Publications by authors named "Hiroto Hatabu"

285 Publications

Suspected Interstitial Lung Disease in COPDGene.

Am J Respir Crit Care Med 2022 Aug 5. Epub 2022 Aug 5.

Brigham and Women\'s Hospital, Division of Pulmonary and Critical Care Medicine, Boston, Massachusetts, United States;

Rationale: While interstitial lung abnormalities (ILA), specific patterns of incidentally-detected abnormal density on computed tomography (CT), have been associated with abnormal lung function and increased mortality, it is unclear if a subset with incidental interstitial lung disease (ILD) accounts for these adverse consequences.

Objectives: To define the prevalence and risk factors of suspected ILD and assess outcomes.

Methods: Suspected ILD was evaluated in the COPDGene cohort, defined as ILA and at least one additional criterion: definite fibrosis on CT, FVC less than 80% predicted, or DLCO less than 70% predicted. Multivariable linear, longitudinal, and Cox proportional hazards regression models were used to assess associations with St. George's Respiratory Questionnaire (SGRQ), Six-Minute Walk Test (6MWT), supplemental oxygen use, respiratory exacerbations, and mortality.

Measurements And Main Results: Of 4361 participants with available data, 239 (5%) had evidence for suspected ILD while 204 (5%) had ILA without suspected ILD. In multivariable analyses, suspected ILD was associated with increased SGRQ score (mean difference [MD] 3.8points; 95% confidence interval [CI] 0.6-7.1; P=0.02), reduced 6MWT (MD -35m; 95%CI -56m,-13m; P=0.002), greater supplemental oxygen use (odds ratio [OR] 2.3; 95%CI 1.1-5.1; P=0.03) and severe respiratory exacerbations (OR 2.9; 95%CI 1.1-7.5; P=0.03), and higher mortality (hazard ratio 2.4; 95%CI 1.2-4.6; P=0.01) compared to ILA without suspected ILD. Risk factors associated with suspected ILD included self-identified black race (OR 2.0; 95%CI 1.1-3.3; P=0.01) and pack-years smoking history (OR 1.2; 95%CI 1.1-1.3; P=0.0005).

Conclusion: Suspected ILD is present in half of those with ILA in COPDGene and is associated with exercise decrements and increased symptoms, supplemental oxygen use, severe respiratory exacerbations, and mortality.
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http://dx.doi.org/10.1164/rccm.202203-0550OCDOI Listing
August 2022

Serum proteomic profiling of rheumatoid arthritis-interstitial lung disease with a comparison to idiopathic pulmonary fibrosis.

Thorax 2022 Jul 30. Epub 2022 Jul 30.

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA

Although interstitial lung disease (ILD) causes significant morbidity and mortality in rheumatoid arthritis (RA), it is difficult to predict the development or progression of ILD, emphasising the need for improved discovery through minimally invasive diagnostic tests. Aptamer-based proteomic profiling was used to assess 1321 proteins from 159 patients with rheumatoid arthritis with interstitial lung disease (RA-ILD), RA without ILD, idiopathic pulmonary fibrosis and healthy controls. Differential expression and gene set enrichment analyses revealed molecular signatures that are strongly associated with the presence and severity of RA-ILD and provided insight into unexplored pathways of disease. These warrant further study as non-invasive diagnostic tools and future therapeutic targets.
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http://dx.doi.org/10.1136/thorax-2021-217822DOI Listing
July 2022

The relationship between interstitial lung abnormalities, mortality, and multimorbidity: a cohort study.

Thorax 2022 Jul 1. Epub 2022 Jul 1.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA

Background: Interstitial lung abnormalities (ILAs) are associated with increased mortality. It is unclear whether multimorbidity accounts for the mortality association or how strongly ILA is associated with mortality relative to other common age-associated diseases. We determined the association of ILA with all-cause mortality adjusted for multimorbidity, compared mortality associated with ILA and prevalent cardiovascular disease (CVD), diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease and cancer and also determined the association between ILA and these diseases.

Methods: We measured ILA (none, indeterminant, definite) using blinded reads of CT images, prevalent chronic diseases and potential confounders in two observational cohorts, the Framingham Heart Study (FHS) (n=2449) and Age, Gene/Environment Susceptibility - Reykjavik Study (AGES-Reykjavik) (n=5180). We determined associations with mortality using Cox proportional hazards models and between ILA and diseases with multinomial logistic regression.

Results: Over a median (IQR) follow-up of 8.8 (1.4) years in FHS and 12.0 (7.7) years in AGES-Reykjavik, in adjusted models, ILAs were significantly associated with increased mortality (HR, 95% CI 1.95, 1.23 to 3.08, p=0.0042, in FHS; HR 1.60, 1.41 to 1.82, p<0.0001, in AGES-Reykjavik) adjusted for multimorbidity. In both cohorts, the association of ILA with mortality was of similar magnitude to the association of most other diseases. In adjusted models, ILAs were associated only with prevalent kidney disease (OR, 95% CI 1.90, 1.01 to 3.57, p=0.0452) in FHS and with prevalent CVD (OR 1.42, 1.12 to 1.81, p=0.0040) in AGES-Reykjavik.

Conclusions: ILAs were associated with mortality adjusted for multimorbidity and were similarly associated with increased mortality compared with several common chronic diseases. ILAs were not consistently associated with the prevalence of these diseases themselves.
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http://dx.doi.org/10.1136/thoraxjnl-2021-218315DOI Listing
July 2022

Blood gene expression risk profiles and interstitial lung abnormalities: COPDGene and ECLIPSE cohort studies.

