Chronic idiopathic urticaria (CU) has been associated with other autoimmune diseases and basophil-activating autoantibodies to FcεRI or IgE. It is unknown whether patients with systemic-autoimmune diseases have a similar prevalence of these autoantibodies.
To compare the prevalences of basophil-activating autoantibodies (elevated CU Index) in patients with CU, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Clinical characteristics and laboratory studies were examined for an association with the CU Index.
Adult patients, 27 with CU, 27 with RA, and 26 with SLE, and 20 healthy controls were compared on the basis of the CU Index panel, anti-IgE, and antithyroid antibodies.
The CU Index values were significantly higher in the CU group when compared with the RA group but not when compared with the SLE group. 33% of CU, 23% of SLE, 3.7% of RA, and 15% of controls had apositive CU Index. Elevated antithyroid antibody levels did not correlate with a positive CU Index in any of the groups. An elevated CU Index in the SLE group was not associated with age, sex, ethnicity, disease severity, or history of atopy.
The CU Index values were elevated in patients with CU and SLE. The presence of these autoantibodies did not correlate with disease activity or presence of thyroid antibodies. Functional autoantibodies may not be specific for chronic idiopathic urticaria, and their role in nonurticarial systemic autoimmune diseases requires further investigation.
Assessment of indoor allergen is valuable in exposure research and evaluation of allergic individuals. Collection methods range from grab vacuum samples to filtration devices located in the breathing range of an individual. For practical purposes, many research studies use analysis of collected house dust to evaluate allergen reservoirs.
To test the hypothesis that house dust collected from the family vacuum is equivalent to house dust collected by a technician following standard protocol.
Homes from a healthy homes demonstration project (n = 41) were sampled using a specific Department of Housing and Urban Development–suggested protocol in the bedroom of the child with asthma and a simple grab procedure from the family vacuum. Samples were evaluated for the presence of 5 allergens, Bla g2, Can f1, Der f1, and Der p1 combined as total mite, Fel d1, and Mus m1. Samples were also evaluated for total antigenic protein from 4 fungal taxa, including Alternaria, Aspergillus, Cladosporium, and Penicillium.
All of the allergens and antigens tested showed good correlation between the 2 collection methods. Fungal antigens ranged up to 92,651 nanograms per gram of dust for Aspergillus, and allergens ranged up to 17,928 nanograms per gram of dust for Can f1. The best correlation was for Cladosporium (r = 0.91), and the weakest was for dust mite (r = 0.34).
Allergens and antigens tested from samples collected by protocol and by grab sampling from the home vacuum were highly positively correlated. Grab samples taken from the family vacuum may be a good surrogate for evaluating home allergen exposure.
Forty million children are regularly exposed to environmental tobacco smoke (ETS) each year, increasing their risk for premature death and middle ear and acute respiratory infections. Early life exposure to ETS also is clearly associated with wheezing. However, there is no clear understanding of the influence of ETS on the development of allergic sensitization.
To determine the association of combined exposure to ETS and indoor allergens on IgE sensitization to aeroallergens in children.
This case–control study enrolled 116 cases and 121 controls from low-income families from Kansas City, Missouri. The adjusted odds ratio was calculated using a logistic model to assess the association between ETS and allergic sensitization using dust allergen levels as a covariate.
Thirty-six percent of atopic children and 39% of controls were exposed to ETS (P < .05). Unadjusted analyses showed no significant influence of ETS on IgE sensitization to indoor allergens. Logistic regression analyses also showed no significant influence of ETS on sensitization when adjusted for levels of allergens in the home dust and family history of allergic rhinitis.
These data suggest that ETS exposure was not associated with IgE sensitization to indoor allergens, even when home allergen levels were taken into consideration. Further understanding of how components of tobacco smoke influence the immune response is necessary to interpret the disparate findings across studies.
The relationship between obesity and asthma is an area of debate.
