There were many themes for therapies presented at the 2018 American Academy of Allergy, Asthma & Immunology (AAAAI) and World Allergy Joint Congress in Orlando, Florida, but few rang as loudly as the call for environmental intervention as an adjunct to medication for patients with asthma and allergies.

In a plenary presentation, Elizabeth Matsui, MD, MHS, a professor of pediatrics at Johns Hopkins Medicine, proposed that while the 

 has been met with skepticism, it may be due to the way the data are interpreted. While there have been conflicting results from clinical trials—Matsui pointed to 6 examinations, half successful, half failures&mdash;she noted that clinicians can make sense of these otherwise confounding results.

“We need standardized reporting framework. Interventions may have clinical effects through pathways other than allergen reduction, so interventions should be interpreted in the context of this step,” Matsui said.

While the current guidelines pay little heed to the use of environmental intervention, Matsui noted that in a survey of AAAAI members, 75% reported that they emphasize the importance these interferences with their patients and 66% responded that they provide educational material to patients to aid their practice of it. That majority may be recommending these methods to their patients simply because 

—especially when used in conjunction with inhalants.

“Fluticasone/salmeterol—the combinations are about $3300 per year. It gets a little bit lower when you do the medium dose and the low dose, about $2500 versus $2100,” Wanda Phipatanakul, MD, MS, a professor of pediatrics at Harvard Medical School and the director of the Asthma Clinical Research Center at Boston Children’s Hospital, said during her presentation. “That’s about $1500 per year. The [environmental] intervention, even [when it is] multi-faceted, actually only cost about $1500 annually. [In Morgan’s study in 

] that intervention lasted through the year, and even in the year after the intervention.”

Not only are they successful in lowering the amount patients need to spend, simply educating communities on allergens can prove cost-effective. Phipatanakul pointed to a study published in 

that showed emergency department visits decrease by 46.6%  and hospitalizations decrease by 43.4% over the course of a year for 300 pediatric patients with asthma, while also reducing costs by $878 more than the comparator group.

Additionally, those results were carried over the second year, with an additional average savings of $585 in year 2. “It really had a dose-response decline in cost, and the return on investment was great. It was 50% above break-even costs. It gained a lot of interest—seeing that something that simple could make such a difference,” Phipatanakul said.

While simple education for patients about the interventions can be, and have been, successful, David B. Peden, MD, MS, stressed at the AAAAI/WAO Joint Congress that 

 for environmental allergens can provide even better clinical outcomes.

Peden held that during the 1996 Olympic Games in Atlanta, Georgia, policies restricting pollutant output during the games greatly impacted the asthmatic population in the state. In that timeframe, data revealed that hospitalizations for asthma were reduced by 19.1%, and the number of emergency care visits and hospitalizations decreased 41.6% per day (4.23 per day at baseline; 2.47 per day during the Olympic period). Additionally, during the Olympic period, pediatric emergency department visits decreased 11.1%.

Peden noted that the answer is simple: Cleaner air means healthier lungs.

“Show up in to these [municipal] meetings a white coat, tell them you're a doctor, and help generate change,” Peden, the Andrews Distinguished Professor of Pediatrics, the senior associate dean for translational research at the University of North Carolina, and the director of UNC’s Center for Environmental Medicine, Asthma, and Lung Biology, said. “Tell them what we know—that air pollution is damaging and, in some cases, is killing people.”

Matsui somewhat echoed the sentiment, emphasizing the potential of environmental interventions in places like schools, where they can be beneficial for not just the pediatric patient with allergy or asthma, but for the entire population of the school.

All told, she concluded that the next steps are to alter health care delivery and payment reform, to develop population-level and policy-based interventions, and a framework for random clinical trial reporting.

“Interpreting environmental inventions in random clinical trials is challenging because of mediation by allergen reduction, and population heterogeneity,” she said. “But environmental inventions are effective among pediatric populations when the targeted exposure is reduced, and emerging evidence supports single allergen interventions.”

Environmental Interventions Are Effective in Both Cost and Outcomes

How important is investigation into the effect of pollution on children's health?

I think that's an unmet need. There haven't been a lot of big, successful, preventive pollution studies that we've done. I think it's good use of NIH-funded initiatives — which are our tax dollars &mdash; to try and find in a comprehensive, rigorous way, something that works. As a researcher, as a pediatrician, that's a passion of mine. I want to see if there's any way we can modify disease development, and then let the community know if these measures are available.

The challenge is these studies take time, because to prevent something you have to give when the child's at risk and follow them to see for outcomes. So I think, as researchers, if we continue to move the field, we continue to work on treatments that prevent or reduce disease for those that already have disease, these are things we continue to look at. It's taking things from basic science models and into the clinic. My research is mostly translating these findings into clinical research. I'm focused on bringing things that make sense scientifically and testing. That takes funding, that takes support from the NIH, to find these treatments we can't get without them.

