The Association Between Cyclooxygenase-2 -1195G/A (rs689466) Gene Polymorphism and the Clinicopathology of Lung Cancer in the Japanese Population: A Case-Controlled Study.

The single nucleotide polymorphisms of COX-2 gene, also known as PTGS2, which encodes a pro-inflammatory factor cyclooxygenase-2, alter the risk of developing multiple tumors, but these findings are not consistent for lung cancer. We previously reported that the homozygous COX-2 -1195A genotype is associated with an increased risk for chronic obstructive pulmonary disease (COPD) in Japanese individuals. COPD is a significant risk factor for lung cancer due to genetic susceptibility to cigarette smoke. In this study, we investigated the association between COX-2 -1195G/A polymorphism and lung cancer susceptibility in the Japanese population. We evaluated the genotype distribution of COX-2 -1195G/A using a polymerase chain reaction-restriction fragment length polymorphism assay for 330 newly diagnosed patients with lung cancer and 162 healthy controls. Our results show that no relationship exists between the COX-2 -1195G/A polymorphism and the risk of developing lung cancer. However, compared to the control group, the homozygous COX-2 -1195A genotype increased the risk for lung squamous cell carcinoma (odds ratio = 2.902; 95% confidence interval, 1.171-7.195; p = 0.021), whereas no association is observed with the risk for adenocarcinoma. In addition, Kaplan-Meier analysis shows that the genotype distribution of homozygous COX-2 -1195A does not correlate with the overall survival of patients with lung squamous cell carcinoma. Thus, we conclude that the homozygous COX-2 -1195A genotype confers an increased risk for lung squamous cell carcinoma in Japanese individuals and could be used as a predictive factor for early detection of lung squamous cell carcinoma.

Clinical Management of Asthma by Respiratory Specialists versus General Practitioners: Questionnaire Survey Results Over 6 Years.

BACKGROUND: In Japan, the Ministry of Health, Labour and Welfare population dynamics investigation showed a decrease in the number of deaths related to asthma in recent years. In 2016, the mortality rate was 1.2 deaths per 100,000 population. There were regional differences; Shimane Prefecture had a higher mortality rate (1.6 deaths per 100,000 population in 2016) than other prefectures. In this study, to clarify problems in asthma treatment, we evaluated the status of asthma treatment in Shimane Prefecture. METHODS: We performed three cross-sectional questionnaire surveys, in October 2006, February 2009, and February 2012. We received responses from 78 clinics and hospitals. Subjects were patients with bronchial asthma over 14 years of age who regularly visited an outpatient clinic. Survey items included smoking status, control status assessed using the Asthma Control Test (ACT), treatment, and medication adherence. Doctors board-certified by the Japanese Respiratory Society were defined as respiratory specialists (RSs) and other doctors were defined as general practitioners (GPs). We compared various factors between the RS and GP groups. RESULTS: Clinical data of 2159 patients were available for analysis. The proportion of patients with ACT score ≥ 20 points increased significantly between 2006 and 2012 in the GP group. The rate of inhaled corticosteroid use increased in the GP group from 63.6% to 76.4%. CONCLUSION: It was suggested that asthma control and the rate of inhaled corticosteroid use were related. We should continue educating GPs about asthma treatment.

Oxaliplatin-related interstitial pneumonia with high-grade fever and relative bradycardia as the presenting signs: a case report.

BACKGROUND: Although drug-induced interstitial pneumonia is a well-known adverse side-effect of cancer chemotherapy, the disease is difficult to detect in the early phase. We report a case of oxaliplatin-induced interstitial pneumonia in which eosinophilia and high-grade fever with relative bradycardia were useful presenting signs for the early diagnosis. CASE PRESENTATION: A 76-year-old Japanese woman with postoperative recurrent rectal cancer (peritoneal dissemination and liver metastasis) was admitted to our hospital because of productive cough and consolidation on thoracic computed tomography (CT) images. Two months prior to the consultation, she had started chemotherapy (fluorouracil, oxaliplatin, and bevacizumab). After finishing three courses of chemotherapy, she developed fever and was noted to have relative bradycardia. After another two courses of chemotherapy, she developed productive cough, chest discomfort, and high-grade fever. At this time, thoracic CT revealed patchy areas of consolidation distributed predominantly in the periphery. Despite the administration of tazobacterium/piperacillin, the consolidation seen on CT scans gradually worsened. Fiberoptic bronchoscopy was performed, and bronchoalveolar lavage fluid analysis showed increased lymphocytes, eosinophils, and total cell count but a low CD4/ CD8 ratio. No specific pathogen was identified. With a diagnosis of interstitial pneumonia, prednisolone was started and chemotherapy was temporarily discontinued. Her productive cough gradually decreased, and the infiltrative shadows on the thoracic CT scans improved. CONCLUSION: Although cases of oxaliplatin-related pneumonia with complicating relative bradycardia are not uncommon, drug-induced interstitial pneumonia should be taken into account in the differential diagnosis. In this case, an increased circulating eosinophil count and high-grade fever with relative bradycardia were the first signs of drug-induced interstitial pneumonia.