To investigate the association of elevated body mass index (BMI) at a young age and young adult asthma.
BMI, questionnaires, and serologic tests results were analyzed in participants of a predominantly white, middle-class, population-based birth cohort from Detroit, Michigan at 6 to 8 and 18 years of age. Asthma diagnosis was based on medical record data. Allergen specific IgE was analyzed using UniCAP, with atopy defined as 1 or more allergen specific IgE levels of 0.35 kU/L or higher. Overweight was defined as a BMI in 85th percentile or higher.
A total of 10.6% of overweight males at 6 to 8 years of age had current asthma at 18 to 20 years of age compared with 3.2% of males who were normal or underweight (relative risk [RR], 3.3; 95% confidence interval [CI], 1.0–11.0; P=.048). A total of 19.6% of females who were overweight at 6 to 8 years of age had asthma compared with 10.3% of females who were normal or underweight (RR, 1.9; 95% CI, 0.9–3.9; P=.09). After adjustment for atopy at 6 to 8 years of age, overweight males had an adjusted RR of 4.7 (95% CI, 1.4–16.2; P=.01), and overweight females had an adjusted RR of 1.7 (95% CI, 0.8–3.3; P=.15). Change in BMI between 6 to 8 years of age and 18 to 20 years of age was also examined. Patients with persistently elevated BMI exhibited increased risk of asthma as young adults (RR, 2.4; 95% CI, 1.2–4.7) but not with an increasing BMI (RR, 0.8; 95% CI, 0.3–2.2) or a decreasing BMI (RR, 0.8; 95% CI, 0.3–2.2).
Overweight males 6 to 8 years of age have increased risk of asthma as young adults. Being overweight remains a predictor of asthma after adjustment for early atopy. A similar but not statistically significant trend was also seen among overweight females. Overweight body habitus throughout childhood is a risk factor for young adult asthma.
To reduce symptoms and emergency department (ED) visits, the National Asthma Education and Prevention Program (NAEPP) guidelines recommend early treatment of acute asthma symptoms with albuterol and oral corticosteroids. Yet, ED visits for asthma are frequent and often occur several days after onset of increased symptoms, particularly for children from low-income urban neighborhoods.
To describe home use of albuterol and identify factors associated with appropriate albuterol use.
114 caregivers in the intervention group of a randomized trial to reduce emergent care for low-income, urban children completed a structured telephone interview with an asthma nurse to assess home management of their child’s acute asthma symptoms. Albuterol use as reported by caregivers was categorized as appropriate or inappropriate based on NAEPP recommendations.
Albuterol use for worsening asthma symptoms was categorized as appropriate for only 68% of caregivers and was more likely if the children had an ED visit or hospitalization for asthma in the prior year. The remaining 32% of caregivers used albuterol inappropriately (over or under treatment). Appropriate albuterol use was not associated with caregiver report of having an Asthma Action Plan (AAP) or a recent primary care provider visit to discuss asthma maintenance care.
Caregivers reported they would use albuterol to treat their child’s worsening asthma symptoms, but many described inappropriate use. Detailed assessment of proper albuterol use at home may provide insight into how healthcare providers can better educate and support parents in their management of acute exacerbations and more effective use of AAPs.
Childhood asthma; asthma action plan
Asthma guidelines recommend early home treatment of exacerbations. However, home treatment is often suboptimal and delayed.
To describe antecedent symptoms and signs of asthma exacerbations noticed by parents, and learn when and how parents intensify asthma treatment.
Parents of children 2-12 years old with asthma exacerbations requiring urgent care in the past 12 months completed telephone questionnaires. For some questions, multiple responses were possible and percentages for the frequency of responses may sum to more than 100%.
