| BackgroudChronic obstructive pulmonary disease (COPD) is a chronic disease characterized by irreversible restriction of respiratory airflow and the main symptoms are chronic cough,sputum and dyspnea.COPD is the leading cause of chronic morbidity and mortality worldwide.The prevalence rate of COPD in people over 40 years old is 13.6% with a projected total number of 77.2 million in 2014-2015 in China,which is 65.9% higher than that in 2004,the disease burden was serious.Acute exacerbation of COPD(AECOPD) can further decrease the lung function of patients,thus speeding up the disease process,increasing the risk of death and increasing the financial burden of patients.Influenza and pneumococcus are the two most common pathogens of infectious AECOPD.Seasonal influenza vaccine(SIV) is effective in preventing influenza and related diseases caused by influenza virus,23-valent pneumococcal polysaccharide vaccine(PPSV23) is effective in preventing pneumococcal diseases.China has approved seasonal influenza vaccines and PPSV23 for adults.The World Health Orgnization(WHO),the Advisory Committee on Immunization Practice(ACIP)of Center for Disease Control and Prevention(CDC) in the United States all recommend seasonal influenza vaccination and PPSV23 vaccination for COPD patients.A review of the literature has found systemetic study on the effectiveness,immunogenicity and safety of SIV and PPSV23 in COPD patients was lack in China.ObjectiveWe aimed to assess the effectiveness,immunogenicity and safety of trivalent SIV(TIV)vaccination and PPSV23 vaccination in the same COPD patients cohort,providing evidence for the development of SIV and PPSV23 immunization strategy for COPD patients in China.Methods1.Study on effectiveness of TIV and PPSV23 vaccination in COPD patients.The study site was Tangshan,Hebei Province,and COPD patients were recruited by respiratory physicians from these hospitals to form a cohort.All COPD patients who agreed to participate in the study were followed up regularly by a clinician in the first year of the intervention cohort study,the incidence and cost of outcomes,including AECOPD,pneumonia and related hospitalizations were obtained;free vaccination was provided to all subjects at the end of a one-year follow-up period,and the subjects chose to receive the vaccine according to their wishes.After vaccination,all subjects were followed up for 1 year to collect the incidence and cost of outcomes,including AECOPD,pneumonia and related hospitalizations after vaccination according to the same follow-up pattern and frequency in the previous 1 year.The information obtained was used to calculate the incidence density and cost of AECOPD,pneumonia and related hospitalization before and after the intervention,and the protective effect of the vaccine was obtained by comparing incidence rates and costs before and after the intervention.The vaccination period in our study was October 29 to early November 2019.The period defination of before and after 1 year was 1 November 2018 to the vaccination date plus 14 days and vaccination date+15 days to 30 November 2020 for those vacinees.For those who were not vaccinated,the period was defined as November 1,2018 to November 15,2019 and November 16,2019 to November 30,2020.The defination of before and after period without COVID-19 was from December 1,2018 to January 31,2019 plus (vaccination date add 14 days minus Novemberl,2019) and vaccination date+14 days to 31 January 2020 for vacinees.For those who were not vaccinated,the pre-intervention period was December 1,2018 to January 31,2019 plus 15 days;the post-intervention period was November 16,2019 to January 31,2020.2.Study on immunogenicity of TIV and PPSV23 vaccination in COPD patients The immunogenicity study was conducted at three hospitals in Tangshan,Hebei Province,using an intervention cohort study design.The study was conducted by respiratory physicians from three hospitals who recruited COPD patients who met the inclusion criteria,basic demographic information,such as age,sex,basic severity,and whether or not other diseases were collected using a uniform questionnaire,and blood samples were