Pollen and viruses contribute to spatio-temporal variation in asthma-related emergency department visits.

BACKGROUND: Asthma exacerbations are an important cause of emergency department visits but much remains unknown about the role of environmental triggers including viruses and allergenic pollen. A better understanding of spatio-temporal variation in exposure and risk posed by viruses and pollen types could help prioritize public health interventions. OBJECTIVE: Here we quantify the effects of regionally important Cupressaceae pollen, tree pollen, other pollen types, rhinovirus, seasonal coronavirus, respiratory syncytial virus, and influenza on asthma-related emergency department visits for people living near eight pollen monitoring stations in Texas. METHODS: We used age stratified Poisson regression analyses to quantify the effects of allergenic pollen and viruses on asthma-related emergency department visits. RESULTS: Young children (< 5 years of age) had high asthma-related emergency department rates (24.1 visits/1,000,000 person-days), which were mainly attributed to viruses (51.2%). School-aged children also had high rates (20.7 visits/1,000,000 person-days), which were attributed to viruses (57.0%), Cupressaceae pollen (0.7%), and tree pollen (2.8%). Adults had lower rates (8.1 visits/1,000,000 person-days) which were attributed to viruses (25.4%), Cupressaceae pollen (0.8%), and tree pollen (2.3%). This risk was spread unevenly across space and time; for example, during peak Cuppressaceae season, this pollen accounted for 8.2% of adult emergency department visits near Austin where these plants are abundant, but 0.4% in cities like Houston where they are not; results for other age groups were similar. CONCLUSIONS: Although viruses are a major contributor to asthma-related emergency department visits, airborne pollen can explain a meaningful portion of visits during peak pollen season and this risk varies over both time and space because of differences in plant composition.

Associations between mitochondrial biomarkers, urban residential exposures and childhood asthma outcomes over 6 months.

Determining biomarkers of responses to environmental exposures and evaluating whether they predict respiratory outcomes may help optimize environmental and medical approaches to childhood asthma. Relative mitochondrial (mt) DNA abundance and other potential mitochondrial indicators of oxidative stress may provide a sensitive metric of the child's shifting molecular responses to its changing environment. We leveraged two urban childhood cohorts (Environmental Control as Add-on Therapy in Childhood Asthma (ECATCh); Columbia Center for Children's Environmental Health (CCCEH)) to ascertain whether biomarkers in buccal mtDNA associate with airway inflammation and altered lung function over 6 months of time and capture biologic responses to multiple external stressors such as indoor allergens and fine particulate matter (PM2.5). Relative mtDNA content was amplified by qPCR and methylation of transfer RNA phenylalanine/rRNA 12S (TF/RNR1), cytochrome c oxidase (CO1), and carboxypeptidase O (CPO) was measured by pyrosequencing. Data on residential exposures and respiratory outcomes were harmonized between the two cohorts. Repeated measures and multiple regression models were utilized to assess relationships between mitochondrial biomarkers, respiratory outcomes, and residential exposures (PM2.5, allergens), adjusted for potential confounders and time-varying asthma. We found across the 6 month visits, a 0.64 fold higher level of TF/RNR1 methylation was detected among those with asthma in comparison to those without asthma ((parameter estimate (PE) 0.64, standard error 0.28, p = 0.03). In prospective analyses, CPO methylation was associated with subsequent reduced forced vital capacity (FVC; PE -0.03, standard error 0.01, p = 0.02). Bedroom dust mouse allergen, but not indoor PM2.5, was associated with higher methylation of TF/RNR1 (PE 0.015, standard error 0.006, p = 0.01). Select mtDNA measures in buccal cells may indicate children's responses to toxic environmental exposures and associate selectively with asthma and lung function.

Association of a Housing Mobility Program With Childhood Asthma Symptoms and Exacerbations.

