Can Microbes Protect from Asthma? Twitter summary from the 2019 WSAAI meeting

Donata Vercelli spoke on "Can Microbes Protect from Asthma? Studies with Amish & Hutterite Gut Microbiota".

Asthma & allergy are to a large extent environmental diseases that can be treated but not cured.

Erika von Mitius showed a "farm effect" in Alpine Europe, where exposure to cows, hay and unpasteurized milk lead to protection from allergies and asthma. Since then we have been asking and answering why this occurs with relations to genetics, specific farm exposures, and what other components of the farm environments are responsible for protection.

Recent NEJM article addressed two genetic similar populations from a specific region in Europe who settled in different areas of the US - the Amish and Hutterites. Their origins are only 800 km apart in Europe. But while they are very similar in origins (genetics), diet, religion, etc., their farming is very different. Amish non-mechanized single-family farms. Hutterites: large, industrial farming. So for asthma and allergic sensitization Amish are 3-4x lower than Hutterites. While there are differences in cell types (eosinophils, neutrophils, etc) there are no major difference in T regulatory cells.

Asthma protection requires innate immunity. Inflammation appears to generate a neutrophilic response as opposed to eosinophilic responses. This appears to depend on type of exposures and suggests that microbiome plays a strong relationship with risk of childhood asthma.

Gene expression patterns in PBLs of Amish and Hutterite children differ especially in innate immune pathways. Endotoxin much higher in Amish homes, a proxy for microbial load in these homes: https://twitter.com/MatthewBowdish/status/1087398982991503360

Dust collectors suggested inhalation of Amish, but not Hutterite, dust extract is sufficient to block allergen-induced airway hyperreactivity and eosinophilia in mice- important because even this dust was enough to create this phenotype. Found asthma protection in “Amish mice” requires innate immunity, most notably in MyD88-TRif.

Farm effect involved environmental microbiome: https://twitter.com/MatthewBowdish/status/1087401056202452992

This relationship of the risk of asthma and the gut microbiome happens very early: https://twitter.com/MatthewBowdish/status/1087401767636066304

Amish but not Hutterite fecal microbiota are sufficient to suppress allergen-induced AHR and OVA-specific IgE. Profiles of BAL eosinophilia in germ-free mice associated with Amish fecal microbiota showed regulatory eosinophils with regulatory transcription signatures (Prg3) in Amish mice (inflammatory eos in Hutterites).

What is happening between gut and environment? May be "pioneer taxa" are transferred from mother to infant, then the pioneers create a micro-environment for beneficial microbiota to come from the environment (dust) during the 1st year of life.

Dr. Lozupone talked on gut microbiome and how it affects health and inflammation:

Gut microbes affect your health by competitively excluding pathogens, metabolically transforming your diet and drugs, and modulating your immune system. Excellent summary!

Factors that influence microbiome: age, diet, location. Early microbe exposures influence allergy and asthma likely from epigenetic changes. Different approaches using microbiome therapeutics - transplant ecosystem, prebiotics, probiotics.

Dr. Laidlaw mentioned that they have good success with single day protocols.

Commensal micro-derived butyrate induces differentiation of colonic regulatory T Cells, driving the colon away from inflammation.

Age is associated with the most pronounced differences in the gut microbiome.

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.

What have we learned from aspirin desensitization in AERD? Twitter summary from the 2019 WSAAI meeting

Katherine Woessner presented on "What have we learned from aspirin desensitization in AERD: How can the methods be improved."

AERD is chronic eosinophilic (Type 2) inflammation of sinuses +/- the lungs with sensitivity to all COX-1 inhibiting NSAIDS with age of onset in 3rd or 4th decade. No obvious genetic signature that is associated with AERD.

AERD always has chronic sinus disease but not always with asthma, although it usually develops 1-5 years after onset of rhinitis. Asthma is not necessary to make dx of AERD. It needs CRS and NSAID sensitivity.

