Airway microstructure in idiopathic pulmonary fibrosis: assessment at hyperpolarized 3He diffusion-weighted MRI

Background MRI with inhaled hyperpolarized helium 3 (3He) allows for functional and structural imaging of the lungs. Hyperpolarized gas diffusion-weighted (DW) MRI provides noninvasive and quantitative assessment of microstructural acinar changes in the lungs. Purpose To investigate whether microstructural imaging metrics from in-vivo hyperpolarized 3He DW MRI are sensitive to longitudinal changes in a cohort of participants with idiopathic pulmonary fibrosis (IPF) and to evaluate the reproducibility of these metrics and their correlation with existing clinical measures of IPF disease severity. Materials and Methods In this prospective study, 18 participants with IPF underwent 3He DW MRI at 1.5 T and 11 participants underwent an identical same-day examination for reproducibility assessment. Thirteen participants returned for 6- and 12-month follow-up examinations. Pulmonary function tests, including diffusing capacity of the lungs for carbon monoxide and forced vital capacity, were performed at each examination. The apparent diffusion coefficient (ADC) and stretched exponential model–derived mean diffusive length scale (LmD) from DW MRI was compared with baseline CT fibrosis scores and pulmonary function tests by using Spearman rank correlation coefficient. Longitudinal changes in DW MRI and pulmonary function test measurements were assessed with Friedman tests and post hoc Dunn test. Results 3He ADC and LmD were reproducible (mean Bland-Altman analysis bias, 0.002 cm2 · sec-1 and −1.5 μm, respectively). Elevated ADC and LmD regions qualitatively corresponded to fibrotic regions at CT. ADC and LmD correlated with diffusing capacity of the lungs for carbon monoxide (respectively: r = −0.56, P = .017; and r = −0.54, P = .02) and CT fibrosis score (respectively: r = 0.71, P = .001; and r = 0.65, P = .003). LmD increased by 12 μm after 12 months (P = .001) whereas mean ADC (P = .17), forced vital capacity (P = .12), and diffusing capacity of the lungs for carbon monoxide (P > .99) were not statistically different between examinations. Conclusion Helium 3 diffusion-weighted MRI-derived mean diffusive length scale demonstrates longitudinal changes in lungs affected by idiopathic pulmonary fibrosis

Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID)

Introduction The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD). Methods and analysis The UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment. Ethics and dissemination All contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals. Conclusion This study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD

Residual Lung Abnormalities Following COVID-19 Hospitalization:Interim Analysis of the UKILD Post-COVID Study

RationaleShared symptoms and genetic architecture between COVID-19 and lung fibrosis suggests SARS-CoV-2 infection may lead to progressive lung damage.ObjectivesThe UKILD Post-COVID study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 based on risk strata.MethodsThe Post-HOSPitalisation COVID Study (PHOSP-COVID) was used for capture of routine and research follow-up within 240 days from discharge. Thoracic CTs linked by PHOSP-COVID identifiers were scored for percentage of residual lung abnormalities (ground glass opacities and reticulations). Risk factors in linked CT were estimated with Bayesian binomial regression and risk strata were generated. Numbers within strata were used to estimate post-hospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol driven research follow-up.Measurements and main resultsThe interim cohort comprised 3700 people. Of 209 subjects with linked CTs (median 119 days, interquartile range 83-155), 166 people (79.4%) had >10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (RR 1·21 95%CrI 1·05; 1·40), percent predicted DLcoConclusionsResidual lung abnormalities were estimated in up to 11% of people discharged following COVID-19 related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/)