bluuebunny/crossref_metadata_2025 huggingface dataset:
Linkages Between Internet and Other Media Violence With Seriously Violent Behavior by Youth
Authors: Ybarra Michele L. , Diener-West Marie , Markow Dana , Leaf Philip J. , Hamburger Merle , Boxer Paul
Published: October 2008

OBJECTIVE. The goal was to examine the association between violence in the media and the expression of seriously violent behavior among older children and teenagers in a national sample.

METHODS. The Growing up with Media survey was a national, online survey of 1588 youths that was conducted in August and September 2006. Participants were 10- to 15-year-old youths who had used the Internet at least once in the past 6 months. The main outcome measure was self-reported seriously violent behavior, including (1) shooting or stabbing someone, (2) aggravated assault, (3) robbery, and (4) sexual assault.

RESULTS. Five percent of youths reported engaging in seriously violent behavior in the past 12 months. Thirty-eight percent reported exposure to violence online. Exposures to violence in the media, both online and off-line, were associated with significantly elevated odds for concurrently reporting seriously violent behavior. Compared with otherwise similar youths, those who indicated that many, most, or all of the Web sites they visited depicted real people engaged in violent behavior were significantly more likely to report seriously violent behavior. After adjustment for underlying differences in youth characteristics, respondents' alcohol use, propensity to respond to stimuli with anger, delinquent peers, parental monitoring, and exposures to violence in the community also were associated with significantly increased odds of concurrently reporting seriously violent behavior.

CONCLUSIONS. Exposure to violence in the media is associated with concurrent reports of seriously violent behavior across media (eg, games and music). Newer forms of violent media seem to be especially concerning.
Mitochondrial Oxidative Phosphorylation Disorders Presenting in Neonates: Clinical Manifestations and Enzymatic and Molecular Diagnoses
Authors: Gibson Kate , Halliday Jane L. , Kirby Denise M. , Yaplito-Lee Joy , Thorburn David R. , Boneh Avihu
Published: October 2008

OBJECTIVES. The goals were to examine the frequency of perinatal manifestations of mitochondrial oxidative phosphorylation disorders within a population-based cohort, to characterize these manifestations, to identify a possible association between these manifestations and diagnoses at a later age, and to identify possible associations between perinatal complications and specific disorders.

METHODS. We conducted a retrospective review of clinical and laboratory records for all patients with definitive oxidative phosphorylation disorders who were diagnosed and treated at the Royal Children's Hospital in Melbourne between 1975 and 2006 (N = 107; male/female ratio: 1.41).

RESULTS. Neonatal presentation was recorded for 32 of 107 patients (male/female ratio: 1:1), including 19 who presented on day 1 of life. Prematurity (gestational age of <37 weeks) was noted for 12.6% of the 107 patients. Of the 85 infants with known birth weights, 24 were in the ≤10th percentile for gestational age (11 with complex I deficiency), and 9 of those (6 with complex I deficiency) were in the <3rd percentile. The most common presenting neonatal symptoms after the first day of life were poor feeding, recurrent vomiting, and failure to thrive. We noted 3 main clinical neonatal forms of oxidative phosphorylation disorders (encephalomyopathic, hepatointestinal, and cardiac). Of the 32 infants, 28 died (13 in the neonatal period). Complex I deficiency was identified for 15 neonates, combined complexes I, III, and IV deficiency for 7 neonates, and combined complexes I and IV deficiency for 3 neonates. No neonates had complex IV deficiency. Six neonates had nuclear mutations, and 2 neonates had the mitochondrial DNA 8993T>G mutation.

CONCLUSIONS. Oxidative phosphorylation disorders present commonly in the neonatal period. The combination of nonspecific manifestations such as prematurity and intrauterine growth retardation with early postnatal decompensation or poor feeding or vomiting and persistent lactic acidosis should suggest the possibility of an oxidative phosphorylation disorder.
Trends in Hospitalizations Associated With Pediatric Traumatic Brain Injuries
Authors: Bowman Stephen M. , Bird Tommy M. , Aitken Mary E. , Tilford John M.
Published: October 2008

OBJECTIVES. The goals were to describe trends in pediatric traumatic brain injury hospitalizations in the United States and to provide national benchmarks for state and regional comparisons.

METHODS. Analysis of existing data (1991–2005) from the Nationwide Inpatient Sample, the largest longitudinal, all-payer, inpatient care database in the United States, was performed. Children 0 to 19 years of age were included. Annual rates of traumatic brain injury-related hospitalizations, stratified according to age, gender, severity of traumatic brain injury, and outcome, were determined.

RESULTS. From 1991 to 2005, the estimated annual incidence rate of pediatric hospitalizations associated with traumatic brain injury decreased 39%, from 119.4 to 72.7 hospitalizations per 100 000. The rates decreased for all age groups and for both boys and girls, although the rate for boys remained consistently higher at each time point. Fatal hospitalization rates decreased from 3.5 deaths per 100 000 in 1991–1993 to 2.8 deaths per 100 000 in 2003–2005. The rate of mild traumatic brain injury hospitalizations accounted for most of the overall decrease, whereas nonfatal hospitalization rates for moderate and severe traumatic brain injuries remained relatively unchanged.

