Browsing by Author "Gern, James E."

Now showing 1 - 7 of 7
  • Thumbnail Image
    Item
    Childhood Asthma Incidence, Early and Persistent Wheeze, and Neighborhood Socioeconomic Factors in the ECHO/CREW Consortium
    (American Medical Association, 2022) Zanobetti, Antonella; Ryan, Patrick H.; Coull, Brent; Brokamp, Cole; Datta, Soma; Blossom, Jeffrey; Lothrop, Nathan; Miller, Rachel L.; Beamer, Paloma I.; Visness, Cynthia M.; Andrews, Howard; Bacharier, Leonard B.; Hartert, Tina; Johnson, Christine C.; Ownby, Dennis; Khurana Hershey, Gurjit K.; Joseph, Christine; Yiqiang, Song; Mendonça, Eneida A.; Jackson, Daniel J.; Luttmann-Gibson, Heike; Zoratti, Edward M.; Wright, Anne L.; Martinez, Fernando D.; Seroogy, Christine M.; Gern, James E.; Gold, Diane R.; Children’s Respiratory and Environmental Workgroup (CREW) Consortium; Epidemiology, School of Public Health
    Importance: In the United States, Black and Hispanic children have higher rates of asthma and asthma-related morbidity compared with White children and disproportionately reside in communities with economic deprivation. Objective: To determine the extent to which neighborhood-level socioeconomic indicators explain racial and ethnic disparities in childhood wheezing and asthma. Design, setting, and participants: The study population comprised children in birth cohorts located throughout the United States that are part of the Children's Respiratory and Environmental Workgroup consortium. Cox proportional hazard models were used to estimate hazard ratios (HRs) of asthma incidence, and logistic regression was used to estimate odds ratios of early and persistent wheeze prevalence accounting for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, and region and decade of birth. Exposures: Neighborhood-level socioeconomic indicators defined by US census tracts calculated as z scores for multiple tract-level variables relative to the US average linked to participants' birth record address and decade of birth. The parent or caregiver reported the child's race and ethnicity. Main outcomes and measures: Prevalence of early and persistent childhood wheeze and asthma incidence. Results: Of 5809 children, 46% reported wheezing before age 2 years, and 26% reported persistent wheeze through age 11 years. Asthma prevalence by age 11 years varied by cohort, with an overall median prevalence of 25%. Black children (HR, 1.47; 95% CI, 1.26-1.73) and Hispanic children (HR, 1.29; 95% CI, 1.09-1.53) were at significantly increased risk for asthma incidence compared with White children, with onset occurring earlier in childhood. Children born in tracts with a greater proportion of low-income households, population density, and poverty had increased asthma incidence. Results for early and persistent wheeze were similar. In effect modification analysis, census variables did not significantly modify the association between race and ethnicity and risk for asthma incidence; Black and Hispanic children remained at higher risk for asthma compared with White children across census tracts socioeconomic levels. Conclusions and relevance: Adjusting for individual-level characteristics, we observed neighborhood socioeconomic disparities in childhood wheeze and asthma. Black and Hispanic children had more asthma in neighborhoods of all income levels. Neighborhood- and individual-level characteristics and their root causes should be considered as sources of respiratory health inequities.
