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Asthma phenotype

Rebecca Scherzer, Mitchell H Grayson
OBJECTIVE: It is a well-known fact that there is significant heterogeneity in the origins of asthma in adults and children. This article examines the roots of asthma across the ages including atopy, the role of the microbiome and viral infections, along with comorbidities/confounders such as obesity, aspirin-exacerbated respiratory disease (AERD), neutrophilic asthma, cigarette smoking and the possibility of an asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome. DATA SOURCES: Data was taken from various scientific search engines including PubMed and Science Direct databases...
June 18, 2018: Annals of Allergy, Asthma & Immunology
Omar Tliba, Reynold A Panettieri
Among patients with asthma, heterogeneity exists regarding the pattern of airway inflammation and response to treatment, prompting the necessity of recognizing specific phenotypes. Based on the analysis of inflammatory cell count in induced sputum, patients with asthma can be classified in four unique phenotypes; eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma (PGA). PGA is an asthma phenotype with no evidence of elevated numbers of eosinophils or neutrophils in sputum or blood, and in which anti-inflammatory therapies are ineffective in controlling symptoms...
June 18, 2018: Journal of Allergy and Clinical Immunology
S du Preez, S L Raidal, G S Doran, M Prescott, K J Hughes
BACKGROUND: Exhaled breath condensate (EBC) analysis is a non-invasive method to assess the lower respiratory tract. In humans, EBC hydrogen peroxide (H2 O2 ), pH and leukotriene B4 (LTB4 ) are useful for detection and monitoring of inflammatory lung diseases, including asthma. OBJECTIVES: To determine associations between EBC biomarkers and cytological and endoscopic definitions of lower airway inflammation whilst controlling for sampling and environmental variables...
June 19, 2018: Equine Veterinary Journal
A Khan, G Vandeplas, T M T Huynh, V N Joish, L Mannent, P Tomassen, T Van Zele, L O Cardell, J Arebro, H Olze, U Foerster-Ruhrmann, M L Kowalski, A Olszewska-Ziaber, G Holtappels, N De Ruyck, C van Drunen, J Mullol, P W Hellings, V Hox, E Toskala, G Scadding, V J Lund, W J Fokkens, C Bachert
BACKGROUND: Chronic rhinosinusitis (CRS) is a common yet under-recognised chronic inflammatory disease of the nose and paranasal sinuses that is classified according to the presence (CRSwNP) or absence (CRSsNP) of nasal polyps. METHODS: This paper reports the methodology and descriptive results of the Global Allergy and Asthma European Network (GALEN) rhinosinusitis cohort. We established a large CRS cohort within the GALEN consortium (European FP6 research initiative) to identify inflammatory endotypes, the natural disease course, and its impact on health-related quality of life (HRQoL)...
June 17, 2018: Rhinology
Bart Hilvering, Timothy S C Hinks, Linda Stöger, Emanuele Marchi, Maryam Salimi, Rahul Shrimanker, Wei Liu, Wentao Chen, Jian Luo, Simei Go, Timothy Powell, Jennifer Cane, Samantha Thulborn, Ayako Kurioka, Tianqi Leng, Jamie Matthews, Clare Connolly, Catherine Borg, Mona Bafadhel, Christian B Willberg, Adaikalavan Ramasamy, Ratko Djukanović, Graham Ogg, Ian D Pavord, Paul Klenerman, Luzheng Xue
Human type-2 CD8+ T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia-a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8+ CRTH2+ (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D2 (PGD2 ) and cysteinyl leukotriene E4 (LTE4 ) are also increased in the airways of the same group of patients...
