Central airway collapse greater than 50% of luminal area during exhalation (expiratory central airway collapse ECAC) is associated with cigarette smoking and chronic obstructive pulmonary disease ...(COPD). However, its prevalence and clinical significance are unknown.
To determine whether ECAC is associated with respiratory morbidity in smokers independent of underlying lung disease.
Analysis of paired inspiratory-expiratory computed tomography images from a large multicenter study (COPDGene) of current and former smokers from 21 clinical centers across the United States. Participants were enrolled from January 2008 to June 2011 and followed up longitudinally until October 2014. Images were initially screened using a quantitative method to detect at least a 30% reduction in minor axis tracheal diameter from inspiration to end-expiration. From this sample of screen-positive scans, cross-sectional area of the trachea was measured manually at 3 predetermined levels (aortic arch, carina, and bronchus intermedius) to confirm ECAC (>50% reduction in cross-sectional area).
Expiratory central airway collapse.
The primary outcome was baseline respiratory quality of life (St George's Respiratory Questionnaire SGRQ scale 0 to 100; 100 represents worst health status; minimum clinically important difference MCID, 4 units). Secondary outcomes were baseline measures of dyspnea (modified Medical Research Council mMRC scale 0 to 4; 4 represents worse dyspnea; MCID, 0.7 units), baseline 6-minute walk distance (MCID, 30 m), and exacerbation frequency (events per 100 person-years) on longitudinal follow-up.
The study included 8820 participants with and without COPD (mean age, 59.7 SD, 6.9 years; 4667 56.7% men; 4559 51.7% active smokers). The prevalence of ECAC was 5% (443 cases). Patients with ECAC compared with those without ECAC had worse SGRQ scores (30.9 vs 26.5 units; P < .001; absolute difference, 4.4 95% CI, 2.2-6.6) and mMRC scale scores (median, 2 interquartile range IQR, 0-3) vs 1 IQR, 0-3; P < .001), but no significant difference in 6-minute walk distance (399 vs 417 m; absolute difference, 18 m 95% CI, 6-30; P = .30), after adjustment for age, sex, race, body mass index, forced expiratory volume in the first second, pack-years of smoking, and emphysema. On follow-up (median, 4.3 IQR, 3.2-4.9 years), participants with ECAC had increased frequency of total exacerbations (58 vs 35 events per 100 person-years; incidence rate ratio IRR, 1.49 95% CI, 1.29-1.72; P < .001) and severe exacerbations requiring hospitalization (17 vs 10 events per 100 person-years; IRR, 1.83 95% CI, 1.51-2.21; P < .001).
In a cross-sectional analysis of current and former smokers, the presence of ECAC was associated with worse respiratory quality of life. Further studies are needed to assess long-term associations with clinical outcomes.
Chronic obstructive pulmonary disease (COPD) is associated with a two-to-five fold increase in the risk of coronary artery disease independent of shared risk factors. This association is hypothesized ...to be mediated by systemic inflammation but this link has not been established.
We included 300 participants enrolled in the SPIROMICS cohort, 75 each of lifetime non-smokers, smokers without airflow obstruction, mild-moderate COPD, and severe-very severe COPD. We quantified emphysema and airway disease on computed tomography, characterized visual emphysema subtypes (centrilobular and paraseptal) and airway disease, and used the Weston visual score to quantify coronary artery calcification (CAC). We used the Sobel test to determine whether markers of systemic inflammation mediated a link between spirometric and radiographic features of COPD and CAC.
FEV
/FVC but not quantitative emphysema or airway wall thickening was associated with CAC (p = 0.036), after adjustment for demographics, diabetes mellitus, hypertension, statin use, and CT scanner type. To explain this discordance, we examined visual subtypes of emphysema and airway disease, and found that centrilobular emphysema but not paraseptal emphysema or bronchial thickening was independently associated with CAC (p = 0.019). MMP3, VCAM1, CXCL5 and CXCL9 mediated 8, 8, 7 and 16% of the association between FEV
/FVC and CAC, respectively. Similar biomarkers partially mediated the association between centrilobular emphysema and CAC.
The association between airflow obstruction and coronary calcification is driven primarily by the centrilobular subtype of emphysema, and is linked through bioactive molecules implicated in the pathogenesis of atherosclerosis.
ClinicalTrials.gov: Identifier: NCT01969344 .
Expiratory central airway collapse is associated with respiratory morbidity independent of underlying lung disease. However, not all smokers develop expiratory central airway collapse, and the ...etiology of expiratory central airway collapse in adult smokers is unclear. Paraseptal emphysema in the paratracheal location, by untethering airway walls, may predispose smokers to developing expiratory central airway collapse.
To evaluate whether paratracheal paraseptal emphysema is associated with expiratory central airway collapse.
