川田 奈緒子

PURPOSE: As of March 2023, the number of patients with COVID-19 worldwide is declining, but the early diagnosis of patients requiring inpatient treatment and the appropriate allocation of limited healthcare resources remain unresolved issues. In this study we constructed a deep-learning (DL) model to predict the need for oxygen supplementation using clinical information and chest CT images of patients with COVID-19. MATERIALS AND METHODS: We retrospectively enrolled 738 patients with COVID-19 for whom clinical information (patient background, clinical symptoms, and blood test findings) was available and chest CT imaging was performed. The initial data set was divided into 591 training and 147 evaluation data. We developed a DL model that predicted oxygen supplementation by integrating clinical information and CT images. The model was validated at two other facilities (n = 191 and n = 230). In addition, the importance of clinical information for prediction was assessed. RESULTS: The proposed DL model showed an area under the curve (AUC) of 89.9% for predicting oxygen supplementation. Validation from the two other facilities showed an AUC > 80%. With respect to interpretation of the model, the contribution of dyspnea and the lactate dehydrogenase level was higher in the model. CONCLUSIONS: The DL model integrating clinical information and chest CT images had high predictive accuracy. DL-based prediction of disease severity might be helpful in the clinical management of patients with COVID-19.

PURPOSE: In COPD, exacerbation of the disorder causes a deterioration in the quality-of-life and worsens respiratory dysfunction, leading to a poor prognosis. In recent years, nutritional indices have been reported as significant prognostic factors in various chronic diseases. However, the relationship between nutritional indicators and prognosis in elderly subjects with COPD has not been investigated. PATIENTS AND METHODS: We enrolled 91 subjects who received COPD assessment tests (CAT), spirometry, blood tests, and multidetector computed tomography (MDCT). We divided the subjects into two groups according to age (<75 years (n=57) and ≥ 75 years (n=34)). The prognostic nutritional index (PNI) was used to assess immune-nutritional status and was calculated as 10 x serum albumin + 0.005 x total lymphocyte count. We then examined the relationship between PNI and clinical parameters, including exacerbation events. RESULTS: There was no significant correlation between the PNI and CAT, the FEV1%pred, or low attenuation volume percentage (LAV%). In the elderly group, there were significant differences between the groups with or without exacerbation in the CAT and PNI (p=0.008, p=0.004, respectively). FEV1%pred, neutrophil-to-lymphocyte ratio (NLR) and LAV% did not differ between the two groups. The analytical model combining CAT and PNI improved the prediction of exacerbations in the elderly subjects (p=0.0068). CONCLUSION: In elderly subjects with COPD, CAT were associated significantly with the risk of COPD exacerbation, with PNI also a potential predictor. The combined assessment of CAT and PNI may be a useful prognostic tool in subjects with COPD.

RATIONALE AND OBJECTIVES: Pulmonary endarterectomy (PEA) is one of the most effective treatments for chronic thromboembolic pulmonary hypertension (CTEPH). Right heart catheterization (RHC) is the gold standard assessment for pulmonary circulatory dynamics. However, computed tomography (CT) is less invasive than RHC and can elucidate some of the morphological changes caused by thromboembolism. We hypothesized that CT could facilitate the evaluation of heterogeneous pulmonary perfusion. This study investigated whether CT imaging features reflect the disease severity and changes in pulmonary circulatory dynamics in patients with CTEPH before and after PEA. MATERIALS AND METHODS: This retrospective study included 58 patients with CTEPH who underwent PEA. Pre-PEA and post-PEA CT images were assessed for heterogeneity using CT texture analysis (CTTA). The CT parameters were compared with the results of the RHC and other clinical indices and analyzed with receiver operating characteristic curves analysis for patients with and without residual pulmonary hypertension (PH) (post-PEA mean pulmonary artery pressure ≥ 25 mmHg). RESULTS: CT measurements reflecting heterogeneity were significantly correlated with mean pulmonary artery pressure. Kurtosis, skewness, and uniformity were significantly lower, and entropy was significantly higher in patients with residual PH than patients without residual PH. Area under the curve values of pre-PEA and post-PEA entropy between patients with and without residual PH were 0.71 (95% confidence interval 0.57-0.84) and 0.75 (0.63-0.88), respectively. CONCLUSION: Heterogeneity of lung density might reflect pulmonary circulatory dynamics, and CTTA for heterogeneity could be a less invasive technique for evaluation of changes in pulmonary circulatory dynamics in patients with CTEPH undergoing PEA.

PURPOSE: The quantitative assessment of impaired lung motions and their association with the clinical characteristics of COPD patients is challenging. The aim of this study was to measure respiratory kinetics, including asynchronous movements, and to analyze the relationship between lung area and other clinical parameters. MATERIALS AND METHODS: This study enrolled 10 normal control participants and 21 COPD patients who underwent dynamic MRI and pulmonary function testing (PFT). The imaging program was implemented using MATLAB®. Each lung area was detected semi-automatically on a coronal image (imaging level at the aortic valve) from the inspiratory phase to the expiratory phase. The Dice index of the manual measurements was calculated, with the relationship between lung area ratio and other clinical parameters, including PFTs then evaluated. The asynchronous movements of the diaphragm were also evaluated using a sagittal image. RESULTS: The Dice index for the lung region using the manual and semi-automatic extraction methods was high (Dice index = 0.97 ± 0.03). A significant correlation was observed between the time corrected lung area ratio and percentage of forced expiratory volume in 1 s (FEV1%pred) and residual volume percentage (RV%pred) (r = -0.54, p = 0.01, r = 0.50, p = 0.03, respectively). The correlation coefficient between each point of the diaphragm in the group with visible see-saw like movements was significantly lower than that in the group without see-saw like movements (value = -0.36 vs 0.95, p = 0.001). CONCLUSION: Semi-automated extraction of lung area from Cine MRI might be useful for detecting impaired respiratory kinetics in patients with COPD.

RATIONALE AND OBJECTIVES: Changes in the geometry of the chest wall due to lung hyperinflation occur in COPD. However, the quantitative assessment of impaired lung motions and its association with the clinical characteristics of COPD patients are unclear. This study aimed to investigate the respiratory kinetics of COPD patients by dynamic MRI. MATERIALS AND METHODS: This study enrolled 22 COPD patients and 10 normal participants who underwent dynamic MRI and pulmonary function testing (PFT). Changes in the areas of the lung and mediastinum during respiration were compared between the COPD patients and the normal controls. Relationships between MRI, CT parameters, and clinical measures that included PFT results also were evaluated. RESULTS: Asynchronous movements and decreased diaphragmatic motion were found in COPD patients. COPD patients had a larger ratio of MRI-measured lung areas at expiration to inspiration, a smaller magnitude of the peak area change ratio, and a smaller mediastinal-thoracic area ratio than the normal participants. The lung area ratio was associated with FEV1/FVC, predicted RV%, and CT lung volume/predicted total lung capacity (pTLC). The lung area ratio of the right lower and left lower lungs was significantly correlated with emphysema of each lower lobe. The expiratory mediastinal-thoracic area ratio was associated with FEV1% predicted and RV/TLC. CONCLUSION: Changes in the lung areas of COPD patients as shown on MRI reflected the severity of airflow limitation, hyperinflation, and the extent of emphysema. Dynamic MRI provides essential information about respiratory kinetics in COPD.

