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J Thorac Cardiovasc Surg 2004;127:1564-1573
© 2004 The American Association for Thoracic Surgery
General thoracic surgery |
a Division of Cardiothoracic Surgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
b Department of Diagnostic and Organ Imaging, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
c Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
Received for publication June 25, 2003; revisions received September 3, 2003; revisions received October 2, 2003; accepted for publication October 3, 2003.
* Address for reprints: Anthony P. C. Yim, MD, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
yimap{at}cuhk.edu.hk
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Abstract |
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 Top Abstract Patients and methodsResultsDiscussionAppendixReferences |
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METHODS: A total of 21 patients with incapacitating emphysema who underwent this procedure were studied. All patients had placement of the endobronchial valves into the most emphysematous lung segments. We recorded any major complications or deaths attributed to the procedure and analyzed (1) improvements in the spirometric and functional parameters and quality of life and (2) the radiologic changes compared with the baseline data at 30 and 90 days.
RESULTS: A total of 20 patients had complete follow-up data. There was no mortality in the group studied. The forced expiratory volume at 1 second, forced expiratory volume at 1 second (percentage of predicted), forced vital capacity, and forced vital capacity (percentage of predicted) all improved significantly at 90 days (0.73 ± 0.26 L vs 0.92 ± 0.34 L [P = .009]; 33.3% ± 11.9% vs 42.2% ± 15.0% [P = .006]; 1.94 ± 0.62 L vs 2.25 ± 0.61 L [P = .015]; and 63.3% ± 17.6% vs 73.9% ± 17.1% [P = .012], respectively). The 6-minute walking distance improved at 30 and 90 days (251.6 ± 100.2 m vs 306.3 ± 112.3 m and 322.3 ± 129.7 m; P = .012 and P = .003). The results of the 36-Item Short-Form Health Survey and the St George Respiratory Questionnaire showed significant improvements at 90 days. The Medical Research Council dyspnea grade also improved significantly at 30 and at 90 days (P = .006 and P = .003, respectively).
CONCLUSIONS: Endobronchial valve placement is a safe procedure, with significant short-term improvements in functional status, quality of life, and relief of dyspnea in selected patients with emphysema. A larger study with long-term follow-up is therefore warranted.
Nonetheless, the trauma of operation (even with the thoracoscopic approach) means that only a relatively small percentage of patients with severe emphysema would benefit from such treatment. Patients with very low forced expiratory volume at 1 second (FEV1) and either homogeneous emphysema or a very low carbon monoxide–diffusing capacity (DLCO) are at high risk of death after LVRS,5 and the most recent published data have also indicated that patients with non–upper-lobe disease have a higher operative mortality when undergoing operation.6
Recently, several devices have emerged, based on the bronchoscopic approach, as possible alternatives to LVRS. The most studied of these is the Endobronchial Valve (Emphasys Medical Inc, Redwood City, Calif). By placing these one-way endobronchial valves (EBV) bronchoscopically into the most emphysematous lung segments, air is prevented from entering into the isolated segments, but distal bronchial secretions are allowed to escape (Figure 1). The net result is induced atelectasis of the most emphysematous segments and redirection of air flow (or ventilation) to the least emphysematous lung to reproduce the clinical benefits of LVRS without exposing the patients to the risks associated with a major operation.
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Toma and colleagues8 were the first to report on the clinical experience of this device in a pilot study involving 8 patients with severe emphysema. All had unilateral implantation of the one-way valves. There were no deaths, and pneumothorax was the only reported complication. There was an improvement of the median FEV1 at follow-up after 4 weeks. Likewise, Snell and colleagues9 reported on 10 patients and showed improvement in gas transfer. These studies paved the way for a larger clinical study on safety and feasibility, which forms the basis of this report.
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Patients and methods |
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TopAbstractPatients and methodsResultsDiscussionAppendixReferences |
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/
) scan before and then 30 and 90 days after the placement of these valves. A single-detector spiral CT scanner (HiSpeed Advantage RP Scanner; GE Medical Systems, Milwaukee, Wis) with collimation of 5 mm and pitch at 2:1 was used. For the / scan, 40 mCi of technetium Tc 99m diethylenetriamine pentaacetic acid aerosol was used for the ventilation scan, whereas 5 mCi of 99mTc-labeled macroaggregated albumin was used for the perfusion scan. The signals were then acquired by using a dual-head gamma camera equipped with a low-energy parallel hole general purpose collimator. The energy was set at 140 keV with a 20% symmetrical window, and the images were stored in the format of a 128 x 128 matrix. All the radiologic examinations were then reviewed by 1 radiologist (T.K.Y.). Full pulmonary function tests, including arterial blood gas measurements, were obtained for each patient. Transthoracic echocardiography was performed to assess right heart function and to rule out pulmonary hypertension. Baseline 6-minute walking distance (6MWD) was recorded as an assessment of exercise tolerance. Quality-of-life assessment by using the 36-Item Short-Form Health Survey (SF-36) and the St George Respiratory Questionnaire (both validated for Chinese patients)10,11 was undertaken. The degree of dyspnea experienced by each patient was measured by the Medical Research Council dyspnea grade.
