Browsing by Subject "Asthma"
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Item 4405 Chronic Disease in Indiana – Using a Community Health Matrix to Determine Health Factors for Indiana Counties(Cambridge University Press, 2020-07-29) Wiehe, Sarah; Zych, Aaron; Hinshaw, Karen; Alley, Ann; Claxton, Gina; Savaiano, Dennis; Pediatrics, School of MedicineOBJECTIVES/GOALS: The goal of this project was to inform four chronic disease initiatives, working together on the team Connections IN Health, and counties in Indiana on certain areas of need to assist them in collaborative planning. The chronic diseases focused on include diabetes, cardiovascular disease, stroke, asthma, lung cancer and obesity. METHODS/STUDY POPULATION: Chronic disease health outcomes and social determinants of health indicators were identified in all 92 Indiana counties. Counties were compared by composite z scores in a matrix to determine the 23 counties with the poorest health statistics for diabetes, cardiovascular disease, stroke, asthma, lung cancer, obesity and life expectancy. Qualitative data were used to identify local health coalitions that have the capacity and desire to work with Connections IN Health to improve these health outcomes. With input from partners, the counties were narrowed to 10 that were identified as those with the most need in the specific areas of chronic disease that the initiatives focus on. The team will begin listening sessions with two of these counties to identify strategic partnerships, funding sources, and evidence-based programs to address community-identified health priorities. RESULTS/ANTICIPATED RESULTS: The 23 counties with the poorest health outcomes related to chronic disease and factors were Blackford, Clark, Clay, Fayette, Fulton, Grant, Greene, Howard, Jay, Jennings, Knox, Lake, LaPorte, Madison, Marion, Pike, Scott, Starke, Sullivan, Vanderburgh, Vermillion, Vigo, and Washington. There was significant overlap in low z score rankings for individual health and social determinants of health measures among these 23 counties. The following 10 counties were selected for focus in the next five years based on partner input: Blackford, Clay, Grant, Jennings, Lake, Madison, Marion, Starke, Vermillion, and Washington. The Connections IN Health team has initiated listening sessions in Grant and Vermillion Counties (with data for presentation at the ACTS meeting). DISCUSSION/SIGNIFICANCE OF IMPACT: This mixed methods approach using existing data and partner input on county capacity/readiness directed Connections IN Health to counties with the most need for coalition efforts. Engagement within each county will inform next steps (e.g., capacity building, partnership development, applications for funding, implementation of evidence-based programs) and specific health focus area(s).Item A Between-Sex Comparison of the Genomic Architecture of Asthma(American Thoracic Society, 2023) Zein, Joe G.; Bazeley, Peter; Meyers, Deborah; Bleecker, Eugene; Gaston, Benjamin; Hu, Bo; Attaway, Amy; Ortega, Victor; Pediatrics, School of MedicineItem A matched analysis of the use of high flow nasal cannula for pediatric severe acute asthma(Wiley, 2024) Rogerson, Colin; AbuSultaneh, Samer; Sanchez‐Pinto, L. Nelson; Gaston, Benjamin; Wiehe, Sarah; Schleyer, Titus; Tu, Wanzhu; Mendonca, Eneida; Pediatrics, School of MedicineRationale: The high-flow nasal cannula (HFNC) device is commonly used to treat pediatric severe acute asthma. However, there is little evidence regarding its effectiveness in real-world practice. Objectives: We sought to compare the physiologic effects and clinical outcomes for children treated for severe acute asthma with HFNC versus matched controls. Methods: This was a single-center retrospective matched cohort study at a quaternary care children's hospital. Children ages 2-18 hospitalized for severe acute asthma from 2015 to 2022 were included. Encounters receiving treatment with HFNC within the first 24 h of hospitalization were included as cases. Controls were primarily treated with oxygen facemask. Logistic regression 1:1 propensity score matching was done using demographics, initial vital signs, and medications. The primary outcome was an improvement in clinical asthma symptoms in the first 24 h of hospitalization measured as percent change from initial. Measurements and main results: Of 693 eligible cases, 443 were matched to eligible controls. Propensity scores were closely aligned between the cohorts, with the only significant difference in clinical characteristics being a higher percentage of patients of Black race in the control group (54.3% vs. 46.6%; p = 0.02). Compared to the matched controls, the