One hundred and one parents were enrolled and interviewed; 94% were the children's mothers. 70% of the children were African American and 64% had Medicaid insurance. Parents reported multiple antecedent symptoms and signs (median number per child = 3, range 1-6). These included respiratory symptoms (79%), allergy/cold symptoms (43%), behavioral changes (24%), and other non-specific symptoms (29%). Twenty-three parents reported late respiratory symptoms such as gasping for breath, and using accessory muscles to breath as the earliest antecedent signs. Treatment was most often intensified when the parent noticed cough (55%), shortness of breath (54%), and wheeze (25%), and included adding albuterol (92%), oral corticosteroid (17%), inhaled corticosteroid (8%) or other non-asthma medications (16%).
Although parents described antecedent symptoms and signs of impending asthma exacerbations they consistently noticed in their children, many waited for lower respiratory signs to be present before intensifying treatment. Oral corticosteroids were used infrequently. Interventions to improve the ability of parents and children to accurately recognize worsening symptoms and initiate timely, effective treatment are needed.
Childhood asthma; asthma exacerbation
Ectodermal dysplasia (ED) syndromes are a diverse group of disorders that affect multiple ectodermally derived tissues. Small studies and case reports suggest an increase in atopy and primary immunodeficiencies (PIDs) among patients with ED syndromes.
To determine the prevalence of clinical symptoms suggestive of atopy or immunodeficiency among a large cohort of children with ED syndromes.
A 9-page questionnaire was mailed to families who were members of the National Foundation for Ectodermal Dysplasias. The surveys were completed by parents of children younger than 18 years with a diagnosis of an ED syndrome or carrier state. Portions of the questionnaire were adapted from previously validated questionnaires developed by the International Study of Asthma and Allergies in Childhood (ISAAC).
We received 347 completed questionnaires (41%). When compared with the 13- to 14-year-old children surveyed by ISAAC, we found both all-aged and age-matched children with ED syndromes, respectively, had significantly higher rates of asthma (32.2% and 37.2% vs 16.4%), rhinitis symptoms (76.1% and 78.3% vs 38.9%), and eczema (58.9% and 48.9% vs 8.2%). The prevalence of physician-diagnosed food allergies (20.7%) and PIDs (6.1%) in these ED patients also exceeded known rates in the general pediatric population.
This large-scale, retrospective study demonstrates a greater reported prevalence of symptoms suggestive of atopic disorders and PIDs among children with ED syndromes than the general pediatric population. A combination of genetic and environmental factors in ED syndromes may contribute to breaches of skin and mucosal barriers, permitting enhanced transmission and sensitization to irritants, allergens, and pathogens.
Little is known about factors associated with systemic corticosteroid (SC) use in emergency department (ED) patients with acute asthma.
To determine the patient and system factors associated with delayed use or nonuse of SCs in the ED.
We analyzed the asthma component of the National Emergency Department Safety Study. Patients with acute asthma in 62 urban EDs in 23 US states between 2003 and 2006 were identified. The primary outcome measure was the pattern of SC use in the ED, which was categorized as timely use (≤60 minutes), delayed use (>60 minutes), or nonuse. Multinomial logistic regression was performed to identify factors associated with delayed use or nonuse of SCs.
A total of 2,559 of 3,798 patients with acute asthma (67.4%) received SCs. Of these, the median door-to-SC time was 62 minutes (interquartile range, 35–100 minutes), with 1,319 patients (51.5%) having delayed SC treatment. Nonuse of SCs was largely explained by markers of asthma exacerbations (never intubated for asthma, lower respiratory rate, and higher oxygen saturation). In contrast, in addition to these factors, delayed SC treatment was associated with age of 40 years or older, female sex, longer duration of symptoms, ED presentation between 8 AM and 11:59 PM, and ED with a longer average patient wait time.
Physicians in the ED seem to appropriately administer SCs to higher-acuity asthmatic patients; however, the additional nonmedical factors represent opportunities to improve the timeliness of SC treatment in the ED.
