Optimal Tricuspid Regurgitation Velocity to Screen for Pulmonary Hypertension in Tertiary Referral Centers.

BACKGROUND: A mean pulmonary artery pressure >20 mm Hg now defines pulmonary hypertension. We hypothesize that echocardiographic thresholds must be adjusted. RESEARCH QUESTION: Should tricuspid regurgitation velocity thresholds to screen for pulmonary hypertension be revised, given the new hemodynamic definition? STUDY DESIGN AND METHODS: This multicenter retrospective study included 1,608 patients who underwent both echocardiography and right heart catherization within 4 weeks. The discovery cohort consisted of 1,081 individuals; the validation cohort included 527. Screening criteria for pulmonary hypertension were derived with the use of receiver operating characteristic analysis and the Youden index, assuming equal cost for false-positive and -negative classification. A lower threshold was calculated with the use of a predefined sensitivity: 95%. RESULTS: In the discovery cohort, echocardiographic tricuspid regurgitation velocity had a good discrimination for pulmonary hypertension: area under the curve, 88.4 (95% CI, 85.3-91.5). A 3.4-m/s threshold provided a 78% sensitivity, 87% specificity, and 6.13 positive likelihood ratio to detect pulmonary hypertension; 2.7 m/s had a 95% sensitivity and 0.12 negative likelihood ratio to exclude pulmonary hypertension. In the validation cohort, the discovery threshold of 2.7 m/s provided sensitivity and negative likelihood ratios of 80% and 0.31, respectively. Right cardiac size improved detection of pulmonary hypertension in the lower tricuspid regurgitation velocity groups. INTERPRETATION: Our data support a lower tricuspid regurgitation velocity of approximately 2.7 m/s for screening pulmonary hypertension, with a high sensitivity in tertiary referral centers. Right heart chamber measurements improve the diagnostic yield of echocardiography.

Actinomyces lymphadenitis.

Actinomyces is a gram-positive anaerobe that colonizes the human oral cavity. Its pathogenesis involves the disruption of the mucosal membrane, leading to suppuration and subsequent abscess formation, most commonly in the cervicofacial region. The bacteria form masses consisting of aggregates of branching, filamentous bacilli. They typically spread by direct tissue invasion and less commonly through hematogenous spread. Lymphatic spread is extremely uncommon. To the best of our knowledge, only two cases have been reported with lymph node involvement. Clinically, lymphadenopathy associated with Actinomyces may be misinterpreted as malignancy, causing unnecessary surgical interventions when only antibiotics are warranted. This case highlights the importance of properly diagnosing a rare phenomenon of Actinomyces lymphadenitis.

Rapid On-Site Evaluation in Detection of Granulomas in the Mediastinal Lymph Nodes.

RATIONALE: Rapid On-Site Evaluation (ROSE) of specimens collected by endobronchial ultrasound (EBUS)-guided-transbronchial needle aspiration (TBNA) ensures sample adequacy and triages subsequent biopsy procedures. EBUS-TBNA allows sampling of lymph nodes in granulomatous diseases; however, the ability of ROSE to predict the final diagnosis in this setting has not been well characterized. OBJECTIVES: We performed a retrospective evaluation to study the utility of ROSE in the diagnosis of granulomatous diseases as well as to establish the procedure characteristics that would optimize the concordance between ROSE and final diagnosis. METHODS: Charts of patients with a cytological diagnosis of granuloma by EBUS-TBNA between June 2008 and May 2013 were reviewed. Preliminary ROSE findings and final cytological diagnosis were compared. Patient demographics and procedure variables were assessed using mean (±SD). The variables collected were considered in a logistic regression analysis using concordance as the outcome. MEASUREMENTS AND MAIN RESULTS: In our study, 255 procedures were performed to sample 625 lymph nodes that contained granulomas. An average of 2.4 (±1.2) lymph nodes were biopsied per procedure, with a mean size of 14.4 (±7.9) mm. The concordance between ROSE and the final diagnosis was 81.6%. The concordance rate was not impacted by needle size, lymph nodes size or station, number of stations biopsied, or passes per lymph node. The concordance did improve with the experience of the bronchoscopist (P < 0001). CONCLUSIONS: In this single-center study, there was a high concordance between ROSE and the final cytological diagnosis for mediastinal lymph nodes containing granulomas that were sampled by EBUS-TBNA. ROSE may serve to reduce procedure time, enhance sample triaging, and obviate the need for further invasive testing. The only variable associated with increased concordance was the experience of the operator.

