Association of serum adiponectin with asthma and pulmonary function in the Japanese population.

Conflicting findings have been reported regarding the role of adiponectin in asthma. The aim of this study was to evaluate the association of adiponectin with pulmonary functions and asthma in the Japanese population. First, among a general population that participated in a previous study (group 1), we selected 329 subjects after excluding those with asthma, chronic obstructive pulmonary disease, and a smoking history and examined the associations of the serum total adiponectin levels with pulmonary functions. In a second cohort (group 2) consisting of 61 asthmatic patients and 175 control non-asthmatic subjects, we examined the associations between asthma and the levels of total, high (HMW), middle (MMW) and low (LMW) molecular weight adiponectin isoforms as well as the ratio of each isoform to total adiponectin level. Although the total adiponectin levels were not significantly different between the asthmatic and control subjects in group 2, the levels were significantly and positively associated with the forced expiratory volume in 1 s after adjustments for confounding factors (P < 0.05) in women in group 1. In group 2, the LMW adiponectin level was significantly higher and the MMW/total adiponectin ratio was significantly lower among the asthmatic subjects than among the control subjects after adjustments for confounding factors in both sexes (P < 0.05). The present study showed that a low total adiponectin level may lead to airway narrowing compatible with asthmatic airways in women, and higher LMW adiponectin levels and lower MMW/total adiponectin ratio are significantly associated with current asthma in both sexes.

Sarcoidosis With Multiple Bone Lesions Mimicking Advanced Lung Cancer With Multiple Bone Metastases.

Bone lesions in sarcoidosis are more common than previously known. A 59-year-old female with a history of sarcoidosis was referred due to suspected lung cancer. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) revealed numerous bone lesions in addition to abnormal uptake by pulmonary nodules and mediastinal lymph nodes, which mimicked metastatic advanced lung cancer. Biopsy of bone lesions detected epithelioid cell granuloma consistent with bone sarcoidosis. Moreover, prednisolone treatment was tried to exclude malignant disease. One month after prednisolone administration, bone lesions and other abnormal uptake disappeared on PET/CT. Bone sarcoidosis is often asymptomatic and is discovered incidentally as multiple lesions that may require differentiation from malignant disease. Biopsy of bone lesions and administration of corticosteroids may be useful for accurate diagnosis.

Acute hypercapnic respiratory failure in patients with obesity hypoventilation syndrome during the COVID-19 pandemic: Four case reports.

Obesity hypoventilation syndrome (OHS) can cause acute hypercapnic respiratory failure (AHRF). The onset of AHRF in four patients with OHS during the coronavirus disease 2019 (COVID-19) pandemic is reported in this study. Two men (23 and 45 years old) and two women (both 77 years old) presented to our hospital with AHRF. In the two elderly women, a prolonged supine position due to falls seemed to be the cause of AHRF. Treatment was started with bilevel positive airway pressure for all patients. While one patient died, the condition of the other three improved; they were discharged with continuous positive airway pressure. AHRF due to OHS was rarely reported in the rural region of Japan. It is suggested that increased rates of obesity due to lifestyle changes during the COVID-19 pandemic may be responsible for an increase in the prevalence of OHS-associated AHRF.

Association between body mass index and asthma among Japanese adults: risk within the normal weight range.

BACKGROUND: Increasing amounts of data have shown that some Asian populations are more susceptible to increased weight and development of noncommunicable disease than Western populations. However, little is known about the association between increased weight, particularly within the normal range, and the development of asthma among Asian populations. METHODS: To examine the association between increased body mass index (BMI) and asthma among Japanese adults, data from a nationwide population-based cross-sectional survey of asthma prevalence in Japan were analyzed (n = 22,962; age range 20-79 years). BMIs were classified into 7 categories considering WHO recommendations (cutoff points: 17.00, 18.50, 23.00, 25.00, 27.50 and 30.00), and the association between BMI and the prevalences of asthma as well as asthma symptoms were assessed by multivariate logistic regression. RESULTS: The prevalences of obesity (BMI ≥ 30.00) in this population were relatively low (males 3.0%, females 2.3%). BMI categories of 25.00 or higher in both genders were significantly associated with an increased risk of asthma compared with the reference category (BMI 18.50-22.99). Even in females with a BMI of 23.00-24.99, the prevalence of asthma significantly increased (adjusted odds ratio 1.49, 95% confidence interval 1.16-1.92) compared with that in the reference category. CONCLUSIONS: An increase in the prevalence of asthma among Japanese females starts at a BMI of 23.00, which was relatively lower than those reported from Western countries. This finding suggests that the Japanese population is likely to have asthma with a lesser degree of obesity than Western populations.

