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By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC + mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus. Additionally, we find ITLN-1 protein binds the C-terminus of the MUC5AC mucin and that its deletion in airway epithelial cells partially reverses IL-13-induced mucostasis. Through analysis of nasal airway epithelial brushings, we find that ITLN1 is highly expressed in T2-high asthmatics, when compared to T2-low children. Furthermore, we demonstrate that both ITLN-1 gene expression and protein levels are significantly reduced by a common genetic variant that is associated with protection from the formation of mucus plugs in T2-high asthma. This work identifies an important biomarker and targetable pathways for the treatment of mucus obstruction in asthma., (© 2024. The Author(s).)

BACKGROUND. Closure of a GE Healthcare facility in Shanghai, China, in 2022 disrupted the iodinated contrast media supply. Technologic advances have addressed limitations associated with the use of pulmonary MRA for diagnosis of pulmonary embolism (PE). OBJECTIVE. The purpose of this study was to describe a single institution's experience in the use of pulmonary MRA as an alternative to CTA for the diagnosis of PE in the general population during the iodinated contrast media shortage in 2022. METHODS. This retrospective single-center study included all CTA and MRA examinations performed to exclude PE from April 1 through July 31 (18 weekly periods) in 2019 (before the COVID-19 pandemic and contrast media shortage), 2021 (during the pandemic but before the shortage), and 2022 (during both the pandemic and the shortage). From early May through mid-July of 2022, MRA served as the preferred test for PE diagnosis, to preserve iodinated contrast media. CTA and MRA reports were reviewed. The total savings in iodinated contrast media volume resulting from preferred use of MRA was estimated. RESULTS. The study included 4491 examinations of 4006 patients (mean age, 57 ± 18 [SD] years; 1715 men, 2291 women): 1245 examinations (1111 CTA, 134 MRA) in 2019, 1547 examinations (1403 CTA, 144 MRA) in 2021, and 1699 examinations (1282 CTA, 417 MRA) in 2022. In 2022, the number of MRA examinations was four (nine when normalized to a 7-day period) in week 1, and this number increased to a maximum of 63 in week 10 and then decreased to 10 in week 18. During weeks 8-11, more MRA examinations (range, 45-63 examinations) than CTA examinations (range, 27-46 examinations) were performed. In 2022, seven patients with negative MRA underwent subsequent CTA within 2 weeks; CTA was negative in all cases. In 2022, 13.9% of CTA examinations (vs 10.3% of MRA examinations) were reported as having limited image quality. The estimated 4-month savings resulting from preferred use of MRA in 2022, under the assumption of uniform simple linear growth in CTA utilization annually and a CTA dose of 1 mL/kg, was 27 L of iohexol (350 mg I/mL). CONCLUSION. Preferred use of pulmonary MRA for PE diagnosis in the general population helped to conserve iodinated contrast media during the 2022 shortage. CLINICAL IMPACT. This single-center experience shows pulmonary MRA to be a practical substitute for pulmonary CTA in emergency settings.

Purpose: The purpose of this study was to anatomically correlate ventilation defects with regions of air trapping by whole lung, lung lobe, and airway segment in the context of airway mucus plugging in asthma. Methods: A total of 34 asthmatics [13M:21F, 13 mild/moderate, median age (range) of 49.5 (36.8-53.3) years and 21 severe, 56.1 (47.1-62.6) years] and 4 healthy subjects [1M:3F, 38.5 (26.6-52.2) years] underwent HP 3 He MRI and CT imaging. HP 3 He MRI was assessed for ventilation defects using a semi-automated k-means clustering algorithm. Inspiratory and expiratory CTs were analyzed using parametric response mapping (PRM) to quantify markers of emphysema and functional small airways disease (fSAD). Segmental and lobar lung masks were obtained from CT and registered to HP 3 He MRI in order to localize ventilation defect percent (VDP), at the lobar and segmental level, to regions of fSAD and mucus plugging. Spearman's correlation was utilized to compare biomarkers on a global and lobar level, and a multivariate analysis was conducted to predict segmental fSAD given segmental VDP (sVDP) and mucus score as variables in order to further understand the functional relationships between regional measures of obstruction. Results: On a global level, fSAD was correlated with whole lung VDP ( r = 0.65, p < 0.001), mucus score ( r = 0.55, p < 0.01), and moderately correlated (-0.60 ≤ r ≤ -0.56, p < 0.001) to percent predicted (%p) FEV1, FEF25-75 and FEV1/FVC, and more weakly correlated to FVC%p (-0.38 ≤ r ≤ -0.35, p < 0.001) as expected from previous work. On a regional level, lobar VDP, mucus scores, and fSAD were also moderately correlated (r from 0.45-0.66, p < 0.01). For segmental colocalization, the model of best fit was a piecewise quadratic model, which suggests that sVDP may be increasing due to local airway obstruction that does not manifest as fSAD until more extensive disease is present. sVDP was more sensitive to the presence of a mucus plugs overall, but the prediction of fSAD using multivariate regression showed an interaction in the presence of a mucus plugs when sVDP was between 4% and 10% ( p < 0.001). Conclusion: This multi-modality study in asthma confirmed that areas of ventilation defects are spatially correlated with air trapping at the level of the airway segment and suggests VDP and fSAD are sensitive to specific sources of airway obstruction in asthma, including mucus plugs., Competing Interests: SF receives research support from GE Healthcare and serves on the scientific advisory board of Polarean PLC. KC and CH are currently employees of Imbio LLC. LD and NJ are Principal Investigators in the NHLBI PrecISE Trial network that has relationships with the following companies for drug support and equipment contracts: Glaxo Smith Kline, Laurel, Sun Pharma, Vifor/OM Pharm, Vitaeris/CSL Behring, Vitaflo, Vyaire, Caire Diagnostics, MIR, Propeller Health, ZEPHYRx. NJ reports grants and personal fees from AstraZeneca, and personal fees from GSK and Boehringer Ingelheim for consultations outside the submitted work. LD has consulted with Glaxo Smith Kline, AstraZeneca, Sanofi and OM Pharma during the course of this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Carey, Hotvedt, Mummy, Lee, Denlinger, Schiebler, Sorkness, Jarjour, Hatt, Galban and Fain.)

