BackgroundThe coexistence of COPD and asthma is widely recognized but has not been well described. This study characterizes clinical features, spirometry, and chest CT scans of smoking subjects with both COPD and asthma.MethodsWe performed a cross-sectional study comparing subjects with COPD and asthma to subjects with COPD alone in the COPDGene Study.Results119 (13%) of 915 subjects with COPD reported a history of physician-diagnosed asthma. These subjects were younger (61.3 vs 64.7 years old, p = 0.0001) with lower lifetime smoking intensity (43.7 vs 55.1 pack years, p = 0.0001). More African-Americans reported a history of asthma (33.6% vs 15.6%, p < 0.0001). Subjects with COPD and asthma demonstrated worse disease-related quality of life, were more likely to have had a severe COPD exacerbation in the past year, and were more likely to experience frequent exacerbations (OR 3.55 [2.19, 5.75], p < 0.0001). Subjects with COPD and asthma demonstrated greater gas-trapping on chest CT. There were no differences in spirometry or CT measurements of emphysema or airway wall thickness.ConclusionSubjects with COPD and asthma represent a relevant clinical population, with worse health-related quality of life. They experience more frequent and severe respiratory exacerbations despite younger age and reduced lifetime smoking history.Trial registrationClinicalTrials.gov: NCT00608764

OBJECTIVE This study evaluates the relationships between quantitative CT (QCT) and spirometric measurements of disease severity in cigarette smokers with and without chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS Inspiratory and expiratory CT scans of 4062 subjects in the Genetic Epidemiology of COPD (COPDGene) Study were evaluated. Measures examined included emphysema, defined as the percentage of low-attenuation areas ≤ −950 HU on inspiratory CT, which we refer to as “LAA-950I”; air trapping, defined as the percentage of low-attenuation areas ≤ −856 HU on expiratory CT, which we refer to as “LAA-856E”; and the inner diameter, inner and outer areas, wall area, airway wall thickness, and square root of the wall area of a hypothetical airway of 10-mm internal perimeter of segmental and subsegmental airways. Correlations were determined between spirometry and several QCT measures using statistics software (SAS, version 9.2). RESULTS QCT measurements of low-attenuation areas correlate strongly and significantly (p < 0.0001) with spirometry. The correlation between LAA-856E and forced expiratory volume in 1 second (FEV1) and the ratio of FEV1 to forced vital capacity (FVC) (r = −0.77 and −0.84, respectively) is stronger than the correlation between LAA-950I and FEV1 and FEV1/FVC (r = −0.67 and r = −0.76). Inspiratory and expiratory volume changes decreased with increasing disease severity, as measured by the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) staging system (p < 0.0001). When airway variables were included with low-attenuation area measures in a multiple regression model, the model accounted for a statistically greater proportion of variation in FEV1 and FEV1/FVC (R2 = 0.72 and 0.77, respectively). Airway measurements alone are less correlated with spirometric measures of FEV1 (r = 0.15 to −0.44) and FEV1/FVC (r = 0.19 to −0.34). CONCLUSION QCT measurements are strongly associated with spirometric results showing impairment in smokers. LAA-856E strongly correlates with physiologic measurements of airway obstruction. Airway measurements can be used concurrently with QCT measures of low-attenuation areas to accurately predict lung function.

Smoking-related chronic obstructive pulmonary disease is characterized by distal pruning of the small blood vessels (<5 mm(2)) and loss of tissue in excess of the vasculature. The magnitude of these changes predicts the clinical severity of disease.

