Hrudaya Nath

Pulmonary arterial enlargement and acute exacerbations of COPD

BACKGROUND Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with accelerated loss of lung function and death. Identification of patients at risk for these events, particularly those requiring hospitalization, is of major importance. Severe pulmonary hypertension is an important complication of advanced COPD and predicts acute exacerbations, though pulmonary vascular abnormalities also occur early in the course of the disease. We hypothesized that a computed tomographic (CT) metric of pulmonary vascular disease (pulmonary artery enlargement, as determined by a ratio of the diameter of the pulmonary artery to the diameter of the aorta [PA:A ratio] of >1) would be associated with severe COPD exacerbations. METHODS We conducted a multicenter, observational trial that enrolled current and former smokers with COPD. We determined the association between a PA:A ratio of more than 1 and a history at enrollment of severe exacerbations requiring hospitalization and then examined the usefulness of the ratio as a predictor of these events in a longitudinal follow-up of this cohort, as well as in an external validation cohort. We used logistic-regression and zero-inflated negative binomial regression analyses and adjusted for known risk factors for exacerbation. RESULTS Multivariate logistic-regression analysis showed a significant association between a PA:A ratio of more than 1 and a history of severe exacerbations at the time of enrollment in the trial (odds ratio, 4.78; 95% confidence interval [CI], 3.43 to 6.65; P<0.001). A PA:A ratio of more than 1 was also independently associated with an increased risk of future severe exacerbations in both the trial cohort (odds ratio, 3.44; 95% CI, 2.78 to 4.25; P<0.001) and the external validation cohort (odds ratio, 2.80; 95% CI, 2.11 to 3.71; P<0.001). In both cohorts, among all the variables analyzed, a PA:A ratio of more than 1 had the strongest association with severe exacerbations. CONCLUSIONS Pulmonary artery enlargement (a PA:A ratio of >1), as detected by CT, was associated with severe exacerbations of COPD. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov numbers, NCT00608764 and NCT00292552.).

A combined pulmonary -radiology workshop for visual evaluation of COPD: study design, chest CT findings and concordance with quantitative evaluation

Abstract The purposes of this study were: to describe chest CT findings in normal non-smoking controls and cigarette smokers with and without COPD; to compare the prevalence of CT abnormalities with severity of COPD; and to evaluate concordance between visual and quantitative chest CT (QCT) scoring. Methods: Volumetric inspiratory and expiratory CT scans of 294 subjects, including normal non-smokers, smokers without COPD, and smokers with GOLD Stage I-IV COPD, were scored at a multi-reader workshop using a standardized worksheet. There were 58 observers (33 pulmonologists, 25 radiologists); each scan was scored by 9–11 observers. Interobserver agreement was calculated using kappa statistic. Median score of visual observations was compared with QCT measurements. Results: Interobserver agreement was moderate for the presence or absence of emphysema and for the presence of panlobular emphysema; fair for the presence of centrilobular, paraseptal, and bullous emphysema subtypes and for the presence of bronchial wall thickening; and poor for gas trapping, centrilobular nodularity, mosaic attenuation, and bronchial dilation. Agreement was similar for radiologists and pulmonologists. The prevalence on CT readings of most abnormalities (e.g. emphysema, bronchial wall thickening, mosaic attenuation, expiratory gas trapping) increased significantly with greater COPD severity, while the prevalence of centrilobular nodularity decreased. Concordances between visual scoring and quantitative scoring of emphysema, gas trapping and airway wall thickening were 75%, 87% and 65%, respectively. Conclusions: Despite substantial inter-observer variation, visual assessment of chest CT scans in cigarette smokers provides information regarding lung disease severity; visual scoring may be complementary to quantitative evaluation.