Dynamic magnetic resonance imaging (MRI) provides essential information on the respiratory kinetics in chronic obstructive pulmonary disease (COPD), such as impaired diaphragm and chest wall motions. The purpose of this study was to develop the semi-automated segmentation program of lungs using cine MRI. We enrolled five control participants and five patients with COPD who underwent cine MRI. The coronal balanced FFE images from each subject were used. The procedures were as follows: First, the maximum inspiratory image was selected from the time-sequential series, and the lung area was manually segmented, which was used for a mask image. Second, both mask image and cine image were accumulated to create a weighted cine image. Lung areas were segmented using the k-means method. Finally, lungs were detected as contiguous image regions with similar signal values using the flood-fill technique. We evaluated the correlation coefficients between the lung area segmented by the semi-automated method and those segmented by a pulmonologist. The correlation coefficients between the semi-automated method and the manual segmentations were excellent (r=0.99, p<0.001). The Dice index was also perfect (0.97). The best number of clusters in the k-means method was 8. These results suggested that the new segmentation method can appropriately extract lungs and help analyze respiratory dynamics in patients with COPD.

肺拡散能力(DLco)は、血液中のヘモグロビン濃度(Hb)の低下に伴ってその値も低下するため、Hb補正が推奨されているが、補正の必要な低Hb患者のDLco測定は稀であり、Hb補正はほとんど行われていない。今回、急性骨髄性白血病(AML)の骨髄移植前評価として行ったDLco測定をきっかけに、Hb補正の効果及び今後の結果報告について検討した。患者は57歳男性。初回検査時のVC、FEV1/FVC、FRCは基準範囲内であったが、%DLco値は60.0%と低拡散能であった。この時のHb値は5.9g/dLであり、Hb補正を行うと、%DLco値は96.4%と基準範囲内になった。計3度の検査を実施し、補正値はいずれも基準範囲内であった。Hb補正はHb値が6〜7g/dL以下の重度低Hb患者に有用であり、補正DLco値の報告には、呼吸機能検査ガイドラインで推奨されているCotesの式を用いることが望ましい。(著者抄録)

© Journal of Thoracic Disease. All rights reserved. Background: Rapid on-site evaluation (ROSE) of cytologic material is widely performed because it provides clinicians with instant diagnostic information. However, the utility of ROSE of touch imprint cytology (ROSE-TIC) during transbronchial biopsy (TBB) remains unclear. The aim of this study was to evaluate the feasibility and accuracy of ROSE-TIC for TBB. Methods: A retrospective study was performed on patients who underwent diagnostic bronchoscopy combined with ROSE-TIC. The results of ROSE-TIC, diagnosed as either positive or negative for malignancy, were compared with the histological findings and final diagnosis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated. The success rate of molecular testing on TBB specimens was also assessed. Results: Overall, 460 patients underwent bronchoscopy with ROSE-TIC. Of these, 377 cases (82.0%) were malignant and 83 cases (18.0%) were non-malignant in the final diagnosis. Compared with the histological findings, ROSE-TIC showed sensitivity, specificity, PPV, NPV, and diagnostic accuracy values of 91.1%, 90.4%, 94.8%, 84.0%, and 90.9%, respectively. Compared with the final diagnosis, ROSE-TIC showed sensitivity, specificity, PPV, NPV, and diagnostic accuracy values of 75.3%, 91.6%, 97.6%, 45.0%, and 78.3%, respectively. Seven discordant cases (1.5%) were positive on ROSE-TIC and negative on final diagnosis. The success rates for molecular analysis from TBB samples were 96.6% for EGFR mutation, 87.3% for ALK rearrangement, 93.1% for ROS1 rearrangement, and 96.2% for PD-L1 expression. Conclusions: The accuracy of ROSE-TIC is high. It can be useful for obtaining instant diagnosis, contributing to a high success rate of molecular analysis for targeted therapy.

Background: Rapid on-site evaluation (ROSE) of cytologic material is widely performed because it provides clinicians with instant diagnostic information. However, the utility of ROSE of touch imprint cytology (ROSE-TIC) during transbronchial biopsy (TBB) remains unclear. The aim of this study was to evaluate the feasibility and accuracy of ROSE-TIC for TBB. Methods: A retrospective study was performed on patients who underwent diagnostic bronchoscopy combined with ROSE-TIC. The results of ROSE-TIC, diagnosed as either positive or negative for malignancy, were compared with the histological findings and final diagnosis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated. The success rate of molecular testing on TBB specimens was also assessed. Results: Overall, 460 patients underwent bronchoscopy with ROSE-TIC. Of these, 377 cases (82.0%) were malignant and 83 cases (18.0%) were non-malignant in the final diagnosis. Compared with the histological findings, ROSE-TIC showed sensitivity, specificity, PPV, NPV, and diagnostic accuracy values of 91.1%, 90.4%, 94.8%, 84.0%, and 90.9%, respectively. Compared with the final diagnosis, ROSE-TIC showed sensitivity, specificity, PPV, NPV, and diagnostic accuracy values of 75.3%, 91.6%, 97.6%, 45.0%, and 78.3%, respectively. Seven discordant cases (1.5%) were positive on ROSE-TIC and negative on final diagnosis. The success rates for molecular analysis from TBB samples were 96.6% for EGFR mutation, 87.3% for ALK rearrangement, 93.1% for ROS1 rearrangement, and 96.2% for PD-L1 expression. Conclusions: The accuracy of ROSE-TIC is high. It can be useful for obtaining instant diagnosis, contributing to a high success rate of molecular analysis for targeted therapy.

