Chronic Sinusitis - 2018 WSAAI update

This is a Twitter summary from the 2018 WSAAI meeting. This summary was compiled from the tweets posted by @MatthewBowdish, an allergist/immunologist, who attended the 2018 Western Society of Allergy, Asthma and Immunology (WSAAI) meeting. The tweets were labeled #WSAAI. The text was edited and modified by me.

Rohit Katial on "Chronic Sinusitis: From Nasal Polyps to Biologics.”

There are different phenotypes and endotypes of chronic rhinosinusitis. Chronic rhinosinusitis with and without nasal polyps: https://twitter.com/MatthewBowdish/status/956681812411015168

Different types of defense and inflammation in sinus disease: https://twitter.com/MatthewBowdish/status/956685820609507328

Whether it's sinus disease, asthma or skin, the main issue is what is happening with inflammation which it occurs on the epithelium, with everything else we're dealing with, IgE, IL5, etc., happening downstream: https://twitter.com/MatthewBowdish/status/956687898060845056

Back to the major phenotypes of rhinosinusitis: https://twitter.com/MatthewBowdish/status/956688557485125634

Primary Immunodeficiencies: non-infectious complications - 2018 WSAAI update

This is a Twitter summary from the 2018 WSAAI meeting. This summary was compiled from the tweets posted by @MatthewBowdish, an allergist/immunologist, who attended the 2018 Western Society of Allergy, Asthma and Immunology (WSAAI) meeting. The tweets were labeled #WSAAI. The text was edited and modified by me.

Thomas Fleisher on "Primary Immunodeficiencies: more than just recurrent infections".

There are 2 groups of CVID patients:

1. Infections without complications (1/3): nml life expectancy, effective IgG replacement = good QoL

2. Infections plus other complications (2/3): autoimmunity (30%), GI (15%), granulomatous disease (10%), lymphoma (8%), splenomegaly (30-40%), lymphadenopathy (15%).

Autoimmunity in CVID: https://twitter.com/MatthewBowdish/status/956665155894484992

Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD): 10% CVID; median diagnoses age is in the 4th decade; granulomas can also involve LNs, liver, GI; imaging shows "halo sign" with parenchymal disease more in lower lung, +bronchiectasis; PFT shows restrictive lung disease.

Treatment of GLILD involves immunosuppression, eg rituximab and azathioprine.

Poorer outcomes in CVID associated with presence of non-infectious complications, early age of onset and biomarkers that negatively affect outcome (high IgM and lower IgG at dx, low B cells).

Monitoring CVID patients: https://twitter.com/MatthewBowdish/status/956667548577103872

CVID and CVID-like disorders with defined genetic causes often are associated with findings on immune dysregulation.

CVID plus complications have a poor outcome: https://twitter.com/MatthewBowdish/status/956668257586442240

Do we consider other, more aggressive treatments like bone marrow transplants for these patients?

Newer biomarkers in CVID:

1 - switched (IgD-) memory (CD27+) B cells showed increase risk of granulomas and splenomegaly.

2 - low B cells in US study of CVID patients associated with risk of autoimmunity and lymphoma.

Dr. Charlotte Cunningham Rundles has seen 43 lymphomas in her cohort of 650 CVID patients - Her take home is TAKE NEW COMPLAINTS/CHANGES SERIOUSLY.

CVID-like diseases

Heterozygous (AD) CTLA-4 Mutations are CVID-like: https://twitter.com/MatthewBowdish/status/956670292369158144

CTLA-4 mutations lead to immune dysregulation through Treg dysfunction. Treatment for CTLA-4 haploinsufficiency treated with rapamycin, targeted therapy with a CTLA4 agonist (CTLA4-Ig/Abatacept) and possibly hematopoietic stem cell transplantation.

Other CVID-like diseases include LRBA mutations, gain of function mutations affecting p110delta subunit of phosphatidylinositol-3-OH kinase (PIK3CD), and AR mutations in PIK3R1.

Currently, around 30% of CVID-like patients are now found to have either a monogenic cause (eg CTLA4, PIK3CD) or monogeneic susceptibility (eg TACI).

