Publications by authors named "William J Sheehan"

68 Publications

Adherence rates during a randomized controlled trial evaluating the use of blinded acetaminophen and ibuprofen in children with asthma.

Contemp Clin Trials 2021 Feb 27;104:106334. Epub 2021 Feb 27.

Boston Children's Hospital, Division of Allergy and Immunology, Harvard Medical School, Boston, MA, United States of America. Electronic address:

Background/aims: When conducting clinical trials comparing over-the-counter (OTC) medications, the wide availability of these treatments are a potential challenge to maintaining study integrity. We seek to describe adherence to a study protocol involving widely available OTC medications.

Methods: To prospectively evaluate associations between acetaminophen use and asthma in 300 children aged 1-5 years, we conducted a double blind, randomized, controlled trial where parents administered blinded forms of either acetaminophen or ibuprofen as needed to their children over a 48 week period. Written and verbal instructions encouraged the exclusive use of the blinded study medication and discouraged OTC use. Adherence was determined by evaluating the frequency of use of per-protocol blinded study medication compared to off-protocol use of OTC medications.

Results: 4195 doses of acetaminophen or ibuprofen were received by children during the study which included 3664 doses (87.3%) of blinded study medication adhering to the protocol and 531 doses (12.7%) of OTC products deviating from the protocol with better adherence among those randomized to ibuprofen as compared to acetaminophen (89.5% vs. 85.5% of doses, p < 0.01). Individually, 227 participants (75.7%) remained fully adherent by not receiving any OTC medications. Pre-study preference for either acetaminophen or ibuprofen by the participants' families was not associated with differential rates of adherence to the blinded medication.

Conclusion: This parallel study demonstrated greater than 85% of acetaminophen or ibuprofen doses were blinded study medications adhering to the protocol while less than 15% were OTC deviations from the protocol. This successfully implemented study design provides a template to comparatively evaluate these and other OTC medications.
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http://dx.doi.org/10.1016/j.cct.2021.106334DOI Listing
February 2021

Pediatric asthma exacerbations during the COVID-19 pandemic: Absence of the typical fall seasonal spike in Washington, DC.

J Allergy Clin Immunol Pract 2021 Feb 16. Epub 2021 Feb 16.

Division of Emergency Medicine, Children's National Hospital and George Washington University School of Medicine and Health Sciences, Washington, DC. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2021.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884913PMC
February 2021

Preventing asthma in high risk kids (PARK) with omalizumab: Design, rationale, methods, lessons learned and adaptation.

Contemp Clin Trials 2021 Jan 24;100:106228. Epub 2020 Nov 24.

Harvard Medical School, Boston, MA, United States of America; Brigham and Women's Hospital, Divisions of Pulmonary and Critical Care Medicine and Allergy and Immunology, Boston, MA, United States of America.

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma - viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2-3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma.
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http://dx.doi.org/10.1016/j.cct.2020.106228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887056PMC
January 2021

Predicting outcomes of baked egg and baked milk oral food challenges by using a ratio of food-specific IgE to total IgE.

J Allergy Clin Immunol Pract 2020 Nov 17. Epub 2020 Nov 17.

Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass; Department of Pediatrics, Harvard Medical School, Boston, Mass. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2020.11.004DOI Listing
November 2020

Asthma Prevalence and Mold Levels in US Northeastern Schools.

J Allergy Clin Immunol Pract 2021 Mar 19;9(3):1312-1318. Epub 2020 Oct 19.

Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address:

Background: Asthma is among the most common chronic diseases of children in the United States (US). Mold exposures have been linked to asthma development and exacerbation. In homes, mold exposures have been quantified using the Environmental Relative Moldiness Index (ERMI), and higher home ERMI values have been linked to occupant asthma.

Objective: In this analysis of the School Inner-City Asthma Study (SICAS), we aimed to evaluate the ERMI's applicability to measuring mold in schools compared with homes and to examine the prevalence of asthma in relationship to students' demographics and the physical characteristics of school buildings.

Methods: Northeastern US schools (n = 32) and homes (n = 33) were selected, and the 36 ERMI molds were quantified in a dust sample from each classroom (n = 114) or home. School building characteristics data were collected from SICAS. Asthma prevalence and student demographics data were obtained from government websites. Linear regression and mixed models were fit to assess the association of the current asthma prevalence and physical characteristics of the school, make-up of the student body, and the ERMI metric.

