Today's presentation is going to be about basis score and treatment outcomes in patients with Mycobacterium avium complex pulmonary disease, and as I said, I'm Anika Reddy-Vadialla. I was a research fellow at Mayo Clinic in the Division of Pulmonary and Critical Care Medicine. Currently, I'm an intern in Merit Health Wesley, which is in Mississippi, and on the right is our study team, and Dr. Escalante is our PI and my mentor. I have no financial disclosures. So as you all know, non-tuberculous Mycobacterium pulmonary disease is known for the heterogeneity of its clinical course in terms of progression and treatment response, and prediction of treatment outcomes in these patients can be challenging. In 2021, a new scoring system, basis score, was developed to stratify risk of mortality based on five variables by Korean investigators, Kim and his colleagues. Those variables are BMI less than 18.5, age 65 and more, presence of cavities, elevated ESR, and male sex. However, this validation was conducted in Asian population and included mostly the Korean patients, and it also included Mycobacterium abscesses complex, which is known to be associated with suboptimal treatment outcomes. It is not known if this score can be applied to MAC PD patients in the U.S., or if this can also predict treatment outcomes in non-cavitory MAC PD patients. So through this study, we hypothesized that high basis score is associated with suboptimal treatment outcomes in MAC patients treated with antibiotics and those not treated with antibiotics. And for this, we conducted a retrospective cohort study in which we analyzed clinical, microbiological, and radiological outcomes in patients diagnosed with MAC based on current guidelines. And for this, we included patients without cavities, and we followed them up over, we included those who were followed up over two years, over six-month interval visits, and further categorized them into those treated with antibiotics and those who were managed with only airway clearance and there was no antibiotics. Here we compared the demographics, clinical, radiological, and microbiological findings, and compared the treatment outcomes by basis scores. And for this, we did a crosstab analysis to look out for association between categorical variables, and the continuous data was compared by Mann-Whitney test. So these are the baseline characteristics, and finally, the total number of patients were 104, of which 60 were treated with antibiotics and 44 were non-antibiotic treated patients. In this, again, the mean ages were 66.7 and 73.1 years, respectively. The most common underlying comorbidities seen are pulmonary diseases, in which bronchiectasis was most common, and then came the cardiovascular diseases. Most of the patients in these cohorts had mycobacterium avium compared to the intracellular. And then the treatment outcomes across, when compared between these two groups, clinical improvement, radiological response, and overall response was higher in the non-antibiotic treated group compared to the antibiotic treated group of patients. However, sputum conversion was higher in the antibiotic treated group compared to the non-antibiotic treated group. We further compared the treatment outcomes by basis scores, and in the antibiotic treated group here, on the top is the improvement statistics, and on the bottom is the worsening findings. In clinical improvement, radiological improvement, and overall improvement showed significant association with basis score. You must be wondering why there is no score of four, because we included only non-CAVITRI patients here. And then you can see the treatment outcomes by basis scores in non-antibiotic treated patients. Here, basis score has not shown association with these outcomes. Only the culture conversion was significant. I've included this slide with the same data that was seen in the earlier one, just illustrating the statistics here. Once again, clinical improvement, radiological, and overall improvement showed significant association in antibiotic treated group, and there was no association in the non-antibiotic treated group. So, based on this, we were able to conclude that basis score was associated, in our study, it was associated with clinical and radiological treatment outcomes, but not with culture conversion in those receiving antibiotics. However, our study has certain limitations. This is a retrospective study from a single facility and region, so because of this, we may not be able to generalize this to other areas and ethnicities. It also included mostly the Caucasian race, and as discussed, non-CAVITRI PD only. And we might also have unexpected biases due to missing data of few patients, such as missed follow-up visits in between. And the final conclusion is that basis score may be clinically useful to predict treatment outcomes in MAC patients, those treated with antibiotics, in the U.S. However, we might need additional studies to further validate basis score or any other risk scores in MAC PD patients in various other settings. And this can be a valid parameter to measure disease severity, which can further help in predicting outcomes. Thank you so much. And thanks to my mentor, Dr. Escalante, who's been very supportive, and he played a huge role for me to be here today. And... Thank you. Yeah. So, any questions, feedback for Dr. Wadialla from the audience? Please go ahead. Yes. I'm just curious, what was the deciding factor for patients who got treated versus not? Was it the basis score, or what... Why did some patients get treated and not... So, basis score came in later. That was mainly the physician's