Favorable therapeutic index of the direct factor Xa inhibitors, apixaban and rivaroxaban, compared with the thrombin inhibitor dabigatran in rabbits.

BACKGROUND: Apixaban is an oral, direct factor Xa (FXa) inhibitor in late-stage clinical development. This study assessed effects of the direct FXa inhibitors, apixaban and rivaroxaban, vs. the direct thrombin inhibitor, dabigatran, on venous thrombosis (VT), bleeding time (BT) and clotting times in rabbits. METHODS: We induced the formation of non-occlusive thrombus in VT models by placing threads in the vena cava, and induced bleeding by the incision of cuticles in anesthetized rabbits. Apixaban, rivaroxaban and dabigatran were infused IV to achieve a stable plasma level. Clotting times, including the activated partial thromboplastin time (aPTT), prothrombin time (PT), modified PT (mPT) and thrombin time (TT), were measured. RESULTS: Apixaban, rivaroxaban and dabigatran exhibited dose-related efficacy in preventing VT with EC(50) of 65, 33 and 194 nm, respectively. At doses for 80% reduction of control thrombus, apixaban, rivaroxaban and dabigatran prolonged BT by 1.13 +/- 0.02-, 1.9 +/- 0.1-* and 4.4 +/- 0.4-fold*, respectively (*P < 0.05, vs. apixaban). In the treatment model, these inhibitors equally prevented growth of a preformed thrombus. Antithrombotic doses of apixaban and rivaroxaban prolonged aPTT and PT by <3-fold with no effect on TT. Dabigatran was > or = 50-fold more potent in prolonging TT than aPTT and PT. Of the clotting assays studied, apixaban, rivaroxaban and dabigatran responded the best to mPT. CONCLUSION: Comparable antithrombotic efficacy was observed between apixaban, rivaroxaban and dabigatran in the prevention and treatment of VT in rabbits. Apixaban and rivaroxaban exhibited lower BT compared with dabigatran at equivalent antithrombotic doses. The clinical significance of these findings remains to be determined.

Arterial antithrombotic and bleeding time effects of apixaban, a direct factor Xa inhibitor, in combination with antiplatelet therapy in rabbits.

BACKGROUND: Optimal treatment of arterial thrombosis may include a combination of antiplatelet and anticoagulant drugs. We evaluated apixaban, a direct and highly selective factor Xa inhibitor, in combination with clinically relevant doses of aspirin and/or clopidogrel for prevention of arterial thrombosis in rabbits. METHODS: Studies were conducted in rabbit models of electrically induced carotid artery thrombosis and cuticle bleeding time (BT). Apixaban 0.04 and 0.3 mg kg(-1) h(-1) or aspirin 1 mg kg(-1) h(-1) was infused intravenous (i.v.) continuously from 1 h before artery injury or cuticle bleed until the end of the experiment. Clopidogrel at 3 mg kg(-1) was dosed orally once daily for three days, with the last dose given 2 h before injury. RESULTS: Control thrombus weight and BT averaged 8.6 +/- 0.9 mg and 181 +/- 12 s, respectively (n = 6 per group). Effective doses of apixaban that reduced thrombus weight by 20 and 50% (ED(20) and ED(50)) were 0.04 and 0.3 mg kg(-1) h(-1) i.v., respectively. Addition of aspirin to apixaban ED(20) and ED(50) significantly reduced the thrombus weight from 7.4 +/- 0.5 to 5.3 +/- 0.3 and 3.6 +/- 0.3 mg, respectively, with no significant increases in BT (190 +/- 7 s vs.181 +/- 9 and 225 +/- 11 s, respectively). Addition of aspirin and apixaban (ED(20) dose) to clopidogrel produced a further significant reduction in thrombus weight from 5.3 +/- 0.3 to 0.7 +/- 0.1 mg. This combination of clopidogrel and aspirin with apixaban (ED(20) dose) produced a significant but moderate BT increase of 2.1 times control. CONCLUSIONS: The combination of apixaban and aspirin or apixaban, aspirin and clopidogrel can reduce formation of occlusive arterial thrombosis without excessive increases in BT in rabbits.

Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies.

BACKGROUND: Apixaban is an oral, direct and highly selective factor Xa (FXa) inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases. OBJECTIVE: We evaluated the in vitro properties of apixaban and its in vivo activities in rabbit models of thrombosis and hemostasis. METHODS: Studies were conducted in arteriovenous-shunt thrombosis (AVST), venous thrombosis (VT), electrically mediated carotid arterial thrombosis (ECAT) and cuticle bleeding time (BT) models. RESULTS: In vitro, apixaban is potent and selective, with a K(i) of 0.08 nm for human FXa. It exhibited species difference in FXa inhibition [FXa K(i) (nm): 0.16, rabbit; 1.3, rat; 1.7, dog] and anticoagulation [EC(2x) (microm, concentration required to double the prothrombin time): 3.6, human; 2.3, rabbit; 7.9, rat; 6.7, dog]. Apixaban at 10 microm did not alter human and rabbit platelet aggregation to ADP, gamma-thrombin, and collagen. In vivo, the values for antithrombotic ED(50) (dose that reduced thrombus weight or increased blood flow by 50% of the control) in AVST, VT and ECAT and the values for BT ED(3x) (dose that increased BT by 3-fold) were 0.27 +/- 0.03, 0.11 +/- 0.03, 0.07 +/- 0.02 and > 3 mg kg(-1) h(-1) i.v. for apixaban, 0.05 +/- 0.01, 0.05 +/- 0.01, 0.27 +/- 0.08 and > 3 mg kg(-1) h(-1) i.v. for the indirect FXa inhibitor fondaparinux, and 0.53 +/- 0.04, 0.27 +/- 0.01, 0.08 +/- 0.01 and 0.70 +/- 0.07 mg kg(-1) day(-1) p.o. for the oral anticoagulant warfarin, respectively. CONCLUSIONS: In summary, apixaban was effective in the prevention of experimental thrombosis at doses that preserve hemostasis in rabbits.

Prospective multicenter study of relapse after treatment for acute asthma among children presenting to the emergency department.

OBJECTIVE: Single-center studies have reported varying relapse rates after treatment of patients with acute asthma. We determined the relapse rate after emergency department (ED) treatment in a cohort of children. DESIGN: This was a prospective inception cohort study performed during 1997-1998. SETTING: The study was performed in 44 EDs including both general and pediatric centers. PATIENTS: Children (n = 1184) aged 2 to 17 years who had been admitted to EDs, with acute asthma restricted to 881 patients discharged from the ED. MAIN RESULTS: Two weeks after discharge, families were telephoned to determine relapse. Follow-up data were available for 762 (86%) of the children with a 10% incidence of relapse. On univariate analysis several factors were associated with relapse including current medications and markers of asthma severity. On multivariate analysis the factors associated with relapse were age (OR 1.4 per 5-year increase), use of second-line asthma medications (OR 3.7), exposure to cigarette smoke (OR 0.5), and ED visits within the past year (OR 1.2 per 5 ED visits). CONCLUSIONS: The incidence of relapse among children is lower than that observed among adults and varies with age. Other risk factors such as frequent ED visits are likely markers of chronic asthma severity. Further research should focus on ways to decrease the relapse rate among patients at high risk.

The use of parent report to assess the quality of care in primary care visits among children with asthma.