Respir Res 2022 Jun 17;23(1):157. Epub 2022 Jun 17.

Channing Division for Network Medicine, Brigham and Women's Hospital, Boston, MA, 02115, USA.

Background: Interstitial lung abnormalities (ILA) are radiologic findings that may progress to idiopathic pulmonary fibrosis (IPF). Blood gene expression profiles can predict IPF mortality, but whether these same genes associate with ILA and ILA outcomes is unknown. This study evaluated if a previously described blood gene expression profile associated with IPF mortality is associated with ILA and all-cause mortality.

Methods: In COPDGene and ECLIPSE study participants with visual scoring of ILA and gene expression data, we evaluated the association of a previously described IPF mortality score with ILA and mortality. We also trained a new ILA score, derived using genes from the IPF score, in a subset of COPDGene. We tested the association with ILA and mortality on the remainder of COPDGene and ECLIPSE.

Results: In 1469 COPDGene (training n = 734; testing n = 735) and 571 ECLIPSE participants, the IPF score was not associated with ILA or mortality. However, an ILA score derived from IPF score genes was associated with ILA (meta-analysis of test datasets OR 1.4 [95% CI: 1.2-1.6]) and mortality (HR 1.25 [95% CI: 1.12-1.41]). Six of the 11 genes in the ILA score had discordant directions of effects compared to the IPF score. The ILA score partially mediated the effects of age on mortality (11.8% proportion mediated).

Conclusions: An ILA gene expression score, derived from IPF mortality-associated genes, identified genes with concordant and discordant effects on IPF mortality and ILA. These results suggest shared, and unique biologic processes, amongst those with ILA, IPF, aging, and death.
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http://dx.doi.org/10.1186/s12931-022-02077-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204872PMC
June 2022

Traction Bronchiectasis/Bronchiolectasis on CT Scans in Relationship to Clinical Outcomes and Mortality: The COPDGene Study.

Radiology 2022 May 31:212584. Epub 2022 May 31.

From the Ctr for Pulmonary Functional Imaging, Dept of Radiology (A.H., T. Hino, T. Hida, M.N., V.I.V., G.M.H., H. Hatabu), Pulmonary and Critical Care Division (R.K.P., A.A.M., G.R.W., G.M.H.), Dept of Radiology (R.S.J.E.), and Channing Division of Network Medicine (M.H.C., E.K.S.), Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; Dept of Radiology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan (A.H., M.Y., N.T.); Dept of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan (T. Hida, H. Honda, K.I.); Dept of Radiology, Kansai Medical University, Hirakata, Japan (O.H.); Dept of Radiology, Keio University School of Medicine, Tokyo, Japan (Y.Y., M.J.); Dept of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pa (T.A.); Dept of Radiology, Kansai Rosai Hospital, Amagasaki, Japan (T.J.); Dept of Environmental Health, Harvard TH Chan School of Public Health, Boston, Mass (D.C.C.); and Dept of Radiology, National Jewish Health, Denver, Colo (D.A.L.).

Background The clinical impact of interstitial lung abnormalities (ILAs) on poor prognosis has been reported in many studies, but risk stratification in ILA will contribute to clinical practice. Purpose To investigate the association of traction bronchiectasis/bronchiolectasis index (TBI) with mortality and clinical outcomes in individuals with ILA by using the COPDGene cohort. Materials and Methods This study was a secondary analysis of prospectively collected data. Chest CT scans of participants with ILA for traction bronchiectasis/bronchiolectasis were evaluated and outcomes were compared with participants without ILA from the COPDGene study (January 2008 to June 2011). TBI was classified as follows: TBI-0, ILA without traction bronchiectasis/bronchiolectasis; TBI-1, ILA with bronchiolectasis but without bronchiectasis or architectural distortion; TBI-2, ILA with mild to moderate traction bronchiectasis; and TBI-3, ILA with severe traction bronchiectasis and/or honeycombing. Clinical outcomes and overall survival were compared among the TBI groups and the non-ILA group by using multivariable linear regression model and Cox proportional hazards model, respectively. Results Overall, 5295 participants (median age, 59 years; IQR, 52-66 years; 2779 men) were included, and 582 participants with ILA and 4713 participants without ILA were identified. TBI groups were associated with poorer clinical outcomes such as quality of life scores in the multivariable linear regression model (TBI-0: coefficient, 3.2 [95% CI: 0.6, 5.7; = .01]; TBI-1: coefficient, 3.3 [95% CI: 1.1, 5.6; = .003]; TBI-2: coefficient, 7.6 [95% CI: 4.0, 11; < .001]; TBI-3: coefficient, 32 [95% CI: 17, 48; < .001]). The multivariable Cox model demonstrated that ILA without traction bronchiectasis (TBI-0-1) and with traction bronchiectasis (TBI-2-3) were associated with shorter overall survival (TBI-0-1: hazard ratio [HR], 1.4 [95% CI: 1.0, 1.9; = .049]; TBI-2-3: HR, 3.8 [95% CI: 2.6, 5.6; < .001]). Conclusion Traction bronchiectasis/bronchiolectasis was associated with poorer clinical outcomes compared with the group without interstitial lung abnormalities; TBI-2 and 3 were associated with shorter survival. © RSNA, 2022 . See also the editorial by Lee and Im in this issue.
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http://dx.doi.org/10.1148/radiol.212584DOI Listing
May 2022

Connective tissue disease-related interstitial lung disease (CTD-ILD) and interstitial lung abnormality (ILA): Evolving concept of CT findings, pathology and management.