Pulmonary MR angiography (MRA) is a useful alternative to computed tomographic angiography (CTA) for the study of the pulmonary vasculature. For pulmonary hypertension and partial anomalous pulmonary venous return, a cardiac MR imaging and the pulmonary MRA are useful for flow quantification and planning treatment. For the diagnosis of pulmonary embolism (PE), MRA-PE has been shown to have non-inferior outcomes at 6 months when compared with CTA-PE. Over the last 15 years, pulmonary MRA has become a routine and reliable examination for the workup of pulmonary hypertension and the primary diagnosis of PE at the University of Wisconsin., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A measure of regional gas exchange on HP 129 Xe MRI was able to detect apparent improvements in IPF patients treated with antifibrotic medication after 1 year, while no such improvements were found in patients treated with conventional therapies https://bit.ly/3ZXipzD., Competing Interests: Conflict of interest: A.D. Hahn reports support for the present manuscript from the NIH/NHLBI, American Lung Association and GE Healthcare; and grants or contracts and consulting fees from Polarean PLC outside the submitted work. Conflict of interest: K.J. Carey reports grants or contracts and consulting fees from Imbio Inc., and stock options in Imbio Inc.; and is an employee of Imbio Inc. (all disclosures made outside the submitted work). Conflict of interest: G.P. Barton reports support for the present manuscript from NIAID T32AI007635. Conflict of interest: L.A. Torres reports support for the present manuscript from Flywheel. Conflict of interest: J. Kammerman reports grants or contracts from Polarean PLC outside the submitted work; and patents planned, issued or pending with the Wisconsin Alumni Research Foundation (coinventor on patent related to xenon MRI held by WARF). Conflict of interest: M.L. Schiebler reports support for the present manuscript from the NIH/HLBI; and grants or contracts from the DHHS, PHS, NIH and NIH/NHLBI, outside the submitted work; is the deputy editor of Radiology; and is a shareholder in X-Vax, Inc., Elucent Medical, Inc. and Elucida Oncology, Inc. Conflict of interest: S.B. Fain reports support for the present manuscript from the NIH/NHLBI, American Lung Association and GE Healthcare; grants or contracts from Polarean PLC outside the submitted work; consulting fees from Sanofi/Regeneron and Polarean PLC, outside the submitted work; and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Sanofi/Regeneron and Polarean PLC. The remaining authors have nothing to disclose., (Copyright ©The authors 2023.)

Background: Ferumoxytol, an intravenous iron supplement, is commonly used to treat anemia in pregnancy. Ferumoxytol-enhanced magnetic resonance angiography (Fe-MRA) is a viable off-label alternative to gadolinium-enhanced MRA for assessment of pulmonary embolism (PE) in pregnancy., Purpose: To describe our clinical experience with Fe-MRA in pregnant women with suspected PE., Study Type: Retrospective, observational, cohort., Population: A total of 98 Fe-MRA exams (consecutive sample) performed in 94 pregnant women., Field Strength/sequence: A 1.5 T and 3.0 T, 3D T1-weighted MRA., Assessment: After IRB approval including a waiver of informed consent, electronic health records were reviewed retrospectively for all Fe-MRA exams performed at our institution in pregnant between January, 2017 and March, 2022. The Fe-MRA protocol included 3D-MRA for assessment of pulmonary arteries, and T1-weighted imaging for ancillary findings. Fe-MRA exam duration was measured from image time stamps. Fe-MRA exams were reviewed by three cardiovascular imagers using a 4-point Likert scale for image quality and confidence for PE diagnosis (score 4 = best, 1 = worst), and tabulation of ancillary findings., Statistical Tests: Continuous data are presented as mean ± standard deviation. The overall image quality and confidence score is given as the mean of three readers., Results: The 98 Fe-MRA exams were performed in 94 pregnant women (age 30 ± 6, range 19-48 years, gestational week 23 ± 10, range 3-38 weeks), with four undergoing two Fe-MRA exams during their pregnancy. Median Fe-MRA exam durration was 8 minutes (interquantile range 6 minutes). Overall image quality score was 3.3 ± 0.9. Confidence score for diagnosing PE was 3.5 ± 0.8. One subject was positive for PE (1/94, 1%); 42 of the 94 (45%) subjects Fe-MRA had ancillary findings including hydronephrosis or pneumonia., Conclusion: Ferumoxytol enhanced MRA is a radiation- and gadolinium-free alternative for diagnosis of PE during pregancy., Evidence Level: 4 TECHNICAL EFFICACY: Stage 5., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Although lung volumes are usually normal in individuals with chronic thromboembolic pulmonary hypertension (CTEPH), approximately 20%-29% of patients exhibit a restrictive pattern on pulmonary function testing., Aim: To quantify longitudinal changes in lung volume and cardiac cross-sectional area (CSA) in patients with CTEPH., Methods: In a retrospective cohort study of patients seen in our hospital between January 2012 and December 2019, we evaluated 15 patients with CTEPH who had chest computed tomography (CT) performed at baseline and after at least 6 mo of therapy. We matched the CTEPH cohort with 45 control patients by age, sex, and observation period. CT-based lung volumes and maximum cardiac CSAs were measured and compared using the Wilcoxon signed-rank test and the Mann-Whitney u test., Results: Total, right lung, and right lower lobe volumes were significantly reduced in the CTEPH cohort at follow-up vs baseline (total, P = 0.004; right lung, P = 0.003; right lower lobe; P = 0.01). In the CTEPH group, the reduction in lung volume and cardiac CSA was significantly greater than the corresponding changes in the control group (total, P = 0.01; right lung, P = 0.007; right lower lobe, P = 0.01; CSA, P = 0.0002). There was a negative correlation between lung volume change and cardiac CSA change in the control group but not in the CTEPH cohort., Conclusion: After at least 6 mo of treatment, CT showed an unexpected loss of total lung volume in patients with CTEPH that may reflect continued parenchymal remodeling., Competing Interests: Conflict-of-interest statement: All authors report having no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Rationale: Extrapulmonary manifestations of asthma, including fatty infiltration in tissues, may reflect systemic inflammation and influence lung function and disease severity. Objectives: To determine if skeletal muscle adiposity predicts lung function trajectory in asthma. Methods: Adult SARP III (Severe Asthma Research Program III) participants with baseline computed tomography imaging and longitudinal postbronchodilator FEV 1 % predicted (median follow-up 5 years [1,132 person-years]) were evaluated. The mean of left and right paraspinous muscle density (PSMD) at the 12th thoracic vertebral body was calculated (Hounsfield units [HU]). Lower PSMD reflects higher muscle adiposity. We derived PSMD reference ranges from healthy control subjects without asthma. A linear multivariable mixed-effects model was constructed to evaluate associations of baseline PSMD and lung function trajectory stratified by sex. Measurements and Main Results: Participants included 219 with asthma (67% women; mean [SD] body mass index, 32.3 [8.8] kg/m 2 ) and 37 control subjects (51% women; mean [SD] body mass index, 26.3 [4.7] kg/m 2 ). Participants with asthma had lower adjusted PSMD than control subjects (42.2 vs. 55.8 HU; P  < 0.001). In adjusted models, PSMD predicted lung function trajectory in women with asthma (β = -0.47 Δ slope per 10-HU decrease; P  = 0.03) but not men (β = 0.11 Δ slope per 10-HU decrease; P  = 0.77). The highest PSMD tertile predicted a 2.9% improvement whereas the lowest tertile predicted a 1.8% decline in FEV 1 % predicted among women with asthma over 5 years. Conclusions: Participants with asthma have lower PSMD, reflecting greater muscle fat infiltration. Baseline PSMD predicted lung function decline among women with asthma but not men. These data support an important role of metabolic dysfunction in lung function decline.

