Silver nitrate versus histoacryl in bronchoscopic lung volume reduction
Ahmed Y Shaaban1, Hany M Shaarawy1, Ahmed M Abdelhady1, Mohanad M.H Abbas2
1 Department of Chest Diseases, Faculty of Medicine, Alexandria University, Alexandria, Egypt
2 Department of Chest Diseases, Sporting Students Hospital, Alexandria, Egypt
Correspondence Address:
PhD Ahmed M Abdelhady
Department of Chest Diseases, Faculty of Medicine, Alexandria University, 23, Abdelmonaem Aldaleel Street, Tharwat, Alexandria, 5451104
Egypt
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/ejcdt.ejcdt_46_20
Context It is reported that chronic obstructive pulmonary disease (COPD) has a prevalence of 251 million cases worldwide in 2016. Where medical treatment failed to control or insufficiently control symptoms, and when surgical treatments are contraindicated, bronchoscopic lung volume reduction (BLVR) is considered the last option for patients with different types of severe emphysema. Sclerosing agents, such as vapor ablation or sealants, can be used.
Aim To compare between silver nitrate and N-butyl cyanoacrylate (histoacryl) in BLVR.
Settings and design In this randomized prospective interventional study, we recruited 24 patients with COPD from the Chest Department, Alexandria Main University Hospital, having homogenous or heterogonous emphysema and complaining of severe symptoms despite optimized medical treatment, and they were divided into group I, including 12 patients subjected to BLVRS using silver nitrate, and group II, including 12 patients subjected to BLVRS using histoacryl.
Patients and methods Five parameters, namely, forced expiratory volume in 1 s, 5-min walk test, modified Medical Research Council, COPD assessment test score, and Saint George’s respiratory questionnaire were collected, compared, and statistically analyzed for both groups preoperatively and 12 weeks postoperatively.
Results There were statistically significant improvements in all studied outcomes on postoperative follow-up of both groups. The only statistically significant difference between both groups was in the postoperative Saint George’s respiratory questionnaire, which was slightly better in the silver nitrate arm. None of the major complications occurred in any of the patients.
Conclusion Both silver nitrate and histoacryl show promising results in improving patients with refractory COPD. Although both agents have nearly similar results, silver nitrate is much affordable and easier to use.
Keywords: chronic obstructive pulmonary disease, histoacryl, silver nitrate, volume reduction
It is reported that chronic obstructive pulmonary disease (COPD) has a prevalence of 251 million cases worldwide in 2016. It is also responsible for ∼3.17 million deaths in 2015 (i.e. 5% of all deaths globally in that year) [1]. Where medical treatment failed to control or insufficiently control symptoms, and when surgical treatments are contraindicated, bronchoscopic lung volume reduction (BLVR) is considered the last option for patients with different types of severe emphysema [2].
Over the past decade, many ‘blocking’ and ‘nonblocking’ techniques have been used to control the variable emphysematous distortions. Blocking techniques use unidirectional valves to collapse a single lobe. This treatment is considered highly effective and reversible, although it is only used in the absence of collateral ventilation. In patients who do not qualify for these methods, nonblocking techniques using coils or sclerosing agents, such as vapor ablation or sealants, can be used also [3],[4],[5]. Histoacryl consists of N-butyl-2-cyanoacrylate. This is a sterile, liquid topical skin adhesive that polymerizes in seconds upon being exposed to water or water-containing substances like human tissue [6],[7]. In contrast, silver nitrate is caustic and was being used as an effective antiseptic solution or as stick to remove warts and to cauterize wounds [8]. We aimed to compare silver nitrate versus N-butyl histoacryl in BLVR regarding efficacy and complications.
Patients and methodsIn this randomized prospective interventional study, we recruited 24 patients with COPD from the Chest Department, Alexandria Main University Hospital, with the inclusion criteria of having homogenous or heterogonous emphysema and complaining of severe symptoms despite optimized medical treatment. Patients with any associated pulmonary conditions such as bronchiectasis and pulmonary fibrosis in addition to those having any contraindication to bronchoscopy procedure (e.g. recent cardiac events, noncorrected hypoxemia, and severe bleeding disorders) were excluded. In all procedures, we strictly followed the faculty ethics committee standards, and a written informed consent was taken from each patient.
