Vitamin C prevents cigarette smoke-induced pulmonary emphysema in mice and provides pulmonary restoration.

Vitamin C (VC) is a potent antioxidant and is essential for collagen synthesis. We investigated whether VC treatment prevents and cures smoke-induced emphysema in senescence marker protein-30 knockout (SMP30-KO) mice, which cannot synthesize VC. Two smoke-exposure experiments using SMP30-KO mice were conducted. In the first one (a preventive study), 4-month-old mice received minimal VC (0.0375 g/l) [VC(L)] or physiologically sufficient VC (1.5 g/l) [VC(S)] and exposed to cigarette smoke or smoke-free air for 2 months. Pulmonary evaluations followed when the mice were 6 months of age. The second study began after the establishment of smoke-induced emphysema (a treatment study). These mice no longer underwent smoke exposure but received VC(S) or VC(L) treatment for 2 months. Morphometric analysis was performed, and measurements of oxidative stress, collagen synthesis, and vascular endothelial growth factor in the lungs were evaluated. Chronic smoke exposure caused emphysema (29.6% increases of mean linear intercepts [MLI] and 106.5% increases of destructive index compared with the air-only group) in 6-month-old SMP30-KO mice, and this emphysema closely resembled human chronic obstructive pulmonary disease. Smoke-induced emphysema persisted in the VC(L) group after smoking cessation, whereas VC treatment provided pulmonary restoration (18.5% decrease of MLI and 41.3% decrease of destructive index compared with VC(L) group). VC treatment diminished oxidative stress, increased collagen synthesis, and improved vascular endothelial growth factor levels in the lungs. Our results suggest that VC not only prevents smoke-induced emphysema in SMP30-KO mice but also restores emphysematous lungs. Therefore, VC may provide a new therapeutic strategy for treating chronic obstructive pulmonary disease in humans.

Relationship between quantitative CT metrics and pulmonary function in combined pulmonary fibrosis and emphysema.

PURPOSE: Combined pulmonary fibrosis and emphysema (CPFE) is increasingly recognized, as current reports of its clinical features show. To determine CPFE's physiologic and radiologic features, we conducted quantitative assessment of computed tomography scans to compare with those of chronic obstructive pulmonary disease (COPD). METHODS: In 23 patients with CPFE and 42 patients with COPD, we measured the extent of emphysema (LAA %), parenchymal density, and total cross-sectional areas of pulmonary vessels smaller than 5 mm(2) (%CSA <5) and 5-10 mm(2) (%CSA 5-10). RESULTS: For CPFE, airflow was better, but diffusing capacity for carbon monoxide (DLCO) was worse than for COPD, whereas LAA % was similar for both groups. The %CSA <5 was greater but %CSA5-10 was less in CPFE than COPD. COPD involved a negative correlation between DLCO and LAA % at all lung sites; those factors correlated for CPFE only in the upper lobe (r = -0.535). In contrast, CPFE had a negative correlation between DLCO and parenchymal density in lower lobes (r = -0.453), but COPD showed no correlation in any such sections. In CPFE, no correlation was apparent between LAA in upper lobes and parenchymal density in lower lobes. The annual rate of FVC decline (-169.26 ml/year) in CPFE patients correlated with parenchymal density (r = -0.714). CONCLUSIONS: In CPFE, fibrosis and emphysema apparently existed independently, but both correlate with and likely contribute to the disproportionate reduction in gas exchange. Our study also suggested that pulmonary fibrotic changes may be more important contributors than emphysema for disease progression.

Subcutaneous and muscle layer seroma complicated with thoracentesis.

Diagnostic thoracentesis is a basic and relatively safe diagnostic method for patients with pleural effusion. However, complications of thoracentesis are rare and not well known because of the low incidence. Herein, we report a case of subcutaneous and muscle layer seroma following thoracentesis.

Primary pulmonary lymphoma diagnosed by ultrasound-guided transthoracic needle biopsy.

Ultrasound-guided transthoracic needle biopsy is a relatively safe procedure diagnosing subpleural pulmonary mass and has high sensitivity in the diagnosis of lung cancer. However, the usefulness in other rare malignancies is unknown. This case shows the effectiveness in diagnosing not only lung cancer but also rare malignancies including primary pulmonary lymphoma.

IFN-λ3 and CCL17 as predictors of disease progression in patients with mild to moderate COVID-19: A cohort study in a real-world setting.