judgment based on their clinical progression, the worsening of symptoms, their radiological worsening, and also based on the culture conversions and sputum... Culture conversions. So, we took this patient set and later compared it with the basis score to see how we can predict this further. And were there conditions that were not treated? Was there any sign that they got less follow-up to imaging, less imaging after treatment? Because they didn't get treated, so they didn't get imaging to assess if they had a response. Was there any difference in the... Could you repeat your question, please? I couldn't... Was there any difference in the amount of follow-up that the patients who didn't get treated received because there was no assessing if they had a response? So, from my observation, it was a mixed, both in antibiotic... Those treated and not treated, we did not notice such lost follow-ups in non-antibiotic treated. And also, it was a small population that we had. I must add that all these patients that... make sure they are not in due with the interior of our defense architectures. But I ask all for treatment initially, but have the option to neutralize in the last few months. All right, any other questions? All right, perfect. Thank you everyone. Thank you so much. Applause All right, next we have, let's see. Yeah, next we have a presentation from Alison Michotte, examining the clinical impact of transient and persistent aspergillus in non-CF bronchiectasis. All right, hi everybody. Thanks so much for coming. This is a project that I worked on with Dr. Christina Thornton, who gave an excellent talk yesterday on non-CF bronchiectasis. So this is me. I'm a pulmonary fellow at the University of Calgary in Calgary, Alberta, Canada, and I do not have anything to disclose. So my goals today are to talk to you a bit about patients with non-CF bronchiectasis who develop transient and persistent aspergillus, and we'll talk a bit about their baseline characteristics that differ, as well as differing clinical outcomes. So as many of you are aware, bronchiectasis is very common in our clinical practices, and it's considered the third most prevalent airways disease. And despite this, we don't have a lot of research about non-CF bronchiectasis, and this is largely related to the fact that it's a very heterogeneous group of patients. A lot of what we know is extrapolated for studies pertaining to cystic fibrosis. Now, aspergillus is the number one fungi isolated from lungs of patients with bronchiectasis, and we know that it can be a potential pathogen. And cystic fibrosis has been associated with a multitude of negative clinical outcomes. So the aim of our study was to assess the clinical impact of both transient and persistent aspergillus in non-CF bronchiectasis. So in terms of our study design, we conducted a retrospective single-center study out of the Adult Calgary Bronchiectasis Clinic. This is a centralized bronchiectasis clinic that serves bronchiectasis patients in southern Alberta, which is in Canada. It's one of the only specialized bronchiectasis clinics in our country. So we included patients in whom aspergillus fumigatus was cultured at least once from sputum samples between 1981 and 2016, and then patients were censored if there was not enough clinical data. We divided these patients into three categories. So the first on your left is persistent aspergillus. These are patients for whom there was at least two aspergillus samples cultured from their sputum with a carriage of at least six months. The second group was transient. So for these patients, there was at least one sample that was positive for aspergillus, but they did not meet full criteria for persistence. And then we matched these patients to non-CF bronchiectasis controls based on age, birth cohort, and sex. And then within these three groups, we extracted baseline data, and as well at each visit in our bronchiectasis clinics, our patients do spirometry and they give sputum cultures for us to see what they're growing. We collected clinical data for two years prior to and after their incident aspergillus infection, and we extended this up to five years for lung transplant and death. We used a priori specified confounders for multivariate analysis. These included baseline age, sex, FEV1, and co-infection with pseudomonas aeruginosa and antibiotic history. So in terms of the baseline characteristics, I divided this into two different slides for the purpose of this presentation. So this is the slide that shows the differences between the three groups. You can see here that P values are comparing persistent versus control, because as a spoiler alert, there was no difference with transient aspergillus for any of our outcomes. So what we did notice was differences between persistent aspergillus patients and their controls was that patients tend to have an older age, a lower BMI, lower FEV1 percent predicted, and they tend to have a number of different comorbidities including a higher rate of diabetes, ABPA, more courses of antibiotics in the 48 months surrounding their incident infection, a higher rate of PPI use, and a lower rate of a history of pseudomonas aeruginosa. We looked at a number of other factors, and as you can see, these are all kind of similar with non-significant P values. So there was no differences in sex, comorbidities such as asthma, COPD, malignancy, or immunodeficiencies, smoking status, and medications such as inhaled antibiotics, chronic macrolide use, or inhaled corticosteroids. We also found no difference in patients who had a history of mycobacterial disease or homophilus influenza. We then did a