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Bear with me. Um, I've been asked to talk to you about four different conditions over the next hour. Um, so asthma bronchiectasis pneumonia and TB, so potentially quite a lot of content, um, to, to be covered in those subjects and, uh, I don't wanna make this too, er, sort of dull. So please interrupt with questions. Um, I think probably best if we take questions at the end of each of these sections, um, what, what the slides contain is just kind of core knowledge about these topics. Um, so there's, there's plenty else that can be discussed, um, depending on what you would find useful or interesting. Um, so, uh, questions please as we go along. Um, so what I'm gonna do is for each section, we'll just start with a, with a briefcase just to kind of orient everyone. Kind of what, what kind of cases we see what we're talking about and then I'll, I'll go through the, the subjects then to, to cover hopefully what most of what you need to know. Um, so we'll start with asthma. This is a, a lady that I married recently at, they were all free. 41 year old lady. Um and I met her when she was admitted to the intensive care unit. Um for the few months prior to her admission, she had recurrent episodes of breathlessness and wheeze over several months. And we've seen an EDA few times and her up to her, she had an appointment yet, it was on a medium dose of Symbicort. And when she came up into A&E day before I met her, she was very tach with a high respiratory rate requiring some oxygen um had a normal or slightly high CO2 and so was admitted to ITU for invasive monitoring. Although they fortunately improved with bronchodilator and steroids, didn't need any other ventilatory support. And actually her asthma control then improved on stepping up her inhaled steroid dose and adding long acting antimuscarinic and we continue to follow up and she remains well so far. So asthma, as of course, you know, is an extremely common and very important condition for you to know about. It's probably the most common chronic respiratory disease. 4% of the population of the world have a diagnosis of asthma and about one in 11 people in the UK have a diagnosis of asthma. So it's very, very common. There are two maps up here on the slide illustrate where people have a diagnosis of asthma and where people die of asthma. And the obvious thing on these, these maps is that clearly those places don't overlap very much at all that death, deaths from asthma are probably occurring in locations which are resource limited and people really don't have access to getting a diabetic to getting the right treatment. So clearly on a global scale, there's a great deal to be done to enable people to get access to the treatment that they need from our point of view. One big problem in managing asthma. Well is it, it's often not well diagnosed. Asthma is commonly both under and over diagnosed. Um some data in the the side, as example, say study that went out and just randomly picked up 10,000 people in Copenhagen found that 5% of them had a definite diagnosis of asthma based on data reversibility. And half of that group of people who had definitely had asthma didn't have a diagnosis of asthma. So there's a a large proportion of under diagnosis. But if you take a group of people with a diabetes of asthma, and they'll actually evaluate them physiologically to try and find out whether they actually do have physiological signs of asthma at that time. About a third of people don't. So, um whether or not their prior diagnosis was correct or not, a lot of people currently taking asthma treatment probably don't need that treatment at any, any single point in time. So lots of over diagnosis, over diagnosis and under diagnosis and in part, that's it is actually making an accurate diagnosis of asthma can be very difficult there isn't one single test that that can tell us or even a group of tests that can tell us with certainty who has or hasn't got asthma. And therefore getting that diagnosis correct means uh putting together clinical judgment and his uh the history, physical examination and physiological tests, plus some biomarkers to try and get that diagnosis correct. I think it's useful therefore, to have a clear idea in your head about what we mean when we say the word asthma and the diagnosis of asthma and this World Health Organization asthma definition is actually quite good at summarizing the key aspects of the disease. So worth just going through this actually, just so that it's clear in your head. So it's a disease characterized by recurrent attacks of breathlessness and wheezing which vary in severity and frequency from person to person and in, in an individual vary from hour to hour and day to day. So there's that variability um I in in the symptoms and and physical signs that it's a key hallmark of the condition and the condition is due to inflammation in the air passages in the lungs, affecting sensitive to different nerve endings that easily become irritated in an attack, the lining of the air passage well to cause the airways to narrow and reduce the flow there in and out of the lungs. Again, that's the kind of key physiologic aspect that you need to know about asthma is period airways disease there is no extra coronary asthma. It's all about airway inflammation and narrowing and all about the resulting airflow obstruction that occurs because of that airway narrowing. So, conceptually a fairly straightforward disease to kind of understand what's going on in practice, harder to make sure you get the right people diagnosed and give them the right treatment. So a history of the examination as always is important. Obviously, people present with wheeze cough, breathlessness, a sensation of chest tightness. Those symptoms are usually episodic, sometimes dial, but worse at night or early morning and often triggered by particular factors such as viral infections, exercise, exposure to some allergens, sometimes triggered by medications such as nsaids or beta blockers that they're actually not that isn't as common as um this book might happily suggest. Uh a and patients often have other atopic conditions such as allergic rhinitis and eczema, uh which gives you a clue to that diagnosis being correct. So your physical examination demonstrates polyphonic expiratory wheeze. Then there is clearly small areas of obstruction present and asthma is the most likely explanation for that. But of course, most patients with asthma are well, most of the time. Uh so physical examination is normally well and and so often isn't terribly helpful in outpatients when trying to make a a clear diagnosis. So, physiological tests are very helpful to try and get the diagnosis of asthma correct. Um And I'll go through what we, what we use to try and to try and do that. So we can ask patients to keep a peak flow diary. Um The