Krista Rossi

In patients with inadequately controlled eosinophilic asthma, lung function and patient-reported improved outcomes with reslizumab—a humanized anti-interleukin-5 monoclonal antibody&mdash;improves asthma exacerbation rates.

In a phase 3 double blind, randomized, placebo-controlled clinical trial presented at the 

American Academy of Allergy, Asthma & Immunology (AAAAI) 2019 Annual Meeting

 in San Francisco, CA, this week, investigators reported that patients with late-onset asthma receiving treatment with 

 had a 75% reduction in exacerbations and in hospitalizations due to exacerbations.

This was a statistically significant reduction compared to the overall study population (34% reduction in emergency room [ER] visits and hospitalizations) and those patients with earlier onset of asthma (12% reduction in ER visits and hospitalizations).

In addition, reslizumab treatment resulted in improvement in forced expiratory volume over 1 second (FEV

) and improvements in asthma control and quality of life via patient-reported Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Questionnaire (ACQ6), and Asthma Symptom Utility Index (ASUI). Although there were improvements in these areas among all patients treated with reslizumab, the results were most significant for those with late-onset asthma.

Due to the knowledge that exists between reslizumab and eosinophilic asthma, investigators conducted a post-hoc analysis in order to assess EOS levels and lung function among patients with low FEV

 reversibility (REV) to short-acting beta agonists (SABA).

In their analysis, the team used data from patients with screening EOS ≥400μL and REV ≥12% to SABA. Specifically, the data were pooled from a pair of 52-week placebo-controlled trials of intravenous (IV) reslizumab 3mg/kg (Q4wks) from these patients.

In the lowest-REV/highest-eosinophil (EOS) group, REV by baseline (day of first dose) EOS category and lung function treatment effect were analyzed.

The categorization of patients was conducted by baseline EOS <150 (n= 65), 150—<400 (n= 179), 400–<700 (n= 365), and ≥700/μL (n= 344) and by baseline REV <14% (n= 149), 14–<20% (n= 276), and ≥20% (n= 528).

Trends towards lower mean REV and a higher proportion with REV <14% were seen in patients with higher EOS levels, compared to patients with lower EOS levels.

 6.2% (1.1—11.2), FVC 144mL (-62–350), and FEV

 131mL (-96—357) included the treatment effects at 52 weeks (reslizumab vs placebo) in the low REV (<14%) group, which pooled the 2 highest EOS categories (≥700, 400–<700).

From their results, investigators concluded that in inadequately controlled eosinophilic asthma, higher blood EOS is associated with lower FEV

 REV. They also concluded that in patients with high EOS and low REV, reslizumab treatment results in clinically significant improvements in lung function outcomes.

Additionally, reslizumab may relatively counteract fixed airway obstruction in these patients.

High Peripheral Blood Eosinophil (EOS) Levels Are Associated With Low FEV

 Reversibility (REV) In Patients With Severe Eosinophilic Asthma

The Journal of Allergy and Clinical Immunology.

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Investigators conducted a post-hoc analysis in order to assess eosinophil levels and lung function among patients with low FEV1 reversibility to short-acting beta agonists.

Severe Eosinophilic Asthma Linked to Low FEV1 Reversibility

In urban populations, asthma morbidity has been associated with sensitization and exposure to indoor allergens in recent studies. However, few studies have focused on the Chicago region or included patients with and without asthma.

Due to the lack of Chicago-based asthma studies, a team of investigators assessed adult and pediatric patients in Chicago in order to confirm that sensitization to mouse urine, cockroaches, or dust mites is associated with increased odds of having asthma and increased asthma severity.

From June 2015 through December 2016, investigators conducted a retrospective chart review of 718 patients ages 1-90 years old seen at a Chicago public hospital who underwent in-vitro aeroallergen testing. Patient demographics, aeroallergen sensitivities, physician-diagnosed asthma, and asthma severity included the data collected, which was analyzed using chi-square tests.

 in San Francisco, CA—440 of 718 (61%) patients had a diagnosis of asthma, and a total of 341 out of 718 (47.5%) patients were sensitized to at least 1 of the 3 allergens studied.

