Chronic sinusitis - Twitter summary from #ACAAI18 meeting

Dr. Peters presented on rhinitis and sinusitis: Strongest risk factor for adult life (early onset chronic sinusitis): childhood sinusitis (being diagnosed before 6 years old) rather than AR or maternal asthma.

1 mg nasal rinse with budesonide improved both subjective and objective measures of CRS. Both nasal spray and steroid irrigation improve symptoms after CRS surgery; however, steroid irrigation was superior to nasal steroids.

EDS-FLU significantly improved congestion/obstruction symptoms and nasal polyps grade in CRSwNP.

Literature review with excellent discussion of steroid delivery methods in sinusitis and polyps disease. Appears EDS-Flu and high volume low pressure rinse with budesonide are best.

CRS with peripheral eosinophilia was more significantly associated with acute asthma/COPD exacerbations than CRS without peripheral eosinophilia.

In humid climates indoor dampness & #mold can be significant health hazard predisposed to chronic #sinusitis and other respiratory diseases. Often felt patient advocacy efforts limited by disconnect between our medicine and public health infrastructure:

Chronic rhinitis (CR) with peripheral eosinophilia is associated with acute asthma/COPD exacerbations. Allergic & non-allergic rhinitis associated with higher risk of 30-day asthma/COPD readmission. Would treatment of rhinitis reduce early readmissions?

Defective barrier is associated with allergic rhinitis: azelastine prevents epithelial barrier disruption by blocking histamine receptors.

Symptoms of influenza A Virus infection last longer in allergic rhinitis patients - possibly determined by type III interferons. Allergic individuals may have longer duration of symptoms (fever, sore throat, cough) with viral infection (influenza A virus). Allergic nasal epithelial cells have lower expression of IFN-lambda and have higher susceptibility to viral infection and viral replication. treatment of epithelial cells with exogenous IFN-l suppressed viral replication in allergic epithelial cells. All in vitro of course.

Best current treatment options for CRSwNP

Eosinophilia abundant conditions: CRSwNP, EMRS, and AFR. CRSwNP: IL-5 and IL-13 are present in polyp tissue.

In CRSwNP, interleukins are key in pathogenesis. It adds up to a maladaptive TH2 response.

AFRS: NPs, Erodes bone, they need surgery.

FDA approved administration of local steroids: INS, EDS, and stents.

Sinuva is a mometasone eluting sinus stent - reduced nasal polyps significantly - FDA approved now. RESOLVE trial: mometasone-eluting implant for nasal NP - over 90 days; reduced polyp size, cost-prohibited.

Sinus implant that releases mometasone (Sinuva) more effective that mometasone nasal spray (Nasonex) for nasal polyps.

Optinose exhalation delivery system for fluticasone effective as well. Fluticasone Exhalation Delivery System is an effective alternative for treatment of CRAwNP.

Budesonide nasal rinses: head down forward, concentration matters.

Budesonide 0.5 mg in 1 tsp of saline as a polyposis nasal wash highly effective but needs to be that concentrated to work well. Mix 0.5mg budesonide in 1 tsp of saline - special syringe to drop into position head down, don't try to use a NeilMed bottle head down. 1 budesonide respule in a sinus rinse bottle is much more dilute - has the benefit of better "washing" of all sinus tissues but doesn't match the potency of the "head down" dropper approach. If goal is removing mucus and local allergen impaction the large volume sinus rinse with dilute budesonide helpful, but the need to step up to the more concentrated 0.5 mg budesonide per nostril. Important point - the head has to be completely upside down for the concentrated budesonide solution when patient delivers it. Another option - use the budesonide nebulizer but only breathe through the nose.

Dr. Borish presented next on CRS and biologics - possible merits of biologics for sinusitis.

Chronic Rhinosinusitis is a heavily eosinophilic driven disease giving a clear rationale for mepolizumab and other anti-IL5 therapies.

Mepolizumab: reduces need for repeat surgery in CRS. Mepolizumab has been shown to reduce the need for repeat sinus surgery for CRS. It’s just very expensive and insurance may not cover it for CRS. Anti-IL5 only worked in about 50% of nasal polyps patients in one study though.

Nutshell: three FDA approved treatment options available: INS, EDS, and steroid-eluting stents.

Dexpramipexole: reduces eosinophils in tissue but does not help clinically, thus eosinophils may not be the only driver in CRS.

Lots of mast cells covered in IgE as well as plasma cells in biopsies from CRS patients. Basophils in CRS: local IgE is produced which may not be against aero allergens.

Omalizumab has been shown to improve polyp scores regardless of the presence of allergy.

IL-13 driven goblet cell metaplasia - block this via IL-4R antagonists. IL-4 is a promising therapeutic target due to its ability to perpetuate Th2 survival, differentiation and IL production.

Dupilumab leads to downstream blocking of IL5 production. Dupilumab in CRS: drop in SNOT22 and improved sense of smell. Early readouts from Dupilumab nasal polyps study shows great efficacy thus far.

Monoclonals are likely game changers in treating CRS...and so many other things!

Dr Borish - probably need to target both mast cells and eosinophils in the treatment of CRS. Future of CRS biologics: MC targeting therapies?

Dr. Davis on endoscopic sinus surgery for CRSwNP: surgery is not a cure for inflammatory respiratory disease. Sinus surgery should not be a bloody surgery.

If you can't tell which CT scan is the pre-op vs the post-op, that's a sign of a poor surgery!

CRS surgery: Open up the nose and let the INS in — not to cure. Speaker: It takes 60cc to flood the sinuses properly with saline.

EMRS: CRSwNP+eosinophilic mucin+ASA sensitivity.

ASA desensitization works in about 60% of patients with CRS with nasal polyps and ASA sensitivity to reduce polyp size and improve nasal symptoms. Maintenance dose is 325 mg BID minimum.

AERD: desensitize first, surgery after that. AERD: re: desensitization, some patients might have problems tolerating one. Surgery and mometasone-eluting devices could be a good alternative for these patients.

Thorough complete endoscopic sinus surgery needs to be followed by Allergist follow-up for aggressive local steroid maintenance therapy.

Risk factors for sinus surgery: smoking, allergies and having a previous sinus surgery.

Dr Ellis: FDA guidance document for industry on sinusitis - rhinitis and sinusitis are separate disease process. What I've always said and why we need AR studies for biologics used in asthma. All of the biologics approved for asthma can have benefit in CRS and NP, the problem is identifying in advance who will be the person that responds - no biomarker has arisen as predictive.

Targets of anti-IL-5 monoclonal therapy: CRS with AND without polyps (with evidence of robust eosinophilia on exam), AERD, and EGPA.

If you are ordering a CT scan for sinuses - order a "CT Max/face" not a "screening sinus CT" - almost the same amount of radiation and its needed by the ENT surgeon for surgical planning.

"No pus, no polyps means no antibiotics" (for Rhinosinusitis).

Dr Davis: retrospective review of culture directed vs non culture directed antibiotic therapy of acute exacerbation shows no difference in QOL.

Indications for endoscopic sinus surgery in CRS: Fungal ball (mycetoma- double density on CT scan), to facilitate topical therapies.

Caution patients about OTC sinus rinses where therapies have unclear ingredients - have been cases where the contents were actually toxic to nasal tissues.

Cryotherapy now being offered in some US ENT clinics for treatment of non-allergic rhinitis with prominent rhinorrhea and post nasal drip.

This is a Twitter summary from #ACAAI18 meeting based on tweets by the following allergists: 
@alexeigonzmd @Ismallergy @DrAnneEllis

Sinusitis - different causes and management (click to enlarge the image).

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