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Arzneimittelforschung 2008; 58(6): 297-302
DOI: 10.1055/s-0031-1296510
Antiallergic Drugs · Antiasthmatics · Antitussives · Bronchodilators · Bronchosecretogogues · Mucolytics
Editio Cantor Verlag Aulendorf (Germany)

Effect of an Orally Active Th2 Cytokine Inhibitor, Suplatast Tosilate, on “Atopic Cough”

Yoshihisa Ishiura
1   The Department of Respiratory Medicine, Toyama City Hospital, Toyama, Japan
,
Masaki Fujimura
2   Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
,
Hiroki Yamamoto
1   The Department of Respiratory Medicine, Toyama City Hospital, Toyama, Japan
,
Kouichi Nobata
2   Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
,
Takashi Ishiguro
1   The Department of Respiratory Medicine, Toyama City Hospital, Toyama, Japan
,
Haruhiko Ogawa
2   Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
,
Shigeharu Myou
2   Respiratory Medicine, Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan
› Author Affiliations
Further Information

Publication History

Publication Date:
15 December 2011 (online)

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Abstract

Background

– “Atopic cough” is a new clinical entity that presents with isolated chronic bronchodilator-resistant cough accepted in the Japanese Respiratory Society Guidelines for Management of Cough. The essential features are eosinophilic tracheobronchitis, increased cough reflex sensitivity and an atopic constitution. It has been suggested that activated helper Tlymphocytes and the cytokines which are produced by these cells are involved in the pathogenesis, but the relationship between helper T cell-derived cytokines and the airway cough reflex sensitivity remains unknown.

Methods

– The effect of an orally active Th2 cytokine inhibitor, suplatast tosilate (CAS 94055-76-2, IPD™; 300 mg/day), on the cough response to inhaled capsaicin (CAS 404-86-4) was examined in ten patients with atopic cough. The capsaicin cough threshold, defined as the lowest concentration of capsaicin eliciting five or more coughs, was measured as an index of airway cough reflex sensitivity. The serum total immunoglobulin E (IgE) level and the peripheral blood eosinophil count were also determined after treatment with suplatast tosilate.

Results

– The cough threshold measured after four weeks of treatment with suplatast tosilate was significantly increased compared to the value obtained with placebo, along with a decrease of the serum IgE level and peripheral eosinophil count.

Conclusions

– Th2 cytokines may increase the airway cough reflex sensitivity in patients with atopic cough. Oral administration of suplatast tosilate may be a novel therapy for atopic cough.

Key words

Antiallergic agents - CAS 94055-76-2 - Eosinophilic tracheobronchitis, - IPD™ - Suplatast tosilate, clinical study, effect on cough reflex sensitivity - Th2 cytokines
 

