In recent years, bronchoscopic lung volume reduction (BLVR) coil treatment has become an increasingly used treatment modality for selected patients with severe emphysema.1 Emphysema is characterized by chronic inflammatory structural changes and permanent parenchymal damage in the lungs. Emphysema causes dynamic hyperinflation, loss of elastic recoil, air trapping, decreased exercise capacity, and shortness of breath in advanced stages. With severe emphysema, diaphragmatic and thoracic compression occurs due to the increase in residual volume (RV) and respiratory muscle dysfunction.2 This process progresses over time, leading to hypoxic and hypercapnic respiratory failure. Treatment options for these patients are limited and include smoking cessation, bronchodilators, mucolytics, glucocorticoids, phosphodiesterase-4 inhibitors, respiratory physiotherapy, supplemental oxygen, and sometimes continuous positive airway pressure.3 The mechanical problems caused by emphysema can be treated with lung volume reduction surgery (LVRS) or BLVR, using either coil, valve, or thermal vapor ablation method.4–7
LVRS, which involves the resection of damaged lung parenchyma, is performed in highly selected patients with emphysema. LVRS can improve exercise tolerance, lung function, and quality of life.8 The National Emphysema Treatment Trial (NETT) criteria is often used to determine which patients may benefit from LVRS. However, LVRS is not recommended for patients with a resting oxygen requirement or hypercapnic respiratory failure [partial pressure of carbon dioxide in arterial blood (PaCO2) >60 mm Hg].9
A new and alternative treatment option for patients with heterogenous or homogenous emphysema involves the bronchoscopic placement of nitinol-based endobronchial coils. However, an average of 10 coils is implanted into each lobe of the lung, and only the upper and lower lobes can be used for this application. Each treatment session is applied to only 1 lobe of the lung, and the other lung within 4 to 8 weeks. The compression of the diseased lung lobes increases elasticity of lung, and provides reducing dynamic hyperinflation and air trap. Studies indicate that coil treatment can improve lung function, exercise capacity, and quality of life 6 or 12 months after treatment.10–12 However, the long-term effects of this treatment on arterial blood gas parameters have not been fully investigated. In general, coil treatment is not recommended for patients with a PaCO2>55 mm Hg. However, we believe that patients with hypoxic and chronic hypercapnic respiratory failure may benefit from BLVR coil treatment, which can reduce hyperinflation and thus the ventilatory workload.
The goal of this study is to elucidate the effects of BLVR coil treatment on arterial blood gas parameters in severe emphysema patients with respiratory failure.
This is a retrospective study performed at a single pneumology center in Turkey. In total, this study included 39 patients diagnosed with severe emphysema who underwent bilateral BLVR coil treatment according to the general inclusion and exclusion criteria1,5,11,12 in the literature. The following patients who met inclusion criteria were treated with BLVR coils: (i) postbronchodilator forced expiration volume in 1 s (FEV1) of 15% to 45%; (ii) RV>175%; (iii) 6-minute walking test (6-MWT): 150 to 450 m; (iv) PaCO2<55 mm Hg; (v) bilateral emphysema as detected by computed tomography; (vi) modified British Medical Research Council scores ≥2 and (vii) smoking cessation for >8 weeks before entering the study. Patients who met the following exclusion criteria were not treated with BLVR coils: (i) postbronchodilator change in FEV1>20%; (ii) bullous lesion >4 cm or affecting >30% of hemithorax; (iii) frequent chronic obstructive pulmonary disease (COPD) exacerbation (>2 hospitalizations/y); (iv) pulmonary artery pressure >50 mm Hg; (v) bronchiectasis; (vi) lung cancer; or (vii) use of an oral anticoagulant. All study patients were followed in our center between April 2013 and September 2015. The patients’ baseline and 12-month data were collected from the medical records. Four patients were excluded from the study due to lack of the data, and 2 patients because of settlement change and special reasons. Per the policies of our institution, there is no requirement for ethics committee approval for retrospective studies. Informed consent was obtained from all patients.
For all patients included in the study, a detailed medical history and demographic data were recorded and evaluated retrospectively, including the following: (1) epidemiological data (age, smoking history, use of supplemental oxygen at home); (2) sex; (3) clinical features (radiographic findings, type of emphysema, stage of COPD, etc.); (4) target lobe for treatment; (5) postbronchodilator pulmonary function parameters; and (6) arterial blood gas analyses. Pulmonary function parameters were evaluated with a Body Box 5500 Series pulmonary function testing system (Medisoft, Sorinnes, Belgium). Arterial blood gas samples were taken when patients were in a clinically stable condition and breathing room air. In addition, results from the 6-MWT were recorded.