The imaging of asthma using chest computed tomography (CT) is well-established (Jarjour et al., Am J Respir Crit Care Med 185(4):356-62, 2012; Castro et al., J Allergy Clin Immunol 128:467-78, 2011). Moreover, recent advances in functional imaging of the lungs with advanced computer analysis of both CT and magnetic resonance images (MRI) of the lungs have begun to play a role in quantifying regional obstruction. Specifically, quantitative measurements of the airways for bronchial wall thickening, luminal narrowing and distortion, the amount of mucus plugging, parenchymal density, and ventilation defects that could contribute to the patient's disease course are instructive for the entire care team. In this chapter, we will review common imaging methods and findings that relate to the heterogeneity of asthma. This information can help to guide treatment decisions. We will discuss mucous plugging, quantitative assessment of bronchial wall thickening, delta lumen phenomenon, parenchymal low-density lung on CT, and ventilation defect percentage on MRI as metrics for assessing regional ventilatory dysfunction., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background Idiopathic pulmonary fibrosis (IPF) is a temporally and spatially heterogeneous lung disease. Identifying whether IPF in a patient is progressive or stable is crucial for treatment regimens. Purpose To assess the role of hyperpolarized (HP) xenon 129 ( 129 Xe) MRI measures of ventilation and gas transfer in IPF generally and as an early signature of future IPF progression. Materials and Methods In a prospective study, healthy volunteers and participants with IPF were consecutively recruited between December 2015 and August 2019 and underwent baseline HP 129 Xe MRI and chest CT. Participants with IPF were followed up with forced vital capacity percent predicted (FVC%p), diffusing capacity of the lungs for carbon monoxide percent predicted (DLco%p), and clinical outcome at 1 year. IPF progression was defined as reduction in FVC%p by at least 10%, reduction in DLco%p by at least 15%, or admission to hospice care. CT and MRI were spatially coregistered and a measure of pulmonary gas transfer (red blood cell [RBC]-to-barrier ratio) and high-ventilation percentage of lung volume were compared across groups and across fibrotic versus normal-appearing regions at CT by using Wilcoxon signed rank tests. Results Sixteen healthy volunteers (mean age, 57 years ± 14 [SD]; 10 women) and 22 participants with IPF (mean age, 71 years ± 9; 15 men) were evaluated, as follows: nine IPF progressors (mean age, 72 years ± 7; five women) and 13 nonprogressors (mean age, 70 years ± 10; 11 men). Reduction of high-ventilation percent (13% ± 6.1 vs 8.2% ± 5.9; P = .03) and RBC-to-barrier ratio (0.26 ± 0.06 vs 0.20 ± 0.06; P = .03) at baseline were associated with progression of IPF. Participants with progressive disease had reduced RBC-to-barrier ratio in structurally normal-appearing lung at CT (0.21 ± 0.07 vs 0.28 ± 0.05; P = .01) but not in fibrotic regions of the lung (0.15 ± 0.09 vs 0.14 ± 0.04; P = .62) relative to the nonprogressive group. Conclusion In this preliminary study, functional measures of gas transfer and ventilation measured with xenon 129 MRI and the extent of fibrotic structure at CT were associated with idiopathic pulmonary fibrosis disease progression. Differences in gas transfer were found in regions of nonfibrotic lung. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gleeson and Fraser in this issue.

Rationale: The role of obesity-associated insulin resistance (IR) in airflow limitation in asthma is uncertain. Objectives: Using data in the Severe Asthma Research Program 3 (SARP-3), we evaluated relationships between homeostatic measure of IR (HOMA-IR), lung function (cross-sectional and longitudinal analyses), and treatment responses to bronchodilators and corticosteroids. Methods: HOMA-IR values were categorized as without (<3.0), moderate (3.0-5.0), or severe (>5.0). Lung function included FEV 1 and FVC measured before and after treatment with inhaled albuterol and intramuscular triamcinolone acetonide and yearly for 5 years. Measurements and Main Results: Among 307 participants in SARP-3, 170 (55%) were obese and 140 (46%) had IR. Compared with patients without IR, those with IR had significantly lower values for FEV 1 and FVC, and these lower values were not attributable to obesity effects. Compared with patients without IR, those with IR had lower FEV 1 responses to β-adrenergic agonists and systemic corticosteroids. The annualized decline in FEV 1 was significantly greater in patients with moderate IR (-41 ml/year) and severe IR (-32 ml/year,) than in patients without IR (-13 ml/year, P  < 0.001 for both comparisons). Conclusions: IR is common in asthma and is associated with lower lung function, accelerated loss of lung function, and suboptimal lung function responses to bronchodilator and corticosteroid treatments. Clinical trials in patients with asthma and IR are needed to determine if improving IR might also improve lung function.

