Browsing by Author "Kloepfer, Kirsten M."

Now showing 1 - 10 of 16
  • Thumbnail Image
    Item
    Childhood Respiratory Viral Infections and the Microbiome
    (Elsevier, 2023-10) Kloepfer, Kirsten M.; Kennedy, Joshua L.; Pediatrics, School of Medicine
    The human microbiome associated with the respiratory tract is diverse, heterogeneous, and dynamic. The diversity and complexity of the microbiome and the interactions between microorganisms, host cells, and the host immune system are complex and multifactorial. Furthermore, the lymphatics provide a direct highway, the gut-lung axis, for the gut microbiome to affect outcomes related to respiratory disease and the host immune response. Viral infections in the airways can also alter the presence or absence of bacterial species, which might increase the risks for allergies and asthma. Viruses infect the airway epithelium and interact with the host to promote inflammatory responses that can trigger a wheezing illness. This immune response may alter the host's immune response to microbes and allergens, leading to T2 inflammation. However, exposure to specific bacteria may also tailor the host's response long before the virus has infected the airway. The frequency of viral infections, age at infection, sampling season, geographic location, population differences, and preexisting composition of the microbiota have all been linked to changes in microbiota diversity and stability. This review aims to evaluate the current reported evidence for microbiome interactions and the influences that viral infection may have on respiratory and gut microbiota, affecting respiratory outcomes in children.
  • 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
    Designer covalent heterobivalent inhibitors prevent IgE-dependent responses to peanut allergen
    (National Academy of Sciences, 2019-04-30) Deak, Peter E.; Kim, Baksun; Qayum, Amina Abdul; Shin, Jaeho; Vitalpur, Girish; Kloepfer, Kirsten M.; Turner, Matthew J.; Smith, Neal; Shreffler, Wayne G.; Kiziltepe, Tanyel; Kaplan, Mark H.; Bilgicer, Basar; Pediatrics, School of Medicine
    Allergies are a result of allergen proteins cross-linking allergen-specific IgE (sIgE) on the surface of mast cells and basophils. The diversity and complexity of allergen epitopes, and high-affinity of the sIgE-allergen interaction have impaired the development of allergen-specific inhibitors of allergic responses. This study presents a design of food allergen-specific sIgE inhibitors named covalent heterobivalent inhibitors (cHBIs) that selectively form covalent bonds to only sIgEs, thereby permanently inhibiting them. Using screening reagents termed nanoallergens, we identified two immunodominant epitopes in peanuts that were common in a population of 16 allergic patients. Two cHBIs designed to inhibit only these two epitopes completely abrogated the allergic response in 14 of the 16 patients in an in vitro assay and inhibited basophil activation in an allergic patient ex vivo analysis. The efficacy of the cHBI design has valuable clinical implications for many allergen-specific responses and more broadly for any antibody-based disease.
  • 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
    Dysbiotic lung microbial communities of neonates from allergic mothers confer neonate responsiveness to suboptimal allergen
    (Frontiers Media, 2023-03-10) Bloodworth, Jeffery C.; Hoji, Aki; Wolff, Garen; Mandal, Rabindra K.; Schmidt, Nathan W.; Deshane, Jessy S.; Morrow, Casey D.; Kloepfer, Kirsten M.; Cook-Mills, Joan M.; Pediatrics, School of Medicine
    In humans and animals, offspring of allergic mothers have increased responsiveness to allergens. This is blocked in mice by maternal supplementation with α-tocopherol (αT). Also, adults and children with allergic asthma have airway microbiome dysbiosis with increased Proteobacteria and may have decreased Bacteroidota. It is not known whether αT alters neonate development of lung microbiome dysbiosis or whether neonate lung dysbiosis modifies development of allergy. To address this, the bronchoalveolar lavage was analyzed by 16S rRNA gene analysis (bacterial microbiome) from pups of allergic and non-allergic mothers with a basal diet or αT-supplemented diet. Before and after allergen challenge, pups of allergic mothers had dysbiosis in lung microbial composition with increased Proteobacteria and decreased Bacteroidota and this was blocked by αT supplementation. We determined whether intratracheal transfer of pup lung dysbiotic microbial communities modifies the development of allergy in recipient pups early in life. Interestingly, transfer of dysbiotic lung microbial communities from neonates of allergic mothers to neonates of non-allergic mothers was sufficient to confer responsiveness to allergen in the recipient pups. In contrast, neonates of allergic mothers were not protected from development of allergy by transfer of donor lung microbial communities from either neonates of non-allergic mothers or neonates of αT-supplemented allergic mothers. These data suggest that the dysbiotic lung microbiota is dominant and sufficient for enhanced neonate responsiveness to allergen. Importantly, infants within the INHANCE cohort with an anti-inflammatory profile of tocopherol isoforms had an altered microbiome composition compared to infants with a pro-inflammatory profile of tocopherol isoforms. These data may inform design of future studies for approaches in the prevention or intervention in asthma and allergic disease early in life.