Coronary artery and thoracic calcium on noncontrast thoracic CT scans: Comparison of ungated and gated examinations in patients from the COPD Gene cohort

OBJECTIVE Coronary artery calcification (CAC) and thoracic aortic calcification, (TAC) are frequently detected on ungated multidetector computed tomography (MDCT) performed for lung evaluations. We sought to evaluate concordance of CAC and TAC scores on ungated (thoracic) and electrocardiogaphically (ECG)-gated (cardiac) MDCT scans. METHODS Fifty patients, enrolled in the Genetic Epidemiology of COPD study (COPDGene), were recruited to undergo gated CAC scans with 64-detector row CT, in addition to the ungated thoracic studies already being obtained as part of their study evaluation. Coronary and thoracic calcium were measured similarly (Agatston score, requiring 3 contiguous voxels of >130 Hounsfield units) with low-dose ungated studies and ECG-gated MDCT performed at the same scanning session. Intertechnique scoring variability and concordance were calculated. RESULTS Correlations between gated and ungated CAC and TAC were excellent (r = 0.96). The relative differences (median variability) measured by ECG-gated versus ungated MDCT were relatively high for CAC (44%) but not for TAC (8%). Prevalence of depicted CAC (n = 33; 66%) and TAC (n = 21; 42%) were coincident between ECG-gated and ungated MDCT, respectively (intertechnique concordance, 100%). Bland-Altman plots for CAC showed mean differences of 354 (confidence interval, 169-538) and 16.1 (confidence interval, -89 to 121). CONCLUSION Low-dose ungated MDCT is reliable for prediction of the presence of CAC and assessment of Agatston score. Concordance between methods and between TAC and CAC is high. This technique should allow for atherosclerotic disease risk stratification among patients undergoing ungated lung CT evaluation without requiring additional scanning. Measurement of TAC is almost as accurate from gated CT, and CAC scores are highly concordant.

Genome-wide association study of smoking behaviours in patients with COPD

Background Cigarette smoking is a major risk factor for chronic obstructive pulmonary disease (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 patients with COPD. Methods GWAS were conducted in four independent cohorts encompassing 3441 ever-smoking patients with COPD (Global Initiative for Obstructive Lung Disease stage II or higher). Untyped SNPs were imputed using the HapMap (phase II) panel. Results from all cohorts were meta-analysed. 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 cholinergic receptors, nicotinic, alpha 3/5 (CHRNA3/CHRNA5; eg, p=0.00011 for SNP rs1051730) and cytochrome P450, family 2, subfamily A, polypeptide 6 (CYP2A6; eg, p=2.78×10−5 for a non-synonymous 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 DBH was significantly (p=0.015) associated with smoking cessation. Conclusion The authors identified two candidate regions associated with age at smoking initiation in patients with COPD. Associations of CHRNA3/CHRNA5 and CYP2A6 loci with CPD and DBH with smoking cessation are also likely of importance in the smoking behaviours of patients with COPD.

Usefulness and limitations of transesophageal echocardiography in the assessment of proximal coronary artery stenosis

To assess the usefulness of transesophageal echocardiography in the evaluation of proximal coronary artery stenosis, 111 consecutive patients (mean age 61 years) who had intraoperative transesophageal echocardiography and coronary angiography within 1 week of surgery were studied. Transesophageal echocardiography visualized the entire length of the left main artery (0.2 to 2.2 cm, mean 0.93), 0.2 to 2.2 cm of the proximal left anterior descending artery and 0.1 to 3.4 cm of the proximal left circumflex artery in 103 patients (93%) and 0.1 to 4.6 cm of the proximal right coronary artery in 55 patients (49%). In the coronary artery segments visualized by echocardiography and compared with the corresponding angiographic segments, transesophageal echocardiography correctly identified 23 (96%) of 24 left main stenoses, 11 (78%) of 14 stenoses involving the left anterior descending artery, 6 (75%) of 8 left circumflex stenoses and all 7 stenoses (100%) of the right coronary artery. In all seven patients with ostial stenosis (left main artery in five and right coronary artery in two), the condition was correctly diagnosed by this technique. The sensitivity and specificity of transesophageal echocardiography in the overall evaluation of proximal coronary artery stenosis as customarily defined by angiography were 96% and 99% for the left main artery, 48% and 99% for the left anterior descending artery, 67% and 100% for the left circumflex artery and 37% and 100% for the right coronary artery, respectively. The distance of the stenotic lesion from the origin of the vessel by transesophageal echocardiography also correlated well with that measured by angiography (r = 0.63 to 0.99).(ABSTRACT TRUNCATED AT 250 WORDS)

