Rationale: Adherence to inhaled corticosteroid (ICS) medication is known to be low overall, but tends to be lower among African-American patients when compared with white patients.

Objectives: To understand the factors that contribute to ICS adherence among African-American and white adults with asthma.

Methods: Eligible individuals had a prior diagnosis of asthma, one or more ICS prescriptions, and were members of a large health maintenance organization in southeast Michigan. Individuals were sent a survey that included questions about internal factors (e.g., patient beliefs, knowledge, and motivation) and external factors (e.g., socioeconomic status, barriers to care, social support, and stressors) potentially related to ICS adherence. Adherence was calculated using electronic prescription and fill data. Stepwise regression was used to identify factors associated with adherence before and after stratifying by race-ethnicity.

Measurements and Main Results: Surveys were returned by 1,006 (56.3%) of 1,787 eligible patients. Adjusting for internal factors, but not external factors, diminished the relationship between race-ethnicity and ICS adherence. Among African-American patients, readiness to take ICS medication was the only internal or external factor significantly associated with ICS adherence; it explained 5.6% of the variance in adherence. Among white patients, perceived ICS necessity, ICS knowledge, doctors being perceived as the source of asthma control, and readiness to take medication were the internal factors associated with ICS adherence; these accounted for 19.8% of the variance in adherence.

Conclusions: Factors associated with ICS adherence appear to differ between African-American and white patients, suggesting that group-specific approaches are needed to improve adherence.

Objective

To summarize the existing literature on the association of endotoxin with respiratory diseases and allergic sensitization and to review the potentially modifying effects of endotoxin receptor polymorphisms.

Data Sources

English-language articles were identified from the MEDLINE and PubMed databases using combinations of the following search terms: endotoxin, toll-like receptor, polymorphisms, atopy, asthma, and allergy. Other sources included experts in the field and the bibliographies of pertinent articles.

Study Selection

Relevant articles were selected based on the authors’ expert opinion.

Results

Cross-sectional studies, particularly those of children raised in rural European communities, suggest that early endotoxin exposure may protect against the development of allergic sensitization and atopic asthma. However, endotoxin exposure may also contribute to other nonatopic respiratory disorders and may exacerbate disease in individuals with preexisting asthma. Paradoxically, among individuals exposed to high levels of endotoxin, carriers of a functional mutation in toll-like receptor 4, which reduces cellular responsiveness to endotoxin, may be at lower risk of developing allergic sensitization.

Conclusions

The effect of endotoxin exposure on allergic sensitization and asthma appears to be influenced by the timing of exposure, the presence or absence of preexisting disease, and polymorphisms in the genes that encode endotoxin receptors. Further studies are needed to define the window period for this effect, as well as the underlying immunologic mechanism.

Background

Worsening renal function (WRF) during heart failure (HF) hospitalization is an accepted correlate of poor prognosis. Loop diuretics are increasingly being considered as a potential cause of worsened HF outcomes, perhaps via WRF. However, the magnitude of worsening in renal function attributable to loop diuretics has not been quantified.

Methods

This was a retrospective cohort study of patients who received care from a large health system and had a primary hospital discharge diagnosis of HF between Jan 1, 2000 and June 30, 2008. Patients with preexisting end-stage renal disease were excluded. Daily creatinine (Cr) measurements, furosemide dosing (only loop diuretic on hospital formulary), and radiocontrast dye studies were collected using administrative data. Day-to-day changes in Cr and MDRD estimated glomerular filtration (eGFR) were calculated. The first Cr or eGFR value during hospitalization or in the emergency department was considered baseline. Generalized estimating equations were used to test the association furosemide exposure over previous 2 days to the daily change in Cr and eGFR. Covariates included undergoing radiocontrast study, age, race, gender, and baseline Cr or eGFR.

Results

Among 6071 patients who met inclusion criteria there were a total of 20,645 observations. This cohort was 51% female, 68% African American, and baseline Cr was 1.36 mg/dl. Furosemide exposure was associated with an average daily increase in Cr of 0.021 mg/dL and decrease in eGFR of 0.72 ml/min/1.73m2 (per 100 mg furosemide daily, both p<0.001). Over a typical length of stay of 5 days this would amount to a Cr increase of 0.11 mg/dL or decrease in eGFR of 3.6 ml/min/1.73m2. Furosemide exposure accounted for only 0.4% and 0.1% of the variation in Cr and eGFR changes, respectively. Undergoing radiocontrast study, African American race, and higher age were associated with day-to-day creatinine increases (all p<0.01). Reanaysis after classifying furosemide exposure into low (<40mg/day), medium (40–100mg/day), and high (>100mg/day) and censoring patients-days after radiocontrast exposure did not significantly affect the magnitude of the worsening renal function.

