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Loponen J, Vähätalo I, Tuomisto LE, Niemelä O, Lehtimäki L, Hämäläinen M, Moilanen E, Kankaanranta H, Ilmarinen P. Physical exercise, systemic inflammation and adult-onset asthma: a 12-year follow-up study. J Asthma 2025; 62:714-724. [PMID: 39636329 DOI: 10.1080/02770903.2024.2438096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 09/30/2024] [Accepted: 11/30/2024] [Indexed: 12/07/2024]
Abstract
Objective: Physical exercise in treatment of asthma is scarcely studied with no clear exercise guidelines for asthmatics. We aimed to investigate the associations between physical exercise frequency, systemic inflammation and asthma control. This has not been previously studied in adult-onset asthma. Methods: This study is part of Seinäjoki Adult Asthma Study (SAAS), where 203 patients with adult-onset asthma were evaluated in 2012-2013. Exercise frequency was recorded with a structured lifestyle questionnaire. Study population was divided into two categories by exercise frequency: Low-frequency group exercised ≤2 times/week and high frequency group >2 times/week. Blood inflammatory markers were measured and IL-6 > 1.55 pg/ml and hs-CRP > 4.12 mg/l indicated systemic inflammation. Results: High-exercise frequency group had lower levels of hs-CRP (p = 0.007), IL-6 (p = 0.015), suPAR (p = 0.008) and adipsin (p = 0.031) and higher levels of adiponectin (p = 0.010) than low-exercise frequency group. In logistic multivariate regression models, higher-exercise frequency lowered odds for elevated hs-CRP (OR = 0.37, 95% CI 0.15-0.94) and IL-6 levels (OR = 0.43, 95% CI 0.20-0.91), after adjusting for possible confounding factors. There was no difference in lung function tests, asthma control test or airways questionnaire 20 scores between the exercise frequency groups. However, differences were found in single symptom questions; high-exercise frequency group had less symptoms during light housework and laughing but experienced more limitation of activity in self-reports. Conclusions: Higher-exercise frequency is associated with lower level of systemic inflammation in patients with adult-onset asthma but no clear association was found to asthma outcomes. Exercise frequency may be associated with lesser amount of some individual asthma symptoms.
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Affiliation(s)
- Juho Loponen
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Health Centre Mehiläinen Tampere Keskusta, Tampere, Finland
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Iida Vähätalo
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Leena E Tuomisto
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Onni Niemelä
- Department of Laboratory Medicine and Medical Research Unit, Seinäjoki Central Hospital and University of Tampere, Seinäjoki, Finland
| | - Lauri Lehtimäki
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Allergy Centre, Tampere University Hospital, Tampere, Finland
| | - Mari Hämäläinen
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Eeva Moilanen
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Hannu Kankaanranta
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
- Krefting Research Centre, Institute of Medicine, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg, Sweden
| | - Pinja Ilmarinen
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
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Chaiwong W, Liwsrisakun C, Inchai J, Duangjit P, Bumroongkit C, Deesomchok A, Theerakittikul T, Limsukon A, Tajarernmuang P, Niyatiwatchanchai N, Trongtrakul K, Chitchun C, Chattipakorn N, Chattipakorn SC, Apaijai N, Pothirat C. Biomarkers of Oxidative Stress, Systemic Inflammation and Thrombosis in Adult Asthmatic Patients Treated with Inhaled Corticosteroids During Exposure to Fine Particulate Matter. J Clin Med 2025; 14:2360. [PMID: 40217808 PMCID: PMC11989988 DOI: 10.3390/jcm14072360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2025] [Revised: 03/25/2025] [Accepted: 03/27/2025] [Indexed: 04/14/2025] Open
Abstract
Background/Objectives: Inhaled corticosteroids (ICS) affect oxidative stress and systemic inflammation, which might modify the risk of thrombosis in asthmatic patients exposed to particulate matter with an aerodynamic diameter smaller than 2.5 microns (PM2.5). Therefore, we aim to know the systemic biomarkers of oxidative stress, inflammation, and coagulation in ICS-treated, well-controlled adult asthmatic patients after exposure to PM2.5. Methods: This study was conducted to compare urinary biomarkers of oxidative stress, i.e., 8-hydroxydeoxyguanosine (8-OHdG), and blood biomarkers of inflammation and hypercoagulation, i.e., complete blood count (CBC), high-sensitivity C-reactive protein (hsCRP), fibrinogen, D-dimer, tumor necrosis factor-alpha (TNF-α), and interleukins (IL-6 and IL-8), between well-controlled adult asthmatic patients and healthy controls in low and high-pollution periods. Results: Forty-one ICS-controlled asthmatic patients and twenty controls were included. Urinary 8-OHdG, white blood cells and differential counts, platelets count, hsCRP, IL-6, and IL-8 in the asthma group were not significantly higher than controls during the same period. The D-dimer level of the asthma patients was significantly higher than the controls (p < 0.05). The median level of TNF-α levels during the pollution period in asthma patients was significantly higher than the non-pollution period with levels of 14.3 (9.3, 27.4) and 11.3 (7.8, 21.1) pg/mL, p = 0.041, respectively. Conclusions: During exposure to PM2.5, serum TNF-α was increased while the other markers of oxidative stress and inflammation were not high in ICS-treated asthma. ICS might mitigate PM2.5-induced systemic oxidative stress, inflammation, and hypercoagulation in asthma.
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Affiliation(s)
- Warawut Chaiwong
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
| | - Chalerm Liwsrisakun
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
| | - Juthamas Inchai
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
| | - Pilaiporn Duangjit
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
| | - Chaiwat Bumroongkit
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
| | - Athavudh Deesomchok
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
| | - Theerakorn Theerakittikul
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
| | - Atikun Limsukon
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
| | - Pattraporn Tajarernmuang
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
| | - Nutchanok Niyatiwatchanchai
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
| | - Konlawij Trongtrakul
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
| | - Chittrawadee Chitchun
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
| | - Nipon Chattipakorn
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (N.C.); (S.C.C.); (N.A.)
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Siriporn C. Chattipakorn
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (N.C.); (S.C.C.); (N.A.)
- Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai 50200, Thailand
- Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Nattayaporn Apaijai
- Neurophysiology Unit, Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (N.C.); (S.C.C.); (N.A.)
- Cardiac Electrophysiology Unit, Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
- Center of Excellence in Cardiac Electrophysiology, Chiang Mai University, Chiang Mai 50200, Thailand
| | - Chaicharn Pothirat
- Division of Pulmonary, Critical Care, and Allergy, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand; (W.C.); (J.I.); (P.D.); (C.B.); (A.D.); (T.T.); (A.L.); (P.T.); (N.N.); (K.T.); (C.C.); (C.P.)
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Biener L, Budimovska A, Skowasch D, Pizarro C, Frisch BC, Nickenig G, Stumpf MJ, Schaefer CA, Schahab N. Blood Eosinophil Count in Asthma Is Associated With Increased Abdominal Aortic Diameter and Increased Vascular Stiffness. J Asthma Allergy 2025; 18:245-255. [PMID: 39996013 PMCID: PMC11849428 DOI: 10.2147/jaa.s483504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 12/03/2024] [Indexed: 02/26/2025] Open
Abstract
Background Asthma is associated with atherosclerosis and abdominal aortic aneurysm (AAA). However, the underlying pathomechanisms remain elusive. Blood eosinophil count (BEC) is implicated in both eosinophilic asthma and arterial wall inflammation. Objective To explore the possible association of BEC in asthma and abdominal aortic artery changes. Methods 112 outpatients were prospectively enrolled in this exploratory study. Abdominal aortic diameter was measured using ultrasonography imaging, while vascular speckle tracking was utilized to evaluate vascular strains. Patients were stratified into two groups, with n=66 patients with a BEC of ≥300 n/µL and n=46 patients with <300 n/µL. Both groups exhibited no significant disparities in cardiovascular risk factors; however, the high BEC group was more frequently male. Results The aortic diameter was wider in patients with a BEC ≥300 n/µL (1.46 ± 0.25 cm vs 1.67 ± 0.63 cm, p=0.018). Three patients were diagnosed with an AAA, all had a BEC ≥300 n/µL. Patients with a BEC ≥300 n/µL exhibited lower strain values, indicative of higher vascular stiffness, including radial strain (2.65 ± 1.38% vs 4.46 ± 2.59%; p<0.001). BEC exhibited a positive correlation with abdominal aortic diameter (R²=0.131, b=0.000, p<0.001), and a negative correlation with radial strain values (R²=0.131, b=-0.002, p=0.001) in sex-adjusted linear regression. Conclusion In patients with asthma, blood eosinophil count (BEC) is correlated with a wider aortic diameter and heightened vascular stiffness in the abdominal aorta. Hence, they may be at an elevated risk of developing an AAA.
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Affiliation(s)
- Leonie Biener
- Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Bonn, Germany
| | - Andrea Budimovska
- Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Bonn, Germany
| | - Dirk Skowasch
- Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Bonn, Germany
| | - Carmen Pizarro
- Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Bonn, Germany
| | - Ben Christoph Frisch
- Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Bonn, Germany
| | - Georg Nickenig
- Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Bonn, Germany
| | - Max Jonathan Stumpf
- Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Bonn, Germany
| | - Christian A Schaefer
- Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Bonn, Germany
| | - Nadjib Schahab
- Department of Internal Medicine II - Cardiology, Pneumology and Angiology, University of Bonn, Bonn, Germany
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Kuks PJ, Kole TM, Kraft M, Siddiqui S, Fabbri LM, Rabe KF, Papi A, Brightling C, Singh D, van der Molen T, Kocks JWW, Chung KF, Adcock IM, Bhavsar PK, Kermani NZ, Heijink IH, Pouwels SD, Kerstjens HA, Slebos DJ, van den Berge M. Neutrophilic inflammation in sputum or blood does not define a clinically distinct asthma phenotype in ATLANTIS. ERJ Open Res 2025; 11:00616-2024. [PMID: 39963164 PMCID: PMC11831683 DOI: 10.1183/23120541.00616-2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 09/01/2024] [Indexed: 02/20/2025] Open
Abstract
Introduction Neutrophilic asthma has been suggested to be a clinically distinct phenotype characterised by more severe airflow obstruction and higher exacerbation risk. However, this has only been assessed in few and smaller studies, using different cut-offs to define neutrophilia, and with conflicting results. We used data from ATLANTIS, an observational longitudinal study including a large number of patients with asthma and healthy controls. The aim of the present study was to examine whether neutrophilic inflammation, either in sputum or blood, is more prevalent in asthma and whether it correlates with disease severity. Methods ATLANTIS included 773 asthma patients, with blood collected from 767 (99%) and sputum from 228 patients (30%). Data were available from 244 healthy controls, all providing blood and 126 (52%) providing sputum. Asthma patients were characterised, including parameters of large and small airways disease at baseline and after 6 and 12 months of follow-up. Sputum and blood neutrophilia were defined as values exceeding the upper quartile in asthma patients. Results The prevalence of sputum neutrophilia did not differ between asthma patients and healthy controls. Asthma patients with sputum neutrophilia did not display more severe symptoms, large or small airways disease or more frequent exacerbations. Blood neutrophilia was more common in asthma and was associated with higher body mass index, female sex, current smoking and systemic corticosteroid use. Patients with blood neutrophilia had a statistically significant, but small, increase in residual volume/total lung capacity. Blood neutrophilia was not associated with large or small airways disease or exacerbation risk. Conclusion Sputum and blood neutrophilia do not define a distinct clinical phenotype in asthma.
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Affiliation(s)
- Pauline J.M. Kuks
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Tessa M. Kole
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Monica Kraft
- Samuel Bronfman Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Salman Siddiqui
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Leonardo M. Fabbri
- Section of Respiratory Medicine, Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Klaus F. Rabe
- Dept of Medicine, Christian Albrechts University Kiel (member of the German Center for Lung Research (DZL)), Kiel, Germany
- Lungen Clinic Grosshansdorf (member of the DZL), Grosshansdorf, Germany
| | - Alberto Papi
- Research Centre on Asthma and COPD, University of Ferrara, Ferrara, Italy
| | - Chris Brightling
- Institute for Lung Health, National Institute for Health Research Biomedical Research Centre, University of Leicester, Leicester, UK
| | - Dave Singh
- Centre for Respiratory Medicine and Allergy, University Hospital of South Manchester, University of Manchester, Manchester, UK
| | - Thys van der Molen
- Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Jan Willem W.H. Kocks
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- General Practitioners Research Institute, Groningen, The Netherlands
| | - Kian Fan Chung
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Ian M. Adcock
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Pankaj K. Bhavsar
- National Heart and Lung Institute, Imperial College London, London, UK
| | | | - Irene H. Heijink
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Department of Pathology and Medical Biology, Experimental Pulmonology and Inflammation Research, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Simon D. Pouwels
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Department of Pathology and Medical Biology, Experimental Pulmonology and Inflammation Research, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Huib A.M. Kerstjens
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Dirk-Jan Slebos
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Maarten van den Berge
- Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
- Groningen Research Institute for Asthma and COPD, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Hillson K, Saglani S, Custovic A. Preschool wheeze and asthma endotypes- implications for future therapy. Expert Rev Respir Med 2024; 18:1025-1039. [PMID: 39655566 DOI: 10.1080/17476348.2024.2440468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 12/06/2024] [Indexed: 12/14/2024]
Abstract
INTRODUCTION Preschool wheeze and school-aged asthma present a large healthcare burden. Both conditions are now recognized to be heterogeneous, with similar symptom presentation but likely different underlying lung pathology. AREAS COVERED Current treatment options for preschool wheeze are constrained by extrapolations from the management of school-aged children with asthma. While most cases of asthma at school age are caused by classical atopic, eosinophilic, Type-2 driven asthma, only a quarter of preschool children with wheeze fall into this category. Targeting treatment to specific underlying mechanisms resulting in preschool wheeze may alter the progression to school age asthma. Novel biologics have revolutionized the management of severe, treatment-resistant school age asthma, but a limited evidence base limits their use in young children. There are several potential future non-steroid-based treatment options in development, of which bacterial lysates show the most promise. EXPERT OPINION Effective treatment of preschool wheeze may preserve lung function into later life, which may alter the progression trajectory toward school age asthma. Endotype-driven management will enable more effective treatment of both preschool wheeze and school age asthma.
