Thank you very much, David, for the review of recent advances in therapeutic options for treatment of patients affected by non-tuberculosis mycobacterial diseases. It is now my pleasure to introduce new trial-based evidence, guidelines and individualized approaches to real world management on mag lung disease. Let me start with a patient, 59 year old woman who uh first presented in January 2021. She is a non-cigarette smoker. And she suffers from chronic cough for already about 10 years. She reports night sweats and she's not so sure about weight loss, but perhaps yes. Her main symptom is fatigue. She says by early afternoon, the battery is empty. On presentation, she weighs 59 kg. Her height is 174 centimeters. Blood pressure 135/80. Heart rate 76. Sauration um at rest 98%, and her respiratory rate 12 breaths per minute. She has a pectum excavato. Just normal breath sounds and there's a mid-systolic click indicating possible um mitral valve prolapse. On CT scan, there are occasional nodules, for example, over here and over here and over here, and there are also mild bronchiectasis seen on the CT scan. At lung function testing, she has a normal forced vital capacity of 3.16 L being 100% predicted, and um she has a slight reduction in the forced expiratory vital capacity in the 1st 2nd of 2.14 L, which uh only reaches 79%. And her tiffinal test is 68%, which puts her into a range of mild obstruction. On sputum smear microscopy, there are no acid fast baciliine, but on culture there's growth of mycobacterium intracellulara susceptible to macrolides and amiccain, and the time to culture positivity is 10 days and 4 hours. So, Remember, when is infection or disease? We do have the ATS criteria. Um, actually, those are criteria by the four different societies, ATS, ERS, IDSA, and SSID. Clinical signs and symptoms, imaging, and microbiology. And we also do have the Wollensky criteria adva bacili visible. No, they're not visible here. Repeated isolation of the same species. No, it's one time microbacterium intracellulara. Isolation from a sterile source? No. They are isolated from the sputum, which is not sterile. Is it a pathogenic species? Yes, it can be pathogenic mycobacterium avium complex, the most common non-tuberculose mycobacterium causing disease. But it also can be just a bystander and colonization that um needs to be distinguished by the other criteria. Does this patient have immunodeficiency? We don't know. There is um thought that individuals with mitral valve prolapse and with pectum excavatum were on the lower edge of normal weight. have an inherent immunodeficiency, but this is really very ill-defined and we do not know what the immunodeficiency actually is. So together with the patient the decision was made not to initiate treatment. In this situation, how should physicians monitor patients who are not being treated? For this situation, we have developed a patient diary, which is really useful because as a managing physician with a blink of the eye, you understand whether during the last month, things were stable or deteriorated. This diary has several variables morning temperature, morning body weight, night sweats present, yes or no, cough, you can get points from 1 to 24, meaning during either just 1 hour of the day or during all the 24 hours of the day, the individuals was coughing. Then it's the question about the sputum amount, the sputum color, whether hemoptysis were present, and very important fatigue on a visual analog scale from 1 to 10. And this is entered for every day of the month together with name and date of birth and which mycobacterium, which month this diary refers to and which year. And down here, the managing physician can also enter whether on sputum smear microscopy, bacteria were seen. If so, what was the sputum smear grade, and on sputum culture, were mycobacteria grown? Yes or no? And uh what was the time to culture positivity? We find this very useful tool, and in our patient, this is the data entry from February 2021. You see here that there is very little cough, there are no night sweats, there is no sputum. There is a low amount of fatigue between 2 and 3 out of 10. And body temperature and weight are constant. Now, the patient comes back. In September 2024 With increasing fatigue, chronic cough, night sweats, and weight loss. The imaging study performed at that time shows an increase in nodular bronchiectotic disease. Here, these nodules have increased. here new nodules, nodule also over here. There's an increase in bronchiectasis. See here, the bronchiectotic. Lesions And the lung function has deteriorated. From the previous evaluation, there's an 18% loss in the forced vital capacity, which is now only 82%. There's a 17% loss in the forced expiratory vital capacity in the 1st 2nd, which is now only 62% of predicted, and an 8% loss in the Tino test. On microbiological examination, now this 1 + acid-facili uh visible 3 times in a row, Mycobacterium intracellulara is grown in culture, still susceptible to macrolides and amiccain, and now the time to culture positivity came down from 10 days to 5 days and 23 hours. If you look at the diary, we now see there's a, a, a big increase in fatigue from 2 to 3 out of 10 now to 8 to 10 out of 10. There is no sputum production. There is cough. And there is continuous night sweats, and in comparison to the year 2021, there is also a decrease uh in weight and some low grade temperatures. Now, before we Um, if we initiate treatment for pulmonary disease, this treatment is usually macrolide-based. Azithromycin is better than chlorithromycin, and it's now recommended to use azithromycin and not chlorothromycin. There should be at least 3 active substances macrolide, ambuol, and the third