bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific Oral Tolerance Induction in Food Allergy in Children: Efficacy and Clinical Patterns of Reaction
Authors: Keet Corinne A. , Wood Robert A. 
Published: October 2008

Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. Allergy. 2007;62(11):1261–1269
PURPOSE OF THE STUDY. To evaluate the efficacy of oral tolerance induction as a treatment for cow's milk and egg allergies.
STUDY POPULATION. Forty-seven children aged 0.6 to 12.9 years with positive double-blind, placebo-controlled food challenges to milk or hen's egg were included in this German study. Children with severe eczema were excluded.
METHODS. Subjects were randomly assigned to specific oral tolerance induction or continued avoidance. Treatment involved home escalation over at least 67 days from a dose of 1 drop of cow's milk to 250 mL or from 5 mg of lyophilized hen egg powder to 3500 mg. Subjects continued home dosing for a median of 21 months total, after which time they underwent a secondary period of avoidance for 2 months followed by a food challenge.
RESULTS. At follow-up challenge, 9 (36%) of 25 children in the specific-oral-tolerance-induction group showed permanent tolerance, 3 (12%) of 25 were tolerant with regular intake, 4 (16%) of 25 were partial responders, and 9 (36%) of 25 did not complete the treatment because of adverse effects. In the control group, 7 (35%) of 20 children were tolerant at the study end. Allergen-specific IgE levels decreased in children who developed tolerance both in the control (P &lt; .05) and treatment (P &lt; .001) groups.
CONCLUSIONS. Specific oral tolerance induction may be a valid treatment option for patients with persistent food allergy. However, only a minority of patients had evidence of persistent tolerance once treatment was stopped, with some unable to tolerate the therapy and others seeming to be only transiently desensitized.
REVIEWER COMMENTS. Allergen-specific immunotherapy with injected extracts has proven too dangerous to be a viable treatment method for food allergy. Sublingual or oral immunotherapy, as described here, is a promising alternative to strict avoidance. Although one third of the patients in this study had to withdraw because of adverse effects, the remaining patients were able to incorporate the allergen into their diet at some level. This treatment modality is highly promising, but it is still experimental, carries the potential for significant risk, and requires close monitoring by experienced physicians. Several studies of oral and sublingual immunotherapy for food allergy are ongoing in the United States and Europe.
Functional Patterns of HIV-1-Specific CD4 T-Cell Responses in Children Are Influenced by the Extent of Virus Suppression and Exposure
Authors: Church Joseph A. 
Published: October 2008

Correa R, Harari A, Vallelian F, et al. AIDS. 2007;21(1):23–30
PURPOSE OF THE STUDY. HIV-specific CD4+ T cells seem to play a critical role in antiretroviral immunity and particularly in maintaining cytotoxic T-cell responses. The objective of this study was to evaluate the function of HIV-specific T cells in antiviral treated, HIV-infected children.
STUDY POPULATION. The researchers evaluated 23 HIV-infected children who were treated with antiretroviral therapy for a mean of 7 years.
METHODS. Flow-cytometric analysis was used to measure the ability of HIV-specific T cells to secrete interleukin 2 (IL-2) and interferon γ (IFN-γ) after stimulation of patient cells with p55 gag protein.
RESULTS. Three patterns of intracellular cytokine generation were identified: in 10 subjects, antigen-specific cytokine production was characterized by IL-2 production, 8 subjects’ CD4+ T cells expressed IL-2 and IFN-γ, and 5 subjects’ T cells expressed IFN-γ alone. These 3 groups were then analyzed for factors that might explain the different patterns. The patterns correlated with viral load at the time of functional analysis and over the previous 2 years. The group with dominant IFN-γ responses had high viremia levels, a pattern similar to that observed in patients with uncontrolled viral replication. Patients with combined IL-2 and IFN-γ production had relatively lower viral loads but had experienced viral “blips” over the 2 years before analysis. This pattern was similar to adults who were long-term nonprogressors or those whose conditions continued to progress despite antiretroviral therapy. The subjects with a dominant IL-2 response had very low levels of viremia and had not experienced viral “blips” over the previous 2 years. This pattern was similar to that generally observed in individuals who have cleared the infecting agent. It is important to note that this pattern has not been observed in HIV-infected adults.
CONCLUSIONS. Children with HIV have a higher frequency of HIV-specific CD4+ T cells compared with adults, and their recovery of an IL-2–secreting T-cell pattern indicates a greater capacity for immune restoration in children than adults.
REVIEWER COMMENTS. This elegant study provides a biological rationale for the clinical observation that young children started on antiretroviral therapy have the capacity for remarkable reconstitution of immune functions relative to those reported in adults and older children who have been infected for prolonged periods before antiretroviral therapy. Perhaps it is unfair to compare these results with findings in adults that included patients who were infected for many years before their initiation of therapy. A more appropriate comparative adult group would be those treated within 6 months of their diagnosis. Most importantly, this study demonstrates that children are “different” and that treatment early in infection allows excellent immune reconstitution if viral replication is completely controlled.
Proteinuria in Children Infected With the Human Immunodeficiency Virus
Authors: Church Joseph A. 
Published: October 2008