HFNC cohort had smaller improvements in heart rate (-11.5% [-20.9; -0.9] vs. -14.7% [-22.6;-5.7]; p < 0.01), respiratory rate (-14.3% [-27.9;5.4] vs. -16.7% [-31.5;0.0]; p = 0.03), and pediatric asthma severity score (-14.3% [-28.6;0.0] vs. -20.0% [-33.3;0.0]; p < 0.01) after 24 h of hospitalization. The HFNC cohort also had longer pediatric intensive care unit (PICU) length of stay (LOS) (1.5 days [1.1;2.1] vs. 1.2 days [0.9;1.8]; p < 0.01) and hospital LOS (2.8 days [2.1;3.8] vs. 2.5 days [1.9;3.4]; p < 0.01). When subgrouping to younger patients (2-3 years old), or those with the highest severity scores (PASS > 9), those treated with HFNC had no difference in clinical symptom improvements but maintained a longer PICU LOS. Conclusions: Encounters using HFNC for severe acute pediatric asthma had decreased clinical improvement in 24 h of hospitalization compared to matched controls and increased LOS. Specific subgroups of younger patients and those with the highest severity scores showed no differences in clinical symptom improvement suggesting differential effects in specific patient populations.Item Airway Thiol-NO Adducts as Determinants of Exhaled NO(MDPI, 2021-09-26) Pophal, Megan; Grimmett, Zachary W.; Chu, Clara; Margevicius, Seunghee; Raffay, Thomas; Ross, Kristie; Jafri, Anjum; Giddings, Olivia; Stamler, Jonathan S.; Gaston, Benjamin; Reynolds, James D.; Pediatrics, School of MedicineThiol-NO adducts such as S-nitrosoglutathione (GSNO) are endogenous bronchodilators in human airways. Decreased airway S-nitrosothiol concentrations are associated with asthma. Nitric oxide (NO), a breakdown product of GSNO, is measured in exhaled breath as a biomarker in asthma; an elevated fraction of expired NO (FENO) is associated with asthmatic airway inflammation. We hypothesized that FENO could reflect airway S-nitrosothiol concentrations. To test this hypothesis, we first studied the relationship between mixed expired NO and airway S-nitrosothiols in patients endotracheally intubated for respiratory failure. The inverse (Lineweaver-Burke type) relationship suggested that expired NO could reflect the rate of pulmonary S-nitrosothiol breakdown. We thus studied NO evolution from the lungs of mice (GSNO reductase -/-) unable reductively to catabolize GSNO. More NO was produced from GSNO in the -/- compared to wild type lungs. Finally, we formally tested the hypothesis that airway GSNO increases FENO using an inhalational challenge model in normal human subjects. FENO increased in all subjects tested, with a median t1/2 of 32.0 min. Taken together, these data demonstrate that FENO reports, at least in part, GSNO breakdown in the lungs. Unlike GSNO, NO is not present in the lungs in physiologically relevant concentrations. However, FENO following a GSNO challenge could be a non-invasive test for airway GSNO catabolism.Item Allergic airway recall responses require IL-9 from resident memory CD4+ T cells(American Association for the Advancement of Science, 2022) Ulrich, Benjamin J.; Kharwadkar, Rakshin; Chu, Michelle; Pajulas, Abigail; Muralidharan, Charanya; Koh, Byunghee; Fu, Yongyao; Gao, Hongyu; Hayes, Tristan A.; Zhou, Hong-Ming; Goplen, Nick P.; Nelson, Andrew S.; Liu, Yunlong; Linnemann, Amelia K.; Turner, Matthew J.; Licona-Limón, Paula; Flavell, Richard A.; Sun, Jie; Kaplan, Mark H.; Microbiology and Immunology, School of MedicineAsthma is a chronic inflammatory lung disease with intermittent flares predominately mediated through memory T cells. Yet, the identity of long-term memory cells that mediate allergic recall responses is not well defined. In this report, using a mouse model of chronic allergen exposure followed by an allergen-free rest period, we characterized a subpopulation of CD4+ T cells that secreted IL-9 as an obligate effector cytokine. IL-9-secreting cells had a resident memory T cell phenotype, and blocking IL-9 during a recall challenge or deleting IL-9 from T cells significantly diminished airway inflammation and airway hyperreactivity. T cells secreted IL-9 in an allergen recall-specific manner, and secretion was amplified by IL-33. Using scRNA-seq and scATAC-seq, we defined the cellular identity of a distinct population of T cells with a proallergic cytokine pattern. Thus, in a recall model of allergic airway inflammation, IL-9 secretion from a multicytokine-producing CD4+ T cell population was required for an allergen recall response.Item An IL-9-pulmonary macrophage axis defines the allergic lung inflammatory environment(American Association for the Advancement of Science, 2022) Fu, Yongyao; Wang, Jocelyn; Zhou, Baohua; Pajulas, Abigail; Gao, Hongyu; Ramdas, Baskar; Koh, Byunghee; Ulrich, Benjamin