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Affiliation(s)
- Kushalinii Hillson
- National Heart and Lung Institute, Imperial College London, London, UK
- Paediatric Respiratory Medicine Department, Royal Brompton Hospital, London, UK
| | - Sejal Saglani
- National Heart and Lung Institute, Imperial College London, London, UK
- Paediatric Respiratory Medicine Department, Royal Brompton Hospital, London, UK
- NIHR Imperial Biomedical Research Centre (BRC), London, UK
| | - Adnan Custovic
- National Heart and Lung Institute, Imperial College London, London, UK
- NIHR Imperial Biomedical Research Centre (BRC), London, UK
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He W, Rahman MH, Bajgai J, Abdul-Nasir S, Mo C, Ma H, Goh SH, Bomi K, Jung H, Kim CS, Lee H, Lee KJ. Hydrogen Gas Inhalation Alleviates Airway Inflammation and Oxidative Stress on Ovalbumin-Induced Asthmatic BALB/c Mouse Model. Antioxidants (Basel) 2024; 13:1328. [PMID: 39594470 PMCID: PMC11591407 DOI: 10.3390/antiox13111328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 10/25/2024] [Accepted: 10/29/2024] [Indexed: 11/28/2024] Open
Abstract
Airway inflammatory diseases, such as asthma, are a global public health concern owing to their chronic inflammatory effects on the respiratory mucosa. Molecular hydrogen (H2) has recently been recognized for its antioxidant and anti-inflammatory properties. In this study, we examined the therapeutic potential of H2 in airway inflammation using an ovalbumin (OVA)-induced BALB/c mouse model of allergic asthma. Female BALB/c mice were sensitized and challenged with OVA to induce airway inflammation, and 30 mice were randomly divided into five groups: NT (non-treatment), HTC (3% H2 treatment only), NC (negative control, OVA only), PC (positive control, OVA + intranasal 1 mg/mL salbutamol 50 μL), and HT (H2 treatment, OVA + inhaled 3% H2). Various inflammatory and oxidative stress (OS)-induced markers such as white blood cells (WBCs) and their differential counts, lung histology, cytokine levels such as interleukin (IL)-4, (IL)-5, (IL)-13, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), (IL)-10, reactive oxygen species (ROS), nitric oxide (NO), glutathione peroxidase (GPx), and catalase (CAT), and total immunoglobulin E (IgE) levels were investigated. Our results showed that inhaled H2 significantly reduced inflammatory cell infiltration, OS markers, and pro-inflammatory cytokine expression while upregulating antioxidant enzyme activity. Furthermore, H2 also significantly decreased serum IgE levels, a marker of allergic inflammation. Collectively, our findings suggest that H2 inhalation is a promising treatment option for airway inflammation, offering a novel approach with potential clinical applications.
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Affiliation(s)
- Wenjing He
- Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; (W.H.); (M.H.R.); (J.B.); (S.A.-N.); (C.M.); (H.M.); (S.H.G.); (K.B.); (H.J.); (C.-S.K.)
- Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea
| | - Md. Habibur Rahman
- Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; (W.H.); (M.H.R.); (J.B.); (S.A.-N.); (C.M.); (H.M.); (S.H.G.); (K.B.); (H.J.); (C.-S.K.)
| | - Johny Bajgai
- Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; (W.H.); (M.H.R.); (J.B.); (S.A.-N.); (C.M.); (H.M.); (S.H.G.); (K.B.); (H.J.); (C.-S.K.)
| | - Sofian Abdul-Nasir
- Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; (W.H.); (M.H.R.); (J.B.); (S.A.-N.); (C.M.); (H.M.); (S.H.G.); (K.B.); (H.J.); (C.-S.K.)
- Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea
| | - Chaodeng Mo
- Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; (W.H.); (M.H.R.); (J.B.); (S.A.-N.); (C.M.); (H.M.); (S.H.G.); (K.B.); (H.J.); (C.-S.K.)
- Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea
| | - Hui Ma
- Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; (W.H.); (M.H.R.); (J.B.); (S.A.-N.); (C.M.); (H.M.); (S.H.G.); (K.B.); (H.J.); (C.-S.K.)
- Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea
| | - Seong Hoon Goh
- Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; (W.H.); (M.H.R.); (J.B.); (S.A.-N.); (C.M.); (H.M.); (S.H.G.); (K.B.); (H.J.); (C.-S.K.)
| | - Kim Bomi
- Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; (W.H.); (M.H.R.); (J.B.); (S.A.-N.); (C.M.); (H.M.); (S.H.G.); (K.B.); (H.J.); (C.-S.K.)
| | - Hyeran Jung
- Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; (W.H.); (M.H.R.); (J.B.); (S.A.-N.); (C.M.); (H.M.); (S.H.G.); (K.B.); (H.J.); (C.-S.K.)
| | - Cheol-Su Kim
- Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; (W.H.); (M.H.R.); (J.B.); (S.A.-N.); (C.M.); (H.M.); (S.H.G.); (K.B.); (H.J.); (C.-S.K.)
| | - Hyungdon Lee
- Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon Sacred Heart Hospital, Chuncheon 24253, Republic of Korea
| | - Kyu-Jae Lee
- Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea; (W.H.); (M.H.R.); (J.B.); (S.A.-N.); (C.M.); (H.M.); (S.H.G.); (K.B.); (H.J.); (C.-S.K.)
- Department of Global Medical Science, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea
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7
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Huang S, He Q, Wang X, Choi S, Gong H. Associations of the planetary health diet index (PHDI) with asthma: the mediating role of body mass index. BMC Public Health 2024; 24:2305. [PMID: 39187832 PMCID: PMC11346270 DOI: 10.1186/s12889-024-19856-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 08/22/2024] [Indexed: 08/28/2024] Open
Abstract
BACKGROUND Given the global shifts in environmental conditions and dietary habits, understanding the potential impact of dietary factors and body mass index (BMI) on respiratory diseases, including asthma, is paramount. Investigating these relationships can contribute to the formulation of more effective prevention strategies. The Planetary Health Diet Index (PHDI), a dietary scoring system that balances human health with environmental sustainability, underscores the importance of increasing the consumption of plant-based foods while reducing the intake of red meat, sugar, and highly processed foods. The objective of this study was to assess the association between PHDI and the prevalence of asthma and the mediation effect of BMI in a US general population. METHODS This study utilized data from 32,388 participants in the National Health and Nutrition Examination Survey (NHANES) spanning from 2005 to 2018. Multivariate logistic regression and weighted quantile sum (WQS) regressions were employed to investigate the association between PHDI, individual nutrients, and asthma. Restricted cubic spline (RCS) analysis explored the linear or non-linear relationship between PHDI and asthma. Interaction analyses were conducted on subgroups to validate the findings. Mediation analysis was performed to examine the effect of BMI on the relationship between PHDI and asthma. RESULTS There was a significant negative association between PHDI and asthma. After adjusting for covariates, for every 10-point increase in PHDI, there was a 4% decrease in the prevalence of asthma (P = 0.025). Moreover, as PHDI increased, there was a trend towards lower asthma prevalence (P for trend < 0.05). WQS analyses showed consistent associations (OR = 0.93, 95%CI: 0.88, 0.98), with Fiber, Vitamin C, and Protein significant factors. The dose-response curve indicated a linear association between PHDI and asthma, with higher PHDI associated with lower asthma prevalence. Additionally, BMI is significantly positively associated with asthma (P < 0.001), and BMI decreases as the PHDI increases (β = -0.64, P < 0.001). Mediation analysis indicates that BMI significantly mediates the relationship between PHDI and asthma, with a mediation proportion of 33.85% (P < 0.001). CONCLUSION The results of this study show a strong negative correlation between PHDI and the prevalence of asthma. In addition, BMI mediated this negative relationship.
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Affiliation(s)
- Shaoqun Huang
- Department of Oncology Surgery, Fuzhou Hospital of Traditional Chinese Medicine Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou City, Fujian Province, China
| | - Qiao He
- Graduate School of Tianjin, University of Traditional Chinese Medicine, Tianjin City, China
| | - Xiaoxuan Wang
- Graduate School of Tianjin, University of Traditional Chinese Medicine, Tianjin City, China
| | - Seok Choi
- Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea
| | - Hongyang Gong
- Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea.
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8
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Li Q, Jiang G, Lv Y. Inhibition of phosphoinositide 3-kinase activity attenuates neutrophilic airway inflammation and inhibits pyrin domain-containing 3 inflammasome activation in an ovalbumin-lipopolysaccharide-induced asthma murine model. Mol Biol Rep 2024; 51:698. [PMID: 38811424 PMCID: PMC11136729 DOI: 10.1007/s11033-024-09360-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 02/16/2024] [Indexed: 05/31/2024]
Abstract
BACKGROUND Existing investigations suggest that the blockade of phosphoinositide 3-kinase (PI3K) activity contributes to inflammatory solution in allergic asthma, but whether this inhibition directly attenuates neutrophilic airway inflammation in vivo is still unclear. We explored the pharmacological effects of LY294002, a specific inhibitor of PI3K on the progression of neutrophilic airway inflammation and investigated the underlying mechanism. METHODS AND RESULTS Female C57BL/6 mice were intranasally sensitized with ovalbumin (OVA) together with lipopolysaccharide (LPS) on days 0 and 6, and challenged with OVA on days 14-17 to establish a neutrophilic airway disease model. In the challenge phase, a subset of mice was treated intratracheally with LY294002. We found that treatment of LY294002 attenuates clinic symptoms of inflammatory mice. Histological studies showed that LY294002 significantly inhibited inflammatory cell infiltration and mucus production. The treatment also significantly inhibited OVA-LPS induced increases in inflammatory cell counts, especially neutrophil counts, and IL-17 levels in bronchoalveolar lavage fluid (BALF). LY294002 treated mice exhibited significantly increased IL-10 levels in BALF compared to the untreated mice. In addition, LY294002 reduced the plasma concentrations of IL-6 and IL-17. The anti-inflammatory effects of LY29402 were correlated with the downregulation of NLRP3 inflammasome. CONCLUSIONS Our findings suggested that LY294002 as a potential pharmacological target for neutrophilic airway inflammation.
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Affiliation(s)
- Qun Li
- Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Bengbu Medical University, Anhui, China
| | - Guiyun Jiang
- Department of Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, Anhui, China
| | - Yunxiang Lv
- Department of Pulmonary and Critical Care MedicineAnhui Clinical and Preclinical Key Laboratory of Respiratory DiseaseMolecular Diagnosis Center, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, Anhui, China.
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9
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Tattersall MC, Jarjour NN, Busse PJ. Systemic Inflammation in Asthma: What Are the Risks and Impacts Outside the Airway? THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2024; 12:849-862. [PMID: 38355013 PMCID: PMC11219096 DOI: 10.1016/j.jaip.2024.02.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 01/19/2024] [Accepted: 02/02/2024] [Indexed: 02/16/2024]
Abstract
Airway inflammation in asthma has been well recognized for several decades, with general agreement on its role in asthma pathogenesis, symptoms, propensity toward exacerbation, and decline in lung function. This has led to universal recommendation in asthma management guidelines to incorporate the use of inhaled corticosteroid as an anti-inflammatory therapy for all patients with persistent asthma symptoms. However, there has been limited attention paid to the presence and potential impact of systemic inflammation in asthma. Accumulating evidence from epidemiological observations and cohort studies points to a host of downstream organ dysfunction in asthma especially among patients with longstanding or more severe disease, frequent exacerbations, and underlying risk factors for organ dysfunction. Most studies to date have focused on cognitive impairment, depression/anxiety, metabolic syndrome, and cardiovascular abnormalities. In this review, we summarize some of the evidence demonstrating these abnormalities and highlight the proposed mechanisms and potential benefits of treatment in limiting these extrapulmonary abnormalities in patients with asthma. The goal of this commentary is to raise awareness of the importance of recognizing potential extrapulmonary conditions associated with systemic inflammation of asthma. This area of treatment of patients with asthma is a large unmet need.
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Affiliation(s)
- Matthew C Tattersall
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
| | - Nizar N Jarjour
- Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis
| | - Paula J Busse
- Department of Medicine, Division of Clinical Immunology, Icahn School of Medicine at Mount Sinai School of Medicine, New York, NY
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10
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Listyoko AS, Okazaki R, Harada T, Inui G, Yamasaki A. Impact of obesity on airway remodeling in asthma: pathophysiological insights and clinical implications. FRONTIERS IN ALLERGY 2024; 5:1365801. [PMID: 38562155 PMCID: PMC10982419 DOI: 10.3389/falgy.2024.1365801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 03/07/2024] [Indexed: 04/04/2024] Open
Abstract
The prevalence of obesity among asthma patients has surged in recent years, posing a significant risk factor for uncontrolled asthma. Beyond its impact on asthma severity and patients' quality of life, obesity is associated with reduced lung function, increased asthma exacerbations, hospitalizations, heightened airway hyperresponsiveness, and elevated asthma-related mortality. Obesity may lead to metabolic dysfunction and immune dysregulation, fostering chronic inflammation characterized by increased pro-inflammatory mediators and adipocytokines, elevated reactive oxygen species, and reduced antioxidant activity. This chronic inflammation holds the potential to induce airway remodeling in individuals with asthma and obesity. Airway remodeling encompasses structural and pathological changes, involving alterations in the airway's epithelial and subepithelial layers, hyperplasia and hypertrophy of airway smooth muscle, and changes in airway vascularity. In individuals with asthma and obesity, airway remodeling may underlie heightened airway hyperresponsiveness and increased asthma severity, ultimately contributing to the development of persistent airflow limitation, declining lung function, and a potential increase in asthma-related mortality. Despite efforts to address the impact of obesity on asthma outcomes, the intricate mechanisms linking obesity to asthma pathophysiology, particularly concerning airway remodeling, remain incompletely understood. This comprehensive review discusses current research investigating the influence of obesity on airway remodeling, to enhance our understanding of obesity's role in the context of asthma airway remodeling.
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Affiliation(s)
- Aditya Sri Listyoko
- Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan
- Pulmonology and Respiratory Medicine Department, Faculty of Medicine, Brawijaya University-Dr. Saiful Anwar General Hospital, Malang, Indonesia
| | - Ryota Okazaki
- Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan
| | - Tomoya Harada
- Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan
| | - Genki Inui
- Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan
| | - Akira Yamasaki
- Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan
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Mindus S, Gislason T, Benediktsdottir B, Jogi R, Moverare R, Malinovschi A, Janson C. Respiratory symptoms, exacerbations and sleep disturbances are more common among participants with asthma and chronic airflow limitation: an epidemiological study in Estonia, Iceland and Sweden. BMJ Open Respir Res 2024; 11:e002063. [PMID: 38373820 PMCID: PMC10882325 DOI: 10.1136/bmjresp-2023-002063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Accepted: 02/07/2024] [Indexed: 02/21/2024] Open
Abstract
BACKGROUND Chronic airflow limitation (CAL) is a hallmark of chronic obstructive pulmonary disease but is also present in some patients with asthma. We investigated respiratory symptoms, sleep and health status of participants with and without CAL with particular emphasis on concurrent asthma using data from adult populations in Iceland, Estonia and Sweden investigated within the Burden of Obstructive Lung Disease study. METHODS All participants underwent spirometry with measurements of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) before and after bronchodilation. CAL was defined as postbronchodilator FEV1/FVC below the lower limit of normal. IgE-sensitisation and serum concentrations of eosinophil-derived neurotoxin (S-EDN) were assessed in a subsample. The participants were divided into four groups: no self-reported doctor's diagnosed asthma or CAL, asthma without CAL, CAL without asthma and asthma and CAL: χ2 test and analysis of variance were used in bivariable analyses and logistic and linear regression when analysing the independent association between respiratory symptoms, exacerbations, sleep-related symptoms and health status towards CAL, adjusting for centre, age, sex, body mass index, smoking history and educational level. RESULTS Among the 1918 participants, 190 (9.9%) had asthma without CAL, 127 (6.6%) had CAL without asthma and 50 (2.6%) had CAL with asthma. Having asthma with CAL was associated with symptoms such as wheeze (adjusted OR (aOR) 6.53 (95% CI 3.53 to 12.1), exacerbations (aOR 12.8 (95% CI 6.97 to 23.6), difficulties initiating sleep (aOR 2.82 (95% CI 1.45 to 5.48), nocturnal gastro-oesophageal reflux (aOR 3.98 (95% CI 1.79 to 8.82)) as well as lower physical health status. In these analyses, those with no asthma and no CAL were the reference group. The prevalence of IgE-sensitisation was highest in both asthma groups, which also had higher levels of S-EDN. CONCLUSION Individuals with self-reported asthma with CAL suffer from a higher burden of respiratory and sleep-related symptoms, higher exacerbation rates and lower health status when compared with participants with asthma alone or CAL alone.
