bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Primary Care Follow-up After a Pediatric Emergency Visit for Asthma
Authors: Leo Harvey L.
Published: September 2006

Purpose of the Study.

To identify predictors associated with primary care pediatrician (PCP) follow-up in children evaluated for acute asthma in a pediatric emergency department (ED).

Study Population.

Parents of children aged 2 to 18 years being discharged after asthma treatment in a pediatric ED.

Methods.

Parents were surveyed by coordinators and described their child’s asthma history and perceived benefits and barriers to making a PCP follow-up visit. Bivariate tests and multivariable logistic regression were used to determine association with completion of a follow-up visit within 4 weeks of the ED visit.

Results.

A total of 278 subjects (n = 278) were enrolled; 55% saw their PCP within 4 weeks of the ED visit. Baseline factors that were associated with an increased likelihood of follow-up included a recent hospitalization, >1 ED visit for asthma in the past year, the parent’s assessment that the child had “very severe” asthma, and current daily use of a controller medication. Parental beliefs that taking daily asthma medications and finding out about the causes of asthma attacks were also associated with increased PCP follow-up rate. Parents were less likely to follow-up if they reported a lack of convenient appointments or prolonged waits in the PCP office. A multivariable model including clinical factors, parental beliefs, and the study intervention predicted the likelihood of follow-up.

Conclusions.

Parental beliefs about asthma severity, the benefits of controlling asthma, and organizational barriers to seeing a PCP were associated with follow-up after a pediatric ED visit for asthma.

Reviewer Comments.

Many children receive their first and subsequent follow-up visits for acute asthma attacks in the ED. Unfortunately, this is an inefficient and cost-prohibitive method of managing asthma. This study attempted to identify parental perceptions of their child’s disease and the barriers to proper follow-up. These issues are paramount for the pediatrician caring for these children. Addressing parental concerns and removing barriers to follow-up can improve asthma control and allow for more cost-effective management and proper utilization of health care resources. Both the acute treating physician and practicing pediatrician can influence the possibility of appropriate follow-up and care.
Massive Infection and Loss of Memory CD4+ T Cells in Multiple Tissues During Acute SIV Infection
Authors: Church Joseph A.
Published: September 2006

Purpose of the Study.

It was recently established that both acute HIV and its simian counterpart, simian immunodeficiency virus (SIV), are accompanied by dramatic and selective loss of memory CD4+ T cells. This loss has been shown to primarily occur in mucosal tissues. The extent and mechanisms underlying this depletion have not been defined. The purpose of this study was to investigate these questions in a simian model.

Methods.

Eight rhesus macaque monkeys were infected with a pathogenic strain of SIV. Plasma and tissue samples were collected at various time points by biopsy and necropsy. Lymphocyte subsets were analyzed with standard flow cytometry, and T-cell–associated viral DNA was measured by a highly sensitive quantitative polymerase chain reaction assay.

Results.

This study demonstrated that in this monkey model, memory CD4+ T cells are depleted in multiple tissues during acute SIV infection. In addition, the loss of these cells is explained by a massive infection of these cells by the virus. Specifically, ∼50% of these cells throughout the body are infected by SIV at the peak of infection, and most of the infected cells disappear within several days. Alternative mechanisms are not required. This depletion occurs to a similar extent in all tissues.

Conclusions.

Acute immunodeficiency virus infection results in the loss of ∼50% of all memory T cells within days of infection. This and other studies strongly suggest that this loss, at least in adult animals and humans, is irreversible.

Reviewer Comments.

This study confirms and extends previous findings demonstrating massive memory T-cell loss during acute HIV or SIV infection. The extent to which this loss is recoverable is likely to be very limited. Most interesting is that these authors also noted that naive T cells are highly resistant to SIV infection. These observations are particularly important for infants infected with HIV. Young infants have fewer memory CD4+ T cells, and, therefore, their loss may not be as critical in newborns. In addition, the thymus in young children may be more capable of reconstituting memory T-cell functions if HIV is completely suppressed early. Similar studies should be performed on infant laboratory animals to determine the extent to which recovery is likely in infected children.
BCG Immunization at Birth and Atopic Diseases in a Homogeneous Population of Spanish Schoolchildren
Authors: Maloney Jennifer M. , Sicherer Scott H.
Published: September 2006

Purpose of the Study.

To investigate the effect of vaccination with BCG on the development of atopic diseases in a homogeneous population of Spanish schoolchildren.

Study Population.

Children aged 6 to 7 years who were living in 3 cities (Bilbao, San Sebastian, and La Coruna) and 1 province (Asturias) of the North Atlantic coast of Spain.

Methods.

The International Study of Asthma and Allergies in Childhood (ISAAC) core and environmental questionnaires were used in 4 different centers of the Spanish North Atlantic coast. Bilbao, San Sebastian, and Asturias have a universal BCG immunization policy during the first days of life, whereas La Coruna discontinued this practice in 1989. Except for this center, immunization coverage was >90%. Parents of children aged 6 and 7 years were surveyed from a random sample of schools of Asturias or all schools in the city district among the remainder of the centers.

Results.

