bluuebunny/crossref_metadata_2025 huggingface dataset:
Sublingual Immunotherapy With Once-Daily Grass Allergen Tablets: A Randomized Controlled Trial in Seasonal Allergic Rhinoconjunctivitis
Authors: Jordan Teri J. , Jones Stacie M.
Published: November 2007

Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. J Allergy Clin Immunol. 2006;117:802–809

PURPOSE OF THE STUDY. To examine the efficacy and safety of sublingual immunotherapy (SLIT) in seasonal allergic rhinoconjunctivitis using timothy-grass–allergen tablets.

STUDY POPULATION. The study included 855 patients aged 18 to 65 from 55 centers in Canada and Europe with seasonal allergic rhinoconjunctivitis induced by grass pollen.

METHODS. A double-blind, randomized, parallel-group, placebo-controlled trial was conducted during 2002–2003. Patients had a history of allergic rhinoconjunctivitis during grass-pollen season for at least 2 years with a positive skin-prick–test result and serum-specific immunoglobulin E (IgE) to Phleum pratense. Individuals were randomly assigned to receive placebo or 2500, 25 000, or 75 000 SQ-T sublingual tablets administered daily. Daily diaries of symptoms (0–3) and rescue-medication use from pre–through post–grass-pollen season were kept, and a rhinoconjunctivitis quality-of-life (QoL) questionnaire was completed. Well days were calculated as those with a symptom score of ≤2 and no rescue-medication use.

RESULTS. A total of 790 (92%) participants completed the trial that included a mean duration of treatment of 18 weeks. Treatment with 75 000 SQ-T tabs revealed an improvement in symptom score (16%; P = .0710) and medication score (28%; P = .0470) when compared with placebo. The QoL score and number of well days also revealed improvement of 17% (P = .006) and 18% (P = .041), respectively. The 2 lower doses did not demonstrate significant change from placebo. Preseason treatment for 8 weeks with the 75 000 SQ-T dose showed an increased improvement of symptom score (21%; P = .002) and medication score (29%; P = .012) compared with placebo. In the 75 000 SQ-T group, specific IgG to P pratense was increased after 8 weeks of treatment and tripled posttreatment. Specific IgE levels increased after treatment initialized but remained unchanged thereafter. Therapy was well tolerated with only mild-to-moderate symptoms (consisting of primarily oral pruritis and throat irritation) noted in 53% of the patients.

CONCLUSIONS. Grass-pollen SLIT has a dose-dependent efficacy, is well tolerated, and provides improved QoL for patients with seasonal allergic rhinoconjunctivitis.

REVIEWER COMMENTS. SLIT for grass-pollen allergy holds promise as an alternative future therapy to subcutaneous immunotherapy that is attractive on many levels. Grass-pollen SLIT may have broader coverage range because of improved accessibility and more convenient administration, less discomfort than injections, and decreased risk of IgE-mediated severe systemic reactions. Preseason coverage with SLIT may improve symptoms and reduce medication requirements for treatment of seasonal allergic rhinoconjunctivitis.
ImmunoCAP Phadiatop Infant: A New Blood Test for Detecting IgE Sensitisation in Children at 2 Years of Age
Authors: Skripak Justin , Wood Robert A.
Published: November 2007

Ballardini N, Nilsson C, Nilsson M, Lilja G. Allergy. 2006;61:337–343

PURPOSE OF THE STUDY. To evaluate the efficacy of a blood test, Phadiatop Infant (PI), in determining immunoglobulin E (IgE) sensitization to food and aeroallergens in children at 2 years of age.

STUDY POPULATION. Prospective study of 239 children followed from birth. Families were recruited during pregnancy. For 75% of the participants, 1 or both parents had a history of atopic disease.

METHODS. Clinical evaluation occurred every 6 months through 2 years of age. At 2 years of age, all children underwent skin-prick testing (SPT), allergen-specific IgE testing to a panel of common food and aeroallergens, and the PI blood test. Subjects with ≥1 positive SPT and allergen-specific IgE test were as categorized IgE sensitized. Those with either ≥1 positive SPT or ≥1 positive allergen-specific IgE were labeled as inconclusive. Those with all negative tests were considered non–IgE sensitized. Cutoff for a positive PI test result was >0.35 kU/L.

RESULTS. On the basis of SPT and allergen-specific IgE tests, 26 (11%) of the 239 children were considered IgE sensitized, 182 (76%) were non–IgE sensitized, and 31 (13%) were labeled inconclusive. Using SPT and allergen-specific IgE tests as a reference, in the IgE-sensitized and non–IgE-sensitized groups, the sensitivity of the PI test was 96%, specificity was 98%, positive predictive value (PPV) was 89%, and negative predictive value (NPV) was 99%. When children with any positive SPT or allergen-specific IgE test (ie, the inconclusive group) were included, sensitivity was 82%, specificity was 98%, PPV was 94%, and NPV was 95%. There was a statistically significant association between any clinical symptom of atopic disease and a positive PI test result (odds ratio: 2.7; 95% confidence interval: 1.3–5.5).

CONCLUSIONS. The ability of PI used as an independent test to detect IgE sensitization in young children seems to be a reliable alternative to SPT or allergen-specific IgE antibody testing.

