bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 &lt;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 &gt;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.
Allergy Skin Test Responses During Experimental Infection With Respiratory Syncytial Virus
Authors: Lester Mitchell R. 
Published: November 2007

Skoner DP, Gentile DA, Angelini B, Doyle WJ. Ann Allergy Asthma Immunol. 2006;96:834–839
PURPOSE OF THE STUDY. To determine if a viral upper respiratory infection affects allergy skin-test responsiveness.
STUDY POPULATION. Sixteen adults experimentally exposed to respiratory syncytial virus (RSV).
METHODS. Subjects without concurrent upper or lower airway disease were cloistered and inoculated with 106 plaque-forming units of RSV type B. Daily physical examination and symptom scores were recorded. Nasal lavages were performed and stored at −70°C for RSV-antigen assay and culture. Blood samples were obtained for immunoglobulin E (IgE) measurement on days 0, 2, 4, 6, 8, 10, and 21. Skin-prick testing was performed for 17 locally relevant aeroallergens and controls on days 0, 3, 6, and 21.
RESULTS. Eight patients had ≥1 positive skin-test result at baseline and were considered atopic. Eleven (5 atopic, 6 nonatopic) had evidence of postinoculation RSV infection. Atopic patients had a higher IgE level at baseline as compared with nonatopic subjects (123 ± 80 vs 45 ± 36 IU/mL; P &lt; .01). There was no change in total IgE level in those in the nonatopic group, but the atopic subjects had a nonsignificant increase in IgE level on days 8 and 10 (146 ± 112 IU/mL). Of the 8 nonatopic patients, only 3 had negative skin-test results to all antigens on all 3 postinoculation test days. The mean number of positive wheal responses to allergens for all patients was 1.7 ± 2.3, 4.4 ± 3.8, 3.6 ± 3.5, and 3.9 ± 3.6 at baseline and days 3, 6, and 21, respectively (P &lt; .01 versus baseline for all pairings). For patients with positive skin-test results at baseline, mean wheal and flare area provoked by those allergens increased after RSV exposure. The increased number of positive responses to skin testing was noted for both seasonal and perennial aeroallergens.
CONCLUSIONS. The results may have some implication in explaining complications of RSV infection such as otitis media, asthma exacerbation, and subsequent development of asthma.
REVIEWER COMMENTS. There has long been a chicken-and-egg question when it comes to RSV infection in childhood and subsequent development of asthma. That is, does RSV predispose to later recurrent wheezing illnesses, or does the predisposition to wheeze lead to worse outcomes with RSV infection? Are children with an atopic predisposition more likely to have a severe RSV infection, or are those with severe infection more likely to develop atopy? This small study did not answer the question, but it provides a hint that RSV infection itself might affect immunologic responsiveness to aeroallergens, at least in the short-term. The study results cannot be extrapolated to make any long-term conclusions. Furthermore, the study was undertaken in healthy adults. It would be unethical to intentionally infect infants and toddlers with RSV at an age when they might be most susceptible to the risks of environmental influences on the development of atopy and to the risks of the infection itself.
Wait-and-See Prescription for the Treatment of Acute Otitis Media: A Randomized Controlled Trial
Authors: Adinoff Allen 
Published: November 2007

Spiro DM, Tay KY, Arnold DH, Dziura JD, Baker MD, Shapiro ED. JAMA. 2006;296:1235–1241
PURPOSE OF THE STUDY. Acute otitis media (AOM) is the most common diagnosis for which antibiotics are prescribed for children. Previous trials that have evaluated a “wait-and-see prescription” (WASP) for antibiotics, with which parents are asked not to fill the prescription unless the child either is not better or is worse in 48 hours, have excluded children with severe AOM. None of these trials were conducted in an emergency department. The purpose of this study was to determine if treatment of AOM using a WASP significantly reduces use of antibiotics compared with a standard prescription (SP) and to evaluate the effects of this intervention on clinical symptoms and adverse outcomes related to antibiotic use.
STUDY POPULATION. Children with AOM aged 6 months to 12 years seen in an emergency department in 1 year.
METHODS. A randomized, controlled trial was conducted; patients were randomly assigned to receive either a WASP or an SP. All patients received ibuprofen and otic analgesic drops for use at home. A research assistant who was blinded to group assignment conducted structured telephone interviews 4 to 6, 11 to 14, and 30 to 40 days after enrollment to determine outcomes and monitor filling of the antibiotic prescription and clinical course.
RESULTS. Overall, 283 patients were randomly assigned to either the WASP (n = 138) or SP (n = 145) group. Substantially more parents in the WASP group did not fill the antibiotic prescription (62% vs 13%; P &lt; .001). There was no statistically significant difference between the groups in the frequency of subsequent fever, otalgia, or unscheduled visits for medical care. Within the WASP group, both fever (relative risk: 2.95; 95% confidence interval: 1.75–4.99; P &lt; .001) and otalgia (relative risk: 1.62; 95% confidence interval: 1.26–2.03; P &lt; .001) were associated with filling the prescription.
CONCLUSIONS. The WASP approach substantially reduced unnecessary use of antibiotics in children with AOM seen in an emergency department and may be an alternative to routine use of antimicrobial agents for treatment of such children.
REVIEWER COMMENTS. This study added a few new twists to 2 previous, similar studies: (1) the patients had no previous relationship with the prescribing physician; (2) the patients, overall, were sicker, being seen in an ED; and (3) otic analgesics and ibuprofen were allowed. The use of antibiotics by those in the WASP group was 56% less than those in the SP group. We try in our practice to use a similar approach in our patients who also present with symptoms of acute sinusitis. Still, I wonder how many patients who do not use their prescription just save it for their next episode.
Particulate Levels Are Associated With Early Asthma Worsening in Children With Persistent Disease
Authors: Mahr Todd A. 
Published: November 2007