Background: The objective of this work was to apply quantitative and semiquantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) methods to evaluate lung perfusion in idiopathic pulmonary fibrosis (IPF)., Methods: In this prospective trial 41 subjects, including healthy control and IPF subjects, were studied using DCE-MRI at baseline. IPF subjects were then followed for 1 year; progressive IPF (IPF prog ) subjects were distinguished from stable IPF (IPF stable ) subjects based on a decline in percent predicted forced vital capacity (FVC % pred) or diffusing capacity of the lung for carbon monoxide ( D LCO % pred) measured during follow-up visits. 35 out of 41 subjects were retained for final baseline analysis (control: n=15; IPF stable : n=14; IPF prog : n=6). Seven measures and their coefficients of variation (CV) were derived using temporally resolved DCE-MRI. Two sets of global and regional comparisons were made: control versus IPF groups and control versus IPF stable versus IPF prog groups, using linear regression analysis. Each measure was compared with FVC % pred, D LCO % pred and the lung clearance index (LCI % pred) using a Spearman rank correlation., Results: DCE-MRI identified regional perfusion differences between control and IPF subjects using first moment transit time (FMTT), contrast uptake slope and pulmonary blood flow (PBF) (p≤0.05), while global averages did not. FMTT was shorter for IPF prog compared with both IPF stable (p=0.004) and control groups (p=0.023). Correlations were observed between PBF CV and D LCO % pred (r s = -0.48, p=0.022) and LCI % pred (r s = +0.47, p=0.015). Significant group differences were detected in age (p<0.001), D LCO % pred (p<0.001), FVC % pred (p=0.001) and LCI % pred (p=0.007)., Conclusions: Global analysis obscures regional changes in pulmonary haemodynamics in IPF using DCE-MRI in IPF. Decreased FMTT may be a candidate marker for IPF progression., Competing Interests: Conflict of interest: M.L. Schiebler reports grant funding from the National Heart, Lung, and Blood Institute (NHLBI SARPIII RFA-HL-11-018 and SARP IV 4P01 HL088594-09, R01 HL080414) and ownership of Elucida Oncology Inc., Elucida Medical Inc., Healthmyne Inc., Stemina Biomarker Discovery Inc. and X-Vax Inc. S.B. Fain reports grant funding from the NHLBI (R01 HL126771, R01 HL146689), GE Healthcare, American Lung Association, as well as compensation from Caladarius Biosciences, Polarean PLC and Sanofi/Regeneron. All other authors have nothing to disclose., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

Background Clustering key clinical characteristics of participants in the Severe Asthma Research Program (SARP), a large, multicenter prospective observational study of patients with asthma and healthy controls, has led to the identification of novel asthma phenotypes. Purpose To determine whether quantitative CT (qCT) could help distinguish between clinical asthma phenotypes. Materials and Methods A retrospective cross-sectional analysis was conducted with the use of qCT images (maximal bronchodilation at total lung capacity [TLC], or inspiration, and functional residual capacity [FRC], or expiration) from the cluster phenotypes of SARP participants (cluster 1: minimal disease; cluster 2: mild, reversible; cluster 3: obese asthma; cluster 4: severe, reversible; cluster 5: severe, irreversible) enrolled between September 2001 and December 2015. Airway morphometry was performed along standard paths (RB1, RB4, RB10, LB1, and LB10). Corresponding voxels from TLC and FRC images were mapped with use of deformable image registration to characterize disease probability maps (DPMs) of functional small airway disease (fSAD), voxel-level volume changes (Jacobian), and isotropy (anisotropic deformation index [ADI]). The association between cluster assignment and qCT measures was evaluated using linear mixed models. Results A total of 455 participants were evaluated with cluster assignments and CT (mean age ± SD, 42.1 years ± 14.7; 270 women). Airway morphometry had limited ability to help discern between clusters. DPM fSAD was highest in cluster 5 (cluster 1 in SARP III: 19.0% ± 20.6; cluster 2: 18.9% ± 13.3; cluster 3: 24.9% ± 13.1; cluster 4: 24.1% ± 8.4; cluster 5: 38.8% ± 14.4; P < .001). Lower whole-lung Jacobian and ADI values were associated with greater cluster severity. Compared to cluster 1, cluster 5 lung expansion was 31% smaller (Jacobian in SARP III cohort: 2.31 ± 0.6 vs 1.61 ± 0.3, respectively, P < .001) and 34% more isotropic (ADI in SARP III cohort: 0.40 ± 0.1 vs 0.61 ± 0.2, P < .001). Within-lung Jacobian and ADI SDs decreased as severity worsened (Jacobian SD in SARP III cohort: 0.90 ± 0.4 for cluster 1; 0.79 ± 0.3 for cluster 2; 0.62 ± 0.2 for cluster 3; 0.63 ± 0.2 for cluster 4; and 0.41 ± 0.2 for cluster 5; P < .001). Conclusion Quantitative CT assessments of the degree and intraindividual regional variability of lung expansion distinguished between well-established clinical phenotypes among participants with asthma from the Severe Asthma Research Program study. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Verschakelen in this issue.

Rationale: Cross-sectional analysis of mucus plugs in computed tomography (CT) lung scans in the Severe Asthma Research Program (SARP)-3 showed a high mucus plug phenotype. Objectives: To determine if mucus plugs are a persistent asthma phenotype and if changes in mucus plugs over time associate with changes in lung function. Methods: In a longitudinal analysis of baseline and Year 3 CT lung scans in SARP-3 participants, radiologists generated mucus plug scores to assess mucus plug persistence over time. Changes in mucus plug score were analyzed in relation to changes in lung function and CT air trapping measures. Measurements and Main Results: In 164 participants, the mean (range) mucus plug score was similar at baseline and Year 3 (3.4 [0-20] vs. 3.8 [0-20]). Participants and bronchopulmonary segments with a baseline plug were more likely to have plugs at Year 3 than those without baseline plugs (risk ratio, 2.8; 95% confidence interval [CI], 2.0-4.1; P  < 0.001; and risk ratio, 5.0; 95% CI, 4.5-5.6; P  < 0.001, respectively). The change in mucus plug score from baseline to Year 3 was significantly negatively correlated with change in FEV 1 % predicted ( r p  = -0.35; P  < 0.001) and with changes in CT air trapping measures (all P values < 0.05). Conclusions: Mucus plugs identify a persistent asthma phenotype, and susceptibility to mucus plugs occurs at the subject and the bronchopulmonary segment level. The association between change in mucus plug score and change in airflow over time supports a causal role for mucus plugs in mechanisms of airflow obstruction in asthma.

