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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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Aliwie AK, Jasim AH. Evaluation of asthmatic patient dyspnea in asthma center at Baghdad city. JOURNAL OF EDUCATION AND HEALTH PROMOTION 2025; 14:106. [PMID: 40271265 PMCID: PMC12017420 DOI: 10.4103/jehp.jehp_674_24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Accepted: 07/11/2024] [Indexed: 04/25/2025]
Abstract
BACKGROUND Asthma was a heterogeneous condition, with dyspnea during exercise affecting individuals to a variable degree. The research aims to evaluate dyspnea in an asthmatic patient and to find out the relationship between dyspnea and sociodemographic variables. MATERIALS AND METHODS A cross-sectional study that included 130 patients with asthma in an asthma center in Baghdad City, Iraq was conducted to assess asthmatic patient dyspnea. From 1st September to December 20, 2023, we recruited a total of 130 patients attending outpatient respiratory clinics from three teaching hospitals and centers located in Baghdad, Iraq, the current study used purposive sampling. Data were collected through a pretested self-administered questionnaire. Collected data were coded and put into SPSS Statistics (v25). Inferential and descriptive statistical procedures were conducted. Percentages and frequencies for every item within the asthmatic patient were measured. The mean score attained from the scale was used to measure the subject. RESULT The data reveals that most participants consistently reported experiencing high levels of dyspnea, with a Mean + SD (37.13 ± 8.06). These responses, indicate severe levels of asthma according to their assessment, signifying a prevalent occurrence of this symptom among the respondents. The study shows a highly significant relationship between occupation, education, and smoking with dyspnea at a P value of 0.05. CONCLUSION The results show that the majority in the sample had a severe level of dyspnea, the study shows a highly significant relationship between occupation, education, and smoking with dyspnea at P value of 0.05.
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Affiliation(s)
- Ali Khamies Aliwie
- University of Baghdad, College of Nursing, Department of Adult Nursing, Baghdad, Iraq
| | - Aqeel Habeeb Jasim
- University of Baghdad, College of Nursing, Department of Adult Nursing, Baghdad, Iraq
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Kayikci H, Damadoglu E, Cihanbeylerden M, Tuccar C, Karakaya G, Kalyoncu AF. Clinical characteristics and biological treatment responses of patients with late-onset asthma phenotype. Allergy Asthma Proc 2025; 46:109-118. [PMID: 40011985 DOI: 10.2500/aap.2025.46.240105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2025]
Abstract
Background: The data on subphenotypes and treatment responses to biologicals in late-onset asthma (LOA) is limited. This study aims to compare the clinical characteristics and treatment responses in severe asthma patients receiving biological treatments, categorized into early-onset asthma (EOA) and LOA groups. Methods: Patients treated with omalizumab or mepolizumab for at least six months at a tertiary care adult allergy clinic between December 2015 and December 2023 were included. Patients with persistent respiratory symptoms starting at age ≥40 years were categorized as LOA, while those with onset <40 years were categorized as EOA. Changes in Asthma Control Questionnaire (ACQ-6) scores, forced expiratory volume in one second (FEV1) percentages, and blood eosinophil counts were assessed at baseline and 6 months. The percentage change in FEV1 (liters) at 6 months relative to baseline was measured. Clinical remission rates were evaluated in those completing one year of treatment. Results: Among 87 patients, 38 (43.7%) had LOA and 49 (56.3%) had EOA. Of these, 22 (25.3%) received omalizumab and 65 (74.7%) received mepolizumab, with a mean treatment duration of 24.7 (±19.7) months. LOA patients had higher obesity rates and tobacco consumption compared to EOA patients (p = 0.041 and p = 0.024, respectively). There were no significant differences between LOA and EOA groups in ACQ scores, FEV1 percentage, the percentage change in FEV1 in liters and eosinophil counts (p = 0.531, p = 0.219, p = 0.632, p = 0.700, respectively). Within LOA patients, ACQ scores did not significantly differ between those treated with omalizumab and mepolizumab (p = 0.801). At 6 months, eosinophil counts significantly decreased with mepolizumab but not with omalizumab (p = 0.002). Conclusion: Biological treatment responses were similar between LOA and EOA groups. Omalizumab and mepolizumab showed comparable efficacy, with the exception of eosinophil count changes in LOA patients.
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Grunwell JR, Fitzpatrick AM. Asthma Phenotypes and Biomarkers. Respir Care 2025. [PMID: 40013975 DOI: 10.1089/respcare.12352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/28/2025]
Abstract
Asthma experienced by both adults and children is a phenotypically heterogeneous condition. Severe asthma, characterized by ongoing symptoms and airway inflammation despite high doses of inhaled and/or systemic corticosteroids, is the focus of research efforts to understand this underlying heterogeneity. Clinical phenotypes in both adult and pediatric asthma have been determined using supervised definition-driven classification and unsupervised data-driven clustering methods. Efforts to understand the underlying inflammatory patterns of severe asthma have led to the seminal discovery of type 2-high versus type 2-low phenotypes and to the development of biologics targeted at type 2-high inflammation to reduce the rates of severe asthma exacerbations. Type 2-high asthma is characterized by upregulation of T helper 2 immune pathways including interleukin (IL)-4, IL-5, and IL-13 along with eosinophilic airway inflammation, sometimes allergic sensitization, and responsiveness to treatment with corticosteroids. Type 2-low asthma is poorly responsive to corticosteroids and is not as well characterized as type 2-high asthma. Type 2-low asthma is limited by being defined as the absence of type 2-high inflammatory markers. Choosing a biologic for the treatment of severe asthma involves the evaluation of a panel of biomarkers such as blood eosinophils, total and specific immunoglobulin E/allergic sensitization, and fractional exhaled nitric oxide. In this review, we focus on the underlying pathobiology of adult and pediatric asthma, discuss the different phenotype-based treatment options for adult and pediatric type 2-high with or without allergic asthma and type 2-low asthma, and describe a clinical phenotyping approach to patients to guide out-patient therapy. Finally, we end with a discussion of whether pediatric asthma exacerbations necessitating admission to an ICU constitute their own high-risk phenotype and/or whether it is a part of other previously defined high-risk subgroups such as difficult-to-control asthma, exacerbation-prone asthma, and severe treatment-resistant asthma.
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Affiliation(s)
- Jocelyn R Grunwell
- Dr. Grunwell is affiliated with Division of Critical Care Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia
| | - Anne M Fitzpatrick
- Dr. Fitzpatrick is affiliated with Division of Pulmonary, Allergy/Immunology, Cystic Fibrosis, and Sleep Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia
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Park SY, Fowler S, Shaw DE, Adcock IM, Sousa AR, Djukanovic R, Dahlen SE, Sterk PJ, Kermani NZ, Calhoun W, Israel E, Castro M, Mauger D, Meyers D, Bleecker E, Moore W, Busse W, Jarjour N, Denlinger L, Levy B, Choi BH, Kim SH, Jang AS, Lee T, Cho YJ, Shin YS, Cho SH, Won S, Cruz AA, Wenzel SE, Chung KF, Kim TB. Comparison of Asthma Phenotypes in Severe Asthma Cohorts (SARP, U-BIOPRED, ProAR and COREA) From 4 Continents. ALLERGY, ASTHMA & IMMUNOLOGY RESEARCH 2024; 16:338-352. [PMID: 39155735 PMCID: PMC11331196 DOI: 10.4168/aair.2024.16.4.338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 01/26/2024] [Accepted: 03/06/2024] [Indexed: 08/20/2024]
Abstract
PURPOSE Asthma is a clinical syndrome with various underlying pathomechanisms and clinical phenotypes. Genetic, ethnic, and geographic factors may influence the differences in clinical presentation, severity, and prognosis. We compared the characteristics of asthma based on the geographical background by analyzing representative cohorts from the United States, Europe, South America, and Asia using the Severe Asthma Research Program (SARP), Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED), Program for Control of Asthma in Bahia (ProAR), and Cohort for Reality and Evolution of Adult Asthma in Korea (COREA), respectively. METHODS The clinical characteristics and medications for the SARP (n = 669), U-BIOPRED (n = 509), ProAR (n = 996), and COREA (n = 3,748) were analyzed. Subgroup analysis was performed for severe asthma. RESULTS The mean age was highest and lowest in the COREA and SARP, respectively. The asthma onset age was lowest in the ProAR. The mean body mass index was highest and lowest in the SARP and COREA, respectively. Baseline pulmonary function was lowest and highest in the U-BIOPRED and COREA, respectively. The number of patients with acute exacerbation in the previous year was highest in U-BIOPRED. The mean blood eosinophil count was highest in COREA. The total immunoglobulin E was highest in the ProAR. The frequency of atopy was highest in the SARP. The principal component analysis plot revealed differences among all cohorts. CONCLUSIONS The cohorts from 4 different continents exhibited different clinical and physiological characteristics, probably resulting from the interplay between genetic susceptibility and geographical factors.
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Affiliation(s)
- So-Young Park
- Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea
| | - Stephen Fowler
- Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, University of Manchester and University Hospital of South Manchester, Manchester Academic Health Science Centre, Manchester, UK
| | - Dominic E Shaw
- Respiratory Research Unit, University of Nottingham, Nottingham, UK
| | - Ian M Adcock
- National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK
| | - Ana R Sousa
- Respiratory Therapeutic Unit, GlaxoSmithKlene, Stockley Park, UK
| | - Ratko Djukanovic
- NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences and Human Development and Health, Southampton, UK
| | - Sven-Erik Dahlen
- Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden
| | - Peter J Sterk
- Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, The Netherlands
| | - Nazanin Zounemat Kermani
- National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK
| | - William Calhoun
- Divisions of Pulmonary, Critical Care, and Sleep Medicine, and Allergy/Immunology; and Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX, USA
| | - Elliot Israel
- Department of Medicine, Harvard Medical School, Boston, MA, USA
| | - Mario Castro
- Department of Medicine, University of Kansas School of Medicine, Kansas City, KS, USA
| | - Dave Mauger
- Department of Public Health Sciences, Pennsylvania State University College of Medicine, Hershey, PA, USA
| | - Deborah Meyers
- University of Arizona Arizona Health Sciences Center, Tucson, AZ, USA
| | - Eugene Bleecker
- University of Arizona Arizona Health Sciences Center, Tucson, AZ, USA
| | - Wendy Moore
- Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - William Busse
- UW Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Nizar Jarjour
- UW Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Loren Denlinger
- UW Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Bruce Levy
- Department of Medicine, University of Kansas School of Medicine, Kansas City, KS, USA
| | - Byoung-Hwui Choi
- Department of Internal Medicine, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea
| | - Sae-Hoon Kim
- Department of Internal Medicine, Division of Allergy and Clinical Immunology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - An-Soo Jang
- Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University School of Medicine, Bucheon, Korea
| | - Taehoon Lee
- Department of Internal Medicine, Ulsan University Hospital, Ulsan University School of Medicine, Ulsan, Korea
| | - Young-Joo Cho
- Department of Internal Medicine, Ewha Womans University College of Medicine, Seoul, Korea
| | - Yoo Seob Shin
- Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea
| | - Sang-Heon Cho
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Sungho Won
- Department of Public Health Science, Seoul National University, Seoul, Korea
| | - Alvaro A Cruz
- ProAR Foundation and Federal University of Bahia, Salvador, Brazil.
| | - Sally E Wenzel
- Department of Environmental Medicine and Occupational Health, Graduate School of Public Health, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
| | - Kian Fan Chung
- National Heart and Lung Institute, Imperial College London, and Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK.
| | - Tae-Bum Kim
- Department of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
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Chuang YC, Tsai HH, Lin MC, Wu CC, Lin YC, Wang TN. Cluster analysis of phenotypes, job exposure, and inflammatory patterns in elderly and nonelderly asthma patients. Allergol Int 2024; 73:214-223. [PMID: 38290901 DOI: 10.1016/j.alit.2024.01.001] [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: 05/24/2023] [Revised: 12/03/2023] [Accepted: 12/17/2023] [Indexed: 02/01/2024] Open
Abstract
BACKGROUND Asthma has been identified as different phenotypes due to various risk factors. Age differences may have potential effects on asthma phenotypes. Our study aimed to identify potential asthma phenotypes among adults divided by age as either younger or older than 65 years. We also compared differences in blood granulocyte patterns, occupational asthmagens, and asthma control-related outcomes among patient phenotype clusters. METHODS We recruited nonelderly (<65 years old) (n = 726) and elderly adults (≥65 years old) (n = 201) with mild-to-severe asthma. We conducted a factor analysis to select 17 variables. A two-step cluster analysis was used to classify subjects with asthma phenotypes, and a discriminant analysis was used to verify the classification of cluster results. RESULTS There were three clusters with different characteristics identified in both the nonelderly and elderly asthmatic adults. In the nonelderly patient group, cluster 2 (obese, neutrophilic phenotypes) had a 1.85-fold significantly increased risk of asthma exacerbations. Cluster 3 (early-onset, atopy, and smoker with an eosinophil-predominant pattern) had a 2.37-fold risk of asthma exacerbations and higher oral corticosteroid (OCS) use than cluster 1 (late-onset and LMW exposure with paucigranulocytic blood pattern). Among elderly patients, cluster 2 had poor lung function and more ex-smokers. Cluster 3 (early-onset, long asthma duration) had the lowest paucigranulocytic blood pattern percentages in the elderly group. CONCLUSIONS The novelty of the clusters was found in age-dependent clusters. We identified three distinct phenotypes with heterogeneous characteristics, asthma exacerbations and medicine use in nonelderly and elderly asthmatic patients, respectively. Classification of age-stratified asthma phenotypes may lead to precise identification of patients, which provides personalized disease management.
