bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inner City Asthma Study: Relationships Among Sensitivity, Allergen Exposure, and Asthma Morbidity
Authors: Le Bras Michael , Jones Stacie M. 
Published: September 2006

Purpose of the Study.
To describe the relationship between allergen sensitivities, allergen exposures, and asthma morbidity in children with moderate-to-severe asthma while also exploring geographic variations in indoor allergen levels.

Study Population.
Subjects were children aged 5 to 11 years (n = 937) from 7 inner-city and metropolitan areas across the United States participating in the Inner City Asthma Study.

Methods.
In a fully crossed factorial design, participants were randomly assigned to receive an allergen intervention, bimonthly feedback of the child’s health status to their primary care physicians, both interventions, or no intervention (control group, n = 234). At baseline, a clinical interview with the child’s primary caregiver (including demographics, asthma morbidity, home characteristics, and exposure to tobacco smoke) was conducted with skin-prick tests to aeroallergens. Morbidity was measured at 2-month intervals during a 24-month period. Home visits including a visual inspection and dust-sample collection (dust mite, cockroach, cat and dog dander) were conducted at baseline and every 6 months.

Results.
Of 1059 children tested, 94% had at least 1 positive skin test. Allergen sensitivities varied widely across the study sites, with cockroach (69%), dust mites (62%), and molds (50%) being the most predominant. Cockroach sensitivity was highest in The Bronx, New York, New York City, New York, and Dallas, Texas (81%, 79%, and 79%, respectively), whereas dust mite sensitivities were highest in Dallas and Seattle, Washington (84% and 78%, respectively). At least 30% of the subjects were allergic to cats at all sites. Cockroach levels were highest (&gt;50% of homes) in Chicago, Illinois, New York City, The Bronx, and Dallas and were lower in Seattle and Tucson, Arizona (8% and 11% of homes, respectively). Dust mite levels were highest in Seattle and Dallas. Cockroach levels were higher in high-rise and low-rise apartments, whereas dust mite levels were higher in detached homes. No correlation was seen between animal dander and housing type.

Conclusions.
There were significant differences between geographic study sites and the type of indoor allergen exposure and skin-test sensitivity in this study group. Cockroach predominated in the Northeast, whereas dust mite predominated in the South and Northwest. Although most children in the study were allergic to dust mite and/or cockroaches, only the children who were sensitive and exposed to cockroach had increased asthma morbidity.

Reviewer Comments.
This study demonstrates the association of allergen sensitivities and exposures (particularly cockroach allergens) to increased asthma morbidity in children with moderate-to-severe asthma living in inner-city areas. Physicians can use this knowledge to identify significant risk factors in asthmatic patients, implement appropriate prevention measures (ie, environmental intervention), and more aggressive medical management to decrease the level of asthma morbidity.
Self-Organized Patchiness in Asthma as a Prelude to Catastrophic Shifts
Authors: Thatayatikom Akaluck , Liu Andrew H. 
Published: September 2006

Purpose of the Study.
To reveal self-organized small airway constriction contributing to large ventilation defects in asthmatics.

Study Population.
Mild and moderate asthmatics.

Methods.
Ventilation defects in asthmatics were studied during methacholine bronchoprovocation by using serial dynamic positron emission tomography with a positron-emitter nitrogen-13 tracer and a single terminal-airway model.

Results.
Heterogeneity of ventilation defects in asthmatics was demonstrated. In this model, constriction of terminal bronchioles was the main feature of bronchoconstriction, contributing to nonuniform ventilation defects. Consequently, on the basis of the mechanical interdependence in expansion between airways and surrounding parenchyma, clusters of constricted terminal bronchioles fed by a common tree branch developed and led to large ventilation defects.

Conclusion.
Clustered groups of self-organized terminal bronchiolar constriction, not large airways obstruction, contribute to large ventilation defects in acute asthma.

