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Asthma disproportionately affects African American/Black (AA/B) and Hispanic/Latinx (H/L) patients and individuals with low socioeconomic status (SES), but the relationship between SES and asthma morbidity within these racial/ethnic groups is inadequately understood.To determine the relationship between SES and asthma morbidity among AA/B and H/L adults with moderate to severe asthma using multidomain SES frameworks and mediation analyses.We analyzed enrollment data from the PeRson EmPowered Asthma RElief randomized trial, evaluating inhaled corticosteroid supplementation to rescue therapy. We tested for direct and indirect relationships between SES and asthma morbidity using structural equation models. For SES, we used a latent variable defined by poverty, education, and unemployment. For asthma morbidity, we used self-reported asthma exacerbations in the year before enrollment (corticosteroid bursts, emergency room/urgent care visits, or hospitalizations), and Asthma Control Test scores. We tested for mediation via health literacy, perceived stress, and self-reported discrimination. All models adjusted for age, sex, body mass index, ethnicity, and comorbidities.Among 990 AA/B and H/L adults, low SES (latent variable) was directly associated with hospitalizations (β = 0.24) and worse Asthma Control Test scores (β = 0.20). Stress partially mediated the relationship between SES and increased emergency room/urgent care visits and worse asthma control (β = 0.03 and = 0.05, respectively). Individual SES domains were directly associated with asthma morbidity. Stress mediated indirect associations between low educational attainment and unemployment with worse asthma control (β = 0.05 and = 0.06, respectively).Lower SES is directly, and indirectly through stress, associated with asthma morbidity among AA/B and H/L adults. Identification of stressors and relevant management strategies may lessen asthma-related morbidity among these populations.

BACKGROUND: Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthmatic patients are lacking.OBJECTIVE: We sought to investigate pollution effects in a longitudinal asthma study and effect modification by controller medications.METHODS: We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide, and sulfur dioxide concentrations in 1003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to ZIP/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and forced vital capacity (FVC) percent predicted, FEV1/FVC ratio, and PC20, adjusting for seasonality and confounders.RESULTS: Same-day and 1-week average CO concentrations were negatively associated with postbronchodilator percent predicted FEV1 (change per interquartile range, -0.33 [95% CI, -0.49 to -0.16] and -0.41 [95% CI, -0.62 to -0.21], respectively) and FVC (-0.19 [95% CI, -0.25 to -0.07] and -0.25 [95% CI, -0.43 to -0.07], respectively). Longer-term 4-month CO averages were negatively associated with prebronchodilator percent predicted FEV1 and FVC (-0.36 [95% CI, -0.62 to -0.10] and -0.21 [95% CI, -0.42 to -0.01], respectively). Four-month averaged CO and ozone concentrations were negatively associated with FEV1/FVC ratio (P < .05). Increased 4-month average nitrogen dioxide concentrations were associated with reduced postbronchodilator FEV1 and FVC percent predicted. Long-term exposures to sulfur dioxide were associated with reduced PC20 (percent change per interquartile range, -6% [95% CI, -11% to -1.5%]). Treatment augmented the negative short-term CO effect on PC20.CONCLUSIONS: Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications might not protect but rather worsens the effects of CO on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication.

Background Formal economic evaluation using a model-based approach is playing an increasingly important role in health care decision making. Objective To develop a model by using an objective measure of lung function— prebronchodilator FEV 1 as a percent of predicted (FEV 1 % predicted)—as the primary independent factor to predict the frequency of adverse events related to the exacerbation of asthma on a population level. Methods We developed a Markov simulation model of childhood asthma by using data from the Childhood Asthma Management Program. The primary outcomes were the result of asthma exacerbations defined as hospitalizations, emergency department (ED) visits, and the need for oral corticosteroid therapy. Predicted monthly frequencies for each acute event were based on negative binomial regression equations estimated from the placebo arm of the Childhood Asthma Management Program with covariates of age, prebronchodilator FEV 1 % predicted, time in study, prior hospitalizations, and prior nocturnal awakenings. Results Simulated versus observed mean number of acute events were similar within the placebo and treatment groups. While the trial demonstrated treatment effects of 48% reduction in hospitalizations, 46% reduction in ED visits, and 44% reduction in the need for oral corticosteroid therapy at 48 months, the model simulated similar reductions of 49% in hospitalizations, 41% in ED visits, and 46% in the need for oral corticosteroid therapy. Conclusions Our findings suggest that longitudinal intervention effects may be modeled through FEV 1 % predicted to estimate hospitalizations, ED visits, and need for oral corticosteroid therapy in childhood asthma for planning and evaluation purposes.

