Supplementary Material for: Pretreatment Alveolar Nitric Oxide Levels Predict Improvement of Pulmonary Function 1 Year Following Anti-Asthma Treatments in Patients with Inhaled Corticosteroid-Naïve Asthma

<b><i>Introduction:</i></b> Inhaled corticosteroids (ICS) are fundamental agents to subside airway inflammation and improve forced expiratory volume in 1 s (FEV₁) among asthmatics. Alveolar concentrations of nitric oxide (CANO), as well as the classical fraction of exhaled nitric oxide (FeNO50), are associated with the pathophysiology of asthma. However, the association between pretreatment CANO levels and response to anti-asthma treatments, including ICS, remains unknown. <b><i>Methods:</i></b> We retrospectively analyzed 107 patients newly diagnosed with asthma. ICS in combination with long-acting β₂-agonists (ICS/LABA) was initiated. FEV₁ and FeNO levels were evaluated at diagnosis and were followed up at 6 and 12 months after the treatment intervention. CANO levels were estimated using various expiratory flows of FeNO measurements. Factors associated with annual changes in FEV₁ (ΔFEV₁) were analyzed. Patients with a ΔFEV₁ <i>Results:</i> FEV₁, FeNO50, and CANO levels significantly improved by anti-asthma treatments. The average ΔFEV₁ was 85 (176) mL. Eighty-two patients continuously took ICS/LABA treatment. Higher pretreatment CANO levels and continuous use of LABA were independent predictive factors for the improvement of FEV₁ on multivariate analysis. The decline in FeNO50 and CANO levels by the anti-asthma treatments was significantly greater in 81 responders than in 26 poor-responders. CANO, but not FeNO50, levels at 12 months were significantly higher in poor-responders than in responders (<i>p</i> = 0.009). <b><i>Conclusion:</i></b> Levels of CANO, but not FeNO50, predict changes in pulmonary function in ICS-naïve asthmatics. Meanwhile, persistently high levels of CANO may be related to poor responsiveness to treatments assessed by ΔFEV₁.

<b><i>引言：</i></b> 吸入性糖皮质激素（Inhaled Corticosteroids, ICS）是哮喘患者减轻气道炎症、改善一秒用力呼气容积（Forced Expiratory Volume in 1 Second, FEV₁）的基础治疗药物。肺泡一氧化氮浓度（Alveolar Concentrations of Nitric Oxide, CANO）与呼出气一氧化氮经典组分（Classical Fraction of Exhaled Nitric Oxide, FeNO50）均与哮喘的病理生理机制密切相关。然而，治疗前CANO水平与包括ICS在内的抗哮喘治疗应答之间的关联仍尚不明确。
<b><i>方法：</i></b> 本研究回顾性分析了107例新确诊哮喘患者，予以吸入性糖皮质激素联合长效β₂受体激动剂（Long-Acting β₂-Agonists, LABA，即ICS/LABA）方案治疗。于确诊时检测FEV₁与FeNO水平，并于治疗干预后6、12个月完成随访。通过不同呼气流速下的FeNO检测结果估算CANO水平，分析一秒用力呼气容积年变化量（ΔFEV₁）的相关影响因素。[原文此处存在文本截断，对应内容为Patients with a ΔFEV₁]
<b><i>结果：</i></b> 抗哮喘治疗可显著改善患者的FEV₁、FeNO50及CANO水平。患者平均ΔFEV₁为85（176）mL。其中82例患者持续接受ICS/LABA治疗。多因素分析显示，治疗前较高的CANO水平与持续使用LABA是FEV₁改善的独立预测因子。81例应答者经抗哮喘治疗后FeNO50与CANO水平的下降幅度显著高于26例低应答者。治疗12个月时，低应答者的CANO水平（而非FeNO50）显著高于应答者（<i>p</i>=0.009）。
<b><i>结论：</i></b> CANO水平而非FeNO50可预测未接受过ICS治疗的哮喘患者的肺功能变化。同时，持续高水平的CANO可能与以ΔFEV₁评估的治疗应答不佳相关。