Pediatric pulmonologist Ngoc Ly, MD, MPH, unpacks the latest evidence on asthma medications and regimens for controlling symptoms and reducing emergency visits. Focusing on the right approach for different levels of severity, she discusses how to balance key management goals – such as lowering adherence barriers – and clarifies treatment guidelines. Includes an update on the option known as SMART (single maintenance and reliever therapy).
mm. A majority of people as you know with asthma have mild asthma. Only 5-10% of those would ask me truly have severe asthma. But when we think of complicated asthma with respect to risk and symptoms, we often think of those with severe asthma, But patients with mild asthma are also at risk of serious adverse events. In fact, between 30 to 40% of exacerbation requiring emergency care among patients with mild, asthma. triggers of asthma, exacerbation of variable and includes viruses, pollens, pollution and port hearings with vice is being the most common triggers and here in California. Unfortunately, wildfires have played a significant role in asthma exacerbation in recent years, parents tend to overestimate the child's level of asthma control, which could be a problem in terms of identifying Children with persistent asthma symptoms. An airway information is found in most patients with asthma, even in those with intermittent or infrequent symptoms. This is often seen on spironolactone testing that show evidence of my reversible airflow obstruction and finally, patient with exacerbation requiring an emergency department visits or hospitalization at increased risk for future exacerbation. And this is independent of demographic clinical factors asthma severity and asthma control as clinicians we use our bureau also known as short acting beta agonist or what I will uh refer to as sava in this talk we use it frequently to relieve acute asthma symptoms. But studies have shown that higher use of SABA only treatment is associated with increased risk for adverse clinical outcomes, including increased risk of exacerbation and lower lung function. in a study in 2012, the Publisher show that dispensing three or more canister of a zero per year which average about 1.7 tonnes per day. Is associated with higher risk of severe exacerbation requiring emergency department visits And dispensing more than 12 canister for you. Is associated with higher risk of death and this is really due to uncontrolled asthma. Regular or frequent use of saBA is also associated with adverse effect including beta receptor down regulation, decreased bronco protection, rebound hyper responsiveness and decreased broncho dilator response in v evil beta agonists including both short and long acting beta agonist have been shown to be pro inflammatory even at modest doses. And this is judged by increase in sputum inflammatory cells such as hell cinephile and this is associated with increased asthma hyper responsiveness especially to allergy. So there has been plenty of evidence that I. C. S. Is effective at treating mild asthma. Even at low daily dose I. C. S substantially reduces risk of severe exacerbation. Hospitalizations and deaths. It reduces airway inflammation, improve symptom control and reduces exercise induced bronco construction. Just of note. Children with mild asthma may not have noticeable or recognisable symptoms unless they are exercising and this can be misdiagnosed as exercise induced broncho constriction rather than mild persistent asthma. Now we know that I. C. S. Is effective. But here's the problem Up to 20% of asthma patients prescribed by six for the first time failed to have their prescription filled Non adherence rate among patient would ask my range from 30 to 70%. Usually patients are adherent when they are symptomatic and they under use a total non use when they are asymptomatic. There's also conflicting evidence regarding long term benefit of daily I. C. S. As the disease modified so people are less inclined to stay on daily medication when they're not symptomatic given the problem with adherence. Are there alternatives to daily I. C. S. For maintaining asthma? What about intermittent I. CSU's during acute symptoms in someone with mild persistent asthma is taking as needed. I. C. S. As effective as taking daily ideas with respect to the symptom reduction and risk reduction that I mentioned earlier and what approach should be taken for recommending as needed I. C. S. There are two options. One option is to use both Pcs plus saba inhaler during a. Q. On sets of symptoms. Or alternatively to use a combination of I. C. S. Plus lava that is on the market as a combined um inhaler. So in the next few slides a review data for each of these options and then come back to talk about what is recommended in the updated NIH and gina guidelines. Civil randomized controlled trials have been conducted on the use of as needed I. C. S. And SABA. But most studies of On patients 18 years and older. one study highlighted Hugh known as track Sir treating Children to prevent exacerbation of asthma. Study this intermittent use of I. C. S. And SaBA in Children between the ages of 6 to 18 years now. All these studies as you can see with less than one year duration and the primary outcome varies. For example in the best study the primary outcome was looking at morning peak exploratory flow rate. The Basat study was looking at time to first treatment failure and then the tractor