Importance: Structural racism has been implicated in the disproportionally high asthma morbidity experienced by children living in disadvantaged, urban neighborhoods. Current approaches designed to reduce asthma triggers have modest impact. Objective: To examine whether participation in a housing mobility program that provided housing vouchers and assistance moving to low-poverty neighborhoods was associated with reduced asthma morbidity among children and to explore potential mediating factors. Design, Setting, and Participants: Cohort study of 123 children aged 5 to 17 years with persistent asthma whose families participated in the Baltimore Regional Housing Partnership housing mobility program from 2016 to 2020. Children were matched to 115 children enrolled in the Urban Environment and Childhood Asthma (URECA) birth cohort using propensity scores. Exposure: Moving to a low-poverty neighborhood. Main Outcomes: Caregiver-reported asthma exacerbations and symptoms. Results: Among 123 children enrolled in the program, median age was 8.4 years, 58 (47.2%) were female, and 120 (97.6%) were Black. Prior to moving, 89 of 110 children (81%) lived in a high-poverty census tract (>20% of families below the poverty line); after moving, only 1 of 106 children with after-move data (0.9%) lived in a high-poverty tract. Among this cohort, 15.1% (SD, 35.8) had at least 1 exacerbation per 3-month period prior to moving vs 8.5% (SD, 28.0) after moving, an adjusted difference of -6.8 percentage points (95% CI, -11.9% to -1.7%; P = .009). Maximum symptom days in the past 2 weeks were 5.1 (SD, 5.0) before moving and 2.7 (SD, 3.8) after moving, an adjusted difference of -2.37 days (95% CI, -3.14 to -1.59; P < .001). Results remained significant in propensity score-matched analyses with URECA data. Measures of stress, including social cohesion, neighborhood safety, and urban stress, all improved with moving and were estimated to mediate between 29% and 35% of the association between moving and asthma exacerbations. Conclusions and Relevance: Children with asthma whose families participated in a program that helped them move into low-poverty neighborhoods experienced significant improvements in asthma symptom days and exacerbations. This study adds to the limited evidence suggesting that programs to counter housing discrimination can reduce childhood asthma morbidity.

Comprehensive home environmental intervention did not reduce allergen concentrations or controller medication requirements among children in Baltimore.

OBJECTIVE: To determine if the addition of home environmental control strategies (ECSs) to controller medication titration reduces asthma controller medication requirements and in-home allergen concentrations among children with persistent asthma in Baltimore City. METHODS: 155 children ages 5-17 with allergen-sensitized asthma were enrolled in a 6-month randomized clinical trial of multifaceted, individually-tailored ECS plus asthma controller medication titration compared to controller medication titration alone. Participants had to meet criteria for persistent asthma and have had an exacerbation in the previous 18 months. Allergen sensitization (mouse, cockroach, cat, dog, dust mite) was assessed at baseline and home dust allergen concentrations were measured at baseline, 3 and 6 months. ECS was delivered 3-4 times over the trial. Asthma controller medication was titrated using a guidelines-based algorithm at baseline, 2, 4, and 6 months. The primary outcome was controller medication treatment step at 6 months (0-6, as-needed albuterol to high-dose ICS + LABA). RESULTS: The population was predominately Black (90%), on public insurance (93%), and male (61%). The mean age was 10.1 years (SD 3.3). More than 70% were sensitized to a rodent, >50% to cockroach, and 70% were polysensitized. At 6 months, there were no differences in either treatment step (3.8 [SD 1.4] vs. 3.7 [SD 1.5]) or allergen concentrations between groups. CONCLUSION: Among this predominantly low-income, Black pediatric asthma population, the addition of ECS to controller medication titration reduced neither indoor allergen concentrations nor controller medication requirements compared to controller medication titration alone.

Indoor environmental exposures and obstructive lung disease phenotypes among children with asthma living in poor urban neighborhoods.