Rabinovitch N, Strand M, Gelfand EW. Am J Respir Crit Care Med. 2006;173:1098–1105
PURPOSE OF THE STUDY. To determine if exposure to particulate matter has immediate effects on asthma control in children with persistent disease.
STUDY POPULATION. Seventy-three schoolchildren (aged 6–13 years) with physician-diagnosed asthma in Denver, Colorado, were studied.
METHODS. Over 2 consecutive winters, the subjects were followed daily. The association among ambient fine-particulate levels, bronchodilator use, and urinary leukotriene E4 levels was assessed.
RESULTS. Fine-particulate concentrations peaked in the morning hours during hours when children were commuting to school. Children with severe asthma had a stronger association (+8.1%) than those with mild-to-moderate disease (+1.6%), with increased bronchodilator usage at school on days with an increase of 1 interquartile range in morning maximum fine-particulate levels. Morning maximum fine-particulate levels were also associated with urinary leukotriene E4 measured during school hours (average increase of 6.2% per interquartile-range increase).
CONCLUSIONS. Peak concentrations of ambient fine particulate are associated with early increases in bronchodilator use and urinary leukotriene E4 levels among children with persistent asthma, despite the use of controller medications.
REVIEWER COMMENTS. Managing patients with asthma requires knowing possible triggers. This study examined the timing of particulate associations with disease control in children with moderate or severe asthma who were taking controller medications. The interval between exposure and initiation of health effects was seen to occur within the first few minutes or hours after exposure. The effects were strongest in children with more severe asthma. This effect plus the increase in urinary leukotriene E4 levels suggest that in children with persistent asthma, particulate exposure may lead to early release of mediators related to asthma worsening. This study suggests that in children with poorly controlled asthma, air-pollution effects (well below National Ambient Air Quality standards) may be observed despite the use of daily controller medications.
Lack of Tolerance to the Protective Effect of Montelukast in Exercise-Induced Bronchoconstriction in Children
Authors: Rangsithienchai Pitud A. , Phipatanakul Wanda 
Published: November 2007

de Benedictis FM, del Giudice MM, Forenza N, Decimo F, de Benedictis D, Capristo A. Eur Respir J. 2006;28:291–295
PURPOSE OF THE STUDY. To evaluate montelukast's ability to inhibit exercise-induced bronchoconstriction in children at various time points over a treatment period of 28 days.
STUDY POPULATION. Thirty-two children, ranging in age from 6 to 12 years, with mild-to-moderate asthma.
METHODS. This study was designed as a multicenter, double-blind, randomized, parallel-group, placebo-controlled study. Subjects received either montelukast 5 mg or a placebo given once daily in the evening for 4 weeks. Exercise challenge and a pulmonary-function test were performed at baseline and then again at days 3, 7, and 28.
RESULTS. Montelukast provided significantly more protection against exercise-induced bronchoconstriction than placebo at each time point after treatment began. In addition, there was no significant difference in the percentage decrease of forced expiratory volume in 1 second for each drug at each of the days measured.
CONCLUSIONS. Montelukast provided significant protection for children with mild-to-moderate asthma against exercise-induced bronchoconstriction for a period of 28 days with no tolerance observed to the medication's effects.
REVIEWER COMMENTS. The results of this study parallel those that were run in adults. Montelukast offered effective protection against exercise-induced bronchoconstriction in children as well. The study also confirmed that long-term use is not required for results to be seen, and the protection conferred does not diminish for at least a 28-day period. Longer studies up to ≥12 weeks, paralleling adult studies, are warranted for further evaluation of montelukast's effects. This study was also limited in its sample size and involved only subjects with mild-to-moderate asthma. It would be worthwhile to determine if montelukast would be of the same benefit to severely asthmatic patients. It should be noted that approximately a quarter of the children in the study were taking inhaled steroids on a regular basis, and these patients responded to montelukast in the same way as those who were not on any such medications. This study makes a case for montelukast to be a preferential therapeutic option in children.
Asthma Severity and Atopy: How Clear Is the Relationship?
Authors: Kelso John M. 
Published: November 2007

