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      The potential of anti‐infectives and immunomodulators as therapies for asthma and asthma exacerbations

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          Abstract

          Asthma is responsible for approximately 25,000 deaths annually in Europe despite available medicines that maintain asthma control and reduce asthma exacerbations. Better treatments are urgently needed for the control of chronic asthma and reduction in asthma exacerbations, the major cause of asthma mortality. Much research spanning >20 years shows a strong association between microorganisms including pathogens in asthma onset, severity and exacerbation, yet with the exception of antibiotics, few treatments are available that specifically target the offending pathogens. Recent insights into the microbiome suggest that modulating commensal organisms within the gut or lung may also be a possible way to treat/prevent asthma. The European Academy of Allergy & Clinical Immunology Task Force on Anti‐infectives in Asthma was initiated to investigate the potential of anti‐infectives and immunomodulators in asthma. This review provides a concise summary of the current literature and aimed to identify and address key questions that concern the use of anti‐infectives and both microbe‐ and host‐based immunomodulators and their feasibility for use in asthma.

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          Microbiota regulates immune defense against respiratory tract influenza A virus infection.

          Takeshi Ichinohe, Iris K Pang, Yosuke Kumamoto … (2011)
          Although commensal bacteria are crucial in maintaining immune homeostasis of the intestine, the role of commensal bacteria in immune responses at other mucosal surfaces remains less clear. Here, we show that commensal microbiota composition critically regulates the generation of virus-specific CD4 and CD8 T cells and antibody responses following respiratory influenza virus infection. By using various antibiotic treatments, we found that neomycin-sensitive bacteria are associated with the induction of productive immune responses in the lung. Local or distal injection of Toll-like receptor (TLR) ligands could rescue the immune impairment in the antibiotic-treated mice. Intact microbiota provided signals leading to the expression of mRNA for pro-IL-1β and pro-IL-18 at steady state. Following influenza virus infection, inflammasome activation led to migration of dendritic cells (DCs) from the lung to the draining lymph node and T-cell priming. Our results reveal the importance of commensal microbiota in regulating immunity in the respiratory mucosa through the proper activation of inflammasomes.
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            Exposure to environmental microorganisms and childhood asthma.

            Markus J Ege, Melanie L. Mayer, Anne-Cécile Normand … (2011)
            Children who grow up in environments that afford them a wide range of microbial exposures, such as traditional farms, are protected from childhood asthma and atopy. In previous studies, markers of microbial exposure have been inversely related to these conditions. In two cross-sectional studies, we compared children living on farms with those in a reference group with respect to the prevalence of asthma and atopy and to the diversity of microbial exposure. In one study--PARSIFAL (Prevention of Allergy-Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle)--samples of mattress dust were screened for bacterial DNA with the use of single-strand conformation polymorphism (SSCP) analyses to detect environmental bacteria that cannot be measured by means of culture techniques. In the other study--GABRIELA (Multidisciplinary Study to Identify the Genetic and Environmental Causes of Asthma in the European Community [GABRIEL] Advanced Study)--samples of settled dust from children's rooms were evaluated for bacterial and fungal taxa with the use of culture techniques. In both studies, children who lived on farms had lower prevalences of asthma and atopy and were exposed to a greater variety of environmental microorganisms than the children in the reference group. In turn, diversity of microbial exposure was inversely related to the risk of asthma (odds ratio for PARSIFAL, 0.62; 95% confidence interval [CI], 0.44 to 0.89; odds ratio for GABRIELA, 0.86; 95% CI, 0.75 to 0.99). In addition, the presence of certain more circumscribed exposures was also inversely related to the risk of asthma; this included exposure to species in the fungal taxon eurotium (adjusted odds ratio, 0.37; 95% CI, 0.18 to 0.76) and to a variety of bacterial species, including Listeria monocytogenes, bacillus species, corynebacterium species, and others (adjusted odds ratio, 0.57; 95% CI, 0.38 to 0.86). Children living on farms were exposed to a wider range of microbes than were children in the reference group, and this exposure explains a substantial fraction of the inverse relation between asthma and growing up on a farm. (Funded by the Deutsche Forschungsgemeinschaft and the European Commission.).
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              Community study of role of viral infections in exacerbations of asthma in 9-11 year old children.

