Infection-Related Asthma

Darveaux, Jared I.; Lemanske, Robert F.

doi:10.1016/j.jaip.2014.09.011

Cited by 74 publications

(62 citation statements)

References 81 publications

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“…Importantly, one of the more common adverse events associated with blockade of IL‐17A/IL‐17RA in early clinical trials is the increased susceptibility to bacterial or fungal infections . Thus, the demonstration that low dose anti‐IL‐17A has no impact on responses to bacterial products or the response to infection, while maintaining the ability to influence asthma severity, is a highly relevant observation emerging from the current study—particularly as bacterial or fungal infections are frequent triggers for asthma exacerbations . Thus, we argue that exploration of combined, sub‐therapeutic dosing regimens is an important avenue for future experimental studies.…”

Section: Discussionmentioning

confidence: 82%

Combined administration of anti‐IL‐13 and anti‐IL‐17A at individually sub‐therapeutic doses limits asthma‐like symptoms in a mouse model of Th2/Th17 high asthma

Kim

McAlees

Bischoff

et al. 2018

Clin Experimental Allergy

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Background: Recent studies have demonstrated that Th2 responses have the ability to antagonize Th17 responses. In mouse models of allergic asthma, blockade of Th2-effector cytokines results in elaboration of Th17 responses and associated increases in pulmonary neutrophilia. While these can be controlled by simultaneous blockade of Th17associated effector cytokines, clinical trials of anti-IL-17/IL-17RA blocking therapies have demonstrated increased of risk of bacterial and fungal infections. Identification of minimally effective doses of cytokine-blocking therapies with the goal of reducing the potential emergence of infection-related complications is a translationally relevant goal.Objective: In the current report, we examine whether combined blockade of IL-13 and IL-17A, at individually sub-therapeutic levels, can limit the development of allergic asthma while sparing expression of IL-17A-associated anti-microbial effectors.Methods: House dust mite was given intratracheally to A/J mice. Anti-IL-13 and anti-IL-17A antibodies were administered individually, or concomitantly at sub-therapeutic doses. Airway hyper-reactivity, lung inflammation, magnitude of Th2-and Th17-associated cytokine production and expression of IL-13-and IL-17A-induced genes in the lungs was assessed.Results: Initial dosing studies identified sub-therapeutic levels of IL-13 and IL-17A blocking mAbs that have a limited effect on asthma parameters and do not impair responses to microbial products or infection. Subsequent studies demonstrated that combined sub-therapeutic dosing with IL-13 and IL-17A blocking mAbs resulted in significant improvement in airway hyperresponsiveness (AHR) and expression of IL-13-induced gene expression. Importantly, these doses neither exacerbated nor inhibited production of Th17-associated cytokines, or IL-17A-associated gene expression. Conclusion: This study suggests that combining blockade of individual Th2 andTh17 effector cytokines, even at individually sub-therapeutic levels, may be sufficient to limit disease development while preserving important anti-microbial pathways. Such a strategy may therefore have reduced potential for adverse events associated with blockade of these pathways.

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Section: Discussionmentioning

confidence: 82%

Combined administration of anti‐IL‐13 and anti‐IL‐17A at individually sub‐therapeutic doses limits asthma‐like symptoms in a mouse model of Th2/Th17 high asthma

Kim

McAlees

Bischoff

et al. 2018

Clin Experimental Allergy

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“…In Europe, more than 30 million people are affected, with 6 million suffering severe symptoms and 1.5 million life‐threatening attacks . Asthma onset and acute asthma exacerbations (AAEs) have been strongly associated with respiratory viral and (to a lesser extent) bacterial infections …”

Section: Introductionmentioning

confidence: 99%

Influenza burden, prevention, and treatment in asthma‐A scoping review by the EAACI Influenza in asthma task force

Schwarze

Openshaw

Jha

et al. 2018

Allergy

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To address uncertainties in the prevention and management of influenza in people with asthma, we performed a scoping review of the published literature on influenza burden; current vaccine recommendations; vaccination coverage; immunogenicity, efficacy, effectiveness, and safety of influenza vaccines; and the benefits of antiviral drugs in people with asthma. We found significant variation in the reported rates of influenza detection in individuals with acute asthma exacerbations making it unclear to what degree influenza causes exacerbations of underlying asthma. The strongest evidence of an association was seen in studies of children. Countries in the European Union currently recommend influenza vaccination of adults with asthma; however, coverage varied between regions. Coverage was lower among children with asthma. Limited data suggest that good seroprotection and seroconversion can be achieved in both children and adults with asthma and that vaccination confers a degree of protection against influenza illness and asthma-related morbidity to children with asthma. There were insufficient data to determine efficacy in adults. Overall, influenza vaccines appeared to be safe for people with asthma. We identify knowledge gaps and make recommendations on future research needs in relation to influenza in patients with asthma.

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“…As regards the possible mechanisms of thalassemic patients had higher risk to have asthma, Palma-Carlos et al (12) stated that the hemorheological changes in thalassemia may be a greater rigidity of red blood cells in capillary bed which can contribute to changes in bronchial circulation and bronchial hyperactivity, but no solid evidence supported yet. Recently, we found thalassemic patients had higher incidence of low respiratory tract infection (Yuu et al, just submitted) which may link to higher incidence of asthma or asthma exacerbation (13,14).…”

Section: Discussionmentioning

confidence: 89%

Transfusion-naïve Thalassemia Pediatric Patients have Higher Incidence of Asthma: A Nationwide Population-based Retrospective Cohort Study

Hsieh¹,

Huang²,

Yu³

et al. 2020

Preprint

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Background: Few studies have studied the association between asthma and pediatric transfusion naïve thalassemia. Methods: A nationwide population-based retrospective cohort study was conducted using medical records of selected children from the 2010 Registry for Beneficiaries of the Taiwan National Health Insurance Research Database, with a follow-up period extending to the end of 2013. One thalassemia patient was matched with four control patients without thalassemia according to year of birth, sex, and the propensity score model based on comorbidities. Results: In this study, 794 patients with thalassemia and 3176 controls were included. Transfusion-naïve thalassemia children had higher rates to develop asthma (41.03 vs 36.69 per 1000 person-y; P = 0.032) than the non-thalassemia controls with an adjusted hazard ratio of 1.16 (95% confidence interval (CI) = 1.01–1.33). Boys in the thalassemia cohort had a significantly higher adjusted hazard ratio of asthma than those in the non-thalassemia cohort (adjusted hazard ratio = 1.20, 95% CI = 1.02–1.42). In thalassemic patients without atopic dermatitis, the risk of asthma was 1.25-fold higher than in the non-thalassemic ones (95% CI=1.07–1.47). Conclusions: Transfusion-naïve thalassemia children are more likely to have asthma. We need to pay more attention to it in order to diagnosis asthma earlier and to prevent asthma attacked earlier.

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Infection-Related Asthma

Cited by 74 publications

References 81 publications

Combined administration of anti‐IL‐13 and anti‐IL‐17A at individually sub‐therapeutic doses limits asthma‐like symptoms in a mouse model of Th2/Th17 high asthma

Combined administration of anti‐IL‐13 and anti‐IL‐17A at individually sub‐therapeutic doses limits asthma‐like symptoms in a mouse model of Th2/Th17 high asthma

Influenza burden, prevention, and treatment in asthma‐A scoping review by the EAACI Influenza in asthma task force

Transfusion-naïve Thalassemia Pediatric Patients have Higher Incidence of Asthma: A Nationwide Population-based Retrospective Cohort Study

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