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Affiliation(s)
- Stephanie Mindus
- Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| | | | | | | | - Robert Moverare
- Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
- Thermo Fisher Scientific, Uppsala, Sweden
| | - Andrei Malinovschi
- Department of Medical Sciences: Clinical Physiology, Uppsala University, Uppsala, Sweden
| | - Christer Janson
- Department of Medical Sciences: Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
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12
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Park C, Jang JH, Kim C, Lee Y, Lee E, Yang HM, Park RW, Park HS. Real-World Effectiveness of Statin Therapy in Adult Asthma. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2024; 12:399-408.e6. [PMID: 37866433 DOI: 10.1016/j.jaip.2023.10.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 10/06/2023] [Accepted: 10/11/2023] [Indexed: 10/24/2023]
Abstract
BACKGROUND Blood lipids affect airway inflammation in asthma. Although several studies have suggested anti-inflammatory effects of statins on asthmatic airways, further studies are needed to clarify the long-term effectiveness of statins on asthma control and whether they are an effective treatment option. OBJECTIVE To evaluate the long-term effectiveness of statins in the chronic management of adult asthma in real-world practice. METHODS Electronic medical record data spanning 28 years, collected from the Ajou University Medical Center in Korea, were used to conduct a retrospective study. Clinical outcomes were compared between patients with asthma who had maintained statin use (the statin group) and those not taking statins, whose blood lipid tests were always normal (the non-statin group). We performed propensity score matching and calculated hazard ratios with 95% CIs using the Cox proportional hazards model. Severe asthma exacerbation was the primary outcome; asthma exacerbation, asthma-related hospitalization, and new-onset type 2 diabetes mellitus and hypertension were secondary outcomes. RESULTS After 1:1 propensity score matching, the statin and non-statin groups each included 545 adult patients with asthma. The risk of severe asthma exacerbations and asthma exacerbations was significantly lower in the statin group than in the non-statin group (hazard ratios [95% CI] = 0.57 [0.35-0.90] and 0.71 [0.52-0.96], respectively). There were no significant differences in the risk of asthma-related hospitalization or new-onset type 2 diabetes mellitus or hypertension between groups (0.76 [0.53-1.09], 2.33 [0.94-6.59], and 1.71 [0.95-3.17], respectively). CONCLUSION Statin use is associated with a lower risk of asthma exacerbation, with better clinical outcomes in adult asthma.
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Affiliation(s)
- ChulHyoung Park
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Jae-Hyuk Jang
- Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Chungsoo Kim
- Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea
| | - Youngsoo Lee
- Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Eunyoung Lee
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea; Office of Biostatistics, Medical Research Collaboration Center, Ajou Research Institute for Innovative Medicine, Ajou University Medical Center, Suwon, Republic of Korea
| | - Hyoung-Mo Yang
- Department of Cardiology, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Rae Woong Park
- Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea; Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Republic of Korea.
| | - Hae-Sim Park
- Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Republic of Korea.
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13
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Plavsic A, Bonaci-Nikolic B, Milenkovic B, Miskovic R, Kusic N, Dimitrijevic M, Arandjelovic S, Milosevic K, Buha I, Tomic Spiric V. Asthma Inflammatory Phenotypes: How Can We Distinguish Them? J Clin Med 2024; 13:526. [PMID: 38256660 PMCID: PMC10816410 DOI: 10.3390/jcm13020526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 01/07/2024] [Accepted: 01/16/2024] [Indexed: 01/24/2024] Open
Abstract
BACKGROUND AND OBJECTIVES induced sputum is used to assess different inflammatory phenotypes in asthma, but is not used routinely. We aimed to determine the proportion of inflammatory asthma phenotypes based on induced sputum, to find biomarkers that can discriminate between phenotypes, and to evaluate biomarkers in patients with and without biological therapy in different inflammatory asthma phenotypes. MATERIALS AND METHODS this cross-sectional study investigated clinical characteristics, asthma control tests, skin prick test, impulse oscillometry (IOS), spirometry, induced sputum, biomarkers (IgE, eosinophils, fractional exhaled nitric oxide (FeNO), serum periostin, IL-5, IL-6, IL-8, IL-17A, IL-33) in 80 asthmatics. A total of 17/80 patients were treated with biologics (10 with omalizumab, 7 with benralizumab). RESULTS a total of 31% of patients had eosinophilic asthma (EA), 30% had mixed granulocytic asthma (MGA), 24% had paucigranulocytic asthma (PGA), and 15% had neutrophilic asthma (NA). The difference was found in blood eosinophils (p = 0.002), the highest observed in EA. The cut-off ≥ 240/μL eosinophils, with 64% sensitivity and 72.7% specificity, identified EA (AUC = 0.743, p = 0.001). A higher IL-8 level was associated with NA (p = 0.025). In 63 non-biologic asthma group, eosinophils were higher in EA than in NA, MGA, and PGA (p = 0.012, p = 0.028, and p = 0.049, respectively). A higher IL-17A was associated with EA without biologics (p = 0.004). A significantly higher IL-5 was found in EA treated with biologics, in comparison with EA without biologics (p = 0.043). The number of leucocytes and neutrophils was higher in MGA without biologics (p = 0.049, p = 0.019), while IL-5, IL-6, and IL-8 levels were higher in MGA treated with biologics (p = 0.012, p = 0.032, p = 0.038, respectively). CONCLUSIONS EA and MGA were the most prevalent asthma phenotypes. Blood eosinophils can identify EA, both in patients with and without biologics. Apart from the clinical profile, a broad spectrum of biomarkers for assessing inflammatory phenotypes is necessary for an adequate therapy approach to patients with asthma.
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Affiliation(s)
- Aleksandra Plavsic
- Clinic for Allergy and Immunology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia; (B.B.N.); (R.M.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.M.)
| | - Branka Bonaci-Nikolic
- Clinic for Allergy and Immunology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia; (B.B.N.); (R.M.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.M.)
| | - Branislava Milenkovic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.M.)
- Clinic for Pulmonology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Rada Miskovic
- Clinic for Allergy and Immunology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia; (B.B.N.); (R.M.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.M.)
| | - Natasa Kusic
- Clinic for Allergy and Immunology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia; (B.B.N.); (R.M.)
| | - Milan Dimitrijevic
- Clinic for Allergy and Immunology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia; (B.B.N.); (R.M.)
| | - Snezana Arandjelovic
- Clinic for Allergy and Immunology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia; (B.B.N.); (R.M.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.M.)
| | - Katarina Milosevic
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.M.)
- Department of Pulmonology and Allergology, University Children’s Hospital, 11000 Belgrade, Serbia
| | - Ivana Buha
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.M.)
- Clinic for Pulmonology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia
| | - Vesna Tomic Spiric
- Clinic for Allergy and Immunology, University Clinical Centre of Serbia, 11000 Belgrade, Serbia; (B.B.N.); (R.M.)
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (B.M.)
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van Dijk YE, Rutjes NW, Golebski K, Şahin H, Hashimoto S, Maitland-van der Zee AH, Vijverberg SJH. Developments in the Management of Severe Asthma in Children and Adolescents: Focus on Dupilumab and Tezepelumab. Paediatr Drugs 2023; 25:677-693. [PMID: 37658954 PMCID: PMC10600295 DOI: 10.1007/s40272-023-00589-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/02/2023] [Indexed: 09/05/2023]
Abstract
Severe asthma in children and adolescents exerts a substantial health, financial, and societal burden. Severe asthma is a heterogeneous condition with multiple clinical phenotypes and underlying inflammatory patterns that might be different in individual patients. Various add-on treatments have been developed to treat severe asthma, including monoclonal antibodies (biologics) targeting inflammatory mediators. Biologics that are currently approved to treat children (≥ 6 years of age) or adolescents (≥ 12 years of age) with severe asthma include: anti-immunoglobulin E (omalizumab), anti-interleukin (IL)-5 (mepolizumab), anti-IL5 receptor (benralizumab), anti-IL4/IL13 receptor (dupilumab), and antithymic stromal lymphopoietin (TSLP) (tezepelumab). However, access to these targeted treatments varies across countries and relies on few and crude indicators. There is a need for better treatment stratification to guide which children might benefit from these treatments. In this narrative review we will assess the most recent developments in the treatment of severe pediatric asthma, as well as potential biomarkers to assess treatment efficacy for this patient population.
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Affiliation(s)
- Yoni E van Dijk
- Pulmonary Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
- Pediatric Pulmonology, Emma's Childrens Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Niels W Rutjes
- Pulmonary Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
- Pediatric Pulmonology, Emma's Childrens Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Korneliusz Golebski
- Pulmonary Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
| | - Havva Şahin
- Pediatric Pulmonology, Emma's Childrens Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Simone Hashimoto
- Pulmonary Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
- Pediatric Pulmonology, Emma's Childrens Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Anke-Hilse Maitland-van der Zee
- Pulmonary Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands
- Pediatric Pulmonology, Emma's Childrens Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Susanne J H Vijverberg
- Pulmonary Medicine, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
- Pediatric Pulmonology, Emma's Childrens Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
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15
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Sommer B, González-Ávila G, Flores-Soto E, Montaño LM, Solís-Chagoyán H, Romero-Martínez BS. Phytoestrogen-Based Hormonal Replacement Therapy Could Benefit Women Suffering Late-Onset Asthma. Int J Mol Sci 2023; 24:15335. [PMID: 37895016 PMCID: PMC10607548 DOI: 10.3390/ijms242015335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 10/10/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023] Open
Abstract
It has been observed that plasmatic concentrations of estrogens, progesterone, or both correlate with symptoms in asthmatic women. Fluctuations in female sex steroid concentrations during menstrual periods are closely related to asthma symptoms, while menopause induces severe physiological changes that might require hormonal replacement therapy (HRT), that could influence asthma symptoms in these women. Late-onset asthma (LOA) has been categorized as a specific asthmatic phenotype that includes menopausal women and novel research regarding therapeutic alternatives that might provide relief to asthmatic women suffering LOA warrants more thorough and comprehensive analysis. Therefore, the present review proposes phytoestrogens as a promising HRT that might provide these females with relief for both their menopause and asthma symptoms. Besides their well-recognized anti-inflammatory and antioxidant capacities, phytoestrogens activate estrogen receptors and promote mild hormone-like responses that benefit postmenopausal women, particularly asthmatics, constituting therefore a very attractive potential therapy largely due to their low toxicity and scarce side effects.
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Affiliation(s)
- Bettina Sommer
- Departamento de Investigación en Hiperreactividad Bronquial, Instituto Nacional de Enfermedades Respiratorias ‘Ismael Cosio Villegas’, Calzada de Tlalpan 4502, Colonia Sección XVI, Mexico City CP 14080, Mexico
| | - Georgina González-Ávila
- Laboratorio de Oncología Biomédica, Departamento de Enfermedades Crónico Degenerativas, Instituto Nacional de Enfermedades Respiratorias ‘Ismael Cosio Villegas’, Mexico City CP 14080, Mexico;
| | - Edgar Flores-Soto
- Departmento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City CP 04510, Mexico; (E.F.-S.); (L.M.M.); (B.S.R.-M.)
| | - Luis M. Montaño
- Departmento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City CP 04510, Mexico; (E.F.-S.); (L.M.M.); (B.S.R.-M.)
| | - Héctor Solís-Chagoyán
- Neurociencia Cognitiva Evolutiva, Centro de Investigación en Ciencias Cognitivas, Universidad Autónoma del Estado de Morelos, Cuernavaca CP 62209, Morelos, Mexico;
| | - Bianca S. Romero-Martínez
- Departmento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City CP 04510, Mexico; (E.F.-S.); (L.M.M.); (B.S.R.-M.)
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Bleecker ER, Panettieri RA, Lugogo NL, Corren J, Daizadeh N, Jacob-Nara JA, Deniz Y, Rowe PJ, Khodzhayev A, Soler X, Ferro TJ, Hansen CN. Dupilumab Efficacy in Patients with Type 2 Asthma with and without Elevated Blood Neutrophils. J Immunol Res 2023; 2023:9943584. [PMID: 37901346 PMCID: PMC10602700 DOI: 10.1155/2023/9943584] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 07/06/2023] [Accepted: 07/22/2023] [Indexed: 10/31/2023] Open
Abstract
Introduction Elevated neutrophil counts in blood, sputum, or lung have been associated with poor clinical outcomes and more severe disease in patients with type 2 asthma. In the phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200 and 300 mg every 2 weeks compared with matched placebo significantly reduced severe asthma exacerbations and improved forced expiratory volume in 1 s (FEV1) in patients with uncontrolled, moderate-to-severe asthma. This post hoc analysis explored the efficacy of dupilumab in patients with type 2 asthma enrolled in QUEST with or without elevated blood neutrophil counts. Methods Annualized severe exacerbation rates during the 52-week treatment period and least-squares mean change from baseline in FEV1 over time were evaluated for patients with elevated type 2 biomarkers at baseline (blood eosinophils ≥ 150 cells/µL or fractional exhaled nitric oxide (FeNO) ≥ 20 ppb; and eosinophils ≥ 300 cells/µL or FeNO ≥ 50 ppb) and low (<4,000 cells/µL) or high (≥4,000 cells/µL) neutrophil counts. Results Dupilumab significantly reduced annualized severe exacerbation rates compared with placebo during the 52-week treatment period in patients with elevated type 2 biomarkers, irrespective of baseline neutrophil count (P < 0.0001 for all comparisons). Significant improvements in FEV1 versus placebo were observed as early as Week 2 and over the 52-week treatment period, irrespective of baseline neutrophil count (P < 0.001 for all comparisons). Safety findings were similar across all subgroups, regardless of neutrophil counts at baseline. Conclusions Dupilumab treatment significantly reduced annualized severe exacerbation rates and improved lung function in patients with uncontrolled, moderate-to-severe, type 2 asthma, irrespective of baseline blood neutrophil count. This trial is registered with NCT02414854.
