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Additional file 1. Table S1. Frequency of the CC16 genetic polymorphism (rs3741240). Table S2. Characteristics of non-smoking patients with lung cancer without any pulmonary diseases by BMI group. Table S3. Characteristics of the participants who attended the hospital for routine health check-ups (population 1, n = 357). Table S4. Associations between characteristics and serum CC16 levels in participants who attended the hospital for routine health check-ups (population 1, n = 357). Table S5. Characteristics of the young healthy participants (population 2, n = 137). Table S6. Association between the characteristics of young healthy participants and plasma CC16 levels (population 2, n = 137). Table S7. Characteristics of patients with asthma (population 3, n = 206). Table S8. BMI distribution in patients with severe and non-severe asthma (population 3, n = 206). Table S9. Associations between characteristics and serum CC16 levels in patients with asthma (population 3, n = 206). Fig. S1. Circulating CC16 levels based on the CC16 genetic polymorphism (rs3741240). Fig. S2. Flowchart for conducting CC16, SCBB3A2, and MUC5AC immunohistochemistry in the cancer-free lung tissues of never smoking human participants. Fig. S3. Association of circulating CC16 levels and categorical BMI in the combination of three populations excluding current smokers. Fig. S4. Decreased SCGB3A2 expressing cells in the airways of obese mice and overweight/obese humans. Fig. S5. Comparison of serum CC16 levels and blood SP-A and SP-D levels in obese vs. control mice. Fig. S6. Association of circulatory CC16 with airway hyperresponsiveness in young healthy participants (population 2). Fig. S7. Reduced serum CC16 levels among severe compared to non-severe asthma patients (population 3). Fig. S8. Inverse association of circulatory CC16 and inhaled corticosteroid (ICS) dose in asthma patients (population 3). Fig. S9. Circulatory CC16 levels according to required ICS dose in asthma patients (population 3).

平成30年度宇宙輸送シンポジウム（2019年1月17日-18日. 宇宙航空研究開発機構宇宙科学研究所（JAXA)(ISAS)）, 相模原市, 神奈川県, Space Transportation Symposium FY2018 (January 17-18, 2019. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (JAXA)(ISAS)), Sagamihara, Kanagawa Japan, 資料番号: SA6000136052, レポート番号: STCP-2018-052

平成30年度宇宙輸送シンポジウム（2019年1月17日-18日. 宇宙航空研究開発機構宇宙科学研究所（JAXA)(ISAS)）, 相模原市, 神奈川県, Space Transportation Symposium FY2018 (January 17-18, 2019. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (JAXA)(ISAS)), Sagamihara, Kanagawa Japan, 資料番号: SA6000136055, レポート番号: STCP-2018-055

application/pdf, Azole antifungals are used not only clinically for fungal infections but also used as agricultural fungicides. Recently, azole-resistant Aspergillus fumigatus containing a tandem repeat in the promoter region of cyp51A combined with amino acid substitution(s) appears in the environment in Eurasia, especially in several European countries. Although azole fungicides have been used in Japan, especially in Hokkaido, surveillance and characterization of A. fumigatus in Hokkaido have not been reported. In this study, we collected soil samples from farms that used an azole fungicide in the Tokachi area of eastern Hokkaido, isolated 91 A. fumigatus strains, and determined the minimal inhibitory concentrations of medical azoles required for these strains. Moreover, because causative agent A. fumigatus is ubiquitous in the air and acquired from the environment, we collected 22 clinical isolates of A. fumigatus to measure their susceptibility to medical azoles in a hospital in the Tokachi area. Our data show that almost all A. fumigatus isolates retained susceptibility to medical azoles. Clinical isolates OKH34 and OKH6 showed 8 and 2 mu g/mL of voriconazole, respectively, as the minimal inhibitory concentration. Both isolates did not contain tandem repeat in cyp51A promoter region. An isolate contained G448S mutation in cyp51A conferring voriconazole resistance, which is the first report from Japan. Our data shows the existence of azole-resistant and low azole-susceptible clinical isolates and highlight the necessity for continuous surveillance in Japan because resistant A. fumigatus strains can arise through clinical or environmental selection or could be introduced from overseas.