The patients were divided randomly by sealed envelope-method into two groups: group I included 12 patients who were subjected to BLVRS using silver nitrate, and group II also included 12 patients who were subjected to BLVRS using histoacryl. Spirometry (forced vital capacity technique), 6-min walk test (6MWT), in addition to answering three translated and printed symptomatology questionnaires [modified British Medical Research Council questionnaire (mMRC), COPD assessment test (CAT), and Saint George’s respiratory questionnaire (SGRQ)], were done for all the patients before and 12 weeks after the procedure. Silver nitrate was commercially prepared, after explaining the purpose of usage, using distilled water for dilution with concentration of 2%. Histoacryl was prepared and diluted just before its usage using normal saline with ratio of 1–5 and was applied as fast as possible, owing to it being highly adhesive. The operator chose the target segment for applying the sealant agent according to which segment was mostly distorted in the preoperative computed tomography, and up to two segments in one lung or three segments in both lungs were chosen. Instillation was continued until seeing the bronchial lumen fully sealed. If any of the sealant material was poured outside the targeted segments, it was suctioned as soon as possible before sticking to the wall. Monitoring was continued after the procedure for possible complications, which may be major life-threatening (cardiorespiratory arrest, respiratory failure requiring mechanical ventilation, shock, pneumonia, pneumothorax, arrhythmias, and pulmonary edema) or minor nonlife-threatening (COPD exacerbation, hypoxia, vasovagal reactions, laryngospasm, bronchospasms, fever, hemorrhage, nausea, and vomiting) events.
The Kolmogorov–Smirnov test was used to verify the normality of distribution. Quantitative data were described using mean±SD. Significance of the obtained results was judged at the 5% level. The used tests were Student t test for normally distributed quantitative variables, to compare between two studied groups; paired t test for normally distributed quantitative variables, to compare between two periods; Mann–Whitney test for abnormally distributed quantitative variables, to compare between two studied groups; and Wilcoxon signed ranks test for abnormally distributed quantitative variables, to compare between two periods.
ResultsAll of our patients were males. Comparison between demographics of the two study populations is shown in [Table 1]. There was no statistically significant difference between both groups of patients in the preoperative measures, whereas there were statistically significant improvements in all studied outcomes on postoperative follow-up of both groups. Obviously, there was no statistically significant difference between both groups in the postoperative outcomes, except for the SGRQ, which was slightly better in the silver nitrate arm; however, the degree of improvement was not significantly different ([Table 2]).
None of the major complications occurred in any of the patients. In group I, one patient experienced a short-term low-grade fever and two patients had hypoxia, which was corrected in a couple of days with low flow oxygen. In group II, one patient had a COPD exacerbation and was admitted to the ICU and then he improved after 5 days of antibiotics and a small dose of systemic steroids.
DiscussionUsing a lung sealant to induce sclerosis with the aim of lung volume reduction was first published in 2009 and was tested in advanced, upper lobe predominant emphysema [9]. Before 2015, the only randomized trial assessing this technique was the Aspire trial, which had serious problems in financial resources, and therefore, the trial was terminated prematurely. However, data from the trial have been published for a follow-up period of up to 6 months [10]. The few patients who were treated showed an increased response rate in forced expiratory volume in 1 s (FEV1), symptoms, and 6MWT. Recently, Lieberman et al. [11] evaluated four patients treated with sealants, fibrinogen and thrombin, besides other seven with synthetic polymers (Aeris Therapeutics, Woburn, Massachusetts, USA). Postoperative nodules or consolidations, mostly resolved in biologic sealants patients, whereas in the other group, most became cavitary and then slowly decreased in size, except few that grew and showed higher activity in PET scan in the way that they should be cautiously differentiated from possible malignancy.
