Back to resultsTo Improve Lung Function and Symptoms for Emphysema Patients Using Zephyr Valves (TRANSFORM)
Primary Purpose
COPD, Heterogeneous Emphysema
Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
ELVR (Endoscopic Lung Volume Reduction) with Zephyr Valves
Sponsored by
About this trial
This is an interventional treatment trial for COPD focused on measuring Endoscopic lung volume reduction, Endobronchial valves
Eligibility Criteria
Inclusion Criteria:
- Obtained informed consent.
- Diagnosis of heterogeneous emphysema with a heterogeneity index of ≥10 % between target and adjacent lobes.
- Subjects of both genders of at least 40 years of age.
- 15 % predicted ≤ FEV1≤ 45% predicted.
- TLC > 100% and RV ≥ 180% predicted.
- 150 meters < 6MWD < 450 meters.
- Non-smoker >8 weeks prior to signing the Informed Consent.
- CV negative target lobe.
Additional inclusion criterion French CIP*:
- If treated in France, Subject must be entitled to French social security
Exclusion Criteria:
- Any contraindication for bronchoscopic procedure.
- Evidence of active pulmonary infection.
- History of 2 or more exacerbations requiring hospitalization over the past 12 months.
- Known pulmonary hypertension that according to the physician will be unsuitable for EBV treatment.
- Myocardial infarction or other relevant cardiovascular events in the past 6 months.
- Significant bronchiectasis seen at CT scan.
- Greater than two tablespoons of sputum production per day.
- Prior LVR or LVRS procedure. Criterion 8 French CIP wording*: Prior lung transplant, median sternotomy, LVR or LVRS procedure (including lobectomy).
- Pulmonary nodule requiring follow-up within any lobe.
- Pregnant or nursing women. French CIP wording*: Subject is pregnant or lactating, or plans to become pregnant within the study timeframe.
- Hypercapnia (paCO2 > 7.33 kPa).
- Current diagnosis of asthma.
- > 25mg Prednisolon (or equivalent) use/days.
- Any other condition that as judged by the investigator may make follow-up or investigations inappropriate.
- Evidence of pleural adhesions or earlier pulmonary surgery.
- Severe Bullous Emphysema (> 1/3 Hemithorax)
- Any subject that according to the Declaration of Helsinki is unsuitable for enrollment.
Additional exclusion criteria in the French CIP*:
- History of allergy to silicone and/or nitinol.
- If treated in France, Subject is a "personne vulnerable" as defined by French regulation.
- Simultaneous participation in another drug and/or medical device related clinical.
Sites / Locations
- Universiteit Gent
- AZ Delta
- CHU
- CHU Hôpital Pasteur
- Groupe Hospitalier Pitié Salpétrière
- Hôpital Bichat Claude Bernard
- Charité Campus Virchow-Klinikum
- Ruhrlandklinik Westdeutsches Lungenzentrum
- Thoraxklinik am Universitäts Klinikum Heidelberg
- University Medical Center Groningen
- Skane University Hospital
- Uppsala University Hospital
- Sherwood Forest Hospitals NHS
- West of Scotland Regional Heart & Lung Centre - Golden Jubilee National Hospital
- University Hospital of Wales
- The Royal Brompton Hospital & Harefield NHS Foundation Trust
- Sheffield Teaching Hospitals NHS Foundation Trust
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Endoscopic Lung Volume Reduction
Standard of Care
Arm Description
Patients are implanted with Zephyr Valves
Patients are given Standard Medical Care
Outcomes
Primary Outcome Measures
Forced Expiratory Volume in 1-second (FEV1) - Responders
The percentage of trial participants in the EBV treatment arm meeting the minimally clinically important difference (MCID) of >12% improved forced expiratory volume in one second (FEV1), obtained immediately following bronchodilator therapy, as compared to the percentage in the control arm at 3 months post-procedure.
Secondary Outcome Measures
St George's Respiratory Questionnaire (SGRQ) - Absolute change
Absolute change in the SGRQ in the EBV treatment arm at 3, 6, 12, 18 and 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
The St. George's Respiratory Questionnaire measures health status (quality of life) in patients with diseases of airways obstruction. The questionnaire comprises of two parts:
Part I: Symptoms (frequency & severity) Part II: Activities that cause or are limited by breathlessness; Impacts (social functioning, psychological disturbances resulting from airways disease)
A Total score is calculated which summarizes the impact of the disease on overall health status. Scores range from 0 to 100, with higher scores indicating more limitations.