  • Thumbnail Image
    Item
    Chromosome 17q12-21 Variants Are Associated with Multiple Wheezing Phenotypes in Childhood
    (American Thoracic Society, 2021) Hallmark, Brian; Wegienka, Ganesa; Havstad, Suzanne; Billheimer, Dean; Ownby, Dennis; Mendonca, Eneida A.; Gress, Lisa; Stern, Debra A.; Biagini Myers, Jocelyn; Khurana Hershey, Gurjit K.; Hoepner, Lori; Miller, Rachel L.; Lemanske, Robert F.; Jackson, Daniel J.; Gold, Diane R.; O’Connor, George T.; Nicolae, Dan L.; Gern, James E.; Ober, Carole; Wright, Anne L.; Martinez, Fernando D.; ECHO-CREW; Pediatrics, School of Medicine
    Rationale: Birth cohort studies have identified several temporal patterns of wheezing, only some of which are associated with asthma. Whether 17q12-21 genetic variants, which are closely associated with asthma, are also associated with childhood wheezing phenotypes remains poorly explored. Objectives: To determine whether wheezing phenotypes, defined by latent class analysis (LCA), are associated with nine 17q12-21 SNPs and if so, whether these relationships differ by race/ancestry. Methods: Data from seven U.S. birth cohorts (n = 3,786) from the CREW (Children’s Respiratory Research and Environment Workgroup) were harmonized to represent whether subjects wheezed in each year of life from birth until age 11 years. LCA was then performed to identify wheeze phenotypes. Genetic associations between SNPs and wheeze phenotypes were assessed separately in European American (EA) (n = 1,308) and, for the first time, in African American (AA) (n = 620) children. Measurements and Main Results: The LCA best supported four latent classes of wheeze: infrequent, transient, late-onset, and persistent. Odds of belonging to any of the three wheezing classes (vs. infrequent) increased with the risk alleles for multiple SNPs in EA children. Only one SNP, rs2305480, showed increased odds of belonging to any wheezing class in both AA and EA children. Conclusions: These results indicate that 17q12-21 is a “wheezing locus,” and this association may reflect an early life susceptibility to respiratory viruses common to all wheezing children. Which children will have their symptoms remit or reoccur during childhood may be independent of the influence of rs2305480.
  • Thumbnail Image
    Item
    Community-acquired rhinovirus infection is associated with changes in the airway microbiome
    (Elsevier, 2017) Kloepfer, Kirsten M.; Sarsani, Vishal K.; Poroyko, Valeriy; Lee, Wai Ming; Pappas, Tressa E.; Kang, Theresa; Grindle, Kristine A.; Bochkov, Yury A.; Janga, Sarath Chandra; Lemanske, Robert F., Jr.; Gern, James E.; Department of Pediatrics, IU School of Medicine
  • Thumbnail Image
    Item
    Cord blood sphingolipids are associated with atopic dermatitis and wheeze in the first year of life
    (Elsevier, 2022) Hoji, Aki; Kumar, Rajesh; Gern, James E.; Bendixsen, Casper G.; Seroogy, Christine M.; Cook-Mills, Joan M.; Pediatrics, School of Medicine
    Background: Allergen-sensitized pregnant mice have increased plasma levels of the lipids β-glucosylceramides (βGlcCers) that are transplacentally transferred to the fetus, increased subsets of proinflammatory dendritic cells in the fetal liver and pup lung, and increased allergen-induced offspring lung inflammation. Objective: Our aim was to determine whether these preclinical observations extend to a human association of βGlcCers with wheeze and allergic disease in the prospective Wisconsin Infant Study Cohort. Methods: We measured 74 lipids in cord blood plasma by using mass spectrometry detection of sphingolipids, eicosanoids, and docosinoids, as well as an ELISA for 13-hydroxyoctadecadienoic acid. Lipid profiles were determined by unbiased Uniform Manifold Approximation and Projection dimensional reduction machine learning. Lipid profiles and a proinflammatory lipid index were analyzed for association with maternal allergy and childhood outcomes of wheeze, atopic dermatitis, cord blood leukocytes, and total IgE level at age 1 year. Results: Uniform Manifold Approximation and Projection analysis of lipids defined 8 cluster-specific plasma lipid profiles. Cluster 6 had significantly lower levels of plasma βGlcCers and a higher frequency of cord blood plasmacytoid dendritic cells that mediate anti-inflammatory responses, which is consistent with an anti-inflammatory profile. For clusters and for each infant, a proinflammatory lipid index was calculated to reflect the sum of the proinflammatory lipids minus the anti-inflammatory lipids that were significantly different than in cluster 6. The cluster proinflammatory lipid index was associated with cord blood basophil frequency and with wheeze and atopic dermatitis in the first year of life. The infant inflammatory lipid index was associated with increased risk of wheeze in the first year of life. Conclusion: The cord blood proinflammatory lipid index is associated with early-life atopic dermatitis and wheezing.
