Seung Won Ra

Xenon ventilation imaging using dual-energy computed tomography in asthmatics: initial experience.

Purpose:To assess the feasibility of xenon ventilation computed tomography (CT) for evaluating ventilation abnormality in asthmatics. Materials and Methods:Twenty-two, stable asthmatics (M:F = 10:12; mean age, 57.6) were included. Single-phase, whole-thorax, dual-energy CT was performed using dual-source CT (Somatom Definition, Siemens) after subjects had inhaled 30% xenon for 90 seconds. Parameters include 512 × 512 matrix; 14 × 1.2 mm collimation; 40/140 eff. mAs at 140/80 kV; 0.45 pitch; and 0.33 seconds rotation time. On the color-coded xenon map, the extent of the ventilation defect was visually assessed using a 5-point scale in each lobe (0, absent defect; 1, 0%–25%; 2, 25%–50%; 3, 50%–75%; and 4, 75%–100%), which was defined as defect score. On the weighted average image, airway wall dimensions were measured at 4 segmental bronchi in both upper and lower lobes. Patients were classified into a defect group and a defect-free group based on the presence of defects shown on the xenon map. Pulmonary function test parameters and airway wall dimensions were compared in those 2 groups. Correlation analyses between the defect score, pulmonary function test, and airway wall dimensions were performed. Results:Sixteen asthmatics showed peripheral ventilation defects on the xenon map (defect score, 6.6 ± 4.2). The defect group had a significantly lower forced expiratory volume in 1 second (FEV1) and thicker airway wall than that of the defect-free group (P = 0.04 and 0.02, respectively). The defect score correlated negatively with a ratio of FEV1 and forced vital capacity (FEV1/FVC) (r = −0.44, P = 0.04) and corrected diffusing capacity (r = −0.76, P = 0.04) and correlated positively with total lung capacity, functional residual volume, and residual volume (r = 0.90, P = 0.005; r= 0.99, P < 0.001; r = 0.88, P = 0.008, respectively). Conclusions:The ventilation defects appeared on xenon ventilation CT in asthmatics with more severe airflow limitation and airway wall thickening. The extent of the ventilation defects showed correlations with parameters of pulmonary function test.

Association of lung function genes with chronic obstructive pulmonary disease.

AbstractBackgroundSpirometric measurements of pulmonary function are important in diagnosing and determining the severity of chronic obstructive pulmonary disease (COPD). We performed this study to determine whether candidate genes identified in genome-wide association studies of spirometric measurements were associated with COPD and if they interacted with smoking intensity. MethodsThe current analysis included 1,000 COPD subjects and 1,000 controls recruited from 24 hospital-based pulmonary clinics. Thirteen SNPs, chosen based on genome-wide association studies of spirometric measurements in the Korean population cohorts, were genotyped. Genetic association tests were performed, adjusting for age, sex, and smoking intensity, using models including a SNP-by-smoking interaction term. ResultsPID1 and FAM13A were significantly associated with COPD susceptibility. There were also significant interactions between SNPs in ACN9 and FAM13A and smoking pack-years, and an association of ACN9 with COPD in the lowest smoking tertile. The risk allele of FAM13A was associated with increased expression of FAM13A in the lung.ConclusionsWe have validated associations of FAM13A and PID1 with COPD. ACN9 showed significant interaction with smoking and is a potential candidate gene for COPD. Significant associations of genetic variants of FAM13A with gene expression levels suggest that the associated loci may act as genetic regulatory elements for FAM13A gene expression.

Response patterns to bronchodilator and quantitative computed tomography in chronic obstructive pulmonary disease

Background:  Patients with chronic obstructive pulmonary disease (COPD) show different spirometric response patterns to bronchodilator, such that some patients show improvement principally in expiratory flow (forced expiratory volume in 1 s; FEV1), whereas others respond by improvement of lung volume (forced vital capacity; FVC). The mechanisms of these different response patterns to bronchodilator remain unclear. We investigated the associations between bronchodilator responsiveness and quantitative computed tomography (CT) indices in patients with COPD.

