Results of one - way bronchial valve placement in treatment of emphysema

Nội dung text: Results of one - way bronchial valve placement in treatment of emphysema

1. Journal of military pharmaco-medicine N o7-2017 RESULTS OF ONE-WAY BRONCHIAL VALVE PLACEMENT IN TREATMENT OF EMPHYSEMA Dao Ngoc Bang*; Dong Khac Hung**; Ta Ba Thang*; Nguyen Quang Binh*** SUMMARY Objectives: To evaluate the results of one-way valve placement in treatment severe emphysema in chronic obstructive pulmonary disease. Subjects and methods: This study was a prospective, randomized clinical trial and carried out on 33 stable chronic obstructive pulmonary disease (COPD) patients with localized advanced emphysema. Patients underwent clinical examination, chest computed tomography (CT), measurement of FEV 1, RV, TLC and Raw and arterial blood gases before and at the 3 rd month after therapy. The one-way bronchial valve Zephyr was placed in lobar or segmental bronchi via flexible bronchoscopy. Results: 31 patients were placed one valve, following by one patient with two valves and one patient with 3 valves. 27 valves with the size of 5.5 mm were used. The results were seen at the 3 rd month after therapy that the 6-minute walk distance (6-MWD) increased in 48.48% of patients more than 26 meters; CAT index decreased in 75.76% of patients more than 2 points. The increase of 6-MWD and decrease of CAT and mMRC were significant in comparison with baseline and control group (p < 0.05). FEV 1 improved more than 10% predicted in 9.09% of patients. To compare with the baseline and control group, the increase of FVC and decrease of RV and TLC were significant (p < 0.05). Complications and adverse events were seen after valve insertion rarely and lightly. Conclusions: One-way valve has the efficacy to reduce lung volume in treatment of COPD patients with severe emphysema. The technique was safe. * Keywords: Chronic obstructive pulmonary disease; Emphysema; One-way bronchial valve. INTRODUCTIONS esults of emphysema treatment by internal medicine are unremarkable. Lung volume Emphysema is the constant progressive reduction has proved as a prospect for unrecovered hyperinflammation of air COPD patients with severe emphysema space under the bronchiales and the by its efficacies, such as: decrease of destruction of alveoli’s wall without fibrosis. dyspnea status, improvement of lung It causes limitation of airflow and decrease function and the quality of life, increase of of lung elastic recoil, leading to the physical activities and reduction of frequent progressive status of dyspnoe, frequency of exacerbation in COPD limitation of physical activities and patients [4]. The early results of decrease of life’s quality. Nowadays, the bronchoscopic lung volume reduction with * 103 Military Hospital ** Vietnam Military medical University *** National Hospital of Odontostomatology Corresponding author: Dao Ngoc Bang (bsdaongocbang@yahoo.com.vn) Date received: 15/06/2017 Date accepted: 07/08/2017 78
2. Journal of military pharmaco-medicine n o7-2017 one-way valve were seen in patients with respiratory function recovery; advanced severe emphysema. This technique predominant emphysema in one lobe on intervenes less than surgery, leading to High-Resolution Computed Tomography the minimal light complications and (HRCT), giving up smoking more than 3 adverse events [3]. In Vietnam, this months, no collateral ventilation below the technique has been done firstly in the 103 location of valve [6]. Exclusion criteria Military Hospital from 2014. The purpose were patients who had contraindications of this study: To evaluate the results of of plethysmography measument and flexible one-way valve placement in treatment of bronchoscopy [4]. severe emphysema in chronic obstructive 2. Methods. pulmonary disease. This study was a prospective, SUBJECTS AND METHODS randomized clinical trial to compare two 1. Subjects. methods of