Conclusions

While loop diuretic exposure is statistically associated with WRF among hospitalized HF patients, the associated magnitude of renal function change is very small, and loop diuretics explain little of the variability in renal function during hospitalization. More important explanatory factors likely exist but remain unidentified.

Background

Beta blockers (BB) are a mainstay of heart failure (HF) treatment, yet there is inconclusive data regarding their efficacy in African American individuals.

Methods and Results

We performed a retrospective study of insured patients who received care from a large health system who were hospitalized for HF between January, 2000 and June, 2008, and had a documented ejection fraction <50%. BB exposure was estimated over six-month rolling windows using pharmacy claims data. Proportional hazards regression was used to test the association between BB exposure and all-cause hospitalization or death with adjustment for baseline covariates and other HF medication exposure. We performed analyses stratified by race, and overall with a BB exposure*Race interaction term. A total of 1,094 patients met inclusion criteria (476 white and 618 African American individuals). Median follow up was 2.1 years. In adjusted models BB exposure was associated with lower risk of death or hospitalization in both groups, but more so in white individuals (HR 0.40, 95%CI 0.27, 0.60, p<0.001) compared with African American individuals (HR 0.67, 95%CI 0.48, 0.94, p=0.024). A formal test for interaction indicated that the protection association for BB exposure differed by race (p=0.098, β=0.40). Reanalysis restricted to BBs approved for HF, or HF-specific hospitalizations did not substantively alter the findings.

Conclusion

BB appears to be 40–50% less effective in preventing death or hospitalization among African American patients with HF as compared with white individuals. Further study is needed to better understand BB effectiveness in African Americans with HF.

Background

Asthma is an inflammatory condition often punctuated by episodic symptomatic worsening, and accordingly, individuals with asthma may have waxing and waning adherence to controller therapy.

Objective

To measure changes in inhaled corticosteroid (ICS) adherence over time, and to estimate the effect of this changing pattern of use on asthma exacerbations.

Methods

ICS adherence was estimated from electronic prescription and fill information for 298 participants in the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). For each individual we calculated a moving average of ICS adherence for each day of follow-up. Asthma exacerbations were defined as the need for oral corticosteroids, an asthma-related emergency department visit, or an asthma-related hospitalization. Proportional hazard models were used to assess the relationship between ICS medication adherence and asthma exacerbations.

Results

Adherence to ICS medications began to increase prior to the first asthma exacerbation and continued afterward. Adherence was associated with a reduction in exacerbations, but was only statistically significant among individuals whose adherence was >75% of the prescribed dose (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.41–0.90) when compared with individuals whose adherence was ≤25%. This pattern was largely confined to individuals whose asthma was not well controlled initially. An estimated 24% of asthma exacerbations were attributable to ICS medication non-adherence.

Conclusions

Inhaled corticosteroid adherence varies in the time period leading up to and following an asthma exacerbation, and non-adherence likely contributes to a large number of these exacerbations. High levels of adherence are likely required to prevent these events. [ClinicalTrials.gov number NCT01142947]

BACKGROUND:

The effects of in utero tobacco smoke exposure on childhood respiratory health have been investigated, and outcomes have been inconsistent.

OBJECTIVE:

To determine if in utero tobacco smoke exposure is associated with childhood persistent asthma in Mexican, Puerto Rican, and black children.

PATIENTS AND METHODS:

There were 295 Mexican, Puerto Rican, and black asthmatic children, aged 8 to 16 years, who underwent spirometry, and clinical data were collected from the parents during a standardized interview. The effect of in utero tobacco smoke exposure on the development of persistent asthma and related clinical outcomes was evaluated by logistic regression.