The participation rate was >70%. After excluding those children born outside Spain, there were 6762 immunized and 2828 nonimmunized. After adjusting for gender, age, smoking habits of the father and mother, truck traffic near the household, presence of older and younger siblings, and ownership of a cat or a dog during the first year of the child’s life, the adjusted odds ratios of the BCG-immunized children according to disease outcome were 0.87 for asthma (95% confidence interval [CI]: 0.76–1.00), 0.87 for hay fever (95% CI: 0.75–1.01), and 0.89 for atopic dermatitis (95% CI: 0.76–1.05).

Conclusions.

BCG immunization offers weak protection against atopic diseases in Spanish schoolchildren.

Reviewer Comments.

BCG vaccination has received attention because of its ability to provoke a T-helper (Th)1 response. Many investigators have hypothesized that vaccination with BCG may offer protection from Th2-skewed diseases such as asthma, allergic rhinitis, and atopic dermatitis. Although this study reveals that immunization with BCG offers weak protection against asthma and allergic rhinitis in a homogeneous population, it is important to remember that these diseases are multifactorial, with genetic and environmental influences also impacting pathogenesis.
Hypersensitivity Reactions to Paracetamol in Children: A Study of 25 Cases
Authors: Davis Karla L. , Mikita Cecilia P.
Published: September 2006

Purpose of the Study.

Reports of paracetamol (acetaminophen) allergic and nonallergic hypersensitivity reactions are rare. However, urticaria, angioedema, dyspnea, and allergic and nonallergic anaphylactic reactions have been reported in both children and adults in association with paracetamol administration. Most reactions to paracetamol occur in patients with a nonallergic hypersensitivity to nonsteroidal antiinflammatory drugs (NSAIDs). Alternatively, reactions may result from an allergic hypersensitivity to paracetamol, with tolerance of NSAIDs. This study reports an investigation of 25 children with suspected paracetamol hypersensitivity.

Study Population.

Twenty-five children, aged 8 months to 15 years, with a history of adverse reactions associated with paracetamol administration. In 12 of the 25 children studied, paracetamol adverse reactions were associated with concurrent administration of other medications or biological agents.

Methods.

Diagnosis of paracetamol hypersensitivity was based on either clinical history or the results of an oral challenge test. Reported reactions included urticaria, angioedema, conjunctivitis, dyspnea, and a maculopapular rash. Oral challenge tests with paracetamol were performed in the hospital setting. Paracetamol dosing was initiated at 1 mg and gradually increased until the appropriate cumulative dose for age and weight was achieved. An oral challenge with acetylsalicylic acid was performed in 1 child with a history highly suggestive of paracetamol hypersensitivity.

Results.

Paracetamol hypersensitivity was diagnosed in 1 patient (4%) on the basis of clinical history. The child reported accelerated reactions on 2 occasions, including facial angioedema, conjunctivitis, and dyspnea with wheezing, after isolated intake of paracetamol. Oral challenge to acetylsalicylic acid in this patient induced urticaria and angioedema. Oral challenges to paracetamol in the 24 other children studied were tolerated.

Conclusions.

Results of this study of 25 children with suspected paracetamol hypersensitivity concur with those of previous reports: paracetamol hypersensitivity is rare and is associated with hypersensitivity reactions to antiinflammatory medications.

Reviewer Comments.

Adverse reactions temporally associated with paracetamol may result from reactions to other medications or the underlying conditions for which these medications have been prescribed. Diagnostic evaluation of suspected paracetamol hypersensitivity is complicated further by the lack of validated, available skin or in vitro testing. Adverse reactions to paracetamol can be both allergic and nonallergic in nature. The results of this study underscore the need for careful evaluation for both paracetamol and NSAID hypersensitivity in children with a history suggestive of adverse reactions to paracetamol.
Hospitalization for RSV Bronchiolitis Before 12 Months of Age and Subsequent Asthma, Atopy and Wheeze: A Longitudinal Birth Cohort Study
Authors: Wang Julie
Published: September 2006

Purpose of the Study.

To compare asthma and atopy outcomes of children according to whether they had been admitted to a hospital in the first 12 months with respiratory syncytial virus (RSV)–proven bronchiolitis.

Study Population.

Data from a large, population-based, birth cohort (Avon Longitudinal Study of Parents and Children) were used.

Methods.

Outcomes considered were 12-month prevalence of wheeze at 2 ages (between 30–42 and 69–81 months), cumulative prevalence of doctor-diagnosed asthma at 91 months, and skin-prick test–defined atopy at 7 years. Multivariable logistic-regression models were used to calculate odds ratios for outcomes adjusted for potential confounders.

Results.

A total of 150 infants (1.1% of the cohort) were admitted to a hospital within 12 months of birth with RSV bronchiolitis. The prevalence of wheezing was 28.1% in the RSV group and 13.1% in controls at 30 to 42 months and 22.6% vs 9.6% at 69 to 81 months. The cumulative prevalence of asthma was 38.4% in the RSV group and 20.1% in the controls at 91 months. Atopy was found in 14.6% of those in the RSV group and in 20.7% of the controls at 7 years. RSV bronchiolitis was associated with subsequent wheezing between 30 to 42 months (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.3–3.9) and 69 to 81 months (OR: 3.5; 95% CI: 1.8–6.6) and with the cumulative prevalence of asthma at 91 months (OR: 2.5; 95% CI: 1.4–4.3) but not with atopy (OR: 0.7; 95% CI: 0.2–1.7).

