Results of Bronchoscopic Lung Volume Reduction with One-way Valve in Patients with Severe Emphysema in Vietnam

This is study a prospective, nonrandomized, single center longitudinal study to evaluate the short-term efficacy and safety of BLVR performed by placing one way endobronchial valves.

Thirty patients (all men, median age 65.17 years, range 50 to 70) entered this pilot study during a 3-month period, from Jan 2014 to Apr 2017. Selection criteria: stable COPD patients with FEV1 ≤ 35% pred., TLC ≥ 100% pred., RV ≥150% pred., and heterogeneous emphysema on chest computed tomography (CT); 40≤ age ≤75 years. Exclusion criteria: homogeneous emphysema; currently smoking; PaCO2≥50 mmHg; productive cough¹⁵.

The protocol was approved by the ethical committee of the Military Medical University, authozied by Vietnam Ministry of Health. All patients knew of the BLVR procedure and understood it.

Patients were underwent clinical examination, pulmonary function tests performed with body plethysmography, carbon monoxide diffusion (DLCO) measurement and reversibility test, arterial blood gas analysis, chest X-ray, computed tomography scan, echocardiogram at times: before again 24 hours after the procedure, and after 1 and 3 months. Fiberoptic bronchoscopy was repeated after 1 and 3 months. The exercise tolerance was measured with the 6-minute walk test (6MWT), health-related quality of life measured with COPD assessment test (CAT) score. The degree of dyspnea was measured by the Medical Research Council (MRC) dyspnea grading system. CT thorax was be reviewed by two radiologists independently to demonstrate heterogeneous emphysema with a defined target lobe.

The procedure of one way valve placement: The technique was performed in the bronchoscopy room. Patients were underwent flexible bronchoscopy under local anaesthesia by the technician with more than 5 years of experience in intervention bronchoscopy. The flexible bronchoscope is advanced into the target bronchus are chosen (the target bronchus selection was based on CT). Collateral ventilation was measured by Chartis system (PulmonX, USA). The Zephyr one-way bronchial valve (PulmonX, Redwood City, CA, USA) was used in the study, with the sizes of 4.0 and 5.5 mm. A flexible delivery catheter containing the valve is inserted through the operating channel of the bronchoscope to the targeted bronchus, pushed with a gentle rotation in the selected bronchial orifice, and the valve is delivered. All the patients were controlled the complication of pneumothorax by chest X-ray after the procedure. 28 patients were placed only one valve, 1 patient with two and 1 patient with three valves. 23 valves with the size 5.5 mm diameters and 10 valves with the size 4.0 mm diameters used.

All patients received optimal medical treatment based on Guilines of the Vietnam Ministry of Health at the time of procedure and during the study period.

Characteristics of patients are shown in the Table 1.

Outcome measures: Outcomes will be assessed at 3 months after treatment include the changes of CAT, MRC, 6MWT, and lung function (VC, FVC, FEV1, RV, TLC, Raw). The main safety analysis will be the occurrence of adverse events in the first 3 months: exacerbations, pneumothorax, hemoptysis, blocked valve because of mucus, granulation around the valve.

Statistical analysis: Data analysis was performed using a software program the SPSS 20.0; p values were calculated using a two-tailed, Student t test for matched pairs when normality assumptions were met. For nonparametric results, the Wilcoxon signed-rank test was used. A p value of less than 0.05 was considered to indicate statistical significance.

In our study, most of patients (93.34%) were placed only one valve, with the valves were placed in the right lung was 87.88% of the patients (29 valves), in which the most was placed in the right lower lobe (44.24%), in the right upper lobe 40%, in the right middle lobe 3.64%. 4 valves (12.12%) were placed in the left lung. To compare with some previous trials, the amount of valves were placed more and the valves were placed more in the upper lobes⁴,¹⁴,¹⁹. 28 patients were placed only one valve. This limitation was due to the expenditure of this study. The national trial (managed by Vietnam Ministry of Science and Technology) sponsored only one valve per patient. Besides, this technique has been still not paid by Vietnam Health Insurance. There were 2 patients who were placed the second or third valve by self-financing. In the next time, we continue to to follow up and advise them place next valves when having enough condition. In our patients, the homogeneous emphysema on CT-scanner image was seen more in the lower lobes, with the portion of 66.66% (20 of 30 patients), therefore the amount of valves were placed in the lower lobes the highest. The study of Vietnam authors (2013), which was carried out in stable COPD patients, had the similar results, with homogeneous emphysema seen more in lower lobes¹.

