Persistent elevation of exhaled nitric oxide and modification of corticosteroid therapy in asthma |
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| Authors: | Tsunahiko Hirano Kazuto Matsunaga Hisatoshi Sugiura Yoshiaki Minakata Akira Koarai Keiichiro Akamatsu Tomohiro Ichikawa Kanako Furukawa Masakazu Ichinose |
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| Affiliation: | 1. Third Department of Internal Medicine, Wakayama Medical University, School of Medicine, 811-1 Kimiidera, Wakayama 641-0012, Japan;2. Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan;1. Division of Respiratory Medicine, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan;2. Department of General Medicine, Niigata University Medical and Dental Hospital, Niigata, Japan;1. Department of Integrated Pulmonology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan;2. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1, Tomiokahigashi, Kanagawa-ku, Yokohama City, Kanagawa 236-0051, Japan;3. Department of Respiratory Medicine, Hamamatsu University School of Medicine, 1-20-1, Handayama, Higashi-ku, Hamamatsu City, Shizuoka 431-3192, Japan;4. Department of Molecular and Internal Medicine, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan;5. Second Department of Internal Medicine, Nagasaki University, 1-7-1, Sakamoto, Nagasaki City, Nagasaki 852-8501, Japan;6. Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160-Banchi, Nishioiwake, Seto City, Aichi 489-8642, Japan;7. Department of Respiratory Medicine, National Hospital Organization, Tokyo National Hospital, 3-1-1, Takeoka, Kiyose City, Tokyo 204-8585, Japan;8. Department of Internal Medicine, Himeji Medical Center, 68-Banchi, Honnmachi, Himeji City, Hyogo 670-8520, Japan;9. Department of Internal Medicine, Iwate Medical University, 19-1, Maruuchi, Morioka City, Iwate 020-8505, Japan;10. Department of Internal Medicine, Sapporo Medical University, 16-291, Minamiichijo-nishi, Chuo-ku, Sapporo City, Hokkaido 060-8543, Japan;11. Department of Radiology, Kinki Central Hospital, 3-1, Kurumazuka, Itami City, Hyogo 664-8533, Japan;12. Department of Respiratory Medicine, Toho University, 6-11-1, Omori-nishi, Ota-ku, Tokyo 143-8541, Japan;13. Department of Respiratory Medicine, Toranomon Hospital, 2-2-2, Toranomon, Minato-ku, Tokyo 105-8470, Japan;14. Department of Respiratory Medicine, Japanese Red Cross Medical Center, 4-1-22, Hiroo, Shibuya-ku, Tokyo 150-8935, Japan;15. First Department of Medicine, Hokkaido University, 5-chome, Kita14-Jo-Nishi, Kita-ku, Sapporo City, Hokkaido 060-8648, Japan;p. Department of Respiratory Medicine, Kyoto University, 54-banchi, Kawara-cho, Seigoinn, Sakyo-ku, Kyoto City, Kyoto 606-8507, Japan;q. Department of Internal Medicine, Teikyo University, 2-11-1, Kaga, Itabashi-ku, Tokyo 173-0003, Japan;r. Department of Respiratory Medicine, Tokushima University, 2-50-1, Kuramoto-cho, Tokushima City, Tokushima 770-8503, Japan;s. Department of Respiratory Medicine, Hiratsuka Kyosai Hospital, 9-11, Oiwake, Hiratsuka City, Kanagawa 254-8502, Japan;t. Department of Pulmonary Medicine, Fukushima Medical University, 1-banchi, Hikarigaoka, Fukushima City, Fukushima 960-1295, Japan;u. Department of Respiratory Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka City, Fukuoka 814-0180, Japan;v. Department of Respiratory Medicine, Yamanashi Prefectural Central Hospital, 1-1-1, Fujimi, Kofu City, Yamanashi 400-8506, Japan;1. Department of Chest Medicine, Japan Railway Tokyo General Hospital, Japan;2. Department of Respirology, Graduate School of Medicine, Chiba University, Japan;3. Department of Pathology, Tama-Nagayama Hospital, Nippon Medical School, Japan;4. Department of Pathology, Japanese Red Cross Medical Center, Japan;1. Department of Respiratory Medicine, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan;2. Department of General Thoracic Surgery, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan;3. Department of General Medicine, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-Ku, Tokyo 113-8421, Japan;4. Department of Diagnostic Pathology, Kanto-Rosai Hospital, 1-1 Kizukisumiyoshi-cho, Nakahara-ku, Kawasaki City, Kanagawa Prefecture, Japan |
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| Abstract: | BackgroundPersistent airway inflammation, detected by fractional exhaled nitric oxide (FENO), is occasionally observed in asthmatic patients, even in those treated with inhaled corticosteroids (ICS). However, improvement in residual airway inflammation and pulmonary function through modification of corticosteroid therapy has not been proven.MethodsThirteen asthmatic patients whose FENO levels were over 40 parts per billion (ppb), despite dry-powder ICS therapy, were enrolled. A 3-step change in steroid treatment was undertaken until FENO was less than 40 ppb. In the first step, the powder formula was changed to an ultra-fine particle compound as an equipotent ICS dose. In the second step, the ICS dose was doubled. In the third step, oral corticosteroids were added. We measured pulmonary function and FENO and alveolar NO concentrations (CAlvNO).ResultsDoubling the ICS dose and changing the ICS formula significantly improved FVC (p<0.001), FEV1 (p<0.05), the slope of the single nitrogen washout curve (dN2) (p<0.01), FENO (p<0.001), and CAlvNO (p<0.05), relative to baseline. The reductions in FENO were significantly associated with the improvement in airflow limitation assessed by dN2 (r=0.73, p=0.007). The remaining FENO elevation, even after doubling the ICS dose, did not decrease after oral corticosteroid administration.ConclusionsThese results suggest that modification of ICS therapy can suppress residual FENO elevation, and that reduction in FENO levels is associated with improvement in airflow limitation. However, steroid-resistance mechanisms may exist in some asthmatic patients with sustained FENO elevations. |
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