Chest
Volume 134, Issue 4, October 2008, Pages 824-830
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Special Features
Statins and Interstitial Lung Disease: A Systematic Review of the Literature and of Food and Drug Administration Adverse Event Reports

https://doi.org/10.1378/chest.08-0943Get rights and content

Objective

To systematically review all published case reports and the US Food and Drug Administration adverse event reporting (FDA-AER) database to examine the relationship between statins and interstitial lung disease (ILD).

Data sources

PubMed (1987 to September 2007) and the FDA-AER database (as of June 2007) were searched for reports of ILD in which a statin was listed as a causative suspect.

Review methods

Two authors (one author for Pub Med cases and one for FDA-AER cases) independently abstracted patient data. Given the paucity of information, all case reports and case series in English and French were included. All adverse event reports from the FDA-AER database in which a statin was listed as causative suspect were included.

Results

The literature search using PubMed yielded eight articles describing a total of 14 case reports of ILD in association with statin use. The FDA-AER system database contained 162 cases of reported statin-induced ILD as of June 2007. For every 10,000 reports of a statin-associated adverse event, approximately 1 to 40 reports were for ILD.

Conclusions

Statin-induced ILD is a possible newly recognized side effect of statin therapy. The mechanism of lung injury is not defined. The current review provides novel information from the FDA-AER that supports a possible, although unusual, pulmonary class effect of statins.

Section snippets

Literature Review

We performed a systematic literature search for articles published in English and French from 1987 to September 2007 using PubMed and the search terms “HMG-CoA reductase inhibitors” or “statins” in combination with the terms “drug-induced interstitial lung disease,” “pulmonary fibrosis,” “interstitial pneumonitis,” or “parenchymal lung disease.” Abstracts and relevant articles were retrieved and reviewed in detail. Selected citations from these articles were also examined. Given the paucity of

Statin-Induced Parenchymal Lung Damage

The literature search using PubMed yielded eight articles describing a total of 14 case reports of ILD in association with statin use (Table 1). Hill et al4 in 1995 first described possible statin-induced ILD in a 76-year-old woman accompanying a syndrome of dermatomyositis. The association of statin use with ILD in this report is problematic, however, because the patient had very high anti-nuclear antibody titers and tested positive for a human leukocyte antigen serotype DR3, a known associate

Definition of ILD

ILD, also known as diffuse parenchymal lung disease, comprises a diverse group of disorders that may share similar pathologic findings. They may have cellular infiltration, scarring, and/or architectural disruption of the pulmonary parenchyma involving alveolar lining cells, small and large airways, endothelial basement membranes, and occasionally the pleura.12

Drug-Induced ILD

The lungs are vulnerable targets for many drugs. More than 150 pharmacologic agents have been reported to cause adverse pulmonary

References (34)

  • AA Alsheikh-Ali et al.

    The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis

    Circulation

    (2005)
  • C Hill et al.

    Dermatomyositis with lung involvement in a patient treated with simvastatin

    Aust N Z J Med

    (1995)
  • RE De Groot et al.

    Interstitial lung disease with pleural effusion caused by simvastin

    J Intern Med

    (1996)
  • T Walker et al.

    Potential link between HMG-CoA reductase inhibitor (statin) use and interstitial lung disease

    Med J Aust

    (2007)
  • N Liscoet-Loheac et al.

    Hypersensitivity pneumonitis in a patient taking pravastatin [in French]

    Rev Mal Respir

    (2001)
  • S Lantuejoul et al.

    Statin-induced fibrotic nonspecific interstitial pneumonia

    Eur Respir J

    (2002)
  • Chesnutt M, Murray J, Prendergast P. Interstitial lung disease In: Tierney LM, McPhee SJ, Papadakis MA, eds. Current...
  • Cited by (0)

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

    1

    Dr. Thompson has received grant/research support from Merck, Pfizer, AstraZeneca, and B. Braun; is a consultant for Astra-Zeneca and Merck; is on the Speaker's Bureau for Merck, Pfizer, Abbott, AstraZeneca, and ScheringPlough; and owns stock in Schering Plough, Merck, Illumina, and Zoll. He has other financial or occasional speaking honoraria from Merck, Pfizer, Abbott, AstraZeneca, ScheringPlough, and Reliant.

    2

    Dr. Karas is a consultant for Merck and Abbott, and has received honoraria from Merck and Abbott.

    3

    Dr. Alsheikh-Ali is recipient of a faculty development award from Pfizer and Tufts Medical Center.

    4

    Dr. Fernandez has no conflicts of interests to disclose.

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