Thomas Fleisher also reviewed Omenn Syndrome, RAG deficiency, IPEX, IL10/IL10 Receptor Defects, and APECED.

Diagnostic Evaluation of low IgG:

- Serum IgG between 450 mg/dl and 600 mg/dl. Repeat serum immune globulins for verification. Test antibodies to tetanus and diphtheria and also other protein based vaccines (measles mumps rubella, H zoster) also non conjugated pneumococcal vaccine and test 4 weeks post vaccination.

- Serum IgG between 250 and 450 mg/dl. Repeat serum immune globulins for verification. Test antibodies to tetanus and diphtheria or other protein based vaccines; also non conjugated pneumococcal vaccine and test 4 weeks post vaccination.

- Serum IgG between 150 and 250 mg/dlL. Repeat serum immune globulins for verification; Consider testing antibodies to tetanus and diphtheria or other protein based vaccines; optional, non conjugated pneumococcal vaccine and test 4 weeks post vaccination.
- Serum IgG under 150 mg/dl. Repeat serum immune globulins for verification; no antibody testing required.

References: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904582/

Monitoring of patients with CVID:

- All patients with CVID: Every 12 months Interval history, physical examination, height and weight. Complete blood counts: Hgb, Hct, white blood cells and differential, platelets, and chemistry panel including liver and kidney functions; albumin. Spirometry. Every 6 to 12 months or with weight gain: Serum IgG, consider adding IgA and IgM. Consider chest X-ray at the time of diagnosis.

- CVID patients with lung disease: High Resolution Chest CT every 3 – 4 years or after change of therapy. Complete lung functions with CO diffusion every 12 months.

- CVID patients with with gastrointestinal complications: Upper and/or lower Endoscopy based on GI recommendations.

- CVID patients with evidence of malabsorption including loss of height; women in particular: Bone density, evaluation of nutrients based on history.

References: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904582/

COPD, ACO and the Chronic Airflow Obstruction Phenotype - 2018 WSAAI update

This is a Twitter summary from the 2018 WSAAI meeting. This summary was compiled from the tweets posted by @MatthewBowdish, an allergist/immunologist, who attended the 2018 Western Society of Allergy, Asthma and Immunology (WSAAI) meeting. The tweets were labeled #WSAAI. The text was edited and modified by me.

Mario Castro on "new Directions in COPD, ACO and the Chronic Airflow Obstruction Phenotype".

70% of patients with COPD are younger than 65 yo. COPD is now the 3rd leading cause of death in the US. COPD is now the second leading cause of disability in US. Leading cause of COPD in US is smoking, in the world it's exposure to the burning of biomass.

Cycle of Decline in COPD: https://twitter.com/MatthewBowdish/status/956288378223276032

Lung volumes can be altered in COPD patients both at rest and during exercise. Pulmonary rehab is essential for overcoming alteration of lung volumes in COPD.

Dynamic hyperinflation links dyspnea and activity limitation in COPD: https://twitter.com/MatthewBowdish/status/956289244581933056

GOLD 2018 Algorithm: https://twitter.com/MatthewBowdish/status/956290104800129029

Initial pharmacological management of COPD recommended by GOLD 2018: based on wich group the patient is in: A, B,C, or D: https://twitter.com/MatthewBowdish/status/956291265078808576

Simvastatin and leukotriene inhibitors are not effective in COPD and Dr Castro stops these medications in his COPD patients.

UPLIFT Trial: using long-term LAMA tiotropium showed improved FEV1 vs. control but has no impact on rate of decline in pre/post-bronchodilator FEV1.

Non-pharmacological management of COPD: smoking cessation, patient education, vaccination (PCV13 & 23), pulmonary rehab, oxygen therapy, and surgical as well as non-surgical alternatives.

Asthma-COPD Overlap (ACO)

COPD-Asthma Overlap - 25% of patients with COPD report a history of asthma. Asthma and COPD have common origins ("Dutch hypothesis").

Patients with features of both asthma and COPD have worse outcomes than those with asthma or COPD alone in terms of freq exacerbations, poor QoL, more rapid dec in lung fxn, higher mortality and great health care utilization.

