Subtyping emphysematous COPD by respiratory volume change distributions on CT.

BACKGROUND: There is considerable heterogeneity among patients with emphysematous chronic obstructive pulmonary disease (COPD). We hypothesised that in addition to emphysema severity, ventilation distribution in emphysematous regions would be associated with clinical-physiological impairments in these patients. OBJECTIVE: To evaluate whether the discordance between respiratory volume change distributions (from expiration to inspiration) in emphysematous and non-emphysematous regions affects COPD outcomes using two cohorts. METHODS: Emphysema was quantified using a low attenuation volume percentage on inspiratory CT (iLAV%). Local respiratory volume changes were calculated using non-rigidly registered expiratory/inspiratory CT. The Ventilation Discordance Index (VDI) represented the log-transformed Wasserstein distance quantifying discordance between respiratory volume change distributions in emphysematous and non-emphysematous regions. RESULTS: Patients with COPD in the first cohort (n=221) were classified into minimal emphysema (iLAV% <10%; n=113) and established emphysema with high VDI and low VDI groups (n=46 and 62, respectively). Forced expiratory volume in 1 s (FEV1) was lower in the low VDI group than in the other groups, with no difference between the high VDI and minimal emphysema groups. Higher iLAV%, more severe airway disease and hyperventilated emphysematous regions in the upper-middle lobes were independently associated with lower VDI. The second cohort analyses (n=93) confirmed these findings and showed greater annual FEV1 decline and higher mortality in the low VDI group than in the high VDI group independent of iLAV% and airway disease on CT. CONCLUSION: Lower VDI is associated with severe airflow limitation and higher mortality independent of emphysema severity and airway morphological changes in patients with emphysematous COPD.

Clinical, radiological and pathological features of idiopathic and secondary interstitial pneumonia with pleuroparenchymal fibroelastosis in patients undergoing lung transplantation.

AIMS: Idiopathic pleuroparenchymal fibroelastosis (PPFE) is a rare type of idiopathic interstitial pneumonia, and pathological PPFE is also observed in patients with secondary interstitial pneumonia. This study aimed to evaluate the pathological findings associated with radiological PPFE-like lesions and the clinical and morphological features of patients with pathological PPFE. METHODS AND RESULTS: We retrospectively reviewed the pathology of the explanted lungs from 59 lung transplant recipients with radiological PPFE-like lesions. Pathological PPFE lesions were identified in 14 patients with idiopathic disease and in 12 patients with secondary disease. Pathological PPFE was associated with previous pneumothorax, volume loss in the upper lobes, and a flattened chest. Patients with idiopathic disease and those with secondary disease with pathological PPFE had similar clinical, radiological and pathological findings, whereas fibroblastic foci were more common in patients with idiopathic disease, and patients with secondary disease more frequently showed alveolar septal thickening with elastosis or fibrosis. Post-transplantation survival did not differ between patients with idiopathic and secondary disease with pathological PPFE (log-rank; P = 0.57) and was similar between patients with idiopathic disease with pathological PPFE and those with idiopathic pulmonary fibrosis (IPF) (log-rank; P = 0.62). CONCLUSIONS: Not all patients with interstitial pneumonia with radiological PPFE-like lesions have pathological PPFE. Characteristic clinical features can suggest the presence of pathological PPFE, and idiopathic and secondary cases with pathological PPFE are similar except for fibroblastic foci in idiopathic cases and alveolar septal thickening with elastosis or fibrosis in secondary cases. Patients with pathological PPFE have a similar prognosis to those with IPF after transplantation.

Deep learning-based algorithm improved radiologists' performance in bone metastases detection on CT.