CONCLUSIONS. Although pediatric hospitalization rates for mild traumatic brain injuries have decreased over the past 15 years, rates for moderate and severe traumatic brain injuries are relatively unchanged. Our study provides national estimates of pediatric traumatic brain injury hospitalizations that can be used as benchmarks to increase injury prevention effectiveness through targeting of effective strategies.
Preeclampsia and Risk for Epilepsy in Offspring
Authors: Wu Chun Sen , Sun Yuelian , Vestergaard Mogens , Christensen Jakob , Ness Roberta B. , Haggerty Catherine L. , Olsen Jørn
Published: October 2008

OBJECTIVE. Eclampsia has been found to be a strong risk factor for epilepsy in the offspring, but it is unclear whether the risk also applies to the preceding condition, preeclampsia.

METHODS. We conducted a population-based cohort study of 1537860 singletons born in Denmark (1978–2004). Information on preeclampsia (mild, severe, and unspecified), eclampsia, and epilepsy was obtained from the Danish National Hospital Register. Information on gestational age, birth weight, and Apgar score was obtained from the Danish Medical Birth Registry. We used Cox proportional hazard models to estimate the incidence rate ratio of epilepsy for children who were exposed to preeclampsia or eclampsia in prenatal life.

RESULTS. We identified 45288 (2.9%) children who were exposed to preeclampsia (34823 to mild, 7043 to severe, and 3422 to unspecified preeclampsia) and 654 (0.04%) to eclampsia during their prenatal life. We identified 20260 people who received a diagnosis of epilepsy during up to 27 years of follow-up in the entire cohort. Prenatal exposure to preeclampsia was associated with an increased risk for epilepsy among children with a gestational age at birth of at least 37 weeks. For mild preeclampsia, the incidence rate ratios were 1.16 among children born at term and 1.68 for children born postterm; for severe preeclampsia, the incidence rate ratios were 1.41 among children born at term and 2.57 among children born postterm. No associations between preeclampsia and epilepsy were found among children who were born preterm. Eclampsia was associated with epilepsy with an incidence rate ratio of 1.29 for children born at term and 5.03 for children born postterm.

CONCLUSIONS. Prenatal exposure to both preeclampsia and eclampsia was associated with an increased risk of epilepsy in children born after 37 weeks of gestation.
Candidate Genes and Cerebral Palsy: A Population-Based Study
Authors: Gibson Catherine S. , MacLennan Alastair H. , Dekker Gustaaf A. , Goldwater Paul N. , Sullivan Thomas R. , Munroe David J. , Tsang Shirley , Stewart Claudia , Nelson Karin B.
Published: October 2008

OBJECTIVE. The objective of this study was to examine whether selected genetic polymorphisms in the infant are associated with later-diagnosed cerebral palsy.

METHODS. A population-based case-control study was conducted of 28 single-nucleotide polymorphisms measured in newborn screening blood spots. A total of 413 children with later-diagnosed cerebral palsy were born to white women in South Australia in 1986–1999, and there were 856 control children. Distributions of genotypic frequencies were examined in total cerebral palsy, in gestational age groups, and by types of cerebral palsy and gender. Genotyping was performed by using a TaqMan assay.

RESULTS. For inducible nitric-oxide synthase, possession of the T allele was more common in all children with cerebral palsy and for heterozygotes who were born at term. For lymphotoxin α, homozygous variant status was associated with risk for cerebral palsy and with spastic hemiplegic or quadriplegic cerebral palsy. Among term infants, heterozygosity for the endothelial protein C receptor single-nucleotide polymorphism was more frequent in children with cerebral palsy. In preterm infants, the variant A allele of interleukin 8 and heterozygosity for the β-2 adrenergic receptor were associated with cerebral palsy risk. Interleukin 8 heterozygote status was associated with spastic diplegia. Variants of several genes were associated with cerebral palsy in girls but not in boys.

CONCLUSIONS. Two of the 28 single-nucleotide polymorphisms examined were associated with all types of spastic cerebral palsy in both gestational age groups and others with cerebral palsy in gestational age or cerebral palsy subgroups. Some of these associations support previous findings. There may be a genetic contribution to cerebral palsy risk, and additional investigation is warranted of genes and gene-environment interactions in cerebral palsy.
Fears About HIV Transmission in Families With an HIV-Infected Parent: A Qualitative Analysis
Authors: Cowgill Burton O. , Bogart Laura M. , Corona Rosalie , Ryan Gery , Schuster Mark A.
Published: October 2008

OBJECTIVE. Children of HIV-infected parents may be affected by their parents' disease even if not infected themselves. Because of advances in HIV treatment that have reduced the risk for vertical HIV transmission from mother to child, more HIV-infected adults are having children. Few studies have examined whether families with an HIV-infected parent experience fears about transmission to children and how they address such fears. In this article, we describe transmission-related fears in families with an HIV-infected parent.