Coronavirus disease 2019 (COVID-19) has overwhelmed hospitals worldwide. In Japan, serum interferon lambda 3 (IFN-λ3) and C-C motif ligand (CCL) 17 levels have been used as predictive markers for disease progression to severe COVID-19. However, the relationship between these predictive markers and the disease progression of COVID-19 has not been well evaluated. We retrospectively evaluated the patient characteristics, serum IFN-λ3 and CCL17 levels, and comorbidities of 92 patients with mild (n = 20) and moderate (n = 72) COVID-19 who were hospitalized in our institution. The results of the multivariable analysis showed that the positive rates of IFN-λ3, CCL17, and the combination of these markers were significantly elevated in patients with progressed COVID-19. Furthermore, patients who were negative for both markers did not experience disease progression. This study illustrates the importance of measuring these markers to predict disease severity and progression in patients with COVID-19.

Late relapse of ulcerative colitis presenting as tracheobronchitis: a case report.

BACKGROUND: Lung involvement in inflammatory bowel diseases usually follows colitis. However, the time to lung involvement onset varies depending on the case, and pulmonary lesions are usually not parallel to exacerbations of the colitis. CASE PRESENTATION: A 67-year-old Asian woman with a 38-year history of ulcerative colitis presented to our hospital with a complaint of prolonged dry cough for 2 months. The colitis had remained quiescent for > 35 years with low-dose salazosulfapyridine treatment. Chest computed tomography indicated circumferential thickening of the tracheal wall, while bronchoscopy examination revealed widespread erythematous edema and diffuse narrowing of the bronchial lumen. Biopsy of the bronchial mucosa showed submucosal lymphocytic infiltration. She was diagnosed with ulcerative-colitis-related tracheobronchitis and successfully treated with corticosteroids. CONCLUSIONS: Tracheobronchitis, in our case, occurred despite the longest remission period previously reported. Careful follow-up is necessary for the early recognition and treatment of pulmonary disease in patients with ulcerative colitis, regardless of the disease duration and long-term remission of colitis.

A Case of Tuberculosis-related Cerebral Venous Sinus Thrombosis and Pulmonary Thromboembolism Successfully Treated with Edoxaban.

A 22-year-old woman was admitted to the hospital with complaints of headache and vomiting. Radiological examinations revealed cerebral sinus venous thromboses, pulmonary thromboembolism, and cavities in the left upper lung. Pulmonary tuberculosis was diagnosed based on sputum and gastric aspirate culture. Heparin followed by warfarin was administered. Anti-tuberculosis agents including rifampicin were also initiated. Since the effect of warfarin did not reach the therapeutic level because of interaction with rifampicin, edoxaban was administered and thromboses were ameliorated. This report illustrates rare thrombotic complications in a TB-induced hypercoagulable state and the potential benefits and safety of edoxaban in combination with rifampicin.

Complete lack of vitamin C intake generates pulmonary emphysema in senescence marker protein-30 knockout mice.

Vitamin C (VC) is a potent antioxidant and plays an essential role in collagen synthesis. As we previously reported, senescence marker protein-30 (SMP30) knockout (KO) mice cannot synthesize VC due to the genetic disruption of gluconolactonase (i.e., SMP30). Here, we utilized SMP30 KO mice deprived of VC and found that VC depletion caused pulmonary emphysema due to oxidative stress and a decrease of collagen synthesis by the third month of age. We grew SMP30 KO mice and wild-type (WT) mice on VC-free chow and either VC water [VC(+)] or plain water [VC(-)] after weaning at 4 wk of age. Morphometric findings and reactive oxygen species (ROS) in the lungs were evaluated at 3 mo of age. No VC was detected in the lungs of SMP30 KO VC(-) mice, but their ROS increased 50.9% over that of the VC(+) group. Moreover, their collagen content in the lungs markedly decreased, and their collagen I mRNA decreased 82.2% compared with that of the WT VC(-) group. In the SMP30 KO VC(-) mice, emphysema developed [21.6% increase of mean linear intercepts (MLI) and 42.7% increase of destructive index compared with VC(+) groups], and the levels of sirtuin 1 (Sirt1) decreased 16.8%. However, VC intake increased the MLI 16.2% and thiobarbituric acid reactive substances 22.2% in WT mice, suggesting that an excess of VC can generate oxidative stress and may be harmful during this period of lung development. These results suggest that VC plays an important role in lung development through affecting oxidant-antioxidant balance and collagen synthesis.

