Bradley E. Chipps

Design and baseline characteristics of The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study: a large cohort of patients with severe or difficult-to-treat asthma

BACKGROUND Patients with severe and difficult-to-treat asthma represent a small percentage of asthma patients, yet they account for much of the morbidity, mortality, and cost of disease. The goal of The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study is to better understand the natural history of asthma in these patients. OBJECTIVE To describe the methods and baseline characteristics of the TENOR study cohort. METHODS The TENOR study is a 3-year, multicenter, observational study of patients with severe or difficult-to-treat asthma. From January through October 2001, more than 400 US pulmonologists and allergists enrolled patients. Patients 6 years or older who were considered to have severe or difficult-to-treat asthma by their physicians were eligible. Patients have been receiving care for 1 year or more, have a smoking history of 30 pack-years or less, and have current high medication or health care utilization in the past year. Data are collected semiannually. RESULTS A total of 4,756 patients enrolled and completed a baseline visit. Overall, 73% of the TENOR study patients are adults, 10% are adolescents, and 16% are children. According to physician evaluation, 48% of patients have severe asthma, 48% have moderate asthma, 3% have mild asthma, and 96% have difficult-to-treat asthma. Severe asthmatic patients have the highest health care utilization in the past 3 months (P < .001). CONCLUSIONS The TENOR study is the largest cohort of patients with severe or difficult-to-treat asthma. Although patients are equally divided into moderate or severe asthma categories, most are considered difficult-to-treat. The TENOR study highlights the lack of control in moderate-to-severe asthma and provides a unique opportunity to examine factors related to health outcomes in this understudied population.

Extent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma

Background:  Characterization of uncontrolled asthma burden in a natural treatment setting can influence treatment recommendations and clinical practice. The objective was to characterize and compare the economic burden of severe or difficult‐to‐treat asthma in uncontrolled and controlled patients.

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.

Total serum IgE levels in a large cohort of patients with severe or difficult-to-treat asthma

BACKGROUND Limited data are available on levels of IgE in large cohorts of patients with severe or difficult-to-treat asthma. OBJECTIVE To examine IgE levels and disease in patients from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. METHODS From January 2001 to October 2001, 4,923 patients were screened for inclusion in the study. Of these, 4,756 patients 6 years or older with severe or difficult-to-treat asthma were enrolled and completed a baseline study visit. Total serum IgE levels were measured at the baseline visit and are summarized by geometric means. RESULTS The mean total IgE level of the population is 106.6 IU/mL (95% confidence interval, 101.5-112.0 IU/mL). Children (6-12 years old) and adolescents (13-17 years old) have higher mean IgE levels than adults (> or =18 years old) (P < .001). Males have a higher mean IgE level than females (P < .001). IgE levels are higher among nonwhite patients than white patients (P < .001). Current smokers have higher IgE levels than past smokers or never smokers (P < .001). Among children, patients with severe asthma have a higher mean IgE level (280.2 IU/mL) than patients with moderate (145.8 IU/mL) or mild (137.8 IU/mL) asthma (P < .001). Among adults, patients with childhood-onset asthma have higher IgE levels (124.3 IU/mL [n = 1,348]) than patients with adult-onset asthma (65.7 IU/mL [n = 1,956]) (P < .001). CONCLUSION In patients with severe or difficult-to-treat asthma from the TENOR study, higher total IgE levels were observed in males, children, smokers, nonwhite racial/ethnic groups, and adults with childhood-onset disease. In addition, IgE levels are associated with asthma severity among younger patients.

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.

Section on allergy and immunology

Founded in 1948, the Section on Allergy and Immunology is dedicated to ensuring that children receive the highest quality of allergy and immunology care. To accomplish its mission, the Section provides a number of educational, training, and research programs and continually advocates for improved allergy and immunology care and services. The Section sponsors educational programs for both pediatric generalists and subspecialists at the American Academy of Pediatrics (AAP) National Conference and Exhibition (NCE) each fall and at the American Academy of Allergy Asthma & Immunology annual meeting each spring. The Section’s other educational endeavors include this annual “Best Articles Relevant to Pediatric Allergy and Immunology” supplement to Pediatrics, Visiting Professor Program, Pediatric Asthma Speaker’s Kit, online continuing medical education course on “asthma gadgets,” electronic quality improvement in practice program on asthma diagnosis and management (Education in Quality Improvement for Pediatric Practice [eQIPP], which meets the American Board of Pediatrics maintenance-ofcertification criteria), school nurse allergy tool kit, and a number of public education materials. The Section is also active in contributing to educational programs and resources such as AAP News, educational brochures, clinical reports, and many other endeavors. To support training and promote research in pediatric allergy and immunology, the Section awards travel grants to residents and training fellows to participate and present cases at the AAP NCE and provides outstanding abstract awards for training fellows and junior faculty for presentation at the American Academy of Allergy Asthma & Immunology annual meeting. In close collaboration with other subspecialty societies, the Section is actively involved with initiatives to improve subspecialty education such as the American Board of Allergy and Immunology maintenance-of-certification requirements. Section members represent the AAP in national and government conferences and provide input on federal legislation on behalf of the AAP. For more information on all AAP allergy and immunology resources and initiatives, visit www.aap.org/sections/allergy. The reviews contained in the 2011 synopsis were written by Fellows of the AAP Section on Allergy and Immunology and fellows in allergy and immunology training programs who contributed reviews with their mentors. The editor selected the journals to be reviewed on the basis of the likelihood that they would contain articles on allergy and immunology that would be of value and interest to the pediatrician. Each journal was assigned to a voluntary reviewer who was responsible for selecting articles and writing reviews of their articles. Only articles of original research were selected for review. Final selection of the articles to be included was made by the editor. The 2010–2011 journals chosen for review were Allergy, American Journal of Asthma & Allergy for Pediatricians, Archives of Pediatric and Adolescent Medicine, American Journal of Medicine, American Journal of Respiratory and Critical Care Medicine, Annals of Allergy, Asthma, and Immunology, Annals of Internal Medicine, Archives of Disease in Childhood, Archives of Internal Medicine, Blood, British Journal of Dermatology, British Medical Journal, Chest, Clinical and Experimental Allergy, Clinical Pharmacology and Therapeutics, Critical Care Medicine, European Journal of Pediatrics, European Respiratory Journal, Immunology, Journal of Allergy and Clinical Immunology, Journal of the American Academy of Dermatology, Journal of the American Medical Association, Journal of Applied Physiology, Journal of Experimental Medicine, Journal of Immunology, Journal of Infectious Diseases, Journal of Pediatric Gastroenterology and Nutrition, Journal of Pediatrics, Journal of Pharmacology and Experimental Therapeutics, Lancet, Nature, New England Journal of Medicine, Pediatrics, Medicine, Pediatric Allergy and Immunology, Pediatric Asthma, Allergy & Immunology, Pediatric Dermatology, Pediatric Infectious Disease Journal, and Science. The editor and the Section on Allergy and Immunology gratefully acknowledge the work of the reviewers and their trainees who assisted. The reviewers were Stuart L. Abramson, MD, PhD, Sugar Land, TX; James R. Banks, MD, Arnold, MD; Theresa A. Bingemann, MD, Rochester,

