Terbutaline controlled-release tablets and ipratropium aerosol in nocturnal asthma

The effect of oral terbutaline (controlled-release [CR] tablets) was compared with that of inhaled ipratropium bromide (aerosol) in 21 patients with nocturnal asthma. In a randomized, double-blind, crossover study, 40 μg four times daily, and the two drugs in combination. Each treatment was given for 3 weeks. Before the start of the study, the patients participated in a 1-week run-in period. The mean nocturnal decline in peak expiratory flow rate (PEFR) was 29% in the run-in period and was reduced to 22% in the terbutaline CR period, 27% in the ipratropium period, and 23% in the period with the combination of the two drugs. The mean night PEFR was significantly ( P <0.05) higher in the period with terbutaline CR, as compared with the period with ipratropium. The mean morning PEFR was also highest in the terbutaline CR period. The mean evening PEFR was significantly ( P < 0.05) higher during treatment with terbutaline CR alone or the combination was preferred by as many patients as was treatment with ipratropium alone. When present, adverse reactions were to be milk or moderate.
Treatment with terbutaline CR alone and the combination significantly improved the evening and night PEFR, as compared with ipratropium alone.     

Slight steroid-sparing effect of intravenous immunoglobulin in children and adolescents with moderately severe bronchial asthma

Jakobsson T, Croner S, Kjellman N-IM, Pettersson A, Vassella C, Björkstén B. Slight steroid-sparing effect of intravenous immunoglobulin in children and adolescents with moderately severe bronchial asthma. Twenty subjects (aged 6-20 years) with moderately severe bronchial asthma participated in an open controlled trial with intravenous immunoglobulin (IVIG) given as five monthly infusions with a mean dose of 0.8 g/kg body weight. A follow-up was performed 4 and 14 months after the treatment period. Nine of 14 children in the treatment group completed the trial. Two children experienced severe headache after the first infusion, another two patients were taken off the study for reasons unrelated to the IVIG therapy, and one patient dropped out from lack of motivation. In six of the IVIG-treated children, there was a reduction in the daily intake of inhaled steroids at an unchanged or reduced histamine reactivity. Of the remaining three children, two showed a reduction in bronchial hyperreactivity, but their steroid dose was not reduced. Six patients participated in a reference group to determine seasonal variations of symptoms. One of them improved during the study period, and the condition of the other five deteriorated, as indicated by increased medication without reduced histamine reactivity. After 14 months, there were no significant differences in clinical symptoms, nor in sensitivity to histamine between the treated patients and the controls, as the condition had improved also in the latter. We have thus been able to confirm, in a group larger than those in previously published reports, some clinical improvement of asthma by IVIG therapy at a lower dose than previously used and in children with only moderately severe disease. The effect was still present 4 months after the termination of IVIG therapy but not after 14 months. As the effects were small and temporary and the treatment is complicated and expensive, IVIG therapy cannot at present be recommended for general use. A double-blind, placebo-controlled study of the effect of IVIG in asthma is needed.     

Double-blind evaluation of effectiveness and safety of flunisolide aerosol for treatment of bronchial asthma in children

A double-blind study was carried out in 20 asthmatic children in order to evaluate the therapeutic efficacy and safety of inhaled corticosteroid flunisolide. 0.5 mg of the drug was administered by a jet nebulizer twice daily for 2 months. Respiratory symptoms, pulmonary function values and methacholine PC20-FEV1 were evaluated, as also morning cortisol levels, plasma cortisol increase after ACTH test, and 24-h urinary cortisol excretion. The data obtained show the efficacy of the drug in reducing symptoms. No significant difference was observed in pulmonary function values and in bronchial reactivity results between the two groups. No effect of flunisolide was observed on hypothalamic-pituitary-adrenal function. This study confirms the efficacy and safety of flunisolide (0.5 mg b.i.d.) in the treatment of asthmatic children.     

Fenoterol inhalation powder and aerosol in the treatment of asthma

Twenty patients with asthma were studied. They were given either fenoterol powder or fenoterol MDI for 2-week periods using a double-blind cross-over design. Identical doses of fenoterol (0.2–0.4 mg 2–4 times daily) were given to an individual patient throughout the 4-week study period. Both forms of treatment produced an almost identical bronchodilation, and there were no statistically significant differences in symptoms or side effects. It is concluded that fenoterol powder and fenoterol aerosol are equally effective.     

