Serum Concentrations of Theophylline in Children Treated with Two Daily Doses of a Sustained-Release Theophylline Preparation

Over a 3-month period 22 asthmatic children were treated with a sustained-release theophylline preparation (Nuelin Retard®, Riker) in twice-daily doses. During the first 2 weeks of treatment slight side-effects were observed in 14 children. Over the remaining 10-week period only four children experienced minor side-effects.
Serum theophylline levels 4 hours after tablet administration were measured three times and serum levels just before tablet administration were measured once during the observation period. The average difference between the serum levels of theophylline just before tablet administration and the corresponding serum value 4 hours afterwards was 4.2 μg/ml. The serum values 4 hours after tablet administration showed an insignificant fall throughout the period and patient compliance was assessed as good.
When the average requirements of theophylline in mg/kg found by Wyatt et al. (15) (Table 2) were used as initial doses, few dosage adjustments were necessary and no serum values were greater than 26.2 μg/ml, but in order to avoid serum levels above 20 μg/ml initial doses should be decreased about 10% and final adjustment made with the aid of serum theophylline measurement under steady state conditions.
In children, Nuelin Retard given in two daily doses is capable of maintaining a constant therapeutic serum concentration for the whole 24-hour period.     

Effects of Enprofylline and Theophylline on Exercise-Induced Asthma

Eight asthmatic out-patients with a history of exercise-induced asthma (EIA) were randomly treated with intravenously administered enprofylline 1.5 mg/kg b.wt., theophylline 5 mg/kg b.wt., and placebo immediately prior to a 6-min exercise provocation in this double-blind crossover comparison. A reduction in peak flow of more than 20% was seen in all patients after placebo pre-treatment. Mean plasma concentrations at the start of the exercise test were 3.3 mg/l and 13.2 mg/l after 20 min infusion of enprofylline and theophylline, respectively. The corresponding figures 25 min later were 2.3 and 11.7, respectively. Maximal fall in peak expiratory flow (PEF) after exercise in percent of pre-exercise PEF was 49% +/- 6% (mean +/- SEM), 39% +/- 6% and 24% +/- 5% after infusion of placebo, enprofylline, and theophylline, respectively. Theophylline produced a statistically significant better protection against EIA compared to enprofylline and placebo. Enprofylline produced a slight protection from EIA not statistically significantly different from placebo.     

A Double-Blind Controlled Trial of Elemental Diet in Severe, Perennial Asthma

In a double-blind controlled trial 41 hospitalized adults with severe, perennial asthma of unknown aetiology were allocated to either an antigen-free elemental diet (Vivasorb®) or control diet, i.e. blended ordinary hospital food, for 2 weeks. At the time of entry into the trial all patients were in an active but stable phase of the disease. Medical treatment was given throughout the study as clinically indicated. Peak expiratory flow was measured hourly during the daytime and patients noted their symptoms daily on an assessment form. Validation of variables according to a scoring system indicated that the elemental diet resulted in an improvement of the patients' asthma ( P < 0.05). It is concluded that elemental diet may serve as a diagnostic tool for disclosing alimentary intolerance in patients with perennial asthma.     

Psychopathology and Self-Concept in Asthmatic Children

Fifty-six asthmatic and 56 matched control children and theirparents were administered several psychiatric inventories includingthe child (DICA) and parent (DICA-P) versions of the DiagnosticInterview for Children and Adolescents, the Child Behavior Checklist,the Hopelessness Scale, and the Piers-Harris Children's Self-ConceptScale. While asthmatic children did not differ from controlchildren in self-concept, there was some evidence suggestingthat asthmatic children were at greater risk to psychopathology.Interestingly, severity of asthma appeared to be largely unrelatedto psychiatric problems     

In Vitro Production of IgE and IgG Protein by Blood Mononuclear Cells from Non-Atopic and Atopic Donors