OBJECTIVES: To develop and evaluate a deep learning-based algorithm (DLA) for automatic detection of bone metastases on CT. METHODS: This retrospective study included CT scans acquired at a single institution between 2009 and 2019. Positive scans with bone metastases and negative scans without bone metastasis were collected to train the DLA. Another 50 positive and 50 negative scans were collected separately from the training dataset and were divided into validation and test datasets at a 2:3 ratio. The clinical efficacy of the DLA was evaluated in an observer study with board-certified radiologists. Jackknife alternative free-response receiver operating characteristic analysis was used to evaluate observer performance. RESULTS: A total of 269 positive scans including 1375 bone metastases and 463 negative scans were collected for the training dataset. The number of lesions identified in the validation and test datasets was 49 and 75, respectively. The DLA achieved a sensitivity of 89.8% (44 of 49) with 0.775 false positives per case for the validation dataset and 82.7% (62 of 75) with 0.617 false positives per case for the test dataset. With the DLA, the overall performance of nine radiologists with reference to the weighted alternative free-response receiver operating characteristic figure of merit improved from 0.746 to 0.899 (p < .001). Furthermore, the mean interpretation time per case decreased from 168 to 85 s (p = .004). CONCLUSION: With the aid of the algorithm, the overall performance of radiologists in bone metastases detection improved, and the interpretation time decreased at the same time. KEY POINTS: • A deep learning-based algorithm for automatic detection of bone metastases on CT was developed. • In the observer study, overall performance of radiologists in bone metastases detection improved significantly with the aid of the algorithm. • Radiologists' interpretation time decreased at the same time.

Mycotic pseudoaneurysm in the internal carotid artery secondary to cranial base abscess diagnosed with optic neuritis: a case report.

Aspergillus-induced mycotic aneurysm is difficult to treat and often has poor outcomes with severe symptom progression. Early diagnosis is also difficult, and blood and cerebrospinal fluid tests often fail to reveal any findings. A 74-year-old man presented with recurrent nosebleeds in addition to symptoms of left optic neuritis. Contrast-enhanced computed tomography scan revealed a left internal carotid artery pseudoaneurysm protruding into the left Onodi cells, which was identified as the origin of bleeding. Endovascular left internal carotid artery occlusion was performed. One month postoperatively, external ophthalmoplegia and disorientation occurred. Although antibiotic treatment was continued for 1 month, consciousness loss and haematemesis occurred, and a new contralateral right internal carotid artery pseudoaneurysm ruptured, which resulted in death. At autopsy, Aspergillus infection centred on the skull base was pathologically found, although the sinus mucosal surface was normal. This case suggested a mycotic infection secondary to optic neuritis resulted in a left infectious pseudoaneurysm that spreads to the skull base and formed an aneurysm on the contralateral side 4 months thereafter. Therefore, the possibility that features of the Onodi cells contributed to the spread of inflammation inside and outside the skull and were involved in the formation of aneurysms inside and outside the dura mater was considered for the first time.

Enhancement of acetyl-CoA flux for photosynthetic chemical production by pyruvate dehydrogenase complex overexpression in Synechococcus elongatus PCC 7942.

Genetic manipulation in cyanobacteria enables the direct production of valuable chemicals from carbon dioxide. However, there are still very few reports of the production of highly effective photosynthetic chemicals. Several synthetic metabolic pathways (e.g., isopropanol, acetone, isoprene, and fatty acids) have been constructed by branching from acetyl-CoA and malonyl-CoA, which are key intermediates for photosynthetic chemical production downstream of pyruvate decarboxylation. Recent reports of the absolute determination of cellular metabolites in Synechococcus elongatus PCC 7942 have shown that its acetyl-CoA levels corresponded to about one hundredth of the pyruvate levels. In short, one of the reasons for lower photosynthetic chemical production from acetyl-CoA and malonyl-CoA was the smaller flux to acetyl-CoA. Pyruvate decarboxylation is a primary pathway for acetyl-CoA synthesis from pyruvate and is mainly catalyzed by the pyruvate dehydrogenase complex (PDHc). In this study, we tried to enhance the flux toward acetyl-CoA from pyruvate by overexpressing PDH genes and, thus, catalyzing the conversion of pyruvate to acetyl-CoA via NADH generation. The overexpression of PDH genes cloned from S. elongatus PCC 7942 significantly increased PDHc enzymatic activity and intracellular acetyl-CoA levels in the crude cell extract. Although growth defects were observed in overexpressing strains of PDH genes, the combinational overexpression of PDH genes with the synthetic metabolic pathway for acetate or isopropanol resulted in about 7-fold to 9-fold improvement in its production titer, respectively (9.9 mM, 594.5 mg/L acetate, 4.9 mM, 294.5 mg/L isopropanol). PDH genes overexpression would, therefore, be useful not only for the production of these model chemicals, but also for the production of other chemicals that require acetyl-CoA as a key precursor.

Adaptive Voxel Matching for Temporal CT Subtraction.