Known baseline abnormalities in AERD - decreased PGE2 is main one: https://twitter.com/MatthewBowdish/status/1087452002102083585

“All you need to know about AERD” in one slide: https://twitter.com/MatthewBowdish/status/1087452732892491776

Diagnosing AERD is difficult. History can be problematic. Small amounts of aspirin can often be tolerated, sometimes small amounts of alcohol can augment symptoms. Only way to diagnose AERD is with ASA/NSAID challenge.

83% of AERD patients will react to alcohol (nasal congestion, even wheeze). Patients with AERD appear to be sensitive to all alcohol. Mechanism is unclear.

Reactions to oral Aspirin Challenge: https://twitter.com/MatthewBowdish/status/1087454672925876224

Addition of a Leukotriene Receptor Antagonist (LTRA) does not change the outcome of oral aspirin desensitizations.

Treatment of AERD:

1. Avoid COX-1 inhibitor NSAIDs
2. Highly-selective COX-2 inhibitors and Acetaminophen are generally well-tolerated
3. ASA Desens if needed

Q: Who should get ASA Desens?

A: Pts with recurrent chronic sinusitis/polyps, all AERD pts except those well-controlled on ICS, ICS/LABA & LTMDs, those who require antiplatelet therapy w/ASA or other COX-1 inhibitors.

Optimization of ASA Desensitization: FEV1 over 60% (or 1.5 L). https://twitter.com/MatthewBowdish/status/1087458466195595264

Try to increase FEV1 at baseline. If unable, it may be OK to start since patients might have irreversible airway obstruction.

ASA Desensitization Protocol: https://twitter.com/MatthewBowdish/status/1087458962318880768

Safety of ASA Desensitization:

- Scripps have done more than 1400 challenges with only 3 systemic reactions (all responded to 1 Epi)
-Average time to reaction is 102 minutes
-Typical provoking dose is 45-100 mg ASA

Safety of asa desensitization: note expedited protocols don’t seem to be safe. Reactions can be severe. Need another blocking drug before single day desensitizations: https://twitter.com/RayFirszt/status/1087458667589296128

Cross desensitization to other NSAIDS occurs. However, you can only use ASA for desensitization purposes.

Nasal congestion improves immediately during asa desensitization. However, airway irritability remains unchanged.

Aspirin Dosing after ASA Desensitization:

-81mg ok for cardiovascular diz prevention
-325mg ok to be cross-desensitized to any doses of all NSAIDs
-650mg BID initial starting dose for AERD; about 50% can decrease to 325 mg BID after 1-6 months

https://twitter.com/RayFirszt/status/1087459807592939520

Biologics targeting TH2 inflammation seem to be effective in AERD. Biologics like omalizumab and others (anti-IL5, anti-IL4/13) may have a role in AERD but there have not been big enough studies to show that it works or helps in polyps or ASA challenges, some studies are ongoing as we speak.

“In an ideal world, it would be great to have a clinical test to confirm AERD other than desensitization.”

Salicylates are not COX inhibitors and have no effect in AERD. There is some evidence that low salicylate diet might be helpful.

Bits of Wisdom from the front lines of ASA Desensitization: https://twitter.com/MatthewBowdish/status/1087462072860893184

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.



Drug allergy management in 5 steps (click to enlarge the image).

Bacteriotherapy of eczema: host microbe interactions in pathogenesis of atopic dermatitis - Twitter summary from the 2019 WSAAI meeting

Richard Gallo presented on "Host Microbe Interactions in the pathogenesis of atopic dermatitis."

The size of the skin surface area for microbiota interface is 25 square meters when your take into account the hair follicles. Not only the general size of the hair follicle surface area, but there are also nerve fibers and blood vessels in the hair follicle: https://twitter.com/MatthewBowdish/status/1087466779423662082

The immune system exerts pressure for beneficial interactions but driving microbiota towards commensalism and mutualism and away from competition, amensalism and predation/parasitism. Skin produces antimicrobial peptides (AMPs) that are essential for defense of the skin. AMPS in host control of microbial growth: https://twitter.com/MatthewBowdish/status/1087470294636290049

Another way the skin protects is Reactive Adipogenesis, where AMPs produced by fat cells causes expansion of adipose layer in response to local infections with S aureus. Evidently GI surgeons have used this phenom to find areas of colitis for a century. When they open patients up, they look for the area of the bowel wrapped in more fat..

