The investigators will approach all patients with failed EBV therapy. Patients with less
than 350 ml of volume reduction in the target lobe and persistent dyspnea [score greater
or equal to 2 on the Modified Medical Research Council Dyspnea Scale (mMRC)] after EBV
placement will be considered to have failed EBV therapy due to adhesions or collateral
ventilation being present. Only patients with failed EBV therapy will be approached to
participate in our study. Once the patient agrees to participate and sign the consent,
all the screening information collected as part of the standard of care will be extracted
retrospectively from the medical records including appointment details, 6MWD, and PFTs
results. In addition, during the same visit, health-related quality of life will be
measured using the Saint George Respiratory Questionnaire (SGRQ) and COPD Assessment Test
(CAT), and dyspnea will be assessed with the self-reported mMRC.
VATS Inter-Lobar Fissure Completion and Pleural Adhesiolysis The clinician providing
general anesthesia will be familiar with thoracic anesthesia and complications in
patients with severe COPD undergoing thoracic surgery and endoscopic valve implantation.
Total IV anesthesia will be used during all bronchoscopic procedures. Routine
antimicrobial prophylaxis will be administered at induction. The antimicrobial choice
will be based on the subject's allergies and/or history of resistant organisms.
The experimental procedure will be performed via VATS under inhaled anesthetic agents by
an experienced thoracic surgeon from BIDMC. The clinician providing general anesthesia
will be familiar with thoracic anesthesia and complications in patients with severe COPD
undergoing thoracic surgery and endoscopic valve implantation. A double-lumen
endotracheal tube will be inserted allowing one-lung ventilation and the maximal collapse
of the operative lung. The subject will be placed in lateral decubitus with the operative
side up. Disinfection of the surgical site will be performed with the application of an
antiseptic solution and the subject will be draped in the usual sterile fashion. The
thoracic surgeon will perform multiple rib blocks and inject the skin incisions with
bupivacaine. Through small incisions, the surgeon will create a camera port through the
intercostal space and then the anterior and posterior inferior ports. Electrocautery will
be used for adhesion release of the ipsilateral lung of the target lobe. Dissection and
exposure of the anterior aspect of the hilum will then be performed using electrocautery.
Following the exposure, stapling will be performed on the incomplete fissure adjacent to
the target lobe, using the Endo GIATM (CovidienTM, Mansfield, MA) FDA-approved surgical
stapler. The lung tissue will be dissected until the pulmonary artery is seen, in a
similar fashion to the method used in lobectomies and segmentectomies. Multiple surgical
stapler activations will be used to complete the target fissure along the fissure line.
An attempt at conversion to a complete fissure will be made, though depending on the
anatomy, it may be possible that residual incomplete fissure of up to 5% may be
tolerated. Hemostasis will be evaluated. Sterile water will then be used to fill the
surgical area, followed by lung inflation and inspection to verify for air leaks at the
level of the stapling. If an air leak is detected, suturing, re-stapling, or applying
pleural sealants will be used to seal it. The patient will be monitored closely for air
leaks in the postoperative setting in case there is the persistence of the air leak
despite the measures taken and valve presence, a second intervention will be considered
based on the thoracic surgeon's judgment. Once the fissure is surgically completed, a
chest tube will be placed and connected to a chest drainage system.
In the setting that the thoracic surgeon will not be able to complete the fissure up to
95% due to anatomic restraints, the procedure will then be ended without valve
implantation, as the presence of residual collateral ventilation is expected. All
patients will receive standard of care post-operative management, and subjects will
continue to be followed for any procedure-related adverse events until the event has
subsided or, in case of permanent impairment, until the event stabilizes, and the overall
clinical outcome has been ascertained. At that time, the subject will be withdrawn from
the study and will be considered as an "Enrollment Failure" and recorded as such for
statistical analysis.
Bronchoscopic Evaluation The double-lumen endotracheal tube will be removed, and a
single-lumen tube (8.0 to 8.5 mm) inserted. The lung will be completely re-inflated
before this evaluation to return them to normal anatomy.
Flexible bronchoscopy will be done by the interventional pulmonologist. The bronchoscope
will be passed via the endotracheal tube and the major airways will be examined. The
placement of the EBVs will be assessed. In case one of the valves is not adequately
placed, the interventional pulmonologist will adjust it. If any valve needs to be
replaced, the replacement will be performed at this point. A bronchial wash will be
performed with samples sent for culture. If there are unexpected findings, such as a
lesion suspicious for carcinoma or secretions suggesting infection, then appropriate
clinical samples will be obtained, and the subject will be re-evaluated, the study team
will then determine if the subject will be withdrawn from the study and will be
considered as an "Enrollment Failure" and recorded as such for statistical analysis.
Postoperative Persistent Air-Leak Management In the setting of a persisting air-leak > 5
days after the procedure, the investigator will proceed to the removal of the most
proximal valve from the treated lobe (if the left upper lobe is the treatment lobe, the
removal will be from a lingular segment). If there is a resolution of the air leak within
48 hours, replacement of the valve will be considered and scheduled in 6 weeks. During
the valve replacement procedure, if previously placed valves are observed to be
sub-optimally placed, the investigator may remove and replace any sub-optimally placed
valves.
If the air leak does not resolve within 48 hours after the first valve removal, all
remaining valves will be removed. In the setting of a persistent air-leak despite
previous interventions, further management will be based on the investigator's judgment
and per standard of care (chemical pleurodesis or conservative management). Chest tube
maintenance > 7 days in presence of a persistent air leak will also be considered as a
thoracic serious adverse event and recorded in the AE CRF as part of the study's safety
evaluation.
The management algorithm for persistent air-leaks was adapted from the expert consensus
by Valipour et al. Clinical management of persistent air-leaks may vary depending on
clinical circumstances, so exceptions to these guidelines will not be considered protocol
deviations.
Pneumothorax Management Pneumothorax after valve placement can be an effect of the
desired treatment response that is associated with complete lobe treatment and
atelectasis. The management of pneumothorax is an integral part of the treatment. The
origin is thought to be from the rupture of stretched diseased tissue that is adjacent to
the volume reduced lobe. Management for pneumothorax associated with EBVs will be
conducted according to expert consensus and our internal algorithm, which represents
standard-of-care for pneumothorax management.
Follow-up Period After VATS fissure completion and adhesiolysis, patients will be placed
on a standardized follow-up protocol used for individuals that underwent video-assisted
thoracic surgery. Data from follow-up appointments at 14 days and 3 months will be
collected from the medical records retrospectively including appointment details,
complications, CT-scan results, 6MWD, and PFTs results. Target lung volume reduction
(TLVR) will be assessed at 3 months using the CT scans performed on patients as part of
their standard of care. The only procedures that will be considered research after the
initial surgical intervention would be the measurement of health-related quality of life
with the SGRQ and CAT, and dyspnea assessment with the self-reported mMRC at 3 months.