Background Few studies have examined the effects of in utero smoke exposure (IUS) on lung function in children with asthma, and there are no published data on the impact of IUS on treatment outcomes in children with asthma. Objectives To explore whether IUS exposure is associated with increased airway responsiveness among children with asthma and whether IUS modifies the response to treatment with inhaled corticosteroids (ICSs). Methods To assess the impact of parent-reported IUS exposure on airway responsiveness in childhood asthma, we performed a repeated-measures analysis of methacholine PC 20 data from the Childhood Asthma Management Program, a 4-year, multicenter, randomized, double-masked, placebo-controlled trial of 1041 children age 5 to 12 years comparing the long-term efficacy of ICS with mast cell stabilizing agents or placebo. Results Although improvement was seen in both groups, children with asthma and IUS exposure had on average 26% less of an improvement in airway responsiveness over time compared with unexposed children ( P = .01). Moreover, while children who were not exposed to IUS who received budesonide experienced substantial improvement in PC 20 compared with untreated children (1.25-fold increase; 95% CI, 1.03-1.50; P = .02), the beneficial effects of budesonide were attenuated among children with a history of IUS exposure (1.04-fold increase, 95% CI, 0.65-1.68; P = .88). Conclusion In utero smoke exposure reduces age-related improvements in airway responsiveness among children with asthma. Moreover, IUS appears to blunt the beneficial effects of ICS use on airways responsiveness. These results emphasize the importance of preventing this exposure through smoking cessation counseling efforts with pregnant women.

Although inhaled corticosteroids (ICSs) generally protect against severe exacerbations in asthma, they may result in elevated IgE levels, which are associated with exacerbations.To determine whether variation in the low-affinity IgE receptor gene, FCER2, is associated with severe exacerbations defined as emergency department visits and/or hospitalizations in patients with asthma on ICSs.We resequenced, then genotyped 10 FCER2 single nucleotide polymorphisms (SNPs) in 311 children randomized to inhaled budesonide as part of the Childhood Asthma Management Program. We evaluated the association of FCER2 variants with IgE levels and presence or absence of severe exacerbations over the 4-year clinical trial. We also evaluated differences in cellular expression of the novel FCER2 SNP, T2206C.In white subjects, 3 FCER2 SNPs were significantly associated (P.05) with elevated 4-year IgE level; each was also associated with increased severe exacerbations. Final multivariable models demonstrated associations between T2206C and severe exacerbations in both white and African American children (hazard ratio, 3.95; 95% CI, 1.64-9.51; and hazard ratio, 3.08; 95% CI, 1.00-9.47), despite ICS use. Interaction models supported a true gene-environment effect in white subjects (interaction P = .004). T2206C was also associated with decreased FCER2 expression (P = .02).FCER2 predicts the likelihood of treatment protocol success in asthma. The associations of T2206C with IgE level, severe exacerbations, and FCER2 expression may provide a mechanistic basis for the observed findings.Genetic variation in FCER2 may help form a prognostic model for ICS response in asthma.

