Impact of Non-invasive Ventilation in Hypercapnic COPD

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.