1. • The newly published ERS/ATS guidelines provide clear definitions of asthma severity4
• To our knowledge this is the first study exploring the relationship between EOS elevation and
asthma severity using the new ERS/ATS definition which incorporates symptom ‘control’ -
exacerbations and lung function
• Understanding asthma phenotype (e.g., eosinophilic, neutrophilic, or paucigranulocytic) can help
guide decisions for improved treatment of airway inflammation
• Patients with elevated EOS have 1.8 times greater likelihood of developing severe asthma
• Future research to understand the possible economic implications of these findings is warranted
to help develop policy around more effective methods to manage this uncontrolled population
• Patients treated with high dose ICS plus controller medications or who had SCS use for the
greater part of the year, but did not show presence of exacerbations were included in the
‘non-severe’ asthma group to avoid classifying overtreated patients as having severe asthma
• Including these patients in the ‘Severe’ group would likely lead to underestimation of the impact of
severe asthma and its association with EOS
Elevated EOS significantly increases the likelihood of the occurrence of Severe Asthma based on
the 2014 ERS/ATS Guideline definitions
1) Barnett SB, Nurmagambetov TA. Costs of Asthma in the Unites States: 2002-2007. Journal of Allergy and Clinical
Immunology. 2011; 127:145-52.
2) Birnbaum HG, Ivanova JI, Yu AP, et al. Asthma severity categorization using a claims-based algorithm or pulmonary function
testing. The Journal of Asthma,2009; Vol. 46 (1), pp. 67-72.
3) Casciano J, Krishnan J, Buatti Small M et al. Assessing the Economic Burden and Healthcare Utilization of Patients with
Eosinophilic Asthma. Poster presented at the American College of Allergy, Asthma and Immunology conference, November
2013,Baltimore,MD.
4) Chung KF, Wenzel SE, Brozek JL et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe
asthma. Eur Respir J 2014; 43: 343–373
• Asthma lowers the quality of life and imposes a significant burden on the healthcare system.1
Asthma severity is directly correlated with increased cost and healthcare resource utilization
• It is important to more effectively control severe asthma and identify patients with the greatest
clinical risks of exacerbation2
• Results of a retrospective cohort study in patients with severe asthma indicated that elevated
peripheral blood eosinophil (EOS) levels are associated with more frequent hospital admissions
and greater cost versus non-elevated EOS asthma3
• These results indicate a strong need to assess the phenotype associated with severe asthma to
identify potential populations with high resource use and in effect, aid in the development of better
targeted therapy
• The recently published 2014 European Respiratory Society (ERS) and American Thoracic Society
(ATS) guidelines for the evaluation and management of severe asthma have provided a definition
of severe asthma that incorporates both medication use and clinical indicators4
• In this study, we examine the relationship between blood eosinophil levels and severe asthma
using the definition of severe asthma from the ERS/ATS 2014 guidelines
Assess the association of serum eosinophil levels and severe asthma, defined by ERS/ATS guidelines
Data source
• Patient-level de-identified data from the EMRClaims+ Database (eMAX Health, White Plains NY)
• Includes administrative insurance claims linked with electronic medical records (EMR) as well as
inpatient and outpatient laboratory values and provider billing files
• Contains over 20 million electronic records available for access and approximately 580,000 lives
with linked electronic medical records
Approach
• The initial asthma diagnosis date was defined as the index date, and the 12-month period
following this diagnosis was defined as the assessment period
• We followed patients during the assessment period to check medication use, exacerbations and
lung function results. All patients were required to have at least one month of follow-up after the
assessment period
Inclusion criteria
1. Asthma as a primary or secondary diagnosis defined by the ICD-9-CM code 493.xx between January
2004 and July 2011 resulting in 2 or more medical encounters separated by at least one day
2. Age of at least 12 years at the time of the initial asthma diagnosis encounter
3. Patients with at least 13 months of continuous enrollment after their initial asthma diagnosis
encounter date
4. Patients with at least one peripheral eosinophil (EOS) test result in the assessment period
Exclusion criteria
1. Patients with confounding diseases states of COPD and emphysema, Churg-Strauss syndrome,
Wegener’s granulomatosis, eosinophilia, pulmonary fibrosis, allergic bronchopulmonary
aspergillosis and lung cancer (ICD-9-CM codes: 491.xx-492.xx, 494.xx-496.xx, 277.x, 162.x,
446.4, 288.3, 516.31, 515, 518.6), in the assessment period following the diagnosis date
2. Patient with normal serum EOS while on systemic steroids (based on days of supply plus 14 days;
to account for the masking effect of systemic steroid use on EOS levels) without EOS results
between courses of systemic steroids. Including such patients would likely misclassify patients
with high EOS levels as having normal EOS levels
• Chi-Square analysis showed that proportion of patients with elevated EOS was significantly greater
in the group with Severe asthma compared to Non-severe asthma (30% vs. 19%, p=0.0002)
• Chi-Square analysis showed that a significantly greater proportion of patients with elevated serum
EOS used high dose ICS and controller medications, compared to patients with normal EOS (30%
vs 22%, p=0.0002)
• A significantly greater proportion (Chi-Square testing) of patients with elevated EOS also had
bursts of CS (17% vs. 12%, p=0.002) and airflow limitation (reduced lung function, 10% vs. 5%,
p=0.0002)
• When adjusting for comorbidities using the Charlson Comorbidity Index (CCI), the likelihood of
having severe asthma increased 1.83 times when a patient had elevated EOS compared to
having normal EOS (AOR=1.83 95%CI [1.30,2.56])
• Race was significant in terms of African Americans having lower likelihood of severe asthma
compared to White (AOR=0.56, 95%CI [0.33-0.93])
• Each unit increase in age was associated with greater likelihood of severe asthma (AOR=1.015,
95%CI [1.007-1.024])
Asthma was classified as ‘Severe’ or ‘Non-severe’ based on the 2014 ERS/ATS guidelines.
