Thank you and good evening, everyone. Welcome to tonight's talk about cynonasal aspergillosis. We'll start off talking about diagnosis, and most of the talk will be based on diagnosis because the treatment.

Is a bit more involved, and there are lots of different options. We'll talk through those as we get to the end. But there's quite a lot to talk through, and it's not a particularly common condition for us to see in clinical practise, but it is a quite frustrating, condition.

It can be quite spectacular, with bleeding and erosive type changes, but it can also be quite frustrating as well in terms of diagnosis and, and trying to differentiate it from other conditions, which is what we'll try and spend this evening trying to talk through. So, just to think about what we'll talk through this evening, we'll talk about what Aspergillus is. So we'll talk about the fungal infection that is resulting as a result of that.

And we'll talk about the sigment, the type of cases that see with Aspergillus. We'll talk about the presenting signs. So how These animals present to us and what we should look out for.

And then we'll talk through the diagnosis. So how we make that diagnosis in terms of different tests that we can do. So blood tests, serological testing.

There's also some antigen tests that are available, but they're not very good in terms of how we make a diagnosis. We'll think about imaging, and we'll talk about radiography, we'll think about more advanced cross-sectional imaging, so think a little bit about CT and MRI images, which is what we would do here at referral, but obviously, it's a bit more involved and not particularly accessible to all general practitioners. And then we'll think about rhinoscopy, so what we see when we look in the nasal chambers, what we're looking out for in normal dogs, what we see with aspergillus and the other differentials that we would think about, how we would take biopsies, so how to try and confirm visually that we have a fungal infection.

And then we'll talk through the treatment options. So, as I said, I became very happy to answer any questions at the end, I try and look out for them as we go along as well. But if you're listening later, or there's things that crop up at a later stage, then please feel free to email me.

My email address is there, so [email protected].

Very happy to chat to you about cases or anything that might come up from tonight or from other internal medicine cases. So sin or nasal aspergillosis is essentially a fungal infection of the sinuses and nasal chambers. Aspergillusumatis is a, a fairly ubiquitous fungus.

It's seen in the environment, it's associated with vegetative decay, it's present in the soil, it's present in lots of places, and we can find it in normal dogs as well as in dogs that have aspergillosis and infection with the aspergillosis. So it's typically not something that will cause a disease. We can find it incidentally, we can find it in patients that we're doing biopsies for other reasons or have other diseases.

So it's not always something that will cause a problem with cynonasal infection. So we'll talk about it a little bit in a second as to why that might be the case, why some dogs are OK with this, and why some dogs aren't. Very rarely it can cause systemic infection.

So we can see disseminated Aspergillus, often that's with other species, so things like Aspergillus terrius, which is not that commonly seen in the UK in areas in Australasia, for example, it is seen a little bit more often, but we can see it in the UK, usually associated with quite marked. Immunosuppression, so fungal infections involving lots of areas in the body. But for the purposes of what we're talking about tonight, we're talking about local disease that's present in the nose, in the sinuses, and in the pharynx, and usually this causes nasal signs, associations of sneezing, of nasal discharge, usually associated with the fungus causing inflammation and secondary infection.

And also signs of erosion that we're seeing that the toxin produces this dermatoxin that causes hemolysis and destruction of turbulences within the nose, and that can cause a change in the environment. We see that there's a secondary infection. We can also see quite marked haemorrhage associated with that as well, so quite marked bleeding from the native chambers as well.

So these are the sorts of signs that we would see with with in nasal aspergillosis. We would see that there's sort of this erosive change within the nose, and that's one of the sort of key hallmarks of Aspergillus infection, this erosive type change of the nostrils, where the discharge from the nasal chambers causes erosion and depigmentation of the areas as that material comes through. It's often associated with quite much discharge, and often that discharge starts off as being very mucopurulent, so very sort of pussy discharge, lots of inflammatory cells that are present, and secondary bacterial infection, which will occur as a result of that environment changing, so destruction of the normal turbulence of the nose and secondary bacterial infection happening as a result of that.

The The nose isn't a sterile environment and the mucus clearance from the nose will remove bacteria that are filtered from the very fine turbinate bones in the normal structure of the nose. And if that clearance is disrupted because those turbinates have been destroyed, or there are other areas that are causing a problem, then as a result of that, we will get secondary bacterial infection which causes this mucusy and discharge to form. And then in some cases, we can see really quite profound haemorrhage through destruction and osteolysis, so destruction of the nasal turbinates, but also erosion through blood vessels and nasal bleeding and staxis would be a very sort of dramatic sign of, of synosal aspergillosis, but it can be one of the sort of more worrying things.

So it can be quite difficult to get these blood vessels to stop bleeding. So there are some Large arteries and veins within the nose, and once they start bleeding, putting direct pressure in something that's within the bony box of the nose can be quite hard to do. So, so really quite profound epistaxis can be one of the features that we see with aspergillosis.

And we'll talk about how we might manage that and how we would stop that bleeding to occur later in the talk, because it can be quite tricky, and we end up being, stuck for options on some occasions as to how we get these dogs to stop bleeding. They can be really quite difficult things to try and treat. So having said that, this is a fairly ubiquitous fungus that we find in lots of environments in the environments around, but also in animals that aren't affected.

Why do some dogs develop disease and others don't. So it's sort of thought to be an opportunistic infection. That the fungus ends up in an environment where it can grow essentially on the surface of the nasal turbinates.

So within the sinus, within the turbinates of the nose, usually within the back part of the nose. So in the warm but relatively cool in comparison with the rest of the body, body temperatures with humidity grows. The surface of the nasal turbinates, and that allows it to be essentially outside of the body, which is why it's difficult for the immune system to completely clear it and for for drugs if they're given systemically to get into good concentrations in areas where we have fungal mats and plaques that are forming within that air filled space within the nasal chambers.

But there's thought to be a loss of immunocompetence in that local area, which means that the fungus can take hold, and that will allow it to then grow in that area. So there's various in vitro experiments that have been done looking at immunocompetence, and there there is thought to be a degree of predisposition in patients and breeds that don't have good cell-mediated immunity. So to clear a fungal infection, we need good cell-mediated immunity, essentially good cytotoxic T cell response, or egocytic type response to a fungal infection.

Antibodies aren't going to clear that fungus once it's become established on the surface of the cells. So in breeds where they don't have that good cell-mediated immunity, so thinking of things like German shepherds and Rottweilers, where historically, genetically they have poor cell-mediated immunity that leaves some of the predisposition potentially to aspergillus. And we also see in experimental models that Aspergillu species can produce factors that cause inhibition of lymphocytes.

Both TMB lymphocytes is becoming established and dividing and doing their normal responses in the environment become inhibited as a result of these toxins that are produced, and that then becomes difficult. We can see establishment of infection as a result of that. We also see problems as a result of underlying disease.

So, as a, as a result of Asperger's infection, we can see it as a primary infection and the cause of nasal discharge, but we can also see it when the environment within those has become disrupted. So if we have a neoplasia, a growth that's causing a problem with the environment. Changing with mucus not being cleared in the way we'd expect, we can see secondary Aspergillus infection.

We can see it as a consequence of foreign bodies, so things like grass seeds and bits of, of organic material that have formed within the nasal chambers that are causing a problem, and they will then act as a focus for fungal infection. And trauma can also cause problems as well, other disruption of nasal turbinates, if those turbinates become dislodged and a vascular, then the necrosis associated with that can be a good place for the fungus to take hold and for us to have aspergillu and aspergillosis as a result of that. So there are lots of factors essentially that would enable us to see that there are problems.

