Search

Background: Polymyositis and dermatomyositis-associated interstitial lung disease (PM/DM-ILD) can have variable courses. We evaluated the prognostic value of high-resolution computed tomography (HRCT) in PM/DM-ILD. Methods: The cases of 51 patients newly diagnosed with PM/DM-ILD were retrospectively reviewed. HRCT images at diagnosis were categorized into four radiological patterns based on the major findings and distributions of these abnormalities, and the disease extent on HRCT was scored. The impact of HRCT findings and other clinical parameters on day 90 and overall mortality were analyzed. Results: Of the 51 patients (11 with polymyositis and 40 with dermatomyositis), the lower consolidation/ground-glass attenuation (GGA) pattern was observed in 21 patients (41%), lower reticulation was observed in 23 patients (45%), random GGA was observed in four patients (8%), and other patterns were observed in three patients (6%). Twenty-one patients (42%) were positive for anti-CADM-140. The lower consolidation/GGA pattern, clinically amyopathic dermatomyositis, fever (≥38.0 °C), ferritin levels >500 ng/mL, and the presence of anti-CADM-140 were significantly associated with 90-day mortality in univariate analysis. Multivariate analysis revealed that the lower consolidation/GGA pattern (odds ratio, 23.1; P = 0.02) and the presence of anti-CADM-140 (odds ratio, 14.1; P = 0.03) were independent predictors of 90-day mortality. This HRCT pattern was also associated with a higher 90-day morality rate among anti-CADM-140-positive patients. The lower consolidation/GGA pattern was also associated with overall mortality in univariate analysis, whereas only the presence of anti-CADM-140 was an independent determinant of overall mortality in multivariate analysis. Conclusion: HRCT patterns at diagnosis can help predict the prognosis of patients with PM/DM-ILD as well as the presence of anti-CADM-140. [ABSTRACT FROM AUTHOR]

Background: Recent epidemiological evidence indicates an association between cardiovascular diseases and pulmonary fibrosis. The vascular endothelium acts to maintain vascular homeostasis through multiple mechanisms and impaired endothelial function can contribute to the development, progression and clinical expression of atherosclerosis. Methods: We consecutively recruited 39 newly-diagnosed chronic interstitial pneumonitis/fibrosis patients without any specific etiology. We assessed endothelium-dependent vasodilator response of patients using digital pulse amplitude tonometry and compared the reactive hyperemia index (RHI) with age-, sex- and body mass index-matched control subjects (n = 30). We further investigated the relationships between RHI and clinical characteristics, laboratory cardiovascular risk factors, disease-related factors and circulating levels of inflammatory biomarkers. Results: RHI was significantly lower in patients with chronic interstitial pneumonitis/fibrosis than in control subjects (p = 0.02). While circulating levels of total cholesterol, triglycerides, HbA1c and fasting glucose did not differ significantly between groups, patients with chronic interstitial pneumonitis/fibrosis had significantly lower high density lipoprotein levels and higher low density lipoprotein levels as compared with control subjects. Regarding disease-related factors, RHI was significantly associated with the diffusing capacity for carbon monoxide, alveolar-arterial oxygen pressure difference, 6-min walk distance and end-exercise oxygen saturation. Additionally, circulating levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were inversely correlated with RHI. Conclusions: We confirmed a possible link between pulmonary fibrosis and cardiovascular disease by demonstrating an impairment of endothelium-dependent vasodilator response, which was significantly associated with the severity of pulmonary fibrosis and circulating levels of adhesion molecules. [ABSTRACT FROM AUTHOR]

Abstract: We report a 35-year-old man who presented with pulmonary hemorrhage induced by an epileptic seizure. He had experienced recurrent episodes of massive hemoptysis after epileptic seizures since the age of 28 years. He was admitted to Kyoto University Hospital with massive hemoptysis and hypoxia after an epileptic seizure of a few minutes’ duration. Radiographic signs of infiltrations and hemorrhagic bronchoalveolar lavage fluid were observed. He was intubated and successfully treated with anti-epilepsy drugs and corticosteroids. Epileptic seizures may have induced increased pulmonary vascular permeability and structural damage to the blood–gas barrier, which may have caused pulmonary hemorrhage. Pulmonary hemorrhage could be in the list of differential diagnoses of hemoptysis in patients with epilepsy. [Copyright &y& Elsevier]