Pathophysiology of Atopic Dermatitis involves deficiency of AMP. Patients with AD have deficiencies in AMP that lead to susceptibility to Staph aureus. S. aureus seems to trigger AD also. They are both interdependent on each other. Moisturizers improve barrier repair which leads to a decrease in IL4, while increasing AMP. Blocking IL4 reduces Staph. aureus colonization and correlates with improved disease.

Atopic dermatitis promotes Staph aureus but does Staph aureus cause Atopic Dermatitis? In a couple of recent studies, it's been shown that S aureus preceded development of atopic dermatitis - JACI 2017 139(1):166 and J Invest Dermatol 2017 137(12):2497.

Topical and systemic antibiotics are not effective in atopic dermatitis. Antibiotics did not kill Staph. aureus. Antibiotics only worked if impetigo was present clinically. Bleach baths don’t seem to be more effective than regular baths. Bacteria do not seem to be changed by adding bleach.

Plausible molecular explanations for causal association between S aureus and atopic dermatitis: https://twitter.com/MatthewBowdish/status/1087473587575873536

How can we treat atopic dermatitis related to Staph. aureus without use of antibiotics which seem to be ineffective?

Applying topical bacteriotherapy in a small trial completely eliminated Staph. aureus - this is an exciting application of skin microbiome. There were no adverse events from topical application of microbiome therapy. Effective anti Staph. aureus agent. Microbiome transcriptome diversity improved with the application. Skin inflammation improved only after 1 week of application.

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.



Atopic dermatitis maintenance (click to enlarge the image).

Immunotherapy Basics - COLA Video Lectures by Jay Portnoy, MD (held in 2012)

Immunotherapy Basics - COLA Video Lectures by Jay Portnoy, MD:

Dr. Jay Portnoy reviews the basics of allergen immunotherapy (allergy shots) starting with its history and the extracts used to administer it. Held on August 13, 2012:



Dr. Jay Portnoy describes the process for writing a prescription for allergen immunotherapy (allergy shots). Held on August 13, 2012:

HAE with normal C1 inhibitor (HAE-nl-C1INH) - Twitter summary from the 2019 WSAAI meeting

Dr Zuraw talked about HAE with normal C1 inhibitor.

Women are more commonly affected by HAE with normal C1 than men. HAE with normal C1 can skip generations unlike normal HAE, mainly because it has low penetrance.

UCSD only has two families with Factor XII in their registry, showing just how rare that is. Impact of Factor XII on HAE-nl-C1INH: https://twitter.com/MatthewBowdish/status/1087834677287706625

HAE classification is getting more complicated - 4 types of HAE-nl-C1INH, and counting: https://twitter.com/MatthewBowdish/status/1087837543536578562

Current classification of Angioedema: https://twitter.com/MatthewBowdish/status/1087838090775777280

You cannot separate HAW-nl-C1INH from non-histaminergic bradykinin angioedema except by family history +/- genes.

Clinical findings that help distinguish between HAE and HAE-nl-C1INH: https://twitter.com/MatthewBowdish/status/1087839803570188288

Differentiating HAE normal and deficient C1 inh - note facial swelling: https://twitter.com/RayFirszt/status/1087846754320449537

Current treatment approach for HAE-nl-c1INH: https://twitter.com/MatthewBowdish/status/1087842869988052993

Treatment for HAE n C1inh: progestin and TXA are effective. C1inh can help during active attacks in HAE n C1inh because of deficiency that occurs during angioedema. C1inh cannot be used for prophylaxis. Lanadelumab is a monoclonal Ab against kallikrein. It should work in HAE w normal C1inh.

Phase 2 trial: Factor XIIa monoclonal ab - CSL312. It should work since kallikrein activation goes through factor XII.

Biomarker development for angioedema: measuring kallikrein activity can distinguish between histaminergic and non histaminergic angioedema. 93% PPV and 86% NPV. Patient can’t be on treatment for 1 week prior to test.

