Treatment with protease inhibitors (alfa-1-antitrypsin) may be useful in EoE .
SPINK7 (a serine protease inhibitor) was decreased in biopsies from EoE patients. Reduction of SPINK7 led to epithelial cell disruption and increased inflammatory cytokine production. Serine protease inhibitors MAY be a treatment for EoE.
TH2A cells were identified in atopic individuals and reduce with immunotherapy. TH2A cells could be used as atopic disease biomarkers and a possible therapeutic target. TH2A cells: the future of atopic markers including CRTH2, CD161, and CD49d, with low expression of CD45RB and CD27. TH2A cells are CD4+, CD45RB low,, CD49d+, CRTH2+, CD27-, CD161+. They can produce IL-4, 5, 9, 13.
Pulmonary neuroendocrine cells (PNECs) are potential important cells for target in asthma thought down regulation of ILC2’s cells . PNEC (Pulmonary Neuroendocrine Cells) are lung cells which are increased in patients with asthma. PNEC enhance Il-2 activity and Goblet cell metaplasia through GABA. Could PNEC be a good target for asthma treatment in the future?
IL-33 leads to release of ILC2 precursors from the bone marrow. Alternaria (direct stimulation) and Aspergillosis (though IL-33 gene cleavage) may increase ILC2’s though estimation of IL-33.
Dr. Routes MD with an update on Clinical Immunology: NFKB1: read a review in Cell 168:37-57,2017
It appears NFKb mutation is the single most common monogenic cause of CVID.
NFKB1: 16 pathogenic mutations, rare and limited to CVID, autosomal dominant with 60% penetrant ; decrease memory switched B cells; increase CD21 low B cells. Decreased switched memory B cells are key in PID and autoinflammatory disorders regardless of IgG level. Many of the links are via NFKb.
Decreased NFKB1 phenotypes (AD, 60% penetrant): aphthous ulcers, Behcet-like and hypog (H67R); inflammatory GI tract disease and hypogam (I553M); NO hypogam, decreased switched B cells, necrotizing cellulitis (R157X).
APDS1: sinopulmonary infections, LAN/splenomegaly, bronchiectasis/bronchitis/tracheal nodules, EBV/CMV, HSV, VZV infections; High IgM, IgM+ but not IgG+ B cells in tissue.
CGD carriers can get disease like CGD lite, especially if DHR positivity is below 20%. CGD carrier: nearly 50% had infections and inflammatory disease; DHR test between 20-80%, if less than 20% start prophylaxis with TMP/SMX. X-CGD carriers have increased risk of infections and/or autoimmune manifestations (AIM). Discoid lupus is a common AIM. Patients with abnormal DHR assay (below 20%) could be considered for TMP/sulfa prophylaxis.
Screen & treat mothers, sisters of Chronic Granulomatous Disease patients as carriers at high risk of autoimmune & infection.
BMT can improve survival in scleroderma.
Dr. Li on asthma and lower respiratory diseases. Dupilumab was more effective for asthma if eosinophils were greater than 300. Eosinophilia can occur in 4.1% and hypereosinophilia 1.2% on dupilumab for asthma. Increased FeNO predicted better response to dupilumab.
Dupilumab recently approved for moderate-severe asthma: if eosinophils are higher than 300 or FeNO is elevated, see better response to treatment with this biologic. Hypereosinophilia complication in 1.2% , eosinophilia seen in 4% of patients.
Dupilumab in mod-to-sev asthma: reduces asthma exacerbation rate (0.46 vs 0.87) and increased FEV1 (0.32 vs 0.14 L); eosinophilia/hypereo was reported as an AE Corren et al NEJM.
As needed budesonide-formoterol vs maintenance budesonide in mild asthma: exacerbations - no difference; FEV1 and symptom control - maint budesonide better. As needed budesonide-formoterol was not different from budesonide-formoterol BID in asthma exacerbation rate. Corticosteroid load was lower in the as needed group but symptom control and FEV1 were better with BID. Bateman et al NEJM. Dr Li: there is some evidence for patients to use as needed budesonide-formoterol rather than twice a day.
Quadrupling inhaled corticosteroids reduced the time to first asthma exacerbation in an unblinded, randomized trial by McKeever et al (NEJM). Quadrupling ICS early in asthma exacerbation is an effective strategy. However there was a companion paper that showed different results when blinded. Quadrupling ICS to abort asthma exacerbations: Seem to work — hazard ratio 0.81 (0.71-0.92) in favor; NNT 15.
Jackson in JAMA 2018: even 5x increase Inhaled steroid dose in yellow zone did not prevent exacerbations in children with asthma - might impact growth. So....What do we do with our asthma action plans? https://twitter.com/AllergyHealth/status/1063582176980004864
RIsk factors for severe asthma: older, higher BMI, greater smoking history, lower lung function, lower ACT scores. Severe asthma in Sweden by questionnaire: 1.3% of the cohort, 36% of surveyed showed at least one sign of asthma severity.
Severe asthma is more common than you might think: large study in Sweden shows 36% with signs of severe asthma. Patients more severe were older, had higher BMI, higher rate of smoking history, higher symptom scores. Link: https://twitter.com/AllergyHealth/status/1063483091837104128
TENOR II study: patient reported outcomes; high degree of co-morbid conditions.
For chronic cough clinic: FeNO not helpful for eosinophilic bronchitis but has a potential for cough variant asthma. FeNO not useful for eosinophilic bronchitis, but it does have utility in cough variant asthma. Cough variant #asthma has always been a clinical diagnosis. Can we now use FeNO as a diagnostic test? How could this change our practice / patient experience? Link: https://twitter.com/AllergyHealth/status/1063493191200989184
Eosinophilia in COPD above 300 linked to increased risk of COPD exacerbation. COPD mortality is much greater than asthma mortality. COPD mortality is increasing while asthma mortality is decreasing.
