Impact of Viral Lower Respiratory Tract Infection (LRTI) in Early Childhood (0-2 Years) on Lung Growth and Development and Lifelong Trajectories of Pulmonary Health: A National Institutes of Health (NIH) Workshop Summary

Hitesh Deshmukh; Jeffrey Whitsett; William Zacharias; Sing Sing Way; Fernando D Martinez; Joseph Mizgerd; Gloria Pryhuber; Namasivayam Ambalavanan; Leonard Bacharier; Aruna Natarajan; Robert Tamburro; Sara Lin; Adrienne Randolph; Gustavo Nino; Asuncion Mejias; Octavio Ramilo; NIH Workshop Participants of the ‘Viral Lower Respiratory Tract Infections in Infancy and Early Childhood‐Immunological and Developmental Aspects’

doi:10.1002/ppul.27357

Impact of Viral Lower Respiratory Tract Infection (LRTI) in Early Childhood (0-2 Years) on Lung Growth and Development and Lifelong Trajectories of Pulmonary Health: A National Institutes of Health (NIH) Workshop Summary

Pediatr Pulmonol. 2024 Nov 20:e27357. doi: 10.1002/ppul.27357. Online ahead of print.

Authors

Hitesh Deshmukh^{1

2

3

4}, Jeffrey Whitsett^{1

2

3}, William Zacharias^{2

4}, Sing Sing Way^{3

5}, Fernando D Martinez⁶, Joseph Mizgerd⁷, Gloria Pryhuber⁸, Namasivayam Ambalavanan⁹, Leonard Bacharier¹⁰, Aruna Natarajan¹¹, Robert Tamburro¹², Sara Lin¹¹, Adrienne Randolph^{13

14}, Gustavo Nino¹⁵, Asuncion Mejias¹⁶, Octavio Ramilo¹⁶; NIH Workshop Participants of the ‘Viral Lower Respiratory Tract Infections in Infancy and Early Childhood‐Immunological and Developmental Aspects’

Collaborators

NIH Workshop Participants of the ‘Viral Lower Respiratory Tract Infections in Infancy and Early Childhood‐Immunological and Developmental Aspects’:
N Ambalavanan¹⁷, Leonard B Bacharier¹⁸, Gustavo Nino¹⁹, Bria M Coates²⁰, Hitesh Deshmukh²¹, Melody Duvall²², Matthew Frieman²³, James Gern²⁴, Sarah Gilpin²⁵, Thomas B Kepler²⁶, Michele Kong¹⁷, Richard Locksley²⁷, Thomas Mariani²⁸, Fernando Martinez²⁹, Sharon McGrath-Marrow³⁰, Asuncion Mejias³¹, Lisa Miller³², Joseph Mizgerd³³, Wayne Morgan²⁹, Peter Mourani³⁴, Gloria Pryhuber²⁸, Octavio Ramilo³¹, Adrienne Randolph³⁵, Fariba Rezaee³⁶, Jason Rock²⁶, Jeffrey Jeff Whitsett²¹, Sing Sing Way²¹, William Zacharias²¹, Neil Aggarwal, Marishka Brown, Matthew Craig, James Kiley, Sonnie Kim, Marrah Lachowicz-Scroggins, Sara Lin, Valerie Maholmes, Aruna Natarajan, Robert Tamburro

Affiliations

¹ Divisions of Neonatology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
² Pulmonary Biology, and Infectious Diseases, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
³ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
⁴ Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
⁵ Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
⁶ Asthma and Airway Disease Research Center, The University of Arizona, Tucson, Arizona, USA.
⁷ Pulmonary Center, Boston University School of Medicine, Boston, Massachusetts, USA.
⁸ Division of Neonatology, Department of Pediatrics, Golisano Children's Hospital, University of Rochester Medical Center, Rochester, New York, USA.
⁹ Division of Neonatology, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
¹⁰ Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
¹¹ National Heart, Lung and Blood Institute, Bethesda, Maryland, USA.
¹² Eunice Kennedy Shriver National Institutes of Child Health and Human Development, Bethesda, Maryland, USA.
¹³ Departments of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Departments of Anaesthesia and Harvard Medical School, Cambridge, Massachusetts, USA.
¹⁴ Pediatrics, Harvard Medical School, Cambridge, Massachusetts, USA.
¹⁵ Division of Pediatric Pulmonary and Sleep Medicine, Children's National Hospital, George Washington University, Washington, D.C., USA.
¹⁶ Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
¹⁷ The University of Alabama at Birmingham, USA.
¹⁸ Washington University, St. Louis, USA.
¹⁹ Children's National Hospital, Washington, D.C., USA.
²⁰ Northwestern University Feinberg School of Medicine, Chicago, USA.
²¹ Cincinnati Children's Hospital Medical Center, USA.
²² Boston Children's Hospital, USA.
²³ University of Maryland, USA.
²⁴ University of Wisconsin, USA.
²⁵ Harvard University, USA.
²⁶ Boston University, USA.
²⁷ University of California San Francisco, USA.
²⁸ University of Rochester, USA.
²⁹ The University of Arizona, USA.
³⁰ Johns Hopkins University School of Medicine, USA.
³¹ Nationwide Children's Hospital, USA.
³² University of California Davis, USA.
³³ Boston University, School of Medicine, USA.
³⁴ University of Colorado, USA.
³⁵ Harvard Medical School, USA.
³⁶ Cleveland Clinic, USA.

PMID: 39565217
DOI: 10.1002/ppul.27357

Abstract

Viral lower respiratory tract infections (LRTI) are ubiquitous in early life. They are disproportionately severe in infants and toddlers (0-2 years), leading to more than 100,000 hospitalizations in the United States per year. The recent relative resilience to severe Coronavirus disease (COVID-19) observed in young children is surprising. These observations, taken together, underscore current knowledge gaps in the pathogenesis of viral lower respiratory tract diseases in young children and respiratory developmental immunology. Further, early-life respiratory viral infections could have a lasting impact on lung development with potential life-long pulmonary sequelae. Modern molecular methods, including high-resolution spatial and single-cell technologies, in concert with longitudinal observational studies beginning in the prenatal period and continuing into early childhood, promise to elucidate developmental pulmonary and immunophenotypes following early-life viral infections and their impact on trajectories of future respiratory health. In November 2019, under the auspices of a multi-disciplinary Workshop convened by the National Heart Lung Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, experts came together to highlight the challenges of respiratory viral infections, particularly in early childhood, and emphasize the knowledge gaps in immune, virological, developmental, and clinical factors that contribute to disease severity and long-term pulmonary morbidity from viral LRTI in children. We hope that the scientific community will view these challenges in clinical care on pulmonary health trajectories and disease burden not as a window of susceptibility but as a window of opportunity.

Keywords: mother‐infant dyads; pulmonary immune ontogeny; viral LRTI.

Grants and funding

This research was supported by the US National Heart, Lung, and Blood Institute (NHLBI) and the Eunice Kennedy Shriver National Institute of Child Health, National Institutes of Health (NIH).