J.; Yang, Shuangshuang; Kapur, Reuben; Renauld, Jean-Christophe; Paczesny, Sophie; Liu, Yunlong; Tighe, Robert M.; Licona-Limón, Paula; Flavell, Richard A.; Takatsuka, Shogo; Kitamura, Daisuke; Tepper, Robert S.; Sun, Jie; Kaplan, Mark H.; Microbiology and Immunology, School of MedicineDespite IL-9 functioning as a pleiotropic cytokine in mucosal environments, the IL-9-responsive cell repertoire is still not well defined. Here, we found that IL-9 mediates proallergic activities in the lungs by targeting lung macrophages. IL-9 inhibits alveolar macrophage expansion and promotes recruitment of monocytes that develop into CD11c+ and CD11c- interstitial macrophage populations. Interstitial macrophages were required for IL-9-dependent allergic responses. Mechanistically, IL-9 affected the function of lung macrophages by inducing Arg1 activity. Compared with Arg1-deficient lung macrophages, Arg1-expressing macrophages expressed greater amounts of CCL5. Adoptive transfer of Arg1+ lung macrophages but not Arg1- lung macrophages promoted allergic inflammation that Il9r-/- mice were protected against. In parallel, the elevated expression of IL-9, IL-9R, Arg1, and CCL5 was correlated with disease in patients with asthma. Thus, our study uncovers an IL-9/macrophage/Arg1 axis as a potential therapeutic target for allergic airway inflammation.Item Association between asthma and hypertensive disorders of pregnancy: a secondary analysis of the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be (nuMoM2b) prospective cohort study(Elsevier, 2023) Meislin, Rachel; Bose, Sonali; Huang, Xiaoning; Wharton, Robert; Ponce, Jana; Simhan, Hyagriv; Haas, David; Saade, George; Silver, Robert; Chung, Judith; Mercer, Brian M.; Grobman, William A.; Khan, Sadiya S.; Bianco, Angela; Obstetrics and Gynecology, School of MedicineObjective:: Asthma is one of the most common comorbid conditions in pregnancy. While asthma has been identified as an independent risk factor for cardiovascular disease in the general population, the influence of active asthma during pregnancy on future cardiac risk is unclear. Growing evidence has linked maternal active asthma to adverse pregnancy outcomes (APOs), such as hypertensive disorders of pregnancy (HDP), including preeclampsia which is a well-defined risk factor for future cardiovascular disease including altered cardiac structure and diastolic dysfunction. A thorough understanding of the relationship between pre-existing asthma and APOs may be instrumental in identifying upstream factors contributing to lifetime maternal cardiovascular risk. However, current knowledge of these relationships has been largely derived from retrospective clinical studies, which limit the precision of capturing APOs. Therefore, we investigated associations between pre-existing asthma and individual subtypes of APOs in a secondary analysis of a prospective multi-center cohort of nulliparous individuals with rigorously adjudicated pregnancy outcomes. Study design:: We included participants from the multisite Nulliparous Outcomes in Pregnancy: Monitoring Mothers to be (nuMom2b) cohort, which recruited nulliparous individuals with a viable, singleton gestation between 60/7 and 136/7 weeks. Details of the study design have been previously described, which included medical histories in standardized interviews. This secondary analysis included individuals aged 18 years or older with a live birth and excluded those with a history of pre-pregnancy hypertension or diabetes. For the purposes of this analysis, we defined active asthma as a self-reported history of asthma and on current asthma treatment, including use of bronchodilator, inhaled steroid, or immune modulator, captured at the first trimester visit. The primary outcome was HDP and secondary outcomes included other APOs. Characteristics between participants who did and did not have asthma were compared. Univariate and multivariate logistic regression, described using odds ratios (ORs) and adjusted ORs (aORs) and 95% confidence intervals (95% CI), was used to determine risk of APOs. Models were adjusted for maternal age, study site, insurance type (marker of socioeconomic status), and smoking status at the first trimester visit. Race/ethnicity and body mass index (BMI) were excluded from fully adjusted models as race/ethnicity was considered as a factor reflective of the social determinants of health and BMI was conceptualized as within the casual pathway for developing HDP. The study was approved by all local institutional review boards, and participants gave written informed consent. Analyses were conducted using STATA (MP 17, College Station, TX). Results: Of 8,741 