Department of Clinical Research, Maamora Chest Hospital, MoHP, Alexandria, Egypt.
Department of Biomedical Informatics and Medical Statistics, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Sci Rep. 2023 Aug 16;13(1):13326. doi: 10.1038/s41598-023-40489-8.
Asthma and chronic obstructive pulmonary disease (COPD) are prevalent chronic respiratory disorders that cause significant morbidity and mortality. Some studies evaluated the use of inhaled unfractionated heparin (UFH) in the treatment of asthma and COPD. We aimed to synthesize the available evidence for the efficacy and safety of inhaled heparin in improving lung functions among asthmatic and COPD patients. A comprehensive search was performed using Pubmed, Embase, EBSCO, Scopus, Web of Science, Cochrane CENTRAL, WHO Clinical trials, clinicaltrials.gov, Iranian Clinical trials, Google Scholar, Research Gate, ProQuest Thesis, OVID, and medRxiv databases. Two independent reviewers included all pertinent articles according to PRISMA guidelines, and extract data independently. The two reviewers checked the quality of studies using the ROB2 tool. To determine the pooled effect estimate of the efficacy and safety of inhaled heparin, a meta-analysis was carried out using the R programming language. Publication bias was evaluated using Egger's regression test. The heterogeneity was explained using a meta-regression, and the quality of evidence was assessed by the GRADE approach. Twenty-six studies with a total of 581 patients were included in the qualitative analysis and 16 in the meta-analysis. The primary outcome was treatment success (improvement of lung function) that was measured by standardized mean differences (SMD) of the forced expiratory volume per second (FEV1) either per ml or percentage. Heparin has a large effect on both FEV1% and FEV1 ml when compared to the control group (SMD 2.7, 95% CI 1.00; 4.39; GRADE high, SMD 2.12, 95% CI - 1.49; 5.72: GRADE moderate, respectively). Secondary outcomes are other lung functions improving parameters such as PC20 (SMD 0.91, 95% CI - 0.15; 1.96). Meta-regression and subgroup analysis show that heparin type, dose, year of publication, study design, and quality of studies had a substantial effect. Regarding safety, inhaled heparin showed a good coagulation profile and mild tolerable side effects. Inhaled heparin showed improvement in lung functions either alone or when added to standard care. More large parallel RCTs are needed including COPD patients, children, and other types, and stages of asthmatic patients.
哮喘和慢性阻塞性肺疾病（COPD）是常见的慢性呼吸道疾病，可导致严重的发病率和死亡率。一些研究评估了吸入未分级肝素（UFH）在哮喘和 COPD 治疗中的作用。我们旨在综合评估吸入肝素改善哮喘和 COPD 患者肺功能的疗效和安全性。使用 Pubmed、Embase、EBSCO、Scopus、Web of Science、Cochrane 中央、世界卫生组织临床试验、clinicaltrials.gov、伊朗临床试验、Google Scholar、Research Gate、ProQuest 论文、OVID 和 medRxiv 数据库进行全面检索。两名独立审查员根据 PRISMA 指南纳入所有相关文章，并独立提取数据。两名审查员使用 ROB2 工具检查研究质量。为了确定吸入肝素治疗的疗效和安全性的汇总效果估计，使用 R 编程语言进行了荟萃分析。使用 Egger 回归检验评估发表偏倚。使用元回归解释异质性，并使用 GRADE 方法评估证据质量。定性分析纳入 26 项研究，共 581 例患者，荟萃分析纳入 16 项研究。主要结局是治疗成功（肺功能改善），通过每秒用力呼气量（FEV1）的标准化均数差（SMD）来衡量，FEV1 以毫升或百分比表示。肝素与对照组相比，对 FEV1%和 FEV1 毫升均有较大影响（SMD 2.7，95%CI 1.00；4.39；GRADE 高，SMD 2.12，95%CI -1.49；5.72：GRADE 中）。次要结局是其他改善肺功能的参数，如 PC20（SMD 0.91，95%CI -0.15；1.96）。元回归和亚组分析表明，肝素类型、剂量、发表年份、研究设计和研究质量有显著影响。关于安全性，吸入肝素显示出良好的凝血谱和轻微可耐受的副作用。吸入肝素单独使用或联合标准治疗均可改善肺功能。需要更多的大型平行 RCT 纳入 COPD 患者、儿童和其他类型和阶段的哮喘患者。