Biomarkers for HAE using kallikrein activity: https://twitter.com/RayFirszt/status/1087846989918699520

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.



Different causes of bradykinin-related angioedema. Click here to enlarge the image.

What’s new in food allergy? Twitter summary from the 2019 WSAAI meeting

Dr. Sicherer discussed important papers from the JACI-In Practice on food allergies and anaphylaxis. March 2019 issue will be food allergy centric.

Food allergy themed issue 2018: https://twitter.com/MatthewBowdish/status/1087887030216884225

Wasserman et al on Real World Experience with Peanut OIT: https://twitter.com/MatthewBowdish/status/1087887615972409344

Goals of families doing OIT - 62% wanted to reduce risk of fatal reaction, most thought the risk of death was 1:1,000 to 1:10,000, when data actually suggests risk is 1 in 325,000 over 10 years. An increased threshold from 100 mg to 300 mg peanut in OIT reduces the risk of a reaction by 95%.

Survey for undergoing OIT - motivations include reduce risk of fatal reaction, reduce hassle of avoidance, decrease risks of reaction. This was greater than desire to incorporate foods into diet. QOL: improved after completion of OIT. Low dose OFC to 1.5 mg of peanut likely would allow patients to not worry about precautionary labeling.

Avoidance of peanut precautionary labeling carries individual burdens and costs ($182M per death prevented) - Shaker and Greenhawt.

Baked Potpourri: https://twitter.com/MatthewBowdish/status/1087890228646297600

Baked milk challenges: passing occurs in pts who are younger, with lower IgE. About 70% pass. SPT was not reflective of outcome. If sIGE to milk is less than 8, patients are more likely to pass. They can have serious reactions, more respiratory reactions. Egg allergy leads to more GI reactions.

Dupixent may lead to passing OFCs to foods that were previously not tolerated. Dupilumab and Food Allergy: https://twitter.com/MatthewBowdish/status/1087890535186980864

Any food allergy is a risk factor for asthma with a relative risk of 1.7 to 2.9 depending on specifics.

If you get anaphylactic reactions after VIT, rule out a mast cell disorder, including full workup, beyond just tryptase. Need for lifelong treatment of VIT. Study of 19 patients with severe sting reaction post stopping Venom IT, 18 had clonal mast cell disease, 8 had normal tryptase. Contrary to popular belief, you can get an increase in tryptase during food anaphylaxis, but it's usually 25% rise from baseline rather than over the cut-off of 11ng/ml.

Tryptase and food anaphylaxis: tryptase rose above baseline in 60% of pts. Median rise of 25%. Rise related to severity. Peak is at 2 hrs.

Beta blockers do not seem to block Epi effects in anaphylaxis.

EIA: omega 5 gliadin IgE testing can be helpful in diagnosis. It’s the best predictor of reactivity. You can do an exercise challenges with the suspecting food. You can also do a higher dose food challenge at rest. Cofactors can be exercise and alcohol. sIgE to wheat can be negative.

EoE is prevalent in milk allergic patients. 40% had EoE. 30% were asymptomatic. Risk of EoE in Cow's Milk Allergy: https://twitter.com/MatthewBowdish/status/1087895197705416704

EoE: lots of comorbidities: allergies, immune disorders. EoE Potpourri: https://twitter.com/MatthewBowdish/status/1087895731279560704

EoE: it is rare to outgrow food sensitivity triggering EoE. It occurred only in 9/1,812 patients. EoE was linked to OAS and it improved after removing raw birch-related foods, some patients developed IgE allergies after avoiding foods for EoE. It’s complicated!

Antihistamine allergies: case report to Benadryl, rare event!! But possible. Two papers of allergy/anaphylaxis to antihistamines. It's a rare but it can occur.

There are no detectable food proteins in any common childhood vaccines.

Fructose induced anaphylaxis reported after drinking Coca Cola. Super rare.

FPIES to peanut - there are growing cases with the early introduction following the LEAP study.

There are reported cases of delayed anaphylaxis to shellfish.

Sometimes you need to duplicate SPT, since there can be significant variability, especially when making clinically important decisions.

