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Asthma patients with fixed airflow limitation (FL) are theoretically classified into two phenotypes, that is, coexisting chronic obstructive pulmonary disease (COPD) and asthmatic airway remodeling. However, the precise percentages of such patients are not known.To assess the prevalence of patients with both FL and COPD components in elderly asthma.We evaluated patients by lung diffusion impairment and emphysematous findings in high-resolution computed tomography (HRCT) as candidates for COPD components, as a multicenter, cross-sectional survey. Asthma outpatients ≥ 50 years of age were enrolled from Tohoku University Hospital, Sendai, Japan, and four hospitals (Tohoku Medical and Pharmaceutical University Wakabayashi Hospital, Sendai, JAPAN; Wakayama Medical University Hospital, Kimiidera, Japan; Hiraka General Hospital, Yokote, Japan; Iwate Prefectural Isawa Hospital, Oshu, Japan) with pulmonary physicians from March 1, 2013 to November 30, 2014.The prevalence of patients with FEVNearly half of the patients with FL in elderly asthma show coexisting COPD components when assessed by DLco %predicted and LAA in HRCT.

Lactococcus garvieae is a well-known fish pathogen that has low virulence in humans and is rarely isolated from the blood cultures of endocarditis patients. We describe herein the first reported case of transfusion-transmitted L. garvieae sepsis caused by a contaminated platelet concentrate from a donor who consumed raw octopus before blood donation. Retrospective examination of the laboratory results of the index donor revealed that his haemoglobin levels had been steadily decreasing, which led to the detection of a latent colon cancer. The donors with colon lesions involving a latent cancer may relate an asymptomatic bacteremia.

1016/j.resinv.2014.10.006 he Japanese Respiratory Society. Published by Else of Internal Medicine, Wakayama Medical Universit n; c National Hospital Organization Wakayama Hos raduate School of Medicine, Japan; f Kamei Respirator al, Japan; i NTT East Tohoku Hospital, Japan; j Hirosh spital, Japan; l Minami Tokushima Clinic, Japan; m Hir n; o Tohoku Rosai Hospital, Japan. uthor. Tel.: þ81 73 441 0619; fax: þ81 73 447 2201. kazmatsu@wakayama-med.ac.jp (K. Matsunaga) a-med.ac.jp (K. Akamatsu), tsuna@wakayama-m .pikara.ne.jp (T. Kamei), tsudat@k-you.or.jp (T. Ts i@east.ntt.co.jp (T. Takahashi), hozawa@vesta.ocn ikara.ne.jp (Y. Sakamoto), hrkjmsom@air.ocn.ne.j izusawa.iwate.jp (U. Katsumata), mmiura@tohok hoku.ac.jp (M. Ichinose). by physicians is limited [3], and there is a need for a simple assessment tool that can be used in everyday practice [4]. The modified Medical Research Council (mMRC) scale is a wellvalidated questionnaire that uses a simple grading system to quantify disability associated with breathlessness [5], and current guidelines advocate the use of this scale to assess

