Video Completing the Journey from Diagnosis to Cure in MAC Lung DiseaseTranslating Trial-Based Results to Real World, Side Effect-Mitigating Patient Care Play Pause Volume Quality 900P 654P 524P Fullscreen Captions Transcript Chapters Slides Completing the Journey from Diagnosis to Cure in MAC Lung DiseaseTranslating Trial-Based Results to Real World, Side Effect-Mitigating Patient Care Overview CONTINUE TO TEST Back to Symposium Thank you very much, dear colleagues, Professor Griffith and Professor Aliberti for providing uh evidence for um advances in the area of the care of patients with mac Pulmonary disease. And I will now try to move uh towards the front line of clinical care by providing practical case based approaches to ensure guideline and trial based evidence to translate to real world patient care as outlined before it is difficult to balance decisions for treatment initiation in these patients other than in TB where when we find the tuberculosis mycobacterium tuberculosis bacteria. This is almost always a treatment decision here. It's more difficult. Usually, treatment should be initiated if we see acid fast bali on sputum smear microscopy because that's an indicator of a high bacterial load. Also, treatment should be indicated if we see cavities on thoracic imaging because that is an indicator of advanced disease. Also, if we repeatedly isolate the same species of non tuberculous mycobacteria, that should be an indication to initiate treatment. The same as an immunocompromised host who have more difficulties fighting the infection than immuno competent hosts. Also evaluating uh predictors like the time to culture positivity initially with a low time to culture positivity, their chances for cure are lower. So we may have initially to give a more stronger treatment, to achieve the goal of eradication of the bacteria. Importantly, the pathogenicity of bacteria. While the finding of mycobacterium God, for example, is almost never an indication to initiate treatment. Usually finding of mycobacterium avium complexes and especially finding of Mycoba Kia is an indication to initiate treatment. Also finding bacteria from so-called sterile specimens like lung biopsies. Transbronchial biopsies should favor initiation of treatment as well as when there's limited treatment options. And we want to do all that is possible. On the other hand, there may be indications for watchful waiting, especially in minimal disease and the benefit of non tuberculous mycobacterial infections. From the perspective of a physician is that there's almost never an emergency and we almost always have time to make a decision. And we may have a follow up visit to be sure about having everything together to make the decision for treatment. Also, if there's no progression in the absence of non cavitary disease, we may opt for watchful waiting, especially if there's no patient consent, if there are no other treatment options, and if we don't benefit the patient by treating, we should abstain from treatment and we should always balance the prognosis um of our um therapy versus the quality of life. I would like to start with the presentation of a situation of a patient says 67 year old a female who has a longstanding diagnosis of bronchia disease. In the course of her bronch actis, she underwent right middle lobe lobectomy for hemoptysis. And at that time, cultures had grown Aspergillus. She was treated for six months with Hyro conazole with no benefit and symptoms relief, but with um a um stop of the hemoptysis. Now, hemoptysis came back and she's referred for this recurrent hemoptysis with daily cough, productive of greenish sputum. There's no fever, no uh night sweats, but she experienced about 2 kg of weight loss over the last months and extreme fatigue. This is an axial section of the CT scan showing nodular bronchiectatic involvement of lung pathology very well compatible with non tuberculous mycobacterial infection. But tuberculosis, for example, as one differential could also look like that on thoracic imaging. In January 2020 she had um acid fast bacill one plus seen on sputum smear microscopy and cultures grew mycobacterium avium complex. The same occurred in May and October 2022. Actually, there were slightly more acid fast bacill in May 2020 than in January and in October. But cultures repeatedly grew mycobacterium avium complex, applying the A TSE RSS commit and I DS A definitions for NTM disease. We have three different pillars, clinical radiologically and microbiological um signs and symptoms. So, clinically, she has cough and hemoptysis. She has systemic symptoms like fatigue and weight loss. On imaging. She has nodular bronchos and microbiology had repeatedly shown positive sputum cultures growing mycobacterium avium complex due to the possibility that there would be two diseases in parallel Aspergillus as chronic pulmonary aspergillosis and mycobacterium avium complex lung disease. We did repeated bronchoscopies with transbronchial biopsies and we did not find Aspergillus neither on culture nor on histology of these transbronchial biopsies. There was an induction of airway clearance therapies with nebuli hypertonic saline and oscillating positive airway pressure device or expiratory pressure device. Um She was treated empirically for her gastroesophageal reflux disease. And we initiated after um consulting with her and antibiotics with azithromycin, ethambutol and rin on a daily therapy. The therapy, as you can see here is guideline conform shown from the 2020 guideline for nodular bronchiectatic disease, three drugs, Azithromycin and ethanol. It could be given as a three time weekly dose, but we opted for daily dosing. And in the course of treatment, the A FB smear became pos negative in December 2020 but then became one plus positive. Again, January March and May 2021 and FFB cultures always grew mac despite being on treatment. So success and treatment is defined as achieving culture conversion and this is associated with macrolite susceptibility. Macrolite resistant disease has only a 5 to 15% of success. We check repeatedly for macrolite resistance, but we did not find macro light resistant disease. Also, the radiologic extent of disease is important in nola bronchos, we have about an 80% chance of um eradication of the bacteria. While in cavitary disease, this is less than 50%. So she's in the more beneficial part of the spectrum. Although we did not achieve cultural conversion over six months of treatment. And when cultural conversion, like in this patient is not achieved, we should repeat antimicrobial susceptibility testing. As we've done, we should also look for serum drug levels to assure mal absorption. We also check this and the drug levels were in the normal range and we should change or add to the regimen. Either I am casein intravenously or clofazimine, um perros or go for topical inhaled therapy with Amic liposomal inal suspension, so-called ali, the advantage of the aca liposomal in suspension versus the intravenous formulation of Amic casein can be displayed on this table. You see that the