advantage of that is it, it's easy to do. Uh it's cheaper and patients can take, make repeated measurements of their peak flow. So we can see how it changes within the day and from day to day. Um if a patient is really good at that has, has a good peak flow technique and, and keeps it regularly, that can be very useful. Um And er current guidelines define significant variabilities of at least 20% variability in those er peak flow measurements as illustrative of or variable AFL obstruction. However, many patients do not have a very good peak flow technique. And if the patient hasn't got a good technique, you're not measuring their peak flow, you're just measuring the effort they put into it or however good that is when they did it. So a poor quality peak flow diary is completely useless. And in my experience, most patients, if you ask them to keep a peak flow diary, either forget to do so or forget to bring it back to clinic. So it's very rare that anyone actually brings back a good quality peak flow diary. But if they were to, that could be useful. So instead we often send patients for spirometry and other lung function testing. The advantage of that is that if we, if we observe reversible airflow obstruction, that's probably the best way of confirming a diagnosis of asthma. Unfortunately, as I said previously, most people with asthma are well, most of the time and so most people who we send for spirometry will have normal spirometry. Uh and that definitely does not exclude a diagnosis of asthma. That simply means that they were ok, that they did, they did the test, we can measure exhaled nitric oxide, which is a, a biomarker of eosinophilic airway inflammation that something called pheno that can be fairly easily measured with a, with a little device and access to those devices is improving. The advantage of that is that we're directly measuring part of the pathology of asthma. So that that can help us with diagnosis and guide our therapy. The disadvantage is that other conditions that cause airway inflammation such as high fever, allergic rhinitis are going to elevate your feno as well. And quite a lot of people who don't have any clinical signs of airways disease will have a raised feno. So um lots of false positive results if you were to just rely on pheno and finally, less commonly used, we can do bronchial challenge tests where we look at how kind of irritable the airways are. We do that by asking patients to breathe in a medication at a very small concentration that will cause bronchial constriction, usually something called metacholine, which is essentially synthetic histamine and and in, in anyone, if you're giving them enough metacholine that you will cause bronchoconstriction. But what we do is we measure how much metacholine can be inhaled before you or cause a 20% reduction in in F EV one. And it's that concentration that then is our measure of, of airway hypersensitivity or irritability. So, the advantage of using bronchial challenge is that if a patient's got symptoms that we think might be suggestive of asthma and they have a negative bronchial challenge test, that's the best test to do to tell us that they don't actually have asthma. And there's some other explanation for their symptoms. It has good negative predictive value. Unfortunately, it's quite time consuming. There's limited access to doing a test because you, you need expert physiologists, ability to, to do it. Uh a and many patients will, will not tolerate it because they can cough too much with mecodin or something like that. Um So not, no, not a test that can be kind of utilized at a population level to help us get the diagnosis right. It's for individual patients where it would change management. So other biomarkers can be helpful in, in trying to not only get the diagnosis right, but understand what kind of asthma someone has. Co asthma is not all the same condition, people have different types of asthma or different asthma and management of that. It can be somewhat different depending on what's what's driving the disease. So we measure blood eosinophil counts. Eosinophil asthma is a particular subtype. And now has particular treatments in more severe disease. And we can measure skin prick tests or specific IgE to airborne allergens. That's mainly again to characterize what type of asthma someone has most of the time, you can't really avoid these allergens very well everywhere in the air. And for instance, if people have a pet cat, they're unlikely to want to get rid of the cat. So often not useful in terms of allergenic avoidance, but can be useful in terms of phenotyping someone's asthma. So moving on from how to make a diagnosis to how to treat people with asthma. Historically, there's been a lot of kind of empirical treatment of try an inhaler, see if it gets better if it does. You've got asthma carry on current kind of national guidance from nice is urging people to move away from that a bit and make a bit more use of diagnostic tests and try and get a bit more of a robust diagnosis before giving people treatment that they may well then take for the rest of their lives. The more use of the test I just been describing feno spirometry, broncho reversibility, peak flow diaries me challenge. And although access to those is currently imperfect in the NHS, not from GP practices or, or struggle to be able to investigate people in accordance to the nice guidelines that that is kind of the direction of travel at the moment. And then of course, treating people for asthma means using inhalers, um which is a bit of a, a difficult area for, for many of you because there are many, many, many different types and brands of inhaler and the pharmaceutical companies keep adding new types and brands of inhaler every year. And so it's a very difficult field to really feel completely on top of. I, I'm not familiar with every single inhaler device that's available in the UK. I don't doubt anyone is so it can be difficult, but actually, it's much less complicated than it seems because there are in fact only three types of inhaler. So the key things to know is about any of the inhaler devices is what sort of type of inhaler. It is say there are only three types, there's pressurized meter dose inhalers which can be taken directly into the mouth or that's not usually a good way of doing so via a spacer or a type of device called a breath actuated inhaler where the patient doesn't need to be able to coordinate press in a canister and breathing in at the same time, which often people don't do that well. And apart from PM dis, there are dry powder inhalers of which there are many different brands. The examples on the screen here are the Te Haler, the AHA and the Ellipta device and then soft mist inhalers, which are a different newer kind of device that work a little bit like a pressurized meter dose inhaler but have a different form of