OK, we are looking to the complexity of NTM lung disease, and the idea is to give you some ideas about the persistent care in NTM lung disease. In this symposium, we will address different items, and one of the problems is to introduce the the symposium with some ideas about the individualized care in NTM lung disease. I'm Francesco Blasi. I'm professor of respiratory medicine at the University of Milan, Italy, and head of the respiratory and cystic fibrosis unit in a polyclinical Hospital here in Milan. So these are my disclosures. I think the main problem is why we are here, why NTM lung disease matters. Well, I think that now NTMLD is no longer a niche diagnosis. Clearly there is an increasingly recognized disease, and this is related to different issues. The first one, a larger number of susceptible hosts. We have an aging population with frail patients, immunosuppressed patients that are at risk for NTM. On the other side, we are very good physicians, so we have a longer survival of patients with structural lung disease. We know the introduction of therapy for CF indeed increased the survival of this patient. So and the same is for optimizing COPD treatment. So, uh, our patients with chronic respiratory disease, uh, have a longer survival. On the other side, we have a clear improvement in the microbiology and imaging recognition of the, of the disease. In this case, it's very important because we are thinking to, to the disease and we have the, the way to diagnose the disease. At the end of the day, this lead to a very high clinical and therapeutic burden, and we have to decide if we have to just look to the patient, monitoring his journey or start immediately the treatment. So we have to have a look to this. And I think when we start to think to individualize care in NTMLD, first of all, we have to identify the patient to be treated, and this is important because we need to identify and defining the true disease, NTM lung disease, and particularly the risk of progression of the disease, but this leads to our approach to the patient. In fact, then we we decide when to treat the patient, taking account that make the diagnosis is another thing compared to the treatment thresholds. So we have to make the diagnosis and then to decide if we had to treat the patient now or we had to wait, and we will discuss a little bit about this. And then when we decide to treat, we have to decide how to treat the patient, so tailoring the intensity of the regimen we have to use for our patient, and this is related to different issues, uh, maybe the species of NTM involved in the in the lung disease, the radiology imaging, the smell status, and also the frailty of our patient. And then we have to adapt. Our approach, we assess symptoms, we assess cultures, look to the CT trajectory, and look to the patient's priorities. I think this is most important when you think to the tolerability of this long term treatment. So clearly the individualized care is related to probability to have a disease, the probability to have or to a risk of progression of the disease, the treatment burden, and last but not least, the patient goals in this dynamic pathway. Uh, when you have the isolation, uh, you have to decide what to do, and I think there is something that is clearly important to define the diagnostic threshold and the treatment threshold, as I said before. NTM isolation doesn't mean treatment. NTM isolation leads to a diagnosis of NTM lung disease that requires compatible symptoms, imaging, microbiology criteria, and also exclusion of other causes of lung disease. And then if the diagnostic criteria are met, then we have to look to the progression and the high risk disease. Uh, look into, uh, you know, having an observation of our patient, reassessment, look into quality of life, cultures, radiological evolution, lung function trajectory, and then we can reach this step of treatment. Clearly, if you have a clinical or radiological progression, uh, you have capitary disease, positive smear, uh, and uh you have a particular species of NTM, this leads to the possibility to uh to treat the patient uh in an early stage. But if you look at the uh uh risk of our patient, it's really a triangle where you have the host and mainly related to the age and fragility of the patient, BMI, immunosuppression, comorbidities in our host. And then the damage of the lung structure, a cavitation, bronchiectasis, parenchymal damage, and the kind of pathogen is involved, particularly species and subspecies of NTM, the positivity of MER, the bacterial burden, and also it's important, the drug susceptibility, and this lead to the uh assessment of probability and velocity of progression. So looking to the concern of the high risk of progression of our patient, we can set Uh, 3-step, lower concern, intermediate concern, higher concern, and this is related to many, uh, many items. First, symptoms from minimal to, uh, to, uh, uh, important symptoms and significant symptoms going to low inflammatory burden to significant symptoms with amoris, for example. Clearly, imaging localized non-cavitary radiographic disease to multilobar progressive radiographic findings and you have extensive radiological disease, this means a higher concern of risk