Asthma severity score; acute asthma exacerbation; asthma assessment
Small proline rich protein 2B (SPRR2B) is a skin and lung epithelial protein associated with allergic inflammation in mice that has not been evaluated in human atopic diseases.
To determine whether single-nucleotide polymorphisms (SNPs) in SPRR2B are associated with childhood eczema and with the phenotype of childhood eczema combined with asthma.
Genotyping for SPRR2B and filaggrin (FLG) was performed in 2 independent populations: the Cincinnati Childhood Allergy & Air Pollution Study (CCAAPS; N = 762; birth-age, 4 years) and the Greater Cincinnati Pediatric Clinical Repository (GCPCR;N = 1152; ages 5–10 years). Eczema and eczema plus asthma were clinical outcomes based on parental report and clinician’s diagnosis. Genetic analyses were restricted to whites and adjusted for sex in both cohorts and adjusted for environmental covariates in CCAAPS.
Variants in SPRR2B were not significantly associated with eczema in either cohort after Bonferroni adjustment. Children from both cohorts with the CC genotype of the SPRR2B rs6693927 SNP were at 4 times the risk for eczema plus asthma (adjusted odds ratio, 4.1; 95% confidence interval, 1.5– 10.9; P = .005 in CCAAPS; and adjusted odds ratio, 4.0; 95% confidence interval, 1.8 –9.1; P <.001 in the GCPCR), however. SNPs in SPRR2B were not in strong linkage disequilibrium with the R501X and del2282 FLG mutations, and these findings were independent of FLG.
An SNP in SPRR2B was predictive of asthma among white children with eczema from 2 independent populations. SPRR2B polymorphisms may serve as important predictive markers for the combined eczema plus asthma phenotype.
The incidence of wheeze is unknown and the role of early life wheeze in subsequent health is not clearly understood. Our goal was to calculate the age-specific incidence of wheeze and determine whether wheezing at particular times in early life was predictive of abnormal airway hyperresponsiveness (AHR), percent predicted FEV1 and current asthma at age 6 years.
Using data from a birth cohort study with annual report of wheezing (Childhood Allergy Study) and spirometry and methacholine challenge at age 6 years, the age-specific incidence of wheeze was determined using Kaplan-Meier estimates. Logistic and linear regression models were used to assess the associations between the presence of age-specific wheezing and the outcomes of current asthma, AHR and percent predicted FEV1 at age 6 years.
The 6-year cumulative incidence of wheezing was higher for boys (66.2%, 95% CI 59.8%, 72.6%) than girls (47.6% 95% CI 41.4%, 53.8%). There was no age when wheezing was more strongly associated with either AHR or percent predicted FEV1 at 6 years. Only wheeze in the fifth year among males and in females, both wheezing in the fourth and fifth years were positively predictive of current asthma at age 6. This is likely due to the definition of current asthma (ever doctor diagnosis and either medication or symptoms in last year). Eczema, parental asthma history and total cord blood IgE did not affect these associations.
Wheezing at any particular time in early life may not be predictive of early childhood lung function.
ACT; C-ACT; Hispanic; Spirometry
exhaled nitric oxide; FENO; exhaled breath condensate; cysteinyl leukotrienes; asthma; lung function; exacerbation; hospitalization
Studies looking at use of repeated doses of epinephrine in anaphylaxis are limited.
To determine which patients are most likely to receive repeated doses of epinephrine during anaphylaxis management.
A population-based study, with medical record review was conducted. All patients seen during the study period who met criteria for diagnosis of anaphylaxis were included.
