119. The Moulds: Aspergillus part 2, invasive and chronic disease

Callum and Jame are joined by Iain and Darius to talk through the clinical aspects of managing Aspergillosis with a particular focus on the most severe disease. Listen in to hear about current challenges around the management of both invasive and chronic Aspergillosus.

Notes for this episode here: https://idiots.notion.site/118-Moulds-Aspergillus-ce3ba58d045b47b18d9641b56559c6f5?pvs=74

Transcript

Jame: 0:23

​Hi everyone. Welcome to the Idiots Podcast. That's infectious disease insight of these specialists. I'm Jane. That's Callum. This is Darius and over there's Ian. And we are going to tell you everything you need to know about infectious disease,

0:35

Soon, may the editing come to discontinue the Tazo sun one day when the S piece done, we'll take our leave and go.

Jame: 0:45

Callum, how you doing?

Callum: 0:48

I am, I'm doing good. Darius, how are you doing?

Darius: 0:52

Yeah, I'm doing well. Thank you.

Callum: 0:53

how are you doing, Ian?

Iain: 0:55

I'm very good. Thank you for asking.

Jame: 0:58

now Terrible pun this. Week.

Callum: 1:00

As per Jill, our friend has told us, as per Jill, us, we should stop the punts.

Jame: 1:10

Okay, fine. Okay. Alright, fine. I think you saved that at the last possible moment. Yes. This is at part two, Callum of your aspergillus ces. I have somehow managed to in vagal my way into the fungal episodes for the first time ever having been. Unceremoniously replaced by the treacherous Callum. Much, by the, arguably, much better at podcasting than me, Alyssa Hudson. But now I'm, somehow back. Isn't that right, Callum?

Callum: 1:38

Yeah, we're glad to have you back. So we're really honored to be joined by Professor, professor Darius Armstrong James, who is an infectious diseases and medical mycology, physician at Imperial College in London, and has a specialist interest in fungal disease and general and respiratory infectious diseases. We're also honored to be doubly honored, I to be joined by Dr. Ian Page, who is a consultant in infectious diseases and general medicine at the Western General Hospital in Edinburgh. And he has a subspecialist interest in fungal infections, and in particular chronic pulmonary aspergillosis. So thanks very much for taking time out of your busy schedule to, to join us and I think this is a really important topic to talk about. As with all our sort of fungal episodes, we're shining light on these organisms and diseases, which perhaps don't get as much attention within our, for our specialties and medical education in general.

Jame: 2:32

And yet when it comes to fungal disease in the lung, aspergillus is obviously a very important part of it and we'll have covered the nuts and bolts of it in the previous episode. The infectious disease physician is really only consulted when there's problem either diagnostic or therapeutic. So you only get involved at the end,

Darius: 2:50

well, I mean, that's an interesting point because actually as we know, fungi are opportunistic and therefore many of the patients are who are affected, are other people's patients, so to speak. Rather than IDs patients and within the context of aspergillus and actually probably the vast burden of disease is occurring in people with pre-existing lung disease. So it's the respiratory physicians who pick up these patients and manage them primarily. And, We need better opportunities for ID micro trainees to get involved in their care effectively.

Callum: 3:25

Can I ask a question, Darris?'cause in one of our previous episodes this question was asked and I thought it was actually a really interesting. What was your journey into? A medical and this interest that you've now got in Aspergillus, how, how did that come about?

Darius: 3:40

Entirely accidentally, actually, or accidentally in that, yeah, I mean, I, I went through medical school. I decided through my training postgraduate training that eventually I decided quite late to do id. And then I got quite interested in HIV and tropical medicine and really the intersect there protozoology was of interest. So I, I did a masters in molecular biology at the London School of Hygiene Tropical Medicine. Really, because also I was very interested in research and I'd actually applied to the Welcome for a fellowship to look at uh, trapes, but that didn't work out. And and so I just looked around for available PhDs and there was one that was advertised on Aspergillus. And I thought, well, these fungi, they're probably equally complex as protozoa. And I was really interested in genomics at the time, eukaryotes, so I embarked on this career in aspergillus and it was really just a decision that was made on the spot. But it turned out to be a very good decision because we lack expertise. As I think people know in ology in the uk there's no clear training program. it's somewhat been neglected both scientifically and clinically. And sometimes being brave enough to go into something that's quite niche can pay off, especially if. Is a serious clinical issue that needs experts. So it's, it's worked out very well.