Collateral flow in patients with acute myocardial infarction

To assess the change in angiographically visualized collaterals in evolving acute myocardial infarction (AMI), coronary arteriograms from 53 patients obtained 6.2 +/- 0.2 hours after onset of AMI symptoms were compared with follow-up angiograms obtained 14 +/- 1 days later. Collaterals were graded according to intensity score and percent of distal infarct-related artery visualized. Collateral intensity score and the percent of distal infarct vessel visualized by collaterals at baseline were low, and there was a significant increase in both values at follow-up angiography. The group of 20 patients with occluded infarct vessels at follow-up study accounted for these increases. In 33 patients with patent infarct vessels at repeat angiography, collateral intensity score and percent of segment visualized were unchanged. Among the patients with occluded infarct vessels at baseline and subsequent improvement in left ventricular (LV) ejection fraction (EF), baseline collateral score and percent of segment visualized were significantly greater than in patients in whom LVEF did not improve. Thus, in patients with evolving AMI, (1) angiographically visible collaterals are not extensive within the early hours of AMI, (2) the extent of collaterals on follow-up angiography may not be representative of that on the day of AMI, (3) collaterals are considerably more common 2 weeks after AMI, especially in patients with occluded infarct arteries during follow-up, and (4) collaterals present at the time of AMI are associated with improved LVEF at 2 weeks.

Projected Outcomes Using Different Nodule Sizes to Define a Positive CT Lung Cancer Screening Examination

BACKGROUND Computed tomography (CT) screening for lung cancer has been associated with a high frequency of false positive results because of the high prevalence of indeterminate but usually benign small pulmonary nodules. The acceptability of reducing false-positive rates and diagnostic evaluations by increasing the nodule size threshold for a positive screen depends on the projected balance between benefits and risks. METHODS We examined data from the National Lung Screening Trial (NLST) to estimate screening CT performance and outcomes for scans with nodules above the 4mm NLST threshold used to classify a CT screen as positive. Outcomes assessed included screening results, subsequent diagnostic tests performed, lung cancer histology and stage distribution, and lung cancer mortality. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the different nodule size thresholds. All statistical tests were two-sided. RESULTS In 64% of positive screens (11598/18141), the largest nodule was 7 mm or less in greatest transverse diameter. By increasing the threshold, the percentages of lung cancer diagnoses that would have been missed or delayed and false positives that would have been avoided progressively increased, for example from 1.0% and 15.8% at a 5 mm threshold to 10.5% and 65.8% at an 8 mm threshold, respectively. The projected reductions in postscreening follow-up CT scans and invasive procedures also increased as the threshold was raised. Differences across nodules sizes for lung cancer histology and stage distribution were small but statistically significant. There were no differences across nodule sizes in survival or mortality. CONCLUSION Raising the nodule size threshold for a positive screen would substantially reduce false-positive CT screenings and medical resource utilization with a variable impact on screening outcomes.

Needle-track metastasis after transthoracic needle biopsy.

