Effect of inhaled indomethacin on exercise-induced bronchoconstriction in children with asthma

We evaluated the effect of inhaled indomethacin, a nonsteroidal antiinflammatory drug (NSAID), on exercise-induced bronchoconstriction (EIB) in children with asthma. Nine asthmatic children (7 boys, 2 girls, with a mean +/- SEM age of 11.0 +/- 0.8 yr) with a history of EIB participated in this study. These subjects were pretreated with inhaled indomethacin (3 mg/m2 body surface area [BSA]) or placebo (0.9% saline) according to a double-blind, randomized, crossover design, and underwent an exercise challenge test 15 min after the pretreatment. Inhaled indomethacin significantly attenuated EIB. The mean maximal percent decrease in FEV1 following exercise was 36.1 +/- 5.7% after placebo and 18.0 +/- 4.6% after indomethacin pretreatment (p = 0.0310). Indomethacin also significantly reduced the mean maximal decrease in arterial oxygen saturation after exercise (p = 0.0378). The inhibition of local prostaglandin synthesis and/or ion transport in the airways may be a mechanism involved in the protective potency of inhaled indomethacin.     

Benefits and risks of inhaled glucocorticoids in children with persistent asthma

In children, an inhaled glucocorticoid is currently the medication of choice for the long-term control of persistent asthma. Inhaled glucocorticoids are significantly more effective than nonsteroidal medications on all outcome measures of asthma treatment. They reduce the frequency of symptoms and of acute asthma exacerbations, decrease the need for "rescue" medications, improve airway patency, and reduce airway hyperresponsiveness. These considerable long-term benefits are worth the minimal risks of clinically significant local or systemic adverse effects. An inhaled glucocorticoid should be used in the lowest dose that prevents symptoms and eliminates the need for supplemental courses of ingested glucocorticoids. Pulmonary function and height velocity of children receiving an inhaled glucocorticoid should be monitored at regular intervals.     

Early use of inhaled steroids in children with asthma. Concluding comments

OBJECTIVE: To describe a rare case of right renal agenesia and left pelvic ectopy. To our knowledge, only 10 such cases have been reported in the world literature. METHODS: A 76-year-old male patient who consulted for irritative prostatic syndrome is described. Patient evaluation included IVP and CT. RESULTS: IVP revealed the absence of the right kidney in addition to an anomalous position of the left kidney. The foregoing findings were confirmed by CT. CONCLUSION: This uncommon congenital anomaly is essentially asymptomatic and is generally diagnosed in infants through its complications. In the case described herein, however, this anomaly had been incidentally detected during IVP and CT assessment of a 76-year-old patient who had consulted for irritative prostatic syndrome.     

Overnight protection by inhaled salmeterol on exercise-induced asthma in children

The main aim of the present study was to evaluate whether inhaled salmeterol given in the evening protected against exercise-induced asthma the next morning. Twenty three children (12 males and 11 females) with a mean age of 11 yrs and with exercise-induced asthma participated in a double-blind, randomized, placebo-controlled study. The children inhaled salmeterol 25 micrograms, salmeterol 50 micrograms and placebo by Diskhaler at 10 p.m. on 3 separate days. Next morning, half of the children ran on a motor-driven treadmill for 6 min at submaximal load at 8 a.m. and the remainder at 10 a.m. Lung function was measured by maximal expiratory flow-volume loops before running, immediately after, and 3, 6, 10 and 15 min after running. The mean maximum reduction in forced expiratory volume in one second (FEV1) after treadmill run was 34% before inclusion in the study. Mean maximum fall in FEV1 was significantly greater after placebo: 30% (23-36) 95% confidence interval) than after salmeterol 25 micrograms: 19% (12-23) or salmeterol 50 micrograms: 18% (12-25). In addition to the reduced postexercise bronchoconstriction, pre-exercise lung function (FEV1) was significantly higher both after salmeterol 25 micrograms: 2.4 L.s-1 (2.1-2.7) and salmeterol 50 micrograms: 2.5 L.s-1 (2.2-2.8) than after placebo: 2.2 L.s-1 (1.9-2.5). No significant differences in pre- and postexercise lung function were found between children tested at 8 or 10 a.m., or in relation to salmeterol dosage. Thus, inhaled salmeterol 25 and 50 micrograms offered similar overnight protection against exercise-induced asthma and improved baseline lung function in the morning as compared to placebo.     