Chaparro AI, Mitchell CD, Abitbol CL, et al. J Pediatr. 2008;152(6):844–849
PURPOSE OF THE STUDY. Proteinuria is a common feature of HIV infection and a potential complication of therapy in adult patients. This study was performed to determine the prevalence of proteinuria in a group of children infected with HIV and to assess this process over time and the impact of antiretroviral therapy on it.
STUDY POPULATION. HIV-infected children (N = 286) were studied from 1998 through 2006.
METHODS. Proteinuria was determined by random urine protein/creatinine ratios, with “normal” defined as &lt;0.2 and “nephrotic” defined as &gt;1.0.
RESULTS. A total of 94 (33%) of the children had proteinuria at baseline. Of these, 32 had urine protein range ratios of ≥1.0. Clinically, the mortality rate was higher in those patients with proteinuria. It is important to note that 55 of the 94 patients with baseline proteinuria showed a good response to antiretroviral therapy, as indicated by a decrease in HIV viral load and a substantial reduction in the number of subjects who had proteinuria.
CONCLUSIONS. Control of HIV viremia with antiretroviral therapy reduces progression of HIV-associated proteinuria and improves the survival rate of infected children.
REVIEWER COMMENTS. Proteinuria is a common feature of HIV infection in children. Two features of this patient population may affect the generalizability of the study findings: 85% of the patients were African American or African Caribbean, and the number of individuals with complicating hepatitis B or C was not indicated. Renal disease is more prevalent in HIV-infected black people than white people, particularly with respect to HIV-associated nephropathy. Chronic viral hepatitis may also cause secondary renal disease, likely secondary to an immunocomplex-associated inflammatory process. Regardless of these caveats, the authors’ conclusion is very much warranted: “surveillance of quantitative proteinuria with imaging and chemical indicators of renal dysfunction is very much warranted” for children with HIV infection.
Drug Allergy Claims in Children: From Self-reporting to Confirmed Diagnosis
Authors: Huang Faith , Nowak-Wegrzyn Anna 
Published: October 2008

