To effectively manage this common chronic disease in children, providers must have a firm grasp on categorizing the condition and how to step therapy up (and down). In this guide, pediatric pulmonologist Ngoc Ly, MD, MPH, presents clear definitions; delineates factors in difficult-to-treat asthma; offers keys and caveats on using SMART therapy; and discusses options for severe asthma, including new biologics.
And for those of you who don't know me, my name is not likely. I have been at UCSF for almost 15 years and I see patients down in San Mateo as well at Mission Bay and Oakland. All right, so let's jump to I have really no financial disclosure about this topic. So again today I'm gonna discuss asthma management recommendations by NIH and provide some alternatives to think about. Um talk about factors that may contribute to uncontrolled and difficult to treat asthma. And then if we have time I can review uh the severe asthma treatment options that are available today. So let's talk close about the preschool weezer which is a group of patients that you all see a lot. Uh These are Children between the ages of 0 to 4 years. Um They only wheeze with respiratory track infections and have no symptoms in between infections. Um They have at least three episodes of wheezing triggered by infection in their lifetime or have two episodes in the past year. Now this is the definition by NIH and you know clinically there's some variability in that of course and they must not be on daily and help cortical steroids and they have no prior hospitalization. So the most recent recommendation is that for this group of patients you can prescribe for death nine neb one mg twice a day, which is a high dose for 7 to 10 days at the first sign of a respiratory tract infection. What they've shown is that the benefit of this is that it reduced exacerbation requiring systemic steroids or emergency room visits. However, in the few studies that they have there was a potential effect on growth in the short term. Obviously there's no long term data so we don't know if there's long term consequences I would posed that you know not a lot of kids would need one mg of Destiny died. And so I think it would be reasonable to try 10.5 mg twice daily, which is a medium dose for 7 to 10 days. Now if you do that and you know the first time and the patients still have um trouble then the next time you can obviously use a higher dose now nebulizer, they're not easy to prescribe often in in a short period of time. So the alternative is to do in hell quarter for steroids via an inhaler uh similar dose compatible dose to be Destiny and you can do that twice daily for 7 to 10 days. Now the next group is what we describe a step one asthma. These are the mild, intermittent asthma. They have symptoms less than two times a month and the recommendation is the same. There hasn't been any change to the new guidelines um so that we still recommend short acting beta agonists or albedo as needed. Um But here's my question that I posed, you know if there's data in the younger age group with viral infections and we know that viral infections are the most common trigger for asthma symptoms. It might be beneficial to try intermittent I. CS for 7 to 10 days with your eye in this age group as well. So these are the age age group 4 to 11 years old and then the age 12 and older again the recommendation is the same. So no change for the mild intermittent asthma which are patients with symptoms less than two times per month. Now moving to the step two or the mild persistent asthma for those younger than 12 years of age. And green is the current guideline. Um and in gray is something to consider based on the data that's available today um for us to consider. So these are patients who have symptoms more than two times a month. So the recommendation currently is to put these patients on low daily I. C. S. And then when they have symptoms they can use all bureau as needed. And the regimen is 2 to 4 popsicle bureau every four hours. Now remember if someone's on a low daily dose I. CS there has been no data to show that when a child is sick doubling uh uh you know quite tripling or queen tippling. The dose is gonna make any difference. So the recommendation is please do not do that. If the patient have persistent symptoms may make more sense to give three days or five days of to make the cake of predniSONE. Now there has been some data to suggest that you know if if patients are non adherent and parents are insistent that they not on something daily that you could for these patients who refuse to be on maintenance. That you can consider using al bureau and I. C. S. At the onset of symptoms. And that could be 60 micrograms equivalent of black and methadone Every time you give Alberro you give back on methadone. And so you can do that every four hours. And data have shown that this is safe um and have minimal long term side effects for studies that have followed kids out to two years. So that's a potential option for patients who don't want to be on something daily. Alright for step two for those who are 12 years and older. The recommendations there are two options that was proposed in the new guideline. One same as the young age group to be on a low daily I. CS dose. The second is what I described is Is to use only um as needed. Okay and the the Max Dose I list here is that you shouldn't really exceed 960 microgram for 24 hours if you do then that suggests that the patient might need a short course of predniSONE. Now interestingly in europe you know getting a combination of I. C. S. Plus long acting out bureau is pretty easy. And so they recommend from the gina guideline is that you can just use the combined inhaler taking one puff Every four hours as needed. With a max of six paths for 24 hours? Okay. And the 164 um that I list here are simple court and that's the doses that we have. The 100.5 is the dual era and we'll come back to that in a second when I go to the next step. Okay? So for step three and four these are the moderate persistent asthma. So