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1.  Management of Rodent Exposure and Allergy in the Pediatric Population 
Current allergy and asthma reports  2013;13(6):10.1007/s11882-013-0378-4.
Although rodent allergy has long been recognized as an occupational disease, it has only been in the past decade that it has been recognized as a community-based disease that affects children. Most homes in the US have detectable mouse allergen, but the concentrations in inner-city homes are orders of magnitude higher than those found in suburban homes. Home mouse allergen exposure has been linked to sensitization to mouse, and children with asthma who are both sensitized and exposed to high mouse allergen concentrations at home are at greater risk for symptoms, exacerbations and reduced lung function. Rat allergen is found primarily in inner-city homes and has also been linked to asthma morbidity among sensitized children. The objective of this review is to summarize the scientific literature on rodents and their allergens, the effects of exposure to these allergens on allergic respiratory disease, and to make recommendations, based on this evidence base, for the evaluation and management of mouse allergy in the pediatric population.
PMCID: PMC3840032  PMID: 23912589
Childhood asthma; Inner-city asthma; Rodent allergens; Environmental intervention; Integrated pest management; Pediatric; Rodent exposure; Allergy; Sensitization
2.  Indoor Pollutant Exposures Modify the Effect of Airborne Endotoxin on Asthma in Urban Children 
Rationale: The effect of endotoxin on asthma morbidity in urban populations is unclear.
Objectives: To determine if indoor pollutant exposure modifies the relationships between indoor airborne endotoxin and asthma health and morbidity.
Methods: One hundred forty-six children and adolescents with persistent asthma underwent repeated clinical assessments at 0, 3, 6, 9, and 12 months. Home visits were conducted at the same time points for assessment of airborne nicotine, endotoxin, and nitrogen dioxide (NO2) concentrations. The effect of concomitant pollutant exposure on relationships between endotoxin and asthma outcomes were examined in stratified analyses and statistical models with interaction terms.
Measurements and Main Results: Both air nicotine and NO2 concentrations modified the relationships between airborne endotoxin and asthma outcomes. Among children living in homes with no detectable air nicotine, higher endotoxin was inversely associated with acute visits and oral corticosteroid bursts, whereas among those in homes with detectable air nicotine, endotoxin was positively associated with these outcomes (interaction P value = 0.004 and 0.07, respectively). Among children living in homes with lower NO2 concentrations (<20 ppb), higher endotoxin was positively associated with acute visits, whereas among those living in homes with higher NO2 concentrations, endotoxin was negatively associated with acute visit (interaction P value = 0.05). NO2 also modified the effect of endotoxin on asthma symptom outcomes in a similar manner.
Conclusions: The effects of household airborne endotoxin exposure on asthma are modified by coexposure to air nicotine and NO2, and these pollutants have opposite effects on the relationships between endotoxin and asthma-related outcomes.
PMCID: PMC3863732  PMID: 24066676
childhood asthma; endotoxin; indoor pollution; nitrogen dioxide; second-hand smoke
3.  Mouse allergen is the major allergen of public health relevance in Baltimore City 
Cockroach and mouse allergens have both been implicated as causes in inner-city asthma morbidity in multicenter studies, but whether both allergens are clinically relevant within specific inner-city communities is unclear. Objective: Our study aimed to identify relevant allergens in Baltimore City.
One hundred forty-four children (5–17 years old) with asthma underwent skin prick tests at baseline and had clinical data collected at baseline and 3, 6, 9, and 12 months. Home settled dust samples were collected at the same time points for quantification of indoor allergens. Participants were grouped based on their sensitization and exposure status to each allergen. All analyses were adjusted for age, sex, and serum total IgE level.
Forty-one percent were mouse sensitized/exposed, and 41% were cockroach sensitized/exposed based on bedroom floor exposure data. Mouse sensitization/exposure was associated with acute care visits, decreased FEV1/forced vital capacity percentage values, fraction of exhaled nitric oxide levels, and bronchodilator reversibility. Cockroach sensitization/exposure was only associated with acute care visits and bronchodilator reversibility when exposure was defined by using bedroom floor allergen levels. Mouse-specific IgE levels were associated with poor asthma health across a range of outcomes, whereas cockroach-specific IgE levels were not. The relationships between asthma outcomes and mouse allergen were independent of cockroach allergen. Although sensitization/exposure to both mouse and cockroach was generally associated with worse asthma, mouse sensitization/exposure was the primary contributor to these relationships.
In a community with high levels of both mouse and cockroach allergens, mouse allergen appears to be more strongly and consistently associated with poor asthma outcomes than cockroach allergen. Community-level asthma interventions in Baltimore should prioritize reducing mouse allergen exposure.