propellant and a water based propellent rather than using chemical propellants that, that add to global warming. Uh the titrate and resin that is in the bottom left corner, which can be used for asthma. Although long acting anti is much less important than other drug classes, I'll come on to in a minute. So what do we give via these inhalers? Uh We can give short acting beta agonists. So, albetol, short acting antimuscarinics, ium long acting beta agonists, salmeterol, lanol. There are, there are others no anti antimuscarinics, tropium Heini again, much less important in asthma. But the key sort of um drug class of controlling someone's asthma is inhaled corticosteroids. That's what actually treats the underlying inflammatory problem and treats the disease. So getting people delivering inhaled corticosteroids effectively and getting people onto the right dose is the most important aspect of of chronic disease management in asthma because these medications are given in combination and with a specific device. Um, inhalers are an area that that should be prescribed by brand name and inhaler type rather than generically. You're often encouraged to prescribe generically so that the the most cost effective medication can be given. But inhaler devices are an example of an area that actually is best to prescribe by brand name. So, key aspects uh to think about when managing asthma is is the diagnosis, right? Has the patient been investigated? We are we pretty confident they've got asthma can they use their inhaler correctly? Cos many patients don't have good inhaler technique and clearly it, it doesn't really matter what we're giving them. If it's not coming into the lungs, are they taking their medications? Because adherence to asthma medication is is often not great. Estimated about half prescribed asthma doses are actually taken by the patients. So, so often poor asthma control is because of poor adherence, not because of insufficient treatment. And then finally, do we need to change or escalate that treatment to get them onto the right dose. This is what the current nice guidelines has in terms of the kind of treatment ladder in the interest of time. I'm not going to go through this in great detail. It's there to find if you want it, essentially the key thing to remember in this treatment ladder is that inhaled corticosteroids are the core of it. And then the inhaled corticosteroid doses then escalated and other drugs added in to see if they have clinical benefit. So usually long acting beta agonists or li receptor antagonist and then other things added in for patients who can't be controlled just with inhaled therapy only. We now have a range of biologic drugs to target specific and clarity pathways in asthma, which can be highly effective for patients who can't be managed just with standard therapy. Once we've been through a process of kind of detailed characterization to make sure we know what's driving their asthma and what treatment is going to be most effective up at the top. Uh is uh something that says maintenance and reliever therapy. That's uh a slightly different approach where instead of having a separate reliever and preventer inhaler patients have one inhaler that does both and and varies the dose of that according to, to what you need. So that's what the nice guideline currently say. Nice is a few years out of date, probably now. And there's a more recent kind of approach that's been put forward by a global guideline group called G A, which takes a slightly different approach, particularly people for mild to moderate disease. But they've got two different tracks that people can follow to manage their asthma. Potentially track two is very similar to the current nice guidelines with stepwise progression of asthma asthma medication doses as you gradually go up. But they instead recommend that the patients may be better off on this track one where again a bit like the M at um sort of recommendation, they have a single inhaler for both immediate relief and as a preventer with an inhaled corticosteroid and Formoterol. Um if they've only got mild disease, they use that only as they need it. So if they have no symptoms, they take no medication. That's the key advantage of that, that approach because it's been shown that the patients can have as good control with lower inhaled corticosteroid exposure by doing that. But then if they have regular or ongoing symptoms, most of the time they can increase the dosing and and end up in the very much the same place as on the track to kind of pathway. So that's all about kind of outpatient management and chronic disease management for asthma. Obviously, for most people working in hospital, most of the time, if they're managing asthma, it's about acute asthma admissions and and exacerbations. So a couple of slides on on what to do, which hopefully is fairly straightforward. So the key thing when managing someone who's been admitted to aspirate is to kind of risk, assess how sick they are, where they need to be looked after and the level of monitoring they might need. Um. So acute severe asthma in the current guidelines is defined as having a peak flow less than 50% predicted respiratory rate, pulse above 100 and 10 and unable to complete a sentence in one breath. So those are all indicators of a severe asthma exacerbation that only needs to be looked after in hospital and in an area that they can be monitored quite closely. Features of life threatening asthma are if you've got low oxygen saturations, reduced breath, sounds sinois, poor respiratory effort, hypertension, exhaustion or altered consciousness. All of those are indications that you're starting to actually have ventilatory failure and not getting enough air in and out of the chest because of the airflow obstruction. And when that occur as an asthma is extremely serious sign and the sign that the patient is at risk of respiratory arrest and really needs to be looked after on it or at least kept in an environment such as recess where they can be monitored closely until they improve medical management is I'm, I'm sure you are fairly familiar with nebulized, bronchodilat, albut and IPI steroids, oral prednisoLONE. Where possible IV hydrocortisone if people can't take tablets. Um, IV Magnes himself, it's still on the guidelines. Most asthma specialists are very skeptical, it does very much but it's fairly harmless apart from occasionally causing some hypotension. So it's still there to be considered if people don't immediately respond in truth, I think people mainly need time for the other things to work and to kind of calm medical care to not add to their tachy near by making them too stressed. IV Bronchodilators can be used. Aminophyline salbutamol or salbutamol can be given intravenously. Um But those really require invasive monitoring to do that safely. And so patients really need to be in