BLVR Coil Treatment
Chest computed tomography was performed in all of the study patients, and patients were classified as having either homogenous or heterogenous emphysema. The target lobe was subsequently selected based on the computed tomography findings. All patients were under optimal inhaler and medical therapy for COPD. All RePneu coils (PneumRx Inc., Mountain View, CA) were inserted using a bronchoscopic approach with fluoroscopic guidance while patients were under general anesthesia. Each patient received 8 to 12 coils per lobe. All patients underwent a second coil treatment within 4 to 8 weeks.
Hypoxic respiratory failure was defined based on partial pressure of oxygen in arterial blood (PaO2) ≤55 mm Hg, and hypercapnic respiratory failure was defined based on a PaCO2≥45 mm Hg. All patients were classified according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages. GOLD stage 3 is defined as a FEV1/forced vital capacity (FVC) ratio <0.70 and an FEV1 of 30% to 50% of predicted. GOLD stage 4 is defined as an FEV1/FVC ratio <0.70 and an FEV1 <30% of predicted.13
All data were analyzed using SPSS software (version 14.0; SPSS Inc., Chicago, IL). Descriptive data are presented as the average±SD or median (range). Changes between the baseline and 12-month data were analyzed using the student t test for normal distribution parameters and the Mann-Whitney U test for non-normal distribution parameters. Statistical significance was defined as P<0.05 for the student t test and P<0.01 for the Mann-Whitney U test.
Demographic Data at Baseline
Between July 1, 2013 and May 30, 2015, a total of 78 BLVR coil procedures were performed in 39 patients. The mean age of the 39 patients (6 women and 33 men) who participated in the study was 66.21±8.3 years (range, 47 to 83 y). The average level of cigarette consumption was 30.28 packs per year. Preoperatively, 13 patients (33.2%) had hypoxic respiratory failure and 20 patients (51.2%) had hypercapnic respiratory failure. In addition, 41.0% of the study patients were receiving supplemental oxygen at home. Before the intervention, 35% of patients were classified as GOLD stage 3 and 65% were classified as GOLD stage 4. At baseline, the mean FEV1 was 0.76±0.24 L, which was equal to 27.9±9.5% of predicted. The mean RV was 5.44±0.53 L, which was equal to 242%±31.6% of predicted. The mean RV/total lung capacity ratio was 65.6%±4.20% of predicted. The mean PaO2 was 58.05±9.36 mm Hg and the mean PaCO2 was 46.05±6.67 mm Hg. The mean distance walked during the 6-MWT was 277±65 m (Table 1).
Results 12 Months After Bilateral BLVR Coil Treatment
Significant improvements in the FEV1 (+90 mL, 4.5%), RV (−0.77 L, 33.0%), and 6-MWT results (+60 m, 21.6%) were observed in all patients 12 months after bilateral BLVR coil treatment. Compared with baseline, a significant improvement in the PaO2 (+15.7 mm Hg) and arterial O2 saturation (+5.6%) were also observed 12 months after BLVR coil treatment. No significant improvements were observed in the arterial pH or PaCO2 after treatment (Table 2).
Results by Respiratory Failure
The analysis of patients with hypoxic respiratory failure (PaO2≤55 mm Hg, n=13) showed that after BLVR coil treatment, the average PaO2 significantly increased from 47.84 to 74.31 mm Hg; however, there was no significant change in the average PaCO2 (Table 3). The analysis of patients with hypercapnic respiratory failure (PaCO2≥45 mm Hg, n=20) showed a significant increase in the PaO2 and a significant decrease in the PaCO2 (from 51.60±4.1 to 46.55±6.6 mm Hg; P<0.001) after BLVR coil treatment (Table 4). According to the medical records, 5 of 13 patients (38.4%) with hypoxic respiratory failure stated that their need for supplemental oxygen was reduced after undergoing BLVR coil treatment.
Mild (treatment-related) and serious side effects were observed in the following period. Cough and phlegm were among the most frequent complications. Mild hemoptysis was observed in 3 (7.6%) patients. Three patient (7.6%) developed hiccups after the treatment and that stopped spontaneously over the following days. Pneumothorax was observed in 1 patient and treated with standard tube thoracostomy. During the first 12 months after the procedure, the most frequent and serious complication was COPD exacerbation (35.8%). In addition, 5 patients (12.5%) were hospitalized for any reason during the follow-up period. Pneumonia and pulmonary embolism was observed in 4 (10.1%) and 1 (2.5%) of cases, respectively (Table 5). Furthermore, no one lost their lives during the 12-month follow-up period.
The results of this retrospective study support the hypothesis that BLVR coil treatment improves oxygenation and pulmonary function in patient with severe emphysema. In all, 38.4% of patients with hypoxic respiratory failure experienced a decrease in their daily oxygen requirement after treatment. Similarly, hypercapnic patients showed a significant reduction in their PaCO2 values after BLVR coil treatment. BLVR coil treatment also appears to be beneficial for mildly hypercapnic patients with a PaCO2 of 45 to 55 mm Hg. However, further studies are needed to determine whether BLVR coil treatment can effectively reduce the PaCO2 in patients with more severe hypercapnia. Overall, this study revealed that BLVR coil treatment was effective in the medium term for patients with severe emphysema.
