The purpose of this protocol is to perform a pilot prospective randomized controlled clinical trial to evaluate the potential role of lung fissure completion strategy (experimental intervention) in addition to endobronchial valve (EBV) placement (representing "standard-of-care") in select patients with severe COPD/emphysema and with evidence for <95% fissure completion between adjacent lung lobes. In select patients, lung fissure completion strategy will be performed by either video-assisted thorascopic surgery (VATS)-guided or robotic-guided stapling along the lung fissures in an attempt to reduce collateral ventilation and determine whether or not this experimental strategy will improve outcome following subsequent EBV placement. EBV placement will follow successful VATS-guided or robotic-guided fissure stapling.

The study will enroll approximately 20 patients at BIDMC, and outcomes will focus on procedure-related complications, physiological measurements (ex., FEV1 by pulmonary function testing) and clinical symptoms (i.e., questionnaires). Patient will be followed for 3-month period, receiving usual standard of care during the 3 months of follow-up. The goal of this protocol is to determine if elimination of significant collateral lung ventilation between lung lobes is possible, and whether such strategy to eliminate collateral lung ventilation between lobes improves outcomes following subsequent EBV placement (i.e. promotes atelectasis of diseased lung segments) in the management of severe COPD/emphysema in appropriate candidates. For subjects in the medical management control group, upon completion of the 3-month F/U period, they will be eligible for EBV if they choose.

We plan to approach all EBVs candidates that have < 95% lobar fissure completion. 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 modified Medical Research Council dyspnea scale (mMRC). After completing these questionnaires and indexes, subjects will be randomized by an opaque envelope technique following a block 2-4 pattern to either Group 1 (Combined robotic or VATS-fissure completion and BLVR with EBVs) or Group 2 (Medical management).

Both surgical stapling for fissure completion and EBVs implantation will be performed during the same procedure and under general anesthesia in the operating room. Depending on the duration of the surgical intervention, the endoscopic valve implantation might be deferred and performed within 48 hours, based on the clinical judgment of the PI, surgeon, and anesthesiologist present during the procedure.

Initial Bronchoscopic Evaluation Initial flexible bronchoscopy will be done by the interventional pulmonologist who will perform the endoscopic valve placement as part of the standard of care. The bronchoscope will be passed via the endotracheal tube and the major airways will be examined. 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 to determine if they are eligible to undergo the study procedure later. If so, the procedure will be rescheduled. If not, the subject will be withdrawn from the study and will be considered as an "Enrollment Failure" and recorded as such for statistical analysis.

First Chartis Pulmonary System Evaluation of CV Following initial bronchoscopy, evaluation of CV using the Chartis system (Pulmonx Inc., Redwood, CA, USA), will be performed also as part of the standard of care of the patients. If there is no evidence of CV between the target lobe and the adjacent one, the patient will be withdrawn from the study and EBVs will be placed. On the other hand, if the ChartisTM evaluation is positive for CV, the bronchoscope will be withdrawn, and the patient will undergo robotic or VATS completion of the inter-lobar fissure adjacent to the previously selected target lobe.

Robotic or VATS Inter-Lobar Fissure Completion Surgery will be performed with a robotic or VATS approach under inhaled anesthetic agents by an experienced thoracic surgeon from BIDMC. 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. 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 dissection and exposure of the anterior aspect of the hilum. Stapling will then be performed on the incomplete fissure adjacent to the target lobe, using the Endo GIATM (CovidienTM, Mansfield, MA).

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. If the air leak persists at the site of stapling despite these measures, the subject will still be allowed to proceed to EBVs implantation. Once the fissure is surgically completed, a chest tube will be installed and connected to a digital chest drainage system (ThopazTM Digital Chest Drainage System, Medela Healthcare).

Second Chartis Pulmonary System Evaluation of CV 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. Assessment of CV with the ChartisTM system will be performed once again in the same inter-lobar fissure as before following the previously described methods. If the result is negative for CV or there is an improvement in the evaluation, then we will proceed with EBVs implantation.