              S Johnston, P Pattemore, G. Sanderson … (1995)
              To study the association between upper and lower respiratory viral infections and acute exacerbations of asthma in schoolchildren in the community. Community based 13 month longitudinal study using diary card respiratory symptom and peak expiratory flow monitoring to allow early sampling for viruses. 108 Children aged 9-11 years who had reported wheeze or cough, or both, in a questionnaire. Southampton and surrounding community. Upper and lower respiratory viral infections detected by polymerase chain reaction or conventional methods, reported exacerbations of asthma, computer identified episodes of respiratory tract symptoms or peak flow reductions. Viruses were detected in 80% of reported episodes of reduced peak expiratory flow, 80% of reported episodes of wheeze, and in 85% of reported episodes of upper respiratory symptoms, cough, wheeze, and a fall in peak expiratory flow. The median duration of reported falls in peak expiratory flow was 14 days, and the median maximum fall in peak expiratory flow was 81 l/min. The most commonly identified virus type was rhinovirus. This study supports the hypothesis that upper respiratory viral infections are associated with 80-85% of asthma exacerbations in school age children.
              Article 0 comments Cited 427 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                M. R. Khaitov:
                ORCID: http://orcid.org/0000-0003-4961-9640
                mr.khaitov@nrcii.ru
                Journal
                Journal ID (nlm-ta): Allergy
                Journal ID (iso-abbrev): Allergy
                Journal ID (doi): 10.1111/(ISSN)1398-9995
                Journal ID (publisher-id): ALL
                Title: Allergy
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 0105-4538
                ISSN (Electronic): 1398-9995
                Publication date (Electronic): 10 August 2017
                Publication date (Print): January 2018
                Volume: 73
                Issue: 1 ( doiID: 10.1111/all.2018.73.issue-1 )
                Pages: 50-63
                Affiliations
                [ 1 ] Airway Disease Infection Section National Heart Lung Institute Imperial College London London UK
                [ 2 ] MRC and Asthma UK Centre for Allergic Mechanisms of Asthma London UK
                [ 3 ] Division of Asthma, Allergy & Lung Biology King's College London & Guy's and St Thomas' NHS Trust London UK
                [ 4 ] Department of Pediatric Respiratory Diseases and Allergy The Medical University of Warsaw Warsaw Poland
                [ 5 ] Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics Philipps University Marburg & University Hospital Giessen Marburg Germany
                [ 6 ] The Department of Pediatrics Turku University Hospital Turku Finland
                [ 7 ] National Research Center Institute of Immunology of Federal Medicobiological Agency Moscow Russia
                [ 8 ] Mechnikov Research Institute of Vaccines and Sera Moscow Russia
                [ 9 ] Centre for Inflammation Research University of Edinburgh The Queens Medical Research Institute Edinburgh Edinburgh UK
                Author notes
                [*] [* ] Correspondence

                Musa Khaitov, NRC Institute of Immunology FMBA, Moscow, Russia.

                Email: mr.khaitov@ 123456nrcii.ru

                Author information
                http://orcid.org/0000-0003-4961-9640
                Article
                Publisher ID: ALL13257
                DOI: 10.1111/all.13257
                PMC ID: 7159495
                PubMed ID: 28722755
                SO-VID: a0e858d1-66c6-4845-a266-fddd2c3fa8d2
                Copyright © © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
                License:

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                Date accepted : 16 July 2017
                Page count
                Figures: 3, Tables: 3, Pages: 14, Words: 11306
                Funding
                Funded by: EAACI
                Funded by: RSF , open-funder-registry 10.13039/100000935;
                Award ID: 14‐15‐00894
                Categories
                Subject: Review Article
                Subject: Review Articles
                Custom metadata
                source-schema-version-number 2.0
                cover-date January 2018
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020

                ScienceOpen disciplines: Immunology
                Keywords: anti‐infective,asthma,immunomodulator,infection,lung
                Data availability:
                ScienceOpen disciplines: Immunology
                Keywords: anti‐infective, asthma, immunomodulator, infection, lung

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