Reviewer Comments.
The nature of functional changes of both small and large airways affecting ventilation during acute asthma attacks has been unclear. Previously, MRIs of asthmatic lungs during bronchoprovocation suggested large-airway obstruction as a major cause of large ventilation defects (eg, J Allergy Clin Immunol. 2003;111:1205–1211). In this study, Venegas et al demonstrated the role of clustered terminal bronchiolar constriction resulting in ventilation defects in acute asthma. On the basis of this model, inhaled bronchodilators could be ineffective because the inhaled form might reach only well-ventilated regions and could further impede lung expansion of problematic regions and exacerbate regional ventilation defects. The concept of catastrophic shifts might account for sudden, unexplained, and severe asthma attacks in some patients. Systemic bronchodilators may be needed in some asthmatics to bypass this problem. This line of investigation is further elucidated elsewhere (J Appl Physiol. 2005;99:2388–2397).
Initial High-Dose Nasal Allergen Exposure Prevents Allergic Sensitization to a Neoantigen
Authors: Sharma Hemant , Matsui Elizabeth 
Published: September 2006

Purpose of the Study.
Epidemiologic studies have suggested that high-dose allergen exposure may protect against primary allergic sensitization—the formation of immunoglobulin E (IgE) after initial antigen exposure. This study uses a human nasal allergic sensitization model to evaluate the effect of the dose of the antigen on the rate of primary sensitization to a neoantigen, keyhole limpet hemocyanin (KLH).

Study Population.
Fifty-one healthy nonsmoking atopic subjects aged 18 to 55 years. Atopic status was defined by a positive skin-prick test to at least one aeroallergen; the subjects therefore had a propensity to mount an allergic (IgE) response to respiratory antigen exposure.

Methods.
Subjects underwent a 33-day sensitization protocol including initial exposure to 0.1-, 10-, 1000-, or 100 000-μg doses of intranasal KLH as well as later exposure to adjuvant intranasal diesel exhaust particles. At the conclusion of protocol, antigen-specific IgE, IgG, and IgG4 were measured in nasal lavage samples.

Results.
The rates of allergic sensitization, defined as detectable KLH-specific IgE, for the 0.1-, 10-, 1000-, or 100 000-μg dose groups were 0, 100, 57, and 11%, respectively. Furthermore, the mean KLH-specific IgE levels decreased with increasing doses of initial antigen exposure. Antigen-specific IgG and IgG4 were produced by all subjects, with the highest levels observed in the high-dose group.

Conclusions.
Initial high levels of respiratory antigen exposure may prevent primary allergic sensitization through induction of an antigen-specific non-IgE humoral immune response.

Reviewer Comments.
In children at high risk of allergic sensitization, a means of preventing primary sensitization and inducing durable allergic tolerance would be of great value. This study found that initial high-dose exposure to a neoantigen, KLH, results in a humoral immune response with high levels of antigen-specific IgG, including IgG4, and low levels of KLH-specific IgE. Whether these findings apply to other respiratory antigens remains unclear. The mechanism underlying this induction of tolerance remains unclear, and it is also not known whether this immune response represents durable allergic tolerance. Future studies investigating these issues are needed to move toward potential primary prevention therapy for allergic disease.
The Bronchial Lavage of Pediatric Patients With Asthma Contains Infectious Chlamydia
Authors: Perry Tamara T. 
Published: September 2006

Purpose of the Study.
To examine the frequency of Chlamydia pneumoniae infections in pediatric patients with asthma.

Study Population.
Seventy pediatric patients undergoing flexible fiber-optic bronchoscopy as a part of their ongoing clinical care.

Methods.
Bronchoaveolar lavage (BAL) fluid and blood were examined for the presence of C pneumoniae by smear examination and culture. The BAL and blood samples were cultured on human or mouse macrophages to determine infectivity. Polymerase chain reaction (PCR) amplification of BAL samples was performed to confirm specificity of the culture technique. Blood was examined for total immunoglobulin E (IgE). Blood samples from 70 matched, nonrespiratory control patients were cultured for Chlamydia.