METHODS. We used semistructured qualitative interviews, conducted in person from March 2004 to March 2005, with 33 HIV-infected parents, 27 minor children who were 9 to 17 years of age, 19 adult children, and 15 caregivers (adult family members or friends who helped care for the children and/or parents) to investigate their fears about HIV transmission. The parents are a subset from the HIV Cost and Services Utilization Study, a study of people in care for HIV throughout the United States. We analyzed the interview transcripts for themes related to transmission fears.

RESULTS. In many of the families, participants identified ≥1 HIV transmission–related fear. Themes included specific fears related to blood contact, bathroom items, kissing/hugging, and food. Families addressed their fears by educating children about modes of HIV transmission and establishing rules or taking precautions to reduce the risk for HIV transmission in the household. HIV-infected parents were also concerned about catching opportunistic infections from a sick child.

CONCLUSIONS. Many of the fears experienced by HIV-infected parents and their children were based on misconceptions about modes of HIV transmission. Pediatricians and others who treat these children may be able to offer counseling to allay fears that family members have about household transmission of HIV.
Clinical Implications of Unmanaged Needle-Insertion Pain and Distress in Children
Authors: Kennedy Robert M. , Luhmann Janet , Zempsky William T.
Published: October 2008

Increasing evidence has demonstrated that pain from venipuncture and intravenous cannulation is an important source of pediatric pain and has a lasting impact. Ascending sensory neural pain pathways are functioning in preterm and term infants, yet descending inhibitory pathways seem to mature postnatally. Consequently, infants may experience pain from the same stimulus more intensely than older children. In addition, painful perinatal procedures such as heel lancing or circumcision have been found to correlate with stronger negative responses to venipuncture and intramuscular vaccinations weeks to months later. Similarly, older children have reported greater pain during follow-up cancer-related procedures if the pain of the initial procedure was poorly controlled, despite improved analgesia during the subsequent procedures. Fortunately, both pharmacologic and nonpharmacologic techniques have been found to reduce children's acute pain and distress and subsequent negative behaviors during venipuncture and intravenous catheter insertion. This review summarizes the evidence for the importance of managing pediatric procedural pain and methods for reducing venous access pain.
Behavioral Approaches to Anxiety and Pain Management for Pediatric Venous Access
Authors: Cohen Lindsey L.
Published: October 2008

Pediatric venous access causes unnecessary anxiety and pain in children and, in turn, can have detrimental consequences. Behavioral approaches to pediatric venous access distress management can be organized temporally. Specifically, preparation before the procedure includes providing children with sensory and procedural information in an age-appropriate manner and providing training in coping skills. It is important to consider the timing, format, and content of the approach to provide optimal preparation for the unique circumstances of the individual patient. In addition to the child patient, preparing parents and teaching them which specific behaviors might be most helpful to their child should prove valuable to both patient and parents. During the procedure, there are benefits to providing secure and comfortable positioning. In addition, researchers recommend that adults encourage children to cope and actively engage children in distracting activities. For infants, there is support for the distress-mitigation properties of swaddling, skin-to-skin contact, breastfeeding, and sucrose. After venous access, distraction and encouragement of coping should speed recovery. In sum, research in behavioral approaches to pediatric pain management has provided recommendations for minimizing children's anxiety and pain associated with venous access.
Parental Alcohol Screening in Pediatric Practices
Authors: Wilson Celeste R. , Harris Sion Kim , Sherritt Lon , Lawrence Nohelani , Glotzer Deborah , Shaw Judith S. , Knight John R.
Published: October 2008

OBJECTIVES. Pediatricians are in an ideal position to screen parents of their patients for alcohol use. The objective of this study was to assess parents’ preferences regarding screening and intervention for parental alcohol use during pediatric office visits for their children.

METHODS. A descriptive multicenter study that used 3 pediatric primary care clinic sites (rural, urban, suburban) was conducted between June 2004 and December 2006. Participants were a convenience sample of consecutively recruited parents who brought children for medical care. Parents completed an anonymous questionnaire that contained demographics; 2 alcohol-screening tests (TWEAK and Alcohol Use Disorders Identification Test); and items that assessed preferences for who should perform alcohol-screening, acceptance of screening, and preferred interventions if the screening result was positive.

RESULTS. A total of 929 of 1028 eligible parents agreed to participate, and 879 of 929 completed surveys that yielded sufficient data for analysis. Most participants were mothers. A total of 101 of 879 parents screened positive on either the TWEAK or the Alcohol Use Disorders Identification Test. Parents with a negative alcohol screen (alcohol-negative) were more likely than parents with a positive alcohol screen (alcohol-positive) to report that they would agree to being asked about their alcohol use. There were no significant differences in preferences within alcohol-positive and alcohol-negative groups for screening by the pediatrician or computer-based questionnaire. Most preferred interventions for the alcohol-positive group were for the pediatrician to initiate additional discussion about drinking and its effect on their child, give educational materials about alcoholism, and refer for evaluation and treatment. Alcohol-positive men were more accepting than alcohol-positive women of having no intervention.

