[Influenza immunization, clinical results and serological tests (author's transl)]. Evaluation of cold-adapted, reassortant influenza B virus vaccines in elderly and chronically ill adults. From the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, the Center for Disease Control, and the Bureau of Biologics of the Food and Drug Administration. Summary of clinical trials of influenza vaccines--II. In elderly persons live attenuated influenza A virus vaccines do not offer an advantage over inactivated virus vaccine in inducing serum or secretory antibodies or local immunologic memory. Frequency of adverse reactions after influenza vaccination. Summary of clinical trials of inactivated influenza vaccine - 1978. Trivalent attenuated cold-adapted influenza virus vaccine: reduced viral shedding and serum antibody responses in susceptible adults. Immune response to vaccine against influenza in smokers, non-smokers and, in individuals holding respiratory complications. Safety of and serum antibody response to cold-recombinant influenza A and inactivated trivalent influenza virus vaccines in older adults with chronic diseases. Induction of mucosal antibodies by live attenuated and inactivated influenza virus vaccines in the chronically ill elderly. Trials of live attenuated influenza virus vaccine in patients with chronic obstructive airways disease. (MRC Advisory Group on Pulmonary Function Tests in relation to live influenza vaccines). Evaluation of live, cold-adapted influenza A and B virus vaccines in elderly and high-risk subjects. Benefits of influenza vaccination for low-, intermediate-, and high-risk senior citizens. Relation of chronic disease and immune response to influenza vaccine in the elderly. Clinical efficacy of a vaccine-immunostimulant combination in the prevention of influenza in patients with chronic obstructive pulmonary disease and chronic asthma. The effectiveness of vaccination against influenza in healthy, working adults. Live attenuated influenza virus vaccines in patients with chronic broncho-pulmonary diseases. Clinical and immunological evaluation. Overview of clinical trials of influenza vaccines, 1976. Protective efficacy of combined live intranasal and inactivated influenza A virus vaccines in the elderly. Influenza virus vaccination of patients with chronic lung disease. LONGER TERM EFFECTS OF LIVE INFLUENZA VACCINE IN PATIENTS WITH CHRONIC PULMONARY DISEASE Clinical trials of bivalent influenza A/New Jersey/76-A/Victoria/75 vaccines in the elderly. Increased anti-influenza A virus cytotoxic T cell activity following vaccination of the chronically ill elderly with live attenuated or inactivated influenza virus vaccine. The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial. Acute respiratory illness among immunized and nonimmunized patients with high-risk factors during a split season of influenza A and B. Adverse reactions to influenza vaccine in elderly people: randomised double blind placebo controlled trial.
207 patients of a geriatric department were immunized against influenza with either tween-ether-split-vaccine or subunit-vaccine in a double blind study . For 6 months the following data were daily registered : rest in bed , fever over 38,5 degrees C , rhinitis , laryngopharingitis , bronchitis , pneumonia , enteritis , medication with antibiotics or chemotherapeutics . In cases with fever over 38,5 degrees C blood tests were taken for serological examination . The immune response against influenza A was excellent in both groups , the titer was higher in the subunit group , only one patient showed influenza infection . The immune response against the type B Hongkong was not satisfactory in both groups . The clinical data showed a significant lower incidence of rhinitis , laryngopharingitis and bronchitis in the group immunized with the tween-ether-split-vaccine . This effect was more distinct within the first 3 months after the immunization than within the second 3 months The safety and immunogenicity of two recent cold-adapted reassortant influenza B viruses were evaluated in persons at high risk for influenza-related morbidity and mortality . Ambulatory adults > 65 years old or with chronic high-risk conditions were r and omly assigned to receive parenteral trivalent inactivated influenza vaccine containing either influenza B/Ann Arbor/86 or B/Yamagata/88 hemagglutinin antigens , cold-adapted reassortant influenza B/Ann Arbor/1/86 or B/Yamagata/16/88 viruses ( 10(7.2 ) TCID50 ) , or placebo in double-blind fashion . Cold-adapted vaccine viruses were well tolerated , with similar rates of respiratory symptoms in all groups . There were no changes in spirometry or oxygen saturation following vaccination . Immune