慢性阻塞性肺疾病急性加重期气道病原体季节变化的前瞻性观察队列研究
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摘要
目的探讨COPD急性加重期(AECOPD)慢性细菌性气道感染与病毒暴露之间的关系,以及这些事件的发生率和季节性。方法选取2015年7月到2016年6月间,我院呼吸科招募52例COPD急性加重期患者,男/女分别为29/23例,平均年龄70. 7±9. 9年。患者每月以及在AECOPD发病时接受痰液标本取样,进行细菌培养鉴定和病毒PCR分析,分析研究AECOPD与病原体的相互作用。结果总体上,AECOPD患者痰液样本的细菌(61. 7%vs 47. 3%,χ~2=7. 647,P=0. 0057)和病毒(32. 5%vs 7. 8%,χ~2=48. 8,P <0. 0001)的检出率要高于COPD稳定期患者。最常见的病原菌为非典型流感嗜血杆菌和肺炎链球菌,而最常见的病毒为鼻病毒。痰液样本中细菌与病毒同时检出的比率从COPD稳定期的4. 6%升高到AECOPD的22. 5%(χ~2=37. 38,P <0. 0001)。AECOPD病例的痰液标本的病原菌的分布呈季节性变化。AECOPD的就诊率从低季节的35. 0%上升到高季节的65. 0%,细菌性或病毒性导致的AECOPD的就诊率从低季节的64. 3%到高季节的75. 6%;对于病因阴性的AECOPD,由低季节的35. 7%下降到高季节的24. 4%(χ~2=1. 734,P=0. 1880)。结论 AECOPD病因随季节变化。冬季发病率上升可能是由于病原体存在增加以及非典型流感嗜血杆菌气道感染与病毒感染影响之间的相互作用所致。
Objective To explore the relationship between chronic bacterial airway infection of AECOPD and viral exposure,in order to explain the incidence and seasonality of these events. Methods From July 2015 to June 2016,52 patients with AECOPD were included. The ratio of male/female was 29/23,and the average age was 70. 7 ± 9. 9 years. Patients underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses. Bacterial culture and PCR analysis for virus were carried out. Interactions between exacerbation occurrence and pathogens were investigated. Results Overall,the detection rate of bacteria and virus in sputum samples was significantly higher in patients with AECOPD than in patients as stable stage( 61. 7% vs 47. 3%,χ~2= 7. 647,P =0. 0057; 32. 5% vs 7. 8%,χ~2= 48. 8,P < 0. 0001). The most common bacterial species were non-typeable Haemophilus influenzae( NTHi) and Streptococcus pneumoniae,and the most common virus was rhinovirus. The rate of simultaneous detection of bacteria and viruses in sputum samples increased from 4. 6% at stable phase to 22. 5% at acute exacerbation( χ~2= 37. 38,P < 0. 0001). The distribution of pathogen in sputum specimens of AECOPD cases varied seasonally. AECOPD visits rate increased from 35. 0% in the low season to 65. 0% in the high season,and the rate of AECOPD patients caused by bacterial or virus ranged from 64. 3% in the low season to 75. 6% in the high season,and it decreased from 35. 7% in the low season to 24. 4% in the high season for AECOPD with negative etiology( χ~2= 1. 734,P = 0. 1880). Conclusion AECOPD aetiology varies with season. The high incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effect of viral infection.
Objective To explore the relationship between chronic bacterial airway infection of AECOPD and viral exposure,in order to explain the incidence and seasonality of these events. Methods From July 2015 to June 2016,52 patients with AECOPD were included. The ratio of male/female was 29/23,and the average age was 70. 7 ± 9. 9 years. Patients underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses. Bacterial culture and PCR analysis for virus were carried out. Interactions between exacerbation occurrence and pathogens were investigated. Results Overall,the detection rate of bacteria and virus in sputum samples was significantly higher in patients with AECOPD than in patients as stable stage( 61. 7% vs 47. 3%,χ~2= 7. 647,P =0. 0057; 32. 5% vs 7. 8%,χ~2= 48. 8,P < 0. 0001). The most common bacterial species were non-typeable Haemophilus influenzae( NTHi) and Streptococcus pneumoniae,and the most common virus was rhinovirus. The rate of simultaneous detection of bacteria and viruses in sputum samples increased from 4. 6% at stable phase to 22. 5% at acute exacerbation( χ~2= 37. 38,P < 0. 0001). The distribution of pathogen in sputum specimens of AECOPD cases varied seasonally. AECOPD visits rate increased from 35. 0% in the low season to 65. 0% in the high season,and the rate of AECOPD patients caused by bacterial or virus ranged from 64. 3% in the low season to 75. 6% in the high season,and it decreased from 35. 7% in the low season to 24. 4% in the high season for AECOPD with negative etiology( χ~2= 1. 734,P = 0. 1880). Conclusion AECOPD aetiology varies with season. The high incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effect of viral infection.