CONCLUSIONS. A majority of parents would agree to being screened for alcohol problems in the pediatric office. Regardless of their alcohol screen status, parents are accepting of being screened by the pediatrician, a computer-based questionnaire, or a paper-and-pencil survey. Parents who screen positive prefer that the pediatrician discuss the problem further with them and present options for referral.
Hemodynamic Changes During Weaning From Nasal Continuous Positive Airway Pressure
Authors: Abdel-Hady Hesham , Matter Mohamed , Hammad Ayman , El-Refaay Ahmed , Aly Hany
Published: October 2008

BACKGROUND. Nasal continuous positive airway pressure is frequently used to support preterm infants with respiratory distress syndrome. Little is known about the hemodynamic changes that occur, particularly during the weaning phase when lung compliance has improved and most of the airway pressure can be transmitted to the heart and major blood vessels.

METHODS. We conducted a prospective study on preterm infants (gestational age ≤32 weeks) with resolving respiratory distress syndrome, who were receiving nasal continuous positive airway pressure of 5 cm H2O and 21% oxygen. While cycling nasal continuous positive airway pressure, we performed 2-dimensional M-mode and pulsed Doppler echocardiography on all infants during nasal continuous positive airway pressure and 1 hour after being off nasal continuous positive airway pressure.

RESULTS. A total of 25 preterm infant were studied. The use of nasal continuous positive airway pressure significantly decreased right ventricular output (320 ± 22.7 vs 410.5 ± 44.1 mL/kg per min); right ventricular end diastolic diameter (6 ± 0.7 vs 6.4 ± 0.4 mm), left ventricular end diastolic diameter (11.6 ± 0.9 vs 13.6 ± 0.7 mm), left ventricular end systolic diameter (7.1 ± 0.6 vs 8.3 ± 0.4 mm), left atrial diameter (6.3 ± 0.5 vs 8 ± 0.5 mm), aortic root diameter (6.4 ± 0.3 vs 6.6 ± 0.4 mm), superior vena cava flow (70.2 ± 8.5 vs 91.1 ± 4 mL/kg per minute), and pulmonary maximum velocity (0.6 ± 0.1 vs 0.7 ± 0.1 m/seconds). It significantly increased mean inferior vena cava diameter (4.3 ± 0.5 vs 3.5 ± 0.6 mm), whereas nasal continuous positive airway pressure did not influence left ventricular output, aortic maximum velocity, fractional shortening, heart rate, or mean arterial blood pressure. Changes associated with nasal continuous positive airway pressure were similar in infants with (n = 8) and without (n = 17) patent ductus arteriosus.

CONCLUSIONS. In infants with resolving respiratory distress syndrome, nasal continuous positive airway pressure can impede systemic and pulmonary venous return, but it does not compromise systemic arterial pressure or heart rate. It is not clear whether the degree of these hemodynamic changes can affect the success of weaning off nasal continuous positive airway pressure.
Survey of Pediatricians' Opinions on Donation After Cardiac Death: Are the Donors Dead?
Authors: Joffe Ari R. , Anton Natalie R. , deCaen Allan R.
Published: October 2008

OBJECTIVE. There has been debate in the ethics literature as to whether the donation-after-cardiac-death donor is dead after 5 minutes of absent circulation. We set out to determine whether pediatricians consider the donation-after-cardiac-death donor as dead.

METHODS. A survey was mailed to all 147 pediatricians who are affiliated with the university teaching children's hospital. The survey had 4 pediatric patient scenarios in which a decision was made to donate organs after 5 minutes of absent circulation. Background information described the organ shortage, and the debate about the term “irreversibility” applied to death in donation after cardiac death. Descriptive statistics were used, with responses between groups compared by using the χ2 statistic.

RESULTS. The response rate was 54% (80 of 147). In each scenario, when given a patient described as dead with absent circulation for 5 minutes, ≤60% of respondents strongly agreed/agreed that the patient is definitely dead, ≤50% responded that the patient is in the state called “dead,” and ≤56% strongly agreed/agreed that the physicians are being truthful when calling the patient dead. On at least 1 of the scenarios, 38 (48%) of 147 responded uncertain, disagree, or strongly disagree that the patient is definitely dead. Although the patients in the 4 scenarios were in the identical physiologic state, with absent circulation for 5 minutes, 12 (15%) of 80 respondents did not consistently consider the patients in the state called “dead” between scenarios. Fewer than 5% of respondents answered strongly agree/agree to allow donation after cardiac death while also answering disagree/strongly disagree that the patient is definitely dead, suggesting little support to abandon the dead-donor rule.

CONCLUSIONS. Most pediatrician respondents were not confident that a donation-after-cardiac-death donor was dead. This suggests that additional debate about the concept of irreversibility applied to donation after cardiac death is needed.
Unlicensed Teenaged Drivers: Who Are They, and How Do They Behave When They Are Behind the Wheel?
Authors: Elliott Michael R. , Ginsburg Kenneth R. , Winston Flaura K.
Published: October 2008

OBJECTIVE. The objective of this study was to determine the prevalence and associated risk factors for unlicensed driving among 9th- through 11th-graders.

METHODS. A nationally representative school-based survey of 5665 9th-, 10th-, and 11th-graders ascertained whether students engaged in unlicensed driving and determined associated driving behaviors, risk behaviors, and demographic factors. Unlicensed driving, defined as not having any type of license and “driving on [one's] own” as opposed to learning to drive, or not driving yet was ascertained.