[Synchronous pulmonary hamartoma and lung cancer in a young patient].

A 23-year-old man was admitted for examination of an abnormal shadow in the right lower lung field. A chest CT scan revealed a nodule in the right lower lobe and a calcified nodule in the right upper lobe. A diagnosis of lung adenocarcinoma in the right lower lobe was made by transbronchial cytology. After resection of the right lower lobe and partial resection of the nodule in the right upper lobe were performed, we diagnosed lung adenocarcinoma in the right lower lobe (pathological stage IIIA) and hamartoma in the right upper lobe. Although several authors have reported cases of synchronous pulmonary hamartoma and lung cancer, it is uncommon in young patients. Since patients with hamartoma could also have lung carcinoma, careful observation is needed.

Development of second primary small-cell lung cancer within the irradiated field after chemoradiotherapy: a report of two cases.

Two male smokers developed small-cell lung cancer (SCLC) as the second primary malignancy (SPM) in the irradiated field after concurrent chemoradiotherapy for locally advanced cancer, which could also be considered as a radiation-induced tumour. A 70-year-old man received cisplatin and S-1 and irradiation at 60 Gy for lung adenocarcinoma eight years previously and an 81-year-old man cisplatin and 5-fluorouracil and at irradiation 60 Gy for oesophageal cancer five years previously. They sequentially received chemotherapy for SCLC, the effects of which were limited, and a refractory course was noted. Chemoradiotherapy is an effective treatment strategy for locally advanced cancer but may be relevant to the onset of SCLC as SPM.

Evaluation of a novel urinary antigen test kit for diagnosing Legionella pneumonia.

OBJECTIVES: The aim of this study was to evaluate the diagnostic utility of a novel test kit that could theoretically detect all serogroups of Legionella pneumophila for diagnosing Legionella pneumonia, in comparison with existing kits. METHODS: This study was conducted in 16 hospitals in Japan from April 2016 to December 2018. Three urinary antigen test kits were used: the novel kit (LAC-116), BinaxNOW Legionella (Binax), and Q-line Kyokutou Legionella (Q-line). In addition, sputum culture and nucleic acid detection tests and serum antibody tests were performed where possible. The diagnostic accuracy and correlations of the novel kit with the two existing kits were analyzed. RESULTS: In total, 56 patients were diagnosed with Legionella pneumonia. The sensitivities of LAC-116, Binax, and Q-line were 79%, 84%, and 71%, respectively. The overall match rate between LAC-116 and Binax was 96.8% and between LAC-116 and Q-line was 96.4%. One patient had L. pneumophila serogroup 2, and only LAC-116 showed a positive result, whereas Binax and Q-line did not. CONCLUSIONS: The novel Legionella urinary antigen test kit was useful for diagnosing Legionella pneumonia. In addition, it could detect Legionella pneumonia caused by non-L. pneumophila serogroup 1.

Nationwide cross-sectional population-based study on the prevalences of asthma and asthma symptoms among Japanese adults.

BACKGROUND: Asthma is a common respiratory disease worldwide. However, few reports are available on the prevalences of asthma and asthma symptoms among Asian subjects. METHODS: To determine the prevalences of asthma and asthma symptoms among Japanese subjects, we performed a nationwide cross-sectional, population-based study on Japanese adults aged 20-79 years. Ten areas spread throughout the country were randomly selected. Door-to-door or postal surveys were performed using a translated version of the European Community Respiratory Health Survey questionnaire. RESULTS: The survey was completed by 23,483 participants. The overall response rate was 70.6%. The prevalences of wheeze and current asthma among all participants aged 20-79 years were 10.1% (95% CI: 9.7-10.5%) and 4.2% (95% CI: 4.0-4.5%), respectively. The prevalences among young adults aged 20-44 years were 9.3% (95% CI: 8.7-9.9%) and 5.3% (95% CI: 4.8-5.8%), respectively. The prevalence of current asthma was highest in females aged 30-39 years in comparison with the other gender and age groups. CONCLUSIONS: This nationwide study determined the prevalences of asthma and asthma symptoms among Japanese adults. The results provide fundamental information on the respiratory health of Japanese adults.

