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Archives: Medical Journal Reviews

Medical Journal Review

Posted: May 2010

Reviewed by Juan Carlos Ivancevich, MD, in collaboration with Phil Lieberman, MD.

1. Epinephrine in children with food-related anaphylaxis.
To establish the frequency of children with food-related anaphylaxis requiring >1 dose of epinephrine, the authors performed a medical chart review at Boston hospitals of all children presenting to the Emergency Department (ED) for food-related acute allergic reactions between January 1, 2001, and December 31, 2006. The survey focused on causative foods, clinical presentations, and emergency treatments. The 605 reviewed cases (median age of 5.8 years) represented a study cohort of 1,255 patients (62% males). A variety of foods provoked the allergic reactions, including peanuts (23%), tree nuts (18%), and milk (15%). Approximately half of the children met diagnostic criteria for food-related anaphylaxis. Among those with anaphylaxis, 31% received 1 dose and 3% received >1 dose of epinephrine before their arrival to the ED. In the ED, patients with anaphylaxis received antihistamines (59%), corticosteroids (57%), and epinephrine (20%). Over the course of their reaction, 44% of patients with food-related anaphylaxis received epinephrine, and among this subset of patients, 12% (95% CI: 9-14) received >1 dose. Among children with food-related anaphylaxis who received epinephrine, 12% received a second dose.
Editor's comment: Children at risk for food-related anaphylaxis should carry two doses of epinephrine.
Rudders SA, Banerj Ai, Core B et al., Multicenter Study of Repeat Epinephrine Treatments for Food-Related Anaphylaxis. Pediatrics 2010; 125(4): e711-e7a8
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2. Chlamydial respiratory infections in the pathogenesis of neutrophilic asthma.
The effects of chlamydial infection on the development of asthma were investigated using a BALB/c mouse model of OVA-induced allergic airways disease (AAD). The effects of current and resolved Chlamydia muridarum infection during OVA sensitization on AAD were assessed and compared with uninfected and nonsensitized controls. Current, but not resolved, infection attenuated hallmark features of AAD: pulmonary eosinophil influx, T cell production of IL-5, mucus-secreting cell hyperplasia, and airways hyperresponsiveness (AHR). Current infection also induced robust OVA-driven neutrophilic inflammation and IFN-γ release from T cells. The phenotype of suppressed but persistent Th2 responses in association with enhanced neutrophilia is reminiscent of neutrophilic asthma. This phenotype was also characterized by increased pulmonary IL-12 and IL-17 expression and activation of APCs, as well as by reduced thymus- and activation-regulated chemokine. Inhibition of pulmonary neutrophil influx during infection blocked OVA-induced neutrophilic inflammation and T cell IFN-γ production and reversed the suppressive effects on mucus-secreting cell hyperplasia and AHR during AAD. Thus, active chlamydial respiratory infection during sensitization enhances subsequent neutrophilic inflammation and Th1/Th17 responses during allergen exposure.
Editor's comment: Active chlamydial respiratory infection during sensitization may have a role in the pathogenesis of neutrophilic asthma.
Horvat JC, Starkey MR, Kim RY et al., Chlamydial Respiratory Infection during Allergen Sensitization Drives Neutrophilic Allergic Airways Disease. Journal of Immunology 2010; 184(8): 4159-4169.

3. DRACMA: Diagnosis and Rationale for Action against Cow's Milk Allergy.
In 2008, the World Allergy Organization (WAO) Special Committee on Food Allergy identified Cow's Milk Allergy (CMA) as an area in need of a rationale-based approach, informed by the consensus reached through an expert review of the available clinical evidence, to make inroads against a burdensome, world-wide public health problem. It is in this context that the WAO DRACMA Guidelines document was planned to provide physicians everywhere with a management tool to deal with CMA from suspicion to treatment. Targeted (and tapped for their expertise), both on the DRACMA panel or as reviewers, were allergists, pediatricians (allergists and generalists), gastroenterologists, dermatologists, epidemiologists, methodologists, dieticians, food chemists, and representatives of allergy patient organizations.
Editor's comment: As a result of international cooperation under the umbrella of the WAO arises this invaluable document, a sentinel paper on milk allergy published in the WAO Journal.
Fiocchi A, Brozek J, Schünemann H et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. World Allergy Organization Journal 2010; 3(4); 57-161.
Section 1. Introduction

