impact of non-invasive ventilation in hypercapnic copd

Conditions: Copd; Chronic Obstructive Pulmonary Disease; Hypercapnia; Chronic Respiratory Failure; Hypoventilation

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.


Eligibility criteria:
inclusion criteria: * subjects with previously diagnosed severe copd (fev1 \ 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

Keywords: copd lung non-invasive ventilation hypercapnia hypoventilation