[Long-term survival case of small-cell lung cancer with Lambert-Eaton myasthenic syndrome without anticancer therapy].

A 78-year-old man with complaints of appetite loss and weight loss visited our hospital in November 2006. Positron-emission tomography and computed tomography (PET/CT) showed swollen lymph nodes in the abdominal para-aorta, mediastinum and neck, with intense FDG accumulation. The pathological findings of the cervical lymph nodes revealed small-cell cancer. We diagnosed extensive small-cell lung cancer (SCLC), which occurred primarily in the left upper lobe. As subsequent CT revealed spontaneous shrinkage of the pulmonary nodule and swollen lymph nodes, the clinical course was monitored without anticancer therapy. In February 2007, progressive muscle weakness of the lower extremities developed. In July he was admitted with respiratory failure and required mechanical ventilation. Although we did not administer anticancer therapy due to his poor performance status, he survived for 30 months receiving mechanical ventilation, and the tumors continued to grow moderately. We diagnosed Lambert-Eaton myasthenic syndrome (LEMS) based on the clinical symptoms, the presence of anti-VGCC antibodies and waxing phenomenon on electromyography obtained in April 2009. Chemotherapy with amrubicin shrank the tumors, but his muscle weakness did not improve. Previous reports showed that a prognosis of SCLC with LEMS was better than that without LEMS. In this case, the tumors showed spontaneous regression without any anticancer therapy, and then increased moderately. The immune response was considered to have affected tumor growth.

[Two cases of pulmonary sarcomatoid carcinoma mimicking malignant mesothelioma].

We report 2 cases of pulmonary sarcomatoid carcinoma mimicking malignant mesothelioma. Case 1: A 69 year-old man presented, complaining of right chest pain. The chest X ray film and CT showed tumors in the right chest wall and pleura. Histological findings of specimens obtained from a percutaneous biopsy revealed spindle tumor cells, and the immunohistochemistry showed that the tumor cells were positive for CK-7, AE1/AE3, and vimentin and negative for calretinin, D2-40, and WT-1. We diagnosed pulmonary sarcomatoid carcinoma and started chemotherapy with carboplatin and paclitaxel, but it was ineffective. Case 2: A 68 year-old man was admitted complaining of general malaise. The chest X ray film and CT revealed tumors in the right chest wall. Histological findings showed necrosis and spindle tumor cells which were positive for AE1/AE3 and vimentin, and negative for calretinin, D2-40, and WT-1. We diagnosed pulmonary sarcomatoid carcinoma and started chemotherapy with carboplatin and paclitaxel. However the disease continued to progress and he died 2 months after admission. The pulmonary sarcomatoid carcinoma was reported to have spred to the pleural and chest wall. The present two cases showed prominent chest wall and pleural tumors with obscure primary lung tumors. Therefore, we needed to differentiate sarcomatoid carcinoma from malignant pleural mesothelioma.

Interstitial lung disease induced by docetaxel and ramucirumab chemotherapy after nivolumab treatment.

Three men (aged 64, 65, and 67 years) with advanced lung cancer who had been treated with nivolumab developed interstitial lung disease (ILD) during chemotherapy with docetaxel and ramucirumab. The treatment was clinically effective; however, the patients experienced immune-related adverse effects due to nivolumab therapy: two patients developed ILD and the third developed psoriasis. Because the patients showed progression, docetaxel and ramucirumab chemotherapy was administered. Although two patients showed a clinical response, all patients developed grade 3 ILD during therapy. Furthermore, the patients developed respiratory failure and needed corticosteroid therapy. Although their condition improved owing to the therapy, the patients could not receive additional cancer treatment and died of cancer. On the basis of the results obtained, we speculated that although the regimen of docetaxel and ramucirumab after nivolumab therapy might be effective against non-small cell lung cancer, it might increase the risk for ILD in some patients.

Interstitial pneumonitis associated with infliximab therapy without methotrexate treatment.