Thymic adenocarcinoma with sarcomatoid features characterized by intracaval tumor growth: report of a case.

Primary thymic adenocarcinoma is an extremely rare tumor. This report describes a case of thymic adenocarcinoma with a peculiar pathological feature and clinical course. A 54-year-old man complained of cough, dyspnea, and chest pain. Computed tomography scans revealed an anterior mediastinal mass with intracaval growth into the superior vena cava. No definitive diagnosis could be made after several examinations and palliative radiotherapy was performed. He passed away 56 days after the appearance of the initial symptoms. An autopsy revealed that the mediastinal tumor obstructed not only the superior vena cava but also the pulmonary arteries. The histological findings revealed the tumor to be an adenocarcinoma with sarcomatous features. The tumor was immunohistochemically positive for CD5 and negative for thyroid transcription factor-1. These results suggested the tumor to be a thymic adenocarcinoma with sarcomatoid features; furthermore, the tumor invaded the great vessels, thus resulting in a poor prognosis.

[A case of pulmonary metastases from bladder cancer, suspected of recurrent Wegener's granulomatosis].

A 26-year-old-woman was given a diagnosis of Wegener's granulomatosis and began treatment by both prednisolone and cyclophosphamide at another institution. She was then admitted to our hospital due to progressive multiple pulmonary nodules. A diagnosis of pulmonary metastases from bladder cancer was established with radiological and histological examinations obtained by transbronchial lung biopsy (TBLB) and transurethral resection of the bladder tumor (TUR-Bt). She had already received a total dose of 120 g of cyclophosphamide, which could be related to the development of bladder cancer. On detecting multiple pulmonary nodules in patients with Wegener's granulomatosis treated with cyclophosphamide, it is necessary to consider the possibility of pulmonary metastases form urinary bladder cancer.

[Two cases of familial summer-type hypersensitivity pneumonitis requiring differentiation from bird breeder's lung].

A 74-year-old-man (case 1) was admitted to our hospital because of dry cough, fever, and dyspnea on effort. His daughter-in-law, a 53-year-old-woman (case 2), was also admitted to our hospital on suspicion of hypersensitivity pneumonitis (HP). Their diagnoses of HP were established by radiological, serological, and histological examinations. It was necessary to differentiate between summer-type hypersensitivity pneumonitis (SHP) and bird breeder's lung due to their special environment. Several examinations, including immunological findings of BALF, returning-home provocation test, and antigen inhalation challenge test, enabled us to establish their diagnoses of SHP.

Borderline pulmonary hypertension associated with chronic hypercapnia in chronic pulmonary disease.

Pulmonary hypertension (PH) due to lung diseases is classified as group 3 by the Dana Point classification. Given the basic pathophysiological conditions of group 3 lung diseases and the previously well-known concept of hypercapnic pulmonary vasoconstriction, chronic hypercapnia besides alveolar hypoxia might be another causative factor to increase mean pulmonary arterial pressure (PAm). Two hundred twenty-five subjects with chronic pulmonary diseases were assessed by a right heart catheterization and blood gas parameters. The subjects were classified into the following 4 groups: Hypercapnic Hypoxia (HCHX), Hypercapnic Normoxia (HCnx), Normocapnic Hypoxia (ncHX), and Normocapnic Normoxia (ncnx). Compared with ncnx, the HCHX, HCnx and ncHX groups all showed significantly higher PAm and met the criteria of borderline PH. Multiple regression analysis showed that PaCO2, as well as SaO2, was an independent variable for PAm. Given the poor prognosis with borderline PH, the elimination of excess pulmonary carbon dioxide in hypercapnia could be a considerable treatment strategy in chronic pulmonary disease.

[Evaluation of clinical effectiveness of Pazufloxacin Mesilate in acute exacerbation of chronic respiratory diseases].

Patients with chronic respiratory disease have increased susceptibility to infection, because of impairment of the local immunologic defense mechanism in the airway system, which often results in acute exacerbation. Acute exacerbation of chronic respiratory disease is one of the most important predictors of increased morbidity and mortality, and thus the management in the acute phase is essential for better prognosis. Although the clinical guidelines for the management of respiratory tract infections published by the Japanese Respiratory Society recommend administering fluoroquinolones intravenously in case of hospitalized patients, the clinical evidence is still limited. In this study, we evaluated the efficacy of Pazufloxacin Mesilate (PZFX). an intravenous fluoroquinolone. in patients with chronic respiratory diseases complicated with acute exacerbation caused by acute respiratory infections. As a result, 16 out of 18 cases were successfully treated with PZFX. No adverse event was observed during this study. These results may support the validity of administering intravenous fluoroquinolone in hospitalized patients with acute exacerbation caused by infections, as recommended by the Japanese Respiratory Society.

