The Study Of Distribution Of Atypical Pathogens In Pathogens Of Patients With Acute Exacerbation Of Chronic Obstructive Pulmonary Disease And Related Investigations

Objective:This is a multi-center,prospective study of serological,PCR,and urinary antigen testing in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease,and access to epidemiological data on atypical pathogens in AECOPD patients.The clinical data of the patients were analyzed to grasp the distribution and clinical characteristics of atypical pathogens in AECOPD patients,and the empirical judgment indicators of atypical pathogen infections were proposed.Methods:Clinical specimens(serum,urine,sputum)and data of AECOPD patients were collected from 10 medical institutions in 8 cities in China from March 2016 to November2018.The specimens of the above patients are uniformly transported to the First Hospital of China Medical University for centralized testing.Among them,the Mycoplasma pneumoniae was determined by serological methods(passive agglutination,enzyme-linked immunosorbent assay)and nucleic acid detection;Chlamydia pneumoniae was determined by serology(micro immunofluorescence)and nucleic acid detection;Legionella pneumophila was determined by serology method(indirect immunofluorescence),urine antigen,and nucleic acid detection.Statistical methods were used to compare and analyze the clinical features of the above-mentioned atypical pathogens with positive and negative test results,thus to find clinical features with significant differences and the factors which increase the risk of atypical pathogen infection.Results:Part One:Distribution of atypical pathogens in patients with acute exacerbation of chronic obstructive pulmonary diseaseFor the detection of Mycoplasma pneumoniae,a total of 396 specimens of patients with AECOPD from 10 centers were detected.The results showed that among the three detection methods of Mycoplasma pneumoniae,the positive rate of passive agglutination method was 17.17%(68/396,positive/total);the positive rate of Ig M antibody(ELISA)was only 3.28%(13/396)which is significantly lower than the passive agglutination method(p=0.000);PCR positive rate was only 1.87%(4/214)which is significantly lower than the passive agglutination method(p=0.000).When the three methods were combined,the positive rate of detection was 18.18%(72/396).The positive rate of mycoplasma detection in the Third Hospital of Beijing University and the Central Hospital of Shenyang Medical College were 34%(17/50),which was significantly higher than the overall rate(p=0.008).The positive rate of Zhongshan Hospital affiliated to Fudan University was 2%(1/50),which was significantly lower than the overall positive rate(p=0.004).This study further analyzed the specimens obtained from patients with double serum.The results showed that the positive rate of Mycoplasma pneumoniae detection was 27.44%,which was significantly higher than the overall positive rate(p=0.014).This data may better illustrate the detection rate of mycoplasma in patients with AECOPD.In addition,the monthly and seasonal distribution of Mycoplasma pneumonia related AECOPD around the country and various regions were analyzed.The positive rate in November(41.18%)in Northeast China and December(66.67%)in North China was significantly higher than the overall positive rate(p=0.018,p=0.031).The change of positive rate in each month was further analyzed.The results showed that in November and July in Northeast China and December and May in North China the positive rate increased sharply.Chlamydia pneumoniae was detected by micro-immunofluorescence and real-time PCR in 145 patients from 6 centers.Chlamydia pneumoniae was not detected by the PCR method.The results of micro-immunofluorescence showed that the overall positive rate of Chlamydia pneumoniae was 29.66%(43/145).The positive rate of the Third Hospital of Beijing University was 52.00%(13/25),which was statistically different from the overall positive rate(p=0.028).The positive rate of the First Hospital of China Medical University and Zhongshan Hospital affiliated to Fudan University were 4%(1/25)which is the lowest above all centers and were statistically different from the overall positive rate(p=0.019).The highest positive rate of chlamydial infection was 52.00%(13/25)in North China and 5%(1/20)in West China.The difference was statistically significant.In the monthly distribution,the positive rate in March in North China was significantly higher than the overall positive rate(P=0.006).Further analysis of the change of positive rate indicates that the positive rate in March in North China and November in Northeast China increased sharply.In the detection of Legionella pneumophila,a total of 145 AECOPD patients in 6centers were analyzed.No Legionella was detected in both PCR and urinary antigen.In the serological method,the positive rate of Legionella pneumophila was10.34.