Barriers to asthma care in urban children: parent perspectives.

BACKGROUND: Despite improved treatment regimens for asthma, the prevalence and morbidity from asthma are increasing, especially among underserved, minority children. OBJECTIVE: The purpose of this study was to identify barriers to the treatment of asthma among urban, minority children as perceived by parents. METHODS: Parents were recruited from 4 schools located in low-income, urban areas with high rates of asthma hospitalizations. Focus groups involving parents of children 5 to 12 years old with asthma were conducted using a standardized questionnaire. Parents' comments were analyzed to identify barriers, and 3 independent raters coded parents' comments to assess reliability of interpretation. RESULTS: Forty parents who represented 47 children participated in the focus groups. All parents described their racial background as black. Parents' average age was 36.8 years, 92% were females, 70% were nonmarried, and 38% had less than a high school education. Forty-five percent of children had intermittent or mild asthma and 55% had moderate to severe asthma. The most frequent types of barriers identified by parents were patient or family characteristics (43%), followed by environmental (28%), health care provider (18%), and health care system (11%). Parents were specifically concerned about the use, safety and long-term complications of medications, the impact of limitation of exercise on their child's quality of life, and their own quality of life. CONCLUSIONS: In contrast with the widespread beliefs that access to medical care, health insurance, and continuity of care are the major barriers to quality asthma care, the barriers most frequently reported by parents were related to patient and family characteristics, health beliefs, or to their social and physical environment. To improve asthma management and health outcomes for urban, minority children with asthma, it is critical to tailor education about asthma and its treatment, and address quality of life issues for both children and parents.

Antimurine antibody formation following OKT3 therapy.

OKT3 is an IgG2a murine monoclonal antibody directed against the CD3 antigen receptor of human T lymphocytes. A major concern with OKT3 treatment in solid organ transplant recipients is the development of antimouse antibody, which may preclude retreatment with this agent. We have administered OKT3 on 215 occasions (150 renal, 34 hepatic, 26 cardiac, 5 pancreatic) in 179 patients between April 1982 and December 1988. The mean duration of treatment was 10.5 days (range, 2-22 days). Antimouse antibody data were analyzed on the most recent 133 treatment courses where the antibody status was available pretreatment. Determination of antimouse antibody production was elicited by ELISA technology at days 0, 7, 14, and 28 of OKT3 treatment. Patients were categorized according to the antibody response as follows: (a) absence of antibody; (b) low titer (1:100); or (c) high titer (greater than or equal to 1:1000). Our earlier experience has demonstrated that retreatment with OKT3 is successful in groups a and b. The development of antimurine antibodies was analyzed with regard to the following parameters: (1) The duration of OKT3 treatment; (2) treatment type (prophylactic, primary, or secondary); (3) primary treatment or retreatment; (4) concomitant immunosuppressive regimen (double or triple therapy); (5) dosage of concomitant immunosuppressive drugs; and (6) transplant organ type. The following results were obtained. (1) Duration of treatment had no effect on antibody production (11.0 days in antibody negative and 10.0 days in antibody positive). (2) There was no difference in antibody formation rates for the first treatment of OKT3 when it was used as prophylaxis (26%), primary (19%), or secondary (27%) therapy. (3) Antibody formation rate with first treatment was 29%; with retreatment, patients who were antibody negative following first treatment became positive in 28% of cases, and retreated patients who were low titer positive following first treatment converted to high titer in 57% of cases. (4) Antibody formation was higher in patients receiving double immunosuppressive therapy (36%) than in those receiving triple immunosuppressive therapy (21%) during OKT3 treatment. (5) Concomitant immunosuppression was lower in the antibody-positive group during OKT3 therapy: steroids, 61 mg/day vs. 52 mg/day; azathioprine, 89 mg/day vs. 66 mg/day; CsA, 317 mg/day vs. 186 mg/day. (6) Antibody formation rates were lower in non-renal transplants following first treatment with OKT3 (liver 17%, heart 17%, kidney 28%); this reflects the higher doses of concomitant immunosuppressive therapy used in nonrenal transplants.(ABSTRACT TRUNCATED AT 400 WORDS)

Prophylactic use of OKT3 in immunologic high-risk cadaver renal transplant recipients.

