Pulmonary emphysema subtypes defined by unsupervised machine learning on CT scans.

BACKGROUND: Treatment and preventative advances for chronic obstructive pulmonary disease (COPD) have been slow due, in part, to limited subphenotypes. We tested if unsupervised machine learning on CT images would discover CT emphysema subtypes with distinct characteristics, prognoses and genetic associations. METHODS: New CT emphysema subtypes were identified by unsupervised machine learning on only the texture and location of emphysematous regions on CT scans from 2853 participants in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS), a COPD case-control study, followed by data reduction. Subtypes were compared with symptoms and physiology among 2949 participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study and with prognosis among 6658 MESA participants. Associations with genome-wide single-nucleotide-polymorphisms were examined. RESULTS: The algorithm discovered six reproducible (interlearner intraclass correlation coefficient, 0.91-1.00) CT emphysema subtypes. The most common subtype in SPIROMICS, the combined bronchitis-apical subtype, was associated with chronic bronchitis, accelerated lung function decline, hospitalisations, deaths, incident airflow limitation and a gene variant near DRD1, which is implicated in mucin hypersecretion (p=1.1 ×10-8). The second, the diffuse subtype was associated with lower weight, respiratory hospitalisations and deaths, and incident airflow limitation. The third was associated with age only. The fourth and fifth visually resembled combined pulmonary fibrosis emphysema and had distinct symptoms, physiology, prognosis and genetic associations. The sixth visually resembled vanishing lung syndrome. CONCLUSION: Large-scale unsupervised machine learning on CT scans defined six reproducible, familiar CT emphysema subtypes that suggest paths to specific diagnosis and personalised therapies in COPD and pre-COPD.

Human airway branch variation and chronic obstructive pulmonary disease.

Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts (n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung. The second most common airway branch variant is associated with COPD among smokers, with narrower airway lumens in all lobes, and with genetic polymorphisms within the FGF10 gene. We conclude that central airway branch variation, readily detected by computed tomography, is a biomarker of widely altered lung structure with a genetic basis and represents a COPD susceptibility factor.

The role of initial chest X-ray in triaging patients with suspected COVID-19 during the pandemic.

PURPOSE: The purpose of our research is to evaluate the usefulness of chest X-ray for triaging patients with suspected COVID-19 infection. METHODS: IRB approval was obtained to allow a retrospective review of adult patients who presented to the Emergency Department with a complaint of fever, cough, dyspnea or hypoxia and had a chest X-ray between 12 March 2020 and 26 March 2020. The initial chest X-ray was graded on a scale of 0-3 with grade 0 representing no alveolar opacities, grade 1: < 1/3 alveolar opacities of the lung, Grade 2: 1/3 to 2/3 lung with alveolar opacities and grade 3: > 2/3 alveolar opacities of the lung. Past medical history of diabetes and hypertension, initial oxygen saturation, COVID-19 testing results, intubation, and outcome were also collected. RESULTS: Four hundred ten patient chest X-rays were reviewed. Oxygen saturation and X-ray grade were both significantly associated with the length of stay in hospital, the hazard ratio (HR) of discharge was 1.05 (95% CI [1.01, 1.09], p = 0.017) and 0.61 (95% CI [0.51, 0.73], p < 0.001), respectively. In addition, oxygen saturation and X-ray grade were significant predictors of intubation (odds ratio (OR) of intubation is 0.88 (95% CI [0.81, 0.96], p = 0.004) and 3.69 (95% CI [2.25, 6.07], p < 0.001). CONCLUSIONS: Initial chest X-ray is a useful tool for triaging those subjects who might have poor outcomes with suspected COVID-19 infection and benefit most from hospitalization.

Ambient air pollution and pulmonary vascular volume on computed tomography: the MESA Air Pollution and Lung cohort studies.