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Affiliation(s)
- Yung-Chi Chuang
- Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsin-Hua Tsai
- Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Chih Lin
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Chien Wu
- Division of Pulmonary and Critical Care Medicine, Department of Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yuan-Chung Lin
- Institute of Environmental Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Tsu-Nai Wang
- Department of Public Health, College of Health Science, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
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Al-Moamary MS, Alhaider SA, Allehebi R, Idrees MM, Zeitouni MO, Al Ghobain MO, Alanazi AF, Al-Harbi AS, Yousef AA, Alorainy HS, Al-Hajjaj MS. The Saudi initiative for asthma - 2024 update: Guidelines for the diagnosis and management of asthma in adults and children. Ann Thorac Med 2024; 19:1-55. [PMID: 38444991 PMCID: PMC10911239 DOI: 10.4103/atm.atm_248_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2023] [Accepted: 10/31/2023] [Indexed: 03/07/2024] Open
Abstract
The Saudi Initiative for Asthma 2024 (SINA-2024) is the sixth version of asthma guidelines for the diagnosis and management of asthma for adults and children that was developed by the SINA group, a subsidiary of the Saudi Thoracic Society. The main objective of the SINA is to have guidelines that are up-to-date, simple to understand, and easy to use by healthcare workers dealing with asthma patients. To facilitate achieving the goals of asthma management, the SINA Panel approach is mainly based on the assessment of symptom control and risk for both adults and children. The approach to asthma management is aligned for age groups: adults, adolescents, children aged 5-12 years, and children aged <5 years. SINA guidelines have focused more on personalized approaches reflecting a better understanding of disease heterogeneity with the integration of recommendations related to biologic agents, evidence-based updates on treatment, and the role of immunotherapy in management. The medication appendix has also been updated with the addition of recent evidence, new indications for existing medication, and new medications. The guidelines are constructed based on the available evidence, local literature, and the current situation at national and regional levels. There is also an emphasis on patient-doctor partnership in the management that also includes a self-management plan.
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Affiliation(s)
- Mohamed Saad Al-Moamary
- Department of Medicine, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Sami A. Alhaider
- Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Riyad Allehebi
- Department of Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Majdy M. Idrees
- Department of Medicine, Respiratory Division, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Mohammed O. Zeitouni
- Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Mohammed O. Al Ghobain
- Department of Medicine, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Abdullah F. Alanazi
- Department of Medicine, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
| | - Adel S. Al-Harbi
- Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Abdullah A. Yousef
- Department of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Hassan S. Alorainy
- Department of Respiratory Care, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Mohamed S. Al-Hajjaj
- Department of Paediatrics, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates
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Warm K, Hedman L, Stridsman C, Lindberg A, Rönmark E, Backman H. Age-related differences in associations between uncontrolled asthma, comorbidities and biomarkers in adult-onset asthma. J Asthma 2023; 60:2224-2232. [PMID: 37405375 DOI: 10.1080/02770903.2023.2231078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Accepted: 06/25/2023] [Indexed: 07/06/2023]
Abstract
OBJECTIVE Adult-onset asthma is a recognized but heterogeneous phenotype and has been described to associate with poor asthma control. Knowledge about associations between clinical characteristics including comorbidities and control of adult-onset asthma is limited, especially in older populations. We aimed to study how clinical biomarkers and comorbidities are associated with uncontrolled asthma among middle-aged and older individuals with adult-onset asthma. METHODS Clinical examinations including structured interview, asthma control test (ACT), spirometry, skin prick test (SPT), blood sampling, and measurement of exhaled fractional nitric oxide (FeNO) was performed in a population-based adult-onset asthma cohort in 2019-2020 (n = 227, 66.5% female). Analyses were performed among all included, and separately in middle-aged (37-64 years, n = 120) and older (≥65 years, n = 107) participants. RESULTS In bivariate analysis, uncontrolled asthma (ACT ≤ 19) was significantly associated with a blood neutrophil count ≥5/µl, BMI ≥30, and several comorbidities. In multivariable regression analysis, uncontrolled asthma was associated with neutrophils ≥5/µl (OR 2.35; 95% CI 1.11-4.99). In age-stratified analysis, BMI ≥30 (OR 3.04; 1.24-7.50), eosinophils ≥0.3/µl (OR 3.17; 1.20-8.37), neutrophils ≥5/µl (OR 4.39; 1.53-12.62) and allergic rhinitis (OR 5.10; 1.59-16.30) were associated with uncontrolled asthma among the middle-aged. Among the older adults, uncontrolled asthma was only associated with comorbidities: chronic rhinitis (OR 4.08; 1.62-10.31), ischemic heart disease (OR 3.59; 1.17-10.98), malignancy (OR 3.10; 1.10-8.73), and depression/anxiety (OR 16.31; 1.82-146.05). CONCLUSIONS In adult-onset asthma, comorbidities were strongly associated with uncontrolled asthma among older adults, while clinical biomarkers including eosinophils and neutrophils in blood were associated with uncontrolled asthma among middle-aged.
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Affiliation(s)
- Katja Warm
- The OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Linnea Hedman
- Section of Sustainable Health, The OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Caroline Stridsman
- The OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Anne Lindberg
- The OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Eva Rönmark
- Section of Sustainable Health, The OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Helena Backman
- Section of Sustainable Health, The OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
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Jenkins CR, Singh D, Ducharme FM, Raherison C, Lavoie KL. Asthma and Rhinitis Through the Lifespan of Nonpregnant Women. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2023; 11:3578-3584. [PMID: 37802256 DOI: 10.1016/j.jaip.2023.09.040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 09/22/2023] [Accepted: 09/28/2023] [Indexed: 10/08/2023]
Abstract
Increasingly, clinical practice guidelines advocate a precision medicine-based approach to care for asthma. This focus requires knowledge of not only different asthma phenotypes and their associated biomarkers but also sex and gender differences through the lifespan. Evidence continues to build in favor of different lifetime prevalence, clinical presentations, responses to management, and long-term prognosis of asthma. Women transition through many biological and psychosocial phases in their lives, all of which may interact with, and influence, their health and well-being. Historically, explanations have focused on hormonal effects on asthma in reproductive life, but a greater understanding of mechanisms starting before birth and changing over a lifetime is now possible, with immunologic, inflammatory, and hormonal factors playing a role. This article describes the evidence for the differences in asthma and rhinitis between men and women at different stages of life, the potential underlying mechanisms that contribute to this, and the implications for management and research. Future research studies should systematically report sex differences in asthma so that this knowledge can be used to develop a personalized approach to care, to achieve best possible outcomes for all.
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Affiliation(s)
| | - Dave Singh
- Medicines Evaluation Unit, Manchester University, Manchester, United Kingdom; NHS Foundation Trust, University of Manchester, Manchester, United Kingdom
| | - Francine M Ducharme
- Department of Pediatrics, University of Montréal, Montréal, QC, Canada; Department of Social and Preventive Medicine, School of Public Health, University of Montréal, Montréal, QC, Canada
| | - Chantal Raherison
- Department of Pulmonology, CHU Guadeloupe, French West Indies University, Guadeloupe, French West Indies
| | - Kim L Lavoie
- Department of Psychology, University of Quebec at Montréal (UQAM), Montréal, QC, Canada; Montréal Behavioural Medicine Centre (MBMC), CIUSSS-NIM, Hopital du Sacre-Coeur de Montreal, Montréal, QC, Canada
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10
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Hansen ESH, Rasmusen HK, Hostrup M, Hellsten Y, Backer V. The effect of aerobic exercise training on asthma control in postmenopausal women (ATOM): a randomized controlled pilot study. Eur Clin Respir J 2023; 10:2251256. [PMID: 37674777 PMCID: PMC10478610 DOI: 10.1080/20018525.2023.2251256] [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: 04/13/2023] [Accepted: 08/18/2023] [Indexed: 09/08/2023] Open
Abstract
Objective To evaluate if high-intensity interval training three times weekly for 12 weeks improves asthma control in overweight, postmenopausal women with uncontrolled, late-onset asthma. Methods The reported study is a randomized clinical pilot study (www.clinicaltrials.gov; NCT03747211) that compared 12 weeks of high-intensity interval training (spinning) with usual care. The five-question Asthma Control Questionnaire (ACQ-5) was used as primary outcome. Secondary measures included systemic inflammation and inflammation of the airways, body composition, and cardiac function during exercise. Results We included 12 women with asthma (mean age 65 years (SD 6); mean body mass index 30 kg/m2 (SD 2)) from whom eight were randomized to exercise and four to control. Baseline ACQ-5 was 1.95 (SD 0.53) in the control group and 2.03 (0.54) in the exercise group. Patients had a mean blood eosinophil level of 0.16 × 109cells/L (SD 0.07) and a mean fraction of exhaled nitric oxide of 23 ppb (SD 25). Mixed models showed that participants in the exercise group reduced their ACQ-5 by 0.55 points (95%CI -1.10 to -0.00; P = 0.08) compared with the control group. The exercise group significantly reduced their mean body fat percentage (-2.7%; 95%CI -4.5 to -0.8; P = 0.02), fat mass (-2.8 kg; 95%CI -5.1 to -0.4; P = 0.044) and android fat mass (-0.33 kg; 95%CI -0.60- -0.06; P = 0.038). In analyses of cardiac measures, we saw no significant effects on right ventricular function (fractional area change), diastolic function or left ventricular function. Conclusions Although changes in ACQ-5 were slightly insignificant, these preliminary findings indicate that aerobic exercise training can be used as a means to improve asthma control in overweight, postmenopausal women with asthma.
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Affiliation(s)
- Erik Sören Halvard Hansen
- Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Respiratory Medicine, Copenhagen University Hospital, Hvidovre, Copenhagen, Denmark
- Department of Internal Medicine, Slagelse Hospital, Slagelse, Denmark
| | | | - Morten Hostrup
- Department of Nutrition Exercise and Sports, University of Copenhagen, CopenhagenDenmark
| | - Ylva Hellsten
- Department of Cardiology, Bispebjerg and Frederiksberg Hospital, CopenhagenDenmark
| | - Vibeke Backer
- Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
- Department of Otorhinolaryngology, Rigshospitalet, CopenhagenDenmark
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11
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Solomon Y, Malkamu B, Berhan A, Eyayu T, Almaw A, Legese B, Woldu B. Peripheral blood eosinophilia in adult asthmatic patients and its association with the severity of asthma. BMC Pulm Med 2023; 23:96. [PMID: 36949398 PMCID: PMC10031890 DOI: 10.1186/s12890-023-02383-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 03/11/2023] [Indexed: 03/24/2023] Open
Abstract
BACKGROUND Asthma is a diverse disease with various etiologic bases. Severe asthma can be associated with increased mortality, hospitalization, and decreased quality of life for asthma patients. High blood eosinophil counts were associated with severe asthma, but recent studies have failed to confirm this as a marker of severe asthma among adult asthma patients. As a result, the purpose of this study was to determine the association between the severity of asthma and high blood eosinophil count. METHODOLOGY A simple random sampling technique was used to select 291 asthmatic patients for an institution-based cross-sectional study. Socio-demographic, behavioral, and clinical characteristics were collected by using a pre-tested structured questionnaire. Four milliliters of venous blood were collected from asthmatic patients for complete blood count and peripheral morphology assessment. The eosinophil count was analyzed by the Unicel DxH 800 (Beckman Coulter, Ireland) analyzer. A statistical package for social science version 20 (SPSS) software was used to analyze the data. The non-parametric (Mann-Whitney U) test was used to compare the eosinophil count with different background variables. A binary logistic regression analysis was used to assess the factors associated with eosinophilia. A p-value less than 0.05 in multivariable logistic regression analysis was considered statistically significant. RESULT In this study, the overall magnitude of eosinophilia was 19.6% (95% CI = 14.8-24.1). Being admitted to the emergency department (AOR = 0.25; 95% CI: 0.09-0.69, p = 0.007) and being female (AOR = 0.49; 95% CI: 0.26-0.9, p = 0.025) were shown to have a statistically significant association with eosinophilia. Moreover, the absolute eosinophil count was significantly higher among asthmatic patients infected with intestinal parasitic infection (p < 0.045). CONCLUSION Being female and admission to the emergency department were negatively associated with eosinophilia. Lack of eosinophilia can be related to the low-T2 asthma phenotype. The absolute eosinophil counts were higher among intestinal parasite-infected patients. Therefore, different biomarkers will be considered for the proper diagnosis and management of adult asthma patients.
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Affiliation(s)
- Yenealem Solomon
- Department of Medical Laboratory Science, College of Health Sciences, Debre Tabor University, P.O. Box: 272, Debre Tabor, Ethiopia.
| | - Birhanemaskal Malkamu
- Department of Medical Laboratory Science, College of Health Sciences, Debre Tabor University, P.O. Box: 272, Debre Tabor, Ethiopia
| | - Ayenew Berhan
- Department of Medical Laboratory Science, College of Health Sciences, Debre Tabor University, P.O. Box: 272, Debre Tabor, Ethiopia
| | - Tahir Eyayu
- Department of Medical Laboratory Science, College of Health Sciences, Debre Tabor University, P.O. Box: 272, Debre Tabor, Ethiopia
| | - Andargachew Almaw
- Department of Medical Laboratory Science, College of Health Sciences, Debre Tabor University, P.O. Box: 272, Debre Tabor, Ethiopia
| | - Biruk Legese
- Department of Medical Laboratory Science, College of Health Sciences, Debre Tabor University, P.O. Box: 272, Debre Tabor, Ethiopia
| | - Berhanu Woldu
- Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, University of Gondar, Gondar, Ethiopia
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12
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Association Between Blood Eosinophils and Neutrophils With Clinical Features in Adult-Onset Asthma. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. IN PRACTICE 2023; 11:811-821.e5. [PMID: 36473624 DOI: 10.1016/j.jaip.2022.11.025] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 10/20/2022] [Accepted: 11/14/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Asthma is a disease that can be separated into different phenotypes and endotypes based on the clinical characteristics and the molecular mechanisms of the condition, respectively. OBJECTIVE To assess the association between blood eosinophil and neutrophil counts with clinical and molecular features in patients with adult-onset asthma. METHODS Blood eosinophil and neutrophil counts were measured from 203 patients who took part in the Seinäjoki Adult Asthma Study and attended the 12-year follow-up visit. The patients were then divided into four groups (paucigranulocytic [n = 108], neutrophilic [n = 60], eosinophilic [n = 21], and mixed granulocytic [n = 14]), according to eosinophil and neutrophil levels. The cutoff values used to define the groups were 0.30 × 109 · L-1 for blood eosinophils and 4.4 × 109 · L-1 for blood neutrophils. RESULTS The neutrophilic group had highest body mass index. It was dispensed the highest doses of inhaled corticosteroids during the 12-year follow-up and made the most unplanned respiratory visits. The neutrophilic, eosinophilic, and mixed granulocytic groups had more severe asthma compared with the paucigranulocytic group. The neutrophilic and eosinophilic groups were associated with higher dispensed antibiotics. The eosinophilic group had more nasal polyps, more suspected sinusitis, a greater decline in lung function, and increased levels of periostin, FeNO, and IgE. The neutrophilic group had increased high-sensitivity C-reactive protein, matrix metalloproteinase-9, IL-6, leptin, and soluble urokinase plasminogen activator receptor levels. The mixed granulocytic group showed increased resistin levels together with the neutrophilic group. CONCLUSIONS In addition to blood eosinophils, the blood neutrophil count reflects underlying inflammatory patterns and indicates important differences in asthma clinical features and outcomes.