collected before and after vaccination,influenza hemagglutination inhibition(HI) antibody and 23 serotypes of pneumococcal antibody were detected by the HI testing and Enzyme-linked immunosorbent assay(ELISA).The immunogenicity of TIV was evaluated by seropositive rate,seroprotective rate,seroconversion rate and geometric mean titer(GMT),and the immunogenicity of PPSV23 was evaluated by 2-fold increase rate and geometric mean concentration(GMC).3.Study on safety of TIV and PPSV23 vaccination in COPD patientsThe safety study was conducted in COPD patients receiving TIV and/or PPSV23 provided by our study.All patients needed to stay for 30 minutes after vaccination.The staff of the vaccination unit will follow up actively on the 7th and 28th day after vaccination to understand the occurrence of adverse events after vaccination.The severity of adverse events was judged by the unified standard,and the related information was recorded by the unified questionnaire.The safety of each vaccine was evaluated by analyzing the incidence of adverse events after vaccination.Results1.Study on effectiveness of TIV and PPSV23 vaccination in COPD patients1.1 The effectiveness of preventing any outcomes The incidence density before and after 1 year were 55.96/100 person-year and 17.43/100 person-year in TIV group,85.51/100 person-year and 37.68/100 person-year in PPSV23 group,67.91/100 person-year and 19.93/100 person-year in TIV plus PPSV23 group,19.10/100 person-year and 10.76/100 person-year in unvaccinated group.The effectivenesses in TIV group,PPSV23 group,TIV plus PPSV23 group and unvaccination group were 70%,54%,74%,and 45%.Before and after comparison without COVID-19:The density were 7.34/100 person-month and 1.10/100 person-monthin TIV group,8.70/100 person-month and 3.48/100 person-month in PPSV23 group,9.86/100 person-month and 1.89/100 person-month in TIV plus PPSV23 group,2.64/100 person-months and 1.25/100 person-months in the unvaccinated group.The vaccine effectivenesses were 86%,63%,83% in TIV group,PPSV23 group and TIV plus PPSV23 group.The risk was not significant difference in non-vaccinatted group.1.2 The effectiveness of preventing AECOPDBefore and after 1 year comparision:The incidence density were 53.21/100 person-year and 17.43/100 person-year in TIV group,85.51/100 person-year and 37.68/100 person-year in PPSV23 group,64.19/100 person-year and 18.58/100 person-year in TIV plus PPSV23 group,18.06/100 person-year and 10.76/100 person-year in unvaccinated group The effectiveness in TIV group,PPSV23 group,TIV plus PPSV23 group and unvaccination group after intervention were 70%,54%,72%and 42%.Before and after comparison without COVID-19:The density was 6.61/100 person-month and 1.10/100 person-month,8.70/100 person-month and 3.48/100 person-month in PPSV23 group,8.51/100 person-month and 1.76/100 person-month in TIV plus PPSV23 group,2.36/100 person-months and 1.25/100 person-months in the unvaccinated group.The effectiveness were 84%,63%,82% in TIV group,PPSV23 group and TIV plus PPSV23 group.The risk was not significant difference in nonvaccinated group.1.3 The effectiveness of preventing pneumoniaBefore and after 1 year comparision:The incidence density was 21.10/100 person-year and 8.26/100 person-year in TIV group,40.58/100 person-year and 21.74/100 person-year in PPSV23 group,30.41/100 person-year and 7.77/100 person-year in TIV plus PPSV23 group,9.03/100 person-year and 5.21/100 person-year in unvaccinated group.The effectiveness in TIV group,PPSV23 group,TIV plus PPSV23 group was 59%,53%,73%.The risk was not statistically decreased in un-vaccinated group.Before and after comparison without COVID-19:the density was 4.40/100 person-month and 1.10/100 person-month in TIV group,6.38/100 person-month and 1.74/100 person-month in PPSV23 group,3.92/100 person-month and 0.81/100 person-month in TIV plus PPSV23 group,0.83/100 person-months and 0.69/100 person-months in the unvaccinated group.The effectiveness were 77%,74%,83% in TIV group,PPSV23 group and TIV plus PPSV23 group.The risk was not significant decreased in nonvaccinated group.1.4 The effectiveness of preventing hospitalizationBefore