scholarly journals Efficacy and safety profile of doxofylline compared to theophylline in asthma: a meta-analysis

2019 ◽  
Vol 14 ◽  
Author(s):  
Paola Rogliani ◽  
Luigino Calzetta ◽  
Josuel Ora ◽  
Mario Cazzola ◽  
Maria Gabriella Matera

Background: Oral methylxanthines are effective drugs for the treatment of chronic obstructive respiratory disorders. The novel methylxanthine doxofylline, that has bronchodilator and anti-inflammatory activities, is not affected by the major drawback of theophylline. Nowadays large-scale quantitative synthesis comparing the efficacy and safety profile of doxofylline vs. theophylline in the treatment of asthma is still lacking. Therefore, we performed a quantitative synthesis to compare the efficacy/safety profile of doxofylline and theophylline in asthma. Methods: A pairwise and network meta-analyses were performed to assess the impact of doxofylline vs. theophylline and placebo on the change in asthma events, risk of adverse events (AEs), forced expiratory volume in 1 s (FEV1), and salbutamol use. Results: Data obtained from 696 asthmatic patients were extracted from 4 randomized controlled trials published between 2015 and 2018. Doxofylline was significantly (P < 0.05) more effective than theophylline in reducing the daily asthma events (mean difference − 0.14, 95%CI -0.27 – 0.00) and risk of AEs (relative risk 0.76, 95%CI 0.59–0.99). Doxofylline was as effective as theophylline in improving FEV1, and a trend of superiority (P = 0.058) was detected for doxofylline over theophylline with respect to the reduction in the use of salbutamol as rescue medication. The rank of effectiveness was doxofylline>theophylline> > placebo, and the rank of safety was placebo>doxofylline> > theophylline. Conclusions: Doxofylline is an effective and safe methylxanthine for the treatment of asthma, with an efficacy/ safety profile greater than that of theophylline. Trial registration: Meta-analysis registration: CRD42019119849.

2018 ◽  
Vol 27 (148) ◽  
pp. 180010 ◽  
Author(s):  
Mario Cazzola ◽  
Luigino Calzetta ◽  
Peter J. Barnes ◽  
Gerard J. Criner ◽  
Fernando J. Martinez ◽  
...  

Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile than theophylline. Therefore, we performed a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD.The primary end-point of this meta-analysis was the impact of xanthines on lung function. In addition, we assessed the risk of adverse events by normalising data on safety as a function of person-weeks. Data obtained from 998 COPD patients were selected from 14 studies and meta-analysed using a network approach.The combined surface under the cumulative ranking curve (SUCRA) analysis of efficacy (change from baseline in forced expiratory volume in 1 s) and safety (risk of adverse events) showed that doxofylline was superior to aminophylline (comparable efficacy and significantly better safety), bamiphylline (significantly better efficacy and comparable safety), and theophylline (comparable efficacy and significantly better safety).Considering the overall efficacy/safety profile of the investigated agents, the results of this quantitative synthesis suggest that doxofylline seems to be the best xanthine for the treatment of COPD.


2021 ◽  
Vol 10 (2) ◽  
pp. 269
Author(s):  
Elisabetta Zinellu ◽  
Alessandro G. Fois ◽  
Elisabetta Sotgiu ◽  
Sabrina Mellino ◽  
Arduino A. Mangoni ◽  
...  

Background: Chronic obstructive pulmonary disease (COPD) is a progressive condition characterized by chronic airway inflammation and lung parenchyma damage. Systemic inflammation and oxidative stress also play a role in the pathogenesis of COPD. Serum albumin is a negative acute-phase protein with antioxidant effects and an important marker of malnutrition. The aim of this meta-analysis was to investigate differences in serum albumin concentrations between patients with stable COPD and non-COPD subjects. Methods: A systematic search was conducted, using the terms “albumin” and “chronic obstructive pulmonary disease” or “COPD”, in the electronic databases PubMed and Web of Science, from inception to May 2020. Results: Twenty-six studies were identified on a total of 2554 COPD patients and 2055 non-COPD controls. Pooled results showed that serum albumin concentrations were significantly lower in COPD patients (standard mean difference, SMD = −0.50, 95% CI −0.67 to −0.32; p < 0.001). No significant differences were observed in SMD of serum albumin concentrations between COPD patients with forced expiratory volume in the 1st second (FEV1) < 50% and those with FEV1 > 50%. Conclusions: Our systematic review and meta-analysis showed that serum albumin concentrations are significantly lower in patients with stable COPD compared to non-COPD controls. This supports the presence of a deficit in systemic anti-inflammatory and antioxidant defense mechanisms in COPD.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yaping Wang ◽  
Bin Liu ◽  
Xiuqiong Fu ◽  
Tiejun Tong ◽  
Zhiling Yu

