Polyvinyl alcohol is one of the most widely used embolic agents for BAE as it presents several advantages including high cost-effective, diversity of embolic size depending on offending vessels, easy to handle, durable, etc., meanwhile, the efficacy of BAE with PVA in controlling hemoptysis has been illustrated by enormous evidence before [7, 9, 12, 14, 21]. For example, a retrospective study indicates that BAE with PVA is utilized in the treatment of 334 hemoptysis patients who presents with the most common etiology of pulmonary tuberculosis with technical success rate of 90.7%, and 6.5% procedures were repeated within two months due to technical or clinical failures . Furthermore, another study exhibits that the immediate success rate is achieved in 86% patients, and during the 5-year follow-up, the recurrence rate of hemoptysis was 28% and mortality was 22% in patients who receives BAE using PVA for hemoptysis . As for microspheres, they are compressible hydrogel with several advantages including out-standing biocompatibility, resistance to aggregate, satisfied elasticity, and are applied for the embolization in various arteriovenous, including uterine artery, prostatic artery, for treatment of several diseases [16, 17, 24, 25]. For example, microspheres exhibits greater ability in improving prostatic volume reduction and peak urinary flow compared with non-spherical PVA particles for prostatic artery embolization treatment in patients with lower urinary tracts symptoms . However, its application in BAE treatment for hemoptysis was limited, therefore we explored the treatment efficacy and safety profiles of BAE with microspheres in hemoptysis patients.
According to previous study, the technical and clinical success rates of BAE using PVA in patients with hemoptysis are reported to be 77–100% and 85–99% respectively [7, 14]. In our study, for BAE treatment with PVA, the technical success rate of 100% observed was within the reported range before, while the clinical success rate of 100% was a little above the reported rage before, which might be due to relatively small sample size [7, 14]. In addition, there was no difference of clinical success rate (96.8 vs. 100.0%) between microspheres and PVA groups, which suggested that microspheres presented similar immediate effect on controlling hemoptysis as PVA. The possible reasons might include that (1) The short-term good efficacy of BAE using PVA or microspheres in our study might be attributed to the CTBA evaluation prior to BAE as the regular protocol, which increased the accuracy of identification in the bleeding sources and underlying cause of hemorrhage [3, 4]; (2) Furthermore, the majority of patients presented with mild-to-moderate hemoptysis, thereby decreasing the risk of failure to cannulate the bronchial artery or to facilitate a stable catheter position, which led to technical success rate of both 100% as well as similar clinical success between two groups [5, 26]; (3) In addition, considering that microspheres and PVA were made of the same embolic material and of the same size, these two embolic agents therefore displayed similar technical and clinical success rate [14, 27]. Of note, we found that offending vessels of left bronchial artery rather than right bronchial artery (vs. bilateral bronchial artery) was also an independent predictive factor for increased hemoptysis recurrence risk or mortality risk, which might be explained by that different anatomical structure. Anatomically, left BA is narrower and longer than right BA, which might increase the failure to identify culprit vessels and therefore enhance hemoptysis recurrence risk and mortality risk . Furthermore, interestingly, we found that hemoptysis volume were independent predictive factors for increased hemoptysis recurrence risk or mortality risk, which might be associated with the difficulty of bleed controlling and unstable hemodynamics, increasing hemoptysis recurrence risk .
