bluuebunny/crossref_metadata_2025 huggingface dataset:
Fish Consumption During the First Year of Life and Development of Allergic Diseases During Childhood
Authors: Jarvinen Kirsi M. , Sicherer Scott H.
Published: November 2007

Kull I, Bergström A, Lilja G, Pershagen G, Wickman M. Allergy. 2006;61:1009–1015

PURPOSE OF THE STUDY. To assess the association of fish consumption during the first year of life with development of allergic diseases by age 4.

STUDY POPULATION. A prospective birth cohort of 4089 newborn infants in Sweden.

METHODS. Parental questionnaires at child ages 2 months and 1, 2, and 4 years were administered to collect information on atopic heredity, diet, exposures, and allergic symptoms. When the children were 4 years old, a clinical investigation, including blood sampling for analysis of specific immunoglobulin E (IgE) to common inhalant and food allergens, was performed.

RESULTS. The mean age of introduction of fish in the child's diet was 8.3 months. History of parental allergic disease and onset of eczema or wheeze during the first year of life were associated with delayed introduction of fish in the child's diet. Regular fish consumption during the first year of life was associated with a reduced risk for allergic disease by age 4 (adjusted odds ratio: 0.76; 95% confidence interval: 0.61–0.94) and sensitization (adjusted odds ratio: 0.76; 95% confidence interval: 0.58–1.0) after exclusion of children with onset of eczema or wheeze during the first year of life to avoid disease-related modification of exposure. A dose-dependent reduced risk was observed for all outcomes (asthma, eczema, allergic rhinitis, and sensitization). IgE sensitization to fish was present in 18 of the 2614 children.

CONCLUSIONS. Regular fish consumption before the age of 1 seems to be associated with a reduced risk of allergic disease and sensitization to food and inhalant allergens during the first 4 years of life.

REVIEWER COMMENTS. In recent decades, a decrease in consumption of omega-3 polyunsaturated fatty acids, prevalent especially in oily fish, has been proposed to contribute to the increased prevalence of allergic diseases. The authors postulated that dietary polyunsaturated fatty acids might influence the development of allergic sensitization by increasing the formation of prostaglandin E2, which in turn promotes the formation of a T-helper 2 response and stimulates the formation of IgE. The authors attempted to control for the disease-related modification of exposure by excluding children with very early symptoms of eczema or recurrent wheeze. However, this attempt to control for “reverse causation” added limitation, because the most atopic infants were excluded. As the authors admitted, fish consumption in early life may be associated with a lifestyle that reduces the risk of allergic disease in nondietary ways. Nonetheless, the study presented an interesting observation given concerns about inducing allergy by introducing allergenic foods to infants.
Filaggrin Loss-of-Function Mutations Predispose to Phenotypes Involved in the Atopic March
Authors: Nowak-Wegrzyn Anna
Published: November 2007

Marenholz I, Nickel R, Rüschendorf F, et al. J Allergy Clin Immunol. 2006;118:866–871

PURPOSE OF THE STUDY. To assess the importance of filaggrin loss-of-function mutations in the susceptibility to eczema and associated clinical phenotypes.

STUDY POPULATION. Two large European populations including 1092 children with eczema.

METHODS. The filaggrin mutations were genotyped and tested for association with allergic disorders.

RESULTS. A highly significant association of the filaggrin null mutations with eczema and concomitant asthma was found. These mutations predisposed to asthma, allergic rhinitis, and allergic sensitization only in the presence of eczema. The presence of 2 filaggrin null alleles was an independent risk factor for asthma in children with eczema, and the 2 investigated mutations accounted for ∼11% of eczema cases in the German population.

CONCLUSIONS. These results support the role of filaggrin in the pathogenesis of eczema and in the subsequent progression along the atopic march. The fact that previous expression of eczema is a prerequisite for the manifestation of allergic airways disease and specific sensitization in a large subset of patients highlights the importance of the epidermal barrier in the pathogenesis of these disorders.

REVIEWER COMMENTS. The filaggrin gene encodes a structural protein that is essential for skin-barrier formation. Infants and children with atopic dermatitis are at high risk for developing additional atopic disorders, including food allergy, allergic rhinitis, and asthma. A disrupted skin barrier may be an important portal of entry for environmental and food allergens. In animal models, exposure through the skin predisposes to development of immunoglobulin E sensitization. Early intensive efforts to maintain and restore skin-barrier function may prevent subsequent development of allergic diseases and stop the progression of the atopic march.
Early Intervention of Recent Onset Mild Persistent Asthma in Children Aged Under 11 yrs: The Steroid Treatment As Regular Therapy in Early Asthma (START) Trial
Authors: Bailey Amy , Perry Tamara T.
Published: November 2007

Chen YZ, Busse WW, Pedersen S, Tan W, Lamm CJ, O’Byrne PM. Pediatr Allergy Immunol. 2006;17:7–13

PURPOSE OF THE STUDY. To determine the long-term efficacy of regular inhaled low-dose budesonide in children aged <11 years with recent-onset mild-persistent asthma.

STUDY POPULATION. Children aged 5 to 10 years with current symptoms of mild-persistent asthma during the 3 months preceding trial entry. Patients had no symptoms for >2 years before study entry and had received neither inhaled corticosteroids (ICSs) for ≥30 days nor depot corticosteroid injection in the previous year.

