Inhaled Corticosteroid-Containing Regimens Reduce Hospitalizations and Healthcare Costs among Elderly Asthmatics: Real-World Validation Using the National Health Insurance Claims Database.

The high rates of mortality and hospitalization among elderly asthmatics, as well as their increasing healthcare costs have become an important public health issue. It would be worthwhile to assess whether inhaled corticosteroid (ICS) can resolve these problems. To explore ICS prescription rates for elderly asthmatics and the factors influencing them and to investigate their association with hospitalization and healthcare costs, we analyzed data from the National Health Insurance Claims Database for the same time frame (December 1 to February 28) across three different periods (2011-2012; 2014-2015; and 2017-2018), from which we identified 6,619, 5,619, and 6,880 elderly individuals, respectively. The prescription rates of ICS increased (52.8%, 65.5% and 68.8%, in the first, second and third survey period, respectively) and inversely the hospital admission rates declined (3.7%, 3.2% and 2.5%, in the first, second and third survey period, respectively). The total healthcare costs per month were significantly lower for patients who received ICS-containing regimens than for those who did not. A multivariate analysis revealed that increasing age, rural residence, receiving a prescription from a clinic, hospital admission, and prescription of asthma medications other than ICS were associated with non-prescription of ICS, whereas cross-boundary treatment increased the ICS-prescription rate. Our study suggests that increases in the prescription rate of ICS are associated with reduced hospital admission rates and lower medical costs in the real-world. ICS prescription rates in rural areas and at clinics, which remain low, need to be increased.

A diagnosis of depression should be considered in patients with multiple physical symptoms in primary care clinics.

Although the vast majority of depressed patients visit primary health care clinics, they often remain undiagnosed and untreated. Therefore, early detection in primary care settings is important. There is a high correlation between number of physical symptoms and the presence of depression, yet little has been reported regarding this relationship in Japanese primary care clinics. We examined number of physical symptoms and depression in a department of general medicine of a Japanese hospital. We included patients with unexplained symptoms after multiple tests to rule out organic diseases. Twenty-one common symptoms were assessed using a symptom checklist. Depression was diagnosed using the Patient Health Questionnaire-9, a self-administered questionnaire designed to diagnose depression. Among 386 patients, 105 (27.2%) (average age: 49.7 ± 20.9 years, 28 men and 77 women) met the criteria for depression. Among the 21 symptoms, 14 were significantly more frequent in patients with depression than in those without depression. When patients had neither general fatigue, nor sleep disturbance nor appetite loss, none met the criteria for depression. Number of symptoms was significantly higher in patients with compared with those without depression. The prevalence of depression increased with number of symptoms: 2% (2/100) for 0 or 1 symptom, 42.4% (42/99) for four to five symptoms and 68.7% (22/32) for more than nine symptoms. Japanese primary care physicians can often rule out depression when patients have neither general fatigue, nor sleep disturbance nor appetite loss. A diagnosis of depression should be considered in patients who report multiple physical symptoms.

Effects of smoking cessation on gastric emptying in smokers.

BACKGROUND: Smoking cessation can lead to changes in appetite and weight gain in some patients; thus, smoking cessation may alter gastrointestinal motility. Effects of smoking cessation on gastric emptying in smokers have not been established. AIM: This study sought to determine how smoking cessation affects gastric emptying in smokers. METHODS: Participant group comprised 53 habitual smokers and 12 healthy nonsmokers. Habitual smokers were treated for 2 months with transdermal nicotine patches. Gastric emptying was studied using C acetate breath tests at the beginning of the study, and at 1 week and 9 weeks after cessation of patch use. Maximal CO2 excretion time (Tmax), CO2 excretion half-life (T1/2), and parameters beta and kappa, representing initial and subsequent gastric-emptying phases, respectively, were determined using conventional formulae. RESULTS: Before smoking cessation, Tmax was reached significantly later in smokers (0.94+/-0.3 h, P=0.014) than in controls (0.89+/-0.1 h). At 1 week after the end of treatment, Tmax was significantly decreased (from 1.05+/-0.32 h to 0.72+/-0.64 h, P=0.003). T1/2 also tended to decrease, but not significantly. Although beta was decreased significantly (from 2.46+/-0.40 to 2.17+/-0.58, P=0.022), kappa was unchanged. However, by 9 weeks after the end of treatment, Tmax (1.28+/-0.69 h) had increased to levels seen before treatment. CONCLUSIONS: Smoking cessation temporarily accelerates gastric emptying, and decreases in beta suggest that initial-phase gastric emptying accelerates after smoking cessation. The temporary acceleration of gastric emptying after smoking cessation may be involved in the temporary increase in appetite and weight gain seen after smoking cessation.

Low expression of T-cell co-stimulatory molecules in bone marrow-derived dendritic cells in a mouse model of chronic respiratory infection with Pseudomonas aeruginosa.