BACKGROUND: Air pollution alters small pulmonary vessels in animal models. We hypothesised that long-term ambient air pollution exposure would be associated with differences in pulmonary vascular volumes in a population-based study. METHODS: The Multi-Ethnic Study of Atherosclerosis recruited adults in six US cities. Personalised long-term exposures to ambient black carbon, nitrogen dioxide (NO2), oxides of nitrogen (NO x ), particulate matter with a 50% cut-off aerodynamic diameter of <2.5 µm (PM2.5) and ozone were estimated using spatiotemporal models. In 2010-2012, total pulmonary vascular volume was measured as the volume of detectable pulmonary arteries and veins, including vessel walls and luminal blood volume, on noncontrast chest computed tomography (TPVVCT). Peripheral TPVVCT was limited to the peripheral 2 cm to isolate smaller vessels. Linear regression adjusted for demographics, anthropometrics, smoking, second-hand smoke, renal function and scanner manufacturer. RESULTS: The mean±sd age of the 3023 participants was 69.3±9.3 years; 46% were never-smokers. Mean exposures were 0.80 µg·m-3 black carbon, 14.6 ppb NO2 and 11.0 µg·m-3 ambient PM2.5. Mean±sd peripheral TPVVCT was 79.2±18.2 cm3 and TPVVCT was 129.3±35.1 cm3. Greater black carbon exposure was associated with a larger peripheral TPVVCT, including after adjustment for city (mean difference 0.41 (95% CI 0.03-0.79) cm3 per interquartile range; p=0.036). Associations for peripheral TPVVCT with NO2 were similar but nonsignificant after city adjustment, while those for PM2.5 were of similar magnitude but nonsignificant after full adjustment. There were no associations for NO x or ozone, or between any pollutant and TPVVCT. CONCLUSIONS: Long-term black carbon exposure was associated with a larger peripheral TPVVCT, suggesting diesel exhaust may contribute to remodelling of small pulmonary vessels in the general population.

Associations between emphysema-like lung on CT and incident airflow limitation: a general population-based cohort study.

Emphysema on CT is associated with accelerated lung function decline in heavy smokers and patients with COPD; however, in the general population, it is not known whether greater emphysema-like lung on CT is associated with incident COPD. We used data from 2045 adult participants without initial prebronchodilator airflow limitation, classified by FEV1/FVC<0.70, in the Multi-Ethnic Study of Atherosclerosis. Emphysema-like lung on baseline cardiac CT, defined as per cent low attenuation areas<-950HU>upper limit of normal, was associated with increased odds of incident airflow limitation at 5-year follow-up on both prebronchodilator (adjusted OR 2.62, 95% CI 1.47 to 4.67) and postbronchodilator (adjusted OR 4.38, 95% CI 1.63 to 11.74) spirometry, independent of smoking history. These results support investigation into whether emphysema-like lung could be informative for COPD risk stratification.

CT-based Visual Classification of Emphysema: Association with Mortality in the COPDGene Study.

Purpose To determine whether visually assessed patterns of emphysema at CT might provide a simple assessment of mortality risk among cigarette smokers. Materials and Methods Of the first 4000 cigarette smokers consecutively enrolled between 2007 and 2011 in this COPDGene study, 3171 had data available for both visual emphysema CT scores and survival. Each CT scan was retrospectively visually scored by two analysts using the Fleischner Society classification system. Severity of emphysema was also evaluated quantitatively by using percentage lung volume occupied by low-attenuation areas (voxels with attenuation of -950 HU or less) (LAA-950). Median duration of follow-up was 7.4 years. Regression analysis for the relationship between imaging patterns and survival was based on the Cox proportional hazards model, with adjustment for age, race, sex, height, weight, pack-years of cigarette smoking, current smoking status, educational level, LAA-950, and (in a second model) forced expiratory volume in 1 second (FEV1). Results Observer agreement in visual scoring was good (weighted κ values, 0.71-0.80). There were 519 deaths in the study cohort. Compared with subjects who did not have visible emphysema, mortality was greater in those with any grade of emphysema beyond trace (adjusted hazard ratios, 1.7, 2.5, 5.0, and 4.1, respectively, for mild centrilobular emphysema, moderate centrilobular emphysema, confluent emphysema, and advanced destructive emphysema, P < .001). This increased mortality generally persisted after adjusting for LAA-950. Conclusion The visual presence and severity of emphysema is associated with significantly increased mortality risk, independent of the quantitative severity of emphysema. Online supplemental material is available for this article.