METHODS. Patients were randomly assigned to receive once-daily budesonide 200 μg (1000 children) or placebo (974 children). Patients were followed at weeks 6 and 12 and then subsequently every 3 months for a 3-year period. Patients and their caregivers kept a record of asthma symptoms between visits. At each visit, spirometry was performed, and data were collected on medication compliance and asthma control. The primary end point was the time to the first severe asthma-related event (SARE) or introduction of corticosteroid treatment other than the study medication.

RESULTS. There was a 40% relative-risk reduction of SAREs in the treatment group over the 3-year study visit. Fewer children in the budesonide group required treatment with other corticosteroids as compared with those in the placebo group (12.3% vs 22.7%). There was a trend toward decreased β2-agonist use, decreased systemic corticosteroid use, and improved lung function in the children in the treatment arm.

CONCLUSIONS. The early addition of once-daily budesonide treatment in young children with mild-persistent asthma improves asthma control and lung function and decreases the risk of SAREs.

REVIEWER COMMENTS. Early asthma intervention in children is a topic of much debate, particularly in the very young with mild symptoms. Oftentimes, caregivers are faced with the difficult task of deciding on the right time to initiate an ICS, and the decision may be delayed until a serious event such as hospitalization occurs. This study demonstrates the benefits of using an ICS as early intervention in children <11 years of age to improve lung function and decrease the risks of serious and potentially life-threatening asthma exacerbations. Unlike previous studies in pediatric populations with mild asthma, researchers with this study enrolled patients with relatively newly diagnosed asthma, perhaps before the onset of chronic irreversible inflammatory changes such as basement-membrane thickening. These findings support early intervention to improve lung function and to potentially prevent loss of lung function in hopes of improving long-term outcomes.
Home Environmental Intervention in Inner-City Asthma: A Randomized Controlled Clinical Trial
Authors: Skolnick Helen
Published: November 2007

Eggleston PA, Butz A, Rand C, et al. Ann Allergy Asthma Immunol. 2005;95:518–524

PURPOSE OF THE STUDY. To conduct a randomized, controlled clinical trial to test the efficacy of home-based methods to reduce environmental pollutants and allergen exposure in the homes of asthmatic children living in an inner city.

STUDY POPULATION. One hundred asthmatic children, ranging in age from 6 to 12 years, with physician-diagnosed asthma, current asthma symptoms, and no other chronic lung disease.

METHODS. The families were randomly assigned to a treatment group that received intervention immediately (home-based education, cockroach and rodent extermination, mattress and pillow encasings, and a high-efficiency particulate air cleaner) or to a control group that received intervention at the end of the 1-year trial. In the treatment group, 84% received cockroach extermination, 70% received mouse extermination, and 75% used the air cleaner. Outcomes were evaluated against baseline by home evaluation at 6 and 12 months, clinical evaluation at 12 months, and multiple telephone interviews.

RESULTS. Home particulate concentrations were lower at both 6 and 12 months in the treatment group. Home levels of particulate matter ≤10 μm declined by up to 39% in the treatment group as compared with an increase in the control group (P < .001), and cockroach-allergen levels decreased by 51% in the treatment group (P = .04). The proportion of symptomatic children increased in the control group and decreased in the treatment group, with significant differences seen at 6 months and later. In addition, children in the treatment group were significantly less likely to report daytime symptoms during the first 9 months compared with those in the control group. However, the mean difference in daytime symptoms over 12 months was only marginally significant (P = .07). Other measures of participant morbidity, such as nighttime symptoms, emergency department use, and spirometry findings, were not significantly changed during the study period.

CONCLUSIONS. A tailored program of environmental and behavioral interventions to reduce indoor particulate matter and other relevant allergen levels in low-income, inner-city homes had a modest effect on asthma morbidity.

REVIEWER COMMENTS. It is interesting to note that few of the 69% of the households with smokers in them changed smoking habits. Most likely, the environmental-control measures outlined in this article, implemented as part of a more comprehensive treatment plan including smoking cessation, could contribute more significantly to symptom reduction.
Intermittent Inhaled Corticosteroids in Infants With Episodic Wheezing
Authors: Chipps Bradley E.
Published: November 2007

Bisgaard H, Hermansen MN, Loland L, Halkjaer LB, Buchvald F. N Engl J Med. 2006;354:1998–2005

PURPOSE OF THE STUDY. To determine the effectiveness of inhaled corticosteroid (ICS) in the treatment of wheezing in infants and if early ICS treatment will delay or prevent progression to persistent asthma.

STUDY POPULATION. Pregnant women (N = 798) with the diagnosis of asthma were enrolled onto a cohort study in Denmark. There were 411 newborns enrolled by 1 month of age.

METHODS. The patients were randomly assigned to ICS or placebo with their first episode of wheezing at a median of 10.7 months. Treatment with budesonide 400 μg per day with a spacer or placebo with spacer was begun after the third day of the first wheezing episode and continued for at least 2 weeks. Terbutaline with the same delivery system was provided for as-needed use. Symptoms and β-agonist use were recorded daily for the 3 years of the study. One-hour study visits were conducted every 6 months. Nasal aspirates for viral culture and infant lung-function tests were monitored.

