ANN ARBOR, Mich. – A Michigan Medicine-led research consortium has secured approval for up to $52 million in federal funding to launch a multicenter study examining why some young children recover fully from viral lower respiratory tract infections while others develop severe illness or lasting problems such as asthma.
The project brings together researchers and clinicians from across the United States to study children ages 0 to 24 months who are hospitalized with viral lower respiratory tract infections, including bronchiolitis, pneumonia and pediatric acute respiratory distress syndrome.
The consortium plans to enroll 1,500 children and follow them through at least ages four to five, combining detailed clinical assessments with lung function testing, imaging, environmental exposure measurements, activity and sleep monitoring and advanced molecular analyses.
The goal is to better understand the biological and environmental factors that contribute to resilience and a child's ability to recover and return to healthy lung function, versus vulnerability to ongoing respiratory problems.
“Right now, when a young child is hospitalized with a viral respiratory infection, we have very limited ability to predict what their trajectory will be,” said principal investigator Peter Mourani, M.D., Professor and Associate Chair of Research for the Department of Pediatrics and Division Director of Pediatric Critical Care Medicine at Michigan Medicine and U-M Health C.S. Mott Children's Hospital.
“We don't know which children will recover completely, which may have repeated problems with subsequent infections, and which may go on to have persistent respiratory disease. This study is designed to help us understand those different trajectories and, importantly, identify when and how we might intervene.”
Viral lower respiratory tract infections are a major cause of hospitalization in infants and toddlers. Early-life respiratory illness has also been associated with later respiratory morbidity, including recurrent wheezing and asthma. Yet the biological reasons children can have dramatically different responses to similar infections remain poorly understood.
Researchers will examine multiple potential contributors, including a child's underlying biology and immune response, characteristics of the infecting virus, the airway microbiome, and environmental exposures such as air pollution and tobacco smoke.
“Children's responses to these infections are complex,” Mourani said. “A child's underlying susceptibility, the virus itself, the way the immune system responds, and the environment in which that child lives may all contribute. By studying these factors together, rather than in isolation, we hope to identify patterns that explain why children follow very different paths after an early viral infection.”
The National Heart, Lung, and Blood Institute (NHLBI) has approved the first year of funding for the project, which is called Systematic Phenotyping and Endotyping in Viral Infections in the Young Lung, or SPIN VINYL.
The study will involve 10 enrolling hospitals across the United States, with Michigan Medicine serving as the clinical coordinating center.
The other nine enrolling sites include the Children’s Hospital of Philadelphia, Arkansas Children’s Hospital, Children’s Hospital Colorado, UCSF Benioff Children’s Hospital - San Francisco, UCSF Benioff Children’s Hospital – Oakland, Texas Children’s Hospital, Johns Hopkins All Children's Hospital, Nationwide Children’s Hospital and Children’s National Medical Center.
The study's national reach is intended to help researchers understand how respiratory illness affects children across a broad range of geographic, environmental, socioeconomic and demographic circumstances.
Combining clinical data with advanced biology
During the study, researchers will collect and integrate multiple types of information from participants during and after hospitalization
The biological analyses are designed to characterize the interactions among the child's immune system, the infecting pathogen and the airway microbiome.
The consortium will also use advanced statistical, informatics, machine learning and artificial intelligence methods to identify patterns associated with different disease trajectories.
Ultimately, researchers hope the work will identify measurable biological signatures that could help clinicians recognize children at greater risk for poor outcomes, including children born preterm and those with congenital heart disease, and guide future approaches to prevention and treatment.
For Michigan Medicine, the award represents a significant institutional investment in a nationally coordinated effort to address a major question in pediatric respiratory health.
“Putting this study together required an extraordinary team effort,” Mourani said. “I am incredibly grateful for the support from leadership and colleagues across Michigan Medicine, as well as the collaborators around the country who brought their expertise to this project. This is an opportunity to build something that can have a lasting impact on how we understand and care for children after early-life respiratory infections.”
Other lead investigators include Chaz Langelier, M.D., Ph.D., Professor of Medicine in the Division of Infectious Diseases at University of California San Francisco and Tamara Perry, M.D., Professor of Pediatrics in the Division of Allergy and Immunology at the University of Arkansas for Medical Sciences and President of Arkansas Children’s Research Institute.
Other acknowledgements:
Mary Dahmer, Ph.D., Associate Professor of Pediatrics in the Division of Critical Care and Victoria Blanc, Ph.D. Director of the Central Biorepository at Michigan Medicine, will lead the Biorepository for the Consortium which will be housed at the University of Michigan.
Carey Lumeng, M.D., Ph.D., Professor of Pediatrics and Molecular and Integrative Physiology and Division Director of Pulmonary Medicine at Michigan Medicine will lead the pulmonary function core for the consortium.
The University of Utah will serve as the Data and Analysis Coordinating Center for the SPIN VINYLK Consortium and is led by Kevin Watt, M.D., PhD., Professor of Pediatrics, Chair in Clinical Pharmacology and Chief of the Division of Clinical Pharmacology in the Department of Pediatrics; and Larry Cook, Ph.D. Professor of Pediatrics in the Division of Critical Care at the University of Utah; and Tellen Bennett, M.D., Professor and Vice Chair of Clinical Informatics, in the Department of Biomedical Informatics at the University of Colorado Anschutz Campus.