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13
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Mäkikyrö EMS, Jaakkola MS, Lajunen TK, Malmberg LP, Jaakkola JJK. Subtypes of Adult-Onset Asthma at the Time of Diagnosis: A Latent Class Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:3072. [PMID: 36833767 PMCID: PMC9958800 DOI: 10.3390/ijerph20043072] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 02/02/2023] [Accepted: 02/07/2023] [Indexed: 06/18/2023]
Abstract
INTRODUCTION Only a few previous studies have investigated the subtypes of adult-onset asthma. No previous study has assessed whether these subtypes are different between men and women, or whether these subtypes have different risk factors. METHODS We applied latent class analyses to the Finnish Environment and Asthma Study population, including 520 new cases of adult-onset asthma. We formed subtypes separately between women and men and analyzed the following determinants as potential predictors for these subtypes: age, body mass index, smoking, and parental asthma. RESULTS Among women, the subtypes identified were: 1. Moderate asthma, 2. Cough-variant asthma, 3. Eosinophilic asthma, 4. Allergic asthma, and 5. Difficult asthma. Among men, the subtypes were: 1. Mild asthma, 2. Moderate asthma, 3. Allergic asthma, and 4. Difficult asthma. Three of the subtypes were similar among women and men: Moderate, Allergic, and Difficult asthma. In addition, women had two distinct subtypes: Cough-variant asthma, and Eosinophilic asthma. These subtypes had different risk factor profiles, e.g., heredity was important for Eosinophilic and Allergic asthma (RR for Both parents having asthma in Eosinophilic 3.55 (1.09 to 11.62)). Furthermore, smoking increased the risk of Moderate asthma among women (RR for former smoking 2.21 (1.19 to 4.11)) and Difficult asthma among men but had little influence on Allergic or Cough-variant asthma. Conclusion: This is an original investigation of the subtypes of adult-onset asthma identified at the time of diagnosis. These subtypes differ between women and men, and these subtypes have different risk factor profiles. These findings have both clinical and public health importance for the etiology, prognosis, and treatment of adult-onset asthma.
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Affiliation(s)
- Elina M. S. Mäkikyrö
- Center for Environmental and Respiratory Health Research, Research Unit of Population Health, University of Oulu, FI-90014 Oulu, Finland
- Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland
- Medical Research Center Oulu, Oulu University Hospital, FI-90220 Oulu, Finland
| | - Maritta S. Jaakkola
- Center for Environmental and Respiratory Health Research, Research Unit of Population Health, University of Oulu, FI-90014 Oulu, Finland
- Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland
- Medical Research Center Oulu, Oulu University Hospital, FI-90220 Oulu, Finland
| | - Taina K. Lajunen
- Center for Environmental and Respiratory Health Research, Research Unit of Population Health, University of Oulu, FI-90014 Oulu, Finland
- Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland
- Medical Research Center Oulu, Oulu University Hospital, FI-90220 Oulu, Finland
| | - L. Pekka Malmberg
- Skin and Allergy Hospital, Helsinki University Hospital, University of Helsinki, FI-00280 Helsinki, Finland
| | - Jouni J. K. Jaakkola
- Center for Environmental and Respiratory Health Research, Research Unit of Population Health, University of Oulu, FI-90014 Oulu, Finland
- Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland
- Medical Research Center Oulu, Oulu University Hospital, FI-90220 Oulu, Finland
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14
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McIntyre AP, Viswanathan RK. Phenotypes and Endotypes in Asthma. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023; 1426:119-142. [PMID: 37464119 DOI: 10.1007/978-3-031-32259-4_6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/20/2023]
Abstract
Asthma is a broadly encompassing diagnosis of airway inflammation with significant variability in presentation and response. Advances in molecular techniques and imaging have unraveled the delicate mechanistic tapestry responsible for the underlying inflammatory pathways in asthma. The elucidation of biomarkers and cellular components specific to these inflammatory pathways allowed for the categorization of asthma from generic phenotypes to more specific mechanistic endotypes, with two prominent subgroups emerging based on the level of Type 2 inflammation present - T2 high and T2 low (or non-T2). Sophisticated modeling and cluster analyses using a combination of clinical, physiologic, and biomarker parameters have permitted the identification of subendotypes within the broader T2 umbrella. This mechanistic-driven classification schema for asthma has dramatically altered the landscape of asthma management with the discovery and approval of targeted biologic therapies and has ushered in a new era of personalized precision medicine in asthma.
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Affiliation(s)
- Amanda P McIntyre
- Division of Allergy, Pulmonary & Critical Care, Department of Medicine, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA
| | - Ravi K Viswanathan
- Division of Allergy, Pulmonary & Critical Care, Department of Medicine, University of Wisconsin School of Medicine & Public Health, Madison, WI, USA.
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15
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Cardoso‐Vigueros C, von Blumenthal T, Rückert B, Rinaldi AO, Tan G, Dreher A, Radzikowska U, Menz G, Schmid‐Grendelmeier P, Akdis CA, Sokolowska M. Leukocyte redistribution as immunological biomarker of corticosteroid resistance in severe asthma. Clin Exp Allergy 2022; 52:1183-1194. [PMID: 35305052 PMCID: PMC9790739 DOI: 10.1111/cea.14128] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 02/15/2022] [Accepted: 03/07/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND Earlier studies have suggested that the leukocyte redistribution can be considered as an immunological marker of the clinical response to corticosteroids (CS), representing an easy measurable potential biomarker in severe asthma. OBJECTIVE The aim of this study was to determinate the utility of the leukocyte redistribution as a biomarker of disease heterogeneity in patients with severe asthma and as a bioindicator of potential CS resistance. METHODS We developed an unbiased clustering approach based on the clinical data and the flow cytometry results of peripheral blood leukocyte phenotypes of 142 patients with severe asthma before and after systemic CS administration. RESULTS Based on the differences in the blood count eosinophils, neutrophils and lymphocytes, together with the flow cytometry measurements of basic T cell, B cell and NK cell subpopulations before and after systemic CS administration, we identified two severe asthma clusters, which differed in the cell frequencies, response to CS and atopy status. Patients in cluster 1 had higher frequency of blood eosinophils at baseline, were sensitized to less allergens and had better steroid responsiveness, measured as the pronounced leukocyte redistribution after the administration of systemic CS. Patients in cluster 2 were determined by the higher frequency of B-cells and stronger IgE sensitization status to the multiple allergens. They also displayed higher steroid resistance, as the clinical correlate for the lower leukocyte redistribution after administration of systemic CS. CONCLUSION The flow cytometry-based profiling of the basic populations of immune cells in the blood and its analysis before and after systemic corticosteroid administration could improve personalized treatment approaches in patients with severe asthma.
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Affiliation(s)
| | - Tobias von Blumenthal
- Swiss Institute of Allergy and Asthma Research (SIAF)University of ZurichDavosSwitzerland
| | - Beate Rückert
- Swiss Institute of Allergy and Asthma Research (SIAF)University of ZurichDavosSwitzerland
| | - Arturo O. Rinaldi
- Swiss Institute of Allergy and Asthma Research (SIAF)University of ZurichDavosSwitzerland
| | - Ge Tan
- Swiss Institute of Allergy and Asthma Research (SIAF)University of ZurichDavosSwitzerland
| | - Anita Dreher
- Christine Kühne – Center for Allergy Research and Education (CK‐CARE)DavosSwitzerland
| | - Urszula Radzikowska
- Swiss Institute of Allergy and Asthma Research (SIAF)University of ZurichDavosSwitzerland,Christine Kühne – Center for Allergy Research and Education (CK‐CARE)DavosSwitzerland
| | - Günter Menz
- Hochgebirgsklinik Davos (HGK)DavosSwitzerland
| | - Peter Schmid‐Grendelmeier
- Department of AllergyUniversity Hospital of ZurichZurichSwitzerland,Christine Kühne – Center for Allergy Research and Education (CK‐CARE)DavosSwitzerland
| | - Cezmi A. Akdis
- Swiss Institute of Allergy and Asthma Research (SIAF)University of ZurichDavosSwitzerland,Christine Kühne – Center for Allergy Research and Education (CK‐CARE)DavosSwitzerland
| | - Milena Sokolowska
- Swiss Institute of Allergy and Asthma Research (SIAF)University of ZurichDavosSwitzerland,Christine Kühne – Center for Allergy Research and Education (CK‐CARE)DavosSwitzerland
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16
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Sesé L, Mahay G, Barnig C, Guibert N, Leroy S, Guilleminault L. [Markers of severity and predictors of response to treatment in severe asthma]. Rev Mal Respir 2022; 39:740-757. [PMID: 36115752 DOI: 10.1016/j.rmr.2022.08.009] [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: 03/28/2022] [Accepted: 08/19/2022] [Indexed: 10/14/2022]
Abstract
Asthma is a multifactorial disease with complex pathophysiology. Knowledge of its immunopathology and inflammatory mechanisms is progressing and has led to the development over recent years of increasingly targeted therapeutic strategies. The objective of this review is to pinpoint the different predictive markers of asthma severity and therapeutic response. Obesity, nasal polyposis, gastroesophageal reflux disease and intolerance to aspirin have all been considered as clinical markers associated with asthma severity, as have functional markers such as bronchial obstruction, low FEV1, small daily variations in FEV1, and high FeNO. While sinonasal polyposis and allergic comorbidities are associated with better response to omalizumab, nasal polyposis or long-term systemic steroid use are associated with better response to antibodies targeting the IL5 pathway. Elevated total IgE concentrations and eosinophil counts are classic biological markers regularly found in severe asthma. Blood eosinophils are predictive biomarkers of response to anti-IgE, anti-IL5, anti-IL5R and anti-IL4R biotherapies. Dupilumab is particularly effective in a subgroup of patients with marked type 2 inflammation (long-term systemic corticosteroid therapy, eosinophilia≥150/μl or FENO>20 ppb). Chest imaging may help to identify severe patients by seeking out bronchial wall thickening and bronchial dilation. Study of the patient's environment is crucial insofar as exposure to tobacco, dust mites and molds, as well as outdoor and indoor air pollutants (cleaning products), can trigger asthma exacerbation. Wider and more systematic use of markers of severity or response to treatment could foster increasingly targeted and tailored approaches to severe asthma.
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Affiliation(s)
- L Sesé
- AP-HP, service de physiologie, hôpital Avicenne, Bobigny, France
| | - G Mahay
- Service de pneumologie, oncologie thoracique et soins intensifs respiratoires, CHU Rouen, Rouen, France
| | - C Barnig
- INSERM, EFS BFC, LabEx LipSTIC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, University Bourgogne Franche-Comté, Besançon, France; Service de pneumologie, oncologie thoracique et allergologie respiratoire, CHRU Besançon, Besançon, France
| | - N Guibert
- AP-HP, service de physiologie, hôpital Avicenne, Bobigny, France
| | - S Leroy
- Université Côte d'Azur, Centre Hospitalier Universitaire de Nice, CNRS UMR 7275-FHU OncoAge, service de pneumologie oncologie thoracique et soins intensifs respiratoires, CHU de Nice, hôpital Pasteur, Nice, France
| | - L Guilleminault
- AP-HP, service de physiologie, hôpital Avicenne, Bobigny, France; Institut Toulousain des maladies infectieuses et inflammatoires (Infinity) inserm UMR1291-CNRS UMR5051-université Toulouse III, CRISALIS F-CRIN, Toulouse, France.
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17
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Subtypes of Asthma and Cold Weather-Related Respiratory Symptoms. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19148790. [PMID: 35886638 PMCID: PMC9316622 DOI: 10.3390/ijerph19148790] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 07/05/2022] [Accepted: 07/06/2022] [Indexed: 12/10/2022]
Abstract
(1) Poor asthma control increases the occurrence of cold weather-related symptoms among adult asthmatics. We assessed whether the subtype of asthma, taking into account the severity of the asthma, plays a role in these symptoms. (2) We conducted a population-based cross-sectional study of 1995 adult asthmatics (response rate 40.4%) living in northern Finland using a questionnaire that asked about cold weather-related respiratory symptoms including (1) shortness of breath, (2) prolonged cough, (3) wheezing, (4) phlegm production, and (5) chest pain, as well as questions related to the subtype of asthma. For women, the subtypes identified using latent class analysis were: (1) Controlled, mild asthma, (2) Partly controlled, moderate asthma, (3) Uncontrolled, unknown severity, and (4) Uncontrolled, severe asthma, and for men: (1) Controlled, mild asthma, (2) Uncontrolled, unknown severity, and (3) Partly controlled, severe asthma. (3) According to the subtypes of asthma, more severe and more poorly controlled asthma were related to the increased prevalence of cold weather-related respiratory symptoms when compared with those with mild, controlled asthma. This trend was especially clear for wheezing and chest pain. For example, in men, the adjusted prevalence ratio of wheezing was 1.55 (95% CI 1.09–2.19) in uncontrolled asthma with unknown severity and 1.84 (95% CI 1.26–2.71) in partly controlled severe asthma compared with controlled, mild asthma. (4) Our study provides evidence for the influence of subtypes of asthma on experiencing cold weather-related respiratory symptoms. Both women and men reported more cold weather-related symptoms when their asthma was more severe and uncontrolled compared with those who had mild and well-controlled asthma.