Rheumatoid arthritis-associated autoantibodies and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Adults with interstitial lung disease (ILD) often have serologic evidence of autoimmunity of uncertain significance without overt autoimmune disease. We examined associations of rheumatoid arthritis (RA)-associated antibodies with subclinical ILD in community-dwelling adults. METHODS: We measured serum rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) and high attenuation areas (HAAs; CT attenuation values between -600 and -250 Hounsfield units) on cardiac CT in 6736 community-dwelling US adults enrolled in the Multi-Ethnic Study of Atherosclerosis. We measured interstitial lung abnormalities (ILAs) in 2907 full-lung CTs at 9.5-year median follow-up. We used generalised linear and additive models to examine associations between autoantibodies and both HAA and ILA, and tested for effect modification by smoking. RESULTS: In adjusted models, HAA increased by 0.49% (95% CI 0.11% to 0.86%) per doubling of RF IgM and by 0.95% (95% CI 0.50% to 1.40%) per RF IgA doubling. ILA prevalence increased by 11% (95% CI 3% to 20%) per RF IgA doubling. Smoking modified the associations of both RF IgM and anti-CCP with both HAA and ILA (interaction p values varied from 0.01 to 0.09). Among ever smokers, HAA increased by 0.81% (95% CI 0.33% to 1.30%) and ILA prevalence increased by 14% (95% CI 5% to 24%,) per RF IgM doubling; and HAA increased by 1.31% (95% CI 0.45% to 2.18%) and ILA prevalence increased by 13% (95% CI 2% to 24%) per anti-CCP doubling. Among never smokers, no meaningful associations were detected. CONCLUSIONS: RA-related autoimmunity is associated with both quantitative and qualitative subclinical ILD phenotypes on CT, particularly among ever smokers.

High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study.

Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between -600 and -250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3-11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8-13.0), lower forced vital capacity (FVC) (mean adjusted difference -82 mL, 95% CI -119--44), lower 6-min walk distance (mean adjusted difference -40 m, 95% CI -1--80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43-2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39-1.79).High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.

Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study.

RATIONALE: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. OBJECTIVES: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. METHODS: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below -950 Hounsfield units (-950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. MEASUREMENTS AND MAIN RESULTS: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema-950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. CONCLUSIONS: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature.

CT-Definable Subtypes of Chronic Obstructive Pulmonary Disease: A Statement of the Fleischner Society.

The purpose of this statement is to describe and define the phenotypic abnormalities that can be identified on visual and quantitative evaluation of computed tomographic (CT) images in subjects with chronic obstructive pulmonary disease (COPD), with the goal of contributing to a personalized approach to the treatment of patients with COPD. Quantitative CT is useful for identifying and sequentially evaluating the extent of emphysematous lung destruction, changes in airway walls, and expiratory air trapping. However, visual assessment of CT scans remains important to describe patterns of altered lung structure in COPD. The classification system proposed and illustrated in this article provides a structured approach to visual and quantitative assessment of COPD. Emphysema is classified as centrilobular (subclassified as trace, mild, moderate, confluent, and advanced destructive emphysema), panlobular, and paraseptal (subclassified as mild or substantial). Additional important visual features include airway wall thickening, inflammatory small airways disease, tracheal abnormalities, interstitial lung abnormalities, pulmonary arterial enlargement, and bronchiectasis.

Genome-wide study of percent emphysema on computed tomography in the general population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study.