Eur J Radiol Open 2022 7;9:100419. Epub 2022 Apr 7.

Department of Radiology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine (SKKU-SOM), ChangWon, Gyeongsangnam-do, South Korea.

Connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren syndrome (SS), and mixed connective tissue disease (MCTD). On histopathology of lung biopsy in CTD-related ILDs (CTD-ILDs), multi-compartment involvement is an important clue, and when present, should bring CTD to the top of the list of etiologic differential diagnoses. Diverse histologic patterns including nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia, apical fibrosis, diffuse alveolar damage, and lymphoid interstitial pneumonia can be seen on histology in patients with CTD-ILDs. Although proportions of ILDs vary, the NSIP pattern accounts for a large proportion, especially in SSc, DM and/or PM and MCTD, followed by the UIP pattern. In RA patients, interstitial lung abnormality (ILA) is reported to occur in approximately 20-60% of individuals of which 35-45% will have progression of the CT abnormality. Subpleural distribution and greater baseline ILA involvement are risk factors associated with disease progression. Asymptomatic CTD-ILDs or ILA patients with normal lung function and without evidence of disease progression can be followed without treatment. Immunosuppressive or antifibrotic agents for symptomatic and/or fibrosing CTD-ILDs can be used in patients who require treatment.
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http://dx.doi.org/10.1016/j.ejro.2022.100419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014394PMC
April 2022

The Proteomic Profile of Interstitial Lung Abnormalities.

Am J Respir Crit Care Med 2022 08;206(3):337-346

Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

Knowledge on biomarkers of interstitial lung disease is incomplete. Interstitial lung abnormalities (ILAs) are radiologic changes that may present in its early stages. To uncover blood proteins associated with ILAs using large-scale proteomics methods. Data from two prospective cohort studies, the AGES-Reykjavik (Age, Gene/Environment Susceptibility-Reykjavik) study ( = 5,259) for biomarker discovery and the COPDGene (Genetic Epidemiology of COPD) study ( = 4,899) for replication, were used. Blood proteins were measured using DNA aptamers, targeting more than 4,700 protein analytes. The association of proteins with ILAs and ILA progression was assessed with regression modeling, as were associations with genetic risk factors. Adaptive Least Absolute Shrinkage and Selection Operator models were applied to bootstrap data samples to discover sets of proteins predictive of ILAs and their progression. Of 287 associations, SFTPB (surfactant protein B) (odds ratio [OR], 3.71 [95% confidence interval (CI), 3.20-4.30];  = 4.28 × 10), SCGB3A1 (Secretoglobin family 3A member 1) (OR, 2.43 [95% CI, 2.13-2.77];  = 8.01 × 10), and WFDC2 (WAP four-disulfide core domain protein 2) (OR, 2.42 [95% CI, 2.11-2.78];  = 4.01 × 10) were most significantly associated with ILA in AGES-Reykjavik and were replicated in COPDGene. In AGES-Reykjavik, concentrations of SFTPB were associated with the rs35705950 (mucin 5B) promoter polymorphism, and SFTPB and WFDC2 had the strongest associations with ILA progression. Multivariate models of ILAs in AGES-Reykjavik, ILAs in COPDGene, and ILA progression in AGES-Reykjavik had validated areas under the receiver operating characteristic curve of 0.880, 0.826, and 0.824, respectively. Novel, replicated associations of ILA, its progression, and genetic risk factors with numerous blood proteins are demonstrated as well as machine-learning-based models with favorable predictive potential. Several proteins are revealed as potential markers of early fibrotic lung disease.
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http://dx.doi.org/10.1164/rccm.202110-2296OCDOI Listing
August 2022

Detection of Pulmonary Congestion in Heart Failure With Preserved Ejection Fraction Using Quantitative Chest CT.

JACC Cardiovasc Imaging 2022 04;15(4):638-640

Department of Radiology at University of Massachusetts Memorial Medical Center, Worcester, Massachusetts, USA.

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http://dx.doi.org/10.1016/j.jcmg.2022.01.017DOI Listing
April 2022

Interstitial lung abnormalities are associated with decreased mean telomere length.

Eur Respir J 2022 Feb 3. Epub 2022 Feb 3.

Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Interstitial lung abnormalities (ILA) share many features with idiopathic pulmonary fibrosis (IPF), however it is not known if ILA are associated with decreased mean telomere length (MTL).Telomere length was measured with quantitative polymerase chain reaction in COPDGene and AGES-Reykjavik, and southern blot analysis was used in the Framingham Heart Study (FHS). Logistic and linear regression were used to assess the association between ILA and MTL; Cox proportional hazards models were used to assess the association between MTL and mortality.In all three cohorts ILA were associated with decreased MTL. In COPDGene and AGES-Reykjavik, after adjustment there was greater than two-fold increase in the odds of ILA when comparing the shortest quartile of telomere length to the longest quartile (odds ratio [OR]=2.2, 95% confidence interval [CI] 1.5-3.4, p=0.0001 and OR=2.6, 95% CI 1.4-4.9, p=0.003), respectively. In the FHS, those with ILA had shorter telomeres compared to those without ILA (-767 bp, 95% CI 76-1584 bp, p=0.03). Although decreased MTL was associated with chronic obstructive pulmonary disease (OR=1.3, 95% confidence interval [CI] 1.1-1.6, p=0.01) in COPDGene the effect estimate was less than that noted with ILA. There was no consistent association between MTL and risk of death, when comparing the shortest quartile of telomere length (hazard ratio [HR]=0.82, 95% CI 0.4-1.7, p=0.6 and HR=1.2, 95% CI 0.6-2.2, p=0.5) in COPDGene and AGES-Reykjavik respectively.ILA are associated with decreased mean telomere length when compared to those without ILA.
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http://dx.doi.org/10.1183/13993003.01814-2021DOI Listing
February 2022

Vector-field dynamic x-ray (VF-DXR) using optical flow method in patients with chronic obstructive pulmonary disease.

