Вы находитесь на странице: 1из 40

Nasal Polyps - Pathogenesis and

Treatment Implications

Bastaninejad, Shahin, MD, Assistant Professor of


ORL-HNS, TUMS, AmirAlam Hospital

Importance
NPs have been shown to have a significant
detrimental effect on the quality of life, which
is similar in severity to COPD

Introduction
Nasal polyps appear as grape-like structures
in the upper nasal cavity, originating from
within the ostiomeatal complex
They consist of: loose connective tissue,
oedema, inflammatory cells and some glands
and capillaries, and are covered with varying
types of epithelium, mostly respiratory
pseudostratified columnar epithelium

Eosinophils are the most common


inflammatory cells in nasal polyps (80%),
but Neutrophils, mast cells, plasma cells,
lymphocytes and monocytes are also
present, as well as fibroblasts
IL-5 is the predominant cytokine in nasal
polyposis,
reflecting
activation
and
prolonged survival of eosinophils

In the general population, the prevalence of nasal


polyps is 4% (2.2/1 MF Ratio)
The average age of onset is approximately 42
years
In patients with asthma, a prevalence of 7 to 15%
has been noted whereas, in NSAID sensitivity,
nasal polyps are found in 36 to 96% of patients

Factors associated with NP


Allergy Only Kern state inhalant allergy
as a risk factor for NP, but food allergy is
significantly higher in NP patients (80%)
Asthma NPs are present in 13% in nonatopic asthma (skin prick test and total and
specific IgE negative) and 5% in atopic
asthma
Aspirin sensitivity In patients with
aspirin sensitivity 36-96% have nasal polyps

Factors associated with NP


Genetics NP are frequently found to
run in families HLA-A74 , HLA-DR7
Environmental factors The role of
environmental factors in the development
of NP is Unclear

Hypotheses regarding the


underlying mechanisms
Chronic infection (Fungal/Bacterial)
Aspirin intolerance (Samter)
Aerodynamics alteration with trapping of
polutions
Epithelial cell defects / Epithelial disruptions
Gene deletions (CFTR genes in CF)
Inhalant or food allergens (discussed in
previous page)

Chronic rhinosinusitis
with and without nasal
polyps
Chronic
Rhinosinusitis

Nasal Polyps
20-33% of CRS

The spectrum of sinus disease

Rhinosinusi
tis

PMN
TH1

(INF-gama, IL-8)

EOS
TH17

Nasal Polyps

TH2
(IL-4, IL-5)

Histopathology
Frequent epithelial damage, a thickened
basement membrane, and Edematous to
sometimes fibrotic stromal tissue, with a
reduced number of vessels and glands but
virtually no neural structure
Among the inflammatory cells, Eosinophils
are a prominent and characteristic feature
in about 80% of polyps

H&E staining

.
Immunoperoxidase
staining

Pathomechanism
Eosinophilic inflammation
IL-5 was found to be significantly increased in
nasal polyps
Cytokine IL-5 Eos ECP (E. cationic
protein) progression in pathology

Pathomechanism
Extracellular matrix regulation
Eos TGF-1&2 Fibroblast activity
progression in pathology (increase in extra
cellular matrix formation)

Pathomechanism

Role of Staphylococcus aureus enterotoxins


(SAE)
Multiclonal IgE antibody formation to SAE can be
seen in nasal polyp tissue, but rarely in CRS
It is positive in about 30-50% of the patients with
NP and in about 60-80% of nasal polyp subjects
with asthma

Nasal polyposis: aetiology and


pathogenesis
Epithelial damage
(barrier dysfunction)
chronic microbial
trigger

Hyper IgE Cytokines


Polyclonal IgE

Albumin

Superantigens
S. Aureus enterotoxins: disease
modifiers

Eosinophils

(
apoptosis)
Chemokin
es

IL-5
Eotaxin

ECP

Demo for Pathogenesis


polyps

Mast cell

eosinophil

Arachydonic acid
Cycloxygenase

Prostaglandin

5 lipoxygenase

Leukotrienes

Histamine
Interleukin

Thanks from Dr. R. Cathcart for this demo

cytokines

B cell

Differentials

Encephalocoeles
Gliomas
Dermoid tumours
Haemangiomas
Papillomas / transitional cell papillomas
Nasopharyngeal angiofibromas
Rhabdomyosarcomas
Lymphomas
Neuroblastomas
Sarcomas
Chordomas
Nasopharyngeal carcinomas

Medical Treatments
Corticosteroids
reduce airway eosinophil infiltration by
preventing their increased viability and activation
Directily
Or via reducing the secretion of chemotactic
cytokines by nasal mucosa and polyp epithelial cells

Topical Cort.: effect on poly size and also on


symptoms associated with NP such as nasal
blockage, secretion and sneezing but the effect
on the sense of smell is not high

Postoperative

treatment

with

topical

corticoidsteriods
Postoperative effect on recurrence rate of NP
after polypectomy with intranasal steroids is
well documented and the evidence level is Ib
But in patients who undergone FESS operation
did not show a positive effect of local
corticostoroids over placebo (3mo-1yr-2yr)