St George's Respiratory Questionnaire (SGRQ) - Percent change
Percent change in the SGRQ in the EBV treatment arm at 3, 6, 12, 18 and 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
The St. George's Respiratory Questionnaire measures health status (quality of life) in patients with diseases of airways obstruction. The questionnaire comprises of two parts:
Part I: Symptoms (frequency & severity) Part II: Activities that cause or are limited by breathlessness; Impacts (social functioning, psychological disturbances resulting from airways disease)
A Total score is calculated which summarizes the impact of the disease on overall health status. Scores range from 0 to 100, with higher scores indicating more limitations.
St George's Respiratory Questionnaire (SGRQ) - Responders
Percentage of subject achieving the MCID for SGRQ in the EBV treatment arm at 3, 6, 12, 18 and 24 months, compared to SoC at 3, 6 and 12 months.
The St. George's Respiratory Questionnaire measures health status (quality of life) in patients with diseases of airways obstruction. The questionnaire comprises of two parts:
Part I: Symptoms (frequency & severity) Part II: Activities that cause or are limited by breathlessness; Impacts (social functioning, psychological disturbances resulting from airways disease)
A Total score is calculated which summarizes the impact of the disease on overall health status. Scores range from 0 to 100, with higher scores indicating more limitations.
6-minute walk distance (6MWT) - Absolute change
Absolute change in 6MWD in the EBV treatment arm at 3, 6, 12, 18, 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
6-minute walk distance (6MWT) - Percent change
Percent change in 6MWD in the EBV treatment arm at 3, 6, 12, 18, 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
6-minute walk distance (6MWT) - Responders
Percentage of subject achieving the MCID for 6MWD in the EBV treatment arm at 3, 6, 12, 18 and 24 months, compared to SoC at 3, 6 and 12 months.
Forced Expiratory Volume in 1-second (FEV1) - Absolute change
Absolute change in FEV1 in the EBV treatment arm at 3, 6, 12, 18, 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
Forced Expiratory Volume in 1-second (FEV1) - Percent change
Percentage of subject achieving the MCID for FEV1 in the EBV treatment arm at 6, 12, 18 and 24 months, compared to SoC at 6 and 12 months.
Forced Expiratory Volume in 1-second (FEV1) - Responders
Absolute change in FEV1 in the EBV treatment arm at 3, 6, 12, 18, 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
mMRC (Modified Medical Research Council) score - Responders
Percentage of subject in the EBV treatment arm achieving the MCID for the Modified Scale Research Council Dyspnea Score (mMRC) at 3, 6, 12, 18 and 24 months and the difference between the two arms at 3, 6 and 12 months.
The mMRC (Modified Medical Research Council) stratifies severity of dyspnea in respiratory diseases. The severity of dyspnea is rated on a scale of 0 to 4, with higher scores indicating more limitations.
Target Lobar Volume Reduction (TLVR) - Absolute change
Absolute change in target lobe volume at 45 days in the EBV treatment arm relative to Baseline as assessed by quantitative HRCT analysis (TLVR: Target Lobar Volume Reduction).
Target Lobar Volume Reduction (TLVR) - Percent change
Percent change in target lobe volume at 45 days in the EBV treatment arm relative to Baseline as assessed by quantitative HRCT analysis (TLVR: Target Lobar Volume Reduction).
Target Lobar Volume Reduction (TLVR) - Responders
Percentage of subjects in EBV arm with a TLVR > 350ml at 45 days relative to baseline.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02022683
Brief Title
To Improve Lung Function and Symptoms for Emphysema Patients Using Zephyr Valves
Acronym
TRANSFORM
Official Title
A Multi-center, Prospective, Randomized, Controlled Trial of Endobronchial Valve Therapy vs. Standard of Care in Heterogeneous Emphysema
Study Type
Interventional
2. Study Status
Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
January 28, 2014 (Actual)
Primary Completion Date
January 20, 2017 (Actual)
Study Completion Date
September 27, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pulmonx Corporation
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
To compare the clinical outcomes of Endoscopic Lung Volume Reduction (ELVR) using Pulmonx Zephyr Valves vs. Standard of Care (SoC) in the treatment of heterogeneous emphysema subjects in a controlled trial design setting.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COPD, Heterogeneous Emphysema
Keywords
Endoscopic lung volume reduction, Endobronchial valves
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
97 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Endoscopic Lung Volume Reduction
Arm Type
Experimental
Arm Description
Patients are implanted with Zephyr Valves
Arm Title
Standard of Care
Arm Type
No Intervention
Arm Description
Patients are given Standard Medical Care
Intervention Type
Device
Intervention Name(s)
ELVR (Endoscopic Lung Volume Reduction) with Zephyr Valves
Primary Outcome Measure Information:
Title
Forced Expiratory Volume in 1-second (FEV1) - Responders
Description
The percentage of trial participants in the EBV treatment arm meeting the minimally clinically important difference (MCID) of >12% improved forced expiratory volume in one second (FEV1), obtained immediately following bronchodilator therapy, as compared to the percentage in the control arm at 3 months post-procedure.