Cox proportional hazard ratio looking at risk factors for future exacerbations. And so in this plot, you can see everything on the right of the dotted line, the vertical dotted line increased your risk of pulmonary exacerbations, and things on the left decreased the risk. You can see the dot most to the right is associated with pseudomonal colonization, which is well established in the literature to lead to increased exacerbations in patients with bronchiectasis. What we found was that the second highest risk factor we saw was patients who had persistent aspergillus. Factors that were non-significant included transient aspergillus status, FEV1. There was a 10 towards decreased risk of pulmonary exacerbations in younger patients. And then female sex had an increased risk of pulmonary exacerbations, and then a higher number of exacerbations in the prior year. We looked at a few other clinical outcomes, so I've kind of summarized them all on this slide. And in this slide, I've just included the difference between persistence and controls. We looked at incident exacerbation, lung function, time to next pulmonary exacerbation, and progression to transplant or death. In terms of incident exacerbation, we found that patients with persistent aspergillus were no more likely to experience a pulmonary exacerbation at the time of their incident infection, when this was found in their pseudom compared to controls. They did, however, have a faster annual rate of decline in FEV1, so 2.51% compared to negative 1.31% after adjustment for confounders in our group. They also had an earlier median time to pulmonary exacerbations with patients with persistent aspergillus having 152 days to their next exacerbation compared to 225 days for patients who did not have persistent aspergillus with an adjusted hazard ratio of 2.24. And then we didn't see any difference in terms of progression to lung transplant or death. So the take-home messages from this project is that there's really a paucity of data related to infections in non-cystic fibrosis brachiectasis. However, like in CF in this study, we saw negative consequences that were associated with persistent aspergillus isolation. The reason for this remains unclear. We have theories that this might be related to patients who have chronic aspergillus might have increased inflammation at baseline that leads to worse clinical outcomes. And there was also an interesting association where patients have less pseudomonal colonization if they had aspergillus, and so there's a possibility that they've been exposed to less suppressive antibiotics, and this might lead to worse clinical outcomes. And then, interestingly, clinical outcomes for patients with transient aspergillus were not at all different from controls. So there's a number of limitations to this study. So we had a very small sample size. It was a single-center study and retrospective, and then there's a selection bias because we only included patients at our centralized brachiectasis clinic who might have worse clinical disease. And then, overall, our outcomes show possible associations, and this is not causal data. So our next steps are to complete data extraction from the remainder 150 patients who have attended the brachiectasis clinic between our study dates, and we have up to 40 years of data, so we're really hoping to prolong this out and see what happens over the years, and then eventually compare spetal microbiomes between these different populations. Thank you. Any questions, feedback from the audience? Please go ahead. at an end, or do you have some data? I think sometimes they develop transient infection again, but we really only looked at a couple years of data. We didn't follow them out long-term, so it'd be interesting to see that when we look at things for 40 years, if there was a risk. Sure, like underlying ideology. That's a great question. We haven't specifically looked into that, but that would be something certainly to explore further. Any other questions? So very interesting work, actually. So one question is like, was there any difference in imaging between like the persistent and these different groups? Mm, yeah, we, just because this is a retrospective review, we haven't specifically looked at that. But you do wonder if there are certain imaging characteristics that might make patients more likely to harbor aspergillus for longer periods of time. But again, we'll need to look a bit further into that. I appreciate that question. So this is the topic of my presentation. I am Animesh Rai. I come from Atoshi Referral Center in New Delhi, which is the capital of India. I do not have any specific financial disclosure regarding to my presentation. Now, what we tried to do in this study was to study the role of bronchoalveolar lavage, PCR, a commercial one, aspergineous, and an in-house one, in-house PCR, in the diagnosis of chronic pulmonary aspergillosis, to evaluate the role of galactomelan both in BAL and serum in the diagnosis of CPA, and to compare these two, PCR versus galactomelan. Just to set the ball rolling, CPA is a common problem in our country. Occurs mainly in patients with pre-existing lung diseases. Worldwide, millions of people affected. We estimated, modeled, rather, the prevalence in India recently. Again, a lot of these patients, actually, they are in India. The diagnosis of CPA is established by combined clinical radio-immunomicrobiological criteria, out of which IgG aspergillus, a serological test, is the cornerstone of diagnosis. As you can see, sensitivity is 80 to 90%, so which means that 10 to 20% of patients, they would not be picked up by these