bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exhaled Nitric Oxide in Asthma: Variability, Relation to Asthma Severity, and Peripheral Blood Lymphocyte Cytokine Expression
Authors: Humayun Fawwaz , Leo Harvey L. 
Published: November 2007

Shome GP, Starnes JD 3rd, Shearer M, et al. J Asthma. 2006;43:95–99
PURPOSE OF THE STUDY. To measure and compare exhaled nitric oxide (eNO) levels in patients with asthma and healthy volunteers, to study peripheral blood lymphocyte cytokine expression, and to study the relationship between eNO and intracellular cytokine expression.
STUDY POPULATION. A total of 36 subjects were enrolled onto the study, with 19 asthmatic patients and 17 healthy control subjects.
METHODS. At least once per week for 4 weeks, patients with asthma visited the clinic and underwent a detailed history, physical examination, spirometry, and eNO-level measurement. These patients were maintained on established pharmacologic therapy regimens. A blood sample was taken and analyzed by flow cytometry. eNO was measured by using an NO analyzer. Univariate linear regression analysis was used to determine correlations between continuous variables and eNO concentrations.
RESULTS. eNO levels were significantly elevated in patients with moderate-to-severe asthma compared with those in healthy subjects (18.53 ± 2.00 vs 5.90 ± 0.90 ppb). With treatment, eNO levels in patients with moderate-to-severe asthma decreased to levels near those of the healthy subjects by 4 weeks. Interferon γ expression was decreased in patients with moderate-to-severe asthma. An elevated eNO level was also associated with decreased interleukin 4 and interleukin 13 cytokine expression in CD8 lymphocytes.
CONCLUSIONS. eNO levels were elevated in patients with moderate-to-severe asthma. With 4 weeks of treatment, eNO levels in patients with moderate-to-severe asthma were no different from those in the control subjects. There was decreased interferon γ expression by the CD4- and CD8-positive peripheral blood lymphocytes of patients with moderate-to-severe asthma. Elevated eNO levels were associated with suppression of both T-helper 1 and 2 cytokine expression by the peripheral blood lymphocyte, suggesting a systemic immunomodulatory effect.
REVIEWER COMMENTS. This study adds to the growing information on the utility of eNO levels to monitor asthma-treatment response. It demonstrates how eNO can be used to measure the reduction in airway inflammation as a response to treatment primarily in patients with moderate-to-severe asthma. At this point, it is not clear what the implications are of the association between elevated eNO levels and cytokine suppression.
Sublingual Immunotherapy With Once-Daily Grass Allergen Tablets: A Randomized Controlled Trial in Seasonal Allergic Rhinoconjunctivitis
Authors: Jordan Teri J. , Jones Stacie M. 
Published: November 2007

Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. J Allergy Clin Immunol. 2006;117:802–809
PURPOSE OF THE STUDY. To examine the efficacy and safety of sublingual immunotherapy (SLIT) in seasonal allergic rhinoconjunctivitis using timothy-grass–allergen tablets.
STUDY POPULATION. The study included 855 patients aged 18 to 65 from 55 centers in Canada and Europe with seasonal allergic rhinoconjunctivitis induced by grass pollen.
METHODS. A double-blind, randomized, parallel-group, placebo-controlled trial was conducted during 2002–2003. Patients had a history of allergic rhinoconjunctivitis during grass-pollen season for at least 2 years with a positive skin-prick–test result and serum-specific immunoglobulin E (IgE) to Phleum pratense. Individuals were randomly assigned to receive placebo or 2500, 25 000, or 75 000 SQ-T sublingual tablets administered daily. Daily diaries of symptoms (0–3) and rescue-medication use from pre–through post–grass-pollen season were kept, and a rhinoconjunctivitis quality-of-life (QoL) questionnaire was completed. Well days were calculated as those with a symptom score of ≤2 and no rescue-medication use.