引文
[1] SINDEN N J,STOCKLEY R A. Chronic obstructive pulmonary disease:An update of treatment related to frequently associated comorbidities[J]. Ther Adv Chronic Dis,2010,1(2):43-57.
[2] CASO F,COSTA L,DEL PUENTE A,et al. Pharmacological treatment of spondyloarthritis:Exploring the effectiveness of nonsteroidal anti-inflammatory drugs,traditional disease-modifying antirheumatic drugs and biological therapies[J]. Ther Adv Chronic Dis,2015,6(6):328-338.
[3] DONALDSON G C,WEDZICHA J A. The causes and consequences of seasonal variation in COPD exacerbations[J]. Int J Chron Obstruct Pulmon Dis,2014,9:1101-1110.
[4]中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2013年修订版)[S].中华结核和呼吸杂志,2013,36(4):255-264.
[5] SETHI S. Infection as a comorbidity of COPD[J]. Eur Respir J,2010,35(6):1209-1215.
[6] MALLIA P,FOOTITT J,SOTERO R,et al. Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2012,186(11):1117-1124.
[7] MOLYNEAUX P L,MALLIA P,COX M J,et al. Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2013,188(10):1224-1231.
[8] WILKINSON T M,HURST J R,PERERA W R,et al. Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD[J]. Chest,2006,129(2):317-324.
[9] BAFADHEL M,HALDAR K,BARKER B,et al. Airway bacteria measured by quantitative polymerase chain reaction and culture in patients with stable COPD:Relationship with neutrophilic airway inflammation,exacerbation frequency,and lung function[J]. Int J Chron Obstruct Pulmon Dis,2015,10:1075-1083.
[10] BARKER B L,HALDAR K,PATEL H,et al. Association between pathogens detected using quantitative polymerase chain reaction with airway inflammation in COPD at stable state and exacerbations[J]. Chest,2015,147(1):46-55.
[11] ZWAANS W A,MALLIA P,VAN WINDEN M E,et al. The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease--a systematic review[J]. J Clin Virol,2014,61(2):181-188.
[12] GEORGE S N,GARCHA D S,MACKAY A J,et al. Human rhinovirus infection during naturally occurring COPD exacerbations[J].Eur Respir J,2014,44(1):87-96.
[13] CLARK T W,MEDINA M J,BATHAM S,et al. C-reactive protein level and microbial aetiology in patients hospitalised with acute exacerbation of COPD[J]. Eur Respir J,2014,45(1):76-86.
[14] DAI M Y,QIAO J P,XU Y H,et al. Respiratory infectious phenotypes in acute exacerbation of COPD:An aid to length of stay and COPD Assessment Test[J]. Int J Chron Obstruct Pulmon Dis,2015,10:2257-2263.
[15] OHRUI T,YAMAYA M,SEKIZAWA K,et al. Effects of rhinovirus infection on hydrogen peroxide-induced alterations of barrier function in the cultured human tracheal epithelium[J]. Am J Respir Crit Care Med,1998,158(1):241-248.
[16] OLIVER B G,LIM S,WARK P,et al. Rhinovirus exposure impairs immune responses to bacterial products in human alveolar macrophages[J]. Thorax,2008,63(6):519-525.
[17] BELLINGHAUSEN C,GULRAIZ F,HEINZMANN A C,et al. Exposure to common respiratory bacteria alters the airway epithelial response to subsequent viral infection[J]. Respir Res,2016,17(1):68.
