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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.

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.

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