RESULTS. One (4.2%) in 25 US 9th- through 11th-graders reported that they drove at least 1 hour/week without a license. Unlicensed drivers were more likely to identify as being black or Hispanic, to live in rural or central city districts, and to report lower grades in school. No relationship was found between license status and reported crashes; however, unlicensed teenaged drivers were less likely to report seat belt use, more likely to report driving while under the influence of alcohol or drugs, and more likely to report more trips without a purpose. One fourth (28%) of them had taken a driver's education class, and one half (50%) reported parents as most helpful in learning to drive. Two thirds (66%) of the unlicensed drivers reported most often using a vehicle that others usually drive.

CONCLUSIONS. Considering the high burden of teen crashes, it is important to reach and deliver effective anticipatory guidance to unlicensed teenaged drivers who are at high risk for unsafe driving practices. Parents and driver's education instructors have contact with many of these unlicensed drivers. Clinicians, particularly those in rural and central city districts, should discuss unlicensed driving starting before the legal age of driving while screening for other health risk behaviors. Additional research is needed for better understanding of barriers to licensing among the teen population of licensing age.
Communication About Child Development During Well-Child Visits: Impact of Parents’ Evaluation of Developmental Status Screener With or Without an Informational Video
Authors: Sices Laura , Drotar Dennis , Keilman Ashley , Kirchner H. Lester , Roberts David , Stancin Terry
Published: October 2008

BACKGROUND. The American Academy of Pediatrics recommends periodic administration of standardized developmental screening instruments during well-child visits to facilitate timely identification of developmental delay. However, little is known about how parents and physicians communicate about child development or how screening impacts communication.

OBJECTIVE. Our goal was to examine whether parent-physician communication about child development is affected by (1) administration of a developmental screen or (2) video presentation on child development before well-child visits.

METHODS. Six primary care pediatricians in a practice serving predominantly Medicaid-insured children participated. Fifteen parents of children 9 to 31 months of age per pediatrician were assigned to 1 of 3 previsit conditions (n = 89): (1) usual care; (2) parent completed the Parents’ Evaluation of Developmental Status screen; or (3) parent viewed 5-minute “activation” video before completing the Parents’ Evaluation of Developmental Status. Visits were audiorecorded and coded by blinded raters using a classification system that assesses communication content. Outcomes included visit length, physicians’ questions, information giving, reassurance or counseling about development, and parents’ concerns and requests for developmentally related services.

RESULTS. Mean visit duration was similar for the 3 groups (22.5 minutes). Physicians made more information-giving and counseling statements about development and raised more developmental concerns in group 3 (video plus the Parents’ Evaluation of Developmental Status) than in group 1 (usual care) visits. A trend toward increased use of such communication was also seen in group 2 (Parents’ Evaluation of Developmental Status only). Parents were more likely to raise a developmental concern in group 3 than in group 1. No parent requested early intervention, therapy, or other related services.

CONCLUSIONS. Use of a validated screening test did not increase average visit duration, an important consideration in primary care. Although use of the Parents’ Evaluation of Developmental Status alone led to some increase in parent-physician communication about development and developmental concerns, additional increase in communication was seen with the addition of a brief parent activation video shown before the Parents’ Evaluation of Developmental Status was completed.
Sensitization to Human Milk
Authors: Huang Faith , Nowak-Wegrzyn Anna
Published: October 2008

Schulmeister U, Swoboda I, Quirce S, et al. Clin Exp Allergy. 2008;38(1):60–68

PURPOSE OF THE STUDY. To analyze the specificity and possible biological relevance of immunoglobulin E (IgE) reactivity to human milk antigens in milk-allergic patients.

STUDY POPULATION. Milk-allergic children and adults from different European countries with a positive case history, positive skin-prick reactions, and specific IgE to cow's milk extract were selected.

METHODS. The specificity of IgE reactivity to cow's milk and human milk antigens was analyzed with sera from milk-allergic children and adults by immunoblotting. IgE cross-reactivity between milk antigens was studied by immunoblot inhibition experiments. To demonstrate that IgE reactivity to human milk antigens is not caused by alloreactivity or transmission of foreign antigens, genetically unrelated mothers’ milk samples were analyzed before and after intake of dietary milk products. Skin-prick tests were performed with cow's, sheep's, mare's, and human milk samples.

RESULTS. IgE antibodies to human milk were found in >80% of the tested milk-allergic patients (n = 17). Cross-reactive IgE-reactive human antigens such as α-lactalbumin and non–cross-reactive human milk antigens were identified. Immunoblots showed IgE reactivity to antigens of the same molecular weights in each of the 4 milk samples from unrelated mothers. An immediate-type skin reaction could be elicited with human milk samples in 2 tested patients with IgE reactivity to human milk.

CONCLUSIONS. IgE reactivity to human milk in milk-allergic patients may be caused by cross-sensitization and genuine sensitization, causing allergic symptoms. Sensitization to human milk is common in milk-allergic patients and may require diagnostic testing and clinical monitoring.