OBJECTIVE: To determine the accuracy of parent report and the accuracy of the medical record in documenting physician performance of elements of pediatric asthma care in the primary care setting. METHODS: A convenience sample of 79 English-speaking parents of 4--12-year old children with asthma presenting to medical center--affiliated inner-city primary care pediatric clinics in the Bronx, Dallas, and Chicago was enrolled, and the office visit was audiotaped. Parents were interviewed 1--16 days after the visit by telephone. OUTCOME MEASURES: Accuracy of parent report was the primary outcome. The "reference standard" was an independent evaluation of the audiotaped record of the primary care visit. The National Asthma Education and Prevention Program was used as a guide to select data elements to assess quality of pediatric asthma care during primary care visits. RESULTS: Sufficient documentation was significantly (P <.001) less likely to be present in the medical record than in the follow-up interview for each element of care. When these elements were combined into a cumulative score, 71% of parent interviews but only 37% of medical records scored > or = 5 (out of a possible 6), with 29% of medical records scoring < 3. Parents were able to accurately report (concordance of parent data with audiotape reference standard) whether or not the visit had included performance of 5 of the 6 elements of care. CONCLUSIONS: Our study suggests that parent telephone interview within 2 weeks after the visit is more accurate than the medical record for documentation of the quality of asthma care in pediatric primary care visits. The medical record was not sufficient to assess the quality of primary care related to asthma, primarily because of missing data. Therefore, our data suggest that assessing quality of care using the medical record will not only bias the findings in the direction of more deficient care but will also make improvement in care more difficult. Further validation of our strategy for using parent report to assess the quality of care in primary care visits will require its application in a variety of other primary care settings.

Insurance and quality of care for children with acute asthma.

BACKGROUND: Increasing attention has been paid to the role of insurance in determining quality and outcomes of care. Pressures to reduce health costs and to improve quality have prompted attempts by managed care organizations to decrease the use of the emergency department (ED) for acute asthma, but performance comparisons between insurance types remain rare. METHODS: We used prospective data from the Multicenter Airway Research Collaboration on 965 children with acute asthma presenting to 36 EDs. We compared measures of quality of pre-ED care, acute severity, and short-term outcomes (length of stay, percent relapse, and percent with ongoing symptoms) across 4 different insurance categories: managed care, indemnity, Medicaid, and uninsured. We used multivariate regression to control for differences in education, estimated income, race/ethnicity, and chronic asthma severity and acute asthma characteristics. RESULTS: Children with managed care and indemnity had similar demographic and asthma characteristics, but these children differed significantly from Medicaid and uninsured patients. Managed care and indemnity insured children had similar ratings on all 7 quality measures, with Medicaid and uninsured children ranking significantly lower on most measures, including (1) percent with primary care provider (PCP) (P <.001), (2) percent using ED as usual site of asthma care (P <.001), (3) percent using ED for prescriptions (P <.001), (4) percent with a ratio of >1 of ED visits to acute office visits within the past year (P =.003), and (5) percent visiting their PCP within the week prior to ED visit (P <.001). Children with managed care were more acutely ill than were indemnity, Medicaid, or uninsured children on presentation to the ED (pulmonary index of 4.6, 4.0, 4.2, and 3.9, respectively, P =.007). There were no significant differences in length of hospital stay, relapse, and ongoing exacerbation. CONCLUSIONS: Our results indicate similar quality of care, greater severity of acute asthma, and no worse outcomes for children with managed care compared to children with indemnity insurance. We found uninsured children to have consistently poorer quality of care than insured patients.

Nonpeptide factor Xa inhibitors II. Antithrombotic evaluation in a rabbit model of electrically induced carotid artery thrombosis.

SK549 (mol. wt. 546 Da) is a synthetic, selective inhibitor of human coagulation factor Xa (fXa) (K(i) = 0.52 nM). This study compared the antithrombotic effects of SK549 and a series of benzamidine isoxazoline fXa inhibitors with aspirin, DuP 714 (a direct thrombin inhibitor), recombinant tick anticoagulant peptide, or heparin in a rabbit model of electrically induced carotid arterial thrombosis. Compounds were infused i.v. continuously from 60 min before electrical stimulation to the end of the experiment. Values of ED(50) (dose that increases the carotid blood flow to 50% of the control) were 0.12 micromol/kg/h for SK549, 0.56 micromol/kg/h for aspirin, 0.14 micromol/kg/h for DuP 714, 0.06 micromol/kg/h for recombinant tick anticoagulant peptide, and >100 U/kg/h for heparin. The EC(50) (plasma concentration that increased blood flow to 50% of the control) for SK549 was 97 nM. Unlike aspirin and heparin, SK549 was efficacious and, at 1.5 micromol/kg/h i.v. (n = 9), maintained carotid blood flow at 87 +/- 6% of control level for greater than 90 min. Unlike heparin, SK549 inhibited ex vivo fXa activity but not ex vivo thrombin activity. There was a highly significant correlation between K(i) (fXa) and ED(50) of a series of fXa inhibitors (r = 0. 85, P <.001). Therefore, these results suggest that SK549 is a novel, potent, and effective antithrombotic agent in a rabbit model of arterial thrombosis. It is likely that SK549 exerts its antithrombotic effect through selective inhibition of fXa. Furthermore, SK549 may be clinically useful for the prevention of arterial thrombosis.

