Tmirah Haselkorn

Consistently very poorly controlled asthma, as defined by the impairment domain of the Expert Panel Report 3 guidelines, increases risk for future severe asthma exacerbations in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study

BACKGROUND Identification of patients at risk for asthma exacerbations can assist physicians in addressing disease management and improve asthma-related health outcomes. OBJECTIVE We sought to evaluate whether level of impairment, as defined by the 2007 asthma guidelines, predicts risk for future asthma exacerbations. METHODS The study included children aged 6 to 11 years (n = 82) and adolescent/adult patients aged 12 years and older (n = 725) from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study with data representing all components of the impairment domain of the asthma guidelines at baseline, month 12, and month 24. Patients were categorized into 2 cohorts: (1) consistently very poorly controlled (VPC) asthma from baseline through 2 years of follow-up and (2) improved from VPC asthma at baseline (including patients who improved to not well-controlled or well-controlled asthma), with improvement maintained through 2 years of follow-up. Odds ratios (ORs) and 95% CIs for risk of asthma exacerbations at month 30 were generated by using multivariable logistic regression by age group. RESULTS After adjustment, children with consistently VPC asthma over the 2-year period demonstrated a 6-fold increased risk of hospitalization, emergency department visit, or corticosteroid burst (OR, 6.4; 95% CI, 1.2-34.5) compared with the improved group. Adolescent/adult patients with consistently VPC asthma were more likely to have a corticosteroid burst (OR, 2.8; 95% CI, 1.7-4.8) or have a hospitalization, emergency department visit, or corticosteroid burst (OR, 3.2; 95% CI, 1.9-5.3). CONCLUSIONS Consistently VPC asthma, as defined by the impairment domain of the 2007 asthma guidelines, is strongly predictive of future asthma exacerbations.

Phenotypes determined by cluster analysis in severe or difficult-to-treat asthma

BACKGROUND Asthma phenotyping can facilitate understanding of disease pathogenesis and potential targeted therapies. OBJECTIVE To further characterize the distinguishing features of phenotypic groups in difficult-to-treat asthma. METHODS Children ages 6-11 years (n = 518) and adolescents and adults ages ≥12 years (n = 3612) with severe or difficult-to-treat asthma from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study were evaluated in this post hoc cluster analysis. Analyzed variables included sex, race, atopy, age of asthma onset, smoking (adolescents and adults), passive smoke exposure (children), obesity, and aspirin sensitivity. Cluster analysis used the hierarchical clustering algorithm with the Ward minimum variance method. The results were compared among clusters by χ(2) analysis; variables with significant (P < .05) differences among clusters were considered as distinguishing feature candidates. Associations among clusters and asthma-related health outcomes were assessed in multivariable analyses by adjusting for socioeconomic status, environmental exposures, and intensity of therapy. RESULTS Five clusters were identified in each age stratum. Sex, atopic status, and nonwhite race were distinguishing variables in both strata; passive smoke exposure was distinguishing in children and aspirin sensitivity in adolescents and adults. Clusters were not related to outcomes in children, but 2 adult and adolescent clusters distinguished by nonwhite race and aspirin sensitivity manifested poorer quality of life (P < .0001), and the aspirin-sensitive cluster experienced more frequent asthma exacerbations (P < .0001). CONCLUSION Distinct phenotypes appear to exist in patients with severe or difficult-to-treat asthma, which is related to outcomes in adolescents and adults but not in children. The study of the therapeutic implications of these phenotypes is warranted.

Impact of socioeconomic status, race, and ethnicity on quality of life in patients with cystic fibrosis in the United States.

BACKGROUND Patient-reported outcomes are increasingly used in clinical trials to assess the natural history of chronic diseases and the efficacy of new treatments. Understanding the effects of socioeconomic and minority status on health-related quality of life (HRQOL) will facilitate interpretation of the results of clinical trials and suggest targets for interventions to improve patient care and outcomes. The objective of this study was to examine the effects of socioeconomic and minority status on HRQOL in patients with cystic fibrosis (CF) from childhood through adulthood in a large, comprehensive database containing medical and HRQOL data for patients with CF. METHODS A cross-sectional study was performed using data obtained from the Epidemiologic Study of Cystic Fibrosis on 4,751 patients and 1,826 parents who were non-Hispanic white, African-American, or Hispanic and who completed the Cystic Fibrosis Questionnaire-Revised (CFQ-R), a disease-specific HRQOL measure, during a stable clinic visit. RESULTS Multivariate models assessed the main effects of socioeconomic and minority status on clinical and HRQOL outcomes. Regression models that controlled for disease severity identified the contributions of these two variables to HRQOL. Low socioeconomic status was associated with significantly lower CFQ-R scores for children, parents, and adults on the majority of domains. After controlling for disease severity and socioeconomic status, African-American and Hispanic patients reported worse emotional and social functioning. CONCLUSIONS Low socioeconomic and minority status may affect important clinical and patient-reported outcomes for patients with CF across their life span.

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.