BACKGROUND: Air trapping is an obstructive phenotype that has been associated with more severe and unstable asthma in children. Air trapping has been defined using pre- and postbronchodilator spirometry. The causes of air trapping are not completely understood. It is possible that environmental exposures could be implicated in air trapping in children with asthma. OBJECTIVE: We investigated the association between indoor exposures and air trapping in urban children with asthma. METHODS: Children with asthma aged 5 to 17 years living in Baltimore and enrolled onto the Environmental Control as Add-on Therapy for Childhood Asthma study were evaluated for air trapping using spirometry. Aeroallergen sensitization was assessed at baseline, and spirometry was performed at 0, 3, and 6 months. Air trapping was defined as an FVC z score of less than -1.64 or a change in FVC with bronchodilation of ≥10% predicted. Logistic normal random effects models were used to evaluate associations of air trapping and indoor exposures. RESULTS: Airborne and bedroom floor mouse allergen concentrations were associated with air trapping but not airflow limitation (odds ratio 1.19, 95% confidence interval 1.02-1.37, P = .02 per 2-fold increase in airborne mouse allergen; odds ratio 1.23, 95% confidence interval 1.07-1.41, P = .003 per 2-fold increase in bedroom floor mouse allergen). Other indoor exposures (cockroach, cat, dog, dust mite, particulate matter, and nicotine) were not associated with air trapping or airflow limitation. CONCLUSION: Mouse allergen exposure, but not other indoor exposure, was associated with air trapping in urban children with asthma.

Do upper respiratory viruses contribute to racial and ethnic disparities in emergency department visits for asthma?

BACKGROUND: There are marked disparities in asthma-related emergency department (ED) visit rates among children by race and ethnicity. Following the implementation of coronavirus disease 2019 (COVID-19) prevention measures, asthma-related ED visits rates declined substantially. The decline has been attributed to the reduced circulation of upper respiratory viruses, a common trigger of asthma exacerbations in children. OBJECTIVES: To better understand the contribution of respiratory viruses to racial and ethnic disparities in ED visit rates, we investigated whether the reduction in ED visit rates affected Black, Latinx, and White children with asthma equally. METHODS: Asthma-related ED visits were extracted from electronic medical records at Dell Children's Medical Center in Travis County, Texas. ED visit rates among children with asthma were derived by race/ethnicity. Incidence rate ratios (IRRs) and 95% CIs were estimated by year (2019-2021) and season. RESULTS: In spring 2019, the ED visit IRRs comparing Black children with White children and Latinx children with White children were 6.67 (95% CI = 4.92-9.05) and 2.10 (95% CI = 1.57-2.80), respectively. In spring 2020, when infection prevention measures were implemented, the corresponding IRRs decreased to 1.73 (95% CI = 0.90-3.32) and 0.68 (95% CI = 0.38-1.23), respectively. CONCLUSIONS: The striking reduction of disparities in ED visits suggests that during nonpandemic periods, respiratory viruses contribute to the excess burden of asthma-related ED visits among Black and Latinx children with asthma. Although further investigation is needed to test this hypothesis, our findings raise the question of whether Black and Latinx children with asthma are more vulnerable to upper respiratory viral infections.

Neighborhoods, Caregiver Stress, and Children's Asthma Symptoms.