RESULTS. A total of 294 infants had at least 1 treatment with a total of 1661 episodes (577 episodes were not verified by an investigator). During the entire study, 83% of the ICS and 82% of the placebo days were symptom free. Twenty-four percent of the patients who received ICS and 21% who received placebo developed persistent symptoms. A respiratory virus was isolated in 369 (63%) of 583 episodes, but there was no relation to treatment outcome. Over the 3 years of the study, growth and bone mineral density (ultrasound technique) were not different in the groups.

CONCLUSIONS. Early intervention with ICS did not effect the duration of acute illnesses or progression to persistent disease.

REVIEWER COMMENTS. The results of this very important study were confounded by the effect of delaying 3 days to initiate therapy, the unclear efficacy of the delivery system, and that 40% of the events were not confirmed by the investigators.
Environmental Risk Factors of Rhinitis in Early Infancy
Authors: Kloepfer Kirsten , Perry Tamara T.
Published: November 2007

Bagini JM, LeMasters GK, Ryan PH, et al. Pediatr Allergy Immunol. 2006:17:278–284

PURPOSE OF THE STUDY. To examine the impact of environmental tobacco smoke (ETS) and visible mold exposure on the development of allergic rhinitis, rhinitis, and upper respiratory infection (URI) in early infancy.

STUDY POPULATION. Six hundred thirty-three infants ≥35 weeks’ gestation with at least 1 parent who had 1 of 12 selected allergy symptoms and a positive skin-prick–test result to at least 1 of 15 aeroallergens.

METHODS. The child's birth certificate and a questionnaire format were used to collect demographic data and information on family smoking habits, family health history, pet ownership, day care attendance, breastfeeding, and the infants’ respiratory health history from birth to the time of enrollment. Parents were asked to complete monthly diaries to collect information on their child's upper respiratory symptoms. They must have completed 1 diary before the child's 12-month clinical examination. Allergic rhinitis was defined as having rhinitis symptoms not associated with a cold or chest infection at least once on any diary and a positive skin-prick–test result to ≥1 aeroallergen at the 12-month visit. Study personnel examined the home for mold exposure within 3 weeks of study enrollment.

RESULTS. Infants were nearly 3 times more likely to have allergic rhinitis at 12 months of age (odds ratio [OR]: 2.7; 95% confidence interval [CI]: 1.04–6.8) and twice as likely to have rhinitis (OR: 1.9; 95% CI: 1.1–3.2) when exposed to ≥20 cigarettes per day. Infants were 5 times more likely (OR: 5.1; 95% CI: 2.2–12) to have frequent URIs when exposed to high mold levels. Having older siblings was protective for development of rhinitis and allergic rhinitis at age 1.

CONCLUSIONS. ETS exposure is associated with rhinitis and allergic rhinitis in infants. Mold may be a stronger risk factor for URI than ETS.

REVIEWER COMMENTS. This is one of very few studies to have examined the relevance of home exposures in the first year of life and demonstrated that early environmental exposures likely play a significant role in respiratory health outcomes in infancy. One weakness of the study was the fact that ETS exposure and URI and rhinitis symptoms were collected by parental report and may be subject to significant recall bias or erroneous reporting. Nevertheless, these findings support the need for further research in the areas of early environmental-exposure interventions and the role of gene-environment interactions that affect respiratory health outcomes.
Immune Reconstitution Syndrome After Highly Active Antiretroviral Therapy in Human Immunodeficiency Virus-Infected Thai Children
Authors: Church Joseph A.
Published: November 2007

Puthanakit T, Oberdorfer P, Akarathum N, Wannarit P, Sirisanthana T, Sirisanthana V. Pediatr Infect Dis J. 2006;25:53–58

PURPOSE OF THE STUDY. Immune reconstitution inflammatory syndrome (IRIS) is a clinical phenomenon characterized by paradoxical worsening of the clinical status of patients with HIV who receive highly active antiretroviral therapy. It is presumed that this is a result of improvement in cellular immune functions and secondary immunopathology in response to organisms that had not been recognized previously. This syndrome has been well described in adult patients. The purpose of this study was to describe IRIS after initiation of highly active antiretroviral therapy in HIV-infected children.

STUDY POPULATION AND METHODS. There were 153 HIV-infected children enrolled at initiation of antiretroviral therapy and then followed prospectively.

RESULTS. Of the 153 children, 29 (19%) experienced 32 episodes of IRIS. The median time of onset was 4 weeks after initiation of antiretroviral therapy. Fourteen episodes were caused by mycobacterial organisms, 7 by varicella-zoster virus, 7 by herpes simplex virus, 3 by Cryptococcus neoformans, and 1 by Guillain-Barré syndrome. In general, treatment was not interrupted, and only 2 patients were treated with short courses of corticosteroids. However, 3 patients died as a result of IRIS or its complications. It is important to note that patients who reactivated mycobacterial disease had substantially lower CD4+ T-cell counts at the time that their antiretroviral therapy was started, compared with patients who reactivated herpes viruses.

CONCLUSIONS. IRIS is common among HIV-infected children who initiated antiretroviral therapy in an advanced stage of HIV disease.

