June H. Lee

The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge.

Interleukin 13 (IL13) is a T‐helper type 2 (Th2) cytokine associated with inflammation and pathology in allergic diseases such as bronchial asthma. We have shown that treatment with lebrikizumab, an anti‐IL13 monoclonal antibody, significantly improves prebronchodilator forced expiratory volume in 1 s (FEV1) in a subset of subjects with uncontrolled asthma.

Assessing Productivity Loss and Activity Impairment in Severe or Difficult-to-Treat Asthma

OBJECTIVES Asthma can be associated with substantial productivity loss and activity impairment, particularly among those with the most severe disease. We sought to assess the performance characteristics of an asthma-specific adaptation of the Work Productivity and Activity Impairment Questionnaire (WPAI:Asthma) in patients with either severe or difficult-to-treat asthma. METHODS We analyzed 2529 subjects from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. The WPAI:Asthma was administered at baseline and at 12 months. Asthma control and quality-of-life were simultaneously assessed using the Asthma Therapy Assessment Questionnaire and Mini-Asthma Quality-of-Life Questionnaire, respectively. RESULTS Severe versus mild-to-moderate asthma was associated with a greater percentage of impairment at work (28% vs. 14%), at school (32% vs. 18%), and in daily activities (41% vs. 21%). At baseline, greater asthma control problems correlated with higher levels of impairment as measured by the WPAI (work: r = 0.54, school: r = 0.37, activity: r = 0.55). Over the 12-month follow-up period, improved quality-of-life correlated with decreased levels of impairment (work: r = -0.42, school: r = -0.36, activity: r = -0.48). In multivariate analyses, greater than 10% overall work impairment at baseline predicted emergency visits (OR 2.6 [1.6, 4.0]) and hospitalization (OR 4.9 [1.8, 13.1]) at 12 months. CONCLUSIONS The WPAI:Asthma correlates with other self-reported asthma outcomes in the expected manner and predicts health-care utilization at 12 months when administered to patients with severe or difficult-to-treat asthma.

Gender Differences in IgE-Mediated Allergic Asthma in the Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) Study

Background. The TENOR study consists of a large cohort of subjects with severe or difficult-to-treat asthma. The objective of this analysis was to evaluate demographic and clinical characteristics of subjects 12 years of age or older with immunoglobulin E (IgE)-mediated allergic asthma (skin test positive with an IgE level ≥ 30 to ≤700 IU/mL), and specifically, to assess gender differences in this cohort. Methods. A total of 4,756 subjects were enrolled by 283 US study sites between January and October 2001. Of those subjects 12 years or older at baseline with an IgE measure and who were skin tested (n = 2,843), 1,783 (63%) were skin test positive and had an IgE level between ≥ 30 to ≤ 700 IU/mL. Results. Compared to males, females reported significantly greater healthcare utilization (steroid bursts in previous 3 months: 50% vs 42%, p < 0.001; unscheduled office visits in previous 3 months: 50% vs 36%, p < 0.0001; missed 1+ days of work/school in previous 2 weeks: 14% vs 10%, p < 0.01). Females also reported significantly more asthma control problems and lower asthma-related quality of life (4.6 ± 1.3 vs 5.2 ± 1.2; p < 0.0001); the difference was clinically meaningful. Asthma triggers and allergic comorbidities, such as allergic rhinitis and atopic dermatitis, were more common in female subjects. Despite their overall worse health outcomes, female subjects demonstrated better lung function, had similar treatment patterns, and showed no differences in physician-assessed asthma severity when compared with males. Conclusions. The reasons for these gender differences in subjects with IgE-mediated allergic asthma are complex, but results from this analysis suggest that detailed evaluations of asthma patients, including symptom-related questions and asthma-related healthcare utilization, are needed to accurately assess asthma severity and control.

Association of control and risk of severe asthma‐related events in severe or difficult‐to‐treat asthma patients

Background:  Clinical tools for predicting poor outcomes in asthma patients are lacking. This study investigated the association of asthma control and subsequent severe asthma‐related healthcare events in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study.

