A Multicenter, Prospective, Single-Arm Clinical Investigation of a Modified Staged Treatment Algorithm using the AeriSeal system

1. Subject is willing and able to provide informed consent and to participate in the study.
2. Subject is >= 40 years of age.
3. Subject has a diagnosis of homogenous or heterogeneous upper lobe predominant emphysema confirmed by CT scan.
4. Subject has at least 2 non-adjacent subsegments appropriate for treatment based upon CT scan in 2 different upper lobe segments in each lung (total 4 available subsegments)
5. Subject has clinically significant dyspnea scoring >= 1 on the mMRC scale of 0 - 4
6. Subject has a Six-Minute Walk Test (6MWT) distance >= 250 meters
7. Subject has post-bronchodilator FEV1 <= 45% predicted
8. Subject has Total Lung Capacity >100% predicted
9. Subject has Residual Volume >= 175% predicted
10. Subject has stopped smoking for at least 8 weeks prior to entering the study as confirmed by carboxyhemoglobin or cotinine levels.
11. Subject has received preventive vaccinations against potential respiratory infections consistent with local recommendations or policy.

1. Subject has severe bullous emphysema as judged by the Investigator.
2. Subject has prior lung volume reduction surgery, prior lobectomy or pneumonectomy, prior lung transplantation, prior airway stent placement, prior pleurodesis, or prior endobronchial lung volume reduction therapy of any type
3. Subject has evidence of active respiratory infection
4. Subject has an ongoing COPD exacerbation or bronchospasm
5. Subject has a known allergy to the device components:
a. Polyether block amide - PEBAX®
b. Polyvinyl Alcohol
c. Glutaraldehyde
6. Subject requires ventilatory support (invasive or non-invasive)
7. Subject has DLco < 20% predicted
8. Subject has a post-bronchodilator FEV1 < 20% predicted
9. Subject cannot tolerate corticosteroids or relevant antibiotics
10. Subject has other relevant comorbidities as judged by the Investigator, or is deconditioned and cannot tolerate the stress of post-treatment inflammatory response;
11. Subject has a history of recurrent clinically significant respiratory infections, defined as three (3) or more COPD exacerbations requiring hospitalization during the year prior to enrollment.
12. Subject has severe gas exchange abnormalities as defined by any one of the following:
a. PaCO2 >55 mm Hg
b. PaO2 <45 mm Hg on room air
c. SpO2 < 90% on >= 4 L/min supplemental O2, at rest
13. Subject has Pulmonary hypertension, defined as peak systolic pressure > 45 mm Hg on echocardiogram or right heart catheterization.
14. Subject use of systemic steroids > 20 mg/day or equivalent, immunosuppressive agents, heparins, oral anticoagulants (e.g., warfarin, dicumarol; note: antiplatelet drugs including aspirin and clopidogrel are permitted) within 4 weeks of entering the study.
15. Subject has alpha1 -antitrypsin serum level of <80 mg/kg (i.e. < 11 µmol/L) at Screening
16. Subject*s CT scan indicates the presence of any the following radiologic abnormalities:
a. Pulmonary nodule on CT scan greater than 0.8 cm in diameter (Does not apply if present for 2 years or more without increase in size or if proven benign by biopsy/PET)
b. Radiologic picture consistent with active pulmonary infection, e.g., unexplained parenchymal infiltrate
c. Significant interstitial lung disease
d. Significant pleural disease
17. Subject*s baseline EKG indicates arrhythmias or conduction abnormalities.
18. Subject has high cardiac risk after undergoing cardiac risk assessment in accordance with published guidelines or ischemic heart disease, congestive heart failure, renal failure or cerebrovascular disease :
19. Clinically significant asthma (reversible airway obstruction), chronic bronchitis, or bronchiectasis.
20. Allergy or sensitivity to medications required to safely perform bronchoscopy and the AeriSeal System treatment under general anesthesia or conscious sedation.
21. Participation in an investigational study of a drug, biologic, or device not currently approved for marketing within 30 days prior to entering the study or planned during the course of the study.
22. Body mass index (BMI) < 15 kg/m2 or > 35 kg/m2
23. Female subject pregnant or breast-feeding.
24. Abnormal screening laboratory test results as compared to reference lab normals at individual sites as follows:
a. Blood urea nitrogen > 1.5 x upper limit of normal
b. Creatinine > 1.5 x upper limit of normal
c. Aspartate aminotransferase > 1.5 x upper limit of normal
d. Alanine aminotransferase > 1.5 x upper limit of normal
e. Alkaline phosphatase > 1.5 x upper limit of normal
f. White blood cells (total) absolute < 3 x 109/L or > 1.25 x upper limit of normal
g. Hematocrit < 34 or > 1.25 x upper limit of normal
h. Platelets < 100 or > 450 K/µL
i. Prothrombin time or INR > 1.5 x upper limit of normal
j. Partial thromboplastin time > 1.5x upper limit of normal
k. Positive β-HCG Pregnancy test (if female);
25. Subject has evidence of severe disease which in the judgment of the investigator may compromise survival for the duration of the study (24 months) e.g.:
a. HIV/AIDs
b. Active malignancy
c. Stroke or TIA within 12 months of Screening visit
d. Myocardial infarction within 6 months of Screening visit
e. Congestive heart failure within 6 months of Screening visit defined as clinical evidence of right or left heart failure or left ventricular ejection fraction < 45% on echocardiogram
26. Subject has been diagnosed with diabetes mellitus.
27. Any 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 i.e., alcoholism, high risk for drug abuse or noncompliance in returning for follow-up visits