Abstract: Currently, platinum-based combination chemotherapy is the standard first-line chemotherapy for non-small-cell lung cancer (NSCLC). Historically, platinum-based chemotherapy has been recommended for up to six cycles even for responders, and second-line chemotherapy has been considered when disease progression is confirmed. In spite of extensive investigations into maintenance chemotherapy, no positive data have been obtained; however, the results of recent clinical trials suggest both the safety and efficacy of maintenance chemotherapy in patients with NSCLC, although it is still controversial. In this review, we summarize the major clinical trials of maintenance chemotherapy in patients with NSCLC, and discuss its clinical validity and present future perspectives. [Copyright &y& Elsevier]

Summary: Background: Anti-CADM-140 antibody (anti-CADM-140), also referred to as anti-melanoma differentiation-associated gene 5 (MDA5) antibody, is a myositis-specific antibody identified in the sera of patients with clinically amyopathic dermatomyositis (C-ADM) and is associated with a worse prognosis in dermatomyositis-associated interstitial lung disease (DM-ILD). We sought to determine high-resolution computed tomography (HRCT) features of DM-ILD with anti-CADM-140. Methods: Twenty-five patients newly diagnosed with DM-ILD at Kyoto University Hospital between 2005 and 2009 were retrospectively reviewed. Serum anti-CADM-140 was measured in all patients at their first visit. Chest HRCT images taken prior to treatment were classified based on the dominant findings and their distribution, and compared between patients with and without the antibody. Results: Of 25 DM-ILD patients, 12 were positive and 13 were negative for anti-CADM-140. HRCT patterns differed significantly between anti-CADM-140-positive and negative patients (P = 0.002). Lower consolidation or ground-glass attenuation (GGA) pattern (50.0%) and random GGA pattern (33.3%) were the predominant patterns in anti-CADM-140-positive cases, while lower reticulation pattern (69.2%) was frequently seen in anti-CADM-140-negative cases. Anti-CADM-140-positive cases were also significantly characterized by the absence of intralobular reticular opacities (0% in anti-CADM-140 (+) vs. 84.6% in anti-CADM-140 (−), P < 0.0001). Conclusions: Anti-CADM-140-positive DM-ILD was characterized by lower consolidation or GGA pattern, random GGA pattern, and the absence of intralobular reticular opacities. [Copyright &y& Elsevier]

Summary: Objectives: Antisynthetase syndrome (ASS) is characterized by autoantibodies to aminoacyl-tRNA synthetases (anti-synthetase) and it is frequently associated with interstitial lung disease. The purpose of this study was to elucidate the prevalence and characteristics of the anti-synthetase positive subpopulation among idiopathic interstitial pneumonias (IIPs) and to clarify the importance of screening for these antibodies. Methods: A retrospective study was performed in 198 consecutive cases with IIPs. Screening for six anti-synthetase antibodies was performed in all cases. Clinical profiles of all cases were compared with reference to the presence of anti-synthetase. High-resolution computed tomography (HRCT) findings of anti-synthetase positive cases were also analyzed. Results: 13 cases (6.6%) were positive for anti-synthetase. Anti-EJ was most prevalent, followed by anti-PL-12. Onset ages of anti-synthetase positive cases were younger than those of anti-synthetase negative cases. Extrapulmonary features of ASS were absent in 6 anti-synthetase positive cases (46.2%). Histologically, among 5 UIP with lymphoid follicles and 11 NSIP cases, the prevalence of anti-synthetase positive cases was 8/16 (50%). On HRCT, ground glass opacity and traction bronchiectasis were the major findings in anti-synthetase positive cases, while honeycombing was absent. Conclusions: Anti-synthetase positive cases were not rare among IIPs. Anti-synthetase should be screened for in IIPs, especially in pathological NSIP or UIP with lymphoid follicles. These patients should be screened for anti-synthetase even if no suggestive extrapulmonary manifestation exists. [ABSTRACT FROM AUTHOR]