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Affiliation(s)
- Eugene R. Bleecker
- University of Arizona, College of Medicine, Division of Genomics and Precision Medicine, Department of Medicine, 1230 North Cherry Street, Suite 251, Tucson, AZ 85721, USA
| | - Reynold A. Panettieri
- Child Health Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA
| | | | - Jonathan Corren
- David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | | | | | - Yamo Deniz
- Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA
| | | | | | - Xavier Soler
- Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA
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Scott HA, Ng SH, McLoughlin RF, Valkenborghs SR, Nair P, Brown AC, Carroll OR, Horvat JC, Wood LG. Effect of obesity on airway and systemic inflammation in adults with asthma: a systematic review and meta-analysis. Thorax 2023; 78:957-965. [PMID: 36948588 DOI: 10.1136/thorax-2022-219268] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 02/25/2023] [Indexed: 03/24/2023]
Abstract
BACKGROUND Obesity is associated with more severe asthma, however, the mechanisms responsible are poorly understood. Obesity is also associated with low-grade systemic inflammation; it is possible that this inflammation extends to the airways of adults with asthma, contributing to worse asthma outcomes. Accordingly, the aim of this review was to examine whether obesity is associated with increased airway and systemic inflammation and adipokines, in adults with asthma. METHODS Medline, Embase, CINAHL, Scopus and Current Contents were searched till 11 August 2021. Studies reporting measures of airway inflammation, systemic inflammation and/or adipokines in obese versus non-obese adults with asthma were assessed. We conducted random effects meta-analyses. We assessed heterogeneity using the I2 statistic and publication bias using funnel plots. RESULTS We included 40 studies in the meta-analysis. Sputum neutrophils were 5% higher in obese versus non-obese asthmatics (mean difference (MD)=5.0%, 95% CI: 1.2 to 8.9, n=2297, p=0.01, I2=42%). Blood neutrophil count was also higher in obesity. There was no difference in sputum %eosinophils; however, bronchial submucosal eosinophil count (standardised mean difference (SMD)=0.58, 95% CI=0.25 to 0.91, p<0.001, n=181, I2=0%) and sputum interleukin 5 (IL-5) (SMD=0.46, 95% CI=0.17 to 0.75, p<0.002, n=198, I2=0%) were higher in obesity. Conversely, fractional exhaled nitric oxide was 4.5 ppb lower in obesity (MD=-4.5 ppb, 95% CI=-7.1 ppb to -1.8 ppb, p<0.001, n=2601, I2=40%). Blood C reactive protein, IL-6 and leptin were also higher in obesity. CONCLUSIONS Obese asthmatics have a different pattern of inflammation to non-obese asthmatics. Mechanistic studies examining the pattern of inflammation in obese asthmatics are warranted. Studies should also investigate the clinical relevance of this altered inflammatory response. PROSPERO REGISTERATION NUMBER CRD42021254525.
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Affiliation(s)
- Hayley A Scott
- School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Shawn Hm Ng
- School of Medicine and Public Health, The University of Newcastle, Callaghan, New South Wales, Australia
| | - Rebecca F McLoughlin
- School of Nursing and Midwifery, The University of Newcastle, Callaghan, New South Wales, Australia
- National Health and Medical Research Council, Centre of Excellence in Treatable Traits, New Lambton Heights, New South Wales, Australia
- Asthma and Breathing Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Sarah R Valkenborghs
- School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia
- Active Living Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Parameswaran Nair
- Division of Respirology, McMaster University and St Joseph's Healthcare, Hamilton, Ontario, Canada
| | - Alexandra C Brown
- School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Olivia R Carroll
- School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Jay C Horvat
- School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
| | - Lisa G Wood
- School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, New South Wales, Australia
- Immune Health Research Program, Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia
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Moore LE, Brotto AR, Fuhr DP, Rosychuk RJ, Wong E, Bhutani M, Stickland MK. Impact of airway challenges on cardiovascular risk in asthma - a randomized controlled trial. PLoS One 2023; 18:e0288623. [PMID: 37459335 PMCID: PMC10351735 DOI: 10.1371/journal.pone.0288623] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 06/27/2023] [Indexed: 07/20/2023] Open
Abstract
BACKGROUND People experiencing asthma exacerbations are at increased risk of cardiovascular events. To better understand the relationship between asthma exacerbations and cardiovascular risk, this randomized case-control, cross-over controlled trial assessed the immediate systemic inflammatory and vascular responses to acutely induced pulmonary inflammation and bronchoconstriction in people with asthma and controls. METHODS Twenty-six people with asthma and 25 controls underwent three airway challenges (placebo, mannitol, and methacholine) in random order. Markers of cardiovascular risk, including serum C-reactive protein, interleukin-6, and tumor necrosis factor, endothelial function (flow-mediated dilation), microvascular function (blood-flow following reactive hyperemia), and arterial stiffness (pulse wave velocity) were evaluated at baseline and within one hour following each challenge. The systemic responses in a) asthma/control and b) positive airway challenges were analyzed. (ClinicalTrials.gov reg# NCT02630511). RESULTS Both the mannitol and methacholine challenges resulted in clinically significant reductions in forced expiratory volume in 1 second (FEV1) in asthma (-7.6% and -17.9%, respectively). Following positive challenges, reduction in FEV1 was -27.6% for methacholine and -14.2% for mannitol. No meaningful differences in predictors of cardiovascular risk were observed between airway challenges regardless of bronchoconstrictor response. CONCLUSION Neither acutely induced bronchoconstriction nor pulmonary inflammation and bronchoconstriction resulted in meaningful changes in systemic inflammatory or vascular function. These findings question whether the increased cardiovascular risk associated with asthma exacerbations is secondary to acute bronchoconstriction or inflammation, and suggest that other factors need to be further evaluated such as the cardiovascular impacts of short-acting inhaled beta-agonists.
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Affiliation(s)
- Linn E. Moore
- Pulmonary Division, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
- Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Andrew R. Brotto
- Pulmonary Division, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
- Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
| | - Desi P. Fuhr
- Pulmonary Division, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Rhonda J. Rosychuk
- Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Eric Wong
- Pulmonary Division, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Mohit Bhutani
- Pulmonary Division, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Michael K. Stickland
- Pulmonary Division, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
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Pan R, Kuai S, Li Q, Zhu X, Wang T, Cui Y. Diagnostic value of IL-6 for patients with asthma: a meta-analysis. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2023; 19:39. [PMID: 37173781 PMCID: PMC10182700 DOI: 10.1186/s13223-023-00794-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 04/15/2023] [Indexed: 05/15/2023]
Abstract
BACKGROUND IL-6 is a pleotropic cytokine that acts as a pro-inflammatory mediator and acute-phase response inducer, but has also been reported to possess anti-inflammatory properties. The objective of this study was to assess the validity of serum IL-6 test for diagnosis of asthma. METHODS A literature search was conducted using PubMed, Embase, and Cochrane library from January 2007 to March 2021 to identify relevant studies. Eleven studies were included in this analysis, involving 1977 patients with asthma and 1591 healthy non-asthmatic controls. The meta-analysis was performed using Review Manager 5.3 software and Stata 16.0. Random effect model or fixed effect model (FEM) was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS The meta-analysis results revealed that the serum IL-6 levels were higher in asthmatic patients than healthy non-asthmatic controls (SMD 1.31, 95% CI 0.82-1.81, P < 0.00001). IL-6 levels are significantly elevated in pediatric patients with asthma (SMD 1.58, 95% CI 0.75-2.41, P = 0.0002) and mildly elevated in adult patients with asthma (SMD 1.08, 95% CI 0.27-1.90, P = 0.009). In addition, a subgroup analysis of asthma disease status showed that IL-6 levels were increased in stable (SMD 0.69, 95% CI 0.28-1.09, P = 0.009) and exacerbation asthma (SMD 2.15, 95% CI 1.79-2.52, P < 0.00001) patients. CONCLUSION The results of this meta-analysis suggest that serum IL-6 levels were significantly elevated in asthmatic patients as compared to normal population. IL-6 levels can be used as an auxiliary indicator to distinguish individuals with asthma from healthy non-asthmatic controls.
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Affiliation(s)
- Ruilin Pan
- Clinical Research Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, Jiangsu Province, China
| | - Shougang Kuai
- Department of Clinical Laboratory, Huishan District Hospital, WuXi, 214187, Jiangsu Province, China
| | - Qingqing Li
- Clinical Research Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, Jiangsu Province, China
| | - Xuming Zhu
- Department of Clinical Laboratory, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, Jiangsu Province, China
| | - Tingting Wang
- Department of Clinical Laboratory, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, Jiangsu Province, China.
| | - Yubao Cui
- Clinical Research Center, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, 214023, Jiangsu Province, China.
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Erjefält JS. Anatomical and histopathological approaches to asthma phenotyping. Respir Med 2023; 210:107168. [PMID: 36822489 DOI: 10.1016/j.rmed.2023.107168] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 02/16/2023] [Accepted: 02/16/2023] [Indexed: 02/23/2023]
Abstract
Asthma is typically characterized by variable respiratory symptoms and airflow limitation. Along with the pathophysiology and symptoms are immunological and inflammatory processes. The last decades research has revealed that the immunology of asthma is highly heterogeneous. This has clinical consequences and identification of immunological phenotypes is currently used to guide biological treatment. The focus of this review is on another dimension of asthma diversity, namely anatomical heterogeneity. Immunopathological alterations may go beyond the central airways to also involve the distal airways, the alveolar parenchyma, and pulmonary vessels. Also, extrapulmonary tissues are affected. The anatomical distribution of inflammation in asthma has remained relatively poorly discussed despite its potential implication on both clinical presentation and response to treatment. There is today evidence that a significant proportion of the asthma patients has small airway disease with type 2 immunity, eosinophilia and smooth muscle infiltration of mast cells. The small airways in asthma are also subjected to remodelling, constriction, and luminal plugging, events that are likely to contribute to the elevated distal airway resistance seen in some patients. In cases when the inflammation extends into the alveolar parenchyma alveolar FCER1-high mast cells, eosinophilia, type 2 immunity and activated alveolar macrophages, together with modest interstitial remodelling, create a complex immunopathological picture. Importantly, the distal lung inflammation in asthma can be pharmacologically targeted by use of inhalers with more distal drug deposition. Biological treatments, which are readily distributed to the distal lung, may also be beneficial in eligible patients with more severe and anatomically widespread disease.
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Affiliation(s)
- Jonas S Erjefält
- Unit of Airway Inflammation, Department of Experimental Medical Research, Lund University, Lund, Sweden; Department of Allergology and Respiratory Medicine, Skane University Hospital, Lund, Sweden.
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Ali H, Douwes J, Burmanje J, Gokhale P, Crane J, Pattemore P, Stanley T, Keenan J, Brooks C. Sputum inflammatory, neural, and remodelling mediators in eosinophilic and non-eosinophilic asthma. Ann Allergy Asthma Immunol 2023:S1081-1206(23)00181-3. [PMID: 36958472 DOI: 10.1016/j.anai.2023.03.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2022] [Revised: 01/24/2023] [Accepted: 03/13/2023] [Indexed: 03/25/2023]
Abstract
BACKGROUND Neural and remodelling mechanisms may play a role in asthma, particularly non-eosinophilic asthma (NEA). OBJECTIVE To assess sputum mediators associated with neural, remodelling, and inflammatory mechanisms in eosinophilic asthma (EA), NEA, and non-asthmatics. METHODS 111 participants with and 62 without asthma (14-21 years) underwent sputum induction, exhaled nitric oxide (FeNO), atopy, and spirometry tests. Twenty-four mediators were measured in sputum using ELISA or bead array. EA (n=52) and NEA (n=59) were defined using a sputum eosinophil cut-point of ≥2.5%. RESULTS Elevated levels of nociceptin (median: 39.1 vs 22.4 ng/mL, p=0.03), periostin (33.8 vs 9.4 ng/mL, p=0.01), and eosinophil cationic protein (ECP); (220.1 vs 83.7 ng/mL, p=0.03) were found in asthmatics compared with non-asthmatics. Nociceptin was elevated in EA (54.8 vs 22.4 ng/mL, p=0.02) compared with non-asthmatics. EA had higher levels of inflammatory (ECP: 495.5 vs 100.3 ng/mL, p≤0.01; interleukin-1β: 285.3 vs 209.3 pg/mL, p=0.03; histamine: 5805.0 vs 3172.5 pg/mL, p=<0.01) and remodelling (vascular endothelial growth factor A (VEGF-A); 3.3 vs 2.5 ng/mL, p=0.03; periostin: 47.7 vs 22.1 ng/mL, p=0.04) mediators than NEA. Whilst macrophages were associated with neural mediators e.g. neurokinin A (r=0.27, p=0.01) and nociceptin (r=0.30, p=0.02), granulocytes were associated with inflammatory/remodelling mediators; e.g. ECP and VEGF-A correlated with neutrophils (r=0.53 & r=0.33 respectively, p=<0.01) and eosinophils (r=0.53 & r=0.29 respectively, p≤0.01). CONCLUSION Elevated levels of nociceptin and inflammatory/remodelling markers were found in EA, but no evidence for neural and remodelling pathways was found in NEA. Neural and remodelling mechanisms appear to coexist with inflammation.
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Affiliation(s)
- Hajar Ali
- Research Centre for Hauora and Health Research Massey University, Wellington, New Zealand.
| | - Jeroen Douwes
- Research Centre for Hauora and Health Research Massey University, Wellington, New Zealand
| | - Jeroen Burmanje
- Research Centre for Hauora and Health Research Massey University, Wellington, New Zealand
| | - Prachee Gokhale
- Research Centre for Hauora and Health Research Massey University, Wellington, New Zealand
| | - Julian Crane
- School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand
| | - Philip Pattemore
- Department of Paediatrics, University of Otago, Christchurch, New Zealand
| | - Thorsten Stanley
- Department of Paediatrics and Child Health, University of Otago, Wellington, New Zealand
| | - Jacqueline Keenan
- Department of Surgery, University of Otago, Christchurch, New Zealand
| | - Collin Brooks
- Research Centre for Hauora and Health Research Massey University, Wellington, New Zealand
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Peng X, Li Y, Zhao W, Yang S, Huang J, Chen Y, Wang Y, Gong Z, Chen X, Yu C, Cai S, Zhao H. Blockade of neutrophil extracellular traps ameliorates toluene diisocyanate-induced steroid-resistant asthma. Int Immunopharmacol 2023; 117:109719. [PMID: 36827917 DOI: 10.1016/j.intimp.2023.109719] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 12/27/2022] [Accepted: 01/08/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND AND PURPOSE Toluene diisocyanate (TDI)-induced asthma is characterized by mixed inflammation dominated by neutrophils, and is refractory to steroid treatment. Neutrophil extracellular traps (NETs) play an important role in severe asthma, but their role in TDI-induced asthma models is unclear. This study focused on the role and mechanism of NETs in steroid-resistant TDI-induced asthma. METHODS Induced sputum was collected from 85 asthmatic patients and 25 healthy controls to detect eDNA. A murine TDI-induced asthma model was prepared, and asthmatic mice were given dexamethasone or DNase I. In vitro, the human bronchial epithelial cell line HBE was stimulated with NETs or TDI-human serum albumin (TDI-HSA). RESULTS Asthma patients had higher sputum eDNA compared to healthy subjects. In asthma patients, eDNA was positively correlated with sputum neutrophils, and negatively correlated with FEV1%predicted. Airway inflammation, airway reactivity, Th2 cytokine levels in lymph supernatant, and levels of NETs were significantly increased in the TDI-induced asthmatic mice. These increases were suppressed by DNase I, but not by dexamethasone. Inhibition of NETs improved interleukin (IL)-8 and MKP1 mRNA expression, and reduced phosphorylation of GR-S226 induced by TDI. Inhibition of NETs improved airway epithelial barrier disruption, as well as p38 and ERK signaling pathways in TDI-induced asthmatic mice. In vitro, NETs promoted the expression of IL-8 mRNA in HBE cells, and reduced the expression of MKP1. IL-8 elevation induced by NETs was suppressed by a p38 inhibitor or ERK inhibitor, but not by dexamethasone. Pretreatment with RAGE inhibitor reduced NETs induced p38/ERK phosphorylation and IL-8 levels in HBE cells. CONCLUSION Our data suggest that targeting NETs might effectively improved TDI-induced airway inflammation and airway epithelial barrier function. This may potentially be a treatment for patients with steroid-resistance asthma.
