Department of Microbiology and Immunology, University of Illinois, Chicago, United States; Department of Medicine, Division of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois, Chicago, United States
Juliana Theorell
Department of Medicine, Division of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois, Chicago, United States
Mary Dawn Koenig
Department of Women, Children and Family Health Science, College of Nursing, University of Illinois, Chicago, United States
Lisa Tussing-Humphreys
Department of Medicine and Cancer Center, University of Illinois, Chicago, United States
Diane R Gold
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, United States
Augusto A Litonjua
Division of Pulmonary Medicine, Department of Pediatrics, University of Rochester, Rochester, United States
Emily Oken
Division of Chronic Disease Research Across the Life Course, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, United States
Sheryl L Rifas-Shiman
Division of Chronic Disease Research Across the Life Course, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, United States
David L Perkins
Department of Medicine, Division of Nephrology, University of Illinois, Chicago, United States; Department of Bioengineering, University of Illinois, Chicago, United States
Patricia W Finn
Department of Microbiology and Immunology, University of Illinois, Chicago, United States; Department of Medicine, Division of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois, Chicago, United States; Department of Bioengineering, University of Illinois, Chicago, United States
There are perinatal characteristics, such as gestational age, reproducibly associated with the risk for pediatric asthma. Identification of biologic processes influenced by these characteristics could facilitate risk stratification or new therapeutic targets. We hypothesized that transcriptional changes associated with multiple epidemiologic risk factors would be mediators of pediatric asthma risk. Using publicly available transcriptomic data from cord blood mononuclear cells, transcription of genes involved in myeloid differentiation was observed to be inversely associated with a pediatric asthma risk stratification based on multiple perinatal risk factors. This gene signature was validated in an independent prospective cohort and was specifically associated with genes localizing to neutrophil-specific granules. Further validation demonstrated that umbilical cord blood serum concentration of PGLYRP-1, a specific granule protein, was inversely associated with mid-childhood current asthma and early-teen FEV1/FVCx100. Thus, neutrophil-specific granule abundance at birth predicts risk for pediatric asthma and pulmonary function in adolescence.
