Asthma Exacerbations: Pathogenesis, Prevention, and Treatment

Castillo, Jamee R.; Peters, Stephen P.; Busse, William W.

doi:10.1016/j.jaip.2017.05.001

Cited by 332 publications

(282 citation statements)

References 137 publications

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“…HRV infections throughout the year and in many cases, manifest with symptoms such as nasal congestion, rhinorrhoea, sneezing, sore throat, and cough. HRV is known to be the primary cause of ARI and a severe contributing factor in exacerbations of atopic disease, e.g., asthma as well other conditions such as chronic obstructive pulmonary disease (COPD) [10][11][12][13].…”

Section: Rhinovirus (The "Common" Cold)mentioning

confidence: 99%

The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics

et al. 2018

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The Human Viral Challenge (HVC) model has, for many decades, helped in the understanding of respiratory viruses and their role in disease pathogenesis. In a controlled setting using small numbers of volunteers removed from community exposure to other infections, this experimental model enables proof of concept work to be undertaken on novel therapeutics, including vaccines, immunomodulators and antivirals, as well as new diagnostics.Crucially, unlike conventional phase 1 studies, challenge studies include evaluable efficacy endpoints that then guide decisions on how to optimise subsequent field studies, as recommended by the FDA and thus licensing studies that follow. Such a strategy optimises the benefit of the studies and identifies possible threats early on, minimising the risk to subsequent volunteers but also maximising the benefit of scarce resources available to the research group investing in the research. Inspired by the principles of the 3Rs (Replacement, Reduction and Refinement) now commonly applied in the preclinical phase, HVC studies allow refinement and reduction of the subsequent development phase, accelerating progress towards further statistically powered phase 2b studies. The breadth of data generated from challenge studies allows for exploration of a wide range of variables and endpoints that can then be taken through to pivotal phase 3 studies.We describe the disease burden for acute respiratory viral infections for which current conventional development strategies have failed to produce therapeutics that meet clinical need. The Authors describe the HVC model’s utility in increasing scientific understanding and in progressing promising therapeutics through development.The contribution of the model to the elucidation of the virus-host interaction, both regarding viral pathogenicity and the body’s immunological response is discussed, along with its utility to assist in the development of novel diagnostics.Future applications of the model are also explored.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0784-1) contains supplementary material, which is available to authorized users.

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Section: Rhinovirus (The "Common" Cold)mentioning

confidence: 99%

The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics

et al. 2018

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“…The role of viruses in asthma exacerbations further contributes to pathologic mechanisms in severe allergic asthma [39]. While respiratory viruses (especially rhinovirus) are the most common trigger of asthma exacerbations, the T2-high subgroup appears to be particularly exacerbation prone with viral infections.…”

Section: Introductionmentioning

confidence: 99%

Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Kuruvilla

Lee

2018

Clinic Rev Allerg Immunol

775

719

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The model of asthma as a single entity has now been replaced by a much more complex biological network of distinct and interrelating inflammatory pathways. The term asthma is now considered an umbrella diagnosis for several diseases with distinct mechanistic pathways (endotypes) and variable clinical presentations (phenotypes). The precise definition of these endotypes is central to asthma management due to inherent therapeutic and prognostic implications. This review presents the molecular mechanisms behind the heterogeneity of airway inflammation in asthmatic patients. Asthma endotypes may be broadly regarded as type 2 (T2) high or T2-low. Several biologic agents have been approved for T2-high asthma, with numerous other therapeutics that are incipient and similarly targeted at specific molecular mechanisms. Collectively, these advances have shifted existing paradigms in the approach to asthma to tailor novel therapies.

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“…Asthma is a chronic inflammatory airway disease that is susceptible to triggering factors, such as aeroallergens, air pollutants, and viral infection [1]. Despite major advances in prevention and management, asthma remains a considerable global healthcare burden [2].…”

Section: Introductionmentioning

confidence: 99%

Regional, age and respiratory-secretion-specific prevalence of respiratory viruses associated with asthma exacerbation: a literature review

et al. 2018

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Despite increased understanding of how viral infection is involved in asthma exacerbations, it is less clear which viruses are involved and to what extent they contribute to asthma exacerbations. Here, we sought to determine the prevalence of different respiratory viruses during asthma exacerbations. Systematic computerized searches of the literature up to June 2017 without language limitation were performed. The primary focus was on the prevalence of respiratory viruses, including AdV (adenovirus), BoV (bocavirus), CoV (coronavirus), CMV (cytomegalovirus), EnV (enterovirus), HSV (herpes simplex virus), IfV (influenza virus), MpV (metapneumovirus), PiV (parainfluenzavirus), RV (rhinovirus) and RSV (respiratory syncytial virus) during asthma exacerbations. We also examined the prevalence of viral infection stratified by age, geographic region, type of respiratory secretion, and detection method. Sixty articles were included in the final analysis. During asthma exacerbations, the mean prevalence of AdV, BoV, CoV, CMV, EnV, HSV, IfV, MpV, PiV, RV and RSV was 3.8%, 6.9%, 8.4%, 7.2%, 10.1%, 12.3%, 10.0%, 5.3%, 5.6%, 42.1% and 13.6%, respectively. EnV, MPV, RV and RSV were more prevalent in children, whereas AdV, BoV, CoV, IfV and PiV were more frequently present in adults. RV was the major virus detected globally, except in Africa. RV could be detected in both the upper and lower airway. Polymerase chain reaction was the most sensitive method for detecting viral infection. Our findings indicate the need to develop prophylactic polyvalent or polyvirus (including RV, EnV, IfV and RSV) vaccines that produce herd immunity and reduce the healthcare burden associated with virus-induced asthma exacerbations.

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Asthma Exacerbations: Pathogenesis, Prevention, and Treatment

Cited by 332 publications

References 137 publications

The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics

The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics

Understanding Asthma Phenotypes, Endotypes, and Mechanisms of Disease

Regional, age and respiratory-secretion-specific prevalence of respiratory viruses associated with asthma exacerbation: a literature review

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