Then, it involves centers and networks to get together to help approve these trials and move the field forward. It's really team science now — it's not so much you can have one person looking to find the answers to these things. I think it's great they're now forming groups of network.

Wanda Phipatanakul, MD, MS: The Need for Pollution-Based Health Research

What makes monoclonal antibodies so beneficial for asthma/allergy conditions?

In the last years, we have figured out pathomechanisms — how is it working, why is it a severe disease. A common theme is it has to do with a certain constellation of cells, of T-cells, or elaginophocydes, or eosinophils. It sounds difficult but it's a specific form of inflammation that refined it. The more this is regulated, the more disease the patient has. 

These targets are known nowadays. First, we can endotype the patient — that means we understand which patient is a suitable patient for such therapy. And the therapies target specific molecules in this type 2 inflammation. So, people who do not have type 2 inflammation, we don't have solutions for them at the moment. It's really the minority &mdash; the majority has type 2 inflammation. And we have monoclonal antibodies targeting specific molecules, such as interleukins 4 and 13, in that case. 

If you do that, you dampen down the T-cell activities, the inflammation cools down, the message to the glands is stopped, they don't produce as much secretion, there's not so much formation anymore. And this, by and by over weeks, really cools down the inflammation to a fact that the nasal polyps partially or totally disappear.

Claus Bachert, MD, PhD: Why Monoclonal Antibodies Work for Asthma

Two recent presentations reported improved control of asthma symptoms of patients who switched from omalizumab (Xolair) to mepolizumab (Nucala).

The new analyses of data from the OSMO study — an open-label, single arm study of patients with severe eosinophilic asthma that had not been optimally controlled with omlizumab &mdash; were presented at the joint meeting of the American Academy of Allergy, Asthma and Immunology and the World Allergy Organization (AAAAI/WAO) in Orlando, FL.

Frank Albers, MD, PhD, Global Medical Lead, GlaxoSmithKline, Chapel Hill, North Carolina described improvements in asthma control, quality of life and lung function outcomes at the primary endpoint of 32 weeks after switching biologics.

"Mepolizumab and omalizumab are indicated in distinct asthma prototypes, although some patients with severe eosinophilic asthma (SEA) are eligible for both biologics," Albers told attendees.

The OSMO multi-center study identified 145 patients with SEA who had experienced at least 2 exacerbations in the year prior to study screening despite regular high-dose inhaled glucocorticoids and other controller medication(s) including omalizumab for at least 4 months. The study group had not achieved targeted control of symptoms for an average of 2.5 years while treated with omalizumab.

At baseline, patients with poor asthma control, corresponding to Asthma Control Questionnaire-5 (ACQ-5) score of at least 1.5, discontinued omalizumab and began mepolizumab 100mg subcutaneously every 4 weeks for 28 weeks.

Albers reported that at week 32, the ACQ=5 score had improved by -1.45 points, with 77% experiencing the minimal clinically important difference of at least 0.5-point reduction. Similar improvement was found in the St George's Respiratory Questionnaire (SGRQ) total score. The pre- and post-bronchodilator forced expiratory volume in one second (FEV

) improved at week 32 by 159 ml (Standard Error [SE] ±41) and 120 ml (±36), respectively.

"In uncontrolled patients with SEA, switching directly from omalizumab to mepolizumab resulted in clinically significant improvements in asthma control, health status, and lung function," Albers concluded.

In a separate presentation on analysis of exacerbations and safety outcomes, Dmitry Galkin, MD, PhD, Global Medical Director, GlaxoSmithKline, Raleigh-Durham, North reported that there was also a clinically significant reduction in exacerbations, as well as exacerbations requiring emergency department (ED) visits or hospitalizations. In comparison to 3.26 exacerbation events and 0.63 ED/hospitalizations in the 12 months prior to screening, there was 1.18 and 0.19 events per year, respectively, during the study period. Galkin reported that there were no safety issues arising during the study.

"Patients participating in this (OSMO) study suffered burdensome day to day asthma symptoms and frequently required access to urgent care when their asthma symptoms significant worsened," Ken Chapman, MD, Professor of Medicine, University of Toronto and a co-investigator in both reports, said in a statment. "This study is a valuable addition to our understanding of how to manage patients with biologic therapies."

The presentation on asthma control, quality of life and lung function outcomes from the OSMO study was 

 and the presentation on exacerbations and safety outcomes was 

  at the AAAAI/WAO joint meeting in Orlando, Florida, March 2-5. 

Mepolizumab: A Proven Alternative to Omalizumab

A study in US children and a concurrently published UK study in adults and adolescents examined whether substantially increasing dose of inhaled glucocorticoid for early asthma symptoms can avert full-blown exacerbation.

The studies differed in design (including quintupling a specified low dose in the US, versus quadrupling a previous maintenance dose in the UK) and populations, and they produced different results. While there was no reduction of asthma exacerbations found with high-dose glucocorticoid in the US children, some benefit was evidenced in the adult and adolescent population in the UK.