Malignant Peritoneal Mesothelioma Presenting with Polymyalgia Rheumatica-like Syndrome.

A 30-year-old man was admitted to our hospital because of pain in his proximal extremities. The pain mimicked polymyalgia rheumatica (PMR) and it temporarily improved by a low dose of glucocorticoids, but his symptoms relapsed many times. After six years of glucocorticoid treatment, he developed abdominal pain and ascites, for which he was diagnosed with malignant peritoneal mesothelioma (MPM). His PMR-like symptoms improved with cytoreductive surgery and chemotherapy for MPM. Finally, we diagnosed this PMR-like syndrome to be paraneoplastic syndrome with MPM. Although cases of MPM complicated by PMR-like syndrome are rare, MPM should be taken into account in the differential diagnosis.

Comparison of the chest computed tomography findings between patients with pulmonary tuberculosis and those with Mycobacterium avium complex lung disease.

BACKGROUND: Since the computed tomography (CT) findings of nontuberculous mycobacterial lung disease are similar to those of pulmonary tuberculosis (PTB), we often have difficulty differentiating the two. In this study, we compared the differences in chest CT findings and their locations between cases of PTB and Mycobacterium avium complex lung disease (MACLD). METHODS: The subjects were 100 MACLD patients and 42 PTB patients treated at our hospital from May 2005 to August 2015. The CT findings were retrospectively evaluated. RESULTS: PTB more frequently showed lung shadows with calcification inside the lesion, calcification of the mediastinal/hilar lymph node, and pleural effusion on CT than MACLD, while extensive bronchiectasis and granular/large shadows connected to bronchiectasis were more frequently observed with MACLD than PTB. For cavitary lesions, the thinnest part of the cavity wall with MACLD was thinner than that with PTB. Granular shadows, large shadows, and bronchiectasis were typically distributed to the right upper lobe and left upper division in PTB cases vs. the right intermediate lobe and left lingula in MACLD. CONCLUSIONS: Chest CT findings would therefore be useful for distinguishing PTB and MACLD when typical findings are observed.

The development of a polypoid intrapulmonary bronchogenic cyst in the bronchial lumen.

Intrapulmonary bronchogenic cysts are rare in adults and most are outside the trachea and bronchi. There are reports of clear link with the trachea, but the cyst itself occurs outside the trachea. Thus, bronchoscopy will not reveal the cause, which often leads to a diagnosis by surgical resection. We herein report an extremely rare case of an intrapulmonary bronchogenic cyst that was located entirely within the left main bronchial lumen. Bronchoscopy revealed a shiny and smooth surface mass with abundant blood vessels in the lumen that blocked the left main bronchus. The patient was successfully treated with bronchoscopic resection and remained stable at 16 months of follow-up. To our knowledge, this is the first reported case of an intrapulmonary bronchogenic cyst located entirely within the bronchial lumen.

Up-regulated integrinα4ß1 on systemic lymphocytes and serum IL-17A in interstitial pneumonia.