RATIONALE: Pulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering. OBJECTIVES: To complete a genome-wide association study (GWAS) for the percentage of emphysema-like lung on computed tomography in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung/SNP Health Association Resource (SHARe) Study, a large, population-based cohort in the United States. METHODS: We determined percent emphysema and upper-lower lobe ratio in emphysema defined by lung regions less than -950 HU on cardiac scans. Genetic analyses were reported combined across four race/ethnic groups: non-Hispanic white (n = 2,587), African American (n = 2,510), Hispanic (n = 2,113), and Chinese (n = 704) and stratified by race and ethnicity. MEASUREMENTS AND MAIN RESULTS: Among 7,914 participants, we identified regions at genome-wide significance for percent emphysema in or near SNRPF (rs7957346; P = 2.2 × 10(-8)) and PPT2 (rs10947233; P = 3.2 × 10(-8)), both of which replicated in an additional 6,023 individuals of European ancestry. Both single-nucleotide polymorphisms were previously implicated as genes influencing lung function, and analyses including lung function revealed independent associations for percent emphysema. Among Hispanics, we identified a genetic locus for upper-lower lobe ratio near the α-mannosidase-related gene MAN2B1 (rs10411619; P = 1.1 × 10(-9); minor allele frequency [MAF], 4.4%). Among Chinese, we identified single-nucleotide polymorphisms associated with upper-lower lobe ratio near DHX15 (rs7698250; P = 1.8 × 10(-10); MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10(-8); MAF, 2.6%), which acts on α-linked mannose. Among African Americans, a locus near a third α-mannosidase-related gene, MAN1C1 (rs12130495; P = 9.9 × 10(-6); MAF, 13.3%) was associated with percent emphysema. CONCLUSIONS: Our results suggest that some genes previously identified as influencing lung function are independently associated with emphysema rather than lung function, and that genes related to α-mannosidase may influence risk of emphysema.

Bronchial thermoplasty: Long-term safety and effectiveness in patients with severe persistent asthma.

BACKGROUND: Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. OBJECTIVE: We sought to assess the effectiveness and safety of BT in asthmatic patients 5 years after therapy. METHODS: BT-treated subjects from the Asthma Intervention Research 2 trial (ClinicalTrials.govNCT01350414) were evaluated annually for 5 years to assess the long-term safety of BT and the durability of its treatment effect. Outcomes assessed after BT included severe exacerbations, adverse events, health care use, spirometric data, and high-resolution computed tomographic scans. RESULTS: One hundred sixty-two (85.3%) of 190 BT-treated subjects from the Asthma Intervention Research 2 trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and emergency department (ED) visits and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months before BT treatment (average 5-year reduction in proportions: 44% for exacerbations and 78% for ED visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in years 2 through 5 compared with the first year after BT. Prebronchodilator FEV1 values remained stable between years 1 and 5 after BT, despite a 18% reduction in average daily inhaled corticosteroid dose. High-resolution computed tomographic scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. CONCLUSIONS: These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ED visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking inhaled corticosteroids and long-acting ß2-agonists.

Radiologic implications of the 2011 classification of adenocarcinoma of the lung.

Now the leading subtype of lung cancer, adenocarcinoma received a new classification in 2011. For tumors categorized previously as bronchioloalveolar carcinoma (BAC), criteria and terminology had not been uniform, so the 2011 classification provided four new terms: (a) adenocarcinoma in situ (AIS), representing histopathologically a small (≤3-cm), noninvasive lepidic growth, which at computed tomography (CT) is usually nonsolid; (b) minimally invasive adenocarcinoma, representing histopathologically a small (≤3-cm) and predominantly lepidic growth that has 5-mm or smaller invasion, which at CT is mainly nonsolid but may have a central solid component of up to approximately 5 mm; (c) lepidic predominant nonmucinous adenocarcinoma, representing histopathologically invasive adenocarcinoma that shows predominantly lepidic nonmucinous growth, which at CT is usually part solid but may be nonsolid or occasionally have cystic components; and (d) invasive mucinous adenocarcinoma, histopathologically showing lepidic growth as its predominant component, which at CT varies widely from solid to mostly solid to part solid to nonsolid and may be single or multiple (when multifocal, it was formerly called multicentric BAC). In addition, new histopathologic subcategories of acinar, papillary, micropapillary, and solid predominant adenocarcinoma are now described, all as nonmucinous, predominantly invasive, may include a small lepidic component, and at CT are usually solid but may include a small nonsolid component. The micropapillary subtype has a poorer prognosis than the other subtypes. In addition, molecular genetic correlations for the subcategories of adenocarcinoma of the lung are now a topic of increasing interest. As the new classification enters common use, further descriptions of related correlations can be anticipated.

Lung cancer associated with cystic airspaces.