Having the right shape of nose, dogs that have long noses, medium sized noses, would be more predisposed, but also having the opportunistic infection, being unlucky to come into contact with the fungus in the con in the concentrations that are needed, and also having some immune incompetence that causes the fungus to develop as a result of that. So what sort of breeds do we see? Well, we've talked through some of these things already.

So dogs that have long, and mid-sized noses, I can never pronounce these words, but we, we understand what we mean, not dogs that have very short brachiphallic noses. So having lengthier noses does predispose to having aspergillosis, essentially that the, spores get taken up into the sinuses, and sinuses are relatively large in comparison with dogs that have shorter noses, and the environment of temperature and humidity there is, is better for the fungus to become established. And then breeds where we see this problem with some mediated immunity with German shepherds with Rottweilers obviously are a higher prevalence than in other breeds.

So, dogs with with long noses of any breed can be disposed, and we can see dogs that have short noses, brachycephalic breeds that are affected, but in those it's, it's less. Common and we very rarely see them. We saw a bulldog very recently here that had aspergillosis, but it's quite uncommon for that to happen, mainly because the, the airflow is, is more direct, back into the nasopharynx rather than circulating through the sinuses in the way that it does in dogs with longer noses.

It is occasionally reported in cats. The sort of prevalence in the presentation is, is similar, but they're relatively uncommon. So a handful of cases in the literature, rather than, you know, very regular cases.

So I think, you know, we have a very busy clinic and we probably see one or two Aspergillus cases. A week through both our medicine and surgical services. They tend to be diagnosed through medicine and treated through surgery, but in that regard, you know, it's, it's a relatively frequent thing for us to see in larger breed and longer-nosed dogs.

In brachycephalic, it's not common, and in cats, it's not common either. Usually these are younger dogs. The mean age in studies was about 3 years, but we can see it in very young and very elderly dogs, so it's not something where a breed will completely rule it out.

But it does help us to kind of think of what the likely differentials would be on age, and we'll talk through a case in terms of the sorts of things that we would think about when we're trying to diagnose aspergillu in a second, but in young Animals, infectious things, and aspergilus being one of those infectious things would be more likely in older dogs, we're having a higher prevalence of things like neoplasia and that perhaps is more likely to be a cause. So it does help us to sort of weigh out the possibilities, but it doesn't rule things out. And there's no sex predisposition, so that's been very badly, but we don't see that there's a male or female divide in terms of how we see these cases.

So the normal nose of a dog is quite complicated, and I, I guess we don't think about that too often unless we want to either image the nose, so take radiographs or do three dimensional imaging where we're thinking about CT or MRI or doing rhinoscopy when we're having a look into the nose. And we're very lucky, we have some very fine long endoscopes, and we can get to most of the areas that we can see within the nose, unless you have a nice sort of rhinoscope, it's quite difficult to do that. With a, an auroscope, you can get usually a few centimetres of nasal chambers, which is really nice when you're looking for things like foreign bodies, but it's usually the back part of the nose that's going to be an issue when we think about sinal lasal aspergillosis.

So this is the normal nose, we'll have the very fine turbinate scrolls that are present in the middle, and then at the back, we have the ethmoidal turbinates, which come from the back of the nose, from the area around the crib. For plate, which is the division between the nasal chambers and the brain, where all the olfactory nerves run through, which is important when we're thinking about treatment to see whether this is intact or not. So a lot of the azal drugs, the antifungals that we use will be quite irritative.

Usually with the nasal chamber, that's relatively well tolerated, but if they're getting into the area around the brain into the arachnoid space around where the brain is and irritating the brain itself, and that can cause seizures. And then up into the frontal sinuses the very parts of that, the lateral, the medial, and the rostral aspects of the frontal sinus. Usually you can't drive your scope into the frontal sinus, unless you've got some erosion of the divisions and the openings that are there.

But it's, but it's often the case that with Aspergillus infection, because it's sitting up in the finest sinus and producing dermatoxins, that that will cause erosion, and then we can see up into the sinus, much, much more easily than we would otherwise normally be. So these are the sorts of turbinates patterns that we see. There's lots of functions of these turbinates in the front part of those, they grow from the side.

It's a shelf of bone that forms from theatuses, so at the top, middle, and the bottom, the dorsal, the middle and the ventral meatus of the nose. And this turbinate structure allows us to warm and humidify air, and also philtre out bits of debris, so pollen and bacteria and all sorts of things that shouldn't be in the environment. And obviously aspergilluspores would be part of that, and they're fairly ubiquitous in dogs that are sniffing and in vegetative areas.

And normally we'd have mucus that moves that material back to the back of the nose, and then it's swallowed in the nasopharynx, and we don't worry about it. But if there's an environmental disruption, we have problems, then it will create a change. If we have erosion of these turbinates, which often happens in Aspergillus, we lose this nice fine turbinate here, we're going to lose the ability to philtre and humidify air in the way we would expect, but we also lose that surface for .

Mucous to flow over, and we will often see sort of chronic rhinitis like changes associated with the loss of that turbinate structure, either associated with Aspergillus, but as a consequence of of the disease once the aspergillosis has been treated. So these dogs often do very well with treatment, but they are left with some essential damage as a result of the Aspergillus infection after treatment, and that can be difficult because of this destruction of the normal turbinate pattern that is present. So this is what the, the normal nodes would, would look like.

This is a CT image just scrolling from the front of the nose, coming through the canines there, looking into the nasal chambers. And you can see on both sides of the nose here, we have lots of very tightly packed nasal chambers and turbinates and then going up into the sinuses at the top here, and large turbinate structures, sorry, sinus structures at the top, which enable us to have a very big space, which is where we would normally see potential Aspergilus infections. So, running from the front, we've got canaries in the Opening, you've got the turbulences as they come in from the side, lots of these fine scrolls of bone as we move through back to the ethmoidal areas, and then going up towards the frontal sinuses, the medial after rostral parts, and very big air filled areas here, which is often where we see aspergillu infection.

So very difficult structure to kind of visualise if we're looking at CT and we'll spend more time looking at those images as we go on through the talk, thinking about things that can go wrong and where we would look for problems as a result of that. So if we would have a, a sort of classic nasal history of a dog that has aspergillosis, then we're going to start off by trying to take a history and understand what's causing the problem. And classically with aspergillosis, it's kind of a very sort of insidious type problem.

It starts off that there's some nasal discharge, there's some sneezing, often perhaps some nasopharyngeal irritation as a result of that gagging and wretching, and then that gets gradually worse over time. So the discharge becomes more sort of. Becomes thicker and snottier, and then we may get some erosion as a result of that.

So we might seeing there's some depigmentation of the nay, so we're losing colour as a result of that, and then that's progressing potentially to haemorrhage within the nose and we're getting bleeding and epistaxis as a result. Aspergillus is, occasionally, it will be a bilateral disease, but often it presents being worse on one side compared with the other, and then it progresses and it becomes a bilateral disease. But we would sort of differentiate it from other causes of nasal discharge by sort of looking at the history and then wanting to do other things to confirm that.

So things like foreign bodies will be usually fairly acute, and we'll see that they are fine, and then they start sneezing and they have signs of nasal irritation, usually unilateral. Aspergillus tends to be more insidious, but sometimes it can come on that acutely. Allergic rhinitis tends to get worse at certain times.

