Effects of intravenous infusion of theophylline drugs combined with high-flow respiratory humidifier on serum procalcitonin and lactate clearance rates in elderly patients with COPD secondary to type Ⅱ respiratory failure / 中国医师杂志

Objective:To observe the effect of theophylline intravenous drip combined with high flow respiratory humidifier on serum pro Calcitonin (PCT) and lactate clearance rate (LCR) in elderly patients with chronic obstructive pulmonary disease (COPD) secondary to type II respiratory failure.Methods:We prospectively selected 120 elderly patients with COPD secondary to type II respiratory failure who were admitted to the Affiliated Hospital of Jining Medical University from March 2020 to March 2022. They were randomly divided into the control group ( n=60) and the observation group ( n=60). The control group was treated with non-invasive positive pressure ventilation combined with theophylline intravenous drip, and the observation group was treated with high flow respiratory humidification therapy apparatus combined with theophylline intravenous drip. The sputum viscosity of the two groups was counted, and the pulmonary function [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1), FEV 1/FVC], blood gas analysis, respiratory mechanics, oxygen metabolism, and serum index levels, as well as the difference between acute physiology and chronic health assessment Ⅱ (APACHE Ⅱ) scores after treatment were compared between the two groups. Results:The overall sputum viscosity of the observation group was better than that of the control group ( P<0.05). Before treatment, there was no statistically significant difference in lung function and blood gas analysis indicators between the two groups (all P>0.05); After treatment, the lung function indicators, arterial partial pressure of oxygen (PaO 2), and oxygenation index (PaO 2/FiO 2) of both groups were significantly increased compared to before treatment (all P<0.05), while arterial partial pressure of carbon dioxide (PaCO 2) was significantly decreased compared to before treatment (all P<0.05), and the values of each indicator in the observation group after increasing or decreasing were significantly better than those in the control group (all P<0.05). Before treatment, there was no statistically significant difference in respiratory mechanics and oxygen metabolism indicators between the two groups (all P>0.05); After treatment, the arterial blood oxygen content (CaO 2) in the two groups was significantly higher than that before treatment (all P<0.05), while the oxygen uptake rate (ERO 2) in the two groups and the VO 2 max (VO 2Max), airway peak value, and respiratory resistance in the observation group were significantly lower than those before treatment (all P<0.05), and the values of each index in the observation group after rising or falling were significantly better than those in the control group (all P<0.05). Before treatment, there was no statistically significant difference in serum indicators and APACHE Ⅱ scores between the two groups (all P>0.05); After treatment, LCR and C-reactive protein (CRP) in the observation group were significantly higher than those before treatment ( P<0.05), while the scores of PCT, Interleukin 6 (IL-6), CRP and APACHE Ⅱ were significantly lower than those before treatment (all P<0.05), and the values of each index in the observation group after increase or decrease were significantly better than those in the control group (all P<0.05). Conclusions:Theophylline intravenous drip combined with high flow respiratory humidifier can improve respiratory mechanics, oxygen metabolism, reduce inflammatory reaction, and reduce the impact of disease on life in elderly patients with COPD secondary to type II Respiratory failure.

Roles of Ca2+ sensitive K+ channel, phosphodiesterase inhibitor, and ? adrenergic activity in Tridax procumbens leaf extract relaxation of trachea smooth muscle in male Wistar rats

