we now proceed with some real case scenarios to see how the novel management guidelines apply to clinical practice. So we start with the first case presentation. Let me introduce to you the first patient who is the 67 year old woman with a long standing medical history of Bronchitis. She underwent right middle lobe lobe ectomy for him up to this and at that time culture grew aspergillus. She received treatment with a console with no benefit in symptom relief and all of this was about five years ago. She is now referred to us with recurrent bounds of hypothesis and she reports a daily cough, productive and greenish sputum. She has no fever night sweats but she does have about five kg of weight loss over the last 12 months and she feels extremely fatigued. This is an actual section of her thoracic ct. And you see Nadia lebron cactuses a few small cavities, but on the left upper lope. But basically classical picture of nodule, a bronchial asthmatic lung disease and sputum cultures grow mycobacterium avian complex. First time in january with an acid fast bacillus smear of one plus two plus in may 24,020 october one plus FB smear and another mech culture positive. So to summarize the diagnostic findings, do we have a. T. S. A diagnostic criteria fulfilled or not. First clinical yes she has a cough and a mop texas. She also has symptoms like fatigue and weight loss radiology. She's got a classical imaging for no regular bronchiolitis um microbiology. Um She has more than two uh sputum culture growing mycobacterium avian complex and therefore the guidelines or definitions proposed by the guidelines for non tuberculosis. Mycobacterium pulmonary disease are fulfilled. Also, very importantly, we don't have another diagnosis. We don't have, for example, chronic pulmonary hospital. Oh sis that could be in the differential but that has apparently been treated successfully with the hydrocortisone. Um So she's been instructed to clear the airways with nebulizer, hyper tonic saline um prior to induce calf and also with an oscillating pep device. She's been treated treated empirically for gastroesophageal reflux disease. And we initiated antimicrobial therapy with the standard triple therapy of metal and reef in person. We decided here for daily treatment because of the extent of the Now regular disease guidelines would suggest that in not so extensive uh not regular bronchi ecstatic disease. Also intermittent therapy would be possible, but because of the many nodules that were shown on the imaging and also because of the severity of the symptoms with the weight loss and the severe fatigue. We decided to give the therapy on a daily basis. The culture turned negative after treatment initiation in december 2020 but then on bi monthly um sputum exams, March in May 2021 she again had one plus acid fast bacilli shown on sputum smear microscopy and the sputum cultures were continuously growing mycobacterium avian despite the treatment. So success in treatment is defined as achieving culture conversion and this is associated in micro material avian complex disease especially with mycobacterium with a microlight susceptibility. Um There are in a microlight resistant pathogens. The treatment success is much lower. And also with the radiological pattern disease like in this patient has a much higher chance to achieve cultural conversion than in cafeteria disease. Antimicrobial susceptibility testing is mandatory for micro lights and for amina glucose sites and we also monitor blood serum levels two hours after drug intake to ensure adequate blood levels and which is usually related to adequate absorption. Two at medicines to a failing regimen. The one could in theory add in systemic systemic I. V. M. A. Case in which is recommended by the guideline as an initial therapy. One could also add another active drug for example Cliff as a mean. But the latest clinical evidence suggests that the topical therapy with lipo soma suspended hemi case in per inhalation is probably the best choice for the treatment. And this is because the M. A. Case in in her native suspension versus the intravenous suspension of education has a much better penetration. Um In Al viola macrophages by almost 300 times in the airways by almost 70 times and in lung tissue by more than 40 times. But the plasma level are lower therefore having less adverse events um that are systemic and serious especially auto toxicity and never toxicity. And one can also use the nebulizer form of I. V. Emi casing which is not in liposomes suspension. But here the little animal suspended in negative form of emi casing is advantageous in terms of achieving higher concentrations and the macrophages, macrophages, the airways and also the lung tissue and the adverse events of I. V. Emi casing are substantial. Overall with the daily dozing, authorized weekly dozing with amenities like oocytes. Almost more than one third of all patients experience hearing deficits. Almost 10% of patients experienced this equilibrium And around 15% of the patients experience a decrease in renal function. Those are significant and usually irreversible adverse events. Okay so what what did we achieve? We reinforce the airway clearance therapy with nebulizer, high petulance, tonic saline and continued the caucuses with oscillating pep device. We also continued the therapy of customers are fickle reflux and we performed drug susceptibility testing for mycobacterium complex towards micro lights and amino black sites. And luckily the bacteria were susceptible to both medicines. We