study looked at time to first exacerbation requiring a predniSONE dose. Despite the differences in the study in general the studies found no significant difference in asthma control days quality of life and frequency of our bureau use between intermittent I. C. S. Posada and daily I. C. S. The disadvantage however of I. C. S. Lesabre is having to use two different inhalers back to back during acute exacerbation and there is currently no combined I. C. S. Lesabre inhale on the on the market. On the other hand as I demonstrate that is the combination I. CS plus lava inhaler on the market. But is there evidence for for its effectiveness and safety for as needed use for acute exacerbation. So all randomized control studies have been conducted using simple chord which is a combination of destiny and for Motorola and most studies again were conducted in teenagers and adults. I highlighted two large studies to large randomized control study here on this slide. The signal one study and the sigma to study These are two large study as I mentioned. The first signal one studies over 3500 patients which is 34 of weeks and the ass needed dose. Now if you look at the medium daily exposure to I. C. S. Obviously there was a significant reduction in the daily dose of I. C. S. And those who use it intermittently compared to those who uses daily in looking at the annualized rate of severe exacerbation. There was really no different. Although I didn't depict in the slide what the study shows that as needed. A combination therapy was superior using intermittent saba for acute exacerbation. So in the sigma to study the buddhist money for medical use as needed was non inferior to buddhist night maintenance therapy with regard to the rate of severe exacerbation. As you can see here And the change in Asthma control based on the a. c. q. five. Um It was a little bit better on the daily I. C. S. But not significant. Uh And for those of you who are not familiar with the A. C. Q. Five it consists of five questions about asthma symptoms they're in the previous week. Um In the A. C. T. That we often use its symptoms in the previous four weeks. And you have a score from 0-6. The minimal important difference .5 and you can see the difference between these two interventions only .11 and then finally again the Iranian daily those exposure to SCS is much lower in those who are on the s need podesta nightly. So in summary there is less asthma exacerbation and less day to day symptoms. With daily I. C. S. Um In mild persistent asthma which we know now with as needed therapy there is a risk reduction for severe exacerbation but you're sacrificing day to day symptom control on the flip side. You do have the advantage of improving adherence and lower I. C. S. Uh Mhm. We don't have them as within less than a year. Now the advantage of using the combined I. CS. Plus four monaural as compared to I Csaba again is that it's one inhaler instead of you to inhale. So based on these studies um changes to the current recommendations were made to the Gina Guidelines in 2019. Um And changes to the NIH guidelines in 2020 which I'll come back to. So how do we then adapt this intermittent I. CS. Plus Laba used to those with moderate asthma. Their benefit to reducing daily I. C. S dosed by using the combination of I. C. S. Plus Laba for control as well as for rescue versus the typical daily I. C. S. Lewis lava and as needed suburb. This is really the smart recommendations that is made by the NIH in 2020. So what is smart therapy stand for basically. It's a single inhaler maintenance and reliever therapy and it's in hell. Cortical steroids and former federal because studies were only conducted in the combinations of I. C. S. Plus former federal. Uh This is the inhaler that is recommended and uh just to emphasize for Metro is a long acting beta attractiveness but it also have a rapid onset of action. So it's the only inhalers used for for start therapy adult that contains former federal and not ones that contains sell mineral which doesn't have the fast onset of action. Okay so are there any evidence for this? So more again most studies are done in teenagers and adults With one randomized controlled trial that include Children between the ages of 4-11 years. Um And these were conducted in patients with moderate severe persistent asthma. Um And when they compare the smart study to same and hire those I. C. S. Lava plus as needed SaBA. They found that the smart study was superior when they compare smart with higher dose of various cassava. They also found that the smart um therapy were superior. So the potential benefit. So in comparison to current management in the studies that will review Smart they're smart treatment consistently reduce asthma exacerbation requiring unscheduled medical visits or systemic cortical steroids and in some study improve astra control and quality of life because not our study shows symptom reduction with smart treatment. I did not give Smart Appoint for symptom reduction reduce exposure to oral court oral cortical steroids and to I. C. S. Treatment suggests that smart treatment might reduce future cortical steroid associated home And in Children between the ages of 4-11 years and maybe a lower risk of growth suppression among those taking smart versus daily higher dose I. c. s. treatment. Again these were based on short term data. Were there any potential risk with the Smart therapy? None of the studies