In the year, so in the spring and in the autumn, usually associated with irritative changes, so sneezing, gagging, wretching, and some discharge, but usually a clear or serous discharge rather than becoming mucopurulent, whereas Aspergillus tends to get gradually worse and progressively get worse over time. And trying to work out whether it comes from one side or both sides is, is useful when we're trying to work out where we are with our history. Usually Aspergillus will be worse on one side than the other, but it's, it's often bilateral disease, and we usually do treat both sides if we find that there is Aspergillus infection.

Things like tumours will usually be unilateral, so they're present on one side, although things like lymphoma can affect both sides. Foreign bodies will be usually unilateral in the front part of the nose, will have bilateral signs if they're in the nasopharynx at the back, whereas allergic rhinitis or things. Like inflammatory rhinitis is a lymphocytic plasmacytic rhinitis, will be present on both sides and have very even sides.

So, it's often difficult to differentiate those things and asking owners which side the dog is having discharge on is different, because as you're looking at the dog and as they're understanding which side of the dog it is, is often difficult. So you determining your left and right, and the dog's left and right is often useful. But knowing whether it's right or left sided is helpful when you're thinking about which side you're going to sort of scope or which side might be worse in terms of treatment.

And then other things that we're gonna want to know about in terms of history will be the general health of the animal, whether there's any problems, and then thinking more specifically about whether there might be aspergillus infection, whether there are any neurological signs associated with whether the crier from plate may be affected, whether there may be any irritative meningitis like signs of. Associated with that, seizures and things like that will be the things that we're concerned about, but any change in mentation, and, and doing a full sort of clinical exam where we're thinking about looking at the cranial nerves would be really helpful in terms of looking at things that might be causing a problem, when we're thinking about how we go forward with treatment. So they want to examine the patient, and we're going to do a full clinical exam, obviously, to, to look at everything and all the body structures.

We're going to think about the nose specifically, and think about whether there's airflow through both the nostrils. Easier said than done to think about whether there is good airflow. We can use a hair or little bits of bandage to see whether there's airflow.

We're using a glass slide to see if we get compensation. Lots of dogs will let you do that. Some won't, so don't get better and try to do it.

It's not the end of the world, but again, it helps you to understand whether it's left or right sided. Looking to see whether there's any pain around when you're touching the head is helpful, and whether there's any pain or retropulsion of the bulbus is on both sides, and we can see that in association with Aspergillus, but if there's any nasal tumours or any footative disease, then it could be hard to retropulse the globe, and that will make it more difficult to do that. So as a result of that, neoplasia will become more likely as a result.

Looking for dental disease, we often forget that as a cause of nasal discharge, but we often see bacterial nasal rhinitis secondary to, dental disease and tooth root abscesses, feeling the lymph nodes, see if there's asymmetry with those, that may be things that we can aspirate and make a diagnosis. A lot of the nasal tumours will metastasize to the lymph nodes, so we don't always have to take biopsies from the mass itself to be able to make that diagnosis and the lymph node aspirate can be helpful. Whether there's any facial asymmetry, so whether there's any mass that's causing a mass effect, and then depigmentation with the nose, which is what we'll see with Aspergillus would be very helpful.

And often these dogs are quite painful. So they may not overtly show that they're painful in the sense that when you're touching the bony bridge of the nose and around the skull, that they're helpful, but kind of stroking the head or patting the head or The thing that kind of it's uncomfortable if you're going towards them would make them shy away from you. And so that, that often is a key sort of hallmark of Aspergillu, that these animals don't really like you getting close to their head or doing anything that is percussive on the top of their head and and and sort of shying away from being stroked in that sort of location.

So these are sort of dimentation type changes that we see. So we're gonna want to make an evaluation, try and understand what's happening, and we usually go through a fairly logical pathway in terms of trying to make a diagnosis, and we usually sort of start off with general blood work, so haematology, biochemistry to try and look for any systemic evidence of disease. With Aspergillu specifically because it's essentially growing on the outside of the nasal chambers, you usually don't see that there's any overt biochemistry or haematological changes.

We may see that it's an inflammatory leukogram with a neutro monocytosis and an increasing globulins as an inflammatory response, but generally, that's quite mild, and any response we see in terms of inflammation is generally secondary to there being a bacterial infection or more established inflammation that is present, and that being the response that we're seeing. If there's haemorrhage, it's important that we think about coagulation, so we'd want to know where we are with, with Mashret to see if we have had blood loss, looking to see where we are with the platelets for primary coagulation and potentially doing some secondary coagulation tests, so PT and APT or a whole blood clotting test where we just put blood in a glass tube, hold it in your hand and rock it backwards and forwards and see that it's, it's clotting. Normally, whole blood will clot within about 4 to 6 minutes, so it just gives you a good idea as to whether the blood is able to clot or not.

And then it's really nice if we have blood tests that will give us a yes no answer as to whether a disease crisis might be present. And there are lots of blood tests that have been developed looking for Aspergillus, looking for the antigen, and so when we look for the fungus itself in in blood samples, and those historically have not been particularly good because we can find aspergillu in animals that are normal. And so, Whilst they do pick up a lot of the ones that have disease, so that they have a reasonable sensitivity, the specificity is quite poor because it allows us to diagnose cases that don't actually have Aspergillu.

So there are lots of falsely positive results. So we have to use other tests, and the, the antibody-based tests are the best ones where we're looking for the body's response to the fungus being present. But again, they're not 100% sensitive and specific, so there are some problems in doing that.

So, in general, we tend to use that as a helpful guide, but alongside other tests that help us to understand what's happening. And that's in general, looking with imaging to see whether there's a destructive pattern, to see whether we can see that there's a loss of turbinate structure, and we can do that with radiographs or with more advanced image. To have a look in the nose and again assess to see whether we have any destructive pattern that might be present to look for evidence of fungal plaques.

And if we can see fungal plaques to take some biopsies of them and look to see whether we can see the fungus that's there, but usually visualising them. I'll show you some pictures. They're very obviously fungal plaques, and you can usually make a diagnosis just by visualising them.

Or doing flushes or blind biopsies will help us to understand that. And in some cases, if we're really suspicious that we might have aspergillosis, where you know, we have a really destructive pattern, but we can't really define exactly what the cause of that is, we've looked in all different ways, then we will sometimes treat these dogs for Aspergillus and see what the response to treatment is because often it can be quite tricky to to formalise and be completely sure that we have a diagnosis. So to go through this pathway, I thought I'd show you a case which would be helpful in terms of how we would work through things.

So this is Hector, he's the dog that I've shown you his, his deep implemented nose. So this dog does have Apergillus, and we, we go on and show you diagnosis of X-rays, the bets or and RCT scans for this dog and also our rhinoscopy findings. So it's a nice case to sort of follow through in terms of what was happening.

He is quite severely affected. He's a 9 year old German Shepherd cross. He had an 8-week history of sneezing and progressive nasal discharge, sort of started off with sort of being muoid, both sides, and then became progressively more bloody and sticky and thick and and quite disgusting, kept sort of sneezing it all over the owner's house, which, you know, Hector wasn't too bothered by this, but the owners were, were not particularly happy by what was going on.

Did have some response to antibiotics, but it didn't clear up completely, so they suggest that there's some secondary infection. Because of that sticky thick mucoid discharge and, and changes in the nasal chambers, but it didn't resolve. So actually, primarily, bacterial rhinitis is quite rare in dogs.

We can see it's secondary to dental disease, but usually anti antibiotic responsive nasal disease means that we've got something else that's changing the environment within the nose, rather than it's the primary bacterial problem that's causing the issues. So we don't see that that's the cause of the problem, it's something else that's causing a predisposition to secondary infection. So some of this dog's in good body condition.