Pseudomonas (P.) aeruginosa frequently colonizes the respiratory tract of patients with chronic respiratory tract infections such as diffuse panbronchiolitis (DPB). The number of dendritic cells (DCs) that play a central role in immune functions as antigen-presenting cells is reportedly increased in the bronchiolar tissues of patients with DPB. However, the functions of DCs in chronic P. aeruginosa respiratory tract infection have not been defined. Here, we assessed the functions of DCs and the effect of macrolide antibiotics that are therapeutic agents for DPB, in a murine model of DPB caused by P. aeruginosa. Mice were intubated with either P. aeruginosa- or saline-precoated tubes for 80 days. Thereafter, the expression of T-cell co-stimulatory molecules (CD40, CD80, and CD86) and cytokine secretion (interleukin (IL)-10, IL-6, IL-12p40, and tumor necrosis factor (TNF)-alpha) on bone marrow-derived DCs stimulated by lipopolysaccharide were examined by flow cytometry and enzyme-linked immunosorbent assays. The expression of co-stimulatory molecules was significantly decreased in mice infected with P. aeruginosa compared to the saline-treated control mice, but production of these cytokines did not significantly differ between the two groups. Pretreatment with clarithromycin ex vivo decreased CD40 expression on DCs obtained from P. aeruginosa-infected mice and also decreased the production of IL-6, IL-12p40 and TNF-alpha by DCs. These findings suggest that chronic P. aeruginosa infection alters DC functions and that macrolides function as anti-inflammatory agents by modulating the functions of DCs in chronic P. aeruginosa infection.

[Two cases of pleomorphic carcinoma with severe systemic inflammation].

We report two cases of pleomorphic carcinoma with fever and severe inflammatory reaction. In case 1, an abnormal mass shadow was found on the chest X-ray film of a 63-year-old man with bloody sputum. After right upper lobectomy, the tumor was diagnosed as pleomorphic carcinoma. About 7 months after surgical operation, he had fever and chest pain. Although his test results showed leukocytosis and his elevated serum CRP level indicated some infection, there were no signs of bacterial or fungal infection. Further examination revealed metases of lung cancer in the left adrenal gland, mediastinal and iliac lymph nodes. Serological study revealed elevated level of G-CSF, likely due to G-CSF producing metastatic tumors. In case 2, a 77-year-old man presented with continuous high fever. Examinations revealed elevated serum CRP level and multiple nodular shadows and enlarged supraclavicular and mediastinal lymph nodes on the chest CT, suggesting some infectious, connective tissue, or lymphoproliferative diseases. He was finally found to have pleomorphic carcinoma of the lung by histological examination of lymph nodes. The continuous high fever seemed to be a tumor-related fever, because it rapidly disappeared after administration of naproxen.

[Case of nonspecific interstitial pneumonia associated with aortitis syndrome].

A 32-year-old woman was admitted to our hospital because of fever and back pain. Two months previously, she had been given a diagnosis of bacterial pneumonia based on the same symptoms and recovered after antibiotic treatment. Chest CT scans on admission showed a consolidation and thickened pleura in the right lower lobe. Bronchoalveolar lavage fluids showed an alveolar hemorrhage. Lung biopsy specimens showed thickened pulmonary arteries and fibrotic nonspecific interstitial pneumonia (NSIP). Three years later, she was admitted with fever and pain of the left arm and aortitis syndrome was diagnosed. In this case of NSIP pattern associated with aortitis syndrome we speculate that repeated pulmonary infarction and alveolar hemorrhages caused the NSIP pattern.

Elevated serum beta-defensins concentrations in patients with lung cancer.

BACKGROUND: Beta-defensins (HBDs) are expressed in lung epithelial cells and act as antimicrobial agents. Most lung cancers that originate from pulmonary epithelial cells may produce HBDs. MATERIALS AND METHODS: We measured serum HBD-1 and HBD-2 levels in healthy subjects (HS), patients with lung cancer and patients with pneumonia by radioimmunoassay. RESULTS: Serum HBD-1 levels were higher in patients with lung cancer than HS and patients with pneumonia. Serum HBD-2 levels were higher in patients with lung cancer than HS. When cut-off values for positive HBD-1 were set at mean + 2SD of HS, the sensitivity and specificity of HBD-1 for the whole group of patients with lung cancer were 76.4 and 94.0%, respectively, and the proportion of patients with HBD-1-positive lung cancer and clinical stage I was 69.2%. CONCLUSION: Serum HBDs levels were high in patients with lung cancer and the serum HBD-1 level could be used as an auxiliary diagnostic tool for lung cancer.

High-BAL fluid concentrations of RANTES in nonspecific interstitial pneumonia compared with usual interstitial pneumonia.