Tsutomu Tamada,1 Hisatoshi Sugiura,1 Tsuneyuki Takahashi,2 Kazuto Matsunaga,3 Keiji Kimura,4 Uichiro Katsumata,5 Daisuke Takekoshi,1 Toshiaki Kikuchi,1 Ken Ohta,6 Masakazu Ichinose1 1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, 2Nippon Telegraph and Telephone East Corporation Tohoku Hospital, Sendai, 3Division of Respiratory Medicine and Infectious Disease, Graduate School of Medicine, Yamaguchi University, Ube, 4Hiraka General Hospital, Yokote, 5Iwate Prefectural Isawa Hospital, Oshu, 6National Hospital Organization, Tokyo National Hospital, Kiyose, Tokyo, Japan Abstract: Asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) was proposed by the science committees of both Global Initiative for Asthma (GINA) and Global Initiative for Chronic Obstructive Lung Disease (GOLD). However, the definition of ACOS has remained unclear all over the world, and the prevalence rate of ACOS is basically dependent on the patient’s symptoms or the physician’s opinion, based on questionnaire testing. In the current case report, we investigated the prevalence rate of COPD patients with high levels of fractional exhaled nitric oxide (FENO) or immunoglobulin E (IgE) as candidate markers of ACOS in COPD, as a multicenter, cross-sectional study. Outpatients with COPD were enrolled from Tohoku University Hospital, Sendai, Japan, and five hospitals (Tohoku University Hospital, Sendai, Japan; NTT East Tohoku Hospital, Sendai, Japan; Wakayama Medical University Hospital, Kimiidera, Japan; Hiraka General Hospital, Yokote, Japan; Iwate Prefectural Isawa Hospital, Oshu, Japan) with pulmonary physicians from March 1, 2013 to February 28, 2014. When they were estimated using 35 ppb as the cutoff value of FENO, the prevalence rate of ACOS was 16.3% in COPD. When estimated by both FENO and IgE, the high-FENO/high-IgE group was 7.8% in COPD. To the best of our knowledge, this study is the first to detect the prevalence rate of ACOS in COPD populations by using objective biomarkers. The results from the current study should be useful to identify the subgroup requiring early intervention by inhaled corticosteroids/long-acting beta agonist combination in COPD in order to improve the long-term management for ACOS. Keywords: FENO, IgE, ICS, LABA, airway inflammation, atopic factors

We studied the effects of angiotensin converting enzyme (ACE) inhibitors on cough responses to bradykinin (BK), substance P (SP) and citric acid in a double blind, random study on 10 hypertensive patients receiving ACE inhibitors. Of these patients, five had reported cough with ACE inhibitors. Cough responses to citric acid were similar between patients with and without cough, and SP up to 10(-5) M did not cause cough in any of the subjects. BK caused cough at 13.4 +/- 1.2 (-log M) in 5 patients with cough associated with ACE inhibitors, but it did not cause cough at concentrations up to 10(-5) M in other 5 patients. One month after the withdrawal of ACE inhibitors, 5 patients were free from cough symptoms, and BK did not cause cough up to 10(-5) M in these patients, except for one who coughed at 10(-9) M, without changes in responses to citric acid. BK caused cough at 14.3 +/- 0.7 (-log M) although BK1-7, a major metabolite of BK by ACE, caused cough at 5.7 +/- 0.7 (-log M) in another 3 patients with cough associated with ACE inhibitor. These results suggest that impaired metabolism of BK induced by ACE inhibitors may relate to the manifestation of cough in hypertensive patients receiving ACE inhibitors.

Using 30 anesthetized cats, we examined whether oxygen radicals produce airway constriction or hyperresponsiveness. In one group, we administered aerosolized xanthine (0.1%) for 3 min followed by aerosolized xanthine oxidase (XO) (1 U/ml) for 5 min in order to generate oxygen radicals enzymatically in the airways. Pulmonary resistance (RL) instantaneously increased from 14.8 +/- 0.9 to 30.8 +/- 1.4 cm H2O/L/s (p less than 0.01). The increase in RL was significantly depressed by prior administration of polyethylene glycol-superoxide dismutase (PEG-SOD) or polyethylene glycolcatalase (PEG-CAT). In a second group, in order to examine changes in airway responsiveness, we studied acetylcholine (ACh) challenge before and 30, 60, and 120 min after inhalations of xanthine and XO. After xanthine-XO, the airways were hyperresponsive to ACh at 30 and at 60 min (p less than 0.05) but not at 120 min. The geometric means of ACh provocative concentrations that caused an increase in RL of 10 cm H2O/L/s above the baseline value before and 30, 60, and 120 min after xanthine-XO were 0.25, 0.045, 0.073, and 0.15%, respectively. The increase in responsiveness to ACh was significantly correlated with the increase in RL after xanthine-XO inhalation (r = 0.88, p less than 0.05). These data support the concept that oxygen radicals generated by xanthine-XO inhalation may induce bronchoconstriction and airway hyperresponsiveness.