REVIEWER COMMENTS. As the prevalence of atopic diseases in the population increases, early identification of IgE-sensitized, atopic children is desirable. The PI test seems to be a reasonable alternative that does not require the placement of SPT or the selection of specific antigens for SPT or blood tests. In this study, the correlation of the PI test with SPT or blood-test results was good. The correlation with clinical symptoms was not quite as convincing. In terms of individual allergic symptoms, a positive PI test result only correlated significantly with eczema. This was probably limited by the fact that children were only followed up to age 2, when asthma and rhinoconjunctivitis are more frequently infection related than allergic.
Clinical Efficacy and Safety of Sublingual Immunotherapy With Tree Pollen Extract in Children
Authors: Jarvinen Kirsi M. , Sicherer Scott H.
Published: November 2007

Valovirta E, Jacobsen L, Ljørring C, Koivikko A, Savolainen J. Allergy. 2006;61:1177–1183

PURPOSE OF THE STUDY. To investigate the clinical efficacy, safety, and dose-response relationship of sublingual immunotherapy (SLIT) in children suffering from rhinoconjunctivitis with or without asthma.

STUDY POPULATION. Eighty-eight children (aged 5–15 years) in Finland with a history of tree-pollen–induced allergic rhinoconjunctivitis with or without seasonal asthma. Skin-prick test, specific immunoglobulin E, and conjunctival provocation test were used to confirm allergy to tree pollen.

METHODS. Randomized, double-blind, placebo-controlled dose-response study using a glycerinated mixture of pollen from birch, hazel, and alder trees. Three groups receiving SLIT 5 days per week for up to 18 months were given an accumulated weekly dose of 24 000 U (dose group 1), an accumulated weekly dose of 200 000 U (dose group 2), or placebo.

RESULTS. In the birch-pollen season, dose group 2 showed a significant reduction in both symptom (P = .01) and medication (P = .04) scores compared with those in the placebo group, but dose group 1 showed only a significant reduction of symptom scores (P = .03). No serious adverse events were reported. Oral local reactions were the most common adverse effect, ranging from 25% of patients in the placebo group to 50% in group 2.

CONCLUSIONS. SLIT with tree-pollen extract provided dose-dependent benefits in tree-pollen–allergic children in terms of significantly reduced symptoms and medication use. The treatment was well tolerated.

REVIEWER COMMENTS. The use of allergen-specific immunotherapy by the sublingual route, SLIT, has been increasing in clinical practice in Europe. SLIT is especially attractive for use in children, because it is a noninjection form of immunotherapy. This study showed a modest reduction (∼40%) in both symptom and medication scores. This is an interesting disease-modifying therapy that will need more studies to characterize efficacy and safety and to compare the results to that of subcutaneous immunotherapy before wider use can be recommended.
Parental Knowledge and Use of Epinephrine Auto-injector for Children With Food Allergy
Authors: Le Bras Michael , Perry Tamara T.
Published: November 2007

Pouessel G, Deschildre A, Castelain C, et al. Pediatr Allergy Immunol. 2006:17:221–226

PURPOSE OF THE STUDY. To assess parental use and knowledge of an epinephrine autoinjector (EAI), Anapen, prescribed for their food-allergic child(ren), and to examine the availability of emergency kits and personalized care plans.

STUDY POPULATION. The parents of 152 food-allergic children prescribed an EAI between June 2000 and March 2003 at 1 of 5 children's hospitals in northern France.

METHODS. An anonymous-questionnaire format was used to collect details on the child's clinical manifestations of allergies, EAI education by a health care provider, verification of proper EAI use at each follow-up visit, availability of a personalized care plan at school, physician instructions in case of allergic reaction, and medications available at home or outside the home. Parents were also asked to list symptoms that required epinephrine (open-ended item).

RESULTS. One hundred nine families representing 111 children completed and returned the survey. The majority (90%) of families had the use of Anapen demonstrated (76% with a trainer device), and 83% had received written instructions. Nineteen percent had a repeat demonstration at follow-up visits, and 10% never received a demonstration; yet, 88% of parents felt that they could use an EAI in an emergency. Only 54% of school-aged children had a personalized care plan, and 11% had an EAI at school with no personalized care plan. Only 48% of the parents could list >1 symptom that required an EAI. There was no difference in the quality of instructions between pediatricians and allergists and no difference in knowledge between parental socioeconomic groups.

CONCLUSIONS. EAIs and personal care plans were insufficiently available at schools and in daily life. Proper EAI use and education were unsatisfactory.

REVIEWER COMMENTS. This study emphasized the importance of extensive and repeated education about food-allergy risks and measures that need to be in place in case of an emergency. Although a majority of parents felt that they knew how to use an EAI, many could not recognize >1 symptom that would require the use of an EAI, and nearly half of the patients did not have an EAI or emergency plan available at school. A disturbing number (10%) of parents never received EAI education, and for those who received education, only a few (19%) had a review of instructions at follow-up. Repeated EAI education is important, because skills acquired at the initial visit are likely to be lost if they are not practiced, and failure to reiterate the importance of knowing how or when to use an EAI may contribute to parents’ indifferent attitude about carrying an EAI or submitting an appropriate personal care plan to the child's school.
The Impact of Spirometry on Pediatric Asthma Diagnosis and Treatment
Authors: Talwar Hanna , Leo Harvey L.
Published: November 2007

Holt EW, Tan J, Hosgood HD. J Asthma. 2006;43:489–493

PURPOSE OF THE STUDY. To evaluate the use of spirometry as a diagnostic tool in a pediatric asthma-management program at an inner-city community health clinic.