Temporal subtraction (TS) technique calculates a subtraction image between a pair of registered images acquired from the same patient at different times. Previous studies have shown that TS is effective for visualizing pathological changes over time; therefore, TS should be a useful tool for radiologists. However, artifacts caused by partial volume effects degrade the quality of thick-slice subtraction images, even with accurate image registration. Here, we propose a subtraction method for reducing artifacts in thick-slice images and discuss its implementation in high-speed processing. The proposed method is based on voxel matching, which reduces artifacts by considering gaps in discretized positions of two images in subtraction calculations. There are two different features between the proposed method and conventional voxel matching: (1) the size of a searching region to reduce artifacts is determined based on discretized position gaps between images and (2) the searching region is set on both images for symmetrical subtraction. The proposed method is implemented by adopting an accelerated subtraction calculation method that exploit the nature of liner interpolation for calculating the signal value at a point among discretized positions. We quantitatively evaluated the proposed method using synthetic data and qualitatively using clinical data interpreted by radiologists. The evaluation showed that the proposed method was superior to conventional methods. Moreover, the processing speed using the proposed method was almost unchanged from that of the conventional methods. The results indicate that the proposed method can improve the quality of subtraction images acquired from thick-slice images.

Serum matrix metalloproteinase levels in polymyositis/dermatomyositis patients with interstitial lung disease.

OBJECTIVE: We aimed to clarify the clinical significance of serum levels of MMPs in interstitial lung disease (ILD) complicated with PM/DM (PM/DM-ILD). METHODS: We retrospectively analysed serum levels of seven subsets of MMPs in 52 PM/DM-ILD patients diagnosed at Kyoto University Hospital or Tenri Hospital from January 2005 to December 2014. The patients were sub-grouped based on the presence of anti-amimoacyl-tRNA synthetase antibody (anti-ARS antibody), anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 antibody) or lack of the antibodies (ARS-ILD, MDA5-ILD and other-ILD groups, respectively) and independently analysed. Eighteen PM/DM patients without ILD and 55 healthy control were also analysed. Associations between serum levels of MMPs and clinical findings including mortality were analysed. RESULTS: Among the MMPs analysed, MMP-7 serum levels in the ARS-ILD group were significantly higher compared with those in any of the other groups of PM/DM patients or in healthy controls. On the other hand, in the MDA5-ILD group, serum MMP-7 levels >5.08 ng/ml were associated with worse overall survival both in univariate (P = 0.017; odds ratio 18.0; 95% CI 1.69, 192.00) and multivariate (P = 0.027; odds ratio 14.60; 95% CI 1.11, 192.00) analyses. Immunohistochemical analysis suggested that MMP-7 was expressed in type II alveolar epithelial cells adjacent to the fibrotic lesions. CONCLUSION: Serum MMP-7 levels were higher in anti-ARS antibody-positive PM/DM-ILD patients, while higher serum MMP-7 levels among anti-MDA5 antibody-positive PM/DM-ILD patients were associated with a worse prognosis. Fibrotic processes may be associated with the elevation of serum MMP-7 levels.

CT temporal subtraction improves early detection of bone metastases compared to SPECT.

OBJECTIVES: To compare observer performance of detecting bone metastases between bone scintigraphy, including planar scan and single-photon emission computed tomography, and computed tomography (CT) temporal subtraction (TS). METHODS: Data on 60 patients with cancer who had undergone CT (previous and current) and bone scintigraphy were collected. Previous CT images were registered to the current ones by large deformation diffeomorphic metric mapping; the registered previous images were subtracted from the current ones to produce TS. Definitive diagnosis of bone metastases was determined by consensus between two radiologists. Twelve readers independently interpreted the following pairs of examinations: NM-pair, previous and current CTs and bone scintigraphy, and TS-pair, previous and current CTs and TS. The readers assigned likelihood levels to suspected bone metastases for diagnosis. Sensitivity, number of false positives per patient (FPP), and reading time for each pair of examinations were analysed for evaluating observer performance by performing the Wilcoxon signed-rank test. Figure-of-merit (FOM) was calculated using jackknife alternative free-response receiver operating characteristic analysis. RESULTS: The sensitivity of TS was significantly higher than that of bone scintigraphy (54.3% vs. 41.3%, p = 0.006). FPP with TS was significantly higher than that with bone scintigraphy (0.189 vs. 0.0722, p = 0.003). FOM of TS tended to be better than that of bone scintigraphy (0.742 vs. 0.691, p = 0.070). CONCLUSION: Sensitivity of TS in detecting bone metastasis was significantly higher than that of bone scintigraphy, but still limited to 54%. TS might be superior to bone scintigraphy for early detection of bone metastasis. KEY POINTS: • Computed tomography temporal subtraction was helpful in early detection of bone metastases. • Sensitivity for bone metastasis was higher for computed tomography temporal subtraction than for bone scintigraphy. • Figure-of-merit of computed tomography temporal subtraction was better than that of bone scintigraphy.

