A biweekly overview of recent studies published by Institute investigators and their collaborators spans a wide variety of topics, including:

The FDA Sentinel System; using epigenetics to measure the effects of breastfeeding; the pharmacogenetics of bronchodilator response; ventilator-associated pneumonia in COVID-19 patients; gestational diabetes risk factors; biologically actionable insights into inhaled corticosteroid  response in asthma patients

For all faculty publications, see our Publications page. For up-to-date media coverage and research findings, visit In the Media, and follow us on Twitter. To search for a subject matter expert, visit our Investigator Directory.
 

A roadmap for the Sentinel System focusing on 4 priority areas
The Sentinel System is a major component of the FDA approach to active medical product safety surveillance. While Sentinel has historically relied on large quantities of health insurance claims data, leveraging longitudinal electronic health records (EHRs) that contain more detailed clinical information, as structured and unstructured features, may address some of the current gaps in capabilities. A team including Judith Maro and Darren Toh identifies key challenges when using EHR data to investigate medical product safety in a scalable and accelerated way, outline potential solutions, and describe the Sentinel Innovation Center’s initiatives to put solutions into practice by expanding and strengthening the existing system with a query-ready, large-scale data infrastructure of linked EHR and claims data. Results, published in NPJ | Digital Medicine describe their initiatives in four strategic priority areas.

Institute Investigator(s): Judith Maro, Darren Toh

Using epigenetics to measure the benefits of breastfeeding
The role of breastfeeding in modulating epigenetic factors has been suggested as a possible mechanism conferring its benefits on child development but it lacks evidence. Using extensive DNA methylation data from the ALSPAC child cohort, a team including Marie-France Hivert characterized the genome-wide landscape of DNA methylation variations associated with the duration of exclusive breastfeeding and assessed whether these variations mediate the association between exclusive breastfeeding and BMI over different epochs of child growth. Results were published in BMC Clinical Epigenetics.

Institute Investigator(s): Marie-France Hivert
 

Current knowledge gaps and possible future directions of the pharmacogenetics of bronchodilator response
A new review led by Joanne Sordillo with Sharon Lutz, Ann Wu, and colleagues, published in Current Allergy and Asthma Reports, looks at the knowledge gaps that exist in bronchodilator response to albuteral, and also describes potential new approaches. The study team emphasizes that many of the genome-wide association studies are primarily conducted in Caucasian populations, meaning that the findings may not be applicable across racial/ethnic populations. They suggest that future studies with higher populations of minority participants are needed to close knowledge gaps.  

Institute Investigator(s): Sharon Lutz, Joanne Sordillo, Ann Wu
 

The incidence, risk factors, and clinical characteristics of ventilator-associated pneumonia in COVID-19 patients
A study team including Michael Klompas conducted a systematic literature review of 16 studies to summarize the available evidence regarding the incidence, risk factors, and clinical characteristics of ventilator-associated pneumonia (VAP) in patients undergoing mechanical ventilation because of acute respiratory distress syndrome secondary to SARS-CoV-2 infection (C-ARDS). They found that COVID-19 patients who require mechanical ventilation for ARDS have a high risk (>50%) of developing VAP, most commonly because of Gram-negative bacteria. The review, published in Current Opinion in Critical Care, suggests that further work is needed to elucidate the disease-specific risk factors for VAP, strategies for prevention, and how best to differentiate between bacterial colonization versus superinfection.

Institute Investigator(s): Michael Klompas

Studying women with gestational diabetes risk factors
Despite recommendations to screen women with diabetes risk factors for hyperglycemia in the first trimester, criteria for normal glucose values in early pregnancy have not been firmly established. A team including Marie-France Hivert compared glucose levels in early pregnancy with those later in gestation and outside of pregnancy in women with diabetes risk factors. Results, published in Diabetologia, suggest that fasting glucose declines in the first trimester in women with diabetes risk factors. Post-load glucose increases later in pregnancy. Study findings may inform criteria for diagnosing hyperglycemia early in pregnancy.

Institute Investigator(s): Marie-France Hivert
 

Biologically actionable insights into inhaled corticosteroid response in asthma patients
Inhaled corticosteroid (ICS) response among patients with asthma is influenced by genetics, but biologically actionable insights based on associations have not been found. A team including Mei-Sing Ong, Joanne Sordillo, and Ann Wu examined functionally relevant ICS response genetic associations by integrating complementary multiomics datasets. Findings, published in Journal of Allergy and Clinical Immunology, suggest that BIRC3 should be prioritized for further functional studies of ICS response.

Institute Investigator(s): Mei-Sing Ong, Joanne Sordillo, Ann Wu