Background Airway mucus plugs in asthma are associated with exacerbation frequency, increased eosinophilia, and reduced lung function. The relationship between mucus plugs and spatially overlapping ventilation abnormalities observed at hyperpolarized gas MRI has not been assessed quantitatively. Purpose To assess regional associations between CT mucus plugs scored by individual bronchopulmonary segment and corresponding measurements of segmental ventilation defect percentage (VDP) at hyperpolarized helium 3 ( 3 He) MRI. Materials and Methods In this secondary analysis of a Health Insurance Portability and Accountability Act-compliant prospective observational cohort, participants in the Severe Asthma Research Program (SARP) III (NCT01760915) between December 2012 and August 2015 underwent hyperpolarized 3 He MRI to determine segmental VDP. Segmental mucus plugs at CT were scored by two readers, with segments scored as plugged only if both readers agreed independently. A linear mixed-effects model controlling for interpatient variability was then used to assess differences in VDP in plugged versus plug-free segments. Results Forty-four participants with asthma were assessed (mean age ± standard deviation, 47 years ± 15; 29 women): 19 with mild-to-moderate asthma and 25 with severe asthma. Mucus plugs were observed in 49 total bronchopulmonary segments across eight of 44 patients. Segments containing mucus plugs had a median segmental VDP of 25.9% (25th-75th percentile, 7.3%-38.3%) versus 1.4% (25th-75th percentile, 0.1%-5.2%; P < .001) in plug-free segments. Similarly, the model estimated a segmental VDP of 18.9% (95% CI: 15.7, 22.2) for mucus-plugged segments versus 5.1% (95% CI: 3.3, 7.0) for plug-free segments ( P < .001). Participants with one or more mucus plugs had a median whole-lung VDP of 11.1% (25th-75th percentile, 7.1%-18.9%) versus 3.1% (25th-75th percentile, 1.1%-4.4%) in those without plugs ( P < .001). Conclusion Airway mucus plugging at CT was associated with reduced ventilation in the same bronchopulmonary segment at hyperpolarized helium 3 MRI, suggesting that mucus plugging may be an important cause of ventilation defects in asthma. © RSNA, 2021 Online supplemental material is available for this article.

This commentary will discuss the use of advanced non-invasive imaging methodology for the pulmonary vascular system with special attention to a rubric for the imaging and clinical team to use for any particular clinical situation.

The clinical importance of interstitial lung abnormality (ILA) is increasingly recognized. In July 2020, the Fleischner Society published a position paper about ILA. The purposes of this article are to summarize the definition, existing evidence, clinical management, and unresolved issues for ILA from a radiologic standpoint and to provide a practical guide for radiologists. ILA is a common incidental finding at CT and is often progressive and associated with worsened clinical outcomes. The hazard ratios for mortality range from 1.3 to 2.7 in large cohorts. Risk factors for ILA include age, smoking status, other inhalational exposures, and genetic factors (eg, gene encoding mucin 5B variant). Radiologists should systematically record the presence, morphologic characteristics, distribution, and subcategories of ILA (ie, nonsubpleural, subpleural nonfibrotic, and subpleural fibrotic), as these are informative for predicting progression and mortality. Clinically significant interstitial lung disease should not be considered ILA. Individuals with ILA are triaged into higher- and lower-risk groups depending on their risk factors for progression, and systematic follow-up, including CT, should be considered for the higher-risk group. Artificial intelligence-based automated analysis for ILA may be helpful, but further validation and improvement are needed. Radiologists have a central role in clinical management and research on ILA., (© RSNA, 2021.)

Importance: The utility of cardiac magnetic resonance imaging (MRI) as a screening tool for myocarditis in competitive student athletes returning to training after recovering from coronavirus disease 2019 (COVID-19) infection is unknown., Objective: To describe the prevalence and severity of cardiac MRI findings of myocarditis in a population of competitive student athletes recovering from COVID-19., Design, Setting, and Participants: In this case series, an electronic health record search was performed at our institution (University of Wisconsin) to identify all competitive athletes (a consecutive sample) recovering from COVID-19, who underwent gadolinium-enhanced cardiac MRI between January 1, 2020, and November 29, 2020. The MRI findings were reviewed by 2 radiologists experienced in cardiac imaging, using the updated Lake Louise criteria. Serum markers of myocardial injury and inflammation (troponin-I, B-type natriuretic peptide, C-reactive protein, and erythrocyte sedimentation rate), an electrocardiogram, transthoracic echocardiography, and relevant clinical data were obtained., Exposures: COVID-19 infection, confirmed using reverse transcription-polymerase chain reaction testing., Main Outcomes and Measures: Prevalence and severity of MRI findings consistent with myocarditis among young competitive athletes recovering from COVID-19., Results: A total of 145 competitive student athletes (108 male and 37 female individuals; mean age, 20 years; range, 17-23 years) recovering from COVID-19 were included. Most patients had mild (71 [49.0%]) or moderate (40 [27.6%]) symptoms during the acute infection or were asymptomatic (24 [16.6%]). Symptoms were not specified or documented in 10 patients (6.9%). No patients required hospitalization. Cardiac MRIs were performed a median of 15 days (range, 11-194 days) after patients tested positive for COVID-19. Two patients had MRI findings consistent with myocarditis (1.4% [95% CI, 0.4%-4.9%]). Of these, 1 patient had marked nonischemic late gadolinium enhancement and T2-weighted signal abnormalities over multiple segments, along with an abnormal serum troponin-I level; the second patient had 1-cm nonischemic mild late gadolinium enhancement and mild T2-weighted signal abnormalities, with normal laboratory values., Conclusions and Relevance: In this case series study, based on MRI findings, there was a low prevalence of myocarditis (1.4%) among student athletes recovering from COVID-19 with no or mild to moderate symptoms. Thus, the utility of cardiac MRI as a screening tool for myocarditis in this patient population is questionable.

