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The management of acute asthma exacerbations in children remains controversial and the latest guidelines (Expert Panel Report [EPR]-3 2007 and the Global Initiative of Asthma 2008) leave several questions unanswered. This review summarizes the most up-to-date information on the practical prevention and control of asthma attacks in children, and describes the 20-year experience of a major tertiary asthma clinic with the administration of inhaled corticosteroids in this setting. The following subjects are discussed: the knowledge and skills required by the parents regarding asthma and its treatment, how to prevent or minimize exacerbations in asthmatic children, the drugs used in the treatment of exacerbations and their order of administration, and the steps to follow after discharge from the emergency department or after a severe asthma exacerbation. The efficacy of inhaled corticosteroids in the management of acute asthma exacerbations in children, both at home and in the emergency department, is discussed in detail. The goal of asthma-management programs is to arm parents with the skills and knowledge to prevent, detect and successfully control most exacerbations of asthma in children at home.

Objective: The role of inhaled corticosteroids in the treatment of acute asthma exacerbations in children is controversial. This study compared the effect of inhaled budesonide and inhaled fluticasone in controlling acute asthma exacerbations in young children at home., Methods: In a quasi-randomized crossover design, children aged 5 months to 5 years with severe recurrent asthma episodes were treated either with inhaled budesonide 200 mcg or inhaled fluticasone 125 mcg delivered with a similar spacer. At the onset of asthma exacerbations, 2 puffs of inhaled terbutaline followed by inhaled budesonide or fluticasone was administered using one of the following treatment protocols: 1 4-day protocol for a relatively mild exacerbation; 2 8-day protocol for exacerbations that were more severe or uncontrolled by the 4-day protocol; and 3 8-day protocol + azithromycin for exacerbations uncontrolled by the 8-day protocol or possibly associated with infection with atypical agents. Children were followed for 2 months after each exacerbation. Good response was defined as the absence of asthma symptoms for at least 2 weeks from completion of treatment., Results: One hundred children were recruited: 36 were treated with budesonide, 21 with fluticasone, and 44 with both on different occasions. The groups were similar for preliminary data. Good response was noted in 87% of the budesonide group, 85% of the fluticasone group, and 86% of the budesonide/fluticasone group. By protocol, rates of good response were 84%, 83%, and 94% for the 4-day, 8-day, and 8-day+azithromycin treatment protocols, respectively; corresponding symptom-free periods after treatment were 4.0, 4.9, and 4.3 weeks. None of the children received oral corticosteroids., Conclusion: Acute asthma exacerbations in young children can be effectively controlled at home with the use of high repetitive doses of inhaled budesonide or inhaled fluticasone, initially together with beta(2)-agonists, given at the beginning of the attack, for a period of 4-8 days.

The use of systemic corticosteroids, together with bronchodilators and oxygen therapy, has become established for the management of acute asthma. These agents are undoubtedly effective, but are also associated with problems such as metabolic adverse effects. Inhaled corticosteroids (ICS) offer potential benefit in the acute setting because they are delivered directly to the airways. They are also likely to reduce systemic exposure, which would lead in turn to reductions in rates of unwanted systemic effects. In order to evaluate the role of budesonide in the management of acute asthma exacerbations we conducted a review of the literature and critically evaluated the rationale for the use of ICS in general in this setting. Trials in adults and children requiring treatment for acute exacerbation of asthma have shown clinical and/or spirometric benefit for budesonide when delivered via nebulizer, dry powder inhaler, or aerosol in the emergency department, hospital and follow-up settings. The efficacy seems to benefit from high doses given repeatedly during the initial phase of an acute exacerbation. These acute effects are likely to be linked to the drug's distinctive pharmacokinetic and pharmacodynamic profile. The current evidence base revealed encouraging results regarding the efficacy of the ICS budesonide in patients with wheeze and acute worsening of asthma. Future studies should focus on the efficacy of these agents in more severe asthma worsenings.

