Video Real World Case Management: Evaluating and Managing Patients with Advanced MAC Lung Disease/Refractory Features Play Pause Volume Quality 960P 640P 512P Fullscreen Captions Transcript Chapters Slides Real World Case Management: Evaluating and Managing Patients with Advanced MAC Lung Disease/Refractory Features Overview Continue to Test Back to Symposium I would like to now I would now like to present clinical case of a patient with pulmonary disease as a real world case management scenario. It's a 45 year old woman. She's a logistic expert and works in an office approximately five years. Uh prior to the first presentations she experienced increased frequency of respiratory infections. She is now complaining for persistence cough over a period of five months and two months prior to a diagnosis of mac pulmonary disease. She had an X ray and a thoracic ct. And the physician at that time we're considering the diagnosis of pulmonary tuberculosis. You see here four sections of external city slides with a um capitation and the right upper lobe and no djula infiltrations. And some natural a particular infiltrations in the on both lung fields and also a capitation in the right lower lobe and some. Uh huh. Who fibra bronchi actresses both in the middle open and the lingua. And again a um cavity on the left lower lobe are in the fisher on between the lower lobe and the middle lobe on the left side. Um She underwent a bronchoscopy and the bronco al viola lavash by culture. Mycobacterium Kimera which belongs to the mycobacterium avian complex was cultured and it was susceptible to clarify amazing And to education just to remind the family tree of micro bacteria. Again starting here on the at six o'clock and moving counterclockwise from the rapid growers of the mycobacterium obsesses complex. And then moving all the way to mycobacterium a. V. Um complex which I highlight for better visibility here on the right side there's several species and every year professor totally from Italy is um updating the filo genetic tree of micro bacteria which is then uh including novel subspecies. You see that mycobacterium que mira is belonging to the Mycobacterium avian complex and it sits between mycobacterium interests and laura and mycobacterium avian and some other rare species. It has some fame because it was found that heater cooler units that are used in cardiac surgery were contaminated with mycobacterium Kimera. And during open heart surgery micro bacteria. Avian a. Mycobacterium Kimera was blasted into the air falling into the operative cities during heart surgery. And patients that underwent heart surgery where the acetic cooler units were actually infected got infected through this through these results into the operating wound and developed over the next years um disseminated infections with mycobacterium camera with a high morbidity and mortality rate. The patient first had no therapy following identification of this organism. And on months three the treating physician had a follow up thoracic cT scan which showed progressive disease And then decided on months five how that treatment should be initiated with acid for mason. FM. Digital and refund reform person. According to the guidelines On months seven there was another follow up thoracic city without improvement. And at that point in time the patient was referred to our hospital on admission which was now months seven after the initial diagnosis of pulmonary disease, the patient was healthy appearing A woman with un remarkable clinical examination, the heart rate was 80 beats per minute. The blood pressure was 110 over 70. The respiratory rate was 16. So they were normal. The blood gas analysis with a ph of 7.46. And the PCO two of 34 np 02 of 18 were normal with a normal by carbon-based success. And the peripheral saturation was 96%. Was also normal lung function test Reviewed normal results with an FV. one of 74% and an f. v. c. of 77%. Um and F. E. V. One divided by V. C. The so called tiffin oh test of 78%. The diffusion capacity was also normal with 86%. She was not coughing but she was on complaining of a drive cough once in a while there was also no shortness of breath and on the acid fast bacilli were seen with one plus on B. I. L. Micros microscopy because we could not obtain and disputed. And again from the B. A. L. Mycobacterium came era was isolated. We did additional examinations and look for the levels of immunoglobulins to look for A. I. G. Uh for deficiency which is not present. We had did not find any indication for syria dyskinesia. There by electron microscopy evaluation of the nasal mucosa. The sweat test to uh make a diagnosis or excludes the diagnosis of cystic fibrosis was normal. And also we have performed human genomic Exxon sequencing where no cystic fibrosis associated mutation was identified. The cT scan at that point in time showed a progressive disease. Now with more no djula um patterns and more extensive patchy patterns of infiltration. We then decided for a treatment intensive ation and added to S. Three missing FM brittle and reform person ivy. Education plus