Summary: Background: Obstructive sleep apnea (OSA) has both systemic and local effects partly through the increased oxidative stress caused by intermittent hypoxia and reoxygenation. However, lung-specific biomarkers in OSA have not been fully assessed in comparison with systemic biomarkers such as C-reactive protein (CRP), although results of a recent study having a small sample size indicated KL-6 as one candidate. Methods: Subjects of the present study were 197 patients suspected to have OSA. In addition to polysomnography, we also measured serum levels of KL-6, surfactant protein-D (SP-D) and CRP and pulmonary function. We examined the relationships of different biomarkers with OSA severity and pulmonary function. Results: The apnea/hypopnea index (AHI) was significantly positively correlated with serum KL-6 levels even after adjustment for body mass index (BMI) and smoking (p = 0.03), but not with SP-D and CRP. Also, a significant trend for an increase in serum KL-6 was noted in accordance with the severity of OSA even after adjustment for BMI and smoking (β coefficient = 0.18, p = 0.02). Additionally, elevated KL-6 levels were significantly associated with restrictive lung function disturbance and gas exchange derangement after adjustment for obesity and smoking, which contrasted with CRP whose elevations were significantly associated with worsened airflow limitation and increased lung volume. Conclusions: Serum KL-6 levels may reflect the degree of subclinical lung injury associated with OSA independently of obesity or smoking, unlike CRP. We consider that KL-6 can be a potential candidate as a lung-specific biomarker of OSA and might provide complementary information on systemic biomarkers in assessing OSA. [Copyright &y& Elsevier]

Abstract: Although small-cell lung cancer (SCLC) generally shows an excellent response to initial chemotherapy, most patients finally relapse and salvage chemotherapy is considered. Usually, the response to salvage chemotherapy significantly differs between sensitive and refractory relapse. Sensitive relapse is relatively chemosensitive and re-challenge with the same drugs as used in the initial chemotherapy has been used historically, while refractory relapse is extremely chemo-resistant and its prognosis has been abysmal. To date, a number of clinical trials have been carried out for relapsed SCLC; however, the number of randomized trials is quite limited. At present, topotecan is the only drug approved by the US Food and Drug Administration for relapsed SCLC, and is considered the standard second-line chemotherapy in many countries. More recently, amrubicin has also shown more favorable antitumor activity, and is the most promising at present. Unfortunately, targeted agents have failed to demonstrate effectiveness for SCLC. Better understanding of the molecular mechanisms is clearly needed. [Copyright &y& Elsevier]

Summary: Background: The level at which arterial carbon dioxide tension (PaCO2) a few months after introduction of long-term non-invasive positive pressure ventilation (NPPV) is associated with a favorable prognosis remains uncertain. Methods: Data on 184 post-tuberculosis patients with chronic restrictive ventilatory failure who were receiving long-term domiciliary NPPV were examined retrospectively. Average PaCO2 3–6 months after NPPV (3- to 6-mo PaCO2) and potential confounders were analyzed with discontinuation of long-term NPPV as the primary outcome. The effects of 3- to 6-mo PaCO2 on annual hospitalization rates due to respiratory deterioration from 1 year before to 3 years after the initiation of NPPV were examined. The effect of the difference between the PaCO2 value at the start of NPPV (0-mo PaCO2) and the PaCO2 value 3- to 6-mo later (d-PaCO2) on continuation rates for NPPV was also assessed in patients who initiated NPPV while in a chronic state. Results: Patients with relatively low 3- to 6-mo PaCO2 values maintained a relatively low PaCO2 6–36 months after NPPV (p < 0.0001) and had significantly better continuation rates (p < 0.03) and lower hospitalization rates from the 1st to 3rd year of NPPV (p = 0.008, 0.049, 0.009, respectively) than those with higher levels. The 0-mo PaCO2 (p = 0.26) or d-PaCO2 (p = 0.86) had no predictive value. Conclusion: A relatively low 3- to 6-mo PaCO2 value was predictive of long-term use of NPPV. The target values for 3- to 6-mo PaCO2 may, therefore, be less than 60 mmHg in post-tuberculosis patients, although more studies are needed. [Copyright &y& Elsevier]