Major criteria in Asthma-COPD Overlap (ACO): previous h/o asthma before 40yo, bronchodilator response to salbutamol greater than 15% and 400mL, and sputum eosinophilia.

Minor criteria in ACO: IgE greater than 100 IU or history of atopy, 2 separated bronchodilator responses to salbutamol greater than 12% and 200 mL, and blood eosinophils >5%.

Asthma-COPD overlap (ACO) is not a single disease entity.

Potential phenotype-targeted therapies in severe asthma: https://twitter.com/MatthewBowdish/status/956298377557245953

Dr Castro will utilize COPD Action Plans on some of their patients, especially those who have been admitted for COPD exacerbations.

Insect Venom Allergy - 2018 WSAAI update

This is a Twitter summary from the 2018 WSAAI meeting. This summary was compiled from the tweets posted by @MatthewBowdish, an allergist/immunologist, who attended the 2018 Western Society of Allergy, Asthma and Immunology (WSAAI) meeting. The tweets were labeled #WSAAI. The text was edited and modified by me.

Cem Akin on "Venom Hypersensitivity".

56-94% of US population reported at least one insect sting; prevalence of large local rxns 2-26%; prevalence of systemic rxns 0.2-0.8% of kids and 0.5-3% of adults.

Risk factors for systemic reactions to insect stings: age older than 45, male, concurrent cardiovascular disease, beta-blocker & ACEI use, atopic background, previous systemic rxn, multiple stings, recent sting, serum tryptase higher than 5ng/mL.

Insect stings are the 3rd most common cause of anaphylaxis
in US emergency departments; 10% of all pts presenting w/anaphylaxis, 20% of all fatal anaphylaxis in US, equals ~40 deaths per year in the US (may be under-reported).

Hymenoptera Taxonomy: https://twitter.com/MatthewBowdish/status/956244710389006336

Honeybees: herbivorous, hairy bodies, non-aggressive, evisceration upon stinging, usually accidental sting, nests are above ground and in trees.

Yellow jackets are carnivorous, scavengers, highly aggressive, stings more frequently in autumn, nests are in the ground and in cracks in buildings.

Yellow hornets (aka aerial yellow jacket, so similar behavior) are aggressive esp with vibration, nests are in trees and shrubs.

White-face hornet have black and white color, three white stripes at end of body, omnivorous, aggressive and can squirt venom from stinger into the eyes of nest intruders causing temporary blindness.

Paper wasps have nests in open combs located in eaves of the house, not as aggressive, feed on other insects and have dangling legs.

Fire ants bite to get hold, sting from abdomen, will sting repeatedly nearby and live in colonies nested in the soil that can be 1-2 ft in diameter.

Hymenoptera stinging insects: https://twitter.com/MatthewBowdish/status/956247166497902592

Fire ants are distributed in the southern sections of the US and leave sterile pustules that are clustered, develop 24 hours after sting and are due to alkaline pH - image from Akin: https://twitter.com/MatthewBowdish/status/956247782704136192

Honeybee allergens: https://twitter.com/MatthewBowdish/status/956248099109744640

Honey bee venom: major allergens (phospholipase A2 - Api m1); each sting ~50mcg of venom, small subset of patients monosensitized to minor antigens and may not respond to venom IT as well and have a higher relapse rate after d/c IT.

Vespid allergens: https://twitter.com/MatthewBowdish/status/956248892948987904

Antigen 5 is major vespid allergenic protein; there is extensive cross-reactivity within subfamily Vespinae (yellow jackets & hornets), but not much with Polistinae (wasps).

Venom skin testing recommended 3-6 weeks after systemic event: https://twitter.com/MatthewBowdish/status/956249893684719616

Skin testing is preferred, but now people often use blood test first plus serum tryptase, and then skin test to negative venoms from blood work.

You definitely want to consider basal serum tryptase in patients with anaphylaxis, especially with severe or hypotensive reactions and negative test results, to look for systemic mastocytosis.

Small subset of patient with convincing history are negative to both blood and skin testing (~1%). So, you can repeat testing 3-6 months later.

Fire ant skin testing is done with whole-body extract.