The diagnostic yield using ultrasound-guided needle-aspiration for subpleural primary lung cancer is not affected by the radiological properties of the lesions resulting from computed tomography.

BACKGROUND: It is well known that ultrasound-guided needle-aspiration (USGNA) for intrapulmonary subpleural lesion in contact with the pleura is useful and safe, and its diagnostic yield is high. However, reports concerned with the analyses of cases with intrapulmonary subpleural lesion which could not be diagnosed using USGNA are limited. The objective of this study is to clarify the radiological properties of subpleural primary lung cancer which obstruct diagnosis by USGNA. METHODS: The consecutive cases with subpleural primary lung cancer whose radiological properties could be confirmed by thoracic computed tomography (CT) without contrast enhancement (CE), and examined by USGNA at our hospital between January 1999 and December 2014 have been analyzed. All cases were given pathological diagnoses of primary lung cancer. The diagnostic yield by USGNA was calculated, and the properties of the lesions of the subjects were analyzed by means of thoracic CT without CE images and pathological findings. RESULTS: 87 consecutive cases (41-86 year olds, 75 males, 12 females) were analyzed. The overall diagnostic yield by USGNA was 86.2%. There was no statistically significant difference regarding the diagnostic yield concerning radiological properties such as cavities, small airspaces and low density areas in the lesions and their sizes. However, the diagnostic yield for the cases with squamous cell carcinoma was statistically significantly low (p=0.02). CONCLUSION: Although the diagnostic yield of USGNA is not distorted by the radiological properties of lesions, it is statistically significantly low in cases with squamous cell carcinoma.

COPD assessment test as a possible tool for evaluating health-related quality of life in lymphangioleiomyomatosis.

BACKGROUND: Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease that causes an obstructive ventilatory impairment similar to chronic obstructive pulmonary disease (COPD) and impairs the health-related quality of life (HRQoL). Here, we extended the use of the COPD assessment test (CAT) to patients with chronic respiratory diseases other than COPD. Specifically, the CAT was administered to patients with LAM for the first time. METHODS: Using data from 25 patients with LAM at Juntendo University who participated in the Multicenter Lymphangioleiomyomatosis Sirolimus Trial for Safety (MLSTS), we evaluated changes in pulmonary function, responses to HRQoL questionnaires (the CAT, St. George׳s Respiratory Questionnaire [SGRQ], EuroQOL Visual Analogue Scale [EuroQOL-VAS], and Functional Performance Inventory [FPI]), and the association between pulmonary function and HRQoL during a 24-month period of sirolimus treatment. RESULTS: Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and CAT total scores improved over the 24 months of sirolimus treatment (5.33 ± 1.20 ml/month, 2.61 ± 1.16 ml/month, and -0.127 ± 0.022 score/month, respectively), whereas SGRQ total score, EuroQOL-VAS score, and FPI score did not. Most pulmonary functions at baseline were associated with the CAT breathlessness score during the first year. Longitudinal changes in FEV1, FEV1%predicted, or FEV1/FVC correlated significantly with the scores of CAT total, CAT breathlessness, and SGRQ activity. When analyzed by stepwise multivariate regression within a linear mixed-effects model, CAT breathlessness and confidence scores were significantly associated with a change in FEV1 from the baseline value (P = 0.0011, and P = 0.0441). CONCLUSION: Our results suggest that the CAT is a useful instrument for assessing HRQoL in sirolimus-treated patients with LAM.

Impact of Airflow Limitation on Comorbidities and Postoperative Complications in Patients Undergoing Thoracic Surgery: A Retrospective Observational Study.