Tumor necrosis factor (TNF)-α inhibitors are increasingly being used to treat rheumatoid arthritis. Infliximab (INF) is a TNF-α inhibitor that is usually used in combination with methotrexate (MTX). Interstitial lung disease (ILD) during combination therapy has been attributed to MTX rather than INF. However, INF-associated ILD without combination with MTX has recently been reported. We describe herein a case of severe ILD secondary to INF without MTX therapy.

[A case of bronchiolitis with IgG4-positive plasma cells infiltration associated with Mikulicz's disease and autoimmune pancreatitis].

A 23-year-old Japanese man was admitted to our hospital because of dry cough and lacrimal gland swelling. Laboratory findings showed hypergammaglobulinemia (4859 mg/dl), hypocomplementemia (CH50 13 U/ml), and hyperamylasemia. CT revealed a marked swelling of the bilateral lacrimal glands, diffuse patchy infiltration in the bilateral lung fields, and enlargement of the whole pancreas. Gallium citrate scintigraphy showed abnormal accumulation in the bilateral lacrimal glands, submandibular glands, and both lung fields. Biopsy specimens from the salivary gland revealed dense lymphoplasmacytic infiltration and abundant IgG4-positive plasma cells. Furthermore, open lung biopsy showed a marked peribronchial lymphoplasmacytic and eosinophilic infiltration with IgG4-positive plasma cells. These findings fulfilled the criteria of Mikulicz's disease and autoimmune pancreatitis, and support the recently proposed concept of IgG4-related systemic disease.

Hyperprogressive Disease in Lung Cancer with Transformation of Adenocarcinoma to Small-cell Carcinoma during Pembrolizumab Therapy.

Hyperprogressive disease (HPD) is a paradoxical phenomenon involving the acceleration of tumor progression after treatment with immune checkpoint inhibitors (ICIs). A 66-year-old male smoker with advanced lung adenocarcinoma started pembrolizumab for progressive disease following first-line chemotherapy. He developed HPD after two cycles, and a re-biopsy revealed transformation to small-cell carcinoma. He subsequently underwent two lines of chemotherapy for small-cell carcinoma until progression and ultimately died. Transformation to small-cell carcinoma may be a cause of HPD during ICI therapy. The possibility of pathological transformation should be considered in cases of HPD with resistance to ICI therapy.

Successful treatment of non-tuberculous mycobacterial pleurisy with acute fever by antimycobacterial therapy.

We report two cases of pleurisy caused by non-tuberculous mycobacteria followed by pneumothorax. The onset of pleurisy was accompanied by acute fever. Cultured samples of the pleural effusions from the two patients, an 80-year-old man and an 87-year-old woman, were ultimately found to contain Mycobacterium intracellulare and Mycobacterium kansasii, respectively. Both patients were initially administered antibiotics, but their fevers persisted. Therefore, different combinations of antimycobacterial drugs were used, which reduced the fever in a few days. In these patients, pleurisy caused by non-tuberculous mycobacteria followed by pneumothorax was characterised by acute fever and improvement in the fever after administration of antimycobacterial drugs; however, the aetiology remains to be clarified.

Mycobacterium bovis-induced Aneurysm after Intravesical Bacillus Calmette-Guérin Therapy: A Case Study and Literature Review.

Mycobacterium bovis infection after intravesical Bacillus Calmette-Guérin (BCG) therapy is rare. A 65-year-old Japanese man with history of bladder cancer and intravesical BCG therapy, presented with low-grade fever. An aneurysm with perianeurysmal fluid was suspected and endovascular aortic repair was performed. After 160 days, he developed blood-streaked sputum and computed tomography images revealed that the perianeurysmal fluid area was increasing in size. A multiplex polymerase chain reaction using sputum identified M. bovis. Treatment with anti-tuberculosis drugs reduced the size of the perianeurysmal fluid area. After intravesical BCG therapy, the possibility of M. bovis infection should be considered, thus further investigations are required.

Ionizing radiation suppresses FAP-1 mRNA level in A549 cells via p53 activation.

Ionizing radiation (IR) is known to upregulate cell surface Fas through p53 activation in various cells. However, the signaling pathway intermediating between p53 activation and cell surface Fas upregulation remains to be elucidated. Recently, Fas-associated phosphatase-1 (FAP-1) has been reported to associate with Fas and inhibit cell surface Fas expression. We evaluated the expression of FAP-1 mRNA following IR in A549 cells. Ionizing radiation inhibited the expression of FAP-1 mRNA. Pretreatment with p53 inhibitor pifithrin alpha cancelled the IR-induced downregulation of FAP-1 mRNA. These results suggest that IR-induced p53 activation may upregulate cell surface Fas via the down-modulation of FAP-1.