Jame: 5:10

Yeah, and I feel that skills as mycologist will be required more and more as, and more and more people get lung disease becoming immunocompromised,

Darius: 5:19

yeah, I think that's right. One of the interesting things has been that in id, we don't have many. Chronic cohorts so we can easily build clinics around, but actually really a fruitful one for that. You can, I really advocate for people trying to develop specialty clinics. There's all kinds of stuff that's chronic, they are chronic infections in the most part.

Jame: 5:40

And do you have that, do you have a specialist mycology clinic or is it a mycology lung clinic

Darius: 5:45

we've got two. So we've got a specialist, respiratory mycology clinic. We've actually got two. We've got one at the Bronson, is the biggest cardio respiratory center in the UK apparently. And then we have further clinic Imperial College Healthcare run by Meg Coleman, my colleague. And then in addition, we've got an extra pulmonary clinic. For the non respiratory mycology, that's yeah, I mean, it's fascinating.

Callum: 6:14

So Ian, the same question to you, which would be, How was it that you came to be interested in chronic pulmonary acidosis? What was your sort of career path, in getting into this area?

iain-page_2_04-30-2025_151133: 6:27

Yeah, that's, an interesting question actually.'cause I, I'm a full-time clinician now. I'm, I'm not, an active academic and I had no intention whatsoever of developing an interest in fungal medicine. When I entered my training, my interest was more looking at infectious diseases through global health, and I wanted to do a global health PhD and in particular was interested in tuberculosis. But the opportunity that popped up, was for me to look at, chronic pulmonary aspergillosis complicating tb. And I took on a PhD in Manchester, where I did some lab work looking at serology, but also went out to Uganda to measure how common chronic pulmonary aspergillosis was after people had been treated for pulmonary tb. So that kind of got my, interest in it. And then I did, clinical work at the same time at the UK National Aspergillosis Center in Manchester, which is the main place that has a large cohort of chronic pulmonary aspergillosis patients in the uk. I must say, once I started doing it through that kind of unintentional pathway, I came to believe it was one of the more interesting areas than infectious diseases because you've got a really challenging disease that has a high midterm mortality if it's not treated. But if you get the treatment right, you really can help that group of patients. And the sort of skills that us ID doctors have them, from HIV medicine where we look at drug interactions, toxicity counseling, close relationships to our patients. of those are the skills that are useful for treating chronic pulmonary aspergillosis well. And once I got used to doing that, I kind of got hooked and wanted to keep doing it.

Callum: 8:01

Wow. It's really interesting to, to hear like career paths.'cause I think sometimes when you're a junior person in your career, you look to your sort of seniors and think that they had it all figured out. And then when you actually delve into how people got to where they are, it's, as you say, it's accidental.

Darius: 8:15

The interesting thing about the NHS is that it's self automating in many regards, and it just does what it does, which is based on what's been happening, but not completely responsive to, the needs of the population.

Callum: 8:28

Hmm.

Darius: 8:29

For what I guess people might call strong personalities, carving out a career in something that doesn't have a career path is basically where it's at and that's effectively where I've had to go, essentially. So everything we do is not stuff that's normally funded through standard NHS funding.

Callum: 8:52

So I guess we've had a little bit of a discussion there about fungal infections and mycology in general, So specifically about aspergillus. So I. I think, certainly throughout my career it's always been something considered and, discussed, particularly in the ICU setting, but it something that's very difficult to diagnose. So I guess our first question would be, what's the spectrum of clinical disease they differ in severity?

