Publications by authors named "David A Lynch"

281 Publications

Functional imaging of COPD by CT and MRI.

Authors:
David A Lynch

Br J Radiol 2021 Sep 19:20201005. Epub 2021 Sep 19.

Department of Radiology, National Jewish Health, Denver, CO, United States.

This commentary reviews the contribution of imaging by CT and MRI to functional assessment in chronic obstructive pulmonary disease (COPD). CT can help individualize the assessment of COPD by quantifying emphysema, air trapping and airway wall thickening, potentially leading to more specific treatments for these distinct components of COPD. Longitudinal changes in these metrics can help assess progression or improvement. On hyperpolarized gas MRI, the apparent diffusion coefficient of provides an index of airspace enlargement reflecting emphysema. Perfusion imaging and measurement of pulmonary vascular volume on non-contrast CT provide insight into the contribution of pulmonary vascular disease to pulmonary impairment. Functional imaging is particularly valuable in detecting early lung dysfunction in subjects with inhalational exposures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1259/bjr.20201005DOI Listing
September 2021

Impact of CFTR Therapy on Chronic Rhinosinusitis and Health Status: Deep Learning CT Analysis and Patient Reported Outcomes.

Ann Am Thorac Soc 2021 Aug 26. Epub 2021 Aug 26.

National Jewish Health, Medicine and Pediatrics, Denver, Colorado, United States;

Rationale: Elexacaftor/tezacaftor/ivacaftor (ETI) in triple combination improves pulmonary health for people with cystic fibrosis (PwCF) however its impact on objective measures of sinus disease and health utility is unestablished.

Objectives: To evaluate the impact of ETI on chronic rhinosinusitis (CRS) and general health status incorporating computed tomography (CT), quality-of-life (QOL) and productivity loss.

Methods: Adult PwCF+CRS with CF transmembrane conductance regulator genotype F508del/F508del or F508del/minimal function who clinically initiated ETI participated in a prospective, observational study. The primary endpoint was change in percent sinus CT opacification (%SO) after 6 months of ETI assessed via deep learning-based methods. Secondary endpoints included changes in sinonasal QOL, health utility value and productivity loss, which were evaluated monthly via validated metrics.

Results: 30 PwCF provided baseline data; 25 completed the study. At baseline, the cohort had substantial CRS, with mean 22-question SinoNasal Outcome Test (SNOT-22) score 33.1 and mean sinus CT %SO 63.7%. At 6-month follow-up, %SO improved by mean 22.9% (p<0.001). %SO improvement trended toward greater magnitude for those naïve to prior modulator therapy (p=0.09). Mean SNOT-22 scores and health utility improved by 15.3 and 0.068 [6.8%] (all p<0.007). Presenteeism, activity impairment and overall productivity loss improved (all p<0.049). Improvements in SNOT-22 scores and health utility occurred by one month and remained improved over the study.

Conclusions: ETI is associated with substantial improvements in sinus CT opacification and productivity loss, and clinically meaningful improvements in sinonasal QOL and health utility. Most improvements were rapid, robust and durable over the study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.202101-057OCDOI Listing
August 2021

CT of Post-Acute Lung Complications of COVID-19.

Radiology 2021 Nov 10;301(2):E383-E395. Epub 2021 Aug 10.

From the Departments of Medicine (J.J.S.) and Radiology (D.A.L.), National Jewish Health, 1400 Jackson St, Denver, CO 80205; Division of Pulmonary, Sleep and Critical Care Medicine, Department of Medicine (B.H., R.C.), and Department of Radiology (J.P.K.), NYU Langone Health, NYU Grossman School of Medicine, New York, NY.

The acute course of COVID-19 is variable and ranges from asymptomatic infection to fulminant respiratory failure. Patients recovering from COVID-19 can have persistent symptoms and CT abnormalities of variable severity. At 3 months after acute infection, a subset of patients will have CT abnormalities that include ground-glass opacity (GGO) and subpleural bands with concomitant pulmonary function abnormalities. At 6 months after acute infection, some patients have persistent CT changes to include the resolution of GGOs seen in the early recovery phase and the persistence or development of changes suggestive of fibrosis, such as reticulation with or without parenchymal distortion. The etiology of lung disease after COVID-19 may be a sequela of prolonged mechanical ventilation, COVID-19-induced acute respiratory distress syndrome (ARDS), or direct injury from the virus. Predictors of lung disease after COVID-19 include need for intensive care unit admission, mechanical ventilation, higher inflammatory markers, longer hospital stay, and a diagnosis of ARDS. Treatments of lung disease after COVID-19 are being investigated, including the potential of antifibrotic agents for prevention of lung fibrosis after COVID-19. Future research is needed to determine the long-term persistence of lung disease after COVID-19, its impact on patients, and methods to either prevent or treat it. © RSNA, 2021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2021211396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369881PMC
November 2021

Interstitial Lung Abnormalities: State of the Art.

Radiology 2021 10 10;301(1):19-34. Epub 2021 Aug 10.

From the Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, MA 02115 (A.H., H.H.); Department of Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Osaka, Japan (A.H.); Department of Radiology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wis (M.L.S.); and Department of Radiology, National Jewish Health, Denver, Colo (D.A.L.).

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2021204367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487219PMC
October 2021

Metamotivation in people diagnosed with schizophrenia: A conceptual introduction and qualitative study.

Schizophr Res 2021 Jul 26. Epub 2021 Jul 26.

New York State Psychiatric Institute, Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York-Presbyterian, United States of America.

Negative symptoms, such as avolition, are considered to be some of the most debilitating symptoms of schizophrenia, yet the mechanisms that contribute to their formation and persistence are poorly understood. In this article, we introduce a novel concept, metamotivation, as having potential implications for avolition, a core negative symptom. Metamotivation is defined as the ability to identify, monitor, and self-regulate motivation in service of goal attainment. In order to explore the potential applicability of metamotivation to schizophrenia spectrum populations, qualitative data from semi-structured interviews were thematically analyzed from 21 people diagnosed with schizophrenia or schizoaffective disorder. Four core themes emerged from the analysis: motivation as unmalleable, motivation as self- regulated primarily through rewards and/or a focus on task outcome, motivation as effortless actions, and motivation as a pleasurable feeling. We discuss these findings with respect to potential inadequacies/errors in motivational knowledge that may occur in people with schizophrenia, which may in turn be implicated in the development and maintenance of avolition. We conclude that metamotivation is a valuable concept for understanding schizophrenia with important research and clinical implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2021.06.003DOI Listing
July 2021

Detection and Early Referral of Patients With Interstitial Lung Abnormalities: An Expert Survey Initiative.