responses to both types of vaccine were modest , with serum antibody responses occurring significantly more frequently and with higher magnitude in those receiving inactivated than in those receiving cold-adapted vaccine . Cold-adapted , reassortant influenza B vaccines are safe in the elderly and those with chronic illness but are not optimally immunogenic in this group These studies indicate that the high-risk and normal pediatric population s can be safely and effectively immunized with a two-dose regimen of the influenza A/New Jersey/76 virus vaccine . In addition , the studies have demonstrated important differences between split-product and whole-virus vaccines in the pediatric age group . Furthermore , reactogenicity from the whole-virus vaccine administered in the schedules employed was acceptable after the first dose and negligible after the second dose . More detailed examination of the data will undoubtedly yield additional information of importance to current and future use of inactivated influenza vaccines in children In a double-blind , r and omized trial , 102 healthy elderly subjects were inoculated with one of four preparations : ( i ) intranasal bivalent live attenuated influenza vaccine containing cold-adapted A/Kawasaki/86 ( H1N1 ) and cold-adapted A/Bethesda/85 ( H3N2 ) viruses ; ( ii ) parenteral trivalent inactivated subvirion vaccine containing A/Taiwan/86 ( H1N1 ) , A/Leningrad/86 ( H3N2 ) , and B/Ann Arbor/86 antigens ; ( iii ) both vaccines ; or ( iv ) placebo . To determine whether local or systemic immunization augmented mucosal immunologic memory , all volunteers were challenged intranasally 12 weeks later with the inactivated virus vaccine . We used a hemagglutination inhibition assay to measure antibodies in sera and a kinetic enzyme-linked immunosorbent assay to measure immunoglobulin G ( IgG ) and IgA antibodies in sera and nasal washes , respectively . In comparison with the live virus vaccine , the inactivated virus vaccine elicited higher and more frequent rises of serum antibodies , while nasal wash antibody responses were similar . The vaccine combination induced serum and local antibodies slightly more often than the inactivated vaccine alone did . Coadministration of live influenza A virus vaccine did not alter the serum antibody response to the influenza B virus component of the inactivated vaccine . The anamnestic nasal antibody response elicited by intranasal inactivated virus challenge did not differ in the live , inactivated , or combined vaccine groups from that observed in the placebo group not previously immunized . These results suggest that in elderly persons cold-adapted influenza A virus vaccines offer little advantage over inactivated virus vaccines in terms of inducing serum or secretory antibody or local immunological memory . Studies are needed to determine whether both vaccines in combination are more efficacious than inactivated vaccine alone in people in this age group PURPOSE Although concern about side effects constitutes a major deterrent to patient compliance with recommendations for influenza vaccination , there is a paucity of data about the frequency of adverse reactions to newer trivalent vaccines . Our aim was to determine the frequency of adverse reactions to influenza vaccine in older , chronically ill persons , many of whom are at high risk for influenza-related morbidity . PATIENTS AND METHODS We conducted a telephone survey of 40 % of the patients who were vaccinated at a walk-in flu shot clinic . The subjects were r and omly assigned to two groups . To determine postvaccine symptom rates , Group I was interviewed seven days after vaccination . Group II was interviewed 21 days after vaccination in order to control for baseline symptom rates . Both groups were queried about  fever , disability , and flu-like illness  in the week preceding the interview . RESULTS Of 816 patients selected , 650 ( 79.6 % ) completed the interview . The mean age of the subjects was 63 , and more than two thirds were at risk for influenza-related morbidity . The frequencies of self-reported fever ( 5.3 % versus 5.1 % , p = 0.91 ) and disability ( 10.4 % versus 9.3 % , p = 0.65 ) were similar in the two groups . However , a significantly higher proportion of Group I subjects reported a flu-like illness compared to the Group II subjects ( 14.2 % versus 8.7 % , p = 0.03 ) . Although Group I subjects were more likely to report flu-like illness within two days of vaccination compared to a similar time interval for Group II subjects , there was no corresponding clustering of disability after vaccination . CONCLUSION We conclude that the overall frequency of symptoms in both groups was low ; however , the absolute