Attitudes toward death-related choices.

In 99 high school students, attitudes toward abortion, capital punishment, and suicide were not associated.

Emergency care of asthma.

Children with asthma frequently receive care in the emergency department (ED). The factors associated with presentation to the ED are complex and must be considered when developing a treatment plan and disposition. The diagnosis and assessment must be rapid and focused, and treatment must be initiated promptly. Objective measures should be used where possible to assess the response to therapy and determine readiness for discharge. This Article reviews the essential components of diagnosis, assessment, and treatment of pediatric asthma in the ED, and it reviews the key elements of discharge planning.

Do obese inner-city children with asthma have more symptoms than nonobese children with asthma?

OBJECTIVE: To test whether obesity is associated with decreased peak expiratory flow rates (PEFR), increased asthma symptoms, and increased health service use. DESIGN/METHODS: Secondary analysis of data from a cross-sectional convenience sample. SETTING: Emergency departments (EDs) and primary care clinics in 8 inner-city areas in 7 cities. PARTICIPANTS: One thousand three hundred twenty-two children aged 4 to 9 years with asthma. MEASURES: Obesity was defined as a body mass index (BMI, weight/height(2)) >95th percentile. Nonobese children were those with a BMI between the 5th and 95th percentile. Underweight children with a BMI <5th percentile were eliminated from the study. Demographic and anthropometric data were obtained during a baseline interview with the primary caretaker and the child. Symptoms, health service use data and measurements of PEFR were obtained by parental report during the baseline interview and at 3-month intervals by telephone interview over the following 9-month period. RESULTS: Obese (n = 249) and nonobese (n = 1073) children did not differ in terms of age, gender, family income, passive smoke exposure, caretaker's mental health, and skin test reactivity to indoor allergens. Obese children were more often Latino (28% vs 17%) and, in the 3 months before the baseline interview, were more likely to have used oral steroids (30% vs 24%). There were no differences between groups in terms of baseline PEFR scores. During the 9 months after baseline assessment, the obese group had a higher mean number of days of wheeze per 2-week period (4.0 vs 3.4), and a greater proportion of obese individuals had unscheduled ED visits (39% vs 31%). There were no differences between the groups in terms of frequency of hospitalization, or in nocturnal awakening. CONCLUSIONS: In our sample of inner-city children with asthma, obese children used more medicine, wheezed more, and a greater proportion had unscheduled ED visits than the nonobese children.

Acetaminophen and ibuprofen dosing by parents.

