Trung N. Tran

High Blood Eosinophil Count Is a Risk Factor for Future Asthma Exacerbations in Adult Persistent Asthma

BACKGROUND Exacerbation-associated uncontrolled asthma represents a major public health problem. The relationship of elevated blood eosinophils to this process needs study. OBJECTIVE To determine whether a high blood eosinophil count is a risk factor for future asthma exacerbations in adult persistent asthma. METHODS By using electronic pharmacy and health care data from Kaiser Permanente Southern California, 2392 patients, ages 18 to 64 years, were identified who met the Health Effectiveness Data and Information Set 2-year criteria for persistent asthma, did not manifest chronic obstructive pulmonary disease and other major illnesses, and had a blood eosinophil determination in 2010. Exacerbations (primary outcome) were defined as asthma outpatient visits that required systemic corticosteroid dispensing within ±7 days or asthma emergency department visits or hospitalizations. A period of ≥8 days defined a new exacerbation. Multivariate modelling used negative binomial and Poisson regression to examine the association between a blood eosinophil count determined in 2010 and risk of exacerbations, and ≥7 short-acting β2-agonist (SABA) canisters dispensed (secondary outcome) in 2011 by adjusting for demographics, comorbidities, and asthma burden. RESULTS The rate of asthma exacerbations in 2011 was 0.41 events per person year (95% CI, 0.37-0.45). Eosinophil count ≥400/mm(3) in 2010 was a risk factor for asthma exacerbations in 2011 (adjusted rate ratio 1.31 [95% CI, 1.07-1.60]; P = .009) and ≥7 SABA dispensed (adjusted risk ratio 1.17 [95% CI, 1.03-1.1.33]; P = .015). CONCLUSION A high blood eosinophil count is a risk factor for increased future asthma exacerbations and excessive short-acting β2-agonist use after adjustment of potential confounders in adults with persistent asthma, which suggests a higher disease burden in patients with asthma and with high blood eosinophil counts.

Overlap of atopic, eosinophilic, and TH2-high asthma phenotypes in a general population with current asthma

BACKGROUND Atopic, eosinophilic, and TH2-high asthma phenotypes may overlap, but the extent is unknown. Understanding the overlap across these phenotypes may be useful in guiding asthma patient care. OBJECTIVE To examine the frequency and overlap of atopic, eosinophilic, and TH2-high asthma phenotypes. METHODS We analyzed 2005 to 2006 data from the National Health and Nutrition Examination Survey. Patients with asthma were identified based on the participant self-report. Eosinophilic asthma was defined as a blood eosinophil cutoff point of ≥150, 300, or 400/μL. Atopic asthma was defined as having an allergen-specific IgE level of ≥0.35 IU/mL for any of the 9 perennial allergens tested. TH2-high asthma was defined as a total serum IgE of ≥100 IU/mL and a blood eosinophil count of ≥140/μL. RESULTS The study included 269 children and 310 adults. Depending on the eosinophil cutoff used, 31% to 78% of children and 21% to 69% of adults with asthma were classified as having eosinophilic asthma. In addition, 63% of children and 61% of adults were classified as having atopic disease and 48% of children and 37% of adults as having TH2-high asthma. At a higher eosinophil cutoff point, a greater proportion of eosinophilic asthma can be classified as atopic or TH2 high, but a lower proportion of atopic or TH2-high asthma can be classified as eosinophilic. Approximately 70% or more of children and adults with asthma were 1 of these 3 phenotypes. CONCLUSION A considerable overlap among eosinophilic, atopic, and TH2-high asthma phenotypes exists in a general asthma population.