The production of IgE and IgG protein by human peripheral blood mononuclear cells in culture has been examined. Cells obtained from 18 grass-sensitive donors during the grass pollen season and from 11 atopic dermatitis patients (total serum IgE levels greater than 960 ng/ml), spontaneously produced significant amounts of IgE but not IgG with time. Similar results were obtained using B-cell enriched preparations from both groups. Cells from 16 non-atopic donors had mean levels of pre-formed IgE similar to those of grass pollen-sensitive donors, but there was no increase in culture IgE with time. Treatment of mononuclear cells with pokeweed mitogen did not influence the production of IgE but markedly increased the amount of IgG synthesized by non-atopic and atopic donor cells. Slight, but significant increases in culture IgE, but not IgG, were seen following a 7-day mixed lymphocyte reaction involving both unrelated non-atopic donor cells and the lymphoblastoid B-cell line, Raji. Treatment of cells with 50 HA units of influenza A/Hong Kong/1/68 (H3N2) virus or with 0.02% v/v (240 IU/ml) of a purified beta-interferon preparation did not alter IgE or IgG produced.     

Bioavailability of Theophylline from Three Different Tablets in Asthmatic Patients and Their Bronchodilating Effects in Combination with Terbutaline Inhalation

The bioavailability of three different theophylline tablets (microcrystallinic theophylline, Theolair®, Nuelin®, 3M Riker), choline theophyllinate as a new film-coated tablet (Teovent®, Ferrosan, Sweden) and theophyllaminopropanol (Oxyphylline® Draco, Sweden) was investigated in eight adult asthmatics in a randomized, double-blind, cross-over study.
Effects on ventilatory capacity (FEV₁ and FVC), circulation (heart rate and blood pressure) and skeletal muscle tremor were followed. The theophylline concentration was determined by gas chromatography. Forty-five minutes after theophylline administration the plasma concentrations were almost the same for all four formulations. The bioavailability was also almost identical. The half-life for intravenous theophylline in these asthmatics was 7.4 ± 0.64. The three tablet formulations had equal effect on FEV₁ and the effect was sustained throughout the 6-h period.
Six hours after theophylline administration five terbutaline inhalations induced the same further increase in FEV₁. The results indicate that theophylline alone has only a moderate acute bronchodilating effect at recommended plasma concentrations but gives a good effect when combined with inhaled β₂-adrenostimulants.     

Inhibitory Effect of N-(3'', 4''-dimethoxycinnamoyl) Anthranilic Acid (N-5'') on SRS-A Mediated Bronchoconstriction in the Guinea Pig in Vivo

Slow-reacting substance of anaphylaxis (SRS-A) is an important factor mediating bronchoconstriction in asthma. We developed a guinea pig model for SRS-A-mediated bronchoconstriction induced by antigen inhalation. Using this model, we investigated the effect of N-(3', 4'-dimethoxycinnamoyl) anthranilic acid (N-5'), a new anti-allergic drug, on the bronchoconstriction. FPL 55712 inhibited most of the bronchoconstriction induced by antigen inhalation. N-5' inhibited the antigen-induced bronchoconstriction in a dose-dependent fashion. Intraperitoneal administration of 200 mg/kg N-5' was effective for 40 min after antigen inhalation, while the effect of 60 mg/kg lasted only 7 min. On the other hand, 200 mg/kg N-5' showed no inhibitory effect on the bronchoconstriction caused by direct inhalation of leukotriene C4, a component of SRS-A. These findings indicate that one of the anti-allergic actions of N-5' is due to inhibition of synthesis and/or release of SRS-A.     

Food and Fasting Absorption of a Single Dose of a Sustained Release Theophylline Sprinkle Formulation in Children

The bioavailability and absorption pattern of theophylline from a single dose of a slow release theophylline sprinkle product (Somophyllin) were investigated in 10 asthmatic children both in fasting conditions and after a standardized breakfast. Theophylline given intravenously was used as a reference. The fasting absorption of Somophyllin was rather fast with peak serum theophylline levels 3-5 h (mean 3.7 h) after dosing. Food produced a small but statistically significant reduction in the rate of absorption of theophylline, so that the mean time to peak serum theophylline level was 5.6 h (range 4-8 h) after food. In no case was there any important difference between the absorption profiles on the test days, and the bioavailability was complete after both fasted and fed intake of the product (92.5% and 105%, respectively). It is suggested that to obtain the optimum absorption profile children should take Somophyllin with food rather than between meals.     

