Infection status and genetic characteristics of adenovirus in patients with acute exacerbation of chronic obstructive pulmonary disease
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摘要:
目的 了解慢性阻塞性肺疾病急性加重期（acute exacerbation of chronic obstructive pulmonary disease，AECOPD）患者的呼吸道病毒感染情况及腺病毒感染特点。 方法 收集2020年11月至2021年4月安徽省蚌埠市某三甲医院AECOPD住院重症患者咽拭子，采用实时荧光定量PCR（qPCR）方法筛查16种常见呼吸道病毒，对腺病毒（ADV）阳性样本扩增腺病毒六邻体基因，构建进化树。 结果 AECOPD患者呼吸道样本中呼吸道病毒检出率为38.38%（109/284），其中，ADV检出率最高，为27.81%（79/284）。 重症患者ADV感染以C1型为主，同时，有B、C和D等多个亚型存在。 结合临床数据，AECOPD患者中，感染ADV的较未感染ADV的病程长、预后差。 结论 临床应对AECOPD患者的呼吸道病毒感染情况进行有效监测，以提高诊断和治疗效果。 -
关键词:
- 慢性阻塞性肺疾病急性加重 /
- 呼吸道病毒感染 /
- 重症患者 /
- 腺病毒 /
- 流行病学
Abstract:Objective To investigate the respiratory tract virus infection and the characteristics of adenovirus infection in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods From November 2020 to April 2021, throat swabs from the severe patients with AECOPD in a class III hospital in Bengbu, Anhui province, were collected. Real-time fluorescent quantitative PCR (qPCR) was used to detect 16 common respiratory viruses, including adenovirus (ADV). The hexon genes of ADV were amplified followed with the phylogenetic analysis. Results The detection rate of respiratory viruses was 38.38% (109/284), and the detection rate of ADV was highest (27.81%, 79/284) in these AECOPD patients. ADV infection was mainly caused by subtype C1 virus, and there were multi subtypes such as B, C and D. Combined with clinical data, the AECOPD patients infected with ADV had a longer course of disease and poorer prognosis compared with the AECOPD patients without ADV infection. Conclusion Effective monitoring of respiratory virus infection in AECOPD patients should be carried out in clinical practice to improve the clinical diagnosis and treatment. -
图 1 腺病毒六邻体基因片段序列进化树
注：红色、粉色、绿色、浅绿色、天蓝色、浅蓝色、深蓝色分别代表ADV-C1、C5、B7、B3、D17、D19、D27型序列
Figure 1. Gene evolution tree of adenovirus hexon gene segment
表 1 不同年龄组慢性阻塞性肺疾病急性加重期患者的临床特征（例）
Table 1. Clinical characteristics of AECOPD patients among different age groups
年龄组
（岁）病例数 男性 女性 慢性阻塞性肺疾病特定症状 血气分析 咳嗽咳痰 活动气喘 Ⅰ型呼吸衰竭 Ⅱ型呼吸衰竭 低氧血症 咳嗽伴咳痰 干咳 mMRC3级 mMRC4级 27～ 8 3 5 7 1 0 8 0 7 1 50～ 17 6 11 10 7 3 14 1 15 1 60～ 75 57 18 58 17 11 64 0 71 4 70～ 126 108 18 98 28 13 113 5 111 10 80～ 54 42 12 41 13 5 49 2 50 2 90～96 4 3 1 2 2 0 4 0 4 0 合计 284 219 65 205 65 32 252 8 258 18 
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表 2 慢性阻塞性肺疾病急性加重期患者临床呼吸道症病毒感染谱
Table 2. Clinical spectrum of respiratory syndrome virus infection in patients with AECOPD
感染病毒
种类病毒 病例数（例） 1种 腺病毒 58 巨细胞病毒 8 博卡病毒 2 鼻病毒 2 甲型流感病毒 2 呼吸合胞病毒 1 冠状病毒HUK1 1 冠状病毒NL63 1 冠状病毒229E 1 冠状病毒OC43 1 乙型流感病毒 1 1型副流感病毒 1 3型副流感病毒 1 人偏肺病毒 1 2种 腺病毒＋巨细胞病毒 2 腺病毒＋呼吸合胞病毒 3 腺病毒＋冠状病毒HKU1 1 腺病毒＋冠状病毒NL63 2 腺病毒＋冠状病毒229E 3 腺病毒＋冠状病毒OC43 1 腺病毒＋鼻病毒 2 腺病毒＋肠道病毒 3 腺病毒＋2型副流感病毒 1 腺病毒＋人偏肺病毒 1 巨细胞病毒＋肠道病毒 1 呼吸合胞病毒＋冠状病毒229E 1 呼吸合胞病毒＋乙型流感病毒 1 呼吸合胞病毒＋肠道病毒 1 鼻病毒＋3型副流感病毒 1 博卡病毒＋肠道病毒 1 3种 腺病毒＋呼吸合胞病毒＋3型副流感病毒 1 腺病毒＋巨细胞病毒＋1型副流感病毒 1 呼吸合胞病毒＋肠道病毒＋人偏肺病毒 1
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表 3 慢性阻塞性肺疾病急性加重期重症患者腺病毒感染单因素分析
Table 3. Univariate analysis on adenovirus infection in severe patients with AECOPD
因素 A组（n=79） B组（n=30） C组（n=175） A组和B组比较 A组和C组比较 统计量 P值 统计量 P值 性别a 男性 64 27 128 0.705 0.401 1.827 0.1765 女性 15 3 47 年龄（岁） 73.94±8.74 71.37±11.65 71.16±9.83 −1.077 0.282 2.0405 0.0413 病程（d） 17.66±7.97 14.8±10.84 12.52±11.87 −2.019 0.044 5.3345 ＜.0001 发热（>37.5 ℃）a 是 43 27 47 11.972 ＜0.001 18.0879 ＜.0001 否 36 3 128 白细胞计数b 10.45±4.32 11.02±4.72 11.05±5.29 0.79 0.429 −0.5959 0.5512 中性粒细胞计数b 6.45±3.79 7.00±4.10 7.19±4.83 0.536 0.592 −0.7233 0.4695 淋巴细胞计数b 1.49±0.86 1.55±1.05 1.34±0.71 −0.092 0.927 1.2656 0.2056 嗜酸性粒细胞计数b 0.38±0.34 0.53±0.79 0.41±0.45 0.312 0.755 −0.0055 0.9956 吸入糖皮质激素a 是 61 28 158 3.77 0.052 7.8266 0.0051 否 18 2 17 活动后气喘a mMRC4级 66 28 158 1.7556 0.1852 2.3748 0.1233 mMRC3级 13 2 17 呼吸性衰竭a 是 74 29 163 / 1.000 0.0243 0.8761 否 5 1 12 心力衰竭a 是 41 5 28 11.065 ＜0.001 35.4516 ＜0.0001 否 38 25 147 预后a 恶化 18 0 15 2.064 0.039 −8.0139 ＜0.0001 差 39 19 15 缓解 22 11 145 注：A组为腺病毒感染组，B组为非腺病毒感染组，C组为无病毒感染组；a. 数值为病例数（例）；b. 数值为均数±标准差（×109/L）；
/. 采用fisher确切概率法
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