The relationship between bronchial edema and airway responsiveness was studied in cats in situ. Five cats were exsanguinated, and the bronchial arteries were perfused. We monitored pulmonary resistance (RL), and the provocative dose of acetylcholine (ACh) required to produce a 300% increase in RL (PD300) was determined. Bronchial vascular permeability was measured by quantifying extravasation of Evans blue (EB) dye. Bradykinin (BK) and ACh were administered via the bronchial arteries to increase leakage and bronchoconstriction, respectively. BK preperfusion (for 30 min) significantly increased bronchial vascular permeability to four times the control values (p < 0.05). BK preperfusion did not alter baseline RL but caused hyperresponsiveness to ACh, with log [PD300 (mole)] of -6.53 +/- 0.42 (mean +/- SD) and -6.90 +/- 0.30, before and after BK, respectively (p < 0.01). Furthermore, the maximal airway narrowing after BK was 58% higher than before BK (p < 0.01). Histologic study showed peribronchial edema after BK. The enhancement of maximal airway narrowing was significantly correlated with the degree of EB dye extravasation. These results suggest that BK causes airway hyperresponsiveness to ACh and increases maximal airway narrowing, possibly because of airway edema.

We have investigated whether proteases released during antigen inhalation cause dysfunction of the nonadrenergic noncholinergic inhibitory nervous system (NANCIS). Frequency-response (F-R) studies of NANCIS were performed before and after Ascaris antigen (ASC) inhalation using actively sensitized cats. NANC dilatatory effects were obtained by stimulating bilateral cervical vagi under cholinergic and beta-adrenergic blockade and serotonin-induced bronchoconstriction, and assessed by maximal percent relaxation (rmax) and the frequency causing 50% of maximal relaxation (EF50). ASC inhalation caused a transient increase in pulmonary resistance in all animals. One hour after ASC inhalation, pulmonary resistance returned to the baseline value, but ASC inhalation significantly attenuated NANC inhibitory activities: rmax decreased from 82.2 +/- 4.7 (mean +/- SE) to 64.3 +/- 11.2% (p less than 0.05), and the geometric mean of EF50 increased from 1.7 to 4.3 Hz (p less than 0.05). Dilatatory effects of infused VIP, a possible neurotransmitter of NANCIS, was also attenuated after ASC inhalation. Pretreatment with leupeptin (3 mg/kg) abolished ASC-induced impairment of NANC inhibitory activities. By contrast, dilatatory effects of adrenergic nerve stimulation were not affected by ASC inhalation. These results suggest that NANC inhibitory activities can be impaired after ASC inhalation, and that this impairment of NANCIS may be due to effects of proteases released during allergic reaction.

To examine the effect of nonadrenergic noncholinergic (NANC) inhibitory nerve stimulation on the antigen inhalation with allergic animals, changes in pulmonary resistance (RL) and arterial plasma histamine concentration ([H]) caused by inhalation of Ascaris suum antigen were studied in five control (Group A) and five nerve-stimulated (Group B) cats, which were anesthetized and mechanically ventilated. All animals were actively sensitized with Ascaris antigen before the experiment. After cholinergic and beta-adrenergic blockade with intravenously administered atropine (3 mg/kg) and propranolol (2 mg/kg), inhalation of the antigen (1:100 dilution) was performed for 3 min. For Group B, bilateral cervical vagi were stimulated electrically for 1 min before the antigen inhalation and successively every 30 s until 5 min had passed from the onset of inhalation. RL and [H] were determined before, during, and after antigen inhalation in both groups. Baseline RL and [H] did not differ significantly between groups (16.3 +/- 2.2 (mean +/- SE) cm H2O/L/s and 14.0 +/- 0.7 ng/ml, respectively, for Group A; 14.4 +/- 1.3 and 15.6 +/- 2.7, respectively, for Group B). Increases in RL and [H] of Group B after the antigen inhalation were significantly depressed, compared with Group A (p less than 0.01 and p less than 0.05, respectively, two-way ANOVA). The increase in RL 5 min after antigen inhalation was 113 +/- 19% for Group A and 28 +/- 8% for Group B, and the increase in [H] at the same point was 36.3 +/- 9.1 ng/ml for Group A and 4.4 +/- 1.4 ng/ml for Group B.(ABSTRACT TRUNCATED AT 250 WORDS)