Eur Radiol Exp 2022 01 31;6(1). Epub 2022 Jan 31.

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

Background: We assessed the difference in lung motion during inspiration/expiration between chronic obstructive pulmonary disease (COPD) patients and healthy volunteers using vector-field dynamic x-ray (VF-DXR) with optical flow method (OFM).

Methods: We enrolled 36 COPD patients and 47 healthy volunteers, classified according to pulmonary function into: normal, COPD mild, and COPD severe. Contrast gradient was obtained from sequential dynamic x-ray (DXR) and converted to motion vector using OFM. VF-DXR images were created by projection of the vertical component of lung motion vectors onto DXR images. The maximum magnitude of lung motion vectors in tidal inspiration/expiration, forced inspiration/expiration were selected and defined as lung motion velocity (LMV). Correlations between LMV with demographics and pulmonary function and differences in LMV between COPD patients and healthy volunteers were investigated.

Results: Negative correlations were confirmed between LMV and % forced expiratory volume in one second (%FEV) in the tidal inspiration in the right lung (Spearman's rank correlation coefficient, r = -0.47, p < 0.001) and the left lung (r = -0.32, p = 0.033). A positive correlation between LMV and %FEV in the tidal expiration was observed only in the right lung (r = 0.25, p = 0.024). LMVs among normal, COPD mild and COPD severe groups were different in the tidal respiration. COPD mild group showed a significantly larger magnitude of LMV compared with the normal group.

Conclusions: In the tidal inspiration, the lung parenchyma moved faster in COPD patients compared with healthy volunteers. VF-DXR was feasible for the assessment of lung parenchyma using LMV.
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http://dx.doi.org/10.1186/s41747-021-00254-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802288PMC
January 2022

Dark-Field Chest Radiography in the Detection of Emphysema.

Radiology 2022 04 11;303(1):128-129. Epub 2022 Jan 11.

From the Center for Pulmonary Functional Imaging (H.H.) and Department of Radiology (H.H., B.M.), Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, MA 02115.

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http://dx.doi.org/10.1148/radiol.212910DOI Listing
April 2022

Tumor Growth Rate After Nadir Is Associated With Survival in Patients With -Mutant Non-Small-Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor.

JCO Precis Oncol 2021 11;5:1603-1610

Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA.

Purpose: To investigate the association between tumor volume growth rate after the nadir and survival in patients with -mutant advanced non-small-cell lung cancer (NSCLC) treated with erlotinib.

Materials And Methods: Seventy-one patients with -mutant advanced NSCLC treated with erlotinib were studied for computed tomography tumor volume kinetics during therapy. The tumor growth rate after nadir was obtained using a previously published analytic module for longitudinal volume tracking to study its relationship with overall survival (OS).

Results: The median tumor volume for the cohort was 19,842 mm at baseline and 4,083 mm at nadir. The median time to nadir was 6.2 months. The tumor growth rate after nadir for logV (the natural logarithm of tumor volume measured in mm) was 0.11/mo on average for the cohort (SE: 0.014), which was very similar to the previously validated reference value of 0.12/mo to define slow and fast tumor growth. The OS of 48 patients with slow tumor growth (≤ 0.12/mo) was significantly longer compared with 23 patients with fast tumor growth (> 0.12/mo; median OS: 37.8 25.0 months; = .0012). In Cox models, tumor growth rate was also associated with survival (regression coefficient: 3.9903; = .0024; faster rate leads to increased hazards), after adjusting for time to nadir (regression coefficient: -0.0863; = .0008; longer time to nadir leads to decreased hazards) and smoking history.

Conclusion: In patients with -mutant advanced NSCLC treated with erlotinib, slower tumor growth rates after nadir were associated with longer OS, providing a rationale for using tumor growth rates to guide precision therapy for lung cancer.
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http://dx.doi.org/10.1200/PO.21.00172DOI Listing
November 2021

Associations of Monocyte Count and Other Immune Cell Types with Interstitial Lung Abnormalities.

Am J Respir Crit Care Med 2022 04;205(7):795-805

Department of Medicine, Columbia University, New York, New York.

Higher blood monocyte counts are associated with worse survival in adults with clinically diagnosed pulmonary fibrosis. Their association with the development and progression of interstitial lung abnormalities (ILA) in humans is unknown. We evaluated the associations of blood monocyte count, and other immune cell types, with ILA, high-attenuation areas, and FVC in four independent cohorts. We included participants with measured monocyte counts and computed tomographic (CT) imaging enrolled in MESA (Multi-Ethnic Study of Atherosclerosis,  = 484), AGES-Reykjavik (Age/Gene Environment Susceptibility Study,  = 3,547), COPDGene (Genetic Epidemiology of COPD,  = 2,719), and the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points,  = 646). After adjustment for covariates, a 1-SD increment in blood monocyte count was associated with ILA in MESA (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.0-1.8), AGES-Reykjavik (OR, 1.2; 95% CI, 1.1-1.3), COPDGene (OR, 1.3; 95% CI, 1.2-1.4), and ECLIPSE (OR, 1.2; 95% CI, 1.0-1.4). A higher monocyte count was associated with ILA progression over 5 years in AGES-Reykjavik (OR, 1.2; 95% CI, 1.0-1.3). Compared with participants without ILA, there was a higher percentage of activated monocytes among those with ILA in MESA. Higher monocyte count was associated with greater high-attenuation areas in MESA and lower FVC in MESA and COPDGene. Associations of other immune cell types were less consistent. Higher blood monocyte counts were associated with the presence and progression of interstitial lung abnormalities and lower FVC.
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http://dx.doi.org/10.1164/rccm.202108-1967OCDOI Listing
April 2022

Screening for preclinical parenchymal lung disease in rheumatoid arthritis.