The aim of the study was to determine if doxycycline causes tooth staining in young children. A dentist examined 31 randomized children who had been treated with doxycycline and 30 children who had not received doxycycline. Mean age of the children was 10.4 -/+ 2.1 years. Mean age at receipt of the first doxycycline treatment was 4.1 -/+ 1.6 years, and mean number of doxycycline courses was 2.0 -/+ 1.3. No tooth staining was detected by the dentist in any of the children in either group. These findings indicate that treatment with doxycycline in children aged 2 to 8 years is not associated with tooth staining.

Objective: Otitis externa (OE), also known as "swimmer's ear", is an inflammation or infection of the external auditory canal. Many risk factors have been identified, mainly excessive moisture in the canal from swimming., Study Design/methods: To study the leading risk factors of otitis externa. Eighty-seven children aged 3.5-12 years (mean 68+/-6.5 months) who were diagnosed with otitis externa from December 1999 to March 2001 were studied for age, sex, cerumen cleaning habits, signs and symptoms. Findings were compared to an age-matched control group of 90 children without otitis externa., Results: Sixty-one children (70.1%) in the study group had their ears cleaned with a cotton-tip applicator (Q-tip) during the 10 days preceding the diagnosis of otitis externa. In the control group, only 31 (34%) used applicators routinely during the 10 days prior to diagnosis (P<0.001). Other risk factors for otitis externa were swimming in a pool (34%), wax removal (5.8%) and ventilation tubes (1.1%)., Conclusions: Use of a cotton-tip applicator to clean the ear seems to be the leading cause of otitis externa in children and should be avoided.

Acute cerebellar ataxia is a relatively common neurologic disorder among children. Our aim was to characterize the clinical picture, etiology, and prognosis of acute cerebellar ataxia. The medical records of all children with a diagnosis of acute cerebellar ataxia hospitalized in our center and Hasharon Medical Center from 1990 to 2001 were reviewed. The diagnosis of acute cerebellar ataxia was based on the following criteria: acute onset of ataxia with or without nystagmus; absence of known genetic predisposing factors, such as familial degenerative disorders; and absence of drug intoxication, bacterial meningitis, and metabolic disorders. Thirty-nine children were identified; 54% were male; mean age at presentation was 4.8 +/- 3.8 years. All patients were observed for at least 1 year. A prodromal febrile illness was noted in 74.4%: varicella, 31%; mumps, 20%; nonspecific viral infection, 15.4%; mycoplasma, 5%; Epstein Barr virus, 3%. Latency from the prodromal illness to the onset of ataxia was 8.8 +/- 7.4 days. The most common associated neurologic findings were nystagmus and dysmetria. Full gait recovery took less than 2 weeks on average, and the longest duration of neurologic signs was 24 days (mumps-related). Acute cerebellar ataxia in childhood is a self-limited disease. The recovery was faster than that reported in previous publications and was complete in all children without any neurologic sequelae. Imaging studies are needed only in atypical presentation or if there is no spontaneous improvement after 1 to 2 weeks.

Introduction: There are no available data on the safety of recommended schedules for the initiation of treatment with budesonide inhalation suspension in children with recurrent wheezing episodes. We compared the safety of high and low starting dose of budesonide by measuring their effect on plasma cortisol concentration., Methods: A randomized double-blind, placebo-controlled design was used. Twenty-nine children ages 6 months to 3 years were divided into three groups: (1) high starting dose: 1 mg budesonide inhalation suspension twice daily followed by a stepwise decrease of 25% every second day for 8 days (n = 11); (2) low starting dose: 0.25 mg twice daily for 8 days (n = 11); (3) placebo (n = 7). The 8 AM (fasting) and 1-hour post-ACTH stimulation plasma cortisol concentrations were measured before and 10 days after initiation of budesonide treatment., Results: Before treatment and after 8-10 days of treatment, there was no significant difference in mean serum cortisol concentration in the high starting dose, low-dose and placebo groups, either at 8 AM or at 1 hour after ACTH stimulation., Conclusion: The administration of nebulized suspension of budesonide at a high starting dose (2 mg/day for 2 days) followed by a rapid stepwise decrease over 8 days was safe, causing similar changes in serum cortisol levels to low-dose budesonide suspension or placebo.

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.