A general clinical exam is, is fairly unremarkable, but there's quite a lot of crusting over his nose, and these erosive changes on the lateral aspects. This is really quite pathogomonic for Aspergillu infection. We can see it with some of the chronic rhinitises where there's just persistent dripping of of discharge over the nose, but it looks a little bit different.

It's sort of forming the pathway that that discharge would form rather than the sort of erosive type change. And he was really quite shy on us examining his head, especially sort of patting on his head, and didn't like his globes being pushed back. There was no resistance to that, but it was uncomfortable.

There was discharge present on both nostrils, which was a thick mucoid, slightly bloody discharge, and there was good air. Flow on both sides, and we could hear normal inspiratory noise over the larynx when he was at rest. So he's breathing through his nose, and there's normal movement there.

So he was, he was sort of doing OK, generally, but there was obviously signs of chronic bilateral inflammatory disease within the nose that was causing him to be quite uncomfortable. So when we think about the problems with this, he's sneezing and he's got nasal discharge, there's a relatively broad list of differentials for causes of sneezing. So things that are causing inflammation within the nose, so things like foreign bodies or tumours, things that change the environment, so infections, fungal things would be the most likely, because we're saying bacterial things are quite uncommon.

But in cats, for example, there's a whole list of viral type causes in other places. So Scandinavia and the states, they see, Nasal mites, which are quite funky. We don't have them in the UK, although there is one case report of them being seen up on the east coast of Scotland, but they're not something we see here that cause irritation and sneezing, inflammatory diseases like chronic rhinitis and allergic triggers that can cause problems as well.

And then with nasal discharge, there's quite a lot of potential differentials, so things that change the environment within the nose, so foreign bodies, tumours, infections, so the whole list of, of potential causes, and then things that are are more established, these inflammatory rhinitis is, so from true allergic rhinitises through to the more established and difficult to treat immune mediated rhinitis is, I think. Pacytic plasma cytic rhinitis, which could be really quite tricky to treat, and it's quite hard to get under control. And then depending on what that discharge looks like, if you've got epistaxis with trauma or coulopathies or some of the weird and wonderful infectious diseases like leishmaniasis and lichiosis and things like that, that can cause problems, but we don't see those very often in the UK.

So we have some clues here as to what might be causing a problem. We have bilateral discharge here, so that perhaps makes a tumour less likely. It's been insidious in its onset, which perhaps makes foreign body less likely, has normal lymph nodes.

There's no obvious drainage that suggests that there's metastatic disease, got good facial symmetry, so there's not a big mass that's causing distortion. There's a extra portion of the globe, so there's not a mass that's behind the globe that's causing a problem that means you can't push it back. There's some pain there, which suggests that there's inflammation.

And it's it's quite established, so that makes tumour perhaps less likely, unless it's causing a pressure effect. Asperger's will definitely cause discomfort. There's no evidence of any dental disease, so secondary bacterial infection again, is less likely.

And we've got nasal de pigmentation. So Aspergillus would be at the top of the list of things that are causing a problem here, then probably things like immune mediated rhinitis, which would be the other differentials and things like tumours and foreign bodies, a little bit loud to lower down that list in terms of what we're going to look for. So thinking about what investigations we should plan, we, we sort of talk through how we'd want to do some blood work to try to understand where we are with the general health of this dog.

And this dog, the CBCT was normal. He had some mild elevations to liver enzymes that are probably age related and didn't turn out to be a problem. His coagulation times were normal.

And then we did some aspergillu serology. This always takes a little bit of time to come back, so it's not really contemporaneous with, with the investigations that were done. But it's useful to have those results.

This came back negative, which I've told you that he does have Asperger. We document that he has Aspergillu. So this is a test that isn't always 100% accurate.

So it's important that we understand that there isn't a 100% accuracy with any of the tests that we do, no matter what the laboratories that sell you the test tell you that there will be. It depends what you compare as a gold standard. And if you test against things that have root growing disease, And we know they definitely certainly have that disease, which is what's needed for a gold standard.

You absolutely certainly have to know that that is the disease process is present. Specificity and sensitivity are often much better than they are in clinical practise, where we're using diseases that are developing and they don't have as clear signs. So the sensitivity and specificity we're seeing the numbers of false positives and false negatives we get will be different in general practise compared with any laboratory situation.

So we know that there are different antibody tests that are used and they have relatively high specificity. So if you find a positive result, you can usually believe that the sensitivity is moderate. So depending on which study and which test you look at, about sort of 80, 85%, so there will be some, some falsely negative results that that actually do have the disease, but you don't get a positive result as a.

Of that. So they're reasonable things to use, but we usually use them in combination with other things, and imaging would be the test that we would use alongside them. So don't rely on them to tell you yes or no, as we, you know, do with other tests like Cushing's investigations and the the test for anti stronglu, for example, when we know that there isn't a 100% yes no answers with, with the tests that we have.

The antigen tests have been less good, as we said, the, the sensitivity and specificity are quite low, and that means that we don't tend to use them. Glatamanen is a, the synthetic polysaccharide that's produced by Aspirus and some other fungal species as well. And it was suggested that that might be helpful to see whether the infection was present.

It's a really expensive test to run. I mean, it is quite Useful in humans for some of the other fungal infections you see. So things like peelliomyces and other random systemic infections that we see with funguses in people.

But in dogs, it doesn't seem to be that useful. So, currently, we don't, we don't recommend that. We've done some studies here looking at it and there's utility in Aspergillus, and it's not that helpful to, to be honest.

So it's not a test that's worth investing the money in. So here we, we have a clinical suspicion that this dog has Aspergillus but we've not been able to diagnose it. So we're gonna be wanting to think about some imaging, maybe doing some rhinoscopy, taking some biopsies, trying to prove the disease process is present.

And if we're doing imaging of the nodes, it depends on what we have available to us as to how we might want to image it, as to where we are in terms of the available facilities, but also the finance that the owners have, because taking some radiographs is obviously going to be cheaper than doing cross-sectional imaging, but doing cross sectional imaging where we've got 3 dimensional imaging of the nose is going to give us a lot more information as to the structure, but also the areas that we might want to evaluate if we're looking. To see whether we have a tumour or if we have a foreign body or the the area where Aspergilus might be as to how we might go forward with that. So, three dimensional imaging is going to be better than taking radiographs.

The radiographs are a good way, as a good starting point to understand what's happening in the disease process. Ob we need to do radiographs well, because we can introduce a lot of error by not having perfectly positioned radiographs in the nose, and we're tilting it. Side to side and causing our own artefacts, but they're a good place to start for investigating nasal disease if we're looking to see if there's a change in capacity.

There's unilateral disease, that would be quite helpful, is there a loss of turb detail. All of these things will help us to make a diagnosis in that regard. If they don't make a diagnosis, then MRI or CT will be helpful, and we are often happy, at least historically, to treat these dogs from doing X-rays and rhinos.

Where we can see what's happening with those who don't always need to have MRI and CT. But MRI and CT are helpful when we're thinking about things like the crepiform plate, and also when we're thinking about nasal investigations, if we're thinking about metastatic disease, CT will be really useful to help us to understand what's going on in the lungs and see whether they've got any metastasis. If we're thinking about radiotherapy, for example, we need to know that there isn't a progression of the disease to do that.

So MRI is helpful, it gives us good definition of the nose. We'll often do that when we're thinking about involvement of the nasal chambers and also the brain, and we can get really good detail of the nose from MRI. CT gives us a good definition of the nose as well, but less good definition of what's happening within the brain, so it makes it more difficult for us to see the soft tissue structures, but often that isn't necessarily something that is important when we're thinking about aspergillosis.