Carroll WD, Lenney W, Child F, et al. Arch Dis Child. 2006;91:405–409
PURPOSE OF THE STUDY. The term “atopy” can refer to allergic conditions such as allergic rhinitis, asthma, eczema, and food allergy, which cluster in families. It can also be defined as the tendency to generate an immunoglobulin E (IgE) response to specific allergens. Is there a relationship between such IgE responses and the severity of asthma?
STUDY POPULATION. The study included 400 children (aged 7–18 years) with asthma (documented episodes of wheezing in the previous 12 calendar months and physician diagnosis).
METHODS. Patients completed a standardized observer-administered International Study of Asthma and Allergies in Childhood questionnaire and underwent baseline spirometry, skin-prick testing (SPT) to dust mites, grass mix, cat, dog, cockroach and Alternaria, and measurement of total serum IgE level. Atopy was defined as at least 1 SPT wheal &gt;3 mm or a total serum IgE level of &gt;100 IU/mL.
RESULTS. Total IgE was associated with increased asthma-severity score, decreased forced expiratory volume in 1 second (FEV1) (mean IgE with FEV1 &lt; 80% predicted: 812; mean IgE with FEV1 &gt; 80%: 449), and risk of hospital admission (mean IgE with hospitalization in last year: 726; no hospitalization: 392). Increasing skin-prick–test reactivity was associated with increased risk of hospital admission (mean sum of SPT wheals with hospitalization in last year: 12.1 mm; no hospitalization: 6.5 mm).
CONCLUSIONS. In children with asthma, increasing atopy is associated with increasing asthma severity.
REVIEWER COMMENTS. The majority of children with asthma have allergy, and the more allergy they have, the worse their asthma is. This is almost certainly a causal relationship; not surprisingly, inhaling things to which you are allergic can worsen your asthma. This reinforces the importance of assessing the allergic status of all children with asthma and reducing the exposure for those whose allergies are amenable to environmental control (dust mites, furry pets, mold, and cockroach).
The Atopy Patch Test in the Diagnostic Workup of Suspected Food-Related Symptoms in Children
Authors: Nowak-Wegrzyn Anna 
Published: November 2007

Mehl A, Rolinck-Werninghaus C, Staden U, et al. J Allergy Clin Immunol. 2006;118:923–929
PURPOSE OF THE STUDY. To determine the utility of atopy patch tests (APTs) in the diagnostic evaluation of food allergy.
STUDY POPULATION. A cohort of 437 children (median age: 13 months; 90% with atopic dermatitis) who were referred for evaluation of suspected food allergy.
METHODS. Specific serum immunoglobulin E (sIgE) measurements, skin-prick tests (SPTs), APTs, and controlled oral food challenges were performed.
RESULTS. The outcomes of 873 oral challenges with cow's milk, hen's egg, wheat, and/or soy were analyzed. One thousand seven hundred single APTs were performed. As a single parameter, the APTs showed the best specificity compared with sIgE measurements, SPTs, or both. Combining the APT with either the SPT or sIgE measurement resulted in improved sensitivity and specificity. Decision points for sIgE measurement and for the SPT showed lower values when combined with a positive APT result. By including the APT in the evaluation, only between 0.5% and 7.0% (99% predicted probability) and between 6% and 14% (using 95% predicted probability) of children would fulfill the criteria for avoiding an oral food challenge.
CONCLUSIONS. Although the predictive capacity of the APT is improved when combined with sIgE measurement or the SPT, oral food challenges become superfluous in only 0.5% to 14.0% of study patients. In addition, the APT is time-consuming and demands a highly experienced test evaluator. For daily clinical practice, the APT adds only a small predictive value to the standard SPT and sIgE measurement in the diagnostic workup of suspected food-related symptoms in children with atopic dermatitis.
REVIEWER COMMENTS. The APT is presumed to reflect late-phase clinical reactions. However, even with late onset of symptoms (&gt;2 hours after food ingestion), the performance of the APT was not consistent in the children with atopic dermatitis. The question that remains unanswered is whether the APT could be used to diagnose non–IgE-mediated gastrointestinal reactions to foods, such as allergic eosinophilic esophagitis/gastroenteritis or food protein–induced enterocolitis syndrome.
Cysteinyl Leukotrienes Regulate Th2 Cell-Dependent Pulmonary Inflammation
Authors: Sharma Hemant P. , Matsui Elizabeth C. 
Published: November 2007