a critical care area if they're sick enough to need intravenous bronchodilators. Uh It's also important to try and you know, control people's long term as asthma management at all steps in the process. They, they do document smoking status and address tobacco dependency when people come in with asthma and then almost everyone with asthma when they get admitted, get better over the next few days. The other important kind of aspect is that all these things that need to happen before they're discharged. So everyone who needs admitted with asthma, someone during that admission needs to make sure that their inhaler technique has been reviewed and that adherence to their medications has been reviewed and discussed with the patient, the regular medication needs to be reviewed and but often increased if they've come in exacerbating on whatever they were on before they need a personal asthma action plan, which kind of goes through with them, how to self manage their asthma and how to change things according to their symptoms, smokers who adit an asthma exacerbation need to have their tobacco dependency addressed and they need some form of follow up ideally in hospital clinics if possible, but certainly at least for their, for their GP. So that was a quick run through asthma. Uh key messages take home from this, er, so critically review the basis for asthma diagnosis. It, it's often wrong. Er, and it's often useful to, to have a think about whether that's correct and, and to try and do something about it if you're, if you're doubting that inhaling a technique and adherence is very important aspect of making sure people's asthma can be controlled. Self management is really important that people should be confident enough to vary their asthma do according to what they need and not to depend on healthcare professionals telling them what to do and people need to be on the right level of treatment which will change over time and therefore need need to vary according to what, what patients need. So that was a quick whiz to asthma and we're gonna move on to pois shortly. Any questions about that before I move on, sweetie? Can you hear me? Great. I will move on then. So bronchi, slightly less common condition. Uh again, I'll start with a kind of case vignette just to orientate everyone. This is AAA patient line 71 71 year old man, history of recurrent respiratory infection since childhood. So all through his life, uh had a history of severe whooping cough infection, pertussis, infection as a child as a possibly uh airways disease related to that and immunological investigations and no underlying immunodeficiency identified as significant airflow obstruction and consistently gross pseudomonas from his sputum samples, does what he can to try and clear his airway. Just regular chest physiotherapy takes carbocysteine as a mucolytic has in the past tried hypertonic saline as well. Um has tried nebuli antibiotics to try and reduce his exacerbation frequency but found that it is difficult to tolerate. So unfortunately, despite everything we can do to try and optimize his management still needs to come into hospital about twice a year for intravenous antibiotics to try and reduce the pseudomonas colonization of his airways which tend to build up. And as you can see on his CT scan, he's got quite extensive cystic bronchiectasis, mainly in the lower and lower lobes and the middle lobe here affecting the lower parts of his chest. So, bronchiectasis is a chronic condition characterized by airway dilatation, airway wall, thickening, er and retention of airway secretions. So, it's an airway clearance and airway infection and problem essentially and tends to manifest as persistent cough, recurrent or difficult to clear infections and may be associated with breathlessness or even respiratory failure. If it gets severe enough, people with bronchiectasis have increased bacterial populations in the airways, particularly organisms such as stare haemophilus influenzae pseudomonas and nontuberculous mycobacterial species. The kind of things that you don't find very much of in healthy airways can exist in much higher levels in the airways in in. So where we do identify a AAA cause, the most common cause is prior infections such as pneumonia, measles, whooping cough, tuberculosis. Actually, most patients, we don't find an underlying cause. Most idiopathic in nature, the bronchiectasis can occur as a consequence of many other underlying problems all to do with airway mucociliary clearance or or airway immune defense. So things like cystic fibrosis, of course, primary ci dyskinesia, some primary immunodeficiencies, particularly if you're deficient in, in anti production, such as in common, variable immunodeficiency, secondary the immuno deficiencies. Again, particularly if you can't free antibody properly properly and you have secondary hypergammaglobulinemia. But there are other associations with inflammatory conditions such as rheumatoid arthritis and inflammatory bowel disease that may be due to the immunosuppressant medications that are given in those conditions. But actually, it's probably due to some problem with immune response in those conditions that's inherent to the disease rather than being iatrogenic in nature. And then of course, as a condition, it can complicate asthma, allergic broncho, aspergillosis, aspergillosis where an excessive inflammatory response to Aspergillus causes airway damage, resulting in bronchiectasis. So lots of underlying causes that all end up in the same place with difficulties with airway immunity and airway clearance. So to make a clear diagnosis of, of bronchi, you usually need a CT scan to see those area changes. Um And then we investigate to look for underlying causes such as measuring immunoglobulin levels, looking for underlying conditions such as rheumatoid arthritis, some further immunological testing and HIV testing and occasionally looking for signs of cystic fibrosis or primary dyskinesia. If there are other clinical features that might suggest the presence of those diagnoses, or if the patient is particularly young. Of course, almost, almost all people with cystic fibrosis have that diagnosis identified in childhood. But occasionally people do get into adulthood with CF variants that are clinically significant. When we see people with bronchi, we often should send sputum cultures so that we know what pathogens are colonizing the airway and can guide antibiotic decisions in the future. And it's worth evaluating impairment in lung function. So that we can understand, for instance, whether the bronchitis might be helpful. Really the most important aspect of management of bronchi is, is trying to optimize airway clearance to, to reduce that, that um kind of blockage of the airways with sputum and reduce the the bacterial load in the airways. And chest physiotherapy is a key intervention