Chest 2021 Jun 29. Epub 2021 Jun 29.

Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI.

Background: Interstitial lung abnormalities (ILA) may represent undiagnosed early-stage or subclinical interstitial lung disease (ILD). ILAs are often observed incidentally in patients who subsequently develop clinically overt ILD. There is limited information on consensus definitions for, and the appropriate evaluation of, ILA. Early recognition of patients with ILD remains challenging, yet critically important. Expert consensus could inform early recognition and referral.

Research Question: Can consensus-based expert recommendations be identified to guide clinicians in the recognition, referral, and follow-up of patients with or at risk of developing early ILDs?

Study Design And Methods: Pulmonologists and radiologists with expertise in ILD participated in two iterative rounds of surveys. The surveys aimed to establish consensus regarding ILA reporting, identification of patients with ILA, and identification of populations that might benefit from screening for ILD. Recommended referral criteria and follow-up processes were also addressed. Threshold for consensus was defined a priori as ≥ 75% agreement or disagreement.

Results: Fifty-five experts were invited and 44 participated; consensus was reached on 39 of 85 questions. The following clinically important statements achieved consensus: honeycombing and traction bronchiectasis or bronchiolectasis indicate potentially progressive ILD; honeycombing detected during lung cancer screening should be reported as potentially significant (eg, with the Lung CT Screening Reporting and Data System "S-modifier" [which indicates clinically significant or potentially significant noncancer findings]), recommending referral to a pulmonologist in the radiology report; high-resolution CT imaging and full pulmonary function tests should be ordered if nondependent subpleural reticulation, traction bronchiectasis, honeycombing, centrilobular ground-glass nodules, or patchy ground-glass opacity are observed on CT imaging; patients with honeycombing or traction bronchiectasis should be referred to a pulmonologist irrespective of FVC and diffusion capacity values; and patients with systemic sclerosis should be screened with pulmonary function tests for early-stage ILD.

Interpretation: Guidance for identifying clinically relevant ILA, with subsequent referral and follow-up, was established. These results lay the foundation for developing practical guidance on managing patients with ILA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.06.035DOI Listing
June 2021

Small Airway Disease and Emphysema Are Associated with Future Exacerbations in Smokers with CT-derived Bronchiectasis and COPD: Results from the COPDGene Cohort.

Radiology 2021 09 22;300(3):706-714. Epub 2021 Jun 22.

From the Division of Pulmonary Diseases and Critical Care, the University of Texas Health Science Center at San Antonio, San Antonio, Tex (D.J.M., A.A., M.I.R.); Department of Radiology, University of California, San Diego, Calif (A.Y.); Division of Sleep Medicine and Circadian Disorders (W.W.), Division of Pulmonary and Critical Care Medicine, Department of Medicine (W.R.D., A.A.D.), and Department of Radiology (R.S.J.E.), Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115; Department of Radiology, St. Luke's International Hospital, Chuo-ku, Tokyo, Japan (Y.O.); Quinnipiac University School of Medicine, Hamden, Conn (C.M.); South Texas Veterans Health Care System, San Antonio, Tex (A.A., M.I.R.); Pulmonary Disease and Critical Care Medicine, Mayo Clinic, Rochester, Minn (T.R.A.); Division of Pulmonary, Critical Care & Sleep Medicine, New York University School of Medicine, New York, NY (A.B.); Department of Pathophysiology and Transplantation, University of Milan Internal Medicine, and Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy (S.A.); Department of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, Colo (K.A.Y., G.L.K.); Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Ala (J.M.W.); and Department of Radiology, National Jewish Health, Denver, Colo (D.A.L.).

Background Chronic obstructive pulmonary disease (COPD) and bronchiectasis can overlap and share pathologic features, such as small airway disease (SAD). Whether the presence of SAD and emphysema in smokers with CT-derived bronchiectasis is associated with exacerbations is unknown. Purpose To assess whether SAD and emphysema in smokers with CT-derived bronchiectasis are associated with future exacerbations. Materials and Methods SAD and emphysema were quantified using the parametric response map method in former and current heavy smokers with and without bronchiectasis at CT from the COPDGene Study (from July 2009 to July 2018). Exacerbations were prospectively assessed through biannual follow-up. An exacerbation was defined as an increase in or new onset of respiratory symptoms treated with antibiotics and/or corticosteroids. Severe exacerbations were defined as those that required hospitalization. The association of a high burden of SAD (≥15.6%) and high burden of emphysema (≥5%) at CT with exacerbations was assessed with generalized linear mixed models. Results Of 737 participants, 387 (median age, 64 years [interquartile range, 58-71 years]; 223 women) had CT-derived bronchiectasis. During a 9-year follow-up, after adjustment for age, sex, race, body mass index, current smoking status, pack-years, exacerbations before study entry, forced expiratory volume in 1 second, or FEV, and bronchiectasis severity CT score, high burden of SAD and high burden of emphysema were associated with a higher number of exacerbations per year (relative risk [RR], 1.89 [95% CI: 1.54, 2.33] and 1.37 [95% CI: 1.13, 1.66], respectively; ≤ .001 for both). Results were comparable among participants with bronchiectasis meeting criteria for COPD ( = 197) (RR, 1.67 [95% CI: 1.23, 2.27] for high burden of SAD and 1.51 [95% CI: 1.20, 1.91] for high burden of emphysema; ≤ .001 for both). Conclusion In smokers with CT-derived bronchiectasis and chronic obstructive pulmonary disease, structural damage to lung parenchyma and small airways was associated with a higher number of exacerbations per year. Clinical trial registration no. NCT00608764 © RSNA, 2021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2021204052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409101PMC
September 2021

Design and rationale of a randomised, double-blind trial of the efficacy and safety of pirfenidone in patients with fibrotic hypersensitivity pneumonitis.

ERJ Open Res 2021 Apr 7;7(2). Epub 2021 Jun 7.

Clinical and Translational Research Unit, National Jewish Health, Denver, CO, USA.