Asthma in older adults: observations from the Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study

BACKGROUND The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) was a 3-year, multicenter, observational study of 4,756 patients 6 years or older with severe or difficult-to-treat asthma by physician evaluation. More than 280 pulmonologist and allergist sites across the United States participated. OBJECTIVE To compare health care utilization (HCU), medication use, asthma control, and quality of life (QoL) in older (> or =65 years; n = 566) and younger (18-64 years; n = 2,912) adult patients in TENOR. METHODS Patients had to be under a physicians care for at least 1 year and have high medication use or HCU in the past year. Heavy smokers (> or =30 pack-years) and patients with cystic fibrosis were excluded. RESULTS Although older patients in TENOR had worse lung function as measured by decreased percent predicted forced expiratory volume in 1 second (FEV1) (P < .001), they had significantly lower HCU compared with younger patients. They also had higher use of inhaled corticosteroids and better QoL than younger patients. Older patients reported fewer problems controlling their asthma (P < .001) but reported worse communication with their physicians (P = .02). CONCLUSIONS Older patients in TENOR appeared to do better than younger patients, despite having worse lung function. Older patients in TENOR may have received more aggressive care than older asthmatic patients in other studies, based on a higher use of inhaled and oral corticosteroids. Whether differences in treatment or disease influenced other physiologic or inflammatory outcomes that contribute to the disconnect between HCU and FEV1 awaits further study.

TENOR risk score predicts healthcare in adults with severe or difficult-to-treat asthma

The aim of the present study was to predict which patients with severe or difficult-to-treat asthma are at highest risk for healthcare utilisation can be predicted so as to optimise clinical management. Data were derived from 2,821 adults with asthma enrolled in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. Multiple potential predictors were assessed at baseline using a systematic algorithm employing stepwise logistic regression. Outcomes were asthma-related hospitalisations or emergency department (ED) visits within 6 months following baseline. Overall, 239 subjects (8.5%) reported hospitalisation or ED visits at follow-up. Predictors retained after multivariate analysis were as follows: younger age; female sex; non-white race; body mass index ≥35 kg·m-2; post-bronchodilator per cent predicted forced vital capacity <70%; history of pneumonia; diabetes; cataracts; intubation for asthma; and three or more steroid bursts in the prior 3 months. A final risk score derived from the logistic regression model ranged from 0–18 and was highly predictive (c-index: 0.78) of hospitalisation or ED visits. This tool was re-tested in a prospective validation using outcomes at 12- to 18-months follow-up among the same cohort (c-index: 0.77). The risk score derived is a clinically useful tool for assessing the likelihood of asthma-related hospitalisation or emergency department visits in adults with severe and difficult-to-treat asthma.

Racial disparities in asthma-related health outcomes in severe or difficult-to-treat asthma

BACKGROUND The underlying reasons for racial disparities in asthma morbidity are not well understood. Multivariate epidemiologic studies evaluating the presence and extent of racial differences in a large cohort of adults with severe or difficult-to-treat asthma are lacking. OBJECTIVE To analyze an extensive array of clinical and patient-reported outcomes, using multivariate analysis with a sequential approach, to explain racial differences in asthma-related outcomes in one of the largest cohorts of difficult-to-treat asthmatic patients. METHODS Black and white patients (> or = 18-years-old at baseline) were included (n = 2,128). Differences between the 2 racial groups were assessed using several outcome measures at month 12. Assessments were adjusted for confounding variables using a sequence of statistical models. RESULTS Most patients were white (88.6%). Blacks were slightly younger, less educated, and more likely to live in urban areas than whites. Blacks were more likely to have severe asthma and to be treated with 3 or more long-term controllers. Poorer quality of life, more asthma control problems, and higher risk of emergency department visits were observed in blacks compared with whites; differences were not explained by adjustment for broad sets of confounding variables. Differences in asthma-related health outcomes remained statistically significant after adjusting for asthma severity. CONCLUSIONS Asthma is a serious health problem in blacks and is not explained by differences in demographics, severity, or other health conditions.

