Biomedical subjects

Stanley Szefler

Publications and source records attributed to Stanley Szefler.

7 recordsLinked to original sources

PubMed2006

Summary proceedings from the bronchopulmonary dysplasia group.

Despite improvements in neonatal care, bronchopulmonary dysplasia (BPD) continues to occur in approximately one third of newborns who have birth weights of <1000 g and contributes to significant morbidity in this population. Gaps in knowledge about the prevention and treatment of BPD remain, resulting in unintended short- and long-term sequelae. In addition to chronic lung disease, preterm newborns with BPD are more likely to develop language delay, cerebral palsy, and cognitive impairments compared with preterm newborns without BPD. The pulmonary group identified 3 critical needs to enhance the design of clinical trials in neonates with BPD: (1) identify the stages of BPD; (2) define BPD more clearly; and (3) identify subtypes of BPD patients. The group determined that trials are needed for 3 areas of BPD: (1) prevention of BPD; (2) treatment of evolving BPD; and (3) treatment of established BPD. The severity of BPD is defined as mild, moderate, and severe, and subgroups among those with BPD are described. Here we identify gaps in basic science and pharmacologic knowledge that hamper investigators' ability to conduct effective BPD clinical trials and provide a list of drugs to be studied in BPD trials. Priorities for drug-class evaluation by stage of BPD are given. The pulmonary group proposes a BPD clinical-trials framework that varies according to the different stages of BPD and describes characteristics of the overall design for BPD clinical trials. Finally, we discuss trial-design issues that are common to all neonatal studies.

Adrenal Cortex Hormones↗

PubMed2005

Ciclesonide, a novel inhaled steroid, does not affect hypothalamic-pituitary-adrenal axis function in patients with moderate-to-severe persistent asthma.

BACKGROUND: Inhaled corticosteroids (ICSs) reduce local airway inflammation, which is an underlying cause of asthma symptoms. However, potential systemic side effects associated with ICS use are a major concern for asthmatic patients. METHODS: Adult patients (n = 60; > or = 18 years of age) with moderate-to-severe asthma were randomized to receive 4 weeks of treatment with ciclesonide (CIC), 320 microg bid (CIC 640), CIC, 640 microg bid (CIC 1280), fluticasone propionate (FP), 440 microg bid (FP 880), FP 880 microg bid (FP 1760), or placebo (PBO) [all doses expressed as ex-actuator; comparable to ex-valve doses of 800 and 1,600 microg/d for CIC and 1,000 and 2,000 microg/d for FP, respectively]. RESULTS: After 29 days of treatment, CIC 640, CIC 1280, and FP 880 had no significant effect on the mean serum cortisol area under the curve for 0 to 24 h (AUC0-24h). FP 1760 produced a statistically significant suppression in mean serum cortisol AUC0-24h compared to PBO (p = 0.0009; 95% confidence interval [CI] -117.5 [corrected] to -32.1). Results obtained with cosyntropin stimulation revealed no statistically significant differences among the groups. The CIC 640 group demonstrated a significant increase compared to the PBO group in 24-h urinary cortisol levels from baseline at week 4 (p = 0.0224; 95% CI, 0.0023 to 0.0283), while the other treatment groups revealed no change in this parameter. The incidence of treatment-emergent adverse events was similar in all groups, and all adverse events were mild or moderate in severity. CONCLUSION: Treatment with moderate and high doses of CIC does not result in hypothalamic-pituitary-adrenal-axis suppression as compared with PBO.

Administration, Inhalation↗

PubMed2004

Measuring adherence with the Doser CT in children with asthma.

Non-adherence with prescribed asthma treatment causes compromised treatment effectiveness, including greater morbidity, mortality, and health care utilization costs. As a result, there is an increasing interest in measuring patient adherence behaviors. Electronic monitoring devices offer a promising method for assessing patient adherence behavior patterns. The reliability of the Doser Clinical Trials (CT) (Meditrack Products, Hudson, MA), an inexpensive, pressure-actuated device that monitors metered-dose inhaler (MDI) usage, was evaluated in a field study of outpatient pediatric asthmatics. Canister weight and various Doser CT measures of patient medication use were compared to determine the reliability and usefulness of the device. Doser CTs were dispensed to 16 research subjects for use on corticosteroid MDIs over a period of several months. One Doser CT per month was dispensed to each subject. Doser CTs were collected at 30-60 day intervals, with a total of 61 months of Doser CT data obtained across the subjects. MDI canister weights were monitored for a subset of 6 subjects. Usable Doser CT data were summarized and average adherence estimates were computed. Adherence estimates differed from one another and the adherence estimate, as measured by canister weight, was significantly higher than each Doser CT estimate. However, overall, the Doser CT showed adequate reliability as evidenced by high correlations among the Doser CT estimates of adherence and the existing gold standard of canister weight. The Doser CT is likely to be useful for monitoring MDI use in clinical care and research, potentially providing greater accuracy than the standard of canister weight.