Conclusions.

In a population-based birth cohort, RSV bronchiolitis was associated with subsequent wheezing and asthma but not with the development of atopy by 7 years of age.

Reviewer Comments.

Because infants who have severe RSV infection have recurrent wheezing later in life, RSV has been suggested to be a risk factor for asthma. Some also postulate that early RSV infection may predispose children to atopy; however, this has been controversial. Henderson et al show in their large prospective cohort that severe RSV infection requiring hospitalization is associated with wheezing but not atopy. These results indicate that RSV infection may be a risk factor for nonallergic asthma.
A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients
Authors: Gern James E.
Published: September 2006

Purpose of the Study.

The American Academy of Pediatrics, in their evidence-based guidelines for treatment of otitis media and sinusitis, endorse the use of cephalosporin antibiotics for patients with reported allergies to penicillin. Many physicians, however, remain reluctant to prescribe such agents. This article reviews evidence in support of the American Academy of Pediatrics recommendations for administration of cephalosporins to penicillin-allergic children.

Study Population and Methods.

The author reviewed data from published studies related to penicillin and cephalosporin allergies in children and adults and in animal models.

Results.

Included in this review is an examination of the types and incidence of reactions to penicillins and cephalosporins, the frequency of cross-reactivity between these 2 groups of agents, and a thorough discussion of the clinical guidelines related to penicillin and cephalosporin allergy. Experimental and clinical studies that suggest that side chain–specific antibodies predominate in the immune response to cephalosporins, thereby explaining the lack of cross-sensitivity between most cephalosporins and penicillins. Specific recommendations for the treatment of patients on the basis of their responses to previously prescribed agents are summarized.

Conclusions.

The author concludes that there is a low but measurable (0.5%) attributable risk associated with administration of a first-generation or selected second-generation cephalosporin to a patient with penicillin allergy. This increased risk is not present for third- or fourth-generation cephalosporins or for second-generation molecules with non–cross-reactive side chains.

Reviewer Comments.

This is a very careful, comprehensive, and clinically useful review article. I recommend this article to physicians who would like to understand the evidence base and immunologic concepts underlying the use of cephalosporins in penicillin-allergic individuals.
A Multisite Randomized Trial of the Effects of Physician Education and Organizational Change in Chronic Asthma Care: Cost-effectiveness Analysis of the Pediatric Asthma Care Patient Outcomes Research Team II (PAC-PORT II)
Authors: Smart Brian A.
Published: September 2006

Purpose of the Study.

To estimate the cost-effectiveness of 2 different asthma care interventions: a peer leader–based physician behavior-change intervention (PLE) and a practice-based redesign called the planned asthma care intervention (PACI).

Study Population.

Participants were 638 children (aged 3–17 years) with mild-to-moderate asthma. More than half of the subjects were on maintenance medication.

Methods.

This was a 3-arm cluster-randomized trial conducted in 42 primary care practices. These practices were randomly assigned to PLE (n = 226), PACI (n = 213), or usual care (n = 199). The PLE strategy involved training a pediatrician at each of the practice sites as an asthma expert and champion. This leader provided support, education, and feedback to the other members of the practice with regard to asthma management. The PACI strategy included all the components of the PLE arm and also included scheduled asthma care visits with an asthma nurse, who provided standardized assessments, care planning, coordination with the primary care physician, and self-management tools. Practices in the usual-care arm received copies of the National Asthma Education and Prevention Program Expert Panel Report 2 and patient-information handouts 12 months into the study. The subjects were followed for 2 years. The primary outcome was symptom-free days (SFDs). Costs included asthma-related health care utilization and intervention.

Results.

Patients in the usual-care arm of the study had in increase in SFDs of 14.8 per year. Patients in the PLE and PACI arms had an additional gain of 6.5 and 13.3 SFDs per year, respectively, compared with the usual-care arm. When the costs of development were excluded, the cost for SFDs gained compared with usual care was $18 for PLE and $68 for PACI.

Conclusions.

It is possible to increase SFDs in children and to move organizations toward guideline recommendations for asthma management. However, the improvements were associated with an increase in the costs associated with asthma care.

Reviewer Comments.

This trial was designed to provide cost analyses to both health care providers and health maintenance organizations. It is difficult, however, to establish a threshold for cost-effectiveness. The authors cite other trials to provide a context for this question. For example, the cost-effectiveness of inhaled corticosteroids in the treatment of children ranges from $7 to $12 per SFD gained. A social worker–based intervention had a cost-effectiveness ratio of $9 per SFD gained. What is it worth to patients, their families, and their health care providers to have an extra SFD?
Early Respiratory Infections, Asthma, and Allergy: 10-Year Follow-up of the Oslo Birth Cohort
Authors: Singh Anne Marie , Moss Mark H.
Published: September 2006

Purpose of the Study.

As one dimension of the hygiene hypothesis, early infections may protect against the development of atopic disease. However, there are few long-term follow-up studies of the influence of early respiratory infections. This study investigates associations between early respiratory infections and diagnosed asthma, allergic rhinitis, and skin-prick sensitization in children at 10 years of age.