to do that. Often patients are given positive airway pressure devices like the Arabica are illustrated here which help to to clear secretions from the chest, sometimes mucolytic medications. So, carbocysteine or nebulized hypertonic saline tend to be the ones that are used most commonly can again help to, to aid away clearance antibiotic treatment for exacerbations is important. So in people with bronchiectasis, we would normally treat for longer. So 10 to 14 days rather than 5 to 7 and and often with an antibiotic that has a broader spectrum of action than in treating a chest infection in people with completely healthy lungs because the range of bacteria that are present is much more diverse. Occasionally we can treat the underlying cause. So for instance, if there's immunoglobulin deficiency, that can sometimes be replaced. Uh for instance, in people with a primary immune deficiency in people who have very frequent exacerbations in more than two or so a year, antibiotic, prophylaxis can be helpful to try and reduce that. There's quite a lot of evidence now for use of azithromycin at a prophylactic dose and, but other antibiotics can have a role as well. There's a message saying that someone's lost audio to everyone else. Here, I carry on until summer goes to him. And so sorry, as I say, inhaled medications can be helpful. Generally, if you've got air flow obstruction and inhaling might be helpful to relieve that. Um We, they're very cautious about using inhaled corticosteroids having said that they're so important in asthma causing bronchiectasis to have a much more complex role. They can be useful if there's adverse airway inflammation in a kind of asthma type phenotype. Um, but obviously, in general, they're going to increase the risk of infection. And of course, patients should be immunized against respiratory pathogens where it's possible to do so. So, influenza and pneumococcus, et cetera, COVID, there's going to be RSP immunizations coming to local practice soon and I hope is that all of this management stops. What otherwise is a vicious cycle of worsening air airway damage where the build up of secretions in the airways leads to increased infection and that infection damages the airways further, leading to further build up of secretions and go around and around and around getting worse and worse airways. So hopefully, if we manage exacerbations properly and trying to reduce exacerbation frequency, we can prevent that vicious cycle of problems. So, a quick summary of bronchiectasis. So bronchiectasis is diseases arising from difficulty with airway clearance or airway immune responses resulting in those structural changes that can be seen on, on CT it may be and the most common cause is prior infection that's damaged the airways and then led to this vicious cycle of of ongoing worsening damage from further episodes of infection or maybe due to another underlying condition. And the core aspects of management are about optimizing airway clearance, treating exacerbations to hopefully prevent a progressive change and preventing exam exacerbations where we can immunization and antibiotic, prophylaxis. Any questions about any of that before I move on to talk about pneumonia, I give you five seconds great. So quick summary of pneumonia again in here, quick case, a patient that I saw recently, a 68 year old man who was admitted in July this year, he smokes. He presented with breathlessness, cough and chest over the past few days prior to admission on his chest X ray, you can see some consolidation in the right lower zone adjacent although not continuous with the right heart border. Er, and he had ACR P of 484 when he came into the hospital, er, his curb 65 score, which I'll come on to in a bit more detail in a minute too. Er, so he was admitted treated with curb ox and Clarithromycin. 24 hours later, we found that his urine pneumococcal antigen was positive. And so he made the assumption that it was a pneumococcal pneumonia that he was admitted with. And his antibiotic choice was therefore narrowed to amoxicillin on its own. He, he improved well and was discharged after a five day admission. Although actually I saw him in clinic recently. And even some months later, he's still not quite fully recovered from this quite severe illness that he had over the summer. So pneumonia is of course a bacterial infection of the lung parenchyma. And it's useful when thinking about pneumonia to differentiate community require and healthcare associated pneumonia. Because the the microbiology of those two problems differs. The most common bacterial cause of community po pneumonia is streptococcus pneumonia. As in the case, we just presented, but there are lots of other bacteria that can cause pneumonia. So, staph aureus glupa strep KC, he influenza mola catra negative organisms such as E coli, particularly if you've been in the hospital recently, lots of different bugs can cause it. And then there are these what we call atypical organisms such as mycoplasma, pedophilia, legionella Coxiella. These are all organisms that are difficult to culture and won't usually be cultured from sputum or blood cultures and realistically can only normally be detected either by serology or by molecular genetic tests which can be done. PCR tests on sputum samples. Occasionally it can be positive. In reality, it's often a case of just trying to provide appropriate antibiotic cover to make sure that any likely causative organism is covered with the antibiotics chosen. Hence, our patient previously was treated with Coamoxiclav and Erythromycin, which will cover atypical organisms and most of the kind of standard organisms until some evidence of the underlying causative organism was found occasionally fungal organisms can cause pneumonia although it's very uncommon in the UK, in people who are significantly immunocompromised. Risk factors in pneumonia include age. So, pneumonia is much more common in young Children than the very elderly cigarette smoking, air pollution and particulate matter from indoor fires, cooking over woods day, that sort of thing. It's a big risk matter for pneumonia HIV. Infection massively increases your risk in particular of pneumococcal pneumonia, excess alcohol consumption exposure to Children, which I mean, the number of Children in the household increases your risk of pneumonia probably because they introduce you to lots of respiratory viruses. And of course, winter, the frequency of pneumonia goes up a lot in the winter months again, probably because of more exposure to respiratory viruses which then triggers bacterial infection as a consequence. This figure next to here is a map of, um, pneumonia incidents, plotted against, ah, some kind of socioeconomic parameters. I put it here just to show how massively concentrated it is in Louisville, in Kentucky, in America. I put it here just to show how massively