Iain: 9:19

So yeah, it's, the really interesting thing about Aspergillus, is that it's an organism where exposure happens to, most people at some point, and yet you have this completely different range of disease that I think only comes down to how the host reacts to the organism, which, differs quite a bit from other infections that we're used to treating. So there's a lovely wee graph that you'll see with a spectrum going from, on the one hand. There other immunosuppressed people who may have a really invasive, aggressive aspergillus disease that can be fatal within days. And then you have a subacute immunosuppressed group. Folks who might have things like diabetes or liver disease or drug induced immunosuppression where they can get a kind of a subacute invasive pulmonary aspergillosis coming on over weeks. You've got your allergic group who have things like, asthma which is fungal, sensitized, and your allergic bronchopulmonary aspergillosis. And then the people that I see, most of which is the chronic pulmonary aspergillosis who have cavitary disease and a minority of patients with end stage disease may have aspergillomas inside their cavities. So, very different clinical diseases on very different timescales depending on how the host interacts with the organism.

Callum: 10:30

Thanks Ian. So, I guess as you're saying It's all, you know, it's about the immune response or I guess lack thereof. So if we had to a set patient, I These entities are so separate clinically, aren't they? It's hard to say, like with aspergillosis, what is the signs and symptoms that someone might present with, but. Say we're, at the end of the spectrum that you're dealing with is our, chronic lung disease and the patient has got invasive aspergillosis. Are, or is there any sort of clinical, Signs or symptoms that these patients present that makes it, more likely to be fungal that's causing a deterioration their lung disease Or is that quite hard to, to. unpick?

Iain: 11:11

Yeah, so I'd suggest the real challenge that the people who get these diseases are folks generally who have underlying illness. And if you think about chronic pulmonary aspergillosis, it occurs almost exclusively in people that have other chronic lung diseases. I. Often things that would cause such as COPD, prior tuberculosis, sarcoidosis, things like that. And the symptoms of having a aspergillus top of that can be very similar to the symptoms of a bacterial infection or the symptoms of just a progression of the underlying lung disease. And even when chronic pulmonary aspergillosis as a clear diagnosis I have a lady on the ward just now more unwell and trying to tell whether it's progression of the aspergillosis or a secondary infection with a bacteria is very challenging. And I find myself looking at. The duration of the deterioration. If it's, progression the it may be subacute over the course of, weeks or a couple of, months. if it's a bacterial infection, it would be more likely to be acute in a few days. And I think it's really important to get cultures to see if you can grow bacteria. then that is more consistent with, bacterial infection. Obviously do swabs as well. See if you can find evidence of it being something else. If you're trying to COPD with an exacerbation who's not known to have chronic pulmonary osis, and you're trying to decide is this exacerbation caused by a bacteria a fungus? That, that's fairly tricky. because the clinical presentation pretty similar between the two, other than the fact that fungus would be more subacute.

Jame: 12:41

There, Ian, you're using the cultures and things like that to exclude non aspergillus causes, not to try and, the aspergillus and, Ian,

Iain: 12:50

yes, I think in. So you do different tests in different circumstances, and I don't want to give a sort of a catchall, always do these tests, but thinking patient that's got CPA that's known and diagnosed, who's more acutely unwell? I think the main thing I'm looking for with and radiology is to see, is there a new. Disease, an acute additional infection. And cultures can be helpful for that. things like PCR testing providers that. we do can be helpful for that. I find it helpful to look at the radiology. If you can do a thorax, somebody that's got apical cavities abnormality, if they've got progression aspergillosis, what you might see is that those cavities. It might be getting bigger, but perhaps more importantly, you could have increasing infiltrates and fibrosis around about the increasing adjacent pleural thickening, maybe new forming. whereas somebody who's got, a bacterial infection more normal changes of consolidation perhaps in a different location in the lung. And that might help you tease out the difference, is always very challenging. So

Callum: 13:51

so, my understanding there, is that, it's just really hard to pick this out patient's history or even a clinical examination that what is aspergillus and what is just their underlying lung disease? So, maybe di could I ask you,'cause Ian touched on some of the diagnostics there. So, what's of diagnostic approach for patients with, for more severe end of the aspergillus, I guess Ian's mentioned a couple of things there about radiology, cultures, et cetera. What are the useful investigations and, a diagnostic approach, generally