Background: Although traditional use of Tridax procumbens aqueous leaf extract (TPALE) in the management of respiratory disorders is documented, validated scientific evidence is scarce. Aim and Objectives: Trachea smooth muscle (TSM) relaxant activity of TPALE ingestion was investigated in the presence or absence of key TSM relaxant agents. This was with the aim at elucidating relaxant activity of TPALE on TSM. Materials and Methods: Contractile activity of TSM excised from TPALE treated (100 mg/kg) and non-treated rats was assessed pre - and post-incubation in salbutamol (10?4 M), theophylline (10?4 M), caffeine (10?4 M), naringin (10?4 M), and naringenin (10?4 M) using organ chamber connected to a force isometric transducer (Model 7004; Ugo-Basile VArese, Italy). Results: TPALE treatment significantly inhibited contractile activity in TSM. TPALE treated rats showed significantly inhibited contractile activity of the TSM pre (45.6%) and post-incubation (35%) in theophylline when compared to control pre (90.6%) and post-incubation (60%). Incubation of TSM from control and TPALE treated rats in salbutamol, significantly inhibited contractile activity (33.2%) and (37.2%), respectively. After incubation in caffeine, TSM from TPALE treated rats showed significant inhibition in the contractile activity (30.7%) as TSM from control postincubation (38.4%). TSM of TPALE-treated group pre-incubation showed significant inhibition in contractile activity (41.8%) when compared to the TSM of TPALE-treated Group (59.3%) and control (64.5%) post-incubation in naringin. However, incubation of TSM of TPALE-treated rats in naringenin significantly inhibited contractile activity (40.4%) when compared to pre-incubation (45%) and control pre - and post-incubation, respectively (52% and 90%). Conclusion: Calcium-activated K+ channels, ?2 adrenergic stimulation, and antioxidant activity contribute to the mediation of relaxant activity by TPALE in TSM.

Theophylline attenuates bleomycin-induced oxidative stress in rats: The role of IL-6, NF-κB, and antioxidant enzymes

Abstract The purpose of this study was to evaluate the antifibrotic and antioxidant roles of theophylline (Theo), a bioactive compound, in bleomycin (BLM)-induced pulmonary fibrosis in Wistar albino rats. Assigned into 4 groups were 32 Wistar albino rats, comprising the control group (administered 0.9% isotonic saline), BLM group (treated with BLM at a dose of 2.5 mg/kg), BLM+Theo group (treated with Theo at a dose of 75 mg/kg + BLM at a dose of 2.5 mg/kg), and Theo group (treated with Theo at a dose of 75 mg/kg). In the BLM group, a significant decrease was observed in the catalase and glutathione peroxidase enzyme activities, and reduced glutathione (GSH) (p < 0.05, p< 0.05, p< 0.001, respectively), while the malondialdehyde (MDA) levels (p< 0.001) were significantly elevated when compared to the control group. However, the MDA levels in the BLM+Theo group were also significantly higher than in the control group (p< 0.01). Similarly, the GSH levels were significantly higher in the BLM+Theo group than in the BLM group (p< 0.05). The results indicated that Theo reduced the BLM-induced activation of nuclear factor-kappaB (NF-κB) and decreased interleukin-6 (IL-6) levels, together with significant amelioration of the immunohistochemical and histopathological architecture in the lung tissues. It was concluded that the administration of Theo had a positive effect on the GSH level, and activation of NF-κB and IL-6 expression, which were significant proinflammatory markers in the BLM-treated rats.

Opioid-free general anesthesia and induced recovery from anesthesia in a patient with myotonic dystrophy type-1: a case report / Anestesia geral sem opioide e recuperação induzida da anestesia em paciente com distrofia miotônica tipo-1: relato de caso

Abstract Myotonic dystrophy type-1 (Steinert disease) is an autosomal dominant, progressive multisystem disease in which myotonic crisis can be triggered by several factors including pain, emotional stress, hypothermia, shivering, and mechanical or electrical stimulation. In this report, dexmedetomidine-based general anesthesia, in combination with a thoracic epidural for laparoscopic cholecystectomy in a patient with Steinert disease, is presented. An Aintree intubation catheter with the guidance of a fiberoptic bronchoscope was used for intubation to avoid laryngoscopy. Prolonged anesthetic effects of propofol were reversed, and recovery from anesthesia was accelerated using an intravenous infusion of theophylline.

