Particle analysis of surgical lung biopsies from deployed and non-deployed US service members during the Global War on Terrorism

by Leslie Hayden, James M. Lightner, Stacy Strausborger, Teri J. Franks, Nora L. Watson, Michael R. Lewin-Smith

The role that inhaled particulate matter plays in the development of post-deployment lung disease among US service members deployed to Southwest Asia during the Global War on Terrorism has been difficult to define. There is a persistent gap in data addressing the relationship between relatively short-term (months to a few years) exposures to high levels of particulate matter during deployment and the subsequent development of adverse pulmonary outcomes. Surgical lung biopsies from deployed service members and veterans (DSMs) and non-deployed service members and veterans (NDSMs) who develop lung diseases can be analyzed to potentially identify residual deployment-specific particles and develop associations with pulmonary pathological diagnoses. We examined 52 surgical lung biopsies from 25 DSMs and 27 NDSMs using field emission scanning electron microscopy (FE-SEM) with energy dispersive x-ray spectroscopy (EDS) to identify any between-group differences in the number and composition of retained inorganic particles, then compared the particle analysis results with the original histopathologic diagnoses. We recorded a higher number of total particles in biopsies from DSMs than from NDSMs, and this difference was mainly accounted for by geologic clays (illite, kaolinite), feldspars, quartz/silica, and titanium-rich silicate mixtures. Biopsies from DSMs deployed to other Southwest Asia regions (SWA-Other) had higher particle counts than those from DSMs primarily deployed to Iraq or Afghanistan, due mainly to illite. Distinct deployment-specific particles were not identified. Particles did not qualitatively associate with country of deployment. The individual diagnoses of the DSMs and NDSMs were not associated with elevated levels of total particles, metals, cerium oxide, or titanium dioxide particles. These results support the examination of particle-related lung disease in DSMs in the context of comparison groups, such as NDSMs, to assist in determining the strength of associations between specific pulmonary pathology diagnoses and deployment-specific inorganic particulate matter exposure.

Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions

Introduction

Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions.

Methods and analysis

The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare.

Ethics and dissemination

The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.