PMCID: PMC3800085  PMID: 23810154
Inner-city asthma; childhood asthma; mouse allergen; cockroach allergen; indoor allergens
4.  Dose-response Relationships between Mouse Allergen Exposure and Asthma Morbidity Among Urban Children and Adolescents 
Indoor air  2012;23(4):268-274.
Home mouse allergen exposure is associated with asthma morbidity, but little is known about the shape of the dose-response relationship or the relevance of location of exposure within the home.
Asthma outcome and allergen exposure data were collected every three months for 1 year in 150 urban children with asthma. Participants were stratified by mouse sensitization and relationships between continuous measures of mouse allergen exposure and outcomes of interest were analyzed.
Every ten-fold increase in the bed mouse allergen level was associated with an 87% increase in the odds of any asthma-related health care use among mouse sensitized (OR (95% CI): 1.87 (1.21–2.88)), but not non-mouse sensitized participants. Similar relationships were observed for emergency department visit and unscheduled doctor visit among mouse sensitized participants. Kitchen floor and bedroom air mouse allergen concentrations were also associated with greater odds of asthma-related healthcare utilization; however, the magnitude of the association was less than that observed for bed mouse allergen concentrations.
In this population of urban children with asthma, there is a linear dose-response relationship between mouse allergen concentrations and asthma morbidity among mouse-sensitized asthmatics. Bed and bedroom air mouse allergen exposure compartments may have a greater impact on asthma morbidity than other compartments.
PMCID: PMC3562552  PMID: 23067271
Mouse allergen; inner-city asthma; childhood asthma; exposure compartments; indoor allergens; asthma morbidity
5.  Asthma Outcomes: Asthma Symptoms 
Respiratory symptoms are commonly used to assess the impact of patient-centered interventions.
At the request of National Institutes of Health (NIH) institutes and other federal agencies, an expert group was convened to propose which measurements of asthma symptoms should be used as a standardized measure in future clinical research studies.
Asthma symptom instruments were classified as daily diaries (prospectively recording symptoms between research visits) or retrospective questionnaires (completed at research visits). We conducted a systematic search in PubMed and a search for articles that cited key studies describing development of instruments. We classified outcome instruments as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011.
Four instruments (3 daily diaries, 1 for adults and 2 for children; and 1 retrospective questionnaire for adults) were identified. Minimal clinically important differences have not been established for these instruments, and validation studies were only conducted in a limited number of patient populations. Validity of existing instruments may not be generalizable across racial-ethnic or other subgroups.
An evaluation of symptoms should be a core asthma outcome measure in clinical research. However, available instruments have limitations that preclude selection of a core instrument. The working group participants propose validation studies in diverse populations, comparisons of diaries versus retrospective questionnaires, and evaluations of symptom assessment alone versus composite scores of asthma control.
PMCID: PMC4263029  PMID: 22386505
Asthma Symptom Utility Index; Asthma Symptom Diary Scales; Pediatric Asthma Caregiver Diary
6.  Being overweight increases susceptibility to indoor pollutants among urban children with asthma 
Both being overweight and exposure to indoor pollutants, which have been associated with worse health of asthmatic patients, are common in urban minority populations. Whether being overweight is a risk factor for the effects of indoor pollutant exposure on asthma health is unknown.
We sought to examine the effect of weight on the relationship between indoor pollutant exposure and asthma health in urban minority children.
One hundred forty-eight children (age, 5–17 years) with persistent asthma were followed for 1 year. Asthma symptoms, health care use, lung function, pulmonary inflammation, and indoor pollutants were assessed every 3 months. Weight category was based on body mass index percentile.
Participants were predominantly African American (91%) and had public health insurance (85%). Four percent were underweight, 52% were normal weight, 16% were overweight, and 28% were obese. Overweight or obese participants had more symptoms associated with exposure to fine particulate matter measuring less than 2.5 μm in diameter (PM2.5) than normal-weight participants across a range of asthma symptoms. Overweight or obese participants also had more asthma symptoms associated with nitrogen dioxide (NO2) exposure than normal-weight participants, although this was not observed across all types of asthma symptoms. Weight did not affect the relationship between exposure to coarse particulate matter measuring between 2.5 and 10 μm in diameter and asthma symptoms. Relationships between indoor pollutant exposure and health care use, lung function, or pulmonary inflammation did not differ by weight.
Being overweight or obese can increase susceptibility to indoor PM2.5 and NO2 in urban children with asthma. Interventions aimed at weight loss might reduce asthma symptom responses to PM2.5 and NO2, and interventions aimed at reducing indoor pollutant levels might be particularly beneficial in overweight children.