these patients have symptoms most days, they're waking up at night more than one times a week plus or minus low lung function. If you have the capacity to measure their lung function. This is where the drastic change occurred from the NIH guidelines, something called Smart which is single inhaler maintenance and reliever therapy um which um is basically I. CS plus for mineral. And the reason why for material is recommended over other types of long acting beta agonist. Is that the material have this short acting as well as long acting. And so that's the only inhaler that's recommended at this point I think although the NIH had went through the data and I understand the reasoning for recommending Smart but there's still a lot of confusion and so if your patient is adherent to the current management and they are well control on medium dose I CS plus alaba I find that you should continue them on um the current therapy and use rescue albedo as needed. Okay I'm gonna go through the next few slides on. What if you're gonna do? Smart what options you have for step 34 for those 4 to 11 years old, you have two options. Either you use symbol court 80/4 20.5 or DeLara 50/5 microgram. And the reason why these two inhalers are available is because they're the only inhaler right now that have for metal in it. Okay so um step three, the only difference between step three and step four. Step four you have low long function and step three you might have normal lung function. So you start a maintenance at one puff one times per day for step three and one puff two times per day for step four. And then every time they have symptoms they take the same inhaler one puff as needed. And it's important to remember that the Max Dose that is recommended for this age group is eight puff within 24 hours. Okay so they cannot exceed a puff for 24 hours. Now for the older age group basically the same concept except you use a higher dose 1 64 4.5 and 100 per five. Um Either one part 1 to 2 times a day or two puffs two times per day depending on the steps and then the same one path Pierre. And um now these kids 12 years and older the ma the max recommended doses 12 puffs for 24 hours. There is an asthma guideline that you can download um from the internet if you choose to use the smart guideline. Uh And basically the same green um orange or yellow and red. Um and you can click off what dose and and the recommendations of what the max is and what to do when a patient is in the red cell. So if you decide to do smart you could try to modify this form and use it on your patient. There's something to consider about the smart uh regimen first if you were to prescribe it. Um. Oops okay um there is like a warning. I don't know why my slide is not coming up. So give me a second. Okay so there's a warning that comes up. That symbol court is not used to relieve certain breathing problems and will not replace a rescue inhaler and a maximum of four parts per day if you exceed this it can cause death. And so of course the pharmacist is always gonna call you particularly if they're not familiar with the smart and I've done a few phone calls about this and so there's something to remember. So because it's off label for Pierre and use insurance might not cover it and so you have to use it case by case. Um each inhaler usually last a month and so you might not get approval for more than one inhaler for a month. The potential issues is that you know you might risk undoing previous teaching of having two inhaler one as a rescue and one as a maintenance. Although for patients who are non adherent and can't remember where they place their inhaler this might be a good option because they only have to remember one inhaler. You really need to have a clear asthma action plan to prevent overuse. Now I have seen patient who overuse and end up having adrenal suppression. So um is not completely benign now. The role of short acting beta agonist Alberro in in people who choose to use smart is unclear. Like do we not prescribe short acting or bureau anymore or do we still continue to prescribe sort of acting our bureau particularly at school um that patient might not have access to their inhaler then it may be difficult to track the frequency of ethnic you so that might be a problem. And then so you have a risk of either over using or under using uh if you use smart. So although clinical trial has been great and demonstrated safety but you have to remember these are short trial. Um and in a clinical trial unlike real life, there's always someone monitoring you. And so it's not the same. Okay. Again, most studies are in teenagers and adults and the long term efficacy and safety is unknown. Although the as I mentioned a short term safety seemed favorable. I think we need to have more real world data now, regardless of whether you choose to use smart or continue to use current previous recommendation for asthma control. It's very important uh that things to consider in managing asthma. They found that 49 to 54% of adults make at least one mistake With a metered dose inhaler. Okay. And it's much higher in in Children for dry powder or D. P. I. Up to 94% of adult who takes the D. P. I do it doesn't you know do it incorrectly. They either inhaled too forcefully or the way they shake the inhaler. It the pills drops out of the container. So these are the things that considered and then there's always confusion between what is a controller and a rescue inhaler. So this needs to be clearly explained to the patient. And I just wanted to show this picture of uh an image that show a patient taking the inhaler without a space. So and you can see the green is the um medication majority sits in the mouth or in the stomach. Now if you use a spacer although there's still some residual in the spacer you can see that there's more delivery to the lung. So always use a spacer for the metered dose inhaler. Even in adult patients. And then the other things you want to consider the particle size. Now typically the bigger particle size usually the dry powders tend to be