Rheumatology (Oxford) 2022 Aug;61(8):3234-3245

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Objectives: Pulmonary disease is a common extraarticular manifestation of RA associated with increased morbidity and mortality. No current strategies exist for screening this at-risk population for parenchymal lung disease, including emphysema and interstitial lung disease (ILD).

Methods: RA patients without a diagnosis of ILD or chronic obstructive pulmonary disease underwent prospective and comprehensive clinical, laboratory, functional and radiological evaluations. High resolution CT (HRCT) scans were scored for preclinical emphysema and preclinical ILD and evaluated for other abnormalities.

Results: Pulmonary imaging and/or functional abnormalities were identified in 78 (74%) of 106 subjects; 45% had preclinical parenchymal lung disease. These individuals were older with lower diffusion capacity but had similar smoking histories compared with no disease. Preclinical emphysema (36%), the most commonly detected abnormality, was associated with older age, higher anti-cyclic citrullinated peptide antibody titres and diffusion abnormalities. A significant proportion of preclinical emphysema occurred among never smokers (47%) with a predominantly panlobular pattern. Preclinical ILD (15%) was not associated with clinical, laboratory or functional measures.

Conclusion: We identified a high prevalence of undiagnosed preclinical parenchymal lung disease in RA driven primarily by isolated emphysema, suggesting that it may be a prevalent and previously unrecognized pulmonary manifestation of RA, even among never smokers. As clinical, laboratory and functional evaluations did not adequately identify preclinical parenchymal abnormalities, HRCT may be the most effective screening modality currently available for patients with RA.
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http://dx.doi.org/10.1093/rheumatology/keab891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9348774PMC
August 2022

Interstitial Lung Abnormalities, Emphysema, and Spirometry in Smokers.

Chest 2022 04 3;161(4):999-1010. Epub 2021 Nov 3.

Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA. Electronic address:

Background: Most pulmonary conditions reduce FVC, but studies of patients with combined pulmonary fibrosis and emphysema demonstrate that reductions in FVC are less than expected when these two conditions coexist clinically.

Research Question: Do interstitial lung abnormalities (ILAs), chest CT imaging findings that may suggest an early stage of pulmonary fibrosis in individuals with undiagnosed disease, affect the association between emphysema and FVC?

Study Design And Methods: Measures of ILA and emphysema were available for 9,579 and 5,277 participants from phases 1 (2007-2011) and 2 (2012-2016) of the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease Study (COPDGene), respectively. ILA were defined by Fleischner Society guidelines. Adjusted linear regression models were used to assess the associations and interactions among ILA, emphysema, measures of spirometry, and lung function.

Results: ILA were present in 528 (6%) and 580 (11%) of participants in phases 1 and 2 of COPDGene, respectively. ILA modified the association between emphysema and FVC (P < .0001 for interaction) in both phases. In phase 1, in those without ILA, a 5% increase in emphysema was associated with a reduction in FVC (-110 mL; 95% CI, -121 to -100 mL; P < .0001); however, in those with ILA, it was not (-11 mL; 95% CI, -53 to 31; P = .59). In contrast, no interaction was found between ILA and emphysema on total lung capacity or on diffusing capacity of carbon monoxide.

Interpretation: The presence of ILA attenuates the reduction in FVC associated with emphysema.
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http://dx.doi.org/10.1016/j.chest.2021.10.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9005862PMC
April 2022

Prediction Model for Tumor Volume Nadir in EGFR-mutant NSCLC Patients Treated With EGFR Tyrosine Kinase Inhibitors.

J Thorac Imaging 2021 Sep 15. Epub 2021 Sep 15.

Departments of Imaging Medical Oncology, Dana Farber Cancer Institute Departments of Radiology Medicine, Brigham and Women's Hospital Department of Biostatistics, Harvard Chan School of Public Health, Boston, MA.

Purpose: In patients with advanced non-small cell lung cancer (NSCLC) and oncogenic driver mutations treated with effective targeted therapy, a characteristic pattern of tumor volume dynamics with an initial regression, nadir, and subsequent regrowth is observed on serial computed tomography (CT) scans. We developed and validated a linear model to predict the tumor volume nadir in EGFR-mutant advanced NSCLC patients treated with EGFR tyrosine kinase inhibitors (TKI).

Materials And Methods: Patients with EGFR-mutant advanced NSCLC treated with EGFR-TKI as their first EGFR-directed therapy were studied for CT tumor volume kinetics during therapy, using a previously validated CT tumor measurement technique. A linear regression model was built to predict tumor volume nadir in a training cohort of 34 patients, and then was validated in an independent cohort of 84 patients.

Results: The linear model for tumor nadir prediction was obtained in the training cohort of 34 patients, which utilizes the baseline tumor volume before initiating therapy (V0) to predict the volume decrease (mm3) when the nadir volume (Vp) was reached: V0-Vp=0.717×V0-1347 (P=2×10-16; R2=0.916). The model was tested in the validation cohort, resulting in the R2 value of 0.953, indicating that the prediction model generalizes well to another cohort of EGFR-mutant patients treated with EGFR-TKI. Clinical variables were not significant predictors of tumor volume nadir.

