Chronic Obstructive Pulmonary Disease, Chronic Respiratory Failure, Copd, Hypercapnia, Hypoventilation
Conditions
Keywords
copd, lung, non-invasive ventilation, hypercapnia, hypoventilation
Brief summary
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.
Interventions
DEVICEHigh-intensity non-invasive ventilation
Single night of high-intensity non-invasive ventilation
Sponsors
University of California, San Diego
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Paired difference in morning level of high sensitivity troponin between baseline and NIV nights | 1 day | Comparing morning levels of high sensitivity troponin between baseline and NIV nights |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Paired difference in sleep quality by Richards-Campbell Sleep Questionnaire between baseline and NIV night | 1 day | Questionnaire: 5 questions, 0 to 100 on visual analog scale, with higher scores indicating better sleep. Total score reported as mean of 5 components. |
| Paired difference in sleep quality by arousal index between baseline and NIV night | 1 day | Arousal index: Index reported as events/hour. Minimum 0, no maximum, with higher scores indicating worse sleep. |
| Paired difference in overnight increase in high sensitivity troponin between baseline and NIV night | 1 day | Troponin assay: Minimum 0, no maximum, with higher values worse. |
| Paired difference between Morning psychomotor vigilance testing score between baseline and NIV night | 1 day | Psychomotor vigilance score: Reported as number of lapses. Minimum 0, no maximum, with higher values worse. |
| Paired difference in morning exhaled nitric oxide level between baseline and NIV night | 1 day | Exhaled nitric oxide assay: Minimum 0, no maximumm with higher values worse. |
| Paired difference in heart rate variability during sleep between baseline and NIV night | 1 day | Comparing difference in heart rate variability during sleep between baseline and NIV night |
Countries
United States
Outcome results
None listed