Increased levels of lactic dehydrogenase (LDH) in cerebrospinal fluid (CSF) have been reported in association with several intracranial pathologies. We studied LDH isoenzymes in the CSF of children with infantile spasms. CSF samples collected from 12 patients (aged 4-9 months) with infantile spasms were analyzed for total LDH isoenzymes activity, and were compared to samples from 15 normal children. Mean total LDH activity in the CSF was 34.62 +/- 6.52 U/l. Patients with infantile spasms had a lower LDH-1 percentage and higher LDH-3 percentage; the differences from the control group were statistically significant (p < 0.01). LDH-4 and LDH-5 had similar values in both groups. Infantile spasm is apparently associated with a distinct LDH isoenzyme pattern in the CSF. More studies are needed to confirm the rise in LDH-2, LDH-3 and to determine the optimum time of analysis., (Copyright 2003 S. Karger AG, Basel)

Background: Neurologic impairment is not considered a clinical manifestation of diskitis in children and has seldom been associated with it in the medical literature., Objective: To describe neurologic findings and their implications in children with diskitis., Study Design: Retrospective medical records review of children discharged with a diagnosis of diskitis between January 1992 and December 2000. The study included children in whom the diagnosis was based on the presence of clinical findings, laboratory evidence of an inflammatory process, and findings on imaging studies compatible with diskitis., Results: Neurologic findings of decreased muscle strength or hyporeflexia in the lower extremities were found in 7 (41%) of 17 children who met the diagnostic criteria for diskitis. Five of the 7 underwent magnetic resonance imaging, 2 of whom demonstrated intraspinal inflammatory involvement., Conclusions: Neurologic impairment does not exclude the diagnosis of diskitis and may be a common manifestation of the disease in children. Nevertheless, when neurologic findings are present, advanced imaging studies are needed to exclude intraspinal involvement.

Fixed drug eruption (FDE) is manifested as localized, circumscribed, round or oval plaques that characteristically recur in the same site with each use of the offending drug. The drugs most commonly implicated are phenolphthalein, barbiturates, antibiotics, salicylates, contraceptives, and anticonvulsants. FDE can appear on different parts of the body. The sites of predilection are the lips, genitalia, and sacral area. There are no reports of large series of pediatric patients with FDE involving the genitalia. We describe 15 boys with genital FDE associated with several drugs. Their average age at diagnosis was 3.2+/-2.2 years (range 6 months-8 years). The clinical presentation usually consisted of swelling and erythema of the penis and/or scrotum associated with pruritus, restlessness, urinary retention, and painful micturation. The diagnosis was supported by clinical history. The causative drugs were identified and confirmed by a provocation test, resolution after the drug was stopped, and a positive migration inhibiting factor (MIF) test. Genital FDE in children is uncommon, but the drugs associated with this entity are in such widespread use in pediatric practice that its recognition may be important, especially considering its easy treatability.

Levels of lactic dehydrogenase (LDH) in the cerebrospinal fluid (CSF) have been used to evaluate a variety of neurologic disorders. However, few studies have been performed on neonates. CSF samples were collected from 39 neonates, 19 aged 1-4 weeks and 20 aged 5-8 weeks with neonatal fever. Findings were compared to those in 15 infants mean age 10 +/- 6.4 months with suspected nervous system disease and normal CSF findings. Mean total LDH activity in the CSF was significantly higher in the first month of life than in the second month of life and compared with the control group (p <0.001). The LDH isoenzyme pattern was also different, with lower values of LDH-1 than LDH-2 and -3 in the study groups. Differences were significant among all three groups for LDH-1 (p <0.001) and between the whole study group and the controls for LDH-2 and -3 (p <0.001). We propose reference values for total LDH activity and LDH isoenzyme distribution in the CSF of normal neonates.

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.

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.