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18
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Ross MK, Eckel SP, Bui AAT, Gilliland FD. Asthma clustering methods: a literature-informed application to the children's health study data. J Asthma 2022; 59:1305-1318. [PMID: 33926348 PMCID: PMC8664642 DOI: 10.1080/02770903.2021.1923738] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 03/16/2021] [Accepted: 04/25/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVE The heterogeneity of asthma has inspired widespread application of statistical clustering algorithms to a variety of datasets for identification of potentially clinically meaningful phenotypes. There has not been a standardized data analysis approach for asthma clustering, which can affect reproducibility and clinical translation of results. Our objective was to identify common and effective data analysis practices in the asthma clustering literature and apply them to data from a Southern California population-based cohort of schoolchildren with asthma. METHODS As of January 1, 2020, we reviewed key statistical elements of 77 asthma clustering studies. Guided by the literature, we used 12 input variables and three clustering methods (hierarchical clustering, k-medoids, and latent class analysis) to identify clusters in 598 schoolchildren with asthma from the Southern California Children's Health Study (CHS). RESULTS Clusters of children identified by latent class analysis were characterized by exhaled nitric oxide, FEV1/FVC, FEV1 percent predicted, asthma control and allergy score; and were predictive of control at two year follow up. Clusters from the other two methods were less clinically remarkable, primarily differentiated by sex and race/ethnicity and less predictive of asthma control over time. CONCLUSION Upon review of the asthma phenotyping literature, common approaches of data clustering emerged. When applying these elements to the Children's Health Study data, latent class analysis clusters-represented by exhaled nitric oxide and spirometry measures-had clinical relevance over time.
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Affiliation(s)
- Mindy K. Ross
- Pediatrics, Pediatric Pulmonology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Sandrah P. Eckel
- Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Alex A. T. Bui
- Radiology, University of California, Los Angeles, Los Angeles, CA, USA
| | - Frank D. Gilliland
- Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
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Son JH, Park JS, Lee JU, Kim MK, Min SA, Park CS, Chang HS. A genome-wide association study on frequent exacerbation of asthma depending on smoking status. Respir Med 2022; 199:106877. [DOI: 10.1016/j.rmed.2022.106877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 04/13/2022] [Accepted: 05/08/2022] [Indexed: 10/18/2022]
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Baek EJ, Jung HU, Ha TW, Kim DJ, Lim JE, Kim HK, Kang JO, Oh B. Genome-Wide Interaction Study of Late-Onset Asthma With Seven Environmental Factors Using a Structured Linear Mixed Model in Europeans. Front Genet 2022; 13:765502. [PMID: 35432474 PMCID: PMC9005993 DOI: 10.3389/fgene.2022.765502] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 02/28/2022] [Indexed: 11/30/2022] Open
Abstract
Asthma is among the most common chronic diseases worldwide, creating a substantial healthcare burden. In late-onset asthma, there are wide global differences in asthma prevalence and low genetic heritability. It has been suggested as evidence for genetic susceptibility to asthma triggered by exposure to multiple environmental factors. Very few genome-wide interaction studies have identified gene-environment (G×E) interaction loci for asthma in adults. We evaluated genetic loci for late-onset asthma showing G×E interactions with multiple environmental factors, including alcohol intake, body mass index, insomnia, physical activity, mental status, sedentary behavior, and socioeconomic status. In gene-by-single environment interactions, we found no genome-wide significant single-nucleotide polymorphisms. However, in the gene-by-multi-environment interaction study, we identified three novel and genome-wide significant single-nucleotide polymorphisms: rs117996675, rs345749, and rs17704680. Bayes factor analysis suggested that for rs117996675 and rs17704680, body mass index is the most relevant environmental factor; for rs345749, insomnia and alcohol intake frequency are the most relevant factors in the G×E interactions of late-onset asthma. Functional annotations implicate the role of these three novel loci in regulating the immune system. In addition, the annotation for rs117996675 supports the body mass index as the most relevant environmental factor, as evidenced by the Bayes factor value. Our findings help to understand the role of the immune system in asthma and the role of environmental factors in late-onset asthma through G×E interactions. Ultimately, the enhanced understanding of asthma would contribute to better precision treatment depending on personal genetic and environmental information.
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Affiliation(s)
- Eun Ju Baek
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea
| | - Hae Un Jung
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea
| | - Tae-Woong Ha
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea
| | - Dong Jun Kim
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea
| | - Ji Eun Lim
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Korea
| | - Han Kyul Kim
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Korea
| | - Ji-One Kang
- Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Korea
| | - Bermseok Oh
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea.,Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Korea
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Benson VS, Hartl S, Barnes N, Galwey N, Van Dyke MK, Kwon N. Blood eosinophil counts in the general population and airways disease: a comprehensive review and meta-analysis. Eur Respir J 2022; 59:2004590. [PMID: 34172466 PMCID: PMC8756293 DOI: 10.1183/13993003.04590-2020] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 05/26/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND The clinical context for using blood eosinophil (EOS) counts as treatment-response biomarkers in asthma and COPD requires better understanding of EOS distributions and ranges. We describe EOS distributions and ranges published in asthma, COPD, control (non-asthma/COPD) and general populations. METHODS We conducted a comprehensive literature review and meta-analysis of observational studies (January 2008 to November 2018) that included EOS counts in asthma, severe asthma, COPD, control and general populations. Excluded studies had total sample sizes <200, EOS as inclusion criterion, hospitalised population only and exclusively paediatric participants. RESULTS Overall, 91 eligible studies were identified, most had total-population-level data available: asthma (39 studies), severe asthma (12 studies), COPD (23 studies), control (seven studies) and general populations (14 studies); some articles reported data for multiple populations. Reported EOS distributions were right-skewed (seven studies). Reported median EOS counts ranged from 157-280 cells·µL-1 (asthma, 22 studies); 200-400 cells·µL-1 (severe asthma, eight studies); 150-183 cells·µL-1 (COPD, six studies); and 100-160 cells·µL-1 (controls, three studies); and 100-200 cells·µL-1 (general populations, six studies). The meta-analysis showed that observed variability was mostly between studies rather than within studies. Factors reportedly associated with higher blood EOS counts included current smoking, positive skin-prick test, elevated total IgE, comorbid allergic rhinitis, age ≤18 years, male sex, spirometric asthma/COPD diagnosis, metabolic syndrome and adiposity. CONCLUSION EOS distribution and range varied by study population, and were affected by clinical factors including age, smoking history and comorbidities, which, regardless of severity, should be considered during treatment decision-making.
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Affiliation(s)
- Victoria S Benson
- Epidemiology, Value Evidence and Outcomes (VEO), Global Medical R&D, GlaxoSmithKline, Brentford, UK
| | - Sylvia Hartl
- Dept of Respiratory and Critical Care Medicine and Ludwig Boltzmann Institute for Lung Health, Clinic Penzing, WiGev and Sigmund Freud University, Medical School, Vienna, Austria
| | - Neil Barnes
- Respiratory Therapy Area, GlaxoSmithKline, Brentford, UK
- William Harvey Institute, Barts and The London School of Medicine and Dentistry, London, UK
| | | | - Melissa K Van Dyke
- Epidemiology, Value Evidence and Outcomes (VEO), Global Medical R&D, GlaxoSmithKline, Upper Providence, PA, USA
| | - Namhee Kwon
- Respiratory Research and Development, GlaxoSmithKline, Brentford, UK
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22
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Calco GN, Proskocil BJ, Jacoby DB, Fryer AD, Nie Z. Metformin prevents airway hyperreactivity in rats with dietary obesity. Am J Physiol Lung Cell Mol Physiol 2021; 321:L1105-L1118. [PMID: 34668415 PMCID: PMC8715020 DOI: 10.1152/ajplung.00202.2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 09/15/2021] [Accepted: 10/15/2021] [Indexed: 11/22/2022] Open
Abstract
Increased insulin is associated with obesity-related airway hyperreactivity and asthma. We tested whether the use of metformin, an antidiabetic drug used to reduce insulin resistance, can reduce circulating insulin, thereby preventing airway hyperreactivity in rats with dietary obesity. Male and female rats were fed a high- or low-fat diet for 5 wk. Some male rats were simultaneously treated with metformin (100 mg/kg orally). In separate experiments, after 5 wk of a high-fat diet, some rats were switched to a low-fat diet, whereas others continued a high-fat diet for an additional 5 wk. Bronchoconstriction and bradycardia in response to bilateral electrical vagus nerve stimulation or to inhaled methacholine were measured in anesthetized and vagotomized rats. Body weight, body fat, caloric intake, fasting glucose, and insulin were measured. Vagally induced bronchoconstriction was potentiated only in male rats on a high-fat diet. Males gained more body weight, body fat, and had increased levels of fasting insulin compared with females. Metformin prevented development of vagally induced airway hyperreactivity in male rats on high-fat diet, in addition to inhibiting weight gain, fat gain, and increased insulin. In contrast, switching rats to a low-fat diet for 5 wk reduced body weight and body fat, but it did not reverse fasting glucose, fasting insulin, or potentiation of vagally induced airway hyperreactivity. These data suggest that medications that target insulin may be effective treatment for obesity-related asthma.
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Affiliation(s)
- Gina N Calco
- Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon
| | - Becky J Proskocil
- Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon
| | - David B Jacoby
- Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon
| | - Allison D Fryer
- Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon
| | - Zhenying Nie
- Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon
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Li Y, Wang C, Peng M. Aging Immune System and Its Correlation With Liability to Severe Lung Complications. Front Public Health 2021; 9:735151. [PMID: 34888279 PMCID: PMC8650611 DOI: 10.3389/fpubh.2021.735151] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 10/08/2021] [Indexed: 12/22/2022] Open
Abstract
Aging is considered to be a decline in physical and physiological events that extensively affect the body's immunity, and is linked with deterioration in both innate and adaptive immune responses. The immune system exhibits profound age-associated variations, known as immunosenescence, comprising a significantly low production of B and T lymphocytes in bone marrow and thymus, a decreased function of mature lymphocytes in secondary lymphoid tissues, a decrease in the synthesis of fresh naïve T cells, and reduced activation of T cells. Elderly individuals face a greater risk for many diseases particularly respiratory diseases due to their poor response to immune challenges as vigorously as the young. The current review explored the aging immune system, highlight the mortality rates of severe lung complications, such as pneumonia, COVID-19, asthma, COPD, lung cancer, IPF, and acute lung injury, and their correlation with aging immunity. This study can be helpful in better understanding the pathophysiology of aging, immune responses, and developing new approaches to improve the average age of the elderly population.
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Affiliation(s)
- Yongtao Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Chengfei Wang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Meilian Peng
- Department of Maternity, Zhejiang Provincial People's Hospital, Hangzhou, China
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24
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Singh T, Bello B, Jeebhay MF. Characterizing Inflammatory Cell Asthma Associated Phenotypes in Dental Health Workers Using Cytokine Profiling. FRONTIERS IN ALLERGY 2021; 2:747591. [PMID: 35387066 PMCID: PMC8974759 DOI: 10.3389/falgy.2021.747591] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 10/11/2021] [Indexed: 11/24/2022] Open
Abstract
Cytokines elicit a pro-inflammatory response by modifying the airway microenvironment in patients with acute or chronic asthma. The expression pattern of several distinct cytokines could be a useful discriminator in asthma. This study aimed to identify asthma subject groupings based on common inflammatory patterns and to determine the relationship between these identified patterns and asthma-associated clinical indices. A sub-group of 76 dental healthcare workers (HCWs) identified from a larger cross-sectional study of 454 dental HCWs in five dental institutions were evaluated further. A self-administered questionnaire elicited the health and employment history of subjects. Sera were analyzed for atopic status, latex sensitization, and 12 cytokines (IL-1β, 3, 4, 5, 6, 7, 8, 10, 12p70, eotaxin, GM-CSF, TNF-α). Pre and post-bronchodilator spirometry was performed on all HCWs. Data clustering and factor analysis were used to identify inflammatory cluster patterns of cytokines. Associations between the cytokine cluster groupings and relevant asthma-associated clinical indices were determined using multivariate logistic regression. The classification of asthma subtype based on cytokine patterns demonstrated both eosinophilic and neutrophilic inflammatory responses. Four phenotypically distinct subgroups relating to the severity of inflammation (acute or chronic) of the cell types were identified. Cytokine determinants for the neutrophilic subtype included IL-1β, 6, 8, 10, 12p70, and TNF-α whereas for the eosinophilic subtype these included IL-3, 4, 5, 7, eotaxin, and GM-CSF. The multivariate models showed a significant association between work-related chest symptoms and all four inflammatory patterns. However, stronger associations were observed for the acute neutrophilic (OR = 6.00, p < 0.05) compared to acute and chronic eosinophilic responses (OR = 4.30, p < 0.05; OR = 4.93, p < 0.05), respectively. Subjects with airway obstruction were more likely to have a mixed cellular infiltrate. The odds of work-exacerbated asthma were increased in acute or chronic eosinophilia (OR = 7.75 and 8.12; p < 0.05), respectively as well as with acute neutrophilia (OR = 6) sub-type. This study demonstrated that neutrophilic inflammatory cell asthma phenotypes coexist with eosinophilic inflammatory phenotypes suggesting a possible dual pathway for asthma in dental health workers, probably due to mixed exposures to high molecular weight (e.g., latex) and low molecular weight (e.g., acrylates) agents.
