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Respiration 2001;68:41–45

Bronchial Hyperresponsiveness and Exhaled Nitric Oxide in Patients with Cardiac Disease

Nishimura Y. · Yu Y. · Kotani Y. · Nishiuma T. · Lin S. · Maeda H. · Yokoyama M.

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First Department of Internal Medicine, Kobe University School of Medicine, Kobe, Japan

Corresponding Author

Yoshihiro Nishimura, MD

First Department of Internal Medicine, Kobe University School of Medicine

7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan)

Tel. +81 78 382 5846, Fax +81 78 382 5859

E-Mail nishiy@med.kobe-u.ac.jp

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Background: Increased concentrations of exhaled nitric oxide (NO) correlate with increased airway inflammation and measurement of exhaled NO is a noninvasive method for the management of bronchial asthma. In various cardiac diseases, bronchial hyperresponsiveness is observed, as is bronchial asthma. However, there have been few studies on the relationship between exhaled NO and bronchial responsiveness in cardiac diseases. Objective: The aim of this study was to clarify the association between exhaled NO and bronchial hyperresponsiveness in patients with cardiac disease. Methods: We measured expired NO and bronchial responsiveness to inhaled methacholine in 19 patients with cardiac diseases and 17 with bronchial asthma. We divided the cardiac disease patients into two groups according to their bronchial responsiveness to inhaled methacholine: BHR(+) group consisted of 12 patients with bronchial hyperresponsiveness and BHR(–) group consisted of 7 patients without bronchial hyperresponsiveness. Results: The concentration of exhaled NO in the asthmatic patients was significantly higher than that in the BHR(+) and BHR(–) groups (142.0 ± 17.0, 33.6 ± 6.4 and 42.3 ± 10.3 ppb, respectively, p < 0.01). There was no significant difference in exhaled NO between BHR(+) and BHR(–) groups. There were also no significant differences in the parameters of bronchial hyperresponsiveness between the cardiac BHR(+) and bronchial asthma groups. These results indicate that bronchial hyperresponsiveness in patients with cardiac diseases is not a consequence of eosinophilic inflammation or of exhaled NO. Conclusion: We conclude that bronchial hyperresponsiveness in patients with cardiac diseases can occur independently of NO production.