Darius: 14:20

Yeah, so I. The Diagnostic approach. I mean, there's, there's a few things in the history that might make you think that someone's got osis, And this has been discussed, quite a bit guidelines, writing, et i. People who've got hemoptysis or coughing up mucus plugs or unexplained weight loss night sweats, you might worry about that. In terms of the kind of diagnosis, it depends on the patient group, as Ian said. So if we're thinking about fungal sensitization and asthma or allergic bronchs. the entry point for that is to conduct an asper specific IgE. And if that's positive, you then go on to do the rest of the workup, which would be a total IgE and asper IgG, some form of radiological imaging and sputum examination. For CPA actually, to formally diagnose CPA then it's really the radiological appearances, best, seen by CT aspergillus igG that are useful although sort of psychological criteria like positive sputum cultures can be helpful. You iTU earlier. That's a really interesting area because ITU associated ass probably comes in two different forms. The first one is COPD related, of course a lot of cOPD patients related, end up in ITU and, they can have quite clearly invasive that you can see radiologically. the other one is associated with respiratory viruses and A RDS typically, COVID or influenza. Within that context, is actually quite complex. The influenza patients have a more invasive form and you may get a lactam and signal in peripheral blood, but the COVID ones can be very difficult to diagnose, and primarily their diagnosis driven by BAL Gm, but even the radiology. Can be really subtle And you can have a traer bronchial form that won't necessarily know radiologically, but is apparent. Bronchoscopy. So, The chronic acidosis, I think is more straightforward to diagnose that serological criteria are quite sensitive. Invasive is much more tricky. We use serum but serum glactomannan is only really in the context of people with angio VAs, which generally means that they've of neutrophils. It said that the reason for that is because the aspergillus actually needs to invade the the blood in order to be able to, give enough and signal into the essentially. But whether or not that's true, I don't know. so yeah, it I think within the context of CPA, around 10% of chronic pulmonary osis patients may be so-called sero Negative s done a lot of work on that and probably could much better comment on it, and i think that's partly driven by their HLA status, I suspect, than the fact that there are many astrogen probably around 35, according to the world health Organization. And we don't measure all of them. do You wanna comment? on that at all?

Iain: 17:53

Yeah, a few things to say I mean, I guess on the ICU cases, one thing that's really jumped out at me looking at case series in recent years is that I'd often perceived that invasive aspergillosis in ICU was really quite rare. And I'm not sure I think that anymore. I've seen, autopsy series saying that, something like one or 2% Autopsies done from all ICU deaths in a secondary care hospital had evidence of invasive aspergillosis. I've seen case series in patients with flu from Europe in recent years, suggesting that I can't remember the precise number, but it was something like 15% of their. Patients intubated with flu went on to get invasive aspergillosis data from the COVID pandemic, from Wales, suggesting that, something like 25% of patients with COVID in ICU got invasive fungal infections, one of which was aspergillosis. To comment on the diagnosing CPA. One thing that I think is important often I think CPA get diagnosed'cause people don't send the test and that I. If you've got an underlying lung such as say, sarcoidosis, that causes cavities anyway and the patient's deteriorating then you know, only a patients with CPA have an Asperger. And it could be difficult to tease out whether the progression on the radiology is due to the underlying disease getting worse or the development of CPA on top of the disease. And one thing I think we agreed in the upcoming BSMM diagnostic guidance if you've got cavitary lung disease, which is progressive in nature, then we would recommend doing an aspergillus IgG as part of a screening test for chronic pulmonary And then that will be interpreted in the clinical And radiological context, of course. But one has to send the test in terms of the rate of seronegative disease. And in our UK cohorts at the Manchester Reference Center, we only found about 1% of our cases were seronegative. And I compared the performance of lots of different forms of testing. And they're really not the same. For example, you'll often hear the term precipitins used when people are discussing aspergillus serology. And that technically affirms to, old fashioned precipitation in gel testing, which is probably only positive in about 60% of CPA patients who are positive by Eliza. But what complicates matters is that a lot of labs refer to EA testing as precipitants, when in fact the test they're giving you is an Eliza IgG. And that really muddies the water. So I think when you see different, seronegative levels being reported by different clinical groups. It may be that they're using different testing techniques. But certainly, a very large majority of patients with CPA would have a positive aspergillus IgG and there is a group that do not often where they have some sort of an immune deficit, but that is a small group and I think, that consistently comes outta different reports from different centers.