The response to combination therapy treatment regimens in severe/difficult-to-treat asthma

The aim of the present study was to assess the response of high-dose salmeterol/fluticasone combination (SFC) and low-dose SFC compared with regimens without inhaled corticosteroid (ICS) plus long-acting β-agonist (LABA) in a large cohort with severe or difficult-to-treat asthma. Subjects were administered low-dose SFC (100/50 or 250/50 μg) or high-dose SFC (500/50 μg), and a control group received medications that could include ICS or LABA but not both. The present authors calculated unadjusted and propensity score-adjusted differences in outcomes consistent with components of asthma control, comparing high-dose and low-dose SFC cohorts with controls. The low-dose SFC cohort had higher asthma-related quality of life and fewer asthma control problems compared with controls. The high-dose SFC cohort had higher forced expiratory volume in one second but higher odds of having severe asthma compared with controls. The present results support the evidence that some asthmatics achieve better outcomes while receiving a low-dose salmeterol/fluticasone combination, but also suggest that those on a high-dose salmeterol/fluticasone combination fail to achieve significant improvement in many control-related health outcomes as compared with similar patients not receiving salmeterol/fluticasone combination. These findings suggest a limited value of high-dose salmeterol/fluticasone combination compared with the alternatives. While additional studies are needed, the present findings call for alternative therapeutic approaches in severe/difficult-to-treat asthma for those unable to attain asthma control with or without salmeterol/fluticasone combination.

Insurance status and asthma-related health care utilization in patients with severe asthma

BACKGROUND Medicaid insurance has been associated with worse asthma outcomes, but the degree to which demographic factors contribute to this relationship has not been well explored. OBJECTIVE To evaluate whether insurance status is independently associated with health care utilization (HCU) and asthma control when demographic differences are taken into account. METHODS We used baseline data from adults with severe asthma in the Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study. HCU was defined as hospitalization or emergency department visit for asthma in the past 3 months. Asthma control was evaluated using the Asthma Therapy Assessment Questionnaire. Multiple logistic regression was used to compare HCU and asthma control in patients with Medicaid vs those with private health insurance. RESULTS Of 1315 patients analyzed, 130 (9.9%) had Medicaid insurance and 1,185 (90.1%) had private insurance. Medicaid insurance was associated with younger age, female sex, race other than white, obesity, active smoking, lower education level, and unemployment. In unadjusted analyses, Medicaid patients had significantly higher HCU (odds ratio [OR], 3.08; 95% confidence interval [CI], 2.11-4.50) and poorer asthma control (OR, 2.56; 95% CI, 1.84-3.57) compared with patients with private insurance. After adjusting for demographic differences, insurance status was no longer associated with HCU (OR, 1.43; 95% CI, 0.92-2.23), and the strength of its association with asthma control was reduced (OR, 1.67; 95% CI, 1.17-2.40). CONCLUSIONS Medicaid insurance is not associated with increased HCU in patients with severe asthma once demographic factors have been taken into account but remains modestly associated with poorer asthma control.

Subspecialty differences in asthma characteristics and management

OBJECTIVE To determine the nature and extent to which asthma characteristics and management differ between allergy and pulmonary subspecialists. PATIENTS AND METHODS We used baseline data from 3342 adults enrolled in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study, a multicenter, observational cohort recruited from subspecialty practices across the United States. Information on physician subspecialty, asthma history, allergic status, lung function, medication use, and recent health care use was collected from January 1, 2001, through April 30, 2004, via study coordinator-administered interviews and self-administered validated questionnaires. RESULTS In the TENOR study, 2407 patients (72%) were treated by allergists and 935 (28%) by pulmonologists. Patients treated by pulmonologists were more likely to be black, be less educated, and have lower incomes than those treated by allergists. Pulmonary patients had more severe asthma as indicated by physician assessment, Global Initiative for Asthma classification, lung function, and number of asthma control problems. Regular use of a short-acting beta-agonist and systemic corticosteroid use were also higher among pulmonologist-treated patients than allergist-treated patients, consistent with greater asthma severity. Although evidence of allergic disease was prevalent in both types of patients, those treated by an allergist were more likely to receive skin testing or immunotherapy. In multivariate analyses adjusted for demographic differences, patients treated by pulmonologists were more likely to report health care use for asthma in the past 3 months. CONCLUSION In general, asthma patients treated by pulmonologists have lower socioeconomic status, have more severe disease, require more medication, and report greater health care use than those treated by allergists.