Hypersensitivity pneumonitis (HP) is an immunologically mediated form of lung disease resulting from inhalational exposure to any of a large variety of antigens. A subgroup of patients with HP develops pulmonary fibrosis (fibrotic HP; FHP), a significant cause of morbidity and mortality. This study will evaluate the safety and efficacy of the antifibrotic pirfenidone in treating FHP. This single-centre, randomised, double-blind, placebo-controlled trial is enrolling adults with FHP (ClinicalTrials.gov: NCT02958917). Study participants must have fibrotic abnormalities involving ≥5% of the lung parenchyma on high-resolution computed tomography scan, forced vital capacity (FVC) ≥40% and diffusing capacity of the lung for carbon monoxide ≥30% of predicted values. Study participants will be randomised in a 2:1 ratio to receive pirfenidone 2403 mg·day or placebo. The primary efficacy end-point is the mean change in FVC % predicted from baseline to week 52. A number of secondary end-points have been chosen to evaluate the safety and efficacy in different domains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/23120541.00054-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181708PMC
April 2021

Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort.

Chest 2021 Oct 21;160(4):1245-1254. Epub 2021 May 21.

Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, MD.

Background: Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV progression in current smokers.

Research Question: Is use of ACEi and ARB associated with less progression of emphysema and FEV decline among individuals with COPD or baseline emphysema?

Methods: Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume <-950 Hounsfield units [HU]), 15th percentile of the attenuation histogram (attenuation [in HU] below which 15% of voxels are situated plus 1,000 HU), and lung function decline over 5 years between ACEi and ARB users and nonusers in those with spirometry-confirmed COPD, as well as all participants and those with baseline emphysema. Effect modification by smoking status also was investigated.

Results: Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV % predicted, 0.83; 95% CI, -0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema.

Interpretation: Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline.

Trial Registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.05.007DOI Listing
October 2021

The Role of Surgical Lung Biopsy in the Diagnosis of Fibrotic Interstitial Lung Disease: Perspective from the Pulmonary Fibrosis Foundation.

Ann Am Thorac Soc 2021 10;18(10):1601-1609

Department of Pulmonary and Critical Care Medicine, Kaiser Permanente San Francisco, San Francisco, California; and.

Diagnosis of interstitial lung disease (ILD) requires a multidisciplinary discussion approach that includes clinicians, radiologists, and pathologists. Surgical lung biopsy (SLB) is currently the recommended standard in obtaining pathologic specimens for patients with ILD requiring a tissue diagnosis. The increased diagnostic confidence and accuracy provided by microscopic pathology assessment of SLB specimens must be balanced with the associated risks in patients with ILD. This document was developed by the SLB Working Group of the Pulmonary Fibrosis Foundation, composed of a multidisciplinary group of ILD physicians, including pulmonologists, radiologists, pathologists, and thoracic surgeons. In this document, we present an up-to-date literature review of the indications, contraindications, risks, and alternatives to SLB in the diagnosis of fibrotic ILD; outline an integrated approach to the decision-making around SLB in the diagnosis of fibrotic ILD; and provide practical information to maximize the yield and safety of SLB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1513/AnnalsATS.202009-1179FRDOI Listing
October 2021

Comparison of CT Lung Density Measurements between Standard Full-Dose and Reduced-Dose Protocols.

Radiol Cardiothorac Imaging 2021 Apr 22;3(2):e200503. Epub 2021 Apr 22.

Imbio LLC, 1015 Glenwood Ave, Minneapolis, MN 55405 (C.R.H.); School of Medicine and Public Health, Division of Radiology, University of Michigan, Ann Arbor, Mich (C.R.H.); Department of Radiology, National Jewish Health, Denver, Colo (A.S.O., D.A.L., S.M.H.); Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio (N.A.O.); and Thirona, Nijmegen, the Netherlands (J.P.C.).

Purpose: To evaluate the reproducibility and predicted clinical outcomes of CT-based quantitative lung density measurements using standard fixed-dose (FD) and reduced-dose (RD) scans.

Materials And Methods: In this retrospective analysis of prospectively acquired data, 1205 participants (mean age, 65 years ± 9 [standard deviation]; 618 men) enrolled in the COPDGene study who underwent FD and RD CT image acquisition protocols between November 2014 and July 2017 were included. Of these, the RD scans of 640 participants were also reconstructed using iterative reconstruction (IR). Median filtering was applied to the RD scans (RD-MF) to investigate an alternative noise reduction strategy. CT attenuation at the 15th percentile of the lung CT histogram (Perc15) was computed for all image types (FD, RD, RD-MF, and RD-IR). Reproducibility coefficients were calculated to quantify the measurement differences between FD and RD scans. The ability of Perc15 to predict chronic obstructive pulmonary disease (COPD) diagnosis and exacerbation frequency was investigated using receiver operating characteristic analysis.

Results: The Perc15 reproducibility coefficients with and without volume adjustment were as follows: RD, 29.43 HU ± 0.62 versus 32.81 HU ± 1.70; RD-MF, 7.42 HU ± 0.42 versus 19.40 HU ± 2.65; and RD-IR, 7.10 HU ± 0.52 versus 22.46 HU ± 3.91. Receiver operating characteristic curve analysis indicated that Perc15 on volume-adjusted FD and RD scans were both predictive for COPD diagnosis (area under the receiver operating characteristic curve [AUC]: FD, 0.724 ± 0.045; RD, 0.739 ± 0.045) and for having one or more exacerbation per year (AUCs: FD, 0.593 ± 0.068; RD, 0.589 ± 0.066). Similar trends were observed when volume adjustment was not applied.

Conclusion: A combination of volume adjustment and noise reduction filtering improved the reproducibility of lung density measurements computed using serial FD and RD CT scans.© RSNA, 2021.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/ryct.2021200503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098098PMC
April 2021

Automated CT Staging of Chronic Obstructive Pulmonary Disease Severity for Predicting Disease Progression and Mortality with a Deep Learning Convolutional Neural Network.

Radiol Cardiothorac Imaging 2021 Apr 8;3(2):e200477. Epub 2021 Apr 8.

Department of Radiology (K.A.H., N.Y., T.R., S.K., A.H.) and Department of Medicine (D.J.C.), University of California San Diego, 9452 Medical Center Dr, La Jolla, CA 92037; Department of Mathematics and Statistics, San Diego State University, San Diego, Calif (K.A.H.); and Department of Radiology, National Jewish Health, Denver, Colo (D.A.L.).

Purpose: To develop a deep learning-based algorithm to stage the severity of chronic obstructive pulmonary disease (COPD) through quantification of emphysema and air trapping on CT images and to assess the ability of the proposed stages to prognosticate 5-year progression and mortality.