PMCID: PMC3889705  PMID: 23403052
Asthma; overweight; obesity; indoor pollutants childhood asthma; inner-city asthma
7.  Environmental assessment and exposure reduction of cockroaches: A practice parameter 
The Journal of allergy and clinical immunology  2013;132(4):10.1016/j.jaci.2013.04.061.
This parameter was developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the joint Council of Allergy, Asthma & Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing “Environmental assessment and remediation: a practice parameter.” This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single person, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. The findings and conclusions in this manuscript are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC).
PMCID: PMC3864888  PMID: 23938214
Allergy; cockroach; sensitization; disease; morbidity
8.  Indoor pollutant exposure is associated with heightened respiratory symptoms in atopic compared to non-atopic individuals with COPD 
BMC Pulmonary Medicine  2014;14(1):147.
Indoor particulate matter (PM) has been linked to respiratory symptoms in former smokers with COPD. While subjects with COPD and atopy have also been shown to have more frequent respiratory symptoms, whether they exhibit increased susceptibility to PM as compared to their non-atopic counterparts remains unclear. The aim of this study was to determine whether atopic individuals with COPD have greater susceptibility to PM compared to non-atopic individuals with COPD.
Former smokers with moderate to severe COPD were enrolled (n = 77). PM2.5, PM with diameter <2.5 micrometers, was measured in the main living area over three one-week monitoring periods at baseline, 3, and 6 months. Quality of life, respiratory symptoms and medication use were assessed by questionnaires. Serum was analyzed for specific IgE for mouse, cockroach, cat, dog and dust mite allergens. Atopy was established if at least one test was positive. Interaction terms between PM and atopy were tested and generalized estimating equation analysis determined the effect of PM concentrations on health outcomes. Multivariate models were adjusted for age, sex, education, race, season, and baseline lung function and stratified by atopic status.
Among atopic individuals, each 10 μg/m3 increase in PM was associated with higher risk of nocturnal symptoms (OR, 1.95; P = 0.02), frequent wheezing (OR, 2.49; P = 0.02), increased rescue medication use (β = 0.14; P = 0.02), dyspnea (β = 0.23; P < 0.001), higher St. George’s Respiratory Quality of Life score (β = 2.55; P = 0.01), and higher breathlessness, cough, and sputum score (BCSS) (β = 0.44; P = 0.01). There was no association between PM and health outcomes among the non-atopic individuals. Interaction terms between PM2.5 and atopy were statistically significant for nocturnal symptoms, frequency of rescue medication use, and BCSS (all P < 0.1).
Individuals with COPD and atopy appear to be at higher risk of adverse respiratory health effects of PM exposure compared to non-atopic individuals with COPD.
PMCID: PMC4174661  PMID: 25205263
COPD; Atopy; Allergic sensitization; Pollutants; Particulate matter; PM; Indoor air; Susceptibility
9.  Effects of Allergic Phenotype on Respiratory Symptoms and Exacerbations in Patients with Chronic Obstructive Pulmonary Disease 
Rationale: Chronic obstructive pulmonary disease (COPD) guidelines make no recommendations for allergy diagnosis or treatment.
Objectives: To determine whether an allergic phenotype contributes to respiratory symptoms and exacerbations in patients with COPD.
Methods: Two separate cohorts were analyzed: National Health and Nutrition Survey III (NHANES III) and the COPD and domestic endotoxin (CODE) cohort. Subjects from NHANES III with COPD (n = 1,381) defined as age > 40 years, history of smoking, FEV1/FVC < 0.70, and no diagnosis of asthma were identified. The presence of an allergic phenotype (n = 296) was defined as self-reported doctor diagnosed hay fever or allergic upper respiratory symptoms. In CODE, former smokers with COPD (n = 77) were evaluated for allergic sensitization defined as a detectable specific IgE to perennial allergens. Bivariate and multivariate models were used to determine whether an allergic phenotype was associated with respiratory symptoms and exacerbations.
Measurements and Main Results: In NHANES III, multivariate analysis revealed that individuals with allergic phenotype were more likely to wheeze (odds ratio [OR], 2.1; P < 0.01), to have chronic cough (OR, 1.9; P = 0.01) and chronic phlegm (OR, 1.5; P < 0.05), and to have increased risk of COPD exacerbation requiring an acute doctor visit (OR, 1.7; P = 0.04). In the CODE cohort, multivariate analysis revealed that sensitized subjects reported more wheeze (OR, 5.91; P < 0.01), more nighttime awakening due to cough (OR, 4.20; P = 0.03), increased risk of COPD exacerbations requiring treatment with antibiotics (OR, 3.79; P = 0.02), and acute health visits (OR, 11.05; P < 0.01). An increasing number of sensitizations was associated with a higher risk for adverse health outcomes.
