Please select the eligibility criteria that correspond to the clinical trial below.
Title: Non-invasive Ventilation in Patients With Severe Chronic Obstructive Pulmonary Disease and Lung Emphysema (COPD)
Brief Summary: Non-invasive ventilation is frequently applied in patients with acute exacerbation of COPD, but no evidence exists about the effect of long term application/home application.

This study tests the hypothesis, that a daily, 6 hour application of non-invasive ventilation over one year improves survival, exercise capacity, and quality of life in patients with advanced stages of COPD.


Options:
A: Inclusion Criteria:

* Between 40 and 80 at baseline visit
* Never smokers: \<1 pack-year history of smoking
* Never smokers: Must meet lung function criteria based on spirometry without inhaled bronchodilators
* Current or former smokers: \>20 pack-year history of smoking
* Current or former smokers: Must meet lung function criteria based on spirometry with inhaled bronchodilators

Exclusion Criteria:

* Dementia or other cognitive dysfunction which in the opinion of the investigator would prevent the participant from consenting to the study or completing study procedures
* Plans to leave the area in the next 3 years
* Smoking history of \> 1 pack-year but \<21 pack-years
* BMI \> 40 kg/m2 at baseline exam
* Prior significant difficulties with pulmonary function testing
* Hypersensitivity to or intolerance of albuterol sulfate or ipratropium bromide or propellants or excipients of the inhalers
* Non-COPD obstructive lung disease, severe kyphoscoliosis, neuromuscular weakness, or other conditions, including clinically significant cardiovascular and pulmonary disease, that, limit the interpretability of the pulmonary function measures.
* History of Interstitial lung disease
* History of Lung volume reduction surgery or lung resection
* History of lung or other organ transplant
* History of endobronchial valve therapy
* History of large thoracic metal implants (e.g., AICD (automatic implantable cardioverter/defibrillator) and/or pacemaker)
* Currently taking \>=10mg a day/20mg every other day of prednisone or equivalent systemic corticosteroid
* Currently taking any immunosuppressive agent
* Current illicit substance abuse, excluding marijuana
* History of or current use of IV Ritalin
* History of or current use of heroin
* History of illegal IV drug use within the last 10 years or more than 5 instances of illegal IV drug use ever
* Known HIV/AIDS infection
* History of lung cancer or any cancer that spread to multiple locations in the body
* History of or current exposure to chemotherapy or radiation treatments that, in the opinion of the investigator, limits the interpretability of the pulmonary function measures.
* Diagnosis of unstable cardiovascular disease including myocardial infarction in the past 6 weeks, uncontrolled congestive heart failure, or uncontrolled arrhythmia
* Any illness expected to cause mortality in the next 3 years
* Active pulmonary infection, including tuberculosis
* History of pulmonary embolism in the past 2 years
* Known diagnosis of primary bronchiectasis
* Currently institutionalized (e.g., prisons, long-term care facilities)
* Known to be a first degree relative of another, already enrolled participant (i.e., biological parent, biological sibling)
* Never smokers only: Current diagnosis of asthma
* Women only: Cannot be pregnant at baseline or plan to become pregnant during the course of the study
B: Inclusion Criteria:

* At least 10 pack-years of cigarette smoking (although a of nonsmoking controls is also being enrolled)
* Self-designation of non-Hispanic white or African-American

Exclusion Criteria:

* Other lung diseases (except for asthma in participants with COPD)
* Pregnant
* Cancer (other than skin cancer) in the 5 years prior to study entry
* Received antibiotics for a COPD exacerbation in the 1 month prior to study entry
* First- or second-degree relative of a previously enrolled study participant
C: Inclusion criteria:

* COPD Subjects
* A COPD subject will be eligible for inclusion in this study only if all of the following criteria apply:
* Male or female subjects, aged 40-75 years inclusive
* A baseline (post-bronchodilator) FEV1 \<80% of predicted normal and a baseline (post-bronchodilator) FEV1/FVC ratio 70%
* Current or ex-smokers with a smoking history of at least 10 pack-years (number of pack years = (number of cigarettes per day / 20) x number of years smoked e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years).
* A signed and dated written informed consent is obtained prior to participation
* Able to comply with the requirements of the protocol and be available for study visits over 3 years

Control Subjects - Current/Ex Smokers

* A control subject will be eligible for inclusion in this study only if all of the following criteria apply:
* Male or female subjects, aged 40-75 years inclusive, who are free from significant disease as determined by history, physical examination and screening investigations
* Baseline (post-bronchodilator) FEV1 \>85% of predicted normal. FEV1/FVC ratio \>70%
* Current or ex-smokers with a smoking history of at least 10 pack-years (number of pack years = (number of cigarettes per day / 20) x number of years smoked e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years).
* A signed and dated written informed consent is obtained prior to participation.
* Able to comply with the requirements of the protocol and be available for study visits over 3 years