BACKGROUND: Neighborhood and caregiver characteristics have each been linked to children's asthma outcomes, but less is known about how caregiver psychosocial functioning may explain the link between neighborhood characteristics and asthma outcomes. OBJECTIVE: To examine associations between neighborhood safety, caregiver stress and depressive symptoms, and children's asthma outcomes, and to evaluate whether caregiver stress and depressive symptoms mediate the relationship between neighborhood safety and asthma outcomes. METHODS: We analyzed baseline data from a prospective cohort study of the effects of a housing mobility program on children's asthma-related outcomes. Age- and sex-adjusted models evaluated associations of neighborhood safety, and caregiver stress and depressive symptoms, with children's asthma symptoms and exacerbations. RESULTS: Participants were 140 low-income children with persistent asthma (98% Black participants; 53% males; mean age, 9.0 years) with an average of 7.1 ± 5.3 maximum symptom days per 2 weeks. Lower neighborhood safety, and higher caregiver stress and depressive symptoms, were associated with higher asthma symptoms, but not exacerbations, in adjusted models (eg, for neighborhood safety, maximum symptom days: odds ratio, 1.41; 95% CI, 1.07-1.88; for caregiver stress, maximum symptom days: odds ratio, 1.08; 95% CI, 1.01-1.15; for depressive symptoms, maximum symptom days: odds ratio, 1.05; 95% CI, 1.00-1.11). Exploratory analyses suggested that caregiver stress partially mediated associations between neighborhood safety and asthma symptoms for children in unsafe neighborhoods. CONCLUSIONS: Neighborhood safety was associated with children's asthma symptoms independent from caregiver stress and depressive symptoms, although for children in unsafe neighborhoods, caregiver stress may partially mediate this association. Findings suggest the importance of targeting multiple systems to improve children's asthma outcomes.

Indoor Environmental Factors May Modify the Response to Mouse Allergen Reduction Among Mouse-Sensitized and Exposed Children with Persistent Asthma.

BACKGROUND: Whether concomitant home exposures modify the effectiveness of mouse allergen reduction among mouse-sensitized children with asthma is unknown. OBJECTIVE: To determine whether a lower baseline home mouse allergen level, lower particulate matter 10 µ or less (PM10), and the absence of sensitization and exposure to other indoor allergens are associated with greater improvements in asthma associated with mouse allergen reduction. METHODS: A secondary analysis of a randomized clinical trial of a home mouse allergen intervention was performed to examine the effect of 3 indoor factors on the relationship between mouse allergen reduction and a range of asthma outcomes. RESULTS: Participants (N = 297) were predominantly minority (78% African American, 22% Hispanic) and publicly insured (88%). Higher baseline mouse allergen levels were associated with a greater response to mouse allergen reduction for several symptom and exacerbation outcomes. Lower indoor PM10 levels were associated with a greater response to mouse allergen reduction for several symptom outcomes, but not exacerbation outcomes. Overall, sensitization and exposure to other indoor allergens did not appear to modify the effect of mouse allergen reduction. CONCLUSIONS: In this population of predominantly low-income children with persistent asthma and mouse sensitization, mouse allergen reduction was associated with improvements in asthma, especially among those with high baseline mouse allergen exposure. Lower indoor PM10 was associated with greater improvements in asthma symptoms.

Material Hardship and Indoor Allergen Exposure among Low-Income, Urban, Minority Children with Persistent Asthma.

Traditional measures of socioeconomic status (SES) are associated with asthma morbidity, but their specific contributions are unclear. Increased exposure to indoor allergens among low SES children is an important consideration. Material hardship, a concept describing poor access to basic goods and services, may explain the relationship between low SES and indoor allergen exposure, and thereby, the increased risk of asthma morbidity. We sought to (i) describe the specific hardships experienced by low-Income, urban, minority children with asthma and indoor allergen sensitization and (ii) determine if material hardship is associated with indoor allergen exposure in this population. We conducted a cross-sectional analysis of children undergoing the baseline assessment for a clinical trial of home environmental modification. Participants were scored in five domains of material hardship. Domain scores were assigned based on caregiver responses to a questionnaire and were summed to generate a total material hardship score. Linear regression was used to examine the relationship between material hardship scores and bedroom floor concentrations of five common indoor allergens. Participants experienced high levels of material hardship in each of the five domains, with 33% not having access to a car, 35% not being able to pay utility bills, and 28% not being able to pay rent in the past year. Each one-point increase in material hardship was associated with an increase in cockroach allergen of 16.2% (95% CI 9.4%, 24.6%) and an increase in mouse allergen of 9.4% (95% CI 1.0%, 18.5%). After adjusting for traditional measures of SES, including household income, health insurance type, caregiver education, and caregiver employment status, the association between material hardship and cockroach allergen, but not mouse allergen, remained. These data suggest that a significant proportion of families of low-income, minority children with asthma may experience material hardship, and that they may be at greater risk of cockroach allergen exposure than their peers with similar income, but without material hardship.