Assessment of serum myeloperoxidase in children with bronchial asthma

BACKGROUND: The role of neutrophils and myeloperoxidase (MPO) - assumed to be a marker of neutrophil activation - in bronchial asthma is still unclear, and the literature is controversial. METHODS: To investigate the participation of neutrophils and their products in childhood asthma, we assessed neutrophil counts and serum MPO in 175 children with bronchial asthma. Ninety of them were asymptomatic, and 85 of them were symptomatic within the last 2 weeks before examination. Bacterial infection of the lower respiratory tract (LRTI) was present in 34 and viral infection in 49 patients. As controls, 45 patients with cystic fibrosis, 23 patients with bacterial LRTI, and 87 healthy children were recruited. RESULTS: Median neutrophil counts (3135 cells/microl) and serum MPO levels (352 microg/l) were not different in children with bronchial asthma from healthy controls (2220 cells/microl and 401 microg/l, respectively), whereas in patients with cystic fibrosis and bacterial LRTI, neutrophil counts and MPO levels were increased. Asthmatic children with bacterial infection had significantly higher serum MPO and neutrophil counts then asthmatic children with viral infection or without infection. In addition, a significant correlation was found between serum MPO and neutrophil counts and C-reactive protein (CRP), and between neutrophil counts and CRP, but no relationship was detected for serum MPO and disease activity or lung function. CONCLUSIONS: Our data indicate that serum MPO - a marker of neutrophil activation - does not contribute to the assessment of the inflammatory process in childhood asthma. In addition, measurement of serum MPO appears not to be useful in assessing the participation of the neutrophil in asthmatic children. However, assessment of MPO may be useful to distinguish between bacterial and viral infection.     

The effect of astemizole on bronchial hyperresponsiveness and exercise-induced asthma in children

The ability of the new generation H1-receptor antagonist, astemizole, to prevent histamine-induced airway obstruction and exercise-induced asthma (EIA) was studied in 20 children with asthma. The study was a randomised clinically controlled trial of oral astemizole versus placebo in a cross-over study. In each of the two treatment periods the children were tested at days 0, 6, 15 and 22 of therapy. The two treatment periods were separated by a washout period of 50 days, and at each visit a bronchial challenge with increasing concentrations of histamine followed by an exercise test was performed, and peak flow and asthmatic symptom score were recorded daily. The children tolerated significantly higher mean concentrations of histamine when treated with astemizole compared with placebo (P less than 0.001). Astemizole postponed the response to exercise, but no change in the maximal response was found. No differences between the treatment periods were found regarding frequency of asthmatic symptoms or the daily recording of peak flow.     

Nitric oxide synthase in bronchial epithelium and nitric oxide metabolites in the lungs of rats with bronchial asthma after fenoterol inhalation

Nitric oxide synthase of the bronchial epithelium and concentrations of nitric oxide metabolites (NO₂ ⁻ and NO₃ ⁻) in bronchoalveolar lavage fluids were measured in rats with bronchial asthma after fenoterol inhalation. It was suggested that nitric oxide-ergic mechanisms can mediate the effects of inhaled β₂-adrenergic agonists. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 176–179, August, 2000     

A double-blind dose-response study of budesonide by inhalation in patients with bronchial asthma

Budesonide by inhalation and placebo were tested in 18 patients with moderate chronic bronchial asthma. Three dose levels of budesonide were used (25, 100 and 400 micrograms q.i.d.) and the patients were to take two puffs q.i.d. in all periods. The active treatment was investigated using double-blind cross-over technique, and placebo at the end of the trial. The duration of each treatment period was 2 weeks. The study showed a high drop-out frequency while on placebo and that the PEF values were influenced in a dose-dependent way by budesonide. In spite of the double-blindness the patients had a tendency towards overuse of the trial aerosol on the lowest dose, but they used significantly less than prescribed during the period with the highest dose. No side effects were reported.     