OBJECTIVE: The objectives of this study were to determine the frequency of lung cancers associated with a discrete cystic airspace and to characterize the morphologic and pathologic features of the cancer and the cystic airspace. MATERIALS AND METHODS: We reviewed all diagnosed cases of lung cancer resulting from baseline screening (n=595) and annual screening (n=111) in the International Early Lung Cancer Action Program to identify those abutting or in the wall of a cystic airspace. We also reviewed the pathologic specimens. RESULTS: A total of 26 lung cancers were identified abutting or in the wall of a cystic airspace. Of these, 13 were identified at baseline (13/595, 2%) and 13 at annual screening (13/111, 12%), which was significant (p<0.0001). The median circumferential portion of wall involved was less for the annual cancers than for the baseline ones, but this difference did not reach significance (90° vs 240°, p=0.07). The diagnosis was adenocarcinoma in all but three cases. Histologic analysis showed that the cystic space was a bulla, a fibrous walled cyst without a defined lining, or a pleural bleb and that in all but one case, the tumor was eccentric relative to the airspace and the wall of the airspace was unevenly thickened. CONCLUSION: At annual repeat CT screening, the finding of an isolated cystic airspace with increased wall thickness should raise the suspicion of lung cancer.

Idiopathic pulmonary fibrosis and lung cancer: future directions and challenges.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of pulmonary scarring. New treatments slow disease progression and allow pulmonary fibrosis patients to live longer. Persistent pulmonary fibrosis increases a patient's risk of developing lung cancer. Lung cancer in patients with IPF differs from cancers that develop in the non-fibrotic lung. Peripherally located adenocarcinoma is the most frequent cell type in smokers who develop lung cancer, while squamous cell carcinoma is the most frequent in pulmonary fibrosis. Increased fibroblast foci in IPF are associated with more aggressive cancer behaviour and shorter doubling times. Treatment of lung cancer in fibrosis is challenging because of the risk of inducing an exacerbation of fibrosis. In order to improve patient outcomes, modifications of current lung cancer screening guidelines in patients with pulmonary fibrosis will be necessary to avoid delays in treatment. 2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) computed tomography (CT) imaging can help identify cancer earlier and more reliably than CT alone. Increased use of wedge resections, proton therapy and immunotherapy may increase survival by decreasing the risk of exacerbation, but further research will be necessary.

Quantifying normal lung in pulmonary fibrosis: CT analysis and correlation with %DLCO.

BACKGROUND: Chest CT scans are routinely obtained to monitor disease progression in pulmonary fibrosis. However, radiologists do not employ a standardized system for quantitative description of the severity of the disease. Development and validation of a grading system offers potential for enhancing the information that radiologists provide clinicians. STUDY DESIGN AND METHODS: Our retrospective review analyzed 100 sequential patients with usual interstitial pneumonitis (UIP) on HRCT scans from 2018 and 2019. A radiologic scoring system evaluated the percent of normal lung on the basis of a 0-5 point scale per lobe (findings for the right middle lobe were included in the right upper lobe score), yielding an overall additive numerical score on a scale of 20 (completely normal lung) to 0 (no normal lung). Two radiologists quantified the percentage of normal lung by consensus agreement. Percent DLCO as well as demographic data were obtained from the medical record. Statistical analysis was performed using Spearman correlation to assess correlation between grade and percent DLCO. RESULTS: 96 patients met the inclusion criteria; average age was 71, 68% were male. Score on CT scan ranged from 18 to 4; average 10.9, SD 3.58. The single-breath diffusing capacity (percent DLCO) ranged from 88% to 17%; mean 44.5%, SD 14.3%. Spearman's correlation for CT score and percent DLCO was 0.622, P < 0.001. CONCLUSION: This scoring system quantifying the amount of normal lung on chest CT of patients with UIP correlated significantly with percent DLCO (P < 0.001) and appears to offer a promising quantitative measure to assess severity of disease.

Hypersensitivity pneumonitis: Airway-centered pulmonary fibrosis on chest CT.