Pulmonary functional imaging may be defined as the regional quantification of lung function by using primarily CT, MRI, and nuclear medicine techniques. The distribution of pulmonary physiologic parameters, including ventilation, perfusion, gas exchange, and biomechanics, can be noninvasively mapped and measured throughout the lungs. This information is not accessible by using conventional pulmonary function tests, which measure total lung function without viewing the regional distribution. The latter is important because of the heterogeneous distribution of virtually all lung disorders. Moreover, techniques such as hyperpolarized xenon 129 and helium 3 MRI can probe lung physiologic structure and microstructure at the level of the alveolar-air and alveolar-red blood cell interface, which is well beyond the spatial resolution of other clinical methods. The opportunities, challenges, and current stage of clinical deployment of pulmonary functional imaging are reviewed, including applications to chronic obstructive pulmonary disease, asthma, interstitial lung disease, pulmonary embolism, and pulmonary hypertension. Among the challenges to the deployment of pulmonary functional imaging in routine clinical practice are the need for further validation, establishment of normal values, standardization of imaging acquisition and analysis, and evidence of patient outcomes benefit. When these challenges are addressed, it is anticipated that pulmonary functional imaging will have an expanding role in the evaluation and management of patients with lung disease., (© RSNA, 2021 .)

Over the past few decades, pulmonary imaging technologies have advanced from chest radiography and nuclear medicine methods to high-spatial-resolution or low-dose chest CT and MRI. It is currently possible to identify and measure pulmonary pathologic changes before these are obvious even to patients or depicted on conventional morphologic images. Here, key technological advances are described, including multiparametric CT image processing methods, inhaled hyperpolarized and fluorinated gas MRI, and four-dimensional free-breathing CT and MRI methods to measure regional ventilation, perfusion, gas exchange, and biomechanics. The basic anatomic and physiologic underpinnings of these pulmonary functional imaging techniques are explained. In addition, advances in image analysis and computational and artificial intelligence (machine learning) methods pertinent to functional lung imaging are discussed. The clinical applications of pulmonary functional imaging, including both the opportunities and challenges for clinical translation and deployment, will be discussed in part 2 of this review. Given the technical advances in these sophisticated imaging methods and the wealth of information they can provide, it is anticipated that pulmonary functional imaging will be increasingly used in the care of patients with lung disease. © RSNA, 2021 Online supplemental material is available for this article.

Rationale: The relative roles of mucus plugs and emphysema in mechanisms of airflow limitation and hypoxemia in smokers with chronic obstructive pulmonary disease (COPD) are uncertain. Objectives: To relate image-based measures of mucus plugs and emphysema to measures of airflow obstruction and oxygenation in patients with COPD. Methods: We analyzed computed tomographic (CT) lung images and lung function in participants in the Subpopulations and Intermediate Outcome Measures in COPD Study. Radiologists scored mucus plugs on CT lung images, and imaging software automatically quantified emphysema percentage. Unadjusted and adjusted relationships between mucus plug score, emphysema percentage, and lung function were determined using regression. Measurements and Main Results: Among 400 smokers, 229 (57%) had mucus plugs and 207 (52%) had emphysema, and subgroups could be identified with mucus-dominant and emphysema-dominant disease. Only 33% of smokers with high mucus plug scores had mucus symptoms. Mucus plug score and emphysema percentage were independently associated with lower values for FEV 1 and peripheral oxygen saturation ( P  < 0.001). The relationships between mucus plug score and lung function outcomes were strongest in smokers with limited emphysema ( P  < 0.001). Compared with smokers with low mucus plug scores, those with high scores had worse COPD Assessment Test scores (17.4 ± 7.7 vs. 14.4 ± 13.3), more frequent annual exacerbations (0.75 ± 1.1 vs. 0.43 ± 0.85), and shorter 6-minute-walk distance (329 ± 115 vs. 392 ± 117 m) ( P  < 0.001). Conclusions: Symptomatically silent mucus plugs are highly prevalent in smokers and independently associate with lung function outcomes. These data provide rationale for targeting patients with mucus-high/emphysema-low COPD in clinical trials of mucoactive treatments.Clinical trial registered with www.clinicaltrials.gov (NCT01969344).

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mm Hg and classified into five different groups sharing similar pathophysiologic mechanisms, hemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicine in the evaluation of PH: (a) Is noninvasive imaging capable of identifying PH? (b) What is the role of imaging in establishing the cause of PH? (c) How does imaging determine the severity and complications of PH? (d) How should imaging be used to assess chronic thromboembolic PH before treatment? (e) Should imaging be performed after treatment of PH? This systematic review and position paper highlights the key role of imaging in the recognition, work-up, treatment planning, and follow-up of PH. This article is a simultaneous joint publication in Radiology and European Respiratory Journal . The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. © 2021 RSNA and the European Respiratory Society. Online supplemental material is available for this article.

Background Radiologists are proficient in differentiating between chest radiographs with and without symptoms of pneumonia but have found it more challenging to differentiate coronavirus disease 2019 (COVID-19) pneumonia from non-COVID-19 pneumonia on chest radiographs. Purpose To develop an artificial intelligence algorithm to differentiate COVID-19 pneumonia from other causes of abnormalities at chest radiography. Materials and Methods In this retrospective study, a deep neural network, CV19-Net, was trained, validated, and tested on chest radiographs in patients with and without COVID-19 pneumonia. For the chest radiographs positive for COVID-19, patients with reverse transcription polymerase chain reaction results positive for severe acute respiratory syndrome coronavirus 2 with findings positive for pneumonia between February 1, 2020, and May 30, 2020, were included. For the non-COVID-19 chest radiographs, patients with pneumonia who underwent chest radiography between October 1, 2019, and December 31, 2019, were included. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated to characterize diagnostic performance. To benchmark the performance of CV19-Net, a randomly sampled test data set composed of 500 chest radiographs in 500 patients was evaluated by the CV19-Net and three experienced thoracic radiologists. Results A total of 2060 patients (5806 chest radiographs; mean age, 62 years ± 16 [standard deviation]; 1059 men) with COVID-19 pneumonia and 3148 patients (5300 chest radiographs; mean age, 64 years ± 18; 1578 men) with non-COVID-19 pneumonia were included and split into training and validation and test data sets. For the test set, CV19-Net achieved an AUC of 0.92 (95% CI: 0.91, 0.93). This corresponded to a sensitivity of 88% (95% CI: 87, 89) and a specificity of 79% (95% CI: 77, 80) by using a high-sensitivity operating threshold, or a sensitivity of 78% (95% CI: 77, 79) and a specificity of 89% (95% CI: 88, 90) by using a high-specificity operating threshold. For the 500 sampled chest radiographs, CV19-Net achieved an AUC of 0.94 (95% CI: 0.93, 0.96) compared with an AUC of 0.85 (95% CI: 0.81, 0.88) achieved by radiologists. Conclusion CV19-Net was able to differentiate coronavirus disease 2019-related pneumonia from other types of pneumonia, with performance exceeding that of experienced thoracic radiologists. © RSNA, 2021 Online supplemental material is available for this article.

