bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Asthma Outcomes in a High-Morbidity Pediatric Population: Results of an Emergency Department-Based Randomized Clinical Trial
Authors: Smart Brian A. 
Published: November 2007

Teach SJ, Crain EF, Quint DM, Hylan ML, Joseph JG. Arch Pediatr Adolesc Med. 2006;160:535–541
PURPOSE OF THE STUDY. To determine if an emergency department–based asthma follow-up clinic could improve outcomes within a high-morbidity pediatric population.
STUDY POPULATION. Four hundred eighty-eight patients (aged 12 months to 17 years) from an emergency department at an urban tertiary care pediatric hospital with previous physician-diagnosed asthma and ≥1 unscheduled visit in the last 6 months and/or ≥1 hospitalization in the last 12 months.
METHODS. The subjects were recruited while they were still in the emergency department for their acute care visits. The subjects were randomly assigned to either a single visit to an asthma clinic located in the emergency department, where they met with an asthma educator and a physician, or the control group, which received printed information about asthma. Follow-up telephone interviews were conducted at 1, 3, and 6 months after enrollment.
RESULTS. One hundred seventy-two (70.5%) of the subjects who were randomly assigned to the intervention attended the clinic, and 167 of these subjects were prescribed inhaled corticosteroids. Compared with children in the control group, those in the intervention group had significantly fewer unscheduled visits for asthma care (mean: 1.39 vs 2.34; relative risk: 0.60); at 6 months, reported significantly more use of inhaled corticosteroids (49.3% vs 26.5%; relative risk: 2.03); reported “no limitation in daytime quality of life” significantly more often (43.8% vs 34.4%; relative risk: 1.36); and reported “no functional limitations in quality of life” significantly more often (49.8% vs 40.8%; relative risk: 1.33).
CONCLUSIONS. A single follow-up visit to an emergency department–based asthma clinic resulted in significant improvements in care and outcomes for a high-morbidity pediatric population.
REVIEWER COMMENTS. This study was unique in that the emphasis was on follow-up in a clinic in the emergency department where care was first given, rather than a primary care office. This intervention seems to have been more successful than previously published emergency department–based studies that focused on improving rates of follow-up with primary care providers. There are a number of possible explanations for these findings, including the fact that many families use the emergency department as a de facto primary care office and the comprehensive nature of the emergency department–clinic visit. Costs were not analyzed, and there may be other barriers to other emergency departments adopting an intervention of this type, but these results are promising.
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 &lt;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 &gt;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 &lt;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 &lt; .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.