背景:体力活动是囊性纤维化治疗管理的关键需求。摄氧量的最高值(VO2peak)是评估这些患者身体活动的适当工具。然而,还有几个其他有价值的CPET参数描述运动耐量(Wpeak,VO2VT1,VO2VT2,VO2/HRpeak,等。),并帮助更好地了解特定治疗的效果(VE,VT,VD/VT等).有限的数据显示CFTR调节剂处理后这种改善的结果不明确。Elexacaftor/tezacaftor/ivacaftor药物可改善肺功能和生活质量,而其对CPET的影响尚未得到充分证明。
方法:我们在2019年1月至2023年2月期间完成了两次CPET测量的10例青少年囊性纤维化患者进行了单组前瞻性观察研究。在此期间,elexacaftor/tezacaftor/ivacaftor治疗开始在所有这些。药物开始后至少一年,在基线时进行第一次CPET,然后进行受控CPET。我们专注于解释新疗法对其影响的数据。我们假设治疗后心肺适应性改善。我们应用了Wilcoxon符号秩检验。在进行CPET时,对数据进行了年龄调整,以消除青少年患者的年龄偏倚。
结果:我们观察到峰值工作量的显着改善,VO2峰值,VO2VT1,VO2VT2,VE/VCO2斜率,VE,VT,RQ,VO2/HR峰值和RR峰值。VO2峰的平均变化为5.7mL/kg/min,或参考值的15.9%(SD±16.6;p=0.014)。VO2VT1提高了参考值的15%(SD±0.1;p=0.014),VO2VT2提高了0.5(SD±0.4;p=0.01)。其他参数没有差异。
结论:开始elexacaftor/tezacaftor/ivacaftor治疗后,运动耐量得到改善。我们建议仅CFTR调制器不足以恢复物理解构,但应该辅以身体活动和呼吸理疗。需要进一步的研究来检查CFTR调节剂和物理治疗对心肺运动耐量的影响。
BACKGROUND: Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO2peak) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (Wpeak, VO2VT1, VO2VT2, VO2/HRpeak, etc.), and helping to better understand the effect of specific treatment (VE, VT, VD/VT etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated.
METHODS: We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients.
RESULTS: We observed significant improvement in peak workload, VO2 peak, VO2VT1, VO2VT2, VE/VCO2 slope, VE, VT, RQ, VO2/HR peak and RR peak. The mean change in VO2 peak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO2VT1 improved by 15% of the reference value (SD ± 0.1; p= 0.014), VO2VT2 improved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters.
CONCLUSIONS: Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.