Time Frame
Between baseline and 3 months
Secondary Outcome Measure Information:
Title
St George's Respiratory Questionnaire (SGRQ) - Absolute change
Description
Absolute change in the SGRQ in the EBV treatment arm at 3, 6, 12, 18 and 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
The St. George's Respiratory Questionnaire measures health status (quality of life) in patients with diseases of airways obstruction. The questionnaire comprises of two parts:
Part I: Symptoms (frequency & severity) Part II: Activities that cause or are limited by breathlessness; Impacts (social functioning, psychological disturbances resulting from airways disease)
A Total score is calculated which summarizes the impact of the disease on overall health status. Scores range from 0 to 100, with higher scores indicating more limitations.
Time Frame
Between Baseline and 3, 6, 12, 18 and 24 months
Title
St George's Respiratory Questionnaire (SGRQ) - Percent change
Description
Percent change in the SGRQ in the EBV treatment arm at 3, 6, 12, 18 and 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
The St. George's Respiratory Questionnaire measures health status (quality of life) in patients with diseases of airways obstruction. The questionnaire comprises of two parts:
Part I: Symptoms (frequency & severity) Part II: Activities that cause or are limited by breathlessness; Impacts (social functioning, psychological disturbances resulting from airways disease)
A Total score is calculated which summarizes the impact of the disease on overall health status. Scores range from 0 to 100, with higher scores indicating more limitations.
Time Frame
Between Baseline and 3, 6, 12, 18 and 24 months
Title
St George's Respiratory Questionnaire (SGRQ) - Responders
Description
Percentage of subject achieving the MCID for SGRQ in the EBV treatment arm at 3, 6, 12, 18 and 24 months, compared to SoC at 3, 6 and 12 months.
The St. George's Respiratory Questionnaire measures health status (quality of life) in patients with diseases of airways obstruction. The questionnaire comprises of two parts:
Part I: Symptoms (frequency & severity) Part II: Activities that cause or are limited by breathlessness; Impacts (social functioning, psychological disturbances resulting from airways disease)
A Total score is calculated which summarizes the impact of the disease on overall health status. Scores range from 0 to 100, with higher scores indicating more limitations.
Time Frame
Between Baseline and 3, 6, 12, 18 and 24 months
Title
6-minute walk distance (6MWT) - Absolute change
Description
Absolute change in 6MWD in the EBV treatment arm at 3, 6, 12, 18, 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
Time Frame
Between Baseline and 3, 6, 12, 18, 24 months
Title
6-minute walk distance (6MWT) - Percent change
Description
Percent change in 6MWD in the EBV treatment arm at 3, 6, 12, 18, 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
Time Frame
Between Baseline and 3, 6, 12, 18, 24 months
Title
6-minute walk distance (6MWT) - Responders
Description
Percentage of subject achieving the MCID for 6MWD in the EBV treatment arm at 3, 6, 12, 18 and 24 months, compared to SoC at 3, 6 and 12 months.
Time Frame
Between Baseline and 3, 6, 12, 18, 24 months
Title
Forced Expiratory Volume in 1-second (FEV1) - Absolute change
Description
Absolute change in FEV1 in the EBV treatment arm at 3, 6, 12, 18, 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
Time Frame
Between Baseline and 3, 6, 12, 18, 24 months
Title
Forced Expiratory Volume in 1-second (FEV1) - Percent change
Description
Percentage of subject achieving the MCID for FEV1 in the EBV treatment arm at 6, 12, 18 and 24 months, compared to SoC at 6 and 12 months.
Time Frame
Between Baseline and 6, 12, 18 and 24 months
Title
Forced Expiratory Volume in 1-second (FEV1) - Responders
Description
Absolute change in FEV1 in the EBV treatment arm at 3, 6, 12, 18, 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
Time Frame
Between Baseline and 3, 6, 12, 18, 24 months
Title
mMRC (Modified Medical Research Council) score - Responders
Description
Percentage of subject in the EBV treatment arm achieving the MCID for the Modified Scale Research Council Dyspnea Score (mMRC) at 3, 6, 12, 18 and 24 months and the difference between the two arms at 3, 6 and 12 months.