REVIEWER COMMENTS. Ideally, this type of experience will become less common as patients have access to antiretroviral therapy before profound immunosuppression. However, we had a recent experience with a nonadherent teenager who, after developing disseminated Mycobacterium avium complex, decided to take his medication; a serious IRIS picture developed with persistent high-grade fever, severe abdominal pain, and dramatic intraabdominal adenopathy. Symptoms resolved rapidly with initiation of corticosteroid therapy. The challenge in such patients is to balance the management of their underlying HIV disease, their complicating opportunistic infection, and their immunosuppression to allow for resolution of the infection, reconstitution of immune function, and reduction in the complexity of their treatment regimen.
Upregulation of PD-1 Expression on HIV-Specific CD8+ T Cells Leads to Reversible Immune Dysfunction
Authors: Church Joseph A.
Published: November 2007

Trautmann L, Janbazian L, Chomont N, et al. Nat Med. 2006;12:1198–1202

PURPOSE OF THE STUDIES. Recent evidence from a mouse model of chronic viral infection suggests a crucial role for the programmed death 1 (PD-1)/programmed death 1 ligand (PD-L1) signaling pathway in downregulating the functions of virus-specific CD8+ T cells. PD-1 is an inhibiting receptor that negatively regulates activated T cells, and it is markedly upregulated on the surface of “exhausted” virus-specific CD8+ T cells in mice. HIV similarly induces a virus-specific impairment of T-cell functions. The purpose of these 2 studies was to investigate the expression of PD-1 on HIV-specific T cell in patients infected with the virus.

STUDY POPULATION AND METHODS. Both studies evaluated subjects with HIV and healthy controls and compared PD-1 expression in these individuals on virus-specific T cells. A panel of MHC class I tetramers were used to identify HIV-specific CD8+ T cells. PD-1 expression was then measured on tetramer-positive cells. PD-1 expression was also analyzed on cytomegalovirus-specific, Epstein-Barr virus–specific, and vaccinia virus–specific CD8+ T cells from HIV-negative controls.

RESULTS. The findings in these studies were remarkably similar. PD-1 was significantly upregulated on HIV-specific T cells, and expression correlated with impaired HIV-specific CD8+ T-cell function as well as predictors of disease progression: HIV viral load, a reduced capacity for cytokine production, and decreased proliferation of HIV-specific CD8+ T cells. Cytomegalovirus-specific CD8+ T cells from the same donors did not upregulate PD-1 and seemed to maintain functional integrity. Blockade of the PD-1/PD-1L pathway result reversed immune dysfunction.

CONCLUSIONS. The PD-1/PD-1L pathway is associated with significant HIV-specific T-cell exhaustion. The accumulation of HIV-specific dysfunctional T cells in an infected host may prevent the renewal of a functionally competent HIV-specific CD8+ T-cell response.

REVIEWER COMMENTS. HIV has proven remarkably adept at inhibiting the very system that evolved to control it. Expression of a negative regulator of activated T cells, PD-1, is markedly increased on HIV-specific CD8+ T cells when HIV engages the T-cell receptor. Such T cells have been termed “exhausted” because they fail to respond as fully activated effector cytotoxic T cells. Surprisingly, blockade of PD-1 engagement with its ligand results in a restoration of T-cell function. This observation suggests a target for enhancing the function of exhausted T cells in HIV-infected individuals. However, much has to be learned about the importance of this pathway in the control of normal T-cell activation. T-cell activation seems to be an intrinsic component of HIV pathogenesis; therefore, blocking this activation may be useful. However, it would be potentially dangerous to be unable to turn off an activated immune response to a routine infection.
Potent Antiretroviral Effect of MK-0518, a Novel HIV-1 Integrase Inhibitor, in Patients With Triple-Class Resistant Virus
Authors: Church Joseph A.
Published: November 2007

Grinsztejn B, Nguyen BY, Katlama C, et al. Presented at: the 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 27–30, 2006; San Francisco, CA. Abstract H-16706

PURPOSE OF THE STUDY. Although there are >20 antiretroviral agents available in developed countries, multiple factors limit the construction of combinations of drugs that are capable of effective viral suppression. New agents are clearly needed, particularly for individuals with limited options. MK-0518 is a member of a new class of antiretroviral agents, integrase inhibitors. The purpose of this study was to generate preliminary information on the potency of MK-0518 in the treatment of individuals with triple-class–resistant virus.

STUDY POPULATION AND METHODS. There were 178 HIV-infected patients enrolled and assigned to 1 of 3 doses of MK-0518 or placebo. They were followed for 24 weeks, and antiretroviral responses were evaluated.

RESULTS. MK-0518 showed remarkable potency at all doses tested. Approximately 60% of the patients who received active drug achieved <50 copies per mL of plasma HIV RNA. Strikingly, ∼50% of the individuals with no active agent left in their background regimens achieved undetectable viral loads. MK-0518 was generally well tolerated at all doses, with headache being the most frequent adverse effect.

CONCLUSIONS. MK-0518 had remarkable potent antiretroviral activity in individuals with limited treatment options. The availability of this new class of antiretroviral drug will markedly enhance the options available for patients who are running out of options.