Conclusion: The linear model was built to predict the tumor volume nadir in EGFR-mutant advanced NSCLC patients treated with EGFR-TKIs, which provide an important metrics in treatment monitoring and therapeutic decisions at nadir such as additional local abrasive therapy.
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http://dx.doi.org/10.1097/RTI.0000000000000615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8920948PMC
September 2021

Axillary Lymphadenopathy After Coronavirus Disease 2019 Vaccinations in Patients With Thoracic Malignancy: Incidence, Predisposing Factors, and Imaging Characteristics.

J Thorac Oncol 2022 01 29;17(1):154-159. Epub 2021 Sep 29.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Objectives: Axillary lymphadenopathy from coronavirus disease 2019 (COVID-19) vaccine is an emerging phenomenon during unprecedented mass vaccinations, which can be incidentally found on computed tomography (CT) scans. This study investigated the incidence, predisposing factors, and imaging characteristics of vaccine-related axillary lymphadenopathy in patients with thoracic malignancy who underwent CT scans before and after COVID-19 vaccinations.

Methods: The study included patients with thoracic malignancies who received two doses of mRNA-based COVID-19 vaccinations and had prevaccine and postvaccine chest CT scans. Postvaccine chest CT scan results were reviewed for increase in size of lymph nodes in the axilla and subpectoral areas, comparing with the prevaccine scan results. The cases with lymphadenopathy were further reviewed independently by two radiologists referring to clinical information to find whether lymphadenopathy was attributed to the vaccinations.

Results: Vaccine-related axillary lymphadenopathy was noted in 21 of 232 patients (9.0%). The median short-axis diameter of the largest node was 7 mm (range: 5-14 mm). The median number of increased nodes was 4 (range: 1-10). The median time to the postvaccine scan revealing lymphadenopathy was 1.7 weeks (range: -2.9 to 6.6) from the second dose. Vaccine-related lymphadenopathy was noted more often in women than in men (18 of 144, 12.5% versus 3 of 88, 3.4%, respectively; p = 0.019) and with mRNA-1273 vaccines than BNT162b2 vaccines (6 of 28, 21% versus 15 of 204, 7.4%, respectively; p = 0.026).

Conclusions: The incidence of lymphadenopathy was 9%, with a median onset time of 1.7 weeks after the second vaccine dose. Female sex and vaccine type (mRNA-1273 vaccine) were associated with higher frequency of lymphadenopathy, providing initial observations to inform further investigations in larger cohorts.
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http://dx.doi.org/10.1016/j.jtho.2021.08.761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423658PMC
January 2022

Dark-Field Chest X-ray Imaging: An Evolving Technique in the Century-Old History of Chest X-ray Imaging.

Radiology 2021 11 24;301(2):396-397. Epub 2021 Aug 24.

From the Center for Pulmonary Functional Imaging (H.H.) and Department of Radiology (H.H., B.M.), Brigham and Women's Hospital and Harvard Medical School, Boston, 75 Francis St, Boston, MA 02215.

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http://dx.doi.org/10.1148/radiol.2021211603DOI Listing
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.
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http://dx.doi.org/10.1148/radiol.2021204367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487219PMC
October 2021

Tumor Response Dynamics During First-Line Pembrolizumab Therapy in Patients With Advanced Non-Small-Cell Lung Cancer.

JCO Precis Oncol 2021 19;5. Epub 2021 Mar 19.

Department of Medical Oncology and Department of Medicine, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA.

The objectives of the study were to characterize the tumor burden dynamics on serial computed tomography scans in patients with advanced non-small-cell lung cancer treated with first-line pembrolizumab and to identify imaging markers for prolonged overall survival (OS).

Materials And Methods: Eighty-eight patients treated with first-line pembrolizumab monotherapy were evaluated on serial computed tomography scans to characterize their quantitative tumor burden during therapy. Tumor burden dynamics were studied for the association with OS.

Results: The overall response rate was 42% (37/88), with the median tumor burden changes at the best overall response of -18.3% (range, -100.0% to +103.6%). Response rates were higher in men than in women ( = .05) and in patients with higher programmed cell death ligand-1 expression levels ( = .02). Tumor burden stayed below the baseline burden throughout therapy in 55 patients (63%). In an 8-week landmark analysis, patients with tumor burden below the baseline burden during the first 8 weeks of therapy had longer OS compared with patients who had ≥ 0% increase (median OS, 30.7 16.2 months; hazard ratio [HR] = 0.44; = .01). In the extended Cox models, patients whose tumor burden stayed below the baseline burden throughout therapy had significantly reduced hazards of death (HR = 0.41, = .003, univariate; HR = 0.35, = .02, multivariate). Only one patient (1.1%) experienced pseudoprogression with initial tumor increase and subsequent tumor regression.

Conclusion: In patients with advanced non-small-cell lung cancer treated with first-line single-agent pembrolizumab, tumor burden reduction below the baseline burden during therapy was an independent marker for prolonged OS, which may serve as a practical guide for treatment decisions.
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http://dx.doi.org/10.1200/PO.20.00478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232801PMC
March 2022

Vector-Field dynamic X-ray (VF-DXR) using Optical Flow Method.

Br J Radiol 2022 Apr 8;95(1132):20201210. Epub 2021 Jul 8.

