Supplementary Material for: Alveolar Nitric Oxide and Peripheral Oxygen Saturation in Frequent Exacerbators with Asthma: A Pilot Study

Introduction: Asthmatics can experience recurrent exacerbations (AEs), irrespectively of asthma severity. Airway inflammatory monitoring could be fundamental to optimize the asthma management. The present study evaluated whether exhaled NO concentrations in proximal and distal respiratory compartments are different in AE-prone patients in combination with T2 blood biomarkers and resting oxygen saturation (SpO2). Methods: In this observational cross-sectional study, 91 mild-to-severe asthmatics were enrolled. Clinical characteristics, blood and lung function parameters including SpO2, and FENO were evaluated. On 50 randomly selected patients, CANO and JawNO were also analyzed. Then, patients were stratified in frequent exacerbators (FEs) or non-frequent exacerbators (nFEs), according to AE frequency in the previous year (phase I). Chart data were re-evaluated through a 12-month follow-up period post exhaled NO measurement to detect occurrence of novel AE (phase II). Results: FE asthmatics had poorer asthma control and required higher therapeutic intensity (p < 0.05). FENO, CANO, and JawNO were similar between FE and nFE. FE exhibited higher total serum IgE levels and residual volume values but reduced SpO2 than nFE (p < 0.05); SpO2<96.5% characterized the FE patient (odds ratio = 2.94). In phase II, CANO was higher in the group with novel AE at 1-month post-NO measurement (p < 0.05), but not afterward. A higher prevalence of CANO >6 ppb was detected in asthmatics who developed AE within 1 month, suggesting its potential clinical use as biomarker in predicting near-future AE (RR = 11.20). Conclusion: AE-susceptible asthmatics are characterized by air trapping and distal airway inflammation in conjunction with lower oxygen saturation. CANO and SpO2 could exert specific roles, respectively, in predicting AE and monitoring FE asthmatics.

引言：哮喘患者无论病情严重程度如何，均可出现反复发作的急性加重（acute exacerbations，AEs）。气道炎症监测对于优化哮喘管理可能至关重要。本研究旨在评估易出现急性加重的患者，其近端和远端呼吸道腔室的呼出气一氧化氮浓度，联合T2型血液生物标志物及静息血氧饱和度（SpO2）后是否存在差异。
方法：本项观察性横断面研究共纳入91名轻度至重度哮喘患者。研究人员对患者的临床特征、血液及肺功能参数（包括SpO2与呼出气一氧化氮分数（fractional exhaled nitric oxide，FENO））进行了评估。在50名随机选取的患者中，还额外分析了中心呼出气一氧化氮（central airway nitric oxide，CANO）与颌部呼出气一氧化氮（jaw nitric oxide，JawNO）。随后，依据前一年的急性加重发作频率，将患者分为频繁急性加重组（frequent exacerbators，FEs）与非频繁急性加重组（non-frequent exacerbators，nFEs）（阶段I）。在完成呼出气一氧化氮检测后，对患者开展为期12个月的随访，重新审查病历数据以检测新发急性加重的发生情况（阶段II）。
结果：频繁急性加重组哮喘患者的哮喘控制情况更差，且需要更高强度的治疗（p < 0.05）。两组患者的FENO、CANO及JawNO水平无显著差异。频繁急性加重组患者的血清总IgE水平与残气量更高，但静息血氧饱和度较非频繁急性加重组更低（p < 0.05）；静息血氧饱和度<96.5%可作为频繁急性加重患者的特征指标（优势比=2.94）。在阶段II中，呼出气一氧化氮检测后1个月内出现新发急性加重的患者，其CANO水平更高（p < 0.05），但该差异在后续随访中未再现。在1个月内出现急性加重的哮喘患者中，CANO>6ppb的检出率更高，这提示CANO有望作为预测近期急性加重的生物标志物（相对危险度=11.20）。
结论：易出现急性加重的哮喘患者以气道陷闭与远端气道炎症为特征，同时伴随血氧饱和度降低。CANO与SpO2可分别在预测急性加重及监测频繁急性加重哮喘患者方面发挥特定作用。