BACKGROUND: Combined pulmonary fibrosis with emphysema (CPFE) is a clinically meaningful syndrome characterized by coexisting upper-lobe emphysema and lower-lobe interstitial fibrosis. However, ambiguous diagnostic criteria and, particularly, the absence of objective methods to quantify emphysematous/fibrotic lesions in patients with CPFE confound the interpretation of the pathophysiology of this syndrome. We analyzed the relationship between objectively quantified computed tomography (CT) measurements and the results of pulmonary function testing (PFT) and clinical events in CPFE patients. MATERIALS AND METHODS: We enrolled 46 CPFE patients who underwent CT and PFT. The extent of emphysematous lesions was obtained by calculating the percent of low attenuation area (%LAA). The extent of fibrotic lesions was calculated as the percent of high attenuation area (%HAA). %LAA and %HAA values were combined to yield the percent of abnormal area (%AA). We assessed the relationships between CT parameters and other clinical indices, including PFT results. Multivariate analysis was performed to examine the association between the CT parameters and clinical events. RESULTS: A greater negative correlation with percent predicted diffusing capacity of the lung for carbon monoxide (DLCO %predicted) existed for %AA (r = -0.73, p < 0.001) than for %LAA or %HAA alone. The %HAA value was inversely correlated with percent predicted forced vital capacity (r = -0.48, p < 0.001), percent predicted total lung capacity (r = -0.48, p < 0.01), and DLCO %predicted (r = -0.47, p < 0.01). Multivariate logistic regression analysis found that %AA showed the strongest association with hospitalization events (odds ratio = 1.20, 95% confidence interval = 1.01-1.54, p = 0.029). CONCLUSION: Quantitative CT measurements reflected deterioration in pulmonary function and were associated with hospitalization in patients with CPFE. This approach could serve as a useful method to determine the extent of lung morphology, pathophysiology, and the clinical course of patients with CPFE.

Background: Role-play (RP) and peer review (PR) are occasionally used in training and evaluating communication skills in clinical clerkship (CC). Thus, we evaluated the effect of combining RP and PR during student-oriented CC rounds.Methods: Clerkship students conducted medical interviews with and performed physical examinations on their patients, which were reviewed by five peer students who observed their performance while role-playing as senior physicians or patients' families. The peer reviewers then provided feedback to the students. The performance of the students was evaluated based on a mini-clinical evaluation exercise (Mini-CEX) and a professionalism mini-evaluation exercise (P-MEX) before and after the rounds by two attending physicians. After the CC, the students responded to questionnaires about the rounds.Results: Seventy-five students completed the rounds, and the duration of each round was 41.7 ± 7.1 min. Their communication skills and professionalism abilities on Mini-CEX and P-MEX showed significant improvement after the rounds. Improvements in medical interviewing and physical examinations were also noted. Additionally, the students recognized the importance of multiple viewpoints in patient care through experiences of the rounds.Conclusions: Combining RP and PR with CC rounds improves the students' clinical performance and professionalism and promotes their awareness of the importance of multiple viewpoints in patient care.

PURPOSE: Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury that frequently shows fatal outcomes. As radiographic predictive factors, some reports have focused on the region of ill-aerated lung, but none have focused on well-aerated lung. Our objective was to evaluate the relationship between computed tomography (CT) volume of the well-aerated lung region and prognosis in patients with ARDS. METHOD: This retrospective observational study of a single intensive care unit (ICU) included patients with ARDS treated between April 2011 and May 2013. We identified 42 patients with ARDS for whom adequate helical CT scans were available. CT images were analyzed for 3-dimensional reconstruction, and lung region volumes were measured using automated volumetry methods. Lung regions were identified by CT attenuation in Hounsfield units (HU). RESULTS: Of the 42 patients, 35 (83.3 %) survived 28 days and 32 (76.2 %) survived to ICU discharge. CT lung volumetry was performed within 144.5 ± 76.6 s, and inter-rater reliability of CT lung volumetry for lung regions below -500 HU (well-aerated lung region) were near-perfect. Well-aerated lung region showed a positive correlation with 28-day survival (P = 0.020), and lung volumes below -900 HU correlated positively with 28-day survival and ICU survival, respectively (P = 0.028, 0.017). Survival outcome was better for percentage of well-aerated lung region/predicted total lung capacity ≥40 % than for <40 % (P = 0.039). CONCLUSIONS: CT lung volumetry of the well-aerated lung region using an automated method allows fast, reliable quantitative CT analysis and potentially prediction of the clinical course in patients with ARDS.

The migration of lung fibroblasts plays a pivotal role in wound repair and fibrotic processes in the lung. Although the receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of lung diseases, its role in lung fibroblast migration is unclear. The current study examined the effect of three different RAGE ligands, namely, high mobility group box 1 (HMGB1), S100A12, and N-epsilon-(carboxymethyl) lysine (CML), on human fibronectin-directed human fetal lung fibroblast (HFL-1) migration. HMGB1 augmented, whereas S100A12 inhibited, HFL-1 migration in a concentration-dependent manner. CML did not affect HFL-1 migration. The effect of HMGB1 was not through RAGE. However, the effect of S100A12 was mediated by RAGE, but not Toll-like receptor 4. S100A12 did not exert a chemoattractant effect, but inhibited HFL-1 chemotaxis and/or chemokinesis. Moreover, S100A12 mediated HFL-1 migration through p38 mitogen-activated protein kinase (MAPK) but not through nuclear factor-kappa B, protein kinase A, phosphatase and tensin homolog deleted on chromosome 10, or cyclooxygenase. In addition, western blot analysis showed that S100A12 augmented p38 MAPK activity in the presence of human fibronectin. In conclusion, S100A12 inhibits lung fibroblast migration via RAGE-p38 MAPK signaling. This pathway could represent a therapeutic target for pulmonary conditions characterized by abnormal tissue repair and remodeling.

<p>現在の心音・呼吸音の聴診訓練は，模擬患者と聴診訓練用マネキンを併用して行われている．この方法は様々な生体音で訓練が行える一方で，リアリティの欠如や，移動・設置が困難であるという欠点がある．我々は拡張現実技術を用いて模擬患者上に様々な症例の心音・呼吸音を再現し，医療面接と聴診手技を模擬患者に対して訓練可能とするシステムEARSを提案してきた．EARSは，聴診器に設置された赤外LEDと模擬患者に張り付けた反射マーカを，カメラユニットで検知することで聴診位置を取得する．しかし従来のEARSには，設置が煩雑，診察動作によって動作不良が発生する恐れがある，といった問題点があった．そこで本研究では，システム設置の煩雑さの解消と聴診器位置検出性能の向上を目的として，カメラユニットを聴診器に搭載したカメラ一体型聴診器デバイスの開発を行った(図参照)．さらに，聴診器位置検出に用いるチェストピースや反射マーカが遮蔽された際の聴診位置の検出法を考案した．提案システムの設置の簡便さ，聴診器検出性能について評価を行い，従来型と比較して性能向上を確認した．また，実際の医学教育現場に導入しアンケートによる評価を行った．</p>

