Pioch Charlotte O, Ziegahn Niklas, Allomba Christine, Busack Leonie M, Schnorr Alexandra N, Tosolini Apolline, Fuhlrott Bent R, Zagkla Styliani, Othmer Till, Syunyaeva Zulfiya, Graeber Simon Y, Yoosefi Mehrak, Thee Stephanie, Steinke Eva, Röhmel Jobst, Mall Marcus A, Stahl Mirjam
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; German Center for Lung Research (DZL), associated partner, Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.
J Cyst Fibros. 2024 Sep;23(5):863-869. doi: 10.1016/j.jcf.2024.03.003. Epub 2024 Mar 19.
In health, nitric oxide (NO) shows high concentrations in the upper airways, while nasal NO (nNO) is significantly lower in patients with sinonasal inflammation, such as people with cystic fibrosis (PwCF). In PwCF treated with elexacaftor/tezacaftor/ivacaftor (ETI; PwCF-ETI), clinical improvement of sinonasal symptoms and inflammation was observed. We therefore hypothesised that ETI may increase nNO in PwCF.
25 PwCF-ETI underwent nNO measurement at baseline and after 3 to 24 months of ETI treatment. NNO was measured using velum closure (VC) techniques in cooperative patients and tidal breathing (TB) for all patients. As controls, 7 CF patients not eligible for ETI (PwCF-non ETI) and 32 healthy controls (HC) were also repeatedly investigated.
In PwCF-ETI, sinonasal symptoms, lung function parameters and sweat chloride levels improved from baseline to follow-up whereas there was no change in PwCF-non ETI and HC. NNO increased from a median (IQR) value at baseline to follow-up from 348.2 (274.4) ppb to 779.6 (364.7) ppb for VC (P < 0.001) and from 198.2 (107.0) ppb to 408.3 (236.1) ppb for TB (P < 0.001). At follow-up, PwCF-ETI reached nNO values in the normal range. In PwCF-non ETI as well as HC, nNO did not change between baseline and follow-up.
In PwCF-ETI, the nNO values significantly increased after several months of ETI treatment in comparison to baseline and reached values in the normal range. This suggests that nNO is a potential non-invasive biomarker to examine sinonasal inflammatory disease in PwCF and supports the observation of clinical improvement in these patients.
在健康状态下，一氧化氮（NO）在上呼吸道中浓度较高，而在患有鼻窦炎症的患者中，如囊性纤维化患者（PwCF），鼻腔一氧化氮（nNO）水平显著降低。在接受依列卡福/替扎卡福/依伐卡福（ETI；PwCF-ETI）治疗的PwCF患者中，观察到鼻窦症状和炎症有临床改善。因此，我们推测ETI可能会增加PwCF患者的nNO水平。
25例PwCF-ETI患者在基线时以及接受ETI治疗3至24个月后进行了nNO测量。对于配合的患者，使用软腭闭合（VC）技术测量nNO，所有患者均进行潮气呼吸（TB）测量。作为对照，还对7例不符合ETI治疗条件的CF患者（PwCF-非ETI）和32例健康对照者（HC）进行了反复研究。
在PwCF-ETI患者中，从基线到随访期间，鼻窦症状、肺功能参数和汗液氯化物水平均有所改善，而PwCF-非ETI患者和HC患者则无变化。对于VC测量，nNO从基线时的中位数（IQR）值348.2（274.4）ppb增加到随访时的779.6（364.7）ppb（P<0.001）；对于TB测量，从198.2（107.0）ppb增加到408.3（236.1）ppb（P<0.001）。随访时，PwCF-ETI患者的nNO值达到正常范围。在PwCF-非ETI患者以及HC患者中，基线和随访之间nNO没有变化。
在PwCF-ETI患者中，与基线相比，经过数月的ETI治疗后nNO值显著增加，并达到正常范围。这表明nNO是一种潜在的非侵入性生物标志物，可用于检测PwCF患者的鼻窦炎性疾病，并支持观察到的这些患者的临床改善情况。