Do Baseline Asthma and Allergic Sensitization Characteristics Predict Responsiveness to Mouse Allergen Reduction?

BACKGROUND: Mouse allergen reduction is associated with improvements in asthma among sensitized and exposed children, but whether clinical characteristics predict responsiveness to allergen reduction is unclear. OBJECTIVE: To examine the effects of clinical characteristics on relationships between mouse allergen reduction and asthma outcomes. METHODS: We performed a secondary analysis of data from a randomized clinical trial of a mouse allergen intervention, examining the effects of atopy, demographic characteristics, lung function, asthma control, and asthma severity on relationships between mouse allergen reduction and asthma outcomes. RESULTS: Participants were predominantly low-income and minority (78% black, 22% Hispanic), and had persistent asthma. Among less atopic participants (<6 positive skin prick test results), each 50% reduction in mouse allergen was associated with fewer symptoms (incidence rate ratio [95% CI]: maximal symptoms: 0.94 [0.92-0.96]). There was little effect of mouse allergen reduction on symptoms among more atopic participants (P > .05). The interactions between atopic status and mouse allergen reduction were statistically significant for all symptom outcomes; however, there was no evidence that atopic status influenced the effect of mouse allergen reduction on exacerbation-related outcomes. Older children (≥9 years) tended to experience greater improvement in some asthma outcomes with reduction in mouse allergen exposure than younger children. There was no evidence that either mouse-specific IgE or lung function influenced the effect of mouse allergen reduction on any asthma outcomes. CONCLUSIONS: Although there may be variability in the clinical response to mouse allergen reduction among low-income, minority children with asthma, there were no clinical characteristics that clearly identified a subgroup at which the intervention should be targeted.

Reduction in mouse allergen exposure is associated with greater lung function growth.

BACKGROUND: Current childhood asthma therapies have little effect on lung function trajectory. OBJECTIVE: We sought to determine whether mouse allergen exposure reduction is associated with lung function growth in mouse-sensitized/exposed asthmatic children. METHODS: Three hundred fifty mouse-sensitized/exposed asthmatic children (5-17 years old) were enrolled in a 1-year randomized trial of integrated pest management plus education versus education alone. Prebronchodilator/postbronchodilator spirometry was performed at baseline and 6 and 12 months, and bedroom floor mouse allergen levels were measured every 3 months. Mouse allergen reduction was defined as a 75% or greater decrease in mouse allergen levels from baseline. Treatment groups were combined for analyses because there were no differences in outcomes between groups. Changes in lung function over time were modeled, adjusting for age, sex, race, atopy, group, and bronchodilator reversibility and including an interaction term (allergen reduction*time). RESULTS: The study population was predominantly black (79.4%) and low income (66.3% [<$30,000]). At baseline, the median mouse allergen level was 5.7 µg/g (interquartile range, 1.5-22.8 µg/g), and the mean (SD) prebronchodilator FEV1/forced vital capacity ratio was 80.2% (9.0%). Ninety-two (26.3%) participants had 75% or greater reduction in mouse allergen levels. For a 10-year-old black boy, 75% or greater allergen reduction was associated with an increase in prebronchodilator FEV1 of 238 mL/y (95% CI, 177-299 mL/y), whereas less than 75% allergen reduction was associated with an increase in prebronchodilator FEV1 of 131 mL/y (95% CI, 97-166 mL/y). Estimated differences in prebronchodilator and postbronchodilator FEV1 growth were as follows: 107 mL/y (95% CI, 37-177 mL/y; Pint = .003) and 48 mL/y (95% CI, -17 to 113 mL/y; Pint = .15), respectively. Estimated differences in prebronchodilator and postbronchodilator forced expiratory flow at 25% to 75% of vital capacity growth were as follows: 182 mL/y (95% CI, 61-304 mL/y; Pint = .003) and 181 mL/y (95% CI, 48-314 mL/y; Pint = .008), respectively. CONCLUSION: Mouse allergen reduction is associated with greater increases in prebronchodilator FEV1 and prebronchodilator/postbronchodilator forced expiratory flow at 25% to 75% of vital capacity over 1 year among sensitized/exposed asthmatic children.