Materials And Methods: In this retrospective study, an algorithm using co-registration and lung segmentation was developed in-house to automate quantification of emphysema and air trapping from inspiratory and expiratory CT images. The algorithm was then tested in a separate group of 8951 patients from the COPD Genetic Epidemiology study (date range, 2007-2017). With measurements of emphysema and air trapping, bivariable thresholds were determined to define CT stages of severity (mild, moderate, severe, and very severe) and were evaluated for their ability to prognosticate disease progression and mortality using logistic regression and Cox regression.

Results: On the basis of CT stages, the odds of disease progression were greatest among patients with very severe disease (odds ratio [OR], 2.67; 95% CI: 2.02, 3.53; < .001) and were elevated in patients with moderate disease (OR, 1.50; 95% CI: 1.22, 1.84; = .001). The hazard ratio of mortality for very severe disease at CT was 2.23 times the normal ratio (95% CI: 1.93, 2.58; < .001). When combined with Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging, patients with GOLD stage 2 disease had the greatest odds of disease progression when the CT stage was severe (OR, 4.48; 95% CI: 3.18, 6.31; < .001) or very severe (OR, 4.72; 95% CI: 3.13, 7.13; < .001).

Conclusion: Automated CT algorithms can facilitate staging of COPD severity, have diagnostic performance comparable with that of spirometric GOLD staging, and provide further prognostic value when used in conjunction with GOLD staging.© RSNA, 2021See also commentary by Kalra and Ebrahimian in this issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/ryct.2021200477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098086PMC
April 2021

Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COPD.

Respir Res 2021 Apr 27;22(1):127. Epub 2021 Apr 27.

Research and Development, GlaxoSmithKline, Collegeville, PA, USA.

Background: Soluble receptor for advanced glycation end products (sRAGE) is a proposed emphysema and airflow obstruction biomarker; however, previous publications have shown inconsistent associations and only one study has investigate the association between sRAGE and emphysema. No cohorts have examined the association between sRAGE and progressive decline of lung function. There have also been no evaluation of assay compatibility, receiver operating characteristics, and little examination of the effect of genetic variability in non-white population. This manuscript addresses these deficiencies and introduces novel data from Pittsburgh COPD SCCOR and as well as novel work on airflow obstruction. A meta-analysis is used to quantify sRAGE associations with clinical phenotypes.

Methods: sRAGE was measured in four independent longitudinal cohorts on different analytic assays: COPDGene (n = 1443); SPIROMICS (n = 1623); ECLIPSE (n = 2349); Pittsburgh COPD SCCOR (n = 399). We constructed adjusted linear mixed models to determine associations of sRAGE with baseline and follow up forced expiratory volume at one second (FEV) and emphysema by quantitative high-resolution CT lung density at the 15th percentile (adjusted for total lung capacity).

Results: Lower plasma or serum sRAGE values were associated with a COPD diagnosis (P < 0.001), reduced FEV (P < 0.001), and emphysema severity (P < 0.001). In an inverse-variance weighted meta-analysis, one SD lower log-transformed sRAGE was associated with 105 ± 22 mL lower FEV and 4.14 ± 0.55 g/L lower adjusted lung density. After adjusting for covariates, lower sRAGE at baseline was associated with greater FEV decline and emphysema progression only in the ECLIPSE cohort. Non-Hispanic white subjects carrying the rs2070600 minor allele (A) and non-Hispanic African Americans carrying the rs2071288 minor allele (A) had lower sRAGE measurements compare to those with the major allele, but their emphysema-sRAGE regression slopes were similar.

Conclusions: Lower blood sRAGE is associated with more severe airflow obstruction and emphysema, but associations with progression are inconsistent in the cohorts analyzed. In these cohorts, genotype influenced sRAGE measurements and strengthened variance modelling. Thus, genotype should be included in sRAGE evaluations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-021-01686-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076883PMC
April 2021

Practical application and validation of the 2018 ATS/ERS/JRS/ALAT and Fleischner Society guidelines for the diagnosis of idiopathic pulmonary fibrosis.

Respir Res 2021 Apr 26;22(1):124. Epub 2021 Apr 26.

Department of Pathology, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114, USA.

Background: Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) is essential to inform prognosis and treatment. In 2018, the ATS/ERS/JRS/ALAT and Fleischner Society released new diagnostic guidelines for usual interstitial pneumonitis (UIP)/IPF, adding Probable UIP as a CT category based on prior studies demonstrating this category had relatively high positive predictive value (PPV) for histopathologic UIP/Probable UIP. This study applies the 2018 ATS/ERS/JRS/ALAT and Fleischner Society guidelines to determine test characteristics of CT categories in academic clinical practice.

Methods: CT and histopathology were evaluated by three thoracic radiologists and two thoracic pathologists. Comparison of consensus categorization by the 2018 ATS and Fleischner Society guidelines by CT and histopathology was performed.

Results: Of patients with CT UIP, 87% (PPV, 95% CI: 60-98%) had histopathologic UIP with 97% (CI: 90-100%) specificity. Of patients with CT Probable UIP, 38% (PPV, CI: 14-68%) had histopathologic UIP and 46% (PPV, CI: 19-75%) had either histopathologic UIP or Probable UIP, with 88% (CI: 77-95%) specificity. Patients with CT Indeterminate and Alternative Diagnosis had histopathologic UIP in 27% (PPV, CI: 6-61%) and 21% (PPV, CI: 11-33%) of cases with specificities of 90% (CI: 80-96%) and 25% (CI: 16-37%). Interobserver variability (kappa) between radiologists ranged 0.32-0.81.

Conclusions: CT UIP and Probable UIP have high specificity for histopathologic UIP, and CT UIP has high PPV for histopathologic UIP. PPV of CT Probable UIP was 46% for combined histopathologic UIP/Probable UIP. Our results indicate that additional studies are needed to further assess and refine the guideline criteria to improve classification performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12931-021-01670-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074481PMC
April 2021

Client, clinician, and administrator factors associated with the successful acceptance of a telehealth comprehensive recovery service: A mixed methods study.

Psychiatry Res 2021 06 15;300:113871. Epub 2021 Mar 15.