The study in 254 children aged 5-11 years of age was reported by lead author Daniel Jackson, MD, Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, and colleagues at multiple sites in the US including representatives from the National Heart, Lung and Blood Institute AsthmaNet. 

 at the 2018 American Academy of Allergy, Asthma, and Immunology/ World Allergy Organization (AAAAI/WAO) Joint Congress in Orlando, FL.

"In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes," Jackson and colleagues wrote.

The rate of severe asthma exacerbations was the primary outcome in the US study, and  time to the first severe exacerbation was the primary measure in the UK study.  Tricia McKeever, PhD, Department of Epidemiology and Public Health, University of Nottingham, Nottingham, UK, and colleagues reported that among the approximate 1,900 participants, 45% in the high dose ICS group experienced a severe asthma exacerbation in the year after randomization compared to 52% receiving standard dose, with the corresponding adjusted hazard ratio of 0.81.

"Our trial involving adults and adolescents showed that a temporary quadrupling of the dose of inhaled glucocorticoids at the time of worsening asthma control resulted in a lower rate of severe exacerbations of asthma than no increase in the dose (45% vs 52%),” McKeever and colleagues reported.

The children in the US study had mild-to-moderate persistent asthma and had experienced at least 1 asthma exacerbation treated with systemic glucocorticoid in the previous year. They received 48 weeks of maintenance fluticasone propionate (Flovent), 2 inhalations of 44mcg/inhalation twice daily, and randomly assigned to either 44 mcg or the quintupled dose of 220 mcg/inhalationations twice daily for 7 days at the early signs of loss of asthma control.

Jackson and colleagues found no difference between the groups in the number of exacerbations, or in secondary measures including time to first exacerbation, rate of treatment failure, and symptom scores. The only notable difference between the groups, they point out, was that the high dose group was exposed to a greater amount of glucocorticoid without apparent benefit.

The UK study compared time to first severe exacerbation after randomization to one of 2 self-management plans for episodes of decreased asthma control, that maintained or quadrupled their previous glucocorticoid dose in addition to increasing bronchodilator medication. Although the increased bronchodilator could have confounded  distinguishing between glucocorticoid dose effects, McKeever and colleagues attribute the difference in exacerbations to the temporary quadrupling of inhaled glucocorticoid.

In an editorial accompanying the studies, Philip Bardin, PhD, Monash Lung and Sleep Unit and Hudson Institute of Medical Research, Monash University and Medical Centre, Melbourne, Australia questioned whether the level of benefit found in the UK study warranted exposure to additional glucocorticoid.

"Given the adrenal suppression caused by quadrupling the dose of inhaled glucocorticoids, equivalent to a regular course of prednisolone, it will be difficult to convince clinicians that an exacerbation-prevention strategy involving high doses of inhaled glucocorticoids is merited," Bardin wrote.

 inhaled glucocorticoid dose in children and the study of 

 the dose in adults and adolecents to determine whether asthma exacerbations can be prevented were published online in the 

US, UK Studies Examine Whether Increasing Glucocorticoid Reduces Asthma Exacerbations

For reducing grass pollen allergy symptoms, more is better.

A 1-year follow-up of different administration schedules for recombinant grass pollen vaccine (BM32) indicated that more injections provided greater clinical benefit than less, according to a presentation at the joint meeting of the American Academy of Allergy, Asthma and Immunology and the World Allergy Organization (AAAAI/WAO) in Orlando, FL.

Petra Zieglmayer, MD, reported that in a placebo-comparative analysis of 3, 4, and 5 monthly-injection BM32 prior to grass pollen season, the subjects receiving 5 active injections demonstrated the greatest symptom reduction relative to placebo during the peak pollen period. 

No group sustained treatment effect into the next season, however.

Zieglmayer has previously commented on the rationale for developing the recombinant product, in an assessment of its mechanisms, safety and efficacy that she published with colleagues.

"Current allergy vaccines are based on natural allergen extracts which are often of poor quality — eg., varying allergen compositions, lack of important allergens, contaminations &mdash; and may induce severe immediate and late phase side effects," Zieglmayer and colleagues wrote.

Additional problems associated with the natural allergen extracts that prompted the group to develop a recombinant vaccine alternative included inconvenient treatment schedules, multiple administrations of gradually increasing doses and, in sensitive patients, the possibility of side effects preventing reaching a fully effective maintenance dose.

"Progress made regarding the molecular characterization of the disease-causing allergens has now opened the door for new forms of allergen-specific immunotherapy which allow reduced side effects and targeting of specific pathways of the allergic immune response," researchers wrote.

The researchers describe BM32 as a B cell epitope-based allergy vaccine, which is based on fusion proteins consisting of non-allergenic peptides derived from the IgE binding sites of disease-causing allergens (that do not bind IgE themselves) and PreS, a surface protein from hepatitis B which serves as a non-allergenic carrier protein providing T cell help.