Pulmonary MRI provides structural and quantitative functional images of the lungs without ionizing radiation, but it has had limited clinical use due to low signal intensity from the lung parenchyma. The lack of radiation makes pulmonary MRI an ideal modality for pediatric examinations, pregnant women, and patients requiring serial and longitudinal follow-up. Fortunately, recent MRI techniques, including ultrashort echo time and zero echo time, are expanding clinical opportunities for pulmonary MRI. With the use of multicoil parallel acquisitions and acceleration methods, these techniques make pulmonary MRI practical for evaluating lung parenchymal and pulmonary vascular diseases. The purpose of this Fleischner Society position paper is to familiarize radiologists and other interested clinicians with these advances in pulmonary MRI and to stratify the Society recommendations for the clinical use of pulmonary MRI into three categories: (a) suggested for current clinical use, (b) promising but requiring further validation or regulatory approval, and (c) appropriate for research investigations. This position paper also provides recommendations for vendors and infrastructure, identifies methods for hypothesis-driven research, and suggests opportunities for prospective, randomized multicenter trials to investigate and validate lung MRI methods., (© RSNA, 2020.)

Competing Interests: The authors declare no conflicts of interest.

Background: There is an unmet need for an objective biomarker to predict asthma exacerbations., Objective: Our aim was to assess the ventilation defect percent (VDP) on hyperpolarized helium-3 magnetic resonance imaging as a predictor of exacerbation frequency following imaging., Methods: Subjects underwent hyperpolarized helium-3 and conventional clinical measurements, including pulmonary function tests, during a period of disease stability, and exacerbations were recorded prospectively over the following 2 years. We used a Poisson regression tree model to estimate an optimal VDP threshold for classifying subjects into high- versus low-exacerbation groups and then used statistical regression to compare this VDP threshold against conventional clinical measures as predictors of exacerbations., Results: A total of 67 individuals with asthma (27 males and 40 females, 28 with mild-to-moderate asthma and 39 with severe asthma) had a median VDP of 3.75% (1.2% [first quartile]-7.9% [third quartile]). An optimal VDP threshold of 4.28% was selected on the basis of the maximum likelihood estimation of the regression tree model. Subjects with a VDP greater than 4.28% (n = 32) had a median of 1.5 exacerbations versus 0.0 for subjects with a VDP less than 4.28% (n = 35). In a stepwise multivariate regression model, a VDP greater than 4.28% was associated with an exacerbation incidence rate ratio of 2.5 (95% CI = 1.3-4.7) versus a VDP less than or equal to 4.28%. However, once individual medical history was included in the model, VDP was no longer significant. Nonetheless, VDP may provide an objective and complementary quantitative marker of individual exacerbation risk that is useful for monitoring individual change in disease status, selecting patients for therapy, and assessing treatment response., Conclusion: VDP measured with magnetic resonance imaging shows promise as a biomarker of prospective asthma exacerbations., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The Framingham Heart Study (FHS) is one of the largest and established longitudinal populational cohorts. CT cohorts of the FHS since 2002 provided a unique opportunity to assess non-cardiac thoracic imaging findings. This review deals with image-based phenotyping studies from recent major publications regarding interstitial lung abnormalities (ILAs), pulmonary cysts, emphysema, pulmonary nodules, pleural plaques, normal spectrum of the thymus, and anterior mediastinal masses, concluding with the discussion of future directions of FHS CT cohorts studies in the era of radiomics and artificial intelligence., (© 2020 The Author(s).)

Background: Accurate diagnosis of pulmonary embolism (PE) using contrast enhanced MRA (CE-MRA) requires awareness of both the direct and indirect findings of PE., Purpose: To evaluate reader agreement of the direct and indirect findings of PE on CE-MRA., Methods: We evaluated pulmonary artery diameter, right ventricle/left ventricle ratio, and clot/vessel lumen signal intensity ratio. Also, eight direct and eight indirect findings of PE were interpreted twice by two radiologists with different experience levels. The prevalence, and intra- and inter-reader agreement for the direct and indirect findings of PE were recorded. Statistical analysis of the measurements was assessed using intraclass correlation while Cohen's kappa test determined inter- and intra-reader agreement., Results: We reviewed 66 positive CE-MRA exams, 10 of which cases were used for training. The largest PE for each of the remaining 56 cases (40 woman) were included in this analysis (38.9 ± 19.7 (mean age (years) ± S.D.)). The highest interobserver agreement for the direct findings were vessel cutoff (κ = 0.52, 95 % CI = (0.30, 0.74), p < .0001) and bright clot (κ = 0.51, 95 % CI = (0.26, 0.78), p = .0001). The highest interobserver agreement for the indirect findings were for atelectasis (κ = 0.67, 95 % CI = (0.49, 0.87), p < .0001), pleural effusions (κ = 0.56, 95 % CI = (0.32, 0.79), p = 0001) and blank slate sing (κ = 0.56, 95 % CI = (0.18, 0.94), p < .0001)., Conclusion: The indirect findings of atelectasis and pleural effusion had better interobserver reproducibility than the direct findings of vessel cutoff and bright clot. The intraobserver reproducibility of the direct and indirect findings is dependent on experience level., Summary Statement: Using contrast enhanced magnetic resonance angiography for the diagnosis of pulmonary embolism, the indirect findings of atelectasis and pleural effusion had better interobserver reproducibility than the direct findings of vessel cutoff and bright clot., (© 2020 The Author(s).)