Elhanafy et al. [12] aimed at assessing the effectiveness and safety of silver nitrate use in the bronchoscopic reduction of lung volume in patients with emphysema. A total of 12 patients with homogeneous and heterogeneous emphysema were included in their study. They demonstrated protection in terms of medical complications during a 3-month follow-up and effectiveness in terms of gas trapping, spirometry, diffusing capacity, exercise tolerance, dyspnea, and health-related quality-of-life improvements from baseline. Their results showed changes from baseline in FEV1% predicted (27.29±10.56 vs. 55.43±17.43%) in heterogeneous group and (22.80±4.66 vs. 36.60±8.82) in homogenous group, which was considered as statistically significant improvement. Another more recent Egyptian study of Atta et al. [13] which was conducted in 2017 tried to evaluate the effectiveness of biological BLVR in patients with COPD using autologous blood mixed with tranexamic acid. They found significant improvement in FEV1%. The mean preintervention and postintervention FEV1% was 33.170±5.415 and 38.66±5.090, with P value more than 0.001. Most recently, Khattab et al. [14] found a highly significant improvement in FEV1 after volume reduction using histoacryl gel in their single upper lobe emphysematous bullae group, whereas the improvement was insignificant in the heterogeneous upper lobe emphysema group. In the same study, there was also a highly significant improvement in 6MWT from a preoperative mean of 212 m (IR=165–288 m) to 264 (IR=180–348 m) postoperatively (P<0.001). Snell et al. [15] also proved that the use of vapor ablation in BLVR had significant effect on patient fitness regarding 6MWT with an average change of 23.5±10.4 and 46.5±10.6 m 3 and 6 months postintervention, respectively, which was a statistically significant change (P<0.001). Moreover, they reported reduction in mMRC by a mean of 0.9±0.2 points at 6 months (P<0.001) and by at least one point in 63% of patients.
Intepe et al. [16] investigated the effect of endobronchial valve and coil treatments on respiratory functions and quality of life in patients with emphysema. They found that both techniques had major postintervention changes in mMRC. Their results showed that the mean preoperative and postoperative mMRC for valve technique was 3.6 and 2.4, respectively, whereas for coil technique, it was 3.6 and 2.6, respectively. Although the improvement was much less than our study, but it was still statistically significant. The previously mentioned study of Atta et al. [13] also reported significant improvement in mMRC postvolume reduction by autologous blood.
Regarding SGRQ, the previously mentioned study of Elhanafy et al. [12] matched our results in showing statistically significant improvement in SGRQ total domain scores in both heterogeneous and homogeneous emphysema groups (5.8±8.3 and 13.2±12.27, respectively). Mizumori et al. [17] aimed to study the effects of BLVR using transbronchial infusion of autologous blood and thrombin in patients with severe COPD. They used SGRQ in only two cases in their study owing to methodological issues. In both patients, improvement was statistically significant: −15.6 points and −11.9 points. In the same context, Snell et al. [15] showed improvements in the SGRQ total score of 12.4±2.7 points (P<0.001) in GOLD stage III patients group and 16.3±4.5 (P=0.002) points in GOLD stage IV.
Obviously, the presenting study is unique in some aspects. One of these is comparing silver nitrate versus histoacryl in BLVR. We were also the first to add assessment of CAT score before and after BLVR. Although an important limitation besides our relatively small size of patients sample is the inability to use volumetry in assessing the radiographic data of the patients, despite that some patients showed clear radiological improvement of the emphysematous bullae by the expertise eye ([Figure 1]). We could not objectively assess this owing to lack of training to use the volumetry software, which was available at our Radiology Department.
Figure 1 Radiological improvement in a case of silver nitrate group. (a, b) Preintervention. (c, d) Postintervention. ConclusionBoth silver nitrate and histoacryl showed promising results from the symptomatology point of view in improving patients complaining of COPD despite optimized medical treatment. Although both agents have nearly similar results, silver nitrate is much affordable and easier to use in BLVR than histoacryl, with very much lower cost of the former.
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