Results: Levels of outdoor group 2 molds were significantly (P < .01) greater in schools compared with homes. The presence of air-conditioning in school buildings correlated significantly (P = .02) with lower asthma prevalence.

Conclusion: The prevalence of asthma in student bodies is associated with many factors in schools and homes.
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http://dx.doi.org/10.1016/j.jaip.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946701PMC
March 2021

The efficacy of a novel monitoring device on asthma control in children with asthma.

Ann Allergy Asthma Immunol 2020 09 20;125(3):352-354. Epub 2020 Jun 20.

Department of Asthma, Allergy, and Immunology, Boston Children's Hospital, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2020.06.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7483778PMC
September 2020

Aeroallergen Sensitization, Serum IgE, and Eosinophilia as Predictors of Response to Omalizumab Therapy During the Fall Season Among Children with Persistent Asthma.

J Allergy Clin Immunol Pract 2020 10 4;8(9):3021-3028.e2. Epub 2020 May 4.

Children's National Hospital and George Washington University School of Medicine and Health Sciences, Washington, DC.

Background: Perennial aeroallergen sensitization is associated with greater asthma morbidity and is required for treatment with omalizumab.

Objective: To investigate the predictive relationship between the number of aeroallergen sensitizations, total serum IgE, and serum eosinophil count, and response to omalizumab in children and adolescents with asthma treated during the fall season.

Methods: This analysis includes inner-city patients with persistent asthma and recent exacerbations aged 6-20 years comprising the placebo- and omalizumab-treated groups in 2 completed randomized clinical trials, the Inner-City Anti-IgE Therapy for Asthma study and the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations study. Logistic regression modeled the relationship between greater degrees of markers of allergic inflammation and the primary outcome of fall season asthma exacerbations.

Results: The analysis included 761 participants who were 62% male and 59% African American with a median age of 10 years. Fall asthma exacerbations were significantly higher in children with greater numbers of aeroallergen-specific sensitizations in the placebo group (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.11-1.60; P < .01), but not in the omalizumab-treated children (OR, 1.08; 95% CI, 0.91-1.28; P = .37), indicating a significant differential effect (P < .01). Likewise, there was a differential effect of omalizumab treatment in children with greater baseline total serum IgE levels (P < .01) or greater baseline serum eosinophil counts (P < .01). Multiple aeroallergen sensitization was the best predictor of response to omalizumab; treated participants sensitized to ≥4 different groups of aeroallergens had a 51% reduction in the odds of a fall exacerbation (OR, 0.49; 95% CI, 0.30-0.81; P < .01).

Conclusions: In preventing fall season asthma exacerbations, treatment with omalizumab was most beneficial in children with a greater degree of allergic inflammation.
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http://dx.doi.org/10.1016/j.jaip.2020.03.051DOI Listing
October 2020

Obesity may enhance the adverse effects of NO exposure in urban schools on asthma symptoms in children.

J Allergy Clin Immunol 2020 10 18;146(4):813-820.e2. Epub 2020 Mar 18.

Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address:

Background: Sparse data address the effects of nitrogen dioxide (NO) exposure in inner-city schools on obese students with asthma.

Objective: We sought to evaluate relationships between classroom NO exposure and asthma symptoms and morbidity by body mass index (BMI) category.

Methods: The School Inner-City Asthma Study enrolled students aged 4 to 13 years with asthma from 37 inner-city schools. Students had baseline determination of BMI percentile. Asthma symptoms, morbidity, pulmonary inflammation, and lung function were monitored throughout the subsequent academic year. Classroom NO data, linked to enrolled students, were collected twice per year. We determined the relationship between classroom NO levels and asthma outcomes by BMI stratification.

Results: A total of 271 predominantly black (35%) or Hispanic students (35%) were included in analyses. Fifty percent were normal weight (5-84th BMI percentile), 15% overweight (≥85-94th BMI percentile), and 35% obese (≥95th BMI percentile). For each 10-parts per billion increase in NO, obese students had a significant increase in the odds of having an asthma symptom day (odds ratio [OR], 1.86; 95% CI, 1.15-3.02) and in days caregiver changed plans (OR, 4.24; 95% CI, 2.33-7.70), which was significantly different than normal weight students who exhibited no relationship between NO exposure and symptom days (OR, 0.90; 95% CI, 0.57-1.42; pairwise interaction P = .03) and change in caregiver plans (OR, 1.37; 95% CI, 0.67-2.82; pairwise interaction P = .02). Relationships between NO levels and lung function and fractional exhaled nitric oxide did not differ by BMI category. If we applied a conservative Holm-Bonferroni correction for 16 comparisons (obese vs normal weight and overweight vs normal weight for 8 outcomes), these findings would not meet statistical significance (all P > .003).