Study Population.

A total of 2540 Norwegian children were followed prospectively from birth to the age of 10 years in the Oslo Birth Cohort.

Methods.

Information on child’s health and environmental exposures, including experiences with respiratory infections, was recorded at birth and at 6 and 12 months. Current symptoms and “ever” doctor-diagnosed asthma and allergic rhinitis were compared with these early life exposures. A subset of the cohort underwent skin-prick testing.

Results.

“Ever” diagnosis of asthma was positively associated with measures of early life infection. Current asthma was related to lower respiratory tract infection (adjusted odds ratio [aOR]: 2.1; 95% confidence interval [CI]: 1.3–3.0) and croup (aOR: 2.3; 95% CI: 1.3–4.2) in the first year. ORs for allergic rhinitis and skin-prick sensitization were smaller but “mainly positive.” Birth order and child care attendance at 1 year of age were not significantly associated with any of the studied outcomes.

Conclusions.

Early respiratory infections did not protect against the development of atopic disease during the first 10 years of life. Rather, infections increased the risk for asthma at age 10.

Reviewer Comments.

The hygiene hypothesis has been used to explain an inverse relation between early-life infection and allergic disease. Although a number of studies have described the relationship of early childhood infections and atopic disease, few have done so prospectively. This study, with its ORs near 1 with narrow CIs, shows a positive relationship of infections to atopy. Thus, it does not support the view of protection with increasing infection, bringing to light that this relationship is not as simple or direct as was first described. Additional prospective studies with long-term follow-up are required to further define this relationship. In addition, these results support previous conclusions that early childhood infection may be associated with an increased risk for future development of asthma. There continues to be many unanswered questions regarding the risks in susceptible hosts.
A Prospective, Randomized, Double-blind, Placebo-Controlled Multi-centre Study on the Efficacy and Safety of Sublingual Immunotherapy (SLIT) in Children With Seasonal Allergic Rhinoconjunctivitis to Grass Pollen
Authors: Skripak Justin , Wood Robert A.
Published: September 2006

Purpose of the Study.

Subcutaneous immunotherapy (SCIT) for seasonal allergic rhinitis is a well-established, effective, and potentially curative therapy. This study evaluated an alternate route for immunotherapy: the oral mucosa and gastrointestinal tract.

Study Population.

Ninety-seven children, aged 3 to 14 years, with seasonal allergic rhinitis and proven sensitivity to grass pollen were studied.

Methods.

Sensitivity to grass pollen was confirmed by positive skin-prick test, grass pollen–specific immunoglobulin E, and conjunctival provocation test. Patients were enrolled in a prospective, double-blind trial comparing sublingual immunotherapy (SLIT) to placebo. The treatment duration was 32 months. The primary outcome measure was the change in a multiple-symptom/medication score (which measured eye, nasal, and lung symptoms and rescue-medication use) after treatment. Data collected included patient-reported symptom scores and medication use, total and antigen-specific immunoglobulin E, skin-prick test, conjunctival provocation test, nasal provocation test, spirometry, exhaled nitric-oxide concentration, atopic dermatitis score, and eosinophilic cationic protein in nasal lavage fluid.

Results.

The multiple-symptom/medication score was significantly reduced by SLIT to 77.3% of the placebo group (P = .049). This overall score was affected mainly by a large reduction in rescue-medication usage among those in the treatment group (67% of placebo; P = .0025). There was no significant difference in any individual-symptom score.

Conclusion.

SLIT had a positive effect on rescue-medication usage but no significant effect on symptoms alone.

Reviewer Comments.

SLIT represents an alternative therapy with multiple potential advantages to SCIT, including the elimination of injections and improved safety profile. Several studies in adults and children have found improvement in symptom scores as well as reductions in medication use to the point where this is now being used in clinical practice in place of SCIT in many European countries. Additional studies, including investigation of optimal dosing and the potential to use multiple allergens, are needed to further define the future role of SLIT in the United States.
Passive Immunization During Pregnancy for Congenital Cytomegalovirus Infection
Authors: Maloney Jennifer M. , Sicherer Scott H.
Published: September 2006

Purpose of the Study.

To investigate the effectiveness of cytomegalovirus (CMV)-specific hyperimmune globulin for primary CMV infection during pregnancy as a preventive therapy for fetal CMV infection.

Study Population.

One hundred fifty-seven pregnant women from 8 Italian cities with a primary CMV infection diagnosed via serologic testing.

Methods.

Women were placed in 1 of 2 groups. The therapy group comprised women who underwent amniocentesis and whose amniotic fluid contained either CMV detected by culture or CMV DNA detected by polymerase chain reaction. The group was offered intravenous CMV-specific hyperimmune globulin at a dose of 200 U per kg of maternal weight. Additional intravenous, intraumbilical-cord, or intra-amniotic doses were administered if evidence of persistent fetal involvement was present on ultrasound. Women with CMV-positive amniotic fluid who declined to receive hyperimmune-globulin infusions were followed as a comparison group. Those in the prevention group, consisting of women with a recent primary infection before 21 weeks’ gestation or who declined amniocentesis, were offered monthly hyperimmune globulin (100 U/kg intravenously). Pregnant women who declined monthly administration of hyperimmune globulin were followed as a comparison group.