BACKGROUND: Acetaminophen and ibuprofen are two of the most commonly used medications in children. It is our experience that parents often misdose these medications. Misdosing may lead to unintended toxicity or inadequate symptomatic improvement. There are limited data on the extent of misdosing of these antipyretics. We sought to determine the prevalence of and risk factors for inaccurate dosing by parents seeking care for their children in the emergency department (ED). METHODS: A cross-sectional observational study was performed in an urban academic pediatric ED. Two hundred patients 10 years of age and younger who were given a known dose of acetaminophen or ibuprofen in the 24 hours prior to the ED visit were enrolled. The treating physician completed a questionnaire for each patient. Caregivers were asked about quantity and frequency of antipyretic use prior to the ED visit, the source of information used to determine dosage, and which factor (eg, age, sex, height, weight, height of fever, severity of illness) they considered most important in determining the correct dosage of medication. Doses of 10 to 15 mg/kg for acetaminophen and 5 to 10 mg/kg for ibuprofen were considered accurate. RESULTS: Overall, 51% of patients received an inaccurate dose of medication, including 62% of patients given acetaminophen and 26% of patients given ibuprofen. Infants < 1 year old were more likely to receive an inaccurate dose (RR 1.40, P < 0.04, 95% CI = 1.06-1.86). Caregivers who stated that medication dosage was based on weight were less likely to give an inaccurate dose of medication (RR 0.71, P < 0.03, 95% CI = 0.52-0.97). CONCLUSIONS: Over half of the caregivers surveyed gave an inaccurate dose of acetaminophen or ibuprofen, particularly to infants. Caregivers who reported that antipyretic dosage was based on weight were less likely to misdose medication, suggesting a valuable role for patient education.

Nonpeptide factor Xa inhibitors: I. Studies with SF303 and SK549, a new class of potent antithrombotics.

A series of benzamidine isoxazoline derivatives was evaluated for their inhibitory potency against purified human factor Xa (fXa) and in a rabbit model of arteriovenous shunt thrombosis for their antithrombotic activities, expressed as K(I) and IC(50), respectively. A highly significant correlation was found between K(I) and IC(50) (r = 0.93, P <.0001). The antithrombotic effects of SF303 [mol. wt. 536; K(I): fXa, 6.3 nM; thrombin, 3,100 nM; trypsin, 110 nM; tissue plasminogen activator >20,000 nM; plasmin, 2,500 nM] and SK549 [mol. wt. 546; K(I): fXa, 0.52 nM; thrombin, 400 nM; trypsin, 45 nM; tissue plasminogen activator >33,000 nM; plasmin, 890 nM] were compared with recombinant tick anticoagulant peptide [K(I)(fXa) = 0.5 nM], DX-9065a [K(I)(fXa) = 30 nM], and heparin or low molecular weight heparin (dalteparin) in a rabbit model of arteriovenous shunt thrombosis. ID(50) values for preventing arteriovenous shunt-induced thrombosis were 0.6 micromol/kg/h for SF303, 0.035 micromol/kg/h for SK549, 0.01 micromol/kg/h for recombinant tick anticoagulant peptide, 0.4 micromol/kg/h for DX-9065a, 21 U/kg/h for heparin, and 23 U/kg/h for low molecular weight heparin. SK549 produced a concentration-dependent antithrombotic effect with an IC(50) of 0.062 microM. To evaluate its potential oral efficacy, SK549 was given intraduodenally at a dose of 5 mg/kg; it produced a peak antithrombotic effect of 59 +/- 4% with a duration of action greater than 6.7 h. Therefore, our study suggests that SF303, SK549, and their analogs represent a new class of synthetic fXa inhibitors that may be clinically useful as antithrombotic agents.

A randomized clinical trial to reduce asthma morbidity among inner-city children: results of the National Cooperative Inner-City Asthma Study.

OBJECTIVE: To evaluate a family-focused asthma intervention designed for inner-city children 5 to 11 years old with moderate to severe asthma. STUDY DESIGN: Randomized, multisite, controlled trial to minimize symptom days (wheeze, loss of sleep, reduction in play activity) measured by a 2-week recall assessed at 2-month intervals over a 2-year follow-up period. The intervention was tailored to each family's individual asthma risk profile assessed at baseline. RESULTS: Averaged over the first 12 months, participants in the intervention group (n = 515) reported 3.51 symptom days in the 2 weeks before each follow-up interview compared with 4.06 symptom days for the control group (n = 518), a difference of 0.55 (95% CI, 0.18 to 0.92, P =.004). The reduction among children with severe asthma was approximately 3 times greater (1.54 d/2 wk). More children in the control group (18.9%) were hospitalized during the intervention compared with children in the intervention group (14. 8%), a decrease of 4.19% (CI, -8.75 to 0.36, P =.071). These improvements were maintained in the intervention group during the second year of follow-up, during which they did not have access to the asthma counselor. CONCLUSIONS: We demonstrated that an individually tailored, multifaceted intervention carried out by Masters-level social workers trained in asthma management can reduce asthma symptoms among children in the inner city.