BACKGROUND: The presence of pulmonary hypertension (PH) and treatment with anticoagulant agents could potentially increase the risk for bleeding/hemodynamic complications associated with bronchoscopic procedures. The aim of this study was to assess the safety of diagnostic flexible bronchoscopy (FB) in patients with PH. METHODS: A retrospective review of clinical records of patients with echocardiographic evidence of PH (right ventricular systolic pressure [RVSP] > 40 mm Hg) who underwent diagnostic FB between 2004 and 2016 at a single facility in Japan was conducted. Patients with no clinical evidence suggestive of PH who underwent FB during the same period were enrolled as a pairwise-matched control group; factors used in matching included age, sex, and performed procedures. RESULTS: Overall, there were 45 patients in the PH group and 90 patients in the control group. Six (13%) patients in the PH group had severe PH (RVSP > 61 mm Hg). Forceps biopsies and transbronchial needle aspirations were performed in 62% and 13% of patients, respectively, in the PH group, and 58% and 13% of patients, respectively, in the control group. The total incidence of bleeding during FB was not significantly different between the two groups (18% versus 16%; p = 0.742). Vital signs recorded 2 h after FB were also not significantly different between the two groups. There were no episodes of cardiac arrhythmias or deaths associated with the FB procedures. CONCLUSIONS: The data suggest that diagnostic FB procedures can be performed safely in patients with echocardiographic evidence of PH.

BACKGROUND: Some patients with chronic obstructive pulmonary disease (COPD) have asthma-like features. However, there have been few reports on the structural lung abnormalities found in this patient population. Multi-detector computed tomography (MDCT) can detect emphysematous low-attenuation areas (LAA) within the lung, airway thickness (wall area percentage, WA%), and the loss of pulmonary vasculature as the percentage of small pulmonary vessels with cross-sectional area (CSA) less than 5 mm2 (%CSA<5). We analyzed differences in structural lung changes over time between patients with COPD and those with COPD with asthma-like features using these CT parameters. MATERIAL AND METHODS: We performed pulmonary function tests (PFTs), MDCT, and a COPD assessment test (CAT) in 50 patients with COPD and 29 patients with COPD with asthma-like features at the time of enrollment and two years later. We analyzed changes in clinical parameters and CT indices over time and evaluated differences in structural changes between groups. RESULTS: The CAT score and FEV1 did not significantly change during the follow-up period in either group. Emphysematous LAA regions significantly increased in both groups. The %CSA<5 showed a small but significant increase in COPD patients, but a significant decrease in patients with COPD with asthma-like features. The WA% at the distal bronchi was significantly decreased in COPD, but did not significantly change in COPD with asthma -like features. CONCLUSION: Emphysematous LAA increased in patients with COPD with and without asthma-like features. The %CSA<5 and WA% at the distal bronchi did not change in parallel with LAA. Furthermore, changes in %CSA<5 were significantly different between patients with COPD and those with COPD with asthma-like features. Patients with COPD with asthma-like features may have different longitudinal structural changes than those seen in COPD patients.

BACKGROUND: The 6-min walk test (6MWT) is commonly performed to assess functional status in patients with chronic thromboembolic pulmonary hypertension. However, changes in heart rate and oxygen saturation (SpO2 ) patterns during 6MWT in patients with chronic thromboembolic pulmonary hypertension remain unclear. METHODS: Thirty-one subjects with chronic thromboembolic pulmonary hypertension were retrospectively evaluated to examine the relationships between the change in heart rate (Δheart rate), heart rate acceleration time, slope of heart rate acceleration, heart rate recovery during the first minute after 6MWT (HRR1), change in SpO2 (ΔSpO2 ), SpO2 reduction time, and SpO2 recovery time during 6MWT, and the severity of pulmonary hemodynamics assessed by right heart catheterization and echocardiography. RESULTS: Subjects with severe chronic thromboembolic pulmonary hypertension had significantly longer heart rate acceleration time (144.9 ± 63.9 s vs 96.0 ± 42.5 s, P = .033), lower Δheart rate (47.4 ± 16.9 vs 61.8 ± 13.6 beats, P = .02), and lower HRR1 (13.3 ± 9.0 beats vs 27.1 ± 9.2 beats, P < .001) compared to subjects with mild chronic thromboembolic pulmonary hypertension. Subjects with severe chronic thromboembolic pulmonary hypertension also had significantly longer SpO2 reduction time (178.3 ± 70.3 s vs 134.3 ± 58.4 s, P = .03) and SpO2 recovery time (107.6 ± 35.3 s vs 69.8 ± 32.7 s, P = .004) than did subjects with mild chronic thromboembolic pulmonary hypertension. Multivariate linear regression analysis showed only mean pulmonary arterial pressure independently was associated with heart rate acceleration time and slope of heart rate acceleration. CONCLUSIONS: Heart rate and SpO2 change patterns during 6MWT are predominantly associated with pulmonary hemodynamics in subjects with chronic thromboembolic pulmonary hypertension. Evaluating heart rate and SpO2 change patterns during 6MWT may serve as a safe and convenient way to follow the change in pulmonary hemodynamics.

Background: Although appropriate sedation is recommended during flexible bronchoscopy (FB), patients are at risk for hypoventilation due to inadvertent oversedation. End-tidal capnography is expected as an additional useful monitor for these patients during FB. Objectives: The aim of this study was to evaluate the benefit of additional end-tidal capnography monitoring in reducing the incidence of hypoxemia during FB in patients under sedation. Methods: Patients undergoing FB under moderate sedation without tracheal intubation were randomly assigned to receive standard monitoring including pulse oximetry or additional capnography monitoring. Bronchoscopy examiners for the only capnography group were informed of apnea events by alarms and display of the capnography monitor. Results: A total of 185 patients were enrolled. Patient characteristics were well balanced between the two groups. Hypoxemia (at least one episode of pulse oximeter oxygen saturation [SpO(2)] <90%) was observed in 27 out of 94 patients in the capnography group (29%) and in 42 out of 91 patients in the control group (46%; p = 0.014), resulting in an absolute risk difference of -17.4% (95% confidence interval, -31.1 to -3.7). In the capnography group, hypoxemia duration was shorter (20.4 vs. 41.7 s, p = 0.029), severe hypoxemic events (SpO(2) <85%) were observed less frequently (16 [17%] vs. 29 [32%], p= 0.019), and the mean lowest SpO(2) value was higher (90.5 vs. 87.6%, p = 0.002). Conclusion: End-tidal capnography monitoring can reduce the incidence and duration of hypoxemia during FB in nonintubated patients under sedation. (C) 2018 S. Karger AG, Basel