Results.
Forty-two patients undergoing bronchoscopy had asthma and 28 had various other respiratory diseases. Thirty-eight (54%) BAL samples were positive for Chlamydia by PCR and 22 (31%) samples were positive for Chlamydia by culture. Of the positive BAL samples, 28 (74%) of 38 PCR-positive and 14 (64%) of 22 culture-positive samples were from children with asthma. Culture-positive blood samples were found in 24 (34%) of 70 respiratory patients and 8 (11%) of 70 nonrespiratory controls. In the blood culture–positive respiratory group, 17 (71%) of 24 were from children with asthma. Elevated total serum IgE was associated with BAL culture–positive results, and this relationship was stronger than total IgE and asthma diagnosis.

Conclusions.
Viable C pneumoniae organisms are frequently present in the lung lavage in a cohort of predominately asthmatic pediatric patients.

Reviewer Comments.
Results from this study suggest that infectious C pneumoniae may be common in BAL fluid of children with asthma. Historically, C pneumoniae has been associated with exacerbation and increased incidence of respiratory conditions in adults, but studies to examine similar associations in children have not been performed. This is the first investigation to report viable and infectious C pneumoniae in the BAL fluid of children with asthma. These findings are intriguing and should encourage investigators to examine the clinical implications of Chlamydia infection among pediatric patients with asthma.
Comparative Efficacy and Safety of Low-Dose Fluticasone Propionate and Montelukast in Children With Persistent Asthma
Authors: Duplantier John E. 
Published: September 2006

Purpose of the Study.
To evaluate efficacy, safety, health outcomes, and cost-effectiveness of fluticasone propionate (FP) versus montelukast in children with asthma

Study Population.
Children aged 6 to 12 years with persistent asthma.

Methods.
Multicenter, randomized, double-blind, double-dummy, parallel-group study of 342 children with persistent asthma. Children received either FP 50 μg twice daily via Diskus or montelukast 5 mg once daily for 12 weeks. The primary efficacy variable was percent change in morning predose forced expiratory volume in 1 second at the end point.

Results.
Compared with montelukast, children treated with FP experienced a significantly greater increase in mean percent forced expiratory volume in 1 second, mean morning peak expiratory flow rate, and mean evening peak expiratory flow rate. Children treated with FP also experienced significantly greater reductions in total supplemental albuterol use, mean nighttime albuterol use, and mean nighttime symptom scores compared with children treated with montelukast. There were no significant differences between the groups for daytime asthma symptom scores, daytime albuterol use, percent symptom-free days, or adverse events. Parent and physician satisfaction ratings were significantly higher for FP treatment. The daily total asthma-related cost per patient in the FP group was approximately one third of the cost in the montelukast group.

Conclusions.
FP was significantly more effective than montelukast in improving pulmonary function, asthma symptoms, and rescue albuterol use. Both therapies had similar safety profiles.

Reviewer Comments.
Comparative studies in adults and adolescents have previously shown greater efficacy with inhaled corticosteroids versus leukotriene receptor antagonists. This 12-week study reports similar findings for children 6 to 12 years of age with persistent asthma. Based on efficacy, cost, and safety profiles, low-dose inhaled corticosteroids should be considered first-line therapy in this age group.
An Immunoepidemiological Approach to Asthma: Identification of in-Vitro T-Cell Response Patterns Associated With Different Wheezing Phenotypes in Children
Authors: Simons Elinor 
Published: September 2006

Purpose of the Study.
To determine if variations in clinical asthma phenotypes are the result of differences in underlying T-cell immune responses to inhalant allergens.

Study Population.
One hundred forty-seven children (aged 8.6–13.5 years) and 25 of their siblings (aged 7.4–17.4 years) were recruited from 194 members of a birth cohort studied prospectively for asthma development.

Methods.
Wheeze and asthma were defined by parental questionnaire. Atopy was defined as at least 1 positive skin-prick test for environmental or food allergens. Increased bronchial hyperreactivity (BHR) was defined as a ≥20% drop in forced expiratory volume in 1 second after inhaled histamine up to 7.8 μmol/L. T-cell responses to allergens and mitogens, blood eosinophils, and immunoglobulin E (IgE) were measured and compared with clinical phenotypes.

