المؤلفون: Rosenkranz, Melissa A, Dean, Douglas C, Bendlin, Barbara B, Jarjour, Nizar N, Esnault, Stephane, Zetterberg, Henrik, Heslegrave, Amanda, Evans, Michael D, Davidson, Richard J, Busse, William W

المساهمون: Université de Lille, Inserm, CHU Lille, University of Wisconsin-Madison, Sahlgrenska University Hospital Gothenburg, 302294, University College of London London UCL, University of Minnesota

مصطلحات موضوعية: Adolescent, Adult, Aged, Asthma, Biomarkers, Diffusion Magnetic Resonance Imaging, Female, Humans, Male, Middle Aged, Neurodegenerative Diseases, Neuroimaging, Severity of Illness Index, Young Adult, tau Proteins, GFAP, NfL, dementia, diffusion-weighted imaging, inflammation, neurodegeneration

الوصف: Epidemiologic studies have shown that Alzheimer's disease (AD) and related dementias (ADRD) are seen more frequently with asthma, especially with greater asthma severity or exacerbation frequency. To examine the changes in brain structure that may underlie this phenomenon, we examined diffusion-weighted magnetic resonance imaging (dMRI) and blood-based biomarkers of AD (phosphorylated tau 181, p-Tau181), neurodegeneration (neurofilament light chain, NfL), and glial activation (glial fibrillary acidic protein, GFAP). dMRI data were obtained in 111 individuals with asthma, ranging in disease severity from mild to severe, and 135 healthy controls. Regression analyses were used to test the relationships between asthma severity and neuroimaging measures, as well as AD pathology, neurodegeneration, and glial activation, indexed by plasma p-Tau181, NfL, and GFAP, respectively. Additional relationships were tested with cognitive function. Asthma participants had widespread and large-magnitude differences in several dMRI metrics, which were indicative of neuroinflammation and neurodegeneration, and which were robustly associated with GFAP and, to a lesser extent, NfL. The AD biomarker p-Tau181 was only minimally associated with neuroimaging outcomes. Further, asthma severity was associated with deleterious changes in neuroimaging outcomes, which in turn were associated with slower processing speed, a test of cognitive performance. Asthma, particularly when severe, is associated with characteristics of neuroinflammation and neurodegeneration, and may be a potential risk factor for neural injury and cognitive dysfunction. There is a need to determine how asthma may affect brain health and whether treatment directed toward characteristics of asthma associated with these risks can mitigate these effects. ; 149;2

وصف الملف: application/octet-stream

العلاقة: The journal of allergy and clinical immunology; J Allergy Clin Immunol; http://hdl.handle.net/20.500.12210/88227Test

الإتاحة: https://doi.org/20.500.12210/88227Test
https://hdl.handle.net/20.500.12210/88227Test

المؤلفون: Bernau, Ksenija, Leet, Jonathan P, Esnault, Stéphane, Noll, Andrea L, Evans, Michael D, Jarjour, Nizar N, Sandbo, Nathan

المساهمون: University of Wisconsin School of Medicine and Public Health

المصدر: ISSN: 0091-6749 ; Journal of Allergy and Clinical Immunology ; https://hal.univ-lille.fr/hal-04507242Test ; Journal of Allergy and Clinical Immunology, 2018, Journal of Allergy and Clinical Immunology, 142, pp.1360-1363.e3. ⟨10.1016/j.jaci.2018.05.037⟩.

مصطلحات موضوعية: Adult, Bronchi, Cell Degranulation, Cell Movement, Cells, Cultured, Eosinophils, Fibroblasts, Humans, Immunoglobulin G, Interleukin-6, Interleukin-8, Neutrophils, Phenotype, [SDV]Life Sciences [q-bio]

الوصف: International audience

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/29936102; hal-04507242; https://hal.univ-lille.fr/hal-04507242Test; PUBMED: 29936102

الإتاحة: https://doi.org/10.1016/j.jaci.2018.05.037Test
https://hal.univ-lille.fr/hal-04507242Test

المؤلفون: Evans, Michael D, Esnault, Stéphane, Denlinger, Loren C, Jarjour, Nizar N

المساهمون: University of Wisconsin School of Medicine and Public Health

المصدر: ISSN: 0091-6749 ; Journal of Allergy and Clinical Immunology ; https://hal.univ-lille.fr/hal-04507248Test ; Journal of Allergy and Clinical Immunology, 2018, Journal of Allergy and Clinical Immunology, 142, pp.415-423. ⟨10.1016/j.jaci.2017.09.035⟩.