risk of a flu-like illness was 5.5 % higher during the first week following influenza vaccination when compared with the third week after the injection . These symptoms did not result in a decreased ability to perform usual daily activities This report summarizes the clinical trials of the A/USSR/77 ( H1N1 ) influenza vaccines  performed in 1978 . A total of 2,091 subjects participated in these trials . The results of these clinical trials indicated that two doses of H1N1 viral antigen were necessary to produce serum titers of hemagglutinin-inhibiting ( HAI ) antibody of greater than 1:40 in 80 % or more of the test subjects younger than 25 years of age , who were unlikely to have experienced natural infection during the earlier period of prevalence of H1N1 virus ( 1947 - 1957 ) . Only one dose of the A/Texas/77 ( H3N2 ) or B/Hong Kong/72 antigen was necessary to stimulate equivalent titers of HAI antibody in serum . Thus , previous natural exposure to H1N1 viruses primed individuals 26 years of age or older to respond to H1N1 antigens . No major differences in antigenicity were noted between whole-virus and split-virus vaccines . No differences in reaction indexes measuring systemic reactions were noted when vaccine types were compared . Only one vaccine was associated with a reaction index appreciably higher than that of placebo . The relatively uniform antibody responses observed were attributed to the newer methods of vaccine st and ardization introduced after the clinical trials in 1976 . No cases of vaccine-related neurological problems , including Guillain-Barré syndrome , were found during these trials . Vaccines containing 7 - 21 micrograms of each viral antigen were antigenic and were well tolerated Trivalent cold-adapted recombinant ( CR ) influenza virus vaccines containing types A ( H1N1 and H3N2 ) and B viruses were evaluated in two double-blind , placebo-controlled trials . Susceptible adults were r and omly assigned to receive the following vaccines by intranasal drops 1 month apart : two doses of trivalent vaccine , bivalent CR influenza A ( Bi A ) vaccine followed by monovalent B ( Mono B ) vaccine or vice versa , or two doses of placebo . All vaccines were well tolerated . Shedding of each of the three vaccine viruses was reduced after the first dose of trivalent vaccine compared with primary vaccination with Bi A or Mono B. Shedding was also reduced after second vaccinations , whether homologous ( trivalent-trivalent ) or heterologous ( Bi A/Mono B or Mono B/Bi A ) . Reduced viral shedding was associated with reduced serum antibody responses . Thus , both simultaneous and sequential inoculations of susceptible adults with CR influenza vaccine viruses result in reduced viral shedding and serum antibody responses Levels of antibody against influenza virus were evaluated in serum pairing sample s from individuals immunized against influenza  by Hemagglutination Inhibition and Single Radial Hemolysis tests . For this purpose , groups of smokers , non-smokers and , of those holding respiratory complications , were formed . Results of serologic titrations pointed out to an increase in the level of antibodies for the smoker and non-smoker groups , with significant degrees of difference up to P < 0.001 difference between both averages after immunization . However , in the group of respiratory complications no significant differences ( P > 0.05 ) were found out between the averages antibody levels for the subtype A ( H1N1 ) and the Type B ( vaccine components ) ; an increase only at the level of antibodies was registered , with differences among the averages of the antibody levels , for the subtype A ( H3N2 ) ( vaccine component ) at degrees of P < 0.01 and P < 0.001 on the titration of the SRH and HI tests , respectively . It can demonstrate that immunization against influenza presents a good protection for the smoker and non-smoker groups ; however , in the group of respiratory complications it only occurred with the subtype A ( H3N2 ) , indicating that this subtype presents good antigenicity since it has induced better formation of antibodies , even in defective organisms Forty older adults with chronic diseases were vaccinated intranasally with either influenza A/California/10/78 ( H1N1 ) ( CR37 ) or influenza A/Washington/897/80 ( H3N2 ) ( CR48 ) virus . No clinical ly significant morbidity or decrement in pulmonary function occurred postvaccination . Two ( 15 % ) recipients of CR37 virus and twelve ( 44 % ) recipients of CR48 virus became infected with vaccine virus , as indicated by a fourfold rise in serum hemagglutination inhibition antibody titer ; a fourfold rise in serum immunoglobulin G ( IgG ) or IgA antibody titer , indicated by