Burden of Chronic Oral Corticosteroid Use by Adults with Persistent Asthma

BACKGROUND Chronic oral corticosteroid (C-OCS) use in asthma is an indicator of disease severity, but its risk factors are largely unknown. OBJECTIVE To describe patient characteristics and disease burden associated with C-OCS use by adults with persistent asthma. METHODS We identified 9546 patients aged 18 to 64 years in a large managed care organization who met the Healthcare Effectiveness Data and Information Set 2-year criteria (2009-2010) for persistent asthma. A subgroup had blood eosinophil counts. We calculated cumulative OCS dispensed per patient in 2010 and examined the distribution of disease characteristics by average daily amounts of OCS dispensed. C-OCS use was defined as 2.5 mg/d or more. Baseline factors (2010) associated with C-OCS use during follow-up (2011) were investigated by multivariable Poisson regression. RESULTS At baseline, 782 (8.2%) patients were C-OCS users. Compared with patients who received no or less than 2.5 mg/d OCS, C-OCS users were older and more often female and ethnic minorities; and had more comorbidities, asthma specialist care, greater step-care level, controllers, asthma exacerbations, and greater blood eosinophil counts (all P < .01). Baseline factors significantly associated with C-OCS use in the follow-up year included (1) demographic characteristics: older age, females, blacks versus whites, and whites versus others/unknown ethnicities; (2) disease burden: more asthma emergency department or hospitalization visits, greater step-care level, excessive short-acting β2-agonist dispensed, theophylline use, asthma specialist care, and nasal polyposis; (3) greater blood eosinophil counts; and (4) most strongly, C-OCS use. CONCLUSIONS C-OCS use was associated with more asthma burden, comorbidities, and greater blood eosinophil counts. Prior C-OCS use was the strongest predictor of future C-OCS use.

Adherent uncontrolled adult persistent asthma: Characteristics and asthma outcomes

Asthma control depends on many factors of which patients’ demographic characteristics, asthma severity, medication selection/efficacy, comorbidities, and adherence play important roles. To provide optimal systemwide asthma care management and manage costs, health care organizations are challenged to identify high-risk uncontrolled patients. Frequency of asthma exacerbations, excessive use of short-acting b2-agonists (SABAs), and adherence to asthma medication dispensing represent 3 integral asthma parameters available from administrative data to help in the identification of such high-risk patients with asthma to deliver more intensive care. Accordingly, we sought to identify, characterize, and determine asthma outcomes in a subgroup of high-risk patients with uncontrolled asthma who were adherent to controller medication and compare them with the rest of the cohort with persistent asthma. We conducted a retrospective cohort study (see Figure E1, A, in this article’s Online Repository at www.jaci-inpractice.org) of adult patients with persistent asthma from a large managed care organization to compare characteristics and outcomes of a highrisk uncontrolled, high-adherent subgroup with those of other patients with persistent asthma. Electronic administrative pharmacy and health care data from Kaiser Permanente Southern California were used to identify 9546 patients aged 18 to 64 years who met the Health Effectiveness Data and Information Set (HEDIS) 2-year criteria for persistent asthma in 2009 and 2010, did not manifest chronic obstructive lung disease and other major illnesses (Figure E1, B, in this article’s Online Repository at www. jaci-inpractice.org), and were continuously enrolled health plan members with pharmacy benefit from 2009 to 2011. Asthma exacerbations were defined as asthma emergency department (ED) visits or hospitalizations or asthma outpatient visits encoded for acute exacerbations, status asthmaticus, acute asthma attack, uncontrolled asthma, or asthmatic bronchitis requiring systemic corticosteroid dispensing within 7 days of the visit. At least 8 days separated a new exacerbation. Excessive SABA dispensing was defined as 7 or more canisters dispensed per year. Adherence was determined on the basis of a number of controller canister equivalents dispensed in a year (canisters of inhaled controller medications or 30-day supplies of oral controller medications). Nine or more controller canister equivalents dispensed met HEDIS 75% level adherence criteria and was considered high-adherence. Using baseline data during 2010, the following risk and adherence levels were defined: (1) high-risk: 2 or more asthma exacerbations or 7 or more SABA canisters dispensed, (2) low-risk: fewer than 2 asthma exacerbations and fewer than 7 SABA canisters dispensed, (3) highadherence: 9 or more controller canister equivalents dispensed, and (4) low-adherence: fewer than 9 controller canister equivalents dispensed. From these definitions, adult patients with persistent asthma were categorized into 4 groups on the basis of asthma risk and adherence in 2010: high-risk, high-adherent (N 1⁄4 1031), high-risk, low-adherent (N 1⁄4 2472), low-risk, high-adherent (N 1⁄4 2505), and low-risk, low-adherent (N 1⁄4 3538) (Figure E1, B, in this article’s Online Repository at www.jaci-inpractice.org). Negative binomial and Poisson regression models with robust error variance were used to estimate the adjusted rate ratio and risk ratio, respectively, and their 95% CIs, and to derive the P values. The analyses were adjusted for the following characteristics in 2010: age, sex, race/ethnicity, geocoded education, various types of health insurance, length of health plan enrollment, obesity, comorbidities (Charlson comorbidity index, gastroesophageal reflux, rhinitis, chronic sinusitis, pneumonia, eczema, nasal polyps), smoking status, allergist care, and Global Initiative for Asthma (GINA) step-care level. SAS (version 9.3 for Windows, SAS Institute, Cary, NC) was used for all analyses, with statistical significance level set at P < .05 (2-tailed). Baseline characteristics in 2010 revealed that high-risk patients exhibited more obesity, active smoking, Charlson comorbidity index, and other individual comorbidities, and by definition, more asthma exacerbations and excessive SABA use than did lowrisk patients (Table I). In addition, high-risk, high-adherent patients appeared to have higher levels of GINA step-care than did all other subgroups, including the high-risk, low-adherent subgroup. The high-adherent patients more often received allergist care than did the low-adherent groups, but this care was of only low frequency (25.5% in the high-risk, high-adherent and 24.2% in the low-risk, high-adherent subgroups). The highrisk, low-adherent subgroup also had a high frequency of no inhaled corticosteroid or low-dose inhaled corticosteroid treatment (>40%), emphasizing the need for this group of patients to receive higher step-care treatment with more intensive controller therapy to improve asthma control. During the outcome year in 2011, the overall rate of asthma exacerbations in the entire adult cohort with persistent asthma was 0.32 events per person-year (95% CI, 0.31-0.34). Compared with the low-risk subgroups, the high-risk subgroups exhibited statistically more asthma exacerbations, higher frequencies of asthma ED/hospitalizations, and 7 or more SABA canisters dispensed (P < .001) (Table II; see Table E1 in this article’s Online Repository at www.jaci-inpractice.org). In multivariate analyses, compared with both the low-risk, high-adherent and the low-risk, low-adherent subgroups,

