Once-daily budesonide inhalation powder (Pulmicort Turbuhaler) maintains pulmonary function and symptoms of asthmatic children previously receiving inhaled corticosteroids.

BACKGROUND: The incidence of pediatric asthma has increased dramatically over the past few decades, with approximately 5% of American children affected by the disease. OBJECTIVES: To compare the efficacy and safety of once-daily budesonide Turbuhaler with placebo in asthmatic children previously treated with orally inhaled corticosteroids. METHODS: This randomized, double-blind, placebo-controlled, multicenter (17 centers) study included 274 male and female children (aged 6 to 17 years) with a history of asthma for at least the previous 6 months. Patients received placebo or budesonide Turbuhaler (200 microg or 400 microg) once daily for 12 weeks. Efficacy variables included mean changes from baseline in forced expiratory volume in 1 second (FEV1), AM and PM peak expiratory flow rates (PEFRs), nighttime and daytime asthma symptom severity scores, patient discontinuations, use of beta2-agonists as breakthrough medication, forced vital capacity (FVC), and midexpiratory flow rate between 25% and 75% of FVC (FEF25%-75%). Safety was evaluated by adverse events, physical examinations, vital signs, and laboratory tests. RESULTS: Baseline characteristics were comparable among treatment groups. Percentage of predicted FEV1 at baseline was 76.6 +/- 6.9 for placebo, 77.5 +/- 7.1, and 77.0 +/- 7.8 for the budesonide Turbuhaler 200 microg and 400 microg groups, respectively. Significantly (P < or = 0.024) more placebo patients (24%) discontinued treatment because of disease deterioration or no improvement than budesonide Turbuhaler 200 microg (11%) or 400 microg patients (10%). Patients receiving budesonide Turbuhaler experienced significant improvements in FEV1 compared with patients receiving placebo (P < or = 0.015). Significant (P < or = 0.041) improvements over placebo also were observed in AM and PM PEFRs, FVC, FEF25%-75%, nighttime and daytime asthma symptoms, and amount of beta2-agonist used in both budesonide Turbuhaler groups. Adverse events were generally mild or moderate in intensity and similar among treatment groups. CONCLUSIONS: Once-daily budesonide Turbuhaler is effective and safe in children with persistent asthma previously maintained on at least twice-daily dosing regimens of inhaled corticosteroids.

Dose-ranging study of a new steroid for asthma: mometasone furoate dry powder inhaler.

A new formulation of mometasone furoate (MF) for administration by dry powder inhaler (DPI) was evaluated for the treatment of asthma. A 12-week, double-blind, placebo-controlled dose-ranging study compared the efficacy and safety of three doses of MF DPI (100, 200 and 400 mcg b.i.d) with beclomethasone dipropionate (BDP) 168 mcg b.i.d. administered by metered dose inhaler in 365 adult or adolescent patients being treated with inhaled glucocorticoids. The mean change from baseline to endpoint (last treatment visit) for forced expiratory volume in 1 sec (FEV1) was the primary efficacy variable. Secondary efficacy variables included other objective measures of pulmonary function [forced vital capacity (FVC), forced expiratory flow 25-75% (FEV25-75%.) and peak expiratory flow rate (PEFR)] as well as subjective measures of therapeutic response (patients' daily evaluation of asthma symptoms and physicians' evaluation). At endpoint, all four active treatments were significantly more effective than placebo (P < 0.01) in improving FEV1 (MF DPI 5 to 7%, BDP 3%, placebo -6.6%) and all other measures of pulmonary function (FVC: MF DPI 4 to 5%, BDP 2%, placebo -4.7%; FEF25-75%: MF DPI 6 to 18%, BDP 7.5%, placebo -9.5%; PEFR (AM): MF DPI 5 to 10%, BDP 5.7%, placebo -7%). A consistent trend was observed for better improvement in patients treated with MF DPI 200 mcg b.i.d. than with MF DPI 100 mcg b.i.d., with no apparent additional benefit of MF DPI 400 mcg b.i.d. Results for the MF DPI 100 mcg b.i.d. and BDP 168 mcg b.i.d. treatment groups were similar. Patients' and physicians' subjective evaluations of symptoms found similar improvement in the MF DPI 200 and 400 mcg b.i.d. treatment groups, which were slightly better than that in the MF DPI 100 mcg b.i.d. group. Symptoms tended to worsen in the placebo group. MF DPI was well tolerated at all dose levels and the most frequently reported treatment-related adverse effects were headache, pharyngitis and oral candidiasis. No evidence of HPA-axis suppression was detected in any treatment group. In summary, all doses of MF DPI were well tolerated and significantly improved lung function and MF DPI 400 mcg (200 mcg b.i.d.) was the optimal dose in this study of patients with moderate persistent asthma.