Conclusions: Obese BMI status appears to increase susceptibility to classroom NO exposure effects on asthma symptoms in inner-city children. Environmental interventions targeting indoor school NO levels may improve asthma health for obese children. Although our findings would not remain statistically significant after adjustment for multiple comparisons, the large effect sizes warrant future study of the interaction of obesity and pollution in pediatric asthma.
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http://dx.doi.org/10.1016/j.jaci.2020.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501199PMC
October 2020

Proximity to major roadways and asthma symptoms in the School Inner-City Asthma Study.

J Allergy Clin Immunol 2020 01 23;145(1):119-126.e4. Epub 2019 Sep 23.

Harvard Medical School, Boston, Mass; Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass. Electronic address:

Background: Traffic proximity has been associated with adverse respiratory health outcomes. Less is known about the combined impact of residential and school exposures on pediatric asthma.

Objective: We sought to use spatial analysis methodology to analyze residential and school proximity to major roadways and pediatric asthma morbidity.

Methods: The School Inner-City Asthma Study (n = 350) recruited school-aged children with asthma. Each participant's school and home addresses were geocoded, and distances from major roadways were measured to calculate a composite measure accounting for both home and school traffic exposure. Generalized estimating equation models were clustered by subject and adjusted for age, race/ethnicity, sex, income, environmental tobacco smoke, controller medication, upper respiratory tract infections, and seasonality.

Results: The majority of participants (62%) attended schools within 100 m from major roadways, and 40% also resided within 100 m of major roadways. In multivariate analyses major roadway proximity was independently associated with increased asthma symptom days. At greater than the threshold of 100 m, children had 29% less odds of a symptom day over the past 2 weeks for each 100-m increase in distance from a major roadway (odds ratio, 0.71; 95% CI, 0.58-0.87; P < .01). Children farther from a major roadway also had significantly less reported health care use (odds ratio, 0.63; 95% CI, 0.47-0.85; P < .01) and were significantly less likely to have poor asthma control (odds ratio, 0.80; 95% CI, 0.69-0.94; P < .01). There was not a meaningful association between distance to a major roadway and lung function outcomes.

Conclusions: Proximity to a major roadway, a composite measure of home and school exposure but primarily driven by home exposure, was associated with greater asthma morbidity. More studies are needed to evaluate the independent effect of school distance to a roadway on asthma morbidity.
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http://dx.doi.org/10.1016/j.jaci.2019.08.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949366PMC
January 2020

Racial and socioeconomic differences in school peanut-free policies.

J Allergy Clin Immunol Pract 2020 01 15;8(1):340-342.e1. Epub 2019 Jul 15.

Boston Children's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2019.06.036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960368PMC
January 2020

Inner-City Asthma in Childhood.

Immunol Allergy Clin North Am 2019 05;39(2):259-270

Division of Allergy and Immunology, Department of Pediatrics, Children's National Health System, 111 Michigan Avenue Northwest, Washington, DC 20010, USA; George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

The inner-city is a well-established and well-studied location that includes children at high risk for high asthma prevalence and morbidity. A number of intrinsic and extrinsic risk factors contribute to asthma in inner-city populations. This review seeks to explore these risk factors and evaluate how they contribute to increased asthma morbidity. Previous literature has identified risk factors such as race and ethnicity, prematurity, obesity, and exposure to aeroallergens and pollutants. Environmental and medical interventions aimed at individual risk factors and specific asthma phenotypes have contributed to improved outcomes in the inner-city children with asthma.
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http://dx.doi.org/10.1016/j.iac.2018.12.008DOI Listing
May 2019

Association between fungal spore exposure in inner-city schools and asthma morbidity.

Ann Allergy Asthma Immunol 2019 06 20;122(6):610-615.e1. Epub 2019 Mar 20.