REVIEWER COMMENTS. Abstracts presented at scientific meetings are usually not appropriate for a “best-articles-published” series. However, the impact of MK-0518 will be extraordinary. With 3 additional new drugs recently or soon to be available, we will soon have the ability to “salvage” patients with multiresistant virus.
Reduced Lung Function at Birth and the Risk of Asthma at 10 Years of Age
Authors: Yu Joyce E. , Sicherer Scott H.
Published: November 2007

Håland G, Carlsen KC, Sandvik L, et al. N Engl J Med. 2006;355:1682–1689

PURPOSE OF THE STUDY. To evaluate whether reduced lung function at birth predicts the development of asthma and markers of obstructive airway diseases by 10 years of age.

STUDY POPULATION. A prospective cohort of 616 10-year-old Norwegian children from the Environmental and Childhood Asthma (ECA) study who were initially enrolled as healthy term infants and had undergone lung-function testing and passive respiratory mechanics evaluation shortly after birth.

METHODS. Lung function at birth was measured by calculating the fraction of time to peak expiratory flow to total expiratory time (tPTEF/tE) on the basis of tidal breathing flow-volume loops. Respiratory mechanics at birth were assessed by calculating respiratory system compliance and resistance during passive maneuvers. Data at the 10-year follow-up were collected during 2 clinical visits including forced expiratory flow-volume loops, methacholine-challenge tests, a treadmill exercise test, and skin-prick testing for common inhalant and food allergens. Parents also completed a validated International Study of Asthma and Allergies in Childhood questionnaire on airway symptoms, asthma-medication use, and previous physician-diagnosed asthma. The follow-up assessments and interviews were blinded with regard to the lung-function measurements at birth.

RESULTS. In this cohort, the prevalence of a history of asthma was 20.2%, and prevalence of current asthma was 11.1%. Children with a tPTEF/tE at or below the median at birth were more likely at 10 years of age to have a history of asthma (24.3% vs 16.2%; P = .01), current asthma (14.6% vs 7.5%; P = .005), severe bronchial hyperresponsiveness (9.1% vs 4.9%; P = .05), and inhaled corticosteroid use (5.9% vs 2.4%; P = .02). Children with respiratory system compliance at or below the median were more likely to have a history of asthma (27.4% vs 14.8%; P = .001) and current asthma (15.0% vs 7.7%; P = .009). Decreased lung-function measurements did not consistently correlate with percent predicted forced flow-volume loops and exercise testing.

CONCLUSIONS. Reduced lung function at birth may be a risk factor for the development of asthma by 10 years of age.

REVIEWER COMMENTS. Other studies to date have shown that infants with reduced lung function have an increased risk for wheezing and asthma in the first few years of life. This study suggests that measuring lung function at birth may be useful in predicting which infants will develop asthma by late childhood. Knowing these risks may allow for directed therapy and prevention.
High-Dose Inhaled Fluticasone Does Not Replace Oral Prednisolone in Children With Mild to Moderate Acute Asthma
Authors: Virnig Christine , Moss Mark H.
Published: November 2007

Schuh S, Dick PT, Stephens D, et al. Pediatrics. 2006;118:644–650

PURPOSE OF THE STUDY. To evaluate whether there is a significant difference in the degree of impairment in forced expiratory volume at 1 second (FEV1) in children with mild-to-moderate acute asthma treated with either inhaled fluticasone or oral prednisolone.

STUDY POPULATION. Sixty-nine children aged 5 to 17 years with a previous history of wheezing who presented to a tertiary care pediatric emergency department (ED) with acute asthma and an FEV1 between 50% and 79% predicted.

METHODS. This randomized, double-blind, double-dummy trial randomly assigned patients to receive either 2 mg of fluticasone via metered-dose inhaler (MDI) in the ED along with 500 μg of fluticasone via Diskus twice daily for 5 days (n = 35) or 2 mg/kg oral prednisolone in the ED along with 1 mg/kg prednisolone once daily for 5 days (n = 34). All children received scheduled, nebulized albuterol and ipratropium bromide in the ED and were given scheduled salmeterol and rescue albuterol on ED discharge. FEV1 was measured at baseline, 4 hours, and 48 hours.

RESULTS. At 4 hours, the patients in the prednisolone group had a significantly greater increase in FEV1 (29.8% ± 15.5%) compared with those in the fluticasone group (19.1% ± 12.7%; P = .001). By 48 hours, the difference in FEV1 between the groups was no longer statistically significant. In addition, the number of unscheduled asthma visits by 48 hours after ED discharge was significantly greater in the fluticasone group (4 of 32) than the prednisolone group (0 of 34).

CONCLUSIONS. Children with mild-to-moderate acute asthma improve faster on oral prednisolone than inhaled fluticasone.