Background The effects of inhaled corticosteroid (ICS) preparations on bone health have been debated. Multiple analyses have been published examining the question, with mixed results. Objectives We examined how assumptions about the effect of ICS on bone mineral density (BMD) influence the cost-effectiveness of ICS in asthma. Methods We developed a mathematical simulation model to estimate clinical outcomes and costs for a cohort with mild/moderate asthma. The analysis conformed to reference case recommendations of the US Panel on Cost-Effectiveness in Health and Medicine. Sensitivity analysis evaluated the stability of our results to uncertainty in treatment duration, age at treatment, and ICS dose. Results Assuming a dose of 200 μg twice per day of ICS, a literature-based average effect of ICS on BMD and a 10-year time horizon, we observed a minimal increase in the costs attributed to hip fracture and incremental cost effectiveness ratio of $26,000 per quality-adjusted life-year and $14.00 per symptom-free day gained. Over an extended the time horizon (lifetime), the incremental cost effectiveness ratio increased to $42,000/quality-adjusted life-year. Only under a scenario of high-dose ICS, a lifetime horizon, and a large effect of ICS on BMD did the potential impact of ICS on BMD dramatically affect the economic attractiveness of therapy. Conclusion To minimize any potential impact, use of the lowest effective dose of ICS and measures to target and intervene in high-risk individuals are warranted. However, ICS therapy in mild/moderate asthma compares favorably with commonly accepted interventions over a wide range of assumptions regarding this treatment and its effects on BMD.

In last month’s Journal, Szefler et al presented an article from the National Heart, Lung, and Blood Institute Childhood Asthma Research and Education (CARE) Network on the characterization of response to 2 common therapies for childhood asthma. The article establishes a definition of response as the percent change in prebronchodilator FEV1 7.5%. The importance of the article is that it selected a working definition of response and then attempted to assess whether predictors of response could be determined. The article by Szefler et al takes a systematic look at one definition of response and serves as an example for future discussion of how one characterizes a responder. A limitation in the interpretation of the asthma literature is the inconsistency in the definition of response. The heterogeneity and variability of asthma make it difficult to achieve consensus for this term. This is compounded by the lack of a standardized means to assess asthma control, a measure of response. Should response to an intervention be defined primarily by objective parameters, subjective symptom reports, or a composite measure? Is the observed response to an intervention clinically as well as statistically significant, and how has the choice of primary outcome and sample size influenced these results? In addition, which parameters should be more appropriately thought of as markers of disease severity than measures of response? If these issues are difficult for the specialist and researcher to resolve, how can we provide guidance to our primary care colleagues when they read the asthma literature? The definition of responder is increasingly important as the number of assessment tools multiplies beyond traditional clinical trials to include observational investigations, studies of patients with specific phenotypes

Studies examining the influence of provider behavior and patterns of care delivery on the use of anti-inflammatory asthma therapy have been limited to selected populations or have been unable to assess the appropriateness of therapy for individuals. We have previously reported the influence of sociodemographic variables and asthma severity on reported use of asthma medications in the United States.We sought to examine the influence of patterns of care delivery and clinician behavioral factors on the use of anti-inflammatory medication by patients with asthma.We performed a cross-sectional national random digit dial household telephone survey in 1998 of adult patients and parents of children with current asthma. Respondents were classified as having current asthma if they had a physician's diagnosis of asthma and were either taking medication for asthma or had asthma symptoms during the past year.One or more persons met the study criteria for current asthma in 3273 (7.8%) households in which a screening questionnaire was completed. Of the 2509 persons (721 children16 years of age) with current asthma interviewed, 507 (20.1%) reported current use of anti-inflammatory medication. In a multiple logistic regression model controlling for asthma symptoms, reported anti-inflammatory use was significantly associated with patients reporting their physician having an excellent ability to explain asthma management (odds ratio [OR], 1.47; 95% CI, 1.09-1.98), scheduling regular visits to a physician for asthma (OR, 1.30; 95% CI, 1.02-1.64), having a written asthma action plan (OR, 1.63; 95% CI, 1.29-2.06), and being of white, non-Hispanic ethnicity (OR, 1.53; 95% CI, 1.19-1.98), along with markers of greater asthma morbidity, missing 6 or more days from work or school in the past year (OR, 1.29; 95% CI, 1.01-1.65), and hospitalization for asthma in the past year (OR, 1.74; 95% CI, 1.19-2.53). Anti-inflammatory use was less likely to be reported with younger age (OR, 0.82; 95% CI, 0.73-0.94), lower long-term asthma symptom burden (OR, 0.82; 95% CI, 0.71-0.94), use of 4 or fewer reliever inhaler canisters in the past year (OR, 0.50; 95% CI, 0.43-0.58), and smoking (OR, 0.50; 95% CI, 0.37-0.68).How asthma care is delivered influences the use of anti-inflammatory medication. Strategies to increase regular evaluation by a physician interested in asthma, particularly for minority patients, and to increase a physician's ability to communicate asthma management to patients might improve use of anti-inflammatory therapy among patients with asthma.