  • References

  • 1 Brightling CE, Ward R, Goh KL, Wardlaw AJ, Pavord ID. Eosinophilic bronchitis is an important cause of chronic cough. Am J Respir Crit Care Med. 1999; 160: 40610-
    PubMedGoogle Scholar
  • 2 Carney IK, Gibson PG, Murree-Allen K, Saltos N, Olson LG, Hensley MI. A systematic evaluation of mechanisms in chronic cough. Am J Respir Crit Care Med. 1997; 156: 211-216
    PubMedGoogle Scholar
  • 3 Ayik SO, Basoglu OK, Erdinc M, Bor S, Veral A, Bilgen C. Eosinophilic bronchitis as a cause of chronic cough. Respir Med. 2003; 97: 695-701
    CrossrefPubMedGoogle Scholar
  • 4 Fujimura M, Sakamoto S, Matsuda T. Bronchodilator-resis-tive cough in atopic patients: bronchial reversibility and hyperresponsiveness. Intern Med. 1992; 31: 447-452
    CrossrefPubMedGoogle Scholar
  • 5 Fujimura M, Ogawa H, Yasui M, Matsuda T. Eosinophilic tracheobronchitis and airway cough hypersensitivity in chronic non-productive cough. Clin Exp Allergy. 2000; 30: 41-47
    CrossrefPubMedGoogle Scholar
  • 6 Fujimura M, Ogawa H, Nishizawa Y, Nishi K. Comparison of atopic cough with cough variant asthma: is atopic cough a precursor of asthma?. Thorax. 2003; 58: 14-18
    CrossrefPubMedGoogle Scholar
  • 7 Fujimura M, Nishizawa Y, Nishitsuji M, Abo M, Kita T, Nomura S. Longitudinal decline in pulmonary function in atopic cough and cough variant asthma. Clin Exp Allergy. 2003; 33: 588-594
    CrossrefPubMedGoogle Scholar
  • 8 Committee for the Japanese Respiratory Society Guidelines for Management of Cough Kohno S, Ishida T, Uchida Y, Kishimoto H, Sasaki H, Shioya T. et al The Japanese Respiratory Society guidelines for management of cough. Respirology. 2006; 11: 135- S-186S
    CrossrefPubMedGoogle Scholar
  • 9 Fujimura M. Cough variant asthma and related disorders: atopic cough (in Japanese). Arerugi no rinsho. 1996; 16: 22-27
    PubMedGoogle Scholar
  • 10 Shioya T, Satake M, Kagaya M, Sano MA, Watanabe A, Fukui S et al. Antitussive effects of the Hl-receptor antagonist epinastine in patients with atopic cough (eosinophilic bronchitis). Arzneimittel-Forschung (Drug Research). 2004; 54: 207-212
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Fujimura M, Nishi K, Ohka T, Yasui M, Kasahara K. Bronchial biopsy and sequential bronchoalveolar lavage in atopic cough: In view of the effect of histamine Hl-receptor antagonists. Allergol lnt. 2000; 49: 135-142
    PubMedGoogle Scholar
  • 12 Shirai T, Suzuki K, Inui N, Suda T, Chida K, Nakamura H. Thl/Th2 profile in peripheral blood in atopic cough and atopic asthma. Clin Exp Allergy. 2003; 33: 84-89
    CrossrefPubMedGoogle Scholar
  • 13 Yanagihara Y, Kiniwa M, Ikizawa T, Shida N, Matsuura N, Koda A. Supression of IgE production by IPD-1151T (su-platast tosilate), a new dimethylsulfonium agent: Regulation of human IgE response. Jap J Pharmacol. 1993; 61: 23-39
    CrossrefPubMedGoogle Scholar
  • 14 Tamaoki J, Kondo M, Sakai N, Aoshiba K, Tagaya E, Nakata J et al. Effect of suplatast tosilate, a Th2 cytokine inhibitor, on steroid-dependent asthma: a double blind randomized study. Lancet. 2000; 356: 273-278
    CrossrefPubMedGoogle Scholar
  • 15 Sano Y, Suzuki N, Yamada H, To Y, Ogawa C, Ohta K, Adachi M. Effects of suplatast tosilate on allergic eosinophilic airway inflammation in patients with mild asthma. J Allergy Clin Immunol. 2003; 111: 958-966
    CrossrefPubMedGoogle Scholar
  • 16 Shioya T, Satake M, Sano M, Kagaya M, Watanabe A, Sato K et al. Effect of suplatast tosilate, a Th2 cytokine inhibitor, on cough variant asthma. Eur J Clin Pharmacol. 2002; 58: 171-176
    CrossrefPubMedGoogle Scholar
  • 17 Ishiura Y, Fujimura M, Nobata K, Myou S, Oribe Y, Abo M et al. Th2 cytokine inhibition and cough in asthmatic and bronchitic patients. Ann Med. 2004; 36: 623-629
    CrossrefPubMedGoogle Scholar
  • 18 American Thoracic Society. Standarization of spirometry: 1987 update. Am Rev Respir Dis. 1987; 136: 1285-1298
    CrossrefPubMedGoogle Scholar
  • 19 Cockcroft DW, Ruffin RE, Dolovich J, Hargreave FE. Allergen-induced increase in non-allergic bronchial reactivity. Clin Allergy. 1977; 7: 503-513
    PubMedGoogle Scholar
  • 20 Fujimura M, Sakamoto S, Kamio Y, Matsuda T. Effects of methacholine-induced bronchoconstriction and procater-ol-induced bronchodilation on cough receptor sensitivity to inhaled capsaicin and tartaric acid. Thorax. 1992; 47: 441-445
    CrossrefPubMedGoogle Scholar
  • 21 Ishiura Y, Fujimura M, Saito M, Shibata K, Nomura M, Nakatsumi Y et al. Additive effect of continuous low-dose ofloxacin on erythromycin therapy for sinobronchial syndrome. Respir Med. 1995; 89: 677-684
    CrossrefPubMedGoogle Scholar
  • 22 Ishiura Y, Fujimura M, Yamamori C, Nobata K, Myou S, Kurashima K et al. Thromboxane antagonism and cough in chronic bronchitis. Ann Med. 2003; 35: 135-139
    CrossrefPubMedGoogle Scholar
  • 23 Fujimura M, Kamio Y, Hashimoto T, Matsuda T. Cough receptor sensitivity and bronchial responsiveness in patients with only chronic nonproductive cough: in view of effect of bronchodilator therapy. J Asthma. 1994; 31: 463-472
    CrossrefPubMedGoogle Scholar
  • 24 Liu Q. Effect of histamine H1-receptor antagonist on antigen-induced increase of sensitivity in guinea pigs. Allergol Int. 2000; 49: 237-243
    CrossrefPubMedGoogle Scholar
  • 25 Kay AB. Allergy and allergic diseases. First of two parts. JV Engl]Med. 2001; 344: 30-37
    PubMedGoogle Scholar
  • 26 McGarvey L, Morice AH. Atopic cough: little evidence to support a new clinical entity. Thorax. 2003; 58: 736-737 author reply 737-738
    CrossrefPubMedGoogle Scholar
  • 27 Fujimura M, Ogawa H. Atopic cough: little evidence to support a new clinical entity; author reply. Thorax. 2003; 58: 737-738
    PubMedGoogle Scholar
  • 28 Gibson PG. Atopic cough. Thorax. 2004; 59: 449-
    PubMedGoogle Scholar
  • 29 Brightling CE. Chronic cough due to nonasthmatic eosinophilic bronchitis: ACCP evidence-based clinical practice guidelines. Chest. 2006; 129: 116- S-121S
    CrossrefPubMedGoogle Scholar
  • 30 Brightling CE, Symon FA, Birring SS, Bradding P, Pavord ID, Wardlaw AJ. TH2 cytokine expression in bronchoalveolar lavage fluid T lymphocytes and bronchial submucosa is a feature of asthma and eosinophilic bronchitis. J Allergy Clin Immunol. 2002; 110: 899-905
    CrossrefPubMedGoogle Scholar