Metastasis along the needle track (NTM) after a transthoracic needle biopsy (TNB) is considered a very rare complication. A survey of the membership of the Society of Thoracic Radiology and a review of the English-language literature were conducted to assess the incidence of this complication and its predisposing factors and natural history. A questionnaire was sent to all radiology departments in the United States and Canada that had a senior member of the Society of Thoracic Radiology. The total number of TNB between 1978 and 1993 and occurrences of NTM were elicited. If an NTM was encountered, information on the size of the nodule, proximity to the pleura, histology, size of the biopsy needle, and the interval between biopsy and NTM and outcome of the patient was elicited. The incidence of NTM was estimated using binomial proportions. Results of the literature survey were tabulated to provide similar information. One hundred sixty-five questionnaires were mailed and 75 responses were received. Approximately 68,346 TNB were reported. Five departments reported a total of eight NTM, resulting in an incidence of 0.012%. The average interval between TNB and NTM was 2.6 months. There were no predictable risk factors. The outcome was known in only 11 patients; 4 patients died by the time of reporting (2 after 14 months and 1 each after 6 and 9 months). From the results of this survey, the incidence of NTM after TNB is approximately 0.012%. This small risk is random and unavoidable

Determinants of arterial stiffness in COPD

BackgroundCardiovascular morbidity and mortality is high in patients with chronic obstructive pulmonary disease (COPD) and arterial stiffness is a potentially modifiable risk factor with added predictive value beyond that obtained from traditional risk factors. Arterial stiffness has been the target of pharmacologic and exercise interventions in patients with COPD, but the effects appear limited to those patients with more significant elevations in arterial stiffness. We aimed to identify predictors of increased arterial stiffness in a cohort with moderate to severe COPD.MethodsAortic pulse wave velocity (aPWV) was measured in subjects with moderate to severe COPD enrolled in a multicenter randomized controlled trial. Subjects were categorized into quartiles based on aPWV values and factors affecting high arterial stiffness were assessed. Multivariate models were created to identify independent predictors of high aPWV, and cardiovascular disease (CVD).Results153 patients were included. Mean age was 63.2 (SD 8.2) years and mean FEV1 was 55.4 (SD 15.2) % predicted. Compared to the quartile with the lowest aPWV, subjects in the highest quartile were older, had higher systolic blood pressure (SBP), were more likely to be current smokers, and had greater burden of thoracic aortic calcification. On multivariate analyses, age (adjusted OR 1.14, 95%CI 1.05 to 1.25, p = 0.003) and SBP (adjusted OR 1.06, 95% CI 1.02 to 1.09, p = 0.001) were independent predictors of elevated aPWV. Body mass index, therapy with cholesterol lowering medications and coronary calcification were independent predictors of CVD.ConclusionsElevated arterial stiffness in patients with COPD can be predicted using age, blood pressure and thoracic aortic calcification. This will help identify subjects for enrollment in clinical trials using aPWV for assessing the impact of COPD therapies on CV outcomes.Trial registrationClinicaltrials.gov NCT00857766

Coronary artery to right ventricle fistula in heart transplant recipients: A complication of endomyocardial biopsy

In a series of 74 heart transplant recipients undergoing annual coronary angiography, a coronary artery to right ventricle fistula was observed in 4 patients, an incidence rate of 5.4%, which is much higher than the expected incidence of congenital coronary artery fistula (0.1% to 0.2%). A traumatic origin of the fistulas is unlikely because none of the heart donors had evidence of chest trauma. An endomyocardial biopsy-related etiology of the fistulas is postulated. All fistulas were located in the biopsy sampling area. Patients with a fistula underwent more biopsies before the diagnosis compared with patients without a fistula (20 +/- 11 versus 14 +/- 6, p = 0.05). At least one large arteriole (diameter greater than 0.16 mm) was found on pathologic examination of the biopsy specimens from each of the patients with a fistula (100%) but in only 2 (16.7%) (p less than 0.01) of 12 randomly selected patients without a fistula. The size of the fistula appears to be hemodynamically insignificant in all four patients, judging from angiographic size, normal intracardiac pressures and normal cardiac output values at rest. The diagnosis of a coronary artery to right ventricle fistula is possible and should be entertained at the time of coronary angiography of heart transplant recipients. The clinical significance of the finding is unclear. As long as endomyocardial biopsy remains the diagnostic method of identifying tissue rejection, prevention of the described complication is unlikely.