BACKGROUND: To evaluate the chest CT appearance of patients with a clinicopathologic diagnosis of hypersensitivity pneumonia. METHODS: IRB approval was obtained for a retrospective review of patients with a preoperative CT scan, a surgical pathology report from a transbronchial biopsy or wedge resection consistent with hypersensitivity pneumonitis, and a pulmonary consultation, which also supported the diagnosis. The pathology report was evaluated for granulomas, airway-centered fibrosis, microscopic honeycombing, and fibroblast foci. The medical records were reviewed for any known antigen exposure. Patients were separated into two groups; those with and without a known antigen exposure. The CT scans were assessed for distribution of fibrosis: upper lobe or lower lobe predominance, airway-centered versus peripheral distribution, three-density pattern, and honeycombing. RESULTS: 264 pathology reports included the term chronic hypersensitivity pneumonitis (CHP). Thirty-eight of the patients had a pulmonologist who gave the patient a working diagnosis of CHP. The average age of these patients was 64 years, and 21/38 were women. Seventeen of the 38 patients had at least one antigen exposure described in the medical records. All the patients had fibrosis along the airways on chest CT. Both known antigen exposure and no known antigen patients had upper and lower lung-predominant fibrosis. There were more patients with hiatal hernias in the unknown antigen group. Honeycombing was an uncommon finding. CONCLUSION: Airway-centered fibrosis was present on chest CT in all 38 patients with CHP (100%), with or without known antigen exposure.

Novel Subtypes of Pulmonary Emphysema Based on Spatially-Informed Lung Texture Learning: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study.

Pulmonary emphysema overlaps considerably with chronic obstructive pulmonary disease (COPD), and is traditionally subcategorized into three subtypes previously identified on autopsy. Unsupervised learning of emphysema subtypes on computed tomography (CT) opens the way to new definitions of emphysema subtypes and eliminates the need of thorough manual labeling. However, CT-based emphysema subtypes have been limited to texture-based patterns without considering spatial location. In this work, we introduce a standardized spatial mapping of the lung for quantitative study of lung texture location and propose a novel framework for combining spatial and texture information to discover spatially-informed lung texture patterns (sLTPs) that represent novel emphysema subtype candidates. Exploiting two cohorts of full-lung CT scans from the MESA COPD (n = 317) and EMCAP (n = 22) studies, we first show that our spatial mapping enables population-wide study of emphysema spatial location. We then evaluate the characteristics of the sLTPs discovered on MESA COPD, and show that they are reproducible, able to encode standard emphysema subtypes, and associated with physiological symptoms.

Associations of D-Dimer with Computed Tomographic Lung Abnormalities, Serum Biomarkers of Lung Injury, and Forced Vital Capacity: MESA Lung Study.

Rationale: The coagulation cascade may play a role in the pathogenesis of interstitial lung disease through increased production of thrombin and fibrin deposition. Whether circulating coagulation cascade factors are linked to lung inflammation and scarring among community-dwelling adults is unknown. Objectives: To test the hypothesis that higher baseline D-dimer concentrations are associated with markers of early lung injury and scarring. Methods: Using the MESA (Multi-Ethnic Study of Atherosclerosis) cohort (n = 6,814), we examined associations of baseline D-dimer concentrations with high attenuation areas from examination 1 (2000-2002; n = 6,184) and interstitial lung abnormalities from examination 5 computed tomographic (CT) scans (2010-2012; n = 2,227), and serum MMP-7 (matrix metalloproteinase-7) and SP-A (surfactant protein-A) from examination 1 (n = 1,098). We examined longitudinal change in forced vital capacity (FVC) from examinations 3-6 (2004-2018, n = 3,562). We used linear logistic regression and linear mixed models to examine associations and adjust for potential confounders. Results: The mean (standard deviation) age of the cohort was 62 (10) years, and the D-dimer concentration was 0.35 (0.69) ug/ml. For every 10% increase in D-dimer concentration, there was an increase in high attenuation area percentage of 0.27 (95% confidence interval (CI), 0.08-0.47) after adjustment for covariates. Associations were stronger among those older than 65 years (P values for interaction < 0.001). A 10% increase in D-dimer concentration was associated with an odds ratio of 1.05 for interstitial lung abnormalities (95% CI, 0.99-1.11). Higher D-dimer concentrations were associated with higher serum MMP-7 and a faster decline in FVC. D-dimer was not associated with SP-A. Conclusions: Higher D-dimer concentrations were associated with a greater burden of lung parenchymal abnormalities detected on CT scan, MMP-7, and FVC decline among community-dwelling adults.