Cleophas. I mean. And after two months later um education as a lippo's amal innovative suspension became available in europe and the patient already complained about some hearing difficulties. So we changed the ivy and the casing to the innovative um lippo's um are uh I'm a case and suspension. We kept the other medication with oral hasn't promising attributable. Remember sit in cafes I mean and performed another cT scan on uh that is this is the cT scan from month seven. And sorry, this is the cT scan from month 18 which shows slight improvement um of the patchy um nebula fiber optic pattern um and also decrease in the size of the present cavities the patient is unable to produce and is still unable to produce and dispute. And we have abstained currently from performing another bronco al viola lavage. The patient's diary is actually improving. Um So in summary, it's a story about it difficult to treat women with MAC pulmonary disease caused by mycobacterium camera. She progressed on guideline based therapy and now has stable disease with a slight improvement on guideline based therapy plus the mucus in little small innovative suspension and prophecy me. The question is now went to stop therapy because it's not producing and disputing. We cannot really identify the time of culture conversion. But after the last B. A. L. On month seven we did not have any positive culture and perhaps we can leave this for the discussion. Thank you dr longer for that. Very interesting case. I'd like to continue discussing real world. Uh Mac management by presenting another case. This is a 53 year old Caucasian woman from Florida with a history of Bronchi exorcist, recurrent respiratory infections. In previous treatment for my Quebec trim navy. Um about two years ago she was treated with a non guideline based regimen of clareth remission and moxie flexes. Now she presents with chronic cough, mostly dry in nature and fatigue of several months. She has underlying Children's for which she received plaque when ill On exam, she's thin, she has a low body mass index. She has a few squeaks on her pulmonary exam From a laboratory perspective, mildly elevated c reactive protein and mild anemia. She has a C. T. That you see here with mainly right middle lobe in legal bronchi excesses but it's probably not so easy to see but they're scattered tree and but in other areas of the lung. So she had induced sputum sent three. These were all afb smear negative but ultimately all culture positive And my Quebec chairman camera was identified. So which of the following are considered risk factors for progression of Michael young jeezy. Is that a low body mass index? Race, ethnicity? Female sex or infection with mycobacterium camera? Well, I mean, these are all important issues to consider. The one that has shown up in several studies now is low body mass index and and the cut point is about less than 18.5. She was right at that cut point. Now race and ethnicity. There's been variable data on this, but nothing very consistent comes out. Female sex may be a risk factor for getting disease, but it hasn't been shown to be a risk factor for progression. In fact, male sex has been associated with progression and infection within camera has also not been associated with progression. Actually, some some data suggests that mycobacterium interest secularity. Maybe more pathogenic than a VM or camera. So I think the low body mass index are very common finding in our patients is the right answer. So a line probe assay was performed on her specimen. She had no R. R. L. Or R. R. S. Mutations. So that means that this looks like an isolate that is macro light and education susceptible. And I would say she's very lucky because she received a regiment a week regiment. One that we know has been associated with an increased risk of developing macro light resistance. And that's when you compare when you combine excuse me a macro light with a floor corn alone eventually stereotypic results confirmed this. She was started on a three drug regimen of azithromycin revamping and the family. It'll. So how would you administer this regiment in this particular patient? Would you give it daily three times a week, two times a week Or daily for two months and then switch to intermittent therapy. This is one of those cases where we would recommend or ask you to consider three times a week. Therapy just non cava terry mackerel is susceptible disease. If capitation was president on the other hand, we would give daily, we really have no recommendation that recommends two times a week in any setting or daily for two months and intermittent. So three times a week after six months her speed on cultures remain culture positive. Although Markoff has actually improved chest cT has really minimally changed. However. So what do we do now? She's six months out of guideline based therapy. Um you know she she says for sure she's adhering to the regimen. Um tolerating it actually pretty well but she's still culture positive. So which of the following have been associated with culture conversion to negative and treatment