BACKGROUND AND AIMS: In interstitial pneumonia (IP), lymphocytes play an important role in lung injury and the involvement of integrinα4ß1 on leukocytes has previously been reported in animal models. Although the integrinα4ß1 expression level is known to be up-regulated by inflammatory cytokines, the involvement of interleukin (IL)-17A is unclear. The purpose of this study is to address the possible involvement of integrinα4ß1 on circulating lymphocytes and its correlation with serum IL-17A in interstitial lung diseases (ILDs). METHODS: We measured the expression levels of integrinα4ß1 on peripheral lymphocytes and the serum concentration of IL-17A and IL-23 in subjects with ILDs (n = 27; 14 males and 13 females, 66.7 ± 7.8 years old) and control subjects (n = 10; 5 males and 5 females, 66.6 ± 4.6 years old). RESULTS: Recombinant IL-17A up-regulated expression levels of integrinα4ß1 on healthy human lymphocytes in an in vitro experiment. Expression levels of integrinα4ß1 were significantly higher in those with acute hypersensitivity pneumonitis (HP) and non-specific IP (NSIP) compared with control. Serum IL-17A concentration was also significantly increased in acute HP and NSIP subjects compared with control. And IL-17A concentration positively correlated with integrinα4ß1 expression level (P < 0.05). Serum IL-23 was below the minimal detectable level in all subjects. CONCLUSIONS: These findings suggest that up-regulated levels of integrinα4ß1 on systemic lymphocytes and elevated serum IL-17A might be involved in the extravasation of lymphocytes in IP.

Comparison of clinical management of young and elderly asthmatics by respiratory specialists and general practitioners.

BACKGROUND: Asthmatic death in the elderly is a serious problem worldwide. Differences in clinical skill between respiratory specialists (RS) and general practitioners (GP) are important in asthma control. The aim of this study was to compare asthma management between RS and GP. METHODS: A cross-sectional survey was carried out in Shimane, Japan, in February 2009 using a questionnaire about patient background, treatment, asthma control test (ACT) and adherence to treatment. We secured the cooperation of 48 clinics (39 private clinics and 9 general hospitals). Asthmatics were divided into the elderly and young groups, and also into the RS and GP groups. RESULTS: Clinical data of 779 patients were available for analysis. Elderly patients constituted 464 (RS group: 192, GP group: 272), while those of the young group were 315 (RS group: 207, GP group: 108). RS prescribed inhaled corticosteroids (ICSs) to their elderly and young patients more than GP. The total ACT score was higher in young RS group than in young GP group, but no such difference was noted in the elderly. Despite more asthma-related symptoms, the ACT showed that elderly GP asthmatics used fewer rescue inhalers than elderly RS. Self-assessment was higher in elderly GP than elderly RS asthmatics. Adherence to therapy was better in elderly patients than young patients. CONCLUSIONS: Elderly asthmatics treated by GPs underestimated the severity of their asthma and asthmatics seen by GPs were undertreated. The results stress the need to engage patients in educational activities, to adhere to guidelines, and to improve the coordination between GP and RS.

Multiple logistic regression analysis of risk factors in elderly pneumonia patients: QTc interval prolongation as a prognostic factor.

BACKGROUND: Acute pneumonia is a serious problem in the elderly and various risk factors have already been reported, but the involvement of QTc interval prolongation remains uncertain. The aim of this study was to elucidate the prognostic factors for the development of pneumonia in elderly patients and to study the possible involvement of QTc interval prolongation. METHODS: The subjects were 249 hospitalized pneumonia patients more than 65 years old in Aki-Ohta Hospital from January 2010 to December 2013. Community-acquired pneumonia patients and nursing care and healthcare-associated pneumonia patients were included in the study. The pneumonia severity index, vital signs, blood chemistry data and ECG findings were retrospectively compared using multiple logistic regression analysis. RESULTS: 39 patients died within 30 days from onset. The clinical features related to poor prognosis were: advanced age, past history of cerebral vascular disease and/or diabetes mellitus, decreased serum albumin level, higher CURB-65 or PORT index scores and QTc interval prolongation. Patients showing a prolonged QTc interval had a higher mortality than those with a normal QTc interval. A prolonged QTc interval was not related to serum calcium concentration and/or treatment with QTc prolongation drug, clarithromycin or azithromycin, but related to age, lower albumin concentration and past history of diabetes mellitus. CONCLUSIONS: These findings suggest potential prognostic factors for pneumonia in elderly patients, including a prolonged QTc interval (> 0.44 seconds).

Cyclooxygenase 2 1195G > A polymorphism is associated with chronic obstructive pulmonary disease in Japanese and Chinese patients.

