**7. Conclusions**

Considerable advances have been made in antibody therapeutics for severe asthma over the last decade. Increasing numbers of biological therapies will be introduced to clinical settings. Therefore, it will be of great importance for clinicians to consider the target and mechanism of action of each therapeutic antibody when selecting an appropriate treatment option for individual patients with severe asthma. The current selection and treatment strategies of antibody therapeutics are primarily based on Th2 type disease and eosinophilic inflammation. Further studies are necessary to compare the effects of each antibody type and clarify their effects against airway remodeling and hypersensitivity, and to guide decision making regarding appropriate antibody therapeutics by establishing a real phenotype classification that will predict the response of patients to antibody treatments. Importantly, a better understanding of non-Th2 type immunological mechanisms is urgently required to help develop treatment strategies using antibodies against non-Th2 type signaling cascades.

**Funding:** This work was supported in part by Japan Agency for Medical Research and Development: JP20fk0108129; Japan Agency for Medical Research and Development: JP21lm0203007; GlaxoSmithKline (United States): A-32; Japan Society for the Promotion of Science: JP21K16118; Japan Society for the Promotion of Science: JP21K08194, the Japan Intractable Diseases (Nanbyo) Research Foundation: 2020B02, and Smoking Research Foundation: 2021Y007 Takeda Science Foundation.

**Institutional Review Board Statement:** The experimental protocol for data involving human participants followed the Ethical Guidelines of the Japan Ministries of Health and Labour for Medical and Health Research Involving Human Subjects. All experiments were conducted in accordance with the principles laid out in the Declaration of Helsinki.

**Informed Consent Statement:** The study was approved by the Institutional Review Board of the National Hospital Organization, Osaka Toneyama Medical Centre (TNH-P-2021007). The IRB committee waived the requirement for informed consent for a retrospective review of participant data. The opt-out recruitment method was applied to provide an opportunity to decline participation for all patients. Members of the IRB committee were as follows; Tsuyoshi Matsumura, Toshihiko Yamaguchi, Noriyuki Takeuchi, Yukiyasu Takeuchi, Taku Shiomi, Makiko Sawamoto, Hiroyuki Ueno, Akihiro Takechi, Teruaki Masumoto, Motomu Shimoda, Hironori Tsukada, and Minako Nakano.

**Data Availability Statement:** The datasets supporting the conclusions of this article are included within the article. The data sets generated and analyzed in this study are available from the corresponding author on reasonable request.

**Acknowledgments:** We thank E. Akiba for assistance with data collection and helpful discussions. We also thank J. Ludovic Croxford, from Edanz (https://jp.edanz.com/ac) (accessed on 7 September 2021) for editing a draft of this manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **Abbreviations**