STUDY POPULATION. The study profiled 56 pediatric patients who presented with respiratory symptoms that were indicative of an acute asthma exacerbation.

METHODS. Clinicians recorded each patient's history of asthma symptoms as well as heart rate, respiratory rate, and pulse oximetry. Patients then were assessed for current asthma symptoms and given an initial assessment of asthma, upper respiratory infection, or both. An initial treatment plan for nonreactive airway management, albuterol, yellow-zone management, and/or prednisone/prelone treatment was recorded. After the initial symptom-based diagnosis, a pulmonary-function test was performed by using spirometry measurements. The clinician concluded the visit by making a final assessment of asthma or upper respiratory infection and assigned a final treatment plan that was based on standardized asthma plans.

RESULTS. The most frequently reported physical symptom was general coughing (73.2%), followed by nighttime cough (50.0%), wheezing (35.7%), and trouble sleeping because of cough (21.4%). Approximately two thirds of the patients in this population had abnormal values of forced expiratory volume in 1 second. Physicians changed 30.4% of the patients’ treatment plans after viewing spirometry results.

CONCLUSIONS. Spirometry is an objective tool that can help prevent misclassification of asthma severity and inappropriate use of asthma medication among pediatric patients with asthma. The use of spirometry made an impact in asthma diagnosis at this inner-city clinic: nearly one third of the patients had their treatment plans changed after the spirometry results were viewed.

REVIEWER COMMENTS. The emphasis of this study was to examine the impact of spirometry results on physician behavior in the acute setting. It demonstrates that when clinicians follow the National Asthma Education and Prevention Program guidelines for recommended spirometry use, there were considerable differences in recommendations for treatment. Ensuring appropriate diagnosis cannot solely rely on patients’ signs and symptoms; thus, pediatricians should consider spirometry in asthmatic children.
Immunotherapy With a Ragweed-Toll-Like Receptor 9 Agonist Vaccine for Allergic Rhinitis
Authors: Yu Joyce E. , Sicherer Scott H.
Published: November 2007

Creticos PS, Schroeder JT, Hamilton RG, et al. N Engl J Med. 2006;355:1445–1455

PURPOSE OF THE STUDY. The conjugate compound of the ragweed antigen, Amba1, and an immunostimulatory DNA sequence containing a CpG motif is associated with a suppression of T-helper 2 cellular and cytokine responses via binding to toll-like receptor 9 (TLR9). This study investigated whether Amba1-immunostimulatory oligodeoxyribonucleotide conjugate (AIC) is a safe and effective immunotherapy for ragweed-sensitized patients.

STUDY POPULATION. A randomized, double-blind, placebo-controlled, phase 2 clinical trial in which 25 participants with a history of fall allergic rhinitis aged 23 to 60 years were assigned to receive a vaccine containing either AIC or placebo.

METHODS. Participants received a total of 6 weekly injections before the ragweed season. The primary clinical end point was the change in albumin level in nasal secretions assessed by a posttreatment nasal allergen challenge. Postchallenge rhinitis symptoms were also scored. Secondary clinical end points included the rhinitis visual analog score, daily nasal symptom diary score, use of relief medication, a rhinoconjunctivitis quality-of-life questionnaire, and skin-test sensitivity. Immunologic evaluation included measuring Amba1- and ragweed-specific immunoglobulin (Ig) G and IgE and cytokine levels.

RESULTS. There was no affect on the primary end point with AIC treatment. However, during the 2 posttreatment ragweed seasons, subjects in the group that received AIC had better peak-season rhinitis visual analog scores, peak-season daily nasal-symptom diary scores, and midseason rhinoconjunctivitis quality-of-life scores. Those in the AIC group also had decreased peak-season use of relief medications and antihistamine and decongestant use in the second season posttherapy. AIC was associated with a rise in the Amba1-specific IgE level after treatment but was not associated with an increase in the Amba1-specific IgE level during either posttreatment ragweed season. There were no vaccine-associated serious adverse reactions.

CONCLUSIONS. AIC may have a potential therapeutic role in the treatment of ragweed-allergic individuals.

REVIEWER COMMENTS. Current allergen immunotherapy involves frequent dosing over 3 to 5 years, which can lead to compliance issues, and may be associated with systemic allergic reactions. The described vaccine is devised to be less likely to trigger allergic reactions during therapy and to enhance nonallergic immune responses to increase efficacy. This study was limited by the small number of patients and the lack of long-term follow-up. However, it suggests that conjugated allergen vaccines may be an option in the future as shorter, safe, and effective immunotherapy regimens that may warrant consideration for use in children.
Does Antibiotic Exposure During Infancy Lead to Development of Asthma? A Systemic Review and Metaanalysis
Authors: Kewalramani Anupama , Bollinger Mary E.
Published: November 2007

Marra F, Lynd L, Coombes M, et al. Chest. 2006;129:610–618

PURPOSE OF THE STUDY. To determine the association between antibiotic exposure in the first year of life and the development of childhood asthma by conducting a meta-analysis.