PURPOSE: To assess the frequency of airflow limitation (AFL), and the relationship between AFL and preoperative comorbidities or postoperative complications in patients who had undergone thoracic surgery. METHODS: The medical records of patients who underwent non-cardiac thoracic surgery at our institution between August 1996 and January 2013 were retrospectively reviewed. On the basis of preoperative pulmonary function tests, patients were classified with those with FEV1/FVC <70% [AFL(+) group] or with FEV1/FVC ≥70% [AFL(-) group]. Patient characteristics, preoperative comorbidities and postoperative complications were compared between the groups. RESULTS: Of the 3667 patients assessed, 738 (20.1%) were allocated to the AFL(+) group. AFL was an independent risk factor for three preoperative comorbidities: chronic obstructive pulmonary disease (odds ratio [OR]: 4.65), bronchial asthma (OR 4.30) and cardiac diseases (OR 1.41). Airflow limitation was also an independent risk factor for postoperative respiratory failure including long-term oxygen therapy (OR 2.14) and atelectasis (OR 1.90) in the patients who underwent lobectomy or partial resection of the lung. CONCLUSIONS: Our retrospective study revealed that careful attention needs to be paid to airflow limitation in patients who undergo non-cardiac thoracic surgery since it appears to be an important feature of preoperative comorbidities and to increase postoperative complications.

Do respiratory comorbidities limit the diagnostic usefulness of ultrasound-guided needle aspiration for subpleural lesions?

BACKGROUND: The usefulness of ultrasound-guided needle aspiration for subpleural lesions has been reported. However, no reports have evaluated its usefulness and safety in patients with respiratory comorbidities such as chronic obstructive pulmonary disease (COPD) and interstitial pneumonia (IP), which can increase the risk of iatrogenic pneumothorax. In this study, we evaluated the influence of chronic respiratory diseases (CRDs) on the usefulness and safety of ultrasound-guided needle aspiration for subpleural lesions. METHODS: Between January 2000 and September 2011, we examined 144 patients with intrapulmonary subpleural lesions. We retrospectively reviewed clinical data, including lesion size on thoracic computed tomography (CT), ultrasound findings, pathological findings obtained by ultrasound-guided needle aspiration, final diagnosis, and complications. RESULTS: A positive definitive diagnosis was obtained in 74.3% of all 144 patients; 84.7% patients with malignant diseases, including lung cancer; and 26.9% patients with benign diseases. Of the 144 patients, 64 belonged to the CRD group and 80 to the non-CRD group. The former included 31 patients with COPD, six with emphysematous changes on thoracic CT, 17 with IP, and 10 with other diseases. The positive rate of diagnosis for malignant diseases was 84.7% in the CRD group, which was the same as that in the non-CRD group. With regard to complications related to ultrasound-guided aspiration, there were only two cases of pneumothorax in the CRD group and one in the non-CRD group. CONCLUSION: Ultrasound-guided aspiration is safe and useful for subpleural lesions, particularly malignant lesions, even in patients with respiratory comorbidities such as COPD and IP.

Solitary fibrous tumor of the pleura: ultrasonographic imaging findings of 3 cases.

Solitary fibrous tumor (SFT) of the pleura is a rare tumor of mesenchymal origin. Although radiographic findings of thoracic computed tomography and magnetic resonance imaging in the evaluation of SFTs of the pleura have been documented, the value of ultrasonography is uncertain. We presented the ultrasonographic findings of 3 pathologically proven cases of SFTs arising from the visceral pleura. In all the cases, thoracic ultrasonography demonstrated homogeneous, hypoechoic, hemicycle, extrapulmonary lesions, which showed respiratory movement with the adjacent lung, consistent with pedunculated tumors. Preoperative thoracic ultrasonography could be useful in the evaluation of patients with pleural tumors, especially SFTs.

Malignant lymphoma with diffuse cardiac involvement detected by multiple imaging examinations: a case report.

INTRODUCTION: In malignant lymphoma, cardiac involvement, which usually forms pathologically focal and firm nodules in the cardiac walls, is considered to be a late manifestation of the disease. CASE PRESENTATION: We describe the case of a 71-year-old Asian Japanese woman whose first presentation of lymphoma was congestive heart failure. Multiple imaging examinations and laboratory findings led to a presumed diagnosis of a malignant lymphoma. A tissue diagnosis of the mediastinal mass could not be performed due to our patient's generally poor condition. Our patient received corticosteroid therapy, but died 42 days after her admission. An autopsy revealed lymphoid cells encircling her ventricular wall and infiltrating her endocardium. A histological examination confirmed the diagnosis of diffuse large B-cell lymphoma. CONCLUSION: Imaging examinations such as echocardiography, computed tomography with three-dimensional reconstruction, and gallium-67-citrate scintigraphy could clearly detect the diffuse cardiac involvement antemortem. A combination of these imaging techniques could provide a working diagnosis and allow empirical initiation of treatment in patients with poor general condition.