treatment for patients with advanced emphysema, including LVR 66 patients were diagnosed as stable valve combined optimal medical therapy COPD with severe emphysema, treated in and optimal medical therapy alone. the Tuberculosis and Lung Diseases Department, 103 Hospital from January Patients underwent clinical examination, 2014 to May 2017. Patients were divided blood testes, ECG, echocardiography, into 2 groups: standard chest X-ray, chest CT, spirometry, plethysmography and arterial - Treatment group (group I): 33 patients blood gases test before therapy. with severe emphysema and stable COPD underwent one-way valve placement and Patients in treatment group underwent optimal medical therapy. flexiable bronchoscopy (Fujinon, Japan) - Control group (group II): 33 patients with the chanel for instrumention of 2.8 mm with severe emphysema and stable COPD to control the status of bronchial tree, underwent only optimal medical therapy. determine the lobal or segmental bronchi needed to place valve and clean the Diagnosis of stable COPD based on GOLD standards (2013). The severity of airway. Collateral ventilation was controlled emphysema was determined by chest by Chartis system (PulmonX, USA). The computed tomography (CT) and diameter of bronchi was measured by measurment of residual volume (RV). catheter in order to select one-way Zephyr Patient selection based on the standards valve (PulmonX, USA) with suitable sizes. of the Guidelines for Internal Respiratory Valve was inserted into the catheter, Techniques of the Vietnam Ministry of delivered via the instrumental chanel of Health (2014): severe obstructive airway bronchoscope to target bronchi and (20% pred. < FEV1 < 50% pred.); TLC placed to occlude segmental or lobal ≥ 100% pred., RV ≥ 150% pred. After bronchi leading to the target lobe. After bronchodilator inhalation and before that, the activity of valve was controlled. 79
3. Journal of military pharmaco-medicine N o7-2017 At the end of therapy, patients went back mas index (BMI) and 6-minute walk distance to their room and were followed and (6-MWD), indexes of respiratory function treated complications and adverse events such as vital capacity (VC), forced vital of the technique. capacity (FVC), forced expiratory volume All patients were treated by optimal in one second (FEV 1), residual volume medical therapy for stable COPD followed (RV), total lung capacity (TLC) and airway guidelines of GOLD (2013). They were resistance (Raw). Evaluating early examined again after 1 and 3 months. By complications (within 1 week after every time, they were estimated clinical therapy) and later adverse events (in status (degree of dyspnoe based on 1 to 3 months after therapy). modified Medical Research Coucil-mMRC, Data was recorded and analysed in the COPD Assessment test-CAT index, body software SPSS 20.0. RESULTS 1. Characteristics of patients. Table 1: Clinical characteristics of 2 groups. Group I Group II Indexes p (n = 33) (n = 33) 65.70 ± 7.32 65.91 ± 6.69 > 0.05 Age ( X ± SD) (years) Male 33 (100%) 33 (100%) > 0.05 29.68 ± 11.73 23.49 ± 11.32 < 0.05 Smoking ( X ± SD) (pack/year) 7.83 ± 3.58 7.38 ± 5.68 > 0.05 Duration of disease ( X ± SD) (years) 18.61 ± 2.44 17.90 ± 2.47 > 0.05 BMI ( X ± SD) (kg/m²) 20.12 ± 3.43 18.64 ± 2.95 > 0.05 CAT ( X ± SD) 2.52 ± 0.80 2.24 ± 0.87 > 0.05 mMRC ( X ± SD) 302.00 ± 59.53 303.64 ± 60.03 > 0.05 6-MWD ( X ± SD) (m) The patients in 2 groups had high mean of age with long duration of disease, low BMI and high CAT score. The ability of physical activity decreased, with the short 6-MWD (302.00 ± 59.53 meters in treatment group and 303.64 ± 60.03 meters in controlled group). There was no difference between 2 groups in the average age, BMI, CAT and 6-MWD. However, the patients in the group I smoked more than ones in the group II. 80