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

Objectives: To explore the feasibility of Vector-Field DXR (VF-DXR) using optical flow method (OFM).

Methods: Five healthy volunteers and five COPD patients were studied. DXR was performed in the standing position using a prototype X-ray system (Konica Minolta Inc., Tokyo, Japan). During the examination, participants took several tidal breaths and one forced breath. DXR image file was converted to the videos with different frames per second (fps): 15 fps, 7.5 fps, five fps, three fps, and 1.5 fps. Pixel-value gradient was calculated by the serial change of pixel value, which was subsequently converted mathematically to motion vector using OFM. Color-coding map and vector projection into horizontal and vertical components were also tested.

Results: Dynamic motion of lung and thorax was clearly visualized using VF-DXR with an optimal frame rate of 5 fps. Color-coding map and vector projection into horizontal and vertical components were also presented. VF-DXR technique was also applied in COPD patients.

Conclusion: The feasibility of VF-DXR was demonstrated with small number of healthy subjects and COPD patients.

Advances In Knowledge: A new Vector-Field Dynamic X-ray (VF-DXR) technique is feasible for dynamic visualization of lung, diaphragms, thoracic cage, and cardiac contour.
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http://dx.doi.org/10.1259/bjr.20201210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9153721PMC
April 2022

Pulmonary Functional Imaging: Part 2-State-of-the-Art Clinical Applications and Opportunities for Improved Patient Care.

Radiology 2021 06 13;299(3):524-538. Epub 2021 Apr 13.

From the Department of Radiology, Penn Medicine, University of Pennsylvania, Philadelphia, Pa (W.B.G.); Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM), Seoul, South Korea (K.S.L.); Department of Radiology, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wis (M.L.S.); Departments of Medicine and Medical Biophysics, Robarts Research Institute, Western University, London, Canada (G.P.); Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (J.B.S.); Department of Radiology and Joint Research Laboratory of Advanced Medical Imaging, Fujita Health University School of Medicine, Toyoake, Japan (Y.O.); and Center for Pulmonary Functional Imaging, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, MA 02215 (H.H.).

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.
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http://dx.doi.org/10.1148/radiol.2021204033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165948PMC
June 2021

Pulmonary Functional Imaging: Part 1-State-of-the-Art Technical and Physiologic Underpinnings.

Radiology 2021 06 6;299(3):508-523. Epub 2021 Apr 6.

From the Department of Radiology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan (Y.O.); Joint Research Laboratory of Advanced Medical Imaging, Fujita Health University School of Medicine, Toyoake, Aichi, Japan (Y.O.); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan (Y.O.); Department of Radiology, Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea (J.B.S.); Department of Medicine, Robarts Research Institute, and Department of Medical Biophysics, Western University, London, Canada (G.P.); Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine (SKKU-SOM), Seoul, Korea (K.S.L.); Department of Radiology, Penn Medicine, University of Pennsylvania, Philadelphia, Pa (W.B.G.); Departments of Medical Physics and Radiology (S.B.F., M.L.S.), UW-Madison School of Medicine and Public Health, Madison, Wis; and Center for Pulmonary Functional Imaging, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St, Boston, MA 02215 (H.H.).

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
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http://dx.doi.org/10.1148/radiol.2021203711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165947PMC
June 2021

Interstitial lung abnormality (ILA) and nonspecific interstitial pneumonia (NSIP).

Eur J Radiol Open 2021 16;8:100336. Epub 2021 Mar 16.

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

This review article aims to address mysteries existing between Interstitial Lung Abnormality (ILA) and Nonspecific Interstitial Pneumonia (NSIP). The concept and definition of ILA are based upon CT scans from multiple large-scale cohort studies, whereas the concept and definition of NSIP originally derived from pathology with evolution to multi-disciplinary diagnosis. NSIP is the diagnosis as Interstitial Lung Disease (ILD) with clinical significance, whereas only a part of subjects with ILA have clinically significant ILD. Eventually, both ILA and NSIP must be understood in the context of chronic fibrosing ILD and progressive ILD, which remains to be further investigated.
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http://dx.doi.org/10.1016/j.ejro.2021.100336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995484PMC
March 2021

Determinants of Chest X-Ray Sensitivity for COVID- 19: A Multi-Institutional Study in the United States.

Radiol Cardiothorac Imaging 2020 Oct 24;2(5):e200337. Epub 2020 Sep 24.

Department of Internal Medicine, University of Maryland School of Medicine, Midtown Campus, 827 Linden Avenue, Baltimore, MD 21201 (S.S., T.S., S.R.C.); Department of Physician Assistant Studies, Massachusetts General Hospital Institute of Health Professions, 55 Fruit St, Boston, MA 02114 (H.C.); Department of Radiology, University of Maryland School of Medicine, Downtown Campus, 22 S Greene St, Baltimore, MD 21201 (A.H., C.S.W., R.H.); Department of Pediatric Radiology, Texas Children's Hospital, 6621 Fannin St, Houston, TX 77030 (J.A.H.); and Department of Radiology, The Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02114 (F.L.J., H.H., S.C.B., K.S., T.A., A.R.H., M.M.H.).

Purpose: To evaluate the sensitivity, specificity, and severity of chest x-rays (CXR) and chest CTs over time in confirmed COVID-19+ and COVID-19- patients and to evaluate determinants of false negatives.

Methods: In a retrospective multi-institutional study, 254 RT-PCR verified COVID-19+ patients with at least one CXR or chest CT were compared with 254 age- and gender-matched COVID-19- controls. CXR severity, sensitivity, and specificity were determined with respect to time after onset of symptoms; sensitivity and specificity for chest CTs without time stratification. Performance of serial CXRs against CTs was determined by comparing area under the receiver operating characteristic curves (AUC). A multivariable logistic regression analysis was performed to assess factors related to false negative CXR.