The primary end point was any major complication or death attributed to the procedure within the study period. The secondary end points of the study were related to the degree of improvement in the lung function, 6MWD, and health-related quality of life (HRQOL) when compared with the baseline data at 30 and 90 days. The results were analyzed with SPSS for Windows version 11.0 (SPSS Inc, Chicago, Ill).
The protocol was formally approved by the University ethical committee (equivalent to the institutional review board). Nearly all these patients (except 1 with pleurodesis [patient 7] and another who already had LVRS [patient 17]) were candidates for LVRS. All patients knew and understood LVRS. Our procedure was offered to them as a new, investigational, and possibly alternative procedure. They understood that LVRS remained an option if this failed. All patients were given a choice of therapy, but none declined this procedure when it was offered. Informed consent was obtained from each patient.
Procedure
The procedure was performed in the operating room under total intravenous anesthesia with 2,6-dispropylphenol or propofol (Diprivan). The patient was kept in assisted spontaneous ventilation throughout the procedure and placed supine with the head slightly extended. The target areas for EBV placement were previously selected primarily on the basis of / scan in conjunction with pulmonary CT scan. A ventilating rigid bronchoscope with a Hopkins telescope (Efer-Dumon Bronchoscope; Efer, La Ciotat, France) was introduced through the mouth into the airway and was then connected to a 3-chip camera system (Stryker 784; Stryker, Kalamazoo, Mich) with the tip of the bronchoscope positioned at the target lobar orifice (usually one of the upper lobes). The rigid telescope was then exchanged for a flexible bronchoscope, which passed through the rigid bronchoscope to reach each of the target segmental bronchial orifices. A guide wire (0.035-inch external diameter) was threaded through the instrument channel of the flexible bronchoscope into the segmental bronchus. With a modified Seldinger technique, a carrier loaded with the EBV of the appropriate size (3 diameter sizes of 4.0-5.5 mm, 5.0-7.0 mm, and 6.5-8.5 mm are available) was placed at the segmental bronchial orifice, and the EBV was deployed. The entire procedure was visually monitored by the video bronchoscope. Depending on the exact morbid anatomy, 1 or more valves were placed in the endobronchial tree. For some patients, some segments appeared to be more affected than others within the same lobe (especially for the lower lobe). Overall, 28 lobes were targeted in the 20 patients. Complete lobar occlusion was undertaken in 16 lobes, and 45 valves were placed (2.81 valves per lobe targeted). Incomplete lobar occlusion was performed in the remaining 12 lobes, and 32 valves were used (2.67 valves per lobe targeted). We placed the valves only in the most affected segments, rather than indiscriminately in all segments of the lobe. In 1 patient (patient 17), we were unable to place the valve at the apical segment of the right upper lobe because of technical reasons—the guide wire flipped out of the target segment every time as the introducer was advanced.
Postoperative care and follow-up
Chest radiographs and arterial blood gas measurements were performed after surgery, and noninvasive arterial oxygen saturation was continuously monitored. The patients were encouraged to cough (assisted by physiotherapists) to clear any mucus or air remaining behind the valve. All patients received a prophylactic 10-day total course of antibiotics (amoxicillin/clavulanate or roxithromycin), as well as inhaled salbutamol and ipratropium bromide. At the time of discharge, patients were given a wallet card that can be presented to health-care providers, with a brief explanation of the procedure and contact information for the enrolling physician. Participants in the study were invited to contact the hospital for any advice or assistance at any time after the study. Follow-up was weekly for the first month and then twice monthly thereafter, with specific investigations performed at different time points.
Statistical analysis
All descriptive statistics were expressed as mean ± SD for continuous variables and as median (range) for ordinal data. Paired 2-tailed t tests were used to analyze quantitative continuous variables comparing the means for the group. Repeated-measures analysis of variance was performed to compare the means of the variables that had been measured at more than 1 occasion for each individual at the 3 time points (before the procedure and 30 and 90 days after the procedure). Bonferroni correction was used to adjust the observed significance level when multiple comparisons of the means were made. The Friedman test and the Wilcoxon signed-rank test were used for ordinal variables. All statistical analysis was performed with SPSS for Windows version 11.0.
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Results |
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TopAbstractPatients and methodsResultsDiscussionAppendixReferences |
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Radiologic assessments
EBVs were placed in 28 pulmonary lobes in 20 patients (Table 2). A total of 17 patients with 23 targeted lobes had complete CT evaluation at each follow-up for the degree of induced collapse. The degree of collapse of the respective lobes seen in the CT scans was categorized arbitrarily into 4 grades: grade 0 (0% collapse), grade 1 (
25% collapse), grade 2 (25% to 75% collapse), and grade 3 (>75% collapse). It is interesting to note that only 10 (43%) of the 23 lobes showed some degree of collapse after the placement of the EBVs during the entire follow-up period. Six of these 10 lobes remained unchanged throughout the follow-up period, whereas 2 lobes showed mild re-expansion and the remaining 2 showed no collapse at all in the first month but had a delayed collapse at the third month (Table 5) . For those 13 pulmonary lobes that showed no collapse throughout the 3-month follow-up period, the serial / scintigraphic findings of the respective lobes also remained static.