BACKGROUND: Everolimus (ERL), a mammalian target of rapamycin (mTOR) inhibitor, has been used for the management of several advanced cancers. ERL frequently causes lung injury, although the clinical and radiographic features have not been clarified. The aim of this study was to assess the clinical features of ERL-induced lung injury and determine the associated risk factors. METHODS: This single-center, retrospective study included 45 patients (29 men, 16 women; age, 12-78 years) who had received ERL at our hospital between August 2010 and March 2016. Drug-induced lung injury (DILI) was diagnosed using the Japanese Respiratory Society criteria. We obtained information regarding the clinical course, symptoms, clinical findings, blood test findings, and chest computed tomography findings from the patients' medical records. Risk factors for DILI onset were investigated using the Wilcoxon rank sum test. RESULTS: Fifteen patients (33%) were diagnosed with DILI. The median time from ERL administration to DILI onset was 64 days. High Serum Krebs von den Lungen-6 (KL-6) levels and a low estimated glomerular filtration rate (eGFR) before ERL administration were found to be significant risk factors for DILI. KL-6 and lactate dehydrogenase (LDH) were significantly elevated at the onset of DILI. All 15 patients recovered; 11 were without steroids. CONCLUSIONS: Our results suggest that patients with high KL-6 levels and a low eGFR at baseline are at increased risk of ERL-induced lung injury. In addition, KL-6 and LDH may be useful biomarkers of ERL-induced lung injury.

BACKGROUND: Re-biopsy by bronchoscopy is an important part of treatment for patients with relapsed lung cancer; however, some patients refuse to undergo a re-examination due to discomfort during their first bronchoscopy. The aim of the present study was to determine factors causing discomfort during bronchoscopy and to identify the factors that affect patients' reluctance to undergo repeat examinations via a questionnaire administered immediately after the initial bronchoscopy. METHODS AND FINDINGS: We evaluated 283 patients who underwent bronchoscopy at Chiba University Hospital between September 2015 and March 2017. Following bronchoscopy, the patients answered a questionnaire regarding the procedure. We identified patient characteristics and factors related to bronchoscopy that were associated with patients' reluctance to undergo re-examination. Two hundred nine patients were ultimately enrolled in the study. The factors affecting patient tolerance for re-examination were female sex (odds ratio [OR], 2.81; 95% confidence interval [CI], 1.43-5.53), discomfort during the examination (OR, 1.70; 95% CI, 1.13-2.56), and unexpectedness of discomfort during the examination (OR, 1.83; 95% CI, 1.19-2.81). Patients experienced discomfort most frequently owing to throat anesthesia (n = 50 [24%]). CONCLUSIONS: Comfort during bronchoscopy is an important factor influencing patient tolerance for re-examination. Expectations of discomfort during bronchoscopy, as indicated by instructions provided before examination, and throat anesthesia are also important factors. Detailed explanations about bronchoscopy and improvement of the methods of throat anesthesia could decrease patient discomfort and may help decrease patients' reluctance to undergo re-examinations.

BACKGROUND: Dilatation of the pulmonary artery and right ventricle on chest computed tomography images is often observed in patients with pulmonary hypertension. The clinical significance of these image findings has not been defined in chronic thromboembolic pulmonary hypertension. We investigated whether the pulmonary arterial and right ventricle dilatation was associated with poor outcome in chronic thromboembolic pulmonary hypertension. METHODS: This was a retrospective cohort investigation in 60 subjects with inoperable chronic thromboembolic pulmonary hypertension diagnosed consecutively between 1997 and 2010 at Chiba University Hospital. Digital scout multi-detector chest computed tomography images were obtained. The main pulmonary arterial to ascending aortic diameter ratio and the right ventricular to left ventricular diameter ratio were calculated. RESULTS: Main pulmonary arterial to ascending aortic diameter ratio ranged from 0.85 to 1.84, and right ventricular to left ventricular diameter ratio ranged from 0.71 to 2.88. During the observation period of 1284.5days (range, 21-4550days), 13 patients required hospitalization due to worsening; 6 of them died. Kaplan-Meier analysis showed significant differences in hospitalization between the patients with main pulmonary arterial to ascending aortic diameter ratio of ≥1.1 and <1.1 (log-rank test, p=0.014) and between the patients with right ventricular to left ventricular diameter ratio of ≥1.2 and <1.2 (log-rank test, p=0.013). There was a significant difference in the prognosis between the patients with RV/LV ratio≥1.2 and those with RV/LV ratio<1.2 (log-rank test, p=0.033). CONCLUSIONS: Main pulmonary arterial to ascending aortic diameter ratio measured using enhanced CT images was associated with the risk for first clinical exacerbation, and right ventricular to left ventricular diameter ratio was associated with the risk for poor prognosis in inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: Apnea developing as a result of oversedation is a potential clinical problem in patients undergoing flexible bronchoscopy (FB) under sedation. However, there are no reports of evaluation using a standardized method of the frequency of occurrence of apnea episodes during FB under sedation. The aim of this study was to investigate the frequency of apnea episodes during FB under sedation in the clinical setting by end-tidal capnography. METHODS: This study was a single-institution retrospective review of a prospectively maintained database and medical records, including capnographic data, from April 2015 to March 2016. We enrolled patients who were sedated with midazolam and underwent diagnostic FB under end-tidal capnographic monitoring. Apnea was defined as cessation of airflow for more than 10 s. RESULTS: Data from a total of 121 eligible patients were analyzed. A total of 131 apnea episodes (median duration 33 s) were recorded in 59 patients (48.8%). Prolonged apnea episodes lasting for more than 30 s occurred in 24 patients (19.8%). Furthermore, 55 apnea episodes (42.0%) were followed by a decline of the SpO2 by ≥4% from the baseline. CONCLUSIONS: In this study, end-tidal capnography revealed the occurrence of apnea episodes at a high frequency in patients undergoing FB under sedation in the clinical setting.