Abstract Background The traditional Chinese medicine formula Si-Jun-Zi-Tang (SJZT) has a long history of application in the treatment of functional dyspepsia (non-ulcer dyspepsia, FD)-like symptoms. SJZT-based therapies have been claimed to be beneficial in managing FD. This study aimed to assess the efficacy and safety of SJZT-based therapies in treating FD by meta-analysis. Methods Systematic searches for RCTs were conducted in seven databases (up to February 2019) without language restrictions. Data were analyzed using Cochrane RevMan software version 5.3.0 and Stata software version 13.1, and reported as relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs). The primary outcome was response rate and the secondary outcomes were gastric emptying, quality of life, adverse effects and relapse rate. The quality of evidence was evaluated according to criteria from the Cochrane risk of bias. Results A total of 341 potentially relevant publications were identified, and 12 RCTs were eligible for inclusion. For the response rate, there was a statically significant benefit in favor of SJZT-based therapies (RR = 1.23; 95% CI 1.17 to 1.30). However, the benefit was limited to modified SJZT (MSJZT). The relapse rate of FD patients received SJZT-based therapies was lower than that of patients who received conventional medicines (OR = 0.23; 95% CI 0.10 to 0.51). No SJZT-based therapies-related adverse effect was reported. Conclusion SJZT-based prescriptions may be effective in treating FD and no serious side-effects were identified, but the effect on response rate appeared to be limited to MSJZT. The results should be interpreted with caution as all the included studies were considered at a high risk of bias. Standardized, large-scale and strictly designed RCTs are needed to further validate the benefits of SJZT-based therapies for FD management. Trial registration Systematic review registration: [PROSPERO registration: CRD42019139136].


2019 ◽  
Author(s):  
Jinping Zheng ◽  
Nanshan Zhong ◽  
Changzheng Wang ◽  
Li Ping Wei ◽  
Xiang Dong Zhou ◽  
...  

Abstract Background In the Phase III InforMing the PAthway of COPD Treatment (IMPACT) trial, fluticasone furoate [FF]/umeclidinium [UMEC]/vilanterol [VI] single-inhaler triple therapy resulted in lower rates of moderate/severe exacerbations than dual therapy with FF/VI or UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease (COPD) and a history of exacerbations. Here we present the result in the subpopulation of patients enrolled in China. Methods The IMPACT trial was a 52-week, randomized, double-blind, parallel-group, multicenter trial. Patients (≥40 years of age) with COPD and ≥1 moderate/severe exacerbations in the prior year were randomized 2:2:1 to once-daily FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg administered via the Ellipta inhaler. Endpoints, assessed in the overall intent-to-treat (ITT) population and in patients from China, included annual rates of exacerbations, time-to-first on-treatment moderate/severe exacerbation, and change from baseline in trough forced expiratory volume in 1 second (FEV1) at Week 52. Results Of the 10,355 patients randomized, 535 (5.2%) were from China. In the China cohort, the rate of on-treatment moderate/severe exacerbations was 0.81 per year with FF/UMEC/VI versus 0.96 with FF/VI (rate ratio [RR]: 0.84; 95% confidence interval [CI]: 0.64, 1.11; p=0.227) and 0.80 with UMEC/VI (RR: 1.02; 95% CI: 0.72, 1.44; p=0.929). Hazard ratio for time-to-first moderate/severe exacerbation was 0.84 (95% CI: 0.63, 1.11; p=0.218) for FF/UMEC/VI versus FF/VI, and 0.89 (95% CI: 0.62, 1.27; p=0.516) for FF/UMEC/VI versus UMEC/VI. Improvements in mean change from baseline in trough FEV1 were observed for FF/UMEC/VI versus FF/VI (treatment difference 137 mL; 95% CI: 86, 188; p<0.001) and FF/UMEC/VI versus UMEC/VI (treatment difference 63 mL; 95% CI: 0, 125; p=0.0.050) in China. Health status was also improved with FF/UMEC/VI versus both dual therapies. Broadly, these results were in the same direction as those seen in the overall ITT population. No new safety signals were identified. Conclusions In the China cohort of the IMPACT trial, single-inhaler triple therapy with FF/UMEC/VI versus dual therapy with FF/VI or UMEC/VI reduced the rate and risk of exacerbations, and improved lung function and quality of life similar to the overall ITT population. Trial registration: NCT02164513 (GSK study number CTT116855).


2021 ◽  
pp. 1-14
Author(s):  
Mi Su ◽  
Yongyan Song

<b><i>Background:</i></b> Genetic factors were suggested to have influence on the development of post-traumatic stress disorder (PTSD). The possible association between catechol-O-methyltransferase (<i>COMT</i>) Val158Met polymorphism and PTSD has been evaluated in several studies. But the results were still controversial. Therefore, we conduct this meta-analysis to address these issues. <b><i>Methods:</i></b> The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched for eligible studies. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to estimate the association between <i>COMT</i> Val158Met polymorphism and PTSD. <b><i>Results:</i></b> Five articles including 6 studies with 893 cases and 968 controls were finally included in the present meta-analysis. The pooled analyses did not demonstrate a significant association between the <i>COMT</i> Val158Met polymorphism and PTSD in any of the selected genetic models: allele model (OR = 1.13, 95% CI: 0.97–1.31), dominant model (OR = 1.17, 95% CI: 0.93–1.46), recessive model (OR = 1.44, 95% CI: 0.78–2.66), and additive model (OR = 1.54, 95% CI: 0.85–2.80). Subgroup analyses suggested that the Hardy-Weinberg equilibrium status of genotype distributions could influence the relationship of <i>COMT</i> Val158Met polymorphism and PTSD. <b><i>Conclusions:</i></b> The present meta-analysis suggested that the <i>COMT</i> Val158Met polymorphism may not be associated with the PTSD risk. Further large-scale and population-representative studies are warranted to evaluate the impact of the <i>COMT</i> Val158Met polymorphism on the risk of PTSD.


