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Correspondence |

Statins Reduce Lung Inflammation by Promoting the Clearance of Particulate Matter From Lung TissuesStatins Inhibit Innate Immunity in the Lung FREE TO VIEW

Robert P. Young, BMedSci, MBChB, DPhil; Raewyn J. Hopkins, RN, MPH
Author and Funding Information

From the School of Biological Science and Faculty of Medicine and Health Science, The University of Auckland.

Correspondence to: Robert P. Young, BMedSci, MBChB, DPhil, School of Biological Science and Faculty of Medicine and Health Science, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand; e-mail: roberty@adhb.govt.nz


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;144(1):358-359. doi:10.1378/chest.13-0496
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Published online
To the Editor:

We read with interest the article by Miyata and colleagues1 (February 2013) in which the authors reported that lovastatin attenuates lung inflammation in a rabbit model by attenuating macrophage and neutrophil recruitment and activation. We outline here why this is such an important finding.

There is growing interest in the potential role of statins as adjunct therapy in COPD. Human and animal studies suggest that statins reduce both pulmonary and systemic inflammation, which is characterized by reductions in IL-8, IL-6, and C-reactive protein.2 In a published review, we suggested that this immunomodulatory effect is directed by the bronchial epithelium, mediated primarily through the innate immune system (neutrophils and macrophages), and critical to the pathobiology underlying chronic aeropollutant-induced airway disease (eg, COPD) (Fig 1).2 This might partly explain why corticosteroid treatment, targeting primarily the adaptive immune system, does not significantly improve important clinical outcomes in COPD, such as slowing the progression of disease or reducing mortality. The study by Miyata et al1 elegantly demonstrates that inhibition of the innate immune system has an important effect on the response of the lungs to chronic aeropollutant exposure and how this may be inhibited through systemic-based therapy.

Figure Jump LinkFigure 1. Proposed relationship among pulmonary inflammation, systemic inflammation, and COPD-related comorbidities. *Statins have been shown to attenuate both pulmonary and systemic inflammation through their effects on the innate immune response and NFκB/STAT3-mediated inflammatory pathways. CRP = C-reactive protein; ETS = environmental tobacco smoke; MΦ = macrophage; NFκB = nuclear factor κB; PMN = polymorphic neutrophil; SAD = small airways disease; STAT3 = signal transducer and activator of transcription 3; TNFα = tumor necrosis factor-α.Grahic Jump Location

The importance of the finding that statin therapy effectively inhibits both pulmonary and systemic inflammation goes beyond that of COPD.2 Evidence from a large prospective study of patients with COPD showed that systemic inflammation conferred its greatest risk on susceptibility to lung cancer.3 A recent population-based study showed that statin therapy reduced mortality for a number of cancers by about 20% to 30%, particularly those linked with smoking and obesity.4 In absolute terms, we estimate that 42% of all the lives saved with statin therapy were from a reduction in death from lung cancer specifically. That statins reduce the risk of lung cancer or deaths from lung cancer is consistent with the literature2 and concurs with our understanding of the adverse effects of systemic inflammation on epithelial cancers.2-4 Moreover, Arimura and colleagues5 recently showed that systemic inflammation was responsible for DNA damage in the airways of mice and was mediated through macrophages, further implicating systemic inflammation in lung cancer (reverse effect) (Fig 1).

We conclude that statin therapy provides a powerful immunomodulatory action that has a profound effect on the innate immune system in the lung, specifically cytokine-driven inflammation that characterizes aeropollutant-based airways disease (ie, COPD and its comorbidities). We suggest that it is time to examine statins as adjunct therapy to inhaler-based treatment in COPD.

References

Miyata R, Bai N, Vincent R, Sin DD, Van Eeden SF. Statins reduce ambient particulate matter-induced lung inflammation by promoting the clearance of particulate matter <10 μm from lung tissues. Chest. 2013;143(2):452-460. [CrossRef] [PubMed]
 
Young RP, Hopkins R, Eaton TE. Pharmacological actions of statins: potential utility in COPD. Eur Respir Rev. 2009;18(114):222-232. [CrossRef] [PubMed]
 
Thomsen M, Dahl M, Lange P, Vestbo J, Nordestgaard BG. Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186(10):982-988. [CrossRef] [PubMed]
 
Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Engl J Med. 2012;367(19):1792-1802. [CrossRef] [PubMed]
 
Arimura K, Aoshiba K, Tsuji T, Tamaoki J. Chronic low-grade systemic inflammation causes DNA damage in the lungs of mice. Lung. 2012;190(6):613-620. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Proposed relationship among pulmonary inflammation, systemic inflammation, and COPD-related comorbidities. *Statins have been shown to attenuate both pulmonary and systemic inflammation through their effects on the innate immune response and NFκB/STAT3-mediated inflammatory pathways. CRP = C-reactive protein; ETS = environmental tobacco smoke; MΦ = macrophage; NFκB = nuclear factor κB; PMN = polymorphic neutrophil; SAD = small airways disease; STAT3 = signal transducer and activator of transcription 3; TNFα = tumor necrosis factor-α.Grahic Jump Location

Tables

References

Miyata R, Bai N, Vincent R, Sin DD, Van Eeden SF. Statins reduce ambient particulate matter-induced lung inflammation by promoting the clearance of particulate matter <10 μm from lung tissues. Chest. 2013;143(2):452-460. [CrossRef] [PubMed]
 
Young RP, Hopkins R, Eaton TE. Pharmacological actions of statins: potential utility in COPD. Eur Respir Rev. 2009;18(114):222-232. [CrossRef] [PubMed]
 
Thomsen M, Dahl M, Lange P, Vestbo J, Nordestgaard BG. Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186(10):982-988. [CrossRef] [PubMed]
 
Nielsen SF, Nordestgaard BG, Bojesen SE. Statin use and reduced cancer-related mortality. N Engl J Med. 2012;367(19):1792-1802. [CrossRef] [PubMed]
 
Arimura K, Aoshiba K, Tsuji T, Tamaoki J. Chronic low-grade systemic inflammation causes DNA damage in the lungs of mice. Lung. 2012;190(6):613-620. [CrossRef] [PubMed]
 
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