REVIEWER COMMENTS. Systemic corticosteroids are both historically and currently the mainstay treatment for acute asthma, given their ability to reduce hospitalizations, decrease relapses, regain asthma control, and improve lung function. However, the risks associated with the frequent use of oral corticosteroids have led researchers to search for an alternative treatment for acute asthma. Although previous studies have shown oral corticosteroids to be superior to inhaled steroids in severe acute asthma, the question remains as to whether inhaled corticosteroids could be used in mild and moderate asthma exacerbations. This study addressed this question and determined that oral corticosteroids are superior to inhaled steroids, even for mild exacerbations of asthma, in regard to relapse rate and time to FEV1 improvement. These findings support the current use of oral steroids for treatment of mild-to-moderate acute asthma.
A Prospective Controlled Study of Neurodevelopment in HIV-Uninfected Children Exposed to Combination Antiretroviral Drugs in Pregnancy
Authors: Church Joseph A.
Published: November 2007

Alimenti A, Forbes JC, Oberlander TF, et al. Pediatrics. 2006;118(4). Available at: www.pediatrics.org/cgi/content/full/118/4/e1139

PURPOSE OF THE STUDY. The effective treatment of HIV-infected women with antiretroviral agents has dramatically reduced the incidence of HIV infection in their newborn infants. However, an ongoing concern has been the potential adverse effects of the antiretroviral agents themselves on the neurodevelopment of HIV-uninfected children who were exposed to combination HIV medications. The purpose of this study was to investigate the neurodevelopment of HIV-infected children exposed to combination anti-HIV therapy in pregnancy compared with children not exposed to this therapy.

STUDY POPULATION. A total of 39 antiretroviral therapy–exposed and 24 control children were assessed.

METHODS. This was a prospective, controlled, cross-sectional study. The Bailey Scales of Infant Development and Vineland Adaptive Behavior scales were performed at 18 to 36 months of age. Control children were born to HIV-uninfected women with similar anticipated social and economic backgrounds. Results were compared by using analysis of covariance and χ2 analysis.

RESULTS. All scores were lower for children who were exposed prenatally to antiretroviral therapy. However, when maternal substance use during pregnancy was controlled for, there were no significant differences between the groups in any of the domains assessed. Children in both groups who were exposed to maternal substance use scored significantly lower in most domains than children who were not exposed.

CONCLUSIONS. HIV and antiretroviral therapy–exposed HIV-uninfected children had lower development and adaptive behavior scores compared with children who were not exposed to HIV or anti-HIV drugs. It is important to note that these differences were not significant when maternal substance use was considered. In this prospective study, exposure to perinatal anti-HIV therapy was not associated with neurodevelopmental abnormalities.

REVIEWER COMMENTS. This small study demonstrated that maternal substance use impacted the neurodevelopment of children to a far greater extent than exposure to anti-HIV drugs. In this study, at least, any negative impact of antiretroviral drugs on infant neurodevelopment was masked by the maternal substance use. This is not to say that exposure to combination anti-HIV medications may not have an impact on childhood development. Studies with similar designs to this one, in larger numbers of children for whom maternal substance use is not a confounding factor, will be required to address this issue fully.
Enabling Parents Who Smoke to Prevent Their Children From Initiating Smoking: Results From a 3-Year Intervention Evaluation
Authors: Smart Brian A.
Published: November 2007

Jackson C, Dickinson D. Arch Pediatr Adolesc Med. 2006;160:56–62

PURPOSE OF THE STUDY. To evaluate effects of a home-based antismoking socialization program on the initiation of smoking among children whose parents smoke.

STUDY POPULATION. Parents who were current smokers and had a third-grader who had not tried smoking were eligible. The study included 776 children who completed an interview 3 years after initial randomization of 873 parent-child pairs; 371 were in the intervention group, and 405 were in the control group.

METHODS. This was a 3-year randomized, controlled trial. During 3 months, the intervention group received 5 printed activity guides, parenting tip sheets, child newsletters, and incentives. One year later, this group also received a booster activity guide. The control group only received fact sheets about smoking.

RESULTS. Initiation of smoking was reported by 19% of children in the control group versus 12% of those in the intervention group (adjusted odds ratio: 2.16; P < .001).

CONCLUSIONS. Children in the preinitiation phase of smoking who receive antismoking socialization from their parents are less likely to initiate smoking, even if their parents smoke. The authors defined antismoking socialization as internalization of attitudinal and behavioral norms against initiation of smoking, acceptance of parental monitoring of access to cigarettes and affiliation with peers who have tried smoking, expectations of negative consequences for trying smoking, and expectations of positive consequences for not smoking, which is much more than simply telling children that they should not smoke.

REVIEWER COMMENTS. This study is remarkable in that it demonstrated that, contrary to the “common-sense” view that parents who smoke can do little to discourage smoking by their children, active antismoking socialization, even by parents who smoke, can significantly reduce rates of smoking by their children.
Lung Function and Exercise Capacity in Young Adults Born Prematurely
Authors: Mahr Todd A.
Published: November 2007

Vrijlandt EJ, Gerritsen J, Boezen HM, Grevink RG, Duiverman EJ. Am J Respir Crit Care Med. 2006;173:890–896

PURPOSE OF THE STUDY. To determine long-term effects of prematurity on lung function (volumes, diffusing capacity) and exercise capacity in ex-preterm infants compared with healthy peers.

STUDY POPULATION. Preterm participants (n = 42) and healthy term controls (n = 48) were recruited for lung-function and exercise tests.

METHODS. Part of a prospective nationwide Dutch study, children born in 1983 with a gestational age of <32 weeks and/or a birth weight under 1500 g were followed up to 19 years of age. Measurements included spirometry, diffusing capacity (DLco), and bicycle ergometer test.