METHODS. A search of all available electronic databases (Medline, Embase, EBM databases, Web of Science, PapersFirst, ProceedingsFirst, and the Cochrane database) for the period between January 1966 and September 2004 was performed. Studies included populations receiving at least 1 prescription for an antibiotic during the first year of life. The primary outcome was the development of physician-diagnosed asthma between the ages of 1 and 18 years. Only studies published in English and those that reported odds ratios (ORs) were included.

RESULTS. Review of 2042 references yielded 8 studies that met criteria; 4 were retrospective, and 4 were prospective. The studies were reported between 1999 and 2004 and included sample sizes between 263 and 21 129 children. All retrospective studies used questions from the International Study of Asthma and Allergies in Childhood survey. Five studies were used to determine if there was a dose-response relationship between the number of antibiotic courses received and the risk of childhood asthma. These 5 studies included 27 167 children and 3392 asthma cases. The pooled OR for the 8 studies was 2.05 (95% confidence interval [CI]: 1.41–2.99). The association between antibiotic use in the first year of life and asthma was significantly higher in the retrospective studies (OR: 2.82; 95% CI: 2.07–3.85) than in the prospective studies (OR: 1.12; 95% CI: 0.88–1.42). The overall OR for the dose-response association of antibiotic use in the first year of life and asthma was 1.16 (95% CI: 1.05–1.28), but there was a trend toward a stronger association in the retrospective studies than in the prospective studies.

CONCLUSIONS. Meta-analysis of the impact of antibiotics in the first year of life revealed a possible increase in later development of asthma in childhood on the basis of only the retrospective study results. Additional study is needed to determine a causal relationship.

REVIEWER COMMENTS. This meta-analysis was the first to address the question of whether antibiotic use in the first year of life is associated with subsequent development of asthma. On the basis of the analysis, exposure to at least 1 antibiotic in the first year of life seems to be a risk factor for the development of childhood asthma; however, when the analysis was stratified by the subtypes of studies (prospective versus retrospective), only the pooled results from the retrospective studies yielded a positive association. All of the 95% CIs for the prospective studies crossed 1.00, which brings into question the association between exposure to antibiotics in the first year of life and the subsequent development of childhood asthma. Additional large-scale, prospective studies will be needed to confirm or refute the association.
Pediatric Emergency Department Anaphylaxis: Different Patterns From Adults
Authors: Kelso John M.
Published: November 2007

Braganza SC, Acworth JP, Mckinnon DR, Peake JE, Brown AF. Arch Dis Child. 2006;91:159–163

PURPOSE OF THE STUDY. Data on acute pediatric anaphylaxis presentations to the emergency department (ED) are limited.

STUDY POPULATION. Patients under 16 years of age who presented to a metropolitan, pediatric teaching hospital ED in Australia over a 3-year period with generalized allergic reactions (skin and/or gastrointestinal symptoms) and anaphylaxis (respiratory, cardiovascular, or hypotensive symptoms) that satisfied relevant International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes.

METHODS. Medical charts were reviewed for incidence, comorbidities, likely etiology, clinical features, management, and disposal.

RESULTS. There were 526 children with generalized allergic reactions (9.3 per 1000 ED presentations) and 57 with anaphylaxis (1 per 1000 ED presentations) included. There were no fatalities. For anaphylaxis cases, a cause was recognized in 68% (food: 56% of total; drug: 5%; sting: 5%; other: 2%), cutaneous features were present in 83%, a past history of asthma was reported in 37%, adrenaline was used in 39%, and follow-up was arranged for 81% (only 28% with an allergy clinic).

CONCLUSIONS. The incidence of generalized allergic reactions of 9.3 in 1000 was greater than in the adults.

REVIEWER COMMENTS. Food, drug, and stinging-insect reactions are the primary causes of anaphylaxis in children (as in adults). Although skin symptoms are present in the majority, the lack of such symptoms should not exclude the diagnosis. All children who suffer an anaphylactic event deserve a consult to an allergist who can confirm the diagnosis, determine or confirm the cause, and instruct the patient on avoidance measures, emergency treatment for subsequent events should they occur, and provide a prognosis regarding possible resolution.
The Influence of Pulmonary Function Testing on the Management of Asthma in Children
Authors: James John M.
Published: November 2007

Nair SJ, Daigle KL, DeCuir P, Lapin CD, Schramm CM. J Pediatr. 2005;147:797–801

PURPOSE OF THE STUDY. To assess how preevaluation pulmonary-function tests (PFTs) influenced management decisions in children with asthma, beyond what was obtained from history and physical examination alone.

STUDY POPULATION. Children with asthma (N = 367) aged 4 to 18 years.

METHODS. Physicians and nurse practitioners in the outpatient pulmonary office evaluated the children and made initial treatment recommendations before reviewing the specific spirometry results. Any changes based on the test results were documented.