4. Journal of military pharmaco-medicine n o7-2017 Table 2: Respiratory function characteristics of 2 groups before technique. Group I Group II Indexes p (n = 33) (n = 33) Respiratory function indexes 76.09 ± 21.26 73.27 ± 13.05 > 0.05 VC ( X ± SD) (%Pred) 60.18 ± 15.92 68.18 ± 12.76 < 0.05 FVC ( X ± SD) (%Pred) 34.67 ± 15.02 35.36 ± 11.35 > 0.05 FEV1 ( X ± SD) (%Pred) 32.39 ± 12.50 29.36 ± 11.99 > 0.05 MVV ( X ± SD) (%Pred) 250.27 ± 73.88 253.73 ± 72.83 > 0.05 RV ( X ± SD) ((%Pred) 138.12 ± 24.01 143.21 ± 28.31 > 0.05 TLC ( X ± SD) ((%Pred) 9.04 ± 4.31 9.52 ± 4.02 > 0.05 Raw ( X± SD) (cm H 20/l/sec) Arterial blood gases 72.21 ± 7.66 78.52 ± 14.83 < 0.05 PaO 2 ( X ± SD) (mmHg) 43.73 ± 4.56 43.39 ± 9.58 > 0.05 PaCO 2 ( X ± SD) (mmHg) The mean of VC, FEV1, FVC and PaO 2 decreased and the opposite was seen in RV, TLC, Raw and PaCO 2 in the both groups of patients. Mean of FEV1 in both groups belonged to the COPD stage III of GOLD 2013. RV and TLC increased so much, corresponding to severe emphysema. Mean of Raw was so high in the both groups. PaO 2 decreased quite much and PaCO 2 had the trend to go up, but mean of PaCO 2 still belonged to the normal limitation. There was no difference in FEV1, VC, RV, TLC and Raw between 2 groups (p > 0.05). However, the means of FVC and PaO 2 of patients in the group II were significant higher than ones in the group I (p < 0.05). Figure 1: Position of severe emphysema on CT-scan images. In this study, severe emphysema located most in the lower lobe, with the portion of 60.61% in the group I and 96.97% in group II. The rate of severe emphysema located in the upper lobe in the group I was significant higher than it in the group II. No patient in the group II had severe emphysema in the middle lobe. 81
5. Journal of military pharmaco-medicine N o7-2017 2. Quantity and position of bronchial valves. Table 3: Indexes n % Size 4.0 mm 9 25.00 5.5 mm 27 75.00 Total of valves 36 100 Quantity of valve per patient 1 valve 31 94.94 2 valves 1 3.03 3 valves 1 3.03 Total of patients 33 100 Position of valves Right upper lobe 8 22.22 Right middle lobe 4 11.11 Right lower lobe 20 55.55 Left upper lobe 2 5.56 Left lower lobe 2 5.56 Total of valves 36 100 The rate of valve with the size 5.5 mm used was 75.00%. 31 patients were treated with only one (94.94%), 1 patient (3.03%) with two and 1 patient (3.03%) with three valves. The portion of valve located in the right lung was 88.88%, in which the most was seen in the right lower lobe (55.55%). Only 4 valves (11.12%) were located in the left lung. 3. Results of bronchoscopy lung volume reduction with one-way bronchial valve in treatment of emphysema. Table 4: Changes of clinical characters of patients in 2 groups after 3 months. Index Group I Group II p Before 3 months later Before 3 months technique (1) (2) treatment (3) later (4) (n = 33) (n = 33) (n = 23) (n = 23) BMI (kg/m²) p2,1 > 0.05 18.61 ± 2.44 18.58 ± 2.55 17.61 ± 2.70 17.58 ± 2.70 p > 0.05 X ± SD 2,4 p4,3 > 0.05 Change -0.03 ± 0.38 -0.03 ± 0.10 > 0.05 82
6. Journal of military pharmaco-medicine n o7-2017 CAT (points) 20.12 ± 3.42 17.79 ± 3.39 18.78 ± 3.10 17.65 ± 3.71 p2,1 < 0.01 X ± SD p2,4 > 0.05 p4,3 < 0.01 Change -2.33 ± 1.27 -1.13 ± 1.36 < 0.05 Decrease ≥ 2 25 (75.76) 11 (47.82) < 0.05 points (n) (%) 6-MWD (m) 302.00 ± 59.53 333.48 ± 307.39 ± 67.89 326.74 ± p2,1 < 0.01 X ± SD 62.69 88.72 p2,4 > 0.05 p4,3 < 0.05 Change 31.48 ± 26.30 19.35 ± 36.03 > 0.05 Increase ≥ 26 m 16 (48.48) 5 (21.74) < 0.05 (n) (%) mMRC (points) 2.03 ± 1.05 2.26 ± 0.92 2.09 ± 0.79 p < 0.01 X ± SD 2.52 ± 0.80 2,1 p2,4 > 0.05 p4,3 < 0.01 Change -0.48 ± 0.57 -0.17 ± 0.49 < 0.05 After 3 month therapy, BMI of patients in the both groups changed insignificantly. The patients in the group I witnessed the significant increase of 6-MWD (p < 0.01), with 16 patients (48.48%) more than 26 meters. Most of patients in the group I decreased CAT index significantly (p < 0.01), with the improvement more than 2 points in 75.76% of patients. The similar trend was seen in the