沙丁胺醇、丙酸倍氯米松和溴化异丙托品联合雾化吸入治疗慢性阻塞性肺疾病急性加重

目的 探讨沙丁胺醇、丙酸倍氯米松和溴化异丙托品三者联合雾化吸入对慢性阻塞性肺疾病急性加重(AECOPD)患者肺功能及动脉血气的影响.方法 以本院2011年1月至2014年1月收治的AECOPD患者108例为研究对象,随机数字表分为对照组(n=54)和联合治疗组(n=54).对照组采用常规治疗,联合治疗组加用沙丁胺醇、丙酸倍氯米松和溴化异丙托品雾化吸入治疗.治疗前及治疗后第7天进行两组患者动脉血气分析,记录动脉血pH值、动脉血氧分压(PaO2)和动脉血二氧化碳分压(PaCO2);并测定肺功能,记录第1秒用力呼气容积(FEV1)、FEV1占预计值％(FEV1％pred)和用力肺活量(FVC).结果 血气分析显示,治疗前两组患者动脉血pH值、PaO2和PaCO2差异均无统计学意义(均P＞0.05).治疗后两组患者动脉血pH值、PaO2和PaCO2均较治疗前显著改善(均P＜0.05).与对照组比较,治疗后联合治疗组患者PaO2明显增加[(79.5±9.4) mmHg比(64.0±7.7) mmHg,P＜0.05;1mmHg=0.133 kPa],PaCO2明显降低[(49.3±11.5)mmHg比(61.0±12.2)mmHg,P＜0.05].治疗后两组患者动脉血pH值差异无统计学意义(P＞0.05).治疗前两组患者FEV1、FEV1 ％pred、FVC差异均无统计学意义(均P＞0.05).治疗后两组患者FEV1、FEV1％pred、FVC均较治疗前有显著改善(均P＜0.05).与对照组比较,治疗后联合治疗组患者FEV1、FEV1％ pred、FVC均显著升高[(1.35±0.14)L比(1.18±0.11)L,(61.15±9.51)％比(54.55±8.71)％,(2.49±0.16)L比(2.19±0.17)L,均P＜0.05].结论 沙丁胺醇、丙酸倍氯米松和溴化异丙托品三者联合雾化吸入治疗AECOPD疗效较好.     

Prevalence and predictors of bronchial hyperresponsiveness in children aged 7-16 years

To study the prevalence and possible predictors of bronchial responsiveness we examined a cross-section of 527 children aged 7-16 years from Copenhagen. The method used included an interview with the child and the parents, skin prick test with common allergens and se-IgE. Bronchial responsiveness was measured by a histamine inhalation test. We found that 79 (16%) of the children had bronchial hyperresponsiveness (BH), defined as a 20% fall in FEV1 with a provoking concentration of histamine (PC20) at 8 mg/ml or less. Atopic symptoms defined as asthma, rhinitis or eczema were significantly (P less than 0.001) correlated to BH both in prevalence and degree of BH. None of the children with urticaria had BH. The degree of bronchial responsiveness was also significantly influenced (P less than 0.001) by family disposition to atopy, whereas we found no correlation between BH and "passive" smoking, specific skin test in unselected children, or elevation of IgE in children without atopic symptoms. We conclude that BH is severest in children with asthma, independent of elevated IgE or positive skin prick test. Children with rhinitis, dermatitis, or asymptomatic BH have the same degree of BH; this differed from that in children with asthma.     

HLA antigens in Greek children with allergic bronchial asthma

Abstract:  The aim of our study was to investigate the genetic linkage between mite allergic bronchial asthma and HLA class I and II antigens and haplotypes. Sixty Greek children with allergic bronchial asthma due to mite sensitivity ( Dermatophagoides pteronyssinus and Dermatophagoides farinae ) and their family members were typed for HLA class I and II antigens (total 263 subjects). One hundred and twenty-five healthy, unrelated Greek children without medical history of atopy were also typed as control group. Major histocompatibility complex class I and II gene analysis revealed that only HLA-DRB1*04 and HLA-DQA1*0301 alleles are possibly important factors in the development of atopic asthma in Greek children with sensitivity to mites. No significant differences among the HLA-DRB1*04 subtypes have been established. Transmission disequilibrium test revealed that no specific HLA-A, -B, -DRB1, -DQA1 and -DQB1 alleles were transmitted preferentially to the affected children. HLA-DQB1*0301-4 alleles were associated with high levels of total serum immunoglobulin E in affected children. The study of the HLA haplotypes failed to demonstrate any significant association between any extended or natural selection haplotype and mite allergic bronchial asthma in Greek children.     