RESULTS. Spirometry results were abnormal in 45% of the visits, related to underlying asthma severity but not to clinical findings. PFT results changed management decisions in 15% of the visits. This frequency was not affected by the patient's age, disease severity, symptom control, or examination findings. When spirometry results did not change treatment decisions, the provider was more likely to maintain therapy (58%) than to increase (17%) or decrease (24%) therapy. In contrast, when spirometry results did change treatment decisions, the provider was more likely to increase therapy (75%) than to maintain (20%) or decrease (5%) therapy.

CONCLUSIONS. Without PFTs, providers often overestimated the degree of asthma control. This incorrect assessment could have resulted in suboptimal therapy.

REVIEWER COMMENTS. This was a very practical clinical study that addressed a common clinical scenario that physicians who treat asthma face daily in clinical practice. Ideally, the patient's presenting clinical history, physical examination, and PFT result should all be factored into the final clinical decision regarding asthma therapy. The data from this investigation demonstrate that spirometry results were abnormal in almost one half of the visits, and this was related to underlying asthma severity and not clinical findings. When the spirometry results did not enter into the management decision, therapy was generally maintained; however, when spirometry results were factored in, the provider was more likely to increase therapy. With this in mind, proper interpretation of PFT data should help prevent overestimation of the degree of asthma control and help prevent suboptimal therapy. An obvious extension of this investigation would be the examination of serial PFTs in patients with asthma to identify clinically relevant trends in these data to assist in the best possible decision-making regarding ongoing asthma therapy and control.
Age Related, Structured Educational Programmes for the Management of Atopic Dermatitis in Children and Adolescents: Multicentre, Randomised Controlled Trial
Authors: Otsu Kanao , Phipatanakul Wanda
Published: November 2007

Staab D, Diepgen TL, Fartasch M, et al. BMJ. 2006;332:933–938

PURPOSE OF THE STUDY. To determine the effects of age-related, structured educational programs on the management of moderate-to-severe atopic dermatitis in childhood and adolescence.

STUDY POPULATION. A total of 992 of 1010 patients who were eligible for the study were given random group assignment. Children aged 3 months to 18 years were enrolled in group sessions of standardized intervention programs for atopic dermatitis once weekly for 6 weeks in a multicenter trial in Germany.

METHODS. The study was a randomized, controlled intervention trial. The 3 participating groups were parents of children with atopic dermatitis who were 3 to 7, 8 to 12, or 13 to 18 years old. Participants were recruited from 7 hospitals in Germany. The inclusion criteria were (1) diagnosis of atopic dermatitis according to predefined criteria, (2) eczema duration of at least 3 months, and (3) severity of eczema of at least 20 points on the scoring-of-atopic-dermatitis scale. Each treatment group received a tailored (age-specific) educational program once weekly for 2 hours over the course of 6 weeks. The control groups did not receive any education. Participants in the intervention and control groups were followed up at 6 and 12 months. Primary outcome measures were the differences in severity of eczema based on the scoring-of-atopic-dermatitis scale as well as parents’ quality of life over 12 months.

RESULTS. Significant improvements in severity of eczema were seen in all intervention groups compared with control groups after 12 months on the basis of the severity score. Moreover, improvement in quality of life for mothers of children aged 3 months to 7 years was significantly greater in the intervention group for all 5 subscales of the quality-of-life questionnaire and for mothers of children aged 8 to 12 years for 3 of the subscales.

CONCLUSIONS. Age-related educational programs for the control of atopic dermatitis in children and adolescents are effective in the long-term management of the disease.

REVIEWER COMMENTS. This study showed that educational interventions that use a multidisciplined approach that addresses psychosocial, pharmacologic, and nutritional factors served to decrease the severity of atopic dermatitis in the intervention groups. However, severity of disease was seen to decrease as well in the control groups that did not participate in the interventional programs despite having similar pharmacologic interventions in both groups. The authors attributed this finding to the assumption that the control groups were also highly motivated and tried to optimize therapies. Nonetheless, such standardized educational/support groups seem to have beneficial consequences in children as well as parents dealing with this chronic illness.
Effect of Probiotic Supplementation for the First 6 Months of Life on Allergen- and Vaccine-Specific Immune Responses
Authors: Oh Miae , Sicherer Scott H.
Published: November 2007

Taylor AL, Hale J, Wiltschut J, Lehmann H, Dunstan JA, Prescott SL. Clin Exp Allergy. 2006;36:1227–1235

PURPOSE OF THE STUDY. To determine if probiotic dietary supplementation in the first 6 months of life could modify allergen- and vaccine-specific immune responses.

STUDY POPULATION. One hundred seventy-eight term infants born to women with a history of allergic disease and a positive prick-skin test result were enrolled in Australia between July 2002 and March 2005.

METHODS. In a randomized double-blind, placebo-controlled design, 3 × 109 colony-forming units of Lactobacillus acidophilus (LARVI-A1; Probiomics, Eveleigh, New South Wales, Australia) was administered daily to term infants for the first 6 months of life. Peripheral blood mononuclear cell cytokine responses to tetanus toxoid (TT), house dust mite (HDM), ovalbumin, β-lactoglobulin, Staphylococcus enterotoxin B, and phytohemagglutinin were measured at 6 months of age.