Resumo A Distrofia Miotônica (DM) tipo-1 (Doença de Steinert) é uma doença multissistêmica progressiva autossômica dominante em que a crise miotônica pode ser desencadeada por vários fatores, incluindo dor, estresse emocional, hipotermia, tremores e estímulo mecânico ou elétrico. O presente relato descreve anestesia geral realizada com dexmedetomidina em combinação com peridural torácica para colecistectomia laparoscópica em paciente com Doença de Steinert. Para evitar laringoscopia, a intubação traqueal foi realizada utilizando cateter de intubação Aintree guiado por broncofibroscopia óptica. Os efeitos anestésicos prolongados do propofol foram revertidos e a recuperação anestésica foi acelerada pelo uso de infusão intravenosa de teofilina.

Formulation And In-Vitro Evaluation Of Theophylline Hydrochloride Effervescent Floating Tablets: Effect Of Polymer Concentration On Tablet Buoyancy

Objective: This study was undertaken to formulate a floating drug delivery system of theophylline hydrochloride using different concentrations of a chosen polymer and then investigate how polymer concentration affects buoyancy and drug release properties of the tablets. Methods: Hydroxypropyl methylcellulose (HPMC) at different concentration levels of 15% (F1), 20% (F2) and 30% (F3) was used to form the three formulation batches of floating tablets. Wet granulation method was used for the granule preparation while Sodium bicarbonate and citric acid were used as the gas generating agent. The physical properties of the granules and the floating tablets were evaluated. Also determined were the physicomechanical properties, buoyancy and swelling characteristics of the tablets. The in vitro drug release study was carried out according to the USP I (basket method) for 8h in 900 ml 0.1N HCl at 50 rpm. Samples withdrawn at the regular predetermined time were analyzed spectrophotometrically at a wavelength of 271 nm and data obtained statistically analyzed by one-way analysis of variance (ANOVA). The differences between means were considered significant at P<0.05. Results: The result showed that polymer (HPMC) concentration significantly (p>0.05) increased swelling index and improved floating lag time, it had no significant effect on the total floating time. Percentage drug release at the end of 8 h was 100%, 98.2% and 96.13% for formulation F1, F2 and F3, respectively. All three formulations followed the Higuchi drug release kinetics model and the mechanism of drug release was the non Fickian diffusion with exponents of 0.46, 0.51 and 0.56 for the respective batch. Conclusion: Batch F3 gave a better-controlled drug release and floating properties in comparison to batch F1 and F2 thus Polymer concentration influenced the onset of floating and controlled the release of Theophylline.

Comparison of Efficacy and Safety of Theophylline, Doxophylline and Acebrophylline as an Add-On in the Management of Chronic Obstructive Pulmonary Disease

COPD is defined by GOLD as a disease characterized by airflow limitation that is not fully reversible. The chronic airflow limitation characteristic of COPD is caused by small airway disease (obstructive bronchiolitis) and parenchymal destruction (emphysema). We wanted to compare the efficacy and safety of theophylline, doxophylline and acebrophylline in the management of stable COPD patients.METHODSA prospective observational study was conducted in Burdwan Medical College and Hospital where 125 newly diagnosed adult stable COPD patients were divided into three groups each of which received theophylline, doxophylline or acebrophylline as add-on therapy over the standard for COPD. The study was conducted over a period of 13 months for spirometric parameters, severity of dyspnoea, quality of life. Assessment of adverse drug reactions was done by Naranjo’s causality assessment scale.RESULTSPatients of all three groups showed statistically significant difference in improvement in spirometric parameters and modified medical research council score and quality of life within each group. Few adverse effects like nausea were found in 2 (5.88%) patients of theophylline group, 2 (6.06%) patients of doxophylline group, and 2 (6.06%) patients of acebrophylline group. Palpitation was found in 1 (2.94%) patient of theophylline group while headache was found in 2 (6.06%) patients of acebrophylline group. Thus, it is seen that cardiological complications are more in theophylline group.CONCLUSIONSIn this study, all patients had shown some form of improvement in spirometry parameters after treatment which was maximum with doxophylline. Adverse effects were similar and non-serious in all the study patients.