antibodies. Hence, the role of other microbiological investigations. In this case, what we have studied was PCR and galactomelan, both in serum and BAL. Prospective study done in the chest clinic of a tertiary referral center. I've already mentioned that, right? So, done over a period of five months, study was ethically approved. So, this is the study flow. In all, 210 patients were included. According to the physician's discretion, 161 underwent bronchoscopy, 49 did not. So, those who underwent bronchoscopy had their BAL, galactomelan, PCR, as well as serum galactomelan sent. In the remaining 49 who did not undergo bronchoscopy, only serum galactomelan was sent. So, overall, we got the diagnosis. Now, all these patients, they were CPA-suspect patients, they were adults, and we got a diagnosis of CPA in a total of 88 patients, that is 42% patients. So, these are the comparison of the demographics. Age-wise, CPA patient a little older, history of TB more common in CPA group. Symptom-wise, cough and hemoptysis more common in the CPA group. Lab and radiological investigations, as expected, aspergillus IgE, aspergillus IgG, more positive in CPA group. Cavity, fungal ball, bronchiectasis more common in the CPA group. Microbiological findings, since around 36 patients in the non-CPA group, they had pulmonary tuberculosis ultimately. So, gene expert, MGIT, they were more common in the non-CPA group, while the fungal test, they were more common in the CPA group. Right, so the types of CPA, most common was chronic cavitary pulmonary aspergillosis in around 82%. Next common was aspergillus nodule. Briefly, the comparison of the galactomelan PCR in the two groups, we saw the absolute value of bal-galactomelan and serum-galactomelan, they were higher in the CPA group. This was expected, but what was not expected was the PCR, it was numerically higher in the non-CPA group. Numerically higher, again, for aspergillus PCR, the difference was not significant. For the PCR in-house, the number was higher in the non-CPA group, as well as, it was statistically significant. We calculated the diagnostic accuracy, bal-galactomelan, sensitivity was around 47%, specificity 64%, serum-galactomelan, 29% sensitivity, and the specificity was considerably higher, 87%. If you would see the aspergillus PCR and the in-house PCR, again, if you look at the specificity, very poor specificity, mid-30s, end of 30s, so not very good performance. Finally, what we also did was we compared PCR and the galactomelan in patients with, sorry, in these patients, and we compared it with the IgG aspergillus. What we saw was, again, similar results, bal-galactomelan, serum-galactomelan, sensitivity, specificity was higher for bal-galactomelan, specificity higher for serum-galactomelan. Again, the PCR values, if you would look at the specificity, they were very poor, again, in the 30s, 40s range. We also calculated the diagnostic accuracy in those subgroup of patients with chronic cavitary pulmonary aspergillosis, and we saw more or less similar results. Bal-galactomelan, serum-galactomelan was better. The PCR performance was not that good. We did an ROC analysis, and we saw the best cutoff was 0.46 for serum, 0.69 for bal-galactomelan. Since a lot of these patients, they also had PCR positivity, we did a logistic regression to see if any of these factors could predict PCR positivity, but none of these factors, I'm sorry about this, probably it's not visible, gender, cavity, bronchiectasis, IgG, aspergillus antibody positivity, none of these factors could actually predict PCR positivity. So just to discuss the important points, what we found out was PCR was not a good modality, slightly better for serum-galactomelan and bal-galactomelan, but again, nothing to be very excited about. We reviewed the literature, we saw that different parts of the world had actually thrown up different specificity sensitivity and cutoff. Only study from India was done from a neighboring Indian territory, and it showed similar cutoff, but different diagnostic accuracy. The reasons for modest performance of the galactomelan assay, we feel that it was probably because a lot of our patients had pre-existing lung disease, so probably aspergillus was a colonizer, so that led to galactomelan positivity. Also, we had shown in a previous study, drugs or food habits may lead to false galactomelan positivity. Similarly, for PCR poor performance, we thought that aspergillus colonization would be a common reason, and also, it may be due to the fact that this aspergillus kit was not validated in Indian population specifically. So I would like to conclude by saying, PCR, not a good willing test. GM assays in bal and serum may be better, however, they have to be used in conjunction with the other clinical radio microbiological characteristics. These are my acknowledgements. I'm really indebted to my institute, my department, my research team, my ohana, as people would call it over here, and a shout out to CHESS 2023. I'm really having a great time over here. Yes, and I'm looking forward to the rest of the conference. Thank you so much. Thank you. Right, it's a nice question. So the gold standard was the, so chronic pulmonary aspergillus will normally be diagnosed by a combined ERS IDSA guidelines, which takes into consideration clinical, radio, immuno and microbiological criteria. It was not culture. It was antibody plus symptoms for three months, plus suggestive radiological findings. That's it, you know, because culture doesn't really come into the criteria of diagnosis of chronic pulmonary aspergillosis. So PCRs, I mean, you know, PCRs, what we, PCRs have not been used