%(15/145).In this study,Legionella pneumophila type 1-14 was detected,and type 6 Legionella pneumophila was up to 60.00%(9/15),and type 1 serotype was only20.00%(3/15).Three and more serotypes were 40%(6/15)of positive patients.Among the 6 centers,the positive rate of the Third Hospital of Beijing University was 16%(4/25),and the positive rate of the First Hospital of China Medical University and Zhongshan Hospital affiliated to Fudan University was 4%(1/25).Among the four regions,the highest positive rate was in North China which was 16%(4/25),no statistical difference was observed among different regions.In the monthly and seasonal distribution,the positive rate of Legionella pneumophila began to increase sharply from March,and the positive rate in April and May was significantly higher than the overall positive rate;then there was a sudden drop in June.Thus indicates that AECOPD patients who were admitted to the hospital at the time above should alert to the infection of Legionella pneumophila.Part Two:Comparative analysis of clinical data of atypical pathogen infection in patients with acute exacerbation of chronic obstructive pulmonary diseaseIn the analysis of clinical characteristics,in the detection of Mycoplasma pneumoniae,55 clinical data were analyzed individually from a total of 377 patients,of which 18.30%(69 cases)were positive for mycoplasma.The results of statistical analysis showed that Pa CO₂of mycoplasma pneumoniae positive patients was 47.46±12.76 mm Hg,which was significantly lower than that of negative patients.In the laboratory examination,the BUN of patients with positive Mycoplasma pneumoniae test result was 6.12±2.24mmol/L,which was lower than that of the negative group(8.21±10.16 mmol/L,p=0.003)suggesting that AECOPD patients with low BUN were more susceptible to have Mycoplasma pneumoniae infection.The rate of mechanical ventilation(including invasive and non-invasive ventilation)in patients with positive Mycoplasma pneumoniae was 14.71%,which was significantly lower than that in negative patients(27.62%,p=0.027).No other indicators showed statistical differences.Logistic regression analysis showed that OR value of Pa CO₂was 0.963,95%CI was 0.934-0.993(P=0.0017),OR value of oxygenation index was 0.994,95%CI was 0.992-0.997(P=0.000).In the detection of Chlamydia pneumoniae,55 clinical data were analyzed individually from a total of 145 patients,of which 29.66%(43 cases)were positive for Chlamydia pneumoniae.Statistical analysis showed that in the past history,there was no statistical difference between the positive patients and the negative patients,but in the smokers,the results showed that the positive patients had a smoking volume of 62.33±40.11 pack-year which was significantly higher than the negative group(44.10±25.60 pack-year,P=0.036).In addition,the rate of concomitant disease or complications in the positive group was 80.95%,which was significantly higher than that in the negative group(57.43%,p=0.007).Among the proportion of acute exacerbations more than twice in the past 1 year,the proportion of patients in the positive group was 34.21%,which was significantly lower than that in the negative group(55.91%,p=0.024).Logistic regression analysis showed that the OR value of concomitant diseases or complications was 0.266,95%CI was 0.082-0.862(P=0.027),and the OR value of smoking volume was 1.021,95%CI was 1.005-1.036(P=0.009).In the detection of Legionella pneumophila,55 clinical data were analyzed individually from a total of 145 patients,of which 10.34%(15 cases)were positive for Legionella pneumophila.Statistical analysis only showed two indicators with statistically significant.In the pulmonary function test,the FEV₁/FVC of patients with positive Legionella test was 62.95±3.30,which was significantly higher than that of the negative group(50.80±14.54,p=0.000).In the blood gas analysis,we found that the HCO₃^-of the positive group was 26.33±5.63 mmol/L,which was significantly lower than the negative group(30.47±6.82 mmol/L,p=0.044).No statistical differences were found in other comparative clinical data.Logistic regression analysis showed no statistical difference.Conclusion:Part One:Distribution of atypical pathogens in patients with acute exacerbation of chronic obstructive pulmonary diseaseAtypical pathogens play an important role in the acute exacerbation of chronic obstructive pulmonary disease.The positive rate of Mycoplasma pneumoniae in AECOPD patients was 18.18%,the positive rate of Chlamydia pneumoniae was 29.66%,and the positive rate of Legionella pneumophila was 10.34%(the most common serotype was type 6).The positive rates of Mycoplasma pneumoniae and Chlamydia pneumoniae vary between cities and regions.There was no significant regional difference in the positive rates of Legionella pneumophila.In terms of time distribution,Mycoplasma pneumoniae showed a sharp increase of positive rate in the colder months(November in Northeast China and December in North China)and the hotter months(July in Northeast China and May in North China).Chlamydia pneumoniae showed a sharp increase of positive rate in the Northeast China in November and North China in March.The positive rate of Legionella pneumophila began to increase sharply in March,and continued to increase in April and May,but plummeted in June.We recommend that AECOPD patients in the above areas are alert to atypical pathogens when they are admitted to the hospital at the time above.In the detection of atypical pathogens,serological method is superior to PCR and urine antigen method.Part Two:Comparative analysis of clinical data of atypical pathogen infection in patients with acute exacerbation of chronic obstructive pulmonary diseasePatients with Mycoplasma pneumoniae infection showed lower Pa CO₂,lower BUN,lower proportion of mechanical ventilation(including invasive and non-invasive ventilation);and both the increase of Pa CO₂were protective factors for Mycoplasma pneumoniae infection.Patients with Chlamydia pneumoniae infection showed higher smoking index and the proportion of concomitant diseases or complications,lower proportion of greater than or equal to 2 times of acute exacerbations.The increase in smoking was a risk factor for Chlamydia pneumoniae infection and the concomitant disease or complications were protective factors for Chlamydia pneumoniae infection.Patients with Legionella pneumophila infection showed higher FEV₁/FVC values,less airflow restriction and lower HCO₃^-level.The two factors were not associated with the risk of Legionella pneumophila infection.