June 15, 2018: Mucosal Immunology
Chiara Scelfo, Carla Galeone, Francesca Bertolini, Marco Caminati, Patrizia Ruggiero, Nicola Facciolongo, Francesco Menzella
Asthma is a chronic obstructive respiratory disease characterised by bronchial inflammation. Its biological and clinical features have been widely explored and a number of pharmacological treatments are currently available. Currently several aspects of asthma pathophysiological background remain unclear, and this is crucial for the traditional asthma phenotype approach as well as for new endotype definition. In this scenario, the identification of new molecular and clinical biomarkers may be helpful in order to better understand the disease, define specific diagnostic tools and highlight relevant novel targets for pharmacology treatments...
2018: F1000Research
Zala Jevnikar, Jörgen Östling, Elisabeth Ax, Jenny Calvén, Kristofer Thörn, Elisabeth Israelsson, Lisa Öberg, Akul Singhania, Laurie C K Lau, Susan J Wilson, Jonathan A Ward, Anoop Chauhan, Ana R Sousa, Bertrand De Meulder, Matthew J Loza, Frédéric Baribaud, Peter J Sterk, Kian Fan Chung, Kai Sun, Yike Guo, Ian M Adcock, Debbie Payne, Barbro Dahlen, Pascal Chanez, Dominick E Shaw, Norbert Krug, Jens M Hohlfeld, Thomas Sandström, Ratko Djukanovic, Anna James, Timothy S C Hinks, Peter H Howarth, Outi Vaarala, Marleen van Geest, Henric K Olsson
BACKGROUND: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) with asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthma is unclear. OBJECTIVE: To explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthma. METHODS: An IL-6TS gene signature, obtained from air-liquid interface (ALI) cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R, was used to stratify lung epithelium transcriptomic data (U-BIOPRED cohorts) by hierarchical clustering...
June 11, 2018: Journal of Allergy and Clinical Immunology
Paloma Campo, Ibon Eguiluz-Gracia, Gador Bogas, María Salas, Carmen Plaza Serón, Natalia Pérez, C Mayorga, M J Torres, Mohammed Shamji, Carmen Rondon
A significant proportion of rhinitis patients without systemic IgE-sensitization tested by skin prick test and serum allergen-specific IgE (sIgE) display nasal reactivity upon nasal allergen provocation test (NAPT). This disease phenotype has been termed local allergic rhinitis (LAR). LAR is an underdiagnosed entity affecting children and adults from different parts of the world, with moderate-to-severe symptoms, impairment of quality of life and rapid progression to symptom worsening. LAR is a stable phenotype and not merely an initial state of AR...
June 14, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Annette Fox, Kim L Harland, Katherine Kedzierska, Anne Kelso
Effector CD8+ T cells generally produce type-1 cytokines and mediators of the perforin/granzyme cytolytic pathway, yet type-2-polarized CD8+ cells (Tc2) are detected in type-2 (T2) cytokine-driven diseases such as asthma. It is unclear whether T2 cytokine exposure during activation is sufficient to polarize human CD8+ T cells. To address this question, a protocol was developed for high-efficiency activation of human CD8+ T cells in which purified single cells or populations were stimulated with plate-bound anti-CD3 and anti-CD11a mAb for up to 8 days in T2 polarizing or neutral conditions, before functional analysis...
2018: Frontiers in Immunology
Eun Lee, Young-Ho Kim, Hyun-Ju Cho, Ji-Sun Yoon, Sungsu Jung, Song-I Yang, Hyung Young Kim, Ji-Won Kwon, Ju-Hee Seo, Hyo Bin Kim, So Yeon Lee, Soo-Jong Hong
BACKGROUND: Bronchial hyperresponsiveness (BHR), one of the key features of asthma, shows a diverse natural course in school-aged children, but, studies on BHR phenotypes are lacking. OBJECTIVE: We classified BHR phenotypes according to onset age and persistence in children and investigated the characteristics and factors associated with each phenotype in a longitudinal study. METHODS: We analyzed 1,305 elementary school children from the Children's HEalth and Environmental Research (CHEER) study, a 4-year prospective follow-up study with 2-year intervals starting at a mean age of 7 years...
