Oral montelukast versus inhaled beclomethasone in 6- to 11-year-old children with asthma: results of an open-label extension study evaluating long-term safety, satisfaction, and adherence with therapy.

This 6-month, open-label extension study of a previously described base study compared oral montelukast with inhaled beclomethasone in terms of safety, forced expiratory volume in one second (FEV1) measurements, parent and patient satisfaction with treatment, asthma-related medical resource utilization, school absenteeism, and parental work loss in children with asthma. A total of 124 of 266 asthmatic children, 6 to 11 years of age, who enrolled in the base study entered a 6-month open-label extension study (74 boys, 50 girls) and were re-randomized (2:1 ratio) to receive once-daily oral montelukast (n = 83) or inhaled beclomethasone 100 mcg three times daily (n = 41). Children were evaluated in the clinic prior to re-randomization (Month 0) and at regular visits at 1, 3, and 6 months. Children and their parents showed a significantly higher overall satisfaction for montelukast at 6 months than for inhaled beclomethasone (p = 0.001 and p < 0.05, respectively). According to parents, montelukast was more convenient (p < 0.001), less difficult to use (p = 0.005), and was used as instructed more of the time (p = 0.006) compared with beclomethasone. Oral corticosteroid use was similar in the montelukast (13% of patients) and beclomethasone (17%) treatment groups. The montelukast treatment group was more adherent with their regimen than the inhaled beclomethasone treatment group; almost twice as many children on montelukast compared with inhaled beclomethasone were highly compliant (82% versus 45%). The two study groups were similar with respect to overall safety, change in FEV1, asthma-related medical resource utilization, school absenteeism, and parental work loss. Montelukast represents a safe and effective asthma treatment regimen to which children with asthma are more likely to adhere.

Successful treatment of rheumatic chorea with carbamazepine.

Carbamazepine has been used successfully in the treatment of different movement disorders and was recently reported to be effective for nonhereditary chorea. In view of the significant side effects associated with the drugs currently used to treat chorea, we sought to further evaluate the efficacy of carbamazepine in children with rheumatic chorea. The study was prospective and included 10 children with chorea (eight females and two males; age range = 7-16 years) referred to our Pediatric Rheumatology Clinic between 1995 and 1999. Nine had rheumatic fever and one had antiphospholipid antibody syndrome that later evolved to systemic lupus erythematosus. All were treated with carbamazepine. Improvement was evident within 2-14 days of initiation of low doses of carbamazepine (4-10 mg/kg daily). The plasma drug levels were 2.8-8.2 microg/mL (therapeutic antiepileptic range = 8-12 microg/mL). The chorea disappeared within 2-12 weeks. The duration of treatment was 1-15 months. No side effects were observed. Recurrence was observed in three patients who received a second trial of carbamazepine with a good response. We suggest that carbamazepine may serve as a first-line treatment for rheumatic chorea.

Effect of naproxen, a prostaglandin inhibitor, on acute otitis media and persistence of middle ear effusion in children.

Prostaglandins are thought to be of importance in the pathophysiology of otitis media with effusion (OME), and the possibility of reducing the frequency and persistence of this condition by using prostaglandin inhibitors has been suggested. In a double blind manner, naproxen was administered to children with acute otitis media, in addition to amoxicillin, and its influence on the subsequent occurrence and persistence of middle ear effusion was evaluated. Eighty-one children participated in the study. No significant difference was found in the number of patients with tympanograms consistent with OME in the two groups. After 10 days of treatment, 63% in the naproxen and 58% in the placebo group, and after 30 days, 41% and 59%, respectively, had type B tympanograms. Similarly, there were no differences between the two groups with respect to other parameters studied (duration of otalgia, fever, otoscopic findings). No side effects related to naproxen were observed.

Arachidonic acid metabolites in middle ear effusions of children.

Middle ear effusions (MEEs) from 78 children (98 ears) with otitis media were examined for products of arachidonic acid (AA) metabolism, including leukotrienes B4, C4, D4, and E4 and prostaglandins D2 and E2, by high-performance liquid chromatography. Leukotrienes B4 and D4 were recovered most frequently: 59% and 54%, respectively. Leukotriene B4 was found in highest concentration, 1.29 +/- 3.46 ng/0.1 mL. The concentrations of leukotrienes B4 (p less than .03), (4 (p less than .01), and E4 (p less than .02) were significantly higher in culture-positive than in culture-negative MEEs. Neither the concentration nor the type of AA metabolite correlated with bacterial species isolated, chronicity of effusion, age of subject, or consistency of MEE. These data suggest that the AA metabolites are synthesized relatively frequently during otitis media of childhood. Leukotriene B4 is the most frequently detected AA metabolite in MEEs and is highly associated with the presence of viable bacteria.