So what sort of views should we take when we do radiographs? Well, it's nice to have 3 views of the skull. So we'd like a deviant rule, so putting the plate within the mouth so we can see what's happening within the nose, a lateral skull, which is perhaps the least useful of views, but it's still nice to have it for completeness, and a skyline frontal sinus when we're shooting the radiograph at the the beam, at the radiograph at the top of the sinus.

So we're sky lining the sinus and we can see what's happening within the sinus cavities. And then 3 views of the chest, if there's any evidence of metastatic disease, we'll see that because you know, if you see something like this with cannonal metastasis within the chest, we we're very likely to have nasal tumour that's metastasized, and that gives us our diagnosis. So knowing and understanding that would be helpful.

So just to, you know, technically, and truly correctly, 3 views would be needed to completely rule out my static disease, but just evaluating the chest would help us to understand there's nothing that's causing a problem. So what do we see with Aspergillus? Well, we see this destructive pattern, we see this loss of turbinate definition.

So we can see the dental arcades on both sides. We've got the phone in the middle, which is giving us the left and the right side. And we've lost the normal, very fine turbinate structure that we have here.

We've got empty spaces, and we've got soft tissue opacity that's kind of Irregularly replacing that, which is mucoid material, which is present in the nose as a result of the nose being very cavernous and us having a lot of space as a result of that. So, this is Hector's radiograph, and he has very marked bilateral destructive change in the nasal chamber and a loss of that normal fine soft tissue turbinate detail that is present. So this is lateral radiograph and you can kind of see that there is, again, a loss of that sort of normal turbulent definition.

It just looks a bit emptier than you'd expect, but the lateral is quite hard for us to interpret. It's not perfectly superimposed, but it's not too bad, but it allows us to look for areas and and sort of assess the sort of bony structures that are here, and also to look at the the native pharynx and the the sort of corral parts of the upper airway, which is, which is better as well. So Those areas can be evaluated on those radiographs.

In some areas, we would see it's hard in these sort of, you know, brackyphalic breeds, it's really hard to actually use the lateral at all, and also the ventral would be more difficult here, but if we have some erosive change in this stuff. This is the bulldog I was talking about that we saw recently, this is erosive change, in the, area around the frontal sinus as a result of Asperger's infections. So the laterals can be helpful, but they're probably the least useful of those views.

And then we have the skyline frontal sinus view which helps us to see whether we have soft tissue change within the frontal sinus or whether there's any erosive type change that might be present as a result of Aspergillu infection. And here we can see that there is a difference in soft tissue opacity right compared with left. We've got soft tissue opacity within the right frontal sinus, whereas the left is nice and air filled and looks very normal.

So we have a difference in those two areas that is causing a problem. So there's, there's occlusion of the right side, drainage, and there's an increase in soft tissue density on the right side that is causing a problem. Now, 3 dimensional cross-sectional imaging is useful because it helps us to have a better understanding of that fine density and that bony tissue that is present within the nose.

Now, the difficulty within the nose, it's quite hard sometimes to see those structures, and so having an MRI or CT is really useful in that respect. So these are sort of MRI images of dogs that have aspergillu. You can see that there's a big space that's present in the nose as a result of that.

And we've got lots of erosion of the normal turbinates up towards the frontal sinus, and we've got this soft tissue material that is present up here as well. So much, a lot of evidence of destructive change. Erosion as a result of that, then this would be the sort of transverse.

Basis here and also because this is T2 so this is picking up a water image that's telling us where there's muoid material we've got lots of mucus that's present in the nose as well, so very destructive changes on the MRI scan. And CT just says that a little bit more clearly because we lose a we get a bit more definition of the bony structures. This is a dog that has unilateral unilateral aspergillosis present on this left side.

The right side here looks very normal, the normal scrolls of bone, but the right side here is very empty. We have very little material that is present within the right side of the nose. And then this is CT.

This is actually a heck of CT and you can see that the nose here looks very empty. And as we're looking at the nose here, you can see that the normal, very fine, very full appearance of the nose is missing. You've got very big empty spaces that are present.

So you've got a very marked destructive pattern that is present because of the erosion, the toxins that are present. And then some very angry looking frontal sinuses that have lots of material. Within them, that shouldn't normally be there and erosive type changes a result of that, some fluid that is forming.

So this is a very erosive type disease. It's very generalised on both sides of the nose, and we're having lots of empty spaces result that sorts of damage normal turbulence, which is why we get the secondary infections, and once we clear up the aspergillu infection, a longer term inflammatory and chronics as a result of that. There lots of other things that we can pick up on CT and weird and wonderful things, sort of has a peanut here that have been inhaled, so it allows us to, to look for foreign bodies.

And we can also see tumours quite nicely. They give us a lot more definition. So here we've got a, a very big mass.

It's just well defined. You can see those in terms of the difference between the two sides of what we're looking at. In comparison with a destructive type rhinitis where we've got a lot of loss of space, and we've got something that's taking up that space within the nose and that's sort of soft tissue density.

So this is a very large nasal carcinoma, that's taking up all the space on the right side of the nose and it's very clearly a soft tissue mass in comparison with the destructive change that we see with nasal aspergillosis. So that will allow us to to look at the nose and to have a good understanding of what's happening with imaging. We want to try and then take some samples of the nose and have a better look, and rhinoscopy is usually the way that we do that, to try and confirm that we do have a fungal infection before we then think about going on to do a treat.

In terms of how we would want to try and treat the fungal infection that's there. Rhinoscopy is also quite helpful because it allows us to do some curettage and to remove any fungal plaques that are present, and that's one of the things that's really key to having successful treatment, is removing as much of the fungal material and fungal plaques as possible from the nose. So rhinoscopy is hard because you need a nice rhinoscope.

We use our bronchoscopes, flexible bronchoscopes, which are 3.9 m in diameter, but any small scope will be fine to be able to have a look in the nose, an arthroscope, or even your laparoscope would be fine to, to look to some degree, which scope, a very nice look in the nose. It depends whether you're sort of more medically or surgically trained just the way forward.

When we're doing rhinoscopy, we usually look from the back of the nose first with a retroflex flexible scope, and then we'll look from the front of the nose and try and establish what's happening. And I just wanted to spend a few minutes just talking about what the normal anatomy was when we're thinking about Aspergillus, which really destroys that anatomy to help us to understand what we would see when we do see Aspergillus. So you can get quite lost when it's aspergillus because essentially the nose just becomes a very big space and you lose a lot of the normal landmarks that are helpful for understanding where you are with the scope.

So normally we do retro retrograde rhinoscopy first, essentially looking from the back of the nose forward, which is why it's retroflexed, have the animal in sternal recumbency so sitting up, you hold the animal's head in the position which we normally do for intubation, and you flex the scope back so it forms a J-shape. And you push the scope into the mouth and hook it back over the soft palate so you look forward at yourself. So this is a radiographic image, it's actually fluoroscopy, so it's the opposite way round to radiograph, but this is the scope in the J shaped position, hooked over the back of the soft palate, looking at the back of the nose.

And what you'll see there is is normal turbinates, so you'll see the coal openings on both sides. This is the boma as it runs backwards towards the back edge of the skull, so it divides the left side and the right side and the nasal septum. You should see nice open holes here.

The last which is you probably won't see anything that is pathogamonic, but the areas that we're looking at here would be classically where we would see things like grass, blade. For bodies, and also things like near places where we have masses and growths in that sort of area, that are usually fairly obvious to see they're a bit more tricky to biopsy to feed the scope, the biopsy forces up to the scope before you flex it, rather than trying to feed the biopsy forceps around that 180 degree flexion, because that can damage your scope, but we try to take some small biopsies of that area to confirm what's going on. So the bit we're most interested in when we're thinking about Aspergillus will be looking from the front of the nose backwards.

