Inhaled Corticosteroid Therapy in Adult Asthma. Time for a New Therapeutic Dose Terminology

Beasley, Richard; Harper, James; Bird, Grace; Maijers, Ingrid; Weatherall, Mark; Pavord, Ian D.

doi:10.1164/rccm.201810-1868ci

Cited by 99 publications

(61 citation statements)

References 43 publications

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“…By targeting the glucocorticoid receptor, ICS inhibit the release of cytokines and other proinflammatory mediators, decrease eosinophil and mast cell recruitment, and inhibit nuclear transcription factors, thus suppressing adhesion molecule function and inducible nitric oxide synthase 1‐4 . However, the largest clinical benefits are seen at low‐dose ICS, with diminishing returns due to increased systemic adverse events at higher doses 5 …”

Section: Introductionmentioning

confidence: 99%

Dupilumab is effective in type 2‐high asthma patients receiving high‐dose inhaled corticosteroids at baseline

Bourdin

Papi

Corren

et al. 2020

Allergy

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Background: Dupilumab blocks the shared receptor component for interleukin (IL)-4/ IL-13, key drivers of type 2 inflammation. In phase 2b (NCT01854047) and phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200/300 mg every 2 weeks (q2w) reduced severe exacerbations, improved prebronchodilator (pre-BD) forced expiratory volume in 1 second (FEV 1) and quality of life measures, and it was generally well tolerated in patients with uncontrolled, persistent (phase 2b), or moderate-to-severe (phase 3) asthma. Methods: In patients on high-dose inhaled corticosteroids (ICS) with type 2-high asthma (subgroups including baseline blood eosinophils ≥150/300 cells/µL and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb), annualized severe exacerbation rates over the treatment period, changes from baseline in pre-BD FEV 1 and asthma control (5-item asthma control questionnaire [ACQ-5]) were analyzed. Results: In high-dose ICS type 2-high subgroups, dupilumab 200/300 mg q2w vs placebo in the phase 2b (24 weeks) and phase 3 (52 weeks) studies significantly reduced severe exacerbations by 55%-69%/57%-60% (all P<.05) and 53%-69%/48%-66%

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Section: Introductionmentioning

confidence: 99%

Dupilumab is effective in type 2‐high asthma patients receiving high‐dose inhaled corticosteroids at baseline

Bourdin

Papi

Corren

et al. 2020

Allergy

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“…Reduced expression of Nr3c1 may lead to glucocorticoid resistance, which gives rise to the inflammatory response [ 35 ]. Actually, many individuals with asthma rely on corticosteroid medications to control asthma symptoms [ 36 ]. However, in animal experiments, Nr3c1 apparently revealed a large gap in lung tissues of normal mice and ubiquitously expressed lower in most allergic mice lung tissues ( Figure 5(b) ); this is the reason why we did not test it in subsequent animal studies.…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology‐Based Study on the Mechanism of Pinellia ternata in Asthma Treatment

Lyu

Chen

Xia

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Background. Pinellia ternata (PT), a medicinal plant, has had an extensive application in the treatment of asthma in China, whereas its underlying pharmacological mechanisms remain unclear. Methods. Firstly, a network pharmacology method was adopted to collect activated components of PT from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets of PT were assessed by exploiting the PharmMapper website; asthma-related targets were collected from the OMIM website, and target-target interaction networks were built. Secondly, critical nodes exhibiting high possibility were identified as the hub nodes in the network, which were employed to conduct Gene Ontology (GO) comment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. Finally, the tissue expression profiles of key candidate genes were identified by the Gene Expression Omnibus (GEO) database, and the therapeutic effect of PT was verified by an animal experiment. Results. 57 achievable targets of PT on asthma were confirmed as hub nodes through using the network pharmacology method. As revealed from the KEGG enrichment analysis, the signaling pathways were notably enriched in pathways of the T-cell receptor signaling pathway, JAK-STAT signaling pathway, and cytokine-cytokine receptor interaction. The expression profiles of candidate genes including Mmp2, Nr3c1, il-10, il-4, il-13, il-17a, il-2, tlr4, tlr9, ccl2, csf2, and vefgα were identified. Moreover, according to transcriptome RNA sequencing data from lung tissues of allergic mice compared to normal mice, the mRNA level of Mmp2 and il-4 was upregulated ( P < 0.001 ). In animal experiments, PT could alleviate the allergic response of mice by inhibiting the activation of T-helper type 2 (TH2) cells and the expression of Mmp2 and il-4. Conclusions. Our study provides candidate genes that may be either used for future studies related to diagnosis/prognosis or as targets for asthma management. Besides, animal experiments showed that PT could treat asthma by regulating the expression of Mmp2 and il-4.

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“…Prolonged use and higher doses of ICS are associated with a progressive risk of systemic adverse effects, including adrenal suppression, diabetes, cataracts, glaucoma, osteoporosis, and fractures. Unlike the plateau effect of efficacy outcomes, which occurs with higher ICS doses, there is no plateau to the risk of adverse effects [11]. Community studies from Australia and Scotland suggest patients are often inappropriately prescribed, and remain on, high doses of ICSs [12,13].…”

Section: Introductionmentioning

confidence: 99%

Health and cost impact of stepping down asthma medication for UK patients, 2001–2017: A population-based observational study

et al. 2020

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Background Guidelines recommend stepping down asthma treatment to the minimum effective dose to achieve symptom control, prevent adverse side effects, and reduce costs. Limited data exist on asthma prescription patterns in a real-world setting. We aimed to evaluate the appropriateness of doses prescribed to a UK general asthma population and assess whether stepping down medication increased exacerbations or reliever use, as well as its impact on costs. Methods and findings We used nationwide UK primary care medical records, 2001-2017, to identify 508,459 adult asthma patients managed with preventer medication. Prescriptions of higher-level medication: medium/high-dose inhaled corticosteroids (ICSs) or ICSs + add-on medication (longacting β2-agonist [LABA], leukotriene receptor antagonist [LTRA], theophylline, or long-acting muscarinic antagonist [LAMA]) steadily increased over time (2001 = 49.8%, 2017 = 68.3%). Of those prescribed their first preventer, one-third were prescribed a higher-level medication, of whom half had no reliever prescription or exacerbation in the year prior. Of patients first prescribed ICSs + 1 add-on, 70.4% remained on the same medication during a mean follow-up of 6.6 years. Of those prescribed medium/high-dose ICSs as their first preventer, 13.0% already had documented diabetes, cataracts, glaucoma, or osteopenia/osteoporosis. A cohort of 125,341 patients were drawn to assess the impact of stepping down medication: mean age 50.4 years, 39.4% males, 39,881 stepped down. Exposed patients were stepped down by dropping their LABAs or another add-on or by halving their ICS dose (halving their mean-daily dose or their inhaler dose). The primary and secondary outcomes were, respectively, exacerbations and an increase in reliever prescriptions. Multivariable regression was used to assess outcomes and determine the prognostic factors for initiating stepdown. There was no increased exacerbation risk for each possible medication stepdown

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Inhaled Corticosteroid Therapy in Adult Asthma. Time for a New Therapeutic Dose Terminology

Cited by 99 publications

References 43 publications

Dupilumab is effective in type 2‐high asthma patients receiving high‐dose inhaled corticosteroids at baseline

Dupilumab is effective in type 2‐high asthma patients receiving high‐dose inhaled corticosteroids at baseline

Network Pharmacology‐Based Study on the Mechanism of Pinellia ternata in Asthma Treatment

Health and cost impact of stepping down asthma medication for UK patients, 2001–2017: A population-based observational study

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