Severe refractory asthma: an update

Wener, Reinier; Bel, Elisabeth H.

doi:10.1183/09059180.00001913

Cited by 37 publications

(34 citation statements)

References 110 publications

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“…The spectrum of heterogeneity in asthma includes patients with severe disease, whose symptoms remain inadequately controlled despite treatment with current therapies 1, 2 . Importantly, heterogeneity within severe asthma also has been described 3, 4 .…”

Section: Introductionmentioning

confidence: 99%

The airway microbiome in patients with severe asthma: Associations with disease features and severity

Huang

Nariya

Harris³

et al. 2015

Journal of Allergy and Clinical Immunology

403

408

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Background Asthma is heterogeneous, and airway dysbiosis is associated with clinical features in mild-moderate asthma. Whether similar relationships exist among patients with severe asthma is unknown. Objective To evaluate relationships between the bronchial microbiome and features of severe asthma. Methods Bronchial brushings from 40 participants in the BOBCAT study (Bronchoscopic Exploratory Research Study of Biomarkers in Corticosteroid-refractory Asthma) were evaluated using 16S rRNA-based methods. Relationships to clinical and inflammatory features were analyzed among microbiome-profiled subjects. Secondarily, bacterial compositional profiles were compared between severe asthmatics, and previously studied healthy controls (n=7), and mild-moderate asthma subjects (n=41). Results In severe asthma, bronchial bacterial composition was associated with several disease-related features, including body-mass index (BMI; Bray-Curtis distance PERMANOVA, p < 0.05), changes in Asthma Control Questionnaire (ACQ) scores (p < 0.01), sputum total leukocytes (p = 0.06) and bronchial biopsy eosinophils (per mm2; p = 0.07). Bacterial communities associated with worsening ACQ and sputum total leukocytes (predominantly Proteobacteria) differed markedly from those associated with BMI (Bacteroidetes/Firmicutes). In contrast, improving/stable ACQ and bronchial epithelial gene expression of FKBP5, an indicator of steroid responsiveness, correlated with Actinobacteria. Mostly negative correlations were observed between biopsy eosinophils and Proteobacteria. No taxa were associated with a T-helper type 2-related epithelial gene expression signature, but expression of Th17-related genes was associated with Proteobacteria. Severe asthma subjects, compared to healthy controls or mild-moderate asthmatics, were significantly enriched in Actinobacteria, although the largest differences observed involved a Klebsiella genus member (7.8 fold-increase in severe asthma, padj < 0.001) Conclusions Specific microbiota are associated with and may modulate inflammatory processes in severe asthma and related phenotypes. Airway dysbiosis in severe asthma appears to differ from that observed in milder asthma in the setting of inhaled corticosteroid use.

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Section: Introductionmentioning

confidence: 99%

The airway microbiome in patients with severe asthma: Associations with disease features and severity

Huang

Nariya

Harris³

et al. 2015

Journal of Allergy and Clinical Immunology

403

408

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“…Inhaled short acting β 2 -agonists represent the most common front-line emergency department treatment for acute exacerbations due to their well-known rapid bronchodilatory effect [11–13] β 2 -agonists, while generally considered safe may have significant side effects [14] and approximately one fifth to one third of patients do not respond to front-line treatment with short acting β 2 -agonists and ultimately require hospitalisation [15]. Furthermore, a clinically significant proportion of asthma patients are refractory to conventional treatments, posing a challenge for their management [16]. A new class of bronchodilators working through a different mechanism would be a useful addition for treating acute asthma.…”

Section: Introductionmentioning

confidence: 99%

Nebulized perflubron and carbon dioxide rapidly dilate constricted airways in an ovine model of allergic asthma

et al. 2014

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BackgroundThe low toxicity of perfluorocarbons (PFCs), their high affinity for respiratory gases and their compatibility with lung surfactant have made them useful candidates for treating respiratory diseases such as adult respiratory distress syndrome. We report results for treating acute allergic and non-allergic bronchoconstriction in sheep using S-1226 (a gas mixture containing carbon dioxide and small volumes of nebulized perflubron). The carbon dioxide, which is highly soluble in perflubron, was used to relax airway smooth muscle.MethodsSheep previously sensitized to house dust mite (HDM) were challenged with HDM aerosols to induce early asthmatic responses. At the maximal responses (characterised by an increase in lung resistance), the sheep were either not treated or treated with one of the following; nebulized S-1226 (perflubron + 12% CO2), nebulized perflubron + medical air, 12% CO2, salbutamol or medical air. Lung resistance was monitored for up to 20 minutes after cessation of treatment.In additional naïve sheep, a segmental bronchus was pre-contracted with methacholine (MCh) and treated with nebulized S-1226 administered via a bronchoscope catheter. Subsequent bronchodilatation was monitored by real time digital video recording.ResultsTreatment with S-1226 for 2 minutes following HDM challenge resulted in a more rapid, more profound and more prolonged decline in lung resistance compared with the other treatment interventions. Video bronchoscopy showed an immediate and complete (within 5 seconds) re-opening of MCh-constricted airways following treatment with S-1226.ConclusionsS-1226 is a potent and rapid formulation for re-opening constricted airways. Its mechanism(s) of action are unknown. The formulation has potential as a rescue treatment for acute severe asthma.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0098-x) contains supplementary material, which is available to authorized users.

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“…facing a wide range of problems and diseases, and always bearing in mind possible common features and links between different conditions. Thus, the article by WENER and BEL [4] informs us how we can learn to distinguish between ''difficult-tocontrol'' and ''severe refractory'' asthma, as well as how to practically manage these difficult situations. The review by GARCIA et al [5] illustrates the possible role of anti-interleukin-5 compounds in the treatment of severe eosinophilic asthmatic patients with a history of frequent exacerbations.…”

Section: @Erspublicationsmentioning

confidence: 99%

Future perspectives on rare pulmonary diseases and rare presentations of common disorders

Harari¹,

Humbert²,

Cottin³

2013

European Respiratory Review

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Severe refractory asthma: an update

Cited by 37 publications

References 110 publications

The airway microbiome in patients with severe asthma: Associations with disease features and severity

The airway microbiome in patients with severe asthma: Associations with disease features and severity

Nebulized perflubron and carbon dioxide rapidly dilate constricted airways in an ovine model of allergic asthma

Future perspectives on rare pulmonary diseases and rare presentations of common disorders

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