. Uh and uh Mac relied again the clinical trials are important and I think that biomarker identification is is very important. And we really hope that the new Phase three clinical trial can clearly improve our clinical practice and give us new weapon in our armamentarium to manage our patients and with this. I thank you very much for your attention Published February 3, 2022 Created by
