Nationwide survey of refractory asthma with bronchiectasis by inflammatory subtypes
Authors: Nomura Natsuko , Matsumoto Hisako , Yokoyama Akihito , Nishimura Yoshihiro , Asano Koichiro , Niimi Akio , Tohda Yuji , Harada Norihiro , Nagase Hiroyuki , Nagata Makoto , Inoue Hiromasa , Kondo Mitsuko , Horiguchi Takahiko , Miyahara Nobuaki , Hizawa Nobuyuki , Hojo Masayuki , Hattori Noboru , Hashimoto Naozumi , Yamasaki Akira , Kadowaki Toru , Kimura Tomoki , Miki Mari , Taniguchi Hirokazu , Toyoshima Mikio , Kawamura Tetsuji , Matsuno Osamu , Sato Yoko , Sunadome Hironobu , Nagasaki Tadao , Oguma Tsuyoshi , Hirai Toyohiro ,   the BEXAS study, Ohnishi Hisashi , Imaizumi Kazuyoshi , Fujita Masaki , Suda Takafumi , Takaki Yoichi , Kijima Takashi , Tobino Kazunori , Hoshino Makoto , Imokawa Shiro , Hiraoka Noriya , Sugita Takakazu , Ikeda Naomi Miho , Ohnishi Kayoko Okamura Hisashi , Terada-Hirashima Junko , Isogai Sumito , Imaizumi Kazuyoshi , Hirano Ryosuke , Fujita Masaki , Fujisawa Tomoyuki , Suda Takafumi , Takaki Yoichi , Higaki Naoko , Miyamoto Shintaro , Nakashima Taku , Iwamoto Hiroshi , Mikami Koji , Minami Toshiyuki , Takahashi Ryo , Kijima Takashi , Tobino Kazunori , Hoshino Makoto , Imokawa Shiro , Tsuji Taisuke , Hiraoka Noriya , Ikeue Tatsuyoshi , Sugita Takakazu , Kunichika Naomi , Tomari Shinya , Okochi Yasumi , Mato Naoko , Hagiwara Koichi , Dobashi Kunio , Taooka Yasuyuki , Machida Kentaro , Tanosaki Takae , Masaki Katsunori , Fukunaga Koichi , Sano Akiko , Iwanaga Takashi , Higashimoto Yuji , Matsumoto Masataka , Takatsuki Kiyonobu , Nagata Kazuma , Tachikawa Ryo , Tomii Keisuke , Kaneko Masahiro , Tomioka Hiromi , Nagano Tatsuya , Yamane Mayuka , Yoshida Chieko , Sakagami Takuro , Seto Yurie , Kaneko Yoshiko , Takayama Koichi , Terada Satoru , Nishi Kenta , Tajiri Tomoko , Nakamura Saya , Wakahara Keiko , Ito Takefumi , Nakano Takako , Yamashita Takafumi , Takata Shohei , Seri Yoshihiro , Mizumori Yasuyuki , Tsukamoto Hiroaki , Kagami Ryogo , Nakahara Yasuharu , Ishii Yukio , Kita Toshiyuki , Hidaka Kouko , Minakuchi Masayoshi , Tsuboi Tomomasa , Tamaki Shinji , Matsuki Takanori , Kida Hiroshi , Tomita Katsuyuki , Abe Takashi , Shindoh Joe , Taniguchi Akihiko , Azuma Masato , Kataoka Mikio , Ogawa Haruhiko , Matsumoto Takeshi , Aihara Kensaku , Nakagome Kazuyuki , Miyajima Satsuki , Hashimoto Kentaro , Shiota Tetsuhiro , Yamaguchi Masafumi , Nakano Yasutaka , Otsuka Kojiro , Yasuo Masanori , Hanaoka Masayuki , Yamada Takashi , Shirai Toshihiro , Iwasaki Yoshinobu , Mineshita Masamichi , Tsuburai Takahiro , Komase Yuko , Koh Hidefumi , Hasegawa Koichi , Kita Hideo , Murakami Koji , Sugiura Hisatoshi , Ichinose Masakazu , Kutsuzawa Tomoko , Oguma Tsuyoshi , Tanaka Jun , Kono Yuta , Abe Shinji , Nakamura Morio , Orimo Mami , Tagaya Etsuko , Matsuda Toshiaki , Harada Tomoya , Iijima Hiroaki , Kawabata Hiroki , Yatera Kazuhiro , Masuko Hironori , Morishima Yuko , Nakanishi Masanori , Yamamoto Nobuyuki , Inoue Sumito , Hamada Kazuki , Yamaji Yoshikazu , Hirano Tsunahiko , Matsunaga Kazuto 
Published: December 2022

Abstract
Rationale
Bronchiectasis and bronchiolitis are differential diagnoses of asthma; moreover, they are factors associated with worse asthma control.

Objective
We determined clinical courses of bronchiectasis/bronchiolitis-complicated asthma by inflammatory subtypes as well as factors affecting them.

Methods
We conducted a survey of refractory asthma with non-cystic fibrosis bronchiectasis/bronchiolitis in Japan. Cases were classified into three groups, based on the latest fractional exhaled NO (FeNO) level (32 ppb for the threshold) and blood eosinophil counts (320/µL for the threshold): high (type 2-high) or low (type 2-low) FeNO and eosinophil and high FeNO or eosinophil (type 2-intermediate). Clinical courses in groups and factors affecting them were analysed.

Results
In total, 216 cases from 81 facilities were reported, and 142 were stratified: 34, 40 and 68 into the type 2-high, -intermediate and -low groups, respectively. The frequency of bronchopneumonia and exacerbations requiring antibiotics and gram-negative bacteria detection rates were highest in the type 2-low group. Eighty-seven cases had paired latest and oldest available data of FeNO and eosinophil counts; they were analysed for inflammatory transition patterns. Among former type 2-high and -intermediate groups, 32% had recently transitioned to the -low group, to which relatively low FeNO in the past and oral corticosteroid use contributed. Lastly, in cases treated with moderate to high doses of inhaled corticosteroids, the frequencies of exacerbations requiring antibiotics were found to be higher in cases with more severe airway lesions and lower FeNO.

Conclusions
Bronchiectasis/bronchiolitis-complicated refractory asthma is heterogeneous. In patients with sputum symptoms and low FeNO, airway colonisation of pathogenic bacteria and infectious episodes are common; thus, corticosteroids should be carefully used.