European Journal of Pediatrics,
Год журнала:
2025,
Номер
184(4)
Опубликована: Март 24, 2025
This
study
aimed
to
explore
the
characteristics
of
bronchial
mucus
plug
formation
and
its
risk
factors.
A
total
578
children
who
underwent
bronchoalveolar
lavage
treatment
between
January
2022
June
2024
at
Department
Pediatric,
Women
Children's
Hospital
Ganzhou
were
assessed
in
this
study.The
fluid
was
tested
by
next-generation
sequencing.
The
resistance
genes
macrolides
Mycoplasma
pneumoniae
(MP)
detected
polymerase
chain
reaction.
Data
related
basic
information,
clinical
characteristics,
etiology
statistically
analyzed.
Logistic
regression
analysis
performed
identify
independent
factors
for
formation.
There
312
cases
group
266
non-mucus
group.
older,
had
longer
hospital
stays,
exhibited
a
higher
incidence
fever,
experienced
more
complications,
rates
hormone
use
when
compared
those
(P
<
0.05).
detection
rate
MP
macrolide
significantly
than
According
logistic
analysis,
macrolide-resistant
(MRMP)
acted
as
an
factor
plugs
children.
Conclusion:
Bronchial
common
with
infection,
often
accompanied
fever
prolonged
hospitalization.
MRMP
thus
identified
European Respiratory Journal,
Год журнала:
2023,
Номер
62(2), С. 2202153 - 2202153
Опубликована: Июль 6, 2023
Recent
studies
demonstrated
that
the
triple
combination
cystic
fibrosis
transmembrane
conductance
regulator
(CFTR)
modulator
therapy
elexacaftor/tezacaftor/ivacaftor
(ETI)
improves
lung
function
and
reduces
pulmonary
exacerbations
in
(CF)
patients
with
at
least
one
F508del
allele.
However,
effects
of
ETI
on
downstream
consequences
CFTR
dysfunction,
i.e.
abnormal
viscoelastic
properties
airway
mucus,
chronic
infection
inflammation
have
not
been
studied.
The
aim
this
study
was
to
determine
longitudinal
mucus
rheology,
microbiome
CF
or
two
alleles
aged
≥12
years
throughout
first
12
months
therapy.In
prospective
observational
study,
we
assessed
sputum
microbiome,
markers
proteome
before
1,
3
after
initiation
ETI.In
total,
79
allele
10
healthy
controls
were
enrolled
study.
improved
elastic
modulus
viscous
(all
p<0.01).
Furthermore,
decreased
relative
abundance
Pseudomonas
aeruginosa
increased
α-diversity
all
time
points.
In
addition,
reduced
interleukin-8
(p<0.05)
free
neutrophil
elastase
activity
points
p<0.001),
shifted
towards
healthy.Our
data
demonstrate
restoration
by
properties,
over
therapy;
however,
levels
close
reached.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(3), С. 1933 - 1933
Опубликована: Фев. 5, 2024
The
respiratory
mucus,
a
viscoelastic
gel,
effectuates
primary
line
of
the
airway
defense
when
operated
by
mucociliary
clearance.
In
chronic
diseases
(CRDs),
such
as
asthma,
obstructive
pulmonary
disease
(COPD),
and
cystic
fibrosis
(CF),
mucus
is
overproduced
its
solid
content
augments,
changing
structure
properties
determining
derangement
essential
mechanisms
against
opportunistic
microbial
(virus
bacteria)
pathogens.
This
ensues
in
damaging
airways,
leading
to
vicious
cycle
obstruction
infection
responsible
for
harsh
clinical
evolution
these
CRDs.
Here,
we
review
features
normal
pathological
(i.e.,
sputum
CF,
COPD,
asthma),
i.e.,
mucin
content,
(mesh
size),
micro/macro-rheology,
pH,
osmotic
pressure,
ending
with
awareness
that
biomarkers
(mucins,
inflammatory
proteins
peptides,
metabolites)
might
serve
indicate
acute
exacerbation
response
therapies.
There
are
some
indications
old
novel
treatments
may
change
structure,
properties,
biomarker
sputum;
however,
wealth
work
still
needed
embrace
measures
correlates
severity
association
(or
even
substitutes
of)
functional
tests.
