Oesophageal mucosal integrity in non-erosive reflux disease and refractory GORD.
Abstract
Background:
20
to
30%
of
patients
with
GORD
respond
inadequately
to
conventional
therapy.
Most
of
these
patients
belong
to
the
non-‐erosive
reflux
disease
group.
Despite
not
having
oesophagitis,
in
these
patients
oesophageal
mucosal
integrity
appears
to
be
impaired.
Aims:
To
study
the
dynamic
in
vitro
and
in
vivo
properties
of
oesophageal
mucosal
integrity
in
patients
with
non-‐erosive
reflux
disease,
and
to
test
the
feasibility
of
a
topical
mucosal
protectant
therapy.
Methods:
In
vitro
studies
of
mucosal
integrity
were
done
on
human
oesophageal
biopsies
using
Ussing
chambers.
Change
in
transepithelial
electrical
resistance
(TER)
on
exposure
to
acidic
solutions
was
measured.
Integrity
was
assessed
in
vivo
by
measuring
impedance
change
and
subsequent
recovery
after
oesophageal
acid
perfusion
in
symptomatic
patients.
Proximal
and
distal
oesophageal
mucosal
integrity
was
assessed
in
vitro
and
in
vivo.
The
effect
of
in
vitro
topical
application
of
an
alginate-‐based
solution
on
acid-‐induced
changes
in
mucosal
integrity
was
tested.
Results:
In
vitro
exposure
of
biopsies
to
acidic
and
weakly
acidic
solutions
caused
a
greater
impairment
of
integrity
in
symptomatic
patients
than
in
controls.
In
vivo
oesophageal
acid
perfusion
causes
a
profound
drop
in
distal
oesophageal
impedance
that
is
slow
to
recover.
Recovery
is
slower
in
patients
with
non-‐erosive
reClux
disease
than
in
patients
with
functional
heartburn,
and
a
low
baseline
impedance
is
associated
with
painful
perception
of
acid.
Proximal
oesophageal
sensitivity
appears
unrelated
to
impaired
mucosal
integrity,
but
rather
to
a
distinct
sensory
afferent
nerve
distribution.
Topical
pre-‐treatment
with
an
alginate
solution
is
able
to
prevent
acid-‐induced
changes
in
integrity
in
vitro.
Conclusion:
Patients
with
non-‐erosive
reClux
disease
have
a
distinct
mucosal
vulnerability
to
acidic
and
weakly
acidic
solutions
that
may
underlie
persistent
symptoms.
A
topical
therapeutic
approach
may
be
a
feasible
add-‐on
strategy
to
treat
GORD
in
the
future.
2
Authors
Woodland, Philip JohnCollections
- Theses [3706]