Effects of Oral Theophylline Combined with Oral and Inhaled β2-Adrenostimulants in Asthmatics

The acute ventilatory, cardiovascular and tremorogenic effect of a high oral dose of terbutaline (5 mg) was compared with that of half the dose (2.5 mg) combined with 280 mg anhydrous theophylline orally in the randomized, double-blind, cross-over study in eight asthmatics. After 120 min, when steady-state bronchodilation was achieved, five terbutaline inhalations (1.25 mg terbutaline sulphate) were added to both treatment regimens. The mean maximum plasma concentration of theophylline was then 7 micrograms/ml (39 mumol/l). Inhalation of a beta 2-adrenostimulant had a very good additional effect without increasing side effects in these patients with good inhalation technique. The oral low-dose combination gave significantly better bronchodilation than the high dose of terbutaline alone and caused significantly less tremor. Although the combination only had an additive bronchodilating effect, it may offer important clinical advantages. If the patient cannot use the metered dose aerosol, an oral low dose combination should be preferred to a single high dose of either theophylline or beta 2-adrenostimulants. In patients with good inhalation technique but not controlled by inhalation from a metered dose aerosol alone, a combination of oral theophylline and terbutaline in "sub-optimal" dose and an inhaled beta 2-agonist in individually titrated optimal dose gave a maximal bronchodilating effect with minimum side effects.     

Comparison of the Protective Effect of Ketotifen and Disodium Cromoglycate on Exercise-Induced Asthma in Asthmatic Boys

Fourteen boys with a mean age of 12.2 years were studied with respect to the protective effect of ketotifen on exercise-induced asthma (EIA) in comparison with disodium cromoglycate (DSCG). All had a positive history of EIA and a post-exercise fall in FEV1 of more than 20%. A double blind cross-over technique was used with a 1 week wash-out period between the two treatment alternatives. Both drugs gave some, but not significant protection for EIA and no differences between the two active substances tested were found. Great individual differences in the response to the two drugs were noted.     

长期吸入糖皮质激素对支气管哮喘患者血清leptin、IL-13和IL-2水平的影响

目的:观察支气管哮喘患者血清leptin、IL-13和IL-2水平的变化并探讨长期吸入糖皮质激素后对支气管哮喘患者血清leptin、IL-13和IL-2的影响.方法:4采用酶联免疫吸附法(ELISA),分别检测70例支气管哮喘患者采用吸入糖皮质激素治疗前、治疗3、6、12个月后及60例对照者血清IL-13和IL-2水平...     

Effect of different monotherapies on serum nitric oxide and pulmonary functions in children with mild persistent asthma

Introduction

Common medications used to treat mild persistent asthma are glucocorticoids, leukotriene receptor antagonists and theophylline. The aim of the study was to evaluate monotherapy with either inhaled steroids, oral leukotriene receptor antagonist or theophylline in Egyptian children with mild persistent asthma by determining their clinical, laboratory and spirometric responses to treatment.

Material and methods

Thirty-nine mild asthmatic children between 8 and 13 years of age were included in the study. Patients were classified according to therapy received into four groups: oral leukotriene receptor antagonist (montelukast), inhaled corticosteroid (fluticasone propionate), sustained-release (SR) theophylline, and no treatment. Pulmonary function testing was performed at the start of therapy and 8 weeks later using spirometry. Eosinophil count and serum nitric oxide were estimated in the blood. Minitab statistical package was used for analysis of data.

Results

Follow-up after 8 weeks revealed significant improvement in FEV1% in groups 1 (p < 0.01) and 3 (p < 0.05), significant improvement in PEFR in groups 1 (p < 0.05) and 2 (p < 0.01), significant decline in serum NO levels in groups 1 (p < 0.05) and 2 (p < 0.05), as well as significant improvement in eosinophil count in groups 1, 2 and 3 (p < 0.01, < 0.001, < 0.01 respectively). There was a statistically significant positive correlation between the decline in serum NO and the decline in blood eosinophil % in group 2 (p < 0.05).