RESULTS:

Children with persistent asthma had a higher odds of exposure to in utero tobacco smoke, but not current tobacco smoke, than did children with intermittent asthma (odds ratio [OR]: 3.57; P = .029). Tobacco smoke exposure from parents in the first 2 years of life did not alter this association. Furthermore, there were higher odds of in utero tobacco smoke exposure in children experiencing nocturnal symptoms (OR: 2.77; P = .048), daily asthma symptoms (OR: 2.73; P = .046), and emergency department visits (OR: 3.85; P = .015) within the year.

CONCLUSIONS:

Exposure to tobacco smoke in utero was significantly associated with persistent asthma among Mexican, Puerto Rican, and black children compared with those with intermittent asthma. These results suggest that smoking cessation during pregnancy may lead to a decrease in the incidence of persistent asthma in these populations.

Background

Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans.

Methodology/Principal Findings

We evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA) Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV1) per pack-year of smoking (−5.7 ml FEV1/ smoking pack-year) compared with smokers with lower African ancestry (−4.6 ml in FEV1/ smoking pack-year) (interaction P value  = 0.17). Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV1 decline in Health ABC and independently replicated in CARDIA.

Conclusions/Significance

African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking.

Worsened renal function (WRF) during heart failure (HF) hospitalization is associated with in-hospital mortality, but there are limited data regarding its relationship to long-term outcomes after discharge. The influence of WRF resolution is also unknown. This retrospective study analyzed patients who received care from a large health system and had a primary hospital discharge diagnosis of HF between 1/2000 and 6/2008. Renal function was estimated from creatinine levels during hospitalization. The first available value was considered baseline. WRF was defined a creatinine increase of ≥0.3mg/dl on any subsequent hospital day compared to baseline. Persistent WRF was defined as having WRF at discharge. Proportional hazards regression, adjusting for baseline renal function and potential confounding factors, was used to assess time to re-hospitalization or death. Among 2465 patients who survived to discharge, 887 (36%) developed WRF. Median follow up was 2.1 years. In adjusted models, WRF was associated with higher rates of post-discharge death or re-hospitalization (HR 1.12, 95%CI 1.02 – 1.22). Among those with WRF, 528 (60%) had persistent WRF while 359 (40%) recovered. Persistent WRF was significantly associated with higher post-discharge event rates (HR 1.14, 95%CI 1.02 – 1.27), whereas transient WRF showed only a non-significant trend towards risk (HR 1.09 95%CI 0.96-1.24). In conclusion, among patients surviving hospitalization for HF, WRF was associated with increased long-term mortality and re-hospitalization, particularly if renal function did not recover by the time of discharge.

Background

Inhaled corticosteroid (ICS) non-adherence is common among patients with asthma; however, interventions to improve adherence have often been complex and not easily applied to large patient populations.

Objective

To assess the effect of supplying patient adherence information to primary care providers.

Methods

Patients and providers were members of a health system serving southeast Michigan. Providers (88 intervention; 105 control) and patients (1,335 intervention; 1,363 control) were randomized together by practice. Patients were age 5–56 years; had a diagnosis of asthma; and had existing prescriptions for ICS medication. Adherence was estimated using prescription and fill data. Unlike clinicians in the control arm, intervention arm providers could view updated ICS adherence information on their patients via electronic prescription software, and further details on patient ICS use could be viewed by selecting that option. The primary outcome was ICS adherence in last 3-months of the study period.

Results

At study end for the intention-to-treat analysis, ICS adherence was not different among patients in the intervention arm when compared with those in the control arm (21.3% vs. 23.3%, respectively; P=0.553). However, adherence was significantly higher among patients whose clinician elected to view their detailed adherence information (35.7%) when compared with both control arm patients (P=0.026) and intervention arm patients whose provider did not view adherence data (P=0.002).

Conclusions

Overall, providing adherence information to clinicians did not improve ICS use among patients with asthma. However, patient use may improve when clinicians are sufficiently interested in adherence to view the details of this medication use.

BACKGROUND

Self-identified race or ethnic group is used to determine normal reference standards in the prediction of pulmonary function. We conducted a study to determine whether the genetically determined percentage of African ancestry is associated with lung function and whether its use could improve predictions of lung function among persons who identified themselves as African American.

METHODS

We assessed the ancestry of 777 participants self-identified as African American in the Coronary Artery Risk Development in Young Adults (CARDIA) study and evaluated the relation between pulmonary function and ancestry by means of linear regression. We performed similar analyses of data for two independent cohorts of subjects identifying themselves as African American: 813 participants in the Health, Aging, and Body Composition (HABC) study and 579 participants in the Cardiovascular Health Study (CHS). We compared the fit of two types of models to lung-function measurements: models based on the covariates used in standard prediction equations and models incorporating ancestry. We also evaluated the effect of the ancestry-based models on the classification of disease severity in two asthma-study populations.