one which is usually rivampicin or clofazamine. In severe disease or in severe nodular bronchiectic um, sorry, in severe disease with cavities or in severe nodular bronchiectic disease. Um, or in macro light resistance, an aminoglycoside should be added. Consider also Amica and liposomal inhaled suspension when options are limited. In less severe nodular bronchiectotic disease, the guideline committee has decided based on evidence that therapy could be in an interval 3 times per week. The duration of treatment should be for 12 months beyond the time of culture conversion. Information from the convert studies that looked at the effect of adding amiccaindiposomal innovative uh suspended, um. Medicine. But in those who had treatment failure on optimized uh treatment for 6 months, who received add-on. Alice There was a marked increase in uh the percentage of patients who achieved uh culture conversion. And this increase is sustainable with a 54% of um sustainable culture conversion success. There is much higher penetration of amiccain if it is given in in suspended liposomes then uh with IV amiccain, about 200-fold increase um with the Um, liposomal in a suspended form of Amicain versus the IV form. However, the plasma concentrations of uh the IV form are much higher than when um amiccain is inhaled. Very importantly, before the decision for treatment is made and treatment is actually initiated, physicians should have a road map and a tick list of what uh to consider before treatment is initiated. The physician needs to make the decision to initiate treatment. However, the patient also needs also to agree to that decision to initiate the treatment. And other caretakers like outpatient caretakers, physiotherapists, um, etc. should be uh involved about and informed about that decision. There should be counseling on adverse events and uh treatment monitoring. Counseling on cigarette smoking discontinuation if patients are smoking. A baseline body mass index should be recorded. I should also be counseling on nutrition. Which is very important. We see many patients that are underweight. We see very few patients who are overweight with non-tuberculosis mycobacterial pulmonary disease. Baseline imaging studies like we did here should be performed to have a comparator to um uh later on and to judge on the effect of treatment. Surgical options should also be considered, and this is especially if there's localized fibro cavitary disease. Studies on treatable immunodeficiencies should be performed. Those are um evaluations of uh the HIV status and also checking for interferon gamma uh autoantibodies. Adjunct therapy options should be considered. Drug susceptibility testing and the baseline time to culture positivity should be recorded. What obstacles have to be expected and shared with the patient um prior to therapy and expected in the course of therapy? Adverse events. Drug drug interactions, non-adherence, insufficient drug levels, non-culture conversion, and paradoxical reactions. Now if we look at the effect on the treatment of our patient, we see that in this situation in mid September 2024. We gradually see an increase already in the first month of fatigue going down from 10 to only 4 out of 10, a decrease in the hours in which the patient had to cough, now only 4, and the decrease in the intensity, um, there was no sputum anymore, no sputum, uh, production. And of course, uh there was uh no night sweats anymore after the initiation of therapy with occasional um exceptions. In the next month, in November 2024, you see that that trend continues. Fatigue is going down. Now only 2 out of 10, um, there's no cough, no sputum production, no night sweats anymore, and a stable weight, actually, the weight is, um, the patient is gaining a little bit of weight. So in summary, Screen for Mac PD in patients with known risk factors. And those are patients with non-cystic fibrosis bronchiectasis and those with persistent cough. Balance the decision about treatment carefully. Not all patients need to have an initiation of treatment right away, but in case of doubt, the guideline committee favors a decision for treatment rather than no treatment. Or deferring treatment. Use a checklist before initiating the treatment and see that all the points on your checklist are ticked. Provide adequate treatment. The first hit is the best. And still with the latest um surveys on whether physicians follow guidelines or not, the majority of individuals receive treatment that is not based on guideline evidence. This has to change. If there are limited options, consider antimicrobial intensification at the first step. In the European Union by the European Medicines Agency, Amicain in the form of liposomal suspended drug that can be inhaled, is licensed for the treatment of patients with limited treatment options. It is not licensed for patients or is not restricted in license for patients who have treatment failure. This indication is important because um if your patient needs an intensified therapy. Patients should receive um the best therapy upfront and not when the treatment has failed already. Monitor treatment and for treatment monitoring, the diary uh is a very um good tool. Diabetics. Patients affected by asthma, they have diaries where they enter their blood sugar levels or they peak flow. Patients with NTM disease should should monitor their health status in a diary and report this every month to their managing physician and also expect obstacles and mitigate uh side effects. To be sure that the best possible outcome can be achieved. With this, I thank you very much for your attention and for staying with us today. I hope this was a useful webinar and I wish you all the best.
Related Presenters