The cohort included 208 patients (55.8% female). Anaphylaxis treatment included epinephrine in 104(50%) cases. Repeated doses were used in 27(13.0%) patients (48.1% female). The median age of those who received repeated doses was 18.9 years (IQR 10-34) versus 31.1 years (IQR 15-41), p=0.065 for those who did not. The inciting agents were food (29.6%), insects (11.1%), medications (22.2%), others (7.4%) and unknown (29.6%). Patients who received repeated doses were more likely to have wheezing (p=0.028), cyanosis (p=0.001), hypotension and shock (p=0.032), stridor and laryngeal edema (p=0.007), nausea and emesis (p=0.043), arrhythmias (p<0.01) and cough and less likely to have urticaria (p=0.049). They were more likely to be admitted to hospital (48.2% vs 15.6%, p=0.0007). There was no significant difference in history of asthma between patients who received repeated doses and those who did not (p=0.168).
Thirteen percent of patients received repeated doses of epinephrine. Patients were younger and were more likely to present with wheezing, cyanosis, arrhythmias, hypotension and shock, stridor, laryngeal edema, cough, nausea, and emesis, and less likely to have urticaria. History of asthma did not predict use of repeated doses of epinephrine. Our results help identify high risk patients who may benefit from carrying more than one dose of epinephrine.
Sensitivity to mold has been associated with asthma incidence, persistence, and severity.
To examine the relationship between skin test reactivity (STR) to molds and specifically to Alternaria and asthma severity in a group of ethnically diverse children in Connecticut.
Demographics and STR to 14 local allergens, including Alternaria, Penicillium, and mold mix, were obtained for 914 Puerto Rican, African American, and non-Hispanic white children.
A total of 126 children (14%) had a positive skin test result to mold, and 58 (6%) demonstrated STR to Alternaria. Compared with non-Hispanic white children, there was no difference in the likelihood of being sensitized to Alternaria for Puerto Rican and African American children (odds ratio [OR], 0.7; 95% confidence interval [CI], 0.3–1.5; and OR, 0.9; 95% CI, 0.4–2.2; respectively). In an adjusted analysis, Alternaria STR was associated with severe, persistent asthma (OR, 3.4; 95% CI, 1.2–8.6) but did not predict increasing asthma severity. STR to cat (OR, 2.5; 95% CI, 1.3–4.9) and dog (OR, 2.9; 95% CI, 1.3–6.0) was also associated with severe persistent asthma. Alternaria STR was associated with severe persistent asthma independent of the total number of positive skin test results.
Mold and Alternaria STR were uncommon among children in Connecticut. Alternaria STR was not associated with increasing asthma severity but was associated with severe, persistent asthma independent of the total number of positive skin test results. There was no association between ethnicity and Alternaria STR.
Asthma is a significant disease among children, and its prevalence has increased notably during the last 2 decades. A traditional Korean medicine, So-Cheong-Ryong-Tang (SCRT), has been used for the treatment of asthma in Asia for centuries, but its mechanism for reducing bronchopulmonary inflammation in asthma has yet to be elucidated.
To investigate whether the herbal extract SCRT inhibits inflammation in a mouse model of cockroach allergen–induced asthma.
A house dust extract containing endotoxin and cockroach allergens was used for immunization and 2 additional pulmonary challenges in BALB/c mice. Mice were treated with SCRT or vehicle 1 hour before each pulmonary challenge. Respiratory parameters were evaluated by whole-body plethysmography and forced oscillation methods 24 hours after the last challenge. Bronchoalveolar lavage (BAL) fluid was collected, and histologic sections of lung were prepared either 4 or 24 hours after the last house dust extract challenge.
SCRT treatment significantly reduced the hyperreactivity of the airways as measured by whole-body plethysmography and direct measurement of airway resistance. Inflammation was significantly inhibited by SCRT treatment as demonstrated by reduced plasma IgE levels and improved pulmonary histologic characteristics. SCRT significantly reduced the number of neutrophils in the BAL fluid and also significantly reduced the BAL levels of CXC chemokines, providing a potential mechanism for the reduced inflammation. In a similar fashion, SCRT reduced eosinophil recruitment and BAL levels of eotaxin and RANTES.
These data indicate that SCRT treatment alleviates asthma-like pulmonary inflammation via suppression of specific chemokines.