Identification of structural analogues xanthine, theophylline and theobromine by surface-enhanced Raman spectroscopy / 药学实践杂志

Objective To distinguish the structural analogues xanthine, theophylline and theobromine by surface-enhanced Raman spectroscopy. Methods Concentrated silver colloid enhancement reagent was prepared as the Raman substrate to increase the number of "hot spots" per unit area, improve the sensitivity of surface-enhanced Raman spectroscopy, enhance the signal strength of the samples and achieve the effective discrimination of structural analogues. Meanwhile, the feasibility of surface-enhanced Raman spectroscopy in practical application was verified by determining serum samples of three mixtures. Results The concentrated silver colloid greatly increased the Raman intensity of the three structural analogues. The spectra of each individual compound and the mixture in the serum system was obtained. The detection limit of the three substances in aqueous solution were 0.005, 0.01 and 0.005 μmol/L respectively. Conclusion Surface-enhanced Raman spectroscopy is a potent technique for distinguishing structural analogues. It is rapid, sensitive and nondestructive to samples. Hence, it can be widely used in the fields of detection, analysis, clinical treatment and diagnosis.

A retrospective study of theophylline-based therapy with tracheal collapse in small-breed dogs: 47 cases (2013–2017)

Theophylline acts as a bronchodilator and has an anti-inflammatory effect. In addition, theophylline can be applied in patients where there are concerns regarding the side-effects of corticosteroids. This retrospective case series evaluated theophylline-based therapy in tracheal collapse (TC) canine patients. Forty-seven dogs with TC that received theophylline-based therapy during 2013–2017 were investigated. A fluoroscopic examination was performed to diagnose and grade TC. Theophylline was prescribed (7.5–30 mg/kg PO q12h) and the theophylline serum concentrations were measured. Coughing was assessed using a coughing scoring scale. The mean coughing score decreased after the theophylline-based therapy compared with that observed before treatment. Clinical improvements were observed in 46/47 patients (97.9%). As the intrathoracic TC grading increased, the final theophylline dosage also increased (p value 0.019). The symptom-free period (SFP) with therapy was 189.7 ± 194.45 days (range, 0–720 days) and there was no statistically significant correlation between the SFP and age, sex, or TC grade on fluoroscopy. Although theophylline has generally been used as a third-line treatment, it was used as the main treatment in this study and most patients showed improvements. Dogs have a wider therapeutic index of serum concentrations than humans, and any undesirable effects were easily overcome. With further research, this therapy may prove to be a useful approach, but its safety for long-term use in the treatment of canine TC patients needs to be established.

Effect and Mechanism of Phosphodiesterase Inhibitors on Trabecular Outflow

PURPOSE: Phosphodiesterase (PDE) inhibitors increase matrix metalloproteinase (MMP) production by inhibiting re-uptake of adenosine and may potentiate nitric oxide (NO) activity. This study was performed to investigate the effects and mechanisms of PDE inhibitors on trabecular outflow in cultured human trabecular meshwork cells (HTMCs). METHODS: Primary HTMC cultures were exposed to 0, 20, and 50 µM dipyridamole (DPD) or theophylline (TPN). Permeability through the HTMC monolayer was assessed using carboxyfluorescein. The production of NO was assessed using the Griess assay and MMP-2 levels were measured via Western blotting. RESULTS: DPD significantly increased permeability accompanied with increased nitrite concentration and MMP-2 levels (all p 0.05). When treated with DPD and TPN together, both permeability and nitrite production were increased; however, MMP-2 levels showed no difference compared to DPD exposure alone (p > 0.05). CONCLUSIONS: DPD increased trabecular permeability accompanied with increased nitrite production and MMP-2 levels. PDE inhibitors may increase trabecular outflow by increasing MMP-2 levels and by potentiating NO activity through cyclic GMP in HTMC.