We analyzed paired inspiratory and expiratory computed tomography scans from participants enrolled in a multicenter study (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) of smokers aged 45 to 80 years. Expiratory central airway collapse was defined as greater than or equal to 50% reduction in cross-sectional area of the trachea during expiration. In a nested case-control design, participants with and without expiratory central airway collapse were included in a 1:2 fashion, and inspiratory scans were further analyzed using the Fleischner Society criteria for presence of centrilobular emphysema, paraseptal emphysema, airway wall thickening, and paratracheal paraseptal emphysema (maximal diameter ≥ 0.5 cm).
A total of 1,320 patients were included, 440 with and 880 without expiratory central airway collapse. Those with expiratory central airway collapse were older, had higher body mass index, and were less likely to be men or current smokers. Paratracheal paraseptal emphysema was more frequent in those with expiratory central airway collapse than control subjects (16.6 vs. 11.8%; P = 0.016), and after adjustment for age, race, sex, body mass index, smoking pack-years, and forced expiratory volume in 1 second, paratracheal paraseptal emphysema was independently associated with expiratory central airway collapse (adjusted odds ratio, 1.53; 95% confidence interval, 1.18-1.98; P = 0.001). Furthermore, increasing size of paratracheal paraseptal emphysema (maximal diameter of at least 1 cm and 1.5 cm) was associated with greater odds of expiratory central airway collapse (adjusted odds ratio, 1.63; 95% confidence interval, 1.18-2.25; P = 0.003 and 1.77; 95% confidence interval, 1.19-2.64; P = 0.005, respectively).
Paraseptal emphysema adjacent to the trachea is associated with expiratory central airway collapse. The identification of this risk factor on inspiratory scans should prompt further evaluation for expiratory central airway collapse. Clinical trial registered with ClinicalTrials.gov (NCT 00608764).
Chest computed tomography is acquired in the axial plane, but sternal injuries may be missed on axial images. This study hypothesized that sagittal sternal reconstruction images improve detection of ...sternal injury and radiologist's confidence in diagnosis compared to axial images. Five radiologists independently reviewed first axial images and on a different day sagittal images of a retrospective set of trauma cases recording presence/absence of a sternal injury and/or adjacent hematoma. The reviewer's confidence in the presence/absence of a sternal injury was assessed on a 5-point scale.
Sagittal reconstructions generally yielded higher interreader agreement and confidence indices on statistical analysis.
This edited book expands the current scholarship on teaching world languages for social justice and equity in K-12 and postsecondary contexts in the US. Over the past decade, demand has been growing ...for a more critical approach to teaching languages and cultures: in response, this volume brings together a group of scholars whose work bridges the fields of world language education and critical approaches to education. Within the current US context, the chapters address the following key questions: (1) How are pre-service or in- service world language teachers/professors embedding issues, understandings, or content related to social justice, human rights, access, critical pedagogy and equity into their teaching and curriculum? (2) How are teacher educators preparing language teachers to teach for social justice, human rights, access and equity?
Severe myocarditis associated with electrical conduction abnormalities and occasionally heart failure has been well documented following treatment with immune checkpoint blockade with an estimated ...incidence of less than 1%. However, the incidence, early detection, and management of less severe immune-related myocarditis are unknown since most immunotherapy trials have not included routine cardiac monitoring. Herein, we provide the first description of subclinical or smoldering myocarditis with minimal signs and symptoms following immune checkpoint blockade with a single dose of ipilimumab and nivolumab.
Our patient was diagnosed with immune checkpoint blockade-induced myocarditis based upon an acute rise in serum cardiac troponin I beginning 2 weeks after the initial dose of ipilimumab/nivolumab consistent with the reported median onset of clinical myocarditis at 17 days, as well as a lack of other causes despite extensive cardiac evaluation. The patient initially presented with intractable nausea with no known gastrointestinal etiology. High dose glucocorticoid therapy led to rapid resolution of nausea and a four-fold decrease in troponin I over 4 days. Serum troponin I spiked again following a steroid taper to 13 times the upper limit of normal with endomyocardial biopsy revealing collagen fibrosis and lymphocytic inflammation predominantly comprised of CD8+ T cells consistent with chronic smoldering myocarditis. Serum anti-striated muscle antibodies were also detected with no evidence of rhabdomyolysis. Serum cardiac troponin I levels as an indicator of ongoing myocyte damage gradually improved with chronic prednisone at 10 mg daily. Late addition of intravenous immunoglobulin was associated with rapid normalization of creatine kinase-myocardial band.
This case demonstrates that subclinical, smoldering myocarditis may occur following immune checkpoint blockade, with evidence of both humoral and cell-mediated immunity responsive to corticosteroid therapy. This experience supports early monitoring for myocarditis with serial electrocardiograms and serum troponin I determinations in large, prospective cohorts of patients receiving combination immune checkpoint blockade as early detection and initiation of immunosuppression may forestall fulminant presentation of this disease and limit myocardial damage.
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