Control Subjects - Non-smokers

* A non-smoking control subject will be eligible for inclusion in this study only if all of the following criteria apply:
* Male or female subjects, aged 40-75 years inclusive, who are free from significant disease as determined by history, physical examination and screening investigations
* Baseline (post-bronchodilator) FEV1 \>85% of predicted normal. FEV1/FVC ratio \>70%
* Non-smokers with a smoking history of \< 1 pack-year (number of pack years = (number of cigarettes per day / 20) x number of years smoked).
* A signed and dated written informed consent is obtained prior to participation.
* Able to comply with the requirements of the protocol and be available for study visits over 3 years

Exclusion Criteria:

COPD Subjects

* A COPD subject will not be eligible for inclusion in this study if any of the following criteria apply:
* Known respiratory disorders, or disorders identified at screening/visit 1 (including identification on the first CT scan), other than COPD (e.g.: lung cancer, sarcoidosis, tuberculosis, lung fibrosis, cystic fibrosis)
* Known history of significant inflammatory disease, other than COPD (e.g. rheumatoid arthritis and Lupus)
* Known to be severely alpha-1-antitrypsin deficient (PI SZ or ZZ)
* Having undergone lung surgery (e.g. lung reduction, lung transplant)
* Have cancer or have had cancer in the 5 years prior to study entry
* Serious, uncontrolled disease (including serious psychological disorders) likely to interfere with the study or impact on subject safety
* Is enrolled in a long term blinded drug study (subjects in open label studies may be considered and subjects in short blinded studies (approx less than 12 weeks may be considered following consultation with sponsor) or a study where there is significant radiation exposure (e.g.: CT scans)
* Have, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse
* Have received a blood transfusion in the 4 weeks prior to study start
* Has experienced a moderate or severe exacerbation (requiring oral corticosteroid, antibiotics or hospitalisation) within the last 4 weeks. All courses of oral corticosteroids and antibiotics must be completed at least 2 weeks before study start
* Is on long term oral corticosteroids (long term is considered use for more than 3 consecutive months)
* Unable to walk
* Subject is a participating investigator, sub-investigator, study co-ordinator, or employee of a participating investigator, or is an immediate family member of the aforementioned.

Control Subjects

* A control subject will not be eligible for inclusion in this study if any of the following criteria apply:
* Known respiratory disorders, or disorders identified at screening/visit 1 including identification on the first CT scan (e.g.: COPD, asthma, lung cancer, sarcoidosis, tuberculosis, lung fibrosis)
* Known history of significant inflammatory disease (eg rheumatoid arthritis and Lupus)
* Known to be severely alpha-1-antitrypsin deficient (PI SZ or ZZ)
* Having undergone lung surgery (e.g. lung reduction, lung transplant)
* Have cancer or have had cancer in the 5 years prior to study entry
* Serious, uncontrolled disease (including serious psychological disorders) likely to interfere with the study
* Is enrolled in a long term blinded drug study (subjects in open label studies may be considered and subjects in short blinded studies (approx less than 12 weeks may be considered following consultation with sponsor) or a study where there is significant radiation exposure (e.g.: CT scans)
* Have, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse.
* Have received a blood transfusion in the 4 weeks prior to study start
* Is on long term oral corticosteroids (long term is considered use for more than 3 consecutive months)
* Subject is a participating investigator, sub-investigator, study co-ordinator, or employee of a participating investigator, or is an immediate family member of the aforementioned.
D: Inclusion Criteria:

* Moderate or severe COPD with insufficiency of the ventilatory pump (according to GOLD stage IV). Stable disease since four weeks or more prior to randomisation. The COPD might be caused by whatever reason (smoking, Alpha-1 antitrypsin deficiency, ....). Smokers can be included.
* Capillary PCO2 of 7 kPa (51,8 mmHg) or maximally 10 kPa (74 mmHg), combined with a pH of 7.35 or above. These gases must be measured after 30 minutes breathing room air in sitting position. Patients on long term oxygen treatment must inhale oxygen in their prescribed dose.
* Only patients in the age of 18 years or above can be included.
* Written information about all aspects of the study (available in German language) must be provided for each patient. Written informed consent prior to any measure of this protocol is necessary for inclusion.

Exclusion Criteria:

* Patients with a PCO2 of 10 kPa (74 mmHg) or above. These patients can be re-evaluated for inclusion after 4 weeks.
* Diseases of the lung or thorax besides COPD: Advanced pulmonary fibrosis, advanced bronchiectases, active tuberculosis, post tuberculosis syndrome, pneumonia, severe kyphoscoliosis, tracheostoma, neuromuscular diseases, or any other disorder, which might result in elevated PCO2.
* Patients on NIV.
* Body mass index of 35 kg/m² or above.
* Severe cardiac disease, NYHA IV, instable angina, severe cardiac arrhythmia, especially of ventricular origin (atrial fibrillation is not an exclusion criterion).
* Malignoma
* Disorders of the basal brain nerves with derangement of swallowing, or reflexes of swallowing and choking.
* Local derangement of the face, skin, tongue, upper airways, larynx and upper oesophagus.
* Severe chronic diseases except COPD, hindering the patient to follow the schedule of this study.

Answer: D