Summary: Background: The current mainstream treatment for COPD is bronchodilators alone or in combination. The effects of a β2-agonist, tulobuterol, administered transdermally, have been reported to last for 24h. However, there are no reports on the efficacy of tulobuterol combined with an anticholinergic. In this study, we investigated the efficacy and safety of transdermal tulobuterol combined with inhaled tiotropium in COPD. Methods: After a 2-week run-in period, 103 stable COPD patients aged ≥40 years were randomized into two groups: inhaled tiotropium (18μg, Tio group) or transdermal tulobuterol (2mg) combined with inhaled tiotropium (18μg, Tio+Tulo group) for 8 weeks. Primary endpoints were pulmonary function and severity of dyspnea. The St. George''s Respiratory Questionaire (SGRQ) score was a secondary endpoint. Results: In both groups, FEV1 and FVC as well as dyspnea improved significantly after 8 weeks. In a comparison of both groups, percentage changes in IC and morning and evening peak expiratory flow were significantly greater in the Tio+Tulo group than in the Tio group. In addition, significant improvement in SGRQ score was observed in the Tio+Tulo group only. The risk of adverse events related to the study drugs was not increased. Conclusion: In COPD patients, additional administration of transdermal tulobuterol to inhaled tiotropium produced significant benefits in dyspnea and SGRQ score as well as pulmonary function. These benefits may be due to a reduction in pulmonary hyperinflation resulting from improvement of peripheral airflow obstruction through tulobuterol via the systemic circulation. [Copyright &y& Elsevier]

We conducted hospital-based contact investigations of 55 serial sputum smear-positive tuberculosis (TB) patients and 771 health care workers (HCWs) from 2006-2013. HCWs who made contact with TB patients in the absence of appropriate airborne precautions were evaluated using interferon gamma release assays to identify TB infection. Twenty-nine HCWs (3.8%) were newly diagnosed with TB infection. The 10 TB patients responsible for transmission had a duration of contact of >7 days by multivariate analysis. [ABSTRACT FROM AUTHOR]

Summary: Background: Long-term noninvasive positive pressure ventilation (NPPV) is associated with an excellent survival rate, especially in post-tuberculosis patients. Nothing is currently known on which method of ventilatory support is associated with a better continuation of long-term NPPV, which itself might lead to longer survival. Methods: One hundred and eighty four post-tuberculosis patients, who started NPPV at the Kyoto University Hospital group and the National Tokyo Hospital from June 1990 to August 2007, were examined retrospectively. Ventilator mode (an assisted mode or a pure controlled mode) and potential confounders were examined with the discontinuation of NPPV as the primary outcome. Results: Patients treated with a pure controlled mode had significantly better continuation rates (hazard ratio, 3.09; 95% confidential interval, 1.75–5.47; p =0.0001) and better survival rates (Log-rank test; p =0.0031) than those treated with an assisted mode. Female gender and no pulmonary lesions were also associated with a significantly better probability of continuing NPPV. The five- and ten-year probabilities of continuing NPPV for 106 patients with a pure controlled mode were 68.3% and 41.4%, respectively, while those for 76 patients with an assisted mode were 46.7% and 12.7%, respectively. Conclusions: Patients treated with pure controlled ventilation had significantly better continuation rates and survival rates than those treated with assisted ventilation. Prospective randomized controlled trials are needed to verify the effectiveness of a pure controlled mode in patients with not only restrictive thoracic disease but also other diseases including chronic obstructive pulmonary disease. [Copyright &y& Elsevier]