New York State Psychiatric Institute, Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, and NewYork-Presbyterian, 1051 Riverside Drive, Box 100, New York, NY 10032, United States. Electronic address:

The coronavirus disease 2019 SARS-CoV-2 (COVID-19) crisis and subsequent social distancing recommendations resulted in increased use of telehealth within recovery-oriented behavioral health services (RS). Populations with serious mental illness (SMI) rely on psychosocial treatment, care coordination, and pharmacotherapy to achieve recovery goals and increase community engagement. This program evaluation of a group-based RS used mixed methods to better understand the multiple factors that contributed to successful telehealth conversion. Clients' service utilization over an 18-week period was collected to determine acceptance and the client characteristics associated with utilization (n = 72). Clients completed a treatment satisfaction questionnaire that was distributed ten weeks following telehealth conversion. Qualitative interviews explored staff perspectives on factors that impacted conversion, acceptance, and utilization. Initial staff skepticism gave way to acceptance, while the demands of resourcefulness, flexibility, and competency were emphasized. Clients' treatment utilization remained stable, while the number of missed/cancelled sessions were less frequent over time, especially for clients with a history of psychosis. Clients reported high overall satisfaction, but a preference for in-person treatment. Within this clinic serving middle to high socioeconomic status (SES) clients, clinicians and clients alike found the virtual group-based RS to be feasible and acceptable while in-person treatment was not an option.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psychres.2021.113871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141021PMC
June 2021

Executive Summary: Diagnosis and Evaluation of Hypersensitivity Pneumonitis: CHEST Guideline and Expert Panel Report.

Chest 2021 Aug 15;160(2):595-615. Epub 2021 Apr 15.

American College of Chest Physicians, Glenview, IL.

Background: The purpose of this summary is to provide a synopsis of evidence-based and consensus-derived guidance for clinicians to improve individual diagnostic decision-making for hypersensitivity pneumonitis (HP) and decrease diagnostic practice variability.

Study Design And Methods: Approved panelists developed key questions regarding the diagnosis of HP using the PICO (Population, Intervention, Comparator, and Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. The quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus.

Results: The systematic review of the literature based on 14 PICO questions resulted in 14 key action statements: 12 evidence-based, graded recommendations, and 2 ungraded consensus-based statements. All evidence was of very low quality.

Interpretation: Diagnosis of HP should employ a patient-centered approach and include a multidisciplinary assessment that incorporates the environmental and occupational exposure history and CT pattern to establish diagnostic confidence prior to considering BAL and/or lung biopsy. Additional research is needed on the performance characteristics and generalizability of exposure assessment tools and traditional and new diagnostic tests in modifying clinical decision-making for HP, particularly among those with a provisional diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.03.067DOI Listing
August 2021

Diagnosis and Evaluation of Hypersensitivity Pneumonitis: CHEST Guideline and Expert Panel Report.

Chest 2021 Aug 20;160(2):e97-e156. Epub 2021 Apr 20.

American College of Chest Physicians, Glenview, IL.

Background: The purpose of this analysis is to provide evidence-based and consensus-derived guidance for clinicians to improve individual diagnostic decision-making for hypersensitivity pneumonitis (HP) and decrease diagnostic practice variability.

Study Design And Methods: Approved panelists developed key questions regarding the diagnosis of HP using the PICO (Population, Intervention, Comparator, Outcome) format. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and vetted evaluation tools were used to assess the quality of included studies, to extract data, and to grade the level of evidence supporting each recommendation or statement. The quality of the evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Graded recommendations and ungraded consensus-based statements were drafted and voted on using a modified Delphi technique to achieve consensus. A diagnostic algorithm is provided, using supporting data from the recommendations where possible, along with expert consensus to help physicians gauge the probability of HP.

Results: The systematic review of the literature based on 14 PICO questions resulted in 14 key action statements: 12 evidence-based, graded recommendations and 2 ungraded consensus-based statements. All evidence was of very low quality.

Interpretation: Diagnosis of HP should employ a patient-centered approach and include a multidisciplinary assessment that incorporates the environmental and occupational exposure history and CT pattern to establish diagnostic confidence prior to considering BAL and/or lung biopsy. Criteria are presented to facilitate diagnosis of HP. Additional research is needed on the performance characteristics and generalizability of exposure assessment tools and traditional and new diagnostic tests in modifying clinical decision-making for HP, particularly among those with a provisional diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.03.066DOI Listing
August 2021

Practical Imaging Interpretation in Patients Suspected of Having Idiopathic Pulmonary Fibrosis: Official Recommendations from the Radiology Working Group of the Pulmonary Fibrosis Foundation.

Radiol Cardiothorac Imaging 2021 Feb 25;3(1):e200279. Epub 2021 Feb 25.

Department of Radiology, University of Kentucky, 800 Rose St, HX-315B, Lexington, KY 40536 (S.H.); Department of Radiology, University of Chicago, Chicago, Ill (J.H.C.); Department of Radiology, Columbia University, New York, NY (J.L.); Department of Imaging Sciences, University of Rochester, Rochester, NY (K.K.J.); and Department of Radiology, National Jewish Health, Denver, Colo (D.A.L.).

Imaging serves a key role in the diagnosis of patients suspected of having idiopathic pulmonary fibrosis (IPF). Accurate pattern classification at thin-section chest CT is a key step in multidisciplinary discussions, guiding the need for surgical lung biopsy and determining available pharmacologic therapies. The recent approval of new treatments for fibrosing lung disease has made it more critical than ever for radiologists to facilitate accurate and early diagnosis of IPF. This document was developed by the Radiology Working Group of the Pulmonary Fibrosis Foundation with the goal of providing a practical guide for radiologists. In this review, the critical imaging patterns of IPF, pitfalls in imaging classifications, confounding imaging findings with other fibrotic lung diseases, and reporting standards for cases of lung fibrosis will be discussed. Published under a CC BY 4.0 license. See also the commentary by White and Galvin in this issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/ryct.2021200279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977697PMC
February 2021

Predicting response to cognitive training for schizophrenia using results from two studies with different outcomes.

Schizophr Res 2021 05 23;231:61-66. Epub 2021 Mar 23.

New York State Psychiatric Institute, Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, and New York-Presbyterian, 1051 Riverside Drive, New York, NY 10032, United States. Electronic address:

Background: Collaborative data sharing between research groups provides an opportunity to explore the basis for the heterogeneity in cognitive training outcomes reported in the schizophrenia literature. The current analyses focused on the contribution of site and participant characteristics to these heterogeneous outcomes.