Healthcare resource use and costs of severe, uncontrolled eosinophilic asthma in the UK general population

Background Little is known about the prevalence of severe, uncontrolled eosinophilic asthma (SUEA) and associated costs. Aims We sought to determine the prevalence of SUEA and compare asthma-related healthcare resource use (HCRU) and associated costs with overall means for a general asthma population. Methods This cohort study evaluated anonymised medical record data (December 1989 through June 2015) from the Clinical Practice Research Datalink and the Optimum Patient Care Research Database to study UK patients with active asthma (diagnostic code and one or more drug prescriptions in the baseline year), aged 5 years and older, without concomitant COPD, and with recorded eosinophil count. SUEA was defined as two or more asthma attacks during 1 baseline year preceding a high blood eosinophil count (≥0.3×109/L) for patients prescribed long-acting β2-agonist (LABA) and high-dosage inhaled corticosteroids (ICS) during baseline plus 1 follow-up year. We compared asthma-related HCRU and associated direct costs (2015 pounds sterling, £) during the follow-up year for SUEA versus the general asthma population. Results Of 363 558 patients with active asthma and recorded eosinophil count, 64% were women, mean (SD) age was 49 (21) years; 43% had high eosinophil counts, 7% had two or more attacks in the baseline year and 10% were prescribed high-dosage ICS/LABA for 2 study years. Overall, 2940 (0.81%; 95% CI 0.78% to 0.84%) patients had SUEA. Total mean per-patient HCRU and associated costs were four times greater for SUEA versus all patients (HCRU and cost ratios 3.9; 95% CI 3.7 to 4.1). Conclusions Less than 1% of patients in a general asthma population had SUEA. These patients accounted for substantially greater asthma-related HCRU and costs than average patients with asthma.

Characteristics and Outcomes of HEDIS-Defined Asthma Patients with COPD Diagnostic Coding.