Association between Smoking Status and Obesity in a Nationwide Survey of Japanese Adults.

OBJECTIVE: A positive association between the number of cigarettes smoked per day and obesity has been reported, whereas how other smoking-related indices, such as pack-years and duration of smoking, are related with obesity has been less investigated. We analyzed the age-adjusted cross-sectional association between smoking and obesity in a general Japanese population. METHODS: We used data from a nationwide epidemiological study of Japanese adults (N = 23,106). We compared the prevalence of obesity (defined as body mass index ≥ 25kg/m2) among groups classified by smoking behavior, pack-years, number of cigarettes per day, duration of smoking, and duration and time of smoking cessation. RESULTS: In men, current smokers had a lower odds ratio (OR) for obesity of 0.80 (95% confidence interval (CI): 0.72-0.88) compared to non-smokers, whereas past smokers had a higher OR of 1.23 (95% CI: 1.09-1.37) compared to current smokers. In women, there were no differences in obesity between the three groups classified by smoking behavior. However, in both sexes, the prevalence of obesity tended to increase with pack-years and the number of cigarettes per day, but not with duration of smoking in current and past smokers. Further, in male smokers, the risks for obesity were markedly higher in short-term heavy smokers compared with long-term light smokers, even with the same number of pack-years. Regarding the impact of smoking cessation, female past smokers who quit smoking at an age > 55-years had an elevated OR of 1.60 (95% CI:1.05-2.38) for obesity. CONCLUSIONS: In a general Japanese population, obesity is progressively associated with pack-years and number of cigarettes per day, but not with the duration of smoking. When investigating the association between obesity and cigarette smoking, the daily smoking burden and the duration of smoking require to be independently considered.

Association of the polymorphisms in the 5'-untranslated region of PTEN gene with type 2 diabetes in a Japanese population.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is known to act as a lipid phosphatase hydrolyzing phosphatidylinositol (PI)(3,4,5)P(3) to PI(4,5)P(2). Since the PI3-kinase product, PI(3,4,5)P(3), is an important second messenger leading to the metabolic action of insulin, PTEN functions as a potent negative regulator of insulin signaling and its gene is one of the possible candidates involved in susceptibility to the development of type 2 (non-insulin-dependent) diabetes. In the present study, we investigated the polymorphisms of the PTEN gene in Japanese patients with type 2 diabetes and non-diabetic control subjects. We identified three mutations of the gene in the type 2 diabetes patients. Among these mutations, the frequency of the substitution of C with G at position -9 (-9C-->G) (SNP1), located in the untranslated region of exon 1, was significantly higher in type 2 diabetic patients than in control subjects. In addition, transfection of the PTEN gene with SNP1 resulted in a significantly higher expression level of PTEN protein compared with that of the wild-type PTEN gene in Cos1 and Rat1 cells. Furthermore, insulin-induced phosphorylation of Akt in HIRc cells was decreased more greatly by transfection of SNP1 PTEN gene than that of wild-type PTEN gene. These findings suggest that the change of C to G at position -9 of the PTEN gene is associated with the insulin resistance of type 2 diabetes due possibly to a potentiated hydrolysis of the PI3-kinase product.

[Marked improvement of Lambert-Eaton myasthenic syndrome resulting from treatment for small cell lung carcinoma].

A 68-year-old man was admitted to our hospital because of muscle weakness. A complete medical examination led to a diagnosis of small cell lung carcinoma (SCLC) with Lambert-Eaton myasthenic syndrome (LEMS) and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Four courses of chemotherapy (carboplatin + etoposide) and one of radiotherapy with a total dose of 45 Gy to the mediastinum were performed and resulted in a partial response in the SCLC. After the second course of chemotherapy, the serum level of antivoltage-gated Ca2+ channel (VGCC) antibody decreased from 190 pg/ml to 120 pg/ml. Marked improvement of the muscle weakness was recognized only after 3 courses of chemotherapy. The patient, who had had difficulty in standing, recovered enough to be able to climb stairs after 4 courses of chemotherapy. Marked improvement of LEMS was achieved by treatment for small cell lung carcinoma.