Efficacy and safety of budesonide inhalation suspension (Pulmicort Respules) in young children with inhaled steroid-dependent, persistent asthma.

BACKGROUND: Inhaled glucocorticosteroids are indicated for the treatment of persistent asthma; however, many young children are unable to effectively use currently available inhalers. OBJECTIVE: We sought to evaluate the efficacy and safety of 3 different twice daily doses of budesonide inhalation suspension (Pulmicort Respules) in inhaled steroid-dependent asthmatic children. METHODS: This was a 12-week, randomized, double-blind, placebo-controlled, parallel-group study involving 178 children (age range, 4 to 8 years) at 17 centers in the United States. Budesonide inhalation suspension doses of 0.25 mg, 0.50 mg, or 1.0 mg twice daily were administered by means of a jet nebulizer and air compressor system. Efficacy was assessed by recording at home nighttime and daytime asthma symptom scores, use of rescue medication, pulmonary function tests, and treatment discontinuation because of worsening symptoms. Safety was assessed by reported adverse events and changes in baseline and adrenocorticotrophic hormone-stimulated plasma cortisol levels in a subset of patients. RESULTS: Baseline demographics, symptom scores, and pulmonary function data were similar across treatment groups. All doses of budesonide inhalation suspension were superior to placebo in improving nighttime and daytime asthma symptom scores (P

Dose-related efficacy of budesonide administered via a dry powder inhaler in the treatment of children with moderate to severe persistent asthma.

OBJECTIVE: To determine the efficacy and safety of budesonide delivered by an inhalation-driven dry powder inhaler (Turbuhaler) in children with moderate to severe persistent asthma. STUDY DESIGN: In our randomized, double-blind, placebo-controlled, parallel-group, multicenter study, a total of 404 children with asthma, who were aged 6 to 18 years and who had been receiving inhaled glucocorticosteroid therapy, were randomly assigned to receive either 100, 200, or 400 micrograms of budesonide or placebo twice daily for 12 weeks. At baseline, mean forced expiratory volume in 1 second (FEV1) was 74.6% (range, 30.7% to 123.3%) of the predicted normal value. RESULTS: Patients in each of the three budesonide treatment groups showed significant dose-related improvements in lung function (morning peak expiratory flow and FEV1), in asthma symptoms, and with a significant decrease in inhaled beta 2-agonist use in comparison with placebo. Improvements were evident within 2 weeks and were maintained throughout the 12 weeks. Budesonide treatment had no significant effect on hypothalamic-pituitary-adrenal axis function, and the incidence of reported adverse events was similar in all treatment groups. CONCLUSION: Budesonide administered via a dry powder inhaler provided dose-related improvements in lung function and clinical status and was well tolerated by children (6 to 18 years of age) with moderate to severe persistent asthma.

The effects of triamcinolone acetonide aqueous nasal spray on adrenocortical function in children with allergic rhinitis.

BACKGROUND: Suppression of adrenocortical function, a risk associated with oral corticosteroids, is minimized with intranasal corticosteroids. Triamcinolone acetonide (TAA) aqueous nasal spray, at therapeutic doses, has no measurable effect on adrenocortical function in adults with allergic rhinitis. OBJECTIVE: This double-blind, placebo-controlled study compared the effect of once-daily TAA aqueous nasal spray (220 or 440 microg) with placebo on adrenocortical function after 6 weeks of treatment in pediatric (children 6 to 12 years of age) patients with allergic rhinitis. The pharmacokinetic profile of TAA was examined after once-daily intranasal administration of TAA aqueous nasal spray 440 microg for 6 weeks. METHODS: Eighty children received TAA aqueous nasal spray 220 microg or 440 microg or placebo for 6 weeks. Adrenocortical function was assessed by analyzing plasma cortisol levels before stimulation (0 hour) and at 30 and 60 minutes after a rapid 1-hour intravenous cosyntropin stimulation test performed before treatment and after 6 weeks of treatment. Samples for pharmacokinetic evaluation were collected from 19 patients at baseline (0 hour) and at 0.5, 1, 1.5, and 6 hours after the final dose of study medication. RESULTS: After 6 weeks, no significant effects on adrenocortical function were observed at 30 or 60 minutes after cosyntropin stimulation with either dose of TAA aqueous nasal spray. TAA concentrations in plasma showed rapid elimination of the drug, with little or no accumulation. CONCLUSIONS: TAA aqueous nasal spray (220 or 440 microg/day) has no measurable effect on adrenocortical function in pediatric patients with allergic rhinitis. Pharmacokinetic parameters after 440 microg/day of TAA aqueous nasal spray indicate a rapid decline of plasma drug levels, with little or no systemic accumulation of study drug.