Results.

In the therapy group, 31 women received hyperimmune globulin, only 1 (3%) of whom gave birth to an infant with symptomatic CMV disease, compared with 7 (50%) of 14 women who did not receive hyperimmune globulin. Thus, hyperimmune-globulin therapy was associated with a significantly lower risk of congenital CMV disease (adjusted odds ratio: 0.02; 95% confidence interval: −∞ to 0.15; P < .001). In the prevention group, 37 women received hyperimmune globulin, 6 (16%) of whom had infants with congenital CMV infection, compared with 19 (40%) of 47 women who did not receive hyperimmune globulin. Thus, hyperimmune-globulin therapy was associated with a significantly lower risk of congenital CMV infection (adjusted odds ratio: 0.32; 95% confidence interval: 0.10 to 0.94; P = .04). No adverse effects resulted from CMV-specific hyperimmune globulin administration.

Conclusions.

Treatment of pregnant women with CMV-specific hyperimmune globulin is safe, and the findings of this nonrandomized study suggest that it may be effective in the treatment and prevention of congenital CMV infection. A controlled trial of this agent may be appropriate.

Reviewer Comments.

The risk of congenital CMV infection is high after primary maternal CMV infection. Although the majority of congenitally acquired CMV infections are asymptomatic, symptomatic infections result in significant morbidity and possible mortality. The implementation of CMV-specific hyperimmune globulin may reduce or prevent the devastating effects of symptomatic congenital CMV.
Exposure to Pets, and the Association With Hay Fever, Asthma, and Atopic Sensitization in Rural Children
Authors: Skripak Justin , Wood Robert A.
Published: September 2006

Purpose of the Study.

To evaluate the effect of exposure to animals on the development of hay fever, asthma, and atopy.

Study Population.

Cross-sectional study of 2618 families of Swiss, German, and Austrian decent, living in a rural location. Families were assigned to 1 of 2 categories: farming and nonfarming.

Methods.

Information was collected by standardized questionnaire and interview. Mattress dust was collected and measured for content of endotoxin and cat allergen. Specific immunoglobulin E levels to multiple common allergens and immunoglobulin G4 to cat were measured.

Results.

Complete data were available for 812 children. Among them, 319 were farmers’ children and 493 were nonfarmers’ children. In the entire group, early (<1-year-old) and current exposure to cats was associated with a reduced risk of wheezing and grass pollen sensitization. Current contact with dogs was inversely associated with hay fever, asthma, and sensitization to cat allergen and grass pollen. Early exposure to dog did not have any significant effects. When farm-animal contact was controlled for, most of these associations were weakened but were strongest in farmers’ children.

Conclusions.

There was an inverse relationship between dog exposure and asthma, hay fever, and allergy. However, much of this protective effect was explained by exposure to farm animals.

Reviewer Comments.

There are several studies that report pet exposure to be associated with a reduced risk for atopic disease. In this study, the primary outcome of decreased clinical manifestations of atopy was confounded by exposure to farm animals. Although the exposure to pets did not show an overall statistically significant association, the results approached significance, and a larger study population may have revealed significant differences. Also, the study ultimately found that animal exposure is most likely to provide a protective effect when the total level of exposure is highest (ie, those children exposed to pets and farm animals).
The Safety of Sublingual-Swallow Immunotherapy: An Analysis of Published Studies
Authors: Bollinger Mary Beth
Published: September 2006

Purpose of the Study.

To perform a meta-analysis of all published controlled studies concerning sublingual-swallow immunotherapy (SLIT) to determine rates of adverse events (AEs).

Study Population.

Subjects were from 25 published studies (primarily European) aged 5 to 60 years (6 studies only enrolled children, 9 only adults, and the remainder a mix of both).

Methods.

A systematic Medline review from 1986 to May 2004 was performed. Twenty-five published double-blind, placebo-controlled studies using SLIT that included efficacy and safety data were analyzed. Twelve studies used a high allergen dose (defined as 50–500 times the standard subcutaneous dose), and 13 used a low allergen dose (defined as 1–50 times the subcutaneous dose). AEs were defined as local or systemic: local included oral itching and/or swelling and gastrointestinal complaints, and systemic reactions included skin reactions and ocular, nasal, and chest symptoms. The rates of AEs were compared between the groups. The allergens used in the studies included mites, grasses, trees, and ragweed (single-allergen treatments).

Results.

Combining the studies, there were a total of 445 subjects (405 placebo) in the high-allergen-dose group and 302 subjects (285 placebo) in the low-allergen-dose group. Children accounted for 103 total active-dose subjects. A total of 904 AEs were reported in the 198 553 active-allergen doses given, with 694 local reactions and 210 systemic reactions, with a rate of 0.15 to 0.2 reactions per patient. There were no reports of anaphylaxis. Overall, subjects in the low-allergen-dose group had significantly more local reactions than those in the high-dose group. However, there was no significant difference in the number of patients with AEs between the high- and low-allergen-dose groups when compared as a ratio of the number of SLIT doses received.

Conclusions.

This analysis found that local reactions were common with SLIT but were mild and self-resolved. Systemic reactions occurred rarely and were not dose dependent. The authors conclude that SLIT is safe for use in adults and children.