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Affiliation(s)
- Xianru Peng
- Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
| | - Yuemao Li
- Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Wenqu Zhao
- Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Shuluan Yang
- Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Junwen Huang
- Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Ying Chen
- Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Yanhong Wang
- Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Zhaoqian Gong
- Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Xin Chen
- Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, China.
| | - Changhui Yu
- Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Shaoxi Cai
- Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
| | - Haijin Zhao
- Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
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Li J, Shujaat S, Shaheen E, Berne JV, Politis C, Jacobs R. Postoperative complications in asthmatic patients following orthognathic surgery: A two-year follow-up study. JOURNAL OF STOMATOLOGY, ORAL AND MAXILLOFACIAL SURGERY 2023; 124:101388. [PMID: 36652979 DOI: 10.1016/j.jormas.2023.101388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 01/14/2023] [Indexed: 01/16/2023]
Abstract
BACKGROUND Lack of evidence exists related to the incidence of postoperative complications in asthmatic patients following orthognathic surgery. The present study aimed to assess the incidence and risk factors of postoperative complications in asthmatic patients following orthognathic surgery. MATERIAL AND METHODS A retrospective cohort study was conducted which consisted of two groups of patients i.e., asthmatic and systemically healthy patients, who underwent conventional orthognathic surgical procedures (Le Fort I osteotomy, bilateral sagittal split osteotomy, and genioplasty). The recorded postoperative complications in both groups of patients included infection, relapse, altered facial sensation, temporomandibular joint disorder, respiratory complications, and hemorrhage-related events. The association between baseline variables and complications for identifying the possible risk factors was assessed using bivariate analysis and a logistic regression model. RESULTS A total of 886 patients underwent orthognathic surgery over a period of 6-years. Following the eligibility criteria, 16 patients were recruited in the asthmatic group and 278 patients were systemically healthy. The most common complications in the asthmatic patients were altered sensation (37.5%) followed by TMJ disorder (25.0%) and relapse (18.8%). These patients were associated with an increased risk of relapse (P = 0.048) compared to healthy patients. Following adjustment of baseline variables, increased risk of relapse was still associated with asthma (odds ratio [OR]. = 4.704, P = 0.027). CONCLUSION Asthmatic patients suffer from a significantly higher risk of relapse and need to be closely monitored following orthognathic surgery to ensure a stable outcome. Asthma does not seem to have a significant impact on other postoperative complications.
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Affiliation(s)
- Jiqing Li
- Department of Imaging & Pathology, Faculty of Medicine, KU Leuven and Department of Oral and Maxillofacial Surgery, OMFS-IMPATH Research Group, University Hospitals Leuven, Leuven, Belgium.
| | - Sohaib Shujaat
- Department of Imaging & Pathology, Faculty of Medicine, KU Leuven and Department of Oral and Maxillofacial Surgery, OMFS-IMPATH Research Group, University Hospitals Leuven, Leuven, Belgium; King Abdullah International Medical Research Center, Department of Maxillofacial Surgery and Diagnostic Sciences, College of Dentistry, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia
| | - Eman Shaheen
- Department of Imaging & Pathology, Faculty of Medicine, KU Leuven and Department of Oral and Maxillofacial Surgery, OMFS-IMPATH Research Group, University Hospitals Leuven, Leuven, Belgium
| | - Jonas Ver Berne
- Department of Imaging & Pathology, Faculty of Medicine, KU Leuven and Department of Oral and Maxillofacial Surgery, OMFS-IMPATH Research Group, University Hospitals Leuven, Leuven, Belgium
| | - Constantinus Politis
- Department of Imaging & Pathology, Faculty of Medicine, KU Leuven and Department of Oral and Maxillofacial Surgery, OMFS-IMPATH Research Group, University Hospitals Leuven, Leuven, Belgium
| | - Reinhilde Jacobs
- Department of Imaging & Pathology, Faculty of Medicine, KU Leuven and Department of Oral and Maxillofacial Surgery, OMFS-IMPATH Research Group, University Hospitals Leuven, Leuven, Belgium; Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden
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Qiu X, Xu S, Lu Y, Luo Z, Yan Y, Wang C, Ji J. Development of mRNA vaccines against respiratory syncytial virus (RSV). Cytokine Growth Factor Rev 2022; 68:37-53. [PMID: 36280532 DOI: 10.1016/j.cytogfr.2022.10.001] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 10/04/2022] [Accepted: 10/05/2022] [Indexed: 02/06/2023]
Abstract
Respiratory syncytial virus (RSV) is a single-stranded negative-sense RNA virus that is the primary etiologic pathogen of bronchitis and pneumonia in infants and the elderly. Currently, no preventative vaccine has been approved for RSV infection. However, advances in the characterization, and structural resolution, of the RSV surface fusion glycoprotein have revolutionized RSV vaccine development by providing a new target for preventive interventions. In general, six different approaches have been adopted in the development of preventative RSV therapeutics, namely, particle-based vaccines, vector-based vaccines, live-attenuated or chimeric vaccines, subunit vaccines, mRNA vaccines, and monoclonal antibodies. Among these preventive interventions, MVA-BN-RSV, RSVpreF3, RSVpreF, Ad26. RSV.preF, nirsevimab, clesrovimab and mRNA-1345 is being tested in phase 3 clinical trials, and displays the most promising in infant or elderly populations. Accompanied by the huge success of mRNA vaccines in COVID-19, mRNA vaccines have been rapidly developed, with many having entered clinical studies, in which they have demonstrated encouraging results and acceptable safety profiles. In fact, Moderna has received FDA approval, granting fast-track designation for an investigational single-dose mRNA-1345 vaccine against RSV in adults over 60 years of age. Hence, mRNA vaccines may represent a new, more successful, chapter in the continued battle to develop effective preventative measures against RSV. This review discusses the structure, life cycle, and brief history of RSV, while also presenting the current advancements in RSV preventatives, with a focus on the latest progress in RSV mRNA vaccine development. Finally, future prospects for this field are presented.
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Affiliation(s)
- Xirui Qiu
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, China
| | - Siyan Xu
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yang Lu
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zichen Luo
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yangtian Yan
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chuyue Wang
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jianjian Ji
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, China.
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Vähätalo I, Lehtimäki L, Tuomisto LE, Karjalainen J, Niemelä O, Ilmarinen P, Kankaanranta H. Long-Term Use of Short-Acting β 2-Agonists in Patients With Adult-Onset Asthma. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2022; 10:2074-2083.e7. [PMID: 35398551 DOI: 10.1016/j.jaip.2022.03.027] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Revised: 03/15/2022] [Accepted: 03/25/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Short-term studies have associated high use of short-acting β2-agonists (SABA) with increased risk of exacerbations, emergency visits, and asthma-related costs. However, no studies exist on long-term SABA use, and previous studies on the topic have not included information about adherence to inhaled corticosteroids (ICS) nor disease control, both affecting the need of SABA. OBJECTIVE To evaluate the clinical characteristics of SABA and ICS usage in newly diagnosed adult-onset asthma patients during a 12-year follow-up period. METHODS In the Seinäjoki Adult Asthma Study, 203 patients with adult-onset asthma were followed for 12 years. Information on dispensed SABA and ICS during the follow-up was obtained from the Finnish Social Insurance Institution. High SABA use was defined as ≥36 canisters in 12 years, corresponding to an average of ≥3 dispensed canisters/y. RESULTS Patients were dispensed median 6 (interquartile range: 3-16) SABA canisters and 48 (18-67) ICS canisters over 12 years, corresponding to 2 (1-4) and 11 (5-16) puffs/week, respectively. Only 10% of the patients were classified as high SABA users during this period. Obesity (body mass index ≥30) and high Airways Questionnaire 20 symptom scores at baseline predicted high long-term SABA use (incidence rate ratio: 1.53 [1.01-2.30] and 1.04 [1.00-1.08], respectively). High SABA users had higher ICS adherence, higher blood neutrophil counts, more comorbidities, and used more oral corticosteroid and antibiotic courses versus low SABA users. CONCLUSION High SABA use was infrequent in patients with confirmed adult-onset asthma. However, as high SABA use is associated with more severe asthma, these patients should be recognized in clinical practice.
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Affiliation(s)
- Iida Vähätalo
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; Tampere University Respiratory Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
| | - Lauri Lehtimäki
- Tampere University Respiratory Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Allergy Centre, Tampere University Hospital, Tampere, Finland
| | - Leena E Tuomisto
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; Tampere University Respiratory Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Jussi Karjalainen
- Tampere University Respiratory Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Allergy Centre, Tampere University Hospital, Tampere, Finland
| | - Onni Niemelä
- Tampere University Respiratory Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Department of Laboratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Pinja Ilmarinen
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; Tampere University Respiratory Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Hannu Kankaanranta
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; Tampere University Respiratory Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Krefting Research Centre, Institute of Medicine, Department of Internal Medicine and Clinical Nutrition, University of Gothenburg, Gothenburg, Sweden
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26
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Kim JY, Stevens P, Karpurapu M, Lee H, Englert JA, Yan P, Lee TJ, Pabla N, Pietrzak M, Park GY, Christman JW, Chung S. Targeting ETosis by miR-155 inhibition mitigates mixed granulocytic asthmatic lung inflammation. Front Immunol 2022; 13:943554. [PMID: 35958610 PMCID: PMC9360579 DOI: 10.3389/fimmu.2022.943554] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2022] [Accepted: 07/01/2022] [Indexed: 11/13/2022] Open
Abstract
Asthma is phenotypically heterogeneous with several distinctive pathological mechanistic pathways. Previous studies indicate that neutrophilic asthma has a poor response to standard asthma treatments comprising inhaled corticosteroids. Therefore, it is important to identify critical factors that contribute to increased numbers of neutrophils in asthma patients whose symptoms are poorly controlled by conventional therapy. Leukocytes release chromatin fibers, referred to as extracellular traps (ETs) consisting of double-stranded (ds) DNA, histones, and granule contents. Excessive components of ETs contribute to the pathophysiology of asthma; however, it is unclear how ETs drive asthma phenotypes and whether they could be a potential therapeutic target. We employed a mouse model of severe asthma that recapitulates the intricate immune responses of neutrophilic and eosinophilic airway inflammation identified in patients with severe asthma. We used both a pharmacologic approach using miR-155 inhibitor-laden exosomes and genetic approaches using miR-155 knockout mice. Our data show that ETs are present in the bronchoalveolar lavage fluid of patients with mild asthma subjected to experimental subsegmental bronchoprovocation to an allergen and a severe asthma mouse model, which resembles the complex immune responses identified in severe human asthma. Furthermore, we show that miR-155 contributes to the extracellular release of dsDNA, which exacerbates allergic lung inflammation, and the inhibition of miR-155 results in therapeutic benefit in severe asthma mice. Our findings show that targeting dsDNA release represents an attractive therapeutic target for mitigating neutrophilic asthma phenotype, which is clinically refractory to standard care.
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Affiliation(s)
- Ji Young Kim
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, OH, United States
- Division of Pharmaceutics and Pharmacology, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
| | - Patrick Stevens
- Comprehensive Cancer Center, Biomedical Informatics Shared Resources, The Ohio State University College of Medicine, Columbus, OH, United States
| | - Manjula Karpurapu
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, OH, United States
| | - Hyunwook Lee
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, OH, United States
| | - Joshua A. Englert
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, OH, United States
| | - Pearlly Yan
- Comprehensive Cancer Center, Division of Hematology, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, United States
| | - Tae Jin Lee
- Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Navjot Pabla
- Division of Pharmaceutics and Pharmacology, College of Pharmacy and Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States
| | - Maciej Pietrzak
- Comprehensive Cancer Center, Biomedical Informatics Shared Resources, The Ohio State University College of Medicine, Columbus, OH, United States
| | - Gye Young Park
- Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - John W. Christman
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, OH, United States
| | - Sangwoon Chung
- Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, OH, United States
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Lin TY, Chang PJ, Lo CY, Lo YL, Yu CT, Lin SM, Kuo CHS, Lin HC. Interaction Between CD34 + Fibrocytes and Airway Smooth Muscle Promotes IL-8 Production and Akt/PRAS40/mTOR Signaling in Asthma. Front Med (Lausanne) 2022; 9:823994. [PMID: 35547213 PMCID: PMC9081978 DOI: 10.3389/fmed.2022.823994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Accepted: 03/29/2022] [Indexed: 11/23/2022] Open
Abstract
Background The circulating progenitor cells of fibroblasts (fibrocytes) have been shown to infiltrate the airway smooth muscle compartment of asthma patients; however, the pathological significance of this discovery has yet to be elucidated. This study established a co-culture model of airway smooth muscle cells (ASMCs) and fibrocytes from asthmatic or normal subjects to evaluate innate cytokine production, corticosteroid responses, and signaling in ASMCs. Methods CD34+ fibrocytes were purified from peripheral blood of asthmatic (Global Initiative for Asthma treatment step 4–5) and normal subjects and cultured for 5∼7 days. In a transwell plate, ASMCs were co-cultured with fibrocytes at a ratio of 2:1, ASMCs were cultured alone (control condition), and fibrocytes were cultured alone for 48 h. Measurements were obtained of interleukin-8 (IL-8), IL-6, IL-17, thymic stromal lymphopoietin, and IL-33 levels in the supernatant and IL-33 levels in the cell lysate of the co-culture. Screening for intracellular signaling in the ASMCs after stimulation was performed using condition medium from the patients’ co-culture (PtCM) or IL-8. mRNA and western blot analysis were used to analyze AKT/mTOR signaling in ASMCs stimulated via treatment with PtCM or IL-8. Results Compared with ASMCs cultured alone, IL-8 levels in the supernatant and IL-33 levels in the ASMCs lysate were significantly higher in samples co-cultured from asthmatics, but not in those co-cultured from normal subjects. Corticosteroid-induced suppression of IL-8 production was less pronounced in ASMCs co-cultured with fibrocytes from asthma patients than in ASMCs co-cultured from normal subjects. ASMCs stimulated using PtCM and IL-8 presented elevating activated AKT substrate PRAS40. Treatment with IL-8 and PtCM increased mRNA expression of mTOR and P70S6 kinases in ASMCs. Treatment with IL-8 and PtCM also significantly increased phosphorylation of AKT and mTOR subtract S6 ribosomal protein in ASMCs. Conclusion The interaction between ASMCs and fibrocytes from asthmatic patients was shown to increase IL-8 and IL-33 production and promote AKT/mTOR signaling in ASMCs. IL-8 production in the co-culture from asthmatic patients was less affected by corticosteroid than was that in the co-culture from normal subjects. Our results elucidate the novel role of fibrocytes and ASMCs in the pathogenesis of asthma.
