and chronic rhinosinusitis (CRS)

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Transcript and chronic rhinosinusitis (CRS)

Pathogenesis AND
treatment of
Chronic
Rhinosinusitis
1
OVERVIEW:
Acute rhinosinusitis (ARS) and chronic rhinosinusitis (CRS)
are defined as symptomatic inflammation of the nose and
paranasal sinuses with the distinction between the two based
on the duration of the complaints.
Although ARS is widely considered to be an infectious
disorder.
CRS, on the other hand, is typically described more broadly
as an inflammatory disorder, and the importance of specific
microbial agents in driving the process remains controversial.
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Pathogenesis of CRS
CRS is primarily idiopathic; however, small numbers of
patients have an established association with
systemic immunologic or genetic diseases.
Broad theories on the etiology and pathogenesis of CRS
have been proposed that place particular emphasis on
either specific microbial agents or host defects
Pathogenesis of CRS
Viruses, fungi, bacteria, allergens, and other foreign
materials interface with the Sinonasal epithelium.
In patients with CRS, this interaction results in
persistent mucosal inflammation and the
Secondary symptom complex associated with the
disorder. The microbial agent most commonly
associated with CRS is Staphylococcus aureus
Pathogenesis of CRS
The staphylococcal superantigen hypothesis is the most
widely established microbial hypothesis of
CRS pathogenesis. The central tenet proposes that S.
aureus sequestered within epithelial cells or
in a biofilm format secretes exotoxins, which results in
multiple effects that foster eosinophilic polyp formation
Pathogenesis of CRS
The host response to exogenous stimulation begins with epithelial
cell activation that leads to the secretion of cytokines and chemokines
that are important not only in triggering the innate immune
response but also in shaping the appropriate adaptive immune
response.
Defects anywhere along these complex indicating pathways may
predispose to the development of CRS
Pathogenesis of CRS
The immune barrier hypothesis is the most widely
accepted host-centered hypothesis and proposes
that local defects in the mechanical and innate immune
barrier result in increased microbial
colonization and increased inflammatory stimulation of the
sinonasal mucosa. A compensatory adaptive immune
response is then initiated.
… At present, factors that have been associated
with the etiology and pathogenesis of CRS
include :
fungi, resistant bacteria, superantigens,
biofilms, atopy, mucociliary dysfunction,
environmental irritants, acquired sinonasal
obstruction (especially of the ostiomeatal
complex), osteitis, and genetic or epigenetic
variation of the host.
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Overall concept of CRS

Overall, this leads to the concept that CRS pathogenesis is best described as a
dysfunctional interaction that occurs at the site of interface between the host and the
environment: the sinonasal mucosa (Fig. 45-1).
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The immune barrier hypothesis
The immune barrier hypothesis proposes that defects in the
mechanical barrier and/or the innate immune response of the
sinonasal epithelium manifests as CRS.7 Increased microbial
colonization and accentuated barrier damage lead to increased
stimulation of the immune system with a compensatory adaptive
immune response (Fig. 45-2).
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mucosal immunity of the respiratory tract rather or
the systemic immune system problem
… In other words, a dysfunctional immune response to
exogenous factors at the sinonasal mucosal border leads to
the mucosal inflammation, radiographic changes, and
symptoms that characterize CRS.
Interestingly, epidemiologic studies on idiopathic CRS
patients have demonstrated a strong association with asthma
but only a weak, if any, association with other chronic
inflammatory disorders.
This suggests that the key host factors associated with CRS
development are likely specific to the mucosal immunity of
the respiratory tract rather than the systemic immune system.
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biofilm hypothesis
The biofilm hypothesis suggests that biofilms, in
particular staphylococcal biofilms, can serve as
etiologic agents that cause CRS. It can be speculated
that a defect in the immune barrier might facilitate
formation of biofilms, which would suggest a role in
pathogenesis rather than etiology.
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CONCLUSIONS:
Delineation of the etiology and pathogenesis of CRS remains a
work in progress, and the current hypotheses vary in terms of
points of emphasis, scope, and supportive evidence. Each may
very well describe parts of this complex syndrome.
Moreover, the hypotheses are less in conflict than they might
appear. Inherent immune and barrier defects should predispose to
the establishment of biofilms as well as to stimulation by fungi
and bacteria. Both fungi and bacteria have substantial intrinsic
protease activities, which may degrade tight junctions and
accentuate host barrier compromise.The presence of intracellular
S. aureus in epithelial cells from CRSwNP, but not CRSsNP or
controls, supports the concept of defective local immune and/or
barrier function..
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Treatment options in CRS