© 2001 S. Karger AG, Basel


  1. Cabanes LR, Weber SN, Matran R, Regnard J, Richard MO, Degeorges ME, Lockhart A: Bronchial hyperresponsiveness to methacholine in patients with impaired left ventricular function. N Engl J Med 1989;320:1317–1322.
  2. Pison C, Malo JL, Rouleau J, Chalaoui J, Ghezzo H, Malo J: Bronchial hyperresponsiveness to inhaled methacholine in subjects with chronic left heart failure at a time of exacerbation and after increasing diuretic therapy. Chest 1989;96:230–235.
    External Resources
  3. Nishimura Y, Maeda H, Yokoyama M, et al: Bronchial hyperreactivity in patients with mitral valve disease. Chest 1990;98:1085–1090.
  4. Nishimura Y, Maeda H, Hashimoto A, Tanaka K, Yokoyama M: Relationship between bronchial hyperreactivity and the symptoms of cardiac asthma in patients with non-valvular left ventricular failure. Jpn Circ J 1996;60:933–939.
  5. Kageshita T, Nishimura Y, Nakata H, et al: Bronchial hyperresponsiveness in patients with vasospastic angina pectoris (VSAP) (abstract in English). Nippon Kyobu Shikkan Gakkai Zasshi 1997;35:1035–1039.
  6. Saitoh Y, Sasaki F, Ishizaki T, Miyabo S, Kanamori K, Mifune J: Bronchial hyperresponsiveness to acetylcholine in patients with vasospastic angina pectoris. Chest 1994;105:364–367.
  7. Nishimura Y, Maeda H, Nakamura H, Hashimoto A, Yahata T, Nakamura H, Tanaka K, Yokoyama M: Alterations of bronchial reactivity to inhaled histamine in canine pulmonary congestion. Jpn Circ J 1997;61:787–794.
  8. Eichacker PQ, Seidelman MJ, Rothstein MS, Lejemtel T: Methacholine bronchial reactivity testing in patients with chronic congestive heart failure. Chest 1988;93:336–338.
    External Resources
  9. Chua TP, Laloo UG, Worsdell MY, Kharitonov S, Chung KF, Coats AJS: Airway and cough responsiveness and exhaled nitric oxide in non-smoking patients with stable chronic heart failure. Heart 1996;76:144–149.
    External Resources
  10. Bousquet J, Michel FB: International concensus report on diagnosis and management of asthma. Allergy 1992;47:129–132.
    External Resources
  11. Pin I, Gibson PG, Kolendowicz R, et al: Use of induced sputum counts to investigate airway inflammation in asthma. Thorax 1992;47:25–29.
  12. Satouchi M, Maeda H, Yu Y, Yokoyama M: Clinical significance of the increased peak levels of exhaled nitric oxide in patients with bronchial asthma. Intern Med 1996;35:270–275.
    External Resources
  13. Mongreno RH, Hogg JC, Pare PD: Mechanics of airway narrowing. Am Rev Respir Dis 1986;133:1171–1180.
  14. Spann JF, Hurst JW: The recognition and management of heart failure; in Hurst JW (ed): The Heart, ed 6. New York, McGraw-Hill, 1985, p 349.
  15. American Thoracic Society: Standard for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. Am Rev Respir Dis 1987;136:225–244.
  16. Kharitonov S, Alving K, Barnes PJ: Exhaled and nasal nitric oxide measurements: Recommendations. Eur Respir J 1997;10:1683–1693.
  17. Persson MG, Wiklund NP, Gustafsson LE: Endogenous nitric oxide in single exhalations and the change during exercise. Am Rev Respir Dis 1993;148:1210–1214.
  18. Takishima T, Hida W, Sasaki H, et al: Direct-writing recorder of the dose response curve of the airway to methacholine: Clinical application. Chest 1981;80:600–606.
  19. Kharitonov SA, O’Connor BJ, Evans DJ, Barnes PJ: Allergen-induced late asthmatic reactions are associated with elevation of exhaled nitric oxide. Am J Respir Crit Care Med 1995;151:1894–1899.
  20. Kharitonov SA, Yates D, Barnes PJ: Increased nitric oxide in exhaled air of normal human subjects with upper respiratory tract infections. Eur Respir J 1995;8:295–297.
  21. Alving K, Weitzberg E, Lundberg JM: Increased amount of nitric oxide in exhaled air of asthmatics. Eur Respir J 1993;6:1368–1370.
  22. Adcock IM, Brown CR, Kwon OJ, Barnes PJ: Oxidative stress induces NF-kB DNA-binding and inducible NOS mRNA in human epithelial cells. Biochem Biophys Res Commun 1994;199:1518–1524.
  23. Asano K, Chee CB, Gaston B, Lilly CM, Gerard C, Drazen JM, Stamler JS: Constitutive and inducible nitric oxide synthase gene expression, regulation, and activity in human lung epithelial cells. Proc Natl Acad Sci USA 1994;91:10089–10093.
  24. Winlaw DS, Smythe GA, Keogh AM, Schyvens CG, Spratt PM, Macdonald PS: Increased nitric oxide production in heart failure. Lancet 1994;344:373–374.
  25. Sumino H, Sato K, Sakamaki T, Masuda H, Nakamura T, Kanda T, Nagai R: Decreased basal production of nitric oxide in patients with heart disease. Chest 1998;113:317–322.

Article / Publication Details

First-Page Preview
Abstract of Clinical Investigations

Published online: February 14, 2001

Number of Print Pages: 5
Number of Figures: 1
Number of Tables: 1

ISSN: 0025-7931 (Print)
eISSN: 1423-0356 (Online)

For additional information: https://www.karger.com/RES