Reviewer Comments.

SLIT has been widely used in Europe in recent years, has been found to be efficacious by other studies, and has a good safety profile (supported by the meta-analysis). Another article in this same journal (Clin Exp Allergy. 2005;35:560–564) found SLIT to be safe in children younger than 5 years. SLIT is being studied in the United States as well and may be an option in the near future for treatment of allergic rhinitis.
Asthma-Related Health Care Resource Use Among Asthmatic Children With and Without Concomitant Allergic Rhinitis
Authors: Randolph Christopher
Published: September 2006

Purpose of the Study.

To determine the incremental effect of allergic rhinitis on health care resource use in children with asthma.

Study Population.

Children (aged 6–15 years) with asthma and >1 asthma-related encounter with a general practitioner (GP) during a 12-month follow-up period were included from the United Kingdom medical plus general-practice database, including 2 million office patient visits per year to >500 GPs.

Methods.

This was a population-based historical cohort investigation. Asthma and allergic rhinitis were determined by diagnosis codes and drug codes for appropriate medications.

Results.

Of 9522 children with asthma, 1879 (19.7%) had allergic rhinitis recorded in the GP medical charts. Compared with children with asthma alone, children with comorbid allergic rhinitis experienced more GP visits (4.4 vs 3.4) and more of them were hospitalized for asthma (1.4% vs 0.5%) during the 12-month follow-up period. In multivariable regression analyses, comorbid allergic rhinitis was an independent predictor of hospitalization for asthma (odds ratio: 2.34; 95% confidence interval [CI]: 1.41–3.91) and was associated with increases in the number of asthma-related GP visits (mean increase: 0.53; 95% CI: 0.52–0.54) and asthma drug costs (mean increase [British pounds]: £6.7; 95% CI: £6.5–£7.0). The association between allergic rhinitis and higher costs of prescriptions for asthma drugs was independent of asthma severity, measured indirectly by the intensity of use of asthma drugs.

Conclusions.

Children with comorbid allergic rhinitis incurred greater prescription drug costs and experienced more physician visits and hospitalizations for asthma than did children with asthma alone. A unified treatment strategy for asthma and allergic rhinitis, as recommended by the Allergic Rhinitis and Its Impact on Asthma initiative, might reduce the costs of treating these conditions.

Reviewer Comments.

This is a useful study emphasizing the impact of allergic rhinitis on asthma, with implications for better therapeutic approaches. The study may have actually underestimated the impact of allergic rhinitis, because the data are retrospective and diagnosed allergic rhinitis was estimated at only 19.7%, compared with rates as high as 50% among children with asthma in other studies.
Early Childhood Environment Related to Microbial Exposure and the Occurrence of Atopic Disease at School Age
Authors: Skripak Justin , Wood Robert A.
Published: September 2006

Purpose.

There has been much interest in the effect of various microbial exposures early in life on the subsequent development of atopic disease. This study aimed to examine the effects of several exposure types on atopic sensitization.

Study Population.

This was a cross-sectional study of 4111 Dutch schoolchildren aged 8 to 13 years.

Methods.

A questionnaire evaluating day care attendance before age 4, cats or dogs in the home before age 2, siblings, history of doctor-treated airway disease before age 2, and current respiratory status was used. Atopic status was tested by either skin-prick testing or antigen-specific immunoglobulin E levels to multiple common antigens.

Results.

Complete data were available for 1555 of the participants. Atopic sensitization was less frequent in children who attended day care (adjusted odds ratio: 0.74; 95% CI: 0.56–0.99) or had a pet in the home (adjusted odds ratio: 0.78; 95% CI: 0.61–0.99). There was no statistically significant association between the presence of siblings or the occurrence of doctor-treated airway disease and atopy.

Conclusion.

Day care attendance and having a pet in the home may provide a protective effect against atopic sensitization.

Reviewer Comments.

This study attempts to help clarify factors that may be associated with the primary development of atopy, which has been an area of great interest, especially given the rising prevalence of allergic disease. The results are consistent with many other studies indicating that microbial exposure early in life may have a preventive effect. Additional studies, including prospective cohorts, are being performed to define these associations more clearly. With luck, one day we will be able to use this information to design effective preventive strategies.
The Efficacy and Safety of Heat-Killed Lactobacillus paracasei for Treatment of Perennial Allergic Rhinitis Induced by House-Dust Mite
Authors: Wang Julie
Published: September 2006

Purpose of the Study.

Live Lactobacillus paracasei 33 (LP33) may effectively improve the quality of life for patients with perennial allergic rhinitis. It has been demonstrated that heat-killed lactic acid bacteria suppress specific immunoglobulin E synthesis and stimulate interleukin-12 production in animals. The aim of this study, therefore, was to evaluate the efficacy of heat-killed LP33 in the treatment of allergic rhinitis induced by house-dust mite in human subjects.

Study Population.

A total of 90 patients older than 5 years with perennial allergic rhinitis characterized by intermittent or continuous nasal symptoms for >1 year were enrolled in a randomized, double-blind, placebo-controlled trial and assigned to 3 treatment groups.

Methods.