Comparative efficacy and safety of once-daily versus twice-daily loratadine-pseudoephedrine combinations versus placebo in seasonal allergic rhinitis.

The objective of this study was to compare the efficacy and safety of Claritin-D 24 Hour (once daily) with that of Claritin-D 12 Hour (twice daily) and placebo in the treatment of patients with seasonal allergic rhinitis (SAR). In this double-blind, placebo-controlled, multicenter study, 469 patients with moderate-to-severe SAR symptoms were treated for 2 weeks with one of the following: Claritin-D 24 Hour (a combination tablet formulation of loratadine 10 mg in the coating and pseudoephedrine sulfate 240 mg in an extended-release core), Claritin-D 12 Hour (a combination tablet formulation of loratadine 5 mg in the tablet coating and 120 mg pseudoephedrine sulfate, 60 mg in the coating and 60 mg in the core), or placebo. Claritin-D 24 Hour and Claritin-D 12 Hour were consistently superior to placebo (P < 0.01) in reducing total, nasal, and nonnasal symptom scores. Patients in the Claritin-D 24 Hour and Claritin-D 12 Hour groups also had significantly greater (P

Effectiveness of fluticasone propionate in patients with moderate asthma: a dose-ranging study.

This study was undertaken to evaluate the efficacy and safety of fluticasone propionate, an inhaled corticosteroid, in adolescents and adults with moderate asthma who were previously taking inhaled corticosteroids. After a 2-week, open-label screening period, a double-masked, randomized, parallel-group, dose-ranging study was conducted over 12 weeks in 21 outpatient centers throughout the United States. Patients (N = 304) > or = 12 years of age with moderate asthma previously treated with inhaled corticosteroids and beta-sympathomimetic bronchodilators were enrolled. Patients were assigned to receive placebo or fluticasone propionate 100, 250, or 500 micrograms twice daily via a metered-dose inhaler without a spacer device. These doses refer to the amount of fluticasone propionate released from the valve of the metered-dose inhaler; the corresponding doses released from the activator of the metered-dose inhaler are 88 micrograms, 220 micrograms, and 440 micrograms, respectively. Between baseline and end point, mean values of forced expiratory volume in 1 second decreased 0.31 L in the placebo group and improved 0.39 L, 0.30 L, and 0.43 L in patients receiving 100-micrograms, 250-micrograms, and 500-micrograms fluticasone propionate, respectively. The differences between placebo and all treatment groups were statistically significant. More patients were withdrawn from placebo (72%) than from fluticasone propionate (13% to 16%) because of failure to meet predetermined asthma stability criteria. Differences in baseline-to-end point changes in morning peak expiratory flow rate, physician overall assessments and patient-rated assessment of symptoms, and albuterol use for symptom control also significantly favored each fluticasone propionate group over placebo. There were essentially no differences in efficacy among the three fluticasone propionate groups. Treatment-related adverse events occurred in 8% of placebo-treated patients and 13% to 15% of fluticasone propionate-treated patients; these events were mainly localized to the oropharynx/ larynx. A 12-week course of fluticasone propionate (100, 250, and 500 micrograms twice daily) was well tolerated and more effective than placebo based on maintenance of asthma stability, pulmonary function tests, physician and patient assessments, and rescue bronchodilator use. No dose-related effects were observed with the dosages of fluticasone propionate used in this study.

Fluticasone propionate aqueous nasal spray is safe and effective for children with seasonal allergic rhinitis.