Conclusions: Among individuals with COPD, evidence of an allergic phenotype is associated with increased respiratory symptoms and risk of COPD exacerbations.
PMCID: PMC3778754  PMID: 23668455
atopy; allergic sensitization; allergy; chronic obstructive pulmonary disease
10.  Performance of the halogen immunoassay to assess airborne mouse allergen-containing particles in a laboratory animal facility 
Airborne mouse allergen is a risk factor for respiratory diseases. Conventional assessment techniques provide mass-based exposure estimates that may not capture completely the inhalation risk of airborne allergen particles. In contrast to mass-based estimates, the halogen immunoassay (HIA) combines immunoblotting and microscopy to directly assess allergen-containing particles. We evaluated the HIA for the assessment of airborne mouse allergen and compared the results to the enzyme linked immunosorbent assay (ELISA). Particulate matter (PM)10 and PM2.5 samples (30 min, 4 l/m) were collected in a mouse facility before, during, and after disturbance of soiled bedding. Concentrations of Mus m 1-positive particles (haloed particles (HPs)) and intensities of the haloes were determined with the HIA. Although HPs/m3 were positively correlated with mass concentration (statistically significant only with Mus m 1 concentration on PM10), replicates of mass concentration showed higher variability than HPs/m3. After disturbance, most of the HPs were in the PM2.5 fraction. Mean haloes intensities were similar before, during, and after disturbance. The HIA was able to measure allergen-containing particles with less variability than the ELISA, detected the shift of HPs to smaller particles after disturbance, and may suggests similar halo intensity by particles detected during and after disturbance. Our findings suggest that the HIA can be used to assess indoor concentrations of mouse allergen particles and their morphological characteristics.
PMCID: PMC4028687  PMID: 22805992
halogen immunoassay; haloed particles; mouse allergen
11.  In-Home Air Pollution Is Linked to Respiratory Morbidity in Former Smokers with Chronic Obstructive Pulmonary Disease 
Rationale: The effect of indoor air pollutants on respiratory morbidity among patients with chronic obstructive pulmonary disease (COPD) in developed countries is uncertain.
Objectives: The first longitudinal study to investigate the independent effects of indoor particulate matter (PM) and nitrogen dioxide (NO2) concentrations on COPD morbidity in a periurban community.
Methods: Former smokers with COPD were recruited and indoor air was monitored over a 1-week period in the participant’s bedroom and main living area at baseline, 3 months, and 6 months. At each visit, participants completed spirometry and questionnaires assessing respiratory symptoms. Exacerbations were assessed by questionnaires administered at clinic visits and monthly telephone calls.
Measurements and Main Results: Participants (n = 84) had moderate or severe COPD with a mean FEV1 of 48.6% predicted. The mean (± SD) indoor PM2.5 and NO2 concentrations were 11.4 ± 13.3 µg/m3 and 10.8 ± 10.6 ppb in the bedroom, and 12.2 ± 12.2 µg/m3 and 12.2 ± 11.8 ppb in the main living area. Increases in PM2.5 concentrations in the main living area were associated with increases in respiratory symptoms, rescue medication use, and risk of severe COPD exacerbations. Increases in NO2 concentrations in the main living area were independently associated with worse dyspnea. Increases in bedroom NO2 concentrations were associated with increases in nocturnal symptoms and risk of severe COPD exacerbations.
Conclusions: Indoor pollutant exposure, including PM2.5 and NO2, was associated with increased respiratory symptoms and risk of COPD exacerbation. Future investigations should include intervention studies that optimize indoor air quality as a novel therapeutic approach to improving COPD health outcomes.
PMCID: PMC3734614  PMID: 23525930
indoor air; chronic obstructive pulmonary disease; particulate matter; nitrogen dioxide; exacerbations
13.  Both Variability and Level of Mouse Allergen Exposure Influence the Phenotype of the Immune Response in Workers at a Mouse Facility 
The role of natural aeroallergen exposure in modulating allergen-specific immune responses is not well understood.
To examine relationships between mouse allergen exposure and mouse-specific immune responses.
New employees (n=179) at a mouse facility underwent repeated assessment of mouse allergen exposure, skin prick testing (SPT), and measurement of mouse-specific IgG. Relationships between the mean level of exposure, variability of exposure (calculated as log standard deviation), and time to development of immunologic outcomes were examined using Cox proportional hazards models.