Detection of suspected brain infarctions on CT can be significantly improved with temporal subtraction images.

OBJECTIVE: To assess whether temporal subtraction (TS) images of brain CT improve the detection of suspected brain infarctions. METHODS: Study protocols were approved by our institutional review board, and informed consent was waived because of the retrospective nature of this study. Forty-two sets of brain CT images of 41 patients, each consisting of a pair of brain CT images scanned at two time points (previous and current) between January 2011 and November 2016, were collected for an observer performance study. The 42 sets consisted of 23 cases with a total of 77 newly developed brain infarcts or hyperdense artery signs confirmed by two radiologists who referred to additional clinical information and 19 negative control cases. To create TS images, the previous images were registered to the current images by partly using a non-rigid registration algorithm and then subtracted. Fourteen radiologists independently interpreted the images to identify the lesions with and without TS images with an interval of over 4 weeks. A figure of merit (FOM) was calculated along with the jackknife alternative free-response receiver-operating characteristic analysis. Sensitivity, number of false positives per case (FPC) and reading time were analyzed by the Wilcoxon signed-rank test. RESULTS: The mean FOM increased from 0.528 to 0.737 with TS images (p < 0.0001). The mean sensitivity and FPC improved from 26.5% and 0.243 to 56.0% and 0.153 (p < 0.0001 and p = 0.239), respectively. The mean reading time was 173 s without TS and 170 s with TS (p = 0.925). CONCLUSION: The detectability of suspected brain infarctions was significantly improved with TS CT images. KEY POINTS: • Although it is established that MRI is superior to CT in the detection of strokes, the first choice of modality for suspected stroke patients is often CT. • An observer performance study with 14 radiologists was performed to evaluate whether temporal subtraction images derived from a non-rigid transformation algorithm can significantly improve the detectability of newly developed brain infarcts on CT. • Temporal subtraction images were shown to significantly improve the detectability of newly developed brain infarcts on CT.

Temporal subtraction of computed tomography images improves detectability of bone metastases by radiology residents.

OBJECTIVE: Temporal subtraction of CT (TS) images improves detection of newly developed bone metastases (BM). We sought to determine whether TS improves detection of BM by radiology residents as well. METHODS: We performed an observer study using a previously reported dataset, consisting of 60 oncology patients, each with previous and current CT images. TS images were calculated using in-house software. Four residents independently interpreted twice the 60 sets of CT images, without and with TS. They identified BM by marking suspicious lesions likely to be BM. Lesion-based sensitivity and number of false positives per patient were calculated. Figure-of-merit (FOM) was calculated. Detectability of BM, with and without TS, was compared between radiology residents and board-certified radiologists, as published previously. RESULTS: FOM of residents significantly improved by implementing TS (p value < 0.0001). Lesion-based sensitivity, false positives per patients, and FOM were 40.8%, 0.121, and 0.657, respectively, without TS, and 58.1%, 0.0958, and 0.796, respectively, with TS. These findings were comparable with the previously published values for board-certified radiologists without TS (58.0%, 0.19, and 0.758, respectively). CONCLUSION: The detectability of BM by residents improved markedly by implementing TS and reached that of board-certified radiologists without TS. KEY POINTS: • Detectability of bone metastases on CT by residents improved significantly when using temporal subtraction of CT (TS). • Detections by residents with TS and board-certified radiologists without TS were comparable. • TS is useful for residents as it is for board-certified radiologists.

Clinical significance of self-reported cough intensity and frequency in patients with interstitial lung disease: a cross-sectional study.