traditionally in chronic pulmonary aspergillosis outside of research. They have been used in invasive pulmonary aspergillosis. But the understanding is if PCR, you know, there are organisms in the airway, they will be picked up by PCR. But in this case, what we saw was that was not good enough, probably because aspergillus is ubiquitous. It's there everywhere. It cannot really tell us which human being, which patient would be developing, you know, a reaction to it and would have a, would develop a disease in reaction to it. Did I answer your question or it was a little? No, so it's not really a part of the gold standard, but some studies have evaluated and found out, you know, a cutoff of one may be used. But it's not there in the, you know, the core clinical criteria or microbiological criteria for diagnosing CPA. Please. I think IgE is more important than specific IgG. Right, so chronic pulmonary aspergillosis, specific IgG is more important. For allergic bronchopulmonary aspergillosis, it's the other way around. So it's the allergic sensitization. So it's IgE, which is more important. So if I can say from my experience, so, you know, galactomannan tests, what we have realized is not, does not really lead you on either for diagnosing chronic pulmonary aspergillosis, invasive pulmonary aspergillosis. I'm talking about BAL, BAL galactomannan. In our setup, it does not really lead you on because, you know, as I said, probably a lot of conditions like food, antibiotics, peptazo, et cetera, which we feel may, you know, have, may lead to a false positive reaction. And also treatment-wise, I mean, in patients who are diagnosed, who are confirmed to have invasive pulmonary aspergillosis, in those subsets, we often see the galactomannan level decreases on treatment. But then again, you know, again, nothing to be really very excited about that we can use this in isolation without tracking the clinical profile of the patient. I'm sorry, did I answer your question? It was a little roundabout answer. All right. Thank you very much. I think we are past 10 minutes, so we'll have to move on. Sure. Thank you so much. Good morning. So I will present the evaluation of TB, different forms of clinical manifestation of TB from the perspective of a physician-turned-immunologist. So we started our journey with the belief and with solid evidence, clinical evidence, that immune system can contain TB infection. It can prevent the conversion of infection to, from conversion of infection to the disease, active disease. And we also showed that level of immune containment, the strength of immune response, can indeed influence the manifestation of localized relatively indolent disease entity like pleural effusion, which responds very well to treatment, as opposed to the miliarity tuberculosis, which is disseminated. So we started our journey with this belief that immune containment is an important determinant in deciding what will be the clinical form manifested by the disease. And we started that and we continued that in MDR-TB as well. So first we showed that indeed most of us in our part of the world, in the Asian and other countries where TB is very endemic, we find that we are infected, but we don't develop active disease. That itself suggests that. And TB is a bacilli which is very difficult to clear off completely. We cannot sterilize our body. Somewhere, in some part, some mycobacteria will be sitting the rest of our life, but we don't develop disease. Very few of us, we develop disease. And that too happens when there is some immune perturbations like HIV infection and post-transplant that we do in our department in post-BMT and even after post-treatment of rituximab in rheumatoid arthritis. It suggests that the Th1-like or inflammatory immune response or granuloma-promoting immune response is very critical, and that has some role to offer the containment, endogenous containment of the disease itself. And we showed that this response varies in different entities, clinical entities, from pleural effusion. So we believe, like leprosy, it is a spectrum of immune response that dictates the clinical form of the disease that is to be manifested. And we showed that there is indeed influx of FOXP3-positive T cells, and they suppress the gamma-interferon-positive cells, which are not actually exactly sufficient because in pleural effusion, we get tons of gamma-interferon-producing cells in pleural tap, but there is no protection from the disease. We have indolent disease, but still we have disease. So it suggests that gamma-interferon is very important, but it is not alone sufficient. So there must be something else. And now we have shown that it is indeed the polyfunctional T cells, which releases gamma and TNF, both in a proportionate manner, so that there is proportionate amount, so that it is dominantly the non-apoptotic death of the mycobacteria-inflected or infected mycophages. And if it is non-apoptotic, if it is apoptotic, then probably it will not cause further dissemination of the disease, leading to disseminated or miliary tuberculosis. And we also found that in patients in bronchial lavage, there is actually enhancement or heightened expression or heightened function of PD-1 and L-1 axis that is manifested by overexpression on T cells and mycophages, their ligands, and so on. And we showed that we can rescue this immune response by inhibiting certain molecules like PD-1 and TM3, and PD-1 can rescue much more response, especially the gamma interferon and polyfunctional T cell response, when we retrieve the T cells from the bowel, as opposed to the peripheral blood of the same patients. So that