Inhaled corticosteroids versus sodium cromoglycate in children and adults with asthma.

BACKGROUND: Inhaled corticosteroids (ICS) and sodium cromoglycate (SCG) have become established as effective controller medications for children and adults with asthma, but their relative efficacy is not clear. OBJECTIVES: To compare the relative effectiveness and adverse effects of ICS and SCG among children and adults with chronic asthma. SEARCH STRATEGY: Systematic search of the Cochrane Airways Group's special register of controlled trials (to Feb. 2004), hand searches of the reference lists of included trials and relevant review papers, and written requests for identification of additional trials from pharmaceutical manufacturers. SELECTION CRITERIA: Randomized controlled trials comparing the effect of ICS with SCG in children and adults with chronic asthma. DATA COLLECTION AND ANALYSIS: All studies were assessed independently for eligibility by three review authors. Disagreements were settled by consensus. Trial authors were contacted to supply missing data or to verify methods. Eligible studies were abstracted and fixed- and random-effects models were implemented to pool studies. Separate analyses were conducted for paediatric and adult studies. Subgroup analyses and meta-regression models were fit to explore heterogeneity of lung function outcomes by type of RCT, category of ICS or SCG dosage, asthma severity of participants, and study quality on outcomes. MAIN RESULTS: Of 67 identified studies, 17 trials involving 1279 children and eight trials involving 321 adults with asthma were eligible. Thirteen (76%) of the paediatric studies and six (75%) of the adult studies were judged to be high quality. Among children, ICS were associated with a higher final mean forced expiratory volume in 1 second [FEV1] (weighted mean difference [WMD] 0.07 litres, 95% confidence interval [CI] 0.02 to 0.11) and higher mean final peak expiratory flow rate [PEF] (WMD 17.3 litres/minute, 95% CI 11.3 to 23.3) than SCG. In addition, ICS were associated with fewer exacerbations (WMD -1.18 exacerbations per year, 95% CI -2.15 to - 0.21), lower asthma symptom scores, and less rescue bronchodilator use than SCG. There were no group differences in the proportion of children with adverse effects. Among adults, ICS were similarly associated with a higher mean final FEV1 (WMD 0.21 litres, 95% CI 0.13 to 0.28) and a higher final endpoint PEF (WMD 28.2 litres/minute, 95% CI 18.7 to 37.6) than SCG. ICS were also associated with fewer exacerbations (WMD -3.30 exacerbations per year, 95% CI -5.62 to -0.98), lower asthma symptom scores among cross-over trials but not parallel trials, and less rescue bronchodilator use than SCG. There were no differences in the proportion of adults with adverse effects. In subgroup analyses involving lung function measures, paediatric and adult studies judged to be of high quality had results consistent with the overall results. Lung function measures in children were higher in studies with medium BDP-equivalent steroid dosages than low BDP-equivalent dosages, while adult studies could not be compared by steroid dosage since they all incorporated similar dosages. There were no significant differences in lung function by the asthma severity of participants for adult or child studies. AUTHORS' CONCLUSIONS: ICS were superior to SCG on measures of lung function and asthma control for both adults and children with chronic asthma. There were few studies reporting on quality of life and health care utilization, which limited our ability to adequately evaluate the relative effects of these medications on a broader range of outcomes. Although there were no differences in adverse effects between ICS and SCG, most trials were short and may not have been of sufficient duration to identify long-term effects. Our results support recent consensus statements in the U.S. and elsewhere that favour the use of ICS over SCG for control of persistent asthma.

Patient self-management of acute asthma: adherence to national guidelines a decade later.

BACKGROUND AND OBJECTIVES: Children in the emergency department (ED) with acute asthma were enrolled to assess the impact of asthma on their activities of daily living and evaluate their access to care and preventive strategies, determine the proportion who adhered to the National Heart, Lung, and Blood Institute (NHLBI) guidelines for proper steps to take at home during an acute asthma exacerbation, and compare adherence rates for those with persistent and mild intermittent asthma. DESIGN AND METHODS: Children 2 to 18 years old who presented to the Children's Hospital of Philadelphia's ED with acute asthma exacerbations were enrolled prospectively. Parents and patients completed the 108-item Asthma Exacerbation Response Questionnaire with a focus on determining the home management steps they took both at the onset of the asthma exacerbation and just before coming to the ED. RESULTS: Among the 433 children studied, 76% had at least 1 doctor visit, 75% had at least 1 ED visit, and 43% had at least 1 hospitalization for asthma in the preceding 12 months. Overall, 64% had persistent asthma by NHLBI criteria, yet just 4% were cared for by an allergist or pulmonologist, 38% took daily anti-inflammatory therapy, and 18% received a daily inhaled corticosteroid. Also, 48% did not use a holding chamber with their metered-dose inhalers, and 66% did not use their peak flow meters. Regarding exacerbation response, 71% did not have a written action plan, and 89% did not maintain a symptom diary. Both at the onset of wheezing and just before coming to the ED, administration of a beta2-agonist was the only step that the majority of children performed. One-third or fewer followed the other steps recommended by the NHLBI, including using a peak flow meter, beginning oral corticosteroids, calling or going to see the doctor, or going to the ED. Children with persistent asthma were not more adherent to the guidelines than those with mild intermittent disease. CONCLUSIONS: Asthma has a significant adverse effect on the lives of these children. The NHLBI guidelines, first published a decade ago, were designed to reduce asthma's increasing morbidity and mortality, but this study uncovered a high rate of nonadherence with many aspects of the guidelines, including preventive strategies and home management of an exacerbation.