The Effect of Theophylline on Improvement of Renal Function in Asphyxiated Neonates: A Systematic Review and Meta-analysis

The purpose of this systematic review and meta-analysis was to assess the preventive effect of theophylline on acute kidney injury and the ameliorative effect of theophylline on renal function in asphyxiated neonates. A literature search of the PubMed/Medline, Embase, and Cochrane Library databases for information published up to February 2019 was conducted. All studies that reported the incidence rate of acute kidney injury, serum creatinine level, and glomerular filtration rate after the randomized administration of theophylline or placebo were included. In total, eight studies involving 498 neonates were eligible. The incidence rate of acute kidney injury was significantly lower in the theophylline group than in the placebo group (risk ratio [RR]: 0.42, 95% confidence interval [CI]: 0.32–0.55, p < 0.001). The changes in serum creatinine level in the theophylline group were significantly higher than those in the placebo group from the first day of life to 3 and 5 days of age (weighted mean difference [WMD]: −0.51, 95% CI: −0.62 to −0.40, p < 0.001, and WMD: −0.26, 95% CI: −0.34 to −0.18, p < 0.001, respectively). The changes in glomerular filtration rate in the theophylline group were significantly higher than those in the placebo group from the first day of life to 3 days of age and the last day of follow-up (WMD: 12.30, 95% CI: 9.39–15.21, p < 0.001, and WMD: 9.35, 95% CI: 6.43–12.27, p < 0.001, respectively). These results suggested that theophylline has a beneficial effect on the prevention of acute kidney injury in neonates with perinatal asphyxia.

Design and Optimization of the Formulation and Technology of Theophylline Gel Matrix Sustained-release Tablets Based on QbD Concept / 中国药房

OBJECTIVE： To design and optimize the formulation and technology of Theophylline hydrophilic gel matrix sustained-release tablets （self-made sustained-release tablets for short） based on the concept of “Quality by Design” （QbD）. METHODS： Diluent type， tablet diameter， the property of adhesive （ratio of different adhesive types）， the amount of adhesive were regarded as critical process parameters （CPPs）. Similarity factor of dissolution curves of self-made Theophylline sustained-release tablets and reference preparation and its accumulative release rate at different time points were regarded as critical quality attributes （CQAs）. L18（34） orthogonal tablet was adopted for design and trial， and secondary polynomial regression model was established. By using Modde 12.0 software， the design space and its acceptable range （PAR） were calculated through the optimal model. The optimal formulation and technology of Theophylline sustained-release tablets was determined， and validation test and Monte Carlo simulation verification were conducted. RESULTS： The optimal model with good coincidence， accuracy， validity and reproducibility was obtained， which could better fit the relationship between CQAs and CPPs. The design space and PAR value were obtained by further calculation （The optimum value of diluent was lactose； tablet diameter was 9.07-9.33 mm， and the optimal value was 9.20 mm； ratio of HPMC K4M to HPMC was 0.50-0.83， and the optimal value was 0.80； total amount of HPMC was 0.036 0-0.041 3 g per tablet， and the optimal value was 0.038 g per tablet）. The optimal formulation and technology included that ratio of theophylline， HPMC K4M and HPMC K100M were 50％， 15.48％ and 3.87％， respectively； the rest was filled with lactose and the diameter of the tablet was 9.20 mm. The results of validation confirmed that self-made Theophylline sustained-release tablets had similar in vitro release behavior compared with reference preparation. CONCLUSIONS： Based on the concept of QbD， the formulation and technology of Theophylline sustained-release tablets can meet the requirements of design， and the CPPs can be adjusted within the PAR range to meet the requirements of CQAs. This shows that the QbD concept is scientific and effective in the design and optimization of the formulation and technology of sustained and controlled release preparations.

