Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomised Controlled Trial of Home Mechanical Ventilation in Hypercapnic Chronic Obstructive Pulmonary Disease Patients Post Acute Hypercapnic Exacerbation
Brief Summary: This study is designed to investigate the effect of home mechanical ventilation (HMV) in patients with severe chronic obstructive pulmonary disease (COPD). The purpose of the trial is to test the hypothesis that HMV and longterm oxygen therapy (LTOT) increases admission free survival compared with LTOT alone. More specifically, compared with LTOT, HMV and LTOT reduces hospital re-admission in COPD patients who remain persistently hypercapnic following an acute exacerbation requiring non-invasive ventilation (NIV).


Options:
A: Inclusion Criteria:

* Patients with COPD
* Acute hypercapnic exacerbation of COPD at least 2 weeks previously
* Tolerated non-invasive ventilation during acute hypercapnic exacerbation
* Chronic hypoxia requiring LTOT (PaO2 \<7.3kPa or a PaO2 \>7.3 and \<8.0kPa and one of the following: secondary polycythaemia; nocturnal hypoxaemia SaO2 \<90% for \>30% of the time; peripheral oedema; or PHT)
* Chronic hypercapnia (PaCO2 \>7kPa)
* ≥20 pack year smoking history
* FEV1/FVC \<60%
* FEV1 at \<50% predicted

Exclusion Criteria:

* Persistent hypercapnic respiratory failure with acidosis (defined as pH \<7.30 after bronchodilators)
* Development of worsening hypercapnic respiratory failure with acidosis during initiation of LTOT therapy
* Failure to tolerate NIV during the acute illness preceding trial identification
* Post extubation or decannulation following AHRF requiring intubation
* Restrictive lung disease causing hypercapnia i.e. obesity hypoventilation and chest wall disease, however these patients will be included if the FEV1/FVC ratio is \<60% and the FEV1 \<50% if the predominant defect is considered to be obstructive by the center clinician.
* Clinical features of severe OSA
* BMI \>35kg/m2
* Unstable coronary artery syndrome
* Cognitive impairment that would prevent informed consent into the trial
* Psychiatric disease necessitating anti-psychotic medication, ongoing treatment for drug or alcohol addiction, persons of no fixed abode post-discharge
* Patients undergoing renal replacement therapy
* Age \<18 years
* Pregnant
* Inability to comply with the protocol
B: Inclusion Criteria:

* Patient admitted with a NIV-requiring exacerbation of COPD
* COPD with a FEV1/FVC \<0.7 after bronchodilatation.
* ≥ 1 acute hypercapnic respiratory failure (AHRF \*).
* Optimal medical treatment of COPD, ie. inhaled steroids, long-acting β2-agonist Tiotropium, according to GOLD guidelines.
* Address in Capital Region
* Patients are able to give verbal consent and sign a written consent form and understand Danish-

Exclusion Criteria:

* Severely depressed level of consciousness / confusion / non-cooperative.
* Respiratory rate \<12/min
* Severe hypoxia, such as requiring more than 15L O2/min.
* Large amounts of sputum.
* Vomiting and high risk for aspiration.
* Inability to accept NIV.
* Recent abdominal, facial or upper airway surgery.
* Malignancy or life expectancy \<6 months because of disease other than COPD
* Known obstructive sleep apnea syndrome (OSA)
* Metabolic acidotic component - StHCO3- \< 20 mM
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

* Newly diagnosed with OSA on overnight polysomnogram (PSG) with RDI between 5 and 30
* Score of greater than 11 on the Epworth Sleepiness Scale (ESS) on two administrations of the instrument (performed at prescreening and screening), each completed on a different day to avoid sporadic values and confirm the presence of excessive daytime sleepiness
* Stable medical history and no change in medications, including hypertension medications, in the 3 months prior to study entry
* Stable psychiatric history and no change in psychotropic medications in the 3 months prior to study entry
* Has access to a telephone

Exclusion Criteria

* Diagnosis of another sleep disorder in addition to OSA based on PSG, e.g., periodic limb movement disorder (greater than 10 limb movements per hour of sleep with arousal); central sleep apnea (greater than 5 or more central apneas); insomnia; sleep hypoventilation syndrome; or narcolepsy
* Previous treatment for sleep apnea with nasal CPAP, oral appliance, home oxygen therapy, uvulopalatopharyngoplasty, tracheotomy, or other surgery for OSA
* Oxygen or bi-level CPAP required for treatment of OSA
* Unable to return for study instructions or follow-up testing
* Medically unstable condition (e.g., heart attack, congestive heart failure, Cheyne-Stokes breathing, unstable angina, uncontrolled thyroid disease, unstable diabetes, depression or psychosis, ventricular arrhythmias, cirrhosis, or recently diagnosed cancer) in the 3 months prior to study entry
* Regular use (greater than 3 times per week) of sedative, hypnotic, or alerting medications (such as Modafinil) in the 3 months prior to study entry
* Chronic nasal congestion that would prevent the use of a nasal mask, in the 3 months prior to study entry
* History of automobile accidents due to excessive daytime sleepiness
* Employed in transportation-related safety sensitive occupation such as an airline pilot, truck driver, or train engineer
* Night shift worker regularly experiencing jet lag, or a history of irregular work schedules in the 6 months prior to study entry
* Regular use of alcohol as determined by answering yes to one or more of the questions on the CAGE questionnaire (i.e., alcohol dependent)
* Recent or recurring history of substance abuse leading to tolerance or dependence
* Pregnant; women must either be postmenopausal or confirmed not pregnant by a urine pregnancy test
* Unable to perform study tests, e.g., inability to communicate verbally; inability to write and read in English; less than a 5th grade reading level (evaluated using Flesch-Kincaid assessment); visual impairment; hearing impairment; cognitive impairment (e.g., previous head injury); or upper extremity motor deficit (e.g., previous stroke or spinal cord injury)
* Residing with an individual who is currently using CPAP treatment

Answer: A