Objectives The purposes of this study are to evaluate the normal range of quantitative CT (QCT) measures of lung attenuation and airway parameters measurements in healthy non-smoking adults and to identify sources of variation in those measures and possible means to adjust for them. Materials and Methods Within the COPDGene® study, 92 healthy non-Hispanic White non-smokers [29 male, 63 female, mean age 62.7 (SD 9.0), BMI 28.1 (SD 5.1)] underwent volumetric CT at full inspiration and at the end of a normal expiration. On QCT analysis (Pulmonary Workstation 2, VIDA Diagnostics), inspiratory low attenuation areas were defined as lung tissue with attenuation values ≤ −950 Hounsfield Units (HU) on inspiratory CT (LAAI-950). Expiratory low attenuation areas were defined as lung tissue ≤ −856 HU on expiratory CT (LAAE-856). We used simple linear regression to determine the impact of age and gender on QCT parameters and multiple regression to assess the additional impact of total lung capacity and functional residual capacity measured by CT (TLCCT and FRCCT), scanner type, and mean tracheal air attenuation. Airways were evaluated using measures of airway wall thickness (AWT), inner luminal area (ILA), wall area percent (WA%) and standardized thickness of an airway with inner perimeter of 10mm (Pi10). Results Mean %LAAI-950 was 2.0 (SD 2.7), and mean %LAAE-856 was 9.2 (SD 6.8). Mean %LAAI-950 was 3.6 (SD 3.2) % in men, compared with 1.3 (SD 2.0) in women (P<0.001). The %LAAI-950 did not change significantly with age (P=0.08) or BMI (P=0.52). %LAAE-856 did not show any independent relationship with age (P=0.33), gender (P=0.70), or BMI (P=0.32). On multivariate analysis, %LAAI-950 showed a direct relationship to TLCCT (P=0.002) and an inverse relationship to mean tracheal air attenuation (P=0.003), and %LAAE-856 was related to age (P=0.001), FRCCT (P=0.007) and scanner type (P<0.001). Multivariate analysis of segmental airways showed that ILA and WA% were significantly related to TLCCT (P<0.001) and age (0.006). WA% was also associated with gender (P=0.05), axial pixel size (P=0.03) and slice interval (P=0.04). Lastly, AWT is strongly influenced by axial pixel size (P<0.001). Conclusions Although the attenuation characteristics of normal lung differ by age and gender, these differences do not persist on multivariate analysis. Potential sources of variation in measurement of attenuation-based quantitative CT parameters include depth of inspiration/expiration, and scanner type. Tracheal air attenuation may partially correct variation due to scanner type. Sources of variation in QCT airway measurements may include age, gender, BMI, depth of inspiration, and spatial resolution.

Purpose To evaluate associations between pulmonary function and both quantitative analysis and visual assessment of thin-section computed tomography (CT) images at baseline and at 15-month follow-up in subjects with idiopathic pulmonary fibrosis (IPF). Materials and Methods This retrospective analysis of preexisting anonymized data, collected prospectively between 2007 and 2013 in a HIPAA-compliant study, was exempt from additional institutional review board approval. The extent of lung fibrosis at baseline inspiratory chest CT in 280 subjects enrolled in the IPF Network was evaluated. Visual analysis was performed by using a semiquantitative scoring system. Computer-based quantitative analysis included CT histogram-based measurements and a data-driven textural analysis (DTA). Follow-up CT images in 72 of these subjects were also analyzed. Univariate comparisons were performed by using Spearman rank correlation. Multivariate and longitudinal analyses were performed by using a linear mixed model approach, in which models were compared by using asymptotic χ tests. Results At baseline, all CT-derived measures showed moderate significant correlation (P < .001) with pulmonary function. At follow-up CT, changes in DTA scores showed significant correlation with changes in both forced vital capacity percentage predicted (ρ = -0.41, P < .001) and diffusing capacity for carbon monoxide percentage predicted (ρ = -0.40, P < .001). Asymptotic χ tests showed that inclusion of DTA score significantly improved fit of both baseline and longitudinal linear mixed models in the prediction of pulmonary function (P < .001 for both). Conclusion When compared with semiquantitative visual assessment and CT histogram-based measurements, DTA score provides additional information that can be used to predict diminished function. Automatic quantification of lung fibrosis at CT yields an index of severity that correlates with visual assessment and functional change in subjects with IPF. RSNA, 2017.

Background Cigarette smoking is a major risk factor for COPD and COPD severity. Previous genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) associated with the number of cigarettes smoked per day (CPD) and a Dopamine Beta-Hydroxylase (DBH) locus associated with smoking cessation in multiple populations. Objective To identify SNPs associated with lifetime average and current CPD, age at smoking initiation, and smoking cessation in COPD subjects. Methods GWAS were conducted in 4 independent cohorts encompassing 3,441 ever-smoking COPD subjects (GOLD stage II or higher). Untyped SNPs were imputed using HapMap (phase II) panel. Results from all cohorts were meta-analyzed. Results Several SNPs near the HLA region on chromosome 6p21 and in an intergenic region on chromosome 2q21 showed associations with age at smoking initiation, both with the lowest p=2×10−7. No SNPs were associated with lifetime average CPD, current CPD or smoking cessation with p<10−6. Nominally significant associations with candidate SNPs within alpha-nicotinic acetylcholine receptors 3/5 (CHRNA3/CHRNA5; e.g. p=0.00011 for SNP rs1051730) and Cytochrome P450 2A6 (CYP2A6; e.g. p=2.78×10−5 for a nonsynonymous SNP rs1801272) regions were observed for lifetime average CPD, however only CYP2A6 showed evidence of significant association with current CPD. A candidate SNP (rs3025343) in the DBH was significantly (p=0.015) associated with smoking cessation. Conclusion We identified two candidate regions associated with age at smoking initiation in COPD subjects. Associations of CHRNA3/CHRNA5 and CYP2A6 loci with CPD and DBH with smoking cessation are also likely of importance in the smoking behaviors of COPD patients.