American Journal of Respiratory and Critical Care Medicine,
Год журнала:
2024,
Номер
209(11), С. 1338 - 1350
Опубликована: Янв. 23, 2024
Pharmacological
improvement
of
cystic
fibrosis
transmembrane
conductance
regulator
(CFTR)
function
with
elexacaftor/tezacaftor/ivacaftor
(ETI)
provides
unprecedented
improvements
in
lung
and
other
clinical
outcomes
patients
(CF).
However,
ETI
effects
on
impaired
mucosal
homeostasis
host
defense
at
the
molecular
cellular
levels
airways
CF
remain
unknown.
For
idiopathic
pulmonary
fibrosis
(IPF),
interleukin
11
(IL-11)
is
a
pivotal
cytokine
that
stimulates
the
transformation
of
fibroblasts
into
myofibroblasts,
thus
accelerating
progression
fibrosis.
Here,
we
develop
an
innovative
inhalable
small
interfering
RNA
(siRNA)
delivery
system
termed
PEI-GBZA,
which
demonstrates
impressive
efficiency
in
loading
siIL-11
targeting
IL-11
(siIL-11)
and
substantially
suppresses
differentiation
myofibroblasts
epithelial-mesenchymal
transition
(EMT),
reduces
neutrophil
macrophage
recruitment,
ultimately
relieves
established
fibrotic
lesions
IPF
model.
PEI-GBZA
prepared
by
modifying
low-molecular-weight
polyethylenimine
(PEI)
with
4-guanidinobenzoic
acid
(GBZA).
The
resulting
may
effectively
encapsulate
through
variety
interactions
such
as
hydrophobic,
hydrogen
bonding,
electrostatic
interactions,
creating
stable
carrier/siIL-11
nanoparticles
(PEI-GBZA/siIL-11
NPs).
Upon
inhalation,
PEI-GBZA/siIL-11
NPs
demonstrate
effective
retention
lesions,
leading
to
marked
mitigation
disease
bleomycin-induced
Impressively,
this
inhalation
therapy
exhibits
negligible
systemic
toxicity.
This
work
provides
universal
noninvasive
therapeutic
platform
holds
significant
promise
for
respiratory
diseases.
potential
clinical
application
substantial,
offering
frontier
treatment
potentially
other
disorders.
Journal of Clinical Investigation,
Год журнала:
2022,
Номер
132(8)
Опубликована: Март 3, 2022
The
respiratory
tract
surface
is
protected
from
inhaled
pathogens
by
a
secreted
layer
of
mucus
rich
in
mucin
glycoproteins.
Abnormal
accumulation
cardinal
feature
chronic
diseases,
but
the
relationship
between
and
during
exacerbations
poorly
understood.
We
identified
elevations
airway
5AC
(MUC5AC)
MUC5B
concentrations
spontaneous
experimentally
induced
obstructive
pulmonary
disease
(COPD)
exacerbations.
MUC5AC
was
more
sensitive
to
changes
expression
exacerbation
therefore
predictably
associated
with
viral
load,
inflammation,
symptom
severity,
decrements
lung
function,
secondary
bacterial
infections.
functionally
related
as
Muc5ac-deficient
(Muc5ac-/-)
mice
had
attenuated
RV-induced
(RV-induced)
exogenous
glycoprotein
administration
augmented
inflammatory
responses
increased
release
extracellular
adenosine
triphosphate
(ATP)
human
epithelial
cell
cultures.
Hydrolysis
ATP
suppressed
augmentation
inflammation
mice.
Therapeutic
suppression
production
using
an
EGFR
antagonist
ameliorated
immunopathology
mouse
COPD
model.
coordinated
virus
induction
suggests
that
non-Th2
mechanisms
trigger
hypersecretion
Our
data
proinflammatory
role
for
infection
suggest
inhibition
may
ameliorate
ACS Nano,
Год журнала:
2023,
Номер
17(3), С. 2813 - 2828
Опубликована: Янв. 31, 2023
The
penetration
behavior
of
nanoparticles
in
mucous
depends
on
physicochemical
properties
the
and
mucus
microenvironment,
due
to
particle–mucin
interactions
presence
mucin
mesh
space
filtration
effect.
To
date,
it
is
still
unclear
how
surface
influence
their
behaviors
various
physiological
pathophysiological
conditions.