In the trial reported by Zieglmayer at the congress, 124 subjects were randomized to receive a different number of monthly active or placebo injections in a 4-month period prior to the 2016 grass pollen season.  Symptoms were evaluated on a 4-point scale comprising 4 nasal symptoms (runny nose; blocked nose; sneezing; itchy nose) and 2 ocular symptoms (itchy/red eyes; watery eyes).

 In the primary measure of combined score from the Symptom Scores and Medication Scores (SMS), the mean daily SMS during the pollen peak following 3, 4, or 5 pre-season monthly injections of BM32 improved by 15%, 3%, and 25%, respectively, versus placebo. There was no further treatment effect demonstrated during the grass pollen peak in 2017.

"Five active injections demonstrated the best immediate clinical efficacy, but no sustained effect," Zieglmayer said. "BM32 was safe and well tolerated."

Clinical Efficacy of a Recombinant Grass Pollen Vaccine One Year after a 4 Month Treatment Course

Journal of Allergy and Clinical Immunology.

Unnatural Allergen Eases Grass Pollen Allergy

A study comparing asthma symptoms and risk factors among adult smokers and non-smokers was presented in the same week that a published study provided evidence of those symptoms varying with the age of initial exposure to smoking.

Bilun Gemicioglu, MD, PhD, from the IU Cerrahpasa Faculty of Medicine's Department of Pulmonary Diseases, in Istanbul, Turkey, presented a comparison of smoker and non-smoker adult asthmatics at the joint meeting of the American Academy of Allergy, Asthma and Immunology and the World Allergy Organization (AAAAI/WAO) in Orlando, Florida March 2 to 5, 2018.

Gemicioglu acknowledged that smoking is a well-known trigger for asthma patients, but explained that the study sought to compare the presentation of asthma symptoms between adult smokers and non-smokers, as well their risk factors and comorbidities.

The investigators identified 500 patients living in the urban area of Istanbul who had been diagnosed with asthma for at least one year, comprising 353 smokers, 88 ex-smokers, and 59 who had never smoked.  Each was surveyed on symptoms, habits, and circumstances over a year follow-up with a web-based data entry program.

There were no statistically significant group differences in reported symptoms such as a cough, wheeze, chest tightness, and dyspnea.  There were also no differences in such risk factors as pet sensitivity, home heating methods or presence of mold.

Comorbidities occurring in both groups included allergic conjunctivitis and rhinitis.  Smokers and ex-smokers did have a higher incidence of atopic dermatitis (13.9% and 12.7%) compared to non-smokers (3.4%), and smokers had, expectedly, a higher incidence of hypertension.

"Smoker and ex-smoker asthma patients of the urban area had similar asthma symptoms and risk factors," Gemicioglu told attendees, "but they had higher hypertension and allergic dermatitis comorbidities than non-smoker asthma patients."

In a study published online one day after the meeting in 

, Bircan Erbas, PhD, Department of Public Health, La Trobe University, Melbourne, Australia, and colleagues also acknowledge well-known links between smoking and asthma.

"There is a plethora of evidence to suggest that smokers compared to non-smokers have a higher risk of asthma," Erbas and colleagues observe.  "Therefore, we know that smoking is harmful for respiratory health when comparing with a reference group of non-smokers."

What has not been well studied, they point out, is whether those risks differ depending on when in life the exposure to smoking occurs. 

"The relative importance of early life smoking exposure, the age of starting smoking as well as total pack-years of smoking among ever-smokers is not known," Erbas and colleagues indicated.

Their study identified over 10,000 adults (5,348 men) from 29 centers in 14 countries who reported to be current or former smokers on the European Community Respiratory Health Survey (ECRHS I) initiated in 1991-1994.  The study cohort was stratified by the window of exposure: from maternal smoking 

 and smoking in the household during postnatal and childhood period to smoking in adolescence and in adulthood.

Among the findings was that respiratory symptoms and asthma were more frequent in adults if their mother smoked during pregnancy; and, in men, also if mother smoked during their childhood.  Wheeze and ≥3 respiratory symptoms declined with later smoking debut among women.

"Among ever smokers, smoking exposure in each stage of the lifespan show persistent harmful effects for adult respiratory health, while women appeared to be more vulnerable to an early age of smoking debut and amount of smoking in adulthood," Erbas and colleagues reported.

The study comparing asthma symptoms and risk factors in smokers and non-smokers was described in 

 at the AAAAI/WAO meeting in Orlando Florida, March 2-5.

Clearing the Air on Effects of Smoking in Asthma

Monitoring fractional exhaled nitric oxide (FeNO) in asthma patients with a history of exacerbations has been linked to a reduction of asthma-related inpatient hospitalization (IR) or emergency department (ED) claims, according to a new study.

In analysis presented at the 2018 American Academy of Allergy, Asthma, and Immunology (AAAAI)/World Allergy Organization (WAO) Joint Congress in Orlando, FL, researchers built on recent data that showed asthma exacerbation benefits through FeNO monitoring. In a recent meta-analysis study, FeNO monitoring was associated with 40-50% reduction in exacerbation risk for patients with asthma.