Methods: Data from two independent studies, from New York (NY) and Los Angeles (LA), were combined to yield a sample of 132 outpatient adults with schizophrenia/schizoaffective disorder. While similar treatment doses, cognitive exercises and outcome measures were used, sites differed in use of coaching, group discussion and compensation. Between-site differences in participant demographic and baseline clinical characteristics were tested. Regression examined predictors of change in cognition (MCCB) and functional capacity (UPSA) which could explain site differences in treatment effects.

Results: Medium to large treatment effect size differences in MCCB and UPSA favored the NY site over LA. When the studies were combined, the effect of site was significant for both outcomes with a medium effect size difference. After controlling for background characteristics, the effect of site was reduced for both outcomes, but remained significant for cognition. Improvement in UPSA was associated with better baseline MCCB (p < 0.001), lower baseline UPSA (p < 0.001) and younger age (p = 0.019). The overall model with site, baseline scores, and participant background characteristics explained about 30% to 40% of the variance in outcomes.

Discussion: Participant and treatment characteristics are both predictive of outcomes, but treatment characteristics may be more consequential to cognitive gain, while participant characteristics may be more consequential to change in functional capacity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2021.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222143PMC
May 2021

FOOTPRINTS study protocol: rationale and methodology of a 3-year longitudinal observational study to phenotype patients with COPD.

BMJ Open 2021 03 22;11(3):e042526. Epub 2021 Mar 22.

Department of Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany.

Introduction: A better understanding is needed of the different phenotypes that exist for patients with chronic obstructive pulmonary disease (COPD), their relationship with the pathogenesis of COPD and how they may affect disease progression. Biomarkers, including those associated with emphysema, may assist in characterising patients and in predicting and monitoring the course of disease. The FOOTPRINTS study (study 352.2069) aims to identify biomarkers associated with emphysema, over a 3-year period.

Methods And Analysis: The FOOTPRINTS study is a prospective, longitudinal, multinational (12 countries), multicentre (51 sites) biomarker study, which has enrolled a total of 463 ex-smokers, including subjects without airflow limitation (as defined by the 2015 Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy report), patients with COPD across the GOLD stages 1-3 and patients with COPD and alpha1-antitrypsin deficiency. The study has an observational period lasting 156 weeks that includes seven site visits and additional phone interviews. Biomarkers in blood and sputum, imaging data (CT and magnetic resonance), clinical parameters, medical events of special interest and safety are being assessed at regular visits. Disease progression based on biomarker values and COPD phenotypes are being assessed using multivariate statistical prediction models.

Ethics And Dissemination: The study protocol was approved by the authorities and ethics committees/institutional review boards of the respective institutions where applicable, which included study sites in Belgium, Canada, Denmark, Finland, Germany, Japan, Korea, Poland, Spain, Sweden, UK and USA; written informed consent has been obtained from all study participants. Ethics committee approval was obtained for all participating sites prior to enrolment of the study participants. The study results will be reported in peer-reviewed publications.

Trial Registration Number: NCT02719184.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-042526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986686PMC
March 2021

Progression of traction bronchiectasis/bronchiolectasis in interstitial lung abnormalities is associated with increased all-cause mortality: Age Gene/Environment Susceptibility-Reykjavik Study.

Eur J Radiol Open 2021 10;8:100334. Epub 2021 Mar 10.

Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.

Purpose: The aim of this study is to assess the role of traction bronchiectasis/bronchiolectasis and its progression as a predictor for early fibrosis in interstitial lung abnormalities (ILA).

Methods: Three hundred twenty-seven ILA participants out of 5764 in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study who had undergone chest CT twice with an interval of approximately five-years were enrolled in this study. Traction bronchiectasis/bronchiolectasis index (TBI) was classified on a four-point scale: 0, ILA without traction bronchiectasis/bronchiolectasis; 1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; 2, ILA with mild to moderate traction bronchiectasis; 3, ILA and severe traction bronchiectasis and/or honeycombing. Traction bronchiectasis (TB) progression was classified on a five-point scale: 1, Improved; 2, Probably improved; 3, No change; 4, Probably progressed; 5, Progressed. Overall survival (OS) among participants with different TB Progression Score and between the TB progression group and No TB progression group was also investigated. Hazard radio (HR) was estimated with Cox proportional hazards model.

Results: The higher the TBI at baseline, the higher TB Progression Score (P < 0.001). All five participants with TBI = 3 at baseline progressed; 46 (90 %) of 51 participants with TBI = 2 progressed. TB progression was also associated with shorter OS with statistically significant difference (adjusted HR = 1.68, P < 0.001).

Conclusion: TB progression was visualized on chest CT frequently and clearly. It has the potential to be the predictor for poorer prognosis of ILA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejro.2021.100334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960545PMC
March 2021

QIBA guidance: Computed tomography imaging for COVID-19 quantitative imaging applications.

Clin Imaging 2021 Sep 25;77:151-157. Epub 2021 Feb 25.

Duke University, United States of America.

As the COVID-19 pandemic impacts global populations, computed tomography (CT) lung imaging is being used in many countries to help manage patient care as well as to rapidly identify potentially useful quantitative COVID-19 CT imaging biomarkers. Quantitative COVID-19 CT imaging applications, typically based on computer vision modeling and artificial intelligence algorithms, include the potential for better methods to assess COVID-19 extent and severity, assist with differential diagnosis of COVID-19 versus other respiratory conditions, and predict disease trajectory. To help accelerate the development of robust quantitative imaging algorithms and tools, it is critical that CT imaging is obtained following best practices of the quantitative lung CT imaging community. Toward this end, the Radiological Society of North America's (RSNA) Quantitative Imaging Biomarkers Alliance (QIBA) CT Lung Density Profile Committee and CT Small Lung Nodule Profile Committee developed a set of best practices to guide clinical sites using quantitative imaging solutions and to accelerate the international development of quantitative CT algorithms for COVID-19. This guidance document provides quantitative CT lung imaging recommendations for COVID-19 CT imaging, including recommended CT image acquisition settings for contemporary CT scanners. Additional best practice guidance is provided on scientific publication reporting of quantitative CT imaging methods and the importance of contributing COVID-19 CT imaging datasets to open science research databases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinimag.2021.02.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906537PMC
September 2021

Ground glass and fibrotic change in children with surfactant protein C dysfunction mutations.

Pediatr Pulmonol 2021 07 11;56(7):2223-2231. Epub 2021 May 11.