The mMRC (Modified Medical Research Council) stratifies severity of dyspnea in respiratory diseases. The severity of dyspnea is rated on a scale of 0 to 4, with higher scores indicating more limitations.
Time Frame
Between Baseline and 3, 6, 12, 18 and 24 months
Title
Target Lobar Volume Reduction (TLVR) - Absolute change
Description
Absolute change in target lobe volume at 45 days in the EBV treatment arm relative to Baseline as assessed by quantitative HRCT analysis (TLVR: Target Lobar Volume Reduction).
Time Frame
Between baseline and 45 days
Title
Target Lobar Volume Reduction (TLVR) - Percent change
Description
Percent change in target lobe volume at 45 days in the EBV treatment arm relative to Baseline as assessed by quantitative HRCT analysis (TLVR: Target Lobar Volume Reduction).
Time Frame
Between baseline and 45 days
Title
Target Lobar Volume Reduction (TLVR) - Responders
Description
Percentage of subjects in EBV arm with a TLVR > 350ml at 45 days relative to baseline.
Time Frame
Between baseline and 45 days
Other Pre-specified Outcome Measures:
Title
Adverse Events
Description
Adverse events (condition/procedure related AE's, SAE's, ADE's and SADE's) occurring up to 24 months post EBV placement and up to 12 months post randomization (for any remaining subjects in the SoC group).
Time Frame
Between baseline and 24 months
Title
PaO2 - Absolute change
Description
Absolute change in PaO2 in the EBV treatment arm at 3 months relative to Baseline.
Time Frame
Between baseline and 3 months
Title
PaO2 - Percent change
Description
Percent change in PaO2 in the EBV treatment arm at 3 months relative to Baseline.
Time Frame
Between baseline and 3 months
Title
Residual Volume (RV) - Absolute change
Description
Absolute change in residual volume (RV) in the EBV treatment arm at 3, 6 and 12, 18 and 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
Time Frame
Between Baseline and 3, 6 and 12, 18 and 24 months
Title
Residual Volume (RV) - Percent change
Description
Percent change in residual volume (RV) in the EBV treatment arm at 3, 6 and 12, 18 and 24 months relative to Baseline and the difference between the two arms at 3, 6 and 12 months.
Time Frame
Between Baseline and 3, 6 and 12, 18 and 24 months
Title
EQ-5D Summary Index - Absolute change
Description
Absolute change relative to Baseline in the EBV treatment arm at 3, 6, 12, 18 and 24 months of the EQ-5D Summary Index and the difference between the two arms at, 3, 6 and 12 months.
EQ-5D is a standardized instrument used to measure health-related quality of life for a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ VAS.
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale. This can be used as a quantitative measure of health outcome that reflects the patient's own judgement. The scores on these five dimensions can be presented as a health profile or can be converted to a single summary index number (utility) reflecting preferability compared to other health profiles.
Time Frame
Between Baseline and 3, 6, 12, 18 and 24 months
Title
EQ-5D Summary Index Percent change
Description
Percent change relative to Baseline in the EBV treatment arm at 3, 6, 12, 18 and 24 months of the EQ-5D Summary Index and the difference between the two arms at, 3, 6 and 12 months.
EQ-5D is a standardized instrument used to measure health-related quality of life for a wide range of health conditions and treatments. The EQ-5D consists of a descriptive system and the EQ VAS.
The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale. This can be used as a quantitative measure of health outcome that reflects the patient's own judgement. The scores on these five dimensions can be presented as a health profile or can be converted to a single summary index number (utility) reflecting preferability compared to other health profiles.
Time Frame
Between Baseline and 3, 6, 12, 18 and 24 months
Title
Mean number of additional hospitalizations and/or visits caused by respiratory conditions
Description
The mean number of visits (Number of participants reporting visits/total number of visits) caused by respiratory conditions during the study period will be recorded for health economical purposes in both treatment and control subjects.
Time Frame
Between baseline and 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Obtained informed consent.
Diagnosis of heterogeneous emphysema with a heterogeneity index of ≥10 % between target and adjacent lobes.
Subjects of both genders of at least 40 years of age.
15 % predicted ≤ FEV1≤ 45% predicted.
TLC > 100% and RV ≥ 180% predicted.
150 meters < 6MWD < 450 meters.
Non-smoker >8 weeks prior to signing the Informed Consent.
CV negative target lobe.