Advanced emphysema patients are characterized as having hypoxic or hypercapnic respiratory failure. Many patients with advanced emphysema require portable or fixed supplemental oxygen therapy, which considerably decreases their mobility and quality of life. Moreover, some COPD patients who develop hypercapnia require noninvasive positive pressure ventilation (NPPV) treatment.14 However, the use of NPPV is limited in these patients due to patient tolerability and the risk of complications such as pneumothorax, aspiration, hypotension, eye irritation, and face injuries.15 Moreover, neither supplemental oxygen therapy nor NPPV can cure the underlying disease processes such as the loss of elastic recoil and mechanical compression.
The NETT study showed that LVRS was effective, but only in patients with predominantly upper lobe emphysema.4 In addition, the short-term mortality rate for these patients is as high as 7.9% and the rate of pulmonary complications is as high as 29.8% in the first 90 days postoperatively. Therefore, the NETT study showed that LVRS increases the risk of pulmonary complications and death. According to the NETT criteria, LVRS is not recommended for patients with a PaCO2>60 mm Hg.9 In recent years, reports have shown that LVRS has been successfully used in hypercapnic patients with end-stage emphysema who were bridged with extracorporeal life support before surgery.16,17
Presently, BLVR coil therapy has become an alternative treatment option for patients with end-stage emphysema. Recent studies have shown that BLVR coil therapy improves patients’ respiratory function, exercise capacity, and ability to perform activities of daily living.5,10–12,18 A recently published study (REVOLENS), which included 100 patients, is randomized prospective trial of BLVR coil treatment. In that study, the authors found a 9% increase in the mean FEV1, a decrease in the mean RV, and improvement in lung function 6 months after the procedure. In addition, a 15% improvement in the mean FVC, a 6% improvement in the 6-MWT, and a 9% improvement in overall quality of life were reported after treatment.11 The largest randomized prospective study of coil treatment (RENEW) indicate median FEV1 increases of 7%, median RV reduction of 0.31 L, and an increase of 14.6 m in the 6-MWT.19 In our study, 84.6% of the patients had either hypoxic or hypercapnic respiratory failure. We observed similar improvements in lung function parameters and the walking test in these patients after bilateral BLVR coil treatment. We found that after BLVR coil treatment, the mean FEV1 increased by 4.5%, the mean RV decreased by 33.0%, and the mean distance walked during the 6-MWT increased by 60 m.
Hypoxia and hypercapnia seem to be the natural endpoints of end-stage emphysema. Although hypoxia can be treated with long-term oxygen therapy, hypercapnic respiratory failure is associated with a poor prognosis and a lower survival rate.20 A recent study conducted by Liao et al14 showed that long-term, NPPV decreases the PaCO2 and decreases mortality in stable COPD patients with hypercapnic respiratory failure.
Presently, there is insufficient evidence and data regarding BLVR in patients with chronic respiratory insufficiency. However, a review of the literature indicates that this treatment is not recommend for patients with PaCO2>55 mm Hg.5,11,12 One observational study by Simon et al21 reported that BLVR coil treatment had a positive effect on PaCO2 (decreased from 53±5 to 48±4 mm Hg) and improved pulmonary function. The results of our study are both similar and different compared with previously reported data. First, we found no significant difference between PaCO2 values at baseline and 12 months after BLVR coil treatment in patients with hypoxic respiratory failure. Second, 51.2% of patients with mild hypercapnia (PaCO2 of 45 to 55 mm Hg), showed a decrease in their PaCO2 value after BLVR coil treatment.
This study does have some limitations. First, this is a single-center, retrospective study with a limited sample size; therefore, the results should be interpreted with caution. Second, we only included a small number of patients with hypercapnia (n=20). However, our findings are similar to the results of previously published studies.
Currently, there are no published studies investigating the effects of BLVR coil treatment in patients with respiratory failure. In this study, the mean PaO2 was observed to increase significantly from 58.05±9.36 to 73.82±13.3 mm Hg after BLVR coil treatment. Moreover, BLVR coil treatment improved the PaO2 and PaCO2 in the medium term in patients with hypercapnic respiratory failure. However, further studies are needed to evaluate the long-term effects of BLVR coil treatment on arterial blood gas parameters and oxygen requirements in advanced emphysema patients with respiratory failure.
BLVR coil treatment is reliable and effective in emphysema patients who have hypoxic or mild hypercapnic respiratory failure. Besides improving lung function, BLVR coil treatment can significantly increase PaO2 and decrease PaCO2 in the medium term.
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