Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Controlled Trial on the Cardiovascular Effects of Lung Volume Reduction Surgery in Patients With Chronic Obstructive Pulmonary Disease
Brief Summary: A randomised controlled trial will be performed to evaluate the effects of lung volume reduction surgery (LVRS) in patients with COPD on systemic inflammation, oxidative stress, endothelial function, arterial stiffness and blood pressure. We hypothesize that LVRS will lead to a reduction of systemic inflammation, oxidative stress, arterial stiffness and blood pressure and to improved endothelial function.

For this purpose 30 patients with severe/very severe COPD (GOLD III-IV) and pulmonary emphysema who are to undergo LVRS will be randomised to one of two groups: group 1 receiving immediate LVRS and group 2 receiving LVRS after a delay of 3 months.

Measures of systemic inflammation, oxidative stress, endothelial function, arterial stiffness and blood pressure will be measured at baseline and 3 months after surgery and no surgery, respectively (group 2 receiving surgery only after a delay of 3 months will serve as control group) to investigate the effects of LVRS on the described outcomes.


Options:
A: Inclusion Criteria:

1. Willing and able to provide informed consent
2. Age ≥ 40 years
3. On optimal medical therapy\* for more than 1 month
4. Advanced upper lobe predominant emphysema confirmed by CT scan
5. Two (2) subsegments appropriate for treatment in 2 different upper lobe segments in each lung based upon CT scan (total 4 available subsegments)
6. MRCD score of ≥ 2 post pulmonary rehab (using modified MRCD scale of 0-4)
7. 6MWT distance ≥ 150 m post pulmonary rehab
8. Spirometry 15 minutes after administration of a bronchodilator showing BOTH:

   1. FEV1 \< 50% predicted
   2. FEV1/FVC ratio \< 70%
9. Plethysmographic lung volumes showing BOTH:

   1. TLC \> 100% predicted
   2. RV \> 150% predicted
10. DLco ≥ 20% and ≤ 60% predicted
11. Blood gases and oxygen saturation showing BOTH:

    1. SpO2 ≥ 90% on ≤ 4 L/min supplemental O2
    2. PaCO2 \< 65 torr
12. Smoking history of ≥ 20 pack-years with abstinence for 16 weeks

Exclusion Criteria:

1. Prior lung volume reduction surgery, lobectomy or pneumonectomy, or lung transplantation
2. Requirement for ventilator support (other than CPAP or BPAP for sleep apnea)
3. Three (3) or more COPD exacerbations requiring hospitalization within 1 year of Screening visit or a COPD exacerbation requiring hospitalization within 8 weeks
4. Use of systemic steroids \> 20 mg/day or equivalent immunosuppressive agents, heparins, oral anticoagulants or investigational medications

   Exclusion Criteria (continued):
5. a-1 antitrypsin serum level of \< 80 mg/dL (immunodiffusion) or \< 11 µmol/L (nephelometry)
6. CT scan: Presence of any of the following radiologic abnormalities:

   1. Pulmonary nodule on CT scan greater than 1.0 cm in diameter
   2. Radiologic picture consistent with active pulmonary infection
   3. Significant interstitial lung disease
   4. Significant pleural disease
   5. Giant bullous disease
7. Clinically significant asthma
8. Clinically significant bronchiectasis
9. Pulmonary hypertension
10. Allergy or sensitivity to medications required to safely perform AeriSeal System treatment under general anesthesia or conscious (moderate procedural) sedation
11. Participation in an investigational study of a drug, biologic, or device not currently approved for marketing
12. Body mass index \< 15 kg/m2 or \> 35 kg/m2
13. Female patient pregnant or breast-feeding or planning to be pregnant in the next year
14. Any abnormal screening laboratory test result
15. Significant comorbidity including any of the following:

    1. HIV/AIDs
    2. Active malignancy
    3. Stroke or TIA within 12 months
    4. Myocardial infarction within 12 months
    5. Congestive heart failure within 12 months
16. Any condition that would interfere with the intent of the study or would make participation not in the best interest of the patient such as alcoholism, high risk for drug abuse or noncompliance in returning for follow-up visits
B: Inclusion Criteria:

* clinical diagnosis of advanced upper lobe emphysema
* age \>/= 40 years
* clinically significant dyspnea
* failure of standard medical therapy to relieve symptoms (inhaled beta agonist \& inhaled anticholinergic)
* pulmonary function tests within protocol-specified ranges (post bronchodilator FEV1 \< 45% predicted \& experiencing \< 30% or 300 mL improvement using bronchodilator; total lung capacity \> 110% predicted; residual volume \> 150% predicted)
* 6 Minute Walk Distance \>/= 150 m

Exclusion Criteria:

* alpha-1 protease inhibitor deficiency
* homogeneous emphysema
* tobacco use within 4 months of initial visit
* body mass index \< 15 kg/m2 or\> 35 kg/m2
* clinically significant asthma, chronic bronchitis or bronchiectasis
* allergy or sensitivity to procedural components
* pregnant, lactating or unwilling to use birth control if required
* prior lung volume reduction surgery, lobectomy, pneumonectomy, lung transplant, endotracheal valve placement, airway stent placement or pleurodesis
* comorbid condition that could adversely influence outcomes
* inability to tolerate bronchoscopy under conscious sedation (or anesthesia)
* history of renal infarction or renal failure
C: Inclusion criteria:

* Dyspnea at rest or at minimal physical activity, severe limitation of exercise capacity (6-min walk distance \< 350 m).
* Acceptance of an increased perioperative mortality (approximately 2 %) and/or morbidity (long lasting hospitalization due to prolonged air leaks)
* COPD (GOLD guidelines) with severe obstructive ventilatory defect (FEV1 \<35% predicted)
* Functional aspects of lung emphysema, i.e. irreversible hyperinflation with a residual volume to total lung capacity ratio (RV/TLC) of \>0.65 and an impaired total lung diffusion capacity (DLCO), usually \< 40% predicted.
* Pulmonary emphysema confirmed by high resolution computer tomography

Exclusion criteria: - Current smokers

* Age \> 75years
* "Vanishing" lung or diffuse lung emphysema on CT, FEV1 \<20% predicted and DLCO \<20% predicted, and hypercapnia (PaCO2 \>7.3kPa)
* Overt active coronary artery disease, severe left ventricular function impairment
* Pulmonary hypertension with a mean pulmonary artery pressure \>35 mmHg at rest
* Acute bronchopulmonary infection, bronchiectasis on high resolution tomography
* Pulmonary cachexia (body mass index \<18kg/m2)
* Neoplastic disease with a life expectancy of less than 2 years
* Addiction to alcohol/drugs
* Relevant renal (creatinine \>150ug/ml), active gastroenterological (GI-bleeding in the previous year, abnormal liver function, active inflammatory bowel disease) or active neurological disease.
D: Inclusion Criteria:

* clinical diagnosis of advanced upper lobe predominant emphysema
* age \>/= 40 years
* clinically significant dyspnea
* failure of standard medical therapy to relieve symptoms (inhaled beta agonist and inhaled anticholinergic)
* pulmonary function tests within protocol-specified ranges (post bronchodilator FEV1 \< 45% predicted and experiencing \< 30% or 300 mL improvement using bronchodilator; TLC \> 110% predicted; RV \> 150% predicted)
* 6 Minute Walk Distance \>/= 150 m

Exclusion Criteria:

* alpha-1 protease inhibitor deficiency
* homogeneous disease
* tobacco use within 4 months of initial visit
* body mass index \< 15 kg/m2 or \> 35 kg/m2
* clinically significant asthma, chronic bronchitis or bronchiectasis
* allergy or sensitivity to procedural components
* pregnant, lactating or unwilling to use birth control if required
* prior lung volume reduction surgery, lobectomy, pneumonectomy, lung transplant, endobronchial valve placement, airway stent placement or pleurodesis
* comorbid condition that could adversely influence outcomes
* inability to tolerate bronchoscopy under conscious sedation (or anesthesia)

Answer: C