Exertional Desaturation as a Predictor of Rapid Lung Function Decline in COPD

Background: To date, no clinical parameter has been associated with the decline in lung function other than emphysema severity in COPD. Objectives: The main purpose of this study was to explore whether the rate of lung function decline differs between COPD patients with and without exertional desaturation. Methods: A total of 224 subjects were selected from the Korean Obstructive Lung Disease cohort. Exertional desaturation was assessed using the 6-min walk test (6MWT), and defined as a post-exercise oxygen saturation (SpO2) of <90% or a ≥4% decrease. The cohort was divided into desaturator (n = 47) and non-desaturator (n = 177) groups. Results: There was a significant difference between the desaturator and non-desaturator groups in terms of the change in pre-bronchodilator forced expiratory volume in 1 s (FEV1) over a 3-year period of follow-up (p = 0.006). The mean rate of decline in FEV1 was greater in the desaturator group (33.8 ml/year) than in the non-desaturator group (11.6 ml/year). A statistically significant difference was also observed between the two groups in terms of the change in the St. Georges Respiratory Questionnaire (SGRQ) total score over 3 years (p = 0.001). Conclusions: This study suggests, for the first time, that exertional desaturation may be a predictor of rapid decline in lung function in patients with COPD. The 6MWT may be a useful test to predict a rapid lung function decline in COPD.

Distinguishing tuberculosis from Mycobacterium avium complex disease using an interferon-gamma release assay.

SETTING The QuantiFERON-TB Gold (QFT-G) test can be used to distinguish between tuberculosis (TB) and non-tuberculous mycobacterial disease, but a high background TB infection rate may pose a problem. Although the QuantiFERON-TB (QFT) test, the first-generation QFT-G test, employs a non-specific PPD antigen, avium sensitin is also used as a stimulating antigen. OBJECTIVE To evaluate the utility of these two interferon gamma release assays (IGRAs), QFT-G and QFT, and the tuberculin skin test (TST), to differentiate TB from Mycobacterium avium complex (MAC) disease in an intermediate TB burden country. METHODS We compared the diagnostic performance of these three tests in 38 prospectively enrolled patients with TB and 40 with MAC lung disease. RESULTS The TST yielded positive results in 70.6% of TB and 47.5% of MAC patients; the proportions were respectively 89.5% and 34.3% for QFT-G and 86.8% and 35.3% for QFT. The three tests were of similar accuracy, sensitivity and specificity in diagnosing TB. CONCLUSION Our findings indicate that the TST and IGRAs could not discriminate between active TB and MAC disease or latent TB infection in a TB-endemic area.

Chronic Obstructive Pulmonary Disease Assessment Test Can Predict Depression: A Prospective Multi-Center Study

This study was conducted to investigate the association between the chronic obstructive pulmonary disease (COPD) assessment test (CAT) and depression in COPD patients. The Korean versions of the CAT and patient health questionnaire-9 (PHQ-9) were used to assess COPD symptoms and depressive disorder, respectively. In total, 803 patients with COPD were enrolled from 32 hospitals and the prevalence of depression was 23.8%. The CAT score correlated well with the PHQ-9 score (r=0.631; P<0.001) and was significantly associated with the presence of depression (β±standard error, 0.452±0.020; P<0.001). There was a tendency toward increasing severity of depression in patients with higher CAT scores. By assessment groups based on the 2011 Global Initiative for Chronic Obstructive Lung Disease guidelines, the prevalence of depression was affected more by current symptoms than by airway limitation. The area under the receiver operating characteristic curve for the CAT was 0.849 for predicting depression, and CAT scores ≥21 had the highest accuracy rate (80.6%). Among the eight CAT items, energy score showed the best correlation and highest power of discrimination. CAT scores are significantly associated with the presence of depression and have good performance for predicting depression in COPD patients.

Validation of the lower limit of normal diffusing capacity for detecting emphysema.

Background: Diffusing capacity for carbon monoxide (DLco) has been regarded as reliable for detecting emphysema. The lower 5th percentile of the reference population has been used as the lower limit of normal (LLN) for DLco, without clinical validation. Objectives: We performed this study to validate the LLN for DLco and to determine the optimum cutoff LLN value for detecting emphysema. Methods: A total of 197 COPD patients and 103 healthy adult subjects were included. COPD patients with emphysema were defined as COPD patients in whom volumetric CT showed that the volume fraction of the lung at less than –950 Hounsfield units at full inspiration was more than 15%. All other COPD patients were defined as COPD patients without emphysema. All measured DLco values were transformed to estimates of reference population percentiles. ROC curve analysis was used to validate and to determine the optimum cutoff percentile value as the LLN for DLco. Results: Of the 197 COPD patients, 126 were classified as having emphysema and 71 as without emphysema. On ROC curve analysis, the lower 5th percentile used as the LLN for DLco had a sensitivity of 68.3% and a specificity of 98.1% to differentiate COPD patients with emphysema from healthy subjects. The lower 9th percentile was the best LLN cutoff value for detecting COPD patients with emphysema. Conclusion: The lower 5th percentile of the reference population may not be the best LLN cutoff value for DLco for detecting emphysema.

