Statins in Asthma: Potential Beneficial Effects and Limitations

Bhattacharjee, Dipanjan; Chogtu, Bharti

doi:10.1155/2015/835204

Cited by 30 publications

(25 citation statements)

References 132 publications

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“…There have been a number of studies and reviews that have examined the efficacy of statins in asthma, as these cholesterol-lowering agents have anti-inflammatory and anti-oxidant effects and are a mainstay of risk reduction in cardiovascular disease (48)(49)(50). However, statins have not been demonstrated to be consistently effective for the treatment of asthma, which may reflect a variety of factors that have been reviewed elsewhere (48). We have found that serum cholesterol levels are not associated with blood eosinophil counts, serum periostin levels, or FEV 1 , which suggests that modifying cholesterol levels alone may not be sufficient to manage asthma control.…”

Section: Discussionmentioning

confidence: 99%

High density lipoproteins and type 2 inflammatory biomarkers are negatively correlated in atopic asthmatics

Barochia

Gordon

Kaler

et al. 2017

Journal of Lipid Research

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Blood eosinophil counts and serum periostin levels are biomarkers of type 2 inflammation. Although serum levels of HDL and apoA-I have been associated with less severe airflow obstruction in asthma, it is not known whether serum lipids or lipoprotein particles are correlated with type 2 inflammation in asthmatics. Here, we assessed whether serum lipids and lipoproteins correlated with blood eosinophil counts or serum periostin levels in 165 atopic asthmatics and 163 nonasthmatic subjects with and without atopy. Serum lipids and lipoproteins were quantified using standard laboratory assays and NMR spectroscopy. Absolute blood eosinophils were quantified by complete blood counts. Periostin levels were measured using the Elecsys® periostin assay. In atopic asthmatics, blood eosinophils negatively correlated with serum HDL cholesterol and total HDL particles measured by NMR spectroscopy (HDL). Serum periostin levels negatively correlated with total HDL In contrast, blood eosinophil counts positively correlated with serum triglyceride levels. This study demonstrates for the first time that HDL particles were negatively correlated, whereas serum triglycerides were positively correlated, with blood eosinophils in atopic asthmatics. This supports the concept that serum levels of HDL and triglycerides may be linked to systemic type 2 inflammation in atopic asthma.

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Section: Discussionmentioning

confidence: 99%

High density lipoproteins and type 2 inflammatory biomarkers are negatively correlated in atopic asthmatics

Barochia

Gordon

Kaler

et al. 2017

Journal of Lipid Research

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“…However, results from these RCTs have produced equivocal and at times conflicting results. While asthmatics may benefit from added statin therapy by reducing airway inflammation, consistent improvement in lung function or symptoms has not been definitively established in these RCTs [51,52,55]. Although these results can be characterized as equivocal at best [57–60], statins did reduce sputum eosinophils [54,55], macrophages [56], leukotriene B 4 , sputum proinflammatory cytokines and growth factors [53].…”

Section: The Mevalonate Pathway Statins and Relevance To Asthmamentioning

confidence: 99%

“…Indeed, no RCTs have investigated patients with severe asthma or determined the most effective statin or statin class to use. These RCTs also utilized relatively small sample sizes (<75 participants), had varied study designs, used different corticosteroid treatment regimens, and administered oral statin doses typically used to treat hyperlipidemia [95]. Importantly, these clinical trials did not assess primary end-points such as acute exacerbation requiring systemic corticosteroid treatment, ED visits, hospitalizations, and/or respiratory failure [87].…”

Section: The Mevalonate Pathway Statins and Relevance To Asthmamentioning

confidence: 99%

“…In addition, statins have biological plausibility in various lung disease models based on positive animal and cell culture data [31,32,35,36,42–50]. 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].…”

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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“…The low levels of statins in the lungs are unfavourable since the main pharmacological targets of statins are the airway epithelium, alveolar macrophages, fibroblasts, endothelial cells and inflammatory cells which are responsible for the inflammatory cascade in chronic airway diseases. Other Additional issues that need to be considered include the different types of statin which may exert variousanti-inflammatory efficacies, the required optimal dose to be delivered to the airways for effective therapeutic effectoutcomes, the duration of statin treatment required before therapeutic effects could can be observed, whether statins are better as an alternative sole therapy or as an adjunct/combination with other therapies, and finally if statins are only eaffective in a particularspecific patient population phenotype[105].…”

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confidence: 99%

Repurposing of statins via inhalation to treat lung inflammatory conditions

Bradbury

Traini

Ammit

et al. 2018

Advanced Drug Delivery Reviews

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Despite many therapeutic advancements over the past decade, the continued rise in chronic inflammatory lung diseases incidence has driven the need to identify and develop new therapeutic strategies, with superior efficacy to treat these diseases. Statins are one class of drug that could potentially be repurposed as an alternative treatment for chronic lung diseases. They are currently used to treat hypercholesterolemia by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, that catalyses the rate limiting step in the mevalonate biosynthesis pathway, a key intermediate in cholesterol metabolism. Recent research has identified statins to have other protective pleiotropic properties including anti-inflammatory, anti-oxidant, muco-inhibitory effects that may be beneficial for the treatment of chronic inflammatory lung diseases. However, clinical studies have yielded conflicting results. This review will summarise some of the current evidences for statins pleiotropic effects that could be applied for the treatment of chronic inflammatory lung diseases, their mechanisms of actions, and the potential to repurpose statins as an inhaled therapy, including a detailed discussion on their different physical-chemical properties and how these characteristics could ultimately affect treatment efficacies. The repurposing of statins from conventional anti-cholesterol oral therapy to inhaled anti-inflammatory formulation is promising, as it provides direct delivery to the airways, reduced risk of side effects, increased bioavailability and tailored physical-chemical properties for enhanced efficacy.

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Statins in Asthma: Potential Beneficial Effects and Limitations

Cited by 30 publications

References 132 publications

High density lipoproteins and type 2 inflammatory biomarkers are negatively correlated in atopic asthmatics

High density lipoproteins and type 2 inflammatory biomarkers are negatively correlated in atopic asthmatics

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

Repurposing of statins via inhalation to treat lung inflammatory conditions

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