intrigued us to see how this can impact the outcome of the treatment, because it is not alone the chemotherapy, be it cancer or any other infectious material, especially for the chronic infectious diseases, chronic inflammatory diseases, where actually overexpression of checkpoint inhibitors. It is basically the drug and immune response, drug-immune interface that actually controls the disease in the final sense. Drugs definitely helps to bring the threshold level of the pathogenic element below certain level, where immune system can take over successfully. And if in active disease there is suppression of immune response, it is better we rescue the immune response so that drug and rescued immune response can join hands together, have a synergism, and offer better clearance, which will have major impact in the disease transmission in case of tuberculosis. So here we show that with treatment there is reduction of the bacilli, and there is reduction of the regulatory T cells. So whatever suppression is there, probably that was triggered by the bacillary load or many other factors maybe, we don't know exactly. But where there is a failure, those patients which fail to show the reduction of the Treg cells here, and most of them, 76% of them, they are eventually diagnosed as MDR tuberculosis. And recently, it is unpublished, we have demonstrated that in MDR TB, actually the response elicited against TB bacteria is very weak, and Treg cells play a significant role. And Treg cells and PD-1 axis, which is more expressed on Treg cells, they play a significant impact in that higher suppression in MDR tuberculosis of immune response. And if we treat the patients, there is gain of immune function, and that matches with the disease clearance. But again, if that fails, those patients are eventually, 76%, I guess, I think this is old data, 76% of those who don't show the reduction of Treg cells and PD-1 in their peripheral blood, they develop MDR tuberculosis eventually. So here we show that there is gain of immune function, and that gain is more in the local disease site, in the bronchial valvular of the patients. And this gain, we can see that this is the gamma interferon, and PD-1 is the strongest element, even though we are now starting with various other checkpoint inhibitor molecules, and they actually work all together to suppress the immune response in active TB patients, as opposed to the LTBI cases. So we studied, so the TNF was tightly associated with conversion from LTBI to active disease. TNF is a double-edged sword. It is required. It is required, but it is not, it can cause damage as well. So we showed that rescue of that function, double-positive cells are important, and if they are rescued, if that function is rescued, this is the, so bacillary clearance is significantly higher in those patients, in the BAL-derived cells. And we followed the MDM model here, microphage infection model. And we did some mice study. This is also published. There are two papers actually back-to-back in the same journal. We show that these together can actually work synergistically to offer better clearance in the mice infection system, although mice does not actually truly reflect the human disease. Mice does not have any latency, which is a dominant feature in human tuberculosis. So based on this, our journey from bench side, we have been allowed by our agencies and European Commission, we have been awarded Horizon 2020 grant, which is a hefty grant. So we are actually, this is a pilot-level study to do the PD-1 trial, if we can rescue the immune response and to see its effect, its safety in tuberculosis, it is a repurposing of the drug, and also its efficacy in sputum conversion. I will show the very brief early indication. So we studied these two doses, and if you see that week four and week eight level, the conversion is much, much, much higher. This is very early data, this is just end of the first year of study. So therefore, by rescuing the immune system, especially the polyfunctional T-cells, we can offer earlier sputum conversion, especially in MDR and XDR, which is going to have a major or significant impact in the disease transmission. Here we believe that this molecular intervention will actually offer a better impact on the disease dissemination, epidemiology of the disease dissemination in community, because if we can do early conversion by immune rescue, it is always better. So with that, we don't have any financial, it is funded by European Commission and Department of Biotechnology, Government of India. And these are the people who are involved. The clinical trial is run, he's a military person, he has now gone back to army. And these are our all students, most of them have been exported to this country, but few of them, they are still in India, they are conducting nice work. And this is my collaborator, and another collaborator, we use our MDM system, and this is all. Thank you very much for your patient hearing. I am Dr. Noor Kang from the Samsung Medical Center in Seoul, Korea. I have nothing to disclose. Well the basic objective of this study was to explore the different characteristics of the sputum microbiome in NTMPD patients based on their treatment outcome status, whether they were refractory or not. The incidence and prevalence of the NTM infection in South Korea is increasing annually, and the most common NTM infection is the NTM pulmonary disease, or NTMPD. Well the situation is not just in South Korea, U.S. is facing the same, similar situation, and NTMPD is becoming a global medical burden worldwide. The most common causative organism in NTMPD patients is the mycobacterium