and after 1 year comparision:The incidence density was 35.78/100 person-year and 17.43/100 person-year in TIV group,50.72/100 person-year and 31.88/100 person-year in PPSV23 group,46.62/100 person-year and 16.55/100 person-year in TIV plus PPSV23 group,14.58/100 person-year and 10.42/100 person-year in unvaccinated group.The effectiveness in TIV group,PPSV23 group,TIV plus PPSV23 group were 58%,46%,69%.The risk was not significant decreased in nonvaccination group.Before and after comparison without COVID-19:the density was 5.87/100 person-month and 0.73/100 person-month in TIV group,6.38/100 person-month and 2.32/100 person-month in PPSV23 group,7.30/100 person-month and 0.81/100 person-month in TIV plus PPSV23 group,1.94/100 person-months and 1.25/100 person-months in the unvaccinated group.The effectiveness were 88%,91% in TIV group and TIV plus PPSV23 group.The risk was not significant decreased in PPSV23 group and nonvaccinated group.1.5 Disease costsBefore and after 1 year comparision:the cost savings per person due to vaccination and non-vaccine interventions were 1340.88 yuan in TIV group,580.07 yuan in PPSV23 group,2125.26 yuan in TIV plus PPSV23 group and 256.42 yuan in unvaccinated group.Before and after comparison without COVID-19:the average cost savings per person were 1,314.92 yuan in TIV group,739.24 yuan in PPSV23 group,1450.80 yuan in TIV plus PPSV23 group and 125.37 yuan in unvaccinated group.2.Study on immunogenicity of TIV and PPSV23 vaccination in COPD patientsFive weeks after TIV vaccination,the sero-positive rates of H1N1,H3N2 and B were 100%.The sero-protective rates were 96.6%,93.2% and 98.9%,and the seroconversion rates were 81.8%,87.5% and 75.0% respectively.Seroprotection rates and seroconversion rates were not related to age,disease severity or comorbodities.The GMT (1:) of HI antibodies against H 1N 1,H3N2 and type B before and after vaccination were 18.8,12.2,31.8 and 267.0,190.3,201.1,respectively.The GMT of H1N1 antibody after vaccination was the highest.Four weeks after PPSV23 vaccination,the 2-fold rate of 23 serotypes ranged from 65.2%(type 3) to 94.4% (type 2).The GMCs before vaccination was 0.38 ug / ml (type 3) to 6.90 ug/ml (type 14),and those after vaccination was 1.03 ug/ml (type 3) to 30.36 ug/ml (type 14).There were significant differences in the 2-fold increase rate and GMCs before and after vaccination among different serotypes.The 2-fold increase rate and GMCs before and after vaccination were not related to age,severity of COPD or comorbidities for most serotypes.3.Study on safety of TIV and PPSV23 vaccination in COPD patientsThe reported incidence of adverse events in COPD patients after TIV or PPSV23 vaccination was 6.06% and 6.44%,respectively.There was no significant difference between the two vaccines.The main adverse events reported were local reactions such as pain,induration,redness and swelling at the inoculation site,and systemic reactions such as fever,allergic reaction and limb weakness.The most common local adverse reactions of the two vaccines were pain at the inoculation site,and the reported incidence rates were 3.50% and 6.19% respectively.The most common systemic adverse reaction was fever,with the incidence of 1.63% and 0.62% respectively.The severity of adverse events was mainly grade 1,and the most serious adverse event was grade 2.ConclusionTIV and PPSV23 vaccination can effectively reduce the risk of AECOPD,pneumonia and related hospitalization in COPD patients.The effect of preventing AECOPD was the best.It can be concluded that the effect of the TIV plus PPSV23 group is better than the other two vaccination groups,and the effect of TIV is better than PPSV23.Non-vaccine interventions since the COVID-19 epidemic have also been effective in reducing the risk of AECOPD.The immunogenicity and safety of TIV and PPSV23 were good in COPD patients.Based on the results of this study,it is recommended to use the immunization strategy of SIV and PPSV23 vaccine to prevent the occurrence of AECOPD,pneumonia and related hospitalizations to reduce the burden of COPD disease. |
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