TAMURA, G., SAKAI, K., TANIGUCHI, Y., IIJIMA, H., HONMA, M., KATSUMATA, U., MARUYAMA, N., AIZAWA, T. and TAKISHIMA, T. Neurokinin A-Induced Bronchial Hyperresponsiveness to Methacholine in Japanese Monkeys. Tohoku J. Exp. Med., 1989, 159 (1), 69-73-The present study was designed to investigate whether neurokinin A (NKA) and substance P (SP) increase bronchial responsiveness to methacholine (MCh). Before and 1, 2, 3 and 4 weeks after three Japanese monkeys had inhaled 10-8M NKA and 10-8M SP for 2min, bronchial responsiveness to inhaled MCh was evaluated. Pulmonary flow resistance (R1) and dynamic lung compliance (Cdyn) were used as pulmonary function tests. Dose-response curves of R1 to inhaled MCh were shifted to the left 1 to 4 weeks after NKA treatment, compared with that obtained before treatment. However, SP treatment did not change the R1 dose-response curve. Thus, bronchial responsiveness to MCh was increased by inhalation of 10-8M NKA in Japanese monkeys.

We developed a device to measure inhaled aerosol deposition in the lung from the difference in particle size distribution of the aerosol during inspiration and expiration. To measure quantity and size distribution of nebulized aerosol particles directly at the subject's mouth we used a He-Ne gas laser scattering technique. To test the reliability of the instrument, we measured particle size distributions of saline aerosols generated by four kinds of nebulizer and compared the results with those from a Malvern 2600D particle sizer as a standard of comparison. Measured mass median diameters (MMDs) were almost identical by both methods. Aerosol deposition in five normal subjects showed that the deposition fraction of the particles increased the larger the particle sizes inhaled. The data suggest that the newly developed aerosol spectrometer can directly analyze aerosol particle size distribution at the mouth during tidal breathing, and that the instrument is useful for quantitative analysis of aerosol inhaled and of inhaled aerosol deposition.

To elucidate the mechanisms of airway hyperresponsiveness induced by viral infection, we examined histologically and analyzed bronchoalveolar lavage (BAL) fluid using dogs infected with influenza C and noninfected control dogs. Airway responsiveness was assessed as inhaled acetylcholine concentration required to increase pulmonary resistance by 5 cm H2O/L/s (ACh PC). Airway responsiveness was determined before and 2 wk after virus or vehicle inoculation in infected and control dogs, and BAL and histologic studies were performed after the final challenge. Differential cell numbers and histamine concentration were determined in the BAL fluids of both groups. The ACh PC of control dogs did not change with the vehicle inoculation. However, that of infected dogs decreased two to five times as much as their initial value with viral infection. Histologic studies revealed diffuse epithelial damage in the central airways of infected dogs, but infiltrated cell counts within the airway tissue of both groups were not significantly different. From BAL analysis, mast cell number and the histamine concentration of infected dogs increased significantly compared with those of control dogs (3.1 +/- 0.4 x 10(5) versus 0.9 +/- 0.3 x 10(5) cells/ml and 7.3 +/- 1.7 versus 1.9 +/- 0.5 ng/ml, respectively). Luminal mast cell number and epithelial damage score in each dog was correlated with the increase in airway responsiveness. These findings indicate that airway inflammation in virus-induced hyperreactive dogs is characterized by epithelial damage and luminal increase in mast cells and related mediators, and these changes may be related to the appearance of virus-induced airway hyperreactivity.

KATSUMATA, U., SEKIZAWA, K., INOUE, H., SASAKI, H. and TAKISHIMA, T. Inhibitory Actions of Procaterol, a Beta-2 Stimulant, on Substance P-Induced Cough in Normal Subjects during Upper Respiratory Tract Infection. Tohoku J. Exp. Med., 1989, 158 (1), 105-106 - We studied substance P (SP)-induced cough in normal subjects without and with colds, and the effects of orally administered procaterol on SP-induced cough in normal subjects with colds. SP aerosols caused cough at a concentration of approximately 10-15M in subjects with colds whereas it did not cause cough at a concentration of up to 10-5M in subjects without colds. Procaterol (50μg) completely inhibited SP-induced cough in normal subjects with colds. These results suggest that cough response to SP remarkably increases during colds and that beta-2 stimulant may be a useful tool for treatment of cough during colds in normal subjects