Bibliographic updates

Claude Molina & Jacques Gayraud

1.      Airways smooth muscle enlargement and severe asthma
2.      Drug allergies documented in electronic health records
3.      Omalizumab facilitates Rapid Oral Desensitization for Peanut Allergy
4.      Symptomatic treatment of pollen-related allergic Rhino - conjunctivitis
5.      Sublingual Immunotherapy tablets (SLIT) or Pharmacotherapy for Allergic Rhinitis

1. Airways smooth muscle (ASM) enlargement and Severe Asthma (SA)
M.Aubier et al JACI 2016 138 3 729-739
The increase in ASM is a component of airways remodeling in SA. The French authors sought to compare, by bronchial biopsies in 12 controls, 24 patients with moderate and 105 SA, ASM area (enlargement = more than 15% of total mass) with clinical and pathobiological characteristics (cellular and mitogenic factors in Broncho-alveolar lavages).

Analyses across ASM quartiles demonstrated that patients with the highest quartile, were younger, rather male, and has lower asthma control after one year of optimal management of. ASM enlargement occurs independently of features of airways inflammation or remodeling, whereas it was associated with Protease active receptor 2 (PAR 2) over expression, higher alveolar Tryptase and KLK levels. Targeting PAR 2 seems to be a novel therapeutic option in SA.

2. Drug allergies documented in electronic health records
L.Zhou et al Allergy 2016 Sept 71 9 1305-1313
The authors aimed to describe the prevalence of common drug allergies and patient characteristics documented in a large healthcare network from 1990 to 2013 in Boston large tertiary care hospitals. Among 1 766 328 patients 35% ad at least one reported drug allergy with an average of 1,95 per patient. The most commonly reactions were due to penicillin (12%), sulfonamide antibiotics (7,4%), opiates (6,8%), NSAID (3,5%). Drug allergies were most prevalent among females and white patients except for NSAID, ACE inhibitors, and thiazide diuretics more prevalent in black patients.

The relative proportion to ACE inhibitors and Statins have more doubled since early 2000, while allergies to antibiotics decrease emphasizing the role of increased exposure, usage overtime, and modern day therapy, as well as geographical and environmental factors which must be taken into account.                                                                         

As for Pharmacogenomics or Pharmacogenetics (D.A.KahnJACI October 2016 943-955) their clinical utility has not been established.

3. Omalizumab (O) facilitates Rapid Oral Desensitization (ROD) for Peanut Allergy (PA) :
A.J.Mac Ginnitie et al 2016 August in press
In a double-blind placebo control trial 37 subjects, median age 10years, IgE = median 90mg, who failed a food challenge to ≤100mg of peanut protein (pp) were randomized to O =29 or placebo = 8. After 12 weeks of treatment, the children underwent a DOR of 250mg of pp. over 6 hours followed by weekly dose increases up to 2000mg. O or Placebo were discontinued and subjects continued on 2000mg of pp daily. 12 weeks later, the children underwent a challenge to 4000mg. If tolerated, they continued on this dose daily. The results are as follow: Of 29 O (27 of whom received DOR) 23 tolerated 2000 mg pp 6 weeks after stopping study versus 22,5mg for placebo (P= 0,0011). 12weeks later 22 tolerated 4000mg after discontinuing study drug.

Conclusion: O allows patients with peanut allergy to be rapidly desensitized. Additional studies are needed to confirm these observations

4. Symptomatic treatment of pollen-related allergic Rhino-conjunctivitis( AR)
J.B.Wartna et al Allergy October 2016 Accepted article
In a randomized trial, 150 children, aged 6-18 years with pollen related AR were treated in 3 parallel groups: intra-nasal corticosteroids (INCS) either daily, or on demand (fluticasone propionate) or oral anti-histamine (levocetirizine) on demand for 3 months during grass pollen season. The trial shows that INCS daily was not superior to INCS on demand (22% versus 30% of symptom free-days: not significant) or anti-histamine (15%) not significant.

On-demand strategy has the advantage of lower corticosteroid exposure and less costs.

5. Sublingual Immunotherapy tablets (SLIT) or Pharmacotherapy for Allergic Rhinitis (AR)
S.R.Durham et al :JACI October 2016 1081-1088
In spite of heterogeneity of the study design, (randomized and placebo-controlled) and use of rescue medications in SLIT tablet’s trials, effects of nasal symptoms with grass (3094 adults) and ragweed tablets (658 patients) during the pollen season, and HDM-tablets during 8 weeks of perennial rhinitis (1768 patients) were nearly as great as with corticoids

(mometasone furoate 200mg) and greater than with montelukast (10mg) or desloratadine (5mg). .
House-dust-mite tablets offer the additional benefit of long term efficacy.

Comments and questions may be sent to:
Claude Molina                                                  
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Jacques Gayraud
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Last updated 27 December 2016