Fijačko Vladimir, Labor Marina, Fijačko Mirjana, Škrinjarić-Cincar Sanda, Labor Slavica, Dumbović Dubravčić Iva, Bačun Tatjana, Včev Aleksandar, Popović-Grle Sanja, Plavec Davor
Department of Pulmonology, University Hospital Center Osijek, Osijek, Croatia.
Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia.
Wien Klin Wochenschr. 2018 Apr;130(7-8):247-258. doi: 10.1007/s00508-017-1307-7. Epub 2018 Jan 10.
No specific (only subgroup) recommendations for the use of long-acting muscarinic antagonists in chronic obstructive pulmonary disease (COPD) exist. The aim of this exploratory hypothesis generating study was to assess whether different phenotypic/endotypic characteristics could be determinants of the short-term ineffectiveness of the initial tiotropium bromide monotherapy in treatment naïve moderate to severe COPD patients.
A total of 51 consecutively recruited COPD patients were followed for 3 months after the initial evaluation and prescribed initial treatment (tiotropium). Short-term treatment ineffectiveness was assessed as a composite measure comprising COPD exacerbations, need for additional treatment, and no improvement in functional parameters, e.g. 6‑min walking test (6MWT), body-mass index, airflow obstruction, dyspnea, and exercise (BODE) index and forced expiratory volume in 1 s (FEV), and as single components.
Treatment ineffectiveness was significantly associated with baseline hemoglobin level, COPD assessment test (CAT) score, modified Medical Research Council (mMRC) scale and BODE index (p = 0.002). Incident exacerbation during the follow-up was associated with baseline bronchoalveolar lavage fluid (BALF) alpha-amylase level and CAT score (p < 0.001), and change in treatment with leukocyte count, 6MWT desaturation and fatigue (p < 0.001). No improvement in 6MWT was associated with baseline CAT score, body mass index, mMRC, fatigue, 6MWT and BODE index (p = 0.002). No improvement in BODE index was associated with leukocyte count, serum interleukin 8 (IL-8) and BALF albumin levels (p < 0.001); and no improvement in FEV with CAT score, baseline vital capacity and BALF tumor necrosis factor alpha (TNF-alpha) level (p < 0.001).
Our results suggest that there is a possibility to identify predictors of short-term tiotropium ineffectiveness in patients with moderate to severe COPD.
对于长效毒蕈碱拮抗剂在慢性阻塞性肺疾病（COPD）中的应用，尚无具体（仅针对亚组）推荐意见。本探索性假设生成研究的目的是评估不同的表型/内型特征是否可能是初始噻托溴铵单药治疗对未接受过治疗的中度至重度COPD患者短期无效的决定因素。
对51例连续招募的COPD患者在初始评估并给予初始治疗（噻托溴铵）后进行3个月的随访。短期治疗无效被评估为一项综合指标，包括COPD急性加重、额外治疗需求以及功能参数无改善，如6分钟步行试验（6MWT）、体重指数、气流受限、呼吸困难和运动（BODE）指数以及第1秒用力呼气容积（FEV），并作为单一成分进行评估。
治疗无效与基线血红蛋白水平、COPD评估测试（CAT）评分、改良医学研究委员会（mMRC）量表和BODE指数显著相关（p = 0.002）。随访期间的急性加重与基线支气管肺泡灌洗液（BALF）α-淀粉酶水平和CAT评分相关（p < 0.001），以及与白细胞计数、6MWT血氧饱和度下降和疲劳导致的治疗变化相关（p < 0.001）。6MWT无改善与基线CAT评分、体重指数、mMRC、疲劳、6MWT和BODE指数相关（p = 0.002）。BODE指数无改善与白细胞计数、血清白细胞介素8（IL-8）和BALF白蛋白水平相关（p < 0.001）；FEV无改善与CAT评分、基线肺活量和BALF肿瘤坏死因子α（TNF-α）水平相关（p < 0.001）。
我们的结果表明，有可能识别中度至重度COPD患者短期噻托溴铵治疗无效的预测因素。
