Efficacy and safety of inhaled heparin in asthmatic and chronic obstructive pulmonary disease patients: a systematic review and a meta-analysis.

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.