I'm Francesco Blasi. I'm professor of respiratory medicine at the University of Milan. I'm uh the head of the respiratory and cystic fibrosis unit at Polyclinic Hospital in Milan. Uh, I will discuss with you, uh, a, a case to, uh, just apply the uh new trial and based evidence and guidelines to the approach, uh, in the management of NTM lung disease. Uh, the case is a 59-year-old woman, uh, the, uh, coming to our clinic in January 2021. She's a non-smoker. She had chronic cough, uh, some night sweats, and some weight loss, not very clear. She reported some fatigue. And uh the examination is 59 kg, 164 centimeters. Uh, the blood pressure is normal, heart rate is normal, saturation is normal, respiratory rate is normal. There is a pectum excavatum, uh, but normal breath sounds and just a mid systolic click on the heart examination. The CT scan showed something, uh, shows some um. Uh, lesion in, in the lungs, some, uh, uh, treating bad evidence, some bronchiectasis, uh, nothing terrible, but something is there. The pulmonary function is fine. There's nothing to say. It's just some obstruction, but not, not so, so, so bad. Uh, looking to macrobiology, uh, the, uh, uh, sputum, the smear of the sputum was negative. One of the three, culture of sputum was positive for, uh, Mycobacterium intercellularre that was susceptible to macroli dynamicoin, and the time to culture positivity, that is one of the most important, uh, uh, item in, in, in the, in the evaluation of our patient was 10 day 4 hours. So the decision in this case was Not treatment now, uh, but monitoring, strict monitoring of our patient. And clearly how can we monitor our patients? Clearly we have to define the visits and schedule, but we can also use a clinical diary for the patients, and I think this is quite useful because The, the, the uh symptoms and signs of the involvement of, of the lung and also the general involvement like temperature, weight, night sweats, and fatigue and so on, and also some data on sputum microscopy and sputum culture. So this could be interesting to use for for our patient and to report the situation. In our patient, we had no fever, weight, it was stable. We had some night sweats, no cough always, only a few days of sputum, uh, some fatigue. She reported some fatigue, but nothing else. Uh, after 3 years, we, uh, of, uh, Follow up. The patient reported an increased fatigue, uh, still chronic cough that was most disturbing, night sweats, and weight loss. We performed a new CT scan. Uh, the, there was a, uh, deterioration in the CT scan, some new area of involvement in the lung, uh, some new bronchiectasis, some mucous plaque, uh, something is changing in, in the, in the CT scan. And if you look at lung function testing, uh, there was a, a decrease in the lung function, particularly uh FEVC, and FEV1, so more obstructive patients, and microbiology was positive. There was a uh smear positive on, on uh uh sputum, 3 positive samples for, uh, again, mycobacterial intercellularre. Still susceptible to macrolide ammicain and the time to culture positivity shortened to 5 days. And the clinical diary of the patient showed something, fever, weight loss, night sweat, cough was important, sputum amount was clearly important, and fatigue is very high. So symptoms is increasing, sputum is, is worsening, and uh CT scan is worsening. So, we had to treat the patient and we clearly it's a macrolide-based therapy where we know where the azithromycin is the leading antibiotic. Uh, we need at least 3 active substances macrolide, azithromycin, tambutol, and then we can choose in between rifampicin and clofazamine. Uh, I think that most of us will be, will go for chlorfazamine now. Uh, in any case, it's important to address the severity of the disease if cavities are present, if nodular bronchitasis or macro resistance or Amicain, streptotomycin resistance, uh, uh, strain, and you can consider to add Amicain liposomal inhale suspension, uh, when we have limited option in, in our patient. In less severe nodular bronchiassis disease, we know that we can go for a 3 day per week therapy, uh, and the duration, it must be at least 12 months uh beyond the time of culture conversion. Uh, the Amicain, uh, liposomal in L, uh, is, uh, quite important. There are very good data that show a, a clear effect on culture conversion with a significant improvement in, uh, in, in culture conversion in, in patients treated and also a very high sustainable success with culture negative inpatient uh admitted to ALIC. And another point important is why it's so effective, but probably it's also related to the penetration in the key cells, uh, macrophages, airways, lung tissue, and plasma, and you can see that clearly in macrophages and airways, the concentration of of Alice is quite higher when compared to IV amiosin. So, uh, when we, uh, Treat the decision is important. We have to discuss with the patient because it's a complex treatment with a problem with tolerability, a problem with long-term therapy, and so we need to have A very, very adherent patient with the patient that is ready to share all the problems with his physician. So we have to discuss with the patient and taking the decision together and we have also to involve the caretakers. Sometimes it's important to have some ia around the patient. And clearly the importance to counseling on cigarette smoking discontinuation if is the case, a monitoring schedule, uh, having the possibility to in any case to have a surgical control to just to have. The possibility to have an option for surgical intervention if needed and certainly uh try to control the comorbidities and uh trying to uh to to really to to control the situation, the overall situation. Because we know that we have, we'll have obstacles. Adverse events for sure, drug-drug interaction, particularly in an elderly patient. The problem, the problem of non-adherence, and we know how important in this case is adherence for all disease, but in this case, it's quite important. Uh, we can have insufficient drug levels. Uh, we have very good studies from, uh, the Netherlands looking into the drug levels, particularly azithromycin, uh, uh, or uh amicain, amicain, and, uh, the non-culture convention and react, paradoxical reaction that should be explained to our patient. So summarizing is clearly that the, when we have the, an NTM lung disease, uh we have uh the importance to address the risk factors in our patient, try to understand the risk of progression, uh, balance our decision uh about treatment with discussing with the patient, try to have the, the patient on our side. Uh, the checklist before initiating treatment is maybe very important to understand the level of activity of a disease, and you have to provide adequate treatment. It's clearly that the first it is the best, so uh it's very important to, to start in the right way. And take account that some limited options are important, so we have to consider to, to use an intensification of the antimicrobial therapy as a first step, maybe using ALIC and monitor the treatment. So explaining to the the patient how important it is to come to the clinic and having the, the dire card carefully um done and coming to the visit uh without uh avoiding visits and try to explain to the patient and to explain probably to ourselves the obstacles and try to mitigate the side effects for our patient. And so I'm ready to discuss with all of you. Thank you very much.
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