Systemic steroids :
Is effective in polyp reduction and nasal symptoms
associated with NP, even on sense of smell
Oral corticosteroids for 10 days (20-40mg) there
are reports with 21 days and also higher doses (up
to 50mg) of prednisolone
The benefit of oral steroids, however, remains less
definitive with little randomized data available and
the risk of systemic effect from oral steroids use
in severe cases

Antibiotics:
There is also increasing evidence in vitro of the
anti-inflammatory effects of macrolides
The exact mechanism of action is not known, but
it probably involves down regulation of the local
host immune response as well as a downgrading
of the virulence of the colonizing bacteria

Regimens (12wk also you can try 6wk):


Erythromycin Ethylsuccinate: 400 q6h up to
2wk, then 400 q12h up to 10wk
Clarithromycin: 500 q12h up to 2wk, then 500
daily up to 10wk
AZM 2011 lack of efficacy in treatment
of CRS with or without NP

Antihistamines:
Cetirizine in a dose of 20 mg/day for three
months,

significantly

reduced

sneezing,

rhinorrhoea and obstruction compared to


placebo but with no effect on polyp size
So it is recommended in allergic patients with
NP

Antileukotrienes:
There are a few case controlled trials indicate
that

antileukotriene

beneficial

effect

on

treatment
nasal

may

have

symptoms

in

patients with chronic/persistent rhinosinusitis


and nasal polyposis

Capsaicin:
It is a neurotoxin that depletes substance P with
some other neurokinins and neuropeptides, leading
to long-lasting damage to unmyelinated axons
Tested in Eosinophilic non allergic non asthmatic NP
capsaicin significantly increased NSAV (nosesinuses air volume) and very significantly
improved subjective and endoscopy scores, but did
not significantly alter ECP

Method of Capsaicin delivery:


for 3 consecutive days patients received: 0.5
ml 30 mmol/L capsaicin solution sprayed into
each nostril, and 100 mmol/L of capsaicin
solution on days 4 and 5, respectively

Furosemide:
It exhibited an anti-inflammatory effect
Also it acts on Na/Cl transporter and reduce tissue
edema, too
Passali (2003) - RCT-n=177, post polypectomy
furosemide vs. placebo vs. mometasone. Results after 5yr
F/U:
17% recurrence with furosemide
30% recurrence with placebo
24% recurrence with mometasone

Method of furosemide delivery:


delivery
Furosemide diluted in physiological solution (2
ml of furosemide in 2 ml of saline)
administered as nasal puffs (2 puffs per nostril
a day, each puff corresponding to 50 micg) for
30 days.
Frist 2yrs: every other mounth (12/24mo)
Next 2yrs: 1mo on, 2mo off (8/24mo)
In 5th yr: 2mo in a year (2/12mo)

Strength of evidence for


treatment of CRS vs. NP
Intervention

Chronic rhinosinusitis

Corticosteroids TopicalA
A
Systemic / C
Antibiotics Oral short term < 2w C
Oral long term (12w)
C
C
Antimycotics Topical / Systemic D D
Antihistamines D B
Anti-leukotrienes /
C
Nasal saline douche C
D
Decongestants DD
Allergen avoidance D D

Nasal polyps

Guideline in our country


INCS for undisclosed time ?
Macrolide administration for 6 to 12wks
Oral corticosteroids for 10-20 days (20-40mg)
Montelukast (10mg/day)
In allergic patients: Cetrizine 20mg/day for 3mo

Scheme for experimental polyp treatment


polyps

Mast cell

eosinophil

2
Arachydonic acid
Cycloxygenase

Prostaglandin

cytokines

5 lipoxygenase

3
1

Leukotrienes

Histamine

B cell

Interleukin

polyposis
Anti-IgE?

An
t

Anti-CCR3?
i Ig

Eotaxin
Tacrolimus?

IgE

-5
L
I
ti
An

IL-5

Corticosteroids?

Anti-LTs?

ECP
Antibiotics?

Anti-IL-5?

Anti-fungal?

Surgical Treatments
Surgical treatments, including Polypectomy
alone or in combination with FESS, rarely
result in long term control of polyposis and are
typically combined with medical treatment
When hyposmia is the primary symptom, no
additional benefit seems to be gained from
surgical treatment. If nasal obstruction is the
main problem after steroid txy, surgical
treatment is indicated

When to proceed with surgical therapy?


when medical therapy fails to control symptoms
when the patient is not suitable for oral steroids
when total nasal obstruction occurs
when there is persistent infection or complications

Simple polypectomy vs. FESS!? Dalziel


(2003) - meta-analysis :
Symptom improvement

FESS 78-88%
Simple 43-84%

Recurrence

28%
35%

7%
difference!!

When is it logical to perform FESS instead of a


simple polypectomy operation?

Severe and extensive disease


Underlying diseases (Asthma, Samter, Allergic
fungal, CF,)
Revision cases when pathology is not localized

Bastaninejad MD

Похожие интересы