Effect of threshold on the correlation between airflow obstruction and low attenuation volume in smokers assessed by inspiratory and expiratory MDCT.

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.

CD40 amplifies Fas-mediated apoptosis: a mechanism contributing to emphysema.

Excessive apoptosis and prolonged inflammation of alveolar cells are associated with the pathogenesis of pulmonary emphysema. We aimed to determine whether CD40 affects alveolar epithelial cells and endothelial cells, with regard to evoking apoptosis and inflammation. Mice were repeatedly treated with agonistic-anti CD40 antibody (Ab), with or without agonistic-anti Fas Ab, and evaluated for apoptosis and inflammation in lungs. Human pulmonary microvascular endothelial cells and alveolar epithelial cells were treated with agonistic anti-CD40 Ab and/or anti-Fas Ab to see their direct effect on apoptosis and secretion of proinflammatory molecules in vitro. Furthermore, plasma soluble CD40 ligand (sCD40L) level was evaluated in patients with chronic obstructive pulmonary disease (COPD). In mice, inhaling agonistic anti-CD40 Ab induced moderate alveolar enlargement. CD40 stimulation, in combination with anti-Fas Ab, induced significant emphysematous changes and increased alveolar cell apoptosis. CD40 stimulation also enhanced IFN-γ-mediated emphysematous changes, not via apoptosis induction, but via inflammation with lymphocyte accumulation. In vitro, Fas-mediated apoptosis was enhanced by CD40 stimulation and IFN-γ in endothelial cells and by CD40 stimulation in epithelial cells. CD40 stimulation induced secretion of CCR5 ligands in endothelial cells, enhanced with IFN-γ. Plasma sCD40L levels were significantly increased in patients with COPD, inversely correlating to the percentage of forced expiratory volume in 1 s and positively correlating to low attenuation area score by CT scan, regardless of smoking history. Collectively CD40 plays a contributing role in the development of pulmonary emphysema by sensitizing Fas-mediated apoptosis in alveolar cells and increasing the secretion of proinflammatory chemokines.

A Case of Candidemia after Long-term Presence of Urethral Foreign Bodies.

A 52-year-old man presented to our hospital complaining of general malaise, cough, and fever. Total body computed tomography revealed scattered pneumonia and urethral foreign bodies that had been inserted during adolescence. Candida glabrata was detected in blood and urine cultures. Based on these findings, the patient was diagnosed with candidemia that developed due to Candida urinary tract infection, complicated by septic pulmonary embolism and severe diabetes mellitus. Candidemia likely persisted despite the initiation of intravenous antifungal therapy and control of blood sugar level. Therefore, surgical removal of the urethral foreign bodies was performed, which resulted in resolution of the patient's symptoms. Herein, we report a rare case of candidemia complicated by Candida urinary tract infection that developed due to the long-term presence of urethral foreign bodies. A multidisciplinary therapeutic approach, including surgical removal of the infected foreign bodies, is effective in such cases. This case indicates that long-term presence of foreign bodies and acquired immune dysfunction can be risk factors for candidemia. Therefore, detailed history should be obtained and systemic examination should be performed to identify the complicating risk factors on diagnosis of candidemia.

Tiotropium bromide attenuates respiratory syncytial virus replication in epithelial cells.

BACKGROUND: Respiratory syncytial virus (RSV) infection could be related to airway inflammation as well as exacerbation of chronic obstructive pulmonary disease (COPD). Tiotropium bromide decreases the frequency of exacerbation in patients with COPD; however, the mechanisms of tiotropium bromide to reduce the chances of exacerbation have not been defined. One potential mechanism could be that tiotropium bromide protects against RSV infection in epithelial cells. OBJECTIVE: To examine whether tiotropium bromide affects RSV replication in HEp-2 cells. METHODS: The supernatant titer of RSV was calculated by methylcellulose plaque assay after RSV innoculation. Intracellular RSV and ICAM-1 mRNA were measured by PCR. Syncytium formation was observed by light microscopy. Intracellular RSV fusion protein and RhoA protein were detected by Western blot analysis. Furthermore, RhoA activity, ICAM-1 expression and inflammatory cytokines in cultured supernatant were measured by binding assay, immunofluorescence staining and ELISA, respectively. RESULTS: Tiotropium bromide decreased the supernatant titer of RSV, and it inhibited syncytium formation, RhoA activation and ICAM-1 expression. Moreover, it suppressed the production of IL-6 and IL-8 after RSV infection. CONCLUSIONS: The antiviral effects of tiotropium bromide regarding RSV replication are partly due to inhibition of RhoA activity and ICAM-1 expression. Tiotropium bromide decreases RSV replication and may modulate airway inflammation by reducing the production of inflammatory cytokines.

The Relationship of Bone Mineral Density in Men with Chronic Obstructive Pulmonary Disease Classified According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Combined Chronic Obstructive Pulmonary Disease (COPD) Assessment System.

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.

Prevalence and Responsiveness to Treatment of Lung Abnormalities on Chest Computed Tomography in Patients With Microscopic Polyangiitis: A Multicenter, Longitudinal, Retrospective Study of One Hundred Fifty Consecutive Hospital-Based Japanese Patients.