Rebelo Gomes E, Fonseca J, Araujo L, Demoly P. Clin Exp Allergy. 2008;38(1):191–198
PURPOSE OF THE STUDY. To assess the prevalence of self-reported adverse drug reactions and drug allergy in a pediatric population and confirm the diagnosis in children with suspected drug allergy.
STUDY POPULATION. Patients (n = 1426) responded to an initial cross-sectional survey. A total of 60 of 67 patients with reported drug allergy were evaluated at an allergy clinic.
METHODS. The first phase included a cross-sectional survey that assessed the life occurrence of adverse drug reactions and self-reported drug allergy in the outpatient clinic of a pediatric hospital. The second phase involved a diagnostic workup in children with parent-reported drug allergy, including detailed clinical history and in vitro and in vivo investigations. Specific immunoglobulin E (IgE) level determination for β-lactams, prick and intradermal skin testing for β-lactams, local anesthetics and sulfonamides, and patch tests (if a delayed reaction was reported) were performed. If all other investigations were inconclusive and a provocation test was not contraindicated, this test was performed.
RESULTS. The prevalence of self-reported adverse drug reactions and drug allergy were 10.2% and 6.0%, respectively. The frequency of a medical diagnosis of drug allergy was 3.9%. The majority of the suspected allergic reactions were nonimmediate cutaneous events attributed to β-lactam antibiotics in younger children. Of 60 patients evaluated in the allergy clinic, 39 patients had a plausible clinical history, and additional investigation including a skin test, IgE-level measurement, and possible provocation tests were conducted. Drug allergy was diagnosed in 3 children on the basis of positive responses in skin (n = 1) and oral provocation (n = 2) tests.
CONCLUSIONS. Although adverse drug reactions and suspected drug allergy are frequently reported in children, after a complete evaluation, only a few of these reactions can be attributed to immediate and nonimmediate drug allergy. Overall, 94% of the patients could tolerate the initially suspected drug.
REVIEWER COMMENTS. This study underscores a serious problem: patients who experience or perceive a drug reaction are often classified as being truly allergic when this may not be the case. Such overdiagnosis and misdiagnosis may result in suboptimal medication choices. These results show that only 6% of the patients with initially suspected drug allergy were truly allergic. This study demonstrates the importance of a complete and detailed history, with consideration of additional testing including skin-prick tests, specific IgE-level determination, and provocation tests. It should be noted that for nonimmediate drug allergy, an oral provocation test may require prolonged treatment to observe for symptoms. Such provocation tests would not be undertaken for severe previous reactions (eg, toxic epidermal necrolysis).
Pollen Grains Induce a Rapid and Biphasic Eczematous Immune Response in Atopic Eczema Patients
Authors: Maloney Jennifer M. 
Published: October 2008

Eyerich K, Huss-Marp J, Darsow U, et al. Int Arch Allergy Immunol. 2008;145(3):213–223
PURPOSE OF THE STUDY. To investigate the relationship between eczematous reactions in subjects with immunoglobulin E–mediated allergy to pollen grains.
STUDY POPULATION. Two populations were evaluated: one population included subjects with atopic eczema who were sensitized to grass or birch pollen and who had a positive atopy patch test, and the second population included subjects without atopic eczema or atopy but who had a positive atopy patch test to nickel. In addition, as control populations, healthy volunteers and atopic subjects with eczema and sensitization to grass or birch but without a positive atopy patch test were included.
METHODS. Atopy patch tests with native pollen grains were performed to delineate the effect of native pollen grains on human skin of healthy and atopic individuals. A nickel patch test served as an established model of contact dermatitis. Skin-site samples were taken for biopsy 6 to 96 hours after allergen application and investigated immunohistochemically.
RESULTS. Histology of positive patch tests showed an influx of mononuclear cells (predominantly CD4+, CD25+, and CD45RO+). This influx was detected earlier in the pollen patch-test reactions compared with the immune response to nickel. A biphasic cytokine response could be detected in skin samples from the pollen patch test: interleukin 5 dominated in the early phase, and interferon γ dominated in the late phase. The nickel patch test was continuously dominated by interferon γ.
CONCLUSIONS. Pollen grains induce eczematous reactions in susceptible individuals. This reaction seems clinically and immunohistochemically similar to the contact hypersensitivity reaction to nickel but follows a faster kinetic and a biphasic course: T-helper 2 and immunoglobulin E in the early (24-hour) phase and T-helper 1 predominance in the late (96-hour) phase.
REVIEWER COMMENTS. This article highlights the importance of understanding that type 1 allergy-inducing antigens such as pollens can exacerbate atopic eczema in susceptible individuals. Physicians should remember to discuss this with their atopic patients before the start of pollen season.
Impact of Interview Mode on Accuracy of Child and Parent Report of Adherence With Asthma Controller Medication
Authors: Kaplan Michael S. 
Published: October 2008