RESULTS

African ancestry was inversely related to forced expiratory volume in 1 second (FEV1) and forced vital capacity in the CARDIA cohort. These relations were also seen in the HABC and CHS cohorts. In predicting lung function, the ancestry-based model fit the data better than standard models. Ancestry-based models resulted in the reclassification of asthma severity (based on the percentage of the predicted FEV1) in 4 to 5% of participants.

CONCLUSIONS

Current predictive equations, which rely on self-identified race alone, may misestimate lung function among subjects who identify themselves as African American. Incorporating ancestry into normative equations may improve lung-function estimates and more accurately categorize disease severity. (Funded by the National Institutes of Health and others.)

Purpose

To investigate the association of the thiazolidinediones (TZDs), rosiglitazone and pioglitazone, together and individually on the risk of cardiovascular outcomes and all-cause mortality, using time-updated propensity score adjusted analysis

Methods

We conducted a retrospective cohort study in a large vertically integrated health system in southeast Michigan. Cohort inclusion criteria included adult patients with diabetes treated with oral medications and followed longitudinally within the health system between January 1, 2000 and December 1, 2006. The primary outcome was fatal and non-fatal acute myocardial infarction. Secondary outcomes included hospitalizations for congestive heart failure, fatal and non-fatal cerebrovascular accidents and transient ischemic attacks, combined coronary heart disease events, and all-cause mortality.

Results

19,171 patients were included in this study. Use of TZDs (adjusted hazard ratio [aHR] with propensity adjustment [PA], 0.92; 95% confidence interval [CI] 0.73–1.17), rosiglitazone (aHR with PA, 1.06; 95% CI 0.66–1.70), and pioglitazone (aHR with PA, 0.91; 95% CI 0.69–1.21) was not associated with a higher risk of acute myocardial infarction. However, pioglitazone use was associated with a reduction in all-cause mortality (aHR with PA, 0.60; 95% CI 0.42–0.96). Compared with rosiglitazone, pioglitazone use was associated with a lower risk of all outcomes assessed, particularly congestive heart failure (P = 0.013) and combined coronary heart disease events (P = 0.048).

Conclusions

Our findings suggest that pioglitazone may have a more favorable risk profile when compared to rosiglitazone, arguing against a singular effect for TZDs on cardiovascular outcomes.

Purpose

The purpose of this study was to apply the self-determination theory (SDT) model of health behavior to predict medication adherence, quality of life, and physiological outcomes among patients with diabetes.

Methods

Patients with diabetes (N = 2,973) receiving care from an integrated health-care delivery system in 2003 and 2004 were identified from automated databases and invited to participate in this study. In 2005, patients responded to a mixed telephone-and-mail survey assessing perceived autonomy-support from health-care providers, autonomous self-regulation for medication use, perceived competence for diabetes self-management, medication adherence, and quality of life. In 2006, we used pharmacy-claims data to indicate medication adherence and we assessed patients’ non-HDL cholesterol, HbA1c, and glucose levels.

Results

The SDT model of health behavior provided adequate fit to the data. As hypothesized, perceived autonomy-support from health-care providers related positively to autonomous self-regulation for medication use, which in turn related positively to perceived competence for diabetes self-management. Perceived competence then related positively to quality of life and medication adherence, and the latter construct related negatively to non-HDL cholesterol, HbA1c, and glucose levels.

Conclusions

Health-care providers’ support for patients’ autonomy and competence around medication use and diabetes self-management related positively to medication adherence, quality of life, and physiological outcomes among patients with diabetes.

Background

Accurately indentifying heart failure (HF) patients from administrative claims data is useful for both research and quality of care efforts. Yet, there are few comparisons of the various claims data criteria (also known as claims signatures) for identifying HF patients. We compared various HF claim signatures to assess their relative accuracy.

