Trial Evaluating the Rate of Pneumothorax in Severe Emphysema Secondary to Endoscopic Volume Reduction with Two-stage ZEPHYR® Valves Versus Endoscopic Volume Reduction with One-stage ZEPHYR® Valves

Inclusion Criteria:

Patient able to give informed consent and participate in the study

• Age ≥ 35 years old and ≤ 80 years old at the time of signing the consent

• Emphysema (homogeneous or heterogeneous) on a recent CT scan (< 6 months).Heterogeneous emphysema defined by a difference of at least 15% destruction (threshold 910HU) between two adjacent lobes.

• Destruction ≥ 50% (threshold 910 HU) of the target lobe on the chest scanner

• Smoking quit for 3 months

• Dyspnea ≥ 2 according to the modified Medical Research Council (mMRC) questionnaire)

• Post-bronchodilator FEV between 15 and 50% theoretical

• Post-bronchodilator total lung capacity ≥ 100% theoretical and post-bronchodilatorresidual volume ≥ 175% theoretical

• Distance traveled during the TM6M ≥ 100m

• Member of or beneficiary of a social security scheme

Exclusion Criteria:

• Asthma considered as main diagnosis

• Recurrent exacerbations: (>3 over the last year or 2 requiring hospitalization)

• Myocardial infarction or stroke in the 6 months prior to inclusion

• Symptoms of heart failure in the 6 months prior to inclusion

• Chest CT abnormalities: giant bulla (occupying more than a third of the pulmonaryfield), paraseptal emphysema, pulmonary nodule greater than 0.8cm (not applicablepulmonary nodules known for more than a year and stable), fibrosing interstitialpneumonitis, dilated bronchi

• Pulmonary tomoscintigraphy:

• Patients for whom the least perfused lobe is not the one with the highestemphysema destruction score

• Patients with homogeneous emphysema for whom the perfusion delta (difference inperfusion between the ipsilateral lung and the treated lobe) is less than 10%

• Arterial blood gas analysis in ambient air: Hypoxemia in ambient air (PaO2 < 45mmHg). Hypercapnia (PaCO2 > 55 mmHg)

• Echocardiography:

• Left Ventricular Ejection Function < 45%

• Systolic pulmonary arterial pressure > 45 mmHg

• History of pneumonectomy, lung surgery homolateral to the lobe targeted forendoscopic lung volume reduction

• History of pneumothorax homolateral to the lobe targeted for endoscopic lung volumereduction

• History of endoscopic volume reduction

• Oral corticosteroid therapy > 20 mg/day within the 4 weeks preceding inclusion

• Symptomatic bronchial dilatations, bronchial colonization with pseudomonasaeruginosa, multi-resistant bacteria or aspergillus origin

• Metastatic cancer undergoing treatment or whose treatments ended less than 5 yearsago

• Pregnant or breastfeeding women

• Nickel allergy

• Patient under guardianship, curatorship or under judicial protection

• Participation in another interventional clinical research

• Any other condition which, in the opinion of the investigator, could interfere withthe objective of the study or would cause the subject's participation in the studyto be suboptimal, in particular (non-exhaustive list) unweaned alcoholism, substanceabuse, non-compliance with usual follow-up visits)

secondary exclusion criteria:

• Evidence of collateral ventilation measured by the Chartis system