So we look from the back first, and then we pack off the back of the nose using swabs, and we look from the front of the nose, and we usually look with just air to start off with, but it can be very difficult because muoid material can block the scope. So then you usually flood the nasal chamber by using saline through the scope so you can have better visual acuity of what's happening. But obviously you have to be quite careful with that because you need to have the patient anaesthetized the ET tube that's well cuffed in place so we're not putting any fluid down the airway, and having the back of the pharynx packed with with swabs and with packs so that we're not inhaling that material is helpful.

And then we usually look at the better side first, so we can sort of understand what the normal anatomy would be, and then we look at the worst side, so we can look at where the problem might be after that. So we have the dog sitting up in sternal recumbency. Usually I have something in the mouth like this is as an incontinence pad, so just an absorptive pad in the mouth.

So it's protecting in between a waterproof sheet between where we're putting the fluid into the nose and your anaesthetic tube and your HME. And your anaesthetic circuit underneath, so fluid, if it does run out of the nose, runs onto this pad and forward and off of the dog, not running into your anaesthetic circuit. We'll have packs in the back of the nasopharynx, and these are just tucked in around your ET tube so that you're not having any risk of any interlayered material.

And then looking at the nose, we'll we'll look at the better side first, as we said. This is us looking forward at the left side of the dog. So this is the left nostril.

So this is the nasal septum here, and then we're looking at the dorsal, the middle, and the ventroatus. So we have shelves of bone that come in from the side of the nose that create these three different divisions. The also meatus doesn't really go anywhere.

It's a blind ending sort of tunnel. The middle and the ventral meatus kind of go together to meet at the back of the nose, which is where we'll see the ethmoidal turbinates coming forward. So this is kind of moving back as a result of that.

We often see a little bit of muoid material. This is sort of a little bit. More perhaps than we would expect.

It looks a bit abnormal. And then as we get towards the back of the nose, we see these ethmoidal turbinates coming from the cripple form plate coming towards us, and these look quite abnormal. They look like sort of growths that are coming towards you from the back of the nose and coming from the crip of form plate that's causing a problem.

So this is sort of change that we would see with aspergillosis. We often see that there's a lot of discharge and a lot of disruption. This looks nothing like the picture that I've shown you with these nice fine skulls of bone dividing it into the dorsal, middle and ventral meatus.

We've just got a big cavernous hole where there's a lot of inflammation, so it looks red and it's quite annoyed. There's a lot of mucoid material, and there are some small fungal plaques here, although it's a little bit difficult to tell exactly what's happening. This is a fibroscope, so visual acuity here is a little bit less.

We've got this sort of pixelated image, so it's it's not quite as good as some of the sort of video bronchoscopes that we use now. And this is looking up towards the frontal sinus. So this is the frontal laser ostium, which is the opening between the nasal chamber and the frontal sinus.

We rarely see the nasal frontal osteum unless there's erosion. There's usually a lot of ethmoidal turbate around this area, that means you can't get up into that area that's causing a problem. So looking at Hector's video from his endoscopy, this is us looking in the nose on the left side and looking back.

So this is just going in through the areas and expecting to see that nice division from turbinates between the middle dorsal ventralum meatuses, and we can't see that at all. Everything looks really red, so it's very inflamed and looks very abnormal. And as we start to move back and we're doing the endoscopy, you can see that's a lot of destruction.

Everything looks very open, it's very easy to see what's going on. This is the axillary recess here, which we And don't normally see, and then we're looking backwards towards the back of the nose here. This area should be filled with ethmoidal turbates, and then this is the nasal frontal osteon as we go up towards the frontal sinus, down here is the coal opening, so we go towards the back of the nose.

And these are fungal plaques, which are growing on the surface of the frontal sinus here. So we can see that there's fungal material, mats material, which is growing on the surface of the of the frontal sinus. And we would try and take some samples of this so we could make a diagnosis of aspergillosis, so we can look at that cytologically, but all So to debride and to remove as much of that material as possible, because we can try and kill it with antifungals, but actually physically removing the source of that infection is helpful.

So through the endoscope, we would reduce forceps, we can use little baskets and and and grabbing forceps to try and remove and take away as much of that material as possible. It's quite laborious. It takes a bit of time, but it definitely helps to improve the situation and your effectiveness when you're trying to treat aspergillu and having better outcomes as a result of that.

So if we did some biopsies of that, we would usually see that there's lots of fungus, and fungus mats like this are really helpful. So this is just stained with with classic sort of HME staining or a diffritic type stain. We can see that there are these fungal filaments, so these are the fungal filaments that are present, and Asperger just has these kind of round heads at the top, which makes us so very suspicious that this would be aspergillus.

You can't tell for sure that it is because some of the penicilium species look very similar, but seeing those mats, seeing that destructive process, finding the fungus there in those areas that really makes the diagnosis for this patient. And people like doing nasal flushes. We're not that keen on nasal flushes.

I think if you pick up some, sort of exfoliated material, then they can be helpful. So things like lymphoma will exfoliate, sometimes Aspergillu will exfoliate, so we have to be careful that we've got enough of it, and then we can make a diagnosis so that's exactly what's causing a problem. We can see that that's definitely the big fungal disease that is present, but it can be tricky for us to be absolutely certain that Aspergillus is present, and that's what's causing the problem.

So we're careful with that morphology. And some people like to culture that material as well. Nasal cultures are tricky because the bacteria and things that we pick up as a cause of the, infection there may not be the cause of the dog's clinical signs.

So the bacterial infection is quite uncommon, it's quite rare, but usually that's something that's secondarily infected rather than it's the primary cause of what's going on. So usually that bacterial infection. Is secondary to another underlying disease process as we said, and usually we'll see that there's an improvement with that treatment rather than that's the sort of fixative type disease process.

We will see there's an infection secondary to a tumour or some sort of fungal infection that's causing a problem, rather than it's the primary disease process that's causing a problem. So biopsies can be really helpful if we can see the area that we want to biopsy and we can get to the area where there's fungal plaque, then we'll try and take a biopsy from that area, so we can see that. We have these nice nasal biopsy forceps that are rigid forceps that have little cupped areas on both sides.

So these cupped areas here will allow us to grab areas of fungal material, and also to grab tissue that looks inflamed, so we can take samples of that so that we can look at it under the microscope. Hope can make a diagnosis. Either do that blindly, or we can do it alongside the endoscope.

And if we can do it alongside the scope, so we can see where we're visually taking biopsies from them, that can be really helpful. If we can't, then we would do it blindly, and we would take the forceps alongside the scope, so we can see and we can biopsy the areas that look abnormal. If not, then we would do it by the end we would usually try to go as far back in the nose as possible, but you don't go beyond the me Canthus of the eye.

If you go beyond the medial cancer of the eye, then that can be difficult. So usually you take the forceps as far back as you can open them, push them back onto the turbinates, close them, and then remove and usually you get a decent piece of soft tissue as a result of that. And you can look at that in a formal pot and have a good understanding of what's going on.

So, biopsies of inflammatory tissue, neoplastic tissue, and also fungal disease will enable you to to make that diagnosis. Now, because the nose is usually very inflamed, and usually the nasal turbulence are quite delicate and quite sensitive, we will see that there's quite a bit of bleeding after we've taken biopsies, and that's to be expected. We'll often see quite a lot of blood, and sometimes that can be quite spectacular, but usually the degree of blood loss is quite small, so we don't see that there's a lot of bleeding as a result of that.