Methods

In this retrospective study, we identified 4174 patients who received care from a large health system in southeast Michigan and who had ≥1 HF encounter between January 1, 2004 and December 31, 2005. Four hundred patients were chosen at random and a detailed chart review was performed to assess which met the Framingham HF criteria. The sample was divided into 300 subjects for derivation and 100 subjects for validation. Sensitivity, specificity,, and area under the curve (AUC) were determined for the various claim signatures. The criteria with the highest AUC were retested in the validation set.

Results

Of the 400 patients sampled, 65% met Framingham HF criteria, and 56% had at least one B-type Natriuretic Peptide (BNP) measurement. There was substantial variation between claims signatures in terms of sensitivity (range 15%-77%) and specificity (range 69%-100%). The best performing criteria in the derivation set was if patients met any one of the following: ≥2 HF encounters, any hospital discharge diagnosis of HF, or a BNP ≥200 pg/ml. These criteria showed a sensitivity of 76%, specificity of 75%, and AUC of 0.754 for meeting the Framingham HF criteria. This claims signature performed similarly in the validation set.

Conclusion

Claim signatures for HF vary greatly in their relative sensitivity and specificity. These findings may facilitate efforts to identify HF patients for research and quality improvement efforts.

A highly heritable and reproducible measure of asthma severity is baseline pulmonary function. Pulmonary function is largely determined by airway smooth muscle (ASM) tone and contractility. The large conductance, voltage and calcium-activated potassium (BK) channel negatively regulates smooth muscle tone and contraction in ASM. The modulatory subunit of BK channels, the β1-subunit, is critical for proper activation of BK channels in smooth muscle and has shown sex hormone specific regulation. We hypothesized that KCNMB1 genetic variants in African Americans may underlie differences in bronchial smooth muscle tone and thus pulmonary function, possibly in a sex-specific manner. Through resequencing of the KCNMB1 gene we identified several common variants including a novel African-specific coding polymorphism (C818T, R140W). The C818T SNP and four other KCNMB1 variants were genotyped in two independent groups of African American asthmatics (n = 509) and tested for association with the pulmonary function measure – forced expiratory volume (FEV1) % of predicted value. The 818T allele is associated with a clinically significant decline (−13%) in FEV1 in both cohorts of asthmatics among males but not females (Pcombined = 0.0003). Patch clamp electrophysiology studies of the BK channel expressed with the 140Trp variant of the β1-subunit demonstrated significantly reduced channel openings, predicted by the loss of pulmonary function observed. African American male asthmatics carrying the 818T allele (10% of population) are potentially at risk for greater airway obstruction and increased asthma morbidity. Female asthmatics may be insulated from the deleterious effects of the 818T allele by estrogen-mediated upregulation in BK channel activity.

Background

Innate immune system stimuli, such as endotoxin, seem to affect allergy risk. Previously, we described gene-environment interactions between the endotoxin receptor polymorphism C-260T of the CD14 gene and endotoxin exposure on total serum IgE level; however, the mechanism of this interaction is not known.

Objective

To examine whether this gene-environment interaction affects early CD4+Foxp3− or CD4+Foxp3+ lymphocyte numbers.

Methods

Participating children were part of a birth cohort in the Detroit metropolitan area. Participants were genotyped for the CD14 C-260T polymorphism. Endotoxin exposure was estimated from dust measured in the home when children were 6 months old. Intracellular Foxp3 protein expression, a regulatory T-cell marker, was used to characterize CD4+ lymphocytes in blood samples collected at the age of 12 months; total serum IgE level was also measured at this time. Because race/ethnicity may confound or modify genetic associations, all analyses were stratified by race/ethnicity.

Results

We observed a significant gene-environment interaction between CD14 C-260T genotype and endotoxin exposure on CD4+ lymphocyte numbers, particularly CD4+Foxp3− lymphocytes. Stratified analyses suggest effect modification by race/ethnicity on CD4+Foxp3+ lymphocyte numbers, with a significant interaction in African American children but not in white children. The interaction between CD14 C-260T genotype and endotoxin exposure on total IgE levels was opposite that observed for CD4+ lymphocyte numbers, suggesting reciprocal relationships.

Conclusions

A gene-environment interaction between endotoxin and CD14 C-260T genotype on IgE levels may be the result of an upstream, opposing effect on CD4+Foxp3+ and CD4+Foxp3− lymphocyte numbers. Race/ethnicity may affect which of these cell populations is affected by this gene-environment interaction.