Purposes:To provide a new detailed visual assessment scheme of computed tomography (CT) for chronic obstructive pulmonary disease (COPD) by using standard reference images and to compare this visual assessment method with quantitative CT and several physiologic parameters. Materials and Methods:This research was approved by the institutional review board of each institution. CT images of 200 participants in the COPDGene study were evaluated. Four thoracic radiologists performed independent, lobar analysis of volumetric CT images for type (centrilobular, panlobular, and mixed) and extent (on a six-point scale) of emphysema, the presence of bronchiectasis, airway wall thickening, and tracheal abnormalities. Standard images for each finding, generated by two radiologists, were used for reference. The extent of emphysema, airway wall thickening, and luminal area were quantified at the lobar level by using commercial software. Spearman rank test and simple and multiple regression analyses were performed to compare the results of visual assessment with physiologic and quantitative parameters. Results:The type of emphysema, determined by four readers, showed good agreement (k = 0.63). The extent of the emphysema in each lobe showed good agreement (mean weighted k = 0.70) and correlated with findings at quantitative CT (r = 0.75), forced expiratory volume in 1 second (FEV 1 ) (r = 20.68), FEV 1 /forced vital capacity (FVC) ratio (r = 20.74) (P , .001). Agreement for airway wall thickening was fair (mean k = 0.41), and the number of lobes with thickened bronchial walls correlated with FEV 1 (r = 20.60) and FEV 1 /FVC ratio (r = 20.60) (P , .001). Conclusion:Visual assessment of emphysema and airways disease in individuals with COPD can provide reproducible, physiologically substantial information that may complement that provided by quantitative CT assessment.q RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup /suppl

IMPORTANCE e-Cigarette, or vaping, product use-associated lung injury (EVALI) has caused more than 2800 illnesses and 68 deaths in the United States. Better characterization of this novel illness is needed to inform diagnosis and management. OBJECTIVE To describe the clinical features, bronchoscopic findings, imaging patterns, and outcomes of EVALI. DESIGN, SETTING, AND PARTICIPANTS This case series of 31 adult patients diagnosed with EVALI between June 24 and December 10, 2019, took place at an academic medical center in Salt Lake City, Utah. EXPOSURES e-Cigarette use, also known as vaping. MAIN OUTCOMES AND MEASURES Symptoms, laboratory findings, bronchoscopic results, imaging patterns, and clinical outcomes. RESULTS Data from 31 patients (median [interquartile range] age, 24 [21-31] years) were included in the study. Patients were primarily men (24 [77%]) and White individuals (27 [87%]) who used e-cigarette products containing tetrahydrocannabinol (THC) (29 [94%]). Patients presented with respiratory (30 [97%]), constitutional (28 [90%]), and gastrointestinal (28 [90%]) symptoms. Serum inflammatory markers were elevated in all patients. Bronchoscopy was performed in 23 of 28 inpatients (82%) and bronchoalveolar lavage (BAL) revealed the presence of lipid-laden macrophages (LLMs) in 22 of 24 cases (91%). BAL samples tested positive for Pneumocystis jirovecii (3 patients [13%]), rhinovirus (2 patients [8%]), human metapneumovirus and Aspergillus (1 patient each [4%]); all except human metapneumovirus were determined to be false-positives or clinically inconsequential. The exclusive or dominant computed tomography (CT) pattern was organizing pneumonia in 23 of 26 cases (89%). Patients received antibiotics (26 [84%]) and corticosteroids (24 [77%]), and all survived; 20 patients (65%) seen in follow-up showed marked improvement, but residual symptoms (13 [65%]), radiographic opacities (8 [40%]), and abnormal pulmonary function tests (8 of 18 [44%]) were common. CONCLUSIONS AND RELEVANCE In this case series, patients with EVALI characteristically presented with a flu-like illness with elevated inflammatory markers, LLMs on BAL samples, and an organizing pneumonia pattern on CT imaging. Bronchoscopic testing for infection had a high incidence of false-positive results. Patients had substantial residual abnormal results at early (continued) Key Points Question What are the typical clinical, radiographic, and bronchoscopic findings and clinical outcomes of e-cigarette, or vaping, product use-associated lung injury (EVALI)? Findings This case series of 31 patients found that EVALI typically presented as a flu-like illness with elevated inflammatory markers and an organizing pneumonia pattern on computed tomography imaging. Bronchoscopy showed lipid-laden macrophages and had a high rate of false-positive results for infection. Meaning The findings of this study suggest that EVALI has a characteristic clinical and radiographic presentation and that bronchoscopy has limited utility in its evaluation.