A 33-year-old man with multiple bilateral pulmonary pseudoaneurysms.

A 33-year-old man, never smoker, presented with acute-onset dyspnea secondary to bilateral pulmonary emboli. Echocardiography at the time revealed a right atrial myxoma, for which he underwent resection, followed by anticipated lifelong therapeutic anticoagulation therapy.

Burden of cardiovascular disease in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and atherosclerotic vascular disease share several etiopathogenic factors. PURPOSE: To compare the prevalence of self-reported cardiovascular and cerebrovascular disease (CCVD) between COPD and non-COPD subjects using the National Health and Nutrition Examination Survey (NHANES) database. Among subjects without pre-existent CCVD, the short-term and lifetime risks of future CCVD were also compared between the two groups. METHODS: Pooled NHANES 2007-2010 data were analyzed in May 2012 and April 2013. Based on predicted Framingham risk, subjects without self-reported CCVD were classified as follows: high short-term risk, low short-term/high lifetime risk, and low short-term/low lifetime risk for future CCVD. RESULTS: Estimated self-reported CCVD prevalence was 20.0% and 7.4% in COPD and non-COPD groups, respectively (p<0.001). On multivariable analysis, COPD was an independent risk factor for prevalent self-reported CCVD (prevalence ratio=1.4, 95% CI=1.1, 1.8). Among subjects without CCVD, there were significant differences in predicted future CCVD risk between the two groups. In the non-COPD group, prevalence of high short-term risk, low short-term/high lifetime risk, and low short-term/low lifetime risk was 18.9%, 62.7%, and 18.4%, respectively. In the COPD group, corresponding prevalence estimates were 35.8%, 53.2%, and 11.1%, respectively. Men and women had significantly different risk factor profiles for future CCVD. CONCLUSIONS: The prevalence of self-reported CCVD was significantly higher in subjects with COPD than in those without COPD. Among subjects without pre-existent CCVD, the risk of future CCVD was significantly higher in the COPD group than in the non-COPD group.

The natural history of lung function after lung transplantation for α(1)-antitrypsin deficiency.

RATIONALE: Lung transplantation (LT) is an established treatment for end-stage lung diseases, including chronic obstructive pulmonary disease (COPD) associated with α1-antitrypsin deficiency (AATD). OBJECTIVES: We sought to compare the post-transplantation course of patients with AATD and AAT-replete COPD. METHODS: Between June 1991 and January 2008, a total of 231 patients with AAT-replete COPD and 45 with AATD underwent LT at Cleveland Clinic. Data reviewed included baseline recipient, donor, and surgical data; all spirometry evaluations; acute cellular rejection (ACR) events; and survival data. Endpoints included temporal change in FEV1, severity of ACR, and survival. A longitudinal temporal decomposition model was used for analysis. MEASUREMENTS AND MAIN RESULTS: Comparison of overall rates of FEV1 decline in AATD and AAT-replete patients with COPD showed no significant differences (P > 0.09). However, although the single LT patients had similar trends in FEV1 in both groups, patients with AATD with double LT declined faster (P < 0.002) than the AAT-replete patients. No differences in the frequency or severity of ACR episodes were observed (P = 0.32). Furthermore, there was no difference in early or late mortality between patients with AATD and patients with AAT-replete COPD (P > 0.09). CONCLUSIONS: Although overall the post-LT FEV1 slope, severity of ACR, and survival among patients with AATD is similar to that of AAT-replete patients with COPD, patients with AATD with double LT have a faster rate of FEV1 decline. These findings support the eligibility of patients with AATD for LT, and suggest the need for additional studies to better understand the difference between single and double LT in AATD.