Background: TGF-β1 can modulate airway inflammation and exaggerate airway remodeling. A polymorphism of a promoter region of TGFB1, C-509T, might be associated with the development of asthma, but its pathophysiologic relevance remains poorly understood. Objective: We investigated relations of the C-509T polymorphism to airflow obstruction, sputum eosinophilia, and airway wall thickening, as assessed by means of computed tomography, in 85 patients with stable asthma. Methods: The CC, CT, and TT genotypes were examined by means of PCR and restriction enzyme fragment length polymorphism. At a selected bronchus, 3 indices of airway wall thickness were measured with an automatic method. Results: The CC, CT, and TT genotypes were found in 22, 46, and 17 patients, respectively. Serum TGF-β1 levels were significantly associated with the polymorphism and were increased in the CT/TT genotypes. FEV1 and sputum eosinophil percentages were also significantly associated with the polymorphism and were both decreased in the CT/TT genotypes. The polymorphism was unrelated to airway wall thickness. Conclusion: In addition to increased serum TGF-β1 levels, the T allele of the C-509T polymorphism is related to increased airflow obstruction but attenuated eosinophilic inflammation. The former relation is not attributed to thickening of the central airway walls. The latter relation might reflect the anti-inflammatory effect of TGF-β1. The C-509T polymorphism has a complex role in asthma pathophysiology, presumably because of the diverse functions of TGF-β1 and its various interactions with cells and humoral factors in vivo. [Copyright &y& Elsevier]

Summary: Significant relationships between the psychological status and poor asthma outcomes are often reported. However, most of these studies are cross-sectional and none have evaluated how the psychological status progresses over time during the management of asthma patients. Therefore, we examined the longitudinal changes in the psychological status of asthma patients, and compared them with changes in other clinical measurements. Eighty-seven outpatients with stable asthma after 6 months of treatment were enrolled in this study. The psychological status was evaluated using the Hospital Anxiety and Depression Scale (HADS), the health status using the Asthma Quality of Life Questionnaire (AQLQ) and the St. George''s Respiratory Questionnaire (SGRQ). The patient''s pulmonary function, peak expiratory flow values and airway hyperresponsiveness were measured at entry and every year thereafter over a 5-year period. Using mixed effects models to estimate the slopes, the HADS anxiety and depression scores did not change significantly over time (p=0.71 and 0.72, respectively). The changes in the HADS scores correlated noticeably with changes in the AQLQ and SGRQ scores, but not with changes in the physiological measurements. The baseline HADS anxiety and depression scores were significantly correlated to the subsequent annual changes in each measurement. The psychological status remained clinically stable over the 5-year study period in patients with stable asthma. Changes in the psychological status were significantly correlated to changes in the health status. The baseline HADS scores were a useful indicator in detecting patients who would show subsequent deterioration in their psychological status. [Copyright &y& Elsevier]

Summary: Goals of effective management of patients with chronic obstructive pulmonary disease (COPD) include relieving their symptoms and improving their health status. We examined how such patient reported outcomes would change longitudinally in comparison to physiological outcomes in COPD. One hundred thirty-seven male outpatients with stable COPD were recruited for the study. The subjects health status was evaluated using the St. George''s Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Disease Questionnaire (CRQ). Their dyspnoea using the modified Medical Research Council (MRC) scale and their psychological status using the Hospital Anxiety and Depression Scale (HADS) were assessed upon entry and every 6 months thereafter over a 5-year period. Pulmonary function and exercise capacity as evaluated by peak oxygen uptake on progressive cycle ergometry were also followed over the same time. Using mixed effects models to estimate the slopes for the changes, scores on the SGRQ, the CRQ, the MRC and the HADS worsened in a statistically significant manner over time. However, changes only weakly correlated with changes in forced expiratory volume in 1s (FEV1) and peak We demonstrated that although changes in pulmonary function and exercise capacity are well known in patients with COPD, patient reported outcomes such as health status, dyspnoea and psychological status also deteriorated significantly over time. In addition, deteriorations in patient reported outcomes only weakly correlated to changes in physiological indices. To capture the overall deterioration of COPD from the subjective viewpoints of the patients, patient reported outcomes should be followed separately from physiological outcomes. [Copyright &y& Elsevier]