4. Determinants of childhood allergic rhinitis (AR).
To identify environmental exposures and host factors during infancy that predict allergic rhinitis (AR) at age 3 years, high-risk children were followed annually from ages 1 to 3 years. AR was defined as sneezing, runny, or blocked nose in the prior 12 months and a positive skin prick test (SPT) response to 1 or more aeroallergens. The exposures and clinical outcomes were determined with environmental and standardized medical questionnaires. Dust samples of the primary activity area were analyzed for house dust endotoxin (HDE) and (1-3)-beta-D-glucan. Fine particulate matter sampled at 27 monitoring stations was used to estimate personal elemental carbon exposure attributable to traffic exposure. Of 361 children in this analysis, 116 had AR, and 245 were nonatopic and nonsymptomatic. Prolonged breast-feeding in African American children, and multiple children in the home during infancy, were protective against AR. Food SPT response positivity and tree SPT response positivity in infancy increased the risk of AR at age 3 years. HDE exposure was associated with AR; the effect was dependent on exposure level. Elemental carbon attributable to traffic and environmental tobacco smoke exposure showed no effect on AR.
Editor's comment: Prolonged breast-feeding during infancy reduced the risk of AR.
Codispoti CD, Levin L, Lemasters GK et al., Breast-feeding, aeroallergen sensitization, and environmental exposures during infancy are determinants of childhood allergic rhinitis. The Journal of Allergy and Clinical Immunology 2010; 125(5): 1054-1060

5. Electronic health record (EHR) and compliance with National Asthma Education Prevention Program (NAEPP) guidelines.
The authors conducted a prospective cluster-randomized trial in 12 primary care sites over 1 year to determine if clinical decision support (CDS) embedded in an Electronic Health Record (EHR) would improve clinician adherence to national asthma guidelines in the primary care setting. Practices were stratified for analysis according to whether the site was urban or suburban. Children aged 0 to 18 years with persistent asthma were identified by ICD 9 codes for asthma. The 6 intervention-practice sites had CDS alerts imbedded in the EHR. Outcomes of interest were the proportion of children with at least 1 prescription for controller medication, an up-to-date asthma care plan, and the performance of office-based spirometry. Increases in the number of prescriptions for controller medications, over time, was 6% greater (P = .006) and 3% greater for spirometry (P = .04) in the intervention urban practices. Filing an up-to-date asthma care plan improved 14% (P = .03) and spirometry improved 6% (P = .003) in the suburban practices with the intervention. They concluded that, using a cluster-randomized trial design, CDS in the EHR, at the point of care, improved clinician compliance with NAEPP guidelines.
Editor's comment: The disseminate use of HER with CDS may improve many aspects of the clinical care.
Bell LM, Grundmeier R, Localio R, et al., Electronic Health Record-Based Decision Support to Improve Asthma Care: A Cluster-Randomized Trial. Pediatrics 2010; 125(4): e770-e777.