Avoidance counseling: https://twitter.com/MatthewBowdish/status/956251514305048576

Large local reactions

Large local reaction peaks in size 24-48 hours, defined as more than 10cm diameter swelling, resolves over 3-10 days, treated with cold compresses, NSAIDs, oral antihistamines, oral pred 2-5 days, epipen?

5-10% of patients with large local reactions will progress to systemic symptoms on subsequent sting.

Venom IT may reduce large local reactions. May be useful in pts with high frequency of stings, extremely large locals, personal h/o CV disease and/or to alleviate patient’s anxiety.

Risk of systemic reactions: https://twitter.com/MatthewBowdish/status/956252692099227649

Also, those above age 16 with cutaneous reactions are unlikely to go on to systemic reactions and venom IT not necessarily indicated (based on each patient's individual risks, however).

In systemic reactions, venom IT is indicated for reduction of future risk of anaphyalxis: https://twitter.com/MatthewBowdish/status/956253452329353217

Summary of Venom IT indications: https://twitter.com/MatthewBowdish/status/956253698291716096

2017 Parameter Update: "...in patients receiving IT, there is limited and conflicting evidence that these medications increase the risk of anaphylaxis."

H1 blockers reduce large local reactions and mild systemic rxns but not anaphylaxis; montelukast may improve large local reactions.

Risk of systemic reactions to venom IT:

-traditional protocol - less than 5%
-rush protocols 5-10%
- ultrarush protocol 0-28% (median 11%)

Duration of Venom IT: https://twitter.com/MatthewBowdish/status/956255163626373120

Relapse rate after discontinuing VIT greater with: very severe rxn on previous stings, elevated basal serum tryptase, systemic rxn during VIT (injection or sting), less than 5 yrs maintenance VIT, honeybee anaphylaxis, frequent exposure.

Venom IT in systemic mastocytosis patients: https://twitter.com/MatthewBowdish/status/956256240010641408

Image source: Bee, Wikipedia, GNU Free Documentation License.

Rhinovirus-Induced Asthma Exacerbations - 2018 WSAAI update

This is a Twitter summary from the 2018 WSAAI meeting. This summary was compiled from the tweets posted by @MatthewBowdish, an allergist/immunologist, who attended the 2018 Western Society of Allergy, Asthma and Immunology (WSAAI) meeting. The tweets were labeled #WSAAI. The text was edited and modified by me.

Larry Borish on "Rhinovirus-Induced Asthma Exacerbations: How it happens and implications for treatment."

September and May Epidemics of Asthma Exacerbations in Kids in North America - 80% are due to rhinovirus: https://twitter.com/MatthewBowdish/status/956232214806609921

Rhinovirus is truly the perfect pathogen because it doesn't ever kill its host and it doesn't make you so sick that you have to stay home, allowing for easier spread.

Rhinovirus occurs year-round: https://twitter.com/MatthewBowdish/status/956233009757282305

But it's not just the rhinovirus leading to exacerbations, it's the rhinovirus infection occurring during the allergy seasons (Fall: ragweed/Alternaria; Spring: grass pollen)).

Most asthma exacerbation in children and adolescents occur in association with rhinovirus infection. This trend reflects concomitant presence of allergic sensitization to aeroallergens expressed at the time of infection.

Two schools of thoughts on why rhinovirus associated with asthma exacerbations: https://twitter.com/MatthewBowdish/status/956235171988213760

Humoral mechanisms of RV-induced upper respiratory rhinitis during lower respiratory asthma exacerbations: https://twitter.com/MatthewBowdish/status/956236188389552128

In studies using rhinovirus challenges, symptoms are worse in allergic asthmatics and last longer despite receiving similar viral loads.

Dr Borish points out that when he does studies using nasal epithelial cells, he grows them up in culture and then studies are done on the great(x5)-grandchildren cells. How do those cells remember they are asthmatic epithelial cells and make IL25, IL33 and TSLP?

Conclusions: https://twitter.com/MatthewBowdish/status/956240801238953985

Image source: Molecular surface of a rhinovirus, Wikipedia, GNU Free Documentation License.