BACKGROUND: Recent advances in multidetector computed tomography (MDCT) facilitate acquiring important clinical information for managing patients with COPD. MDCT can detect the loss of lung tissue associated with emphysema as a low-attenuation area (LAA) and the thickness of airways as the wall area percentage (WA%). The percentage of small pulmonary vessels <5 mm2 (% cross-sectional area [CSA] <5) has been recently recognized as a parameter for expressing pulmonary perfusion. We aimed to analyze the longitudinal changes in structural abnormalities using these CT parameters and analyze the effect of exacerbation and smoking cessation on structural changes in COPD patients. METHODS: We performed pulmonary function tests (PFTs), an MDCT, and a COPD assessment test (CAT) in 58 patients with COPD at the time of their enrollment at the hospital and 2 years later. We analyzed the change in clinical parameters including CT indices and examined the effect of exacerbations and smoking cessation on the structural changes. RESULTS: The CAT score and forced expiratory volume in 1 second (FEV1) did not significantly change during the follow-up period. The parameters of emphysematous changes significantly increased. On the other hand, the WA% at the distal airways significantly decreased or tended to decrease, and the %CSA <5 slightly but significantly increased over the same period, especially in ex-smokers. The parameters of emphysematous change were greater in patients with exacerbations and continued to progress even after smoking cessation. In contrast, the WA% and %CSA <5 did not change in proportion to emphysema progression. CONCLUSION: The WA% at the distal bronchi and the %CSA <5 did not change in parallel with parameters of LAA over the same period. We propose that airway disease and vascular remodeling may be reversible to some extent by smoking cessation and appropriate treatment. Optimal management may have a greater effect on pulmonary vascularity and airway disease than parenchymal deconstruction in the early stage of COPD.

Objective Osteoporosis, which is now recognized as a major comorbidity of chronic obstructive pulmonary disease (COPD), must be diagnosed by appropriate methods. The aims of this study were to clarify the relationships between bone mineral density (BMD) and COPD-related clinical variables and to explore the association of BMD with the updated Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification in men. Methods We enrolled 50 Japanese men with clinically stable COPD who underwent dual-energy X-ray absorptiometry (DEXA), pulmonary function testing, and computerized tomography (CT) and who had completed a questionnaire (COPD assessment test [CAT]). We determined the association between the T-score and other tested parameters and compared the BMD of patients in each GOLD category. Results Twenty-three of the 50 patients (46.0%) were diagnosed with osteopenia, and 7 (14.0%) were diagnosed with osteoporosis. The BMD findings were significantly correlated with the CAT score, forced expiratory volume in 1 second percentage predicted (FEV1% predicted), low attenuation volume percentage (LAV%), and percentage of cross-sectional area of small pulmonary vessels (%CSA) on CT images. Notably, the median T-score of the GOLD category D participants was significantly lower than that of the participants in each of the other categories (A [-0.98], B [-1.06], C [-1.05], and D [-2.19], p<0.05). Conclusion Reduced BMD was associated with airflow limitation, extent of radiographic findings, and a poor quality of life (QOL) in patients with COPD. The BMD of GOLD category D patients was the lowest of all of the patients evaluated, and category D patients may benefit from active intervention for osteoporosis.

BACKGROUND: Pulmonary vascular resistance (PVR) is an important parameter in the management of patients with chronic thromboembolic pulmonary hypertension (CTEPH), and numerous noninvasive methods for PVR prediction have been proposed. However, a systematic evaluation of the methods that are specific for CTEPH has not been conducted. We compared a variety of echocardiography-derived prediction indices with direct right heart catheterization (RHC) to identify the most reliable noninvasive indicator of PVR in patients with CTEPH. PATIENTS AND METHODS: Echocardiography and RHC were performed sequentially in 40 patients (mean age: 62.4±11.4 years; 30 females) with CTEPH. We measured the peak flow velocity of tricuspid regurgitation (TRV), tricuspid regurgitation pressure gradient (TRPG), right ventricular outflow tract (RVOT) time-velocity integral (TVIRVOT), left ventricular outflow tract (LVOT) time-velocity integral (TVILVOT), cardiac output at RVOT (CORVOT), and the LVOT (COLVOT) using echocardiography. The parameters TRV/TVIRVOT, TRV/TVILVOT, TRV/CORVOT, TRV/COLVOT, TRPG/TVIRVOT, TRPG/TVILVOT, TRPG/CORVOT, and TRPG/COLVOT were then calculated to predict the PVR. Finally, correlations between these echocardiographic predictors of PVR and the PVR data obtained from RHC (PVRRHC) were assessed. RESULTS: The mean pulmonary arterial pressure and PVRRHC were 32.1±11.4mmHg and 5.4±2.9 Wood units, respectively. TRV/TVIRVOT, TRV/TVILVOT, TRV/COLVOT, TRPG/TVIRVOT, TRPG/TVILVOT, TRPG/CORVOT, and TRPG/COLVOT were all significantly correlated with the PVRRHC, and TRPG/COLVOT was the most strongly correlated with the PVRRHC (r=0.807, p<0.001). CONCLUSIONS: Echocardiographic measurement of TRPG/COLVOT is a reliable noninvasive predictor of PVR in CTEPH patients.

BACKGROUND: Limitations in airflow are detected in some patients with sarcoidosis in association with a poor prognosis. The impulse oscillation system (IOS) is used to treat patients with obstructive lung disease, as it can sensitively detect increased airway resistance. OBJECTIVES: To investigate the characteristics of parameters obtained with IOS in patients with sarcoidosis. METHODS: Forty-six pulmonary sarcoidosis patients at Chiba University Hospital and 20 healthy controls were enrolled. The subjects underwent IOS, pulmonary function testing and multidetector computed tomography. We evaluated the correlations between these indices in the pulmonary sarcoidosis patients and compared the pulmonary sarcoidosis patients with the healthy controls. RESULTS: The ratio of V50/V25, percentage of wall area (WA%), resistance at 5 Hz (R5) and difference between the R5 and R20 (R5-R20) values of the patients with pulmonary sarcoidosis were significantly increased compared to those observed in the controls. Inverse weak correlations were observed between the R5-R20 values and the forced expiratory volume in one second (r = -0.56; p <0.001). The R5-R20 values were correlated with the V50/V25 (r = 0.42; p < 0.005) and WA% (r = 0.43; p < 0.05) values. The WA% values were also significantly correlated with the V50/V25 (r = 0.32; p < 0.05) and R5 (r = 0.33; p < 0.05) values. CONCLUSIONS: IOS parameters were found to be significantly correlated with pulmonary function parameters and the airway wall thickness in pulmonary sarcoidosis patients. IOS is considered to be useful for detecting early manifestations of airflow limitation in pulmonary sarcoidosis patients.

BACKGROUND: The estimation of emphysematous changes is very sensitive to computed tomography (CT) threshold level. In clinical practice, the predetermined threshold is usually set at -950 Hounsfield units (HU) for the detection of low attenuation volume (LAV). However, threshold levels that are tightly connected to pulmonary function abnormalities have not been determined. PURPOSE: To determine the threshold level for calculating an LAV that closely reflects airflow limitation in patients with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: Seventy-six consecutive non-COPD smokers and COPD patients underwent paired inspiratory and expiratory multidetector CT (MDCT). LAV% was segmented every 10 HU between -1000 and -750 HU to examine the correlation between LAV% and indexes of obstructive impairment. RESULTS: LAV% gradually increased as the threshold level increased on both inspiratory and expiratory images. LAV% on inspiratory images was higher than that on expiratory images at all threshold levels between -1000 and -750 HU. The threshold level that correlated with obstructive impairment differed between the two images: -930 HU on inspiratory and -870 or -880 HU on expiratory images. CONCLUSION: LAV% dramatically changed according to the threshold level on both inspiratory and expiratory images, indicating that LAV% is dependent on the attenuation threshold level in patients with COPD. The threshold linking LAV% to airflow limitation was higher on expiratory than on inspiratory images.