Background: In patients with asthma, treatment for associated conditions, such as rhinitis, is recommended. It is unknown whether this treatment can reduce the risk for emergency department (ED) visits for asthma. Objectives: We sought to determine whether treatment with intranasal steroids or prescription antihistamines in persons with asthma is associated with a reduced risk for ED visits caused by asthma. Methods: We performed a retrospective cohort study of members of a managed care organization aged greater than 5 years who were identified during the period of October 1991 to September 1994 as having a diagnosis of asthma by using a computerized medical record system. The main outcome measure was an ED visit for asthma. Results: Of the 13,844 eligible persons, 1031 (7.4%) had an ED visit for asthma. The overall relative risk (RR) for an ED visit among those who received intranasal corticosteroids, adjusted for age, sex, frequency of orally inhaled corticosteroid and β-agonist dispensing, amount and type of ambulatory care for asthma, and diagnosis of an upper airways condition (rhinitis, sinusitis, or otitis media), was 0.7 (95% confidence interval [CI], 0.59-0.94). For those receiving prescription antihistamines, the risk was indeterminate (RR, 0.9; 95% CI, 0.78-1.11). When different rates of dispensing for intranasal steroids were examined, a reduced risk was seen in ED visits in those with greater than 0 to 1 (RR, 0.7; 95% CI, 0.57-0.99) and greater than 3 (RR, 0.5; 95% CI, 0.23-1.05) dispensed prescriptions per year. Conclusions: Treatment of nasal conditions, particularly with intranasal steroids, confers significant protection against exacerbations of asthma leading to ED visits for asthma. These results support the use of intranasal steroids by individuals with asthma and upper airways conditions. (J Allergy Clin Immunol 2002;109:636-42.)

Background: Asthma is the most common chronic disease among children and the most frequent cause of hospitalization. Appropriate pharmacotherapy is a cornerstone of published national guidelines for the care of children with asthma. Objective: The goal was to compare the baseline pharmacotherapy and health care utilization from 1996 to 1997 in children with asthma at managed care organizations (MCOs). Methods: A common protocol was used to extract the study sample from 3 MCOs with automated claims and pharmacy databases. Children were selected if they were 3 to 15 years old as of June 1997 with 1 or more encounters (outpatient, emergency department visit, hospitalization) with an asthma diagnosis in the previous year. Results: Of the 13,352 children studied, less than 40% were given controllers during the 12-month interval, with ranges of 15% to 77% by level of bronchodilator use, 31% to 44% by age, and 38% to 42% by MCO. Among children given 6 or more bronchodilators, controller dispensing ranged from 73% to 89% among the 3 MCOs. Variability was most evident for inhaled corticosteroids, for which dispensing ranged from 51% to 70%. Rates of asthma hospitalization and emergency department visits also differed among the MCOs, ranging from 21 to 37 per 1000 person-years and 37 to 142 per 1000 person-years, respectively. Conclusion: Five years after dissemination of national guidelines for care, the pattern of asthma therapy does not reflect guideline recommendations. Variation among health care organizations with respect to asthma therapy and utilization of health services exists. In addition, controller medications may not be used by all children who could benefit from them. (J Allergy Clin Immunol 2000;106:1108-14.)