Bender BG, Bartlett SJ, Rand CS, Turner C, Wamboldt FS, Zhang L. Pediatrics. 2007;120(3). Available at: www.pediatrics.org/cgi/content/full/120/3/e471
PURPOSE OF THE STUDY. To examine the effect of different modes of reporting adherence on the accuracy of self-administration of inhaled corticosteroids in asthmatic children under conditions mimicking a clinical trial.
STUDY POPULATION. A total of 104 asthmatic children, 8 to 18 years old, who were being treated for asthma with regular use of inhaled corticosteroids were studied. One parent was required to participate with each child.
METHODS. Each parent/child pair was assigned to 1 of 3 self-reporting modes: audio computer-assisted self-interview (ACASI), face-to-face interview with a member of the study staff, or self-administered paper-and-pencil questionnaire. The same mode was administered at each study visit for any given parent/child pair: baseline and at 1, 2, 3, and 4 months. Corticosteroid metered-dose inhalers were fitted with an electronic chronometer that captured the time and date of metered-dose inhaler dispensing, freshly initialized at baseline and at each study visit. Adherence was determined by dividing the number of puffs recorded by the number of puffs prescribed. Self-assessment of adherence was determined similarly for the 3 modes. The recall time frames were 1 week and 1 day. The primary outcome was self-reporting discrepancy (percent adherence recorded minus percent self-adherence self-reported). A positive discrepancy score represented underreporting, a negative score represented overreporting, and zero represented exact reporting. Adequate accuracy was considered when the discrepancy score was ±25%.
RESULTS. Children and parents overrepresented adherence for both the 1-week and 1-day monitoring periods. Adherence discrepancy was the greatest in the ACASI mode (adequate accuracy for children and parents, respectively, was 32% and 27% for 1-day recall and 47% and 38% for 1-week recall). The best accuracy was for the 1-day recall in children interviewed face-to-face (50% adequate). Larger discrepancies were observed in both children and parent with the other modes.
CONCLUSIONS. Self-reporting of adherence was insufficient even under the best of circumstances regardless of the mode of self-reporting used in this study.
REVIEWER COMMENTS. The recently updated National Asthma Education and Prevention Program report underscored the need to address adherence when considering a step up in asthma medication. Inaccurate accounting for adherence may taint clinical trials that examine treatment outcomes and on which guidelines are based. Several studies have used electronic chronologs to monitor adherence. Even then, dose dumping (dispensing several puffs in the air over a short period to boost the number of dispensings recorded) has been reported. You can lead a patient to an inhaler, but you can’t make them inhale.
The Neglected Role of Antibody in Protection Against Bacteremia Caused by Nontyphoidal Strains of Salmonella in African Children
Authors: Shreffler Wayne G. 
Published: October 2008

MacLennan CA, Gondwe EN, Msefula CL, et al. J Clin Invest. 2008;118(4):1553–1562
PURPOSE OF THE STUDY. To investigate whether specific antibody protects against nontyphoidal Salmonella (NTS) bacteremia.
POPULATION STUDIED AND METHODS. Admissions for NTS bacteremia during 1 year were reviewed (N = 352). Sera from 65 healthy Malawian children (median age, 24 months: range, 3–107 months) was used for in vitro NTS-killing assays. Purified immunoglobulin G (IgG) from patient sera was used to delineate the role of antibody versus complement. Immunoglobulin and complement deposition on bacteria was also assessed by flow cytometry. Complement dependency was tested by heat inactivation and by using C9-deficient serum.
RESULTS. Overall, 82% of the children with NTS bacteremia were &lt;36 months old, but there was a nonuniform distribution with fewer-than-expected cases in children &lt;4 months old (actual: 9.7% vs 16.7%), suggesting a role for passive humoral immunity. From healthy donors, 9 of 25 children &lt;16 months of age had serum with normal in vitro killing, whereas 40 of 40 children &gt;16 months of age did so. NTS killing in vitro was complement and membrane attack complex dependent. Effective killing corresponded to a specific IgG or IgM Salmonella titer of 1.5 U and was associated with the deposition of complement (C3 and C9) measured by flow cytometry. Resistance to killing by alternative complement activation was mediated by long-chain lipopolysaccharide and the rck gene product.
CONCLUSIONS. Salmonella-specific antibody that overcomes the complement resistance of NTS develops by 2 years of life in Malawian children and is mediated by specific IgG or IgM antibody.
REVIEWER COMMENTS. NTS is the most common cause of bacteremia in Malawi and much of tropical Africa and is associated with high rates of mortality even with appropriate culture facilities and access to antibiotics. The finding that specific antibody is protective against this invasive, facultative intracellular pathogen supports the importance of vaccine development for this pathogen.
Children's Respiratory Health and Mold Levels in New Orleans After Katrina: A Preliminary Look
Authors: Petersen Maureen M. , Mikita Cecilia P. 
Published: October 2008