Results: COVID-19+ CXR severity and sensitivity increased with time (from sensitivity of 55% at ≤2 days to 79% at >11 days; p<0.001 for trends of both severity and sensitivity) whereas CXR specificity decreased over time (from 83% to 70%, p=0.02). Serial CXR demonstrated increase in AUC (first CXR AUC=0.79, second CXR=0.87, p=0.02), and second CXR approached the accuracy of CT (AUC=0.92, p=0.11). COVID-19 sensitivity of first CXR, second CXR, and CT was 73%, 83%, and 88%, whereas specificity was 80%, 73%, and 77%, respectively. Normal and mild severity CXR findings were the largest factor behind false-negative CXRs (40% normal and 87% combined normal/mild). Young age and African-American ethnicity increased false negative rates.

Conclusion: CXR sensitivity in COVID-19 detection increases with time, and serial CXRs of COVID-19+ patients has accuracy approaching that of chest CT.
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http://dx.doi.org/10.1148/ryct.2020200337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605075PMC
October 2020

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

Spectrum of Pulmonary Fibrosis from Interstitial Lung Abnormality to Usual Interstitial Pneumonia: Importance of Identification and Quantification of Traction Bronchiectasis in Patient Management.

Korean J Radiol 2021 05 21;22(5):811-828. Epub 2020 Dec 21.

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

Following the introduction of a novel pathological concept of usual interstitial pneumonia (UIP) by Liebow and Carrington in 1969, diffuse interstitial pneumonia has evolved into UIP, nonspecific interstitial pneumonia (NSIP), and interstitial lung abnormality (ILA); the histopathological and CT findings of these conditions reflect the required multidisciplinary team approach, involving pulmonologists, radiologists, and pathologists, for their diagnosis and management. Concomitantly, traction bronchiectasis and bronchiolectasis have been recognized as the most persistent and important indices of the severity and prognosis of fibrotic lung diseases. The traction bronchiectasis index (TBI) can stratify the prognoses of patients with ILAs. In this review, the evolutionary concepts of UIP, NSIP, and ILAs are summarized in tables and figures, with a demonstration of the correlation between CT findings and pathologic evaluation. The CT-based UIP score is being proposed to facilitate a better understanding of the spectrum of pulmonary fibrosis, from ILAs to UIP, with emphasis on traction bronchiectasis/bronchiolectasis.
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http://dx.doi.org/10.3348/kjr.2020.1132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076826PMC
May 2021

Psychological impact of genetic and clinical screening for pulmonary fibrosis on asymptomatic first-degree relatives of affected individuals.

Thorax 2021 06 22;76(6):621-623. Epub 2021 Jan 22.

Division of Pulmonary Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, Massachusetts, USA.

Screening for pulmonary fibrosis may help to identify early stages of the disease. We assessed the psychological impact of screening undiagnosed first-degree relatives of patients with pulmonary fibrosis by administering two validated measures after participants received their results: the Decisional Regret Scale and the Feelings About genomiC Testing Results Questionnaire. More than 90% of relatives reported either no or mild decisional regret. Increased measures of decisional regret and negative feelings were present in those found to have a low diffusion capacity of carbon monoxide or interstitial lung abnormalities. Results of telomere length and genetic testing did not significantly impact regret.
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http://dx.doi.org/10.1136/thoraxjnl-2020-216244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238310PMC
June 2021

Interstitial lung abnormalities in patients with stage I non-small cell lung cancer are associated with shorter overall survival: the Boston lung cancer study.

Cancer Imaging 2021 Jan 19;21(1):14. Epub 2021 Jan 19.

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

Background: Interstitial lung abnormalities (ILA) can be detected on computed tomography (CT) in lung cancer patients and have an association with mortality in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study is to demonstrate the significance of ILA for mortality in patients with stage I NSCLC using Boston Lung Cancer Study cohort.

Methods: Two hundred and thirty-one patients with stage I NSCLC from 2000 to 2011 were investigated in this retrospective study (median age, 69 years; 93 males, 138 females). ILA was scored on baseline CT scans prior to treatment using a 3-point scale (0 = no evidence of ILA, 1 = equivocal for ILA, 2 = ILA) by a sequential reading method. ILA score 2 was considered the presence of ILA. The difference of overall survival (OS) for patients with different ILA scores were tested via log-rank test and multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) including ILA score, age, sex, smoking status, and treatment as the confounding variables.

Results: ILA was present in 22 out of 231 patients (9.5%) with stage I NSCLC. The presence of ILA was associated with shorter OS (patients with ILA score 2, median 3.85 years [95% confidence interval (CI): 3.36 - not reached (NR)]; patients with ILA score 0 or 1, median 10.16 years [95%CI: 8.65 - NR]; P <  0.0001). In a Cox proportional hazards model, the presence of ILA remained significant for increased risk for death (HR = 2.88, P = 0.005) after adjusting for age, sex, smoking and treatment.

Conclusions: ILA was detected on CT in 9.5% of patients with stage I NSCLC. The presence of ILA was significantly associated with a shorter OS and could be an imaging marker of shorter survival in stage I NSCLC.
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http://dx.doi.org/10.1186/s40644-021-00383-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816399PMC
January 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.
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http://dx.doi.org/10.1016/j.chest.2020.11.027DOI Listing
March 2021
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