We performed a retrospective analysis of all patients admitted to our institution with a diagnosis of infantile hypertrophic pyloric stenosis (IHPS) during a 10-year period from 1985-95 in order to assess the possible association between IHPS and urinary tract infections (UTIs). All 285 patients with IHPS had radiological or ultrasonographic confirmation of that diagnosis and underwent the Ramstedt procedure. Those who continued to be symptomatic were evaluated for UTI by urine analysis and culture. Positive cases were further evaluated for urinary system anomalies. The male:female ratio of IHPS was 3.4:1. Concomitant UTI was diagnosed in 8 patients by suprapubic aspiration or bladder catheterization. The prevalence of UTI in this series was 2.8%, 20-fold higher than the expected prevalence. Three of the 8 patients with UTI (37.5%) had urinary tract anomalies. These findings suggest an association between IHPS and UTI. We recommend that all IHPS patients be evaluated for UTI and positive cases undergo further evaluation for urinary anomalies.

Background: There are no data currently available on the correct schedule for the initiation of treatment with nebulized suspension of budesonide in children with recurrent wheezing episodes. We compared the efficacy and safety of starting with a high dose followed by a stepwise decrease to a continuous low dose., Methods: In a double-blind design, 42 children aged 6 months to 3 years were randomly allocated to receive either a high starting dose of 1 mg budesonide twice daily followed by a stepwise decrease of 25% every second day for 1 week (group A) or a low dose of 0.25 mg twice daily for 1 week (group B). Efficacy was assessed with daily symptom scores and the systemic effect of the corticosteroids with the adrenocorticotropic hormone test., Results: The two groups were comparable for all parameters evaluated. During the first week of treatment, there was a significant decrease in asthmatic symptomatology only in group A: a 59% decrease for wheezing (p = 0.0001), 39% for diurnal cough (p = 0.036), and 39% for nocturnal cough (p = 0.04). Mean time to clinical response was 3.0 days in group A and 5.7 days in group B (p = 0.02). This early improvement was sustained for the rest of the follow-up period. The high dose starting schedule was not associated with any change in serum cortisol level., Conclusions: The administration of nebulized suspension of budesonide at a high starting dose schedule followed by a rapid (1 week) stepwise decrease yields a significant early improvement in asthma symptoms and causes no change in serum cortisol levels.

Corticosteroids are known to affect the number and function of circulating lymphocytes in humans. The effect of 2 years administration of inhaled budesonide (200 micrograms/day) on the number and function of B and T lymphocytes and T cell subsets was evaluated in 16 young children with severe asthma. The number of T and B cells and T suppressor/cytotoxic cells (CD8 T cell) and T helper/inducer cells (CD4 T cell) before therapy was found to be comparable to the number of cells observed in the healthy control group. Two years administration of inhaled budesonide did not significantly alter the percentage and absolute number of all these cells. The functional activity of T lymphocytes was evaluated by the "local xenogeneic graft versus host reaction" (GVHR). A positive (normal) GVHR was observed in only 5 of the 16 children (31%) in the budesonide group before therapy, compared to 15 of 16 children (94%) in the healthy control group. During the 2 years treatment with inhaled budesonide, the percentage of patients having positive GVHR increased from 31% before therapy to 69% and 77% after 1 and 2 years of therapy (P = 0.05 and 0.02), respectively. The data observed in this study indicate that 2 years administration of inhaled budesonide did not alter the number of B and T lymphocytes and T cell subsets. However, it was associated with improvement in the GVHR function of T cells.

Administration of theophylline to asthmatic children is frequently associated with an adverse influence on their behavior. The efficacy and behavioral effects of the administration of high-dose theophylline (T) and ketotifen (K) in various combinations were evaluated prospectively in a double-blind, placebo controlled study in 55 children with moderately severe perennial asthma. During a baseline period of 2 weeks, theophylline (serum level of 10-20 micrograms/ml) was administered to all the children. After this period the patients were randomly allocated into four comparable groups. The children were treated during a 12-week period with: T+K-Placebo (T group); T+K (T+K group); half-dose T+K (T/2 + K group); or placebo of both T and K (P group). During the 12-week treatment period, as compared to the baseline period, only the three groups of children who received active therapy (T+P, T+K, T/2 + K) showed a similar reduction in the number of days with asthmatic symptomatology, improvement of the total asthmatic symptoms score, and increased PEFR. The behavioral activity of the children (assessed by the Conner's rating scale) improved significantly only in the groups receiving placebo or T/2 + K. The results of this study suggest that a combination therapy of half the recommended therapeutic dose of theophylline with ketotifen can be clinically as effective as therapy with a full dose of theophylline, but with significantly less adverse behavioral effects.