concentrated the pneumonia admissions are and concentrated in areas of socioeconomic deprivation. So, pneumonia is in many ways, one of these conditions that particularly affects people who have adverse socioeconomic conditions. Um, so how to manage pneumonia just depend on, on how severe it is. Um, so risk assessment is very important to understand where you should manage a patient and then how you should manage your patient So severity assessment guides, both antibiotic choice and also location of care in the UK. We tend to use the curb 65 score. It's quite a straightforward score. It's only got five parameters. So confusion having a raised urea, having a respirator rate over 30 low BP or having age over 65 and those scores have been shown to correlate well, with the risk of death from pneumonia, there is another widely used score called the pneumonia severity index. That is much longer, it has many more parameters and makes it difficult to use unless you've got a computer or a device that you can plug it all into. So, code 65 tends to be the severity assessment score that's recommended and used in the UK. You can see if you've got a score of four or five, you've got a between 25 and 30% risk of dying of pneumonia. So a very severe condition in the higher scores there. Obviously, the the core effect of pneumonia management is getting antibiotics, right? Um, by and large, I haven't kind of told you what antibodies to use here because different hospitals will have different protocols particularly guided by their severity scores and by local microbiology information. But for low severity, the micro inflammation becomes a bit less important. So, so generally amoxicillin is, is preferred if you've got low severity of pneumonia and Doxycycline, not on Clarithromycin. If patients allergic to penicillin. Again, anyone who smokes needs to be told that they should stop smoking because smoking is a risk factor for developing pneumonia as well as being good in its own right to stop smoking. People who admitted the pneumonia should all be offered an HIV test. Generally, people who are admitted to hospital should all be offered an HIV test. But in particular, because a pneumonia is an HIV indicated condition because the prevalence is so much higher if you have HIV infection, but everyone should be recommended to have their HIV serology measured if they're admitted to the pneumonia. And then further investigations may be helpful to try and elucidate what the pathogenic organism is. So pneumo can detect pneumococcal sputum cultures can be helpful. Although the sensitivity of that test is quite low, you can do PCR tests for atypical pathogens. But again, the sensitivity is quite low. So a positive can be useful but negative much less so. And patients who come in with pneumonia on the chest X ray, it's always worth thinking about whether they need a follow up chest X ray to make sure that that clears because it is possible that pneumonia can kind of hide a lung cancer. And then we need to make sure it clears to make sure there's no underlying pathology causing a problem. And if people are admitted to hospital with pneumonia, you should really expect them to improve over the two or three or four days after admission. And 48 hours is a good time to kind of review and decide whether people are improving enough. If patients aren't improving. After about 48 hours, it's worth having some thought about why not. So the diagnosis might be wrong, the antibiotic cover might be wrong with insufficient cover and remember that different countries have very different rates of antibiotic resistance. These maps here are some maps of prevalence of resistance to penicillin for pneumococcal at the top and cephalosporins for sa and as you can see, different countries have very different colors in these maps. And it's worth taking a travel history because if people have been abroad, particularly in a country with a high rate of antibiotic resistant, you might need to factor that in when choosing antibiotics and of course, they may have a complication from their pneumonia. In particular pleural infection is is something that, that we worry about and investigate for about one in three patients with the pneumonia will get a parapneumonic effusion. Most of those remain sterile, but people can get infections in that pleural fluid, which is something we need to then actually think about and investigate for if the patient isn't improving. So key message is about pneumonia. Um think about risk factors and severity when assessing patients with pneumonia, consult local guidelines for antibiotic choices, um particularly if you've got severe disease. Uh if you're not improving after a couple of days, then repeat investigations and reevaluate. So you can understand why they're not improving. Patients may need follow up to, to exclude underlying malignancy, uh, or to, to look for a reason why they, they've had a pneumonia if they've had recurrent events, uh, everyone who's admitted the pneumonia, uh, pretty much everyone ought to have an HIV test unless they don't want that to be done. And then final section of this talk, uh, quick run through tuberculosis. Again. Here's a case we saw reasonably recently 2019 actually, but it's a good x-ray. Um So this was a 24 year old of Zambian origin who presented with a six week history of cough. Um and, and surprisingly, her sputum was smear and culture positive and fully sensitive TB. And she did well on TB therapy and this chest X ray just illustrates the the typical changes that you find in pulmonary tuberculosis. She's got right upper zone shadowing a slightly nodular pattern to that shadowing with a cavity up here. Sorry, instantly in her left upper lobe was in right, didn't I left upper lobe er carrot in infiltrate there very typical of, of tuberculosis. So TB is the leading cause of infectious death in the world. I think COVID briefly overtook it but TB is back up there on top, the TB instance is falling but actually quite slowly. So the graph here, estates deaths from TB, which is falling very, very slowly amongst people with HIV. It's falling quite quickly because antiretroviral therapy has been rolled out which massively reduces the chance of dying of TB. But overall TB incidents and TB deaths are only falling quite slowly. The World Health Organization target is to achieve a 90% reduction in TB incidence from 2015 to 2035 or about halfway through that now. And at the moment, it looks unlikely that the world is gonna achieve that 90% target. Uh Unless something fairly dramatic happens in the U KTB incident has been falling since 2010. Um but probably has plateaued in the last few years. So that, that fairly rapid fall, in instance that we saw from about 2010 to about 2019, 20 is probably plateaued in the last couple of years. And again, we're not on track to achieve a 90% reduction by 2035 either based on current trends. So who gets TB risk factors for TB disease? Well, there's a slight male preponderance, there's a slight bulge at the age of 25 to 34. But actually then after that incidence goes up with ages illustrated in the graph here to older people in this is the UK data, older people more likely to get TB than younger people. Of course, migration from a high TB instance, country is very important. 