Quantification of theophylline or paracetamol in milk matrices by high-performance liquid chromatography / 药物分析学报

A simple, accurate and sensitive high-performance liquid chromatography (HPLC) method was developed, validated and applied to the determination of either theophylline or paracetamol in milk-based samples. The method allowed drug quantification in fresh and powdered milk with a relatively short run time of analysis and it was also successfully applied to the quantification of the drugs in solid dosage forms intended for pediatric use. Moreover, the main significant advantages over other published works are the simplicity of the sample preparation, reduced assay time and sample loss. The method meets the International Conference on Harmonization guideline for analytical methods validation regarding specificity,linearity,accuracy,precision, specificity and robustness as required by health authorities and applied by industry while designing and marketing new drug products.The technique encompasses the separation of the analytes with a reverse phase C18column under isocratic conditions and UV detection at 272 nm and 243 nm,respectively,for theophylline and paracetamol. The lower limit of quantification for both drugs was determined as 0.2μg/mL and the between-batch accuracy was 99.7%.This HPLC method allows quantification of theophylline and paracetamol in milk matrices and it can be applied in the design,development and production of milk-based pediatric dosage forms.

Effect of cellulose acetate phthalate and polyethylene glycol on physical properties and release of theophylline from microcapsules

ABSTRACT The present study describes the development of theophylline microcapsules by a non-solvent addition method and the effect of plasticizer addition on microencapsulation. The release was studied in distilled water and the data were analysed by various mathematical models for determining the mechanism of release. Prepared microcapsules were found to be spherical, free flowing and having more than 80% entrapped drug. The polymer - cellulose acetate phthalate and plasticizer - polyethylene glycol was considered to be affecting the properties of microcapsules including drug release (time for 50% drug release, T50). The formulation with the highest proportion of polymer and without plasticizer (F3) showed the slowest release with T50 = 4.3 h, while the formulation with lower proportion of polymer and 20% (w/w) plasticizer (F13 &14) showed the fastest release of drug with T50 values of 1.2 h and 1.3 h, respectively. The drug release from most of the formulations was found to be following Higuchi model. It is concluded from the results of the present study that cellulose acetate phthalate significantly affects the sustained release of the drug in water, whereas the addition of polyethylene glycol slightly enhances the drug release.

RESUMO O presente estudo descreve o desenvolvimento de microcápsulas de teofilina pelo método sem adição de solvente e o efeito da adição de plastificante na microencapsulação. A liberação foi estudada em água destilada e os dados foram analisados por vários modelos matemáticos para determinação do mecanismo de liberação. As microcápsulas preparadas mostraram-se esféricas, livres de corrente e com mais de 80% de fármaco encapsulado. O polímero - ftalato de acetato de celulose e o plastificante - polietileno glicol - afetaram as propriedades das microcápsulas, incluindo a liberação do fármaco (tempo para liberação de 50% do fármaco, T50). A formulação com a maior proporção de polímero e sem plastificante (F3) se mostrou como a de liberação mais lenta, com T50 = 4,3 h, enquanto as formulações com menor proporção de polímero e 20% de plastificante (m/m) (F13 &14) apresentaram a liberação mais rápida do fármaco, com T50 de 1,2 h e 1,3 h, respectivamente. A liberação do fármaco para a maioria das formulações seguiu o modelo de Higuchi. Concluiu-se, dos resultados do presente estudo, que o ftalato do acetato de celulose afeta significativamente a liberação controlada do fármaco em água, enquanto que a adição de polietileno glicol aumenta ligeiramente a liberação do fármaco.

The Effect of Theophylline Retard-20 Tablet for the Treatment of Infantile Asthma / 昆明医科大学学报

Objective To explore the clinical efficacy of theophylline retard-20 tablet in pediatric asthma treatment.Methods From April 2010 to December 2014 in our hospital 136 cases of children with infantile asthma were selected and divided into observation group and control group.Patients in the observation group were treated with sulfate aerosol inhalation therapy,patients in the control group were given oral theophylline retard-20 tablet treatment.After treatment,the treatment results were analyzed.Results In the observation group,functional recovery was found in 37 cases,significant progress in 20 cases,on effect in 11 cases,the total effective rate was 83.82％;Adverse reactions such as pharyngeal discomfort was found in 3 cases,upset stomach in 0 cases,heartburn in 0 cases,the incidence was 4.41％.In the control group,68 functional recovery was found in 19 cases,and remarkable progress in 26 cases,on effect in 23 cases,the total effective rate was 66.18％;Adverse reactions such as pharyngeal discomfort occurred in,4 cases,upset stomach in 3 case,heartburn in 4 cases,the incidence was 14.71％.The effect effective treatment was better than that of control group (P ＜ 0.05),the incidence of adverse reactions in observation group was significantly lower than the control group (P ＜ 0.05).ConcltSior The treatment of infantile asthma with salbutamol sulfate aerosol therapy is very effective and has,clinical significance,is worth further promotion and application.

