nasal polyps - pathogenesis and treatment implications bastaninejad, shahin, md, assistant professor...
TRANSCRIPT
Nasal Polyps - Pathogenesis and Nasal Polyps - Pathogenesis and Treatment ImplicationsTreatment Implications
Bastaninejad, ShahinBastaninejad, Shahin, , MD, Assistant Professor of MD, Assistant Professor of ORL-HNS, TUMS, ORL-HNS, TUMS, Amir’Alam Amir’Alam HospitalHospital
ImportanceImportance
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% 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 rhinosinusitiswith and without nasal
polyps
Chronic Rhinosinusitis Nasal Polyps
Nasal Polyps
The spectrum of sinus disease
Rhinosinusitis PMNPMN EOSEOS
20-33% of CRS
TH1 TH17 TH2
(INF-gama, IL-8) (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
. Immunoperoxidase
staining
H&E 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
Chemokines
TB
Cytokines Hyper IgE
Eosinophils ( apoptosis)
SuperantigensIL-5
ECP
Albumin
Eotaxin
Polyclonal IgE
Epithelial damage (barrier dysfunction)
chronic microbial trigger
S. Aureus enterotoxins: disease modifiers
Demo for Pathogenesis
polyps
eosinophilB cellMast cell
Arachydonic acid
5 lipoxygenase
Leukotrienes
Interleukin
Prostaglandin
Histamine
Cycloxygenase
cytokines
Thanks from Dr. R. Cathcart for this demo
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 but the effect on the sense of smell is not highon 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) 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 macrolidesmacrolides
– 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 treatment may have
beneficial effect on nasal 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 leading to long-lasting damage to unmyelinated axonsto long-lasting damage to unmyelinated axons
– Tested in Eosinophilic non allergic non asthmatic NP– capsaicin significantly increased NSAV (nose-
sinuses air volume) and very significantly very significantly improved subjective and endoscopy scores, but did not significantly alter ECP
• Method of Capsaicin delivery: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 deliveryMethod of furosemide delivery:
– Furosemide diluted in physiological solution (2 (2 ml of furosemide in 2 ml of saline) 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 Nasal polyps
Corticosteroids Topical A A Systemic / C
Antibiotics Oral short term < 2w C D Oral long term (12w) C C
Antimycotics Topical / Systemic DD
Antihistamines D BAnti-leukotrienes / C Nasal saline douche C D Decongestants D DAllergen avoidance D D
Guideline in our countryGuideline 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
eosinophilB cellMast cell
Arachydonic acid
5 lipoxygenase
Leukotrienes
Interleukin
Prostaglandin
Histamine
Cycloxygenase
cytokines
1
2
3
45
Anti IgEAnti-IgE?
Antibiotics? Anti-fungal?
IL-5
ECP
Eotaxin
IgE
Anti IL-5
Anti-IL-5?
Corticosteroids? Anti-LTs?
Anti-CCR3?
Tacrolimus?
Future therapies in nasal polyposis
Surgical Treatments• Surgical treatments, including PolypectomyPolypectomy
alone or in combination with FESS, rarely rarely result in long term control 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 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!? Simple polypectomy vs. FESS!? Dalziel (2003) - meta-analysis :
Symptom improvementSymptom improvement Recurrence Recurrence
FESS 78-88% 28%
Simple 43-84% 35%
7% 7% difference!!difference!!
• When is it logical to perform FESS instead of a When is it logical to perform FESS instead of a
simple polypectomy operation?simple polypectomy operation?
– Severe and extensive disease
– Underlying diseases (Asthma, Samter, Allergic
fungal, CF,…)
– Revision cases when pathology is not localized
Bastaninejad MDBastaninejad MD