Antibiotics

Duration(Short course or Long course)

Oral ,iv,local
Antifungal Medications


Oral ,iv,local
CORTICOSTEROIDS

TOPICAL

systemic

ANTIHISTAMINES

LEUKOTRIENE ANTAGONISTS

SALINE IRRIGATIONS
Antibiotics

— Mucosal colonization with Staphylococcus aureus has been found in 64 percent
of patients with CRS and NP, compared with roughly 30 percent in healthy
individuals or patients with CRS.

In addition, immunoglobulin E (IgE) antibodies directed against Staphylococcal
superantigens have been found in the tissues of a high percentage of colonized
polyposis patients.

Based on these observations, a randomized, double-blind, placebo-controlled trial
was conducted to assess whether doxycycline could reduce nasal polyp size and
provide antiinflammatory effects [80]. Doxycycline (200 mg on the first day
followed by 100 mg once daily for 20 days) caused a small but statistically
significant reduction in polyp size beginning at week 2 and persisting for 12 weeks.
A significant reduction in nasal secretion eosinophil cationic protein (ECP) was also
found after 20 days of doxycycline treatment. However, doxycycline caused no
statistically significant improvement in nasal peak inspiratory flow rate.
MEDICAL TREATMENTS :
:
ANTIBIOTICS
Microbial pathogens have always been considered a fundamental
component of the overall pathophysiology of CRS.
The concept of CRS as a persistent or perhaps recurrent infection
dominated early thinking and was reinforced by the high
prevalence of pathogenic bacteria in sinonasal cultures.
Although the inflammatory nature of CRS is emphasized today,
bacteria certainly may play a role in disease exacerbations and
may to some degree promote the chronic mucosal inflammation
that characterizes the disease.
:Antibacterial Medications
:Oral Medications
Oral antibiotics for CRS can be broken down into macrolide and nonmacrolide
classes.
Although the macrolide class of antibiotics also has antibacterial effects, these
medications have known anti inflammatory properties, which have been
documented both in the upper and lower airways of patients with CRS,
asthma, and cystic fibrosis.
The nonmacrolide antibiotics would include commonly utilized agents such as
penicillins, cephalosporins, and fluoroquinolones among others, all of which
are theorized to work via their antibacterial effects.
DURATION

evidence-based reviews have classified short-term oral antibiotics as
regimens of less than 3 to 4 weeks in duration and long-term oral antibiotics
as those with a duration of 3 months or more.

Thus, routine use of extended courses of short-term(6-8 WEEKS) antibiotics
has not been recommended for CRS.
Nonmacrolide Oral Antibiotics:
Chronic Rhinosinusitis Without Nasal Polyps:
No RCTs have been undertaken to compare oral nonmacrolide antibiotics to
placebo in patients with CRSsNP. The lack of quality data regarding this
treatment option is surprising given the frequency with which it is utilized.
Three RCTs have compared two different antibiotics in patients with CRS, but
none of these studies demonstrated one antibiotic to be superior to another.
Macrolide Oral Antibiotics:
Chronic Rhinosinusitis Without Nasal Polyps:
A large body of evidence has shown efficacy of macrolide antibiotics to improve
outcomes in prospective observational studies, including imaging findings,
mucus cytokines, and patient-reported symptoms.Two RCTs have evaluated
macrolide use in this patient population, utilizing a treatment course of 3
months.
This RCT administered roxithromycin 150 mg daily or placebo for 3 months in
64 patients with refractory CRS, without patients with nasal polyps. The
macrolide group demonstrated a significant improvement in subjective
symptoms, disease-specific QOL, endoscopy findings, and measured
saccharine transit time compared with placebo (P ≤ .01 for all) at the
conclusion of therapy.
No improvement was seen in objective olfactory function, NPIF, or mediators
measured from nasal lavage.
Improvement in QOL was no longer significant at 12 weeks following
completion of therapy. A subgroup analysis based on serum IgE levels
revealed that most of the benefit seen in the study was in patients with
low (<200 μg/L) IgE levels (P < .01).