Darius: 20:46

Yeah, I mean that group, in particular people with CLL or where they've had rituximab, that would be an issue. wouldn't.

Iain: 20:52

yes. That sort of thing.

Jame: 20:54

Okay, so let's talk about treatment. You've got a patient with aspergillosis, either acute or chronic. What are the therapeutic modalities available to us and what's the evidence base behind their use? In aspergillosis? Let's start with chronic, pulmonary aspergillosis, and then we can move on to, acute, if it differs at all, or invasive,

Iain: 21:19

so maybe I'll start with the chronic side, if that's okay. So I mean, it Does differ in terms of the recommendations between chronic and invasive for chronic, you look to give antifungal treatment for chronic pulmonary aspergillosis for at least 12 months, and therefore giving any drug that is not oral is very challenging. And the only group of drugs which are oral are the azoles. Worth just mentioning that Fluconazole has no anti aspergillus activity. So, we're looking at itraconazole, voriconazole are routinely used, and then we have the neuro ones like Posaconazole and Econazole. There are challenges with these drugs in terms of drug interactions, toxicity, the need for therapeutic drug monitoring in a narrow therapeutic window. But I find that if you are, very careful about how you prescribe them and how you monitor patients, I. Most patients can take them. And there have been in the last few years, a couple of trials coming out suggesting that these longer courses of AOLs really can have a positive impact in terms of patient's symptoms, lack of radiological progression and cohort data suggesting that well-treated patients have better survival than untreated patients from historical comparisons. If you can't have azos because of either intolerance or resistance, it gets significantly more difficult. We know that a kind of canons, such as myung can be good over a short period. But giving IVs long term is hard. There's about to be a trial start of giving people weekly resin for six months to see if that's beneficial. That will kick off in the next couple of months.

Jame: 22:48

That was the next Question I had on my lips was, has anybody looked at raise fungi in this context?

Iain: 22:54

Yeah, so the manufacturer are funding a trial, single arm open label trial looking to recruit, something like 60 patients, and give them six months of resin and then document their follow up for a period thereafter. So that would be very interesting to see. The prediction from other kind of canons from the short term follow up data is that it ought to have a positive impact, but it's really nice to see that. Someone's actually generating that data for a more realistic course of treatment duration. And there's various other things that people have tried,, using amphotericin, inhaled amphotericin, direct injection of am terin into cavities, all of which you'll see case reports for. But these are all very challenging things to deliver, and I think that the priority with chronic disease is to try and. Give effective azole therapy in a well monitored, well dosed manner and try and get it right, the first time with those oral drugs if you can.

Jame: 23:47

So, your opat options are amBisome, I take it. You're given liposomal, terin and a Casper fun of your choice.

Iain: 23:55

Yes. And we've got, where I've got some patients I'm managing who can't have azos with cyclical Casper Fungin, where they'll have 21 days and then have a 21 day course planned every three or four months. And I've found, just anecdotally that they respond well to that. But, and then the effects. Continue in terms of symptomatic benefit for a month or two after stopping the drug. But that's my anecdotal experience with a tiny number of patients.

Jame: 24:22

Okay. Do you have an easel

Iain: 24:25

preference. So I tend to prescribe them in order of cost because I think we should be aware of that. Itraconazole is the oldest drug. It's cheapest. Voriconazole and Posaconazole are a bit more expensive. Now that OL's off patent, it's not as bad. And then Isoconazole is,. 10 or 15 times as expensive as the alternatives because it's still on patent. I tend to find that posaconazole is better tolerated than the two older drugs. But the reality is that any patient may tolerate one drug well and another drug less well, and it's a bit of trial and error to find the drug and dose that is right for an individual patient.

