Jessica P. Hollenbach

Loss of DNA Mismatch Repair Imparts a Selective Advantage in Planarian Adult Stem Cells

Lynch syndrome (LS) leads to an increased risk of early-onset colorectal and other types of cancer and is caused by germline mutations in DNA mismatch repair (MMR) genes. Loss of MMR function results in a mutator phenotype that likely underlies its role in tumorigenesis. However, loss of MMR also results in the elimination of a DNA damage-induced checkpoint/apoptosis activation barrier that may allow damaged cells to grow unchecked. A fundamental question is whether loss of MMR provides pre-cancerous stem cells an immediate selective advantage in addition to establishing a mutator phenotype. To test this hypothesis in an in vivo system, we utilized the planarian Schmidtea mediterranea which contains a significant population of identifiable adult stem cells. We identified a planarian homolog of human MSH2, a MMR gene which is mutated in 38% of LS cases. The planarian Smed-msh2 is expressed in stem cells and some progeny. We depleted Smed-msh2 mRNA levels by RNA-interference and found a striking survival advantage in these animals treated with a cytotoxic DNA alkylating agent compared to control animals. We demonstrated that this tolerance to DNA damage is due to the survival of mitotically active, MMR-deficient stem cells. Our results suggest that loss of MMR provides an in vivo survival advantage to the stem cell population in the presence of DNA damage that may have implications for tumorigenesis.

Implementing school asthma programs: Lessons learned and recommendations

Despite significant advances in the treatment of asthma and the development of evidence-based and evidence-informed guidelines, childhood asthma morbidity remains high. One measure of asthma-associated morbidity is school absenteeism. In this rostrum we summarize key themes from 3 articles in this special issue on school-centered asthma programs. All 3 articles in this series describe several common themes that are essential for successful school-based interventions. These themes include the importance of trust and building strong partnerships, the importance of interaction and communication between multiple key stakeholders (ecological framework), the central and often overlooked role of the primary care clinician, the need for sustainable resources, and the importance of context and public policy. We then discuss how to apply the framework of implementation research to inform and evaluate school-based interventions. Finally, we make a series of recommendations for future work.

Childhood Asthma Management and Environmental Triggers

Asthma is the most common chronic disease among children. It cannot be prevented but can be controlled. Industrialized countries experience high lifetime asthma prevalence that has increased over recent decades. Asthma has a complex interplay of genetic and environmental triggers. Studies have revealed complex interactions of lung structure and function genes with environmental exposures such as environmental tobacco smoke and vitamin D. Home environmental strategies can reduce asthma morbidity in children but should be tailored to specific allergens. Coupled with education and severity-specific asthma therapy, tailored interventions may be the most effective strategy to manage childhood asthma.

Exposure to secondhand smoke and asthma severity among children in Connecticut

Objective To determine whether secondhand smoke (SHS) exposure is associated with greater asthma severity in children with physician-diagnosed asthma living in CT, and to examine whether area of residence, race/ethnicity or poverty moderate the association. Methods A large childhood asthma database in CT (Easy Breathing) was linked by participant zip code to census data to classify participants by area of residence. Multinomial logistic regression models, adjusted for enrollment date, sex, age, race/ethnicity, area of residence, insurance type, family history of asthma, eczema, and exposure to dogs, cats, gas stove, rodents and cockroaches were used to examine the association between self-reported exposure to SHS and clinician-determined asthma severity (mild, moderate, and severe persistent vs. intermittent asthma). Results Of the 30,163 children with asthma enrolled in Easy Breathing, between 6 months and 18 years old, living in 161 different towns in CT, exposure to SHS was associated with greater asthma severity (adjusted relative risk ratio (aRRR): 1.07 [1.00, 1.15] and aRRR: 1.11 [1.02, 1.22] for mild and moderate persistent asthma, respectively). The odds of Black and Puerto Rican/Hispanic children with asthma being exposed to SHS were twice that of Caucasian children. Though the odds of SHS exposure for publicly insured children with asthma were three times greater than the odds for privately insured children (OR: 3.02 [2.84,3,21]), SHS exposure was associated with persistent asthma only among privately insured children (adjusted odds ratio (aOR): 1.23 [1.11,1.37]). Conclusion This is the first large-scale pragmatic study to demonstrate that children exposed to SHS in Connecticut have greater asthma severity, clinically determined using a systematic approach, and varies by insurance status.