Usually it does stop quite quickly. Usually we'll keep the animals anaesthetized until that bleeding does stop. Usually then as the animal wakes up from anaesthetic, the bleeding restarts, but, generally you can get that under control.

If the bleeding is more elusive and goes on, then we will try and pack the nose, so using cotton buds or saline swabs to try and put some pressure within the nasal chambers would be helpful. And packing the nose will definitely help to reduce the amount of bleeding that's present. If that doesn't stop, then we can flush with ice saline to try and reduce and cause vascular constriction that works quite nicely, or using 0.5% phenylephrine will work quite well as well.

People tend to use adrenaline to do that. Adrenalines like swabs can cause really quite mild vase of constriction, often some necrosis associated. That, and with these really sort of intractable cases where we have really marked bleeding as a result of Aspergillu erosion, then people have actually tied off the carotids or done fancy things with interventional procedures to reduce blood flow to those areas, but that's a really heroic thing that's needed to be done very infrequently, so it doesn't tend to be things that happen very often.

And if we worried that these animals are bleeding, then we will often try to drop their blood pressure with just a little bit of aromazine, so maybe 0.01, 0.02 meg per kick.

So very, very low amounts of aromazine, to just try and drop the blood pressure, take away anxiety, and treat it to try and get things under control. We have a bit of an unwritten rule here that animals that have had nasal biopsies stay within the hospital overnight because if They go home the same day, see their owner very excited, then often that increases their blood pressure. They start sneezing, then there's bleeding, blood goes everywhere, all the owners, reception in their car, home in the kitchen, and they get back in.

So, generally, we keep them quiet in a kennel overnight here, just to allow things to settle. And, and then they go home the following day. And usually, that makes things a little bit easier and when we're taking nasal biopsies, we tend to see less of a problem as a result of that.

So that's how we take biopsies and hopefully make a diagnosis, and hopefully that allows us to understand that we definitely have Aspergillus. And in the last 10 minutes or so we'll talk through how we would treat things. And there are certainly tend two ways that we would think about treating Aspergil with oral treatments, so antifungal drugs that are given orally, or perhaps better with topical treatments.

So oral treatments tend to be not particularly effective, because if we're giving something that we want to get into a fungal plaque or a fungal map within the nasal chamber, then that will get into the nasal mucosa in reasonably high concentrations, but it's not necessarily going Get into the fungal mass and actually kill the fungus that is present. So oral treatments have not been that effective in treatment of cyan cyno nasal aspergillosis. We usually need to use a debridement, so flushing and physically curettage and removing as much of that fungal material as possible, flushing with saline, and then instilling an antifungal topically and letting it have a good dwell time within the nose to give us a good improvements as a result of that.

So Hector was treated with clotrimazole, which is one of the azoles that we use to treat aspergillus, and lots of different things are used and have good effectiveness. So things like ketoconazole, or aconazole, raconazole, clotrimazole, they all have very good activity against the, the fungus and and aspergillus, but getting them into the right concent. Patients to treat that fungal infection is, is tricky.

So he had two flushes of his nose and did really, really quite well. He did have low grade er nasal discharge for a little bit, but that tended to, to, to be reasonably well controlled with short course of antibiotics and then seems to now have resolved. So he's doing very nicely.

So the outcome for these cases, despite really quite severe infection, can be quite good. So let's have a think about these treatment options in a little bit more detail. We'll start by thinking about oral treatments.

It's not invasive because to do a nasal flush, you have to make a, either have to make a hole into the frontal sinus so you can flush down from the top and remove as much of this fungal material as possible, and then put your fungal, anti-fungal drugs into the frontal sinus, which is tending to be what we do here, it tends to work quite well. Or you You can do a nasal soak where you put the material into the nose and let it sit there for a long period of time. But you can imagine it's quite hard to actually keep a liquid within the nasal chambers.

So we'll talk about how we do that in a second. But it's technically quite challenging. So people will often want the easy option.

The easy option is to send the owners home with some tablets, but it's not that easy because prolonged treatment is needed. So we're talking about sort of 6 to 8 weeks, sometimes longer. And the efficacy isn't that great, so somewhere between sort of 40 to 60, 70%, so we're going to treat maybe half to 2/3 of these cases.

Some of these drugs are quite expensive, so, you know, fluconazole, so, they're reasonably expensive drugs to be given. And they also have some side effects. They, they're quite common, so they cause vomiting, the liver isn't happy about getting rid of them.

Feel quite miserable on them. So as well as having the signs of of nasal discharge and associated pain and inflammation associated with the nose, then they can be quite, you know, quite tricky things to try and treat. So we don't tend to use oral treatments unless there's a good reason why the animal couldn't be anaesthetized and have a flush or unless there's erosion of the crierform plate.

And if there's erosion of the cryptoform plate and system and. Central involvement, then it becomes much more difficult for us to be able to do that. So most of the time we're thinking about doing some sort of topical treatment where we're trying to get high concentrations of the antifungal into the sinus, into the nasal chamber to try and really kill as much of the fungus as possible.

And this is going to be most effective if we remove as much of that fungal material as possible to start off with. Various drugs have been used. We tend to use clotrimazole at the most as much as possible, which is relatively less irritative compared with a lot of the other fungals that are used, so things like Nconazole and forconazole, being more expensive, but Canister, so clotrimazole used for cutaneous and vaginal uses, it's relatively lacking inative constituents for the mucosa.

So. Tends to be quite good. And what we tend to do is to flush and remove as much material as possible, do a soak where we put liquid into the nose, and then use it as a depot with the cream, and the cream will gradually break down within the nasal chambers over the course of 7 to 10 days, sometimes longer, and that leaves you with a long lasting, drip effect of that, antifungal material through the nasal turbinus and hopefully kills the fungus that is present.

There's a couple of ways we can do that. We can do that as a sinus traphination, which requires some surgical skills, so it's not something as a medic that I'm going to tell you how to do this evening. But if you make a hole into the frontal sinus, either surgically or with you have sheeting needle, you can then flush saline through and you can put your canister in, or you can do a nasal soak, which is what's done with foley catheters to try and fill the nasal chambers with the antifungal, and then you have good effective treatment as a result of that.

So this is the sinus trephination. This is dog is anaesthetized looking forward the nose here. These are the same sinuses on both sides, and we've got Yamshidi, so bone marrow needles into the frontal sinuses.

Usually we would debride it endoscopically first and then flush saline through to remove as much of the material that's present down from the frontal sinus, Obviously making sure that we've packed the back of the nose as much as possible, so it's not gonna be any material that's moving in the wrong direction. And then generally, we would flush the 1% solution. So reasonable volume, dogs over 10 kg looking at putting about 50 mLs in both sides, so that we're trying to make sure that we're flushing through, and then we would leave the cream in the frontal sinus so that the cream can gradually break down over time, and we get good contact then over the course of the next week to.

And days, so that we can hopefully get rid of the fungal infection that was present. Now historically, people have used very long dwell times with, with Canister, which is, which is difficult. You need to keep the patient asleep for an hour and move them from side to side to make sure that you're get in good contact.

But by using the cream and putting the depot of the cream in, you can get away with quite short periods of of contact with the solution. To start off with under anaesthesia, and then your depot of cream gives you that longer term action. So there's a nice study looking at this sort of combined irrigation for sort of 5 minute flush with continuous sort of slow dripping of the of the canister liquid, the loremazole through the nasal chambers, and then the depot installation of the cre later stage, and we had, you know, this is a series from Dick White and colleagues at Cambridge, they had about 90% success just with a single flush and 100% success with the other two dogs that needed a second flush.