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Discussion |
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TopAbstractPatients and methodsResultsDiscussionAppendixReferences |
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However, most of the new devices and strategies mentioned previously remain in the animal experimentation phase, and very few have come to clinical study. Early work in the area of internal isolation of lung segments by Sabanathan and associates12 with 2 different designs of bronchial blockers (silicone balloons and occluded stents) in human subjects demonstrated improvement of symptoms in 5 of 8 patients. However, prosthesis migration, expectoration, and development of pneumonia limited the application of this approach. On the basis of information drawn from that study and results from animal models of bronchoscopic lung volume reduction, an ideal endobronchial device should therefore have the following qualities: (1) it should be effective in achieving and sustaining lung volume reduction, (2) the results should be reproducible, (3) the device should preferably be deployable by using a flexible bronchoscope with the patient under local anesthesia, (4) the device should be easily removable by using a flexible bronchoscope, (5) the design of the device should allow no migration or displacement in the airway, (6) bronchial secretions should be allowed to escape, and (7) there should be no pulmonary infection due to sputum retention. A full discussion of the available prototype devices is beyond the scope of this article, and interested readers are referred to the literature regarding the umbrella valve (Spiration, Inc, Redmond, Wash),13 various types of endobronchial blockers, and sealant.14-16
An alternative concept of creating extra-anatomic tracts was initially suggested by Macklem17 on the basis of the theory that the formation of extra pathways between the lung and the chest wall would allow escape of trapped air and thus improve the expiratory flow. This concept was modified, and extra-anatomic tracts can now be created through the bronchoscope between the major airway and the emphysematous lung parenchyma by using a radiofrequency probe (Broncus Technologies, Mountain View, Calif), and stents are then put in place in these iatrogenic tracts to prevent them from collapsing. Lausberg and colleagues18 from the Washington University School of Medicine reported a significant improvement of the FEV1 after nonanatomic tracts were created by using specific radiofrequency probes, followed by placement of expanding stents into each of the passageways by using human emphysematous lungs removed from the time of transplantation. The use of intraoperative endobronchial Doppler imaging is important in guiding the procedure and avoiding vessel perforation in a clinical study.19
The data from this study indicated that bronchoscopic placement of the EBVs is a safe procedure, and significant improvements were seen in pulmonary function, exercise tolerance, dyspnea scores, and HRQOL. Furthermore, admission to the intensive care unit is not mandatory, even in these high-risk patients. Only 3 of 20 patients needed admission to the intensive care unit: 2 for overnight observation because of carbon dioxide retention (but did not require mechanical ventilation) and 1 with postoperative pneumothorax (this patient eventually required another operation, as stated previously).
The exact mechanism for the pneumothorax remains unclear. It is almost certainly due to acute lung volume loss secondary to valve placement, but it begs the question why the remaining lung did not rise up to occupy the space. Pleural adhesion is a possible explanation but may be inadequate to account for the frequency of our observation. We do know, however, that there was no buildup of possible pressure in the pneumothorax space, because there was no air leak from the chest drain and because applying gentle suction did not completely resolve the pneumothorax.
Because no pneumonia was identified during the follow-up period, this suggests that bronchial secretion is being cleared in these isolated segments. It is not entirely unexpected that induced lobar collapse was evident on CT scans in only 10 of the 20 patients at 90 days (Figure 3). One explanation is that excess collateral airflow occurred in the emphysematous lungs20 and prevented the collapse of the target zones in some of our patients. Similar results were also seen in the pilot study conducted by Toma and colleagues,8 in which lobar collapse was evident in only 50% of the patients by using the same valve. This would have explained the fact that neither residual volume nor total lung capacity showed a significant decrease in our study. Even though segmental collapse is not always present, there is nonetheless a trend of improvement in the DLCO. This observation could be explained by airflow being redirected to the relatively healthier portions of the lungs by these one-way valves and hence reducing the / mismatch (Figure 4). More study is definitely needed in this area.
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Radiologically, / scan does not prove to be useful in the follow-up of these patients, because the findings are variable and the scan did not pick up subtle collapse in the lobes. Xenon scan with bronchial blockers may be helpful in delineating the collateral air drift between the segments, and this may help in selecting future patients for the placement of EBVs. Further study on this is currently under way.
In conclusion, this is the first detailed report on the feasibility, short-term outcome, and improvement of HRQOL after EBV placement for emphysema treatment. Our results suggest that a larger multicenter study with long-term follow-up is warranted. Such a trial—the International Endobronchial Valve for Emphysema Palliation Registry—is currently being organized.
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Appendix |
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TopAbstractPatients and methodsResultsDiscussionAppendixReferences |
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Appendix 2: St George Respiratory Questionnaire–Hong Kong
Appendix 3: Medical Research Council grades—degree of dyspnea
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Acknowledgments |
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Footnotes |
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References |
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TopAbstractPatients and methodsResultsDiscussionAppendixReferences |
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