Background: Small airways may have an important role in asthma but are more difficult to assess pathologically than central airways. Computed tomographic indices of lung density are assumed to reflect air trapping and may be a useful noninvasive measure of small airways disease, but their pathophysiological relevance remains undetermined. Objective: To evaluate lung density on high-resolution computed tomography and examine its correlations with clinical and physiologic variables in 29 patients with stable asthma. Methods: Both lungs were scanned at full-inspiratory and full-expiratory phases to quantify percentage of lung field occupied by low attenuation area (LAA%; < −960 Hounsfield units) and mean lung density. Asthma severity, pulmonary function, methacholine airway sensitivity and reactivity, and sputum eosinophil counts were evaluated. Results: The mean lung density increased and LAA% decreased in all patients at expiratory phase compared with inspiratory phase. The inspiratory density indices and expiratory mean lung density correlated only with FEV1/forced vital capacity (FVC). Expiratory LAA% correlated more strongly than other variables with FEV1/FVC and with indices of peripheral airflow obstruction. Expiratory/inspiratory ratios of LAA% and mean lung density correlated, the former more strongly, with disease severity, residual volume/total lung capacity, and airway sensitivity, as well as with indices of global (FEV1 and FEV1/FVC) and peripheral airflow obstruction. Conclusion: Expiratory/inspiratory high-resolution computed tomography is useful for assessing small airways disease in asthma. Small airways involvement is associated with airflow obstruction, airway hypersensitivity, and more severe disease. Clinical implications: Small airways are an important therapeutic target in asthma. [Copyright &y& Elsevier]

Summary: Dyspnoea measurements in chronic obstructive pulmonary disease (COPD) can be broadly divided into two categories: those that assess breathlessness during exercise, and those that assess breathlessness during daily activities. We investigated the relationships between dyspnoea at the end of exercise and during daily activities with clinical measurements and mortality in COPD patients. We examined 143 male outpatients with moderate to very severe COPD. The peak Borg score at the end of progressive cycle ergometry was used for the assessment of peak dyspnoea rating during exercise, and the Baseline Dyspnea Index (BDI) score was used for dyspnoea with activities of daily living. Relationships between these dyspnoea ratings with other clinical measurements of pulmonary function, exercise indices, health status and psychological status were then investigated. In addition, their relationship with the 5-year mortality of COPD patients was also analyzed to examine their predictive ability. Although the BDI score was significantly correlated with airflow limitation, diffusing capacity, exercise indices, health status and psychological status, the Borg score at the end of exercise had non-existent or only weak correlations with them. The BDI score was strongly significantly correlated with mortality, whereas the Borg score was not. Dyspnoea during daily activities was more significantly correlated with objective and subjective measurements of COPD than dyspnoea at the end of exercise. In addition, the former was more predictive of mortality. Dyspnoea with activities of daily living is considered to be a better measurement for evaluating the disease severity of COPD than peak dyspnoea during exercise. [Copyright &y& Elsevier]

Introduction Pulmonary spindle cell carcinoma (SpCC) is a rare subtype of non-small-cell lung cancer (NSCLC) and, in general, is chemoresistance. Case A sixty-five year-old male patient with metastatic pulmonary SpCC was initially treated with cisplatin and docetaxel, but his disease progressed. Then, he received a combination chemotherapy with carboplatin and nab-PTX followed by maintenanced chemotherapy with nab-PTX. Fluorodeoxyglucose (FDG) positron-emission CT revealed a substantial decrease of FDG accumulation in the primary tumor, and the response continued for more than 7 months. Discussion Preclinical models suggested that nab-PTX may reach the tumor microenvironment more efficiently than solvent-based paclitaxel (sb-PTX) and be preferentially taken up by cancer cells. Considering that there is no effective treatment for patients with pulmonary SpCC, nab-PTX may merit further investigation in patients with pulmonary SpCC. [ABSTRACT FROM AUTHOR]