Allergy Testing in Childhood: Using Allergen-Specific IgE Tests

A variety of triggers can induce common pediatric allergic diseases which include asthma, allergic rhinitis, atopic dermatitis, food allergy, and anaphylaxis. Allergy testing serves to confirm an allergic trigger suspected on the basis of history. Tests for allergen-specific immunoglobulin E (IgE) are performed by in vitro assays or skin tests. The tests are excellent for identifying a sensitized state in which allergen-specific IgE is present, and may identify triggers to be eliminated and help guide immunotherapy treatment. However, a positive test result does not always equate with clinical allergy. Newer enzymatic assays based on anti-IgE antibodies have supplanted the radioallergosorbent test (RAST). This clinical report focuses on allergen-specific IgE testing, emphasizing that the medical history and knowledge of disease characteristics are crucial for rational test selection and interpretation.

Evaluating approved medications to treat allergic rhinitis in the United States: an evidence-based review of efficacy for nasal symptoms by class

OBJECTIVE To evaluate how well the medications currently approved in the United States for allergic rhinitis (AR) treat nasal symptoms when examined according to Food and Drug Administration-indicated uses and dosages. DATA SOURCES MEDLINE (1966 onward), EMBASE (1974 onward), and the Cochrane Library (2007) were systematically searched according to the following criteria defined at a roundtable meeting of the authors: randomized controlled trial, at least a 2-week duration, and approved indication and dosage in the United States. STUDY SELECTION Data from studies that met the inclusion criteria were extracted into evidence tables, which were reviewed twice by the full panel of authors. Individual panel members also were asked to comment on abstracts, articles, and summary tables based on their known expertise. The entire faculty approved the selection of studies included in this review. RESULTS Fifty-four randomized, placebo-controlled studies involving more than 14,000 adults and 1,580 children with AR met the criteria for review: 38 studies of seasonal allergic rhinitis (SAR; n = 11,980 adults and 946 children) and 12 studies of perennial allergic rhinitis (PAR; n = 3,800 adults and 366 children). The median percentage changes from baseline for total nasal symptom score for SAR were as follows: nasal antihistamines, -22.2%; oral antihistamines, -23.5%; intranasal steroids (INSs), -40.7%; and placebo, -15.0%. For PAR, the changes were as follows: oral antihistamines, -51.4%; INSs, -37.3%; and placebo, -24.8%. Data for mediator antagonists were limited. CONCLUSIONS The data, although limited, confirm that INSs produce the greatest improvements in nasal symptoms in patients with SAR. In addition, INSs are effective for PAR, but the data were of variable quality, and oral antihistamines may be equally effective for some patients. The reporting of published data should be standardized to permit better comparisons in future studies.

A double-blind controlled trial of anti-Pseudomonas chemotherapy of acute respiratory exacerbations in patients with cystic fibrosis

A double-blind controlled trail of anti-Pseudomonas chemotherapy was carried out in 24 exacerbations of pulmonary disease in patients with cystic fibrosis. Fifteen exacerbations were treated with oxacillin plus sisomicin and carbenicillin (treatment group); nine were treated with oxacillin alone (control group). The planned length of treatment was 14 days. The difference between the failure rate in the treatment group (3/15) and the control group (7/9) was statistically significant (P less than 0.015). The difference in improvement of forced expiratory volume in 1 second was also significant (P less than 0.025). At the end of the study, Pseudomonas aeruginosa was still present in the sputum of all nine patients in the control group, but was not isolated from six of the 15 patients in the treatment group. The data suggest a beneficial role for anti-Pseudomonas chemotherapy in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis.

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.