The ability to predict and prevent future exacerbations has been a consistent focus of asthma research. Although some progress has been made on identifying factors associated with an increased risk of exacerbation at the population and individual levels, no measure or instrument is available for widespread use in the asthma community. In this issue of the Journal, Thamrin et al present a statistical method used to calculate the future exacerbation risk for a patient (as defined by deterioration in percent predicted peak expiratory flow [PEF]) based on the history of fluctuations in lung function (percent predicted PEF). The authors challenge us to reframe our analytic approach to asthma. Frey et al have suggested that a patient with asthma should be thought of as a complex, nonlinear dynamic systems network; such a network exhibits fluctuations over time in physiologic and clinical variables. However, such a system also exhibits memory effects, and although changes can occur over time, the recent past will include most of the pertinent information needed to predict the short-term future risk. Viewingasthma through this framework, it follows that the single best individual parameter to predict the risk of an exacerbation over the next year is the history of an exacerbation in the prior year. The natural history of asthma in any given patient is a summation of personal characteristics (eg, demographics, inflammatory profile, and lungmechanics), genetics, both the physical (exposure to environment [environmental tobacco smoke, pollution, and allergens]) and psychosocial (access to care) environment, and therapy (including adherence). The complex interaction of these factors results in the overall clinical phenotype expressed by a patient, and this helps explain why the recent past is a strong predictor of future events. Modeling asthma as a complex, nonlinear dynamic system also fits with our increasing recognition of the heterogeneity of asthma. Patients with asthma present differently in regard to symptoms, physiologic measures, inflammatory indices, and perception of obstruction; measuring a single parameter at a single point might not

Classifying asthma severity or activity has evolved, but there are no published weighted composite measures of asthma disease activity that account for the relative importance of the many individual clinical variables that are widely used.We sought to develop a weighted and responsive measure of asthma disease activity.Discriminant and multiple regression analyses based on 2 previously conducted clinical trials were used to develop the Asthma Disease Activity Score (ADAS-6).The ADAS-6 demonstrated content validity because its components assess different manifestations of asthma: FEV(1) (percent predicted), Asthma Quality of Life Questionnaire-Symptom domain, rescue β-agonist use, nocturnal awakenings, peak expiratory flow diurnal variability, and rescue β-agonist use diurnal variability. The ADAS-6 demonstrated cross-sectional and longitudinal validity. It was discriminating: it distinguished levels of disease activity and response to different treatment intensities (P.0001). Similar results were obtained with an independent clinical trial. The ADAS-6 was highly responsive to treatment effects, with a standardized effect size exceeding that of other widely used outcome measures. Using ADAS-6 as the primary end point in the montelukast pivotal trials would have significantly reduced the sample size needed to detect a comparable change in outcome. Furthermore, increments in the ADAS-6 predicted the risk of future asthma attacks. A simplified Asthma Disease Activity Score 4-variable version (ADAS-4) demonstrated similar measurement properties.The ADAS-6 and ADAS-4 are novel, weighted, and responsive measures of asthma disease activity. Use of these measures in clinical trials might better separate treatment effects, predict future asthma attacks, and substantially reduce sample size.

Rationale A decision to implement innovative disease management interventions in health plans often requires evidence of clinical benefit and financial impact. The Pediatric Asthma Care PORT II trial evaluated the outcomes of two asthma care strategies in children (ages 3 – 17) – a peer leader based physician behavior change intervention (PLE) and a practice-based redesign (Planned Asthma Care Intervention (PACI)). The purpose of this study is to estimate the cost-effectiveness of the interventions. Methods This was a three-arm cluster randomized trial conducted in 41 primary care practices within 3 managed care organizations. 638 children with mild to moderate persistent asthma were observed for up to two years. Practices were randomized to PLE (N=226), PACI (N=213) or usual care (N=199). The primary outcome was average symptom-free days (SFD) estimated from GEE models. Costs for the interventions, asthma-related hospitalizations, ED visits, office visits and medications were included. Non-medical costs were excluded. Results Mean annual costs per patient were: PACI=$1436, PLE=$970 and Usual Care=$388. The incremental difference in annual SFD for the interventions compared to usual care was 6.5 (95% CI −3.6 to 16.9 days) for PLE and 13.3 (95% CI 2.1 to 24.7 days) for PACI. Compared to usual care the incremental cost-effectiveness ratio (ICER) was $90 per SFD gained for PLE and $79 per SFD gained for PACI. In subgroup analyses, ICERs varied by child's age and baseline medication use. Conclusions The cost-effectiveness ratios of these interventions are greater than those of other asthma interventions tested in other settings.