Conclusions

Inhaled corticosteroids and montelukast have a significant role in controlling the pulmonary functions and the inflammatory process in children with mild persistent asthma, although inhaled corticosteroids seem to yield a better response. Children with mild persistent asthma should receive a controller medication, and SR theophylline may be a good cost-benefit alternative for low socio-economic groups of patients.     

组胺及组胺诱导的抑制因子对SLE外周血单个核细胞功能的影响

组胺能显著地抑制正常人外周血单个核细胞(PBMC)对美洲商陆(PWM)的增生反应和IgG生成,但对活动性系统性红斑狼疮(SLE)患者的抑制作用明显低于对正常人的作用(P<0.01)。组胺所诱导的抑制因子(HSF)也有上述抑制作用。西米替丁和消炎痛均能阻断HSF的生成,提示表达组胺2型受体(H_2R)的细胞以及PGE_2与HSF生成有关。值得注意的是活动性SLE患者的HSF生成能力显著低于正常人的能力(P<0.01),而且患者PBMC对正常人HSF的反应性显著低下,提示活动性SLE患者的“抑制性”T细胞功能低下。     

Influence of Food on the Absorption Rate and Bioavailability of a Sustained Release Theophylline Preparation

Six children and six adults were given a single dose of a sustained release theophylline preparation (Nuelin Retard®) after an overnight fast and later after a standardized breakfast. Food significantly reduced the absorption rate of theophylline whereas the extent of absorption of theophylline was unaffected by food. Under steady state treatment the fluctuations in the serum levels of theophylline were small when the tablets were taken after meals twice a day showing that this dose regimen was sufficient. No characteristic absorption or elimination phases were seen during the steady state dose interval, and the time to peak serum theophylline level showed great variation. Serum theophylline control about 4 h after fasting intake of the tablet is recommended.     

The Action of Dibutyryl Adenosine-3‘:5’-Cyclic Monophosphoric Acid and Theophylline on the Isolated Cat Parotid Gland

In the isolated cat parotid gland intraarterially applied dibutyryl cyclic AMP (db-CAMP) (1.0 mM) produced a slow, but often maintained salivary flow. db-CAMP was also able to potentiate secretion evoked by supramaximal doses of intraarterially applied acetylcholine. Similar secretory effects were obtained also after intraarterial application of theophylline (1.0 mM). The secretory responses due to db-CAMP or theophylline were unaccompanied by measurable acinar membrane potential changes and stayed unchanged after cutting the parasympathetic innervation of the gland and after blocking both cholinergic and β-adrenergic receptors with atropine (10^--⁷ M), and with D-(-)-N-isopropyl-p-nitrophenol-ethanol-amine (INPEA) (10^--⁵ M), respectively. The possibility of the existence of an acinar adenylate cyclase system functionally linked to the β-adrenergic membrane receptor is discussed.     

哮喘儿童垂体-甲状腺功能的研究

目的 探讨不同哮喘状态下,机体内分泌系统中垂体-甲状腺轴的功能状态.方法 选择60例（3～12）岁的哮喘儿童作为研究对象,根据病情分为轻中度哮喘组和重度哮喘组,健康儿童（3～12）岁为对照组,每组30例.用放射免疫分析测定上述儿童血清促甲状腺素（TSH）、三碘甲腺原氨酸（T3）和甲状腺素（T4）水平.结果 重度哮喘组TSH水平增高,而T3和T4水平明显减低,同正常儿童组比较有显著差异（P〈0.01）,但轻中度哮喘组TSH、T3和T4与正常儿童组比较差异无统计学意义.结论 轻、中度哮喘儿童组甲状腺功能基本正常,而重度哮喘儿童组存在甲状腺功能的紊乱.     