In
this
study,
we
have
prepared
a
comprehensive
library
amine-,
carboxyl-,
PEG-modified
silica
(SNPs)
with
controlled
ligand
densities.
Using
multiple
particle
tracking,
studied
mechanism
responsible
for
these
SNPs.
It
was
found
that
PEG-
amine-modified
SNPs
exhibited
pH-independent
immobilization
under
iso-density
conditions,
while
carboxyl-modified
enhanced
movement
only
weakly
alkaline
mucus.
Biophysical
characterizations
demonstrated
amine-
were
trapped
electrostatic
hydrogen
bonding
mucin.
contrast,
high-density
PEGylated
formed
brush
conformation
shields
interactions.
We
further
investigated
property-dependent
using
murine
airway
distribution
model.
This
study
provides
insights
designing
efficient
transmucosal
nanocarriers
prevention
treatment
pulmonary
diseases.
International Archives of Allergy and Immunology,
Год журнала:
2023,
Номер
184(5), С. 481 - 501
Опубликована: Янв. 1, 2023
As
the
first
line
of
defense
against
risk
factors,
nasal
epithelial
barrier
maintains
homeostasis
in
mucosa.
The
composition
contains
physical,
chemical,
immune,
and
microbiological
barriers.
Together,
these
barriers
form
irritations.
Risk
factors
from
both
internal
external
environments
can
disrupt
them.
External
contain
allergens
containing
proteases,
bacteria,
virus,
particulate
matter,
diesel
exhaust
particles,
cigarette
smoke.
In
meantime,
inflammatory
cytokines
also
increase
load
on
barrier.
Taking
into
account
role
mucosa,
some
studies
focus
treatment
allergic
rhinitis
(AR)
chronic
rhinosinusitis
(CRS)
by
restoring
barrier,
progress
has
been
made.
Among
therapeutic
approaches,
histone
deacetylase
(HDAC)
inhibitor
steroid
corticosteroids
are
considered
two
more
studied
categories,
their
roles
repairing
have
demonstrated
AR
CRS.
underlying
mechanism
HDAC
may
be
related
to
transcription
factor
p63.
And
protection
associated
with
disease
susceptibility
gene,
protocadherin-1.
Notably,
manipulation
a
positive
effect
Lactococcus
probiotics
categories
that
worth
being
explored
continuously.
We
here
review
discuss
compositions
Furthermore,
novel
promising
approaches
restore
defective
diseases
were
mentioned.
Science Translational Medicine,
Год журнала:
2023,
Номер
15(699)
Опубликована: Июнь 7, 2023
Unlike
solid
organs,
human
airway
epithelia
derive
their
oxygen
from
inspired
air
rather
than
the
vasculature.
Many
pulmonary
diseases
are
associated
with
intraluminal
obstruction
caused
by
aspirated
foreign
bodies,
virus
infection,
tumors,
or
mucus
plugs
intrinsic
to
disease,
including
cystic
fibrosis
(CF).
Consistent
requirements
for
luminal
O
2
,
surrounding
in
chronic
obstructive
disease
(COPD)
lungs
hypoxic.
Despite
these
observations,
effects
of
hypoxia
(CH)
on
epithelial
host
defense
functions
relevant
have
not
been
investigated.
Molecular
characterization
resected
individuals
a
spectrum
muco-obstructive
lung
(MOLDs)
COVID-19
identified
molecular
features
hypoxia,
increased
EGLN3
expression,
lining
mucus-obstructed
airways.
In
vitro
experiments
using
cultured
chronically
hypoxic
revealed
conversion
glycolytic
metabolic
state
maintenance
cellular
architecture.
Chronically
unexpectedly
exhibited
MUC5B
mucin
production
and
transepithelial
Na
+
fluid
absorption
mediated
HIF1α/HIF2α-dependent
up-regulation
β
γENaC
(epithelial
channel)
subunit
expression.
The
combination
generated
hyperconcentrated
predicted
perpetuate
obstruction.
Single-cell
bulk
RNA
sequencing
analyses
transcriptional
changes
involved
wall
remodeling,
destruction,
angiogenesis.
These
results
were
confirmed
RNA–in
situ
hybridization
studies
MOLD.
Our
data
suggest
that
may
be
central
pathogenesis
persistent
accumulation
MOLDs
damage.