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Affiliation(s)
- Ting-Yu Lin
- Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Po-Jui Chang
- Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chun-Yu Lo
- Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yu-Lun Lo
- Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chih-Teng Yu
- Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Shu-Min Lin
- Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chih-His Scott Kuo
- Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Horng-Chyuan Lin
- Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
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28
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Neutrophils and Asthma. Diagnostics (Basel) 2022; 12:diagnostics12051175. [PMID: 35626330 PMCID: PMC9140072 DOI: 10.3390/diagnostics12051175] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 05/04/2022] [Accepted: 05/05/2022] [Indexed: 02/04/2023] Open
Abstract
Although eosinophilic inflammation is characteristic of asthma pathogenesis, neutrophilic inflammation is also marked, and eosinophils and neutrophils can coexist in some cases. Based on the proportion of sputum cell differentiation, asthma is classified into eosinophilic asthma, neutrophilic asthma, neutrophilic and eosinophilic asthma, and paucigranulocytic asthma. Classification by bronchoalveolar lavage is also performed. Eosinophilic asthma accounts for most severe asthma cases, but neutrophilic asthma or a mixture of the two types can also present a severe phenotype. Biomarkers for the diagnosis of neutrophilic asthma include sputum neutrophils, blood neutrophils, chitinase-3-like protein, and hydrogen sulfide in sputum and serum. Thymic stromal lymphoprotein (TSLP)/T-helper 17 pathways, bacterial colonization/microbiome, neutrophil extracellular traps, and activation of nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 pathways are involved in the pathophysiology of neutrophilic asthma and coexistence of obesity, gastroesophageal reflux disease, and habitual cigarette smoking have been associated with its pathogenesis. Thus, targeting neutrophilic asthma is important. Smoking cessation, neutrophil-targeting treatments, and biologics have been tested as treatments for severe asthma, but most clinical studies have not focused on neutrophilic asthma. Phosphodiesterase inhibitors, anti-TSLP antibodies, azithromycin, and anti-cholinergic agents are promising drugs for neutrophilic asthma. However, clinical research targeting neutrophilic inflammation is required to elucidate the optimal treatment.
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29
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Niemelä T, Kankaanranta H, Vähätalo I, Loponen J, Tuomisto LE, Niemelä O, Hämäläinen M, Moilanen E, Ilmarinen P. Relationship Between Soluble Urokinase Plasminogen Activator Receptor (suPAR) and Disease Outcome in Adult-Onset Asthma. J Asthma Allergy 2022; 15:579-593. [PMID: 35592386 PMCID: PMC9112192 DOI: 10.2147/jaa.s356083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Accepted: 04/17/2022] [Indexed: 11/23/2022] Open
Abstract
Background Objective Methods Results Conclusion
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Grants
- Tampere Tuberculosis Foundation and the Finnish Anti- Tuberculosis Foundation, the Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital (Tampere, Finland), the Medical Research Fund of Seinäjoki Central Hospital (Seinäjoki, Finland), the Research Foundation of the Pulmonary Diseases (Helsinki, Finland), the Ida Montini Foundation (Kerava, Finland), the Pirkanmaa Regional Fund of the Finnish Cultural Foundation (Helsinki, Finland), and the Allergy Research Foundation (Helsinki, Finland)
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Affiliation(s)
- Taito Niemelä
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Hannu Kankaanranta
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
- Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Iida Vähätalo
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Juho Loponen
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Leena E Tuomisto
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Onni Niemelä
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Laboratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Mari Hämäläinen
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Eeva Moilanen
- The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland
| | - Pinja Ilmarinen
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
- Correspondence: Pinja Ilmarinen, Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland, Tel +35 850 420 0596, Email
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30
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Stirpe E, Bardaro F. Alpha1-antitrypsin deficiency and asthma. Monaldi Arch Chest Dis 2022; 92. [PMID: 35225443 DOI: 10.4081/monaldi.2022.2179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 02/16/2022] [Indexed: 11/23/2022] Open
Abstract
α1-antitrypsin deficiency (AATD) is a genetically inherited autosomal-codominant disease with a variable clinical spectrum of lung-related diseases. Pulmonary involvement of α1-antitrypsin deficiency may also include emphysema with variable functional and radiological abnormalities, asthma, and bronchiectasis. Asthma and AATD are mutually exclusive disease entities, but the commonality of neutrophil inflammation across the diseases might suggest common underlying mechanisms of effect. The diseases share many clinical and functional features: patients with AATD commonly first present with asthma-like symptoms; functional alterations may be common to both, such as bronchial hyperresponsiveness or fixed obstruction after bronchial remodeling. It has been recognized that allergy and asthma often coexist with AATD, but the relationship between allergy, asthma and AATD is not clear. Distinguishing AATD from asthma based on presentation and clinical evaluation is not possible. The clinician must assess each of the elements in the context of the whole patient, any patient with difficult-to-manage asthma should be screened for AATD. From the clinician’s point of view, improving diagnosis in this population is fundamental to optimize clinical management. Genetic studies will probably be needed in the future to unequivocally establish the causal link between AATD and asthma.
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31
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Seys SF, Long MB. The quest for biomarkers in asthma: challenging the T2 versus non-T2 paradigm. Eur Respir J 2022; 59:59/2/2102669. [PMID: 35177484 DOI: 10.1183/13993003.02669-2021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Accepted: 10/13/2021] [Indexed: 11/05/2022]
Affiliation(s)
- Sven F Seys
- Allergy and Clinical Immunology Research Group, Dept of Microbiology, Immunology & Transplantation, KU Leuven, Leuven, Belgium
| | - Merete B Long
- Division of Molecular and Clinical Medicine, Medical School, University of Dundee, Dundee, UK
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32
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Wen X, Nian S, Wei G, Kang P, Yang Y, Li L, Ye Y, Zhang L, Wang S, Yuan Q. Changes in the phenotype and function of mucosal-associated invariant T cells in neutrophilic asthma. Int Immunopharmacol 2022; 106:108606. [PMID: 35180624 DOI: 10.1016/j.intimp.2022.108606] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 01/26/2022] [Accepted: 02/01/2022] [Indexed: 12/30/2022]
Abstract
Asthma is a chronic heterogeneous inflammatory disease. Most neutrophilic asthma (NA) cases are severe asthma involving many inflammatory cells and mediators, although the specific pathogenesis is not clear. Mucosal-associated invariant T (MAIT) cells as innate-like T lymphocytes play an important role in the immune response in asthma by producing cytokines. In this study, we evaluated the phenotype and function of circulating MAIT cells in patients with NA and inflammatory-related cytokines in plasma and induced sputum supernatants using flow cytometry. The results showed that the frequency of circulating MAIT cells in asthma patients, particularly NA patients, decreased significantly, and CD8+ MAIT and MAIT Temra cells also decreased significantly. Increased expression of CD69 and PD-1 on MAIT cells indicated excessive activation and depletion, leading to the decrease in MAIT cells. Levels of IL-17A and TNF-α secreted by MAIT cells of NA patients increased, whereas IFN-γ levels decreased, indicating that MAIT cells in NA are biased to the Th17 subtype. MAIT cells were also negatively correlated with clinical parameters, indicating that these cells are related to asthma severity. Pro-inflammatory cytokines in plasma and sputum supernatant increased to varying degrees, whereas IL-10 declined, corresponding with asthma severity. We speculate that increased IL-17A and TNF-α synergistically stimulated respiratory epithelial cells to secrete IL-6 and IL-8, thereby recruiting neutrophils to inflammatory sites and aggravating asthma symptoms. Therefore, MAIT cells could serve as a potential therapeutic target in NA immunity, thus providing a new strategy for the treatment of asthma.
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Affiliation(s)
- Xue Wen
- Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Sichuan 646000, P.R. China.
| | - Siji Nian
- Public Center of Experimental Technology, Immune Mechanism and Therapy of Major Diseases of Luzhou Key Laboratory, the School of Basic Medical Science of Southwest Medical University, Luzhou, Sichuan 646000, China.
| | - Gang Wei
- Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, China.
| | - Pengyuan Kang
- Public Center of Experimental Technology, Immune Mechanism and Therapy of Major Diseases of Luzhou Key Laboratory, the School of Basic Medical Science of Southwest Medical University, Luzhou, Sichuan 646000, China.
| | - Yaqi Yang
- Public Center of Experimental Technology, Immune Mechanism and Therapy of Major Diseases of Luzhou Key Laboratory, the School of Basic Medical Science of Southwest Medical University, Luzhou, Sichuan 646000, China.
| | - Lin Li
- Public Center of Experimental Technology, Immune Mechanism and Therapy of Major Diseases of Luzhou Key Laboratory, the School of Basic Medical Science of Southwest Medical University, Luzhou, Sichuan 646000, China.
| | - Yingchun Ye
- Public Center of Experimental Technology, Immune Mechanism and Therapy of Major Diseases of Luzhou Key Laboratory, the School of Basic Medical Science of Southwest Medical University, Luzhou, Sichuan 646000, China.
| | - Lulu Zhang
- Public Center of Experimental Technology, Immune Mechanism and Therapy of Major Diseases of Luzhou Key Laboratory, the School of Basic Medical Science of Southwest Medical University, Luzhou, Sichuan 646000, China.
| | - Songping Wang
- Department of Respiratory and Critical Care Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province 646000, China.
| | - Qing Yuan
- Public Center of Experimental Technology, Immune Mechanism and Therapy of Major Diseases of Luzhou Key Laboratory, the School of Basic Medical Science of Southwest Medical University, Luzhou, Sichuan 646000, China.
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Tan YY, Zhou HQ, Lin YJ, Yi LT, Chen ZG, Cao QD, Guo YR, Wang ZN, Chen SD, Li Y, Wang DY, Qiao YK, Yan Y. FGF2 is overexpressed in asthma and promotes airway inflammation through the FGFR/MAPK/NF-κB pathway in airway epithelial cells. Mil Med Res 2022; 9:7. [PMID: 35093168 PMCID: PMC8800304 DOI: 10.1186/s40779-022-00366-3] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 01/09/2022] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2 (FGF2) has been reported to be an inflammatory regulator; however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma. METHODS First, FGF2 expression was characterised in clinical asthma samples and the house dust mite (HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2 (rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β (IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting. RESULTS Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples (6.70 ± 1.79 vs. 16.32 ± 2.40, P = 0.0184; 11.20 ± 2.11 vs. 21.00 ± 3.00, P = 0.033, respectively) and HDM-induced asthmatic mouse lung lysates (1.00 ± 0.15 vs. 5.14 ± 0.42, P < 0.001). Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model (R2 = 0.857 and 0.783, P = 0.0008 and 0.0043, respectively). Elevated FGF2 protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration (2.45 ± 0.09 vs. 2.88 ± 0.14, P = 0.0288) and recruited more subepithelial neutrophils after HDM challenge [(110.20 ± 29.43) cells/mm2 vs. (238.10 ± 42.77) cells/mm2, P = 0.0392] without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels (up to 1.41 ± 0.12- or 1.44 ± 0.14-fold change vs. IL-1β alone groups, P = 0.001 or 0.0344, respectively). The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor (FGFR)/mitogen-activated protein kinase (MAPK)/nuclear factor kappa B (NF-κB) pathway. CONCLUSION Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.
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Affiliation(s)
- Yuan-Yang Tan
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China
| | - Hui-Qin Zhou
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China
| | - Yu-Jing Lin
- Department of Pathology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China
| | - Liu-Tong Yi
- Department of Pathology, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China
| | - Zhuang-Gui Chen
- Department of Pediatrics, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, China
| | - Qing-Dong Cao
- Department of Cardiothoracic Surgery, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China
| | - Yan-Rong Guo
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China
| | - Zhao-Ni Wang
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China
| | - Shou-Deng Chen
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China
| | - Yang Li
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China
| | - De-Yun Wang
- Department of Otolaryngology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, 119228, Singapore
| | | | - Yan Yan
- Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China. .,Central Laboratory, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China.
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Schetters STT, Schuijs MJ. Pulmonary Eosinophils at the Center of the Allergic Space-Time Continuum. Front Immunol 2021; 12:772004. [PMID: 34868033 PMCID: PMC8634472 DOI: 10.3389/fimmu.2021.772004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 10/27/2021] [Indexed: 01/01/2023] Open
Abstract
Eosinophils are typically a minority population of circulating granulocytes being released from the bone-marrow as terminally differentiated cells. Besides their function in the defense against parasites and in promoting allergic airway inflammation, regulatory functions have now been attributed to eosinophils in various organs. Although eosinophils are involved in the inflammatory response to allergens, it remains unclear whether they are drivers of the asthma pathology or merely recruited effector cells. Recent findings highlight the homeostatic and pro-resolving capacity of eosinophils and raise the question at what point in time their function is regulated. Similarly, eosinophils from different physical locations display phenotypic and functional diversity. However, it remains unclear whether eosinophil plasticity remains as they develop and travel from the bone marrow to the tissue, in homeostasis or during inflammation. In the tissue, eosinophils of different ages and origin along the inflammatory trajectory may exhibit functional diversity as circumstances change. Herein, we outline the inflammatory time line of allergic airway inflammation from acute, late, adaptive to chronic processes. We summarize the function of the eosinophils in regards to their resident localization and time of recruitment to the lung, in all stages of the inflammatory response. In all, we argue that immunological differences in eosinophils are a function of time and space as the allergic inflammatory response is initiated and resolved.
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Affiliation(s)
- Sjoerd T T Schetters
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.,Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium
| | - Martijn J Schuijs
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.,Laboratory of Immunoregulation and Mucosal Immunology, VIB-UGent Center for Inflammation Research, Ghent, Belgium.,Cancer Research Institute Ghent, Ghent, Belgium
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35
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Kaneko M, Iizuka T, Nakajima T. Inhibition Effect of Eucommia ulmoides Leaf Extract on Interleukin 8 Production by A549 Cells. Biol Pharm Bull 2021; 44:1891-1893. [PMID: 34853273 DOI: 10.1248/bpb.b21-00561] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Asthma is characterized by chronic inflammation of the airway mucosa. As Eucommia ulmoides Oliv. leaf extract (ELE) has been known to have anti-inflammatory properties, herein, we investigated the effect of ELE on interleukin (IL-) 8 production in A549 cells, a human airway epithelial cell line. The addition of ELE 1 h before tumor necrosis factor-alpha (TNFα) stimulation inhibited IL-8 production by A549 cells in a concentration-dependent manner. The addition of geniposidic acid, the main component of ELE, also inhibited IL-8 production. To further investigate the mechanism by which ELE inhibits IL-8 production, the effect of ELE or geniposidic acid on TNFα-stimulated p38 phosphorylation was examined by Western blotting. After 30 min of TNFα stimulation, p38 phosphorylation was inhibited by the addition of ELE or geniposidic acid, suggesting that ELE inhibited IL-8 production in TNFα-stimulated A549 cells by suppressing one of the signal transducers of p38 phosphorylation. These results indicate that ELE can be used as an effective measure against asthma, particularly neutrophilic asthma.
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Affiliation(s)
| | - Toru Iizuka
- Laboratory of Pharmacognosy, Yokohama University of Pharmacy
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36
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The Emerging Roles of T Helper Cell Subsets and Cytokines in Severe Neutrophilic Asthma. Inflammation 2021; 45:1007-1022. [PMID: 34825300 DOI: 10.1007/s10753-021-01598-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2020] [Revised: 06/01/2021] [Accepted: 11/07/2021] [Indexed: 12/11/2022]
Abstract
Neutrophilic asthma (NA) is a severe type of steroid resistant asthma, and so far the immune mechanisms underlying NA are not clear. In this article, we performed a comprehensive assessment of Th-cell subsets and cytokines in severe NA patients. A total of 13 healthy individuals and 31 severe asthma patients were enrolled in this study. Refractory asthma patients were defined as those with eosinophilic asthma (EA, accounted for 32% of asthmatic patients) or NA (68%) according to sputum neutrophil/eosinophil counts or blood eosinophils. Th-cell subsets in peripheral blood mononuclear cells (PBMCs) were analyzed by flow cytometry, and cytokines were detected by cytometric bead array (CBA). The results showed significant differences were observed in Th-cell phenotypes, where the number of Th1 cells were reduced and the numbers of Th2 cells were increased in NA and EA groups, respectively, when compared with healthy controls. Th17 cells were not strongly associated with severe neutrophilic asthma. The frequencies of mucosal-associated invariant T (MAIT) cells were strikingly reduced in severe asthma patients, especially in the NA group. This NA group also showed increased levels of IL-17A, IL-17F, TNF-α, and IL-6 in serum and increased levels of IL-17A, IL-17F, IFN-γ, TNF-α, IL-1β, IL-5, IL-6, and IL-8 in sputum. In addition, sputum IL-6 was positively correlated with TNF-α, IFN-γ, IL-17A, and IL-8. Our results uncovered a controversial role for Th17 cells, which were reduced in severe asthma patients. Severe neutrophilic asthma was associated with a striking deficiency of MAIT cells and high pro-inflammatory cytokine levels.