Caregiver-Reported Asthma Control Predicts Future Visits, Independent of Guideline-Based Control Measures.

BACKGROUND: It is unknown whether caregiver perception of a child's asthma control, independent of guideline-based asthma control assessment, is a predictor of future acute visits. OBJECTIVE: To determine whether caregiver-reported asthma control is an indicator of future risk of acute visit. METHODS: Two study populations of low-income, minority 5- to 17-year-old children with persistent asthma were included. Questionnaires administered at baseline and at 3, 6, 9, and 12 months captured symptoms, short-acting ß-agonist use, acute visits in the previous 3 months, and caregiver-reported asthma control. Well-controlled, not well-controlled, and very poorly controlled asthma were defined using National Asthma Education and Prevention Program guideline-based assessment. Relationships between caregiver-reported control and acute visits in the subsequent 3 months were examined. RESULTS: At baseline, both populations were predominantly black/African American (91% and 79%) with public insurance (85% and 88%) and very poorly controlled asthma (47% and 50%). In both populations, most caregivers reported that their child's asthma was well controlled (73% and 69%). In both populations, participants whose caregivers reported that their child had uncontrolled asthma had greater odds of having an acute visit in the following 3 months as compared with participants whose caregivers reported that their child's asthma was well controlled, independent of guideline-based control, age, sex, race, controller medication, insurance, and atopy (odds ratio [95% CI], 2.4 [1.4-4.2] and 1.6 [1.1-2.4]). CONCLUSIONS: Among predominantly low-income minority children with asthma, caregiver-reported asthma control may provide information about the risk of future acute visit for asthma that is complementary to guideline-based control assessment.

Effect of an Integrated Pest Management Intervention on Asthma Symptoms Among Mouse-Sensitized Children and Adolescents With Asthma: A Randomized Clinical Trial.

Importance: Professionally delivered integrated pest management (IPM) interventions can reduce home mouse allergen concentrations, but whether they reduce asthma morbidity among mouse-sensitized and exposed children and adolescents is unknown. Objective: To determine the effect of an IPM intervention on asthma morbidity among mouse-sensitized and exposed children and adolescents with asthma. Design, Setting, and Participants: Randomized clinical trial conducted in Baltimore, Maryland, and Boston, Massachusetts. Participants were mouse-sensitized and exposed children and adolescents (aged 5-17 years) with asthma randomized to receive professionally delivered IPM plus pest management education or pest management education alone. Enrollment occurred between May 2010 and August 2014; the final follow-up visit occurred on September 25, 2015. Interventions: Integrated pest management consisted of application of rodenticide, sealing of holes that could serve as entry points for mice, trap placement, targeted cleaning, allergen-proof mattress and pillow encasements, and portable air purifiers. Infestation was assessed every 3 months, and if infestation persisted or recurred, additional treatments were delivered. All participants received pest management education, which consisted of written material and demonstration of the materials needed to set traps and seal holes. Main Outcomes and Measures: The primary outcome was maximal symptom days defined as the highest number of days of symptoms in the previous 2 weeks among 3 types of symptoms (days of slowed activity due to asthma; number of nights of waking with asthma symptoms; and days of coughing, wheezing, or chest tightness) across 6, 9, and 12 months. Results: Of 361 children and adolescents who were randomized (mean [SD] age, 9.8 [3.2] years; 38% female; 181 in IPM plus pest management education group and 180 in pest management education alone group), 334 were included in the primary analysis. For the primary outcome, there was no statistically significant between-group difference for maximal symptom days across 6, 9, and 12 months with a median of 2.0 (interquartile range, 0.7-4.7) maximal symptom days in the IPM plus pest management education group and 2.7 (interquartile range, 1.3-5.0) maximal symptom days in the pest management education alone group (P = .16) and a ratio of symptom frequencies of 0.86 (95% CI, 0.69-1.06). Conclusions and Relevance: Among mouse-sensitized and exposed children and adolescents with asthma, an intensive year-long integrated pest management intervention plus pest management education vs pest management education alone resulted in no significant difference in maximal symptom days from 6 to 12 months. Trial Registration: clinicaltrials.gov Identifier: NCT01251224.