larger. So it it's good at depositing at the large airway. but it's not very good at depositing in the small airways and as you get down to take it down, the size is adequate for sort of the small airway. But the extra flying particle like the al vesco or back on methadone, you can have um more delivery into the small airway where typically patients um have most of their symptoms in pediatric patients that tend to be the smaller airway. So something to think about and consider if you're using a high um a dry powder or larger particle size and the patients are not responding. Other factors to consider. And all of you already noticed that, you know, outdoor pollution play a role into asthma severity and asthma exacerbation. Uh tobacco smoke exposure also play a role in asthma development as well as exacerbation. Um indoor allergen. Um And tobacco smoke exposure also causes impaired treatment response and increase upper respiratory tract infection. What are some other things to think about? Certainly comorbidities can coexist with difficult to treat asthma, rhinitis and chronic sinusitis is have been demonstrated to coexist with asthma often. And so these things need to be treated obstructive sleep apnea has been associated with increased asthma symptoms, obesity. Now, interestingly obesity. Um there is new markers idea identify an association of of obesity and asthma and in fact even 5 to 10% weight reduction has been shown to improve asthma control. We know that there's a lot of psychological factors that um is associated with difficult to treat asthma obviously reflux um also contribute to um difficult to treat asthma. However treatment of asymptomatic reflux have not been demonstrated to improve asthma outcome. And then there's a very common association. About 40% of people who have asthma can have vocal cord dysfunction that can um masquerade as asthma as well. Okay so before you change, if a patient is not responding before you change anything, make sure you check inhaler technique, review adherence and barrier to use that like 80% of the time. That's where the problem um are. Then you identify potential risk factors, remove them, assess and manage comorbidities that we talked about. After my treatment strategy had to change device formulation use smart step up therapy. Now if they well control you could consider stepping down therapy but try to do it after three months because there's been data to suggest that if you step down too quickly. Oftentimes patients information will come back and they will have increased symptoms again. Now if you do all that and patients still have poor asthma control um you want to consider that they have severe asthma or that there's something else causing their symptoms and at this point you could consider them for photo evaluation um and therapy. Okay so I just have a few more slides and then um I'll open up to questions and more discussion. Now the severe asthma treatment. These are step five and sticks right And the step step five. The recommendation is daily medium dose I. CS. Laba. Some patients might have um a requirement for adding llama which is a long acting um mastery nick and um antagonist and PR. And Sandra. So there's no change in the guideline. For step five and six and step six is high dose I. CS plus lava. And some of these patients might need oral systemic cortical steroids as well. Now in step five and six you could consider biologics which are the new therapies that are available today. Um Similarly to steroids biologic may improve asthma symptoms, exacerbation rate, lung function um and reduce systemic corticosteroid need. But it has not been shown to modify the disease process per se. Uh And so if you discontinue the medication sometimes the symptoms will come back. What are some of these medications? Okay so there are six medications available for 18 years and younger. Three available for six years and older. And that includes Oh Melissa map. Uh Apple is a map and do pillar map now. Oh melissa has been around for a while. It has to be given in clinic and require observation because of the risk of anaphylaxis and formalism map required 13 to 26 Sub Q injection every 2 to 4 weeks on your weight and your I. G. Level mechanism map can be given at home. So is the the pillow map and both as a Q. Q. One is 13. Every injection given every four weeks and the other one is given every two weeks. So 26 injection for you. There are two for the 12 years and older venereal is a map and tested pillow map. Both can be given at home. Um Eight sub Q. Injection for venereal is a map every eight weeks. With the exception that the first three doses given on day one week for than week eight. And then tell us that um test the pillow map can be given every four weeks. Now. Religion map is a new one and has to be given at the infusion center because it's an I. V. Infusion and not sub Q. And that's given every four weeks. This risk um of uh cancer in this medication. So we often do not recommend it unless they have four response to the other five. Okay so okay so here's the indication. So formalism map. They have to have sensitization to at least one Elgin and an I. G. Uh elevated I. G. Level capitalism map. You just need to center field greater than 1 50 cells per micro leader. Um The pillow map you have to have moderate to severe eosinophilic or oral steroid dependent asthma. But they don't specify the level of us china fill. Uh venereal is a map is the same as Methodism app which is an unofficial count greater than 1 50 dependent on systemic steroids. Now the nice thing about selamat uh has a tele map is that you don't have to have a specific phenotype, so you don't have to have enough ill or allergic um, Mark biomarkers. And so it's available for those who have severe asthma that are not well controlled. And then wrestle is a map again your account and you cannot be used in combination with Globalism app or Methodism Map. So those are the six available medication for the severe asthma. I will end there and we can have more of an open discussion.