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Mikus MS, Kolmert J, Andersson LI, Östling J, Knowles RG, Gómez C, Ericsson M, Thörngren JO, Khoonsari PE, Dahlén B, Kupczyk M, De Meulder B, Auffray C, Bakke PS, Beghe B, Bel EH, Caruso M, Chanez P, Chawes B, Fowler SJ, Gaga M, Geiser T, Gjomarkaj M, Horváth I, Howarth PH, Johnston SL, Joos G, Krug N, Montuschi P, Musial J, Niżankowska-Mogilnicka E, Olsson HK, Papi A, Rabe KF, Sandström T, Shaw DE, Siafakas NM, Uhlen M, Riley JH, Bates S, Middelveld RJM, Wheelock CE, Chung KF, Adcock IM, Sterk PJ, Djukanovic R, Nilsson P, Dahlén SE, James A. Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation. Eur Respir J 2021; 59:13993003.00142-2021. [PMID: 34737220 PMCID: PMC8850689 DOI: 10.1183/13993003.00142-2021] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 06/24/2021] [Indexed: 12/02/2022]
Abstract
Rationale Asthma phenotyping requires novel biomarker discovery. Objectives To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs). Methods An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA. Application of new proteomic panel in two established European asthma cohorts identifies plasma proteins associated with disease severity independently of Type-2 inflammation, suggesting potentially useful novel biomarkers and therapeutic targets.https://bit.ly/3jtTq5m
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Affiliation(s)
- Maria Sparreman Mikus
- Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, Stockholm, Sweden .,Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Johan Kolmert
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.,Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden
| | - Lars I Andersson
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.,Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden
| | | | | | - Cristina Gómez
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.,Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden
| | - Magnus Ericsson
- Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - John-Olof Thörngren
- Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Payam Emami Khoonsari
- Department of Biochemistry and Biophysics, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Solna, Sweden
| | - Barbro Dahlén
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.,Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.,Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Maciej Kupczyk
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.,Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.,Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, University of Lodz, Lodz, Poland
| | | | - Charles Auffray
- European Institute for Systems Biology and Medicine, Lyon, France
| | - Per S Bakke
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Bianca Beghe
- Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy
| | - Elisabeth H Bel
- Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Massimo Caruso
- Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
| | - Pascal Chanez
- Assistance Publique des Hôpitaux de Marseille, Clinique des Bronches, Allergies et Sommeil, Aix Marseille Université, Marseille, France
| | - Bo Chawes
- COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Stephen J Fowler
- Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, The University of Manchester; Manchester Academic Health Science Centre and NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, UK
| | - Mina Gaga
- Respiratory Medicine Dept and Asthma Centre, Athens Chest Hospital "Sotiria", University of Athens, Athens, Greece
| | - Thomas Geiser
- Department for Pulmonary Medicine, University Hospital and University of Bern, Bern, Switzerland
| | - Mark Gjomarkaj
- Institute for Research and Biomedical Innovation, Italian National Research Council, Palermo, Italy
| | - Ildikó Horváth
- Department of Pulmonology, Semmelweis University, Budapest, Hungary
| | - Peter H Howarth
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, and Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | | | - Guy Joos
- Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.,Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
| | - Norbert Krug
- Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany
| | - Paolo Montuschi
- Department of Pharmacology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Jacek Musial
- Department of Internal Medicine, Jagiellonian University Medical College, Krakow, Poland
| | | | - Henric K Olsson
- Translational Science and Experimental Medicine, Research and Early Development, Respiratory & Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden
| | - Alberto Papi
- Division of lnternal and Cardiorespiratory Medicine, University of Ferrara, Ferrara, Italy
| | - Klaus F Rabe
- Department of Internal Medicine, Christian Albrechts University Kiel, Kiel, Germany
| | - Thomas Sandström
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Dominick E Shaw
- Respiratory Research Unit, University of Nottingham, Nottingham, UK
| | - Nikolaos M Siafakas
- Department of Thoracic Medicine, Medical School, University of Crete, Heraklion, Crete, Greece
| | - Mathias Uhlen
- Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, Stockholm, Sweden.,Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - John H Riley
- Respiratory Therapeutic Unit, GlaxoSmithKline, London, UK
| | - Stewart Bates
- Respiratory Therapeutic Unit, GlaxoSmithKline, London, UK
| | - Roelinde J M Middelveld
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.,Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden
| | - Craig E Wheelock
- Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.,Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
| | - Kian Fan Chung
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Ian M Adcock
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Peter J Sterk
- Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Ratko Djukanovic
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, and Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Peter Nilsson
- Department of Protein Science, KTH Royal Institute of Technology, SciLifeLab, Stockholm, Sweden
| | - Sven-Erik Dahlén
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.,Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden
| | - Anna James
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.,Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden
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Puzzovio PG, Levi-Schaffer F. Latest Progresses in Allergic Diseases Biomarkers: Asthma and Atopic Dermatitis. Front Pharmacol 2021; 12:747364. [PMID: 34658882 PMCID: PMC8514744 DOI: 10.3389/fphar.2021.747364] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 09/20/2021] [Indexed: 12/15/2022] Open
Abstract
In the last years, the understanding of the pathologic mechanisms of asthma and atopic dermatitis, both characterized by allergic inflammation, has greatly improved. However, it is evident that both diseases present with high heterogeneity, which complicates the diagnosis and the therapeutic approach of the patients. Moreover, some of the currently available strategies to treat asthma and atopic dermatitis are still mostly controlling the symptoms, but not to lead towards full healing, thus having these two diseases labelled as unmet clinical needs by WHO. Therefore, the "one-size-fits-all" strategy is outdated for asthma and atopic dermatitis, and there is the need of better methods to clearly diagnose the disease and tailor the therapy according to the specific symptomatology. In this regard, the use of biomarkers has been advanced in order to characterize both diseases according to their clinical signs and to facilitate the subsequent treatment. Despite the advancements made in this regard, there is still need for better and more sensitive biomarkers and for less invasive sampling methodologies, with the aim to diagnose specifically each manifestation of asthma and atopic dermatitis and to provide the best treatment with the least suffering for the patients.
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Affiliation(s)
- Pier Giorgio Puzzovio
- Pharmacology and Experimental Therapeutics Unit, Faculty of Medicine, School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Francesca Levi-Schaffer
- Pharmacology and Experimental Therapeutics Unit, Faculty of Medicine, School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel
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Duman B, Borekci S, Akdeniz N, Gazioglu SB, Deniz G, Gemicioglu B. Inhaled corticosteroids' effects on biomarkers in exhaled breath condensate and blood in patients newly diagnosed with asthma who smoke. J Asthma 2021; 59:1613-1620. [PMID: 34376110 DOI: 10.1080/02770903.2021.1962341] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
OBJECTIVE Exposure to cigarette smoke complicates the treatment and management of asthma through a variety of inflammatory effects. This study aimed to investigate the differences between newly diagnosed cases of asthma in smokers and nonsmokers in terms of localized and systemic biomarkers following treatment with inhaled corticosteroids (ICS) or ICS in combination with a long-acting β2 agonist (LABA). METHODS Specimens of exhaled breath condensate (EBC) from newly diagnosed patients with asthma were used to quantify inflammation in the airways, while blood samples were used to assess systemic inflammation. In both samples, the levels of IL-6, LTB4, LTD4, and 8-isoprostane were measured and these were repeated after 3 months of treatment with ICS or ICS + LABA. RESULTS Of the 20 patients, 10 (50%) were nonsmokers with asthma (NSA) and 10 (50%) smokers with asthma (SA). There was no statistically significant difference in the blood or EBC levels of IL-6, LTB4, LTD4, or 8-isoprostane between the groups prior to treatment. Only the decrease in 8-isoprostane level in the EBC samples was found to be significantly greater in the NSA group after treatment (for smokers, the change was 2.91 ± 23.22, while for nonsmokers it was -22.72 ± 33.12, p = 0.022). Post-treatment asthma control was significantly better in the NSA group (p = 0.033). CONCLUSION Monitoring the alterations in 8-isoprostane levels in EBC in patients with asthma who smoke may be helpful in deciding on therapeutic management and switching treatments. Asthma control was better in nonsmokers than in smokers.
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Affiliation(s)
- Berna Duman
- Bezmiâlem Vakıf University School of Medicine, Istanbul, Turkey
| | - Sermin Borekci
- Department of Pulmonary Diseases, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Nilgun Akdeniz
- Department of Immunology, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Sema Bilgic Gazioglu
- Department of Immunology, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Gunnur Deniz
- Department of Immunology, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
| | - Bilun Gemicioglu
- Department of Pulmonary Diseases, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
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40
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Sánchez-Ovando S, Simpson JL, Barker D, Baines KJ, Wark PAB. Transcriptomics of biopsies identifies novel genes and pathways linked to neutrophilic inflammation in severe asthma. Clin Exp Allergy 2021; 51:1279-1294. [PMID: 34245071 DOI: 10.1111/cea.13986] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 06/03/2021] [Accepted: 06/19/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Severe asthma is a complex disease. Transcriptomic profiling has contributed to understanding the pathogenesis of asthma, especially type-2 inflammation. However, there is still poor understanding of non-type-2 asthma, and consequently, there are limited treatment options. OBJECTIVE The aim of this study was to identify differentially expressed genes (DEGs) and pathways in endobronchial biopsies associated with inflammatory phenotypes of severe asthma. METHODS This cross-sectional study examined endobronchial biopsies from 47 adults with severe asthma (neutrophilic asthma (NA) n = 9, eosinophilic asthma (EA) n = 22 and paucigranulocytic asthma (PGA) n = 16) and 13 healthy controls (HC). RNA was extracted and transcriptomic profiles generated (Illumina Humanref-12 V4) and analysed using GeneSpring GX14.9.1. Pathway identification using Ingenuity Pathway Analysis. RESULTS NA had the most distinct profile, with signature of 60 top-ranked DEGs (FC >±2) including genes associated with innate immunity response, neutrophil degranulation and IL-10 signalling. NA presented enrichment to pathways previously linked to neutrophilic inflammation; dendritic cell maturation, Th1, TREM1, inflammasome, Th17 and p38 MAPK, as well as novel links to neuroinflammation, NFAT and PKCθ signalling. EA presented similar transcriptomic profiles to PGA and HC. Despite the higher proportion of bacterial colonization in NA, no changes were observed in the transcriptomic profiles of severe asthma culture positive compared with severe asthma culture negative. CONCLUSIONS & CLINICAL RELEVANCE NA features a distinct transcriptomic profile with seven pathways enriched in NA compared to EA, PGA and HC. All those with severe asthma had significant enrichment for SUMOylation, basal cell carcinoma signalling and Wnt/β-catenin pathways compared to HC, despite high-dose inhaled corticosteroids. These findings contribute to the understanding of mechanistic pathways in endobronchial biopsies associated with NA and identify potential novel treatment targets for severe asthma.
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Affiliation(s)
- Stephany Sánchez-Ovando
- Priority Research Centre for Healthy Lungs, Faculty of Health and Medicine, University of Newcastle, NSW, Australia
| | - Jodie L Simpson
- Priority Research Centre for Healthy Lungs, Faculty of Health and Medicine, University of Newcastle, NSW, Australia
| | - Daniel Barker
- Faculty of Health and Medicine, University of Newcastle, NSW, Australia
| | - Katherine J Baines
- Priority Research Centre for Healthy Lungs, Faculty of Health and Medicine, University of Newcastle, NSW, Australia
| | - Peter A B Wark
- Priority Research Centre for Healthy Lungs, Faculty of Health and Medicine, University of Newcastle, NSW, Australia.,Respiratory and Sleep Medicine, John Hunter Hospital, NSW, Australia
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McNarry MA, Lester L, Ellins EA, Halcox JP, Davies G, Winn CON, Mackintosh KA. Asthma and high-intensity interval training have no effect on clustered cardiometabolic risk or arterial stiffness in adolescents. Eur J Appl Physiol 2021; 121:1967-1978. [PMID: 33778908 PMCID: PMC8192411 DOI: 10.1007/s00421-020-04590-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 12/17/2020] [Indexed: 12/18/2022]
Abstract
PURPOSE Cardiometabolic risk, including arterial stiffness, is increasing in youth. Those with asthma are suggested to be particularly at risk of cardiovascular disease. Efficient and effective strategies are required to prevent the atherosclerotic process in youth. The purpose of this study was to investigate the effect of 6 months high-intensity interval training (HIIT) on cardiometabolic risk in youth with and without asthma. METHODS 65 adolescents (31 mild asthma; 34 non-asthma) were recruited, 32 (16 asthma) of whom were randomly allocated to receive HIIT three times per week for 6 months. At baseline, mid-intervention, post-intervention and at a 3-month follow-up, anthropometric, metabolic and vascular determinants of cardiometabolic risk were assessed. Following principal component analysis (PCA), linear mixed models were used to assess the influence of asthma, HIIT and their interaction. RESULTS Seven factors were identified which explained 88% of the common variance shared among the parameters. Those with asthma demonstrated lower arterial stiffness factor scores mid-intervention (P = 0.047) and lower cholesterol factor scores post-intervention (P = 0.022) but there was no effect of the intervention, or interaction effects, on any PCA-identified factor, at any time-point. HIIT was associated with a lower low-density lipoprotein and diastolic blood pressure at mid-intervention. DISCUSSION Neither arterial stiffness nor clustered cardiometabolic risk are influenced by HIIT in adolescents with or without asthma, despite important changes in blood lipid and pressure profiles. Blood pressure, augmentation and pulse wave velocity should be considered physiologically distinct constructs and as potential markers of cardiovascular health.
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Affiliation(s)
- M A McNarry
- Applied Sports, Technology, Exercise and Medicine Research Centre, College of Engineering, Swansea University, Bay Campus, Swansea, SA1 8EN, UK.
| | - L Lester
- School of Human Sciences, University of Western Australia, Perth, 6009, Australia
| | - E A Ellins
- Swansea University Medical School, Swansea University, Swansea, SA2 8PP, UK
| | - J P Halcox
- Swansea University Medical School, Swansea University, Swansea, SA2 8PP, UK
| | - G Davies
- Swansea University Medical School, Swansea University, Swansea, SA2 8PP, UK
| | - C O N Winn
- Applied Sports, Technology, Exercise and Medicine Research Centre, College of Engineering, Swansea University, Bay Campus, Swansea, SA1 8EN, UK
| | - K A Mackintosh
- Applied Sports, Technology, Exercise and Medicine Research Centre, College of Engineering, Swansea University, Bay Campus, Swansea, SA1 8EN, UK
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42
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Biomarkers in Different Asthma Phenotypes. Genes (Basel) 2021; 12:genes12060801. [PMID: 34070316 PMCID: PMC8226821 DOI: 10.3390/genes12060801] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/18/2021] [Accepted: 05/21/2021] [Indexed: 12/16/2022] Open
Abstract
Asthma is the most common respiratory disease. It has multiple phenotypes thatcan be partially differentiated by measuring the disease’s specific characteristics—biomarkers. The pathogenetic mechanisms are complex, and it is still a challenge to choose suitable biomarkers to adequately stratify patients, which became especially important with the introduction of biologicals in asthma treatment. Usage of biomarkers and an understanding of the underlying pathobiological mechanisms lead to the definition of endotypes. Asthma can be broadly divided into two endotypes, T2-high and T2-low. The right combination of various biomarkers in different phenotypes is under investigation, hoping to help researchers and clinicians in better disease evaluation since theindividual approach and personalized medicine are imperative. Multiple biomarkers are superior to a single biomarker.