Administration, Inhalation↗

PubMed2004

Risk-benefit value of inhaled glucocorticoids: a pharmacokinetic/pharmacodynamic perspective.

Inhaled glucocorticoids induce therapeutic and adverse systemic effects via the same types of receptors. Analysis of the pharmacokinetic/pharmacodynamic parameters of inhaled glucocorticoids generates a risk-benefit value (RBV). Targeted efficacy with minimal adverse effects helps to quantify an appropriate RBV. High lung deposition/targeting, high receptor binding, longer pulmonary retention, and high lipid conjugation are among the pharmacokinetic parameters to be considered for improved efficacy of the compound. Low or negligible oral bioavailability, small particle size and inactive drug at the oropharynx, high plasma protein binding, rapid metabolism, high clearance, and lower systemic concentrations are associated with low risks for adverse effects. Inhaled glucocorticoid potency is enhanced by solution inhalers, which result in higher pulmonary deposition and minimize local adverse effects. These properties, among others, determine the efficacy and safety of inhaled glucocorticoids. Currently available inhaled glucocorticoids do not provide the complete pharmacokinetic/pharmacodynamic parameters to optimize RBV, leaving room for improvement in the development of future agents.

Administration, Inhalation↗

PubMed2003

Role of budesonide as maintenance therapy for children with asthma.

Asthma is a chronic inflammatory disease of the airways. Inhaled corticosteroids are recognized as the preferred long-term control medication for persistent asthma based on their anti-inflammatory properties and significant evidence of efficacy. Inhaled budesonide is the most carefully characterized inhaled corticosteroid for childhood asthma. It is available for administration in children down to six months of age and to date has an excellent safety profile.

Administration, Inhalation↗

PubMed2003

Growth and bone density in children with mild-moderate asthma: a cross-sectional study in children entering the Childhood Asthma Management Program (CAMP).

OBJECTIVES: We sought to determine whether mild-moderate persistent asthma sufficient to produce a decrease in baseline lung function is associated with an adverse effect on growth and bone mineral density (BMD) in children. METHODS: This was a cross-sectional study of 1041 children, 5 to 12 years old (32% ethnic/racial minorities and 40% female), enrolled into the Childhood Asthma Management Program (CAMP). Measures of asthma severity included: Spirometry; bronchial hyperresponsiveness; duration of asthma symptoms; and symptom-based assessment of severity. Multiple regression analyses were used to relate the asthma severity on the primary outcome variables: Height by stadiometry and BMD by dual energy radiographic absorptiometry. RESULTS: The mean +/- SD height percentile was 56.0 +/- 28.5 percentile for the population. The only significant relationship between asthma severity and height percentile was with methacholine bronchoprovocation in girls (beta 2.98, P =.019, covariate multiple regression). The mean +/- SD BMD was 0.65 +/- 0.10 g/cm(2) for the population. The past use of corticosteroids did not adversely affect either growth or BMD. CONCLUSIONS: We found that mild-moderate asthma of as long as 4 to 7 years duration in children does not produce an adverse effect on linear growth or BMD.

Asthma↗

PubMed2000

Long-term effects of budesonide or nedocromil in children with asthma.

BACKGROUND: Antiinflammatory therapies, such as inhaled corticosteroids or nedocromil, are recommended for children with asthma, although there is limited information on their long-term use. METHODS: We randomly assigned 1041 children from 5 through 12 years of age with mild-to-moderate asthma to receive 200 microg of budesonide (311 children), 8 mg of nedocromil (312 children), or placebo (418 children) twice daily. We treated the participants for four to six years. All children used albuterol for asthma symptoms. RESULTS: There was no significant difference between either treatment and placebo in the primary outcome, the degree of change in the forced expiratory volume in one second (FEV1, expressed as a percentage of the predicted value) after the administration of a bronchodilator. As compared with the children assigned to placebo, the children assigned to receive budesonide had a significantly smaller decline in the ratio of FEV1 to forced vital capacity (FVC, expressed as a percentage) before the administration of a bronchodilator (decline in FEV1:FVC, 0.2 percent vs. 1.8 percent). The children given budesonide also had lower airway responsiveness to methacholine, fewer hospitalizations (2.5 vs. 4.4 per 100 person-years), fewer urgent visits to a caregiver (12 vs. 22 per 100 person-years), greater reduction in the need for albuterol for symptoms, fewer courses of prednisone, and a smaller percentage of days on which additional asthma medications were needed. As compared with placebo, nedocromil significantly reduced urgent care visits (16 vs. 22 per 100 person-years) and courses of prednisone. The mean increase in height in the budesonide group was 1.1 cm less than in the placebo group (22.7 vs. 23.8 cm, P=0.005); this difference was evident mostly within the first year. The height increase was similar in the nedocromil and placebo groups. CONCLUSIONS: In children with mild-to-moderate asthma, neither budesonide nor nedocromil is better than placebo in terms of lung function, but inhaled budesonide improves airway responsiveness and provides better control of asthma than placebo or nedocromil. The side effects of budesonide are limited to a small, transient reduction in growth velocity.

Administration, Inhalation↗