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Affiliation(s)
- Tanusha Singh
- Immunology & Microbiology, National Institute for Occupational Health, National Health Laboratory Service, Johannesburg, South Africa
- Department of Environmental Health, Faculty of Health Sciences, University of Johannesburg, Johannesburg, South Africa
- Department of Clinical Microbiology and Infectious Diseases, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa
- *Correspondence: Tanusha Singh
| | - Braimoh Bello
- Immunology & Microbiology Department, Centre for Statistical Analysis and Research, Johannesburg, South Africa
| | - Mohamed F. Jeebhay
- Division of Occupational Medicine and Centre for Environmental & Occupational Health Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
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25
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Andersén H, Ilmarinen P, Honkamäki J, Tuomisto LE, Hisinger-Mölkänen H, Backman H, Lundbäck B, Rönmark E, Lehtimäki L, Sovijärvi A, Piirilä P, Kankaanranta H. Influence of Childhood Exposure to a Farming Environment on Age at Asthma Diagnosis in a Population-Based Study. J Asthma Allergy 2021; 14:1081-1091. [PMID: 34522104 PMCID: PMC8434911 DOI: 10.2147/jaa.s323504] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Accepted: 08/21/2021] [Indexed: 11/26/2022] Open
Abstract
Purpose Asthma is a heterogeneous disease, and factors associated with different asthma phenotypes are poorly understood. Given the higher prevalence of farming exposure and late diagnosis of asthma in more rural Western Finland as compared with the capital of Helsinki, we investigated the relationship between childhood farming environment and age at asthma diagnosis. Methods A cross-sectional population-based study was carried out with subjects aged 20–69 years in Western Finland. The response rate was 52.5%. We included 3864 participants, 416 of whom had physician-diagnosed asthma at a known age and with data on the childhood environment. The main finding was confirmed in a similar sample from Helsinki. Participants were classified as follows with respect to asthma diagnosis: early diagnosis (0–11 years), intermediate diagnosis (12–39 years), and late diagnosis (40–69 years). Results The prevalence of asthma was similar both without and with childhood exposure to a farming environment (11.7% vs 11.3%). Allergic rhinitis, family history of asthma, ex-smoker, occupational exposure, and BMI ≥ 30 kg/m2 were associated with a higher likelihood of asthma. Childhood exposure to a farming environment did not increase the odds of having asthma (aOR, 1.10; 95% CI, 0.87–1.40). It did increase the odds of late diagnosis (aOR, 2.30; 95% CI, 1.12–4.69), but the odds were lower for early (aOR, 0.49; 95% CI, 0.30–0.80) and intermediate diagnosis of asthma (aOR, 0.75; 95% CI, 0.47–1.18). Conclusion Odds were lower for early diagnosis of asthma and higher for late diagnosis of asthma in a childhood farming environment. This suggests a new hypothesis concerning the etiology of asthma when it is diagnosed late. ![]()
Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/BdY2eA86hV8
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Affiliation(s)
- Heidi Andersén
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Pinja Ilmarinen
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Jasmin Honkamäki
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Leena E Tuomisto
- Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Etelä-Pohjanmaa, Finland
| | | | - Helena Backman
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Norrbotten, Sweden
| | - Bo Lundbäck
- Department of Internal Medicine, Krefting Research Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Västra Götaland, Sweden
| | - Eva Rönmark
- Department of Public Health and Clinical Medicine, Umeå University, Umeå, Norrbotten, Sweden
| | - Lauri Lehtimäki
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
| | - Anssi Sovijärvi
- Faculty of Medicine, University of Helsinki, Helsinki, Uusimaa, Finland
| | - Päivi Piirilä
- Faculty of Medicine, University of Helsinki, Helsinki, Uusimaa, Finland
| | - Hannu Kankaanranta
- Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
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Al-Ahmad M, Nurkic J, Othman Y, Jusufovic E, Maher A. Severe asthma in Kuwait population: Phenotype-based approach. Respir Med 2021; 187:106586. [PMID: 34474336 DOI: 10.1016/j.rmed.2021.106586] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 08/23/2021] [Accepted: 08/24/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND There is increasing recognition of marked phenotypic heterogeneity within severe asthma patients. METHODS Severe asthma patients on GINA step 4 or 5 treatment, followed up at Al-Rashed Allergy center Kuwait, were evaluated for: demographics (gender, age, age of asthma onset), comorbidities (allergic rhinitis (AR), chronic rhinosinusitis (CRS), chronic rhinosinusitis with nasal polyposis (CRSwNP), obesity), blood biomarkers (total serum Immunoglobulin E (IgE), peripheral eosinophils), and sensitization to inhalants allergens. RESULTS A total of 169 patients were candidates for biological treatment. Patients were divided in two groups based on level of total IgE as a "low" group with IgE<160 IU/ml (n = 55) and "high" group with IgE≥ 160 IU/ml (n = 114). Both groups were further divided in subgroups, "low" and "high", based on absolute number of eosinophils (Eos) in peripheral blood with <300 cells/μl or ≥ 300 cells/μl. Only 10% of patients were in low IgE/low Eos while majority (46%) were in the high IgE/high Eos group. Mean age of patients was 44.1 year with domination of females (n = 123). Majority of patients were obese. AR, CRS and CRSwNP were more common in group with IgE ≥160 IU/ml, while CRS and CRSwNP in group with Eos ≥300 cells/μl. CONCLUSION The majority of severe asthma patients in Kuwait are obese females with adult-onset asthma (>18 years of age) who were allergic with comorbid conditions including AR, CRS and CRSwNP, which correlates well with the level of Eos.
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Affiliation(s)
- Mona Al-Ahmad
- Microbiology Department, Faculty of Medicine, Kuwait University, Kuwait; Al-Rashed Allergy Center, Ministry of Health, Kuwait.
| | | | | | - Edin Jusufovic
- Medical Faculty, University of Tuzla, Tuzla, Bosnia and Herzegovina.
| | - Ahmed Maher
- Al-Rashed Allergy Center, Ministry of Health, Kuwait.
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27
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Kirenga B, Chakaya J, Yimer G, Nyale G, Haile T, Muttamba W, Mugenyi L, Katagira W, Worodria W, Aanyu-Tukamuhebwa H, Lugogo N, Joloba M, Bekele A, Makumbi F, Green C, de Jong C, Kamya M, van der Molen T. Phenotypic characteristics and asthma severity in an East African cohort of adults and adolescents with asthma: findings from the African severe asthma project. BMJ Open Respir Res 2021; 7:7/1/e000484. [PMID: 32054641 PMCID: PMC7047479 DOI: 10.1136/bmjresp-2019-000484] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 01/16/2020] [Accepted: 01/23/2020] [Indexed: 12/20/2022] Open
Abstract
RATIONALE The relationship between clinical and biomarker characteristics of asthma and its severity in Africa is not well known. METHODS Using the Expert Panel Report 3, we assessed for asthma severity and its relationship with key phenotypic characteristics in Uganda, Kenya and Ethiopia. The characteristics included adult onset asthma, family history of asthma, exposures (smoking and biomass), comorbidities (HIV, hypertension, obesity, tuberculosis (TB), rhinosinusitis, gastro-oesophageal disease (GERD) and biomarkers (fractional exhaled nitric oxide (FeNO), skin prick test (SPT) and blood eosinophils). We compared these characteristics on the basis of severity and fitted a multivariable logistic regression model to assess the independent association of these characteristics with asthma severity. RESULTS A total of 1671 patients were enrolled, 70.7% women, with median age of 40 years. The prevalence of intermittent, mild persistent, moderate persistent and severe persistent asthma was 2.9%, 19.9%, 42.6% and 34.6%, respectively. Only 14% were on inhaled corticosteroids (ICS). Patients with severe persistent asthma had a higher rate of adult onset asthma, smoking, HIV, history of TB, FeNO and absolute eosinophil count but lower rates of GERD, rhinosinusitis and SPT positivity. In the multivariate model, Ethiopian site and a history of GERD remained associated with asthma severity. DISCUSSION The majority of patients in this cohort presented with moderate to severe persistent asthma and the use of ICS was very low. Improving access to ICS and other inhaled therapies could greatly reduce asthma morbidity in Africa.
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Affiliation(s)
- Bruce Kirenga
- College of Health Sciences, Makerere University, Kampala, Uganda
| | - Jeremiah Chakaya
- Kenya Association of Physicians against TB and Lung Diseases (KAPTLD), Nairobi, Kenya
| | - Getnet Yimer
- College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - George Nyale
- Department of Medicine, Kenyatta National Hospital, Nairobi, Kenya
| | - Tewodros Haile
- College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Winters Muttamba
- Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda
| | - Levicatus Mugenyi
- Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda
| | - Winceslaus Katagira
- Lung Institute, Makerere University College of Health Sciences, Kampala, Uganda
| | - William Worodria
- Mulago National Referral Hospital, Uganda Ministry of Health, Kampala, Uganda
| | | | - Njira Lugogo
- Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Moses Joloba
- College of Health Sciences, Makerere University, Kampala, Uganda
| | - Amsalu Bekele
- College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Fred Makumbi
- College of Health Sciences, Makerere University, Kampala, Uganda
| | - Cindy Green
- Medicine, Duke University School of Medicine, Durham, North Carolina, USA
| | - Corina de Jong
- Department of General Practice, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Moses Kamya
- College of Health Sciences, Makerere University, Kampala, Uganda
| | - Thys van der Molen
- University Medical Center Groningen (UMCG), University of Groningen, Groningen, Netherlands
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Raherison-Semjen C, Parrat E, Nocent-Eijnani C, Mangiapan G, Prudhomme A, Oster JP, Aperre de Vecchi C, Maurer C, Debieuvre D, Portel L. FASE-CPHG Study: identification of asthma phenotypes in the French Severe Asthma Study using cluster analysis. Respir Res 2021; 22:136. [PMID: 33947403 PMCID: PMC8097842 DOI: 10.1186/s12931-021-01723-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 04/16/2021] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND In France, data regarding epidemiology and management of severe asthma are scarce. The objective of this study was to describe asthma phenotypes using a cluster analysis in severe asthmatics recruited in a real world setting. METHODS The study design was prospective, observational and multicentric. The patients included were adults with severe asthma (GINA 4-5) followed-up in French Non Academic Hospital between May 2016 and June 2017. One hundred and seven physicians included 1502 patients. Both sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis on a population of 1424 patients. RESULTS Five clusters were identified: cluster 1 (n = 690, 47%) called early onset allergic asthma (47.5% with asthma before 12 years), cluster 2 (n = 153, 10.5%): obese asthma (63.5% with BMI > 30 kg/m2), cluster 3 (n = 299, 20.4%): late-onset asthma with severe obstructive syndrome (89% without atopy), cluster 4 (n = 143, 9.8%): eosinophilic asthma (51.7% had more than 500 eosinophils/mm3), and cluster 5 (n = 139, 9.5%): aspirin sensitivity asthma (63% had severe asthma attacks). CONCLUSIONS In our population of adults with severe asthma followed by pulmonologists, five distinct phenotypes were identified and are quite different from those mentioned in previous studies.
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Affiliation(s)
- Chantal Raherison-Semjen
- Groupe Hospitalier Sud, Hôpital Haut-Lévêque CHU Bordeaux, Pessac, France.
- INSERM U1219 Université de Bordeaux, Bordeaux, France.
| | - Eric Parrat
- Centre Hospitalier de Polynésie Française, Hôpital du Taaone, Papeete, French Polynesia
| | | | - Gilles Mangiapan
- Service de Pneumologie, Centre Hospitalier Intercommunal de Créteil, Créteil, France
| | - Anne Prudhomme
- Clinique Médicale et Cardiologique d'Aressy, Pau, France
| | | | | | | | - Didier Debieuvre
- Service de Pneumologie, Groupe Hospitalier de la Région Mulhouse Sud-Alsace, Hôpital Émile Muller, Mulhouse, France
| | - Laurent Portel
- Centre Hospitalier Robert Boulin de Libourne, Site Robert Boulin, Libourne, France
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29
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Hansen ESH, Hostrup M, Rasmusen HK, Hellsten Y, Backer V. Effect of aerobic exercise training on asthma control in postmenopausal women (the ATOM-study): protocol for an outcome assessor, randomised controlled trial. BMJ Open 2021; 11:e049477. [PMID: 33888532 PMCID: PMC8070869 DOI: 10.1136/bmjopen-2021-049477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
INTRODUCTION Late-onset asthma in postmenopausal women is characterised by poor disease control with daily symptoms and reduced quality of life despite treatment with inhaled antiasthma therapies. These patients represent a phenotype that is characterised by low eosinophilic airway inflammation, severe symptoms, moderate obesity and poor response to inhaled antiasthma therapies, which highlights the need of identification of alternative treatment strategies. Thus, this study aims to evaluate if regular high-intensity aerobic exercise improves symptom control in postmenopausal women with asthma. METHODS AND ANALYSIS This is an ongoing randomised controlled trial planning to enrol 40 postmenopausal women with late-onset asthma. Participants are randomised 1:1 either to supervised exercise training (spinning) three times per week for 12 weeks or to usual care. The primary outcome is change from baseline to follow-up in the Asthma Control Questionnaire. Secondary outcomes are changes in markers of systemic inflammation, airway inflammation, body composition and right ventricular function of the heart. ETHICS AND DISSEMINATION The study is approved by the Ethics Committee in the Capital Region of Denmark nr. H-18028966 and the Danish Data Protection Agency nr. VD-2019-59. The methods used in the study are well known and have a low risk with a chance of substantial improvement in disease control in this patient group. Results are planned to be published in an international peer-reviewed medical journal regardless of outcome. TRIAL REGISTRATION NUMBER NCT03747211.
