JACI Clinical Highlights - July 2008
The following summaries highlight several of the clinically relevant articles featured in the July 2008 issue of The Journal of Allergy and Clinical Immunology (JACI). These articles have been selected by the Editors for their novel findings, outstanding study design, and potential usefulness to practicing clinicians.
EpiPens: Is Two Spare Too Few?
Norton and colleagues in Britain and Ireland address a common issue in anaphylaxis management: How many epinephrine autoinjectors (EAIs) are enough in a school? Most children at risk of anaphylaxis are prescribed two EAIs to be available at school (E = 2n). The authors report the acceptability to parents and schools of a hypothetical change of policy to ensuring a single "named" EAI for each child and the school having a further set of unnamed or generic EAIs for back-up (E = n + 2). They found that parents were more positive than schools about changing from the current model to the proposed model of provision, though reservations were common in both groups, probably reflecting fear of change from a known (if unproven) protocol to a new one. Such a change of EAI provision in one local health authority in the UK would save about £128,000 each year. The study suggests that parents of food-allergic children recognize the financial cost to society of their child's safety at school and are willing to change the anaphylaxis management protocol if a change is safe. Such a change to the model of provision could substantially reduce health care costs for community management of anaphylaxis.
"Allergy rescue medication in schools---modeling a new approach" by Norton et al
(JACI July 2008 Volume 122 No. 1)
Use of SLIT in Stinging Insect Allergy
Sublingual immunotherapy (SLIT) has been reported to be effective in conditions other than respiratory allergy, such as food allergy and atopic dermatitis. Nevertheless, no attempt has been made so far to use it in stinging insect allergy. Severino et al performed a double-blind, placebo-controlled trial to assess whether SLIT might work in hymenoptera allergy. Since this was a proof-of-concept trial, only monosensitized patients with large local reactions due to honeybee stings were enrolled. Large local reactions were evaluated by sting challenges performed before and after treatment. SLIT (or placebo) was given for six months at a dose empirically chosen five times greater than in subcutaneous immunotherapy. Thirty adult patients were enrolled; 26 completed, and no side effect was reported. The median of the peak diameter of the local reaction significantly decreased in the active group (P = .014), with no change in the placebo group. The reduction of the diameter was greater than 50% in 57% of patients. A significant increase in IgG4 was also seen in the active group. The authors conclude that SLIT might be of benefit in hymenoptera allergy and that this deserves further study. In particular, dose-finding trials and in patients with systemic reactions are mandatory.
"Sublingual immunotherapy for large local reactions due to honeybee sting: Double blind placebo controlled trial" by Severino et al
(JACI July 2008 Volume 122 No. 1)
Breast-Feeding Does Not Increase Risk of Asthma or Atopy in Childhood
Although many studies confirm that breast-feeding protects against the development of wheezing illness in early childhood, some recent data suggest that it might increase the risk of atopy and asthma at later ages. Complicating the picture, recent data suggest that reverse causation (mothers altering breast-feeding on the basis of atopic symptoms in the infant) could bias studies. There are relatively few large prospective studies with objective measures of asthma and allergy outcomes in later childhood. Elliott et al therefore examined the role of breast-feeding in both early wheezing and later asthma outcomes, including objective measures of atopy and bronchial hyperresponsiveness, and adjusted for possible reverse causation using prospective data from the large ALSPAC birth cohort. Breast-feeding protected against early wheezing but had no deleterious effects on atopy, bronchial hyperresponsiveness, or asthma diagnosis at the age of seven years. The authors also found no evidence that breast-feeding increased risk of these conditions in subsets defined by other factors, including maternal atopy or asthma, parental smoking, and gender. The tendency of wheezing children to be breast-fed longer than nonwheezing children did not bias results. This study should reassure new mothers that breast-feeding will not increase the risk of asthma or allergies in their babies.
"Prospective study of breastfeeding in relation to wheeze, atopy, and bronchial hyperresponsiveness in the Avon Longitudinal Study of Parents and Children (ALSPAC)" by Elliott et al
(JACI July 2008 Volume 122 No. 1)
Modulation of TIM4 in DCs as a Peanut Allergy Strategy
Feng et al aimed to elucidate the mechanisms of peanut allergy mediated by microbial products and dendritic cells and its relationship to TIM4. Mouse bone marrow-derived dendritic cells (BMDCs) were generated and exposed to cholera toxin (CT) or/and peanut extract (PE) for 24 hours and then adoptively transferred to naive mice. After re-exposure to specific antigen PE, the mice were killed; intestinal allergic status was determined. Increased expression of TIM4 and costimulatory molecules was detected in BMDCs after concurrent exposure to CT and PE. Adoptively transferred CT/PE-conditioned BMDCs resulted in increases in serum PE-specific IgE and skewed TH2 polarization in the intestine. Oral challenge with specific-antigen PE induced mast cell activation in the intestine. Treating with TLR4 siRNA abolished increased expression of TIM4 and costimulatory molecules by BMDCs. Pretreatment with anti-TIM1 or anti-TIM4 antibody abolished PE-specific TH2 polarization and allergy in the intestine. Concurrent exposure to microbial product CT and food antigen PE increases TIM4 expression in DCs and promotes DC maturation that plays an important role in the initiation of PE-specific TH2 polarization and allergy in the intestine. Modulation of TIM4 production in DCs represents a novel approach to the treatment of peanut allergy.
"Disruption of TIM1/TIM4 interaction as a therapeutic strategy in a DC-induced peanut allergy model" by Feng et al
(JACI July 2008 Volume 122 No. 1)
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