Association of group‐specific component exon 11 polymorphisms with bronchial asthma in children and adolescents

Several studies have investigated the association of Group‐specific Component (GC) gene, also known as vitamin D‐binding protein (VDBP), and various respiratory disorder susceptibility with conflicting results. In this sense, we aimed to investigate whether rs7041 and rs4588 variants confer susceptibility to bronchial asthma in a sample of an Egyptian population and to elucidate by in silico analysis the structural and functional impact of these variants. Group‐specific Component polymorphisms rs7041 and rs4588 were genotyped in 192 Egyptian children and adolescents (96 with asthma and 96 healthy controls) by TaqMan single nucleotide polymorphism genotyping assay. The rs7041 GG genotype showed a significantly elevated frequency among patients under codominant, dominant, recessive and allelic models where the patient group had greater carriage rate of G allele [OR 2.15, CI 95% (1.32‐3.50; P = 0.002)], while rs4588 CA and AA genotypes were found to be protective genotypes with controls showing a greater carriage rate of A allele [OR 0.52, CI 95% (0.30 ‐ 0.90; P = 0.02)]. Three haplotype allele combinations were identified with frequencies of GC (44.3%), TC (31.3%) and TA (24.5%) in the total study population. GC haplotype was shown to be more frequent in controls, while TC and TA haplotypes were more predominant in the patient group. Only rs7041 variant showed a significant association with family history and pubertal status. In conclusion, both study GC variants could be implicated in childhood bronchial asthma pathogenesis; rs7041 GG genotype and G allele increased asthma risk while rs4588 AA genotype and A allele conferred protection in the study population.     

Omalizumab therapy for children and adolescents with severe allergic asthma

Omalizumab, a therapeutic humanized monoclonal antibody specific for human IgE, was introduced in clinical practice more than a decade ago as an add-on therapy for moderate-to-severe allergic asthma in patients aged ≥12 years. Omalizumab has been demonstrated to be effective in adults with uncontrolled persistent asthma, with an excellent safety profile. In simple terms, omalizumab works by inhibiting the allergic cascade, that is, by neutralization of the circulating free IgE. This leads to reduction in the quantity of cell-bound IgE, downregulation of high-affinity IgE receptors, and, eventually, prevention of mediator release from effector cells. Evidence is far less abundant on the role of omalizumab in pediatric asthma. Although efficacy and safety of omalizumab in children and adolescents with uncontrolled, persistent allergic asthma has been recognized as well, further studies are needed to clarify a number of open questions in this specific patient population.     

Jet-nebulized beclomethasone dipropionate in the management of bronchial asthma

The efficacy of jet nebulized beclomethasone dipropionate (BDP) in the management of asthma was evaluated in 18 children, 2-26 months old (mean 10 months). The children were selected on the basis of the severity of their symptoms and the lack of effect of conventional treatment. The effect of BDP was evaluated by comparing clinical data before and after the initiation of treatment. Fifteen of the 18 patients experienced a significant clinical improvement during treatment with BDP. BDP "nebulizer solution" is a valuable contribution to the management of severe asthma in young asthmatics.     

Nasal inhalation of budesonide from a spacer in children with perennial rhinitis and asthma

The standard treatment of allergic rhinitis and asthma consists of topical corticosteroids administered intranasally and inhaled through the mouth. Although this therapy is highly effective, and side-effects are few and mild, it may be possible further to improve the therapeutic index and patient compliance with the treatment. In the present study, we evaluated a nasal inhalation system used for the simultaneous treatment of rhinitis and asthma. In principle, it results in an airway deposition of the corticosteroid similar to that of inhaled allergens. Twenty-four children with perennial rhinitis and asthma inhaled budesonide through the nose from a pressurized aerosol, attached to a spacer device, in a double-blind, placebo-controlled, crossover study. Compared with placebo, budesonide treatment resulted in a significant reduction of nasal symptoms (P<0.01) and of asthma symptoms (P<0.05), and in an increase of nasal peak inspiratory flow (P<0.001) and of oral peak expiratory flow (P=0.01). There were no differences between budesonide and placebo in local side-effects, such as dry nose, nosebleed, and hoarseness. We conclude that nasal inhalation of a corticosteroid from a spacer offers a simple and effective treatment for both rhinitis and asthma in children, but it is an open question whether the nasal inhalation system can improve the ratio of antirhinitis/antiasthma effects to side-effects.     