for progression of disease. Clearly, negative or low burden microbiology is quite different when you have m positivity with high microbacterial burden. And you have aggressive species and resistant concern. Here you are in the red line for your patient. And the other point is pulmonary function. It's clearly a preserved pulmonary function and stable weight stay for lower concern. If you go to the more symptoms, weight loss and low BMI, then the concerns are high. And so the most important thing is that if we choose to watchful waiting of our patients, so monitoring the situation of our patients because we think that the risk is low for progression, then we are not in a passive process. We are in a Very active process. We have to be sure that the airway clearance of our patient is started and the physiotherapy is done. The risk factor like smoking cessation is controlled. Smoking is controlled with smoking cessation. The use of inhaled steroids, for example, is a concern. So we have to put together all the problem and control our patient, monitoring the patient, and decide when to intervene because it's clearly it's important to have an early action, but we have clearly a balance between initial observation and starting early the treatment. The uh observation is clearly favored but mildly stable disease, uh, minimal symptoms, uh, uncertain clinical relevance, unexpected toxicity, and also patient preference. We have to discuss with our patients, uh, the, the, the situation. Clearly, if you have a radiological or clinical progression, cavitation, aggressive species, uh, limited pulmonary reserve, this favors treatment, uh, for an early treatment. So it's important to have a longitudinal analysis of our patient, confirm the diagnosis, optimize airway clearance and comorbidities, intensify surveillance, and then when needed, start NTN direct therapy. And clearly CT patterns and species identification can help us to define a prognosis and possibly the clinical management. Clearly the radiological patterns are important. Highway centered diseases are certainly less severe than advanced destructive disease or cavitary disease, and the same is for the species. Clearly. There are different behavior, treatment, different treatment complexity, and different concerns in terms of prognosis of our patient. If you have a mark, if you have a kazi, if you have senopy or abscessus, going from the less problematic to the most problematic like macrobacterial obsession complex. So CT phenotype and species identification are quite important for risk certification in our patients, and the precision care mandate means right patient, right time, right treatment, and clearly we have our backbone by antimicrobial where we look to the root and intensity of treatment, but we have also to take into account in the. If you had to stop or start in a therapy, nutrition and rehabilitation of our patient, airway clearance again, and certainly the concern about toxicity, interaction, and patient goals for the treatment. And we have to measure our success, and there are different items, cultural commersion, symptoms and quality of life improvement, weight and activity recovery, lung function stabilization, radiological stabilization, and tolerability adherence. So at the end of the day, we have to take into account different uh uh problem, the species and subspecies, drug susceptibility, the radiological phenotype. The our patient frailty, renal drug interaction, and patient priorities because patient has the last word in terms of starting the treatment. And then when we try, we start the treatment, we have, we must have a strategy going to the right regimen, right intensity, and right monitoring of our patient related to the different items we had described. And certainly this means that you are not working alone. We have, we are the NTN specialists, but you need a clinical pharmacist, obsess physiotherapist, clinical microbiologists, and along with this, the radiologist, uh, psychologists. The dietician, the CR specialist, the pulmonologist that will maybe follow the patient, and certainly sometimes also the thoracic surgeons. So the multidisciplinary team is very important in the care of NTM lung disease. So at the end of the day, uh, we have to go, uh, a, a frame, a practical framework for, uh, moving from the risk assessments to the, uh, uh, care of the patients. So first we have to confirm the disease, then define the phenotype. The most important thing is estimate the progression risk. Uh, assess the burden and priorities of our patients, observe or prepare or treat the patient, and when we decide to treat, tailor the intensity of our treatment, and for sure we have to reassess and adapt our, our intervention to the tolerability and to the situation of our patient. So, the individualized care for NTM Lyme disease is clearly a longitudinal strategy that separates at the start of our analysis, the diagnosis from the treatment, and then we have to stratify the progression risk, adapt our intervention intensity, and reassess our patient over time. So, this, I want to thank you for your attention and thank my, my group of people working in NTM Clinic. Thank you very much.
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