BACKGROUND: Cyclooxygenase-2 (COX-2) is overexpressed during airway inflammation in chronic obstructive pulmonary disease (COPD) patients. Single nucleotide polymorphisms (SNPs) in the COX-2 promoter might contribute to differential COX-2 expression and subsequent interindividual variability in susceptibility to COPD. We investigated the association between COX-2 (-765G > C, -1195G > A) polymorphisms and COPD susceptibility in Japanese and Chinese patients. METHODS: COX-2 genotypes were determined by polymerase chain reaction, restriction fragment length polymorphism in 230 COPD patients (103 Japanese and 127 Chinese) and 273 healthy controls (129 Japanese and 144 Chinese). RESULTS: The frequency of -1195AA homozygote was significantly higher than the controls in Chinese COPD (adjusted OR = 2.43, 95%CI 1.14 - 4.19), Japanese COPD (adjusted OR = 2.25, 95%CI 1.06 - 4.76) and combined COPD groups (adjusted OR = 2.26, 95%CI 1.34 - 3.99). There was no difference in COX-2 -765G > C polymorphism between COPD and control groups in either Japanese or Chinese, while more Chinese individuals carried the -765C allele than Japanese in both groups (15.3% vs. 2.9% in COPD, 18.8% vs. 5.5% in control). Chinese individuals with the haplotype -765G:-1195A were at higher risk for COPD (adjusted OR = 1.93, 95%CI 1.05 - 3.55). CONCLUSIONS: The COX-2 -1195AA genotype is associated with increased risk for COPD in both Japanese and Chinese individuals. Although COX-2 -765G > C polymorphism was not associated with COPD in either ethnic group, the -765C allele frequency was higher in Chinese than Japanese and haplotype -765G-1195A may confer susceptibility to COPD in Chinese.

Increased expression levels of integrin α9ß1 and CD11b on circulating neutrophils and elevated serum IL-17A in elderly aspiration pneumonia.

BACKGROUND: Repeated aspiration pneumonia is a serious problem in the elderly. In aspiration pneumonia, neutrophils play an important role in acute lung injury, while CD18-independent neutrophil transmigration pathways have also been reported in acid-aspiration pneumonia animal models. However, the involvement of IL-17A and ß1 integrin still remains unclear. The ß1 integrin subfamily integrin α9ß1 has been shown to be expressed on human neutrophils and to mediate adhesion to extracellular matrix proteins including the vascular cell adhesion molecule-1. OBJECTIVES: To elucidate the possible involvement of ß1 integrin subfamily and IL-17A in aspiration pneumonia. METHODS: We analyzed the expression levels of CD11b, CD18 and integrin α9ß1 in circulating neutrophils and serum concentration of IL-17A, IL-22 and IL-23 in elderly aspiration pneumonia patients (n = 32, 14 males and 18 females, 78.8 ± 3.9 years old) at 2 time points (on the day of admission before starting antibiotics and the day after finishing antibiotics) and compared the results with those of a control group (n = 30, 13 males and 17 females, 76.1 ± 3.4 years old). RESULTS: Recombinant IL-17A stimulated integrin α9ß1 and CD11b expression levels in healthy human neutrophils in vitro. The expression levels of integrin α9ß1 and CD11b in circulating neutrophils were significantly higher in pneumonia patients compared with the controls. In addition, serum IL-17A concentration was significantly increased in pneumonia patients. Integrin α9ß1 levels positively correlated with serum IL-17A and CD18 expression levels. CONCLUSIONS: These findings suggest a potential role of integrin α9ß1 expressed in neutrophils and elevated serum IL-17A in extravasation of neutrophils in cases of aspiration pneumonia.

[A case of acute hypersensitivity pneumonia in a worker at a feather duvet factory].

A 44-year-old woman was admitted to our hospital because of a 15-month history of exertional dyspnea, nonproductive cough and fever. Thoracic high-resolution computed tomography (HRCT) showed centrilobular ground-glass opacities distributed in bilateral lung fields. She had worked at a down quilt factory and had been exposed to a large amount of feathers for 5 years. A peripheral lymphocyte proliferation test by positive was positive for pigeon serum. We diagnosed bird-related hypersensitivity pneumonia. After quitting her job, improvement of her clinical symptoms and chest imaging findings were observed and she has been free of relapse.

