Chronic Rhinosinusitis (CRS): Sinonasal Innate Immunity, Microbiome and Sense of Taste
Noam Cohen presented on “Sinonasal Innate Immunity and the Microbiome”.
Rinosinusitis has a huge impact in the US – affects 16% population, $8 B in direct medical costs, 550K surgeries/year, more outpatient abx prescriptions than any other diagnosis, worse QoL surveys than COPD, CHF and Angina.
CRS management: lavage, steroids, antibiotics, possible surgery (FESS). Surgery for Chronic Rhinosinusitis (CRS) is basically a technique that allows access for lavage and medications.
Biofilms leads to increased steroid use, antibiotics, surgery. Why do some patients develop bacterial biofilms? Biofilms tend to form in non polyp CRS as opposed to eosinophilic Polyp CRS.
Biofilms are structured community of bacterial cells enclosed in a self-produced polymeric matrix and adherent to an inert of living surface that leads to bactericidal resistance. Biofilm cycle: https://twitter.com/MatthewBowdish/status/1087411587990745088
How does sense of taste play a role in microbiome in CRS?
Bitter taste receptor T2R38 is expressed in the human sinonasal epithelium, specifically the cilia. Why? Quorum sensing molecules from bacteria stimulates production of Nitric Oxide (NO) through these taste receptors. NO increases ciliary beat frequency and has biocidal and biostatic effects on bacteria. High concentrations inhibit Staph biofilms.
Those who are non-tasters don’t have the same NO production and end up back in the OR. This non-tasters tended to have more bugs that could form biofilms. Non-tasters and those with biofilms tended to have sinus inflammation without polyps (ie Th1 and not Th2 inflammation).
Finding these non-taster, non-polyp patients is important because they have poor outcomes with FESS, suggesting that may be they shouldn’t go to surgery and instead try different interventions.
CRS appears to be related to fairly common genetic polymorphism in bitter taste receptors – if they work, this appears to lead to less biofilms, if don’t work then there are more biofilms. Take home message: things are not so bad for people who are very sensitive to bitter substances.
Bitter taste receptors are called AKA T2R38. If this system is functioning, then you can generate nasal NO to kill bacteria. Otherwise, you generate biofilms, thus needing surgery for CRS.
Patients who are not bitter tasters and are non polyp forming tend not to respond to FESS. All polyp forming patients respond to FESS equally. Bitter tasters and non polyp forming pls respond very well to CRS surgery. Reconsider FESS in patients that cannot taste bitter products and have no evidence of polyps.
Taste receptors are important in sensing presence of different types of bacteria and they use this to communicate to innate immunity and also adaptive immunity through IL25 and ILC2 cells. A common polymorphisms in these taste receptors may explain differences in development of CRS.
Denatonium is a bitter molecule that has strong anti microbial activity. It leads to generations of antimicrobial peptides.
Solitary Chemosensory Cells (SCCs) that interacts with innate immune system like taste receptors but also to adaptive immunity through IL25: https://twitter.com/MatthewBowdish/status/1087421950564003840
Airway Taste Receptors: The Big Picture: https://twitter.com/MatthewBowdish/status/1087422322863104001
Management of Post Surgical CRS: New Technologies
Noam Cohen presented on “Management of Post Surgical CRS: New Technologies”
Principles of Functional Endoscopic Sinus Surgery (FESS):
– drain inspissated/infected secretions
-restore physiologic mucociliary clearance
-improve access for topical therapies
Common Surgical Causes of FESS Failure:
-lateralized middle turbinate
-mucosal stripping w/neo-osteogenesis
Disease recurrence after CRS surgery is due to polyps and biofilms.
Biologic causes of FESS failure:
-pooling of mucus/pus
Consider immune workup in patients with recurrent CRS.
Dr Cohen: 13% of patients with recurrent chronic rhinosinusitis have an IgG, IgA, or IgM deficiency compared to 1% in general population, 23% for “difficult to treat” CRS.
Sinus irrigation works mainly through retrograde flow that penetrates into the opposite sinuses. Sinus surgery improves delivery of topical medications into the sinuses.
You must keep the “Sinus Rinse” bottle clean: https://twitter.com/RayFirszt/status/1088575874050314240
50% of irrigation bottles positive for bacterial growth (manly Pseudomonas) after ESS – have to instruct them to clean bottles daily in hot cycle dishwasher or microwave for 90 seconds.
Post surgery irrigation is very effective, using traditional Neti pots. Remember to clean the bottles. Budesonide irrigations help. Using budesonide irrigations: https://twitter.com/RayFirszt/status/1088576232256462848
Budesonide in sinus rinses Study Conclusions: https://twitter.com/MatthewBowdish/status/1088576698604371970
No evidence of short term adrenal suppression in acute use of budesonide rinses, but some chronic use of budesonide rinses when other steroids also used (eg asthma inhalers) can have adrenal suppression.
BUD irrigations appear to work better than sprays with steroids (INS), but not better than INS with nasal saline irrigations. Use nasal irrigations prior to INS administration, of course, not vice versa.
Recipes for antibiotics for topical irrigations for Gram negative bacteria: https://twitter.com/RayFirszt/status/1088577622563409920
For Gram positive bacteria: https://twitter.com/RayFirszt/status/1088577903715995648
Recent advances in sinonasal drug delivery: https://twitter.com/MatthewBowdish/status/1088578546472120320
EDS delivery system: Xhance exhalation delivery system: Excellent delivery system. Exhalation forces soft palate closed and forces medication to flow retrogradely though contralateral nose and allowing deposition to sinus cavities. CRS studies show 70-80% improvement on Xhance with nasal polyps or not.
Nothing reaches frontal sinuses: EDS delivery system does get medication delivered to the frontal recess. It does not happen with regular nasal sprays either.
Drug eluting stents – consider after CRS surgery. Drug eluting stents designed to sit in nose for 1-3 months: https://twitter.com/MatthewBowdish/status/1088579657203511296
Medical therapy for AERD: ASA desensitization. Monoclonal Ab, LTRA. Desensitize 4-6 weeks after CRS surgery.
Treating AERD aggressively from both surgical and medical aspect important in difficult to treat CRS: https://twitter.com/MatthewBowdish/status/1088580337926426624
Clinical considerations in ASA desensitization in AERD: https://twitter.com/MatthewBowdish/status/1088580919294717952
New drugs for CRS – Biologics: https://twitter.com/MatthewBowdish/status/1088581235469766656
Biologics: dupixent cause a reduction in nasal polyp scoring. Improved sense of smell. Dupixent was administered as 600 mg loading dose, and then 300 mg weekly. How long to treat? Not clear. It was very effective.
Biologics appear to work but questions remain about selection of ideal biologic (biomarkers?), cost, and how long needed to treat.
Verapamil is a 1st generation p-glycoprotein inhibitor, works for polyps, may be able to eventually give topically at higher doses to avoid cardiac side effects. Verapamil might be effective in CRS w NP. Inhibits p glycoprotein. The dose was 80 mg po tid. Topical therapy in future.
CRS Conclusions: https://twitter.com/MatthewBowdish/status/1088582852185227264
If you have unilateral maxillary sinusitis, always consider “bad teeth” as a source, and possible tooth extraction as a remedy.
This is a Twitter summary from the 2019 WSAAI meeting. This summary was compiled from the tweets posted by Matthew Bowdish @MatthewBowdish and Ray Firszt @RayFirszt, who attended the 2019 Western Society of Allergy, Asthma and Immunology (WSAAI) meeting. The tweets were labeled #WSAAI. The text was edited by me.
Sinusitis – different causes and management (click to enlarge the image).
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