RESULTS. A total of 790 (92%) participants completed the trial that included a mean duration of treatment of 18 weeks. Treatment with 75 000 SQ-T tabs revealed an improvement in symptom score (16%; P = .0710) and medication score (28%; P = .0470) when compared with placebo. The QoL score and number of well days also revealed improvement of 17% (P = .006) and 18% (P = .041), respectively. The 2 lower doses did not demonstrate significant change from placebo. Preseason treatment for 8 weeks with the 75 000 SQ-T dose showed an increased improvement of symptom score (21%; P = .002) and medication score (29%; P = .012) compared with placebo. In the 75 000 SQ-T group, specific IgG to P pratense was increased after 8 weeks of treatment and tripled posttreatment. Specific IgE levels increased after treatment initialized but remained unchanged thereafter. Therapy was well tolerated with only mild-to-moderate symptoms (consisting of primarily oral pruritis and throat irritation) noted in 53% of the patients.
CONCLUSIONS. Grass-pollen SLIT has a dose-dependent efficacy, is well tolerated, and provides improved QoL for patients with seasonal allergic rhinoconjunctivitis.
REVIEWER COMMENTS. SLIT for grass-pollen allergy holds promise as an alternative future therapy to subcutaneous immunotherapy that is attractive on many levels. Grass-pollen SLIT may have broader coverage range because of improved accessibility and more convenient administration, less discomfort than injections, and decreased risk of IgE-mediated severe systemic reactions. Preseason coverage with SLIT may improve symptoms and reduce medication requirements for treatment of seasonal allergic rhinoconjunctivitis.
ImmunoCAP Phadiatop Infant: A New Blood Test for Detecting IgE Sensitisation in Children at 2 Years of Age
Authors: Skripak Justin , Wood Robert A. 
Published: November 2007

Ballardini N, Nilsson C, Nilsson M, Lilja G. Allergy. 2006;61:337–343
PURPOSE OF THE STUDY. To evaluate the efficacy of a blood test, Phadiatop Infant (PI), in determining immunoglobulin E (IgE) sensitization to food and aeroallergens in children at 2 years of age.
STUDY POPULATION. Prospective study of 239 children followed from birth. Families were recruited during pregnancy. For 75% of the participants, 1 or both parents had a history of atopic disease.
METHODS. Clinical evaluation occurred every 6 months through 2 years of age. At 2 years of age, all children underwent skin-prick testing (SPT), allergen-specific IgE testing to a panel of common food and aeroallergens, and the PI blood test. Subjects with ≥1 positive SPT and allergen-specific IgE test were as categorized IgE sensitized. Those with either ≥1 positive SPT or ≥1 positive allergen-specific IgE were labeled as inconclusive. Those with all negative tests were considered non–IgE sensitized. Cutoff for a positive PI test result was &gt;0.35 kU/L.
RESULTS. On the basis of SPT and allergen-specific IgE tests, 26 (11%) of the 239 children were considered IgE sensitized, 182 (76%) were non–IgE sensitized, and 31 (13%) were labeled inconclusive. Using SPT and allergen-specific IgE tests as a reference, in the IgE-sensitized and non–IgE-sensitized groups, the sensitivity of the PI test was 96%, specificity was 98%, positive predictive value (PPV) was 89%, and negative predictive value (NPV) was 99%. When children with any positive SPT or allergen-specific IgE test (ie, the inconclusive group) were included, sensitivity was 82%, specificity was 98%, PPV was 94%, and NPV was 95%. There was a statistically significant association between any clinical symptom of atopic disease and a positive PI test result (odds ratio: 2.7; 95% confidence interval: 1.3–5.5).
CONCLUSIONS. The ability of PI used as an independent test to detect IgE sensitization in young children seems to be a reliable alternative to SPT or allergen-specific IgE antibody testing.
REVIEWER COMMENTS. As the prevalence of atopic diseases in the population increases, early identification of IgE-sensitized, atopic children is desirable. The PI test seems to be a reasonable alternative that does not require the placement of SPT or the selection of specific antigens for SPT or blood tests. In this study, the correlation of the PI test with SPT or blood-test results was good. The correlation with clinical symptoms was not quite as convincing. In terms of individual allergic symptoms, a positive PI test result only correlated significantly with eczema. This was probably limited by the fact that children were only followed up to age 2, when asthma and rhinoconjunctivitis are more frequently infection related than allergic.
