Bronchoscopic Lung Volume Reduction (LVR)
Following the landmark study of lung volume reduction surgery (LVRS) reported in 2003 and its finding of serious adverse events related to the surgical intervention, non-surgical approaches have been explored. I reported on some of these previously (Citation1, 2), but there has been significant further progress with transbronchoscopic approaches.
PneumRx Coil
The PneumRx Coil is a Nitinol memory shape wire that is formed as a coil but implanted into an emphysematous lung segment in its straight form through a bronchoscope under fluoroscopic visualization. Immediately after its implantation, the wire begins to resume its coiled configuration and in so doing, gathers up the emphysematous region reducing its volume. Typically, about 10 coils are placed into each lung in 2 sessions separated by a month. Patients are generally able to return home within a day; they experience an improvement in lung function within hours. The improvement continues over several subsequent days or weeks. Reports indicate the procedure is well tolerated and without serious adverse events thus far (Citation3, 4). A video of the coil placement is available at http://www.pneumrx.com/physicians-q10021-c10003-LVRC_Video.aspx.
The PneumRx coil is listed in 4 trials at clinicaltrials.gov, 2 of which are in phase 3 (NCT01220908 and NCT01421082). The second of these trials is in patients who do not have heterogeneous emphysema and would thus not be considered candidates for conventional LVRS. One advantage that one can expect for the PneumRx approach is that its efficacy might be expected to be independent of a complete inter-lobar septum. The manufacturers, PneumRx Inc (Mountain View, CA), claim the procedure is reversible. The device is not currently approved in the United States.
However, the coils have been used in Europe in clinical studies since 2008 and sold there commercially since 2010. To July 2012, over 3,000 coils had been implanted in 350+ patients. Improvements in lung function were accompanied by a mean improvement in SGRQ of 12 points and a mean increase in 6 minute walk test of 22%. A randomized trial, RENEW, of treatment with coils versus usual care is ongoing (NCT01608490).
Aeris Polymeric LVR System
A biologic complex is delivered to emphysematous regions via dual lumen bronchoscope. The biologic complex is a gel consisting of chondroitin sulfate in a fibrin vehicle; thrombin is simultaneously delivered in the second lumen resulting in polymerization of the gel, obstruction of the treated airway and, ultimately, reabsorption of gas in distal regions (Citation5). The most recent report is of a 1-year single-arm Israeli study of 20 emphysematous patients, half of whom had homogeneous disease (Citation6).
The procedure time averaged 15 min, in-hospital stay was 1 day. Mean 1-year improvement in FEV1 was 25%; reduction in TLC was 895 ml; reduction in SGRQ was 7 points. The benefits were apparent at the first review 3 months after the procedure and were maintained at the same level upon study conclusion at 12 months. One treatment-related death resulted from pneumothorax, other than that there were a few instances of COPD exacerbations or pneumonitis. A video of the procedure is available at http://www.aerist.com/aeriseal-system/. Seventeen trials of the Aeris system are listed in clinicaltrials.gov; 8 of them are completed.
InterVapor System
This Uptake Medical Corp. (Tustin, CA) system delivers heated water vapor through a bronchoscope in precise doses to target airways in the emphysematous lung. The treated airway responds with local inflammation and closure of the airway resulting in reabsorption of gas from distal lung regions.
In application, a proprietary software program identifies appropriate target airways from each patient's CT scan. Precisely controlled heated water vapor is generated and delivered to each target airway through a proprietary catheter which isolates the target airway from other airways. Vapor delivery is for a specified duration, typically for 3–10 s, and 3–8 lung segments from one lobe may be treated.
Treatments are followed by a transient increase in symptoms that may require management as for an acute exacerbation. Mean improvements in lung function at 12 months include a modest increase in FEV1 of 86 ml, a reduction in RV of 46 ml, an increase in 6MWD of 18 meters, and an improvement in SGRQ of 11 units (Citation7, 8).
A drawback of this form of LVR is that its efficacy is likely to be limited when inter-lobar septa are incomplete as collateral ventilation will enable diseased regions to remain inflated, a problem that is less likely to occur with the coil or biologic LVR systems. The procedure is not approved in USA. Two completed trials are listed in clinicaltrials.gov. A video is available at the sponsorís web site http://www.uptakemedical.com/about-intervapor/how-it-works.
Several trials continue on the endobronchial valves that I reported on previously (Citation1).
GHK
The Gly-His-Lys (GHK) tripeptide may have a restorative action on alveolar cells of emphysematous lung regions. Investigators at Boston University profiled gene expression from various parts of emphysematous lungs and identified 127 genes whose expression levels differed from normal. Some were increased, including some genes involved with inflammation; others were decreased, including genes involved in tissue repair. The degree of change corresponded to the severity of emphysema in that region. Using the Connectivity Map, the investigators identified GHK as an agent that could reverse the gene expression signature associated with emphysematous changes. Treating cells from emphysema lungs in vitro with GHK restored the abnormal gene expression toward normal (Citation9). The authors suggest that gene expression changes in abnormal tissues may not only provide insights into pathogenesis but also identify therapeutic options for their treatment.
The agent, GHK, is normally present in humans and had been shown previously to accelerate repair of damaged skin cells in vitro. Its potential for COPD treatment is being evaluated in animal models at present. Studies in humans lie ahead.
Acknowledgments
The information found in this column was made available to the author through Citeline's Trial Trove ©. For more information on Trial Trove, please visit www.citeline.com.
References
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- Gross NJ. The COPD Pipeline XVIII. COPD 2012; 9:571–3.
- Herth FJ, Bronchoscopic lung volume reduction with a dedicated coil: a clinical pilot study. Ther Adv Respir Dis 2010; 4:225–231.
- Slebos D-J, Bronchoscopic lung volume reduction coil treatment of patients with severe heterogeneous emphysema. Chest 2012; 142:574–582.
- Criner GJ, Biologic lung volume reduction in advanced upper lobe emphysema: phase 2 results. Am J Respir Crit Care Med 2009; 179:791–798.
- Kramer MR, Bilateral endoscopic sealant lung volume reduction therapy for advanced emphysema. Chest June 2012 doi:10.1378/chest.12-0421.
- Snell G, Bronchoscopic thermal vapour ablation therapy in the management of heterogeneous emphysema. Eur Respir J 2012; 39:1326–1333.
- Herth FJF, Characterization of outcomes one year after endoscopic thermal vapor ablation for patients with heterogeneous emphysema. Int J COPD 2012; 7:397–405.
- Campbell JD, A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK. Genome Med 2012; 4:67 doi:10.1186 /gm367.