By 24 months, 32 (23%) participants had developed a +SPT and 10 (8%) had developed mouse-specific IgG4. The incidence of a +SPT increased as levels of exposure increased from low to moderate, peaking at 1.2 ng/m3 and decreased beyond this point (p=.04). The more variable the exposure was across visits, the lower the incidence of a +SPT (HR [95% CI]: 0.17 [0.07–0.41]). Variability of exposure was an independent predictor of +SPT in a model that included both exposure metrics. In contrast, the incidence of mouse-specific IgG4 increased with increasing levels of mouse allergen exposure (2.9 [1.4–6.0]), and there was evidence of a higher risk of mouse-specific IgG4 with greater variability of exposure (6.3 [0.4–95.2]).
Both level and variability of mouse allergen exposure influence the humoral immune response, with specific patterns of exposure associated with specific immunophenotypes. Exposure variability may be a more important predictor of +SPT, while average exposure level may be a more important predictor of mouse-specific IgG4.
PMCID: PMC3149759  PMID: 21696812
mouse allergen; IgE; IgG4; laboratory animal allergy
14.  Opposing effects of nasal epithelial NQO1 and HO-1 expression on upper and lower airway symptoms in adolescents with asthma 
NQO1 and HO-1 expression in nasal epithelium are inversely correlated indicating that non-NRF2 mechanisms may play an important role in regulation of these genes. Further, NQO1 and HO-1 expression have opposing relationships with upper and lower airways symptoms, suggesting that induction of phase II enzymes could result in pleiotropic clinical effects.
PMCID: PMC3169320  PMID: 21531452
NQO1; HO-1; NRF2; Oxidative Stress; Asthma; Nasal Epithelium
15.  Age- and Atopy-Dependent Effects of Vitamin D on Wheeze and Asthma 
PMCID: PMC3258443  PMID: 21807254
Vitamin D; wheeze; asthma; age
16.  Salivary Inflammatory Mediator Profiling and Correlation to Clinical Disease Markers in Asthma 
PLoS ONE  2014;9(1):e84449.
There is a need for a readily available, non-invasive source of biomarkers that predict poor asthma control.
We sought to determine if there is an association between the salivary inflammatory profile and disease control in children and adults with asthma.
In this cross-sectional study, we collected demographic and clinical information from two independent populations at different sites, resulting in convenience samples of 58 pediatric and 122 adult urban asthmatics. Control was assessed by symptom questionnaire (children) and by Asthma Control Questionnaire and current exacerbation (adults). Saliva was collected in all subjects. We applied principal component analysis to a 10-plex panel of relevant inflammatory markers to characterize marker profiles and determined if profiles were associated with asthma control.
There were similar, strong correlations amongst biologically related markers in both populations: eosinophil-related: eotaxin-1/CCL11, RANTES/CCL5, and IL-5 (p<.001); myeloid/innate: IL-1β, IL-6, MCP-1/CCL2, and IL-8/CXCL8 (p<.001). The first three principal components captured ≥74% of variability across all ten analytes in both populations. In adults, the Principal Component 1 score, broadly reflective of all markers, but with greater weight given to myeloid/innate markers, was associated with Asthma Control Questionnaire score and exacerbation. The Principal Component 3 score, reflective of IP-10/CXCL10, was associated with current exacerbation. In children, the Principal Component 1, 2, and 3 scores were associated with recent asthma symptoms. The Principal Component 2 score, reflective of higher eosinophil markers, was inversely correlated with symptoms. The Principal Component 3 score was positively associated with all symptom outcomes.
The salivary inflammatory profile is associated with disease control in children and adults with asthma.
