Does the highly effective modulator therapy influence airway inflammation in people with cystic fibrosis?

The highly effective modulator therapy (HEMT) improves respiratory health in CF patients but little is known of its direct influence on inflammation. We assumed that the baseline level of proinflammatory markers such as TNFα and TNFβ may influence clinical outcomes in CF patients treated with HEMT. We included 133 CF patients (65 adults and 68 children) before and 3 months after initiating HEMT (Kaftrio, Symkevi, Orkambi). We analysed clinical outcomes (inflammatory markers: neutrophils, IgG; lung function, BMI, vitamin D) before and while on therapy. We also analysed serum levels of inflammatory cytokines (TNFα, TNFβ) using ELISA. In adult patients 3 months after starting HEMT therapy, we observed a significant increase in BMI, lung function and significant decrease in blood neutrophilia and IgG levels. In pediatric patients after 3 months on HEMT we observed significant increase in z scores for FEV1, however other clinical outcomes remained unaltered after therapy. We did not observe significant changes in pro-inflammatory cytokines levels after 3 months of HEMT neither in adults nor in children. After accounting for baseline serum TNFα, we found that children with higher levels at baseline showed significant increase in BMI (p=0.006) and decrease in IgG levels (p=0.016). No such associations were observed for TNFβ. Our observation suggest that 3-month HEMT leads to more significant clinical improvement in adult patients. Lack of significant changes in children may be due to too short period of observation and their better baseline condition. The study was supported by National Science Centre in Poland, grant no. 2016/22/E/NZ5/00383 (A. Szczepankiewicz).