The meta analysis also indicated FeNO monitoring held potential for significant patient cost savings — an indication researchers attempted to verify through their IP/ED association study.

Led by Marc Massanari, PharmD, vice president of Global Medical Affairs at Circassia, the team ran a retrospective observational study of asthma-related claims from a Medicare database. Patients included in the study had at least 2 years of records following an asthma-related IP or ED claim, as well as history of an asthma-related event from within that year.

Of the 2,828 identified patients with asthma, 63 who met the inclusion criteria within the database had a FeNO test completed during the 2-year study. Crossover analysis of patients’ asthma-related IP/ED claims were completed before and during FeNO monitoring.

Researchers reported that 61 (97%) patients had an asthma-related IP/ED event prior to FeNO monitoring, while just 30 (48%) had such an event during FeNO monitoring. IP/ED claims per day prior to FeNO monitoring was 0.026 per patient (

< 0.003) — an estimated care cost of $12,368. In post-FeNO monitoring, IP/ED claims per day were 0.003 per patient (

< 0.0043), which costs an estimated $1340.

Researchers concluded that FeNO monitoring’s effect on IP/ED claims due to asthma was substantial, and the data supports estimates that the practice is a cost-effective measure for asthma management.

the impact of FeNO monitoring was a “dramatic effect” on patients with asthma.

“During monitoring, the likelihood of an attack moved out — in other words, it was extended &mdash; almost two-fold,” Massanari said. “I think it shows the benefit, that FeNO monitoring helps patients stay in better control and free of asthma exacerbation.”

Massanari explained that monitoring FeNO is important for asthma care because of its ability to uncover the airway inflammation aspect of the condition.

“There really is no other biomarker test on the market today that allows a clinician at the bedside to know how inflammation is in a patient’s lung,” Massanari said. “So it’s an important test, and I think it has a very large impact on the clinician to then assess the patient and improve their level of asthma control.”

Comparative Cost Analysis of Monitoring Exhaled Nitric Oxide (FeNO) in Asthma Management

Monitoring FeNO Reduces Asthma Hospitalizations, Saves Costs

How has inflammation changed the scope of asthma care?

It actually goes back to the early 1990s when the first asthma guidelines came out. Those guidelines were written because patients were not receiving sufficient anti-inflammatory therapy, predominately inhaled corticosteroids. So, the guidelines were really written to inform clinicians how to better treat patients.

So it's been around for a really long time, but the tools to access and optimize the inhaled corticosteroid therapy never really existed. Physicians typically rely on traditional tests — spirometry &mdash; that measure airway obstruction but don't have the ability to measure airway inflammation. That's why exhaled nitrous oxide is so unique as a test. Nothing else could do that. Typically, the gold standard for measuring airway inflammation is to look at sputum eosinophils. As you know, sputum eosinophils is very difficult, and it's really only in special centers where they will get patients to produce eosinophils so they can analyze the presence of eosinophils in the sputum.

So this is a test they give at the bed side, it's non-invasive, it's very quick, so that's why I think it's impactful. It has a great indicative potential, because it's easy to use, it's inexpensive, and it's very accurate.

Marc Massanari, PharmD: The History of Inflammation in Asthma

Patients with multiple types of allergic disease and patients with frequent allergic sensitization tend to have more severe cases of allergic disease, according to new research.

A team of researchers in Brazil sought to better understand the links between allergic sensitization and allergic diseases in children and noted that it has long been thought that allergic sensitization is a marker of allergy persistence. Additionally, the presence of multiple allergic diseases has been linked with severity.

To study the question, they performed a cross-sectional study of 470 patients, aged 6 months to 18 years, looking at medical histories and measurements of specific serum Immunoglobulin E (sIgE) for whole allergens and their components.

Those patients were divided into categories: rhinitis and/or asthma (n = 111), atopic dermatitis (n = 99), food allergies (n = 95), and wheezing as infants (n = 80). The researchers found that patients with a food allergy, atopic dermatitis, or multiple allergic diseases were more likely to have more severe disease. They also found that allergic sensitization to mites was present in all 4 groups.

David A. Hill, MD, PhD, a fellow in the division of allergy and immunology at the Children’s Hospital of Philadelphia, told 

 that much is already known about the topic of allergic sensitization and disease, and while he was not involved in the study, it adds detail by looking at the impact of having multiple allergic diseases.

“While there has been a fair amount of research supporting an epidemiological and pathophysiological link between the various allergic manifestations, studies of allergic co-morbidity on disease severity are comparatively lacking,” Hill said.

He added that experts are quite sure that the presence of one allergic manifestation in a patient increases their risk of developing another.

“However, we do not have a good understanding of why this is the case,” he said. “The relationship likely results from a combination of genetic, environmental, and immunologic factors.”