individuals included, 1,521 (17.4%) reported a diagnosis of asthma at the first trimester visit, of whom 588 (38.7%) reported the use of any asthma medication. When comparing participants with and without asthma, a higher proportion of those with asthma reported smoking tobacco in the three months prior to pregnancy (20.7% vs 16.5%) (Table 1). Univariate logistic regression revealed that a diagnosis of asthma was associated with a significantly higher risk of HDP (OR: 1.21 [1.04, 1.42]). Following adjustment, risk of HDP remained significantly higher (aOR: 1.23 [1.06, 1.42]), specifically preeclampsia (aOR: 1.21, [1.02, 1.45]). Secondary analyses in participants with active asthma (ie additional reported use of asthma medication during or before the first trimester) demonstrated a significantly higher risk of HDP (aOR 1.32 [1.06–1.65]) including preeclampsia (aOR 1.27 [1.07–1.51]; in addition to spontaneous preterm birth (aOR 1.60 [1.30–1.96]). Conclusions: In a diverse, nationally representative sample of nulliparous individuals,, a diagnosis of asthma was associated with a significantly higher risk of HDP. Active asthma increased the risk of both spontaneous preterm birth and HDP. This analysis supports the importance of identifying active asthma as a risk factor for APOs associated with a higher risk of future cardiovascular disease.Item Association Between Asthma and Reduced Androgen Receptor Expression in Airways(Endocrine Society, 2022-03-21) McManus, Jeffrey M.; Gaston, Benjamin; Zein, Joe; Sharifi, Nima; Pediatrics, School of MedicineA growing body of evidence suggests a role for androgens in asthma and asthma control. This includes a sex discordance in disease rates that changes with puberty, experiments in mice showing androgens reduce airway inflammation, and a reported association between airway androgen receptor (AR) expression and disease severity in asthma patients. We set out to determine whether airway AR expression differs between asthma patients and healthy controls. We analyzed data from 8 publicly available data sets with gene expression profiling from airway epithelial cells obtained both from asthma patients and control individuals. We found that airway AR expression was lower in asthma patients than in controls in both sexes, and that having AR expression below the median in the pooled data set was associated with substantially elevated odds of asthma vs having AR expression above the median (odds ratio 4.89; 95% CI, 3.13-7.65, P < .0001). In addition, our results suggest that whereas the association between asthma and AR expression is present in both sexes in most of the age range analyzed, the association may be absent in prepubescent children and postmenopausal women. Our results add to the existing body of evidence suggesting a role for androgens in asthma control.Item Asthma Risk Among Individuals With Androgen Receptor Deficiency(American Medical Association, 2021) Gaston, Benjamin; Marozkina, Nadzeya; Newcomb, Dawn C.; Sharifi, Nima; Zein, Joe; Pediatrics, School of MedicineThis study investigates whether androgen receptor deficiency is associated with increased asthma risk.Item Asthma, Allergy and Vitamin E: Current and Future Perspectives(Elsevier, 2022) Cook-Mills, Joan M.; Averill, Samantha H.; Lajiness, Jacquelyn D.; Pediatrics, School of MedicineAsthma and allergic disease result from interactions of environmental exposures and genetics. Vitamin E is one environmental factor that can modify development of allergy early in life and modify responses to allergen after allergen sensitization. Seemingly varied outcomes from vitamin E are consistent with the differential functions of the isoforms of vitamin E. Mechanistic studies demonstrate that the vitamin E isoforms α-tocopherol and γ-tocopherol have opposite functions in regulation of allergic inflammation and development of allergic disease, with α-tocopherol having anti-inflammatory functions and γ-tocopherol having pro-inflammatory functions in allergy and asthma. Moreover, global differences in prevalence of asthma by country may be a result, at least in part, of differences in consumption of these two isoforms of tocopherols. It is critical in clinical and animal studies that measurements of the isoforms of tocopherols be determined in vehicles for the treatments, and in the plasma and/or tissues before and after intervention. As allergic inflammation is modifiable by tocopherol isoforms, differential regulation by tocopherol isoforms provide a foundation for development of interventions to improve lung function in disease and raise the possibility of early life dietary interventions to limit the development of lung disease.