We compared the effect of haematopoietic growth factors granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1, IL-3, and IL-5 on the functional activation of human eosinophils and neutrophils from the same donor. All four colony-stimulating factors (CSF) enhanced the phagocytosis of Candida albicans by eosinophils and increased staphylococcal, but not Candida, killing. GM-CSF and IL-5 had a profound stimulating effect on eosinophil staphylocidal activity. GM-CSF and IL-3 enhanced the generation of leukotriene C4 (LTC4) induced by calcium ionophore A23187 and the release of arylsulphatase and beta-glucuronidase from specific and small granules of eosinophils. In contrast, IL-1 and IL-5 had no effect on degranulation. GM-CSF and IL-1 enhanced phagocytosis of C. albicans by neutrophils, and GM-CSF stimulated degranulation and the release of the enzymes beta-glucuronidase and arylsulphatase from neutrophils while IL-1 stimulated the release of arylsulphatase only. This study indicates that the eosinophil-active colony-stimulating factors can markedly enhance the host defence function of the eosinophil and even make it the equal of the neutrophil in staphylocidal activity. The CSF-activated eosinophil, however, may cause inappropriate inflammation and normal tissue damage.

Segmental antigen bronchoprovocation was used to define the nature of the inflammatory process in allergic airway disease. Bronchoalveolar lavage fluid obtained from allergic rhinitis patients 12 min after segmental antigen instillation (immediate response) revealed a significant increase in histamine and tryptase, but no cellular response. Repeat segmental lavage 48 h later (late response) showed marked and significant increases in both low and normal density eosinophils as well as striking elevations of eosinophil granular protein levels (major basic protein, eosinophil-derived neurotoxin, eosinophil cationic protein, and eosinophil peroxidase). Leukotriene C4, but not tryptase, concentrations were also consistently elevated in late lavage samples. Further, the late lavage samples showed a significant increase in interleukin-5 concentrations that correlated with the presence of eosinophils and eosinophil granular proteins. Neither eosinophils nor soluble mediators of eosinophils increased when normal subjects were similarly challenged with antigen. These data suggest that eosinophils are attracted to the airway during the late-phase allergic reaction and that IL-5 may produce changes in airway eosinophil density and promote the release of granular proteins to cause airway injury.

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.

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.

The role of upper respiratory allergy in the pathogenesis of otitis media with effusion (OME) is an interesting but still unresolved issue. In order to investigate this further, fifteen children with ragweed hayfever were studied for the development of eustachian tube obstruction (ETO), utilizing the nine-step pressure-swallow test, prior to, during, and after seasonal exposure to ragweed pollen. Daily symptom-medication diaries were maintained and serial physical examinations were performed. ETO was found in 60% of the ragweed sensitive children during natural pollen exposure. The development of ETO was found to correlate with ragweed skin test wheal size and daily patient symptom-medication scores (SMS) during pollen exposure. Treatment of hayfever symptoms with pseudoephedrine and/or chlorpheniramine did not prevent most patients from developing ETO. Despite the prevalence of ETO in the study group, only one child developed evidence of middle ear effusion. These findings suggest that children with ragweed hayfever develop eustachian tube (ET) dysfunction during natural pollen exposure. Seasonal allergy induced ETO is not, however, by itself sufficient to produce middle ear effusion.

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.

