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Original Research: COUGH |

Inflammatory Subtypes in Cough-Variant Asthma: Association With Maintenance Doses of Inhaled Corticosteroids

Hirofumi Matsuoka, MD; Akio Niimi, MD, PhD; Hisako Matsumoto, MD, PhD; Masaya Takemura, MD, PhD; Tetsuya Ueda, MD, PhD; Masafumi Yamaguchi, MD, PhD; Makiko Jinnai, MD, PhD; Hideki Inoue, MD; Isao Ito, MD, PhD; Kazuo Chin, MD, PhD; Michiaki Mishima, MD, PhD; Committee for the Japanese Respiratory Society Guidelines for Management of Cough
Author and Funding Information

From the Department of Respiratory Medicine (Drs Matsuoka, Niimi, Matsumoto, Yamaguchi, Jinnai, Inoue, Ito, and Mishima) and the Department of Respiratory Care and Sleep Control Medicine (Dr Chin), Graduate School of Medicine, Kyoto University, Kyoto; and the Department of Respiratory Medicine (Dr Takemura), The Tazuke Kofukai Research Medical Institute, Kitano Hospital, and the Department of Respiratory Medicine (Dr Ueda), Osaka-fu Saiseikai Nakatsu Hospital, Osaka, Japan.

Correspondence to: Akio Niimi, MD, PhD, Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Shogoin, Sakyoku, Kyoto 606-8507, Japan; e-mail: niimi@kuhp.kyoto-u.ac.jp


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2010 American College of Chest Physicians


Chest. 2010;138(6):1418-1425. doi:10.1378/chest.10-0132
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Background:  Sputum cell-subtype profiles in cough-variant asthma (CVA) are unknown.

Methods:  Ninety-eight inhaled corticosteroid (ICS)-naive CVA patients were classified according to sputum eosinophil (eos)/neutrophil (neu) counts, as reported in subjects with asthma, as eosinophilic (E) (eos ≥ 1.0%, neu < 61%; n = 28), neutrophilic (N) (eos < 1.0%, neu ≥ 61%; n = 31), mixed granulocytic (M) (eos ≥ 1.0%, neu ≥ 61%; n = 12), and paucigranulocytic (P) (eos < 1.0%, neu < 61%; n = 27) subtypes. Patient characteristics; sputum levels of eosinophil cationic protein (ECP), IL-8, and neutrophil elastase (NE); and daily ICS doses required to maintain control during follow-up (6, 12, 18, and 24 months) were compared, retrospectively.

Results:  Subtype N patients, predominantly women, were marginally older than the other subtypes, but FEV1, airway responsiveness, and total and specific IgE results did not differ. ECP levels were higher in M and E than in N and P subtypes, being similar between M and E or N and P subtypes. Levels of IL-8 and NE were higher in M than in other subtypes, being similar among the latter. ICS doses were initially similar in all subtypes (800 μg equivalent of beclomethasone) but were higher in M than in N and P subtypes throughout follow-up, with E being intermediate between M and N or P subtypes. ICS doses decreased (halved or quartered) in E, N, and P patients followed for 24 months (P < .0001 for all) but remained unchanged in M subjects. IL-8 and NE levels correlated positively with ECP levels.

Conclusions:  In addition to eosinophils, neutrophils, which are possibly activated in the presence of eosinophils, may participate in the pathophysiology of CVA.

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