National Referral Centre for Adult Cystic Fibrosis, St. Vincent's University Hospital, Dublin, Ireland.
University College Dublin School of Medicine, Dublin, Ireland.
Ann Am Thorac Soc. 2022 Nov;19(11):1818-1826. doi: 10.1513/AnnalsATS.202111-1266OC.
The etiology of cystic fibrosis (CF) pulmonary exacerbations (PEx) is likely multifactorial with viral, bacterial, and non-infectious pathways contributing. To determine whether viral infection status and CRP (C-reactive protein) can classify subphenotypes of PEx that differ in outcomes and biomarker profiles. Patients were recruited at time of admission for a PEx. Nasal swabs and sputum samples were collected and processed using the respiratory panel of the FilmArray multiplex polymerase chain reaction (PCR). Serum and plasma biomarkers were measured. PEx were classified using serum CRP and viral PCR: "" if CRP < 5 mg/L, "" if CRP ⩾ 5 mg/L and no viral infection detected by PCR and "" if CRP ⩾ 5 mg/L and viral infection detected by PCR. Discovery cohort ( = 59) subphenotype frequencies were ) pauci-inflammatory (37%); ) non-viral with systemic inflammation (41%); and ) viral with systemic inflammation (22%). Immunoglobulin G, immunoglobulin M, interleukin-10, interleukin-13, serum calprotectin, and CRP levels differed across phenotypes. Reduction from baseline in forced expiratory volume in 1 second as percent predicted (FEVpp) at onset of exacerbation differed between and (-6.73 ± 1.78 vs. -13.5 ± 2.32%; = 0.025). PEx had a trend toward longer duration of intravenous antibiotics versus (18.1 ± 1.17 vs. 14.8 ± 1.19 days, = 0.057). There were no differences in percent with lung function recovery to <10% of baseline FEVpp. Similar results were seen in local and external validation cohorts comparing a to exacerbation phenotypes. Subphenotypes of CF PEx exist with differences in biomarker profile, clinical presentation, and outcomes.
囊性纤维化（CF）肺部恶化（PEx）的病因可能是多因素的，病毒、细菌和非传染性途径都有贡献。目的是确定病毒感染状态和 C 反应蛋白（CRP）是否可以对 PEx 进行分类，不同的亚表型在结局和生物标志物特征方面存在差异。患者在 PEx 入院时被招募。采集鼻拭子和痰样本，使用 FilmArray 多重聚合酶链反应（PCR）呼吸道检测试剂盒进行处理。测量血清和血浆生物标志物。PEx 使用血清 CRP 和病毒 PCR 进行分类：“”如果 CRP<5mg/L，“”如果 CRP ⩾5mg/L 且未检测到病毒感染，PCR 且“”如果 CRP ⩾5mg/L 且检测到病毒感染，PCR。发现队列（=59）亚表型频率为）少炎型（37%）；）非病毒伴全身炎症（41%）；和）病毒伴全身炎症（22%）。各表型间 IgG、IgM、白细胞介素-10、白细胞介素-13、血清钙卫蛋白和 CRP 水平存在差异。恶化开始时用力呼气量占预计值的百分比（FEVpp）从基线下降的情况在和之间存在差异（-6.73±1.78 对-13.5±2.32%；=0.025）。与相比，PEx 静脉使用抗生素的时间有延长趋势（18.1±1.17 对 14.8±1.19 天，=0.057）。没有肺功能恢复到基线 FEVpp 的 10%以下的患者比例存在差异。在比较与恶化表型的本地和外部验证队列中，也观察到了类似的结果。CF PEx 存在亚表型，其在生物标志物特征、临床表现和结局方面存在差异。