BACKGROUND: The intensity and frequency of cough remain unclear in interstitial lung disease (ILD). The aim of this study was to evaluate the intensity and frequency of cough in idiopathic interstitial pneumonias (IIPs), connective tissue disease-associated interstitial lung disease (CTD-ILD), and chronic hypersensitivity pneumonia (CHP), and examine their associations with clinical indices. METHODS: In this cross-sectional study, the intensity and frequency of cough were evaluated using a 100-mm visual analogue scale. Scores on the Leicester Cough Questionnaire, chronic dyspnoea scale, and a frequency scale for symptoms of gastro-oesophageal reflux disease (FSSG) were collected. The correlations of cough intensity and frequency with potential predictor variables were tested using bivariate and multiple logistic regression analysis. RESULTS: The study included 70 patients with IIPs, 49 with CTD-ILD, and 10 with CHP. Patients with IIPs had the most severe cough intensity among the three patient groups. In patients with IIPs, both the intensity and frequency of cough were negatively associated with the diffusing capacity of the lung for carbon monoxide and positively with the Composite Physiologic Index (CPI). In CTD-ILD, both the intensity and frequency of cough were correlated with a higher FSSG score. In multivariate analysis of patients with ILD, IIPs and the FSSG score were independently associated with both components of cough, and CPI tended to be independently associated with cough frequency. Finally, we examined the features of the differences between cough intensity and frequency in all patients with ILD. Patients in whom cough frequency was predominant had a greater impairment of health status relative to other patients. CONCLUSIONS: Cough intensity was greater in IIPs than in other ILDs. Different clinical indices were associated with patient-reported cough intensity and frequency according to the subtype of ILD. Cough frequency was more strongly associated with health status than was cough intensity. These findings suggest that medical staff could manage patients with ILD by considering cough-related factors when assessing the intensity and frequency of cough.

Clinical significance of radiological pleuroparenchymal fibroelastosis pattern in interstitial lung disease patients registered for lung transplantation: a retrospective cohort study.

BACKGROUND: Radiological pleuroparenchymal fibroelastosis (PPFE) lesion is characterized by pleural thickening with associated signs of subpleural fibrosis on high-resolution computed tomography (HRCT). This study evaluated the clinical significance of radiological PPFE as an isolated finding or associated with other interstitial lung diseases (ILDs) in patients having fibrotic ILDs and registered for cadaveric lung transplantation (LT). METHODS: This retrospective study included 118 fibrotic ILD patients registered for LT. Radiological PPFE on HRCT was assessed. The impact of radiological PPFE on clinical features and transplantation-censored survival were evaluated. RESULTS: Radiological PPFE was observed in 30/118 cases (25%): definite PPFE (PPFE concentrated in the upper lobes, with involvement of lower lobes being less marked) in 12 (10%) and consistent PPFE (PPFE not concentrated in the upper lobes, or PPFE with features of coexistent disease present elsewhere) in 18 (15%). Of these, 12 had late-onset non-infectious pulmonary complications after hematopoietic stem-cell transplantation and/or chemotherapy (LONIPCs), 9 idiopathic PPFE, and 9 other fibrotic ILDs (idiopathic pulmonary fibrosis, IPF; other idiopathic interstitial pneumonias, other IIPs; connective tissue disease-associated ILD, CTD-ILD, and hypersensitivity pneumonia, HP). Radiological PPFE was associated with previous history of pneumothorax, lower body mass index, lower percentage of predicted forced vital capacity (%FVC), higher percentage of predicted diffusion capacity of carbon monoxide, less desaturation on six-minute walk test, and hypercapnia. The median survival time of all study cases was 449 days. Thirty-seven (28%) received LTs: cadaveric in 31 and living-donor lobar in six. Of 93 patients who did not receive LT, 66 (71%) died. Radiological PPFE was marginally associated with better survival after adjustment for age, sex, %FVC, and six-minute walk distance < 250 m (hazard ratio 0.51 [0.25-1.05], p = 0.07). After adjustment for covariates, idiopathic PPFE and LONIPC with radiological PPFE was associated with better survival than fibrotic ILDs without radiological PPFE (hazard ratio 0.38 [0.16-0.90], p = 0.03), and marginally better survival than other fibrotic ILDs with radiological PPFE (hazard ratio, 0.20 [0.04-1.11], p = 0.07). CONCLUSIONS: idiopathic PPFE and LONIPC with radiological PPFE has better survival on the wait list for LT than fibrotic ILDs without radiological PPFE, after adjustment for age, sex, %FVC, and six-minute walk distance.