PMCID: PMC3883659  PMID: 24409298
18.  Occupational Mouse Allergen Exposure Among Non-Mouse Handlers 
This study assessed mouse allergen exposure across a range of jobs, including non-mouse handling jobs, at a mouse facility. Baseline data from 220 new employees enrolled in the Jackson Laboratory (JAXCohort) were analyzed. The baseline assessment included a questionnaire, allergy skin testing, and spirometry. Exposure assessments consisted of collection of two full-shift breathing zone air samples during a 1-week period. Air samples were analyzed for mouse allergen content, and the mean concentration of the two shifts represented mouse allergen exposure for that employee. The mean age of the 220 participants was 33 years. Ten percent reported current asthma and 56% were atopic. Thirty-eight percent were animal caretakers, 20% scientists, 20% administrative/support personnel, 10% materials/supplies handlers, and 9% laboratory technicians. Sixty percent of the population handled mice. Eighty-two percent of study participants had detectable breathing zone mouse allergen, and breathing zone mouse allergen concentrations were 1.02 ng/m3 (0.13–6.91) (median [interquartile range (IQR)]. Although mouse handlers had significantly higher concentrations of breathing zone mouse allergen than non-handlers (median [IQR]: 4.13 ng/m3 [0.69–12.12] and 0.21 ng/m3 [below detection (BD)–0.63], respectively; p < 0.001), 66% of non-handlers had detectable breathing zone mouse allergen. Mouse allergen concentrations among administrative/support personnel and materials/supplies handlers, jobs that generally do not entail handling mice, were median [IQR]: 0.23 ng/m3 [BD–0.59] and 0.63 ng/m3 [BD–18.91], respectively. Seventy-one percent of administrative/support personnel, and 68% of materials/supplies handlers had detectable breathing zone mouse allergen. As many as half of non-mouse handlers may have levels of exposure that are similar to levels observed among mouse handlers.
PMCID: PMC3143460  PMID: 21058157
allergen-specific antibody responses; laboratory animal allergy; mouse allergen
19.  A randomized, double-blind, placebo-controlled study of milk oral immunotherapy for cow’s milk allergy 
Orally administered, food-specific immunotherapy appears effective in desensitizing and potentially permanently tolerizing allergic individuals.
We sought to determine whether milk oral immunotherapy (OIT) is safe and efficacious in desensitizing children with cow’s milk allergy.
Twenty children were randomized to milk or placebo OIT (2:1 ratio). Dosing included 3 phases: the build-up day (initial dose, 0.4 mg of milk protein; final dose, 50 mg), daily doses with 8 weekly in-office dose increases to a maximum of 500 mg, and continued daily maintenance doses for 3 to 4 months. Double-blind, placebo-controlled food challenges; end-point titration skin prick tests; and milk protein serologic studies were performed before and after OIT.
Nineteen patients, 6 to 17 years of age, completed treatment: 12 in the active group and 7 in the placebo group. One dropped out because of persistent eczema during dose escalation. Baseline median milk IgE levels in the active (n = 13) versus placebo (n = 7) groups were 34.8 kUa/L (range, 4.86–314 kUa/L) versus 14.6 kUa/L (range, 0.93–133.4 kUa/L). The median milk threshold dose in both groups was 40 mg at the baseline challenge. After OIT, the median cumulative dose inducing a reaction in the active treatment group was 5140 mg (range 2540-8140 mg), whereas all patients in the placebo group reacted at 40 mg (P = .0003). Among 2437 active OIT doses versus 1193 placebo doses, there were 1107 (45.4%) versus 134 (11.2%) total reactions, with local symptoms being most common. Milk-specific IgE levels did not change significantly in either group. Milk IgG levels increased significantly in the active treatment group, with a predominant milk IgG4 level increase.
Milk OIT appears to be efficacious in the treatment of cow’s milk allergy. The side-effect profile appears acceptable but requires further study.
PMCID: PMC3764488  PMID: 18951617
Cow’s milk; food allergy; IgE; prognosis; desensitization; tolerance; oral immunotherapy
20.  Urinary levels of triclosan and parabens are associated with aeroallergen and food sensitization 
Endocrine-disrupting compounds (EDCs) have immune-modulating effects. We were interested in determining their association with allergic sensitization.
To determine the association between EDCs and allergic sensitization and if this relationship depended on the antimicrobial properties of the EDCs and/or gender.
Data were obtained from the 2005–2006 National Health and Nutrition Examination Survey in which urinary bisphenol A, triclosan, benzophenone-3, and propyl, methyl, butyl and ethyl paraben, and specific IgE were available on 860 children. Aeroallergen and food sensitization were defined as having at least one positive (≥0.35 kU/L) specific IgE to an aeroallergen or a food. Logistic regression was used to determine the association of EDCs and sensitization. Analyses were adjusted for urinary creatinine, age, ethnicity, and poverty index ratio.
The odds of aeroallergen sensitization significantly increased with the level of the antimicrobial EDCs triclosan and propyl and butyl paraben (p≤0.04). The odds of food sensitization significantly increased with the level of urinary triclosan among male subjects (odds ratio for 3rd versus 1st tertile 3.9, p=0.02 for trend). There was a significant interaction between gender and triclosan, with males being more likely to be food sensitized with exposure (p=0.03). Similar associations were not identified for the non-antimicrobial EDCs bisphenol A and benzophenone-3 (p>0.2).
As a group, EDCs are not associated with allergen sensitization. However, levels of the antimicrobial EDCs triclosan and parabens were significantly associated with allergic sensitization. The potential role of antimicrobial EDCs in allergic disease warrants further study as they are commonly used in Western society.