June 7, 2018: Annals of Allergy, Asthma & Immunology
Coraline Radermecker, Renaud Louis, Fabrice Bureau, Thomas Marichal
The contribution of neutrophils to asthma pathogenesis has been mainly studied in the context of non-allergic neutrophilic asthma. However, neutrophils can also be rapidly recruited and are largely present in the airways of allergic eosinophilic asthmatic patients. Under these circumstances, they possess specific phenotypic features distinguishing them from resting blood neutrophils and are endowed with particular functions. The exact contribution of neutrophils to allergic asthma pathogenesis is still unclear, but growing experimental evidence supports the ability of neutrophils or neutrophil-derived products to influence the underlying allergic type 2 immune response and cardinal features of allergic asthma, thus shedding new light on neutrophil biology and functions in an allergic context...
June 5, 2018: Current Opinion in Immunology
Soraia Carvalho Abreu, Miquéias Lopes-Pacheco, Adriana Lopes da Silva, Debora Gonçalves Xisto, Tainá Batista de Oliveira, Jamil Zola Kitoko, Lígia Lins de Castro, Natália Recardo Amorim, Vanessa Martins, Luisa H A Silva, Cassiano Felippe Gonçalves-de-Albuquerque, Hugo Caire de Castro Faria-Neto, Priscilla Christina Olsen, Daniel Jay Weiss, Marcelo Marcos Morales, Bruno Lourenço Diaz, Patricia Rieken Macêdo Rocco
Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Despite recent advances in the understanding of its pathophysiology, asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodeling. Mesenchymal stromal cell (MSC)-based therapy mitigates lung inflammation in experimental allergic asthma; however, its ability to reduce airway remodeling is limited. We aimed to investigate whether pre-treatment with eicosapentaenoic acid (EPA) potentiates the therapeutic properties of MSCs in experimental allergic asthma...
2018: Frontiers in Immunology
Yuanyuan Guo, Chunlin Hong, Yanhong Liu, Huinuan Chen, Xiaohua Huang, Minli Hong
To examine the difference in the fractional exhaled nitric oxide (FeNO) between chronic obstructive pulmonary disease (COPD) patients with asthma-COPD overlap syndrome (ACOS) and patients with Non-ACOS COPD (Non-ACOS) and to investigate the correlation between FeNO levels and the differential cell counts of eosinophils in induced sputum, in order to explore the diagnostic value of FeNO in ACOS.A prospective, case-control study was performed on 53 cases of ACOS group and 53 cases of Non-ACOS group in the Respiratory Medicine Outpatient of Zhangzhou Municipal TCM Hospital, Affiliated to Fujian University of Traditional Chinese Medicine...
June 2018: Medicine (Baltimore)
(no author information available yet)
Eosinophilic chronic obstructive pulmonary disease (COPD) is characterised by a peripheral blood differential eosinophil count of 2% or more. This phenotype is found in roughly 40% of patients with COPD. These patients have an increased frequency of exacerbations, but benefit from inhaled glucocorticoids as part of a triple therapy regime. However, 30-40% of these patients continue to have significant exacerbations, meaning targeted therapy to reduce eosinophil counts could play a role in future therapy. Mepolizumab blocks interleukin-5 and has been associated with a decreased rate of exacerbation in eosinophilic asthma...
June 2018: Breathe
Norrice M Liu, Wim van Aalderen, Karin C L Carlsen, Courtney Coleman, James D Chalmers, Steve Cunningham, Ricardo M Fernandes, Louise J Fleming, Monika Gappa, Bülent Karadag, Fabio Midulla, Marielle W H Pijnenburg, Niels W Rutjes, Franca Rusconi, Jonathan Grigg
The development of new asthma biologics and receptor blockers for the treatment of paediatric severe asthma raises challenges. It is unclear whether there are sufficient children in Europe to recruit into randomised placebo-controlled trials to establish efficacy and safety in this age group. In February 2016, the European Respiratory Society funded a clinical research collaboration entitled "Severe Paediatric Asthma Collaborative in Europe" (SPACE). We now report the SPACE protocol for a prospective pan-European observational study of paediatric severe asthma...