RESULTS. Most lung-function measurements were within the reference ranges for both groups. Preterm birth was associated with lower forced expiratory volume in 1 second (preterm infants: 95% predicted; controls: 110% predicted) and DLcosb, single breath corrected for hemoglobin (88% predicted vs 96% predicted compared with control subjects at follow-up). Exercise capacity was 15% lower in ex-preterm infants than in control subjects. The anaerobic threshold, maximum minute ventilation, and maximum heart rate as percentage predicted were significantly lower in ex-preterm infants compared with control subjects.

CONCLUSIONS. Long-term effects of prematurity were airway obstruction and a lower diffusing capacity compared with control subjects, although mean lung-function parameters were within the reference ranges. Ex-preterm infants had a lower exercise level, which could not be explained by impaired lung function or smoking habits but might be a result of impaired physical fitness.

REVIEWER COMMENTS. We all see ex-preterm patients in our practices, and there have been conflicting data on lung function as adolescents. No previous studies on exercise capacity have been performed. Without the control group included, one could have concluded that almost all participants had lung-function measurements within the reference ranges. Ex-preterm infants reported fewer hours of exercise per week than the control subjects, which might explain their lower level of physical fitness. Diminished exercise capacity did not seem to be a result of impaired lung function or limited ventilation. We might want to encourage all children who were born prematurely to participate in more physical activity and sports at an early age, because this might possibly improve the exercise performance of those in this group.
CCR5 Deficiency Increases Risk of Symptomatic West Nile Virus Infection
Authors: Church Joseph A.
Published: November 2007

Glass WG, McDermont DH, Lim JK, et al. J Exp Med. 2006;203:35–40

PURPOSE OF THE STUDY. Chemokine receptor 5 (CCR5) is critical for survival of mice infected with West Nile virus (WNV). CCR5Δ32 is a defective CCR5 found predominantly in white individuals. Approximately 1% of the white population in the United States have homozygous CCR5Δ32 and completely lack CCR5 function. Individuals with CCR5Δ32 have an innate resistance to infection with HIV, because most HIV that is transmitted sexually or perinatally uses the CCR5 as a coreceptor with CD4 for HIV attachment to target cells. CCR5 inhibitors are in development, because most individuals with homozygous CCR5Δ32 seem to be immunologically normal. The purpose of this study was to determine if the presence of CCR5Δ32 homozygosity increases the risk for symptomatic WNV infection.

STUDY POPULATION AND METHODS. Three cohorts of patients were studied: 2 WNV-positive and 1 WNV-negative but with symptomatic illness in which WNV was considered. Genotypes of CCR5 were defined for each subject in the 3 cohorts.

RESULTS. In the group of healthy white random blood donors, CCR5Δ32 homozygotes represented 1% of the total. In contrast, CCR5Δ32 homozygotes represented over 4% of white subjects in the one WNV cohort and 8% in the second cohort. CCR5Δ32 homozygosity was significantly associated with fatal outcome in one of the cohorts.

CONCLUSIONS. The authors concluded that CCR5 mediates resistance to symptomatic West Nile infection.

REVIEWER COMMENTS. The immune system has evolved over the millennia to provide generally protective functions for the human host. That a particular chemokine receptor was maintained throughout this evolutionary process suggests a survival advantage. One percent of the white population in the United States have a genotype that eliminates functional CCR5. This mutation emerged in northern Europe and probably had no significant negative impact on that population. However, it seems that host defense against WNV depends on sufficient CCR5 engagement. CCR5 blockade is an emerging strategy in the treatment of HIV infection. It is possible that blockade of CCR5 will subsequently result in an increase risk for invasive WNV infection. If the CCR5 inhibitors continue through development, this potential complication must be anticipated.
Association of Indoor Nitrogen Dioxide Exposure With Respiratory Symptoms in Children With Asthma
Authors: Railey Mary Dell , Laubach Susan S. , Williams Larry W.
Published: November 2007

Belanger K, Gent JF, Triche EW, Bracken MB, Leaderer BP. Am J Respir Crit Care Med. 2006;173:297–303

PURPOSE OF THE STUDY. Chronic exposure to indoor nitrogen dioxide (NO2) may be a public health concern. The primary source of residential NO2 is gas-fueled cooking appliances. The authors’ objective was to examine associations of indoor NO2 exposure with respiratory symptoms among children with known asthma.

STUDY POPULATION. Subjects were 728 children younger than 12 years with physician-diagnosed asthma living in Connecticut and southwest Massachusetts. All children had active asthma and had lived at the same address for at least 2 months before NO2 sampling.

METHODS. At enrollment, a research assistant visited the home and recorded family ethnicity, housing characteristics (multifamily versus single family, number of rooms, water leaks, visible mold), presence of smoking in the home, and the use of household appliances fueled by natural gas. Mothers were also asked about number of days of respiratory symptoms experienced by the child and medications used for each month of the previous year. NO2 was measured in each home by using a Palmes tube placed in the main living area for 10 to 14 days after the enrollment visit.

