Download Nasal Polyps

Nasal Polyps - Pathogenesis and
Treatment Implications
Bastaninejad, Shahin, MD, Assistant Professor of
ORL-HNS, TUMS, A m i r ’ A l a m 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
non-atopic 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
Nasal Polyps
Rhinosinusitis
PMN
TH1
(INF-gama, IL-8)
EOS
TH17
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-β1&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
B
T
Hyper IgE  Cytokines 
Polyclonal IgE
Albumin
Superantigens
S. Aureus enterotoxins: disease modifiers
Eosinophils 
( apoptosis)
IL-5
Chemokines
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-1yr2yr)
• 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:
– 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
Corticosteroids
Chronic rhinosinusitis
Topical
Systemic

Antibiotics Oral short term < 2w
Oral long term (12w)

Antimycotics Topical / Systemic
Antihistamines
Anti-leukotrienes
Nasal saline douche
Decongestants
Allergen avoidance
Nasal
polyps
A
/
A
C
C
C
D
C
D
D
/
C 
D
D
D
B
C
D
D
D
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
4
B cell
Interleukin
5
Future therapies in nasal polyposis
Anti-CCR3?
Anti-IgE?
Eotaxin
Tacrolimus?
IgE
Anti-IL-5?
Corticosteroids?
Antibiotics?
IL-5
Anti-LTs?
ECP
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
complications
is
persistent
infection
or
• Simple polypectomy vs. FESS!? Dalziel
(2003) - meta-analysis :
FESS
Simple
Symptom improvement
Recurrence
78-88%
43-84%
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