Patients in groups A and B received 2 capsules per day of live or heat-killed lactic acid bacteria (5 × 109 colony-forming units per capsule), respectively, over a period of 30 days, whereas those in group C received placebo capsules. A modified questionnaire on pediatric rhinoconjunctivitis-related quality of life was administered to all subjects or their parents during each clinical visit.

Results.

The overall quality-of-life score decreased for groups A and B compared with the placebo group in terms of both frequency (9.47 ± 2.89, 6.30 ± 2.19, and −3.47 ± 1.53, respectively; P < .0001) and level of bother (5.91 ± 3.21, 6.04 ± 2.44, and −2.80 ± 1.64, respectively; P = .004) after the 30-day treatment. The efficacy of the heat-killed LP33 was not inferior to the live variant. No obvious adverse effects were reported for either active-treatment group during the study period.

Conclusions.

The results suggest that heat-killed LP33 can effectively improve the overall quality of life for patients with allergic rhinitis and that it may be efficacious as an alternative treatment.

Reviewer Comments.

The hygiene hypothesis suggests that lack of early exposure to microorganisms is a factor in the recent rise in allergic disorders. Studies have shown the certain gut flora, including Lactobacillus, may have immunomodulatory effects that may be beneficial in regulating allergic responses. Concerns over safety of administering live bacteria as a therapeutic agent led Peng and Hsu to investigate the effectiveness of heat-killed lactobacillus in the treatment of allergic rhinitis. The authors demonstrate that the heat-killed version is effective in improving the quality of life of patients suffering from allergic rhinitis.
Learning Preferences of Caregivers of Asthmatic Children
Authors: Leo Harvey L.
Published: September 2006

Purpose of the Study.

To determine the learning styles of the caregivers of asthmatic children seen in a pediatric allergy and immunology clinic.

Study Population.

Parents of asthmatic children seen in a tertiary care pediatric allergy and immunology clinic.

Methods.

Caregivers completed the Visual-Aural-Read/Write-Kinesthetic (VARK) questionnaire anonymously, and the responses were evaluated on the basis of previously validated scoring instructions.

Results.

Analysis of 98 respondents showed that 42% had a single learning-modality preference, and the remaining 58% were multimodal learners. Of those who reported a single mode of learning, 61% preferred kinesthetic, 27% preferred reading/writing, and <1% each preferred aural or visual stimuli. Of all 98 caregivers, 82% included kinesthetic as a learning preference, 59% included reading/writing, 50% included aural stimuli, and 41% included visual stimuli.

Conclusions.

The majority of caregivers preferred the kinesthetic learning method, whether as a single learning preference or in combination with other approaches. Incorporating kinesthetic methods of learning, such as role playing and problem-solving case scenarios, into standardized asthma education curricula may be beneficial to patients and families in terms of understanding and using their regimen.

Reviewer Comments.

This is a novel study that attempted to improve asthma care by identifying the learning preferences of the caretakers of asthmatic children. Asthma regimens can be complex, and simplification and understanding of these regimens can improve overall adherence. Individual caretakers demonstrate multiple modes of learning preference, and the current educational modules should focus on role playing and other visual modalities to enhance the understanding of the caretakers’ asthma knowledge. Streamlining and improving these educational methods could result in significant improvement in medication adherence, symptom recognition, and appropriate utilization of medical care.
The Canadian Childhood Asthma Primary Prevention Study: Outcomes at 7 Years of Age
Authors: Arora Rajiv , Mikita Cecilia P.
Published: September 2006

Purpose of the Study.

To evaluate the effects of a multifaceted intervention program involving high-risk infants on the development of asthma at 7 years of age.

Study Population.

Of the original 545 high-risk infants in the Canadian Childhood Asthma Primary Prevention Study, 380 were evaluated at 7 years of age. Infants at high risk for asthma development were defined as those with at least 1 first-degree relative with asthma or 2 first-degree relatives with other immunoglobulin E–mediated allergic diseases.

Methods.

The initial 545 high-risk infants were randomly assigned before birth to a multifaceted intervention group (n = 279) or the control group (n = 266). The multifaceted intervention program, which was implemented before birth and during the first year of life, included house dust mite–control measures, pet-avoidance measures, avoidance of environmental tobacco smoke, breastfeeding, and/or using partially hydrolyzed whey formula. This study describes the follow-up assessment of 380 subjects at 7 years of age who completed a questionnaire and were evaluated by a pediatric allergist for asthma. Allergy skin testing and methacholine challenge were also performed.

Results.

A significantly lower number of subjects had pediatric allergist–diagnosed asthma in the intervention group (14.9%) than in the control group (23.0%; adjusted relative risk [RR]: 0.44). The prevalence of asthma, defined as wheeze plus bronchial hyperreactivity (methacholine challenge), was also significantly lower in the intervention group when compared with the control group (12.9% vs 25%, respectively; adjusted RR: 0.39). There was no significant difference in the diagnosis of allergic rhinitis or atopic dermatitis, allergen skin-test reactivity, or bronchial hyperreactivity alone between the 2 groups. Symptoms of wheeze and wheeze apart from colds in the last 12 months were significantly lower in the intervention group compared with the control group. There were no significant differences in nocturnal symptoms, exercise-related symptoms, medication use, emergency visits for wheeze, nasal symptoms, or skin rash.