Breathing Institute, Children's Hospital Colorado, Aurora, Colorado, USA.

Introduction: Therapeutics exist to treat fibrotic lung disease in adults, but these have not been investigated in children. Defining biomarkers for pediatric fibrotic lung disease in children is crucial for clinical trials. Children with surfactant protein C (SFTPC) dysfunction mutations develop fibrotic lung disease over time. We evaluated chest computed tomography (CT) changes over time in children with SFTPC dysfunction mutations.

Methods: We performed an institutional review board-approved retrospective review of children with SFTPC dysfunction mutations. We collected demographic and clinical information. Chest CT scans were evaluated using visual and computerized scores. Chest CT scores and pulmonary function tests were reviewed.

Results: Eleven children were included. All children presented in infancy and four children suffered from respiratory failure requiring mechanical ventilation. Those who performed pulmonary function tests had stable forced vital capacities over time by percent predicted, but increased forced vital capacity in liters. CT findings evolved over time in most patients with earlier CT scans demonstrating ground glass opacities and later CT scans with more fibrotic features. In a pilot analysis, data-driven textural analysis software identified fibrotic features in children with SFTPC dysfunction that increased over time and correlated with visual CT scores.

Discussion: We describe 11 children with SFTPC dysfunction mutations. Increases in forced vital capacity over time suggest that these children experience lung growth and that therapeutic intervention may maximize lung growth. Ground glass opacities are the primary early imaging findings while fibrotic features dominate later. CT findings suggest the development of and increases in fibrotic features that may serve as potential biomarkers for antifibrotic therapeutic trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ppul.25356DOI Listing
July 2021

Relationship between Emphysema Progression at CT and Mortality in Ever-Smokers: Results from the COPDGene and ECLIPSE Cohorts.

Radiology 2021 04 16;299(1):222-231. Epub 2021 Feb 16.

From the Division of Pulmonary and Critical Care Medicine, Department of Medicine (S.Y.A., A.A.D., S.E.M., F.N.R., C.L.P., G.R.W.), Applied Chest Imaging Laboratory (S.Y.A., R.S.J.E., A.A.D., S.E.M., F.N.R., C.L.P., G.V.S.F., G.R.W.), and Department of Radiology (R.S.J.E., G.V.S.F.), Brigham and Women's Hospital, 75 Francis St, PBB, CA-3, Boston, MA 02130; Departments of Biomedical Engineering and Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wis (S.B.F.); COPD Foundation, Washington, DC (R.T.S., D.M.); Lung Investigation Unit, Medicine, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, England (R.A.S.); Respiratory and Inflammation Therapy Area, Clinical Development, AstraZeneca, Mölndal, Sweden (L.H.N.); Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Nebraska Medical Center, Omaha, Neb (S.R.); Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Mich (M.K.H.); Department of Radiology, National Jewish Health, Denver, Colo (S.M.H., D.A.L.); and Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Department of Medicine, University of Pittsburgh, Pittsburgh, Pa (F.C.S.).

Background The relationship between emphysema progression and long-term outcomes is unclear. Purpose To determine the relationship between emphysema progression at CT and mortality among participants with emphysema. Materials and Methods In a secondary analysis of two prospective observational studies, COPDGene (, NCT00608764) and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE; , NCT00292552), emphysema was measured at CT at two points by using the volume-adjusted lung density at the 15th percentile of the lung density histogram (hereafter, lung density perc15) method. The association between emphysema progression rate and all-cause mortality was analyzed by using Cox regression adjusted for ethnicity, sex, baseline age, pack-years, and lung density, baseline and change in smoking status, forced expiratory volume in 1 second, and 6-minute walk distance. In COPDGene, respiratory mortality was analyzed by using the Fine and Gray method. Results A total of 5143 participants (2613 men [51%]; mean age, 60 years ± 9 [standard deviation]) in COPDGene and 1549 participants (973 men [63%]; mean age, 62 years ± 8) in ECLIPSE were evaluated, of which 2097 (40.8%) and 1179 (76.1%) had emphysema, respectively. Baseline imaging was performed between January 2008 and December 2010 for COPDGene and January 2006 and August 2007 for ECLIPSE. Follow-up imaging was performed after 5.5 years ± 0.6 in COPDGene and 3.0 years ± 0.2 in ECLIPSE, and mortality was assessed over the ensuing 5 years in both. For every 1 g/L per year faster rate of decline in lung density perc15, all-cause mortality increased by 8% in COPDGene (hazard ratio [HR], 1.08; 95% CI: 1.01, 1.16; = .03) and 6% in ECLIPSE (HR, 1.06; 95% CI: 1.00, 1.13; = .045). In COPDGene, respiratory mortality increased by 22% (HR, 1.22; 95% CI: 1.13, 1.31; < .001) for the same increase in the rate of change in lung density perc15. Conclusion In ever-smokers with emphysema, emphysema progression at CT was associated with increased all-cause and respiratory mortality. © RSNA, 2021 See also the editorial by Lee and Park in this issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2021203531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997617PMC
April 2021

Chest CT Diagnosis and Clinical Management of Drug-Related Pneumonitis in Patients Receiving Molecular Targeting Agents and Immune Checkpoint Inhibitors: A Position Paper From the Fleischner Society.

Chest 2021 03 12;159(3):1107-1125. Epub 2021 Jan 12.

Center for Pulmonary Functional Imaging, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2020.11.027DOI Listing
March 2021

Chest CT Diagnosis and Clinical Management of Drug-related Pneumonitis in Patients Receiving Molecular Targeting Agents and Immune Checkpoint Inhibitors: A Position Paper from the Fleischner Society.

Radiology 2021 03 12;298(3):550-566. Epub 2021 Jan 12.