Akt对哮喘小鼠肺组织VEGF表达的上调作用

目的探讨在哮喘发病机制中,PKB/Akt对哮喘小鼠肺组织VEGF表达的调节作用。方法BALB/c小鼠30只,按随机数字表法均分为正常对照组、哮喘组、PKB/Akt阻断组,免疫荧光、Western blot方法检测各组小鼠肺组织VEGF的表达。结果免疫荧光结果显示:哮喘组肺组织内VEGF阳性产物的平均光密度(MOD)显著高于正常对照组(P<0.01),而PKB/Akt阻断组与哮喘组相比,上述部位VEGF阳性反应产物的MOD值明显降低(P<0.05)。Western blot结果显示:与正常对照组比较,哮喘组小鼠肺组织内VEGF的IDV( integrated density value)与内参照IDV的比值均明显升高(P<0.01),而PKB/Akt阻断组上述部位IL-1β目标带的IDV与内参照IDV的比值均明显低于哮喘组(P<0.05)。结论在NGF介导的哮喘发病机制中,Akt能上调哮喘小鼠肺组织内VEGF的表达。     

NGF对哮喘小鼠气道阻力和肺组织Akt/PKB表达的影响

目的探讨NGF介导的Akt/PKB信号转导通路在哮喘小鼠发病中的作用。方法BALB/c小鼠30只,按随机数字表法随机分为正常对照组、哮喘组、NGF阻断组。利用An iRes2005肺功能仪测小鼠气道阻力,运用免疫组织化学方法测定Akt/PKB的组织表达,M etamoph图像分析系统对结果进行分析。结果哮喘小鼠吸气阻力和呼气阻力明显高于正常组小鼠(P<0.01),NGF阻断组小鼠吸气阻力和呼气阻力明显低于哮喘组。免疫组织化学染色结果显示哮喘组Akt/PKB在肺组织炎性细胞的表达及AK t/PKB阳性炎症细胞数明显多于正常对照组(P<0.05),而NGF阻断组则明显低于哮喘组(P<0.05)。结论NGF介导哮喘气道高反应和炎症反应,Akt/PKB参与了哮喘发病中NGF介导的信号传导。     

儿童情绪与哮喘病情的关系及对IL-8的影响

支气管哮喘是儿童期较常见的一种变态反应性疾病 ,我国小儿哮喘的患病率为 0 .5 %～ 2 % ,个别地区高达 5 %。儿童哮喘的诱发因素除过敏、感染等之外 ,有相当部分与社会心理因素有关。对不易控制的哮喘发作者 ,情绪或行为的紊乱本身与疾病病情关系甚为密切。本研究采用《儿童状态 -特质焦虑问卷》(ＳＴＡ ＩＣ)和《儿童抑郁障碍自评量表》(ＳＤＤＳＣ)对 4 0例轻、中度哮喘患儿的情绪状态进行评定 ,同时采用有效的非创伤性方法检测了其中 33例患儿痰液白细胞介素 - 8(ＩＬ - 8)水平 ,观察不同严重度哮喘患儿的情绪状态及其与痰中ＩＬ - 8水…     

哮喘豚鼠初级传入神经元ERK的表达及NGF的调节作用

目的　探讨细胞外信号调节蛋白激酶 (ERK)在哮喘豚鼠初级传入神经元 (C7 T5脊神经节 )的表达及神经生长因子 (NGF)对ERK的调节作用。方法　利用免疫组织化学结合显微图像分析 ,研究哮喘豚鼠C7 T5脊神经节活化的ERK免疫反应变化。结果　与对照组相比 ,哮喘组豚鼠活化ERK免疫反应在C7 T5脊神经节神经元核内明显上调 (P <0 .0 1) ,其阳性细胞比率明显高于对照组。Anti NGF组豚鼠活化ERK免疫反应在C7 T5脊神经节神经元的核中明显低于哮喘组 (P <0 .0 1)。结论　C7 T5脊神经节神经元活化的ERK可能参与哮喘的发病过程 ,NGF可上调哮喘豚鼠C7 T5脊神经节神经元活化的ERK表达