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Affiliation(s)
- Erik Sören Halvard Hansen
- Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Morten Hostrup
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
| | - Hanne Kruuse Rasmusen
- Department of Cardiology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark
| | - Ylva Hellsten
- Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark
| | - Vibeke Backer
- Centre for Physical Activity Research, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
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30
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Molecular analysis of phenotypic interactions of asthma. Cytokine 2021; 143:155524. [PMID: 33849767 DOI: 10.1016/j.cyto.2021.155524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 03/26/2021] [Accepted: 03/28/2021] [Indexed: 11/22/2022]
Abstract
INTRODUCTION Asthma is a heterogeneous disease characterized by multiples respiratory symptoms; this is a polygenic entity that involves a complex interaction of environmental factors and inherent to the individual. To understand the development of asthma, some phenotypes have been proposed. OBJECTIVE This work's purpose was to explore different molecules related to asthma development and to define each phenotype's specific characteristics. MATERIAL AND METHODS 96 adult patients diagnosed with asthma before any treatment were enrolled in the protocol. Spirometric parameters, circulating leukocytes, serum IgE, body mass index, exhaled nitric oxide (FENO), and leukotrienes (LTB4) in urine were determined in each patient. The presence of asthma phenotypes proposed by the Global Initiative for Asthma (GINA) were explored: A) Allergic asthma, B) Non-allergic asthma, C) Late-onset asthma, D) Asthma with persistent airflow limitation, and E) Asthma with overweight and obesity. RESULTS In the cohort analyzed, we found four of phenotypes proposed by GINA; however, these phenotypes overlapped, due to this, 4 groups were integrated with allergic, non-allergic and obese patients, which were the main phenotypes. The main overlap was that of patients not-obese allergic, and was characterized by earlier onset, elevated levels of IgE, LTB4 and inflammasome related cytokines. Non-allergic patients had a significant association between interleukin (IL)-18 and IL-18 binding protein (BP) with narrow ratio between these cytokines. Finally, LTB4 had remarkable capacity to discriminate between allergic and not allergic patients. CONCLUSIONS Asthmatic phenotypes exist as interrelated characteristics and not as discrete entities. High levels of leukotrienes and IgE are hallmarks in the allergic phenotype of asthma.
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A Systematic Review of Asthma Phenotypes Derived by Data-Driven Methods. Diagnostics (Basel) 2021; 11:diagnostics11040644. [PMID: 33918233 PMCID: PMC8066118 DOI: 10.3390/diagnostics11040644] [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: 03/22/2021] [Revised: 03/30/2021] [Accepted: 03/31/2021] [Indexed: 12/13/2022] Open
Abstract
Classification of asthma phenotypes has a potentially relevant impact on the clinical management of the disease. Methods for statistical classification without a priori assumptions (data-driven approaches) may contribute to developing a better comprehension of trait heterogeneity in disease phenotyping. This study aimed to summarize and characterize asthma phenotypes derived by data-driven methods. We performed a systematic review using three scientific databases, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. We included studies reporting adult asthma phenotypes derived by data-driven methods using easily accessible variables in clinical practice. Two independent reviewers assessed studies. The methodological quality of included primary studies was assessed using the ROBINS-I tool. We retrieved 7446 results and included 68 studies of which 65% (n = 44) used data from specialized centers and 53% (n = 36) evaluated the consistency of phenotypes. The most frequent data-driven method was hierarchical cluster analysis (n = 19). Three major asthma-related domains of easily measurable clinical variables used for phenotyping were identified: personal (n = 49), functional (n = 48) and clinical (n = 47). The identified asthma phenotypes varied according to the sample’s characteristics, variables included in the model, and data availability. Overall, the most frequent phenotypes were related to atopy, gender, and severe disease. This review shows a large variability of asthma phenotypes derived from data-driven methods. Further research should include more population-based samples and assess longitudinal consistency of data-driven phenotypes.
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Eldaboussi S, Qabil A, Lotfi A, Awad A, Abdel Salam E, Alkhamis A, Abuelhassan UE. Saudi Arabian real-life experience with biologic therapy in severe asthma. Multidiscip Respir Med 2021; 16:807. [PMID: 35070293 PMCID: PMC8743612 DOI: 10.4081/mrm.2021.807] [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: 09/13/2021] [Accepted: 11/15/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Severe asthma (SA) is a common health problem associated with increased morbidity and mortality and high medical costs. Biological therapies have emerged in recent decades as promising treatment options for patients with high type 2 (T2) SA. This retrospective observational study from Saudi Arabia aimed to investigate the effects of additional biologics therapy on reducing oral corticosteroid (OCS) consumption, frequency of asthma exacerbations, improvement in lung function, and asthma control. METHODS This multicenter observational study enrolled a cohort of 97 patients from March 2019 to February 2021. Outcomes of anti-IgE, anti-IL5/IL5R, and anti-IL4R therapies in severe type 2 asthma were recorded and analyzed in terms of number of exacerbations (emergency visits or hospitalizations required), asthma symptoms, and use of oral corticosteroids, blood eosinophil count, asthma control according to GINA classification, and FEV1 before and during biologic therapy. RESULTS Ninety-seven patients were included in the analysis The mean age was 46.7±14.1 years, and 69.1% of them were female. The average duration of biological treatment was 16.4±6.8 months. At the time of data collection, the four biologic therapies reduced the exacerbation rate per year from 82/97 (84.5%) to 14/97 (14.4%) with a percent improvement of 83% from 2.9 per year in the year before biologic treatment to 1.6 per year (p<0.001). OCS was reduced from 75/97 (77.3%) to 10/97 (10.3%) for a percent improvement of 86.7%, and the average OCS dose decreased from 7.12 mg to 6.8 mg. Mean blood eosinophil count also decreased after biologic therapy from 750.5±498.5 to 188.0±122.4 cells/μl, most significant result achieved with benralizumab, and mean FEV1 improved from 59.0±12.9% to 76.0±10.2%, most significant result achieved with omalizumab. ll patients had uncontrolled asthma before biologics therapy, but asthma control improved by 91.8% after treatment. CONCLUSIONS Biologic as add-on therapy for high T2 SA was found to reduce asthma exacerbations, systemic glucocorticoid doses, and SA symptoms.
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Affiliation(s)
- Safwat Eldaboussi
- Almoosa Specialist Hospital, Alhasa, Saudi Arabia
- Department of Chest Diseases, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Ahmed Qabil
- Department of Chest Diseases, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
- Al Hayat National Hospital, Riyadh, Saudi Arabia
| | - Ahmed Lotfi
- Al Hayat National Hospital, Riyadh, Saudi Arabia
- Al Hayat National Hospital, Jizan, Saudi Arabia
| | - Amgad Awad
- Almoosa Specialist Hospital, Alhasa, Saudi Arabia
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
| | - Eman Abdel Salam
- Department of Internal Medicine, Faculty of Medicine, Al-Azhar University, Cairo, Egypt
- King Khaled Hospital, Hail, Saudi Arabia
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Quirce S, Heffler E, Nenasheva N, Demoly P, Menzies-Gow A, Moreira-Jorge A, Nissen F, Hanania NA. Revisiting Late-Onset Asthma: Clinical Characteristics and Association with Allergy. J Asthma Allergy 2020; 13:743-752. [PMID: 33408487 PMCID: PMC7781019 DOI: 10.2147/jaa.s282205] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 12/18/2020] [Indexed: 12/12/2022] Open
Abstract
The Global Initiative for Asthma (GINA) 2020 defines late-onset asthma (LOA) as one of the clinical phenotypes of asthma wherein patients, particularly women, present with asthma for the first time in adult life, tend to be non-allergic and often require higher doses of inhaled corticosteroids (ICS) or are relatively refractory to corticosteroid treatment. In this review, we examine the published literature improve the understanding of the following aspects of LOA: 1) the age cut-off for its diagnosis; 2) its distinct clinical phenotypes, characteristics and risk factors; and 3) its association with allergic comorbidities and conditions. Overall, our review reveals that clinicians and researchers have used multiple age cut-offs to define LOA, with cut-off ages ranging from >12 years to ≥65 years. LOA has also been classified into several distinct phenotypes, some of which drastically differ in their clinical characteristics, course and prognosis. Although LOA has traditionally been considered non-allergic in nature, our review indicates that it is commonly associated with allergic features and comorbidities. Our findings suggest that there is an urgent need for the development of more clear clinical practice guidelines that can provide more clarity on the definition and other aspects of LOA. In addition, the association of LOA and allergy needs to be re-examined to frame a more optimal treatment strategy for patients with LOA.
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Affiliation(s)
- Santiago Quirce
- Department of Allergy, La Paz University Hospital, IdiPAZ and Universidad Autónoma de Madrid, Madrid, Spain
| | - Enrico Heffler
- Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, MI, Italy
| | - Natalia Nenasheva
- Department of Allergology and Immunology of Russian Medical Academy for Continuous Medical Education, Moscow, Russian Federation
| | - Pascal Demoly
- Department of Pulmonology, Division of Allergy, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France
| | | | | | - Francis Nissen
- London School of Hygiene and Tropical Medicine, London, UK
| | - Nicola A Hanania
- Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, TX, USA
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Gerday S, Schleich F, Henket M, Guissard F, Paulus V, Louis R. Asthmatics with concordant eosinophilic disease classified according to their serum IgE status. Respir Med Res 2020; 79:100797. [PMID: 33383519 DOI: 10.1016/j.resmer.2020.100797] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 10/14/2020] [Accepted: 11/01/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Eosinophilic inflammation has long been associated with asthma. Looking at systemic and airway eosinophilia, we have recently identified a group of patients exhibiting diffuse eosinophilic inflammation. Among the mechanisms governing eosinophilic inflammation, IgE-mediated mast cell activation is a key event leading to eosinophilia in atopic asthmatics. METHODS We conducted a retrospective study on our asthma clinic database containing more than 1500 patients and identified 205 asthmatics with successful sputum induction and concordant eosinophilic phenotype. This phenotype was defined as a sputum eosinophil count≥3% and a blood eosinophils concentration≥400cells/mm3. IgE-high atopic phenotype was characterized by the presence of at least one positive specific IgE (>0.35kU/L) to common aeroallergens and a raised total serum IgE (≥113kU/L). RESULTS The largest group of asthmatics displaying concordant eosinophilic phenotype had a raised total serum IgE and atopy (45%). IgE-low non-atopic concordant eosinophilic asthma was a predominantly late onset disease, exhibited a more intense airway eosinophilic inflammation (P<0.05), required more often maintenance treatment with oral corticosteroids (P<0.05) but, surprisingly, had a reduced level of bronchial hyperresponsiveness to methacholine (P<0.05) despite similar baseline airway calibre impairment. CONCLUSION The more severe airway eosinophilic inflammation in IgE-low non-atopic asthmatics despite similar treatment with ICS and a higher burden of OCS points to a certain corticosteroid resistance in this asthma phenotype.
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Affiliation(s)
- S Gerday
- Department of Pulmonary Medicine, CHU Sart-Tilman, Liege, GIGA I(3) Research Group, University of Liege, 4000 Liege, Belgium.
| | - F Schleich
- Department of Pulmonary Medicine, CHU Sart-Tilman, Liege, GIGA I(3) Research Group, University of Liege, 4000 Liege, Belgium
| | - M Henket
- Department of Pulmonary Medicine, CHU Sart-Tilman, Liege, GIGA I(3) Research Group, University of Liege, 4000 Liege, Belgium
| | - F Guissard
- Department of Pulmonary Medicine, CHU Sart-Tilman, Liege, GIGA I(3) Research Group, University of Liege, 4000 Liege, Belgium
| | - V Paulus
- Department of Pulmonary Medicine, CHU Sart-Tilman, Liege, GIGA I(3) Research Group, University of Liege, 4000 Liege, Belgium
| | - R Louis
- Department of Pulmonary Medicine, CHU Sart-Tilman, Liege, GIGA I(3) Research Group, University of Liege, 4000 Liege, Belgium
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Machluf Y, Chaiter Y, Tal O. Gender medicine: Lessons from COVID-19 and other medical conditions for designing health policy. World J Clin Cases 2020; 8:3645-3668. [PMID: 32953842 PMCID: PMC7479575 DOI: 10.12998/wjcc.v8.i17.3645] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 05/29/2020] [Accepted: 08/12/2020] [Indexed: 02/05/2023] Open
Abstract
Gender-specific differences in the prevalence, incidence, comorbidities, prognosis, severity, risk factors, drug-related aspects and outcomes of various medical conditions are well documented. We present a literature review on the extent to which research in this field has developed over the years, and reveal gaps in gender-sensitive awareness between the clinical portrayal and the translation into gender-specific treatment regimens, guidelines and into gender-oriented preventive strategies and health policies. Subsequently, through the lens of gender, we describe these domains in detail for four selected medical conditions: Asthma, obesity and overweight, chronic kidney disease and coronavirus disease 2019. As some of the key gender differences become more apparent during adolescence, we focus on this developmental stage. Finally, we propose a model which is based on three influential issues: (1) Investigating gender-specific medical profiles of related health conditions, rather than a single disease; (2) The dynamics of gender disparities across developmental stages; and (3) An integrative approach which takes into account additional risk factors (ethnicity, socio-demographic variables, minorities, lifestyle habits etc.). Increasing the awareness of gender-specific medicine in daily practice and in tailored guidelines, already among adolescents, may reduce inequities, facilitate the prediction of future trends and properly address the characteristics and needs of certain subpopulations within each gender.
