方法:共279例COPD患者符合条件而入选(严重程度分级I to IV 级所占比例分别为: 26, 45, 24, 和5%)。在基线状态下对参与者的肺功能和胸部计算机断层扫描（CT）进行详细评价，并且每6个月分别在吸入支气管扩张剂前后进行肺量计检查。监督患者吸烟状况、急性加重次数和药物治疗情况。根据CT和一氧化碳转移系数(Kco)评估肺气肿的严重程度。
主要结果:应用混合效应模型分析得261例COPD患者吸入支气管扩张剂后FEV1每年下降是-32±24(SD) ml/y 。我们根据每年FEV1的下降速度划分为三组：＜25%为快速下降者，25-75%为缓慢下降者，>75%为维持者 (每年下降的FEV1分别是：-63±2, -31±1, and -2±1 (SE) ml/y）。三组间肺气肿的严重程度（%FEV1除外）有显著性差异。多重逻辑回归分析证明快速下降者与肺气肿的严重程度存在独立的相关性，这一结论是通过CT或者Kco来评价的。维持者肺气肿严重程度较轻,体循环嗜酸性粒细胞水平较高。
Annual Change in Pulmonary Function and Clinical Phenotype in Chronic Obstructive Pulmonary Disease.
Nishimura M, Makita H, Nagai K, Konno S, Nasuhara Y, Hasegawa M, Shimizu K, Betsuyaku T, Ito YM, Fuke S, Igarashi T, Akiyama Y, Ogura S; for the Hokkaido COPD Cohort Study Investigators.
First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, 060-8638, Sapporo, 060-8638,Japan.
RATIONALE: Although the rate of annual decline in forced expiratory volume in one second (FEV1) is one of the most important outcome measures in chronic obstructive pulmonary disease (COPD), little is known about inter-subject variability based on clinical phenotypes.
OBJECTIVES: To examine the inter-subject variability in a 5-year observational cohort study, particularly focusing on emphysema severity.
METHODS: A total of 279 eligible patients with COPD (Stage I to IV: 26, 45, 24, and 5%) participated. We conducted a detailed assessment of pulmonary function and computed tomography (CT) at baseline, and performed spirometry every 6 months before and after inhalation of bronchodilator. Smoking status, exacerbation and pharmacotherapy were carefully monitored. Emphysema severity was evaluated by CT and annual measurements of carbon monoxide transfer coefficient (Kco). MEASUREMENTS AND
MAIN RESULTS: Using mixed effects model analysis, the annual decline in post-bronchodilator FEV1 was -32 ± 24 (SD) ml/y (n=261). We classified the subjects of < the 25th percentile as Rapid decliners, the 25th -75th percentile as Slow decliners, and > the 75th percentile as Sustainers (-63±2, -31±1, and -2±1 (SE) ml/y). Emphysema severity, but not %FEV1, showed significant differences among the three groups. Multiple logistic regression analysis demonstrated that the Rapid decliners were independently associated with emphysema severity assessed either by CT or Kco. The Sustainers displayed less emphysema and higher levels of circulating eosinophils.
CONCLUSIONS: Emphysema severity is independently associated with a rapid annual decline in FEV1 in COPD. Sustainers as well as Rapid decliners warrant specific attention in clinical practice.