Clinical observation on the treatment of low-dose oral theophylline in patents with COPD / 中国医师杂志

Objective To investigate the effects of low-dose,sustained release oral theophylline on the chronic obstructive pulmonary disease (COPD) patient.Methods Fifty-six patients with stable COPD were randomly divided into two group:theophylline group (n =35) that was treated with slow-release theophylline(100 mg,twice daily),and control group (n =21) that was given with placebo.A series of parameters including lung function,quality of life scores,body mass index,airflow obstruction,dyspnea,and exercise capacity index (BODE) score,exercise tolerance,exacerbations,satisfaction with treatments and adverse effects were tested before and 12 weeks after the treatments.Results Forty two patients completed the study,25 cases in the slow-release theophylline group,and 17 cases in the placebo group.The differences of two groups before the treatment were not prominent except the age (P ＞ 0.05).After treated with slow-release theophylline,the forced expiratory volume in one second (FEV1),forced vital capacity (FVC) and the symptom score were slightly increased,but there were no statistically significant differences (P ＞0.05).After theophylline therapy,the quality of life score,including activity ability score,disease activity score and total score,and BODE index score were significantly decreased(P ＜0.05),but 6 minutes walk test (6 MWT) differences were no significant (P ＞0.05).The differences in pulmonary function test,the quality of life score,BODE index score and 6 minutes walk test were no significant between before and after the treatment with the placebo (P ＞ 0.05).Compared to the cases who treated with the placebo group,the patients in slow-release theophylline group reduced the frequencies of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) (3/25 vs 7/17,x2 =4.748,P ＜0.05),and increased the efficacy satisfaction (Z =-2.579,P ＜ 0.05).Slightly adverse reaction was observed in 3 cases in slow-release theophylline group,but it could relieve by oneself,and not affect the common treatment.There was no adverse reaction in the placebo group.Conclusions Low dose,sustained release oral theophylline was efficient in improvement of the quality of life scores and BODE index score.

Effects of low-dose of oral thephylline on sputum inflammatory cells and inflammatory mediators in patients with COPD / 中国医师杂志

Objective To investigate the anti-inflammatory effects of low-dose and sustained release oral theophylline on the chronic obstructive pulmonary disease (COPD) patients.Methods Thirty four patients with stable COPD were randomly divided into two groups:theophylline group (n =18) was treated with slow-release theophylline (100 mg,twice daily),and placebo group (n =16) was given with placebo.Healthy non-smokers (n =12) were taken as control.The course of treatment was 12 weeks both of theophylline group and placebo group.The percentages of Neu/Leu and Mφ/Leu in sputum were detected before and after treatment and the concentrations of interleukin (IL)-17,IL-8,and tumor necrosis factor-α (TNF-et) were detected with enzyme linked immunosobent assay (ELISA).Results (1) Compared to pretreatment with theophylline group,the Neu/Leu was increased [(89 ±4.14)％ vs (83.4 ±6.98)％,P ＜0.05] and the Mφ/Leu was decreased [(6.4 ± 4.11) ％ vs (12.3 ± 6.96) ％,P ＜ 0.05] in the post-treated theophylline group.No significant changes in both Neu/Leu and Mφ/Leu were observed before and after placebo-treatment (P ＞ 0.05).(2) Compared to the control group,the concentrations of TNF-α,IL-8,and IL-17 in the sputum supernatant were significantly increased in both pretreatment and posttreatment with the theophylline or the placebo.Sputum TNF-α,IL-8,and IL-17 levels were significantly decreased in COPD patients who were given theophylline.Compared to pre-treatment with placebo group,the IL-8 and IL-17 levels were significantly increased in the post-treated placebo group (P ＜0.01).There was no significant change in TNF~ level between before and after treatment with the placebo.(3) The concentrations of IL-17,IL-8,and TNF-α in the sputum supernatant were positively correlated with the Neu/Leu counts (r =0.471,0.652,0.466,respectively,all P ＜0.01),negatively correlated with the forced expiratory volume in one second (FEV1 ％) (r =-0.516,-0.652,-0.496,respectively,all P ＜ 0.01).Conclusions Low-dose and sustained-release oral theophylline was efficient in improving airway inflammatory cells and inflammatory mediators,which plays an anti-inflammatory effect.