OBJECTIVE: To determine the prevalence of lung abnormalities on chest computed tomography (CT) in patients with microscopic polyangiitis (MPA), to assess the responsiveness of such abnormalities to initial treatment, and to assess associations between these abnormalities and patient and disease characteristics and mortality. METHODS: We retrospectively identified 167 consecutive hospital-based patients with MPA in 3 hospitals in Japan. We longitudinally collected clinical information for 150 of these patients, for whom CT images obtained before treatment were available. We then determined the presence of 22 imaging components of lung abnormalities in these patients. RESULTS: The vast majority of patients (97%) had at least 1 lung abnormality on chest CT images, including interstitial lung lesions (66%), airway lesions (66%), pleural lesions (53%), and emphysematous lesions (37%). In multivariate analyses, ground-glass opacity was associated with the Birmingham Vasculitis Activity Score, whereas 3 of 4 airway lesions were associated with myeloperoxidase-antineutrophil cytoplasmic antibodies. Latent class analysis identified a distinct group of patients with airway-predominant lung lesions. Airway lesions such as bronchiolitis and bronchovascular bundle thickening were among the components that showed improvement within 3 months of the initial treatment. An idiopathic pulmonary fibrosis pattern was the only chest CT variable that was independently associated with shorter survival. CONCLUSION: Abnormalities in a wide range of anatomic areas, including the whole airway, can be identified in the lungs of patients with MPA before treatment. The prevalence, clustering patterns, and responsiveness to treatment of individual lung abnormalities provide groundwork for informing future studies to understand the pathophysiology of MPA.

Influence of pulmonary emphysema on COPD assessment test-oriented categorization in GOLD document.

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.

[Eosinophilic pleural effusion by dirofilariasis].

A 44-year-old man visited our hospital because of right chest pain. Pleural effusion in the right lung was detected on a chest radiograph. A chest CT scan demonstrated no abnormal lesions in either lung field, but passive atelectasis due to the pleural effusion was present. Since many eosinophils were found in the exudative pleural effusion, a parasitic infection was suspected. An enzyme-linked immunosorbent assay test led to a diagnosis of eosinophilic pleural effusion by dirofilariasis. Pleural effusion disappeared spontaneously and the level of anti-Dirofilaria immitis antibody decreased. Continued careful observation is necessary in such cases.

[A case of pleural effusion associated with allergic bronchopulmonary aspergillosis during a relapse of the disease].

A 61-year-old man with history of bronchial asthma since childhood was admitted to our hospital for examination of eosinophilia and of lung infiltration seen in the chest radiograph. Allergic bronchopulmonary aspergillosis (ABPA) was diagnosed on the basis of the following findings: elevated serum IgE level, positive immediate skin reaction to Aspergillus antigen, the presence of precipitating antibodies against Aspergillus antigen, and central bronchiectasis. Oral prednisolone administration (30 mg daily) was started. During the course of reducing the prednisolone dose by up to 5 mg per day, pleural effusion appeared in the right lung. It was speculated that this eosinophilic exudative effusion was associated with a relapse of ABPA. After treatment with the dose of prednisolone increased to 20 mg per day and with oral itraconazole, the pleural effusion disappeared. We report a rare case of pleural effusion associated with ABPB on relapse.

[A case of solitary nodular pulmonary amyloidosis].

A 64-year-old man without respiratory symptoms was introduced to our hospital because of a nodule of 20 mm in diameter found in the left lung in a periodic health examination. The chest radiograph and CT scan showed a well-defined nodule in the middle of the left lung field, and enlarged mediastinal lymph nodes. Lung cancer was suspected, and transbronchial and CT guided biopsies were performed, but did not lead to a definitive diagnosis. Since the patient refused further examinations, we carefully followed up the nodule in the chest radiograph. After a year and a half, the nodule and the lymph nodes became enlarged, and the patient was admitted to the hospital for a surgical biopsy. Video-assisted thoracoscopic surgery followed by thoracotomy was performed for both a biopsy and nodule resection. Histologically, the nodule tissue was rich in amorphous substances positively stained with Congo Red, which was consistent with amyloidosis. No findings of systemic amyloidosis or secondary amyloidosis were demonstrated.

The effects of emphysema on airway disease: correlations between multi-detector CT and pulmonary function tests in smokers.

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.

Quantitative assessment of cross-sectional area of small pulmonary vessels in patients with COPD using inspiratory and expiratory MDCT.

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.

Decreased lipoprotein lipase in obstructive sleep apnea syndrome.

BACKGROUND: Lipoprotein lipase (LPL) might play a major role in lipid metabolism by hydrolyzing triglyceride-rich lipoproteins. Decreased LPL activity can trigger early inflammatory responses central to atherosclerosis. However, whether repeated apnea-related hypoxemia influences lipid metabolism in patients with obstructive sleep apnea syndrome (OSAS) remain undefined. This investigation determined whether circulating LPL was influenced by repeated apnea-related hypoxemia, and the effect of nasal continuous positive airway pressure (CPAP) therapy on LPL concentrations in OSAS patients. METHODS AND RESULTS: The participants of the study were 155 men with OSAS and 39 men without OSAS. Circulating LPL concentrations decreased with the severity of OSAS. They correlated negatively with serum triglyceride, and the linear regression lines between LPL concentrations and triglyceride in OSAS patients were shifted downward compared with those in non-OSAS patients, suggesting that any pathophysiological factor might decrease LPL activity in OSAS patients. Some OSAS patients were subjected to CPAP therapy for 3 months. CPAP therapy increased LPL concentrations and decreased C-reactive protein (CRP) concentrations. CONCLUSIONS: The present study suggests that repeated apnea-related hypoxemia might affect lipid metabolism and augment inflammatory responses, and CPAP therapy could be effective to decrease inflammatory responses and ameliorate lipid metabolism in patients with OSAS.