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43
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Tyrak KE, Pajdzik K, Jakieła B, Kupryś-Lipińska I, Ćmiel A, Kacorzyk R, Trąd G, Kuna P, Sanak M, Mastalerz L. Biomarkers for predicting response to aspirin therapy in aspirin-exacerbated respiratory disease. Clin Exp Allergy 2021; 51:1046-1056. [PMID: 33905579 PMCID: PMC9292205 DOI: 10.1111/cea.13886] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Revised: 04/12/2021] [Accepted: 04/18/2021] [Indexed: 01/18/2023]
Abstract
Background Aspirin desensitization followed by daily aspirin use is an effective treatment for aspirin‐exacerbated respiratory disease (AERD). Objective To assess clinical features as well as genetic, immune, cytological and biochemical biomarkers that might predict a positive response to high‐dose aspirin therapy in AERD. Methods We enrolled 34 AERD patients with severe asthma who underwent aspirin desensitization followed by 52‐week aspirin treatment (650 mg/d). At baseline and at 52 weeks, clinical assessment was performed; phenotypes based on induced sputum cells were identified; eicosanoid, cytokine and chemokine levels in induced sputum supernatant were determined; and induced sputum expression of 94 genes was assessed. Responders to high‐dose aspirin were defined as patients with improvement in 5‐item Asthma Control Questionnaire score, 22‐item Sino‐Nasal Outcome Test (SNOT‐22) score and forced expiratory volume in 1 second at 52 weeks. Results There were 28 responders (82%). Positive baseline predictors of response included female sex (p = .002), higher SNOT‐22 score (p = .03), higher blood eosinophil count (p = .01), lower neutrophil percentage in induced sputum (p = .003), higher expression of the hydroxyprostaglandin dehydrogenase gene, HPGD (p = .004) and lower expression of the proteoglycan 2 gene, PRG2 (p = .01). The best prediction model included Asthma Control Test and SNOT‐22 scores, blood eosinophils and total serum immunoglobulin E. Responders showed a marked decrease in sputum eosinophils but no changes in eicosanoid levels. Conclusions and Clinical Relevance Female sex, high blood eosinophil count, low sputum neutrophil percentage, severe nasal symptoms, high HPGD expression and low PRG2 expression may predict a positive response to long‐term high‐dose aspirin therapy in patients with AERD.
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Affiliation(s)
- Katarzyna E Tyrak
- 2nd Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Kinga Pajdzik
- 2nd Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Bogdan Jakieła
- 2nd Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Izabela Kupryś-Lipińska
- Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, Lodz, Poland
| | - Adam Ćmiel
- Department of Applied Mathematics, AGH University of Science and Technology, Cracow, Poland
| | - Radosław Kacorzyk
- 2nd Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Gabriela Trąd
- 2nd Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Piotr Kuna
- Department of Internal Medicine, Asthma and Allergy, Medical University of Lodz, Lodz, Poland
| | - Marek Sanak
- 2nd Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland
| | - Lucyna Mastalerz
- 2nd Department of Internal Medicine, Jagiellonian University Medical College, Cracow, Poland
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44
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Alwarith J, Kahleova H, Crosby L, Brooks A, Brandon L, Levin SM, Barnard ND. The role of nutrition in asthma prevention and treatment. Nutr Rev 2021; 78:928-938. [PMID: 32167552 PMCID: PMC7550896 DOI: 10.1093/nutrit/nuaa005] [Citation(s) in RCA: 128] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Asthma is a chronic respiratory condition characterized by airway inflammation and hyperreactivity. Prevalence has continued to rise in recent decades as Western dietary patterns have become more pervasive. Evidence suggests that diets emphasizing the consumption of plant-based foods might protect against asthma development and improve asthma symptoms through their effects on systemic inflammation, oxidation, and microbial composition. Additionally, increased fruit and vegetable intake, reduced animal product consumption, and weight management might mediate cytokine release, free radical damage, and immune responses involved in the development and course of asthma. The specific aim of this review paper is to examine the current literature on the associations between dietary factors and asthma risk and control in children and adults. Clinical trials examining the mechanism(s) by which dietary factors influence asthma outcomes are necessary to identify the potential use of nutritional therapy in the prevention and management of asthma.
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Affiliation(s)
- Jihad Alwarith
- Physicians Committee for Responsible Medicine, Washington, DC, USA
| | - Hana Kahleova
- Physicians Committee for Responsible Medicine, Washington, DC, USA
| | - Lee Crosby
- Physicians Committee for Responsible Medicine, Washington, DC, USA
| | - Alexa Brooks
- Physicians Committee for Responsible Medicine, Washington, DC, USA
| | | | - Susan M Levin
- Physicians Committee for Responsible Medicine, Washington, DC, USA
| | - Neal D Barnard
- George Washington University School of Medicine and Health Sciences, Washington, DC, USA
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45
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Ilmarinen P, Pardo A, Tuomisto LE, Vähätalo I, Niemelä O, Nieminen P, Kankaanranta H. Long-term prognosis of new adult-onset asthma in obese patients. Eur Respir J 2021; 57:13993003.01209-2020. [PMID: 33033149 PMCID: PMC8477896 DOI: 10.1183/13993003.01209-2020] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Accepted: 09/21/2020] [Indexed: 12/19/2022]
Abstract
Background Obesity has been associated with poor outcomes of asthma in cross-sectional studies, but long-term effect of obesity on asthma remains unknown. Aims To study the effects of obesity, found at the time of diagnosis of adult-onset asthma, on 12-year prognosis by focusing on oral corticosteroid (OCS) use and respiratory-related hospital admissions. Methods Patients diagnosed with adult-onset asthma (n=203) were divided into three categories based on diagnostic body mass index (BMI) (<25 kg·m−2, 25–29.9 kg·m−2, ≥30 kg·m−2) and followed for 12 years as part of the Seinäjoki Adult Asthma Study. Self-reported and dispensed OCS were assessed for the 12-year period. Data on hospital admissions were analysed based on medical records. Results 12 years after diagnosis, 86% of the patients who were obese (BMI ≥30 kg·m−2) at diagnosis remained obese. During the follow-up, no difference was found in weight gain between the BMI categories. During the 12-year follow-up, patients obese at diagnosis reported more frequent use of OCS courses (46.9% versus 23.1%, p=0.028), were dispensed OCS more often (81.6% versus 56.9%, p=0.014) and at higher doses (median 1350 (interquartile range 280–3180) mg versus 600 (0–1650) mg prednisolone, p=0.010) compared to normal-weight patients. Furthermore, patients who were obese had more often one or more respiratory-related hospitalisations compared to normal-weight patients (38.8% versus 16.9%, p=0.033). In multivariate logistic regression analyses, obesity predicted OCS use and hospital admissions. Conclusions In adult-onset asthma, patients obese at diagnosis mostly remained obese at long-term and had more exacerbations and respiratory-related hospital admissions compared to normal-weight patients during 12-year follow-up. Weight loss should be a priority in their treatment to prevent this outcome. Obese patients with new adult-onset asthma often remain obese in the long-term and have more exacerbations and respiratory-related hospital admissions during follow-up. High priority should be given to weight loss during treatment to prevent this outcome.https://bit.ly/2G5HtRZ
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Affiliation(s)
- Pinja Ilmarinen
- Dept of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Adrienn Pardo
- Dept of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Leena E Tuomisto
- Dept of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Iida Vähätalo
- Dept of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland
| | - Onni Niemelä
- Dept of Laboratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland.,Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Pentti Nieminen
- Medical Informatics and Statistics Research Group, University of Oulu, Oulu, Finland
| | - Hannu Kankaanranta
- Dept of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland.,Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.,Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
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46
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[Diet and asthma: Better eating for better breathing?]. Rev Mal Respir 2021; 38:278-288. [PMID: 33676796 DOI: 10.1016/j.rmr.2021.02.064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 10/13/2020] [Indexed: 11/22/2022]
Abstract
Inhaled therapies are the cornerstone of asthma treatment. However, according to national and international guidelines, non-pharmacological interventions should not be neglected in asthma. It has been demonstrated that a healthy diet is beneficial to general health. Recently, the effect of diet on asthma has been highlighted in many studies. Two diets have been particularly studied: the Mediterranean diet (high in fruits and vegetables and low in fat) and the Western diet (high in saturated fat and low in fruits and vegetables). A beneficial effect of the Mediterranean diet and deleterious effect of the Western diet on the development or control of asthma has been shown in some studies even after adjustment for overweight. Study findings have not been unanimous, probably related to the complexity of conducting studies on a diet that may change from day to day for any individual subject. In addition, the effect of physical exercise, which is known to be beneficial in asthma, is rarely taken into account in these studies. However, studies on diet are becoming more complex with the use of specific dietary indices, which should bring interesting data in the future.
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47
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Pandey R, Parkash V, Kant S, Verma AK, Sankhwar SN, Agrawal A, Parmar D, Verma S, Ahmad MK. An update on the diagnostic biomarkers for asthma. J Family Med Prim Care 2021; 10:1139-1148. [PMID: 34041141 PMCID: PMC8140254 DOI: 10.4103/jfmpc.jfmpc_2037_20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 12/02/2020] [Accepted: 01/01/2021] [Indexed: 01/13/2023] Open
Abstract
Asthma is a respiratory disorder accounts for ~339 million cases per annum. The initial diagnosis of asthma relies on the symptomatic identification of characters, such as wheeze, shortness of breath, chest tightness, and cough. The presence of two or more of these symptoms may be considered as indicative of asthma. The asthma-diagnostic also involves spirometry test before and after inhaling a bronchodilator like albuterol. Because asthma pathophysiology involves participation of immune system, the cytokines play an important role. The review discusses various molecules that are or may be used as biomarkers for the asthma diagnosis.
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Affiliation(s)
- Rashmi Pandey
- Department of Pulmonary and Critical Care Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Ved Parkash
- Department of Pulmonary and Critical Care Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Surya Kant
- Department of Respiratory Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Ajay K. Verma
- Department of Respiratory Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - S. N. Sankhwar
- Department of Urology, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Avinash Agrawal
- Department of Critical Care Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Devendra Parmar
- Department of Development Toxicology, CSIR IITR, Lucknow, Uttar Pradesh, India
| | - Sheetal Verma
- Department of Microbiology, King George's Medical University, Lucknow, Uttar Pradesh, India
| | - Md. Kaleem Ahmad
- Department of Biochemistry, King George's Medical University, Lucknow, Uttar Pradesh, India
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48
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Nair P, Surette MG, Virchow JC. Neutrophilic asthma: misconception or misnomer? THE LANCET RESPIRATORY MEDICINE 2021; 9:441-443. [PMID: 33577751 DOI: 10.1016/s2213-2600(21)00023-0] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 11/24/2020] [Accepted: 01/06/2021] [Indexed: 01/04/2023]
Affiliation(s)
- Parameswaran Nair
- Department of Medicine, McMaster University, Hamilton, ON, Canada; Firestone Institute for Respiratory Health, St Joseph's Healthcare Hamilton, Hamilton, ON, L8N 4A6, Canada.
| | | | - J Christian Virchow
- Department of Pneumology and Department of Intensive Care Medicine, University of Rostock Medical Clinic, Rostock, Germany
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49
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Tahamtan A, Besteman S, Samadizadeh S, Rastegar M, Bont L, Salimi V. Neutrophils in respiratory syncytial virus infection: From harmful effects to therapeutic opportunities. Br J Pharmacol 2020; 178:515-530. [PMID: 33169387 DOI: 10.1111/bph.15318] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 10/27/2020] [Accepted: 11/02/2020] [Indexed: 12/15/2022] Open
Abstract
Respiratory syncytial virus (RSV) is an important infectious agent in infants and young children. In most cases, RSV infection only causes mild disease, but in some, it requires invasive ventilation. Although antiviral drugs are obvious candidates to treat viral illness, and some have shown antiviral effects in humans, antivirals such as GS-5806, ALX-0171 and ALS-8176 have not yet met their expectations. Since the inappropriate or dysregulated immune response against RSV leads to harmful immune pathology, a robust immune cascade is probably underway by the time patients reach the hospital. RSV infection is associated with a strong neutrophil influx into the airway. It not clear if these cells contribute to antiviral defence or to lung pathology. This article discusses the protective and harmful roles of neutrophils during RSV infection and provides an overview of mechanisms by which neutrophil function could be targeted to prevent tissue injury and preserve homeostasis.
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Affiliation(s)
- Alireza Tahamtan
- Infectious Diseases Research Centre, Golestan University of Medical Sciences, Gorgan, Iran.,Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Sjanna Besteman
- Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands.,Center for Translation Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Saeed Samadizadeh
- Infectious Diseases Research Centre, Golestan University of Medical Sciences, Gorgan, Iran.,Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mostafa Rastegar
- Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Louis Bont
- Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands
| | - Vahid Salimi
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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50
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Zhao Y, Tang Y, Chen L, Lv S, Liu S, Nie P, Aguilar ZP, Xu H. Restraining the TiO 2 nanoparticles-induced intestinal inflammation mediated by gut microbiota in juvenile rats via ingestion of Lactobacillus rhamnosus GG. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2020; 206:111393. [PMID: 33010597 DOI: 10.1016/j.ecoenv.2020.111393] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 08/19/2020] [Accepted: 09/20/2020] [Indexed: 06/11/2023]
Abstract
Human were given a lot of opportunities to ingest TiO2 NPs in the environment. Children have low, sensitive intestinal tolerance, and they could be exposed to higher levels of TiO2 NPs than adults. Few studies have been conducted on the interaction between TiO2 NPs and juvenile intestine phase models. Thus, in this work, weaning rats were orally exposed to TiO2 NPs for 7 and 14 days. Results indicate that Ti accumulated in the intestine, liver, and feces. Inflammatory infiltration damage was observed in the colonic epithelial tissue, and gut microbiota fluctuated with a decreased abundance of Lactobacilli in feces. Oral supplementation with Lactobacillus rhamnosus GG (LGG) lessened TiO2 NPs-induced colonic inflammatory injury, which might due to downregulation of nuclear factor kappa-B (NF-κB). Meanwhile, LGG maintained normal intestinal microbiome homeostasis, thereby improving TiO2 NPs-induced colon injury in juvenile rats. Moreover, fecal microbiota transplant (FMT) experiment indicated possible TiO2 NPs-induced intestinal microbiota disorder led to colonic inflammation. Our works suggested the urgent need for additional studies on the risk safety assessment, mechanism, and prevention of juvenile health damage from exposure to TiO2 NPs.
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Affiliation(s)
- Yu Zhao
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Yizhou Tang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Ling Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Sidi Lv
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Shanji Liu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | - Penghui Nie
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China
| | | | - Hengyi Xu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.
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