Milk allergic patients: if they’re severe, 10% can also be allergic to beef and lamb. Especially with undercooked beef. You can do OFCs with well cooked beef. They likely should avoid undercooked meat.

Studies suggest that 26-41% of those with cold-induced urticaria experience systemic reactions, consider epinephrine auto-injector.

---

Mastering Food Allergy Diagnosis

Scott Sicherer presented on "Mastering Food Allergy Diagnosis".

Recommended Food Allergy Testing: history, physical exam, skin prick test, allergen specific serum IgE, elimination diet, oral food challenge. Have to get a good history before ordering tests, don't test foods that are clearly tolerated.

Not recommended food allergy testing: atopy patch test, intradermal test, "combination of tests," unproven tests (IgG, kinesiology, VEGA, etc).

IgE levels in isolation are difficult to interpret. For example, wheat sIGE tends to run high, even sometimes higher than 100, in patients that tolerate wheat, while cashew sIgE tends to run low and you might be worried about low positive levels. 5% of patients with peanut allergies cross react to legumes. Cow milk allergy cross reacts with goat milk in 92%.

What are the challenges to food allergy diagnosis: chronic symptoms, multiple possible triggers, definite outcomes needed, masqueraders (eg Frey's Syndrome), imperfect tests. Dr Sicherer presented a case of Blepharochalasis masquerading as food allergy.

Frey's Syndrome is a rare neurological disorder (fewer than 20,000 cases in US) that may result from injury or surgery near the parotid glands (which manufacture saliva), damaging the facial nerve. Sx: Sweating and flushing of a patch of skin near the ear that occurs when someone is eating.

Different pathophysiologies for different adverse food reactions: https://twitter.com/MatthewBowdish/status/1087427684332761088’

Epidemiology - Child with peanut allergy who has not eaten tree nuts has a 35% risk of tree nut allergy.

Epidemiology - Sibling of child with peanut allergy who has not eaten peanut has 7% risk of peanut allergy.

Child who has atopic derm has 35% risk of having a food involved if eczema is moderate to severe.

10% of patients with milk allergy are also allergic to beef, especially if undercooked.

Sesame seeds don’t have a lot of protein. Sesame allergic patients can tolerate sesame seeds and still be allergic to sesame, so be careful.

Predictive values but must be taken with grain of salt (at arrow): https://twitter.com/MatthewBowdish/status/1087429515935080449

Component testing with risk: https://twitter.com/MatthewBowdish/status/1087431062660177920

Asamoj JACI 2012 130(2):469-72. Shows isolated Ara h8 patients - 144 Swedish pts, 143 passed OFC, 10% had oral symptoms even to cooked peanut but no systemic rxn.

Those with egg IgE less than 2kU/l likely to do well with baked egg challenge. Those with egg sIgE higher than 10kU/L not likely to do well with baked egg challenge. Those with milk IgE less than 5kU/l likely to do well with baked milk challenge. Those with milk sIgE higher than 35 kU/L not likely to do well with baked milk challenge.

Future food allergy diagnostics and prognostics: Basophil activation, ratios (specific IgE to total IgE), epitopes, more components, calculators, DNA methylation patterns.

Food specific IgE to Total IgE: https://twitter.com/MatthewBowdish/status/1087436815206821888

http://cofargroup.org has a predictive calculator for outgrowing egg and milk allergy.

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.



Adverse Food Reactions (click to enlarge the image).

What’s New in Asthma and Drug Allergy? Twitter summary from the 2019 WSAAI meeting

Michael Schatz discussed Asthma and Drug Allergy in this year's JACI-In Practice.

92% of patients with difficult to control asthma had at least one medical comorbidity. What were those comorbidities? Obesity, anxiety/depression, GERD, cardiovascular disease. Asthma: 90% of pts with severe asthma have at least one comorbidity, 70% have more than 2. Many co-morbidities are bi-directional, ie if you treat one, you get improvement in the other and vice versa.

Non pharma management of asthma: exercise - high intensity, diet - high protein/low glycemic diet - you need both to improve asthma control.