2020 ◽  
Vol 54 (12) ◽  
pp. 1232-1242
Author(s):  
Melissa Lipari ◽  
Pramodini B. Kale-Pradhan ◽  
Sheila M. Wilhelm

Background: Chronic obstructive pulmonary disease (COPD) guidelines recommend both long-acting and dual bronchodilator therapy. It is unclear if there are differences in efficacy and safety. Objective: This meta-analysis evaluates the efficacy of dual therapy with long-acting β-agonist (LABA) + long acting muscarinic antagonist (LAMA) compared with monotherapy with LAMA for COPD. Methods: We searched PubMed, CINAHL, and Web of Science databases from inception through March 2020 to identify English-language, prospective randomized controlled trials (RCTs) that compared dual therapy with monotherapy in adult patients with COPD. Risk of bias was assessed using the Jadad score. Overall analysis was performed using Review Manager 5.3. Treatment effect was determined with the random-effects model using the Mantel-Haenszel method and was reported as mean difference (MD) with 95% CI. Results: A total of 18 RCTs were included (n = 6086; median Jadad score 5/5) that compared LAMA + LABA with LAMA. There was a greater improvement in forced expiratory volume at 1 s (FEV1) with dual therapy compared with LAMA: MD = 0.08; 95% CI = [0.05, 0.11]. There was no difference in St George Respiratory Questionnaire (SGRQ) scores between groups: OR = −0.85; 95% CI = [−1.83, 0.13]. There were no differences in overall adverse events (OR = 1.00; 95% CI = 0.92, 1.09), serious adverse events (OR = 1.01; 95% CI = 0.86, 1.18), or cardiovascular events (OR = 0.88; 95% CI = 0.58, 1.34). Conclusion and Relevance: Dual therapy improves FEV1 and is as safe as LAMA. Dual therapy does not improve SGRQ scores more than LAMA.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S443-S443
Author(s):  
Sandra Varey ◽  
Mandy Dixon ◽  
Alejandra Hernandez ◽  
Ceu Mateus ◽  
Tom Palmer ◽  
...  

Abstract Ways to address the increasing healthcare needs of older people are a priority for the National Health Service (NHS) in England. The NHS England Test Bed programme was designed to trial new models of care that are supported by digital health technologies. This paper reports on findings from one Test Bed programme, the Lancashire and Cumbria Innovation Alliance (LCIA) – a partnership between NHS England, industry and Lancaster University, which ran from 2016 to 2018. A key aim of the LCIA Test Bed was to explore the extent to which supported self-care telehealth technology helped older people with long-term conditions to better self-manage their own care, promoting independence and enabling them to remain at home for longer. Each patient received a combination of health technologies over a six-month period. This paper presents results from the qualitative data that formed part of a large-scale mixed-methods evaluation. Specifically it draws on the analysis of 34 observational interviews with 17 participants with chronic obstructive pulmonary disease (COPD) to understand the role of these technologies in the self-management of their care. The data revealed that the majority of participants felt more confident about self-managing COPD as a result of their participation in the programme. These increases in confidence were the result of participants’ increased knowledge and skills in managing their COPD. The paper demonstrates how patients learned to better manage their respiratory condition, the impact of this learning on their daily lives and that of their family carers, and the implications for healthcare practice.


2019 ◽  
Vol 16 ◽  
pp. 147997311989485 ◽  
Author(s):  
Lok Sze Katrina Li ◽  
Stacey Butler ◽  
Roger Goldstein ◽  
Dina Brooks

To systematically review randomized controlled trials that compared the effectiveness of different types of exercise on the symptom of fatigue in individuals with chronic obstructive pulmonary disease (COPD). MEDLINE, EMBASE, EMcare, PsychINFO, and Cochrane library were searched from inception to October 2018. Studies were included if individuals with COPD were randomized into two or more physical exercise interventions that reported fatigue. Of the 395 full-texts reviewed, 17 studies were included. Fifteen studies reported the impact of exercise on health-related quality of life with fatigue as a subdomain. Reduction in fatigue was observed following endurance, resistance, or a combination of both exercises. There was no significant difference between continuous and interval training ( n = 3 studies, pooled standardized mean difference (SMD) = −0.17, 95% CI = −0.47, 0.12, p = 0.25) or between endurance and resistance training ( n = 3 studies, SMD = −0.35, 95% CI = −0.72, 0.01, p = 0.07) on fatigue in people with COPD. Fatigue reduction is not usually a primary outcome of exercise interventions, but it is frequently a secondary domain. The type of exercise did not influence the impact of exercise on fatigue, which was reduced in endurance, resistance, or a combination of both exercises, enabling clinicians to personalize training to match targeted outcomes.


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