RESULTS. Of the 178 infants who completed the study, blood samples were available from 118 children (60 placebo treated, 58 probiotic treated). Infants treated with probiotics had significantly lower interleukin 10 (IL-10) production to TT vaccine antigen than those in the placebo group (P = .03). Infants treated with probiotics had no significant differences in the levels of T-helper 1 and T-helper 2 cell responses to foods (ovalbumin or β-lactoglobulin) or inhalant allergens (HDM). However, the number of infants who had detectable tumor necrosis factor α and IL-10 responses to HDM were less than those who had received probiotics (P = .046 and 0.014, respectively). In addition, children who received probiotics had decreased productions of IL-5 and transforming growth factor β in response to Staphylococcus enterotoxin B (P = .044 and 0.015, respectively).

CONCLUSIONS. Although there were no consistent effects on allergen-specific responses, children treated with probiotics may have immunomodulatory effects on TT responses. The clinical ramifications of this have yet to be determined.

REVIEWER COMMENTS. It is interesting to note that the TT vaccine-specific responses in IL-10 were significant, whereas the allergen-specific responses were not. However, the clinical implication of this is not known. The authors pointed out that the types of probiotics selected and dosing regimen may be important in regard to immunologic outcomes. Some studies have shown a protective effect of probiotic supplementation on outcomes of atopic dermatitis (some have not), and the effect on allergen-specific responses, if any, remains unclear. This study began to tease out the allergen-specific outcomes. Although clinical atopic dermatitis evaluations were not made during this study, the immunologic effects of probiotics in infants with a maternal history of atopy are seemingly not allergen specific.
The Role of Immune Response to Staphylococcus aureus Superantigens and Disease Severity in Relation to the Sensitivity to Tacrolimus in Atopic Dermatitis
Authors: Maloney Jennifer M.
Published: November 2007

Fukushima H, Hirano T, Shibayama N, et al. Int Arch Allergy Immunol. 2006;141:281–289

PURPOSE OF THE STUDY. To examine the prevalence and role of Staphylococcus aureus superantigens on the pathophysiology and immunosuppressive drug sensitivity in patients with atopic dermatitis (AD).

STUDY POPULATION. Twenty-nine patients with AD and 13 healthy control patients were included in the study.

METHODS. Twenty-nine patients with AD were classified into 2 groups on the basis of their clinical AD scores: a low-score group (n = 14), corresponding to patients with mild-to-moderate AD, and a high-score group (n = 15), corresponding to patients with severe AD. Plasma antistaphylococcal enterotoxin B or toxic-shock syndrome toxin-1 (TSST-1) immunoglobulin E (IgE) levels were measured for the patients and healthy subjects by enzyme-linked immunosorbent assay. Also, individual drug sensitivity was estimated by determining the drug concentrations that would provide 50% inhibition (IC50) of peripheral blood mononuclear cell (PBMC) proliferation in vitro.

RESULTS. The levels of plasma anti-staphylococcal enterotoxin B or TSST-1 IgE in the patients with severe AD were significantly higher than those in the patients with mild-to-moderate AD (P < .05 and P < .01, respectively). When stimulated with concanavalin A in vitro, PBMCs in the patients with severe AD exhibited low sensitivity to the suppressive efficacy of tacrolimus (FK506) as compared with the patients with mild-to-moderate AD (P < .01). Furthermore, there was a significant correlation between the IC50 values of FK506 and plasma anti–TSST-1 IgE levels (P < .01).

CONCLUSIONS. PBMCs in patients with severe AD exhibited lower sensitivity to FK506 and had higher plasma levels of anti–TSST-1 IgE as compared with the patients with mild AD. S aureus superantigens seem to be one of the causes of decreased PBMC sensitivity to FK506; therefore, an alternative treatment would be useful on the basis of individual drug-sensitivity data and anti–TSST-1 IgE levels.

REVIEWER COMMENTS. Patients with AD commonly develop superinfections that require antimicrobial treatment. This study suggests that untreated superinfection may contribute to the ineffectiveness of topical medications that are commonly used as routine skin care for patients with AD. Attentiveness to the presence of concomitant skin infection is necessary for comprehensive skin care for patients with AD.
Improved Preventive Care for Asthma: A Randomized Trial of Clinician Prompting in Pediatric Offices
Authors: Bailey Sally Joo
Published: November 2007

Halterman JS, Fisher S, Conn KM, et al. Arch Pediatr Adolesc Med. 2006;160:1018–1025

PURPOSE OF THE STUDY. To determine if clinician prompting regarding asthma severity and guideline recommendations at the time of an office visit improves the delivery of preventive asthma care.

STUDY POPULATION. Children aged 2 to 12 years (N = 226) with persistent asthma from 2 inner-city pediatric practices in Rochester, New York. Children were at the clinic for a well-child check, asthma care, or non–asthma-related illness care and were randomly assigned to 1 of 2 groups: clinician-prompting group (CPG) or standard-care group (SCG).

METHODS. A baseline survey was conducted to obtain information regarding household demographics, medication use, and environmental tobacco-smoke exposure. Parents of the children who were randomly assigned to the CPG were instructed to give a prompt sheet to their clinician along with a blank asthma action plan form. Parents of the children who were assigned to the SCG also completed baseline assessment interviews but were not given a prompt sheet, and no information regarding the interview was shared with the clinician. Follow-up information was collected within 60 days through telephone interviews.