Effectiveness of inhaled corticosteroids in controlling acute asthma exacerbations in children at home.

Many clinicians advise their patients to increase the dose of inhaled corticosteroids during acute asthma exacerbations, without strong clinical evidence supporting this treatment. This study investigates the effectiveness of inhaled corticosteroids in controlling acute asthma exacerbations in children at home. The study population consisted of children with mild intermittent, mild and moderate persistent asthma aged 1 to 14 years who were treated in our outpatient clinic with inhaled budesonide for 1 year. After participating in an asthma education session, the parents were instructed to initiate treatment with inhaled budesonide at the first signs of asthma exacerbation, starting with 200 to 400 microg budesonide, in combination with beta-2 agonists 4 times a day and followed by a decrease in the dose in 4 to 8 days. Asthma status and peak expiratory flow rates were measured in the 3 monthly follow-up visits. Only children who complied with the treatment regimen and came for follow-up visits regularly were included in the final analysis. One hundred fifty children used our treatment protocol with inhaled budesonide to control their asthma attacks. Clinical improvement of asthma symptoms was achieved after a mean of 1.8 +/- 0.7 days from the beginning of treatment. The parents were able to control 94% of the 1,061 episodes of asthma exacerbation occurring during a cumulative follow-up period of 239 years. In the 3-month period before enrollment, 101 children (67%) had used oral corticosteroids to control their asthma attacks and 50 (33%) were hospitalized. During the entire follow-up period, only 11 children (7%) used oral corticosteroids, and none of the children were hospitalized. The present study demonstrates that children with asthma can control their exacerbations at home using inhaled corticosteroids (budesonide). Treatment, starting with relatively high doses followed by a rapid reduction in dose over 4-8 days, resulted in a decrease in the use of oral steroids and in hospitalization. To achieve good results, patient compliance is essential.

Increased creatine kinase brain isoenzyme concentration in cerebrospinal fluid with meningitis.

CPK-BB (CK-BB) isoenzyme is an intracellular enzyme released in various neurologic conditions, including central nervous system (CNS) infections. Activity of CK-BB in cerebrospinal fluid (CSF) was determined in 80 children by electrophoresis and densitometry. The possible correlation between CNS infection and CK concentrations was assessed. Significantly elevated concentrations of CK activity (P < 0.01) in the CSF were found in children with bacterial meningitis as compared with children with either aseptic meningitis or normal CSF findings. The data suggest the possibility of utilizing CSF CK activity to differentiate between bacterial and viral meningitis in situations where a routine CSF examination is inconclusive.

[Sepsis, disseminated intravascular coagulation (DIC) and hematological aspects as an unusual manifestation of congenital syphilis].

Congenital syphilis is a systemic infectious disease affecting and damaging many organs. It can be treated simply and effectively by penicillin. Our patient presented with sepsis and DIC, which is a rare manifestation, and to our knowledge this is the first reported case at the age of six weeks. We also review the symptoms of the disease focusing on the hematological manifestations of early congenital syphilis, diagnosis and treatment.

Sulfisoxazole prophylaxis of middle ear effusion and recurrent acute otitis media.

The efficacy of sulfisoxazole prophylaxis was evaluated in 32 otitis-prone children in a double-blind cross-over clinical trial. During the sulfisoxazole therapy, seven patients (22%) had nine episodes of acute otitis media (AOM) while 20 patients (63%) receiving placebo had 36 episodes of AOM (P = .001). Although sulfisoxazole appeared to be beneficial in patients aged 2 to 5 years, statistically significant efficacy was noted only in children under 2 years of age. Otitis media with effusion persisting for more than five weeks was observed in ten children (31%) during sulfisoxazole therapy and in 14 children (44%) during the placebo period (P greater than .975). Sulfisoxazole therefore appears effective in preventing recurrent symptomatic AOM but not in reducing the frequency of persistent otitis media with effusion. The importance of careful follow-up of children receiving long-term sulfisoxazole therapy for prevention of recurrent AOM is stressed.

Infantile methemoglobinemia caused by food additives.

A small outbreak of toxic methemoglobinemia occurred among infants in a pediatric ward. Investigation revealed that the most likely source of toxicity was an approved fat preservative which had been added to a soybean infant formula by the manufacturer. This fat preservative contained three phenolic compounds having highly effective antioxygenic properties (butylated hydroxyanisole, butylated hydroxytoluene and propyl gallate). The outbreak ceased when the offending agents were eliminated from the food preparation. It is emphasized that the approval of chemicals for use in the food industry through toxicity studies does not necessarily guarantee against the hazards of toxicity, especially during infancy.

Induction of suppressor T cells in asthmatic children by theophylline treatment.