decrease of mMRC in group I (p < 0.01). In comparison with the group II, the group I had the significant improvement of 6-MWD, CAT and mMRC (p < 0.05). Table 5: Changes of respiratory function indexes of patients in 2 groups after 3 months. Group I Group II p Indexes Before technique 3 months later Before 3 months (1) (2) treatment (3) later (4) (n = 33) (n = 33) (n = 23) (n = 23) VC (%pred) 76.09 ± 21.26 73.97 ± 25.02 76.22 ± 75.78 ± p2,1 > 0.05 X ± SD 13.39 17.47 p2,4 > 0.05 p4,3 > 0.05 Change - 2.12 ± 24.11 -0.43 ± 20.31 < 0.05 FVC (%pred.) 60.18 ± 15.92 67.42 ± 23.98 71.52 ± 71.52 ± p2,1 < 0.05 X ± SD 12.50 13.53 p2,4 > 0.05 p4,3 > 0.05 Change 7.24 ± 18.81 0.00 ± 16.10 > 0.05 83
7. Journal of military pharmaco-medicine N o7-2017 FEV1 (%pred) p > 0.05 X ± SD 2,1 34.67 ± 15.02 35.73 ± 15.05 37.26 ± 33.65 ± p2,4 > 0.05 12.03 10.06 p4,3 < 0.05 Change 1.06 ± 6.45 -3.61 ± 7.24 < 0.05 Increase > 10% (n) 3 (9.09) 1 (4.35) > 0.05 (%) RV (%pred) 250.27 ± 73.,88 215.00 ± 251.43 ± 275.09 ± p2,1 < 0.01 X ± SD 60.70 64.93 88.56 p2,4 < 0.01 p4,3 > 0.05 Change -35.27 ± 62.00 23.65 ± 60.72 0.001 TLC (%pred) 138.12 ± 24.01 126.15 ± 144.70 ± 154.39 ± p2,1 < 0.05 X ± SD 22.25 24.84 35.47 p2,1 < 0.01 p4,3 > 0.05 Change -11,97 ± 27,43 9.70 ± 24.45 < 0.01 Raw (cmH 20/l/sec) 9.04 ± 4.31 10.07 ± 4.50 9.72 ± 4.41 11.13 ± p2,1 > 0.05 X ± SD 4.77 p2,4 > 0.05 p4,3 > 0.05 Change 1.03 ± 3.97 1.41 ± 5.44 > 0.05 After 3 month therapy, the mean of FVC and FEV 1 increased, while RV and TLC decreased. Especially, 3 patients (9.09%) had the improvement of FEV1 more than 10% pred. The improvement of FVC, RV and TLC was significant after therapy (p < 0.05). The patients in the group II had also improvement of respiratory indexes, but insignificantly (p > 0.05). In comparison with group II, the increase of FVC and decrease of RV and TLC of patients in group I was significantly higher (p < 0.05). However, Raw of patients in the both groups increased insignificantly (p > 0.05). Table 6: Complications and adverse events. Complications and adverse events n % Early 4 12.12 Exacerbations of COPD 3 9.09 Pneumothorax 1 3.03 Later 7 21.21 Hemoptysis 2 6.06 Blocked valve because of mucus 3 9.09 Granulation around the valve 2 6.06 The portion of early adverse events was 12.12%, in which 9.09 % of exacerbations of COPD and 3.03% of pneumothorax. The common later adverse events were the blocked valve because of mucus, granulation around the valve and hemoptysis, with the rate following by 9.09%, 6.06% and 6.06%, respectively. 84
8. Journal of military pharmaco-medicine n o7-2017 DISCUSSION * Characteristics of respiratory function : 1. Clinical and respiratory function In this study, severe emphysema was characteristics. seen most in the lower lobe, with the portion of 63.64% in the group I and * Characteristics of age and gender: all 96.97% in the group II. The mean of VC, of patients in the treatment group were FEV , FVC and PaO decreased and the male; with the mean of age was 65.70 ± 1 2 opposite was seen in RV, TLC, Raw and 7.32 years old. This characteristics was similar to it in controlled group. The age of PaCO 2 in two groups of patients. There patients in our study had also no was no difference in FEV 1, VC, RV, TLC difference in comparison with other and Raw between two groups (p > 0.05). studies in the world, such as the study This was the different point of studied about the efficacy of bronchial valve in patients in our trial, with the high portion treatment emphysema was carried out by of severe emphysema was seen in the Sciurba F.C et al (2010) (VENT study) in lower lobe. This difference could be 220 patients, with the mean of age was explained that all of the patients in our 65.34 ± 6.83 years old and the portion of study were in the severe stage of disease, males was 60.4% [8]. In 284 patients who leading to the high rate of pan lobular were located one-way bronchial valve in emphysema. The