Prophylactic OKT3 was administered to 27 immunologic high-risk cadaver renal transplant recipients (multiple transplant and/or panel reactive antibody greater than 50%) as part of a sequential immunosuppressive protocol consisting of OKT3, prednisone, azathioprine, and cyclosporine. The first dose of OKT3 was administered intraoperatively. Patient survival was 100% with a mean follow-up period of 13 months. Graft survival at 1 year was 70% (19 of 27). Eight grafts were lost during the first 6 weeks. Causes of graft loss were hyperacute rejection or primary nonfunction (4), irreversible rejection (2), and technical (2). After the first month, single rejection episodes occurred in four patients and multiple rejection episodes in three patients; all were successfully reversed, and no further graft losses were encountered. Mean serum creatinine level at 1 month posttransplant was 141 mumol/L (1.6 mg/dL), and the average serum creatinine has remained at that level during the follow-up period. No serious infections were encountered. Prophylactic OKT3 administration resulted in depletion of CD3+ lymphocytes from the peripheral circulation throughout therapy, as well as the development of therapeutic serum OKT3 levels. Five of the 27 (22%) patients developed antimurine antibodies during or after OKT3 therapy; four of these patients had low-titer antimurine antibody, and one had high-titer antimurine antibody. First-dose reactions were generally mild in this group of patients. Prophylactic use of OKT3 in this patient population resulted in superior graft survival when compared with a similar group of patients not receiving OKT3.

Immunologic monitoring with Orthoclone OKT3 therapy.

Muromonab-CD3 monoclonal antibody (Orthoclone OKT3) was used 146 times in 123 transplant recipients to treat or prevent rejection. Reversal and prevention of rejection were evaluated 1 week and 1 year after OKT3 therapy. Eighty-one percent (73 of 90) of the rejection episodes in kidney transplant patients were reversed with 67% of these grafts functioning at 1 year. Eighteen of 20 (90%) rejection episodes in liver transplant recipients were reversed, as were 11 of 13 (85%) heart transplant rejection episodes. Only one of five pancreas transplant episodes were reversed. OKT3 was used prophylactically in 18 transplant recipients (13 kidney, four heart, one liver). Immunologic monitoring (lymphocyte subsets, serum OKT3 levels, and antimurine antibodies) was performed during and after OKT3 therapy. Antimurine antibody formation rate was 28% (26 of 94 patients monitored). OKT3 therapy resulted in a rapid depletion of CD3+ cells from the peripheral circulation (less than 20/mm3) and trough serum OKT3 levels of greater than 800 ng/ml by the third day of therapy in all transplant types. Twenty-three patients (14 kidney, five liver, three heart, and one pancreas) were retreated with OKT3; reversal of rejection occurred in 87% of patients (13 of 15) with no antimurine antibodies and in 83% of patients (five of six) with a low antibody titer but did not occur in the two patients with a high antibody titer. Retreatment of patients with no anti-OKT3 antibody resulted in a depletion of CD3+ cells from the peripheral blood, but it took longer than in patients treated with OKT3 for the first time. Similarly, serum OKT3 levels increased slower in retreated patients compared with first treatment. In retreatment patients with a low titer antimurine antibody, often it was necessary to increase the dose of OKT3 to achieve adequate serum OKT3 levels and to deplete CD3+ cells. Antimurine antibody developed de novo in four of the 15 antibody negative patients (27%) who were retreated. Overall, OKT3 was an effective agent in reversing and preventing rejection in solid organ transplantation with few severe side effects and a low mortality. Retreatment with OKT3 should not be considered unless the antibody status of the patient is known. Development of low titer antibodies does not preclude successful retreatment with OKT3. Alternate antirejection therapy, however, should be used in patients with high titer antimurine responses.

Successful retreatment of allograft rejection with OKT3.

OKT3 is a murine monoclonal antibody to the CD3 antigen of human T lymphocytes. The production of human antimurine antibodies after treatment with OKT3 has been perceived as a major limitation to its extended use and reuse. Treatment of 142 patients with 168 courses of OKT3 resulted in the development of antimouse antibody in 28% of the patients. Twenty-six patients (16 kidney, 6 liver, 3 heart, 1 pancreas) have been retreated with 27 courses of OKT3. Eighteen patients had no antimurine antibodies present, and the rejection reversal rate was 83% (15/18). Six patients had a low-titer antimurine antibody present, and rejection reversal occurred in 5 (83%). Rejection was not reversed in 2 patients with a high-titer antibody. Development of antimurine antibody was more frequent in renal transplant recipients (33%) than in hepatic (12%) or cardiac transplant recipients (18%). We believe that this reflects the fact that concomitant immunosuppressive therapy is more likely to be reduced during OKT3 therapy in renal transplant recipients than in hepatic or cardiac transplant recipients. Retreatment of patients with no anti-OKT3 antibody resulted in depletion of CD3+ cells from the peripheral blood, but it took longer than in patients being treated with OKT3 for the first time. Similarly, serum OKT3 levels rose more slowly in retreated patients compared to first treatment. In retreating patients with a low-titer antimurine antibody, it often was necessary to increase the dose of OKT3 in order to achieve adequate serum OKT3 levels and to deplete CD3+ cells. De novo antimurine antibody developed in 4 of the 18 (22%) antibody-negative patients who were retreated. In conclusion, retreatment with OKT3 should not be considered unless the antibody status of the patient is known. Development of low-titer antibodies does not preclude successful retreatment with OKT3; however, alternate antirejection therapy should be used in patients with high-titer antimurine responses.