At 3 months after procedure, the life’s quality and physical ability of patients were improved, with the CAT index decreased significantly in comparison with baseline, in which the average change was 2.73 points and the improvement more than 2 points was seen in 76.67% of patients. The exercise capacity of patients was increased clearly, shown by significant improved 6MWT after 3 months (p<0.05), with 93.33% of the patients increased 6MWT, 46.67% of the patients increased 6MWT more than 26 meters. Our data suggest that the improvement of exercise capacity exercise capacity was the most patients. The degree of dyspnea in patients had a improvement significantly, with the median change of 0.5 score and 43.33% of the patients decreased MRC at 3 months. The decrease of MRC was lower than the improvement of exercise capacity and quality of life. The results in our study have shown the patients with increased 6MWT is higher but 6MWT improvement ≥ 26 m is lower when comparing with the study of Davey C. et al. (2015)⁴. In some other trials, the degree of dyspnea, quality of life (SGRQ score, BODE index) and 6MWT had improved in BLVR patients, but in many different levels¹⁵,¹⁷. These different results may relate to some factors, including the amount of inserted valves, sizes of valves and time of outcome evaluation (3 or 6 months). This study was undertaken at a single center in selecting patients for lung volume reduction at only 3 months, therefore, it shows the initial early results, and we are now following up these patients to evaluate next results.

At 3 months after procedure, the mean of FVC increased, while RV and TLC decreased significantly in comparison with baseline. The mean of FVC was 2.09 ± 0.43 (L) and improved statistically from baseline (p<0.05), with the average of increased FVC of 0.14 (L) and 73.33% of patients increased FVC. The patients had the significant decrease in RV and TLC at 3 months with RV decreased by a mean 0.62 (L) (1.05 - 0.2), TLC decreased by a mean 0.52 (L) (0.77- 2.4) from baseline (P<0.05). The portion of patients with increased FVC was the most, following by reduced RV and decreased TLC. The change of Raw at 3 months was not statistically significant. A similar trend was seen in the study of Hopkinson N.S et al. (2005)⁸, with RV reducing more than TLC, and increased FVC but insignificant improved VC⁸. The changes of pulmonary function in our study was lower than in some previous trials¹⁰,¹⁴,¹⁸. Lung volume reduction treatment is carried out in order to let the emphysema area collapse, leading the decrease of the compression on the normal lung, change of the pulmonary volumes and capacities and improvement of the clinical status of COPD patients. Some authors have shown that the most significant efficacies of bronchial valve in lung volume reduction were seen in the COPD patients with homogeneous emphysema and without collateral ventilation under the place of valve⁴. All of our patients were controlled the collateral ventilation by Chartis system. However, we could not determine the relation between the change of emphysema index on CT-scanner image and the levels of improvements of FVC, FEV1, RV, and TLC at 3 months after the procedure. The study of Hopkinson N.S et al. (2005)⁸ showed that the reduced of RV and TLC of patients happened even as there was no atelectasis on the chest X-ray. So, there is a difference between the changes of pulmonary volumes measured by plethysmography and CT-scanner image⁸. The different results of lung function change depended on the amount and sizes of the valves as well as the time of outcome evaluation.

Following-up after the procedure, some complications were seen, including 3 patients (10.0%) having mild exacerbations of COPD on the first day after the technique with the cause related to infection. These patients recovered after 3 days of treatment. The appearance of infection mainly related to the change of mucosal cleansing after bronchoscopy¹¹. One patient had pneumothorax at the 3rd day after valve placement and recovered after one day treated by chest drain. This patient had dyspnea and wheezing after bronchoscopy and was treated by bronchodilator drugs. So, pneumothorax could relate to the bronchospasm. The previous studies have shown that pneumothorax after valve placement related to the changes of pulmonary volumes more than the procedure¹¹. Two patients (5.88%) had might hemoptysis after 1 week and recovered after 3 days of internal therapy. The common later adverse events included the blocked valve because of mucus after 1 month and granulation around the valve after 2 months, with the rate following by 10.0% and 6.67%. By flexible bronchoscopy, we cleaned mucus and cut the granulation to solve these problems with valves. No valve was removed. There was no death in our study. In some other previous studies, severe complication and death were reported while other complications were similar our results, however, the portion of valve removal in these studies was more than in our¹⁵,¹⁶. In general, the technique of bronchial valve placement via flexible bronchoscopy is acceptable safe, with the mild complications.