Lung Function & Sleep Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2GW, UK.
Respiratory Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2GW, UK.
Int J Chron Obstruct Pulmon Dis. 2021 Mar 29;16:835-840. doi: 10.2147/COPD.S298585. eCollection 2021.
It is known that lung function decline in Alpha-1 Antitrypsin Deficiency (AATD) varies. Those with a rapid decline are at highest risk of poorer outcomes but may benefit most from targeted treatments including augmentation therapy. Current evidence suggests rapid decliners can be identified after 3 years of serial follow-up. It would be advantageous to identify these patients over a shorter time period, especially in mild disease.
Post-bronchodilator spirometry was performed every 6 months for a total of 18 months (4 measurements) by PiZZ AATD patients (ex- or never-smokers) either without spirometric COPD or with mild COPD. Where possible, retrospective spirometry data were included. Decline was assessed using 2 (baseline and 6 month) or four measurements (including baseline, 6, 12 and 18 months) and compared to retrospective decline rates using annual measurements over 3 years.
Seventy-two PiZZ AATD patients were included, with 27 having at least three years of retrospective, annual spirometry. 18-month progression obtained by linear regression showed variable degrees of change with 29 showing no decline, 8 showing slow decline and 35 showing rapid decline. Bland-Altman plots showed that there was no overall agreement between predicted rate of decline using data obtained over 6 months and that obtained over 18 months. Furthermore, there was no agreement between rate of decline from either 6 or 18 months' data when compared to data collected over 3 years. The positive predictive value for rapid decline with 18 months of data compared to 3 years was only 50.0%.
This study suggests serial lung function over 18 months cannot identify AATD patients who have rapidly declining lung function. There is an urgent need for different biomarkers to help identify these patients at the earliest opportunity.
已知α-1 抗胰蛋白酶缺乏症（AATD）患者的肺功能下降情况各不相同。那些肺功能下降速度较快的患者发生不良预后的风险最高，但可能从靶向治疗（包括增敏治疗）中获益最多。目前的证据表明，经过 3 年的连续随访，可以识别出肺功能快速下降的患者。如果能在更短的时间内识别出这些患者，特别是在疾病较轻时，将是有利的。
PIZZ 型 AATD 患者（曾吸烟者或从不吸烟者）在无肺功能 COPD 或仅有轻度 COPD 的情况下，每 6 个月进行一次支气管扩张剂后肺量计检查，共进行 18 个月（4 次测量）。在可能的情况下，还包括回顾性肺量计数据。使用 2 次（基线和 6 个月）或 4 次测量（包括基线、6、12 和 18 个月）评估下降情况，并与 3 年每年测量的回顾性下降率进行比较。
共纳入 72 例 PIZZ AATD 患者，其中 27 例有至少 3 年的回顾性年度肺量计数据。线性回归得到的 18 个月进展显示，变化程度各不相同，29 例无下降，8 例下降缓慢，35 例下降迅速。Bland-Altman 图显示，使用 6 个月获得的数据预测的下降率与使用 18 个月获得的数据之间没有总体一致性。此外，与 3 年收集的数据相比，使用 6 或 18 个月的数据得出的下降率之间也没有一致性。与 3 年数据相比，18 个月数据对快速下降的阳性预测值仅为 50.0%。
本研究表明，18 个月的连续肺功能检查无法识别肺功能快速下降的 AATD 患者。迫切需要不同的生物标志物来帮助尽早识别这些患者。