Kim DC, Hsu FI, Barrett NA, et al. J Immunol. 2006;176:4440–4448
PURPOSE OF THE STUDY. The cysteinyl leukotrienes (cysLTs), derived from the 5-lipoxygenase pathway, play an important role in asthma as smooth muscle constrictors of airways and microvasculature. This study investigated a potential additional role of cysLTs in T-helper 2 (Th2) cell-dependent pulmonary inflammation using an ovalbumin-sensitization and -challenge protocol with mice that lacked LTC4 synthase (LTC4S), the terminal pathway enzyme for cysLT biosynthesis.
METHODS. LTC4S-null mice and wild-type mice underwent intraperitoneal ovalbumin sensitization, followed on days 40, 43, and 46 by intranasal ovalbumin or saline challenge. Pulmonary histology was examined 48 hours after the last challenge. Total and ovalbumin-specific serum immunoglobulin (Ig) levels, cytokine mRNA expression in the lung, cytokine production by parabronchial lymph node cells after in vitro ovalbumin restimulation, delayed-type hypersensitivity, and airway hyperresponsiveness to methacholine 24 hours after the last challenge were measured also.
RESULTS. In the LTC4S-null mice, antigen-induced pulmonary inflammation (eosinophil infiltration and goblet and mast cell hyperplasia) and airway hyperresponsiveness to methacholine were significantly reduced. In addition, antigen-specific serum immunoglobulin E and G1 and Th2 cell cytokine messenger RNA expression in the lung were reduced in LTC4S-null mice compared with wild-type controls. The production of Th2 cytokines by antigen-restimulated parabronchial lymph node cells from LTC4S-null mice was also significantly reduced compared with those from wild-type controls; however, there was no suppression of cutaneous delayed-type hypersensitivity in LTC4S-null mice.
CONCLUSIONS. These findings support a role for cysLTs in the development and/or amplification of a pulmonary Th2 response.
REVIEWER COMMENTS. Two types of leukotriene-based medications have been used to treat patients with bronchial asthma: (1) leukotriene inhibitors that block the actual synthesis of leukotrienes and (2) leukotriene antagonists that inhibit leukotriene function by blocking leukotriene-receptor sites. Previous studies suggested that the main role of cysLTs was smooth muscle constriction of airways and microvasculature. This study, as well as other growing evidence, points to a unique and broader role for cysLTs in the initiation and amplification of the Th2 response in the lung. Future studies should assess the mechanism of this role, specifically the impact of cysLTs on dendritic-cell and T-cell function. Therefore, the therapeutic benefit of leukotriene antagonists may be additionally derived from this broader physiologic role of cysLTs in pulmonary Th2 responses.
Evaluation and Treatment of Community-Acquired Staphylococcus aureus Infections in Term and Late-Preterm Previously Healthy Neonates
Authors: Fortunov Regine M. , Hulten Kristina G. , Hammerman Wendy A. , Mason Edward O. , Kaplan Sheldon L. 
Published: November 2007

OBJECTIVE. We describe the evaluation and treatment of neonatal community-acquired Staphylococcus aureus disease in the era of community-acquired methicillin-resistant S aureus.
METHODS. We retrospectively reviewed the evaluation and treatment of 126 community-acquired S aureus infections of term and late-preterm previously healthy neonates who were ≤30 days of age between August 2001 and July 2006 at Texas Children's Hospital.
RESULTS. S aureus infections included 43 pustulosis, 68 cellulitis/abscess, and 15 invasive infections. We found 84 methicillin-resistant and 42 methicillin-susceptible S aureus isolates. Twenty-one patients received outpatient antibiotics before hospital presentation. Systemic infection evaluation included urine, blood, and cerebrospinal fluid cultures in 79, 102, and 84 neonates, respectively. Culture revealed S aureus urinary tract infections in 1, S aureus bacteremias in 6, and aseptic cerebrospinal fluid pleocytosis of unclear cause in 11 neonates. Physicians admitted 106, transferred 5 to other hospitals, and discharged 15 afebrile patients with topical or oral antibiotics. Clindamycin was the predominant antistaphylococcal intravenous and oral antibiotic for pustulosis and cellulitis/abscess infections. One patient with systemic S aureus and herpes simplex virus infection died. At discharge after inpatient treatment, physicians prescribed no antibiotics for 43 patients and oral or topical antibiotics for 62 patients. Outpatient treatment failed for 1 patient who was discharged after intravenous therapy and was readmitted. Eighty percent (16 of 20) of patients with mastitis alone completed treatment with outpatient oral antibiotics.
CONCLUSIONS. Evaluation and treatment strategies for neonatal community-acquired S aureus disease are varied at our hospital. Prospective studies are needed to determine optimal management strategies.