The Clinical Significance of Body Weight Loss in Idiopathic Pulmonary Fibrosis Patients.

BACKGROUND: The significance of the nutritional status in idiopathic pulmonary fibrosis (IPF) is largely unknown. Temporal body weight (BW) change, a dynamic index of nutrition status, can detect the malnutrition more accurately than the conventional single-point body mass index evaluation. OBJECTIVE: To investigate how the temporal BW change influences the clinical courses of IPF. METHODS: This multicenter study enrolled IPF patients from four referral hospitals of interstitial lung diseases in Japan (the Japanese cohort, the derivation cohort) and the Royal Brompton Hospital (the UK cohort, the validation cohort). The annual rate of BW change from the initial presentation was evaluated. A > 5% decrease of BW was defined as a significant BW loss. RESULTS: Twenty-seven out of 124 patients in the Japanese cohort and 13 out of 86 patients in the UK cohort showed significant BW loss. Patients with BW loss showed significantly worse survival in both cohorts. Multivariate analyses revealed that BW loss was an independent factor for decreased survival (Japanese cohort: p = 0.047, UK cohort: p = 0.013). A 6.1% loss of BW was chosen as the optimal cutoff value to predict the 2-year mortality from the initial presentation. The stratified analysis revealed that a 6.1% or greater BW loss could predict worse survival specifically in cases without a greater than 10% decline in forced vital capacity (FVC). CONCLUSIONS: BW loss is independently associated with the survival of IPF patients, particularly when a decline in the FVC was not observed. Further studies are needed to understand the mechanisms underlying BW loss in IPF.

Temporal Subtraction of Serial CT Images with Large Deformation Diffeomorphic Metric Mapping in the Identification of Bone Metastases.

Purpose To determine the improvement of radiologist efficiency and performance in the detection of bone metastases at serial follow-up computed tomography (CT) by using a temporal subtraction (TS) technique based on an advanced nonrigid image registration algorithm. Materials and Methods This retrospective study was approved by the institutional review board, and informed consent was waived. CT image pairs (previous and current scans of the torso) in 60 patients with cancer (primary lesion location: prostate, n = 14; breast, n = 16; lung, n = 20; liver, n = 10) were included. These consisted of 30 positive cases with a total of 65 bone metastases depicted only on current images and confirmed by two radiologists who had access to additional imaging examinations and clinical courses and 30 matched negative control cases (no bone metastases). Previous CT images were semiautomatically registered to current CT images by the algorithm, and TS images were created. Seven radiologists independently interpreted CT image pairs to identify newly developed bone metastases without and with TS images with an interval of at least 30 days. Jackknife free-response receiver operating characteristics (JAFROC) analysis was conducted to assess observer performance. Reading time was recorded, and usefulness was evaluated with subjective scores of 1-5, with 5 being extremely useful and 1 being useless. Significance of these values was tested with the Wilcoxon signed-rank test. Results The subtraction images depicted various types of bone metastases (osteolytic, n = 28; osteoblastic, n = 26; mixed osteolytic and blastic, n = 11) as temporal changes. The average reading time was significantly reduced (384.3 vs 286.8 seconds; Wilcoxon signed rank test, P = .028). The average figure-of-merit value increased from 0.758 to 0.835; however, this difference was not significant (JAFROC analysis, P = .092). The subjective usefulness survey response showed a median score of 5 for use of the technique (range, 3-5). Conclusion TS images obtained from serial CT scans using nonrigid registration successfully depicted newly developed bone metastases and showed promise for their efficient detection. © RSNA, 2017 Online supplemental material is available for this article.

Chronic Kidney Disease Predicts Survival in Patients with Idiopathic Pulmonary Fibrosis.