Prevention of asthma morbidity: recent advances.

Asthma prevalence has risen substantially in recent decades and is an increasing cause of disability for American children. Concern about the rise in morbidity has led to treatment guidelines and a growing body of clinical research. Recent trials continue to support the role of inhaled corticosteroids as the most effective therapy to control airway inflammation associated with persistent asthma. Growth suppression due to inhaled corticosteroids has also been well documented, although the long-term effects and relative potencies of different agents require further study. Other anti-inflammatory agents such as cromolyn and the new class of leukotriene receptor antagonists have demonstrated benefit in milder patients. Leukotriene receptor antagonists and long-acting beta2-agonists may allow for reduction of inhaled steroid doses. Control of environmental allergens and irritants is essential. New evidence suggests an increasingly important role for allergen immunotherapy.

Hyponatremic seizures in infancy: association with retinal hemorrhages and physical child abuse?

We present two cases of infants with hyponatremic seizures who had an unexpected finding of retinal hemorrhages. A review of the literature found no prior association between hyponatremic seizures and retinal hemorrhages. The retinal hemorrhages found in the first patient were a result of shaken baby syndrome (SBS) and associated with long bone fractures and a subdural hematoma. The second patient had retinal hemorrhages and cerebral edema, presumed to be a result of SBS. We suggest that children who become hyponatremic owing to neglect, lack of education, or intentional water poisoning may be at risk for other forms of child abuse. Additional research needs to be done to further elucidate the relationship between hyponatremic seizures and child abuse.

Ipratropium bromide added to asthma treatment in the pediatric emergency department.

OBJECTIVE: To determine if the addition of ipratropium bromide to the emergency department (ED) treatment of childhood asthma reduces time to discharge, number of nebulizer treatments before discharge, and the rate of hospitalization. METHODS: Patients >12 months of age were eligible if they were to be treated according to a standardized ED protocol for acute asthma with nebulized albuterol (2.5 mg/dose if weight <30 kg, otherwise 5 mg/dose) and oral prednisone or prednisolone (2 mg/kg up to 80 mg). Subjects were randomized to receive either ipratropium (250 microg/dose) or normal saline (1 mL/dose) with each of the first three nebulized albuterol doses. Further treatment after the first hour was determined by physicians blinded to subject group assignment. Records were reviewed to determine the length of time to discharge home from the ED, number of doses of albuterol given before discharge, and the number of patients admitted to the hospital. RESULTS: Four hundred twenty-seven patients were randomized to ipratropium or control groups; these groups were similar in all baseline measures. Among patients discharged from the ED, ipratropium group subjects had 13% shorter treatment time (mean, 185 minutes, vs control, 213 minutes) and fewer total albuterol doses (median, three, vs control, four). Admission rates did not differ significantly (18%, vs control, 22%). CONCLUSIONS: The addition of three doses of ipratropium to an ED treatment protocol for acute asthma was associated with reductions in duration and amount of treatment before discharge.

Expenditures for psychotropic medications in the United States in 1985.

OBJECTIVE: Psychotropic medications have seldom been included in estimates of the costs of mental health services. In the infrequent case that these costs have been assessed, they have been estimated by using national surveys of consumers of health services. The objective of this study was to estimate the costs of prescriptions for psychotropic medications in the United States in 1985 and to assess the difference with the most recent cost estimate from a health services survey (1977). METHOD: Study data were based on retail costs of psychotropic medications reported to the Pharmaceutical Data Service Alpha National Prescription and Sales Audit. The data come from a computerized survey panel of 2,250 pharmacies representative of the more than 14,000 pharmacies nationwide. The database includes all medication prescriptions filled, whether paid with cash or Medicaid or reimbursed by third-party payment. Analyses were limited to psychotropic medication prescriptions. RESULTS: In 1985, $1.45 billion was spent on outpatient psychotropic medications. Nearly $868 million (60% of the total) was spent on antianxiety and sedative-hypnotic medications, while approximately $263 million (18%) was spent on antipsychotic medications, $240 million (17%) on antidepressants, and $84 million (5%) on combination psychotropic medications. These expenditures were much higher than would have been expected given the most recent health services estimate of $513 million. CONCLUSIONS: These results demonstrate the substantial cost of psychotropic medications in 1985. The finding that the cost of psychotropic medications was so high, in contrast to the lower estimate from the 1977 survey, demonstrates the importance of obtaining more frequent cost estimates and basing future estimates on medication databases.

Dopamine D1 receptor development depends on endogenous dopamine.

Profound depletion of forebrain dopamine by 6-hydroxydopamine in neonatal rats (day 3) was associated with up to 82% loss of D1 receptor sites labeled with [3H]SCH-23390 at day 21. Administration of the selective D1 agonist SKF-38393 (days 6-18) abolished the correlation between D1 receptor density and DA concentrations, even with greater than 99% depletion of DA. In intact control animals, there was an inverse correlation between spontaneous variation in levels of DA and D1 receptor site density in forebrain tissue (r = -0.79) which also was abolished by treatment with the D1 agonist. Thus, D1 receptor density may be regulated by reciprocal regulatory processes during normal development, but may fail to develop in the absence of an adequate level of stimulation.

A comparison of manual and MEDLARS reviews of the literature on consultation-liaison psychiatry.

A systematic manual search for articles related to consultation-liaison psychiatry was compared to a computerized search of the same journals during the same period that was done with the Medical Literature Analysis and Retrieval System (MEDLARS). More articles were located with the manual method (94%) than with MEDLARS (65%).