Predictors of Pulmonary Function Response to Treatment with Salmeterol/fluticasone in Patients with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and responses to therapies are highly variable. The aim of this study was to identify the predictors of pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD. A total of 127 patients with stable COPD from the Korean Obstructive Lung Disease (KOLD) Cohort, which were prospectively recruited from June 2005 to September 2009, were analyzed retrospectively. The prediction models for the FEV1, FVC and IC/TLC changes after 3 months of treatment with salmeterol/fluticasone were constructed by using multiple, stepwise, linear regression analysis. The prediction model for the FEV1 change after 3 months of treatment included wheezing history, pre-bronchodilator FEV1, post-bronchodilator FEV1 change and emphysema extent on CT (R = 0.578). The prediction models for the FVC change after 3 months of treatment included pre-bronchodilator FVC, post-bronchodilator FVC change (R = 0.533), and those of IC/ TLC change after 3 months of treatment did pre-bronchodilator IC/TLC and post-bronchodilator FEV1 change (R = 0.401). Wheezing history, pre-bronchodilator pulmonary function, bronchodilator responsiveness, and emphysema extent may be used for predicting the pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD.

Different therapeutic responses in chronic obstructive pulmonary disease subgroups

SETTING Eleven referring hospitals in South Korea. OBJECTIVE To compare therapeutic responses in chronic obstructive pulmonary disease (COPD) subgroups, classified by diffusing capacity of the lung for carbon monoxide (DL(CO)) and lung volume. DESIGN A total of 130 stable male COPD patients were classified into four subgroups according to baseline DL(CO) and residual volume/total lung capacity (RV/TLC) ratio. We compared therapeutic responses to short acting β(2)-agonist (SABA) and 3-month combined inhalation of long-acting β(2)-agonist (LABA) and corticosteroid among patients with these subgroups. RESULTS Among the 130 COPD patients, 41 (31.5%) had normal DL(CO) and RV/TLC, 28 (21.5%) low DL(CO) and normal RV/TLC, 31 (23.8%) normal DL(CO) and high RV/TLC, and 30 (23.1%) low DL(CO) and high RV/TLC. The normal DL(CO)/high RV/TLC subgroup showed a significantly larger flow response (changes in forced expiratory volume in 1 s) to salbutamol than the normal DL(CO)/RV/TLC subgroups, and a larger volume response (changes in forced vital capacity) than the two normal RV/TLC subgroups. The normal DL(CO)/high RV/TLC subgroup also showed significantly larger flow and volume response to 3-month combined inhalation of LABA and corticosteroid than the two normal RV/TLC subgroups. CONCLUSION COPD subgroups classified by DL(CO) and RV/TLC may have different pulmonary function responses to pharmacological treatment.

A Case of Atypical Skull Base Osteomyelitis with Septic Pulmonary Embolism

Skull base osteomyelitis (SBO) is difficult to diagnose when a patient presents with multiple cranial nerve palsies but no obvious infectious focus. There is no report about SBO with septic pulmonary embolism. A 51-yr-old man presented to our hospital with headache, hoarseness, dysphagia, frequent choking, fever, cough, and sputum production. He was diagnosed of having masked mastoiditis complicated by SBO with multiple cranial nerve palsies, sigmoid sinus thrombosis, and septic pulmonary embolism. We successfully treated him with antibiotics and anticoagulants alone, with no surgical intervention. His neurologic deficits were completely recovered. Decrease of pulmonary nodules and thrombus in the sinus was evident on the follow-up imaging one month later. In selected cases of intracranial complications of SBO and septic pulmonary embolism, secondary to mastoiditis with early response to antibiotic therapy, conservative treatment may be considered and surgical intervention may be withheld.