REVIEWER COMMENTS. This is one of the first studies to have addressed the nature and biological relevance of IgE reactivity to human milk. The study demonstrated that sensitization to human milk is common in milk-allergic patients, but additional research is necessary, because it is unclear if patients with positive skin reactions suffered from clinically significant reactions to human milk. One may consider searching for the presence of IgE antibodies to human milk in children who have signs of allergy after breastfeeding. However, the benefits of breastfeeding, including its protective effect against early atopic diseases, must also be considered before advising dietary changes.
The Presence of Rhinovirus in Lower Airways of Patients With Bronchial Asthma
Authors: Williams Larry W.
Published: October 2008

Wos M, Sanak M, Soja J, Olechnowicz H, Busse WW, Szczeklik A. Am J Respir Crit Care Med. 2008;177(10):1082–1089

PURPOSE OF THE STUDY. To determine if there was identifiable rhinovirus in the bronchi of stable asthmatic subjects and whether there is a difference in the prevalence of bronchial rhinovirus in asthmatic subjects versus nonasthmatic controls.

STUDY POPULATION. Adult asthmatic subjects having bronchoscopy for clinical indications were enrolled if they had a forced expiratory volume in 1 second of <80% of predicted and had >12% improvement with bronchodilator or airway hyperreactivity to methacholine. Subjects must have had stable symptoms for at least 2 weeks and no upper airway infection in the previous 3 weeks. Control subjects were nonasthmatic patients who were undergoing diagnostic bronchoscopy for symptoms such as dyspnea, hemoptysis, or tumor or having lobectomy or pulmonectomy for tumor. Controls must not have had upper airway infection within 3 weeks.

METHODS. Mucosal biopsies and lung tissue samples were analyzed by immunohistochemical staining using monoclonal antibody to rhinovirus and by in situ reverse-transcription polymerase chain reaction to identify rhinoviral RNA.

RESULTS. Immunochemical staining showed rhinovirus in 64% (9 of 14) of the bronchial biopsies from asthmatic subjects and in 33% (2 of 6) of the controls. With the polymerase chain reaction method, 73% of biopsies from asthmatic subjects and 22% of the controls had evidence of rhinovirus RNA. Asthmatic subjects who tested positive for rhinovirus had worse pulmonary function and increased serum and tissue eosinophilia and increased tissue leukocytes compared with subjects in the virus-negative group.

CONCLUSIONS. Rhinovirus is more often present in the lower airways of asthmatic patients, and its presence is associated with worse lung function and increased eosinophilic inflammation.

REVIEWER COMMENTS. Traditional teaching has been that rhinovirus does not replicate at 37°C but instead only at the nasal temperature of 35°C. However, our local experience indicates that this may not be an absolute; we have followed an infant with severe combined immunodeficiency with persistent pulmonary infiltrates and respiratory failure who had only rhinovirus grow from bronchoscopy several times and from lung-biopsy tissue. In hosts with supposedly normal immune systems, this study is intriguing and provides a possible therapeutic opening if agents for enterovirus (which includes the rhinovirus group) are eventually available. The studied asthmatic subjects are not a representative population of asthmatic people, because they are a convenience sample with illness for which bronchoscopy was indicated, but the data certainly should stimulate further investigation in better characterized asthmatic people who do not otherwise have an indication for bronchoscopy.
Sensitization Does Not Develop In Utero
Authors: Turbyville Joseph C. , Mikita Cecilia P.
Published: October 2008

Bønnelykke K, Pipper CB, Bisgaard H. J Allergy Clin Immunol. 2008;121(3):646–651

PURPOSE OF THE STUDY. To investigate the relationship of allergen-specific immunoglobulin E (IgE) in cord blood to sensitization in early infancy and the origin of such IgE.

STUDY POPULATION. There were 243 children followed from birth. The patients were part of the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) and, thus, were considered to be at risk for atopy because of a maternal history of asthma.

METHODS. Cord blood IgE was determined at the time of birth and again at 6 months of age. Total IgE, specific IgE to milk and egg, and a cumulative level of specific IgE to a panel of common aeroallergens were analyzed and compared with maternal IgE. Cord blood IgA was also assessed as a marker of maternal contamination of fetal blood, because IgA is not thought to cross the placental barrier during pregnancy.

RESULTS. Specific IgE against mixed allergens was detected in 34 (14%) of the cord blood samples, and specific IgE against single allergens was detected in 22 samples. IgA was detected in 98% of the samples. None of the specific IgE found in cord blood was detected at 6 months of age. Cord blood IgE was not detected in any infants whose mothers were not sensitized, and the infants who did have cord blood IgE detected displayed a “fingerprint match” to maternal IgE. In every case, the IgE for a specific allergen detected in cord blood was the same as that detected in maternal blood, and it was present in a relatively similar concentration to that found in maternal blood. The cord blood IgA level also showed a linear relationship to the IgE level, suggesting that more maternal contamination resulted in higher IgE levels in cord blood.

CONCLUSIONS. IgE in cord blood does not reflect in utero sensitization but seems to reflect maternofetal transfer of IgE.