Specifically ‘Severe’ asthma was defined as:
1. Use of high dose ICS (Table 1) plus a second controller- Long Acting Beta Agonist LABA or
leukotriene modifier/theophylline) during the assessment period,
OR
2. Systemic Corticosteroids (CS) for up to or more than 50% of the assessment period,
AND
3. At least one of the following (to define uncontrolled asthma)
a.Frequent severe exacerbations defined as two or more bursts of systemic CS (> 3 days
each)
b.Serious exacerbations defined as:
i. At least one hospitalization with a diagnosis of asthma as the primary discharge
diagnosis, or
ii. ICU stay, or
iii. Mechanical Ventilation
c. Airflow limitation: after appropriate bronchodilator withhold FEV1 < 80% predicted and
FEV1/FVC less than the lower limit of normal
We defined patients with ‘elevated’ EOS as having at least one EOS result with ≥ 400 cells/µL during
assessment period (else, ‘normal’ EOS)
Data Analysis
• Descriptive analyses included proportion of patients by severity level
• Baseline demographics and comorbidities between patients with severe and non-severe asthma
• Proportion of patients with elevated EOS within both severity groups
• Stratified by EOS levels, the proportion of patients with each individual factor in the definition of
severe asthma (medication use and control factors)
• Chi-Square tests or Fisher Exact tests were used to calculate statistical significance of the
differences in frequencies
• Logistic regression analysis to assess if elevated EOS is a contributing factor to the likelihood of
having severe asthma. Adjusted Odds Ratios (AOR) and 95% Confidence Intervals (95%CI) were
calculated and reported below.
Figure 1: Study Inclusion Criteria, Design, and Measures
The Association of Blood EOS Levels with Severe Asthma Defined by 2014 ERS/ATS Guidelines P48
Authors: Julian Casciano1
, Jerry Krishnan2
, Mary Buatti Small3
, Sanjay Bajpai1
,Chenghui Li4
, Zenobia Dotiwala1
Affiliation: 1
eMAX Health LLC, White Plains, NY; 2
University of Illinois, Medical Center, Chicago,IL; 3
Teva, Frazer, PA; 4
University of Arkansas-Medical Sciences, Little Rock, AR
BACKGROUND
DISCUSSION
LIMITATIONS
CONCLUSIONS
REFERENCES
• Among the 2,164 asthma patients with EOS tests conducted during the assessment period, 9%
(n=184) were classified as those with ‘Severe’ asthma
• Majority (71%) were women
RESULTS
OBJECTIVE
METHODS
Presented at the
Annual ACAAI conference
Atlanta, Georgia
Nov 6-10, 2014
Figure 1: Patient Distribution by EOS Level
Inhaled corticosteroid
Beclomethasone dipropionate ≥ 1000 (DPI or CFC MDI) ≥ 500 (HFA MDI)
Budesonide ≥ 800 (MDI or DPI)
Ciclesonide ≥ 320 (HFA MDI)
Fluticasone propionate ≥ 500 (HFA MDI or DPI)
Mometasone furoate ≥ 800
Triamcinolone acetonide ≥ 2000
Flunisolide ≥ 2000
Daily dose in mg considered as high for
population at least 12 years of age
Table 1: Threshold for High Dose ICS
Female 130 71% 71% 0.967*
18-34 years 23 13% 18%
35-64 years 122 66% 54%
Greater than/equal to 65 38 21% 17%
0-1 120 65% 69%
2-4 58 32% 24%
Greater than/equal to 5 6 3% 3%
Severe
184
Non-severe
1980 P-value
n % n %
1396
362
1065
327
White 96 52% 43%
African American 19 10% 17%
Hispanic 40 22% 25%
Other/unknown 29 16% 15%
852
328
502
298
1367
466
65
Gender
Age groups (years)
Top Comorbidities
Race
Table 2: Baseline Demographics and Comorbidities
<0.0001*
0.041*
0.018*
70%
81%
30%
19%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Severe (n=184) Non-severe (n=1980)
PercentofPatients
Normal EOS (< 400 cells/µL) Elevated EOS (≥ 400 cells/µL)
Figure 2: Association of Predictor Variables with Severe Asthma
82%
1.5%
-25%
-44%
-11%
-5%
0.1%
-40%-60% -20% 0% 20% 40% 60% 80% 100%
Elevated EOS (≥ 400 cells/µL)
vs. Normal EOS
Male (vs. Female)
Age*
Black (vs. White)*
Hispanic (vs. White)
Other (vs. White)
CCI Score
Magnitude in Changes in Odds
IndependentFactors
*Significance at p < 0.05
* Chi-Square test