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Review
. 2018 Oct 15;7(10):356.
doi: 10.3390/jcm7100356.

Drug-Induced Interstitial Lung Disease: A Systematic Review

Sarah Skeoch  1   2 , Nicholas Weatherley  3 , Andrew J Swift  4 , Alexander Oldroyd  5 , Christopher Johns  6 , Conal Hayton  7 , Alessandro Giollo  8   9 , James M Wild  10 , John C Waterton  11   12 , Maya Buch  13 , Kim Linton  14 , Ian N Bruce  15   16 , Colm Leonard  17 , Stephen Bianchi  18 , Nazia Chaudhuri  19
Affiliations
Review

Drug-Induced Interstitial Lung Disease: A Systematic Review

Sarah Skeoch et al. J Clin Med. .

Abstract

Background: Drug-induced interstitial lung disease (DIILD) occurs as a result of numerous agents, but the risk often only becomes apparent after the marketing authorisation of such agents.

Methods: In this PRISMA-compliant systematic review, we aimed to evaluate and synthesise the current literature on DIILD.

Results: Following a quality assessment, 156 full-text papers describing more than 6000 DIILD cases were included in the review. However, the majority of the papers were of low or very low quality in relation to the review question (78%). Thus, it was not possible to perform a meta-analysis, and descriptive review was undertaken instead. DIILD incidence rates varied between 4.1 and 12.4 cases/million/year. DIILD accounted for 3⁻5% of prevalent ILD cases. Cancer drugs, followed by rheumatology drugs, amiodarone and antibiotics, were the most common causes of DIILD. The radiopathological phenotype of DIILD varied between and within agents, and no typical radiological pattern specific to DIILD was identified. Mortality rates of over 50% were reported in some studies. Severity at presentation was the most reliable predictor of mortality. Glucocorticoids (GCs) were commonly used to treat DIILD, but no prospective studies examined their effect on outcome.

Conclusions: Overall high-quality evidence in DIILD is lacking, and the current review will inform larger prospective studies to investigate the diagnosis and management of DIILD.

Keywords: drug-induced interstitial lung disease; drug-induced pneumonitis; pulmonary toxicity.

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Conflict of interest statement

J.C.W. reports grants from the Innovative Medicines Initiatives 2 Joint Undertaking under grant agreement No. 116106 (this Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA), during the conduct of the study; personal fees from Bioxydyn Ltd., outside the submitted work; N.C. reports grants from Boehringer Ingelheim, personal fees from Roche, personal fees from Intermune, outside the submitted work; I.N.B. reports grants and other from GSK, grants from UCB Pharma, other from Merck Serono, other from Astra Zeneca, other from Eli Lilly, grants from Genzyme Sanofi, outside the submitted work.

Figures

Figure 1
Figure 1
Search terms used in Medline, Embase and Cochrane Register of Controlled Trials.
Figure 2
Figure 2
Flow diagram of the review process from abstract review to final inclusion. In total, these 156 articles report approximately 6200 patients with confirmed or suspected DIILD, which was fatal in around 672/2647 (25.4%) cases.
Figure 3
Figure 3
Summary of quality and bias, as assessed using the Grading Recommendations Assessment and Development Evidence (GRADE) method [4]. (A) Summarises risk of bias and (B) summarises quality of included studies.
See this image and copyright information in PMC

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