BACKGROUND: The prevalence of chronic kidney disease (CKD) increases with age as with idiopathic pulmonary fibrosis (IPF). OBJECTIVES: We assessed the prevalence of CKD (stages 3-5) and investigated the relationship of CKD to clinical features and outcomes in patients with IPF. METHODS: This study comprised 123 patients with IPF; 61 subjects with chronic obstructive pulmonary disease (COPD), which was reportedly associated with CKD, were also enrolled as a disease control. CKD (stages 3-5) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. RESULTS: Thirty-seven patients (30%) with IPF and 14 controls (23%) with COPD were diagnosed with CKD, and these frequencies were not significantly different. The patients with IPF and CKD were older (p < 0.01) and had a higher frequency of hypertension (p = 0.048) and ischemic heart disease (p = 0.02) than those with IPF but without CKD. Furthermore, the diffusing capacity of the lung for carbon monoxide (DLCO) and the 6-min walking distance in the patients with CKD were significantly lower (40.0 ± 13.2 vs. 45.9 ± 14.4%, p = 0.04, and 416 ± 129 vs. 474 ± 84 m, p = 0.01, respectively) than in the patients without CKD. The outcome of the patients with CKD showed significantly worse survival compared with the patients without CKD (p = 0.04). Moreover, eGFR remained an independent predictor of survival after adjusting for age and pulmonary function data. CONCLUSION: A substantial percentage of IPF patients have CKD. CKD with a low eGFR was associated with decreased survival in IPF.

Serial perfusion in native lungs in patients with idiopathic pulmonary fibrosis and other interstitial lung diseases after single lung transplantation.

BACKGROUND: Lung perfusions after single lung transplantation (SLT) have not been fully clarified in patients with interstitial lung disease (ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. METHODS: Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the post-operative perfusion ratio in the native lung and clinical parameters, including pre-operative perfusion ratio and computed tomography (CT) volumetric parameters, were evaluated. RESULTS: On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis (IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at three months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. CONCLUSION: The pre-operative perfusion ratio may predict the post-operative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs.

Pleuroparenchymal fibroelastosis and non-specific interstitial pneumonia: frequent pulmonary sequelae of haematopoietic stem cell transplantation.

AIMS: Pulmonary sequelae, reported as chronic graft-versus-host disease (cGVHD), of haematopoietic stem cell transplantation (HSCT) include constrictive bronchiolitis obliterans (CBO), lymphocytic bronchiolitis (LB), and veno-occlusive disease (VOD); recently, pleuroparenchymal fibroelastosis (PPFE) has also been described in bone marrow transplant recipients. The histological features of pulmonary HSCT sequelae have not been described systematically. The aim of the study was to review and identify the histological features of PPFE after bone marrow transplant. METHODS AND RESULTS: A retrospective review of 20 patients who underwent lung transplantation for pulmonary disease following HSCT between 2004 and 2013 was conducted. The patient age at transplantation ranged from 8 years to 57 years (median, 27.5 years). Fifteen patients had cGVHD in other organs (skin, nine; liver, six; salivary gland, six). Lung transplantation was performed at a median of 4.6 years (range, 1.2-14.8 years) post-HSCT. Histologically, all cases had CBO, with concurrent LB in 10, and VOD in three. PPFE was identified in 15 cases (75%), with subpleural (15), paraseptal (11) and centrilobular (13) distributions; and non-specific interstitial pneumonia (NSIP) was identified in 15 cases (75%), with fibrotic (nine) and cellular (six) patterns. PPFE was distributed in all lobes, with a predominance in the upper lobe. NSIP was mostly focal, with two cases having diffuse involvement. CONCLUSIONS: PPFE and NSIP were frequently seen in HSCT patients. Possible causes may include reactions to drugs or radiation, or cGVHD.

Matrix metalloproteinase-10: a novel biomarker for idiopathic pulmonary fibrosis.

BACKGROUND: Matrix metalloproteinases (MMPs) are believed to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF), and MMP-7 has been described as a useful biomarker for IPF. However, little is known regarding the significance of MMP-10 as a biomarker for IPF. METHODS: This observational cohort study included 57 patients with IPF. Serum MMPs were comprehensively measured in all patients, and the relationships between these markers and both disease severity and prognosis were evaluated. Bronchoalveolar lavage fluid (BALF) MMP-7 and -10 levels were measured in 19 patients to investigate the correlation between these markers and their corresponding serum values. Immunohistochemical staining for MMP-10 was also performed in IPF lung tissue. RESULTS: Serum MMP-7 and -10 levels correlated significantly with both the percentage of predicted forced vital capacity (ρ = -0.31, p = 0.02 and ρ = -0.34, p < 0.01, respectively) and the percentage of predicted diffusing capacity of the lung for carbon monoxide (ρ = -0.32, p = 0.02 and ρ = -0.43, p < 0.01, respectively). BALF MMP-7 and -10 levels correlated with their corresponding serum concentrations. Only serum MMP-10 predicted clinical deterioration within 6 months and overall survival. In IPF lungs, the expression of MMP-10 was enhanced and localized to the alveolar epithelial cells, macrophages, and peripheral bronchiolar epithelial cells. CONCLUSIONS: MMP-10 may be a novel biomarker reflecting both disease severity and prognosis in patients with IPF.