In our study, 6-month (PVA vs. microspheres: 9.7% vs. 7.8%) and 1-year (PVA vs. microspheres: 9.7% vs. 8.9%) hemoptysis recurrence rates were similar between BAE using microspheres and BAE using PVA. The incidences of hemoptysis recurrence in our study were a little reduced compared with the data in previous studies, which reported that the hemoptysis-recurrence rate after BAE was estimated to be 10–29% [7, 26]. The possible explanations might include (1) the relatively short follow-up in our study, (2) the exclusion of the patients with lung cancer, which was correlated with a great high likelihood of bleeding recurrence [29, 30]. Furthermore, according to the previous evidence, PVA presented increased aggregation compared with microspheres, which might lead to premature embolization proximal to the intended vascular level, further contributing to higher risk of long-term hemoptysis recurrence rate . However, we did not observe the increased hemoptysis recurrence rate in PVA compared with microspheres in our study, which might be due to relatively small sample size and insufficient follow-up. Furthermore, based on existing evidence, the main causes of recurrent hemoptysis consisted of incomplete embolization of the vessels, revascularization of the collateral circulation or progression of the underlying pulmonary disease rather than embolic agents used, which might explain that microspheres displayed similar hemoptysis recurrence rates as PVA . In addition, 6-month and 1-year mortality were also similar between PVA and microspheres in hemoptysis patients. The possible reasons include that (1) considering the prior data, PVA presented similar hemoptysis recurrence rate compared to microspheres, thereby contributing to the similar hemoptysis-related mortality between PVA and microspheres as well; (2) Based on the previous study, the primary cause for mortality after the treatment of BAE was the underlying progression of disease, and meanwhile considering the similar mechanism and short-term treatment efficacy between PVA and microspheres, therefore, BAE using PVA presented similar mortality to BAE using microspheres. In addition, no correlation of embolic agents with hemoptysis recurrence, mortality, hemoptysis-free survival and overall survival was further validated in multivariate logistic regression analysis. Moreover, further subgroup analysis revealed that there was no difference of clinical success rate, hemoptysis recurrence rate, morality, overall survival between PVA and microspheres in subgroup of bronchiectasis patients and patients with other etiologies, while hemoptysis-free survival was increased in patients receiving BAE using PVA compared with patients receiving BAE using microspheres in subgroup of patients with other etiologies, which might be attributed to the relatively small sample size.
As for adverse events, there was no difference of adverse event incidence between BAE using PVA and BAE using microspheres, and main adverse events were relatively minor and well-tolerated (including cough/expectoration, fever, chest discomfort, nausea/vomiting, abdominal pain, poor appetite and fatigue, ecchymosis at the puncture site, and allergy as well as dyspnea). Theses minor adverse events were common in BAE procedures, which was in accordance with the observation in previous studies . Possible explanations for the lack of major complications included that (1) The size of PVA and microspheres were both 300–500 μm in diameter, which could fit with pulmonary artery and avoid distal occlusion of normal peripheral branches, decreasing the possibility of some major complications (such as: esophageal, bronchial, pulmonary artery necrosis) caused by ischemia ; (2) Furthermore, with the help of routine CTBA evaluation before BAE combined with angiography during procedure, the spinal collaterals were clearly identified, which decreased the possibility of off-target embolization of the spinal artery as well as the risk of BAE-related neurologic complications . Furthermore, considering the comparative cost-efficacy, microsphere (CNY1600/bottle) was cheaper than PVA (CNY1710/bottle), it was more reasonable to use microsphere rather than PVA.
Our study filled the gap to assess the efficacy and safety profile of Chinese local microspheres and further to compare its efficacy and safety with frequently-used PVA for BAE treatment in hemoptysis patients, which observed that microspheres presented similar efficacy on controlling hemoptysis and safety profile as PVA. Meanwhile, considering the more favorable cost of microspheres compared with PVA, the evidence suggested that microsphere might be an alternative option to PVA in BAE treatment. However, the present study still existed some limitations including (1) the sample size was relatively small in our study, which might lead to less statistical validation, more patients from multiple centers were needed for validation; (2) Longer follow-up was needed to observe the adverse events in hemoptysis patients underwent BAE; (3) The majority of patients included were with mild-to-moderate hemoptysis, therefore, more studies were necessary for extending our results in the treatment of massive hemoptysis [5, 26]; (4) As this present study was an observational study, the patients enrolled in our study were not randomized into two groups, which might contribute to selection bias and confounding factors in present study.
In conclusion, BAE with microspheres presents comparable efficacy and safety profiles compared with BAE with PVA for the treatment of hemoptysis, therefore, microspheres may serve as an alternative embolic agent in hemoptysis management.