  • 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
    Exposure: Staphylococcus aureus skin colonization predisposes to food allergy in the Learning Early about Allergy to Peanut (LEAP) and LEAP-On studies
    (Elsevier, 2019-08) Cook-Mills, Joan M.; Kaplan, Mark H.; Turner, Matthew J.; Kloepfer, Kirsten M.; Kumar, Rajesh; Pediatrics, School of Medicine
  • Thumbnail Image
    Item
    In children, the microbiota of the nasopharynx and bronchoalveolar lavage fluid are both similar and different
    (Wiley, 2018-04) Kloepfer, Kirsten M.; Deschamp, Ashley R.; Ross, Sydney E.; Peterson-Carmichael, Stacey L.; Hemmerich, Christopher M.; Rusch, Douglas B.; Davis, Stephanie D.; Pediatrics, School of Medicine
    RATIONALE: Sputum and bronchoalveolar lavage fluid (BALF) are often obtained to elucidate the lower airway microbiota in adults. Acquiring sputum samples from children is difficult and obtaining samples via bronchoscopy in children proves challenging due to the need for anesthesia and specialized procedural expertise; therefore nasopharyngeal (NP) swabs are often used as surrogates when investigating the pediatric airway microbiota. In adults, the airway microbiota differs significantly between NP and BALF samples however, minimal data exist in children. OBJECTIVES: To compare NP and BALF samples in children undergoing clinically indicated bronchoscopy. METHODS: NP and BALF samples were collected during clinically indicated bronchoscopy. Bacterial DNA was extracted from 72 samples (36 NP/BALF pairs); the bacterial V1-V3 region of the 16S rRNA gene was amplified and sequenced on the Illumina Miseq platform. Analysis was performed using mothur software. RESULTS: Compared to NP samples, BALF had increased richness and diversity. Similarity between paired NP and BALF (intra-subject) samples was greater than inter-subject samples (P = 0.0006). NP samples contained more Actinobacteria (2.2% vs 21%; adjusted P = 1.4 × 10-6 ), while BALF contained more Bacteroidetes (29.5% vs 3.2%; adjusted P = 1.2 × 10-9 ). At the genus level several differences existed, however Streptococcus abundance was similar in both sample types (NP 37.3% vs BAL 36.1%; adjusted P = 0.8). CONCLUSION: Our results provide evidence that NP samples can be used to distinguish differences between children, but the relative abundance of organisms may differ between the nasopharynx and lower airway in pediatric patients. Studies utilizing NP samples as surrogates for the lower airway should be interpreted with caution.
  • Thumbnail Image
    Item
    Increased Microbiota Diversity Associated with Higher FEV0.5 in Infants
    (Wiley, 2020-01) Kloepfer, Kirsten M.; Ross, Sydney E.; Hemmerich, Christopher M.; Slaven, James E.; Rusch, Douglas B.; Davis, Stephanie D.; Pediatrics, School of Medicine
  • Thumbnail Image
    Item
    Management of food allergy in the school setting
    (OceanSide, 2020-09-01) Huddleston, Christina M.; Kloepfer, Kirsten M.; Jin, Jay J.; Vitalpur, Girish V.; Pediatrics, School of Medicine
    Food allergy is a growing health and safety concern that affects up to 8% of school-age children. Because children spend a significant part of their day in school, and the overall number of school-age children with food allergy has been increasing, management of food allergies relies on the collaboration of allergists, families, and schools to treat and prevent acute allergic reactions. For schools, this involves policies centered on food allergen avoidance, preparedness with epinephrine autoinjectors, adequate school personnel training, and accommodations for an equal opportunity learning environment. Partnerships with allergists, primary care providers, students, families, school nurses, and school staff are vital for creating individualized and effective care plans that will allow all children, including those with food allergies, a safe and nurturing learning environment.