Atopy, but not obesity is associated with asthma severity among children with persistent asthma.

BACKGROUND AND OBJECTIVE: Obesity is associated with an increased risk of asthma in children. Atopic sensitization is a major risk factor for asthma including severe asthma in children. It is unclear if obesity is associated with worse asthma control or severity in children and how its effects compare to atopy. We sought to examine relationships of weight status and atopy to asthma control and severity among a population of predominantly low income, minority children and adolescents with persistent asthma. METHODS: A cross-sectional analysis of 832 children and adolescents, age range 5-17 years, with persistent asthma was performed. Clinical assessments included asthma questionnaires of symptoms, asthma severity score, health care utilization and medication treatment step, lung function testing, and skin prick testing as well as measures of adiposity. Data were collected between December 2010 and August 2014 from Johns Hopkins Hospital in Baltimore, MD and Children's Hospital of Boston, MA. RESULTS: Obesity was not associated with worse asthma control or severity in this group of predominantly low income, minority children and adolescents with persistent asthma. However, a greater degree of atopy was associated with lower lung function, higher asthma severity score, and higher medication treatment step. CONCLUSION: Atopy may be a more important risk factor for asthma severity than obesity among low-income minority children and adolescents with persistent asthma living in Northeastern cities in the United States.

Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis.

BACKGROUND: Conjugating immunostimulatory sequences of DNA to specific allergens offers a new approach to allergen immunotherapy that reduces acute allergic responses. METHODS: We conducted a randomized, double-blind, placebo-controlled phase 2 trial of a vaccine consisting of Amb a 1, a ragweed-pollen antigen, conjugated to a phosphorothioate oligodeoxyribonucleotide immunostimulatory sequence of DNA (AIC) in 25 adults who were allergic to ragweed. Patients received six weekly injections of the AIC or placebo vaccine before the first ragweed season and were monitored during the next two ragweed seasons. RESULTS: There was no pattern of vaccine-associated systemic reactions or clinically significant laboratory abnormalities. AIC did not alter the primary end point, the vascular permeability response (measured by the albumin level in nasal-lavage fluid) to nasal provocation. During the first ragweed season, the AIC group had better peak-season rhinitis scores on the visual-analogue scale (P=0.006), peak-season daily nasal symptom diary scores (P=0.02), and midseason overall quality-of-life scores (P=0.05) than the placebo group. AIC induced a transient increase in Amb a 1-specific IgG antibody but suppressed the seasonal increase in Amb a 1-specific IgE antibody. A reduction in the number of interleukin-4-positive basophils in AIC-treated patients correlated with lower rhinitis visual-analogue scores (r=0.49, P=0.03). Clinical benefits of AIC were again observed in the subsequent ragweed season, with improvements over placebo in peak-season rhinitis visual-analogue scores (P=0.02) and peak-season daily nasal symptom diary scores (P=0.02). The seasonal specific IgE antibody response was again suppressed, with no significant change in IgE antibody titer during the ragweed season (P=0.19). CONCLUSIONS: In this pilot study, a 6-week regimen of the AIC vaccine appeared to offer long-term clinical efficacy in the treatment of ragweed allergic rhinitis. (ClinicalTrials.gov number, NCT00346086 [ClinicalTrials.gov] .).