From the Department of Radiology, Kansai Rosai Hospital, Amagasaki, Japan (T.J.); Department of Radiology, Samsung Medical Center (K.S.L., H.Y.L.) and Department of Health Sciences and Technology, SAIHST (H.Y.L.), Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, South Korea; Department of Imaging, Dana-Farber Cancer Institute, Boston, Mass (M.N.); Department of Radiology (M.N.) and Center for Pulmonary Functional Imaging (H.H.), Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY (W.D.T.); Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minn (J.H.R.); Department of Medicine, University of British Columbia and Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, Canada (C.J.R.); Department of Radiology, Hospital de Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain (T.F.); Department of Radiology, University of Massachusetts Medical Center, Worcester, Mass (A.A.B.); Departments of Medicine (K.K.B.) and Radiology (D.A.L.), National Jewish Health, Denver, Colo; Department of Radiology, Seoul National University College of Medicine, Seoul, Korea (J.M.G.); Diagnostic and Interventional Radiology, University Hospital Heidelberg, Translational Lung Research Center Heidelberg, member of the German Center of Lung Research, Heidelberg, Germany (H.U.K.); Department of Histopathology, Royal Brompton and Harefield NHS Foundation Trust and National Heart and Lung Institute, Imperial College, London, England (A.G.N.); Complex Operative Unit of Pneumology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Catholic University of the Sacred Heart, Rome, Italy (L.R.); Department of Radiology, Meander Medical Center, Amersfoort, the Netherlands (C.M.S.P.); Department of Radiology, University Hospitals Leuven, Leuven, Belgium (J.V.); Division of Pulmonary and Critical Care Medicine, Lenox Hill Hospital, Northwell Health System, New York, NY (S.R.); Department of Radiology, Duke University School of Medicine, Durham, NC (G.D.R.); Department of Pulmonary, Critical Care and Sleep Medicine, Icahn School of Medicine at Mount Sinai, New York, NY (C.P.); and Clinical Research Center, National Hospital Organization Kinki-Chuo Chest Medical Center, Sakai, Osaka, Japan (Y.I.).

Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others. This article is a simultaneous joint publication in and . The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article. Published under a CC BY 4.0 license.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2021203427DOI Listing
March 2021

Interstitial Lung Abnormality Incidentally Detected on CT: An Important Prognostic Indicator.

Authors:
David A Lynch

Chest 2021 01;159(1):5-6

Department of Radiology, National Jewish Health, Denver, CO. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2020.10.027DOI Listing
January 2021

Structural airway imaging metrics are differentially associated with persistent chronic bronchitis.

Thorax 2021 04 6;76(4):343-349. Epub 2021 Jan 6.

Division of Pulmonary and Critical Care Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.

Background: Chronic bronchitis (CB) is strongly associated with cigarette smoking, but not all smokers develop CB. We aimed to evaluate whether measures of structural airway disease on CT are differentially associated with CB.

Methods: In smokers between ages 45 and 80 years, and with Global Initiative for Obstructive Lung Disease stages 0-4, CB was defined by the classic definition. Airway disease on CT was quantified by (i) wall area percent (WA%) of segmental airways; (ii) Pi10, the square root of the wall area of a hypothetical airway with 10 mm internal perimeter; (iii) total airway count (TAC) and (iv) airway fractal dimension (AFD), a measure of the complex branching pattern and remodelling of airways. CB was also assessed at the 5-year follow-up visit.

Measurements And Main Results: Of 8917 participants, 1734 (19.4%) had CB at baseline. Airway measures were significantly worse in those with CB compared with those without CB: WA% 54.5 (8.8) versus 49.8 (8.3); Pi10 2.58 (0.67) versus 2.28 (0.59) mm; TAC 156.7 (81.6) versus 177.8 (91.1); AFD 1.477 (0.091) versus 1.497 (0.092) (all p<0.001). On follow-up of 5517 participants at 5 years, 399 (7.2%) had persistent CB. With adjustment for between-visits changes in smoking status and lung function, greater WA% and Pi10 were associated with significantly associated with persistent CB, adjusted OR per SD change 1.75, 95% CI 1.56 to 1.97; p<0.001 and 1.66, 95% CI 1.42 to 1.86; p<0.001, respectively. Higher AFD and TAC were associated with significantly lower odds of persistent CB, adjusted OR per SD change 0.76, 95% CI 0.67 to 0.86; p<0.001 and 0.69, 95% CI 0.60 to 0.80; p<0.001, respectively.

Conclusions: Higher baseline AFD and TAC are associated with a lower risk of persistent CB, irrespective of changes in smoking status, suggesting preserved airway structure can confer a reserve against CB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/thoraxjnl-2020-215853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225550PMC
April 2021

Persistent, Progressive Pulmonary Fibrosis and Epithelial Remodeling in Mice.

Am J Respir Cell Mol Biol 2021 06;64(6):669-676

Program in Cell Biology, Department of Pediatrics, and.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease with underlying mechanisms that have been primarily investigated in mice after intratracheal instillation of a single dose of bleomycin. However, the model has significant limitations, including transient fibrosis that spontaneously resolves and its failure to fully recapitulate the epithelial remodeling in the lungs of patients with IPF. Thus, there remains an unmet need for a preclinical model with features that more closely resemble the human disease. Repetitive intratracheal instillation of bleomycin has previously been shown to recapitulate some of these features, but the instillation procedure is complex, and the long-term consequences on epithelial remodeling and fibrosis persistence and progression remain poorly understood. Here, we developed a simplified repetitive bleomycin instillation strategy consisting of three bi-weekly instillations that leads to persistent and progressive pulmonary fibrosis. Lung histology demonstrates increased collagen deposition, fibroblast accumulation, loss of type I and type II alveolar epithelial cells within fibrotic areas, bronchiolization of the lung parenchyma with CCSP cells, remodeling of the distal lung into cysts reminiscent of simple honeycombing, and accumulation of hyperplastic transitional KRT8 epithelial cells. Micro-computed tomographic imaging demonstrated significant traction bronchiectasis and subpleural fibrosis. Thus, the simplified repetitive bleomycin instillation strategy leads to progressive fibrosis and recapitulates the histological and radiographic characteristics of IPF. Compared with the single bleomycin instillation model, we suggest that the simplified repetitive instillation model may be better suited to address mechanistic questions about IPF pathogenesis and preclinical studies of antifibrotic drug candidates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1165/rcmb.2020-0542MADOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456888PMC
June 2021

Imaging of pulmonary hypertension in adults: a position paper from the Fleischner Society.

Eur Respir J 2021 01 5;57(1). Epub 2021 Jan 5.

Université Paris Saclay, Inserm UMR S999, Dept of Pneumology, AP-HP, Pulmonary Hypertension Reference Center, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mmHg and classified into five different groups sharing similar pathophysiologic mechanisms, haemodynamic 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: Is noninvasive imaging capable of identifying PH? What is the role of imaging in establishing the cause of PH? How does imaging determine the severity and complications of PH? How should imaging be used to assess chronic thromboembolic PH before treatment? 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.04455-2020DOI Listing
January 2021
-->