EBVs Placement Bronchoscopic placement of EBVs will then be performed as part of the standard of care of patients since they meet the previously mentioned inclusion criteria and have no CV, same as patients with an initial negative ChartisTM evaluation. The airway sizing system and a calibrated balloon will be used in the previous re-inflated lung to determine the appropriate Zephyr® valves size to treat the target lobe airways. The treatment algorithm is complete occlusion of one lobe by using valves to occlude all segments of the lobe. Either upper or lower lobes may be targeted for treatment. The lobe will have been selected by the CT core laboratory based on imaging with computed tomography. However, the PI can choose the alternate eligible lobe if the airway in the primary eligible lobe is overly challenging for valve implantation, such as difficulty associated with the underlying airway anatomy.

A valve may be removed and replaced with a different size valve during the procedure and a valve may also be removed and replaced to improve the location. However, a valve may not be repositioned during the procedure. It is intended that the investigator occlude all segments of the target lobe by placing valves into segmental or sub-segmental airways. There is anatomic variability in the number and size of segments in a lobe, so this protocol does not have a limit on the number of valves to be used. Subjects who do not have any endobronchial valves placed at the end of the bronchoscopy procedure will be withdrawn.

Follow-up Period After BLVR with EBVs, patients will be placed on a standardized follow-up protocol used for individuals that underwent BLVR. All procedures and appointments following EBV placement will be considered standard of care. 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. 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 every follow-up appointment.

Crossover Group After the patient allocated to the medical management, the arm is followed for 3 months, they will be offered the robotic or VATS fissure completion procedure. It will be completely up to the candidates to undergo the intervention. If they decide that they want to proceed with surgery, the previously described methods will be used including the same surgical technique, same postoperative management, and same follow-up timelines and datapoints.

Inclusion Criteria:

• Age 40 to 75 years.
• Stable with less than 10mg prednisone (or equivalent) daily.
• Nonsmoking for 4 months prior to screening and willing to not smoke during the study duration.
• Completed a supervised pulmonary rehabilitation program less than equal to 12 months prior to the baseline exam or is regularly performing maintenance respiratory rehabilitation if initial supervised therapy occurred greater than 12 months prior.
• Current pneumococcus vaccination.
• Current influenza vaccination.
• Willing and able to complete protocol required study follow-up assessments and procedures.

Exclusion Criteria:

• > 95% fissure completion on high-resolution chest CT-scan (HRCT) or StratX evaluation with a Chartis evaluation negative for collateral ventilation.
• Clinically significant (greater than 4 tablespoons per day) mucus production.
• Myocardial infarction within 6 months of screening.
• Uncontrolled congestive heart failure.
• Three or more pneumonia episodes in last year.
• Three or more COPD exacerbation episodes in the last year.
• Prior lung transplant, LVRS, bullectomy, or lobectomy.
• Clinically significant bronchiectasis.
• Unable to safely discontinue anticoagulants or platelet activity inhibitors for 7 days.
• Uncontrolled pulmonary hypertension (systolic pulmonary arterial pressure >45mmHg) or evidence or history of CorPulmonale as determined by a recent echocardiogram (completed within the last 3 months prior to screening visit).
• Left ventricular ejection fraction (LVEF) less than 40% as determined by a recent echocardiogram (completed within the last 3 months prior to screening visit).
• Resting bradycardia (<50 beats/min), frequent multifocal PVCs, complex ventricular arrhythmia, sustained SVT.
• Post-bronchodilator FEV1 less than 15% or greater than 45% of the predicted value at screening.
• TLC less than 100% predicted (determined by body plethysmography at screening).
• RV less than 150% predicted in patients with heterogeneous emphysema or less than 200% predicted in patients with homogeneous emphysema (determined by body plethysmography at screening).
• DLCO less than 20% of the predicted value at screening.
• Post-rehabilitation 6-minute walk distance less than 100 meters or greater than 450 meters at screening.
• PaCO2 greater than 50mmHg on room air at screening.
• PaO2 less than 45mmHg on room air at screening