76% of TB cases in the UK are born outside of the UK. Um Although actually most of those cases aren't recent migrants, so only 40% of those are people who migrated in the last six years. So just attempting to screen new migrants to the UK, wouldn't have that much impact on RTB instance or that is something is happening and has probably helped to achieve some of the reduction that's occurred within the past few years. As with pneumonia HIV, infection is a profound risk factor for developing tuberculosis. Increased TB rates 10 to 40 fold, having diabetes increases your risk of having TB having genic immunosuppressant suppression. In particular, with biologic agents such as anti TNF therapy increases TB risk and then social risk factors are very important. So, alcohol misuse, drug misuse, homelessness, imprisonment, mental health needs being an asylum seeker and smoking are all risk factors for developing to tuberculosis. So when we talk about the microbacterium tuberculosis complex, we mainly mean mycobacterium tuberculosis, but there are other organisms that fall into that category. So um Bovis M Africanum and micro and, and Capra and a couple of others that are very rarely seen. Um All of those are part of the Mycobacterium tuberculosis complex. And if someone has an infection with them, they have tuberculosis. Tuberculosis is microbacterium tuberculosis is not, I look at human pathogen that's current involved with humans for thousands of years. And there's evidence that mycobacterium TB DNA gets been detected from sle remains from 9000 years ago and it's very likely that TB has been infecting people for longer than that. And so it's very well, co evolved to be a pathogen of humans and to spread from person to person. TB pathogenesis uh is largely airborne in nature. S So um infection is acquired by breathing in droplets containing uh bacilli with the, with the, with the my in them, you can also acquire TB from drinking unpasteurized milk from a cow with TB for instance, which is why milk is pasteurized. Um but generally airborne spread is is how TB gets from person to person. What happens then is you breathe in these little acid fast bacilli into your lungs. They get taken up by macrophages, but the TB can survive within a macrophage and in fact, thrive within a macrophage, often will then lie dormant for a while and not cause disease, but for some time, but then can reactivate at a later point to cause cry disease, which then means that the bugs can get back out into the airways can be coughed up and spread to another person and the cycle can go on like that again. So what happens if you're exposed to TB? Well, actually most people exposed to TB, don't get in, don't get infected at all. So we think about 30% of people if they're exposed to TB will acquire that infection data from things like looking at household contacts with kids who have been in contact with cases made positive TB, about 20 or 30 people in that context will have immunological evidence of TB exposure and infection based on a skin test or into program, a release assay of those people who seem to have become infected and the bugs will go into the lungs that have been recognized by the immune system as being there. They've definitely got in there. Most people again don't get sick. So 95% of people who've been infected with TB, don't get sick, at least early on about 2 to 5% of people will develop active TB disease within about a year or two of exposure. But if you don't get active TB disease, uh within a year or so of exposure, you retain a greater risk of developing active TB later down the line. And about another 5% or so of people will develop TB later on in life if they have been infected. And it's that group that we refer to as having latent TB infection and we try and prevent that kind of later development of disease by, by giving preventative treatment. Oh, I'll take note of that. So I'm sure you're familiar with the typical clinical features of TB, which is persistent cough, weight loss, night sweats. Most people have pulmonary disease. But of course, in the UK, a significant proportion of extra pulmonary disease and the symptoms that they present will depend on where the site of disease is. Um But actually, it's important to remember that although those are the classical symptoms that people will tend to present with many people present without, without those classical symptoms or without any symptoms at all. And some people can present with definitely active TB who are completely asymptomatic and even have normal blood tests. So, subclinical disease where people definitely have active TB disease, but no symptoms is an important problem in TB control because obviously it's very difficult to pick up those people unless you have quite extensive screening methods to try and pick them up. So the absence of symptoms definitely does not in someone doesn't have TB. So here's some pictures illustrating how to test for TB. That's Robert Kock in the 19th century. And there on the other picture is someone with a more modern microscope as you can see much tier desk these days than in the 19th century. That's good. But in many ways, things haven't moved on that much in many settings. So Sputum smear which literally means looking under the microscope to see if you can see how it, but it is still the standard test for TB in many settings. The good thing about Sputum smears is they're quite quick and easy to do and they have a sensitivity of about 50 or 60% for detecting pulmonary TB. Although that is lower in people with HIV, because they're less likely to have carry disease despite having more severe disease and more likely to die of it. So, unfortunately, it doesn't pick up the sickest of people. But nonetheless, a reasonably good test for TB and does correlate with level of infectivity. So we'll pick up the most infectious people. Those F smears can be graded based on how many bugs there are. So graded 123 plus smear positive so that we know how likely a patient is to have infected other people. Ideally, if you're trying to investigate someone for TB, ask them to bring in three different sputum samples on three different days that will give the best yield. There isn't much additional yield of bringing in more than three samples. But bringing in three rather than two is worthwhile doing speech and smears can't distinguish between live and dead bacteria. So aren't very good at uh as a means of following people up