changes of respiratory the study of Valipour A et al (2013), mean function indexes in our study were similar of the age was 63 ± 7.5 years old, in to those in previous studies such as in the which the rate of male was 63% [10]. study of Wan I.Y et al (2006), the mean of * Clinical characteristics: The patients FEV 1 was 30.1 ± 10.7% pred, RV and who were located one-way bronchial TLC followed by 244.3 ± 60.3% pred. and valve had long duration of disease, low 128.4 ± 17.1% pred [11]; Sciurba F.C et al BMI, high CAT score and decreased 6- (2010) studied to place bronchial valve for MWD. This meant that the status of patients with the mean of FEV 1, FVC, nutrition was low and COPD had affected TLC and RV followed by 30 ± 8%, 70 ± much to the life and health of COPD 15%, 124 ± 15% and 216 ± 44% pred [8]. patients. To compare with the studies of 2. Quantity and location of bronchial Sterman et al (2010) and Eberhardt R et valve. al (2012), the patients in our study had similar mean of 6-MWD. However, the The rate of valve with the size 5.5 mm mean of BMI was significantly lower than used was 75.00%. 31 patients was that in previous studies of other authors treated with only one (94.94%), one [2, 9]. The status of nutrition and effects of patient (3.03%) with two and one patient COPD to the quality of life were important (3.03%) with 3 valves. The portion of factors which affected the efficacy of the valve located in the right lung was technique to reduce lung volume by one- 88.88%, in which the most was seen in way bronchial valve in patients with the right lower lobe (55.55%) and only 4 severe emphysema. valves (11.12%) were located in the left 85
9. Journal of military pharmaco-medicine N o7-2017 lung. In our study, the quantity of valve (decrease the CAT point) and increase of was quite few because the patients had to the ability for physical activity in our study pay much for this technique. So that, the was less than that in some previous quantity and location of valve for patients studies, such as being placed averagely in our study were different from that in the 3.8 valve per patient at 6 months after previous studies, such as Wan I.Y.P et al therapy, the patients in the study of (2006) placed 4 ± 1.6 valves per patient, Sciubar F.C et al (2010) had the with the most of valves in the upper lobes significant improvement of the degree of of 2 lungs, in which the portion of valves dyspnea, with the average decrease of in the right upper lung was 39.8% [11]. SQRG was -2.8, mMRC was -0.1 points Park T.S et al (2015) conducted this and the average increase of 6-MWD was technique in 43 patients, with the mean of 9.3 meters. This change was significantly valve per patient was 3, the rate of valve different from that in the controlled group in the right upper lobe, left lower lobe, (p = 0.04) [8]. In the study of Valipour R et right lower lobe and left upper lobe al (2013), at 6 months after placing followed by 41.9%, 34.9%, 14% and 2.3% 1 valve per patient, there was a significant [7]. Davey C et al (2015) placed averagely improvement in the BODE index of the 3 valves per patient (from 1 to 6 valve per treatment group in comparison with that in patient) [1]. controlled group (p < 0.001) [10]. The 3. Results of bronchoscopic lung results of the study of Davey C et al volume reduction with one-way bronchial (2015) had shown that at 3 months after valve. placing averagely 3 valves per patient, 52% of patients increased 6-MWD more * Change of clinical symptoms after than 26 meters and 57% of patients therapy: At 3 months after therapy, BMI of decreased more than 2 CAT points. This patients in both 2 groups changed improvement was significantly different insignificantly. The patients in the group I from that in the controlled group [1]. To witnessed the significant increase of compare with other previous studies, the 6-MWD (p < 0.01), in which 16 patients difference