Reviewer Comments.

Asthma and allergic diseases likely result from a combination of environmental and genetic factors. This study showed that the prevalence of asthma was decreased after an intervention program implemented early in life. Thus, recommending environmental controls as a safe method to decrease the risk of developing asthma in high-risk patients is reasonable. It is unclear from this study whether a specific environmental control or a combination of interventions is more effective. It is interesting that no difference was noted in the prevalence of allergic rhinitis or atopic dermatitis between the groups, which, theoretically, could also be affected by environmental controls.
The PREVASC Study: The Clinical Effect of a Multifaceted Educational Intervention to Prevent Childhood Asthma
Authors: Phipatanakul Wanda
Published: September 2006

Purpose of the Study.

To evaluate the clinical effectiveness of a multifaceted education intervention to prevent childhood asthma.

Study Population.

General practitioners recruited 476 high-risk children during the prenatal period.

Methods.

These high-risk children were randomly assigned to either a control group, receiving usual care, or an intervention group, in which families received instruction from nurses on how to reduce exposure of newborns to dust mite, pet, and food allergens and passive smoking.

Results.

A total of 443 infants were followed up for 2 years. At 2 years of age, those in the intervention group (n = 222) had less asthma-like symptoms, including wheezing, shortness of breath, and nighttime cough, compared with those in the control group (n = 221). No significant differences in total and specific immunoglobulin E were found between the groups. During the first 2 years of life, the incidence of asthma-like symptoms was similar in both groups; however, subanalysis revealed a significant reduction in the females but not in the males in the intervention group.

Conclusions.

The intervention used in this study was not effective in reducing asthma-like symptoms in high-risk children during the first 2 years of life, although it was modestly effective at 2 years. Follow-up is necessary to confirm whether the intervention can actually prevent the development of asthma.

Reviewer Comments.

This is a well-designed study in a primary care environment to investigate the clinical effectiveness of a multifaceted approach to prevent the development of asthma in high-risk children. It seemed that the intervention was moderately able to reduce exposure to dust mite, pet, and food allergens, but no significant effect was observed on parentally observed symptoms or allergen-specific immunoglobulin E in the first 2 years of life. Perhaps a more focused intervention or longer follow-up period would have proven more useful. The effectiveness of a variety of multifaceted randomized intervention trials on asthma prevention has yet to be determined. Although a host of epidemiologic studies have helped identify risk factors, we will all be interested in determining whether any practical interventions may be promising in preventing asthma development.
IL-19 Induced Th2 Cytokines and Was Up-regulated in Asthma Patients
Authors: Sharma Hemant , Matsui Elizabeth
Published: September 2006

Purpose of the Study.

Interleukin-10 (IL-10) has been shown to inhibit allergen-induced airway hyperresponsiveness and inflammation. This study evaluates whether IL-19, a member of the IL-10 family, is associated with asthma.

Study Population.

The authors investigated IL-19 levels in 100 asthmatic patients, aged 3 to 12 years, as well as 50 healthy adults and 50 age-matched children. A dust mite–induced mouse model of asthma was also used to study the association of IL-19 with asthma.

Methods.

Cytokine levels were quantified by enzyme-linked immunosorbent assay. IL-19 levels were measured in all study subjects, but among asthmatic patients, the levels of IL-4 and IL-13 were analyzed in the 27 patients with the highest and 25 patients with the lowest IL-19 levels. By using a dust mite–sensitized murine asthma model, IL-19 levels were measured in asthmatic and control mice. To test whether IL-19 upregulates T-helper 2 (Th2) cytokines, IL-19 complementary DNA was injected into healthy mice using intramuscular electroporation, and serum levels of IL-4, IL-5, IL-10, and IL-13 were later monitored. After injection of IL-19 into asthmatic mice, IL-13 and immunoglobulin E (IgE) levels were measured. To determine if IL-19 could induce Th2 cytokine production in vitro, IL-19 was incubated with CD4+ T cells and IL-4, IL-5, IL-10, and IL-13 levels were quantified in the cell-culture supernatant.

Results.

Among asthmatic patients, the serum level of IL-19 was twice that of healthy controls, and those with a high level of IL-19 also had high levels of IL-4 and IL-13. In the murine asthma model, asthmatic mice also had IL-19 levels twice that of healthy control mice. Injection of the IL-19 gene into healthy mice induced production of IL-4, IL-5, and IL-10 but not IL-13. IL-19 upregulated IL-13 in asthmatic mice and also upregulated IgE production. In vitro, IL-19 was associated with increased IL-4, IL-5, IL-10, and IL-13 production by activated cells.

Conclusions.

IL-19 upregulates production of Th2 cytokines in activated T cells and may be an important molecule in the pathogenesis of asthma.

Reviewer Comments.

The Th2 cytokines upregulated by IL-19 play crucial roles in the pathogenesis of asthma. IL-13 regulates airway hypersensitivity and mucus hypersecretion; IL-4 is critical for IgE antibody switching; and IL-5 plays a key role in eosinophil maturation. The findings from this study suggest that IL-19 is another potentially important molecule in asthma pathogenesis and may be responsible, at least in part, for upregulation of Th2 cytokines that are critical to the development of allergic disease.