So generally this did very well, and this tends to be what we do with most of our patients here, that they have a short, they have a debridement, saline flush, a short 5 minute soak with, clotrimazole solution, and then injection of of depo into the frontal sinus to enable that sort of chronic dripping of the, clotrimazole down with the nasal chamber. The other option, if you're not feeling particularly break about finding the frontal sinuses to do a nasal soak, which is where essentially we block the nasal chamber by putting a foley up behind the the soft palate to block the nasopharyngeal opening, put foleys in the nose at the front to block the naries, and then fill the nasal chamber with latrimazole. Usually we do that with the dog on its back, so in in dorsal recumbency.

So this picture at the bottom, and being Careful to pack the fat of the palate as much as possible, and then still instil the clutch is also sort of runs into the three parts of the frontal sinus at the front here, and you're filling the nasal chamber with the antifungal material, and you get good contact time as a result of that. Now, here, you probably need to use a longer period and know classically what people talk about is doing 50 minutes soak, using 50 mLs of the 1% solution on either side. And you start in dorsal re come and see the animal's back, and then you move through 150 minutes of rotation on each side.

So dorsal, left lateral, right lateral, and then internal. And then once you've done 15 minutes in sternal, you take the the fos out of the area, and you tip the head forward and allow all of that material to be expelled out of the nose so that the nasal chambers are empty by the time you've removed everything else. The And it's waking up and it's not inhaling that material.

And again, this is quite successful, but it's, it's technically challenging to get the foley catheters in the right place. Getting them up around behind the soft pallet is difficult. Using a pair of curved forceps can help you to do that, or feeding it manually in, works quite nicely, but it's, it's tricky to get those into position, and making sure you have a, a really good seal around where those cannulas go in.

So it can be a bit fidgy to get this right, but it does, again, work quite well. If those things don't work, we do sometimes see some really tricky cases where they have really established infection, and those will be ones where we usually treat for a longer period of time. And usually those have indwelling catheters placed into the frontal sinus, so we can flush through on a regular basis.

And usually those sort of amount all flushes are done daily for 7 to 10 days. I'm using aconazole and repeatedly flushing through, and people have used other things as well, things like poverty and iodine, and iodine does kill aspergillu quite nicely, but it can be quite difficult, still and is irrestative, and I just find it hard to do at home. So generally these dogs are hospitalised for, you know, a couple of weeks for that to happen.

And if we really get stuck with them we'll do surgery. So essentially debriding into the nasal chambers, doing a rhinostomy to remove as much of this material as possible, clean and debride that tissue, and the sinuses as well to remove as much of that. But it's, it's rare for that to happen.

If you can do good debridement to good clotrimazole flush, remove as much of that material as possible, then you'll have reasonably good outcomes in these cases. People always worry that aspergillosis is a zoonosis. It can cause problems in people if they're immunosuppressed, but there are no instances of humans being affected by infected dogs, but we do be careful with people that are immunosuppressed, so people with HIV AIDS, we would be very careful to make sure that they're not exposed to animals, they're discharging large amounts of fungal material, but to be honest, that's quite uncommon.

So, we would just be sort of wary of that. It's not something that's passed on as a, as a problem. And the outcomes are quite good.

The, the prognosis, most of the dogs are treated either with a good soak, so 60 minute soak, or with a good debridement, and then a 5 minute slow soak and then a Depo cream do well, just with one treatment. So we're looking at sort of 80, 90% success as a result of that. But any signs that remain after about 14 days, we would give a second treatment, and this really improves the success.

So most dogs can be treated quite well with that second treatment if they haven't completely responded to the first treatment. And we know that there's a good sort of improvement in success if we're going good to bribement as a result. We really careful if the cryppiform plate's not intact.

If there's any damage to crypto, that can be difficult, so we don't want antifungal material moving into the brain. We would use oral therapy in those cases, so oralconazole, if that's the case, to try and treat things, but again, systemic treatments are not as good as the topical treatments, and they can have these sort of long, long term chronic meliis changes as a result of this destructive change. And if there's any doubt, so if there's continuation of clinical signs or if animals aren't responding really well, then follow-up CT and rhinoscopy is helpful in following the cases.

Don't use antibody titers to try and look and see whether they've got a clinical cure or not, because those antibody titers are remaining for quite long periods of time, and they will be positive for 2 to 5 years depending on which test has been used after a clinical episode of aspergillosis, even though that patient has completely responded to the infection that's got over that infection. So I think that's all I wanted to say about Aspergillus. Hopefully we've gone through how we diagnose the conditions, why it's a problem in some breeds and and some animals more than it is in others, the different utilities and the different tests that we have in terms of, of what we might want to use to try and make a diagnosis, and the different options that we have for treatment.

So thanks very much for listening and I'm very happy to answer any questions. Well, thank you very much for that, Sara, that was really, really interesting. As an, I'm a, I'm a veterinary nurse and, having been involved with quite a few of these cases at, at my practise as well, it's been, it's been really interesting for me to learn that a little bit more as well.

So as we've said, if we want, if you've got any questions, if you'd like to type into the question and answer box, and then we can put them questions through to Simon. So I'll just give you a couple of minutes just to see if there's any questions that you would like answering. So I've got a few little questions though, Simon.

Would you ever, use combination therapy where you'd use a systemic and topical treatment together, or would you just tend to pick one or the other? Yeah, we, we tend to use a topical treatment. Most of the time, that's very successful.

Most of the oral ones don't work that well. So if we're using a topical treatment that we'd expect to be effective, we don't tend to use a systemic treatment at the same time. So the only reason that I would pick a systemic treatment would be if we've got disseminated disease, which is quite uncommon, and usually suggests we've got sys suppression, or if you've got erosion of the reform plate in that there's there's CNS involvement, in which case a systemic antifungal would be need to try and treat that, but to be honest, they, they're quite difficult cases to treat and they're generally not ones that do very well unfortunately.

OK. And would you repeat the topical treatments more than 2 times? If you'd had to, if you'd had to repeat it, would you have to, would you repeat it more, more often?

Would you do it a 3rd, 3rd or 4th time? Yeah, usually if we're doing, if we're doing two treatments closer together, so we're doing treatment on day one, and then maybe we're repeating it maybe 14 to 21 days later, so week 2 and week 3, then that's fine. If things aren't responding to that, as in the dog continues to have clinical signs, doing a quick, a third flushing quick succession is unlikely to be effective, we'll probably use something else to try and treat things.

But if that second flush seems to have abated the clinical signs and the dog does well, but those signs recur maybe 3 or 5 months. 4 months later, then a third flush at that stage might be something we can consider. If we haven't controlled things completely with a second flush, we'll then be thinking about using something different, like doing a soak with the mah or something else to try and, see if we can improve things.

So, usually that, that failure with that second flush is more that you haven't debrided things effectively, or that there's some other reason why there's a problem. So there's another pathology, or the dog's immune system isn't allowing it to clear the infection completely. OK, thank you.

Well, there's no questions come through, so clearly you've answered everything that we've, everyone who's been listening this evening has, has been thinking. So again, I'd just like to thank Holly at the webinar vet who's been doing all of the, stuff in the background for us. And I'd like to thank again Simon for a really, really wonderful talk.

And thank you, everyone, for joining us this evening. I hope you all have a peaceful evening, and that the, fireworks are not too bad in your area. OK.

Everyone, take care. Good night.