that were conducted found differences in documented harms between smart therapy and daily I. C. S. Or I. C. S. Lava was saba as a quick relief therapy. So based on these data, Smart is the preferred treatment for step three and above by NIH for Children age four and older And for Gina is recommended for those 12 years and older. So I said for model should be administered as maintenance therapy with 1 to 2 puffs once or twice daily depending on age as my severity and I. C. S. Does in the I. C. S. For medical preparation And 1- two puffs as needed for asthma symptoms. Now the maximum number of recommended pups per day is eight for those Children between the age of 4-11 years And 12 for those 12 and 12 years old and old. And these those recommendation is based on uh 4.5 micrograms inhalation which is the most common preparation used in the studies that were reviewed as well as this is the most common formulation in the United States. So finally data consistently showed that doubling quadrupling Quinn tripling I. C. S dose has no effect, no benefit in the management of acute exacerbation of asthma. In Children with mild or moderate asthma and should not be used. It is better to give three days of one make a cake per day of predniSONE rather than following this escalated regiment, I'll summarize them recommended change just by the NIH and gina guidelines in the next few slides. So this figure summarizes treatment recommendation for Children younger than 12 years of age. Gina recommendation is in orange. An NIH recommendation is in blue. The lower age limit for both the gina and the NIH is a little bit different. Gina recommendation is based on age of 6 to 11 and NIH is age 4 to 11 based on the one study that I described earlier. So for those with intermittent asthma, step one and mild, persistent asthma. Step to the recommendation for this age group have not changed in either guidelines now in the gina guideline Sabah as a rescue Therapy in this age group is recommended for step 2 to step forward. In contrast, NIH recommends SABA as rescue for step two but here's the change. NIH recommends smart therapy for step three and four gina on the other hand still recommend low dose I. C. S. Laba or medium, those I. C. S. For step three And medium, those i. c. s., lava or refer more expert advice in step four. So in the adolescent group the two recommendations differ In step one and 2 for gina. A low dose as needed. I. C. S. For mackerel is recommended for step one. In addition gina also recommend the use of I. C. S. For metal for all for rescue therapy for all steps. Okay I can see the reasoning for recommending as needed. Low dose I. C. S. For step one in the gina guidelines. Um But it's difficult to prescribe I. C. S liable for intermittent use in the United States due to insurance restrictions it's much easier in europe and other countries where you can purchase uh I. C. S. Therapy without a prescription. So for step one continuing to follow NIH guideline of as needed. Sabah probably make the most sense however is important too clearly distinguished those who truly have intermittent asthma from those with my persistent asthma who may have mild baseline symptoms but can have significant exacerbations such as don't viol infection. Okay so for step two in those 12 years and older NIH recommend either to treatment as part of steps to therapy. Either they daily low dose I. C. S. If patients are adhering to it or as needed. I see ESP Asaba for quick therapy. Okay one approach that they suggest is the intermittent therapy is 2 to 4 parts of our bureau followed by 80 to 250. Microgram of black methods own equivalent every four hours as needed for asthma symptoms. Now if you're going to prescribe as needed I. C. S. In step two. It is reasonable to use gina guidelines or gino recommendation. The evidence is convincing for intimate and I. C. S. U. S. For step two. And the advantages that I. C. S. For mackerel is easier than using two inhaler back to back which can be confusing. But the prescription of this depends on john now for step three and four. The two guidelines are similar since Gina recommends I. C. S. For metro as rescue therapy people or steps. So the Smart therapy in the uh NIH and they marked therapy in the gina very similar. So the as needed. I. C. S. Recommendation might not be appropriate for some individuals with asthma because of cost formulary considerations or medication and tolerance with respect to insurance. I. C. S. Is off label for pr and you. So coverage will vary case by case And remember that i. c. s. inhaler typically contain about 100. Actually it does contain about 120 pups. Poor inhaler. Uh So and most kids takes about 1 to 2 puffs twice a day. So a month's supply of I. C. S. Former federal medication. Um That is sufficient for maintenance therapy may not last a month if the inhale is used for as needed therapy as well. You may not get approval for more than one inhaler for a month With respect to smart there is a risk of undoing previous teaching of two inhalers, one maintenance, one rescue. It is, it is also difficult to assess frequency, appear and used without a monitoring device and then most studies on as needed. I. CS four slava have been conducted in those 12 years and older. Now. Long term efficacy and safety is unknown, although the short term safety data is favorable. I think we need more long term data to understand the cumulative those of I. C. S.