refractory disease changing for intermittent to daily therapy, surgical resection addition of education, liposome inhalation, suspension or Alice or all of the above. Well this is a little tougher one I think all of the above. We have data from uh the late launching coz um group at Samsung Medical Center and Seoul Korea that showed that if you take refractory patients who are on intermittent therapy and switched to daily, About 30% of those did culture convert at that time. We also have multiple studies that show that people are not converting to culture if they go undergo surgical resection, 80-100% of those do culture convert. But the only really strong point I think is that in terms of randomized trials, that's what Alice. That's the only drug intervention that has shown been shown through two randomized trials to be associated with culture conversion and refractory setting. So she was started on Alice. The Regimen was changed from three times weekly to Daily Administration and her speed um did convert after it Uh to negative after three months. This was her second time to have MAC. In fact going back in her history was I think she may have even had it another time that was missed in the distant past and she was not treated at that time. So after much discussion, we decided to proceed with that surgical resection. So she had that's resection of her right middle lobe in lane villa. They were separated by about eight weeks. You can see the before and after. And she continued on a three drug regimen for 12 months beyond the time of culture conversion. She at that time did her Alice for six months. Um and she is now years post this and has been uh NTM MAC free ever since. So I think even in difficult settings with recurrent disease refractory disease, we now have tools like Alice uh to help us treat these patients to cure. Yeah, so thank you for your attention and I look forward to the next case. Okay, so this is a difficult case presentation. Many of our NTM patients are difficult but this is probably one of the more difficult patients that I've had to deal with. This is a 66 year old woman who was referred to me with a background history of severe eosinophilic asthma with an F. E. V. One of around 50% predicted she was treated with a combination inhaler of fluted Azzoni for moderate all and had frequent courses of oral premise alone. She also had previous spinal surgery, as you can see in this X ray. She had chronic pain, was on narcotic analgesics and she had an a tonic bow was prone to episodes of quite severe constipation and overflowed. She also had significant gastroesophageal reflux, mixed central and obstructive sleep apnea, likely as a combination of her upper airway anatomy but also her narcotic analgesic use previously. She had experienced trauma barrow trauma to her right ear and had longstanding hearing loss in that ear, she had a developed bilateral modular bronchi excesses and in 2000 and 14 was diagnosed with mycobacterium a. V um infection on bronchial washings. The background medications included celecoxib, paracetamol, morphine, pregabalin is um appraisal laxatives. Her inhalers, as described symptoms at the time of review included cough and shortness of breath. She had no weight loss, no night sweats or hypothesis and her cT scan demonstrated fairly widespread modular tree and blood type changes with some mild bronchial basis. She had no evidence of cavities. This is reflective of her spectrometry showing an F one of around 50 to 54% predicted with some mild bronchodilator. Responsiveness. She had evidence of gas trapping with the residual volume of 157% predicted. But a relatively normal DLC. Oh so on. First reviewing this patient, there are a few options. One could observe for symptomatic and radiological progression. One could start treatment with the triple drug regimen according to guidelines. Either as a daily combination or as a thrice weekly um you could refer her to a specialist micro bacterial service or refer her for airway clearance minimize inhaled an oral steroids and repeat her imaging in six months. So any of these is probably an appropriate option. However, if one is going to observe for symptomatic and radiologic progression then you would want to of course refer for airway clearance, minimize steroid use and repeat the imaging in six months. But given the fact that this lady had lung function of 54% of predicted. She had significant inhaled steroid and oral steward requirement to maintain that lung function. I felt that there was a significant chance that she would progress and she was already symptomatic. Any of these options would have been appropriate. But the physician that we're seeing the patient at the time chose to observe her for symptomatic and radiologic progression. These were follow up scans done four years later which is actually quite a long period of observation given somebody with relatively severe obstructive lung disease who has significant steroid use and comorbidities. And as you can see, not surprisingly the disease has progressed quite significantly with more nah jewels