Clinical Efficacy and Safety of Sublingual Immunotherapy With Tree Pollen Extract in Children
Authors: Jarvinen Kirsi M. , Sicherer Scott H. 
Published: November 2007

Valovirta E, Jacobsen L, Ljørring C, Koivikko A, Savolainen J. Allergy. 2006;61:1177–1183
PURPOSE OF THE STUDY. To investigate the clinical efficacy, safety, and dose-response relationship of sublingual immunotherapy (SLIT) in children suffering from rhinoconjunctivitis with or without asthma.
STUDY POPULATION. Eighty-eight children (aged 5–15 years) in Finland with a history of tree-pollen–induced allergic rhinoconjunctivitis with or without seasonal asthma. Skin-prick test, specific immunoglobulin E, and conjunctival provocation test were used to confirm allergy to tree pollen.
METHODS. Randomized, double-blind, placebo-controlled dose-response study using a glycerinated mixture of pollen from birch, hazel, and alder trees. Three groups receiving SLIT 5 days per week for up to 18 months were given an accumulated weekly dose of 24 000 U (dose group 1), an accumulated weekly dose of 200 000 U (dose group 2), or placebo.
RESULTS. In the birch-pollen season, dose group 2 showed a significant reduction in both symptom (P = .01) and medication (P = .04) scores compared with those in the placebo group, but dose group 1 showed only a significant reduction of symptom scores (P = .03). No serious adverse events were reported. Oral local reactions were the most common adverse effect, ranging from 25% of patients in the placebo group to 50% in group 2.
CONCLUSIONS. SLIT with tree-pollen extract provided dose-dependent benefits in tree-pollen–allergic children in terms of significantly reduced symptoms and medication use. The treatment was well tolerated.
REVIEWER COMMENTS. The use of allergen-specific immunotherapy by the sublingual route, SLIT, has been increasing in clinical practice in Europe. SLIT is especially attractive for use in children, because it is a noninjection form of immunotherapy. This study showed a modest reduction (∼40%) in both symptom and medication scores. This is an interesting disease-modifying therapy that will need more studies to characterize efficacy and safety and to compare the results to that of subcutaneous immunotherapy before wider use can be recommended.
Parental Knowledge and Use of Epinephrine Auto-injector for Children With Food Allergy
Authors: Le Bras Michael , Perry Tamara T. 
Published: November 2007

Pouessel G, Deschildre A, Castelain C, et al. Pediatr Allergy Immunol. 2006:17:221–226
PURPOSE OF THE STUDY. To assess parental use and knowledge of an epinephrine autoinjector (EAI), Anapen, prescribed for their food-allergic child(ren), and to examine the availability of emergency kits and personalized care plans.
STUDY POPULATION. The parents of 152 food-allergic children prescribed an EAI between June 2000 and March 2003 at 1 of 5 children's hospitals in northern France.
METHODS. An anonymous-questionnaire format was used to collect details on the child's clinical manifestations of allergies, EAI education by a health care provider, verification of proper EAI use at each follow-up visit, availability of a personalized care plan at school, physician instructions in case of allergic reaction, and medications available at home or outside the home. Parents were also asked to list symptoms that required epinephrine (open-ended item).
RESULTS. One hundred nine families representing 111 children completed and returned the survey. The majority (90%) of families had the use of Anapen demonstrated (76% with a trainer device), and 83% had received written instructions. Nineteen percent had a repeat demonstration at follow-up visits, and 10% never received a demonstration; yet, 88% of parents felt that they could use an EAI in an emergency. Only 54% of school-aged children had a personalized care plan, and 11% had an EAI at school with no personalized care plan. Only 48% of the parents could list &gt;1 symptom that required an EAI. There was no difference in the quality of instructions between pediatricians and allergists and no difference in knowledge between parental socioeconomic groups.
CONCLUSIONS. EAIs and personal care plans were insufficiently available at schools and in daily life. Proper EAI use and education were unsatisfactory.
