An Evaluation of the AeriSeal System for CONVERTing Collateral Ventilation Status in Patients With Severe Emphysema

Inclusion Criteria: 1. Subject is willing and able to provide informed consent and to participate in the study. 2. Subject is aged ≥ 40 and ≤ 80 years at the time of the ICF signature date. 3. Subject has completed a documented pulmonary rehabilitation (in clinic or home-based) program within 12 months prior to Baseline. 4. Subject has stopped smoking for at least 8 weeks prior to the ICF signature date as confirmed by carboxyhemoglobin or cotinine levels. 5. Subject has a recent HRCT meeting the scan parameter requirements and performed within 3 months of the ICF signature date with the following findings at -910 Hounsfield Units: 1. At least one (1) lobe with segmental emphysema destruction score ≥ 50%. 2. Subject has heterogenous emphysema, defined as difference in emphysema destruction score of ≥ 15 between the density scores of the target lobe and the ipsilateral non-target lobe(s) per QCT report with % voxel density of \< -910 HU. For non-target lobes that include the RML, calculate the combination of non-target lobes as a single density score using volume-weighted percent. 3. LUL, LLL, RUL, RLL, or RUL+RML are targets for valve intervention. 4. Subject has a gap in the interlobar fissure that corresponds to one or more segments and the fissure(s) contacting the target lobe is ≥ 80% complete per QCT report. 5. Subject has 98% of the fissure gap confined to a maximum of 3 segments within the target lobe per Fissure Targeting Report (FTR). 6. Subject has 6MWD ≥ 150 m and ≤ 450 m. 7. Subject has clinically significant dyspnea with an mMRC score of ≥ 2. 8. Subject has post-bronchodilation FEV1 ≥ 15% predicted and ≤ 45% predicted. 9. Subject has an FEV1/FVC ratio of \< 0.7. 10. Subject has post-bronchodilation TLC, measured by body plethysmography, ≥ 100% predicted. 11. Subject has post-bronchodilation RV ≥ 175% predicted, measured by body plethysmography. 12. Subject has post-bronchodilation DLCO ≥ 20% predicted. 13. Subject has received preventative vaccinations against potential respiratory infections, including COVID-19, consistent with local recommendation or policy. 14. Subject is on optimal medical management for more than one month prior to the ICF signature date. 15. Subject has collateral ventilation (CV+) as confirmed per the Chartis assessment prior to the AeriSeal Index Procedure. Exclusion Criteria: 1. Subject has prior lung volume reduction surgery, lobectomy or pneumonectomy, lung transplantation, airway stent placement, pleurodesis, or BLVR of any type, except BLVR using Zephyr Valve with \< 50% TLVR at 6 months, followed by valve removal \> 6 months prior to ICF signature date. 2. Subject has visible radiological abnormality on HRCT scan such as pulmonary nodule greater than 0.8 cm in diameter (does not apply, if present for 2 years or more without increase in size or if deemed benign by biopsy) or active pulmonary infection (e.g., unexplained parenchymal infiltrate, significant interstitial lung disease or significant pleural disease). 3. Post-COVID-19 pathology on CT, including ground glass opacities with or without consolidation, adjacent pleura thickening, interlobular septal thickening, or air bronchograms. 4. Large bullae encompassing greater than 1/3 of the total lung. 5. Subject had 3 or more COPD exacerbations requiring hospitalization within 12 months preceding the ICF signature date or a COPD exacerbation requiring hospitalization within 8 weeks of the ICF signature date. Subjects may be re-considered for future enrollment. 6. Subject has asthma as their primary diagnosis. 7. Subject has chronic bronchitis (defined as greater than 4 tablespoons of sputum production per day) as their primary diagnosis. 8. Subject has clinically significant bronchiectasis. 9. Subjects with evidence of active respiratory infection should be considered for enrollment only after satisfactory resolution. 10. Subject requires invasive ventilatory support. Note: The use of Continuous Positive Airway Pressure (CPAP) or BiPAP devices for sleep apnea is permitted. 11. Subject has severe gas exchange abnormalities as defined by any one of the following tests, conducted at rest, on room air, as tolerated. * PaCO2 ≥ 50 mm Hg (6.7 kPa) * PaO2 \< 45 mm Hg (6.0 kPa) 12. Subject has pulmonary hypertension, defined as mean pulmonary systolic pressure \> 45 mm Hg. 13. Subject has known documented alpha-1 antitrypsin deficiency. 14. Subject has clinically significant hematological disorder. 15. Subject has recent significant unplanned or unexplained weight loss or other relevant comorbidities considered by the investigator to be potentially confounding or limiting to the subject's participation in the study. 16. Subject has non-atrial arrhythmias or conduction abnormalities on EKG. 17. Subject has high cardiac risk after undergoing cardiac risk assessment in accordance with published guidelines (Fleisher 2007) or has ischemic heart disease, congestive heart failure, cerebrovascular disease (stroke or TIA within 6 months of the ICF signature date), serum creatinine \> 2.0 mg/dL (177 μmol/L), or left ventricular ejection fraction (LVEF) \< 45% on echocardiogram. 18. Subject has uncontrolled exercise induced syncope. 19. Subject has evidence of severe disease which in the judgment of the investigator may compromise the anticipated treatment effect or the subject's survival for the duration of at least 12 months. 20. Subject has any other condition that the investigator believes would interfere with the intent of the study or would make participation not in the best interest of the subject including but not limited to alcoholism, high risk for drug abuse, or noncompliance in returning for follow-up visits. 21. Subject cannot tolerate corticosteroids or relevant antibiotics. 22. Subject use of systemic corticosteroids \> 20 mg/day prednisolone or equivalent within four (4) weeks of the ICF signature date. Subjects may be re-considered for future enrollment. 23. Subject use