of the change in clinical (48.48%) had more than 26 meters. Most characteristics after therapy in our study of patients in the group I decreased CAT could be explained by some following index significantly (p < 0.01), with the factors, including the less quantity of improvement was more than 2 points in valves per patient, the disobedience of 75.76% of patients. A similar trend was patients in treatment of stable COPD and seen in the decrease of mMRC in the the short time of follow-up (only in 3 group I (p < 0.01). In comparison with the months). group II, the group I had a significant improvement of 6-MWD, CAT and mMRC * Changes in respiratory function indexes: (p < 0.05). However, the degree of At 3 months after therapy, the mean of improvement in the quality of life FVC and FEV1 increased, while RV and 86
10. Journal of military pharmaco-medicine n o7-2017 TLC decreased. Especially, 3 patients of Sterman D.H et al (2010) changed (9.09%) had the improvement of FEV 1 inappreciably in all of times at 1, 3, 6 and more than 10% predicted. The improvement 12 after the technique [9]. In conclusion, of FVC, RV and TLC was significant after the degree of reduction of RV and TLC therapy (p < 0.05). The patients in the and the change of FEV 1 depended on the group II also had an improvement of quantity of placed valves and the different respiratory indexes, but insignificantly moments of assessment in study. (p > 0.05). In comparison with the group 4. Complications and adverse events. II, the increase of FVC and decrease of The portion of early adverse events was RV and TLC of patients in the group I was 11.76%, in which 9.09% of exacerbations significant higher (p < 0.05). However, of COPD and 3.03% of pneumothorax. Raw of patients in the both groups Sterman D.H et al (2010) followed up 91 increased insignificantly (p > 0.05). That patients after therapy and witnessed that meant that one-way bronchial valve had one patient had respiratory failure and the effect to reduce lung volume and heart attack, 2 patients had to perform improve respiratory function in COPD valve removal because the constant patients. To compare with the previous bronchospasm, 6 patients developed studies, we found that the changes of the pneumonia at the place of valve, respiratory function indexes were lower. 3 patients suffered pneumothorax with In the study of Yim et al (2004), while 2 death [9]. The common later adverse FVC and FEV improved significantly, the 1 events were the blocked valve because of change of RV and TLC after 3 months mucus, granulation around the valve and was not remarkable [12]. Klooster K et al hemoptysis, with the rate following by (2015) showed that the patients who were 9.99%, 6.06% and 6.06%. In the study of placed averagely 4 valves after 6 months Sciubar F.C et al (2010) in 214 patients follow-up witnessed the noticeable after 3 months, the general portion of increase of FEV 1, FVC in comparison with complications was 4.2%, including the controlled group (p < 0.05) [5]. The pneumothorax (4.2%), pneumonia (3.2%), more significant change of FEV 1 was hemoptysis (5.6%), COPD exacerbations seen in the results of the study of Park (7.9%) and 85 valves were removed in T.S et al (2015), with the mean of FEV 1 of 31 patients after 12 months [8]. In our the patients placed averagely 3 valves study, the portion of complications and after 6 months follow-up increasing from adverse events was less than in the 0.68 ± 0.26 to 0.92 ± 0.4 liters [7]. In the previous studies. That may relate directly study of Klooster K et al (2015), patients to the quantity of placed valves, the who were placed averagely 4 valves per duration and times of the technique. In patient decreased RV significantly [5]. general, this technique is relative safe, The mean of RV and TLC of the patients with the low portion and light degree of placed averagely 6.7 valves in the study adverse events. 87