REVIEWER COMMENTS. This study emphasized the importance of extensive and repeated education about food-allergy risks and measures that need to be in place in case of an emergency. Although a majority of parents felt that they knew how to use an EAI, many could not recognize &gt;1 symptom that would require the use of an EAI, and nearly half of the patients did not have an EAI or emergency plan available at school. A disturbing number (10%) of parents never received EAI education, and for those who received education, only a few (19%) had a review of instructions at follow-up. Repeated EAI education is important, because skills acquired at the initial visit are likely to be lost if they are not practiced, and failure to reiterate the importance of knowing how or when to use an EAI may contribute to parents’ indifferent attitude about carrying an EAI or submitting an appropriate personal care plan to the child's school.
The Impact of Spirometry on Pediatric Asthma Diagnosis and Treatment
Authors: Talwar Hanna , Leo Harvey L. 
Published: November 2007

Holt EW, Tan J, Hosgood HD. J Asthma. 2006;43:489–493
PURPOSE OF THE STUDY. To evaluate the use of spirometry as a diagnostic tool in a pediatric asthma-management program at an inner-city community health clinic.
STUDY POPULATION. The study profiled 56 pediatric patients who presented with respiratory symptoms that were indicative of an acute asthma exacerbation.
METHODS. Clinicians recorded each patient's history of asthma symptoms as well as heart rate, respiratory rate, and pulse oximetry. Patients then were assessed for current asthma symptoms and given an initial assessment of asthma, upper respiratory infection, or both. An initial treatment plan for nonreactive airway management, albuterol, yellow-zone management, and/or prednisone/prelone treatment was recorded. After the initial symptom-based diagnosis, a pulmonary-function test was performed by using spirometry measurements. The clinician concluded the visit by making a final assessment of asthma or upper respiratory infection and assigned a final treatment plan that was based on standardized asthma plans.
RESULTS. The most frequently reported physical symptom was general coughing (73.2%), followed by nighttime cough (50.0%), wheezing (35.7%), and trouble sleeping because of cough (21.4%). Approximately two thirds of the patients in this population had abnormal values of forced expiratory volume in 1 second. Physicians changed 30.4% of the patients’ treatment plans after viewing spirometry results.
CONCLUSIONS. Spirometry is an objective tool that can help prevent misclassification of asthma severity and inappropriate use of asthma medication among pediatric patients with asthma. The use of spirometry made an impact in asthma diagnosis at this inner-city clinic: nearly one third of the patients had their treatment plans changed after the spirometry results were viewed.
REVIEWER COMMENTS. The emphasis of this study was to examine the impact of spirometry results on physician behavior in the acute setting. It demonstrates that when clinicians follow the National Asthma Education and Prevention Program guidelines for recommended spirometry use, there were considerable differences in recommendations for treatment. Ensuring appropriate diagnosis cannot solely rely on patients’ signs and symptoms; thus, pediatricians should consider spirometry in asthmatic children.
Immunotherapy With a Ragweed-Toll-Like Receptor 9 Agonist Vaccine for Allergic Rhinitis
Authors: Yu Joyce E. , Sicherer Scott H. 
Published: November 2007

Creticos PS, Schroeder JT, Hamilton RG, et al. N Engl J Med. 2006;355:1445–1455
PURPOSE OF THE STUDY. The conjugate compound of the ragweed antigen, Amba1, and an immunostimulatory DNA sequence containing a CpG motif is associated with a suppression of T-helper 2 cellular and cytokine responses via binding to toll-like receptor 9 (TLR9). This study investigated whether Amba1-immunostimulatory oligodeoxyribonucleotide conjugate (AIC) is a safe and effective immunotherapy for ragweed-sensitized patients.
STUDY POPULATION. A randomized, double-blind, placebo-controlled, phase 2 clinical trial in which 25 participants with a history of fall allergic rhinitis aged 23 to 60 years were assigned to receive a vaccine containing either AIC or placebo.
METHODS. Participants received a total of 6 weekly injections before the ragweed season. The primary clinical end point was the change in albumin level in nasal secretions assessed by a posttreatment nasal allergen challenge. Postchallenge rhinitis symptoms were also scored. Secondary clinical end points included the rhinitis visual analog score, daily nasal symptom diary score, use of relief medication, a rhinoconjunctivitis quality-of-life questionnaire, and skin-test sensitivity. Immunologic evaluation included measuring Amba1- and ragweed-specific immunoglobulin (Ig) G and IgE and cytokine levels.