A comparison of New York City playground hazards in high- and low-income areas.

OBJECTIVE: To compare playground hazards in high- and low-income neighborhoods. DESIGN: Forty-five playgrounds were randomly selected from the 9 New York City community districts that met our study criteria and were divided into high-and low-income groups based on comparison to the median of the median incomes ($24452 per year) of the 9 districts. Playgrounds are maintained by the City of New York Parks and Recreation Department and were assessed by one of us (S.A.S.) using a standardized on-site survey based on the US Consumer Product Safety Commission's guidelines for public playground safety. MAIN OUTCOME MEASURES: Total hazards per play area were subdivided into 3 categories: park design hazards, equipment maintenance hazards, and equipment hazards relating to fall injuries. A play area was defined as an individual set of equipment. RESULTS: Twenty-five (56%) of the parks were located in low-median-income districts and contained 98 (53%) of the total play areas. High- and low-income playgrounds did not differ significantly in the amount or type of equipment, mean fall injury hazards per play area, or mean park design hazards per play area. Low-income districts had a significantly higher mean total hazards per play area (6.1 vs. 4.2; P = .02) and mean equipment maintenance hazards per play area (2.1 vs. 1.0; P = .02). CONCLUSION: Significantly more hazards per play area were identified in the low-income group compared with the high-income group.

Pediatric asthma care in the emergency department: measuring the quality of history-taking and discharge planning.

The National Asthma Education and Prevention Program NAEPP Guidelines include recommendations for history-taking and discharge planning during an asthma visit, but there are no tools to measure performance. The objectives of this study were to define and operationalize key elements of history-taking and discharge planning, to develop a tool for measuring these elements, and to evaluate the quality of history-taking and discharge planning in the emergency department (ED) during visits for asthma using the new tool. Expert opinion and extensive literature review were used to develop a 13-item checklist containing items that should be documented during history-taking and provided during discharge planning for an ED visit for an acute asthma exacerbation by children. A convenience sample of 90 pediatric emergency medicine physicians and allergists rated each item in the checklist. The checklist was used to score audiotapes of asthma visits in the ED. Subjects were 154 parents of asthmatic children aged 4-9 years seeking care in nine inner-city EDs affiliated with asthma centers participating in the National Cooperative Inner-City Asthma Study and the physician/providers who delivered care. Seven of the 13 items on the checklist were rated as required to be performed by more than 90% of the allergist/pediatric emergency medicine physicians. Only 10% of the 154 visits included all seven of the highly rated items, whereas 19% of the visits included three or fewer. Only 7 of the 13 items (54%) were performed in more than 50% of the visits, and 4 items were performed in fewer than 25% of visits. Based on expert ratings, the checklist for measuring elements of history-taking and discharge planning during asthma visits appears to have considerable face validity. In the visits studied, the overall performance of these elements was low. Interventions to improve performance on the checklist might lead to improved care for children with asthma who frequent the ED.

Patient-provider communication during the emergency department care of children with asthma. The National Cooperative Inner-City Asthma Study, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD.

OBJECTIVES: Poor children's reliance on emergency facilities is one factor implicated in the rise of morbidity attributed to asthma. Although studies have examined doctor-patient communication during routine pediatric visits, little data are available about communication during emergency care. This study sought to describe communication during emergency treatment of childhood asthma to learn if a "patient-centered" provider style was associated with increased parent satisfaction and increased parent and child participation. METHODS: This cross-sectional, observational study examined 104 children aged 4 to 9 years and their guardian(s) attending emergency departments in seven cities. Quantitative analysis of provider-family dialogue was performed. Questionnaires measured satisfaction with care, provider informativeness, and partnership. RESULTS: Providers' talk to children was largely supportive and directive; parents received most counseling and information. Children spoke little to providers (mean: 20 statements per visit versus 156 by parents). Providers made few statements about psychosocial aspects of asthma care (mean: three per visit). Providers' patient-centered style with parents was associated with more talk from parents and higher ratings for informativeness and partnership. Patient-centered style with children was associated with five times the amount of talk from children and with higher parent ratings for "good care," but not for informativeness or partnership. CONCLUSIONS: Communication during emergency asthma care was overwhelmingly biomedical. Children took little part in discussions. A patient-centered style correlated with increased parent and child participation, but required directing conversation toward both parents and children.