avium complex, which is also called MAC. Well there are regional variations, but the MAC is the most common species. But the treatments, and the treatment successful rate is different according to the causative organism, and MAC has a quite high treatment successful rate, about 60 percent. But abscisus has the lower successful rate compared to MAC. Well for mycelium it's up to high as 70 percent, but for abscisus, subspecies abscisus, so mycobacterium abscisus abscisus has a low successful rate of 30 to 40 percent. But the underlying pathophysiologic mechanism in this different treatment outcome is poorly understood. For a long microbiome studies have shown that microbiome communities such as bacteria, fungus and virus can impact the development of the human respiratory system by disrupting the microbiome and the host interface. The dysbiosis, which is deviation from the normal microbiome composition, has been reported to be associated with the development and the progression of the respiratory disease, such as asthma, COPD, bronchiectasis, and NTM as well. NTM do not reside in isolation, but they are part in the complex of the microbiome, lung microbiome, and change in this disease status or antibiotic treatment can result in alteration to microbiota among the NTM PD patients. Well in this figure here we can see that patients who were NTM culture positive patients, those are in red bar, and NTM culture negative patients are in green bars. And we can see that their composition is quite different. So what we did was that from our cohort of the NTM PD patients, and those are the patients who agreed to provide their sputum samples serially, we collected the samples. Of total they were 56 patients, and those patients who were not, who didn't receive any treatment, those were treatment nine patients, they were 27 patients, and we excluded these patients. And those patients who were on treatment, but didn't, the treatment duration was less than 12 months, so they weren't either considered as a cure or refractory, so these patients were excluded as well. And those patients who did not have the follow-up samples, so we want to see the stabilized sputum samples, so we excluded this patient as well. And the one patient we excluded because she did not pass the quality control due to technical problem. And we grouped these patients to microbiological cure and the refractory group. These, the treatment outcome, we refer to the NTM NET consensus statement. Briefly speaking, the microbiological cure group is maintaining the multiple consecutive negative cultures after the treatment, and refractory, on the other hand, refers to the sustained positive culture with the causative NTM species, even after the 12 months of the antibiotic treatment. So we collected the patients in the six-month interval, and this microbiological cure, this might be a little bit confusing, so these patients already treated, already completed their treatment. And these patients, refractory group patients, were still ongoing with their treatment. For the sequencing analysis, we used the 16S ribosomal RNA gene, V3 to V4 reason, and alpha diversity, which sees the diversity of the microbiome between the sample, was used, and we analyzed the beta diversity, which to compare the diversity between the samples. And LDA was performed to see the difference between the groups based on the effect size, and significant was, we considered it significant when LDA score was more than 3.0 and P value was less than 0.05. So these are our baseline characteristics. It's a small study, but this was a prospect study, but very small. As shown before, the MAC was the most common causative organism in our cohort, and three patients were diagnosed as MAC, and three patients were diagnosed with intracellulitis. And for abscesses, two patients were diagnosed with mycelium, and three patients were diagnosed with abscesses. And mixed infection, they had both of the MAC, IVM, and intracellular, and MAC and abscesses infection, co-infection. And when the baseline sputum samples of the microbiological cure group and the refractory group were compared, the alpha diversity was higher in the cured group compared to the treatment refractory group. And in the follow-up samples, this was similar, alpha diversity was also higher in the cure group. The beta diversity was analyzed to evaluate the similarity of the bacterial communities in the sputum samples of the two groups. The results showed a different species distribution in this follow-up sputum sample, but not in the baseline sample. But however, all together in total, the different species distribution was observed in the total sputum sample, this combined all together. And in LEF-SE analysis that revealed that the several texas showed a different distribution based on the treatment status, streptococcus, protella, and haemophilus, fusobacterium, and dysuria was highly abundant in the microbiological cure group compared to the refractory groups. So what we found was that in NTM patients, the sputum of the patient who remained the long-term stabilization without recurrence exhibited higher microbial diversity than that of the treatment refractory patients. And several general was identified in the samples of the cured group, and we hope to see, we need some more research on this one, and we are planning to compare the patients with who had never been treated before to patients who is on treatment, so that's our next plan. Thank you for listening. Hello, everyone. First, thank you for offering this great opportunity to share my work in this session. I am Dr. Jung Hee-Jung from ISIM Medical Center