peripheral tree and blood changes and progression of her bronchi excesses. Yeah she underwent a repeat bronchoscopy which again demonstrated micro bacteria. But on this occasion she had mycobacterium interested Lari. You may recall in 2014 she had mycobacterium A. V. Um She also had heavy growth of pseudomonas aeruginosa and Espindola species were isolated. So at this point her treating physician introduced Clareth Hermiston followed by a referendum person followed by a sample toll and she experienced significant side effects as this is not uncommon. She had the metallic taste and nausea associated with erythromycin. She had flu like symptoms from revamp person and then when she started a family told she was vomiting a gP prescribed on dance citron which settled the vomiting but the taste issues persisted. Unfortunately her treating physician had started all of these drugs and said come back and see me in six months. But of course we all understand that these patients do often suffer side effects and do require support. And so not surprisingly, she decided to seek another opinion. She stopped all of the drugs after about four months because after persisting, she ended up with severe cramps, nausea, lethargy sweats. My Alger's peratis excoriation from scratching despite not having a rash. But the underneath that her respiratory symptoms did actually improve. So this patient turns up. What do you do next? Do we repeat the sputum cultures? And if they're negative, observe her and treat a pseudomonas, should we re challenge her with the same drugs? But on a thrice weekly basis, should we re challenge her only with clareth remission and Bambi toll. Should we change the reference person to Clovis? I mean, should we change the corinth remission to Azithromycin? And substitute prophecy? Mean, for Rough Amberson? Or should we find a friend? Because this is quite a difficult but not uncommon scenario. So what I elected to do was to start azithromycin 250 mg daily. Because the the clarets remission is almost certainly the cause of the metallic taste in the Nausea Azithromycin is a much better tolerated option. If a person had caused a flu like illness. And apart from desensitization, it's very difficult to manage that side effects. So I elected to use Cliff as a mean instead. And once she was on those two drugs, I did a slow introduction of a family a toll because it's important to include a family a toll in the regimen to avoid the emergence of macro light resistance. So she tolerated this quite well but didn't quite get to full dose with a mutual unfortunately because her optometrist detected some visual loss, she had four errors on Ishihara testing. Her visual acuity had deteriorated and she also developed some restriction of her visual fields and she had some pain on movement of her eyes. So she stopped the anthem brittle after discussing with me. And then she had confirmation by an ophthalmologist who noted an improvement in a lot of her symptoms when she was reviewed two weeks after stopping her drugs. So we now have a patient who's on azithromycin and Cleophas. I mean what can we do next? Unfortunately she continued on those two drugs alone but then reported some hearing loss. We knew that she'd had a private prior incident where she developed barry trauma to her right ear. But her family and her husband were complaining that she was turning the television up too loud and it was difficult to communicate with her. She reported that it was difficult to discriminate voices. And so she then had some audiology which confirmed a reduction in left ear threshold confirmed compared to pre treatment assessments. So what do we do now? The most likely cause of this is the azithromycin? Um as a cause of the hearing loss. We then have a family toll as a cord cause of the visual loss. So do we just stop the family toll. Do we stop both of the drugs and continue the cliff as a mean and add in something like moxie fluxus in. Do we continue close as a mean and add in IBM moccasin? Should we stop a family toll changes with remission back to clarify remission and add inhaled a moccasin. Should we stop all the drugs, repeat the ct and the sputum cultures? Or should we just go, this is too hard, I better call a friend. So at that point I decided to stop all of her drugs um and see if we could get improvement in both the hearing and the vision. And she then subsequently received intermittent courses of ciprofloxacin, an intravenous therapy for pseudomonas, but she also required predniSONE for her asthma. But importantly, at that point her micro bacterial cultures were negative and her scan actually looked quite a lot better for the bit of treatment that she'd had. So I felt there was no urgency to rush into more treatment. We should just let the dust settle and reassess and so visual changes did resolve back to baseline and a hearing loss improved. So what we did next was re challenge with low dose thrice weekly and am battle because the incidents of ocular toxicity on three times a week at the hospital is much less than went on daily and the hearing loss associated