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Affiliation(s)
- Yossy Machluf
- Shamir Research Institute, University of Haifa, Kazerin 1290000, Israel
| | - Yoram Chaiter
- The Israeli Center for Emerging Technologies in Hospitals and Hospital-based Health Technology Assessment, Shamir (Assaf Harofeh) Medical Center, Zerifin 7030100, Israel
| | - Orna Tal
- The Israeli Center for Emerging Technologies in Hospitals and Hospital-based Health Technology Assessment, Shamir (Assaf Harofeh) Medical Center, Zerifin 7030100, Israel
- Shamir (Assaf Harofeh) Medical Center, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Zerifin 7030100, Israel
- Department of Management, Program of Public Health and Health System Administration, Bar Ilan University, Ramat Gan 5290002, Israel
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Biologics for Severe Asthma: Treatment-Specific Effects Are Important in Choosing a Specific Agent. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2020; 7:1379-1392. [PMID: 31076056 DOI: 10.1016/j.jaip.2019.03.008] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 10/07/2018] [Revised: 02/25/2019] [Accepted: 03/03/2019] [Indexed: 12/19/2022]
Abstract
Patients with uncontrolled severe persistent asthma have greater morbidity, greater use of health care resources, and more impairment in health-related quality of life when compared with their peers with well-controlled disease. Fortunately, since the introduction of biological therapeutics, patients with severe eosinophilic asthma now have beneficial treatment options that they did not have just a few years ago. In addition to anti-IgE therapy for allergic asthma, 3 new biological therapeutics targeting IL-5 and 1 targeting IL-4 and IL-13 signaling have recently been approved by the Food and Drug Administration for the treatment of severe eosinophilic asthma, and approval of more biological therapeutics is on the horizon. These medications decrease the frequency of asthma exacerbations, improve lung function, reduce corticosteroid usage, and improve health-related quality of life. This article reviews the mechanisms of action, specific indications, benefits, and side effects of each of the approved biological therapies for asthma. Furthermore, this article reviews how a clinician could use specific patient characteristics to decide which biologic treatment may be optimal for a given patient.
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Backman H, Jansson SA, Stridsman C, Eriksson B, Hedman L, Eklund BM, Sandström T, Lindberg A, Lundbäck B, Rönmark E. Severe asthma-A population study perspective. Clin Exp Allergy 2020; 49:819-828. [PMID: 30817038 DOI: 10.1111/cea.13378] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Revised: 02/05/2019] [Accepted: 02/11/2019] [Indexed: 01/01/2023]
Abstract
BACKGROUND Severe asthma is a considerable challenge for patients, health-care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study. OBJECTIVE To describe characteristics and estimate the prevalence of severe asthma in a large adult population-based asthma cohort followed for 10-28 years. METHODS N = 1006 subjects with asthma participated in a follow-up during 2012-14, when 830 (mean age 59 years, 56% women) still had current asthma. Severe asthma was defined according to three internationally well-known criteria: the ATS workshop definition from 2000 used in the US Severe Asthma Research Programme (SARP), the 2014 ATS/ERS Task force definition and the GINA 2017. All subjects with severe asthma according to any of these criteria were undergoing respiratory specialist care and were also contacted by telephone to verify treatment adherence. RESULTS The prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS Taskforce), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >90% did not have controlled asthma according to the asthma control test. Severe asthma was related to age >50 years, nasal polyposis, impaired lung function, sensitization to aspergillus, and tended to be more common in women. Further, neutrophils in blood significantly discriminated severe asthma from other asthma. CONCLUSIONS AND CLINICAL RELEVANCE Severe asthma differed significantly from other asthma in terms of demographic, clinical and inflammatory characteristics, results suggesting possibilities for improved treatment regimens of severe asthma. The prevalence of severe asthma in this asthma cohort was 4%-6%, corresponding to approximately 0.5% of the general population.
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Affiliation(s)
- Helena Backman
- Section of Sustainable Health, The OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Sven-Arne Jansson
- Section of Sustainable Health, The OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Caroline Stridsman
- Department of Health Sciences, Luleå University of Technology, Luleå, Sweden
| | - Berne Eriksson
- Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.,Deparment of Internal Medicine, Central County Hospital of Halland, Halmstad, Sweden
| | - Linnea Hedman
- Section of Sustainable Health, The OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Britt-Marie Eklund
- Section of Sustainable Health, The OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Thomas Sandström
- Section of Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Anne Lindberg
- Section of Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
| | - Bo Lundbäck
- Section of Sustainable Health, The OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.,Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Eva Rönmark
- Section of Sustainable Health, The OLIN Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
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Horne E, Tibble H, Sheikh A, Tsanas A. Challenges of Clustering Multimodal Clinical Data: Review of Applications in Asthma Subtyping. JMIR Med Inform 2020; 8:e16452. [PMID: 32463370 PMCID: PMC7290450 DOI: 10.2196/16452] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 12/10/2019] [Accepted: 02/10/2020] [Indexed: 12/27/2022] Open
Abstract
Background In the current era of personalized medicine, there is increasing interest in understanding the heterogeneity in disease populations. Cluster analysis is a method commonly used to identify subtypes in heterogeneous disease populations. The clinical data used in such applications are typically multimodal, which can make the application of traditional cluster analysis methods challenging. Objective This study aimed to review the research literature on the application of clustering multimodal clinical data to identify asthma subtypes. We assessed common problems and shortcomings in the application of cluster analysis methods in determining asthma subtypes, such that they can be brought to the attention of the research community and avoided in future studies. Methods We searched PubMed and Scopus bibliographic databases with terms related to cluster analysis and asthma to identify studies that applied dissimilarity-based cluster analysis methods. We recorded the analytic methods used in each study at each step of the cluster analysis process. Results Our literature search identified 63 studies that applied cluster analysis to multimodal clinical data to identify asthma subtypes. The features fed into the cluster algorithms were of a mixed type in 47 (75%) studies and continuous in 12 (19%), and the feature type was unclear in the remaining 4 (6%) studies. A total of 23 (37%) studies used hierarchical clustering with Ward linkage, and 22 (35%) studies used k-means clustering. Of these 45 studies, 39 had mixed-type features, but only 5 specified dissimilarity measures that could handle mixed-type features. A further 9 (14%) studies used a preclustering step to create small clusters to feed on a hierarchical method. The original sample sizes in these 9 studies ranged from 84 to 349. The remaining studies used hierarchical clustering with other linkages (n=3), medoid-based methods (n=3), spectral clustering (n=1), and multiple kernel k-means clustering (n=1), and in 1 study, the methods were unclear. Of 63 studies, 54 (86%) explained the methods used to determine the number of clusters, 24 (38%) studies tested the quality of their cluster solution, and 11 (17%) studies tested the stability of their solution. Reporting of the cluster analysis was generally poor in terms of the methods employed and their justification. Conclusions This review highlights common issues in the application of cluster analysis to multimodal clinical data to identify asthma subtypes. Some of these issues were related to the multimodal nature of the data, but many were more general issues in the application of cluster analysis. Although cluster analysis may be a useful tool for investigating disease subtypes, we recommend that future studies carefully consider the implications of clustering multimodal data, the cluster analysis process itself, and the reporting of methods to facilitate replication and interpretation of findings.
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Affiliation(s)
- Elsie Horne
- Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom
| | - Holly Tibble
- Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom
| | - Aziz Sheikh
- Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom
| | - Athanasios Tsanas
- Usher Institute, Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom
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Hough KP, Curtiss ML, Blain TJ, Liu RM, Trevor J, Deshane JS, Thannickal VJ. Airway Remodeling in Asthma. Front Med (Lausanne) 2020; 7:191. [PMID: 32509793 PMCID: PMC7253669 DOI: 10.3389/fmed.2020.00191] [Citation(s) in RCA: 240] [Impact Index Per Article: 48.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 04/21/2020] [Indexed: 02/06/2023] Open
Abstract
Asthma is an inflammatory disease of the airways that may result from exposure to allergens or other environmental irritants, resulting in bronchoconstriction, wheezing, and shortness of breath. The structural changes of the airways associated with asthma, broadly referred to as airway remodeling, is a pathological feature of chronic asthma that contributes to the clinical manifestations of the disease. Airway remodeling in asthma constitutes cellular and extracellular matrix changes in the large and small airways, epithelial cell apoptosis, airway smooth muscle cell proliferation, and fibroblast activation. These pathological changes in the airway are orchestrated by crosstalk of different cell types within the airway wall and submucosa. Environmental exposures to dust, chemicals, and cigarette smoke can initiate the cascade of pro-inflammatory responses that trigger airway remodeling through paracrine signaling and mechanostimulatory cues that drive airway remodeling. In this review, we explore three integrated and dynamic processes in airway remodeling: (1) initiation by epithelial cells; (2) amplification by immune cells; and (3) mesenchymal effector functions. Furthermore, we explore the role of inflammaging in the dysregulated and persistent inflammatory response that perpetuates airway remodeling in elderly asthmatics.
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Affiliation(s)
- Kenneth P Hough
- Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Miranda L Curtiss
- Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Trevor J Blain
- Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Rui-Ming Liu
- Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Jennifer Trevor
- Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Jessy S Deshane
- Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Victor J Thannickal
- Division of Pulmonary Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States
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Holgate ST, Walker S, West B, Boycott K. The Future of Asthma Care: Personalized Asthma Treatment. Clin Chest Med 2020; 40:227-241. [PMID: 30691714 DOI: 10.1016/j.ccm.2018.10.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Although once considered a single disease entity, asthma is now known to be a complex inflammatory disease engaging a range of causal pathways. The most frequent forms of asthma are identified by sputum/blood eosinophilia and activation of type 2 inflammatory pathways involving interleukins-3, -4, -5, and granulocyte-macrophage colony-stimulating factor. The use of diagnostics that identify T2 engagement linked to the selective use of highly targeted biologics has opened up a new way of managing severe disease. Novel technologies, such as wearables and intelligent inhalers, enable real-time remote monitoring of asthma, creating a unique opportunity for personalized health care.
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Affiliation(s)
- Stephen T Holgate
- Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, The Sir Henry Wellcome Research Laboratories, Southampton General Hospital, Mail Point 810, Level, Southampton SO166YD, UK.
| | | | | | - Kay Boycott
- Asthma UK, 18 Mansell Street, London E1 8AA, UK
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Age-specific incidence of allergic and non-allergic asthma. BMC Pulm Med 2020; 20:9. [PMID: 31924190 PMCID: PMC6954552 DOI: 10.1186/s12890-019-1040-2] [Citation(s) in RCA: 104] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 12/23/2019] [Indexed: 11/20/2022] Open
Abstract
Background Onset of allergic asthma has a strong association with childhood but only a few studies have analyzed incidence of asthma from childhood to late adulthood in relation to allergy. The purpose of the study was to assess age-specific incidence of allergic and non-allergic asthma. Methods Questionnaires were sent to 8000 randomly selected recipients aged 20–69 years in Finland in 2016. The response rate was 52.3% (n = 4173). The questionnaire included questions on e.g. atopic status, asthma and age at asthma diagnosis. Asthma was classified allergic if also a physician-diagnosed allergic rhinitis was reported. Results The prevalence of physician-diagnosed asthma and allergic rhinitis were 11.2 and 17.8%, respectively. Of the 445 responders with physician-diagnosed asthma, 52% were classified as allergic and 48% as non-allergic. Median ages at diagnosis of allergic and non-allergic asthma were 19 and 35 years, respectively. Among subjects with asthma diagnosis at ages 0–9, 10–19, 20–29, 30–39, 40–49, 50–59 and 60–69 years, 70, 62, 58, 53, 38, 19 and 33%, respectively, were allergic. For non-allergic asthma, the incidence rate was lowest in children and young adults (0.7/1000/year). It increased after middle age and was highest in older age groups (2.4/1000/year in 50–59 years old). Conclusions The incidence of allergic asthma is highest in early childhood and steadily decreases with advancing age, while the incidence of non-allergic asthma is low until it peaks in late adulthood. After approximately 40 years of age, most of the new cases of asthma are non-allergic.
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Bhargava S, Holla AD, Jayaraj BS, Praveena AS, Ravi S, Khurana S, Mahesh PA. Distinct asthma phenotypes with low maximal attainment of lung function on cluster analysis. J Asthma 2019; 58:26-37. [PMID: 31479309 DOI: 10.1080/02770903.2019.1658205] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE Asthma is a heterogeneous disease with varying clinical presentations, severity and ability to achieve asthma control. The present study aimed to characterize clinical phenotypes of asthma in an Indian cohort of subjects using a cluster analysis approach. METHODS Patients with confirmed asthma (N = 100) and at least 6-months of follow-up data, identified by retrospective chart review, were included in this study. Demographics, age at disease onset, disease duration, body mass index, serial spirometry and allergen sensitization were assessed. Asthma control was assessed prospectively using Global Initiative for Asthma and Asthma Control Test. R version 3.4.3 was used for statistical analysis. Ward's minimum-variance hierarchical clustering method was performed using an agglomerative (bottom-up) approach. To compare differences between clusters, analysis of variance using Kruskal-Wallis test (continuous variables) and chi-square test (categorical variables) was used. RESULTS Cluster analysis of 100 treatment-naive patients with asthma identified four clusters. Cluster 1, (N = 40), childhood onset of disease, normal body weight, equal gender distribution and achieved normal lung function. Cluster 2 (N = 16) included adolescent disease-onset, obese, majority males and had poor attainment of maximum lung functions. Cluster 3 (N = 20) were older, late-onset of disease, obese, majority male and had poor attainment of maximum lung function. Cluster 4 (N = 24) had adult-onset of disease, obese, predominantly female and achieved normal lung function. CONCLUSIONS In an Indian cohort of well-characterized patients with asthma, cluster analysis identified four distinct clinical phenotypes of asthma, two of which had poor attainment of maximum lung functions.