Step down RX for asthma who are well controlled for 3 months: stopping LABA was associated with greater decline in lung function and more hospitalizations, maybe we need longer than 3 months of control.

Pts who cough and failed ICS/LABA combo inhaler improved with Spiriva. Likely through modulating cough reflex sensitivity, despite no difference in FEV1.

Only 22% of large group of health care providers used asthma inhalers correctly (JACI-IP 2018;6:987). Most common specific errors of healthcare professionals with not using their inhalers correctly: https://twitter.com/MatthewBowdish/status/1087905408486825984

Check our JACI-IP 2018;6:1246 for interesting article on skin testing for suspected iodinated contrast media hypersensitivity.

For contrast reactions: consider SPT :prick undiluted, ID 1:10 dilution - not irritating. Pretreatment for contrast reactions does not appear to be helpful. Approach to RCM reactions: https://twitter.com/RayFirszt/status/1087908037426204674

Controversies in beta-lactam allergy covered in JACI-IP:

1. Role of skin testing vs direct challenge
2. Length of challenge (single dose vs multiple day)
3. Cephalosporin cross-reactivity with PCN and other cephalosporins

Optimal length of penicillin challenge is unclear. 5 days seems reasonable to rule out delayed non severe reactions.

Current Kaiser San Diego approach: https://twitter.com/MatthewBowdish/status/1087910300773273600

Cross-Reactions between PCN and Cephalosporins mainly related to side-chain similarity JACI-IP 2018;6:1662 - Avoid aminocephalosporins in PCN allergic pts?
https://twitter.com/MatthewBowdish/status/1087912076121501696

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.



Drug allergy management in 5 steps (click to enlarge the image).

Chronic Sinusitis - Twitter summary from the 2019 WSAAI meeting

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

https://twitter.com/MatthewBowdish/status/1087423162671722497

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:

-re-circulation
-lateralized middle turbinate
-retained uncinate
-undissected cells
-mucosal stripping w/neo-osteogenesis
-scarring/stenosis

Disease recurrence after CRS surgery is due to polyps and biofilms.

Biologic causes of FESS failure:

-polyps/edema
-allergic mucin
-persistent infection
-biofilms
-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).

Asthma and Allergic Diseases During Pregnancy - Twitter summary from the 2019 WSAAI meeting

Michael Schatz presented on "Asthma and Allergic Diseases During Pregnancy”.

Asthma increases risk of a number of adverse outcomes in pregnancy including preeclampsia, preterm birth, low birth weight, SGA, neonatal death, and malformations.

Potential mechs for adv outcomes in pregnant women with asthma include common pathogenesis (factors affect both asthma & reproductive fxn), confounding (smoking, race, obesity & depression), poor asthma control (hypoxia, reduced uteroplacental blood flow) & asthma meds.

SABAs - There is substantial reassuring data from large prospective and prospective trials. There are some reports of increased specific malformations w/SABAs in case-control studies, but potential confounding by asthma control/exacerbations. Benefits from SABAs outweigh possible risks.

Substantial safety data for low and medium dose ICS, but possible association with high dose ICS from retrospective database studies may be confounding by severity. ICS in pregnancy: budesonide is most studied. But there was no difference between budesonide and fluticasone, both appeared safe.

LABAs - less data than for ICS or SABA but reassuring data from retrospective cohort studies for both salmeterol and formoterol.

OCS - cohort studies have reported assoc between OCS and preeclampsia, preterm delivery, preterm birth and low birth wt, but potential confounding by severity/control/exacerbations. Conflicting data regarding association of OCS with cleft lip/palate.

Biologics:
Omalizumab: no inc risk of major congenital malforms
Mepolizumab: no evidence of fetal harm in monkeys w/30x max human dose, no human data
Reslizumab: no adv effect in animals with HDs, no human data
Benralizumab: no adv effect in animals, no human data
Dupilumab: no adv events in high doses, no human studies

Asthma Mgt Conclusions: step therapy, budesonide or fluticasone for women starting ICS in pregnancy, LABA salmeterol vs formoterol based on non-preg considerations, montelukast an alt for mild persistent asthma or add-on, tiotropium for uncontrolled on ICS/LABA.