Results.
Ninety-five (55.2%) of the children were atopic, sensitized predominantly to house dust mite (42.4%). Asthma was present in 26 (15.1%) children, of whom 22 (85%) were atopic; BHR was present in 62 (35.9%) children, of whom 45 (73%) were atopic. Atopy was associated with T-helper 2 (Th2) cytokine responses (interleukin-4 [IL-4], IL-5, IL-9, IL-13), whereas Th1 responses (IL-10, interferon-γ [IFN-γ], tumor necrosis factor-α [TNF]) occurred in all children. Skin-prick test wheal size was positively associated with house dust mite allergen-induced IL-5 (P &lt; .0001) and IFN-γ (P = .003) and negatively associated with IL-10. Asthma was associated with eosinophilia and elevated house dust mite–specific IL-5, IL-9, IL-13, and IgE. BHR was associated with eosinophilia, elevated allergen-specific IL-5 and IgE, increased total IgE, and a polyclonal cytokine response (IL-5, IL-13, IFN-γ, and TNF-α). In atopics, current asthma or wheeze was associated with house dust mite allergen-specific IL-5 and IL-13; BHR was associated with IL-5 and IgE. In nonatopics, BHR was associated with increased house dust mite allergen-specific and polyclonal IL-10 and polyclonal IFN-γ and TNF-α.

Conclusions.
In atopic and nonatopic children, distinctive immune-response patterns were identified for asthma and BHR. Immunologic Th1 and Th2 hyperresponsiveness was identified as a hallmark of BHR.

Reviewer Comments.
Modification of T-cell responses has become an increasingly important focus in the investigation of treatments for atopic disease. Although this study further highlights the prominence of Th2-driven responses in atopic individuals, the results also demonstrate allergen-specific and polyclonal Th1 responses associated with BHR in atopic and nonatopic children. These findings suggest a nonantagonistic interaction between Th1 and Th2 pathways in the production of asthma symptoms. Further understanding of the associations between T-cell response patterns and clinical wheezing phenotypes in children may lead to future asthma therapies in this population.
Asthma Phenotypes, Risk Factors, and Measures of Severity in a National Sample of US Children
Authors: Gern James E. 
Published: September 2006

Purpose of the Study.
To determine if there are differences in risk factors and measures of severity between children with different asthma phenotypes.

Study Population.
The authors reviewed data from children aged 6 to 16 years derived from the Third National Health and Nutrition Examination Survey.

Methods.
The authors used questionnaire and skin-prick–testing data to separate children into the following categories: atopic asthma, nonatopic asthma, resolved asthma, frequent respiratory symptoms with no asthma diagnosis, and normal. Multivariate regression was used to determine if demographic or potential risk factors varied between phenotypes and whether measures of severity varied by phenotype.

Results.
A total of 4.8% of children had atopic asthma, 1.9% had nonatopic asthma, 3.4% had resolved asthma, and 4.3% had frequent respiratory symptoms. Mean BMI was higher among children with nonatopic asthma, whereas prenatal maternal smoking was a risk factor for resolved asthma. Atopic and nonatopic asthma were similar for most measures of asthma severity (eg, medication use and lung function), and relatively few children in either group were receiving inhaled corticosteroids (5%–10%). Patients with resolved asthma had fewer symptoms but lung-function impairment similar to that seen with current asthma, whereas children with frequent respiratory symptoms but no asthma diagnosis had normal lung function.

Conclusions.
The authors conclude that asthma risk factors and measures of severity vary between children with different asthma phenotypes.