continued the oral therapy in the morning every day with azithromycin 500 mg plus total 15 mg kilogram body weight plus 600 mg. And we added the innovative therapy with me case in as a lip Osama suspension and 590 mg also every morning. And this quadruple combination therapy led to treatment success In August 2021 acid fast Bacilli were again not visible on sputum smear microscopy and this effect was sustained over the following month and in addition and even more importantly sputum cultures um showed non detectable mycobacterium avian since september 2021. And the negativity of cultures was sustained throughout november and january than 2022 showing that in this patient the addition of education as innovative suspension to the standard triple therapy led to treatment success of a previous failing treatment regimen. Let's move on to another patient. This is a 35 year old male patient who had former substance abuse. He underwent partial right upper lobe lobe ectomy for previous apoptosis and was now again referred for recurrent bouts of him apoptosis complaining about daily calf productive greenish sputum but also has no fever and no night sweats. And again as the first patient is complaining about weight loss and fatigue. His cT scan shows a large cafeteria lesion in the right um lower lobe, the ethical segment of the lower lobe. You can see here the margin between the horizontal fissure between the upper lobe and the lower lobe indicating this is this is segment number six. The upper segment of the lower lobe on the right side. The left line in this section appears quite normal and you can also say that the remainder of the right upper lobe and the remainder of the left lung in other sections also appeared normal. But there is a large cavity In the S. six segment on the right side. Again, cultures grow mycobacterium avian, this is the fella genetic tree of micro bacteria. It starts at six o'clock and it spends to the left side, sorry to the right side. So anti clockwise and with the bacteria of the mycobacterium abscesses complex and it ends um um in the area that is here shaded in brown. The bacteria of the mycobacterium avian complex. Also then at between six and seven o'clock in this form of display. So the microbiome, the bacteria of the mycobacterium avian complex are on the one far side of the end of the fella genetic tree of micro bacteria and opposite of mycobacterium obsesses. So they are not and they're most distantly related with them. And micro bacteria. Avian has a very high mortality systematic literature review of show the poor estimate uh five year mortality of more than one quarter of all the patients and patients who are not treated for mycobacterium avian complex pulmonary disease may progress over six years in more than 95% of all cases. There's a high morbidity and poor quality of life with acceleration, lung dysfunction and reduced health related quality of life irreversible cavities and bronchi activities leading to an increased number and frequent and severity of lung infections and accessible stations. So this is from the 2020 guidelines for the management of mycobacterium avian complex, lung disease. We don't have no doula bronchi ecstatic but we do have cafeteria disease. And the recommendations to treat with three or more drugs as the preferred macro light from ISAN as the preferred reform is in reform person than anthem, brutal and severe disease education or streptomycin ivy as daily therapy. So we started therapy out of five trucks, IVM and metal plus prophecy. Mean which is not recommended by the guideline but which has been found since that it has good clinical activity against mycobacterium avian lung disease and by many experts is used in addition to education also because of a synergistic effect against mycobacterium avian and also other non tuberculosis micro bacteria. We did not have in relative education in liposomes suspension available at that time. If we would we would have used that as initial part of the therapy because the adverse events are much lower than with the I. V. Formulation of the case in the concentration reached in the Al viola macrophages is much higher than we achieved with the I. V. M. Occasion. As shown in the display of the patient number one. What we did do is in an attempt to close the cavity we inserted bronco valves and in combination therapy of bronco valves plus the therapy with ivy Emmy cason azithromycin and total revamp person and cliff as I mean we actually achieved closure of this large cavity here on the left side of the image. You see the pre and post um images in coronal views of this large cavity which projects here to the right upper region of the right lung. It's actually the upper part of the lower lung lobe which you see here on the right side of the image in the superior. Um Two pictures on the left side again, that large cavity um and in the segment as six on the right side which is um after treatment completely closed um due to the effect of antimicrobial therapy and the effect of the valve. And you also see this in the lower right corner of this picture with the excel views complete closure of this large cavity with this combined therapy. Thank you very much for your attention. Thank again very much. My dear colleagues professor at Liberty and Professor Griffith for joining me today here in Barcelona for this um educational session on mycobacterium avian lung disease. And we're happy to answer your questions in the interactive dialogue sessions.
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