Callum: 25:03

Maybe. Maybe we can come to Darius and ask about the treatment. For the more acute setting or ICU. style patient, how does that differ obviously I guess one of the challenges might be, you know, the right patient group and then when you start how long would you go for and would it still be the azo? Obviously it's more complicated because of the sort of potential interactions in that patient group as well.

Darius: 25:27

Yeah, so I think the first thing to say for the acute patients is that. was not advised. I think there was a early study, a long time ago that showed it was inferior to Amin B. and, all the subsequent azo studies, azo studies were done in comparison to So, We wouldn't use Itroconazole. so the options are either a mold active aole, such as for Econazole, post Conazole, or a SAVI Conazole For which, for Econazole and Ares conazole. probably have the best data conazole. Most of the data in the, initial studies for licensing was all around prophylaxis. Andone. Where, there is good data. It was basically a two different dose study trial essentially, rather than a true comparative study But, AmBisome is very effective. The kinins are not as effective, so they should not be used as primary therapy for, invasive asidosis. The Zian says we've got extensive experience of using cyclone chronic pulmonary Astros, and they do seem to be effective and that's very interesting.

Jame: 26:40

so that's Cyclic use of Echo, that's a, recognized, therapeutic

Darius: 26:43

Yeah, yeah. So that seems to work. It's really, I mean it's, the concepts of intermittent dosing are very interested in chronic infection. Because of the interface of the immune system effectively.

Jame: 26:55

If you were using a Casper fun, in invasive disease, you that. You would give it constantly.

Darius: 27:00

Yeah. You'd give a six week. Course you're normally looking at six to 12 week course With radiological resolution as your primary outcome. I think the only other thing that's is that there is tri aole resistance around. And there can be, for Aspergillus tereus there can also be amphotericin resistance. So it's important to know your microbiology. Where there is resistance, then, Obviously a different or combination therapies are reasonable.

Jame: 27:28

Any favorite combinations?

Darius: 27:32

So normally these scenario is that got tray or resistance, and then you would either add an akin. Or you would switch to AmBisome. And the interest there is that within the context of in host resistance, there's a well-recognized phenomenon, of hetero resistance, where not necessarily all the clones are resistant, which we do see with things like Pseudomonas as well. So, yeah, those are the options

Iain: 28:00

And mind, I ask a question of Darius. I just, wonder what you think in terms of giving, dual therapy for invasive or subacute invasive aspergillosis. I do remember seeing a paper that came out a few years ago in terms of adding akin of canon. I think it was a ni fun to, voriconazole that. Was underpowered and the p value was over 0.05 by a little bit, but did seem to suggest that there was a mortality gain for that. Sometimes if I have a patient I'm really truly convinced has subacute invasive aspergillosis, I might use both drugs together. Is that something that you would have as part of your practice?

Darius: 28:38

Yeah, it's an interesting question. We do have quite a large stewardship team at Imperial. I think one of the few NHS funded fungal stewardship practices. So we're quite cautious about combination therapies. The interesting thing about that particular study, is that they did a post hoc sub-analysis, it was a Pfizer funded study, and what they found was that in the subset of patients who had probable as aspergillosis based on galactomannan testing. That the P-value became significant. And the Interpretation of that was that the combination might be helpful in early disease rather than established disease, looking carefully at the cases. So it's very interesting. But I think you are fundamentally correct, it's likely the study was underpowered. Combination studies are very different. Difficult'cause the differences you're looking at are probably less than the difference you would expect from. A single treatment, in terms of efficacy. So that's a really, really hard area. I don't a good developmental roadmap in terms of how we can do trials for. Combinations in this area.

Iain: 29:51

Yeah,'cause I recall, I mean it's a few years since I read it, but I think that trial that came out as being underpowered appeared to have been very challenging to try to do. As I recall, there were many centers, many nations involved over, I think over five years, and they didn't manage to recruit enough patients to adequately power the study. And that's probably not a challenge that's going to go away in terms of people trying to arrange future studies. Should anyone do it.