Boston Children's Hospital, Division of Allergy and Immunology, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address:

Background: Home fungus exposures may be associated with development or worsening of asthma. Little is known about the effects of school/classroom fungus exposures on asthma morbidity in students.

Objective: To evaluate the association of school-based fungus exposures on asthma symptoms in both fungus-sensitized and nonsensitized students with asthma.

Methods: In this prospective study, 280 children with asthma from 37 inner-city schools were phenotypically characterized at baseline and followed-up for 1 year. Fungal spores were collected by using a Burkard air sampler twice during the school year. Clinical outcomes were evaluated throughout the school year and linked to classroom-specific airborne spore sampling. The primary outcome was days with asthma symptoms per 2-week period.

Results: Fungal spores were present in all classroom samples. The geometric mean of the total fungi was 316.9 spores/m and ranged from 15.0 to 59,345.7 spores/m. There was variability in total fungus quantity between schools and classrooms within the same school. Mitospores were the most commonly detected fungal grouping. Investigation of the individual mitospores revealed that exposure to Alternaria was significantly associated with asthma symptom days in students sensitized to Alternaria (OR = 3.61, CI = 1.34-9.76, P = .01), but not in children not sensitized to Alternaria (OR = 1.04, CI = 0.72-1.49, P = .85). Students sensitized to Alternaria and exposed to high levels (≥75th percentile exposure) had 3.2 more symptom days per 2-week period as compared with students sensitized but exposed to lower levels.

Conclusion: Children with asthma who are sensitized to Alternaria and exposed to this fungus in their classroom may have significantly more days with asthma symptoms than those who were sensitized and not exposed.

Clinical Trial Registration: Clinicaltrials.govNCT01756391.
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http://dx.doi.org/10.1016/j.anai.2019.03.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555650PMC
June 2019

Impact of weather and climate change with indoor and outdoor air quality in asthma: A Work Group Report of the AAAAI Environmental Exposure and Respiratory Health Committee.

J Allergy Clin Immunol 2019 05 28;143(5):1702-1710. Epub 2019 Feb 28.

University of California Los Angeles, David Geffen School of Medicine and California NanoSystems Institute, Los Angeles, Calif.

Weather and climate change are constant and ever-changing processes that affect allergy and asthma. The purpose of this report is to provide information since the last climate change review with a focus on asthmatic disease. PubMed and Internet searches for topics included climate and weather change, air pollution, particulates, greenhouse gasses, traffic, insect habitat, and mitigation in addition to references contributed by the individual authors. Changes in patterns of outdoor aeroallergens caused by increasing temperatures and amounts of carbon dioxide in the atmosphere are major factors linked to increased duration of pollen seasons, increased pollen production, and possibly increased allergenicity of pollen. Indoor air pollution threats anticipated from climate changes include microbial and mold growth secondary to flooding, resulting in displacement of persons and need for respiratory protection of exposed workers. Air pollution from indoor burning of mosquito repellants is a potential anticipatory result of an increase in habitat regions. Air pollution from fossil fuel burning and traffic-related emissions can alter respiratory defense mechanisms and work synergistically with specific allergens to enhance immunogenicity to worsen asthma in susceptible subjects. Community efforts can significantly reduce air pollution, thereby reducing greenhouse gas emission and improving air quality. The allergist's approach to weather pattern changes should be integrated and anticipatory to protect at-risk patients.
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http://dx.doi.org/10.1016/j.jaci.2019.02.018DOI Listing
May 2019

Environmental Food Exposure: What Is the Risk of Clinical Reactivity From Cross-Contact and What Is the Risk of Sensitization.

J Allergy Clin Immunol Pract 2018 Nov - Dec;6(6):1825-1832

Paediatric Allergy Group, Department of Women and Children's Health, School of Life Course Sciences, King's College London, Guy's Hospital, London, United Kingdom; Paediatric Allergy Group, School of Immunology & Microbial Sciences, King's College London, Guy's Hospital, London, United Kingdom; Children's Allergy Service, Evelina London, St Thomas' Hospital, London, United Kingdom.