We have developed a method called intersection profile method to construct a 4D-MRI (3D+time) from time-series of 2D-MRI. The basic idea is to find the best matching of the intersection profile from the time series of 2D-MRI in sagittal plane (navigator slice) and time series of 2D-MRI in coronal plane (data slice). In this study, we use 4D-MRI to semiautomatically extract the right diaphragm motion of 16 subjects (8 healthy subjects and 8 COPD patients). The diaphragm motion is then evaluated quantitatively by calculating the displacement of each subjects and normalized it. We also generate phase-length map to view and locate paradoxical motion of the COPD patients. The quantitative results of the normalized displacement shows that COPD patients tend to have smaller displacement compared to healthy subjects. The average normalized displacement of total 8 COPD patients is 9.4mm and the average of normalized displacement of 8 healthy volunteers is 15.3mm. The generated phase-length maps show that not all of the COPD patients have paradoxical motion, however if it has paradoxical motion, the phase-length map is able to locate where does it occur.

BACKGROUND: Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is associated with rapid decline in lung function, poorer health-related quality-of-life outcomes, and frequent exacerbations, compared to COPD alone. Although the numbers of patients with ACOS have increased, there is little established evidence regarding diagnostic criteria and treatment options. Thus, the aim of our study was to clarify the clinical, physiological, and radiological features of patients with ACOS. METHODS: We examined a total of 100 patients with COPD and 40 patients with ACOS, who were selected based on clinical criteria. All patients underwent baseline testing, including a COPD assessment test, pulmonary function tests, and multidetector row computed tomography imaging. Percentage of low attenuation volume, percentage of wall area, and percentage of total cross-sectional area of pulmonary vessels less than 5 mm(2) (%CSA <5) were determined using multidetector row computed tomography. ACOS patients were administered a fixed dose of budesonide/formoterol (160/4.5 μg, two inhalations; twice daily) for 12 weeks, after which the ACOS patients underwent multidetector row computed tomography to measure the same parameters. RESULTS: At baseline, the ACOS patients and COPD patients had a similar degree of airflow limitation, vital capacity, and residual volume. ACOS patients had higher COPD assessment test scores, percentage of wall area, and %CSA <5 than COPD patients. Compared to baseline, budesonide/formoterol treatment significantly increased the forced expiratory volume in 1 second and decreased the degree of airway wall thickness (percentage of wall area) as well as pulmonary microvascular density (%CSA <5) in ACOS patients. CONCLUSION: Our results suggest that ACOS is characterized by an airway lesion-dominant phenotype, in contrast to COPD. Higher %CSA <5 might be a characteristic feature of ACOS.

BACKGROUND: The COPD assessment test (CAT) score is a key component of the multifactorial assessment of COPD in the Global initiative for chronic Obstructive Lung Disease (GOLD) guidelines of 2014. Nevertheless, little is known regarding the differences among COPD categories in terms of clinical parameters such as pulmonary function or radiological findings. Thus, our aims in this study were to evaluate the associations between CAT scores and pulmonary clinical parameters, and to investigate factors that could discriminate between a "less symptomatic group" (categories A and C) and a "more symptomatic group" (categories B and D) among stable COPD patients. METHODS: We enrolled 200 outpatients at Chiba University Hospital. Study subjects were assessed by CAT, pulmonary function testing, and multidetector computed tomography (MDCT). We assessed possible correlations between these indices. RESULTS: CAT scores were negatively correlated with percentage of the forced expiratory volume in 1 second predicted value (FEV1 %predicted) and percentage of the diffusing capacity for carbon monoxide per liter of lung volume predicted value (DLCO/VA [%predicted]) results and positively correlated with low attenuation volume percentage (LAV%) and residual volume to total lung capacity ratios (RV/TLC). In the "more symptomatic group" (category B or D), the mean DLCO/VA (%predicted) was significantly lower and the mean LAV% and RV/TLC was significantly higher than those in the "less symptomatic group" (category A or C), respectively. Interestingly, those in category B had higher mean LAV% compared to those in category C. CONCLUSION: CAT scores were significantly correlated with pulmonary function parameters and emphysematous changes on MDCT. The new GOLD classification system would be a step toward a phenotypic approach, especially taking into account the degree of emphysema and hyperinflation.

BACKGROUND: Management of chronic thromboembolic pulmonary hypertension (CTEPH) has recently improved because of advances in pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), and disease-targeted medications. However, patients with inoperable CTEPH or persistent pulmonary hypertension (PH) after these interventions continue to exhibit impaired exercise capacity and limited quality of life (QOL). METHODS: Eight patients with inoperable or residual CTEPH (mean age, 64±12 years; WHO functional class II/III, 6/2; mean pulmonary artery pressure, 47±13 mmHg) in stable condition and receiving disease-targeted medications participated in a 12-week home-based pulmonary rehabilitation program (muscle strength training, respiratory exercises, and walking) with supervised hospital sessions from March 2012 to January 2014. Efficacy parameters were prospectively evaluated at baseline and at completion of the 12-week program. RESULTS: After completion of the pulmonary rehabilitation program, the 6-minute walking distance (6MWD) (33.3±25.1 m), St. George׳s Respiratory Questionnaire activity score, quadriceps force, and 7-day physical activity level were significantly improved compared with baseline. All subjects completed the rehabilitation program. Although one patient experienced presyncope during the in-hospital exercise sessions, no other severe adverse events or complications of pulmonary rehabilitation were observed. CONCLUSIONS: These findings suggest that home-based pulmonary rehabilitation with closely supervised sessions may safely improve exercise capacity, leg muscle strength, general activity in daily life and health-related QOL in CTEPH patients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation caused by emphysema and small airway narrowing. Quantitative evaluation of airway dimensions by multi-detector computed tomography (MDCT) has revealed a correlation between airway dimension and airflow limitation. However, the effect of emphysema on this correlation is unclear. OBJECTIVE: The goal of this study was to determine whether emphysematous changes alter the relationships between airflow limitation and airway dimensions as measured by inspiratory and expiratory MDCT. METHODS: Ninety-one subjects underwent inspiratory and expiratory MDCT. Images were evaluated for mean airway luminal area (Ai), wall area percentage (WA%) from the third to the fifth generation of three bronchi (B1, B5, B8) in the right lung, and low attenuation volume percent (LAV%). Correlations between each airway index and airflow limitation were determined for each patient and compared between patients with and without evidence of emphysema. RESULTS: In patients without emphysema, Ai and WA% from both the inspiratory and expiratory scans were significantly correlated with FEV1. No correlation was detected in patients with emphysema. In addition, emphysematous COPD patients with GOLD stage 1 or 2 disease had significantly lower changes in B8 Ai than non-emphysematous patients. CONCLUSIONS: A significant correlation exists between airway parameters and FEV1 in patients without emphysema. Emphysema may influence airway dimensions even in patients with mild to moderate COPD.