Dr. Riedl on urticaria, angioedema, and other skin disorders. IL-24 specific IgE is present in CIU patients. This correlates with symptoms, ie higher anti IL-24 IgE leads to worse symptoms.
Patients with chronic spontaneous urticaria (CSU) have IgE to a wide number of autoantigens including IL-24. As many as 80% of pts w CSU have high levels of IgE-anti-IL-24 and these levels correlate w disease activity. Schmetzer et al, JACI.
CSU: 80% of patients have increased IgE anti — IL-24 which trigger MC degranulation; unknown relevance of this finding for CSU. There is also IgE to other auto antigens.
Finally elucidating some possibilities for specific autoimmune mechanisms of Chronic Spontaneous #Urticaria. Could this suggest possible future testing for refractory cases? Will it drive more specific biologic therapies? Link: https://twitter.com/AllergyHealth/status/1063494329262436352
Higher dose of Omalizumab (600 mg Q4 Weeks) improves control of CSU. Predictors of higher doses of omalizumab was higher BMI and age. Updosing of omalizumab to 450-600 mg every 4 weeks for CSU not controlled with regular dosing: achieved 93% control; particularly in patients with higher BMI and older age.
JAMA Derm 2017 Resolution rate of chronic #urticaria in children is low and CU can go on for months or years, 57% evidence of autoimmune cause - Basophil activation test positive. Positive BAT actually good as predictor of earlier resolution.
Montelukast helps angioedema predominant UAS. Leukotrienes might have a more important role in the pathogenesis of angioedema than CSU (urticaria alone or urticaria/angioedema). Montelukast (LTRA) reduces symptom severity and frequency in patients with angioedema-predominant CSU treated with 4 x labeled dose antihistamine without the use of omalizumab - watch out for nightmares from LTRA. The report is from a single center retrospective trial. In angioedema only patients bradykinin mediated disease may be identified by a plasma kallikrein test. Hopefully a new biomarker?
Histamine vs bradykinin induced angioedema: threshold-stimulated kallikrein; high specificity and positive likelihood ratio for bradykinin-mediated angioedema. Dr. Marc Reidl: We definitely need better biomarkers for elucidating histamine v. Bradykinin mediated angioedema - could Threshold-stimulated kallikrein activity assay be a useful new test?
There may be an oral Plasma Kallikrein coming to treat HAE. Very helpful in non GI attacks. Oral plasma kallikrein inhibitor (BCX7353) for prophylaxis in HAE phase II study: 125 mg dose or more resulted in a significantly lower rate of attacks compared to placebo; GI side effects and LFT elevation at higher doses.
Eye-opening data, review of 70 HAE deaths showed 63 of those patients had no HAE diagnosis at time of death, despite family history of HAE. The always important reinforcement, by Dr. Marc Riedl, that every HAE attack is material for on-demand therapies and that these patients should be considered for prophylactic therapies at every office visit. Super useful table by Dr. Riedl on current HAE therapies. No less important is the effort that is being placed on training for self-administration at home: https://twitter.com/JPLopesMD/status/1063525624185159680
Allergy to HDM increases risk of IgE to staph and E. Coli. Atopic dermatitis: IgE reactivation to bacterial antigens is more frequent in patients with HDM vs non HDM sensitization.
Promising study of moderate AD and probiotics: improved in the SCORAD index with the use of Bifidobacterium lactis (CECT 8145;7347;9104). AD and probiotics: an NIH study showing some improvement with the use of Roseomonas mucosa though topical application.
Promising probiotics in AD: topical Roseomonas mucosa and PO specific Bifidobacterium lactis (CECT 8145;7347;9104) - there is a need for more studies.
Human microbiome: 3 lbs, 100 trillion cells - what came first the biome or the atopy? Eosinophilia lung inflammation correlates with lower airway bacterial diversity that include more pathogenic bacteria. Presence of Haemophilus in the lung was an indicator of poor response to Fluticasone.
There may be changes of the gut microbiome in CU. Gut microbiome may even play a role in chronic urticaria and point to possible interventions.
Updates on anaphylaxis, drug allergy and stinging insect hypersensitivity
Delayed recognition, inappropriate treatment of anaphylaxis leading to lawsuits. Though no allergists listed as defendants, we must still take responsibility for educating our colleagues and leading systems improvements in our institutions. There are so many challenges with Epi auto injectors from proper dosing to adequate needle length to cost. It is suggested based on ideal dose that switching from 0.15 to 0.30 epi should occur at 20-25 Kg not 30 as is current practice.
Dr. Montanaro: “Amoxicillin allergy is totally over diagnosed and diagnosis is rarely confirmed.” A very frequently used antibiotic. We should try to alway confirm or discard the diagnosis through the appropriate tests. Remember Drug Provocation Test is GOLD STANDARD.
Another reversal from #ACAAI18: Serum tryptase not very helpful in assessing anaphylaxis risk for venom.
Seasonal decrease in IT dose in season does not change percentage of reactions to IT.
Discussing IT for local allergic rhinitis is interesting for proof of concept but impossible to do in a community practice and mucous IgE testing or nasal allergen challenge are not available.
This is a Twitter summary from #ACAAI18 meeting based on tweets by the following allergists:
@WAOJM @Ismallergy @alexeigonzmd @DocAllergy @AllergyHealth @JPLopesMD