Additional inclusion criterion French CIP*:
- If treated in France, Subject must be entitled to French social security
Exclusion Criteria:
Any contraindication for bronchoscopic procedure.
Evidence of active pulmonary infection.
History of 2 or more exacerbations requiring hospitalization over the past 12 months.
Known pulmonary hypertension that according to the physician will be unsuitable for EBV treatment.
Myocardial infarction or other relevant cardiovascular events in the past 6 months.
Significant bronchiectasis seen at CT scan.
Greater than two tablespoons of sputum production per day.
Prior LVR or LVRS procedure. Criterion 8 French CIP wording*: Prior lung transplant, median sternotomy, LVR or LVRS procedure (including lobectomy).
Pulmonary nodule requiring follow-up within any lobe.
Pregnant or nursing women. French CIP wording*: Subject is pregnant or lactating, or plans to become pregnant within the study timeframe.
Hypercapnia (paCO2 > 7.33 kPa).
Current diagnosis of asthma.
> 25mg Prednisolon (or equivalent) use/days.
Any other condition that as judged by the investigator may make follow-up or investigations inappropriate.
Evidence of pleural adhesions or earlier pulmonary surgery.
Severe Bullous Emphysema (> 1/3 Hemithorax)
Any subject that according to the Declaration of Helsinki is unsuitable for enrollment.
Additional exclusion criteria in the French CIP*:
History of allergy to silicone and/or nitinol.
If treated in France, Subject is a "personne vulnerable" as defined by French regulation.
Simultaneous participation in another drug and/or medical device related clinical.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gunnar Hillerdal, MD, PhD
Organizational Affiliation
Uppsala University Hospital, Sweden
Official's Role
Principal Investigator
Facility Information:
Facility Name
Universiteit Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
AZ Delta
City
Menen
ZIP/Postal Code
8930
Country
Belgium
Facility Name
CHU
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
CHU Hôpital Pasteur
City
Nice
ZIP/Postal Code
06002
Country
France
Facility Name
Groupe Hospitalier Pitié Salpétrière
City
Paris
ZIP/Postal Code
75013
Country
France
Facility Name
Hôpital Bichat Claude Bernard
City
Paris
ZIP/Postal Code
75877
Country
France
Facility Name
Charité Campus Virchow-Klinikum
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Ruhrlandklinik Westdeutsches Lungenzentrum
City
Essen
ZIP/Postal Code
45239
Country
Germany
Facility Name
Thoraxklinik am Universitäts Klinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69126
Country
Germany
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9700
Country
Netherlands
Facility Name
Skane University Hospital
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
Uppsala University Hospital
City
Uppsala
ZIP/Postal Code
751 85
Country
Sweden
Facility Name
Sherwood Forest Hospitals NHS
City
Sutton in Ashfield
State/Province
Nottinghamshire
ZIP/Postal Code
NG17 4JL
Country
United Kingdom
Facility Name
West of Scotland Regional Heart & Lung Centre - Golden Jubilee National Hospital
City
Clydebank
State/Province
West Dunbartonshire Scotland
ZIP/Postal Code
G81 4DY
Country
United Kingdom
Facility Name
University Hospital of Wales
City
Cardiff
ZIP/Postal Code
CF144XW
Country
United Kingdom
Facility Name
The Royal Brompton Hospital & Harefield NHS Foundation Trust
City
London
ZIP/Postal Code
SW3 6NP
Country
United Kingdom
Facility Name
Sheffield Teaching Hospitals NHS Foundation Trust
City
Sheffield
ZIP/Postal Code
S5 7AU
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
28885054
Citation
Kemp SV, Slebos DJ, Kirk A, Kornaszewska M, Carron K, Ek L, Broman G, Hillerdal G, Mal H, Pison C, Briault A, Downer N, Darwiche K, Rao J, Hubner RH, Ruwwe-Glosenkamp C, Trosini-Desert V, Eberhardt R, Herth FJ, Derom E, Malfait T, Shah PL, Garner JL, Ten Hacken NH, Fallouh H, Leroy S, Marquette CH; TRANSFORM Study Team *. A Multicenter Randomized Controlled Trial of Zephyr Endobronchial Valve Treatment in Heterogeneous Emphysema (TRANSFORM). Am J Respir Crit Care Med. 2017 Dec 15;196(12):1535-1543. doi: 10.1164/rccm.201707-1327OC.
Results Reference
derived
Learn more about this trial
To Improve Lung Function and Symptoms for Emphysema Patients Using Zephyr Valves
We'll reach out to this number within 24 hrs