REVIEWER COMMENTS. The questions rarely change, but our answers often do. In recent years, the American Academy of Pediatrics recommended that some parents avoid certain foods during pregnancy to reduce the chance of their child developing atopic disease. These recommendations were based on studies that showed that the human fetus is capable of producing IgE as early as the 20th week of gestation and that cord blood IgE seemed to be a predictor of future atopy. Now the evidence seems to suggest that although sensitization could theoretically occur in utero, it simply does not. This study provides convincing evidence that the IgE in cord blood does not come from the infant but, rather, from the mixing of maternofetal blood, probably at the time of delivery. This study, along with other evidence that has come to light recently, raises questions about whether maternal dietary restriction of allergens during pregnancy impacts allergy outcomes to the avoided food/foods.
Breast-feeding Duration and Infant Atopic Manifestations, by Maternal Allergic Status, in the First 2 Years of Life (KOALA Study)
Authors: James John M.
Published: October 2008

Snijders BEP, Thijs C, Dagnelie PC, et al. J Pediatr. 2007;151(4):347–351

PURPOSE OF THE STUDY. To investigate the potential effect of modification by maternal allergic status on the relationship between breastfeeding duration and infant atopic manifestations in the first 2 years of life.

STUDY POPULATION. Data from 2705 infants of the KOALA Birth Cohort Study (Netherlands) were analyzed.

METHODS. The data were collected by repeated questionnaires at 34 weeks’ gestation and 3, 7, 12, and 24 months postpartum. Total and specific immunoglobulin E measurements were taken on venous blood samples collected during home visits when the infants were 2 years of age. Relationships were analyzed by using logistic regression analysis.

RESULTS. Longer duration of breastfeeding was associated with a lower risk for eczema in infants of mothers without allergy or asthma (Ptrend = .01) and slightly lower risk in those of mothers with allergy but no asthma (Ptrend = .14). There was no such association for asthmatic mothers (Ptrend = .87). Longer breastfeeding duration decreased the risk of recurrent wheeze independent of maternal allergy (Ptrend = .02) or asthma (Ptrend = .06) status.

CONCLUSIONS. The findings show that the relationship between breastfeeding and infant eczema in the first 2 years of life is modified by maternal allergic status. The protective effect of breastfeeding on recurrent wheeze may be associated with protection against respiratory infections.

REVIEWER COMMENTS. The role of diet in preventing and treating atopic disease has been and continues to be an active area of clinical research. Snijders et al found that a longer duration of breastfeeding was associated with a lower risk of eczema in infants of mothers without allergy or asthma. There was a slight effect in mothers with allergy but no asthma, yet no such relationship was observed for asthmatic mothers. It is interesting to note that no effect modification of maternal allergy/asthma on infant IgE or allergen sensitization was observed. Finally, longer breastfeeding reduced the risk of recurrent wheezing independent of maternal allergic or asthma status, which the authors speculated may be the effect of reduced numbers of respiratory infections. Overall, these findings do support the role of breastfeeding in prevention of atopy, and additional studies are needed to better define the influence of maternal and infant diets during this time frame.
Relationship of Body Mass Index With Asthma Indicators in Head Start Children
Authors: Goldsobel Alan B.
Published: October 2008

Vargas P, Perry T, Robles E, et al. Ann Allergy Asthma Immunol. 2007;99(1):22–28

PURPOSE OF THE STUDY. To examine the relationship of BMI and asthma in children in the Head Start program in Arkansas.

STUDY POPULATION. A group of 213 children aged 3 to 5 years with physician-diagnosed asthma were compared with 816 age-matched peer control subjects from the sample of the National Health and Nutrition Examination Survey (NHANES) and with 1024 children in prekindergarten in Arkansas public schools.

METHODS. Caregivers of the children with asthma from the Head Start program were interviewed with a structured questionnaire including the Juniper Asthma Quality of Life Survey, and the children's medical charts were reviewed. One hundred forty-one of the 213 children underwent skin-prick testing. One hundred forty-five of the children had urine cotinine levels measured to determine exposure to environmental tobacco smoke. These data were compared with the 2 reference groups in a cross-sectional analysis.

RESULTS. The prevalence of obesity (BMI > 95th percentile) was significantly higher in the Head Start children with asthma compared with the NHANES children (P < .001) and the prekindergarten children (P < .05). Compared with Head Start children with a BMI at <85th percentile, Head Start asthmatic patients with a BMI at >85th percentile reported significantly more school days missed, lifetime hospitalizations, emergency department visits, activity limitations, and oral corticosteroid bursts. No significant differences were observed in rescue and controller medications, environmental tobacco smoke exposure, prick-puncture allergy testing, quality of life, or nighttime symptoms.

CONCLUSIONS. Obesity (BMI > 95th percentile) was associated with increased asthma prevalence and morbidity. There was no association with the number or type of asthma medications or atopic status.

REVIEWER COMMENTS. This is another study showing the association of obesity and asthma. In this study, 18.8% of the Head Start children with asthma had a BMI at >95th percentile, compared with 10.8% of the NHANES and 14.4% of the prekindergarten general-population children. The mechanisms of association have not been clearly established. Both conditions are characterized by chronic inflammation.
Safety of Open Food Challenges in the Office Setting
Authors: Järvinen Kirsi M.
Published: October 2008

Mankad VS, Williams LW, Lee LA, LaBelle GS, Anstrom KJ, Burks AW. Ann Allergy Asthma Immunol. 2008;100(5):469–474

PURPOSE OF THE STUDY. To examine the safety of open food challenges (OFCs) administered in an office setting.