Samples of nasopharyngeal secretions from a group of 73 infants with bronchiolitis or upper respiratory illness alone during infection with respiratory syncytial virus were analyzed for leukotriene C4 (LTC4) content using a reverse-phase high-pressure liquid chromatography assay with confirmation by radioimmunoassay. Titers of respiratory syncytial virus (RSV)-specific IgE in nasopharyngeal secretion (NPS) specimens were determined using an enzyme-linked immunosorbent assay. The highest concentrations of LTC4 were found in the first 3 to 8 days after the onset of illness, and LTC4 was detectable in progressively lower concentrations in samples obtained up to 28 days after the onset of illness. LTC4 was detected in samples of NPS obtained in the acute phase of illness from 67% of infants with bronchiolitis due to RSV and in 33% of samples of NPS obtained during the same interval from infants with upper respiratory illness alone (p less than 0.025). Concentrations of LTC4 in children with bronchiolitis were 5-fold higher (1271 pg/ml) than the mean concentration of LTC4 in children with upper respiratory illness (224 pg/ml, p less than 0.02). LTC4 was detected in 83% of the children developing an RSV-IgE response and in 24% of subjects not developing an RSV-IgE response (p less than 0.001). Quantities of LTC4 measured in NPS were directly correlated with the magnitude of the RSV-IgE response in secretions (r = 0.33, p less than 0.02). These studies lend support to previous investigations suggesting that severe bronchiolitis due to RSV results from IgE-mediated hypersensitivity reactions to viral antigens, with release of chemical mediators of airway obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Twenty-two children aged 1 to 5 years with history of recurrent upper respiratory infections (URI) were investigated in a double blind cross over clinical study. After a three week observation period, patients received, at random, over two alternating periods of six weeks each, either 2 ml placebo (water) or 1% sodium cromoglycate (SC) solution t.i.d. by means of a home nebulizer. A significant decline in the number of illness days during both the nebulization periods as compared to the pretreatment period was observed (a mean percentage of days of 13.7 and 36.1 respectively, p less than 0.001). Both types of nebulization were equally efficient in reducing URI morbidity. The present study indicates that humidification may have some beneficial effect on reducing the recurrence rate of URI. Sodium cromoglycate was not superior to water for this purpose.

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.

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.

With high-pressure liquid chromatography and specific radioimmunoassay, the concentration of leukotriene C4 (LTC4) was measured in nasopharyngeal secretions (NPS) of groups of children with allergic rhinitis before, during, and after the ragweed-pollen season. Increase LTC4 concentrations in NPS were noted in all the children during the pollen season; the concentration of LTC4 increased from a preseasoned mean of 1.87 +/- 0.43 ng/ml to 5.52 +/- 0.7 ng/ml at the peak of the ragweed season (p less than 0.001). The mean LTC4 concentration 2 weeks after the end of the ragweed season declined only to about 4.45 +/- 1.04 ng/ml. The seasonal variation of LTC4 concentrations and symptom scores of the children paralleled the pattern of the ragweed-pollen count. All children studied were ragweed sensitive, and six children were additionally sensitive to Alternaria (mold). The mold-sensitive children demonstrated higher concentrations of LTC4 in their NPS before and continued to have high LTC4 levels after the peak ragweed season, coinciding with peaks of mold-spore counts. Data presented in this study suggest that mast cells and other target cells in the nasal mucosa of children with allergic rhinitis produce pharmacologically active mediators, such as LTC4, during natural exposure to ragweed or Alternaria.

Secretions from the nose and nasopharynx (NPS) are more readily accessible than tracheobronchial secretions (TBS) for clinical investigations, but it is unclear whether changes in mediator release in the nasopharynx reflect similar changes in the tracheobronchial tree. In order to clarify this question, NPS and TBS were taken from 20 children with tracheotomy and tested for the presence of leukotriene C4 (LTC4) and uteroglobin-like protein (UTG-LP). LTC4 and UTG-LP were measured both when the children were healthy and when they had clinical evidence of an acute respiratory tract illness. The mean concentration of LTC4 in NPS and TBS increased during illness although the mean concentration in NPS was significantly higher than in TBS during respiratory illness. In healthy children UTG-LP was detected only in TBS. During acute respiratory illness the concentration of UTG-LP in TBS decreased but remained significantly higher than in NPS. Data presented in this study indicate that changes in the LTC4 concentration in NPS appear to reflect changes in LTC4 concentration in TBS although the levels of LTC4 in NPS were significantly higher than in TBS. An inverse correlation between the concentrations of LTC4 and UTG-LP in NPS and TBS was demonstrated.