[18] HEINRICH A,HAARMANN H,ZAHRADNIK S,et al. Moraxella catarrhalis decreases antiviral innate immune responses by downregulation of TLR3 via inhibition of p53 in human bronchial epithelial cells[J]. FASEB J,2016,30(6):2426-2434.
[2] CASO F,COSTA L,DEL PUENTE A,et al. Pharmacological treatment of spondyloarthritis:Exploring the effectiveness of nonsteroidal anti-inflammatory drugs,traditional disease-modifying antirheumatic drugs and biological therapies[J]. Ther Adv Chronic Dis,2015,6(6):328-338.
[3] DONALDSON G C,WEDZICHA J A. The causes and consequences of seasonal variation in COPD exacerbations[J]. Int J Chron Obstruct Pulmon Dis,2014,9:1101-1110.
[4]中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2013年修订版)[S].中华结核和呼吸杂志,2013,36(4):255-264.
[5] SETHI S. Infection as a comorbidity of COPD[J]. Eur Respir J,2010,35(6):1209-1215.
[6] MALLIA P,FOOTITT J,SOTERO R,et al. Rhinovirus infection induces degradation of antimicrobial peptides and secondary bacterial infection in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2012,186(11):1117-1124.
[7] MOLYNEAUX P L,MALLIA P,COX M J,et al. Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med,2013,188(10):1224-1231.
[8] WILKINSON T M,HURST J R,PERERA W R,et al. Effect of interactions between lower airway bacterial and rhinoviral infection in exacerbations of COPD[J]. Chest,2006,129(2):317-324.
[9] BAFADHEL M,HALDAR K,BARKER B,et al. Airway bacteria measured by quantitative polymerase chain reaction and culture in patients with stable COPD:Relationship with neutrophilic airway inflammation,exacerbation frequency,and lung function[J]. Int J Chron Obstruct Pulmon Dis,2015,10:1075-1083.
[10] BARKER B L,HALDAR K,PATEL H,et al. Association between pathogens detected using quantitative polymerase chain reaction with airway inflammation in COPD at stable state and exacerbations[J]. Chest,2015,147(1):46-55.
[11] ZWAANS W A,MALLIA P,VAN WINDEN M E,et al. The relevance of respiratory viral infections in the exacerbations of chronic obstructive pulmonary disease--a systematic review[J]. J Clin Virol,2014,61(2):181-188.
[12] GEORGE S N,GARCHA D S,MACKAY A J,et al. Human rhinovirus infection during naturally occurring COPD exacerbations[J].Eur Respir J,2014,44(1):87-96.
[13] CLARK T W,MEDINA M J,BATHAM S,et al. C-reactive protein level and microbial aetiology in patients hospitalised with acute exacerbation of COPD[J]. Eur Respir J,2014,45(1):76-86.
[14] DAI M Y,QIAO J P,XU Y H,et al. Respiratory infectious phenotypes in acute exacerbation of COPD:An aid to length of stay and COPD Assessment Test[J]. Int J Chron Obstruct Pulmon Dis,2015,10:2257-2263.
[15] OHRUI T,YAMAYA M,SEKIZAWA K,et al. Effects of rhinovirus infection on hydrogen peroxide-induced alterations of barrier function in the cultured human tracheal epithelium[J]. Am J Respir Crit Care Med,1998,158(1):241-248.
[16] OLIVER B G,LIM S,WARK P,et al. Rhinovirus exposure impairs immune responses to bacterial products in human alveolar macrophages[J]. Thorax,2008,63(6):519-525.
[17] BELLINGHAUSEN C,GULRAIZ F,HEINZMANN A C,et al. Exposure to common respiratory bacteria alters the airway epithelial response to subsequent viral infection[J]. Respir Res,2016,17(1):68.
[18] HEINRICH A,HAARMANN H,ZAHRADNIK S,et al. Moraxella catarrhalis decreases antiviral innate immune responses by downregulation of TLR3 via inhibition of p53 in human bronchial epithelial cells[J]. FASEB J,2016,30(6):2426-2434.
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