Darius: 30:16

Yeah, that was Kieran MA's study. I know her very well, and I mean, she was, yeah, she was quite scarred, by the experience.

Callum: 30:22

That might be a good segue into our final question, which is I guess what we've heard a couple of things there about, things that we might see in the future,, this rezafungin study and, combination therapy potentially. But what's the sort of upcoming future developments or areas of research in treating patients with, invasive aspergillosis? Because Ian, you just said there that the research climate is quite challenging to get studies in these patients.

Darius: 30:49

So there's a few different studies. There's obviously the rezafungin CPA, which, Ian mentioned aor. They're doing study. Olorofilm, which is basically a mold active, more or less agent, which is orally and IV available. So there's a study ongoing in invasive osis hopefully they'll be able to recruit enough patients to get that over aligned at imperial, Through spin out an imperial a drug called Opal Conazole, was also developed. That I should mention that I have found a share options in, now in phase three studies. That's basically inhaled. post ole like agent that's designed to accumulate in the lungs. So we'll see how that goes. Recruiting at the moment and needs to be extended. and then there are a number of other agents, fosmanogepix is one, that might have utility and a ibrexafungerp which is. an oral glucan inhibitor that isn't from the echinocandin group. So, so there's actually. Potentially three different drug classes plus a topical agent. That might come through if we're lucky. so it's an exciting time

Jame: 32:01

Can I ask if, irea fungi, um, aspergillus trials ongoing? Because that would be thing. I think, if we're talking about raise of fungi, an oral ana canan analog be also

Darius: 32:12

yeah,

Jame: 32:13

You know,

Darius: 32:13

I. can't remember actually. But, um, the interesting thing rexi fun is it that not only oral, but also its tissue distribution is far superior to the kind of Camden. So the potential for it to actually cure infected tissue is higher. So I think that, um. i, I think, yeah.

Iain: 32:34

and I can just chip in on that thing. Yeah. With Irea Fungi, there is a trial that has not published yet, as far as I'm aware, called the Fury trial, where they were giving irea fungi in various conditions, one of which was chronic pulmonary aspergillosis. I saw a early results poster where they had a single CPA case recruited to that trial at that time. My hope is that. By the time they publish it will have a larger number of CPA cases but it may produce information in the not too distant future.

Callum: 33:04

Great to hear about all the sort of potential future areas. One thing that was mentioned there and I wanted to ask more I think Ian, you mentioned the BSMM lung diagnostics guidelines. Is that something that's on horizon of coming out for aspergillus?

Iain: 33:20

so I think, d DiUS may be, perhaps more closely involved with this than I am, but I think it's not just lung diagnostics. I think a view of fungal diagnostics in general has been underway over the last six months or so, and is in the final stages of being written up. so yes, later on this year, one ought to see new guidelines coming from DSMM on the topic of fungal diagnostics.

Darius: 33:42

They're broad, they're broad guidelines. And fungal diagnostics. There's also BTS have a specific acidosis guidelines, so that's effectively, I think, being published imminently. And, the BSMM standards for Diagnostics are, they exist and they're being reworked. basically. So a further updated publication imminently or being submitted, imminently for publication. and then I think the plan is the T DM guidelines are also getting done I, not actually on those ones, but the T DM are gonna get done and there will also be hospital Infection Society, guidelines on fungal disease basically. Probably mostly C, but also some of our work will feed into the. As side of things.

Callum: 34:35

Great. Well, what we'll do is collate all those guidelines when they come out by the this releases, Great. I'll collect those all. And those, papers that you mentioned Ian, about the, under recognition and autopsy cases, we've referred to insurance as Well, I. Along some di graphics. So Alyssa wasn't able to join us today, but she's put a lot of hard work into giving you a summary of, aspergillis and all the things that we've discussed. So thanks again, Alyssa, for doing that.'cause I think it's gonna be something I'm gonna go back to, when trying remember, what we talked about. maybe so I can just maybe throw to each of you now and ask for a closing statement or final thoughts, what you'd like to leave with our listeners. Maybe you go to Ian and then Darius, Any, anything you'd like to leave our listeners with about aspergillosis in general?