Pulmonary vascular assessment commonly relies on computed tomography angiography (CTA), but continued advances in magnetic resonance angiography have allowed pulmonary magnetic resonance angiography (pMRA) to become a reasonable alternative to CTA without exposing patients to ionizing radiation. pMRA allows the evaluation of pulmonary vascular anatomy, hemodynamic physiology, lung parenchymal perfusion, and (optionally) right and left ventricular function with a single examination. This article discusses pMRA techniques and artifacts; performance in commonly encountered pulmonary vascular diseases, specifically pulmonary embolism and pulmonary hypertension; and recent advances in both contrast-enhanced and noncontrast pMRA., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hyperpolarized helium 3 magnetic resonance imaging ( 3 He MRI) is useful for investigating pulmonary physiology of pediatric asthma, but a detailed assessment of the safety profile of this agent has not been performed in children., Objective: To evaluate the safety of 3 He MRI in children and adolescents with asthma., Materials and Methods: This was a retrospective observational study. 3 He MRI was performed in 66 pediatric patients (mean age 12.9 years, range 8-18 years, 38 male, 28 female) between 2007 and 2017. Fifty-five patients received a single repeated examination and five received two repeated examinations. We assessed a total of 127 3 He MRI exams. Heart rate, respiratory rate and pulse oximetry measured oxygen saturation (SpO 2 ) were recorded before, during (2 min and 5 min after gas inhalation) and 1 h after MRI. Blood pressure was obtained before and after MRI. Any subjective symptoms were also noted. Changes in vital signs were tested for significance during the exam and divided into three subject age groups (8-12 years, 13-15 years, 16-18 years) using linear mixed-effects models., Results: There were no serious adverse events, but three minor adverse events (2.3%; headache, dizziness and mild hypoxia) were reported. We found statistically significant increases in heart rate and SpO 2 after 3 He MRI. The youngest age group (8-12 years) had an increased heart rate and a decreased respiratory rate at 2 min and 5 min after 3 H inhalation, and an increased SpO 2 post MRI., Conclusion: The use of 3 He MRI is safe in children and adolescents with asthma.

Objectives: Recent studies with lung MRI (MRI) have shown high sensitivity (Sn) and specificity (Sp) for lung nodule detection and characterization relative to low-dose CT (LDCT). Using this background data, we sought to compare the potential screening performance of MRI vs. LDCT using a Markov model of lung cancer screening., Methods: We created a Markov cohort model of lung cancer screening which incorporated lung cancer incidence, progression, and mortality based on gender, age, and smoking burden. Sensitivity (Sn) and Sp for LDCT were taken from the MISCAN Lung Microsimulation and Sn/Sp for MRI was estimated from a published substudy of the German Lung Cancer Screening and Intervention Trial. Screening, work-up, and treatment costs were estimated from published data. Screening with MRI and LDCT was simulated for a cohort of male and female smokers (2 packs per day; 36 pack/years of smoking history) starting at age 60. We calculated the screening performance and cost-effectiveness of MRI screening and performed a sensitivity analysis on MRI Sn/Sp and cost., Results: There was no difference in life expectancy between MRI and LDCT screening (males 13.28 vs. 13.29 life-years; females 14.22 vs. 14.22 life-years). MRI had a favorable cost-effectiveness ratio of $258,169 in men and $403,888 in women driven by fewer false-positive screens. On sensitivity analysis, MRI remained cost effective at screening costs < $396 dollars and Sp > 81%., Conclusions: In this Markov model of lung cancer screening, MRI has a near-equivalent life expectancy benefit and has superior cost-effectiveness relative to LDCT., Key Points: • In this Markov model of lung cancer screening, there is no difference in mortality between yearly screening with MRI and low-dose CT. • Compared to low-dose CT, screening with MRI led to a reduction in false-positive studies from 26 to 2.8% in men and 26 to 2.6% in women. • Due to similar life-expectancy and reduced false-positive rate, we found a favorable cost-effectiveness ratio of $258,169 in men and $403,888 in women of MRI relative to low-dose CT.

Proposed as a safer alternative to smoking, the use of electronic cigarettes has not proven to be innocuous. With numerous deaths, there is an increasing degree of public interest in understanding the symptoms, imaging appearances, causes of, and treatment of electronic cigarette or vaping product use-associated lung injury (EVALI). Patients with EVALI typically have a nonspecific clinical presentation characterized by a combination of respiratory, gastrointestinal, and constitutional symptoms. EVALI is a diagnosis of exclusion; the patient must elicit a history of recent vaping within 90 days, other etiologies must be eliminated, and chest imaging findings must be abnormal. Chest CT findings in EVALI most commonly show a pattern of acute lung injury on the spectrum of organizing pneumonia and diffuse alveolar damage. The pathologic pattern found depends on when in the evolution of the disease process the biopsy sample is taken. Other less common forms of lung injury, including acute eosinophilic pneumonia and diffuse alveolar hemorrhage, have also been reported. Radiologists and pathologists help play an important role in the evaluation of patients suspected of having EVALI. Accurate and rapid identification may decrease morbidity and mortality by allowing for aggressive clinical management and glucocorticoid administration, which have been shown to decrease the severity of lung injury in some patients. In this review, the authors summarize the current state of the art for the imaging and pathologic findings of this disorder and outline a few of the major questions that remain to be answered., (© RSNA, 2020.)

Background: Relative enlargement of the pulmonary artery (PA) on chest CT imaging is associated with respiratory exacerbations in patients with COPD or cystic fibrosis. We sought to determine whether similar findings were present in patients with asthma and whether these findings were explained by differences in ventricular size., Methods: We measured the PA and aorta diameters in 233 individuals from the Severe Asthma Research Program III cohort. We also estimated right, left, and total epicardial cardiac ventricular volume indices (eERVVI, eELVVI, and eETVVI, respectively). Associations between the cardiac and PA measures (PA-to-aorta [PA/A] ratio, eERVVI-to-eELVVI [eRV/eLV] ratio, eERVVI, eELVVI, eETVVI) and clinical measures of asthma severity were assessed by Pearson correlation, and associations with asthma severity and exacerbation rate were evaluated by multivariable linear and zero-inflated negative binomial regression., Results: Asthma severity was associated with smaller ventricular volumes. For example, those with severe asthma had 36.1 mL/m 2 smaller eETVVI than healthy control subjects (P = .003) and 14.1 mL/m 2 smaller eETVVI than those with mild/moderate disease (P = .011). Smaller ventricular volumes were also associated with a higher rate of asthma exacerbations, both retrospectively and prospectively. For example, those with an eETVVI less than the median had a 57% higher rate of exacerbations during follow-up than those with eETVVI greater than the median (P = .020). Neither PA/A nor eRV/eLV was associated with asthma severity or exacerbations., Conclusions: In patients with asthma, smaller cardiac ventricular size may be associated with more severe disease and a higher rate of asthma exacerbations., Trial Registry: ClinicalTrials.gov; No.: NCT01761630; URL: www.clinicaltrials.gov., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)