Background

US national guidelines recommend assessing short-acting β-agonist (SABA) medication use as a marker of asthma severity and control. However, the relationship between recent SABA use and asthma exacerbations is not currently known.

Objective

To evaluate the proximal relationship between the type and frequency of SABA use and asthma-related outcomes.

Methods

We evaluated SABA use among patients with asthma ages 5 to 56 years who were members of a large health maintenance organization in southeast Michigan. Frequency of use was estimated from pharmacy data assessing the timing and amount of SABA fills. Cox proportional hazards models were used to examine the prospective relationship between average daily SABA use for 3 months and outcomes associated with poor asthma control (ie, oral corticosteroids use, asthma-related emergency department visits, and asthma-related hospitalizations). We separately accounted for SABA metered-dose inhaler (MDI) and SABA nebulizer use.

Results

Of the 2,056 patients who met study criteria, 1,569 (76.3%) had used a SABA medication in their baseline year. After adjusting for potential confounders, SABA nebulizer use was associated with asthma-related emergency department visits (adjusted hazard ratio [aHR], 6.32; 95% confidence interval [CI], 2.38 to 16.80) and asthma-related hospitalizations (aHR, 21.62; 95% CI, 3.17 to 147.57). In contrast, frequency of SABA MDI use was not associated with these outcomes.

Conclusions

Frequency of SABA use during a 3-month period was associated with poor asthma outcomes. The relationship with poor asthma outcomes was strongest for SABA nebulizer use, suggesting that the type of SABA used is also of prognostic importance.

OBJECTIVE

Although poor medication adherence may contribute to inadequate diabetes control, ways to feasibly measure adherence in routine clinical practice have yet to be established. The present study was conducted to determine whether pharmacy claims–based measures of medication adherence are associated with clinical outcomes in patients with diabetes.

RESEARCH DESIGN AND METHODS

The study setting was a large, integrated delivery and financial system serving the residents of southeastern Michigan. The study population consisted of 677 randomly selected patients aged ≥18 years with a diagnosis of diabetes, hypercholesterolemia, and hypertension and who filled at least one prescription for either an antidiabetic, lipid-lowering, or antihypertensive drug in each of the 3 study years (1999–2001). The main outcome measures were HbA1c, LDL cholesterol levels, and blood pressure.

RESULTS

Nonadherent patients had both statistically and clinically worse outcomes than adherent patients. Even after adjusting for demographic and clinical characteristics, nonadherence was significantly associated with HbA1c and LDL cholesterol levels. A 10% increase in nonadherence to metformin and statins was associated with an increase of 0.14% in HbA1c and an increase of 4.9 mg/dl in LDL cholesterol levels. Nonadherence to ACE inhibitors was not significantly associated with blood pressure.

CONCLUSIONS

Claims-based measures of medication adherence are associated with clinical outcomes in patients with diabetes and may therefore prove to be useful in clinical practice. More research is needed on methods to introduce claims-based adherence measurements into routine clinical practice and how to use these measurements to effectively improve adherence and health outcomes in chronic care management.

Strategies for identifying urban youth with asthma have not been described for high school settings. African-American high school students are rarely included in asthma studies, despite a high risk of asthma mortality when compared to other age and race groups. Identification and follow-up of children with uncontrolled respiratory symptoms are necessary to reduce the burden of asthma morbidity and mortality, especially in underserved areas. We describe a process used to identify high school students who could benefit from intervention based on self-report of asthma and/or respiratory symptoms, and the costs associated with symptom-identification. Letters announcing a survey were mailed to parents of 9th–11th graders by an authorized vendor managing student data for the school district. Scan sheets with student identifiers were distributed to English teachers at participating schools who administered the survey during a scheduled class. Forms were completed by 5,967 of the 7,446 students assigned an English class (80% response). Although prevalence of lifetime asthma was 15.8%, about 11% of students met program criteria for enrollment through report of an asthma diagnosis and recent symptoms, medication use, or health care utilization. Another 9.2% met criteria by reported symptoms only. Cost of symptom-identification was $5.23/student or $32.29/program-eligible student. There is a need for school-based asthma programs targeting urban adolescents, and program initiation will likely require identification of students with uncontrolled symptoms. The approach described was successfully implemented with a relatively high response rate. Itemized expenses are presented to facilitate modifications to reduce costs. This information may benefit providers, researchers, or administrators targeting similar populations.