PMCID: PMC3720124  PMID: 22704536
Triclosan; paraben; benzophenone; bisphenol A; endocrine disrupting compound; aeroallergen; sensitization; food; allergy
21.  Higher Serum Folate Levels are Associated with a Lower Risk of Atopy and Wheeze 
Folic acid is known to be associated with inflammatory diseases, but the relationship between folic acid and allergic diseases is unclear.
The purpose of the study was to examine the relationship between serum folate levels and markers of atopy, wheeze, and asthma.
Data were obtained from the 2005–2006 National Health and Nutrition Examination Survey (NHANES) in which serum folate and total IgE levels were measured in 8,083 subjects 2 years of age and older. A high total IgE level was defined as >100kU/L. Allergen-specific IgE levels were measured for a panel of 5 common aeroallergens. Atopy was defined as at least 1 positive allergen-specific IgE level. Doctor-diagnosed asthma and wheeze in the previous 12 months were assessed by questionnaire.
Serum folate levels were inversely associated with total IgE levels (p<.001). The odds of a high total IgE, atopy, and wheeze decreased across quintiles of serum folate, indicating a dose-response relationship between serum folate levels and these outcomes. Each of these associations remained statistically significant after adjusting for age, sex, race/ethnicity and poverty index ratio. Adjusted odds ratios[95% confidence intervals] associated with the fifth quintile (Q5) of folate relative to the first quintile (Q1) were as follows: High IgE: 0.70[0.53–0.92]; atopy: 0.69[0.57–0.85]; and wheeze: 0.60[0.44–0.82]. Higher folate levels were also associated with a lower risk of doctor-diagnosed asthma, but this finding was not statistically significant (OR[95% CI] for Q5 vs. Q1: 0.84 [0.70–1.02]).
Serum folate levels are inversely associated with high total IgE, atopy, and wheeze.
Clinical Implications
Folic acid status may influence the development and/or progression of atopy and wheeze.
PMCID: PMC2693474  PMID: 19409604
asthma; allergy; atopy; folate; NHANES; Centers for Disease Control
22.  Potential mechanisms for the association between fall birth and food allergy 
Allergy  2012;67(6):775-782.
Season of birth has been reported as a risk factor for food allergy, but the mechanisms by which it acts are unknown.
Two populations were studied; 5862 children from the National Health and Nutrition Examination Survey (NHANES) III, 1514 well-characterized food allergic children from the Johns Hopkins Pediatric Allergy Clinic (JHPAC). Food allergy was defined as self report of an acute reaction to a food (NHANES), or as milk, egg and peanut allergy. Logistic regression compared fall or non-fall birth between (1) food allergic and non-allergic subjects in NHANES, adjusted for ethnicity, age, income and sex, and (2) JHPAC subjects and the general Maryland population. For NHANES, stratification by ethnicity and for JHPAC, eczema, was examined.
Fall birth was more common among food allergic subjects in both NHANES (OR: 1.91, 95%CI: 1.31–2.77) and JHPAC/Maryland (OR: 1.31, 95%CI: 1.18–1.47). Ethnicity interacted with season (OR 2.34, 95%CI 1.43–3.82 for Caucasians, OR 1.19, 95%CI 0.77–1.86 for non-Caucasians, p=0.04 for interaction), as did eczema (OR 1.47, 95%CI 1.29–1.67 with eczema, OR 1.00, 95%CI 0.80–1.23 without eczema, p=0.002 for interaction).
Fall birth is associated with increased risk of food allergy, and this risk is greatest among those most likely to have seasonal variation in vitamin D during infancy (Caucasians) and those at risk for skin barrier dysfunction (subjects with a history of eczema), suggesting that vitamin D and the skin barrier may be implicated in seasonal associations with food allergy.
PMCID: PMC3349789  PMID: 22515802
food allergy; season of birth; eczema; vitamin D
23.  Asthma Control, Adiposity and Adipokines among Inner-City Adolescents 
There is an association between adiposity and asthma prevalence, but the relationship to asthma control is unclear.
To understand the relationships among adiposity, gender, and asthma control in inner-city adolescents with asthma.
We prospectively followed 368 adolescents with moderate to severe asthma (ages 12–20 years) living in 10 urban areas for one year. Asthma symptoms and exacerbations were recorded, and pulmonary function and exhaled nitric oxide were measured every 6 weeks. Adiposity measures (BMI, DEXA scans) were made, and blood was collected for allergy markers, adiponectin, leptin, TNF-α, IL-6 and CRP.