For pediatricians, these study results add to the body of knowledge but don’t necessarily change recommendations. Mitchell H. Grayson, MD, the director of the division of allergy and immunology at Nationwide Children’s Hospital, in Ohio, noted that allergic sensitization isn’t the same thing as allergic disease, and thus sensitization in and of itself doesn’t imply anything absent symptoms.

“In general, my recommendation to pediatricians is to not test for things to which the child is not having reactions,” said Grayson. “This has been a problem in the past with food allergy panels—children would be told they were allergic to numerous foods, only because of the test, but they actually were eating the foods without a problem, so they were sensitized and not allergic.”

Furthermore, Grayson noted that there is not much pediatricians can do to stop the so-called atopic march from atopic dermatitis to allergic rhinitis to asthma.

“As such, a child with 1 allergic disease could be considered ‘at risk’ for developing additional allergic diseases,” he said. “I do not tell pediatricians—or families&mdash;to worry about this, as right now there is little we can do to prevent the progression of the disease. We will just treat as they develop.”

Grayson, who also was not involved in the study, added a caveat: there’s some evidence that allergy shots given to patients with allergic rhinitis may prevent further progression of the march.

Allergic diseases in childhood: What allergic sensitization can teach us?

The Journal of Allergy and Clinical Immunology

Allergic Multimorbidity May Cause More Severe Allergic Disease

The makers of a new therapy aimed at depleting eosinophils say their phase 1 study has been a success.

Allakos Inc., a California-based biopharmaceutical firm, 

 last month at the Joint Congress of the American Academy of Allergy Asthma and Immunology and the World Allergy Organization, in Orlando, Florida.

The therapy, AK002, is a humanized Siglec-8 monoclonal antibody that targets eosinophils in the blood. Eosinophils and mast cells are believed to impact the body’s immune system response and are believed to play a role in the pathology of a number of diseases, ranging from gastrointestinal diseases to atopic dermatitis and asthma.

In the double-blind, placebo-controlled study, healthy patients were given AK002 or placebo intravenously in 7 different dosing groups. The therapy achieved its primary endpoint for this study, proving to be safe and well-tolerated. Only mild to moderate infusion reactions were reported, but they resolved quickly, according to the company.

However, the therapy also showed that eosinophils were completely depleted in the blood 1 hour after dosing, regardless of the dosing level. In the 2 highest dosing groups, eosinophil depletion continued for 28 and 84 days, generally increasing with increases in dosing.

AK002 is being investigated as a treatment for eosinophilic gastritis, with or without eosinophilic gastroenteritis. There are currently no approved therapies for those conditions. However, there are therapies for other eosinophilic disorders, such as eosinophilic asthma. Those therapies take a number of different approaches to attack this category of disorders.

Eosinophils help fight off infections and usually make up less than 5% of the white blood cells in the body. Eosinophil levels can become elevated, sometimes due to infections, allergies, or certain gastrointestinal disorders. In some cases, however, eosinophils are elevated and there’s no apparent cause. According to the American Partnership for Eosinophilic Disorders (APFED), such patients may have an eosinophilic disorder.

Many eosinophilic asthma patients respond well to traditional asthma therapies, but a trio of biologics have been developed and approved specifically for eosinophilic asthma. Two of the 3—Mepolizumab and Reslizumab&mdash;work by limiting the bone marrow’s ability to produce eosinophils.

Those 2 biologics were approved within the past 2 years. Gerald Gleich, MD, an eosinophil expert at the University of Utah and a member of the board of directors for APFED, told 

 it’s too early to know what unmet need remains in the eosinophilic asthma community because the unmet needs are “evolving and still being determined.”

“In time, we will have a better understanding as to the long-term effectiveness of these treatments, and how patients are responding to them,” he said.

Gleich added that it will also take time to fully understand the long-term effect of the eosinophil-depletion strategy, in particular. Bradley A. Becker, MD, a professor of allergy and immunology at the University of St. Louis, said an area where early intervention appears to make a difference is with allergen immunotherapy shots.

"There is also data showing the use of allergen immunotherapy [such as allergy shots] in pediatric patients with allergic rhinitis allergic to 1 inhalant allergen can prevent the development of multiple allergies," Becker said. "There is also data the use of allergy shots in children with allergic rhinitis can prevent the development of asthma."

Gleich noted that not all patients will respond favorably to any particular treatment, though he said thus far, the approved eosinophilic asthma therapies appear to be very well tolerated. The major drawback, he said, is the high cost of biologic medications.

Eosinophilic Disorder Therapy AK002 Shows Success in Phase 1

Jonathan Spergel, MD, PhD, a professor of pediatrics at the Children’s Hospital of Philadelphia, sat down with 

 to discuss the overall goal of the AAAAI/WAO 2018 Joint Congress, the biggest and his favorite themes at the conference. He also discussed his biggest clinical takeaways from the meeting and his favorite speaker.

The focus for the most recent meeting down in Orlando, for the American Academy of Allergy Asthma & Immunology, was the role of the environment, sort of a history of asthma, and really, sort of the microbiome involvement in the environmental factors that really sort of lead to asthma, or potentially make asthma worse.