Recent asthma exacerbations predict future exacerbations in children with severe or difficult-to-treat asthma

BACKGROUND Children with severe/difficult-to-treat asthma experience high morbidity including frequent severe exacerbations. More knowledge is required to identify predictors of these exacerbations to reduce their occurrence. OBJECTIVE To investigate the risk of future severe exacerbations (FSEs) in children with severe/difficult-to-treat asthma and recent severe exacerbations (RSEs). METHODS We analyzed the occurrence and association of RSE (defined as 1 or more corticosteroid bursts during the 3 months before each of 3 annual visits) and FSE (defined as 1 or more corticosteroid bursts 6 or 12 months later) in children age 6 to 11 years in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens 3-year observational study. Repeated measures logistic regression analysis assessed the risk of FSE adjusted for demographics and clinical variables. RESULTS In a multivariable model, FSE at 6 months was most strongly predicted by RSE (odds ratio [OR], 3.08; 95% CI, 2.21-4.28) and having 3 to 4 allergic triggers (OR, 2.05; 95% CI, 1.31-3.20). Race (OR, 1.77; 95% CI, 1.25-2.51) and being very poorly controlled according to the impairment component of the National Heart, Lung, and Blood Institute guidelines (OR, 1.59; 95% CI, 1.14-2.23) also significantly predicted FSE. CONCLUSION Recent severe asthma exacerbations are an important independent predictor of FSE in children with severe/difficult-to-treat asthma and should be considered when establishing asthma management plans.

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.

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.

Effect of weight change on asthma-related health outcomes in patients with severe or difficult-to-treat asthma *

OBJECTIVE To evaluate the effects of weight change on asthma control, asthma-related quality of life, number of steroid bursts, and exacerbation of asthma symptoms in a population of adult patients with severe or difficult-to-treat asthma who participated in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. METHODS We categorized 2396 TENOR patients > or = 18 years into three groups (> or = 5 lb loss, stable, > or = 5 lb gain), based on a +/-5 lb (2.27 kg) difference between baseline and 12-month follow-up weight. We used proportional odds and logistic regression models to evaluate the effect of weight change on Asthma Therapy Assessment Questionnaire (ATAQ) and Asthma Quality of Life Questionnaire (AQLQ) scores, exacerbations, and steroid bursts at the 12-month follow-up. RESULTS Asthma patients who gained > or = 5 lb (2.27 kg) during the 12-month interval between baseline and follow-up reported poorer asthma control (adjusted odds ratio [OR]: 1.22; 95% confidence interval [CI]: 1.01-1.49; p=0.04), worse quality of life (least square means: -0.18; 95% CI: -0.30 to -0.06; p=0.003), and a greater number of steroid bursts (OR: 1.31; CI: 1.04-1.66; p=0.02) than patients who maintained their baseline weight or lost > or = 5 lb (2.27 kg). CONCLUSION Increased weight is associated with worse asthma-related health outcomes. Strategies to prevent weight gain could help patients achieve better asthma control and improve asthma-related quality of life.

Assessment of asthma control and asthma exacerbations in the epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) observational cohort.

Patients with severe or difficult-to-treat asthma account for substantial asthma morbidity, mortality, and healthcare burden despite comprising only a small proportion of the total asthma population. TENOR, a multicenter, observational, prospective cohort study was initiated in 2001. It enrolled 4,756 adults, adolescents and children with severe or difficult-to-treat asthma who were followed semi-annually and annually for three years, enabling insight to be gained into this understudied population. A broad range of demographic, clinical, and patient self-reported assessments were completed during the follow-up period. Here, we present key findings from the TENOR registry in relation to asthma control and exacerbations, including the identification of specific subgroups found to be at particularly high-risk. Identification of the factors and subgroups associated with poor asthma control and increased risk of exacerbations can help physicians design individual asthma management, and improve asthma-related health outcomes for these patients.

Asthma control and activity limitations: insights from the Real-world Evaluation of Asthma Control and Treatment (REACT) study.

BACKGROUND Uncontrolled asthma remains prevalent in the United States and confers a substantial burden on the health care system. OBJECTIVES To evaluate the association between uncontrolled asthma and activity limitations in a nationally representative sample of patients with moderate-to-severe-treated asthma and to assess the degree to which demographics and comorbidities were associated with activity limitations. METHODS Patients who participated in the Real-world Evaluation of Asthma Control and Treatment study were surveyed regarding type and degree of activity limitations in 4 categories: outdoor activity, physical activity, daily activity, and environmental triggers. Information about asthma control, demographics, and comorbidities was collected. Multivariable regression was used to assess the association between uncontrolled asthma and activity limitations while adjusting for demographic characteristics and comorbid conditions. RESULTS Uncontrolled asthma was associated with a greater than 2-fold risk of outdoor (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.90-3.51) or physical (OR, 2.62; 95% CI, 1.90-3.61) activity limitations and a 66% increased risk of daily activity limitations (OR, 1.66; 95% CI, 1.09-2.51). Comorbidities associated with activity limitation included hives, chronic sinusitis, arthritis, gastroesophageal reflux disease, hypercholesterolemia, and depression. The observed associations between uncontrolled asthma and activity limitation remained significant after controlling for demographic characteristics and comorbid conditions. CONCLUSIONS Compared with patients with controlled asthma, those with uncontrolled asthma are at higher risk for limitations in outdoor activity, physical activity, and daily activity. To help patients achieve optimal health, asthma management should include routine assessment of activity limitations and assessment and coordinated care for comorbid conditions.