STUDY POPULATION. A total of 109 patients aged ≤18 years who underwent OFCs at the Duke University pediatric allergy-immunology clinic, excluding patients with a history of severe symptoms with previous reactions, were studied. Patient-selection criteria were based on the clinical history, results of skin-prick tests, and food-specific immunoglobulin E (IgE) levels that were much lower than those previously published levels predictive of a high likelihood of a clinical reaction.

METHODS. The authors performed a retrospective medical chart review of OFCs.

RESULTS. Among a total of 150 OFCs, most of which were to milk (n = 39), peanut (n = 37), and egg (n = 29), there were 40 positive test results (27% of all challenges) in 33 patients. Reactions were mild-to-moderate in 92% of the positive challenges. Cutaneous reactions occurred in 68% of the positive challenges, followed by gastrointestinal tract reactions (45%) and upper respiratory tract reactions (38%), excluding laryngeal symptoms. No patient had cardiovascular involvement, received epinephrine, or required hospitalization. Interventions included observation or antihistamine only for 92% of the positive challenges. Food-specific IgE values did not correlate with reaction severity. Of the 23 OFCs to milk, egg, and peanut without a history of clinical reactions, 8 were positive. For negative challenges, median prechallenge food-specific IgE levels approached previously published negative predictive values for these foods (1.22 kUA/L for milk, 0.96 kUA/L for peanut, and 0.65 kUA/L for egg). Negative challenge results for patients allowed the introduction of 19 different foods into the diets of 88 patients.

CONCLUSIONS. The authors concluded that OFCs are a safe procedure in the office setting for patients selected on the basis of food-specific IgE levels that approach negative predictive values and a lack of adverse reactions within the previous year.

REVIEWER COMMENTS. This nice report suggests that open OFCs performed by experienced practitioners in a clinic setting on carefully selected patients can be of significant benefit for patients who are tolerant to a food to avoid unnecessarily restrictive diets. Keeping in mind that the authors detected positive challenges in 4 patients with an undetectable food-specific IgE level and that there was a lack of association between the food-specific IgE level and severity of a reaction, prechallenge skin-prick tests and careful review of the clinical history should be used. Every challenge should be approached with appropriate precautions (emergency medications and equipment readily available) to treat potentially severe reactions.
Recognition, Clinical Diagnosis and Management of Patients With Primary Antibody Deficiencies: A Systematic Review
Authors: Bonilla Francisco A.
Published: October 2008

Wood P, Stanworth S, Burton J, et al. Clin Exp Immunol. 2007;149(3):410–423

PURPOSE OF THE STUDY. To create an evidence-based literature review of clinical diagnosis and management of primary antibody deficiency.

METHODS. Computer literature searches were conducted for randomized clinical trials in medical literature databases including the US National Library of Medicine (Medline), the Excerpta Medica database (EMBASE), the Cochrane Library, the Database of Abstracts of Reviews of Effects (DARE) of the Centre for Reviews and Dissemination (University of York), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) up to June 2006. Reports were rated on the basis of relevance and quality or type of evidence. Disease entities included were X-linked agammaglobulinemia, common variable immunodeficiency, hyper–immunoglobulin M (IgM) syndromes, IgG subclass deficiency with and without IgA deficiency, and specific antibody deficiency. Reports that involved only a limited number of patients were not included.

RESULTS. Individuals who present with recurrent respiratory infections of all types, especially with excessive frequency and severity, should be screened for antibody deficiency. In children, common associations included growth delay and failure to thrive, recurrent fevers without a source, and poor school attendance or performance. Chronic diarrhea was found in 40% to 60% of the patients at all ages. The median delay in diagnosis was 1 year but ranged to >10 years. Delayed diagnosis led to increased risk of bronchiectasis, pulmonary hypertension, and cor pulmonale. Randomized trials of the efficacy of γ-globulin replacement versus placebo do not currently exist. Many observational studies have confirmed the benefit of IgG therapy for reducing infectious morbidity. Higher IgG doses are associated with reduced incidence and severity of infections.

CONCLUSIONS. Delayed diagnosis was common as a result of lack of recognition of presenting symptoms and signs. Delay was less frequent when patients were referred to specialists. Delayed diagnosis led to delayed therapy (IgG) and a higher rate of infections and morbidity. Several areas for additional research were identified, including studies of efficacy and dose of IgG and adjunct therapies (antibiotics), microbiologic study of pathogens, identification of prognostic markers, and effective monitoring of disease (eg, lung function, other organs, cancer). Collaboration and pooling of data among centers nationally and internationally would likely lead to better data.

REVIEWER COMMENTS. This study again points out the human cost of delayed or undiagnosed immunodeficiency and the difficulties in accumulating high-quality data on therapy and outcomes. Several initiatives are taking shape in the United States and abroad to collaborate to answer many of the remaining questions pointed out in this study.