Nocturnal Non-Invasive ventilation in COPD patients with stable hypercapnic respiratory failure: why and in which patient might this be effective?

Application of long-term non-invasive ventilation (NIV) in chronic obstructive
pulmonary disease (COPD) patients with chronic hypercapnic respiratory failure
(CHRF) has recently been shown to improve outcomes when applied with
sufficiently high inspiratory pressures and adequate backup breathing
frequencies (high-intensity NIV). Interestingly, it has been demonstrated that
nocturnal NIV improves not only clinical but also physiological parameters like
arterial carbon dioxide pressure (PaCO¬2¬) and forced expiratory volume in 1
second (FEV1) in patients with stable COPD. However, the mechanism behind these
improvements are unknown. Furthermore, it is unclear whether this improvement
in lung function influences health-related quality of life (HRQoL), the utmost
goal of chronic NIV in COPD, or that other baseline patient- and ventilatory
characteristics are more important in predicting a long-term beneficial effect.
We hypothesize that NIV stabilizes FEV1 via beneficial effects on inflammation
and repair pathways in the airways of patients with COPD. We aim to study this
hypothesis and to investigate the regulation of lung function, markers of
inflammation and repair pathways in airway biopsies, bronchial wash and
bronchial and nasal epithelium in response to home mechanical ventilation. The
second goal of this study is to define a phenotype of patients with COPD, based
on baseline characteristics and biomarkers, such as markers of inflammation,
who will respond to NIV therapy with improvements in lung function and HRQoL.

Objectives:
1) To investigate change in FEV1 after 3 months nocturnal NIV in stable
hypercapnic COPd patients as compared to standard care
2) To investigate the relationship between FEV1 change and modification of
systemic and airway inflammation and remodelling, lung hyperinflation, and
airway morphology.
3) To investigate predictors of a favourable response to chronic NIV in COPD
patients with CHRF.

The study is multicentre randomised controlled study investigating the effects
of NIV on lung function, airway morphology, airway inflammation and remodelling
in hypercapnic COPD patients including a control group that will postpone the
initiation of NIV for 3 months. In addition we will investigate how patient
demographics, patient and disease characteristics and systemic and airway
inflammation predict the response to chronic NIV in severe stable COPD.

The intervention investigated is chronic NIV. NIV will be set as it is in usual
care, supplied through a pressure cycled ventilator (Stellar 100® or Lumis®,
RESMED LtD, Bella Vista NSW 2153, Australia), applying both inspiratory airway
pressure and expiratory airway pressure to the patient.

Chronic NIV has no known serious side effects, and the benefits of chronic NIV
are expected to outweigh the potential side effects in these severe COPD
patients. To study inflammation, a control group is added, as little is known
about the natural course of inflammatory parameters in this patient group. As
patients in stable state are included, we expect no major problems with
postponing the NIV for 3 months in the control group. Bronchoscopies are
absolutely necessary to obtain adequate and unique samples of inflammation in
the airways. Other trials have shown that bronchoscopy is a very safe
procedure, also in patients with severe emphysema. For safety reason, we will
exclude patients with extreme severe gas exchange derangements and instable
cardiac comorbidities for the bronchoscopies. We choose to do so in line with
our prior bronchoscopy trials. Normal discomfort associated with bronchoscopy,
like a sore throat, are to be expected. To limit discomfort, we will perform
the bronchoscopy procedures under conscious sedation. In our hospital we have a
large amount of experience with this procedure during the bronchoscopic lung
volume reduction procedures. In contrast to these procedures however, we will
only collect a bronchial wash and biopsies from the larger airways, which makes
the risk of for, for example a pneumothorax, extremely limited.