RESULTS. The children in the CPG were more likely to have any preventive action related to asthma taken at the visit compared with children in the SCG (86.6% vs 69.3%). Children in the CPG were also more likely to have received an asthma action plan (50.0% vs 23.7%), recommendation for a specific asthma follow-up visit (53.6% vs 36.8%), discussion regarding asthma (75.0% vs 63.2%), and smoke-reduction counseling (57.5% vs 35.4%) compared with those in the SCG. There were no statistical differences in referrals for specialty care, treatment of comorbid conditions, or changes in preventive medications between the 2 groups.

CONCLUSIONS. Clinician prompting regarding asthma severity and care guidelines at the time of an office visit increased the likelihood of delivering preventive asthma care.

REVIEWER COMMENTS. Several studies have demonstrated that health care providers often underestimate asthma severity and have demonstrated poor adherence to National Asthma Education and Prevention Program guidelines. Successful management of asthma requires both accurate determination of asthma severity and proper treatment. This study demonstrates a method that may increase the likelihood of delivering preventive asthma care at non–asthma-related office visits by prompting clinicians. However, as the authors pointed out, although prompting improved the delivery of preventive asthma care, a large percentage of patients in the CPG did not have follow-up–visit recommendations (46.4%), received no asthma action plan (50%), and received no discussion related to asthma (25%). This study demonstrates that a better system needs to be implemented to increase the rate of delivering appropriate preventive care for patients with asthma.
Neonatal-Onset Multisystem Inflammatory Disease Responsive to Interleukin-1β Inhibition
Authors: Yu Joyce E. , Sicherer Scott H.
Published: November 2007

Goldbach-Mansky R, Dailey NJ, Canna SW, et al. N Engl J Med. 2006;355:581–592

PURPOSE OF THE STUDY. Neonatal-onset multisystem inflammatory disease (NOMID) is a chronic inflammatory disease that develops in infancy and is characterized by an urticarial rash, arthropathy, and central nervous system disease, including aseptic meningitis, cerebral atrophy, mental retardation, seizures, and vision and hearing loss. Approximately 60% of patients have a mutation in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, which is involved in the interleukin 1β (IL-1β) pathway. This study evaluated the effect of anakinra (Kineret, Amgen), an IL-1 receptor antagonist, on the various clinical and laboratory aspects of NOMID.

STUDY POPULATION. A cohort of 18 patients aged 4 to 32 years with clinical NOMID (67% with mutations in CIAS1) who had active disease despite treatment with other antiinflammatory agents.

METHODS. Patients were given a daily subcutaneous dose of anakinra. The drug was withdrawn from 11 patients at 3 months with the development of a clinical flare. Thereafter, all patients were continued on daily treatments up to 24 months. Clinical and laboratory assessments were made at 1, 3, and 6 months during therapy with anakinra. Primary end points included changes in a disease-specific daily diary score and changes in the serum levels of acute-phase reactants.

RESULTS. All patients had an immediate response to anakinra with resolution of rash and conjunctivitis. There was an improvement in diary scores at 3 months that was maintained at 6 months. Serum amyloid A, C-reactive protein, and the erythrocyte sedimentation rate significantly declined with treatment. All the patients had headache at baseline, which resolved or improved with therapy, and cochlear and leptomeningeal lesions were improved on MRI. Serum levels of IL-1β, which were initially higher than those in healthy controls, decreased over the first 6 months of therapy. All the patients who underwent a treatment withdrawal experienced rapid improvement of their symptoms after resuming anakinra. Other than injection-site reactions, which resolved with continued treatment, there were no serious adverse events.

CONCLUSIONS. Anakinra may be a safe and effective treatment for patients with NOMID.

REVIEWER COMMENTS. This study suggests that anakinra may have a role in the treatment of other diseases in which IL-1β mediates inflammation (eg, systemic juvenile rheumatoid arthritis). Additional studies are needed to determine its long-term effects and clinical application. This study is an example of how specific immunomodulatory therapy may be useful in treating those diseases that have a defined molecular pathophysiologic profile.
Timing of Initial Exposure to Cereal Grains and the Risk of Wheat Allergy
Authors: Randolph Christopher
Published: November 2007

Poole JA, Barriga K, Leung DYM, et al. Pediatrics. 2006;117:2175–2182

PURPOSE OF THE STUDY. To ascertain the relationship between cereal-grain exposure, wheat, barley, rye, and oats in the infant diet and the subsequent development of wheat allergy.

STUDY POPULATION. A birth cohort of 1612 children followed to a mean age of 4.7 years.

METHODS. A total of 1612 children were enrolled in a birth cohort with questionnaire data, and dietary exposures were determined at 3, 6, 9, 15, and 24 months and annually thereafter. The primary outcome measure was apparent report of wheat allergy. Wheat-specific immunoglobulin E (IgE) levels in children reported to have wheat allergy were obtained. Children with celiac disease with autoimmunity were excluded.