Strategies for identifying urban youth with asthma have not been described for high school settings. African-American high school students are rarely included in asthma studies, despite a high risk of asthma mortality when compared to other age and race groups. Identification and follow-up of children with uncontrolled respiratory symptoms are necessary to reduce the burden of asthma morbidity and mortality, especially in underserved areas. We describe a process used to identify high school students who could benefit from intervention based on self-report of asthma and/or respiratory symptoms, and the costs associated with symptom-identification. Letters announcing a survey were mailed to parents of 9th–11th graders by an authorized vendor managing student data for the school district. Scan sheets with student identifiers were distributed to English teachers at participating schools who administered the survey during a scheduled class. Forms were completed by 5,967 of the 7,446 students assigned an English class (80% response). Although prevalence of lifetime asthma was 15.8%, about 11% of students met program criteria for enrollment through report of an asthma diagnosis and recent symptoms, medication use, or health care utilization. Another 9.2% met criteria by reported symptoms only. Cost of symptom-identification was $5.23/student or $32.29/program-eligible student. There is a need for school-based asthma programs targeting urban adolescents, and program initiation will likely require identification of students with uncontrolled symptoms. The approach described was successfully implemented with a relatively high response rate. Itemized expenses are presented to facilitate modifications to reduce costs. This information may benefit providers, researchers, or administrators targeting similar populations.

Despite medical and scientific advances, racial and ethnic disparities persist in US asthma morbidity and mortality rates. Progress in the elimination of these disparities will involve disentangling the contribution of social constructs, such as race, socioeconomic status, and culture, from that of the physical environment and genetic susceptibility. One approach to reducing asthma disparities is through the traditional disease prevention stages of intervention. As such, primary prevention targets reductions in asthma incidence; secondary prevention is the mitigation of established disease and involves disease detection, management, and control; and tertiary prevention is the reduction of complications caused by severe disease. Once causative factors at each level of disease prevention are understood, this knowledge can be translated into clinical practice and public health policy.

Background

African American patients suffer disproportionately from uncontrolled asthma. Treatment with an inhaled corticosteroid (ICS) is considered first-line therapy for persistent asthma.

Objective

To determine the degree to which African American patients respond to ICS medication and whether the level of response is influenced by other factors, including genetic ancestry.

Methods

Patients aged 12-56 years who received care from a large health system in southeast Michigan and who resided in Detroit were recruited to participate if they had a diagnosis of asthma. Patients were treated with 6 weeks of inhaled beclomethasone dipropionate, and pulmonary function was re-measured after treatment. Ancestry was determined by genotyping ancestry informative markers. The main outcome measure was ICS responsiveness defined as the change in pre-bronchodilator FEV1 over the 6-week course of treatment.

Results

Among 147 participating African American patients with asthma, average improvement in FEV1 following 6 weeks of ICS treatment was 11.6%. The mean proportion of African ancestry in this group was 78.4%. The degree of baseline bronchodilator reversibility was the only factor consistently associated ICS responsiveness as measured by both an improvement in FEV1 and in patient reported asthma control (P=0.001 and P=0.021, respectively). The proportion of African ancestry was not significantly associated with ICS responsiveness.

Conclusions

While baseline pulmonary function parameters appear to be associated with the likelihood to respond to ICS treatment, the proportion of genetic African ancestry does not. This study suggests that genetic ancestry may not contribute to differences in ICS controller response among African American patients with asthma.

Clinical Implications

Although African American patients suffer disproportionately from asthma-related complications, response to ICS controller therapy does not appear to be dependent on an individual’s proportion of African ancestry.

Capsule summary

Personalized medicine will be most beneficial to groups disproportionately affected by disease complications. Here we find baseline bronchodilator reversibility but not African ancestry to be associated with ICS responsiveness among African American patients with asthma.

Background

Medication non-adherence is common and results in preventable disease complications. This study assesses the effectiveness of a multifactorial intervention to improve both medication adherence and blood pressure control and to reduce cardiovascular events.