Clinical efficacy of theophylline combined with tiotropium dry powder in the treatment of stably chronic ;obstructive pulmonary disease / 中国基层医药

Objective To study the clinical efficacy of theophylline combined with tiotropium dry powder in the treatment of stably chronic obstructive pulmonary disease (COPD).Methods 140 patients with stable COPD were divided into the study group and control group according to the random number table method,70 patients in each group.The control group was treated with theophylline,while the study group was treated with theophylline combined with tiotropium dry powder.The quality of life was evaluated by quality of life scale(QLC),the exercise tolerance was estimated by 6min walk distance(6MWD),and the forced expiratory volume in one second(FEV1 ),FEV1 /forced vital capacity(FVC),matrix metalloproteinase enzyme -9(MMP -9)and interleukin -8(IL -8)were detected in two groups before and after treatment.The adverse reactions of two groups were compared.Results After treatment, FEV1 ,FEV1 /FVC of the two groups were (1.49 ±0.04)L,(3.21 ±56.02)% and (1.89 ±0.21 )L,(59.98 ± 2.09)% respectively,which were significantly better than before treatment(t =7.98,9.03,8.03,8.32,all P 0.05).Conclusion Theophylline combined with tiotropium dry powder has an exact efficacy in the treatment of stable COPD,which can improve the lung function and the quality of life of patients.

Analysis of the imprecision of internal quality control of therapeutic drug monitoring in serum(carbamazepine, digoxin, phenytoin, theophylline and valproic acid) in China, 2014 / 国际药学研究杂志

Objective To investigate the coefficient of variations(CV) of internal quality control(IQC) of therapeutic drug monitoring in serum (carbamazepine, digoxin, phenytoin, theophylline and valproic acid), and compare with the quality specification derived from allowable total error (TEa). Methods Data was collected by Web-based submission system, the 175 laboratories which enrolled in 2014 therapeutic drug monitoring in serum external quality assessment (EQA) program attended. The data included: the CV of February of 2014 and long-term cumulative data, method and instrument, etc. Microsoft Excel 2013 and SPSS 13.0 was used to analyze the data.The evaluation standard of EQA was considered as TEa(25%and 20% for digoxin). 1/3TEa (8.33% and 6.67% for digoxin) and 1/4TEa (6.25% and 5% for digoxin)were determined to be the evaluation standard of CV of IQC. Results From 175 laborctories 94, 97, 61, 43 and 116 laboratories reported effective results of IQC material of carbamazepine, digoxin, phenytoin, theophylline and valproic acib, respectively. More than 60% laboratories used Bio-Rad measurement system(63.93%-76.29%). Less than 40%laboratories used other measurement systems(23.71%-36.07%). There were significant differences (P<0.05) of the acceptable rates of CV between test items (χ2: 10.689-19.255, P<0.05). There was no significant difference of the acceptable rate of CV between different measurement systems except valproic acid evaluated by 1/3TEa (P<0.05). Conclusion It is an effective method for clinical laboratories to improve test quality by monitoring the current and cumulative CV of IQC and comparing them against proper evaluation criteria to evaluate if the analysis system can meet specific quality requirements or technical specification.