with macro leads is reportedly less with clarity from ice and than it is with as if from listen. Unfortunately her visual visual problems did recur On three times a week of family told so we stopped that. But she was tolerating clareth remission and a hearing remained unchanged. The ent surgeon was unable to say if a hearing loss was due to the drug but was happy to watch her from ISIS. So she had Cleophas mean 100 mg a day added into peripheral mason, which was gradually increased up to 500 mg twice a day. As you can see the sputum cultures on the right did come back positive, which prompt us to get back onto a treatment regimen. So she continued on these two drugs. What do we do next? As we know, these two drugs in isolation are associated with the emergence of macro lead resistance because we don't have a family a toll in the regiment and we really don't want to get to that point. If we add in a queen alone, we would probably encourage that resistance. We could add in minutes. I clone. We could try revamps and desensitization. We could add in nebulous dedication. Um so fortunately we were able to access inhaled amicus in on compassionate use program. She commenced this in September 2019. She did have some increased shortness of breath associated with its use, which was different to her asthma and she did develop some crackles on Oscar rotation in addition to the wheeze. But we were able to get through with these side effects and right keep her going to complete of course. Um she was able to um sorry we go back one. I'm about to go flat. I've just got to plug my computer in. Yeah, okay. Oh okay. Sorry. Just going back So thankfully we were able to access inhaled amicus in on the compassionate use access program and she commenced this in September 2019. Initially it's use was associated with shortness of breath which she described as being different to her usual asthma. And she had some crackles on Oscar rotation in addition to her usual Wiis. So what do we do with the airway airway side effects of Alice? Do we stop it? As it's possibly going to be allergic Alvey colitis. Should we treat her with predniSONE and assume it's the asthma and continue the Alice. Should we consider some biologic therapy for asthma to try and get better control of that? A sputum sample at the time grew Stenner trophy monos Should we add Cote's remarks is old to treat that. Should we add in Netrokona Soul to treat the aspergillus or should we just push on and see if we can get it through. Unfortunately she was then admitted to hospital with an exacerbation of her asthma and a respiratory viral swab detected rhinovirus and so she had a lot of coughing associated laryngeal spasm exacerbations of her back pain, constipation with overflow, lots of crackles, lots of wheezing and a lot of sim victims. So her Alice was suspended during this illness. But after a course of predniSONE for the exacerbation for her asthma and then commencement of Ben realism ob we were able to restart the Alice. She did have a prolonged admission associated with this illness but her sputum cultures were repeatedly negative for acid fast bacilli. And so we were able to actually continue Alice in combination with clareth remission and cliff as a mean through until september of 2020 when she actually achieved 12 months of negative cultures for her. NTM the institution of Ben realistic the mob was crucial to achieve better asthma control and eliminate oral steroid use. She's only had one exacerbation since she stopped her. NTM antibiotics where she required a very short course of predniSONE and some antibiotics for pseudomonas. But to this date her sputum cultures remain negative AFP's. So the take home points from this case are that it's important to develop good communication and trust because these patients are complicated and they do need a lot of support to get through. Quite complicated treatment at times. The management of underlying diseases is paramount in this lady. It was her asthma but also airway clearance, gastroesophageal reflux. Co infections are all issues that have to be addressed in these patients. In many cases drug toxicity can be managed. It does require time and care. But as you can see from this case, we were able to get this lady through on a combination of medications that did achieve culture sustained culture conversion. It's very important to consider the risk of macro lead resistance when choosing companion drugs in the setting of drug intolerances that patience and persistence can pay pay off. And it's such an exciting time because we are seeing new options for refractory disease that are emerging. Published August 30, 2021 Created by Related Presenters Professor Christoph Lange, MD - Program Chair Medical Director/Clinical DirectorResearch Center BorstelBorstel, Germany Charles Daley, MD Chief, Division of Mycobacterial and Respiratory InfectionsProfessor, Department of MedicineNational Jewish HealthDenver, Colorado, USA Rachel Thomson, MD Director, Mycobacterial DiseasesGallipoli Medical Research InstituteUniversity of QueenslandBrisbane, QLD, Australia