RESULTS. The mean concentration of indoor NO2 was 8.6 ppb in homes with electric ranges and 25.9 ppb in homes with gas stoves. The mean NO2 level measured in multifamily homes was 22.9 ppb, and the mean NO2 level in single-family homes was 10.2 ppb. Measured NO2 (>20 ppb) was associated with ethnicity: white families were least likely to have high exposures, and Hispanic families were the most likely. Among children living in multifamily housing, exposure to gas stoves and high levels of NO2 were associated with wheezing, shortness of breath, and chest tightness. For children in single-family homes, neither exposure to gas stoves nor to measured NO2 was associated with any respiratory symptom.

CONCLUSIONS. The authors concluded that there is an association between exposure to high levels of indoor NO2 and respiratory symptoms in children with physician-diagnosed asthma. This association, however, was limited to children who lived in multifamily homes, probably because of the smaller size (and air volume) of the apartments. The authors also suggested a strong association of NO2 exposure with housing characteristics, lower socioeconomic status, and ethnicity.

REVIEWER COMMENTS. This study demonstrated an association between increased NO2 levels and asthma symptoms of children in multifamily homes. The important potential confounders in the analysis should have been adequately dealt with in the logistic regression analysis used. The biological basis of the association is poorly understood, and the value of intervention to reduce exposure is speculative. Additional studies will be needed to clarify and confirm the association.
Cost of Influenza Hospitalization at a Tertiary Care Children's Hospital and Its Impact on the Cost-Benefit Analysis of the Recommendation for Universal Influenza Immunization in Children Age 6 to 23 Months
Authors: James John M.
Published: November 2007

Hall JL, Katz BZ. J Pediatr. 2005;147:807–811

PURPOSE OF THE STUDY. To calculate the costs of influenza hospitalization at a tertiary care children's hospital as the basis of a cost/benefit analysis of the new influenza vaccine recommendation for children 6 to 23 months old.

STUDY DESIGN. The investigators reviewed the medical charts of all patients diagnosed with influenza and admitted to Children's Memorial Hospital in Chicago, Illinois, in 2002. Total hospital costs were obtained from the business development office.

RESULTS. Thirty-five charts were analyzed. Both of the 2 patients who required mechanical ventilation and 4 of the 6 patients admitted to the ICU had high-risk underlying medical conditions. Nine children were 6 to 23 months old; 4 of these 9 had no preexisting medical conditions. Had all 18 high-risk children over 6 months old been protected from influenza, approximately $350 000 in hospital charges could have been saved.

CONCLUSIONS. Preventing the additional 4 hospitalizations in the otherwise low-risk children 6 to 23 months old for whom vaccine was currently recommended would have cost approximately $281 000 ($46 per child) more than the hospital charges saved. When all children 6 to 23 months old were considered, influenza vaccination would have been less costly than other prophylactic measures. Addition of indirect costs, deaths, outpatient costs, and the cost of secondary cases would favor the cost/benefit ratio for influenza vaccination of all children 6 to 23 months old.

REVIEWER COMMENTS. A few years ago when recommendations were made to immunize all children 6 to 23 months of age with the influenza vaccine, they were not initially accepted with open arms because of an already-busy infant-immunization schedule. This article provided interesting data regarding actual charges of hospitalization for care of children with influenza. Analyzing the ages and underlying medical conditions of these children, as well as using conservative estimates of vaccine efficacy and only direct costs of hospitalization, the investigators predicted substantial cost savings from vaccinating children with underlying medical conditions and modest spending ($46 per child) when vaccinating healthy children 6 through 23 months of age. Recognized limitations of the investigation included extrapolation of findings from a tertiary care center and underrepresentation of children without underlying conditions. Hopefully, in the future, we will have more data such as these that will be useful in assessing the cost/benefit ratio of influenza vaccination recommendations in pediatric patients.
Carbon in Airway Macrophages and Lung Function in Children
Authors: Chipps Bradley E.
Published: November 2007

Kulkarni N, Pierse N, Rushton L, Grigg J. N Engl J Med. 2006;355:21–30

PURPOSE OF THE STUDY. To define the extent of pulmonary-function abnormalities that may be attributed to exposures to particulate matter with a median aerodynamic diameter of <10 μm (PM10) as a result of fossil fuel combustion.

STUDY POPULATION. The study included 114 children (aged 8 to 15 years) without any chronic respiratory condition who were living in the same residence for 1 year. All children had a forced expiratory volume in 1 second (FEV1) of >80% predicted.

METHODS. Pulmonary-function testing and induced sputum were obtained on the same day. PM10 values from all sources were collected for 1 year. The results were controlled for passive tobacco-smoke exposure.

RESULTS. A total of 62 (56%) of the 114 subjects were able to produce sputum. An increase of 1 μg/m3 in PM10 was associated with an increase of 0.10 μm2 in the carbon content of airway macrophages. Each 1.0 μm2 increase in carbon content was associated with a significant decrease in pulmonary function (decrease of 17% in FEV1, 12.9% in forced vital capacity, and 34.7% in forced expiratory flow, midexpiratory phase).

CONCLUSIONS. A significant reduction in pulmonary function resulted from increased exposure to products of fossil fuel combustion.

REVIEWER COMMENTS. The reduction in pulmonary function in this cohort of children who did not have current lower airway symptoms is in the same order of magnitude as patients with moderate persistent asthma, which underscores the need for less toxic energy sources.