INTRODUCTION: Fluticasone propionate aqueous nasal spray, a new topical corticosteroid preparation, is effective when given as 200 micrograms once daily in patients (> 12 years of age) with seasonal allergic rhinitis. STUDY OBJECTIVE: To evaluate the efficacy and safety of fluticasone proprionate aqueous nasal spray in children aged 4 to 11 years with seasonal allergic rhinitis. STUDY DESIGN: Multicenter, randomized, double-blind, placebo-controlled, parallel-group. PATIENTS: Two hundred fifty children aged 4 to 11 years with moderate-to-severe nasal symptoms, a positive skin test reaction to a late-summer or autumn allergen, a history of seasonal allergic rhinitis, and documentation of an unsatisfactory response to conventional treatment. INTERVENTIONS: Children were randomly assigned to receive fluticasone propionate, either 100 micrograms or 200 micrograms, or placebo, given by intranasal spray once daily in the morning for 14 days. MEASUREMENTS AND RESULTS: Severity of nasal symptoms (obstruction, rhinorrhea, itching, and sneezing) was recorded on visual analog scales by investigators at weekly visits and by patients (or adult guardian) daily in the evening. According to investigator and patient ratings, both fluticasone propionate 100 micrograms/d and 200 micrograms/d lowered total nasal symptom scores when compared with placebo. Both dosages of fluticasone propionate were more effective than placebo on the basis of investigator-rated overall clinical evaluation of efficacy at the end of treatment, with significant improvement (as opposed to moderate or mild improvement, no change or worsening) noted in 21% to 29% of the active-treatment groups vs 9% in the placebo group. There were no significant differences between the two fluticasone propionate dosages in any efficacy measurement. Morning plasma cortisol concentrations and frequency of drug-related adverse events were similar in the fluticasone propionate and placebo groups. CONCLUSION: In children as young as 4 years, 100 micrograms of fluticasone propionate aqueous nasal spray given once daily is as effective as 200 micrograms given once daily, the usual adult dose for the treatment of seasonal allergic rhinitis. Both fluticasone propionate dosages were well tolerated and neither dosage appears to interfere with the hypothalamic-pituitary-adrenal axis in children.

Late-onset papilledema following spinal injury. Case report.

Papilledema, is a known complication of various spinal pathologies. It has, however, been only infrequently reported following spinal injury, and may be overlooked in these cases. Presented herein is a 27 year old male who suffered thoracic and lumbar spinal injuries. Papilledema following mild increase in intracranial pressure (IICP) developed 3 weeks following trauma, and subsided within 8 weeks. The importance of routine repeat ophthalmoscopic examinations following spinal injury to detect changes characteristic of IICP is emphasized.

Lumbar spine dimensions in paraparetic patients: a 10 year follow up study.

Lumbar spinal AP radiographs of 13 C3-T11 paraparetic patients taken at about a 10 year interval were compared. The height (H) and maximum width (W) of the interapophysolaminar spaces (IALS), the width of the vertebral bodies at their waist (V) and the relationship between them showed minimal change over the follow up period. The difference between the late and early mean IALS height values increased caudally but was statistically significant only below L5. Subjective evaluation of the consecutive x-ray films revealed few new degenerative abnormalities. It is concluded that the normal aging process, which includes horizontal spreading of the lumbar vertebral bodies and narrowing of the lumbar spinal canal, is not accelerated by paraparesis and may even be retarded by relative immobilization.

Fatal and near-fatal anaphylactic reactions to food in children and adolescents.

BACKGROUND AND METHODS: Reports of fatal or near-fatal anaphylactic reactions to foods in children and adolescents are rare. We identified six children and adolescents who died of anaphylactic reactions to foods and seven others who nearly died and required intubation. All the cases but one occurred in one of three metropolitan areas over a period of 14 months. Our investigations included a review of emergency medical care reports, medical records, and depositions by witnesses to the events, as well as interviews with parents (and some patients). RESULTS: Of the 13 children and adolescents (age range, 2 to 17 years), 12 had asthma that was well controlled. All had known food allergies, but had unknowingly ingested the foods responsible for the reactions. The reactions were to peanuts (four patients), nuts (six patients), eggs (one patient), and milk (two patients), all of which were contained in foods such as candy, cookies, and pastry. The six patients who died had symptoms within 3 to 30 minutes of the ingestion of the allergen, but only two received epinephrine in the first hour. All the patients who survived had symptoms within 5 minutes of allergen ingestion, and all but one received epinephrine within 30 minutes. The course of anaphylaxis was rapidly progressive and uniphasic in seven patients; biphasic, with a relatively symptom-free interval in three; and protracted in three, requiring intubation for 3 to 21 days. CONCLUSIONS: Dangerous anaphylactic reactions to food occur in children and adolescents. The failure to recognize the severity of these reactions and to administer epinephrine promptly increases the risk of a fatal outcome.

Symptomatic postprandial hypotension in high paraplegia. Case report.