Chemokines such as regulated on activation, normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP)-1, monocyte inflammatory protein (MIP)-lalpha have been reported to play an important role in the pathogenesis of interstitial lung diseases. Among idiopathic interstitial pneumonia (IIP), nonspecific interstitial pneumonia (NSIP) has elevated percentages of Lymphocytes in bronchoalveolar lavage (BAL) fluid compared with usual interstitial pneumonia (UIP). These chemokines are candidate mediators for lymphocyte attraction to the lung in NSIR Therefore, we measured the BAL fluid levels of RANTES, MCP-1 and MIP1-alpha in 15 patients with idiopathic NSIP, 20 with idiopathic UIP, 22 with sarcoidosis and 12 healthy volunteers to evaluate the contribution of these chemokines using enzyme-linked immunosorbent assays. The levels of RANTES in BAL fluid were significantly higher in patients with NSIP compared with healthy volunteers (P < 0.01), UIP and sarcoidosis (P < 0.05). In MCP-1, the levels in BAL fluid of NSIP and UIP patients were significantly elevated compared with healthy volunteers and sarcoidosis patients (P < 0.01). These results suggest that RANTES and MCP-1 in BAL fluid may play an important role in inflammatory cell recruitment to the lung in idiopathic NSIP as well as other interstitial lung diseases.

Acute eosinophilic pneumonia with fine nodular shadows.

A 19-year-old woman presented with acute onset of cough and dyspnea. She started smoking two weeks before the appearance of symptoms. On admission, arterial blood gas analysis on room air breathing revealed PaO2 55 Torr. Chest roentgenogram and high resolution computed tomograms showed localized fine nodular shadows at the right lower lung field. Bronchoalveolar lavage fluid revealed a high eosinophil count. Eosinophil infiltration was also observed in transbronchial lung biopsy specimens. The final diagnosis was acute eosinophilic pneumonia (AEP). Although few reports have demonstrated diffuse fine nodular shadows in AEP, localized fine nodular shadows on chest roentgenogram and CT may sometimes be the sign of AEP especially in the early phase of the clinical course.

Availability of cardio-ankle vascular index (CAVI) as a screening tool for atherosclerosis.

BACKGROUND: A novel index, the cardio-ankle vascular index (CAVI), which reflects the stiffness of the aorta, femoral artery, and tibial artery, was recently developed by measuring brachial - ankle pulse wave velocity and blood pressure. METHODS AND RESULTS: In the present study 1,014 Japanese adults from the general population were screened to clarify the correlation between CAVI and other existing markers related to atherosclerosis, including carotid intima - media thickness (CIMT) and homocysteine (HCY). CAVI was strongly associated with age in both men and women. After adjustment for age and sex, CAVI was correlated with systolic and diastolic blood pressures. In addition, CAVI was significantly correlated with total cholesterol hemoglobin A(1c) and total HCY, as well as CIMT. CONCLUSION: CAVI is an appropriate screening tool for atherosclerosis, but further studies are needed to establish a convenient and effective screening system using it.

Sarcoidosis accompanied by systemic lupus erythematosus and autoimmune hepatitis.

A 52-year-old woman was admitted to our hospital for further examination of blurred vision, abnormal lung shadows and an elevated level of angiotensin-converting enzyme. Sarcoidosis was suspected, however, careful history taking revealed the existence of photosensitivity and polyarthralgia. Laboratory tests showed lymphocytopenia, liver dysfunction, hypergammaglobulinemia, and positive anti-nuclear, anti-double stranded DNA and anti-smooth muscle antibodies. Liver biopsy examination showed chronic active hepatitis. She was diagnosed with the triplex of sarcoidosis, systemic lupus erythematosus and autoimmune hepatitis. Marked improvement was noted after corticosteroid therapy.

Increased levels of interleukin-18 in bronchoalveolar lavage fluid of patients with idiopathic nonspecific interstitial pneumonia.

BACKGROUND: Interleukin-18 (IL-18) is a proinflammatory cytokine that can induce interferon-gamma (IFN-gamma), and it plays an important role in T-helper 1 responses. Among idiopathic interstitial pneumonia (IIP), nonspecific interstitial pneumonia (NSIP) has an increased number of lymphocytes in bronchoalveolar lavage (BAL) fluid compared with usual interstitial pneumonia (UIP). However, the difference in their pathogenesis is unclear. OBJECTIVE: The present study aims to investigate the roles of IL-18 in patients with idiopathic UIP and idiopathic NSIP. METHODS: We measured the serum and BAL fluid (BALF) levels of IL-18 and IFN-gamma in 22 patients with IIP (12 with UIP, 10 with NSIP) and 9 healthy volunteers. RESULTS: Lymphocyte proportions in BALF were significantly higher in NSIP than in UIP and healthy subjects. No significant differences were observed in the serum IL-18 levels of all subjects, while the BALF levels of IL-18 in patients with NSIP were significantly higher than in patients with UIP (p < 0.005) and in healthy subjects (p < 0.005). Among all subjects, the levels of IL-18 in BALF correlated significantly with those in serum and the lymphocyte proportions in BALF. The serum IFN-gamma levels of all subjects were below sensitivity, but there was significant reverse correlation between the levels of IFN-gamma and the lymphocyte proportions in BALF. CONCLUSION: The lymphocytosis in BALF of patients with idiopathic NSIP and a part of idiopathic UIP might be associated with the high levels of IL-18.