Atorvastatin in combination with inhaled beclometasone modulates inflammatory sputum mediators in smokers with asthma

Thomson, Neil C.; Charron, Catherine E.; Chaudhuri, Rekha; Spears, Mark; Ito, Kazuhiro; McSharry, Charles

doi:10.1016/j.pupt.2015.01.001

Cited by 31 publications

(23 citation statements)

References 66 publications

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“…It is important to note that this does not necessarily preclude asthmatics with non-Th2/non-type 2 (or type 2-low) inflammation, non-eosinophilic asthma, or neutrophilic predominant asthma where we still know very little [24]. For example, smoking asthmatics may also benefit from statins, but the specific sputum inflammatory cell subtypes relevant to severe asthma have not been fully characterized [53,57]. Overall, both animal and human data suggest that combined statin and corticosteroid therapy has additive and possibly synergistic anti-inflammatory effects in the lungs, something that would be very beneficial in severe asthma [54,90,91].…”

Section: The Mevalonate Pathway Statins and Relevance To Asthmamentioning

confidence: 99%

“…peak expiratory flow rate, forced expiratory volume in the first second (FEV1), forced vital capacity (FVC)), airway inflammation (sputum cell counts and cytokine levels), symptom surveys, and quality-of-life score(s) [53,55–60,87]. However, results from these RCTs have produced equivocal and at times conflicting results.…”

Section: The Mevalonate Pathway Statins and Relevance To Asthmamentioning

confidence: 99%

“…However, several small randomized clinical trials (RCT) using oral statins for the treatment of asthma have yielded conflicting results [51,52]. While results from these RCTs show a consistent anti-inflammatory effect by reducing sputum inflammatory cell counts and cytokine levels [53–56], they do not demonstrate improved clinical outcomes in terms of symptoms or lung function [41,57–60]. The reasons for this disconnect between basic and clinical studies are unclear, but for clinical trials choosing the right disease phenotype and treating for years rather than weeks or months may be necessary to see clinical benefits [41].…”

Section: Introductionmentioning

confidence: 99%

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Innovations in asthma therapy: is there a role for inhaled statins?

Zeki

Elbadawi-Sidhu

2018

Expert Review of Respiratory Medicine

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Introduction Asthma manifests as chronic airflow obstruction with persistent inflammation and airway hyperresponsiveness. The immunomodulatory and anti-inflammatory properties of the HMG-CoA reductase (HMGCR) inhibitors (a.k.a. statins), suggest a therapeutic role in chronic inflammatory lung diseases. However, despite positive laboratory investigations and promising epidemiological data, clinical trials using statins for the treatment of asthma have yielded conflicting results. Inadequate statin levels in the airway compartment could explain these findings. Areas covered HMGCR is in the mevalonate (MA) pathway and MA signaling is fundamental to lung biology and asthma. This article will discuss clinical trials of oral statins in asthma, review lab investigations relevant to the systemic versus inhaled administration of statins, address the advantages and disadvantages of inhaled statins, and answer the question: is there a role for inhaled statins in the treatment of asthma? Expert commentary If ongoing investigations show that oral administration of statins has no clear clinical benefits, then repurposing statins for delivery via inhalation is a logical next step. Inhalation of statins bypasses first-pass metabolism by the liver, and therefore, allows for delivery of significantly lower doses to the airways at greater potency. Statins could become the next major class of novel inhalers for the treatment of asthma.

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Section: The Mevalonate Pathway Statins and Relevance To Asthmamentioning

confidence: 99%

Section: The Mevalonate Pathway Statins and Relevance To Asthmamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Innovations in asthma therapy: is there a role for inhaled statins?

Zeki

Elbadawi-Sidhu

2018

Expert Review of Respiratory Medicine

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“…Abbreviations: CXCR, C-X-C chemokine receptor; FLAP, 5-lipoxygenase-activating protein; IL, interleukin; PDE, phosphodiesterase; PI3K, phosphoinositide 3-kinase; PPARγ,: peroxisome proliferator-activated receptor-γ. sputum samples collected during the previous clinical trial [Braganza et al 2011;Thomson et al 2015]. Sputum mediator concentrations were not reduced by inhaled beclometasone alone.…”

Section: Nonpharmacological Interventionsmentioning

confidence: 99%

Novel approaches to the management of noneosinophilic asthma

Thomson

2016

Ther Adv Respir Dis

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“…In smokers with asthma, atorvastatin treatment resulted in a small improvement in asthma quality of life and symptoms that were associated with reductions in several sputum cytokines, chemokines and growth factors concentrations unresponsive to ICS treatment 101,102 .…”

Section: Statinsmentioning

confidence: 99%

New and developing non-adrenoreceptor small molecule drugs for the treatment of asthma

Thomson

2017

Expert Opinion on Pharmacotherapy

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IntroductionInhaled corticosteroids (ICS) alone or in combination with an inhaled long-acting beta2-agonist (LABA) are the preferred long-term treatment for adults and adolescents with symptomatic asthma. Additional drugs include leukotriene-receptor antagonists, slow-release theophylline and the long-acting muscarinic antagonist (LAMA) tiotropium (approved in 2015). There is a need for more effective therapies, as many patients continue to have poorly controlled asthma. Areas coveredNew and developing long-acting non-adrenoreceptor synthetic drugs for the treatment of symptomatic chronic asthma despite treatment with an ICS alone or combined with a LABA.Data was reviewed from studies published up until November 2016. Expert opinionTiotropium improves lung function and has a modest effect in reducing exacerbations when

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Atorvastatin in combination with inhaled beclometasone modulates inflammatory sputum mediators in smokers with asthma

Cited by 31 publications

References 66 publications

Innovations in asthma therapy: is there a role for inhaled statins?

Innovations in asthma therapy: is there a role for inhaled statins?

Novel approaches to the management of noneosinophilic asthma

New and developing non-adrenoreceptor small molecule drugs for the treatment of asthma

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