My favorite sessions at the last meeting were, I would say, 3 big ones. One was a full-day course, it was a full-day seminar on eosinophilic esophagitis. It was sort of the common highlights of the meeting and what was changing in the field. There are some changing names, definitions, which to me was very interesting. A second big theme was the presidential symposium, which was on the environmental risk factors of asthma, and the third big thing was on the atopic march, which is sort of what predisposes to asthma.

The most valuable thing that I got from these meetings to me personally—and I'm going to talk about this and from 2 perspectives, 1 is from a clinical perspective, and the other is sort of a basic-science-research perspective. From the clinical perspective, is really in the area of 2 things. One was atopic dermatitis&mdash;there's a whole new birth of biologics in the field and this is sort of 1 of the big highlights that are advancing the field, all these biologics and atopic dermatitis in asthma. So that was one big area to me, trying to look at their clinical effectiveness.

Then the second one, from the basic science perspective, is this whole idea of the microbiome, where does the microbiome play, and the weird elements that exist. When we think of microbiome, the idea is really advanced a lot. Originally, when we talked about the microbiome, we thought about it as purely as just classifying and saying, “hey we have this bacteria here, this bacteria here, this bacteria on the elbow, this bacteria on the skin, this bacteria in someone who's sick.” And we're realizing it's a lot more complex than that. It's not only which bacteria, it's the diversity of the bacteria. It's not only bacteria—now we think of other microorganisms and there are viruses and fungi, and they’re all interacting. The diversity plays such a key role in this and it changes over time.

This is sort of thing that I really, from a true science, from a basic science perspective—it’s not really ready to come out for clinical science, but it's really changing of some of our fundamental knowledge on how disease occurs.

For every individual present at the meeting, there's going to be some individual speaker that's going to resonate with them and has this particular thing that creates a light bulb that goes off in their head, and that really depends, I think, on the individual. For me, for instance, Dr. Thomas Platts-Mills, really creates an interesting way of looking at things, but I can’t really say—it depends on the individual. What they're interested in, and how that message resonates with that individual. But one of my favorite speakers is always Dr. Platts-Mills.

Jonathan Spergel, MD, PhD: The Takeaways from AAAAI/WAO 18

 to discuss the role that environmental controls play in the treatment of allergies. He also dove into the challenges of utilizing of cost-effectiveness strategies in different areas.

When we think about the role of environmental controls—these are like those dust mite covers for your mattress and pillow, removing cockroach dander, decreasing cat and allergen exposure&mdash;the data is very confusing because it's not consistent. When we looked at dust mites, in a lot of the studies, the control group had done mostly environmental controls already, so you weren't really decreasing things too substantially. But when you actually decrease things substantially, it makes a difference.

So now we want to think about this in 2 different ways. When we think about environmental controls—if you're allergic to a cat and you move the cat from the environment you're going to do better, but the opposite also occurs, if say, you're not allergic to a dog and you will always avoid the dog and then get exposed, you're actually more likely become allergic to a dog. So again, sort of this whole idea is figuring out what to do when.

That's what the studies have shown. That having 2 big dogs in the house would make you less allergic, but if you're allergic to the dogs, you have to get rid of them. You need to know exactly where you are. That's why the environmental story is not so simple. It's not like, “oh no cats and no dogs.” For some people, it's good to have a dog, and for some people, it's bad to have the dog, so you need to figure out which pile you are in.

When we think about the cost-effectiveness of medications and environmental controls, there are 2 big pockets we tend to think about. Of course, it's a very complex issue because are you just looking here in the United States? This was the world allergy meeting. It's a completely different answer if you're looking in a poor area of Africa if you’re comparing it to Europe. Or if you're looking in Southeast Asia, or you're looking in Taiwan, or China, or Singapore, or Brazil. Every area has different cost-effectiveness issues, so when you think about cost-effectiveness, it's a very complex issue.

Are you comparing just the cost of medicine, and to what? If I say this medicine costs X dollars and by giving someone X dollars they're doing better, so they're having fewer symptoms—what's the cost-effectiveness of making people feel better? People need to consider work, absenteeism from work, kids going to school, future incomes, cost of hospitalizations. So, what's your measure that you're comparing it to? That's why it gets really complex.

When we do cost-effectiveness, you need to make sure what you're comparing apples to apples, and you're comparing things from one thing to another. It’s a very tricky issue and it's also very dependent on what's available and what you can do. We know some medications, like oral steroids, are very cheap and very effective but have lots of adverse effects. So yes, they’re cheap, yes, they're effective, but you would never prescribe them to some people because the adverse effects are too high.

