Impact of Non-invasive Ventilation in Hypercapnic COPD

Failure to accrue subjects. All activity has stopped & no analysis will be done on what has been collected.

Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition worldwide and is a cause of substantial morbidity and mortality. Unfortunately, few therapies have been shown to improve survival. The importance of systemic effects and co-morbidities in COPD has garnered attention based on the observation that many patients with COPD die from causes other than respiratory failure, including a large proportion from cardiovascular causes. Recently, two high profile randomized trials have shown substantial improvements in morbidity and mortality with use of nocturnal non-invasive ventilation (NIV) in COPD patients with hypercapnia. Although the mechanisms by which NIV improves outcomes remain unclear, the important benefits of NIV might be cardiovascular via a number of mechanisms. In contrast to prior trials of NIV in COPD that did not show substantial benefit, a distinguishing feature of these encouraging recent NIV clinical trials was a prominent reduction of hypercapnia, which might be a maker or mediator of effective therapy. Alternatively, improvements might be best achieved by targeting a different physiological measure. Additional mechanistic data are therefore needed to inform future trials and achieve maximal benefit of NIV. Recent work in cardiovascular biomarkers has identified high-sensitivity troponin to have substantial ability to determine cardiovascular stress in a variety of conditions - even with only small changes. In COPD, a number of observational studies have shown that high-sensitivity troponin increases with worsening disease severity, and that levels increase overnight during sleep. This biomarker therefore presents a promising means to study causal pathways regarding the effect of NIV in patients with COPD. With this background, the investigator's overall goals are: 1) To determine whether the beneficial effect of non-invasive ventilation might be due to a reduction in cardiovascular stress, using established cardiovascular biomarkers, and 2) To define whether a reduction in PaCO2 (or alternative mechanism) is associated with such an effect.

Copd, Chronic Obstructive Pulmonary Disease, Hypercapnia, Chronic Respiratory Failure, Hypoventilation

Subjects will undergo a baseline night with standard polysomnography, followed by a treatment night using non-invasive ventilation under polysomnography

Paired difference in sleep quality by Richards-Campbell Sleep Questionnaire between baseline and NIV night

Questionnaire: 5 questions, 0 to 100 on visual analog scale, with higher scores indicating better sleep. Total score reported as mean of 5 components.

Arousal index: Index reported as events/hour. Minimum 0, no maximum, with higher scores indicating worse sleep.

Psychomotor vigilance score: Reported as number of lapses. Minimum 0, no maximum, with higher values worse.

Inclusion Criteria: Subjects with previously diagnosed severe COPD (FEV1 <50% predicted) and daytime hypercapnia (PaCO2 or TcCO2 > 45 mmHg) Exclusion Criteria: Lung disease besides COPD (e.g., pulmonary fibrosis, bronchiectasis, pulmonary arterial hypertension) other than well controlled asthma Unrevascularized coronary artery disease, angina, prior heart attack or stroke, congestive heart failure Uncontrolled hypertension (SBP >160, DBP >95) Unwilling or unable to withhold CPAP during polysomnography Presence of tracheostomy Hospitalization within the past 90 days Prior peptic ulcer disease, esophageal varicies, or gastrointestinal bleeding (< 5 years) Prior gastric bypass surgery Anticoagulant use (other than aspirin) or bleeding diathesis (only for esophageal catheter placement) Chronic liver disease or end-stage kidney disease Allergy to any of the study medications Regular use of medications known to affect control of breathing (opioids, benzodiazepines, theophylline) Insomnia or circadian rhythm disorder Active illicit substance use or >3 oz nightly alcohol use Psychiatric disease, other than controlled depression Pregnancy Prisoners Cognitive impairment, unable to provide consent, or unable to carry out research procedures