Anti-inflammatory effects and clinical efficacy of theophylline and tulobuterol in mild-to-moderate chronic obstructive pulmonary disease.

BACKGROUND: The airway inflammation of chronic obstructive pulmonary disease (COPD) demonstrates a poor response to the anti-inflammatory actions of corticosteroids. However, long-acting beta(2)-agonists and low-dose theophylline are reported to have a possible anti-inflammatory effect in COPD. The aim of this study was to compare the effects of treatment between theophylline and the tulobuterol patch (transdermal patch preparation designed to yield sustained beta(2)-agonistic effects for 24h) on airway inflammation in addition to quality of life (QOL) and pulmonary function in mild-to-moderate COPD. METHODS: The study subjects consisted of 26 patients with COPD who were treated with theophylline or tulobuterol for 8 weeks with a wash-out period of 4 weeks in a randomized open-label crossover study. We prospectively investigated the differential cell counts and levels of inflammatory markers in induced sputum before and after treatment with theophylline and tulobuterol. We also examined pulmonary function and quality of life (QOL) as assessed by St. George's Respiratory Questionnaire. RESULTS: In the induced sputum, the total inflammatory cell count and number of neutrophils were significantly reduced by treatment with low-dose theophylline. Neither of these parameters was significantly changed by treatment with tulobuterol. Pulmonary function measurements such as FEV(1), FEV(1) % pred, FVC, PEF, MEF(50), and MEF(25) were significantly improved by the treatment with low-dose theophylline but not tulobuterol. The total QOL scores, levels of interleukin 8 and myeloperoxidase in the supernatants of induced sputum, and serum levels of hypersensitive C-reactive protein were not significantly changed by either of the treatments. CONCLUSION: These results suggest that treatment with low-dose theophylline but not the tulobuterol patch may have anti-inflammatory effects and improve pulmonary function in mild-to-moderate COPD.

A case of pulmonary asbestosis presenting with temporal arteritis involving multiple medium-sized vessels.

A 76-year-old woman with pulmonary asbestosis was admitted with fever and polymyalgia. She subsequently developed a visual disorder, hemoptysis, and hemoperitoneum. A biopsy of the temporal artery revealed the presence of giant-cell arteritis. CT and angiography showed hemorrhaging from the bronchial and abdominal arteries. These observations suggested temporal arteritis in which medium-sized vessels were involved. This case implies the association between vasculitis and asbestosis, and suggests a problem in the classification of vasculitides.

[Clinical study of 37 pneumonia patients in whom MRSA was identified from sputum].

When we studied the clinical aspects of 37 pneumonia patients with underlying respiratory disease in whom MRSA 1 + was identified from sputum, 43.2% of these 37 pneumonia cases were diagnosed as MRSA colonization. The whole clinical course of these pneumonia patients with MRSA colonization was average 39.5 days, on the other hand, the whole clinical course of MRSA pneumonia group was 55.3 days. We should consider that MRSA must be a cause of pneumonia, in only such cases as follows; (1) patients with unstable diabetes mellitus, or with long-term administration of steroid, (2) patients with infiltrative shadows appeared not only in the lower lobe but also the upper lobe in the chest x-ray films, (3) patients with remarkable decrease of PaO2 or patients who failed to recover within one month from MRSA isolation, (4) patients with nosocomial pneumonia or patients with poor performance status or poor prognosis, (5) patients with purulent sputum containing MRSA or other bacteria such as K. pneumoniae etc and patients who failed to respond to general antibacterial agents.

Increased T-cell receptor mutation frequency in radiation-exposed residents living near the Semipalatinsk nuclear test site.

From 1949 to 1989, 488 nuclear explosions were carried out in Semipalatinsk, and the cancer risk is increased in this region. Measuring somatic-cell mutation frequencies may be a useful tool for evaluating cancer risk within radiation-exposed populations. Here, we report the first evidence of increased T-cell receptor (TCR) mutations in peripheral blood from radiation-exposed residents of Semipalatinsk. The TCR mutation frequency in the highly exposed residents (Dolon and Sarzhal) was significantly higher than in the control group (Kokpekti). There was no statistically significant difference between the control group and the weakly exposed group (Kaynar and Semipalatinsk-city). The TCR mutation assay appeared to be a useful biological dosimeter even after a period of 40 years since radiation exposure. This may be the result of specific conditions, such as the presence of internal exposure.