June 2018: Breathe
Ayşe Kılıç, Marc Santolini, Taiji Nakano, Matthias Schiller, Mizue Teranishi, Pascal Gellert, Yuliya Ponomareva, Thomas Braun, Shizuka Uchida, Scott T Weiss, Amitabh Sharma, Harald Renz
Allergic asthma is a chronic inflammatory disease dominated by a CD4+ T helper 2 (Th2) cell signature. The immune response amplifies in self-enforcing loops, promoting Th2-driven cellular immunity and leaving the host unable to terminate inflammation. Posttranscriptional mechanisms, including microRNAs (miRs), are pivotal in maintaining immune homeostasis. Since an altered expression of various miRs has been associated with T cell-driven diseases, including asthma, we hypothesized that miRs control mechanisms ensuring Th2 stability and maintenance in the lung...
June 7, 2018: JCI Insight
Miriam C N Eller, Karina P Vergani, Beatriz M Saraiva-Romanholo, Leila Antonangelo, Claudio Leone, Joaquim C Rodrigues
BACKGROUND: The phenotypes and endotypes of severe therapy-resistant asthma (STRA) have not been fully elucidated in children. The aim of the present study was to investigate inflammatory markers in the induced sputum of children with STRA and to compare them with those present in a group of children who achieved control. METHODS: A prospective cohort of children (6-18 years of age) diagnosed with severe asthma (GINA criteria) who had undergone treatment for at least 6 months was comprehensively followed for 3 months...
June 5, 2018: Pediatric Pulmonology
Anthony Ca Yii, Tunn-Ren Tay, Xue Ning Choo, Mariko Sy Koh, Augustine Kh Tee, De-Yun Wang
United airways disease (UAD) is the concept that the upper and lower airways, which are anatomically and immunologically related, form a single organ. According to this concept, upper and lower airway diseases are frequently comorbid because they reflect manifestations of a single underlying disease at different sites of the respiratory tract. Allergic asthma-allergic rhinitis is the archetypal UAD, but emerging data indicate that UAD is a heterogeneous condition and consists of multiple phenotypes (observable clinical characteristics) and endotypes (pathobiologic mechanisms)...
June 5, 2018: Allergy
Ke Zu, Liuhua Shi, Robyn L Prueitt, Xiaobin Liu, Julie E Goodman
Asthma, a chronic respiratory disorder with complex etiology and various phenotypes, is a considerable public health concern in the USA and worldwide. While there is evidence suggesting ambient ozone exposure may exacerbate asthma, information regarding the potential role of ozone in asthma development is more limited. Thus, we conducted a critical review of observational epidemiology studies to determine whether long-term ambient ozone exposure is a risk factor for asthma development. We identified 14 relevant studies; 11 evaluated asthma development in children, while three studies, based on a single cohort, assessed this outcome in adults...
February 2018: Inhalation Toxicology
Chengyun Xu, Chaochun Zou, Musaddique Hussain, Wei Shi, Yanan Shao, Ziyan Jiang, Xiling Wu, Meiping Lu, Junsong Wu, Qiangmin Xie, Yuehai Ke, Fanxin Long, Lanfang Tang, Ximei Wu
Sonic hedgehog (SHH) is abundantly expressed and critical for morphogenesis in embryonic lungs; however, SHH expression drops to a much lower level in mice from E17.5 and in humans from the 21st gestational week. We find that SHH expression is robustly upregulated in the airway epithelia of children with asthma or mouse models with allergic airway disease. Specifically, airway-specific SMO loss of function significantly suppresses allergen-induced goblet cell phenotypes, whereas an airway-specific SMO gain of function markedly enhances the goblet cell phenotypes in mouse models with allergic airway disease...
June 4, 2018: Mucosal Immunology
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