to determine whether they're getting better. And sometimes you can be misled because non tuberculous mycobacteria um can look the same and a few other organisms can as well. So we do have better and more modern tests these days to try and get that diagnosis of TB correct. We can do PCR tests which look for the genetic material of TB and can be analyzed directly from sputum samples to try and do so. The most commonly is platform is called gene expert, which can identify the presence of TB DNA and the gene that encodes rifampicin resistance. And so it can tell us whether or not an ISIS is sample is susceptible to has TB and whether it's acceptable to rifampicin or not within a few hours, which has been a big step forward in trying to make rapid and accurate diagnosis of TB. But the the kind of gold standard for diagnosis is to grow the bugs much more sensitive than smears and slightly more sensitive than APCR TB culture that can be done on solid cultures like the lo dentin slope to the top, but actually, that's quite slow and generally now preferred for cultures to be set up in automated liquid cultures such as the machine on the bottom there, where the TB sample, the sputum sample gets put into a little tube and then grown in an incubator. And then if the bugs growing it, it flags up in the machine and someone can then determine if there's TB in that sample which then get sent off to a reference laboratory. And in the UK, what happens next is that the genetic material of those TB isolates is then sequenced and literally the whole genome is sequenced, which allows identification of genes that confer drug resistance and also allows identification or linkage of clusters of cases where TB cases are closely linked to allow us to determine whether there's a likelihood of transmission between people and perhaps go looking for further cases if there does seem to be an outbreak with in which a lot of local transmission has occurred. So treatment for TB hasn't changed very much in the, in the past few decades. Um consists of four drugs taken for two months. Er, so is Rifampicin for Aid Andam Butt and then the is, and I and Rifampicin continued for a further four months. We extend that treatment duration to 12 months if someone has CNS disease or if they have disseminated TB, and we worry that they might have CNS sites of disease and sometimes we extend it beyond six months if someone's got extensive pulmonary disease because we think lots of mycobacteria may need longer to cure them. Occasionally, we add steroid medication. Um We think the inflammatory response is causing a problem. And so that tends to be in CNS disease or meningitis or a CNS tuberculoma or there's pericarditis because it reduces the risk of getting a constrictive pericarditis which can happen. Otherwise, there is evidence over the last couple of years, it's been published suggesting that people with mild disease um and it can be treated for less than six months. So with a four month regimen, there are now two good studies in adults and in Children looking at treating mild disease with a four month regimen, which is probably where things are moving. Although at the moment, that's not standard practice in the UK, very important to make sure that people take their medication treatment. AOR is a core part of what we do in TB treatment. So people are managed alongside TB nurses who are very experienced in trying to support people with TB therapy and if we're worried about adherence, we do encourage patients to have directly therapy that can be done literally directly observed by a patient coming into clinic or adult worker, going to them to observe them taking the tablets or more conveniently these days, people can use video observe therapy whereby they're observed taking a tablet online, a video platform a bit similar to this that actually has been shown to result in a greater proportion of doses being taken because it's clearly much more convenient to do than trying to do that in person. Of course, doctor or what is always going to be uh voluntary. If patients don't, don't want to do that, don't want to take their therapy, it's very difficult to, to then ensure that they do. So. So what can we do to try and reduce the TB numbers to prevent TB? Well, um active case finding, trying to find the cases can be helpful, as I've said in the UK, pre entry screening is occurring or if you migrate to the UK from a high TB incident country, you have a chest X ray to look to see whether you might have before TB, before you come, we do contact tracing. So anyone who's a household contact of someone with Pulmonary TB disease is then tested to see whether they might have acquired infection and might benefit from preventative therapy. And we give latent TB treatment or TB preventive therapy to people who have evidence of, of, of prior TB exposure or infection depending on how you see it uh which can reduce the risk of, of developing active TB disease in the future. Yeah. Uh as I say, contact tracing um will be done for people who are contact or contacts with P or laryngeal or TB. Previously, that was done with a tuberculin skin test. I think most services have now moved over to using blood tests, gamma release assays, which are slightly more specific for TB exposure and a lot more convenient because they don't require the patient to come twice to come and get their skin test read, which needs to be done within a particular time period. And often patients didn't turn up within the right time period. And hence, the test was not effectively read preventative therapy that usually consists of either taking three months of isis and rifampicin or six months of isoniazid. Those are the ones those are regimens recommended by the current nice guidelines that lots of other regimens have been, have been used of different different TB drugs um as well. So brief summary of tuberculosis, which remains an important clinical problem in the UK and globally, clearly not, not very common in the UK, but it's still seen particularly in urban centers and an important thing to know about because missing it can be very significant for that patient. Often diagnoses are delayed for that reason. And so you do need to think about TB, in many different clinical situations, even if the likelihood isn't very high, it's worth thinking about it and perhaps doing tests to try and exclude it. Appropriate sampling and sending appropriate investigations is key. Unless you try and look for the mycobacteria, you won't find them. And it involving specialist TB services is often useful in the diagnostic workup. And essentially in the management, if you've made a diagnosis of TB and that I think is it, I've managed to cover those four topics within the hour allocated. Do me, um, please do, tell me if you've got any questions about any of that. 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