Unilateral pupillary mydriasis from nebulized ipratropium bromide: A false sign of brain herniation in the intensive care unit

Although there are many causes of anisocoria in the intensive care setting, the development of unilateral mydriasis in patients with intracranial hemorrhage or tumor is a neurological emergency, as it may herald the onset of uncal herniation. We describe two patients with a hemiparesis from neurosurgical disorder who subsequently developed a fixed and dilated pupil. The pupillary abnormality was caused by nebulized ipratropium bromide in both cases, and resolved when the medication was discontinued. Nebulized ipratropium may leak from the mask into ipsilateral eye and cause mydriasis in patients with facial weakness. This benign cause of anisocoria in the intensive care setting is distinguished from uncal herniation by the laterality of neurologic findings, and lack of mental status change, ptosis, and extraocular movement impairment.     

Relationship between viral antibodies and bronchial hyperresponsiveness in 495 unselected children and adolescents

The purpose of this study was to investigate whether recent and previous subclinical viral respiratory infection can explain the presence of increased bronchial responsiveness to histamine. We studied a randomly selected population of 495 children and adolescents, aged 7–16 years, from Copenhagen. If the subjects had had symptoms of respiratory infection recently, the examination was postponed for at least 6 weeks. Bronchial hyperresponsiveness (BHR) to inhaled histamine was found in 79 (16%) of the subjects, of whom 28 had asthma. Forty-eight subjects (10%) had increased levels of serum IgM antibodies against either parainfluenza, influenza, adenovirus, or respiratory syncytial virus (RSV), reflecting a recently acquired infection. No association between BHR and antibodies against respiratory viruses was found, as 7 (8.9%) of the 79 subjects with BHR and 41 (9.9%) of the 416 subjects without BHR had viral antibodies. Furthermore, no association between degree of bronchial responsiveness and viral antibodies was found. Moreover, 251 individuals (51%) had signs of earlier RSV infection, i.e. IgG antibodies against RSV. No relationship was found between age of the subjects and the presence of antibodies against either respiratory viruses in general or IgG-RSV. No relationship was found between the presence of antibodies against RSV and BHR; furthermore, evidence of earlier RSV infection was unrelated to the level of lung function and degree of bronchial responsiveness. We conclude that increased bronchial responsiveness in asymptomatic, unselected schoolchildren and adolescents is not likely to be caused by recent or previous viral respiratory infections.     

Treatment of asthma in pre-school children with inhalation of terbutaline in Turbuhaler compared with Nebuhaler

The aim of this study was to evaluate the efficacy, safety and preference of pre-school children with regard to two different devices for treatment of bronchial asthma with terbutaline. Turbuhaler, a powder inhaler preloaded with pure terbutaline for inhalation, was compared with a pressurized metered dose inhaler, attached to a Nebuhaler. The study had an open, cross-over randomized design. Each treatment period consisted of 2 weeks. Diary cards were filled in every morning and evening by the parents regarding PEF, asthma symptoms, extra inhalations of terbutaline, and side effects. Twenty-one children (mean age 3.9 years) were included in the study. A highly significant (P less than 0.001) increase in peak expiratory flow (PEF) was obtained after inhalation with both devices. The PEF values in the mornings after inhalation of terbutaline with Turbuhaler were significantly higher (P = 0.046) than those with Nebuhaler. Further, the PEF baseline values in the evenings before inhalation were also significantly higher (P = 0.03) with Turbuhaler. No difference was found in asthma symptoms and extra medication between the two devices. Side effects were mild and few with both devices. The parents found Turbuhaler easier to handle and 19 of 21 preferred this device for future use.