Compliance with medication regimens for mental and physical disorders

Although the central nervous system (CNS) is often regarded as an immunologically privileged site, it is well established that specific CNS immunoreactivity can be generated through peripheral vaccination with CNS antigens. Dendritic cells (DC) are potent antigen presenting cells of hematopoietic origin that have emerged as a promising tool for cancer immunotherapy capable of evoking significant anti-tumor immunity when pulsed with tumor-associated peptides. To explore a role for DC-based immunization strategies for the treatment of CNS tumors, we developed a brain tumor model using the C3 sarcoma cell line which expresses the tumor-specific, major histocompatibility complex (MHC) class I-restricted peptide epitope E7(49-57). Syngeneic C57Bl/6 mice receiving intravenous (i.v.) injections of bone marrow-derived DCs pulsed with E7 peptide were effectively protected against a subsequent intracerebral challenge with C3 tumor cells. More importantly, this systemic immunization strategy was effective in a therapy model as 67% of animals (10 of 15) with established (day 7) intracerebral C3 tumors treated with 3 weekly injections of E7 peptide-pulsed DCs achieved a long-term survival (>90 days) while no control animals survived beyond day 41. In vivo depletion of CD8+ cells, but not CD4+ or asialo-GM1+ cells, abrogated the efficacy of E7 peptide-pulsed DC therapy of established tumors, indicating a pivotal role of specific CD8+ T-cell responses in mediating the anti-tumor effect. Our findings support the hypothesis that effective CNS anti-tumor immunoreactivity can be generated with DC-based tumor vaccines.     

Posterior subcapsular cataracts, bruises and hoarseness in children with asthma receiving long-term treatment with inhaled budesonide

To study isoform-specific effects of apolipoprotein E (apoE) in vivo, we generated mice with a human APOE*2 allele in place of the mouse Apoe gene via targeted gene replacement in embryonic stem cells. Mice expressing human apoE2 (2/2) have virtually all the characteristics of type III hyperlipoproteinemia. Their plasma cholesterol and triglyceride levels are both twice to three times those in (normolipidemic) mice that are expressing human apoE3 (3/3) made in an identical manner. The 2/2 mice are markedly defective in clearing beta-migrating VLDL particles, and spontaneously develop atherosclerotic plaques, even on a regular diet. An atherogenic diet, high in fat and cholesterol, exacerbates development of atherosclerosis and xanthomas in the 2/2 mice. Thus, comparisons between the 2/2 and 3/3 mice unequivocally demonstrate that a single amino acid difference (Arg158 Cys) in the apoE protein is sufficient to cause type III HLP and spontaneous atherosclerosis in mice.     

Changes in neurokinin A airway responsiveness with inhaled lysine-acetylsalicylate in asthma

Endogenously released cyclooxygenase products modulate the bronchoconstrictor response to various stimuli in asthma. Little is known of the change in airway responsiveness to neurokinin A (NKA) after cyclooxygenase blockade. In this randomized, double-blind, placebo-controlled study, we have investigated the effect of the potent cyclooxygenase inhibitor, lysine acetylsalicylate (L-ASA) administered by inhalation, on the bronchoconstrictor response both to neurokinin A (NKA) and methacholine in nine asthmatic subjects. Subjects attended the laboratory on four separate occasions to receive nebulized L-ASA (solution of 90 mg.mL-1) or matched placebo (glycine, solution of 30 mg.mL-1) 15 min prior to bronchial challenge with NKA or methacholine, in a randomized, double-blind order. Changes in airway calibre were followed as forced expiratory volume in one second (FEV1) and agonist responsiveness, expressed as the provocative concentration causing a 20% fall in FEV1 from baseline (PC20). L-ASA elicited a significant fall in FEV1 from baseline. When compared with placebo, inhaled L-ASA reduced the airway responsiveness to NKA in 8 of the 9 subjects studied, the geometric mean (range) values for PC20 NKA increasing significantly from 153.2 (52.0-258.9) to 303.1 (83.4-668.5) micrograms.mL-1 after placebo and L-ASA, respectively. However, no significant change in airway responsiveness to methacholine was recorded after L-ASA, their geometric mean (range) PC20 values being 1.60 (0.17-9.59) and 1.53 (0.09-14.01) mg.mL-1 after placebo and L-ASA, respectively. The small decrease in airway responsiveness to neurokinin A after administration of lysine acetylsalicylate by inhalation suggests that endogenous prostaglandins may play a contributory protective role in the airway response to neurokinin A in human asthma.     