مصطلحات موضوعية: Adult, Asthma, Biomarkers, Eosinophils, Female, Gene Expression Regulation, Humans, Interleukin-1 Receptor Accessory Protein, Interleukin-4 Receptor alpha Subunit, Male, Middle Aged, Neutrophils, Pulmonary Disease, Chronic Obstructive, Receptors, Interleukin-1, Spirometry, Sputum, Th1 Cells, Th17 Cells, Th2 Cells, Young Adult, IL-1 receptor, lymphocyte, neutrophil, partial least squares, pulmonary function, sputum samples, type 1, type 17

الوصف: International audience ; Various clinical, biologic, or physiologic markers of asthma have been used to identify patient clusters and potential targets for therapy. However, these identifiers frequently overlap among the different asthma groups. For instance, both eosinophil and neutrophil counts are often increased in the airways of asthmatic patients despite their typical association with type 2 and type 17 immune response, respectively. We sought to determine whether inflammatory gene expression is related to patterns of airway inflammation and lung function and identify molecular markers for neutrophilic asthma. Expression levels of 17 genes characterizing type 1, type 2, and type 17 lymphocytes were measured in sputum samples from 48 participants with asthma. The relationships between gene expression levels and sputum cell differentials or measures of pulmonary function were examined by using partial least squares regression. Gene expression levels were strongly associated with cell differentials, explaining 71% of variation in eosinophil counts and 64% of variation in neutrophil counts. The 3 genes with the strongest relationships to sputum neutrophil counts were IL1R1 (standardized regression coefficient [β] = +0.27, P = .005), IL1RAP (β = +0.32, P = .0004), and IL4R (β = +0.29, P = .002). Higher expression levels of IL1R1, IL1RAP, and IL4R were associated with reduced FEV/forced vital capacity ratio (β = -0.11, -0.08, and -0.10; P = .005, .07, and .05). IL-1 receptor appears to be a marker of neutrophilic inflammation and airflow obstruction in patients with asthma, who have a wide range of disease severity. The IL-1 pathway might contribute to airway neutrophilia and is a potential therapeutic target in patients with neutrophilic asthma.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/29103994; hal-04507248; https://hal.univ-lille.fr/hal-04507248Test; PUBMED: 29103994

الإتاحة: https://doi.org/10.1016/j.jaci.2017.09.035Test
https://hal.univ-lille.fr/hal-04507248Test

المؤلفون: 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.

المساهمون: Department of Pediatrics, IU School of Medicine

المصدر: PMC

مصطلحات موضوعية: Rhinovirus, bacteria, asthma

الوصف: 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.

وصف الملف: application/pdf

العلاقة: The Journal of allergy and clinical immunology; Kloepfer, K. M., Lee, W. M., Pappas, T. E., Kang, T., Vrtis, R. F., Evans, M. D., … Gern, J. E. (2014). Detection of Pathogenic Bacteria During Rhinovirus Infection is Associated with Increased Respiratory Symptoms and Exacerbations of Asthma. The Journal of Allergy and Clinical Immunology, 133(5), 1301–1307.e3. http://doi.org/10.1016/j.jaci.2014.02.030Test; https://hdl.handle.net/1805/8658Test

الإتاحة: https://doi.org/10.1016/j.jaci.2014.02.030Test
https://hdl.handle.net/1805/8658Test

المؤلفون: Nyenhuis, Sharmilee M., Schwantes, Elizabeth A., Evans, Michael D., Mathur, Sameer K.

مصطلحات موضوعية: asthma, aging, elderly, neutrophil

الوصف: Post print version of article may differ from published version. The definitive version is available through Elsevier at DOI:10.1016/j.jaci.2009.12.215 ; The airway inflammation in older asthma subjects has parallels to the airway inflammation in neutrophil-predominant severe asthma. This raises the question of whether the clinical features will exhibit additional similarities. ; T. Franklin Williams Scholar Program, co-sponsored by the Atlantic Philanthropies, the American Academy of Allergy, Asthma and Immunology, the John A. Hartford Foundation, and the Association of Specialty Professors (SKM) Hartford Center of Excellence Scholar (SKM) GSK Allergy Fellowship Award (SMN)

العلاقة: Nyenhuis, S. M., Schwantes, E., & Mathur, S. 2010. Neutrophil Inflammatory Mediators in Older Asthma Subjects. Journal of Allergy and Clinical Immunology, 125(2): AB46. DOI:10.1016/j.jaci.2009.12.215; http://hdl.handle.net/10027/7345Test

الإتاحة: https://doi.org/10.1016/j.jaci.2009.12.215Test
http://hdl.handle.net/10027/7345Test