For food-allergic individuals, the typical exposure to food proteins happens during ingestion; however, individuals may be exposed to foods in other ways. In addition to ingestion reactions, allergic patients may have reactions from cutaneous or mucosal exposures to food proteins, with the classic example being a peanut-allergic child touching a counter with peanut butter and then rubbing their eyes. Similar to hands, saliva can also act as a carrier for food proteins. Finally, there is a wealth of new research regarding the presence of food proteins in the environment, for example, within household floor dust. This review will focus on (1) cross-contact of food proteins and (2) environmental food protein exposures. Cross-contact occurs when one type of food comes into contact with another type of food resulting in the mixture of proteins. For food allergies, cross-contact is important when an allergen is inadvertently transferred to a food/meal that is thought to not contain that specific allergen. We will discuss the current literature regarding the presence of detectable food proteins in different locations, how and if these proteins are transferred or eliminated, and the clinical implications of exposures to food proteins under these different scenarios.
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http://dx.doi.org/10.1016/j.jaip.2018.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324195PMC
November 2019

The classroom microbiome and asthma morbidity in children attending 3 inner-city schools.

J Allergy Clin Immunol 2018 06 5;141(6):2311-2313. Epub 2018 Mar 5.

Harvard Medical School, Boston, Mass; Broad Institute of MIT and Harvard University, Cambridge, Mass. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2018.02.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994187PMC
June 2018

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

N Engl J Med 2018 Mar 3;378(10):891-901. Epub 2018 Mar 3.

From the Department of Pediatrics, University of Wisconsin School of Medicine and Public Health (D.J.J., R.F.L.J.), and the University of Wisconsin-Madison (C.A.S.) - both in Madison; the Department of Pediatrics, Washington University in St. Louis School of Medicine and St. Louis Children's Hospital, St. Louis (L.B.B., A.B.); the Department of Public Health Sciences, Penn State University, Hershey (D.T.M., S.B.), and the University of Pittsburgh Asthma Institute at University of Pittsburgh Medical Center-University of Pittsburgh School of Medicine (F.H.) and the Department of Pediatrics, Allegheny General Hospital (D.A.G.), Pittsburgh - all in Pennsylvania; the Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland (J.F.C., R.E.M., K.R.); the Department of Pediatrics, Emory University, Atlanta (A.M.F.); the Divisions of Respiratory Diseases (J.M.G.) and Allergy-Immunology, Boston Children's Hospital (W.P., W.J.S., S.N.B.), Harvard Medical School, and Brigham and Women's Hospital, Harvard Medical School (E.I.) - all in Boston; the Arizona Respiratory Center, University of Arizona, Tucson (W.J.M., F.D.M.); Wake Forest University School of Medicine, Winston-Salem, NC (S.P.P.); the Departments of Pediatrics (M.D.C., N.L.), Epidemiology (M.D.C.), Biostatistics (M.D.C.), and Medicine (S.C.L.), University of California, San Francisco (UCSF), and UCSF Benioff Children's Hospital (M.D.C.) - both in San Francisco; Ann and Robert H. Lurie Children's Hospital of Chicago (J.A.P., R.G.R.), University of Illinois at Chicago (J.A.K., H.V.K.), and the Department of Pediatrics, Stroger Hospital of Cook County, Rush University Medical Center (J.N.M.) - all in Chicago; UCSF Benioff Children's Hospital Oakland, Oakland (M.B., D.L., J.M.); Nemours Children's Health System, Jacksonville (K.B., J.J.L.), and Nemours Children's Hospital, University of Central Florida College of Medicine, Orlando (J.E.L.) - both in Florida; the Department of Pediatrics, National Jewish Health, Denver (R.C., J.T.O.); and the Department of Pediatrics, University of New Mexico, Albuquerque (H.H.R.).

Background: Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited.

Methods: We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids.

Results: The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06).

Conclusions: In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).
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http://dx.doi.org/10.1056/NEJMoa1710988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5972517PMC
March 2018

Advances in environmental and occupational disorders in 2016.

J Allergy Clin Immunol 2017 Dec;140(6):1683-1692

Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass; Division of Harvard Medical School, Boston, Mass. Electronic address:

In this review we highlight recent studies that advance the knowledge and understanding of the effects of various environmental factors and associated immune responses in patients with allergic diseases. This review will focus on new literature regarding allergic and immune responses to a variety of environmental factors, including aeroallergens, stinging insects, fungi, pollutants, viral respiratory tract infections, climate change, and microbial exposures.
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http://dx.doi.org/10.1016/j.jaci.2017.09.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777358PMC
December 2017

Nitrogen dioxide exposure in school classrooms of inner-city children with asthma.