You have to figure all these things out, and I think we when we decide what is cost-effective, you need to look into all these things. One of the hardest things to figure out—it's easy to figure out how much you decrease hospitalizations because that's a very concrete thing, but an improvement of the quality of life is a very tricky thing. How much is it worth for society to make someone feel better every day? Not cough, not sneeze, not itch, not have a rash, and have a more productive life. What is that to society? Until we can really sort of agree on that issue, a lot of the cost-effectiveness research is a little hard to tell about&mdash;it depends on the eye of the beholder.

Jonathan Spergel, MD, PhD: Environmental Controls and Cost-Effectiveness in Allergy

 in Orlando, Florida, to discuss the issue of personalized medicine in the treatment of allergy and asthma, and how most allergic diseases need an interdisciplinary approach to achieve proper treatment.

I think one of the biggest issues in the future, when we think about clinical care, is this issue of personalized medicine because not every patient is the same. We know the difference between mild patients, moderate patients, and severe patients. The mild patients—some can be treated with sort of as-needed medicines and really aren't at risk to progress to more severe disease, while other patients are, if we don't treat them aggressively with [regard to] the mild symptoms&mdash;they're going to progress to more severe disease. 

But then, even with the severe diseases, some severe patients will work well to this treatment and some other ones will work well to that treatment, and some severe patients will end up developing this complication while some of them will not. I think that's going be one of the key things when we think about in the future in terms of therapy and the diagnosis, is deciphering that out—understanding these, what we call endotypes and phenotypes&mdash;who is sick, who is at risk. 

So if you're at risk for, say for food allergy, you are at risk for a severe life-threatening reaction and we need for you to be really careful, avoid the food, and always carry your epinephrine devices with you. [Meanwhile,] you, yeah, if you eat a little bit of a food by mistake, you break out in hives, but we don't need to worry about it with you too much. [It’s] understanding that difference.

Same thing for asthma. You have mild intermittent asthma, you can take medicine as needed. You're a severe dependent asthmatic, and you are at risk for complications, so I need to put you on a biologic—or you're a severe asthmatic, but you’re really controlled with just a combination therapy. So separating that and understanding that, early on, understanding the response to the therapies would be one of the key things I’ll think about in the future.

For treating most allergic diseases, it is often better to do it with an interdisciplinary approach, whether it's asthma, atopic dermatitis, eosinophilic esophagitis. The advantage of this multidisciplinary approach is, depending on each individual disease, you can look at each thing [individually]. 

For example, for atopic dermatitis or eczema, having an allergist and dermatologist and a psychologist really will help the different aspects of disease. A lot of patients with atopic dermatitis have a lot of anxiety [and] behavior issues. You have a rash that's very visible. They have very low self-esteem. They're up at night scratching and itching, so they don't sleep well. They get depressed. So, having a psychiatrist to work with those issues, and working on those things really will help [the] patient’s overall health, and having an allergist and dermatologist—there's slight [differences and it’s] 2 different windows looking at the same disease.

Classically, the dermatologist will focus more on contact dermatitis—a little more so like, “hey, maybe this moisturizer is really causing the problem because he's reacting to the moisturizer,” while the allergist might say, “maybe it's actually that cat in the house” or “they’re allergic to egg, that’s triggering the problem.” Using that multidisciplinary approach, and having multiple people looking at the window, you can make people better. 

You can see the same thing with asthma using multiple physicians or having other providers, such as a psychiatrist, or a social worker. Working on compliance, looking at the home. For asthma, sometimes we can think about the home environment, [and] what you can do for home environment, what things you can do inside the home. You can have someone who's an expert in that [come in] to really look at that, while maybe the physician is more focused on the medical aspects, [and can say,] “hey, this is the right medication.” 

So using that interdisciplinary approach, you can really, not just treat the 1 disease, but the whole person and figure out what's best for that 1 person, and to truly treat them as an individual.

AAAI/WAO 2018 Perspectives

EP 1: Environmental Interventions Are Effective in Both Cost and Outcomes

EP 2: Wanda Phipatanakul, MD, MS: The Need for Pollution-Based Health Research

EP 3: Claus Bachert, MD, PhD: Why Monoclonal Antibodies Work for Asthma

EP 4: Mepolizumab: A Proven Alternative to Omalizumab

EP 5: US, UK Studies Examine Whether Increasing Glucocorticoid Reduces Asthma Exacerbations

EP 6: Unnatural Allergen Eases Grass Pollen Allergy

EP 7: Clearing the Air on Effects of Smoking in Asthma

EP 8: Monitoring FeNO Reduces Asthma Hospitalizations, Saves Costs

EP 9: Marc Massanari, PharmD: The History of Inflammation in Asthma

EP 10: Allergic Multimorbidity May Cause More Severe Allergic Disease

EP 11: Eosinophilic Disorder Therapy AK002 Shows Success in Phase 1

EP 12: Jonathan Spergel, MD, PhD: The Takeaways from AAAAI/WAO 18

EP 13: Jonathan Spergel, MD, PhD: Environmental Controls and Cost-Effectiveness in Allergy

EP 14: Jonathan Spergel, MD, PhD: Interdisciplinary Care and Personalized Medicine for Allergy