Clinical efficacy of low-dose inhaled budesonide once or twice daily in children with mild asthma not previously treated with steroids

The aim of the present study was to examine the efficacy of low-dose inhaled budesonide (BUD) administered via Turbuhaler once or twice daily on symptoms, lung function and bronchial hyperreactivity in children with mild asthma. One hundred and sixty-three children (mean age 9.9 yrs, 56 females/107 males) with mild asthma (forced expiratory volume in one second (FEV1) 103% of predicted, morning peak expiratory flow (PEF) 87% pred, reversibility in FEV1 3%, fall in FEV1 after exercise 10.4% from pre-exercise value) and not previously treated with inhaled steroids, were included in a double-blind, randomized, parallel-group study. After a two-week run-in period, the children received inhaled BUD 100 microg or 200 microg once daily in the morning, 100 microg twice daily or placebo for 12 weeks. Exercise and methacholine challenges were performed before and at the end of treatment. After 12 weeks of therapy, the fall in FEV1 after an exercise test was significantly less in all three BUD groups (43-5.1%) than in the placebo group (8.6%). Bronchial hyperreactivity to methacholine with the provocative dose causing a 20% fall in FEV1 decreased significantly in the BUD 100 microg twice-daily group compared with placebo (ratio at the end of treatment 156%). Changes in baseline lung function (FEV1 and PEF) were less marked than changes in bronchial responsiveness. In conclusion, low doses of inhaled budesonide, given once or twice daily, provided protection against exercise-induced bronchoconstriction in children with mild asthma and near normal lung function.     

Epidemiological study of wheeze, doctor diagnosed asthma, and cough in preschool children in Leicestershire

OBJECTIVE: To determine the cumulative prevalences of wheeze and doctor diagnosed asthma and the point prevalences of recurrent cough and wheeze in children aged 5 years and under. DESIGN: Questionnaire survey of population based random sample of children registered on regional authority's child health index for immunisation; questionnaire completed by parents. SETTING: Leicestershire. SUBJECTS: 1650 white children born in 1985-9 who were surveyed in 1990. MAIN OUTCOME MEASURES: Cumulative prevalences of wheeze and doctor diagnosed asthma and point prevalences of recurrent cough and wheeze by age and sex. RESULTS: There were 1422 replies (86.2%; 726 for boys, 696 for girls). Overall, 11.0% (95% confidence interval 9.4% to 12.6%) of children had formally been diagnosed as having asthma, the cumulative prevalence in boys (12.7%) being somewhat higher than in girls (9.2%) (age adjusted odds ratio 1.47, p = 0.03). As expected, the cumulative prevalence of asthma increased significantly with age (7.5% (13/173) in children under 1 year, 15.9% (61/383) in children of 4 years and over; p < 0.001). The cumulative prevalence of wheeze overall was 15.6% (13.7% to 17.5%), being higher in boys (17.6%) than in girls (13.5%) (odds ratio 1.38, p = 0.03). The overall prevalence of recurrent cough without colds was 21.8% (19.6% to 23.9%), with a non-significant excess in boys (23.1% v 20.4%). The overall prevalence of wheezing attacks during the previous 12 months was 13.0% (11.3% to 14.8%) with a non-significant excess in boys (14.5% v 11.5%). CONCLUSIONS: These findings are baseline results and emphasise the importance of studying the age group of interest rather than relying on the recall of parents of school age children.     

Inhalation of sodium cromoglycate through a spacer device: no effect on symptoms in preschool children with moderate asthma

Recently a randomised placebo controlled trial in a general practice setting showed that inhaler therapy with a spacer device in 218 1-4 year old children with moderate asthma is feasible, but that treatment with cromoglycate was no more effective than placebo. The lack of benefit from the treatment with cromoglycate may have resulted from several points discussed and refuted in this commentary. Major points are the degree of asthma of the children and uncertainty about the amount of medication that reached the lungs. The results of the trial support the intentions of national and international guidelines to withdraw the recommendation of cromoglycate as the first choice in prophylactic asthma treatment.     

Evidence-based family-school interventions with preschool children.

