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

Edwards, Michael R.; Walton, Ross P.; Jackson, David J.; Feleszko, Wojciech; Skevaki, Chrysanthi; Jartti, Tuomas; Makrinoti, H.; Nikonova, Alexandra; Shilovskiy, Igor; Schwarze, Jürgen; Johnston, Sebastian L.; Khaitov, Musa; Asthma, Eaaci Anti-infectives in; Force, Asthma Exacerbations Task

doi:10.1111/all.13257

Cited by 44 publications

(55 citation statements)

References 123 publications

(212 reference statements)

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“…These findings suggest that there are a number of therapeutic opportunities to reduce the frequency and severity of viral respiratory illnesses and hopefully secondary effects on the incidence and exacerbation of asthma (Fig 3). The search goes on for effective antivirals and vaccines for RV and RSV, and several candidates are currently in clinical trials (reviewed by Edwards et al 152 ). Antiviral approaches also include strategies to enhance resistance to multiple respiratory viruses through administration of interferons or other immunostimulatory molecules.…”

Section: Conclusion and Therapeutic Opportunitiesmentioning

confidence: 99%

Role of viral infections in the development and exacerbation of asthma in children

Jartti

Gern

2017

Journal of Allergy and Clinical Immunology

373

372

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Viral infections are closely linked to wheezing illnesses in children of all ages. Respiratory syncytial virus (RSV) is the main causative agent of bronchiolitis, whereas rhinovirus (RV) is most commonly detected in wheezing children thereafter. Severe respiratory illness induced by either of these viruses is associated with subsequent development of asthma, and the risk is greatest for young children who wheeze with RV infections. Whether viral illnesses actually cause asthma is the subject of intense debate. RSV-induced wheezing illnesses during infancy influence respiratory health for years. There is definitive evidence that RSV-induced bronchiolitis can damage the airways to promote airway obstruction and recurrent wheezing. RV likely causes less structural damage and yet is a significant contributor to wheezing illnesses in young children and in the context of asthma. For both viruses, interactions between viral virulence factors, personal risk factors (eg, genetics), and environmental exposures (eg, airway microbiome) promote more severe wheezing illnesses and the risk for progression to asthma. In addition, allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. Treatments that inhibit inflammation have efficacy for RV-induced wheezing, whereas the anti-RSV mAb palivizumab decreases the risk of severe RSV-induced illness and subsequent recurrent wheeze. Developing a greater understanding of personal and environmental factors that promote more severe viral illnesses might lead to new strategies for the prevention of viral wheezing illnesses and perhaps reduce the subsequent risk for asthma.

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Section: Conclusion and Therapeutic Opportunitiesmentioning

confidence: 99%

Role of viral infections in the development and exacerbation of asthma in children

Jartti

Gern

2017

Journal of Allergy and Clinical Immunology

373

372

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“…59,60 Several new molecules have been identified for the treatment of RSV infection and are currently in (advanced) preclinical or clinical development. 72,73…”

Section: Treatment For Rsvmentioning

confidence: 99%

“…There are only a few agents targeting the inhibition of the attachment of RV to the cell or uncoating viral RNA, and their clinical applicability is continuously questioned due to adverse events (pleconaril, vapendavir) or drug resistance (amantadine, rimantadine). 72,73 Prednisolone: In two separate randomized trials, oral corticosteroid, prednisolone, has been shown to increase the time to the physician-confirmed relapse within the following year by 20%-30%…”

Section: Treatment For Rvmentioning

confidence: 99%

“…14 Non-specific antiviral approaches to reduce asthma include strategies aiming at enhancing the patient's resistance to multiple respiratory viruses through the administration of interferons or other immunostimulatory molecules. 72,73 Strategies (microbial and others) to promote healthy epithelial barrier and the development of mucosal immune responses that can better resist viral infection might also help in preventing the development of asthma, as well as bacterial lysates, which may reduce the recurrent wheezing by increasing antiviral activity. 100 However, the level of evidence still remains to be low.…”

Section: Prevention Strategies Of Asthmamentioning

confidence: 99%

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Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Jartti

Smits

Bønnelykke

et al. 2018

Allergy

122

190

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Current data indicate that the “bronchiolitis” diagnosis comprises more than one condition. Clinically, pathophysiologically, and even genetically three main clusters of patients can be identified among children suffering from severe bronchiolitis (or first wheezing episode): (a) respiratory syncytial virus (RSV)‐induced bronchiolitis, characterized by young age of the patient, mechanical obstruction of the airways due to mucus and cell debris, and increased risk of recurrent wheezing. For this illness, an effective prophylactic RSV‐specific monoclonal antibody is available; (b) rhinovirus‐induced wheezing, associated with atopic predisposition of the patient and high risk of subsequent asthma development, which may, however, be reversed with systemic corticosteroids in those with severe illness; and (c) wheeze due to other viruses, characteristically likely to be less frequent and severe. Clinically, it is important to distinguish between these partially overlapping patient groups as they are likely to respond to different treatments. It appears that the first episode of severe bronchiolitis in under 2‐year‐old children is a critical event and an important opportunity for designing secondary prevention strategies for asthma. As data have shown bronchiolitis cannot simply be diagnosed using a certain cutoff age, but instead, as we suggest, using the viral etiology as the differentiating factor.

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“…Acute respiratory tract infections (ARIs) are triggered predominantly not only by RSV and RV, but also influenza virus, coronavirus and parainfluenza virus are significant risk factors for asthma development in children, depending on the load and timing of exposure. Although up to 50% of all children suffer from ARIassociated wheeze, it is yet unknown why some of them develop asthma, while others restore their healthy status [114]. While viral infections shift the immune response to the Th2 side, anti-viral response carried out by mediators of the Th1 axis is reduced [34,115].…”

Section: Infections and The Microbiomementioning

confidence: 99%

Role of early life immune regulation in asthma development

2019

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Development of childhood asthma is complex with a strong interaction of genetic, epigenetic, and environmental factors. Ultimately, it is critical how the immune system of a child responds to these influences and whether effective strategies for a balanced and healthy immune maturation can be assured. Pregnancy and early childhood are particularly susceptible for exogenous influences due to the developing nature of a child's immune system. While endogenous influences such as family history and the genetic background are immutable, epigenetic regulations can be modulated by both heredity and environmental exposures. Prenatal influences such as a mother's nutrition, smoking, or infections influence the complex interplay of innate and adaptive immune regulation as well as peri-and postnatal influences including mode of delivery. Early in life, induction and continuous training of healthy maturation include balanced innate immunity (e.g., via innate lymphoid cells) and an equilibrium of T-cell subpopulations (e.g., via regulatory T cells) to counterregulate potential pro-inflammatory or exuberant immune reactions. Later in childhood, rather compensatory immune mechanisms are required to modulate deviant regulation of a child's already primed immune trajectory. The specific effects of exogenous and endogenous influences on a child's maturing immune system are summarized in this review, and its importance and potential intervention for early prevention and treatment strategies are delineated.

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

Cited by 44 publications

References 123 publications

Role of viral infections in the development and exacerbation of asthma in children

Role of viral infections in the development and exacerbation of asthma in children

Bronchiolitis needs a revisit: Distinguishing between virus entities and their treatments

Role of early life immune regulation in asthma development

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