Understanding clinicians' attitudes toward a mobile health strategy to childhood asthma management: A qualitative study

ABSTRACT Objectives: Mobile technology for childhood asthma can provide real-time data to enhance care. What real-time adherence information clinicians want, how they may use it, and if the data meet their clinical needs have not been fully explored. Our goal was to determine whether pediatric primary care and pulmonary clinicians believe if a sensor-based mobile intervention is useful in caring for patients with asthma. Methods: We recruited participants from 3 urban, primary care and 1 pulmonary practice from July to September 2015 in Hartford, CT. Forty-one participated in four focus groups, which included a demonstration of the technology. Participants were probed with open-ended questions on the type, frequency, and format of inter-visit patient information they found useful. Results: 41 participants (mean age 49 (±13.7) years) were board-certified clinicians (41% MDs and 20% mid-level practitioners), practiced medicine on an average of 19 (±14) years, were primarily white (59%) and women (78%). Clinicians wanted 1) adherence to prescribed inhaler therapy and 2) data on inhaler technique. Clinicians wanted it at the time of a scheduled clinic visit but also wanted inter-visit alerts for excessive use of rescue therapy. Pulmonologists liked the mobile spirometers provision of inter-visit lung function data; pediatricians did not share this view. Concerns with data accuracy were raised due to families who shared inhalers, access to smartphones, and protection of health information. Conclusions: Overall, clinicians view an asthma mobile health technology as enhancing the patient-centered medical home. Pediatric primary care clinicians and pulmonologists want different information from a mobile app.

Building Bridges for Asthma Care: Reducing school absence for inner-city children with health disparities

Background: Children with asthma are at increased risk for experiencing health and educational disparities because of increased school absence. School nurses are well positioned to support asthma management and improve school attendance. Objective: We sought to implement and assess the effect of the Building Bridges for Asthma Care Program on improving school attendance and measures of asthma control. Methods: Children with asthma (age, 5‐14 years) in the Denver Public School System (n = 240) and the Hartford Public School System (n = 223) were enrolled in the Building Bridges Program during the 2013‐2014 and 2014‐2015 school years and followed until the end of the second school year. The primary outcome was school absence, with secondary outcomes, including asthma control, measured based on Childhood Asthma Control Test or the Asthma Control Test scores and rescue inhaler use. Results: Participants experienced a 22% absolute decrease in school absenteeism, the number of children with an Asthma Control Test/Childhood Asthma Control Test score of less than the control threshold of 20 decreased from 42.7% to 28.8%, and bronchodilator use greater than 2 times per week decreased from 35.8% to 22.9% (all changes were significant, P < .01). Conclusions: Children enrolled in the Building Bridges for Asthma Care Program experienced reduced school absence and improved asthma control.

Building Bridges for Asthma Care Program: A School-Centered Program Connecting Schools, Families, and Community Health-Care Providers

Asthma imposes tremendous burden on children, families, and society. Successful management requires coordinated care among children, families, health providers, and schools. Building Bridges for Asthma Care Program, a school-centered program to coordinate care for successful asthma management, was developed, implemented, and evaluated. The program consists of five steps: (1) identify students with asthma; (2) assess asthma risk/control; (3) engage the family and student at risk; (4) provide case management and care coordination, including engagement of health-care providers; and (5) prepare for next school year. Implementation occurred in 28 schools from two large urban school districts in Colorado and Connecticut. Significant improvements were noted in the proportions of students with completed School Asthma Care Plans, a quick-relief inhaler at school, Home Asthma Action/Treatment Plans and inhaler technique (p < .01 for all variables). Building Bridges for Asthma Care was successfully implemented extending asthma care to at-risk children with asthma through engagement of schools, health providers, and families.

Inaccuracy of asthma-related self-reported health-care utilization data compared to Medicaid claims

In asthma, health-care utilization is often used as an outcome measure and to identify cases of poorly controlled asthma. Asthma-related hospitalizations, emergency department (ED) visits, and systemic corticosteroid courses were compared between caregiver report and Medicaid administrative claims over 12 months among children enrolled in a school-based asthma program. The concordance was poor for both caregiver-reported ED visits and systemic corticosteroid courses (k = 0.04 and k = 0.02, respectively) and fair (k = 0.21) for hospitalizations. The percent of caregivers with disagreement among sources was hospitalizations = 75%; ED visits = 75%; and systemic corticosteroids = 84%. The data sources resulted in pronounced differences in estimates at the individual level, suggesting that caregiver-reported data sources are not accurate when using insurance claims as the gold standard. We recommend investigators thoughtfully consider study design when deciding upon the data source for asthma-related utilization.