BACKGROUND: We aimed to study whether pulmonary arterial distensibility (PAD) correlates with hemodynamic parameters in chronic thromboembolic pulmonary hypertension (CTEPH) using electrocardiogram (ECG)-gated 320-slice multidetector computed tomography (MDCT). METHODS AND FINDINGS: ECG-gated 320-slice MDCT and right heart catheterization (RHC) was performed in 53 subjects (60.6±11.4 years old; 37 females) with CTEPH. We retrospectively measured the minimum and maximum values of the cross sectional area (CSA) of the main pulmonary artery (mainPA), right pulmonary artery (rtPA), and left pulmonary artery (ltPA) during one heartbeat. PAD was calculated using the following formula: PAD = [(CSAmaximum-CSAminimum)/CSAmaximum]×100(%). The correlation between hemodynamic parameters and PAD was assessed. Mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) were 40.8±8.7 mmHg and 8.3±3.0 wood units, respectively. PAD values were as follows: mainPA (14.0±5.0%), rtPA (12.8±5.6%), and ltPA (9.7±4.6%). Good correlations existed between mainPAD, with mPAP (r = -0.594, p<0.001) and PVR (r = -0.659, p<0.001). The correlation coefficients between rtPAD and ltPAD with pulmonary hemodynamics were all lower or equal than for mainPAD. CONCLUSIONS: PAD measured using ECG-gated 320-slice MDCT correlates with pulmonary hemodynamics in subjects with CTEPH. The mainPA is suitable for PAD measurement.

OBJECTIVES: Structural and functional changes in pulmonary vessels are prevalent at the initial stages of chronic obstructive pulmonary disease (COPD). These vascular alterations can be assessed using cross-sectional area (CSA) of small pulmonary vessels. However, neither in non-COPD smokers nor in COPD patients it has been defined whether the structural changes of pulmonary vessels detected by paired inspiratory and expiratory CT scans are associated with emphysematous changes. We quantified the CSA and low attenuation area (LAA) and evaluated the changes in these parameters in the inspiratory and expiratory phases. MATERIALS AND METHODS: Fifty consecutive non-COPD smokers and COPD patients were subjected to multi detector-row CT and the percentage of vessels with a CSA less than 5 mm(2) as well as the percentage LAA for total lung area (%CSA<5, %LAA, respectively) were calculated. RESULTS: The %CSA<5 correlated negatively with %LAA. The %CSA<5 was lower in COPD patients with emphysema as compared with non-COPD smokers and COPD patients with or without mild emphysema. In addition, the %CSA<5 was lower in the no/mild emphysema subgroup as compared with non-COPD smokers. The respiratory phase change of %CSA<5 in COPD patients was greater than that in non-COPD smokers. CONCLUSION: The percentage of small pulmonary vessels decreased as emphysematous changes increase, and this decrease was observed even in patients with no/mild emphysema. Furthermore, respiratory phase changes in CSA were higher in COPD patients than in non-COPD smokers.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) has been considered to be caused by single or recurrent pulmonary embolism (PE) arising from deep vein thrombosis (DVT). In Japan, female predominance and association of HLA-B*5201 with CTEPH unrelated to DVT were reported. In acute PE residual proximal DVT is associated with larger obstruction of pulmonary arteries. However, it remains uncertain whether DVT and the type of DVT are associated with clinical phenotype of CTEPH. PURPOSE: To clarify the association of DVT and DVT type with clinical phenotype of CTEPH. METHODS: Among 98 consecutive patients who underwent 16 or 64-slice multidetector CT angiography and indirect venography, 91 patients (66% female, age: 56±3 years) with adequate images were enrolled. The associations of DVT and DVT type with pulmonary hemodynamics, CT obstruction index and other clinical parameters were analyzed. RESULTS: DVT was found in 45 patients (49.5%) (distal: 12, proximal: 33), and was significantly associated with male gender and recurrent type. Furthermore, it was more frequent in HLA-B*5201-negative, and d-dimer positive patients. Compared with distal DVT, proximal DVT was associated with male gender, larger CT obstruction index (48.6±13.0 vs. 34.1±13.2%, p=0.004), and higher mean pulmonary arterial pressure (48.2±12.8 vs. 40.8±7.9 mmHg, p=0.03). Proximal DVT was significantly associated with the central type of CTEPH only in HLA-B*5201-negative patients. CONCLUSIONS: The existence and type of DVT were associated with clinical phenotype of CTEPH, and proximal DVT might contribute to the central type of CTEPH in only HLA-B*5201-negative patients.

BACKGROUND: Right-sided heart catheterization (RHC) and pulmonary digital subtraction angiography (PDSA) are the standard methods used in diagnosing suspected or defi nite chronic thromboembolic pulmonary hypertension (CTEPH). We studied the ability of 320-slice CT imaging to detect simultaneously chronic thromboembolic fi ndings in the pulmonary arteries and pulmonary hemodynamics based on the curvature of the interventricular septum (IVS) in CTEPH . METHODS: Forty-four patients with high clinical suspicion of CTEPH underwent RHC, PDSA, and enhanced double-volume retrospective ECG-gated 320-slice CT scan. We measured the sensitivity and specificity of CT imaging to detect thrombi in the pulmonary arteries compared with PDSA. We also compared IVS bowing (expressed as curvature) measured on the short-axis cine heart image with pulmonary arterial pressure (PAP) obtained by RHC. RESULTS: Compared with PDSA, the sensitivity and specificity of CT imaging to detect chronic thromboembolic findings were 97.0% and 97.1% at the main/lobar level and 85.8% and 94.6% at the segmental level, respectively. The correlation coefficients of IVS curvature with systolic PAP and mean PAP were 2 0.79 ( P , .001) and 2 0.86 ( P , .001), respectively. CONCLUSIONS: The use of 320-slice CT imaging allows for less invasive and simultaneous detection of thrombi and evaluation of pulmonary hemodynamics for the diagnostic work-up of CTEPH.