Symptomatic postprandial decrease in blood pressure has been described in patients with various autonomic disorders, but not in patients with spinal injuries. Presented herein is a 31 year old female patient with traumatic complete paraplegia under the T3 level, in whom postprandial hypotension (PPH) was observed. The PPH was preceded by an increase in insulin level and was followed by an acceleration of heart rate. Oral caffeine prevented the hypotension and alleviated the symptoms. It is suggested that the PPH might be manifested as a result of damage to an upper thoracic spinal baroreflex. Clinical investigation of PPH is recommended for patients with high paraplegia.

Is the appearance of periarticular new bone formation related to local neurological disability?

The present work examined the relationship between the appearance of periarticular new bone formation (PNBF) and the presence of local sensorimotor disability, and the relationship between PNBF and the severity of the motor disability. The study population consisted of 18 patients with spinal cord lesions and 18 patients with traumatic brain injury. The confinement of PNBF below the level of neurological deficit in patients with spinal cord lesions, and mainly to paralysed or paretic limbs in brain injured patients, indicates a possible causal relationship between the presence of sensorimotor disability and PNBF. On the other hand, the high incidence of bilateral PNBF in patients with incomplete spinal lesions and the appearance of PNBF in some nonplegic and even paretic limbs in the brain injured patients, demonstrates the lack of connection between the severity of the motor deficit and the risk of PNBF. It is suggested that local factors which are related to sensorimotor disability are probably involved in PNBF induction, but additional elements may also play a role in the induction of PNBF and in its propagation.

Transverse myelitis associated with mycoplasma pneumoniae: case report.

Acute transverse myelitis (ATM) is a disorder of the spinal region of the central nervous system. In the present case, the clinical course showed ATM associated with mycoplasma pneumoniae (MP) and little recovery; the girl was left with a flaccid paraplegia, and thus differed from other cases in the literature which all reported complete or near-complete recovery.

Effects of exercise on the signal-averaged electrocardiogram in coronary artery disease.

The effects of exercise on the signal-averaged electrocardiogram (SAECG) were investigated in 52 patients with stable coronary artery disease. The SAECG was recorded before and immediately after the exercise test and analyzed at 25 to 250 Hz and 40 to 250 Hz. All patients had SAECG with noise level less than or equal 0.8 microV at 25 Hz and less than or equal to 0.6 microV at 40 Hz and with the difference in noise level between control SAECGs and SAECGs after exercise less than or equal to 0.2 to 0.3 microV. Twenty-eight patients developed ST changes consistent with transient subendocardial ischemia that persisted during the SAECG recording after exercise. There was no significant difference between control SAECGs and SAECGs after exercise in patients with or without a positive exercise test. The absence of significant change on the SAECG was not related to the presence or absence of prior myocardial infarction, site of infarction, development of exercise-induced ventricular arrhythmias or presence of an abnormal recording at baseline. These data suggest that exercise-induced electrophysiologic changes and ventricular arrhythmias may not be related to the anatomic-electrophysiologic substrate that underlies late potentials on the SAECG.

Juvenile Parkinson's disease and its response to L-dopa therapy.

Four youngsters, between the ages of 13-27 years, presented dystonic foot. Two to three years following the appearance of the dystonic foot, cogwheel rigidity and tremor appeared on the dystonic foot side. Treatment with low doses of levodopa/carbidopa consistently reversed the symptoms. "On-off" phenomena appeared in the first years of treatment and persisted for the entire period of 5 to 15 years of illness. No parkinsonian signs were present when the dystonic foot appeared. Based on our observations and on a review of the literature, we conclude that responsiveness to low doses of L-dopa is the major marker of juvenile Parkinson's disease.

Sleep tonus inversion: a feature of juvenile dystonic parkinsonism.

Polysomnographic monitoring of a 16-year-old girl suffering from dopa-responsive dystonic parkinsonism showed a change in the distribution of muscle activity in thigh muscles during different stages of sleep. The hamstring muscles were hypertonic at sleep onset compared with the vastus lateralis of the quadriceps muscles. At the third sleep cycle of each of the 2 nights, the time at which sleep benefit becomes clinically evident, the hypertonia in the hamstring muscles was reversed and the vastus lateralis became more hypertonic. It is suggested that the muscle tonus inversion marks the moment at which the sleep process alleviates the dystonic parkinsonian state manifested at wakefulness as a circardian fluctuation. According to our data, the flexor-extensor tonus inversion during sleep was not yet described in the literature, and may be an associated feature of dopa-responsive dystonic parkinsonism.