RESULTS. There was no affect on the primary end point with AIC treatment. However, during the 2 posttreatment ragweed seasons, subjects in the group that received AIC had better peak-season rhinitis visual analog scores, peak-season daily nasal-symptom diary scores, and midseason rhinoconjunctivitis quality-of-life scores. Those in the AIC group also had decreased peak-season use of relief medications and antihistamine and decongestant use in the second season posttherapy. AIC was associated with a rise in the Amba1-specific IgE level after treatment but was not associated with an increase in the Amba1-specific IgE level during either posttreatment ragweed season. There were no vaccine-associated serious adverse reactions.
CONCLUSIONS. AIC may have a potential therapeutic role in the treatment of ragweed-allergic individuals.
REVIEWER COMMENTS. Current allergen immunotherapy involves frequent dosing over 3 to 5 years, which can lead to compliance issues, and may be associated with systemic allergic reactions. The described vaccine is devised to be less likely to trigger allergic reactions during therapy and to enhance nonallergic immune responses to increase efficacy. This study was limited by the small number of patients and the lack of long-term follow-up. However, it suggests that conjugated allergen vaccines may be an option in the future as shorter, safe, and effective immunotherapy regimens that may warrant consideration for use in children.
Does Antibiotic Exposure During Infancy Lead to Development of Asthma? A Systemic Review and Metaanalysis
Authors: Kewalramani Anupama , Bollinger Mary E. 
Published: November 2007

Marra F, Lynd L, Coombes M, et al. Chest. 2006;129:610–618
PURPOSE OF THE STUDY. To determine the association between antibiotic exposure in the first year of life and the development of childhood asthma by conducting a meta-analysis.
METHODS. A search of all available electronic databases (Medline, Embase, EBM databases, Web of Science, PapersFirst, ProceedingsFirst, and the Cochrane database) for the period between January 1966 and September 2004 was performed. Studies included populations receiving at least 1 prescription for an antibiotic during the first year of life. The primary outcome was the development of physician-diagnosed asthma between the ages of 1 and 18 years. Only studies published in English and those that reported odds ratios (ORs) were included.
RESULTS. Review of 2042 references yielded 8 studies that met criteria; 4 were retrospective, and 4 were prospective. The studies were reported between 1999 and 2004 and included sample sizes between 263 and 21 129 children. All retrospective studies used questions from the International Study of Asthma and Allergies in Childhood survey. Five studies were used to determine if there was a dose-response relationship between the number of antibiotic courses received and the risk of childhood asthma. These 5 studies included 27 167 children and 3392 asthma cases. The pooled OR for the 8 studies was 2.05 (95% confidence interval [CI]: 1.41–2.99). The association between antibiotic use in the first year of life and asthma was significantly higher in the retrospective studies (OR: 2.82; 95% CI: 2.07–3.85) than in the prospective studies (OR: 1.12; 95% CI: 0.88–1.42). The overall OR for the dose-response association of antibiotic use in the first year of life and asthma was 1.16 (95% CI: 1.05–1.28), but there was a trend toward a stronger association in the retrospective studies than in the prospective studies.
CONCLUSIONS. Meta-analysis of the impact of antibiotics in the first year of life revealed a possible increase in later development of asthma in childhood on the basis of only the retrospective study results. Additional study is needed to determine a causal relationship.
REVIEWER COMMENTS. This meta-analysis was the first to address the question of whether antibiotic use in the first year of life is associated with subsequent development of asthma. On the basis of the analysis, exposure to at least 1 antibiotic in the first year of life seems to be a risk factor for the development of childhood asthma; however, when the analysis was stratified by the subtypes of studies (prospective versus retrospective), only the pooled results from the retrospective studies yielded a positive association. All of the 95% CIs for the prospective studies crossed 1.00, which brings into question the association between exposure to antibiotics in the first year of life and the subsequent development of childhood asthma. Additional large-scale, prospective studies will be needed to confirm or refute the association.