< .001) was associated with sensitization to 1 or more allergens. Having sensitization to the individual allergens—mouse (OR 3.52; 

= .01)—were also associated with sensitization to 1 or more allergens.

Among their results, the team found a large number of the mouse-sensitized patients had a diagnosis of asthma (82/99 [82.5%]) even though only 99 (13.8%) asthma patients were sensitized to mice.

Consequently, the team concluded that having moderate or severe asthma (OR 2.38; 

= .005) was more likely among persistent patients sensitized to cockroaches. However, asthma severity did not correlate with sensitization to mouse urine or dust mites.  

This research only further adds to previous studies that point out the need for more 

. In clinical trials examining asthma outcomes, a wide variety of interventions designed to reduce allergens have been studied, but the likelihood of asthma has been shown to increase with the greater the complexity of the environment. 

More specifically, factors are vast and include an expanding list of environmental factors that come with a low-income house that must be considered, such as greater numbers of cockroaches, other pests, less maintenance of carpeting, bedding, and much more.

In the study that consisted of an extensive meta-analysis of 59 randomized controlled trials and 8 non-randomized controlled trials, investigators found that there were some multicomponent interventions that did show some benefit in reducing allergens including air purification multicomponent context, carpet removal multicomponent, HEPA filter, vacuum multicomponent, mattress cover multicomponent, and pest control multicomponent.

However, absolutely none of the studies to date provided strong clinical control of asthma.

Primarily though, there are costs and potential downsides to any of these strategies that are not really considered within any of the studies.

As a result, the team noted that the evidence is inconclusive due to a lack of studies, which are greatly needed.

The authors noted that they would like to know more about the home and personal situation of the individual patients, and that the downsides to any recommendations need more attention and consideration as well.

Indoor Allergen Sensitization Correlates with Asthma in Chicago Public Hospital Patients

Having asthma was associated with sensitization to 1 or more allergens. Having sensitization to the individual allergens&mdash;mouse, cockroach,  and dust mite&mdash;were also associated with sensitization to 1 or more allergens.

Study: Asthma Associated with Indoor Allergen Sensitization 

More severe asthma, poorer quality of life symptoms, and an elevated risk of death from the disease are prevalent in patients hospitalized with acute asthma exacerbation.

Due to this staggering statistic, a team of investigators decided to use cluster analysis to improve the understanding of heterogeneity in patients hospitalized for acute asthma exacerbation by identifying acute exacerbation of asthma phenotypes.

 in San Francisco, CA, this week, asthmatic patients who were hospitalized due to acute exacerbations between January 2009 to April 2014 were prospectively and continuously assessed. By using variables from baseline and follow-up during hospitalization on 825 patients, hierarchical cluster analysis was performed to identify phenotypes.

In their the results, investigators identified 3 clusters. Asthma onset time, prehospital OCS use, and CRP level within the first 24 hours of hospitalization included the 3 most influential variables for cluster assignment.  

In cluster 1 (n= 97), patients were predominantly young, atopic, eosinophilic, and with family history of asthma. In cluster 2 (n= 526), patients were characterized by mild, non-early onset and eosinophilic asthma. In cluster 3 (n= 202), patients mostly consisted of severe and OCS required patients with high inflammatory indices (CRP and IL-6), higher risk of lung infection, and higher burden of comorbidities.  

The highest amount of systemic steroid was used to treat these patients, who were likely to have been admitted to ICU, administered mechanical ventilation, and/or died during hospitalization. These patients also paid the most direct cost for hospitalization and had the longest hospital length stay.   

From their results, investigators identified 3 distinct phenotypes that contribute to hospitalized patients with acute asthma exacerbation. With these phenotypes, physicians can better predict outcomes of patients hospitalized for acute asthma exacerbation and shepherd the development of personalized and precise treatment.    

In a previous study, a team of investigators identified 

. They included (in order of most impactful to least):

Since these traits predict future attacks, Vanessa McDonald, lead study author behind the identified 10 treatable traits, noted that they are considered highly clinically important.

