Hyperinflation in COPD exacerbations

COPD exacerbations are the main driver of quality of life in COPD, of survival,
and of more than 50% of costs incurred in COPD. The latter is above all due to
exacerbations leading to hospitalisation. It is therefore surprising that not
much research has been performed regarding COPD exacerbations requiring
hospitalisation. Among others, it is unclear why some patients require a longer
hospital treatment than others. For individual patients, dyspnea is the most
important complaint during an exacerbation, but this is relatively difficult to
measure and correlates poorly with many more readily measured parameters that
change during an exacerbation. For instance. the differences in both the level
and course of breathlessness during an exacerbation of COPD do not associate
well with the classical parameters that are affected by an exacerbation such as
blood oxygen saturation or lung function. It is well known that dyspnea in a
stable situation is much stronger correlated with hyperinflation than with
oxygen saturation and lung function. We postulate that this increased
hyperinflation is also a strong determinant of the dyspnea as present during
exacerbations.
Bacterial and viral infections both can induce a COPD exacerbation. The first
cells in the line of defense against these infectious agents are the epithelial
cell layers. It may well be that the course of an exacerbation is also related
to changes in the defense mechanisms of eptihelial cells. Therefore more
studies are needed investigating epithelial responses to inhaled stimuli in
e.g. cell cultures and measurements of released cytokines and proteins, as well
as gene-expression profiling. Furthermore epithelial responses can be measured
with ENOS in vivo that unbiasedly measures exhaled organic compounds. Finally,
steroids are the mainstay of treatment of COPD exacerbations, yet differential
response to steroids may affect the outcome as well. Thus we will additionally
investigate steroid responses in vivo and compare this with epithelial
responses in vitro by epithelial cell cultures of the same individuals. In
summary, more knowledge about exacerbations is needed to help understand why
certain patients need to be hospitalized as opposed to others , and what drives
their length of stay.

Objective: The main objective is to establish the strength of the relationship
between improvements in dyspnea and health related Quality of Life (HR-QoL)
with the decrease in hyperinflation during the resolution of a COPD
exacerbation in the hospital. The secondary objectives are to assess whether
dynamic changes in airway inflammation and patency, especially in the small
airways, contribute to changes in hyperinflation. Furthermore, whether the
level and course of hyperinflation, airway epithelial pro-inflammatory
response, epithelial response to steroids, genome-wide gene-expression profiles
and the changes thereof, relate to quality of life and to length of hospital
stay in COPD patients requiring hospitalisation for an exacerbation.

This is a single center cohort study, designed to asses COPD patients admitted
with a COPD exacerbation. A total of 30 COPD patients with an exacerbation will
be included in this study.

Patients will receive all necessary care and treatments as per normal routine.
Participants will encounter some additional measurements mostly during the
hospitalization, and once at the routine follow-up visit after hospitalization.
There are broadly three groups of measurements: those to be performed as much
as possible within 24 hours of admission; those to be performed several times
during hospitalization, and those to be performed once, as soon as possible
during hospitalization. Most measurements will be repeated at the routine
follow-up visit in stable state, approximately 6 weeks after the start of the
hospitalization.