BACKGROUND Little is known of the disease burden of patients with persistent asthma (PA) who also have a chronic obstructive pulmonary disease (COPD) diagnosis code (AS-COPD). OBJECTIVE The objective of this study was to characterize and compare patients with AS-COPD with those with PA without COPD diagnosis, and determine in AS-COPD the relationship between blood eosinophil count and future asthma exacerbations. METHODS This retrospective cohort study used administrative pharmacy and health care utilization data to identify, characterize, and compare the burden and asthma exacerbations in adults with AS-COPD (N = 901) with those with PA (N = 2392). Negative binomial regression and Poisson regression models were used to evaluate the relationships between baseline blood eosinophil counts (high vs low) based on various cutoff points and asthma exacerbations in the follow-up year, adjusting for demographics, comorbidities, and asthma burden. RESULTS Compared with patients with PA, those with AS-COPD were significantly (all P < .001) older, more frequently female, less well educated, more likely to be or have been a smoker, had more comorbidities, received more asthma controller medications, and had greater rates and frequencies of asthma exacerbations, but had similar blood eosinophil counts. The rate of asthma exacerbations/person-year in AS-COPD during follow-up was 1.61 (95% CI, 1.18-2.20). Patients with AS-COPD with a blood eosinophil count ≥400 cells/mm(3) had an increased rate of future asthma exacerbations compared with those whose blood eosinophil count was <400 cells/mm(3) (adjusted rate ratio, 1.44, 95% CI, 1.09-1.90). CONCLUSIONS Compared with patients with PA, those with AS-COPD had more disease burden, but a similar relationship of high blood eosinophil count to more future asthma exacerbations. These findings suggest a common inflammatory component between AS-COPD and PA.

Association between blood eosinophil count and risk of readmission for patients with asthma : Historical cohort study

Background Recent studies have demonstrated an association between high blood eosinophil counts and greater risk of asthma exacerbations. We sought to determine whether patients hospitalized for an asthma exacerbation were at greater risk of readmission if they had a high blood eosinophil count documented before the first hospitalization. Methods This historical cohort study drew on 2 years of medical record data (Clinical Practice Research Datalink with Hospital Episode Statistics linkage) of patients (aged ≥5 years) admitted to hospital in England for asthma, with recorded blood eosinophil count within 1 baseline year before admission. We analyzed the association between high blood eosinophil count (≥0.35x109 cells/L) and readmission risk during 1 year of follow-up after hospital discharge, with adjustment for predefined, relevant confounders using forward selection. Results We identified 2,613 eligible patients with asthma-related admission, of median age 51 years (interquartile range, 36–69) and 76% women (1,997/2,613). Overall, 835/2,613 (32.0%) had a preadmission high blood eosinophil count. During the follow-up year, 130/2,613 patients (5.0%) were readmitted for asthma, including 55/835 (6.6%) with vs. 75/1,778 (4.2%) without high blood eosinophil count at baseline (adjusted hazard ratio [HR] 1.49; 95% CI 1.04–2.13, p = 0.029). The association was strongest in never-smokers (n = 1,296; HR 2.16, 95% CI 1.27–3.68, p = 0.005) and absent in current smokers (n = 547; HR 1.00, 95% CI 0.49–2.04, p = 0.997). Conclusions A high blood eosinophil count in the year before an asthma-related hospitalization is associated with increased risk of readmission within the following year. These findings suggest that patients with asthma and preadmission high blood eosinophil count require careful follow-up, with treatment optimization, after discharge.

Development of the International Severe Asthma Registry (ISAR): A Modified Delphi Study

BACKGROUND The lack of centralized data on severe asthma has resulted in a scarcity of information about the disease and its management. The development of a common data collection tool for the International Severe Asthma Registry (ISAR) will enable standardized data collection, subsequently enabling data interoperability. OBJECTIVES To create a standardized list of variables for the first international registry for severe asthma via expert consensus. METHODS A modified Delphi process was used to reach consensus on a minimum set of variables to capture in ISAR: the core variables. The Delphi panel brought together 27 international experts in the field of severe asthma research. The process consisted of 3 iterative rounds. In each round, all Delphi panel members were issued an electronic ISAR Delphi workbook to complete and return to the ISAR Delphi administrator. Workbooks and result summaries were anonymously distributed by the Delphi administrator to all panel members at subsequent rounds. Finalization of the core variable list was facilitated by 2 face-to-face meetings. RESULTS Of the initial 747 selected variables, the Delphi panel reached a consensus on 95. The chosen variables will allow severe asthma to be assessed against patient demographics and medical history, patient-reported outcomes, diagnostic information, and clinical characteristics. Physician-reported outcomes such as nonadherence and information about treatment and management strategies will also be recorded. CONCLUSIONS This is the first global attempt to generate an ISAR using a common set of core variables to ensure that data collected across all participating countries are standardized.

Health care resource utilization and costs associated with incremental systemic corticosteroid exposure in asthma

Although systemic corticosteroid (SCS) treatment, irrespective of duration or dosage, is associated with adverse outcomes for patients with asthma, the longitudinal effects of this treatment on adverse outcomes, healthcare resource utilization (HCRU), and healthcare costs are unknown.