6. Sweat response increased in asthmatic children.
The researchers studied 82 children with asthma and 51 non-asthmatic healthy children without any other significant chronic diseases aged 6-18 years. They measured transepidermal water loss (TEWL) on palm, volar, mid-forehead, and back skin before and after the children had exercised on a treadmill for 6 minutes or until heart rate had reached 80% of the age-predicted maximum. They found that TEWL on palm skin was higher in asthmatic than non-asthmatic children after exercise, at 22.8 g/m² h versus 15.2 g/m²h. Similar differences between the groups were observed for TEWL on volar, mid-forehead, and back skin. Further analysis showed that these differences in TEWL measurements occurred in boys, but not girls. They also found that, in asthmatic children, those taking anti-inflammatory medications had lower TEWL measurements than those who were not taking such medications. Their results show that asthma is associated with a higher rate of sweating response to exercise in boys, and anti-inflammatory treatment decreases the amount of sweating.
Editor's comment: Even though there is a general conviction among parents of asthmatic children and pediatricians that asthmatic children sweat more than healthy ones, this had not been formally documented previously.
Oflu A, Soyer OU, Tuncer A et al., Eccrine sweat response in children with asthma. Allergy 2010; 65(5): 645-648.

7. Limited allergy preventive effect of dietary interventions in infancy.
The authors conducted a comprehensive review on the present knowledge on risk factors for allergic disease and provide an overview of the literature on allergy prevention, focusing on breastfeeding. They concluded that the most important modifiable risk factors for allergy are maternal smoking behavior and the type of feeding. A smoke-free environment for the child, exclusive breastfeeding for 4-6 months and the postponement of supplementary feeding until 4 months of age are the main measures considered effective. There is no place for restricted diets during pregnancy or lactation. Although meta-analyses suggest that hypoallergenic formula after weaning from breastfeeding grants protection against the development of allergic disease, the evidence is limited and weak. Moreover, all current feeding measures aiming at allergy prevention fail to show effects on allergic manifestations later in life, such as asthma.
Editor's comment: The allergy preventive effect of dietary interventions in infancy is limited.
Kneepkens F and Brand P, Breastfeeding and the prevention of allergy. European Journal of Pediatrics [Published online in Springer open access: 5 February 2010].
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8. Lyprinol, a marine based oil, reduces allergic inflammation and airway hyper-responsiveness.
The authors found that the marine-based oil reduced allergic inflammation and airway hyper-responsiveness in mice. Recent dietary changes, including a decreased omega-3 polyunsaturated fatty acid (PUFA) intake, may have contributed to increased asthma rates, and dietary supplementation with marine oil could have clinical benefits. To investigate, the researchers studied BALB/c mice with ovalbumin-induced allergic airway disease that received either a daily supplement of omega-3 PUFA-rich fish oil or lyprinol, which is a complex mixture of various marine lipids, omega-3 PUFAs, vitamin E and olive oil. They found that bronchoalveolar lavage fluid, lung tissue, and blood from mice that received lyprinol contained significantly lower numbers of eosinophils than those from mice that received fish oil. Mice that received lyprinol also showed reduced airway hyper-responsiveness and decreased mucus hypersecretion in the lung compared with mice that received fish oil. However, supplementation with lyprinol or fish oil was not associated with changes in the release of the Th2 cytokines interleukin (IL)-4, IL-5, IL-13 or interferon (INF)-γ, nor with changes in serum levels of immunoglobulin G (IgG)1 and IgG2a.
Editor's comment: Evidence that supplementation with lyprinol may have beneficial effects in asthma.
Wood LG, Hazlewood LC, Foster PS et al., Lyprinol reduces inflammation and improves lung function in a mouse model of allergic airways disease. Clinical & Experimental Allergy [Published online 16 April 2010 Early View (Articles in advance of print)]