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Affiliation(s)
- Smriti Bhargava
- Department of Pulmonology, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India
| | | | - Biligere S Jayaraj
- Department of Pulmonology, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India
| | | | - Sreenivasan Ravi
- Department of Studies in Statistics, University of Mysore, Mysore, India
| | - Sandhya Khurana
- Division of Pulmonary & Critical Care Medicine, University of Rochester Medical Center, Rochester, NY, USA
| | - Padukudru A Mahesh
- Department of Pulmonology, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India
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Borna E, Nwaru BI, Bjerg A, Mincheva R, Rådinger M, Lundbäck B, Ekerljung L. Changes in the prevalence of asthma and respiratory symptoms in western Sweden between 2008 and 2016. Allergy 2019; 74:1703-1715. [PMID: 31021427 DOI: 10.1111/all.13840] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 02/06/2019] [Accepted: 02/18/2019] [Indexed: 01/22/2023]
Abstract
BACKGROUND Asthma is a common chronic inflammatory disease of the airways, with a noticeable increase in prevalence during the second half of the 20th century. Recent studies assessing the prevalence trends among adults have been inconsistent. We investigated the changes in the prevalence of asthma, respiratory symptoms, and risk factors between 2008 and 2016 in western Sweden. METHODS The West Sweden Asthma Study (WSAS) is a population-based study which started in 2008 (WSAS I) and then repeated in 2016 (WSAS II) in western Sweden. Randomly selected individuals aged 16-75 years (N = 18 087 in 2008 and N = 24 534 in 2016) completed a questionnaire regarding obstructive lung diseases, respiratory symptoms, potential risk factors, and also questions from the GA2 LEN survey. RESULTS The prevalence of reported ever asthma, physician-diagnosed asthma, use of asthma medication, and current asthma increased significantly from 9.6% to 11%, 8.3% to 10%, 8.6% to 9.8%, and 8.1% to 9.1%, respectively, between 2008 and 2016. There were also increases in the prevalence of respiratory symptoms during the same period. The greatest increase occurred in young adults aged 16-25 years. Female gender, allergic rhinitis, obesity, and family history of asthma remained the strongest risk factors for asthma in 2016 as it was in 2008. CONCLUSION There were moderate increases in asthma and respiratory symptoms in adults in western Sweden between 2008 and 2016, the greatest increase occurring in younger adults. The potential risk factors for asthma remained the same during the study period.
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Affiliation(s)
- Eivind Borna
- Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden
| | - Bright I. Nwaru
- Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden
- Wallenberg Center for Molecular and Translational Medicine University of Gothenburg Gothenburg Sweden
| | - Anders Bjerg
- Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden
- Astrid Lindgren Children’s Hospital Karolinska University Hospital Stockholm Sweden
- Department of Women´s and Children´s Health Karolinska Institutet Stockholm Sweden
| | - Roxana Mincheva
- Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden
- Respiratory Medicine & Allergology Department Sahlgrenska University Hospital Gothenburg Sweden
| | - Madeleine Rådinger
- Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden
| | - Bo Lundbäck
- Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden
| | - Linda Ekerljung
- Department of Internal Medicine and Clinical Nutrition, Krefting Research Centre, Institute of Medicine Sahlgrenska Academy, University of Gothenburg Gothenburg Sweden
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Innate lymphoid cells in asthma: pathophysiological insights from murine models to human asthma phenotypes. Curr Opin Allergy Clin Immunol 2019; 19:53-60. [PMID: 30516548 DOI: 10.1097/aci.0000000000000497] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
PURPOSE OF REVIEW The current review describes the role of different types of innate lymphoid cells (ILCs) in the pathogenesis of asthma inflammatory phenotypes by linking findings from murine asthma models with human studies. Novel treatment options are needed for patients with steroid-insensitive asthma. Strategies targeting ILCs, or their upstream or downstream molecules are emerging and discussed in this review. RECENT FINDINGS In eosinophilic asthma, ILCs, and especially type 2 ILCs (ILC2s), are activated by alarmins such as IL-33 upon allergen triggering of the airway epithelium. This initiates IL-5 and IL-13 production by ILC2, resulting in eosinophilic inflammation and airway hyperreactivity. Type 3 ILCs (ILC3s) have been shown to be implicated in obesity-induced asthma, via IL-1β production by macrophages, leading ILC3 and release of IL-17. ILC1s might play a role in severe asthma, but its role is currently less investigated. SUMMARY Several studies have revealed that ILC2s play a role in the induction of eosinophilic inflammation in allergic and nonallergic asthmatic patients mainly via IL-5, IL-13, IL-33 and thymic stromal lymphopoietin. Knowledge on the role of ILC3s and ILC1s in asthmatic patients is lagging behind. Further studies are needed to support the hypothesis that these other types of ILCs contribute to asthma pathogenesis, presumably in nonallergic asthma phenotypes.
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Matsumoto H. Roles of Periostin in Asthma. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2019; 1132:145-159. [PMID: 31037633 DOI: 10.1007/978-981-13-6657-4_15] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Periostin is a matricellular protein that is deeply involved in type-2/eosinophilic airway inflammation and remodeling in asthma. While its expression in airway epithelial cells is correlated with the thickness of airway basement membrane, more importantly, periostin can be detected stably in blood with little variability, reflecting airway type-2 inflammation and remodeling. As for a result, serum periostin can serve as a valuable marker to identify patients with type-2 severe asthma who are insensitive to inhaled corticosteroids, and consequently have the excess decline of pulmonary function with asthma exacerbations. Serum periostin may significantly help to improve management of patients with severe asthma.
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Affiliation(s)
- Hisako Matsumoto
- Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Tay TR, Lee JWY, Hew M. Diagnosis of severe asthma. Med J Aust 2019; 209:S3-S10. [PMID: 30453866 DOI: 10.5694/mja18.00125] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2018] [Accepted: 05/21/2018] [Indexed: 02/01/2023]
Abstract
Patients with asthma that is uncontrolled despite high intensity medication can present in both primary and specialist care. An increasing number of novel (and expensive) treatments are available for patients who fail conventional asthma therapy, but these may not be appropriate for all such patients. It is essential that a rigorous evaluation process be undertaken for these patients to identify those with biologically severe asthma who will require novel therapies, and those who may improve with control of contributory factors. In this article, we describe three key steps in the diagnostic evaluation process for severe asthma. The first step is confirmation of asthma diagnosis with objective evidence of variable airflow obstruction. The second involves management of contributory factors such as non-adherence, poor inhaler technique, ongoing asthma triggers, and comorbidities. The third step involves phenotyping and endotyping of patients with severe asthma. We provide a practical approach to implementing these measures in both primary and secondary care.
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Affiliation(s)
| | | | - Mark Hew
- The Alfred Hospital, Melbourne, VIC
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Distinct Phenotypes of Smokers with Fixed Airflow Limitation Identified by Cluster Analysis of Severe Asthma. Ann Am Thorac Soc 2019; 15:33-41. [PMID: 28910142 DOI: 10.1513/annalsats.201701-065oc] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
RATIONALE Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. OBJECTIVES To explore novel severe asthma phenotypes by cluster analysis when including smoking patients with asthma. METHODS We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. RESULTS Five clinical clusters, including two characterized by low forced expiratory volume in 1 second/forced vital capacity, were identified. When characteristics of smoking subjects in these two clusters were compared, there were marked differences between the two groups: one had high levels of circulating eosinophils, high immunoglobulin E levels, and a high sinus score, and the other was characterized by low levels of the same parameters. Sputum analysis revealed intriguing differences of cytokine/chemokine pattern in these two groups. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 3 years later. CONCLUSIONS This study reveals two distinct phenotypes with potentially different biological pathways contributing to fixed airflow limitation in cigarette smokers with severe asthma.
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Machluf Y, Farkash R, Rotkopf R, Fink D, Chaiter Y. Asthma phenotypes and associated comorbidities in a large cohort of adolescents in Israel. J Asthma 2019; 57:722-735. [PMID: 31017024 DOI: 10.1080/02770903.2019.1604743] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Objectives: Asthma is a multifactorial, heterogeneous, complex and common chronic respiratory disease driven by diverse mechanisms. Although asthma presents various clinical forms with different levels of severity, it is unclear whether asthma severities are a consequence of disease management or varied etiologies. We sought to investigate this question.Methods: This article presents a cross-sectional study of 113,671 Israeli adolescents. Univariate and multivariable logistic regression models were performed to analyze the independent associations between mild asthma and moderate-to-severe asthma phenotypes and coexistent medical conditions within each gender separately. Hierarchical clustering of the odds ratios of the diverse statistically significant medical conditions associated with asthma severity-gender groups was also performed. We focused on the allergic and neurological-cognitive-mental disorders.Results: Among males, two associations were common to both asthma groups (atopic dermatitis and allergic rhinitis), five unique to mild asthma (urticaria/angioedema, Hymenoptera/bee allergies, allergic conjunctivitis, epilepsy and migraine) and two unique to moderate-to-severe asthma (learning disabilities and ADD/ADHD (Attention-deficit disorder/Attention-deficit/hyperactivity disorder)). Among females, two associations were common to both clinical asthma groups (allergic rhinitis and urticaria/angioedema), and five unique to moderate-to-severe asthma (atopic dermatitis, learning disabilities, ADD/ADHD, anxiety/mood disorders and migraine). Allergic rhinitis was the only condition to be associated with all four groups. Learning disabilities and ADD/ADHD were only associated with moderate-to-severe asthma (but not with mild asthma), in both males and females. Hierarchical clustering analysis uncovered two prominent clusters, separating mild from moderate-to-severe asthma.Conclusions: The differences between mild and moderate-to-severe asthma enhance asthma phenotype characterization, with respect to comorbidities, and indicate varied etiologies.
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Affiliation(s)
- Yossy Machluf
- Medical Corps, IDF, Israel.,Shamir Research Institute, University of Haifa, Kazerin, Israel
| | | | - Ron Rotkopf
- Department of Life Sciences Core Facilities, Faculty of Biochemistry, Weizmann Institute of Science, Rehovot, Israel
| | - Daniel Fink
- Shaarei Zedek Medical Center, Jerusalem, Israel
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Papaporfyriou A, Papaioannou AI, Hillas G, Konstantelou E, Tseliou E, Koulouris N, Papiris S, Bakakos P, Kostikas K, Loukides S. Inflammatory profile in optimally treated patients with adult versus early-onset asthma. Postgrad Med 2019; 131:324-329. [PMID: 30920326 DOI: 10.1080/00325481.2019.1600884] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Introduction: The age of asthma onset is often implicated in clinical manifestation, diagnosis, and management of the disease. Aim: To define demographic, clinical and functional features and inflammatory characteristics in induced sputum in patients with adult-onset asthma. Methods: Optimally treated patients from asthma clinics of two tertiary hospitals were included in the study. Patients underwent assessment of demographic characteristics, severity and treatment regimes, pulmonary function tests, and skin prick tests, as well as measurement of blood eosinophils and sputum induction for the assessment of sputum inflammatory cells, IL-8 and IL-13 levels in the supernatant. Results: Of the 333 patients recruited, 234 (70.2%) had adult-onset asthma. Adult-onset asthmatics were older, had a higher BMI, a shorter disease duration, and were less often atopic, compared to patients with early onset asthma. Higher proportions of patients with severe asthma presented increased levels of FeNO and blood eosinophils, both in the early and the adult-onset patient groups. Finally, obese patients with early onset asthma were characterized by less atopy compared to non-obese patients in the same group. Conclusion: Adult-onset asthma was characterized by less sputum eosinophilia, a nonatopic profile and a higher BMI compared to early-onset asthma. The presence of blood eosinophilia and increased FeNO in patients with severe asthma was comparable in the two groups.
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Affiliation(s)
- Anastasia Papaporfyriou
- a 2nd Respiratory Medicine Department , University of Athens Medical School , Athens , Greece
| | - Andriana I Papaioannou
- a 2nd Respiratory Medicine Department , University of Athens Medical School , Athens , Greece
| | - Geogrios Hillas
- b 5th Pulmonary Department , "Sotiria" Chest Diseases Hospital , Athens , Greece
| | - Elissavet Konstantelou
- c 1st Respiratory Medicine Department , University of Athens Medical School , Athens , Greece
| | - Eleni Tseliou
- d 2nd Respiratory Medicine Department , "Sotiria" Chest Diseases Hospital , Athens , Greece
| | - Nikolaos Koulouris
- c 1st Respiratory Medicine Department , University of Athens Medical School , Athens , Greece
| | - Spyros Papiris
- a 2nd Respiratory Medicine Department , University of Athens Medical School , Athens , Greece
| | - Petros Bakakos
- c 1st Respiratory Medicine Department , University of Athens Medical School , Athens , Greece
| | - Konstantinos Kostikas
- a 2nd Respiratory Medicine Department , University of Athens Medical School , Athens , Greece
| | - Stelios Loukides
- a 2nd Respiratory Medicine Department , University of Athens Medical School , Athens , Greece
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Bai C, Jiang D, Wang L, Xue F, Chen O. A high blood eosinophil count may be a risk factor for incident asthma in population at risk. Respir Med 2019; 151:59-65. [PMID: 31047119 DOI: 10.1016/j.rmed.2019.03.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 03/23/2019] [Accepted: 03/26/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Eosinophilia is considered to be associated with allergic disease and may predict asthma exacerbation. Eosinophils contribute to the pathophysiology and pathogenesis of asthma. However, studies on high blood eosinophil counts (BECs) and incident asthma remain scarce. OBJECTIVE To examine whether high BECs are positively associated with incident asthma in adults. METHODS Our study included 57975 participants aged from 20 to 79 years from the Shandong multi-center health check-up longitudinal study for Health Management. All patients with determined baseline BECs were ≥20 years old and free from asthma. We defined incident asthma as self-reported new-onset asthma occurring during the 10-year follow-up period. Multivariate modeling employed Poisson regression and Cox proportional hazards models to verify the association between BEC and incident asthma by adjusting demographics and some relevant comorbidities (rhinitis, nasal polyps, pneumonia, bronchitis, and chronic obstructive pulmonary disease). RESULTS A BEC ≥110 cells/μL was a risk factor for incident asthma (adjusted IRR = 1.62, 95% CI: 1.05-2.50, P = .028) in the Poisson regression. In the Cox proportional hazards model, the BEC cutoff point for incident asthma was also determined to be 110 cells/μL (HR = 1.59, 95% CI: 1.01-2.51, P = .045). CONCLUSION A high BEC is a risk factor for incident asthma, especially when the BEC exceeds 110 cells/μL. This suggests that adults with high BECs are more likely to develop asthma.
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Affiliation(s)
- Chenxiao Bai
- School of Nursing, Shandong University, Jinan, Shandong, China
| | - Di Jiang
- School of Nursing, Shandong University, Jinan, Shandong, China
| | - Liwen Wang
- School of Nursing, Shandong University, Jinan, Shandong, China
| | - Fuzhong Xue
- Department of Biostatistics, School of Public Health, Shandong University, Jinan, Shandong, China.
| | - Ou Chen
- School of Nursing, Shandong University, Jinan, Shandong, China.
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