Clinical impact of high-attenuation and cystic areas on computed tomography in fibrotic idiopathic interstitial pneumonias.

BACKGROUND: Quantitative computed tomography (CT) analysis has been proposed as a means of objectively assessing fibrotic interstitial pneumonia (IP) including idiopathic pulmonary fibrosis (IPF). We investigated whether percentages of high-attenuation areas (HAA%) and cystic areas (CA%) quantified from CT images were useful as indices of fibrotic IP. METHODS: CT images of 74 patients with fibrotic idiopathic interstitial pneumonias (IPF, 36; non-specific interstitial pneumonia, 9; unclassifiable idiopathic interstitial pneumonia, 29) were analyzed via in-house computer software, which automatically calculated HAA%, CA%, mean lung density (MLD), standard deviation of lung density (SD-LD), kurtosis, and skewness from CT attenuation histograms. These indices were compared in each instance with physiologic measures, visual fibrosis score, clinical diagnosis, radiologic CT pattern, and prognosis. RESULTS: HAA% correlated significantly with physiologic measures and visual fibrosis score to a moderate extent (%forced vital capacity, rs = -0.59; % carbon monoxide diffusion capacity, rs = -0.43; fibrosis score, rs = 0.23). Densitometric parameters (MLD, SD-LD, kurtosis, and skewness) correlated significantly with physiologic measures and fibrosis score (|rs| = 0.28-0.59). CA% showed no association with pulmonary functions but differed significantly between IPF and other interstitial pneumonias (IPs) (1.50 ± 2.41% vs. 0.41 ± 0.80%; P < 0.01) and between the definite usual interstitial pneumonia (UIP) pattern and other patterns (1.48 ± 2.38% vs. 0.55 ± 1.19%; P < 0.01). On univariate analysis, HAA%, MLD, SD-LD, kurtosis, skewness, fibrosis score, and definite UIP pattern all correlated with survival, with kurtosis alone identified as a significant predictor of mortality on multivariate analysis (hazard ratio = 0.67; 95% CI, 0.44-0.96; P = 0.03). CONCLUSION: CA% and HAA% are novel quantitative CT indices with differing properties in fibrotic IP evaluations. HAA% largely reflects physiologic impairments, whereas CA% corresponds with diagnosis and HRCT pattern. Of the CT indices examined, kurtosis constituted the strongest predictor of mortality.

Total lesion glycolysis as an IgG4-related disease activity marker.

OBJECTIVES: 2-[18F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) was reported to be useful for monitoring immunoglobulin G4-related disease (IgG4-RD); however, a quantitative FDG-PET/CT analysis such as total lesion glycolysis (TLG) has not yet been conducted. This study aimed to investigate whether TLG would correlate with serum markers in IgG4-RD, and the utility of TLG for disease monitoring. METHODS: This retrospective study included 17 patients (12 men; median age, 62 years) who were followed up at Kyoto University Hospital and underwent FDG-PET/CT from April 2009 to November 2013. TLG was calculated for the involved lesions. Correlations between serum markers [IgG4, soluble IL-2 receptor (sIL-2R), lactate dehydrogenase (LDH), and C-reactive protein (CRP)] and TLG concomitant with FDG-PET/CT scans were investigated. Serial changes in TLG were assessed in patients who underwent follow-up FDG-PET/CT (n = 6). RESULTS: The calculated median (IQL) TLG value was 154.8 (63.7-324.4). A significant correlation was found between the sIL-2R level and TLG (P = 0.001, rs = 0.763). In contrast, no correlations were found between the IgG4, LDH, or CRP levels and TLG. Increased or decreased TLG corresponded with clinical disease improvement or worsening. CONCLUSIONS: TLG correlated significantly with the serum sIL-2R level and may be useful for disease monitoring in IgG4-RD.