  • Thumbnail Image
    Item
    Detection of Pathogenic Bacteria During Rhinovirus Infection is Associated with Increased Respiratory Symptoms and Exacerbations of Asthma
    (Elsevier, 2014-05) Kloepfer, Kirsten M.; Lee, Wai Ming; Pappas, Tressa E.; Kang, Teresa; Vrtis, Rose F.; Evans, Michael D.; Gangnon, Ronald E.; Bochkov, Yury A.; Jackson, Daniel J.; Lemanske, Robert F.; Gern, James E.; Department of Pediatrics, IU School of Medicine
    Background Detection of either viral or bacterial pathogens is associated with wheezing in children, however the influence of both bacteria and virus on illness symptoms has not been described. Objective We evaluated bacterial detection during peak RV season in children with and without asthma to determine if an association exists between bacterial infection and the severity of RV illnesses. Methods 308 children (166 with asthma, 142 without asthma) ages 4–12 years provided five consecutive weekly nasal samples during September, and scored cold and asthma symptoms daily. Viral diagnostics and quantitative PCR for Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were performed on all nasal samples. Results Detection rates were 53%, 17% and 11% for H. influenzae, S. pneumoniae and M. catarrhalis, respectively, with detection of RV increasing the risk of detecting bacteria within the same sample (OR 2.0, 95% CI 1.4–2.7, p<0.0001) or the following week (OR 1.6 (1.1–2.4), p=0.02). In the absence of RV, S. pneumoniae was associated with increased cold symptoms (mean 2.7 (95% CI 2.0–3.5) vs. 1.8 (1.5–2.2), p=0.006) and moderate asthma exacerbations (18% (12%–27%) vs. 9.2% (6.7%–12%), p=0.006). In the presence of RV, S. pneumoniae was associated with increased moderate asthma exacerbations (22% (16%–29%) vs. 15% (11%–20%), p=0.01). Furthermore, M. catarrhalis detected alongside RV increased the likelihood of experiencing cold and/or asthma symptoms compared to isolated detection of RV (OR 2.0 (1.0–4.1), p=0.04). Regardless of RV status, H. influenzae was not associated with respiratory symptoms. Conclusion RV infection enhances detection of specific bacterial pathogens in children with and without asthma. Furthermore, these findings suggest that M. catarrhalis and S. pneumoniae contribute to the severity of respiratory illnesses, including exacerbations of asthma.
  • Thumbnail Image
    Item
    Ecological and individual data both indicate that influenza inhibits rhinovirus infection
    (National Academy of Sciences, 2020-03-31) Kloepfer, Kirsten M.; Gern, James E.; Pediatrics, School of Medicine
  • Thumbnail Image
    Item
    Evolving concepts in how viruses impact asthma
    (Elsevier, 2020-05) Altman, Matthew C.; Beigelman, Avraham; Ciaccio, Christina; Gern, James E.; Heymann, Peter W.; Jackson, Daniel J.; Kennedy, Joshua L.; Kloepfer, Kirsten; Lemanske, Robert F., Jr.; McWilliams, Laurie M.; Muehling, Lyndsey; Nance, Christy; Stokes Peebles, R., Jr.; Pediatrics, School of Medicine
    Over the past decade, there have been substantial advances in our understanding about how viral infections regulate asthma. Important lessons have been learned from birth cohort studies examining viral infections and subsequent asthma and from understanding the relationships between host genetics and viral infections, the contributions of respiratory viral infections to patterns of immune development, the impact of environmental exposure on the severity of viral infections, and how the viral genome influences host immune responses to viral infections. Further, there has been major progress in our knowledge about how bacteria regulate host immune responses in asthma pathogenesis. In this article, we also examine the dynamics of bacterial colonization of the respiratory tract during viral upper respiratory tract infection, in addition to the relationship of the gut and respiratory microbiomes with respiratory viral infections. Finally, we focus on potential interventions that could decrease virus-induced wheezing and asthma. There are emerging therapeutic options to decrease the severity of wheezing exacerbations caused by respiratory viral infections. Primary prevention is a major goal, and a strategy toward this end is considered.