J Allergy Clin Immunol 2018 06 5;141(6):2249-2255.e2. Epub 2017 Oct 5.

Harvard Medical School, Boston, Mass; Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass. Electronic address:

Background: Ambient and home exposure to nitrogen dioxide (NO) causes asthma symptoms and decreased lung function in children with asthma. Little is known about the health effects of school classroom pollution exposure.

Objective: We aimed to determine the effect of indoor classroom NO on lung function and symptoms in inner-city school children with asthma.

Methods: Children enrolled in the School Inner-City Asthma Study were followed for 1 academic year. Subjects performed spirometry and had fraction of exhaled nitric oxide values measured twice during the school year at school. Classroom NO was collected by means of passive sampling for 1-week periods twice per year, coinciding with lung function testing. Generalized estimating equation models assessed lung function and symptom relationships with the temporally nearest classroom NO level.

Results: The mean NO value was 11.1 ppb (range, 4.3-29.7 ppb). In total, exposure data were available for 296 subjects, 188 of whom had complete spirometric data. At greater than a threshold of 8 ppb of NO and after adjusting for race and season (spirometry standardized by age, height, and sex), NO levels were associated highly with airflow obstruction, such that each 10-ppb increase in NO level was associated with a 5% decrease in FEV/forced vital capacity ratio (β = -0.05; 95% CI, -0.08 to -0.02; P = .01). Percent predicted forced expiratory flow between the 25th and 75th percentile of forced vital capacity was also inversely associated with higher NO exposure (β = -22.8; 95% CI, -36.0 to -9.7; P = .01). There was no significant association of NO levels with percent predicted FEV, fraction of exhaled nitric oxide, or asthma symptoms. Additionally, there was no effect modification of atopy on lung function or symptom outcomes.

Conclusion: In children with asthma, indoor classroom NO levels can be associated with increased airflow obstruction.
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http://dx.doi.org/10.1016/j.jaci.2017.08.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5886827PMC
June 2018

Distribution of peanut protein in school and home environments of inner-city children.

J Allergy Clin Immunol 2017 12 21;140(6):1724-1726. Epub 2017 Jun 21.

Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2017.05.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5723220PMC
December 2017

The School Inner-City Asthma Intervention Study: Design, rationale, methods, and lessons learned.

Contemp Clin Trials 2017 09 12;60:14-23. Epub 2017 Jun 12.

Harvard Medical School, Boston, MA, United States; Harvard T.H. Chan School of Public Health, Department of Environmental Health, Boston, MA, United States; Channing Laboratory, Brigham and Women's Hospital, Boston, MA, United States.

Asthma is the most common chronic disease of childhood in the United States, causes significant morbidity, particularly in the inner-city, and accounts for billions of dollars in health care utilization. Home environments are established sources of exposure that exacerbate symptoms and home-based interventions are effective. However, elementary school children spend 7 to 12h a day in school, primarily in one classroom. From the observational School Inner-City Asthma Study we learned that student classroom-specific exposures are associated with worsening asthma symptoms and decline in lung function. We now embark on a randomized, blinded, sham-controlled school environmental intervention trial, built on our extensively established school/community partnerships, to determine the efficacy of a school-based intervention to improve asthma control. This factorial school/classroom based environmental intervention will plan to enroll 300 students with asthma from multiple classrooms in 40 northeastern inner-city elementary schools. Schools will be randomized to receive either integrated pest management versus control and classrooms within these schools to receive either air purifiers or sham control. The primary outcome is asthma symptoms during the school year. This study is an unprecedented opportunity to test whether a community of children can benefit from school or classroom environmental interventions. If effective, this will have great impact as an efficient, cost-effective intervention for inner city children with asthma and may have broad public policy implications.
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http://dx.doi.org/10.1016/j.cct.2017.06.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5557648PMC
September 2017

Caregiver stress among inner-city school children with asthma.

J Allergy Clin Immunol Pract 2017 Jul - Aug;5(4):1132-1134.e3. Epub 2017 Apr 19.

Harvard Medical School, Boston, Mass; Division of Allergy and Immunology, Boston Children's Hospital, Boston, Mass. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2017.02.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503799PMC
June 2019

Impact of school peanut-free policies on epinephrine administration.

J Allergy Clin Immunol 2017 Aug 25;140(2):465-473. Epub 2017 Mar 25.