Iain: 35:15

Yeah, sure. I mean,, I'd say my interest is in the chronic pulmonary aspergillosis, and I think one thing I find really exciting about being involved in this disease is that, it's a disease that, was only really defined properly about 25 years ago. And, we've gone from having a definition to a plausible treatment with the antifungals and then, some internationally recognized guidelines in the last, 10 years having. Multiple new classes of oral antifungals that are mold active coming onto the market in the next few years, I think does potentially open the door to there being better treatments for this condition if that can be confirmed in trials. I think though, because it is such a young condition, we really wanna do all we can to generate data on how best to treat it. And I would just like to end for the little plug for a physician led pan-European network for CPA that's been set up recently called CPA net. And one thing they have done is to create a registry of CPA cases. And anyone that's treating CPA can sign up for this registry and put their cases onto it. And especially if you've got people with. Difficult to treat circumstances like nontuberculous mycobacterial, co-infection or difficult to treat hemoptysis that you've maybe given something like radiotherapy for. Then getting them on that registry so we can generate the data to improve care further would be wonderful.

Callum: 36:41

That sounds really positive and helpful. Thank you, ian Darius, what, have any closing statements or thoughts for the listener?

Darius: 36:48

Yeah, So, I think the only other thing that I would mention is that in the context of aspergillosis in my career, all the pa, all the patients that I've almost invariably there's been some kind of problem with our immune system, and that might not be immediately apparent. So I think aspers is really an infection that finds out people with problems with their immune system. And If you've got someone with Aspers, then always think about immunology.

Callum: 37:15

That's a, that's a great closing statement. I think in our upcoming episodes, we're hoping to do an episode on the novel antifungals. So we'll be covering those ones that you've heard a little bit about there in more detail. We'd also would love to do episodes specifically on the immunology of fungal infections different and I find it a bit hard to get my head around. So, hopefully we can,, expand on those sort of short discussion points that we've had there. So I guess all it remains to say is thanks so much for giving up some of your afternoon, to come and talk to us about Aspergillosis and Aspergillus in general and we'll keep yeah, thanks very on.

Darius: 37:49

Our pleasure. Thanks for the.

Iain: 37:50

Yeah, no, thank you for having me.

Jame: 37:54

Do I have to return to the poll that you're keeping me in now so that Alyssa could come back?

Callum: 37:59

What? actually, this is a question. So is my being a medical mycologist, I see that in quite a lot of people's sort of job titles. Is it like a recognized specialty or subspecialty, or is it more of a job title?

Darius: 38:16

well, that's an interesting one. It's not formally on the specialist register

Callum: 38:20

Okay.

Darius: 38:21

effectively, however, You can be registered as clinical sciences in medical mycology. In addition, there is a in medical mycology, which is an approved hSA career pathway, which i've done, and therefore I call myself a medical mycologist.

Callum: 38:40

I need to check this then, because I feel like as we're doing more and more of these episodes, I'm getting more and more interested in mycology as i'm sure all our listeners are, because it's just such an interesting topic. Isn't.

Iain: 38:51

Absolutely the best topic in infection. No doubt about it.

38:59

​This Mycology series has been supported by the British Society for Medical Mycology. The BSMM aim to bring together clinicians and academic researchers in the field of medical mycology. For more information, you can find the link to their website in our show notes on notion. Please consider joining up to become a member. Thank you for listening to The Idiots Podcast, the UK's premier Infectious Disease podcast. Questions, comments, suggestions. Why don't you send them into Idiots podcasting@gmail.com. Have a five star review in your pocket at Calm, and I would love to have it. Please drop it in your podcast player of choice. If you want to donate to support the show, there's a link to do so in the description. But until next time, I'm Jane. I'm Callum. See you now. Now that the episode's done, we hope you learn and had lots of fun. So go forth and treat people with some of what you now know.