In severe asthma, common traits were allergic sensitization, upper&#8208;airway disease, airflow limitation, eosinophilic inflammation, and frequent exacerbation.

Among the 10 traits found to predict exacerbation risk, the traits found to correlate the strongest with risks of depression, inhaler device polypharmacy, vocal cord dysfunction, and obstructive sleep apnea.

"We report the higher burden experienced by patients with severe asthma compared to non-severe and importantly identify which treatable traits are predictive of future asthma attacks,” McDonald said at the time. “This highlights the usefulness of the treatable traits approach in severe asthma and identifies important targets for treatment.”

Acute Exacerbation of Asthma Phenotypes and Prognosis Identified by Cluster Analysis

Investigators also identified 3 distinct phenotypes that contribute to hospitalized patients with acute asthma exacerbation.

Phenotypes & Prognosis of Acute Asthma Exacerbations Identified

In more than a third of published health study reviews, the potential side effects of health interventions were not fully reported, according to investigators at the University of York.

A health intervention that includes negative outcomes refers to either a drug reaction or an effect of a procedure, like surgery. Since they are rare and long-term, harmful side effects can be challenging to analyze as an outcome of a health intervention.

However, investigators argued that reviews of healthcare interventions should include harmful side effects since they are essential to fully educate medical practice, health policies, and patients. Consequently, a team of investigators from the University of York sought to assess the risk for adverse events reporting bias in systematic reviews of health care interventions registered to PROSPERO.

In 187 systematic reviews published between 2017 and 2018, investigators analyzed the reporting of adverse events in their study. In health research, systematic reviews strive to summarize the results of controlled healthcare interventions and provide evidence of the effectiveness of a healthcare intervention. Overall, the study served as a retrospective cohort study.

Following a screening, systematic review protocols in PROSPERO were only included if they focused on a health care intervention and documented an adverse event as either a primary or secondary outcome.

In order to determine the completeness of reporting for the adverse event outcomes, the included systematic reviews were analyzed. Between both protocol and review, any discrepancies were recorded.

Among the results, the study showed that side effects of the medical intervention under review were not fully reported by 35% of reviewers.

Only 524 (38%) of 1376 protocols for systematic reviews sifted recorded adverse event outcomes. In 2017 and 2018, 186 protocols were published. Of those 186, 146 were included in the analysis.

Of all the included systematic reviews, 65% (95/146) fully reported the adverse event outcomes as intended by the protocol, 8% (12/146) entirely excluded the adverse event outcome, and the remaining 27% (39/146) either partially reported or changed the adverse event outcomes.

“Despite reviewers stating in their own protocols that adverse events should be included in the review, 65% fully reported the event as intended by the protocol, 8% entirely excluded them, and the remaining 27% either partially reported or changed the adverse event outcomes,” Su Golder, PhD, from the University of York's Department of Health Sciences said in a 

From their results, investigators concluded that 35% of PROSPERO-registered systematic reviews had discrepant outcome reporting between the protocol and publication while 62% of reviews did not mention adverse events in their protocol. A need for the encouraged use of harms reporting guidelines and further research into adverse events reporting bias are suggested by the study’s findings.  

"Just over 60%, however, didn't even include adverse events in their protocols, which suggests that a more proactive approach is needed to prompt reviewers to report on potential harmful side effects in their reporting of healthcare interventions,” Golder added.

Although it was not clear why review authors might be missing or only partially reporting adverse events, the reasons may vary. In addition to finding the reasons may be wide-ranging, investigators found noted that the wide range could be due to issues like differences how the original studies had defined or recorded adverse events or simply not having the available space to include details in a word-count sensitive review.

"To prevent bias in reporting of these important features of clinical trials, more work is needed to understand why so many reviewers are not fully including them and perhaps more strict guidance is needed on representing them in review protocols in the first instance,” Golder concluded.

More than one-third of systematic reviews did not fully report the adverse events outcome

Investigators argued that reviews of healthcare interventions should include harmful side effects since they are essential to fully educate medical practice, health policies, and patients.

Krista Rossi

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