Rabito FA, Iqbal S, Kiernan MP, Holt E, Chew GL. J Allergy Clin Immunol. 2008;121(3):622–625
PURPOSE OF THE STUDY. To study indoor air mold levels, lung function, and respiratory symptoms in a sample of children returning to live in New Orleans, Louisiana, immediately after Hurricane Katrina.
STUDY POPULATION. Participants were children aged 7 to 14 years currently residing in greater New Orleans with no plans to move. All study participants were recruited from a private primary school in the Garden District of New Orleans.
METHODS. Parents of all study participants completed a respiratory health symptom questionnaire during February/March and April/May 2006. During these defined study points, the children performed spirometry, and indoor and outdoor air sampling was performed. All data were statistically analyzed to determine if indoor mold levels correlated to the children's respiratory health.
RESULTS. Average indoor and outdoor mold concentrations decreased during the study, although only the reduction in outdoor mold levels reached statistical significance. Pulmonary function of all study participants was &gt;80% of predicted at both study points. Participants were stratified according to asthma history and flooding status, but no lung-function decrements were observed with stratification. A trend was seen in which respiratory symptoms increased after the hurricane and seemed to improve during the study. This difference, however, was only statistically significant for lower respiratory tract symptoms.
CONCLUSIONS. Indoor mold levels were low and pulmonary function in a sample of children living in New Orleans was normal &gt;6 months after Hurricane Katrina.
REVIEWER COMMENTS. The Children's Respiratory Health Study is the first published study to evaluate pediatric respiratory health and indoor mold in the post–Hurricane Katrina environment. Although a small sample size was evaluated, this study provides practitioners with objective, reassuring findings. This study, however, included children who were exposed to limited flood damage. This possible selection bias should not allow us to ignore respiratory symptoms in the pediatric population returning to the more damaged neighborhoods. We look forward to further research studying this at-risk pediatric population.
Transition to Adulthood: Delays and Unmet Needs Among Adolescents and Young Adults With Asthma
Authors: Duplantier John E. 
Published: October 2008

Scal P, Davern M, Ireland M, Park K. J Pediatr. 2008;152(4):471–475
PURPOSE OF THE STUDY. To examine the effect of the transition to adulthood on financial and nonfinancial barriers to care in youths with asthma.
STUDY POPULATION. Studied were adolescents and young adults with asthma. Public-use data from the National Health Interview Survey conducted by the National Center for Health Statistics were analyzed. Data from the years 2000–2005 were pooled to provide a sample of 26 597 adolescents (12–17 years) and 19 998 young adults (18–124 years).
METHODS. Subjects were classified as having delayed care because of financial barriers when during the previous 12 months they had delayed seeking medical care because of concerns about affordability. Similarly, an unmet need because of a financial barrier was identified when during the previous 12 months the respondents indicated that they had failed to receive needed medical care or prescription medication because they could not afford it.
RESULTS. More young adults than adolescents encountered financial barriers that resulted in delays (18.6% vs 8%; P &lt; .05) and unmet needs (26.6% vs 11.4%; P &lt; .05). Delays caused by nonfinancial barriers were similar (17.3% vs 14.9%; P was not significant).
CONCLUSIONS. Delays and unmet needs caused by financial reasons were significantly higher for young adults with asthma compared with adolescents with asthma.
REVIEWER COMMENTS. It is crucial for everyone who treats children with asthma to recognize the potential vulnerability of these patients as they transition to adulthood. Appropriate counseling and written materials regarding health insurance might be helpful, as might providing lists of resources for free or reduced-cost care that are available in the local community.