concentration achieved in Avila macrophages where the disease is actually happening is much higher in the liposomal inal suspension of Muin than you. We can achieve with the IV form. Also the concentration in the airways and the lung tissue is much higher. While on the contrary, plasma concentrations are much lower with the inner form of the suspended um O liposomal suspended AMCA versus the IV form toxicity is a major issue with I VA case with overall auto toity with hearing loss of 37% with auto toity with loss of balance in about 9% and with uh loss of kidney function in about 15%. Uh over the course of treatment and the dosage and frequency of parenteral aminoglycoside administration has no effect on the likelihood of toxicity occurring. But the patient's age, the duration of treatment and the overall cumulative dose they are important. So, to reinforce um her treatment, we changed the treatment, we added nebulized hypertonic saline and an oscillating pep device that she had. We continued the treatment for the gastroesophageal reflux. We did susceptibility testing for macrolides and aminoglycoside showing susceptibility of the bacteria. And then we add two oral azithromycin buol and Rhein in sus um suspended or liposomal, suspended a casein as LS 590 mg daily. And you can see from the convert study that in a patient who is in the similar situation of having treatment failure with um backbone therapy. The uh patients who are in the have received Alice on top of backbone therapy uh do achieve achieve in about 40% of patients um cultural conversion. Whereas in those who did not receive Alice, um this was only the case in less than 10%. And then those who achieved here on the right side, sustainable culture uh conversion, 54% of those uh had sustainable success after 12 months of therapy. So following this change of therapy, we still had a positive culture, but then all the other cultures became negative and they were sustainable negative through September, November and January 2022 when we finally, after a year of um therapy, after culture conversion in uh September 2022 stopped therapy according to the guidelines. The second case is diff different. This is a 35 year old male patient with former substance abuse. He underwent partial right. Apolo prob toy also for hemoptysis. And he again as the first patient was coming for uh recurrent bouts of hemoptysis, daily cough, productive, greenish sputum, no fever, night sweats, weight loss and extreme fatigue. So, while being different, the initial presentation actually looks quite similar but different is that this patient clearly has cavitary lung disease with a large cavity and the right lower lobe, you see here, well, the fissure between the lower and the upper lobe. So, is this a segment? S six and cultures repeatedly grew mycoba avian complex again. Now, mycobacterium avium complex has a associated high mortality in a systematic literature review. The pooled estimate five years mortality rate was 27% and untreated patients with mac pulmonary disease may progress over six years in more than 95% of patients. The high morbidity and the pure qu poor quality of life is going along with accelerated loss in lung function, reduced health related quality of life and irreversible cavities and bronchia tosis. And this in turn leads to decrease lung function, increasing lung infections and excess ations. Patients with severe disease need treatment intensification. Otherwise, uh if treatment cannot be intensified or if combined medical surgical approaches cannot be offered, it is almost impossible to eradicate the patients according to the guidelines from 2020 adding a parenteral aminoglycoside to the initial treatment regimen case of severe fibro cavitary disease is recommended. And you see here patients that are affected by those types of mack lung disease with cavities in the right upper lobe or in the left lung or again here in the right lower lobe for these patients with cavitary disease, at least three drugs based on azithromycin, but with refine and thol. And in addition, in severe forms, ami casein IV is recommended or in rectory cases with Amy casein, liposomal inal suspension or a cases. IV is recommended by the guidelines at this patient uh at the time when the patient presented liposomal uh in a case as a suspension to inhal was not available yet. So we would have considered Alice as part of the combination therapy in the initial treatment regimen if it would have been available. But it was not. Therefore, as we didn't have any other option, we opted to insert endobronchial valves to um with the attempt to bring the cavities to a collapse. And you can see here on the digital view on the left side, the initial um CT scan with this large cavity and then on the right side, how the cavity closed after insertion of the valves. This is also seen here on the uh smaller images. And here also on the axial images. So we indeed were able to bring this cavity to a collapse following valve insertion. And together with the therapy um with the backbone therapy of casein buol and Refin were actually able to cure this patient. And while we are here in Milan, this week, Inmet has issued a news release announcing from the phase three, a rise study showing that adding Alice to a two drug combination of azithromycin and ethe resulted in a a faster cultural conversion and B a higher rate of cultural conversion by six months. C A higher rate of sustained cultural conversion. And very importantly, d a better quality of life in affected patients. We are now eagerly looking forward to the published results from this trial. So optimize treatment outcomes and make pulmonary disease starting from the beginning by screening patients to identify them as early as possible and then to balance the decision about treatment carefully. And in case of doubt, rather initiate treatment, it's important to use a checklist before initiating the treatment and to provide adequate treatment based on guidelines. And the first hit is the best in some countries. It is possible to administer mic casein in the liposomal inal suspended form at the beginning of therapy. And it is compensated by the health insurance companies. So it is worthwhile to talk to the health insurances to get actually the best treatment on board in patients with advanced disease from the beginning, also, it is advised to use antimicrobial biomarkers like the time to culture positivity from the first sputum culture and then from the subsequent sputum culture to access treatment responses and to predict disease severity. And as I said before, in limited treatment option, consider to intensify the antimicrobial treatment. As the first step, it's important to monitor patients, for example, with a patient diary and as they occur very frequently along the way, expect optic obstacles to occur and mitigate side effects. Thank you very much for your attention. Published September 5, 2023 Created by Related Presenters Professor Christoph Lange, MD - Program Chair Medical Director/Clinical DirectorResearch Center BorstelBorstel, Germany