The absolute T-cell numbers and function, and the T-suppressor-cell subset were tested in eleven children with extrinsic asthma prior to and 1 month after theophylline treatment. Low mean T-suppressor-cell number and function was found in the asthmatic children, which returned to normal levels and function after 1 month of theophylline treatment. A normal mean T-cell number was found in this group of children prior to, and 1 month after, theophylline treatment. An obvious correlation between the clinical severity of the asthma and the number of T suppressor cells was found. It is suggested that theophylline most probably activated the T suppressor cells in the asthmatic children.

Complications of mumps requiring hospitalization in children.

UNLABELLED: During the years 1987-1988, an outbreak of mumps was reported among the paediatric population in Israel. Mumps immunization in Israel was not universal at that time and most of the population had not been immunized. During that period, 66 children with evidence of recent mumps parotitis with several complications, i.e. meningo-encephalitis, cerebellar ataxia, arthritis, orchitis, transverse myelitis, deafness and presternal oedema were treated in our department. All patients had recovered completely except one who had permanent hearing loss. CONCLUSION: This paper provides a reminder that mumps, while basically benign, has complications serious enough to lead to hospitalization without immunization.

Release of leukotriene C4 in respiratory tract during acute viral infection.

Groups of children with wheezing during respiratory illness, children without wheezing during respiratory illness, and appropriately matched healthy children were tested for the presence and concentration of leukotriene C4 (LTC4) in nasopharyngeal secretions, employing the techniques of reverse-phase high-pressure liquid chromatography and radioimmunoassay. Although most wheezing children had LTC4 in nasopharyngeal secretions, the concentration of LTC4 among wheezing children who shed respiratory viruses was found to be consistently elevated (mean 1520 +/- 228 pg/0.1 mL) compared with values in wheezing children without evidence of viral infection (mean 709 +/- 147 pg/0.1 mL). In sharp contrast, little or no LTC4 activity was detected in healthy children (mean 106 +/- 77 pg/0.1 mL). These observations suggest that respiratory viruses are stimuli for the release of mediators of inflammation such as LTC4. Thus development of virus-induced bronchospasm may be related in part to direct mucosal cell-virus interaction and the release of pharmacologically active mediators in the respiratory tract.

Efficacy and safety of ketotifen in young children with asthma.

Thirty children (aged 1 to 3 years) with mild to moderate asthma were entered into a 28-week double-blind, crossover study comparing the prophylactic effect of ketotifen and placebo. A patient daily diary card was used to document symptoms and concomitant medications taken during a 2-week baseline and subsequent 12-week drug/placebo period. This was followed by a 2-week washout and 12 more weeks of drug/placebo in a crossover design. Physician assessment was performed at the beginning, at the end of each period, and at 4-week intervals throughout the drug study. No significant difference was observed between ketotifen treatment and placebo treatment in any of the study parameters that were tested. A decrease in concomitant medication usage during the first treatment period with ketotifen was observed. The principle side effect of ketotifen therapy observed in this age group was weight gain. In contrast to studies in adults, no sedation was noted.

Modulation of T-cell subsets in asthmatic children by THF, a thymic hormone.

Induction of theophylline-sensitive T-suppressor cells with THF, a thymic hormone, resulted in elevation of the low levels of these lymphocytes in non-treated asthmatic children. Evaluation, however, by monoclonal OKT8 antibodies did not show changes in the levels of the OKT8+ cells after THF incubation. In the treated asthmatic children, normal levels of theophylline-sensitive T-suppressor cells as well as OKT8+ cells were found. These normal levels were not changed with THF after in vitro incubation.

Safety of 1 year of treatment with budesonide in young children with asthma.

Inhaled budesonide has been demonstrated to be effective and safe when it is used in the prophylaxis of severe asthma in adults and school-age children but has not been studied in younger patients with asthma. Sixteen children, aged 3 1/2 to 7 years, with severe asthma, were treated with budesonide aerosol, 200 micrograms daily, via a spacer for 1 year in an open study. One month after starting budesonide therapy, a significant decrease in the number of days with asthmatic symptomatology, mean symptom scores, use of concomitant antiasthmatic medications, and increase in the peak expiratory flow rates were observed compared with the 1 month run-in period. This improvement was maintained throughout the year with budesonide therapy. During the study period, the height and weight of the children were not significantly deviated from the expected, and their bone age advanced normally. Adrenal function, as evaluated by fasting 8 AM blood cortisol levels and after adrenocorticotropic hormone stimulation, demonstrated no adverse effects with budesonide therapy. The suspectibility to severe infections was low, as evidenced by infrequent use of antibiotics. We conclude that a 12-month administration of inhaled budesonide to preschool-age children is safe and efficient and can be useful in the management of severe asthma in this young age group.