Fifteen studies of family-school interventions with preschool children conducted between 1980 and 2002, and published in peer-reviewed journals, were reviewed and evaluated according to the criteria developed by the Task Force on Evidence-Based Intervention in School Psychology (Division 16 and Society for the Study of School Psychology Task Force, 2003). Results indicate that family-school interventions with preschool children have taken many forms, have targeted a variety of problems and behaviors, and have generally shown positive effects. Efficacious interventions included parent and teacher training, parent education, and behavioral family therapy. Recommendations for future research include increased methodological rigor, replication and extension of current studies, and the completion of longer-term, follow-up investigations to determine whether gains that are made post-treatment are maintained over time. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Epidural emphysema in children with asthma

Arrythmogenic right ventricular dysplasia (ARVD) is an autosomal dominant inherited cardiomyopathy with incomplete penetrance and variable expressivity. Recently, the gene was mapped to 14q23-24. It is being increasingly investigated as a major cause of sudden death at a young age. Anterior polar cataract (APC) is a rare hereditary form of lens opacity. The locus for an APC gene was located tentatively on 14q24qter. We describe a patient with a severe form of ARVD in whom asymptomatic APC was detected by an ophthalmologic examination. His sister had ARVD and similar cataracts. Parents were second cousins but were healthy. This is the first report of possible autosomal recessive inheritance of ARVD. This is also the first time that the combination of ARVD and APC is reported. Three possibilities may explain this concurrence: pleiotropy, contiguous gene syndrome, or coincidence. Our findings suggest placement of an APC gene at 14q23-24.     

Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma

The anti-asthmatic effects of theophylline may supplement those of inhaled steroids in asthma. The aim of the present trial was to study how the addition of theophylline compares to doubling the dose of inhaled steroid in asthmatics who remain symptomatic on beclomethasone dipropionate (BDP) 400 microg x day(-1). The trial was designed as a randomized, double-blind, parallel-group study in several European countries. Sixty nine patients were treated for 6 weeks with theophylline plus BDP 400 microg x day(-1), compared to 64 patients treated with BDP 800 micro x day(-1). The mean+/-SD serum theophylline concentration was 10.1+/-4.2 mg x L(-1). Lung function measurements were made throughout the study and patients kept daily records of peak expiratory flow (PEF), symptoms and salbutamol usage. Forced expiratory volume in one second and PEF at week 6 were significantly increased by both treatments (p<0.01). PEF variability was reduced by about 30% in both groups. There were significant improvements in asthma symptoms and rescue medication use (p<0.001). There were no significant differences between the treatment groups. The study demonstrated clinical equivalence of theophylline plus beclomethasone dipropionate 400 microg x day(-1) and beclomethasone dipropionate 800 microg x day(-1) in patients whose asthma is not controlled on beclomethasone dipropionate 400 microg x day(-1). The results support the use of theophylline as a steroid-sparing agent. The combination of low-dose inhaled steroid plus theophylline is a suitable treatment for moderate asthma.     

Comparison of addition of theophylline to inhaled steroid with doubling of the dose of inhaled steroid in asthma

The anti-asthmatic effect of theophylline may supplement those of inhaled steroids in asthma. The aim of the present trial was to study how the addition of theophylline compares to doubling the dose of inhaled steroid in asthmatics who remain symptomatic on beclomethasone dipropionate (BDP) 400 micrograms/day. The trial was designed as a randomized, double-blind, parallel-group study in several European countries. 69 patients were treated for 6 weeks with theophylline plus BDP 400 micrograms/day, compared to 64 patients treated with BDP 800 micrograms/day. The mean +/- SD serum theophylline concentration was 10.1 +/- 4.2 mg/l. Lung function measurements were made throughout the study and patients kept daily records of peak expiratory flow rate (PEF), symptoms and salbutamol usage. Forced expiratory volume in one second and PEF at week 6 were significantly increased by both treatments (p < 0.01). PEF variability was reduced by about 30% in both groups. There were significant improvements in asthma symptoms and rescue medication use (p < 0.001). There were no significant differences between the treatment groups. The study demonstrated clinical equivalence of theophylline plus beclomethasone dipropionate 400 micrograms/day and beclomethasone dipropionate 800 micrograms/day in patients whose asthma is not controlled on beclomethasone dipropionate 400 micrograms/d. The results support the use of theophylline as steroid-sparing agent. The combination of low-dose inhaled steroid plus theophylline is a suitable treatment for moderate asthma.     

Audiological treatment of preschool children with hearing impairments

A system by which children with impaired hearing are given early audiological treatment is reported. The treatment has been carried out during short admissions to institution alternating with stays at home. Special training and instruction of the parents are important. The authors are of the opinion that this type of preschool training is suitable for regions with scattered population. Even a small institution with a limited staff can give treatment to a considerable number of children.