Methods and Results

In this multi-center, cluster-randomized trial, physicians from hospital-based hypertension clinics and primary care centers across Spain were randomized to receive and provide the intervention to their high-risk patients. Eligible patients were ≥50 years of age, had uncontrolled hypertension, and had an estimated 10-year cardiovascular risk greater than 30%. Physicians randomized to the intervention group counted patients’ pills, designated a family member to support adherence behavior, and provided educational information to patients. The primary outcome was blood pressure control at 6 months. Secondary outcomes included both medication adherence and a composite end-point of all cause mortality and cardiovascular-related hospitalizations. Seventy-nine physicians and 877 patients participated in the trial. The mean duration of follow-up was 39 months. Intervention patients were less likely to have an uncontrolled systolic blood pressure (odds ratio 0.62; 95% confidence interval [CI] 0.50–0.78) and were more likely to be adherent (OR 1.91; 95% CI 1.19–3.05) when compared with control group patients at 6 months. After five years 16% of the patients in the intervention group and 19% in the control group met the composite end-point (hazard ratio 0.97; 95% CI 0.67–1.39).

Conclusions

A multifactorial intervention to improve adherence to antihypertensive medication was effective in improving both adherence and blood pressure control, but it did not appear to improve long-term cardiovascular events.

Background

Inhaled corticosteroids (ICS) are considered first-line treatment for persistent asthma; yet, there is significant variability in treatment response. Dual specificity phosphatase-1 (DUSP1) appears to mediate the anti-inflammatory action of corticosteroids.

Objective

To determine whether variants in the DUSP1 gene are associated with clinical response to ICS treatment.

Methods

Study participants with asthma were drawn from the following multi-ethnic cohorts: the Genetics of Asthma in Latino Americans (GALA) study, the Study of African Americans, Asthma, Genes & Environments (SAGE), and the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). We screened GALA participants for genetic variants that modified the relationship between ICS use and bronchodilator response. We then replicated our findings in SAGE and SAPPHIRE participants. In a group of SAPPHIRE participants treated with ICS for 6 weeks, we examined whether a DUSP1 polymorphism was associated with changes in forced expiratory volume at one second (FEV1) and self-reported asthma control.

Results

DUSP1 polymorphisms, rs881152 and rs34507926, localized to different haplotype blocks and appeared to significantly modify the relationship between ICS use and bronchodilator response among GALA participants. This interaction was also seen for rs881152 among SAPPHIRE, but not SAGE participants. Among the group of SAPPHIRE patients prospectively treated with ICS for 6 weeks, rs881152 genotype was significantly associated with changes in self-reported asthma control but not FEV1.

Conclusion

DUSP1 polymorphisms were associated with clinical response to ICS therapy, and therefore, may be useful in the future to identify asthma patients more likely to respond to this controller treatment.

Clinical implications

These findings further our understanding of ICS pharmacogenetics and will hopefully result in improved tailoring of this controller therapy among individuals with asthma and in better disease control.

Capsule summary

We identified genetic variants in DUSP1 which appeared to mediate the clinical response to inhaled corticosteroid (ICS) medication. These findings may eventually assist in identifying individuals with asthma most likely to respond this controller therapy.

Background

Many allergic conditions occur more frequently in African-American patients when compared with white patients; however it is not known whether this represents genetic predisposition or disparate environmental exposures.

Objective

To assess the relationship of self-reported race and genetic ancestry to allergic sensitization.

Methods

We included 601 women enrolled in a population-based cohort study whose self-reported race was African-American or white. Genetic ancestry was estimated using markers that differentiate West African and European ancestry. We assessed the relationship between allergic sensitization (defined as ≥1 allergen-specific IgE result) and both self-reported race and genetic ancestry. Regression models adjusted for socio-demographic variables, environmental exposures, and location of residence.

Results

The average proportion of West African ancestry in African-American participants was 0.69, whereas the mean proportion of European ancestry in white participants was 0.79. Self-reported African-American race was associated with allergic sensitization when compared with those who reported being white (adjusted odds ratio [aOR] 2.19; 95% confidence interval [CI] 1.22 – 3.93) even after adjusting for other variables. Genetic ancestry was not significantly associated with allergic sensitization after accounting for location of residence (aOR 2.09 for urban vs. suburban residence, 95% CI 1.32 −3.31).

Conclusion

Self-reported race and location of residence appeared to be more important predictors of allergic sensitization when compared with genetic ancestry, suggesting that the disparity in allergic sensitization by race may be primarily due to environmental factors rather than genetic differences.

Clinical Implications

These data suggest that efforts to eliminate disparities in allergic sensitization should focus on contributing environmental factors.