RESULTS. Sixteen children (1%) noted wheat allergy. Children who were first exposed to cereal after 6 months of age had a >4 times prevalence of wheat allergy when compared with children who were first exposed to cereals before 6 months of age, after controlling for family history and allergic disorder and history of food allergy before 6 months of age. All 4 children with detectable wheat-specific IgE were initially given cereal grains after 6 months. Having a first-degree relative with a history of atopy (ie, asthma, eczema, or hives) was also independently associated with an enhanced risk of subsequent development of wheat allergy.

CONCLUSIONS. Delaying first exposure to cereal grains until after 6 months enhanced the risk of subsequent development of wheat allergy. These results do not support delaying introduction of cereal grains for protection against food allergy.

REVIEWER COMMENTS. This study was limited by its dependence of parental report of wheat allergy, although IgE was obtained as well. No formal diagnostic oral food challenges were performed. The possibility of reverse causality was addressed by eliminating confounding factors related to history of food allergy but could still be a potential explanation. The birth cohort also was selected on the basis of HLA-genotype screening and family history of diabetes, which may limit its generalizability. However, the results, that delaying exposure to cereal grains until after 6 months is associated with increased risk of wheat allergy, not a protective outcome, are still provocative. Additional large prospective studies using double-blind, placebo-controlled food challenge to confirm these findings are needed.
Loss-of-Function Variations Within the Filaggrin Gene Predispose for Atopic Dermatitis With Allergic Sensitizations
Authors: Haymore Bret R. , Mikita Cecilia P.
Published: November 2007

Weidinger S, Illig T, Baurecht H, et al. J Allergy Clin Immunol. 2006;118:214–219

PURPOSE OF THE STUDY. Evaluation for genetic basis for impaired epidermal skin barrier in atopic dermatitis (AD).

STUDY POPULATION. White German families with AD (N = 476).

METHODS. Evaluation of the association of the loss-of-function mutations Arg501Xaa and 2282del4 within the filaggrin (FLG) gene by using the transmission-disequilibrium test.

RESULTS. This study revealed prominent associations between the 2 loss-of-function FLG mutations and AD, as previously observed in a traditional Mendelian linkage analysis and case-control cohort analysis approach. In addition, an association of the FLG mutations was made in particular with the extrinsic subtype of AD, which is characterized by high total serum immunoglobulin E levels and concomitant allergic sensitization. Furthermore, FLG mutations were significantly associated with palmar hyperlinearity in patients with AD, which represents a shared feature of AD and ichthyosis vulgaris.

CONCLUSIONS. These data implicate FLG as the first strong genetic factor identified in a common complex disease.

REVIEWER COMMENTS. These findings confirm the importance of FLG as a genetic factor in AD as found by other investigators. This is the strongest genetic evidence to date to identify a cause of the breakdown of the epidermal barrier in AD. Filaggrin may be the “mortar” that is essential within the “bricks” of keratinocytes to maintain the integrity of the epithelial barrier. These findings further support the crucial role of the skin barrier in preventing allergic sensitization.
Improved Asthma Outcomes in a High-Morbidity Pediatric Population: Results of an Emergency Department-Based Randomized Clinical Trial
Authors: Smart Brian A.
Published: November 2007

Teach SJ, Crain EF, Quint DM, Hylan ML, Joseph JG. Arch Pediatr Adolesc Med. 2006;160:535–541

PURPOSE OF THE STUDY. To determine if an emergency department–based asthma follow-up clinic could improve outcomes within a high-morbidity pediatric population.

STUDY POPULATION. Four hundred eighty-eight patients (aged 12 months to 17 years) from an emergency department at an urban tertiary care pediatric hospital with previous physician-diagnosed asthma and ≥1 unscheduled visit in the last 6 months and/or ≥1 hospitalization in the last 12 months.

METHODS. The subjects were recruited while they were still in the emergency department for their acute care visits. The subjects were randomly assigned to either a single visit to an asthma clinic located in the emergency department, where they met with an asthma educator and a physician, or the control group, which received printed information about asthma. Follow-up telephone interviews were conducted at 1, 3, and 6 months after enrollment.

RESULTS. One hundred seventy-two (70.5%) of the subjects who were randomly assigned to the intervention attended the clinic, and 167 of these subjects were prescribed inhaled corticosteroids. Compared with children in the control group, those in the intervention group had significantly fewer unscheduled visits for asthma care (mean: 1.39 vs 2.34; relative risk: 0.60); at 6 months, reported significantly more use of inhaled corticosteroids (49.3% vs 26.5%; relative risk: 2.03); reported “no limitation in daytime quality of life” significantly more often (43.8% vs 34.4%; relative risk: 1.36); and reported “no functional limitations in quality of life” significantly more often (49.8% vs 40.8%; relative risk: 1.33).

CONCLUSIONS. A single follow-up visit to an emergency department–based asthma clinic resulted in significant improvements in care and outcomes for a high-morbidity pediatric population.

REVIEWER COMMENTS. This study was unique in that the emphasis was on follow-up in a clinic in the emergency department where care was first given, rather than a primary care office. This intervention seems to have been more successful than previously published emergency department–based studies that focused on improving rates of follow-up with primary care providers. There are a number of possible explanations for these findings, including the fact that many families use the emergency department as a de facto primary care office and the comprehensive nature of the emergency department–clinic visit. Costs were not analyzed, and there may be other barriers to other emergency departments adopting an intervention of this type, but these results are promising.