Ventilator-associated injury (VAI) in chronic home mechanical ventilation: a paradigm switch in order to improve ventilatory support

Chronic Obstructive Pulmonary Disease (COPD) is a progressive inflammatory
disease characterised by airway and lung parenchyma damage. At end-stage
disease patients may develop chronic hypercapnic respiratory failure. The
underlying process for this is incompletely understood and the role of
respiratory muscle alterations is unclear. Home noninvasive ventilation with
high-intensity ventilatory settings (HI-NIV) has been shown to be effective in
these severe COPD patients. However, in patients being mechanically ventilated
on the intensive care unit for diverse reasons, high-intensity ventilation,
especially high tidal volumes, has been shown to result in ventilator
associated lung and diaphragm injury. Whether this occurs in home
high-intensity NIV, is however completely unknown.

The primary aim of the study is to get insight in the effects of long-term
HI-NIV in severe COPD patients on the respiratory muscles; i.e. the contractile
strength and the structure of single diaphragm and intercostal muscle fibres
and the lungs; i.e. alveolar structure and damage and inflammation, by
comparing COPD patients that had been treated with long-term NIV to patients
that were not treated with long-term NIV prior to lung transplantation. Because
respiratory muscle functioning, lung mechanics and clinical characteristics,
although patients all suffer from end-stage disease, are completely different
in COPD compared to for example advanced stage pulmonary fibrosis, we will, as
a secondary aim, compare the observed changes in respiratory muscle morphology
of COPD patients with respiratory muscle morphology of patients with pulmonary
fibrosis.

In order to investigate this, we will include in a small pilot cohort study
patients being lung transplanted. In these patients there is lung tissue
available and respiratory muscle biopsies will be performed during
lung-transplant surgery.

The burden of the participants is limited. For study purposes, additional
investigations are performed shortly before and during the lung transplant
procedure, consisting of an additional blood sample taken, a broncho-alveolar
lavage just prior before the lung are taken out and respiratory muscle biopsies
(of the diaphragm and intercostal muscles) during the surgery. The procedures
performed to investigate lung architecture are performed in the explanted
lungs. Patients will not be asked to perform additional tests. The additional
procedures performed are not expected to have side-effects or risks.