Serum heavy metals and obstructive lung disease: results from the National Health and Nutrition Examination Survey.

BACKGROUND: Exposure to hazardous heavy metals such as cadmium and lead has been associated with several chronic diseases. Heavy metal exposure may contribute to increased oxidative stress and inflammation in the lungs, resulting in tissue destruction manifesting clinically as obstructive lung disease (OLD). We aimed to evaluate the association between serum cadmium and lead concentration and OLD. METHODS: Pooled cross-sectional data from the National Health and Nutrition Examination Survey 2007-2010 were used. OLD was defined as an FEV 1 /FVC ratio , 0.7 by spirometry. Active smokers were defined as self-reported current smokers or those with measured serum cotinine 10 ng/mL. Serum cadmium and lead levels were measured using mass spectrometry. RESULTS: The prevalence of OLD was 12.4% (95% CI, 10.2%-13.6%). The mean (SE) cadmium levels in the OLD group were significantly higher in comparison with normal control subjects (0.51 [1.04] vs 0.33 [1.02], P , .001). Similarly, mean (SE) serum lead concentration was significantly higher in the OLD group compared with the control population (1.73 [1.02] vs 1.18 [1.0], P , .001). The association between OLD and smoking was significantly attenuated after adjusting for serum cadmium concentration. In addition, we demonstrated a progressive increase in serum cadmium concentrations with worsening FEV 1 % predicted values among smokers in our study population. CONCLUSION: In a large representative sample of the US population, we demonstrated a significant association between OLD and serum cadmium and lead concentrations. Cadmium appeared to partially mediate the association between smoking and OLD. A dose-response effect between increasing cadmium concentration and progressively worsening lung function was observed in smokers.

Serum cystatin C and emphysema: results from the National Health and Nutrition Examination Survey (NHANES).

BACKGROUND: Cystatin C (CysC) is a potent nonorgan-specific cysteine protease inhibitor and may contribute to elastolysis and tissue destruction by a mechanism of protease­antiprotease imbalance. Given the prevalence of CysC in the serum of smokers and its role in tissue destruction, we aimed to evaluate the association between CysC and emphysema. METHODS: Pooled cross-sectional data from the National Health and Nutrition Examination Survey 1999­2002 were used. Emphysema and chronic bronchitis were defined by a self-reported history ascertained using standardized questionnaires. Active smokers were defined as self-reported current smokers or measured serum cotinine ≥10 ng/mL. Nonactive smokers with a serum cotinine level >0.05 ng/mL were defined as environmental tobacco smoke (ETS)-exposed. RESULTS: The prevalence (95% CI) of emphysema was 1.3% (range = 0.9­1.8%). The mean (SE) CysC level in the emphysema group was significantly higher than in normal controls [1,139 (22) vs. 883 (8) µg/L; p = 0.001]. Upon stratification of the study population by C-reactive protein (CRP) concentrations, we demonstrated a progressive increase in the mean serum CysC level with serially increasing CRP concentrations. Active smokers with emphysema had 115.4 (46.5) µg/L higher mean (SE) CysC levels than the normal controls (p < 0.001). Upon adjusted analysis, we observed that nonactive smokers with significant ETS exposure had 31.2 (15.2) µg/L higher mean (SE) serum CysC levels as compared to ETS unexposed nonactive smokers (p = 0.04). CONCLUSION: In a large representative noninstitutionalized US population, we demonstrated an association between emphysema and serum CysC. Active smokers with emphysema had significantly higher CysC levels. These findings suggest that CysC may play a role in the pathogenesis of smoking-related emphysema.