Boston Children's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address:

Background: Children with food allergies spend a large proportion of time in school but characteristics of allergic reactions in schools are not well studied. Some schools self-designate as peanut-free or have peanut-free areas, but the impact of policies on clinical outcomes has not been evaluated.

Objective: We sought to determine the effect of peanut-free policies on rates of epinephrine administration for allergic reactions in Massachusetts public schools.

Methods: In this retrospective study, we analyzed (1) rates of epinephrine administration in all Massachusetts public schools and (2) Massachusetts public school nurse survey reports of school peanut-free policies from 2006 to 2011 and whether schools self-designated as "peanut-free" based on policies. Rates of epinephrine administration were compared for schools with or without peanut-restrictive policies.

Results: The percentage of schools with peanut-restrictive policies did not change significantly in the study time frame. There was variability in policies used by schools self-designated as peanut-free. No policy was associated with complete absence of allergic reactions. Both self-designated peanut-free schools and schools banning peanuts from being served in school or brought from home reported allergic reactions to nuts. Policies restricting peanuts from home, served in schools, or having peanut-free classrooms did not affect epinephrine administration rates. Schools with peanut-free tables, compared to without, had lower rates of epinephrine administration (incidence rate per 10,000 students 0.2 and 0.6, respectively, P = .009).

Conclusions: These data provide a basis for evidence-based school policies for children with food allergies. Further studies are required before decisions can be made regarding peanut-free policies in schools.
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http://dx.doi.org/10.1016/j.jaci.2017.01.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5546995PMC
August 2017

Association Between Allergen Exposure in Inner-City Schools and Asthma Morbidity Among Students.

JAMA Pediatr 2017 01;171(1):31-38

Division of Allergy and Immunology, Boston Children's Hospital, Boston, Massachusetts2Harvard Medical School, Boston, Massachusetts.

Importance: Home aeroallergen exposure is associated with increased asthma morbidity in children, yet little is known about the contribution of school aeroallergen exposures to such morbidity.

Objective: To evaluate the effect of school-specific aeroallergen exposures on asthma morbidity among students, adjusting for home exposures.

Design, Setting, And Participants: The School Inner-City Asthma Study was a prospective cohort study evaluating 284 students aged 4 to 13 years with asthma who were enrolled from 37 inner-city elementary schools in the northeastern United States between March 1, 2008, and August 31, 2013. Enrolled students underwent baseline clinical evaluations before the school year started and were then observed clinically for 1 year. During that same school year, classroom and home dust samples linked to the students were collected and analyzed for common indoor aeroallergens. Associations between school aeroallergen exposure and asthma outcomes during the school year were assessed, adjusting for home exposures.

Exposures: Indoor aeroallergens, including rat, mouse, cockroach, cat, dog, and dust mites, measured in dust samples collected from inner-city schools.

Main Outcomes And Measures: The primary outcome was maximum days in the past 2 weeks with asthma symptoms. Secondary outcomes included well-established markers of asthma morbidity, including asthma-associated health care use and lung function, measured by forced expiratory volume in 1 second.

Results: Among 284 students (median age, 8 years [interquartile range, 6-9 years]; 148 boys and 136 girls), exposure to mouse allergen was detected in 441 (99.5%) of 443 school dust samples, cat allergen in 420 samples (94.8%), and dog allergen in 366 samples (82.6%). Levels of mouse allergen in schools were significantly higher than in students' homes (median settled dust level, 0.90 vs 0.14 µg/g; P < .001). Exposure to higher levels of mouse allergen in school (comparing 75th with 25th percentile) was associated with increased odds of having an asthma symptom day (odds ratio, 1.27; 95% CI, 1.05-1.54; P = .02) and 4.0 percentage points lower predicted forced expiratory volume in 1 second (95% CI, -6.6 to -1.5; P = .002). This effect was independent of allergic sensitization. None of the other indoor aeroallergens were associated with worsening asthma outcomes.

Conclusions And Relevance: In this study of inner-city students with asthma, exposure to mouse allergen in schools was associated with increased asthma symptoms and decreased lung function. These findings demonstrate that the school environment is an important contributor to childhood asthma morbidity. Future school-based environmental interventions may be beneficial for this important public health problem.
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http://dx.doi.org/10.1001/jamapediatrics.2016.2543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5349325PMC
January 2017