9. Passive smoking linked to chronic rhinosinusitis (CRS).
Few studies have focused on secondhand tobacco smoke (SHS) on chronic rhinosinusitis (CRS), although evidence suggests that such a relationship may exist. The authors studied 306 nonsmoking patients, aged 19-88 years, diagnosed with CRS and 306 age-, gender-, and race/ethnicity-matched nonsmoking controls without the condition. Information on socioeconomic status, diet, alcohol consumption, medical history, exposure to air pollution and respiratory irritants at work, and the presence of conditions such as diabetes, asthma, and allergies were collected. The participants also supplied information on SHS exposure at home, work, in public places, and at private social functions during the 5-year period before CRS diagnosis or at study entry. Analysis revealed that patients with CRS were significantly more likely than controls to have been regularly exposed to SHS at home, at work, in public spaces, and at private social functions. After accounting for potential confounding factors, the researchers found that exposure to SHS was significantly associated with an increased risk for CRS, at odds ratios (ORs) of 1.69, 2.81, 1.48, and 2.60 for exposure at home, at work, in public spaces, and at private functions, respectively. They also found that there was a strong, independent dose-response relationship between the number of venues in which SHS exposure occurred and CRS risk, with each additional venue of exposure associated with a 2.03-fold increased risk for CRS. Around 40.0% of CRS diagnoses appeared to be attributable to SHS.
Editor's comment: Exposure to SHS is associated with CRS in a dose-response fashion and independently of environmental and occupational exposures.
Tammemagi CM, Martin C, Davis RM et al. Secondhand Smoke as a Potential Cause of Chronic Rhinosinusitis. A Case-Control Study. Archives of Otolaryngology - Head and Neck Surgery, 2010: 136(4): 327-334.

10. Shared decision making (SDM) and adherence to asthma controller medications.
To compare controller medication adherence and clinical outcomes in 612 adults with poorly controlled asthma, they were randomized to one of two different treatment decision-making models or to usual care. In shared decision making (SDM), nonphysician clinicians and patients negotiated a treatment regimen that accommodated patient goals and preferences. In clinician decision making, treatment was prescribed without specifically eliciting patient goals/preferences. Refill adherence was measured using continuous medication acquisition (CMA) indices-the total days' supply acquired per year divided by 365 days. Cumulative controller medication dose was measured in beclomethasone canister equivalents. In 1 year of follow-up SDM resulted in: significantly better controller adherence and long-acting beta-agonist adherence; higher cumulative controller medication dose; significantly better clinical outcomes (asthma-related quality of life, health care use, rescue medication use, asthma control, and lung function), compared with usual care. In year 2, compared with usual care, SDM resulted in significantly lower rescue medication use. Compared with clinician decision making, SDM resulted in: significantly better controller adherence and long-acting beta-agonist adherence; higher cumulative controller dose; and quantitatively, but not significantly, better outcomes on all clinical measures.
Editor's comment: Negotiating patients` treatment decisions significantly improves adherence to asthma pharmacotherapy and clinical outcomes.
Wilson SR, Strub P, Buist AS et al., Shared treatment decision making improves adherence and outcomes in poorly controlled asthma. American Journal of Respiratory and Critical Care Medicine 2010; 181(6): 566-577.

11. A new nasal secretion collection device and its advantages over nasal lavage techniques.
The concentration of biomarkers is highly variable in nasal secretions because of the diversity of collection methods. A nasal secretion collection device was developed to increase detectability of the assay, standardize the sampling technique, eliminate unknown dilution factor, and minimize analyte loss during the sample processing. The authors demonstrate the performance characteristics of a novel nasal secretion collector and its advantages over nasal lavage techniques. Characteristics of absorption and recovery of the liquid or proteins by different types of polyurethane foam were evaluated. The concentration of immunoglobulins, inflammatory mediators and allergen specific antibodies was comparatively measured in nasal secretions collected by the novel nasal secretion collector and nasal lavages. The concentrations of cytokines, eosinophil cationic protein, and tryptase in nasal secretions obtained by the nasal secretion collector were at least 8-fold higher than those tested in nasal lavages. Furthermore, the levels of immunoglobulins and the grass/weed pollen allergen specific antibodies were 6- to 290-fold increased when the nasal secretion collector was used. The nasal secretion collector was easy to use, non-invasive, and caused minimal discomfort to subjects during sampling.
Editor's comment: This novel nasal secretion collector shows significantly higher detectability and reproducibility than nasal lavages.
Lü FX and Esch RE, Novel nasal secretion collection method for the analysis of allergen specific antibodies and inflammatory biomarkers, Journal of Immunological Methods, 2010; 356(1-2); 6-17

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