Browsing by Author "Lemanske, Robert F."

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    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.
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    Geography, generalisability, and susceptibility in clinical trials
    (Elsevier, 2021) Clougherty, Jane E.; Kinnee, Ellen J.; Cardet, Juan Carlos; Mauger, David; Bacharier, Leonard; Beigelman, Avraham; Blake, Kathryn V.; Cabana, Michael D.; Castro, Mario; Chmiel, James F.; Covar, Ronina; Fitzpatrick, Anne; Gaffin, Jonathan M.; Gentile, Deborah; Israel, Elliot; Jackson, Daniel J.; Kraft, Monica; Krishnan, Jerry A.; Kumar, Harsha Vardhan; Lang, Jason E.; Lazarus, Stephen C.; Lemanske, Robert F.; Lima, John; Martinez, Fernando D.; Morgan, Wayne; Moy, James; Myers, Ross; Naureckas, Edward T.; Ortega, Victor E.; Peters, Stephen P.; Phipatanakul, Wanda; Pongracic, Jacqueline A; Ross, Kristie; Sheehan, William J.; Smith, Lewis J.; Solway, Julian; Sorkness, Christine A.; Wechsler, Michael E.; Wenzel, Sally; White, Steven R.; Holguin, Fernando; Pediatrics, School of Medicine
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    Preventing asthma in high risk kids (PARK) with omalizumab: Design, rationale, methods, lessons learned and adaptation
    (Elsevier, 2021-01) Phipatanakul, Wanda; Mauger, David T.; Guilbert, Theresa W.; Bacharier, Leonard B.; Durrani, Sandy; Jackson, Daniel J.; Martinez, Fernando D.; Fitzpatrick, Anne M.; Cunningham, Amparito; Kunselman, Susan; Wheatley, Lisa M.; Bauer, Cindy; Davis, Carla M.; Geng, Bob; Kloepfer, Kirsten M.; Lapin, Craig; Liu, Andrew H.; Pongracic, Jacqueline A.; Teach, Stephen J.; Chmiel, James; Gaffin, Jonathan M.; Greenhawt, Matthew; Gupta, Meera R.; Lai, Peggy S.; Lemanske, Robert F.; Morgan, Wayne J.; Sheehan, William J.; Stokes, Jeffrey; Thorne, Peter S.; Oettgen, Hans C.; Israel, Elliot; Pediatrics, School of Medicine
    Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In addition, circulating IgE impairs innate anti-viral immune responses. The latter effect could magnify the effects of another early life exposure associated with increased risk of the development of asthma – viral infections. Omalizumab binds to circulating IgE and thus ablates antigen signaling through IgE-related mechanisms. Further, it has been shown restore IFN-α response to rhinovirus and to reduce asthma exacerbations during the viral season. We therefore hypothesized that early blockade of IgE and IgE mediated responses with omalizumab would prevent the development and reduce the severity of asthma in those at high risk for developing asthma. Herein, we describe a double-blind, placebo-controlled trial of omalizumab in 2–3 year old children at high risk for development of asthma to prevent the development and reduce the severity of asthma. We describe the rationale, methods, and lessons learned in implementing this potentially transformative trial aimed at prevention of asthma.