Asakura Takanori, Kimizuka Yoshifumi, Nishimura Tomoyasu, Suzuki Shoji, Namkoong Ho, Masugi Yohei, Sato Yasunori, Ishii Makoto, Hasegawa Naoki
Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
Respirology. 2021 Jan;26(1):112-119. doi: 10.1111/resp.13886. Epub 2020 Jun 29.
The lack of useful biomarkers reflecting the disease state limits the management of Mycobacterium avium complex lung disease (MAC-LD). We clarified the associations between serum KL-6 level, disease progression and treatment response.
Resected lung tissues from MAC-LD patients were immunostained for KL-6. We compared serum KL-6 levels between MAC-LD and healthy control or bronchiectasis patients without nontuberculous mycobacterial lung disease (NTM-LD). Serum KL-6 level was assessed in a prospective observational study at Keio University Hospital between May 2012 and May 2016. We investigated associations between serum KL-6 level and disease progression and treatment response in patients untreated for MAC-LD on registration (n = 187).
The KL-6 alveolar type 2 cell population in the lung and serum KL-6 level were significantly higher in MAC-LD patients than in controls. Serum KL-6 level in bronchiectasis patients without NTM-LD showed no significant increase. Of the 187 patients who did not receive treatment on registration, 53 experienced disease progression requiring treatment. Multivariable Cox analysis revealed that the serum KL-6 level (aHR: 1.18, P = 0.005), positive acid-fast bacilli smear (aHR: 2.64, P = 0.001) and cavitary lesions (aHR: 3.01, P < 0.001) were significantly associated with disease progression. The change in serum KL-6 (ΔKL-6) was significantly higher in the disease progression group; it decreased post-treatment, reflecting the negative sputum culture conversion.
Serum KL-6 level is associated with disease progression and treatment response. Longitudinal assessment combined with AFB smear status and presence of cavitary lesions may aid MAC-LD management.
缺乏反映疾病状态的有用生物标志物限制了鸟分枝杆菌复合群肺病（MAC-LD）的管理。我们阐明了血清KL-6水平、疾病进展和治疗反应之间的关联。
对MAC-LD患者切除的肺组织进行KL-6免疫染色。我们比较了MAC-LD患者与健康对照者或无非结核分枝杆菌肺病（NTM-LD）的支气管扩张患者之间的血清KL-6水平。在2012年5月至2016年5月期间于庆应义塾大学医院进行的一项前瞻性观察研究中评估血清KL-6水平。我们调查了登记时未接受MAC-LD治疗的患者（n = 187）血清KL-6水平与疾病进展和治疗反应之间的关联。
MAC-LD患者肺中的KL-6Ⅱ型肺泡细胞群体和血清KL-6水平显著高于对照组。无NTM-LD的支气管扩张患者血清KL-6水平无显著升高。在登记时未接受治疗的187例患者中，53例经历了需要治疗的疾病进展。多变量Cox分析显示，血清KL-6水平（aHR：1.18，P = 0.005）、抗酸杆菌涂片阳性（aHR：2.64，P = 0.001）和空洞性病变（aHR：3.01，P < 0.001）与疾病进展显著相关。疾病进展组血清KL-6的变化（ΔKL-6）显著更高；治疗后其下降，反映痰培养转阴。
血清KL-6水平与疾病进展和治疗反应相关。结合抗酸杆菌涂片状态和空洞性病变的纵向评估可能有助于MAC-LD的管理。