Burden of wheezing illness among U.S. children reported by parents not to have asthma.

We examined the 12-month prevalence of asthma and wheezing among U.S. children and compared the illness-related burden of children who wheezed with and without an asthma diagnosis. Data were obtained in a cross-sectional telephone survey that tested the performance of a health interview designed to identify children with chronic health conditions. Respondents were 712 primary caretakers of 1388 children under 18 years old in a national probability sample selected by random-digit dialing. Although 51 children identified with asthma and wheezing had more episodes, sleep disturbances, and attacks that limited speech, and received more medical treatment for wheezing than 69 children with wheezing alone, the "undiagnosed" children appeared to be only somewhat less affected by their wheezing. Repeat episodes and burden experienced by children with wheezing alone suggest that the asthma prevalence may be underestimated if based only on the diagnostic label.

Self-reported adherence, management behavior, and barriers to care after an emergency department visit by inner city children with asthma.

OBJECTIVE: The inability to adhere to a prescribed therapeutic program for the treatment of a chronic disease may be responsible in part for continued disease activity. This problem may be more of an issue in the treatment of asthma, a common, potentially lethal chronic condition in which the lack of symptoms may be interpreted as remission. Adherence was one of the key areas of interest for the National Cooperative Inner-City Asthma Study. The focus of this study was to identify those issues reported by families that could adversely affect their adherence to an asthma care program. The identification of barriers to adherence could then form the basis of a successful intervention program. This study describes barriers to adherence, asthma management behavior, and self-reported adherence. METHODS: Patients presenting during an acute attack of asthma at an emergency department (ED) were recruited for this study. The medical record of the ED encounter was abstracted and compared with information that was obtained during a baseline interview 3 to 5 weeks later. During the baseline interview, parents were asked about health care behaviors related to adherence. RESULTS: There were 344 children 4 to 9 years of age living in inner city census tracts in the study. Four areas of adherence (medicine use, appointment-keeping, emergency actions, and asthma attack prevention) were investigated. The parental report of medications prescribed at the ED and the information on the abstracted ED report agreed 94.9% of the time for the beta-agonists, 86.8% for steroids, and 69.4% for cromolyn. Among respondents, 85.4% of parents reported that they are able to follow the ED recommendations almost all of the time; side effects of medicines were a concern for 81.1% of caretakers who were adherent and for 89.5% of caretakers who were nonadherent. Doubts regarding the usefulness of medications occurred in 34.4% of those considered adherent and 54.2% who admitted nonadherence. Medications were forgotten some of the time by 45.2% of the children, and 52.8% tried to get out of taking medicine. Appointments for follow-up care were kept by 69% of those given an appointment in the ED, by an estimated 60.0% of those who were told specifically to call for an appointment, and by an estimated 25.2% of those who were neither given an appointment nor told specifically to make one. Only one third of parents report that they were able to keep the child away from known asthma triggers nearly all of the time. Approximately half avoided allergens; however, only 37.5% reported avoidance of cigarette smoke. The use of preventive medicines occurred in 23.5%. Using a medicine and taking the child to a physician were reported as the first or second action during an acute attack of asthma by 72.1% of respondents. CONCLUSIONS: Adherence to an asthma-management program involves a number of areas: medication, appointment-keeping, prevention, and applying an emergency plan of action. Barriers to adherence may exist in one or all four of these areas, leading to ineffective control of asthma. Recommendations are made for improving the patient-physician partnership to improve adherence.