Human suffering effects of nuclear tests at Semipalatinsk, Kazakhstan: established on the basis of questionnaire surveys.

The main objective of the present paper is to explore the effects of radiation exposure on the inhabitants near the Semipalatinsk Nuclear Tests Site (SNTS), Kazakhstan. Our research team of the Research Institute for Radiation Biology and Medicine, Hiroshima University, started in 2002 to conduct a field research study using questionnaire surveys. The present paper attempts to clarify health effects and mental problems on the inhabitants by using our questionnaire surveys. Among the responses to our survey, the present paper focuses upon responses to the questions concerning their health and mental problems. The data in Semipalatinsk have been compared with the results obtained in a similar survey conducted by Hiroshima and Nagasaki cities. The results show: (1) 33% of the residents replied that they felt bad or had very bad health conditions. (2) 70% of the residents strongly recognized a causal relationship between their bad health conditions and the nuclear tests. (3) The diseases that over 30% of respondents possessed are arthralgia/ lower back pain/ arthritis, high-blood pressure, heart disease and digestive system disease. (4) Acute radiation injuries from 1949 to 1962 that over 20% of respondents experienced were headaches and general malaise. (5) Concerning their mental condition, 22% of respondents felt easily frustrated and agitated and 21% experienced nightmare.

[Trichosporon antibodies (corrected of antigen) and HLA-antigen in summer-type hypersensitivity pneumonitis in a family].

We encountered a family in which all of the three members (the parents, a 45-year-old woman and 51-year-old man, and their 15-year-old daughter) had Trichosporon cutaneum antibodies (corrected of antigen), and two (the parents) suffered from summer-type hypersensitivity pneumonitis in the late summer. The husband complained of dry cough, fever and dyspnea on exertion from July after severe interstitial pneumonitis and was treated with steroid pulse in September 2004. His wife visited our hospital and complained of a common cold-like symptom which progressed in August 2005. The couple were given diagnoses of summer-type hypersensitivity pneumonitis because they were positive for serum anti-Trichosporon mucoides antigen and asahii antigen. Their asymptomatic daughter was positive for these antigens. Both wife and daughter had HLA-DQ 8 (3) and 9 (3) that are suggested to be important HLA antigens related to the occurrence of summer-type hypersensitivity pneumonitis.

Noninvasive positive pressure ventilation in treatment of non-COPD related acute respiratory failure cases.

We used Noninvasive Positive Pressure Ventilation (NPPV) in nine patients with acute respiratory failure (ARF), not related to chronic obstructive pulmonary disease (COPD). After separating the nine patients into a hypercapnic group (five patients) and a non-hypercapnic group (four patients), we investigated its effectiveness in physiological improvement and avoiding intubation. Dyspnea, physiological findings and ABG improved rapidly in both groups without serious adverse effects. The intubation avoidance rate was 66.7% (6 of 9) in total, and 80% in the hypercapnic group and 50% in the non-hypercapnic group. The ratio of PaO2 to FiO2 (P/F ratio) increased during NPPV in most cases where intubation could be avoided. It is worthwhile to use NPPV as a bridging therapy between O2 therapy and invasive ventilation in patients with non-COPD related ARF, regardless of the existence of hypercapnia. Careful monitoring of the P/F ratio and complications is needed to make an appropriate decision whether avoiding intubation will be possible or not.

Legionella micdadei pneumonia diagnosed by culture isolation and DNA-dNA hybridization from bronchial lavage fluid.

An 80-year-old man was admitted because of dyspnea on effort. We suspected an acute exacerbation of chronic heart failure and idiopathic interstitial pneumonia caused by right-sided pneumonia. A nodular shadow in right upper lobe spread and consolidated into the airspace, and it failed to improve despite administration of meropenem trihydrate, vancomycin hydrochloride and clindamycin. A definitive diagnosis of Legionella micdadei pneumonia was made on the basis of this organism being isolated in culture from bronchial lavage fluid and subsequent identification of Legionella micdadei using DNA-DNA hybridization. The airspace consolidation gradually improved following treatment with intravenous erythromycin and minocycline hydrochloride.