Treatment of asthma is similar to usual treatment when pregnant. Use fluticasone or budesonide. You can still use montelukast (Singulair). Spiriva can be considered. Xolair appears OK. Regarding other biologics: continue to use them if already on them and responding.

FeNO is a good marker of asthma control in pregnancy.

MotherToBaby is a service of the non-profit Organization of Teratology Information Specialists (OTIS), a source of information on the safety of medications and other exposures during pregnancy and while breastfeeding. Patients can self register if on medications during pregnancy: https://mothertobaby.org/about-us/

Barriers to asthma control in pregnancy: smoking, clinician under-treatment, adherence, viral infections and obesity.

Allergic rhinitis

There is no data showing a direct effect of rhinitis on perinatal outcomes although snoring is associated with an increase risk of preeclampsia. Rhinitis Management Conclusions: https://twitter.com/MatthewBowdish/status/1088565184359063553

Avoid decongestants in pregnancy - no great data and some safety concerns. Pseudoephedrine would be one of choice. OK to use fluticasone, mometasone and budesonide intranasal steroids.

SPT in pregnancy can be considered. Perform in vitro sIgE, if possible, instead of SPT.

IT during pregnancy - continue if doing well, consider dose reduction.

SCIT/ Immunotherapy - Generally, do not start IT given uncertain propensity for systemic rxns, increased likelihood of systemic rxns during IT build-up, latency of effect, uncertainty of benefit. Continue immunotherapy if patient already receiving IT, pt deriving benefit, has not been prone to systemic rxns, at maintenance or effective dose and consider prophylactic dose reduction.

Epinephrine is associated with birth defects in some studies but some confounders, has the potential to reduce uteroplacental blood flow, still the drug of choice for anaphylaxis and obs suggest benefits outweigh risks. Other aspects of anaphylaxis treatment during pregnancy: https://twitter.com/MatthewBowdish/status/1088571118753968128

CU management in pregnancy: https://twitter.com/RayFirszt/status/1088566319639711744

HAE during pregnancy - use plasma derived C1inh.

Atopic dermatitis (AD) in pregnancy - topical steroids (TCS) at mild moderate potency appear safe. Some fetal growth restrictions at very high dose. There are no human data on topical calcineurin inhibitors (TCI).

Treatment of AD in pregnancy: https://twitter.com/RayFirszt/status/1088567237231792128
https://twitter.com/RayFirszt/status/1088567372166754306

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.



Asthma Treatment Options (click to enlarge the image).

How to maintain your inside garden: Microbiome, Diet, and Inflammatory Disease - Twitter summary from the 2019 WSAAI meeting

Catherine Lozupone presented on "Intersection of Microbiome, Diet, and Inflammatory Disease."

Short term dietary intervention effects on microbiome: https://twitter.com/MatthewBowdish/status/1088589292249595904

Diet shapes the microbiome: https://twitter.com/MatthewBowdish/status/1088593887361359872

You may want to match the microbiome with the type of diet you have. If you like hamburgers and fries, then you might get bacteroides rich microbiome. If you have a healthier diet, then you might get prevotella rich microbiome. Healthy gut microbiome depends on context.

Short chain fatty acids (SCFAs) are produced metabolically from microbiome on high fiber diet (plants). They work to suppress the TH2 system (allergy), and are anti-inflammatory. Only soluble fiber can be converted to SCFAs.

Fecal transplants have been successful at treating C. difficile infection. Diet appears to be related to one's risk of developing C. difficile infection. Therefore, can diet prevent C. difficile infection? Low fat diet is more protective against C. difficile infection. It works through producing less primary bile acids which is needed for C. difficile growth. Soluble fiber producing SCFAs also appears to also work at preventing C. difficile. Western diets leads to less secondary bile acids which help reduce C. difficile. This gets exaggerated when you kill off the normal microbiome when using antibiotics: https://twitter.com/RayFirszt/status/1088599023961796609

Apparently, there are companies that will sequence your gut microbiome for about 100 dollars.

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.