More than 60% of females and 50% of males were above the 85th percentile of BMI-for-age. Higher BMI was associated with more symptom days (R= 0.18, P<0.01) and exacerbations (R=0.18, P=0.06) among females only. Adiponectin was inversely related to asthma symptoms (R=− 0.18, P<0.05) and exacerbations (R=− 0.20, P<0.05) and positively with FEV1/FVC (R=0.15, P<0.05) in males only, independent of body size. There was no relationship between adiposity or adipokines and total IgE, blood eosinophils and exhaled nitric oxide. DEXA provided little additional value in relating adiposity to asthma outcome in this population of adolescents.
Adiposity is associated with poorer asthma control in females. Adiponectin is associated with improved asthma control in males.
PMCID: PMC3596816  PMID: 20226295
Obesity; Asthma; Adipokines; Leptin; Adiponectin
24.  Environmental Issues in Managing Asthma 
Respiratory care  2008;53(5):602-617.
Management of asthma requires attention to environmental exposures both indoors and outdoors. Americans spend most of their time indoors, where they have a greater ability to modify their environment. The indoor environment contains both pollutants (eg, particulate matter, nitrogen dioxide, secondhand smoke, and ozone) and allergens from furred pets, dust mites, cockroaches, rodents, and molds. Indoor particulate matter consists of particles generated from indoor sources such as cooking and cleaning activities, and particles that penetrate from the outdoors. Nitrogen dioxide sources include gas stoves, furnaces, and fireplaces. Indoor particulate matter and nitrogen dioxide are linked to asthma morbidity. The indoor ozone concentration is mainly influenced by the outdoor ozone concentration. The health effects of indoor ozone exposure have not been well studied. In contrast, there is substantial evidence of detrimental health effects from secondhand smoke. Guideline recommendations are not specific for optimizing indoor air quality. The 2007 National Asthma Education and Prevention Program asthma guidelines recommend eliminating indoor smoking and improving the ventilation. Though the guidelines state that there is insufficient evidence to recommend air cleaners, air cleaners and reducing activities that generate indoor pollutants may be sound practical approaches for improving the health of individuals with asthma. The guidelines are more specific about allergen avoidance; they recommend identifying allergens to which the individual is immunoglobin E sensitized and employing a multifaceted, comprehensive strategy to reduce exposure. Outdoor air pollutants that impact asthma include particulate matter, ozone, nitrogen dioxide, and sulfur dioxide, and guidelines recommend that individuals with asthma avoid exertion outdoors when these pollutants are elevated. Outdoor allergens include tree, grass, and weed pollens, which vary in concentration by season. Recommendations to reduce exposure include staying indoors, keeping windows and doors closed, using air conditioning and perhaps high-efficiency particulate arrestor (HEPA) air filters, and thorough daily washing to remove allergens from one’s person.
PMCID: PMC2396450  PMID: 18426614
asthma; pollutants; particulate matter; nitrogen dioxide; sulfur dioxide; secondhand smoke; ozone; allergens
25.  Personal and parental nativity as risk factors for food sensitization 
Immigrants to developed countries have low rates of aeroallergen sensitization and asthma, but less is known about both food allergy and the role of parental immigration status.
To evaluate the relationship between personal and parental nativity on the risk of food sensitization.
3550 subjects <21 years old from the National Health and Examination Survey 2005-2006 were included. Odds ratios were generated using logistic regression which adjusted for race/ethnicity, gender, age, and household income, and accounted for the complex survey design. Nativity was classified as US-born or foreign-born and the age of immigration was estimated. Head of household nativity was used as a proxy for parental nativity. Food sensitization was defined as at least one specific-IgE ≥ 0.35 kU/L to milk, egg or peanut. Aeroallergen specific sensitizations, and the presence of asthma, allergic rhinitis or eczema were also assessed.
Compared to those born outside the US, US-born children and adolescents had higher odds of sensitization to any food (OR 2.05, 95% CI 1.49-2.83, p<0.001). Among the foreign-born, those who arrived before 2 years of age had higher odds of food sensitization than those who arrived later (OR 2.68, 95% CI 1.19-6.08, p=0.02). Within the US-born group, in contrast, children of immigrants were at the highest risk (OR 1.53, 95% CI 1.05-2.24, p=0.02).
While foreign-born children and adolescents are at lower risk of food sensitization compared to those born in the US, among those born in the US, the children of immigrants are at the highest risk.
PMCID: PMC3382052  PMID: 22075329
Food allergy; food sensitization; immigration; nativity; child; hay fever; asthma; eczema; aeroallergen

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