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

The Zephyr® valve was first implanted in 2001. Since then, 5 important studies have proven a clinical superiority compared to the existing standard of care. Bronchoscopic lung-volume reduction with the use of one-way endobronchial valves is a potential treatment for patients with severe emphysema. Loss of lung elastic recoil leads to airflow obstruction, gas trapping, and increased operating lung volumes. Lung volume reduction surgery (LVRS), resection of the most affected of the lung, has been clearly shown to improve outcomes in selected patient groups. The surgical intervention is, however, associated with significant morbidity and an early mortality rate of about 5%. Therefore, there is considerable interest in developing novel treatment approaches that can reduce lung volume and gas trapping, either more safely than LVRS or in patients for whom LVRS is not an option.

In the present study, 244 patients will be randomized. After the selection process, they will all be hospitalized in order to undergo an endoscopic lung volume reduction with Zephyr® valve under general anesthesia. Half of them, the experimental group, will be treated according to Limoges' treatment algorithm (2 stages). For the other half, the control group, the entire lobe will be treated during one procedure will. Both groups will receive the standard of care treatments, according to the Global initiative for chronic Obstructive Lung Disease recommendations (GOLD).

Both groups will be followed for one year:

• All the patients will undergo a thorax CT scan 45 days after implanting the last valve. Three follow-up consultations are planned at 45 days, 6, and 12 months. During these consultations, each patient will complete a Saint-George Respiratory Questionnaire (SGRQ) Test, a plethysmography and a 6-minutes walking test.
• Patients randomized in the experimental group will undergo a plethysmography and a thorax CT scan one day before the second procedure.

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-bronchodilator residual 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 pulmonary field), paraseptal emphysema, pulmonary nodule greater than 0.8cm (not applicable pulmonary nodules known for more than a year and stable), fibrosing interstitial pneumonitis, dilated bronchi
• Pulmonary tomoscintigraphy:

• Patients for whom the least perfused lobe is not the one with the highest emphysema destruction score
• Patients with homogeneous emphysema for whom the perfusion delta (difference in perfusion between the ipsilateral lung and the treated lobe) is less than 10%
• Arterial blood gas analysis in ambient air: Hypoxemia in ambient air (PaO2 < 45 mmHg). 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 for endoscopic lung volume reduction
• History of pneumothorax homolateral to the lobe targeted for endoscopic lung volume reduction
• History of endoscopic volume reduction
• Oral corticosteroid therapy > 20 mg/day within the 4 weeks preceding inclusion
• Symptomatic bronchial dilatations, bronchial colonization with pseudomonas aeruginosa, multi-resistant bacteria or aspergillus origin
• Metastatic cancer undergoing treatment or whose treatments ended less than 5 years ago
• 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 with the objective of the study or would cause the subject's participation in the study to be suboptimal, in particular (non-exhaustive list) unweaned alcoholism, substance abuse, non-compliance with usual follow-up visits)

secondary exclusion criteria:

• Evidence of collateral ventilation measured by the Chartis system