Reviewer Comments.
Studies of children and adults have identified several unique phenotypes of asthma that share the feature of chronic and/or recurrent airflow obstruction. Accurate categorization is crucial in efforts to define genetic and environmental risk factors for asthma, and this work uses a very large national database to help establish environmental correlates to asthma subgroups in children. Notably, resolved asthma was linked to prenatal exposure to tobacco smoke and also to persistent impairment in lung function. Because environmental and lifestyle factors are almost certainly behind the rise in asthma prevalence, this line of research is clearly valuable from a public health perspective.
A National Prospective Study on Childhood Celiac Disease in the Netherlands 1993–2000: An Increasing Recognition and a Changing Clinical Picture
Authors: Duplantier John E. 
Published: September 2006

Purpose of the Study.
To investigate whether the incidence of diagnosed celiac disease (CD) is increasing in the Netherlands and whether the clinical presentation is changing.

Study Population.
Children between the ages of 0 and 14 years with newly diagnosed cases of CD from 1993–2000.

Methods.
Diagnosis of CD was based on biopsy of the small intestine. The following data were collected: age, gender, weight, height, and aspects of the presenting clinical picture.

Results.
The overall crude incidence rate for CD from 1993–2000 was 0.81 per 1000 live births. There was a significant linear increase of the crude incidence from 1993–2000. During the period of 1993–2000 there was a significant increase in the diagnosis of CD with partial villous atrophy of the small-bowel mucosa and a relative decrease in the diagnosis with subtotal villous atrophy. Fewer children are presenting with abdominal distention, chronic diarrhea, and failure to thrive, and more children are presenting with weight &lt;10th percentile, abdominal pain, and lassitude.

Conclusions.
The increase in newly diagnosed cases of CD seems to represent greater awareness of the disease and the availability of serologic tests. The increase in the number of children with CD diagnosed with small-bowel biopsy specimens showing partial villous atrophy suggests increased recognition of milder cases

Reviewer Comments.
In the United States, CD now seems to affect ∼0.5 to 1.0% of the population (10 times higher than previous estimates). In the past, diagnosis of CD has taken an average of 10 years. Serologic screening (eg, tissue transglutaminase immunoglobulin A antibodies) should be considered for children with symptoms of diarrhea, abdominal cramping, pain, and distention as well as short stature and delayed puberty; individuals with Down syndrome or type 1 diabetes mellitus; and first-degree relatives of patients with biopsy-proven CD. Positive serologic tests should be followed up by small-bowel biopsy. Increased awareness of CD allows earlier diagnosis and institution of a gluten-free diet.
Bacterial Contamination of Spacer Devices Used by Asthmatic Children
Authors: Leo Troy , Leo Harvey L. 
Published: September 2006

Purpose of the Study.
To investigate bacterial contamination in spacer devices used by asthmatic children and the device-maintenance procedures practiced by parents.

Study Population.
The study group consisted of 62 consecutive children (aged 2–5 years) attending a clinic. All were enrolled in the study during an acute asthma attack.

Methods.
Spacer devices used by 62 asthmatic children were examined. Swabs taken from the inner surface of the reservoirs and face masks were cultured. Parents were interviewed regarding their spacer-cleaning and -disinfection routines.

Results.
Bacterial contamination was noted in 22 reservoirs (35.5%) and 16 masks (25.8%). Pseudomonas aeruginosa was isolated from 21.0% of the reservoirs and 14.5% of the face masks, Klebsiella pneumoniae from 6.5% and 4.8%, and Staphylococcus aureus from 9.7% and 8.1%, respectively. Only 34 parents (54.8%) reported that they received cleaning and maintenance instructions from the medical staff at initiation of spacer use by their child, and only 38 (61.8%) cleaned the device after each use.

Conclusions.
Bacterial contamination is common in spacer devices. This study demonstrates that contamination rates are significantly lower when parents clean and actually dry (preferably with an air blower) spacer devices after each use. Spacer device maintenance should be emphasized in education programs for managing asthma.

Reviewer Comments.
This study underscores the need for pediatricians and families to be educated about the proper care of spacer devices and the potential risks associated with improper cleaning. In particular, simple cleansing techniques can lessen or eliminate the number of nosocomial infections introduced by poor care of these devices. The benefit of metered-dose inhalers used with spacers and a face mask is high, and it is worthwhile to ensure that patients and health care workers use these devices properly and to their best advantage.