in Seoul, Republic of Korea, and I'm currently a resident. And before going into presentation, I first state that I have no financial conflicts of interest to disclose. Mycobacterium avium complex, or MEK, is the most frequent cause of pulmonary NTM infection worldwide. MEK pulmonary disease, in short, MEK PD, can be classified into two forms according to their CT findings, which being fibrotrapezoid form and nodular bronchiectative form. And the nodular bronchiectative form can be further divided into two types, which is cavitary type and non-cavitary nodular bronchiectative type, in short, NCMB type MEK PD. Intermittent administration, like three times per week, three oral antimicrobial agents comprising macrolide, isambutol, and rifampin is currently recommended for the treatment of NCMB type MEK PD in the ATS-CRS-ESMI-IDSA guideline. This recommendation is largely based on two single center-based retrospective studies, which show similar sputum conversion rates between intermittent and daily regimens. However, the treatment guideline from BTS advises against using this intermittent treatment for a patient with severe NCMB type MEK PD, including those with radiological evidence of severe infection or AFB smear positive respiratory trick sample from the treatment initiation. However, the difference of clinical outcome between intermittent and daily regimen of three oral drugs in patients with NCMB type MEK PD with a sputum AFB smear positivity, which is an indicator of high mycobacterial burden, has not been investigated fully yet. Therefore, today we aim to determine whether there is a difference in sputum culture conversion rate between intermittent and daily regimens for patients with NCMB type MEK PD in relation to sputum AFB smear results. The single center retrospective analysis was conducted based on the medical records extracted from patients who were treated at ASEM Medical Center, which is a tertiary referral center in Seoul Republic of Korea. Patient with NCMB type MEK PD whose treatment was initiated between 2015 to 2021 were selected since the intermittent therapy for NCMB type MEK PD was first adopted at the study center after 2015. However, it was not the only prescribed regimen because either one of intermittent or daily therapy has been chosen at the discretion of attending physician at the time. After going into exclusion and inclusion criteria, the patient who received intermittent or daily treatment of three oral antimicrobial agents for longer than a time period of a year were finally enrolled. A total of 110 patients were finally selected, and 57 received intermittent regimen, and 53 received daily regimen. This is the clinical characteristic table, and the mean age was 62.7 years old, and 70.9% of total were female. There was no statistically significant difference regarding clinical characteristics of patients between these two groups. AFB smear positivity at the treatment initiation was confirmed in 36 out of 110 patients, comprising 32.7% of total. The overall culture conversion rate was 80%, with 88 out of 110 patients achieving culture conversion at their treatment completion. In the intermittent therapy group, 70.2% of patients achieved culture conversion. However, in the daily regimen group, 90.6% achieved culture conversion, and that was statistically significant. This difference in treatment outcome was particularly evident in those 36 patients with initial sputum AFB smear positivity. In these positive AFB smear result patients, 50% of them achieved culture conversion at the treatment completion in the intermittent group. However, when they were treated with daily regimen, 85% of them achieved culture conversion, which also showed a statistically significant difference. However, in the remaining patients with initially negative AFB smear result, the treatment outcome between intermittent and daily regimen group did not differ significantly. So in this retrospective analysis conducted at a single center in South Korea, intermittent treatment resulted in a statistically significantly lower rate of culture conversion than a daily regimen in patients with NC and B-type MEG PD who initially had sputum AFB smear positivity. So our finding supports the BTS guideline, which do not recommend intermittent therapy for MEG PD with AFB smear positivity. As mentioned earlier, the recommendation for intermittent therapy was supported largely by two single-center-based retrospective analysis, and this is one of the two report, and in this article, the similar sputum conversion rates among 99 and 118 patients with NC and B-type MEG PD who were treated with intermittent and daily regimens was confirmed. However, also in this study, patients treated with the intermittent regimen had a significantly worse treatment outcome if they had a positive sputum AFB smear at the treatment initiation. However, no further investigation has been done in the study regarding this relationship between sputum AFB results and clinical treatment outcome. Our findings suggest that prescription of a daily regimen in patients with NC and B-type MEG PD with sputum AFB smear positivity may lead to a higher rate of sputum culture conversion than an intermittent treatment regimen. This result suggests that the therapeutic regimen can be selected according to the mycobacterial burden for the treatment of patients with NC and B-type MEG PD. This is the end of my presentation, and thank you for your attention.

basis score

Mycobacterium avium complex pulmonary disease

MAC-PD

risk of mortality

treatment outcomes

retrospective cohort study

antibiotics

airway clearance

disease severity