Statins and asthma: where we stand, and the next critical steps in research

Abstract

Asthma remains a formidable public health problem with ever increasing annual costs and prevalence. There are 300 million people with asthma worldwide. Per the Centers for Disease Control and Prevention, there are over 25 million Americans with asthma (both children and adults), i.e. one in 12 people have asthma, and this is increasing annually. Asthma results in approximately half a million hospitalizations and two million emergency department (ED) visits per year. In 2007 alone, 185 children and 3262 adults died from asthma, i.e. nine to ten patients die a day from asthma. This resulted in an annual cost of $56 billion in medical costs, lost work/school days, and early deaths. Therefore, we need novel and innovative therapies for asthma. In this Editorial, I review results from a study by Tse et al. evaluating the therapeutic potential of statins, within the context of our current state of knowledge. I review observational studies and clinical trials, highlight some potential pitfalls in clinical trial design, and discuss important questions for future research.

Fungal allergen‐induced IL‐33 secretion involves cholesterol‐dependent, VDAC‐1‐mediated ATP release from the airway epithelium

“…Previous studies using rodent models of asthma and chronic obstructive pulmonary disease have demonstrated that systemic or airway administration of statin compounds (simvastatin, pravastatin or pitavastatin) alleviate airway inflammation, goblet cell hyperplasia/mucin production and initial signs of airway remodeling known to contribute to airway hyper-reactivity and smooth muscle hypertrophy/hyperplasia (Davis et al 2013;Zeki et al 2013Zeki et al , 2015Zeki, 2014;Bhattacharjee et al 2015;Wu et al 2017). Statin drugs specifically inhibit 3-hydroxy-3-methyl-glutaryl-CoA reductase, an enzyme that functions as the rate limiting step in the mevalonate pathway, which leads to cholesterol biosynthesis (Stancu & Sima, 2001;Cerqueira et al 2016).…”

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

“…The effectiveness of statins in asthma is biologically plausible and the inhibition of the MA pathway by statins offers a unique treatment opportunity in severe asthmatics, as this pathway is not affected by corticosteroids, β-agonist therapies, or any other current therapies [87–89]. …”

“…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.…”

“…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]. Finally, to our knowledge, no study has ever determined statin D airway leaving us with no direct knowledge of drug penetration into the airway compartment, and more specifically, the bronchial epithelium.…”

Statins in Asthma: Potential Beneficial Effects and Limitations

“…This in turn might be responsible for variations in the actions of statins against various diseases. Additionally, the question arises as to whether the mucosal epithelial immunity and alveolar capillary barriers in the respiratory compartment interfere with the action of statins [ 121 ].…”