enzyme-linked immunosorbent assay ; isolation of vaccine virus from nasal washings ; or all of these . Within 1 year after cold-recombinant vaccine virus vaccination , 18 vaccines received inactivated trivalent influenza virus vaccine parenterally . Of the vaccinees , 13 ( 72 % ) developed a fourfold rise in serum antibody titer to H1N1 antigen and 16 ( 89 % ) developed a fourfold rise in serum antibody titer to H3N2 antigen . We conclude that administration of these cold-recombinant vaccine viruses to older adults with chronic diseases was safe , but that serum antibody response rates were lower than those achieved with subsequently administered inactivated influenza virus vaccine given parenterally . However , the higher seroconversion rates attained by using the inactivated trivalent influenza virus vaccine do not necessarily mean that it is more efficacious in preventing infection or severe illness or both due to natural wild-type influenza A virus Induction of local antibody responses to influenza A virus hemagglutinin by coadministration of two vaccines was investigated . Fifty elderly nursing home residents received inactivated trivalent influenza virus vaccine intramuscularly and simultaneously were r and omized to receive either bivalent live attenuated influenza A virus vaccine or saline placebo intranasally in a blinded fashion . More significant increases in anti-H1 and -H3 IgA antibodies were detectable in nasal wash specimens of subjects who received live attenuated virus vaccine than in those who received intranasal placebo . The increased anti-hemagglutinin IgA antibody response was of longer duration in recipients of live attenuated vaccine . The change in antibody titers after vaccination was positively correlated with total blood lymphocyte counts measured before vaccination in both vaccinee groups ( P < .05 ) . There was a possible advantage of administering live attenuated with inactivated virus vaccines because of enhanced local antibody responses Three controlled trials of attenuated live influenza vaccines in patients with chronic bronchitis with airways obstruction are described . A recombinant virus with parentage from PR8/34 ( H1N1 ) and A/Alaska/77 ( H3N2 ) was present in the vaccine ( RIT 4199 ) used in the first two trials . In the third trial a cold-adapted recombinant virus vaccine ( A/Washington/80 , H3N2 ) was used . No adverse effects were noted in the first two trials in which half of the patients responded serologically to the vaccine . In the third trial increases in upper respiratory symptoms occurred in the first week after vaccine was inoculated . One patient , who did not respond serologically to the vaccine , developed a temporary sharp decline in FEV1.0 and FVC . We have no explanation other than the preinoculation HI serum antibodies for the low rate of serological response ( 9 of 29 ) in the vaccinated patients in the third trial We have evaluated the use of live cold-adapted influenza A and B virus vaccines in the elderly .  Cold-adapted influenza A and B virus vaccines are safe and modestly immunogenic in individuals over 65 years of age . However , our studies and those of other groups have shown that immune response to cold-adapted vaccines in this age group are modest . Administration of combined cold-adapted influenza A and inactivated influenza vaccine has result ed in slightly higher frequencies of local and systemic humoral immune responses than inactivated vaccine alone in some , but not all , studies . In a double-blind field trial conducted in nursing homes over a 3 year period , combined cold-adapted influenza A ( H3N2 ) and trivalent inactivated influenza vaccine result ed in a 60 % decrease ( 95 % CI , 18 - 82 % ) in the rate of laboratory documented influenza A compared with inactivated vaccine alone . Further studies of multivalent cold-adapted influenza vaccines used in combination with inactivated vaccine should be performed BACKGROUND Vaccination rates for healthy senior citizens are lower than those for senior citizens with underlying medical conditions such as chronic heart or lung disease . Uncertainty about the benefits of influenza vaccination for healthy senior citizens may contribute to lower rates of utilization in this group . OBJECTIVE To clarify the benefits of influenza vaccination among low-risk senior citizens while concurrently assessing the benefits for intermediate- and high-risk senior citizens . METHODS All elderly members of a large health maintenance organization were included in each of 6 consecutive study cohorts . Subjects were grouped according to risk status : high risk ( having heart or lung disease ) , intermediate risk ( having diabetes , renal disease , stroke and /or dementia , or rheumatologic disease ) , and low risk . Outcomes were compared between vaccinated and unvaccinated subjects after controlling for baseline demographic and health characteristics . RESULTS There were more than 20000 subjects in each of the 6 cohorts who provided 147551 person-periods of observation . The pooled vaccination rate was 60 % . There were 101 619 person-periods of observation for low-risk subjects , 15 482 for intermediate-risk , and 30 450 for high-risk subjects . Vaccination over the 6 seasons was associated with an overall reduction of 39 % for pneumonia hospitalizations ( P<.001 ) , a 32 % decrease in hospitalizations for all respiratory conditions ( P<.001 ) , and a 27 % decrease in hospitalizations for congestive heart failure ( P<.001 ) . Immunization was also associated with a 50 % reduction in all-cause mortality ( P<.001 ) . Within the risk subgroups , vaccine effectiveness was 29 % , 32 % , and 49 % for high- , intermediate- , and low-risk senior citizens for reducing hospitalizations for pneumonia and influenza ( for high and low risk , P < or = .002 ; for intermediate risk , P = .11 ) . Effectiveness was 19 % , 39 % , and 33 % ( for each , P < or = .008 ) , respectively , for reducing hospitalizations for all respiratory conditions and 49 % , 64 % , and 55 % for reducing deaths from all causes ( for each , P<.001 ) . Vaccination was also associated with direct medical care cost savings of $ 73 per individual vaccinated for all subjects combined ( P = .002 ) . Estimates of cost savings within each risk group suggest that vaccination would be cost saving for each subgroup ( range of cost savings of $ 171 per individual vaccinated for high risk to $ 7 for low risk ) , although within the subgroups these findings did not reach statistical significance ( for each , P > or = .05 ) . CONCLUSIONS This study confirms that healthy senior citizens as well as senior citizens with underlying medical conditions are at risk for the serious complications of influenza and benefit from vaccination . All individuals 65 years or older should be immunized with this vaccine The ability of elderly patients to mount an adequate immune response to influenza vaccine has been debated . We studied the serum haemagglutination inhibition ( HI ) antibody response in elderly persons to determine whether different degrees of chronic illness were a critical factor in immune response . In autumn 1986 , trivalent split virus vaccine was used to immunize 87 healthy ambulatory elderly adults and 53 institutionalized elderly adults . The pre-vaccination health status of the healthy elderly group was significantly better as measured by the incidence of chronic disorders and drug use ( p less than 0.02 ) and by the Chronic Health Evaluation component of the APACHE severity of disease classification ( p less than 0.001 ) . No group differences were observed in serum HI antibody after immunization with the trivalent influenza vaccine . However , in 28 patients from each group who received the monovalent A/Taiwan/86(H1N1 ) vaccine 1 month after the trivalent vaccine , the percentage with a postvaccination HI titre greater than or equal to 40 was 57 % ( 16 of 28 ) for the healthy elderly vs 7 % ( 2 of 28 ) for the institutionalized elderly ( p = less than 0.001 ) . Geometric mean postvaccination HI titres were 31 and 13 , respectively ( p = 0.004 ) . We concluded that the institutionalized elderly in our study mounted an inferior immune response against the new heterotypic influenza A/Taiwan strain when compared to healthy elderly adults . The Chronic Health Evaluation score may be an effective predictor of a poor immune response to new influenza vaccine strains in the elderly . Increasing age per se and lack of a history of prior influenza immunization did not adversely affect the development of protective levels of serum antibody . ( ABSTRACT TRUNCATED AT 250 WORDS Influenza is a leading cause of morbidity and mortality in patients with chronic respiratory diseases . This study compares two influenza prevention schemes in patients with chronic obstructive pulmonary disease and chronic asthma . We enrolled 66 patients , distributed as follows : Group A : 32 subjects treated with influenza vaccine ; Group B : 34 patients treated with influenza vaccine and bacterial immunostimulant .  The rate of influenza episodes was recorded . Hemoagglutination inhibiting antibody titers for vaccine strains H1N1 , H3N2 , and B were determined at time 0 ( prior to vaccination ) , and on days 30 and 90 following vaccination . We observed a lower rate of influenza episodes in Group B patients ( 8.82 % ) compared to Group A ( 31.25 % ) ( p < 0.05 ) . At day 90 Group B patients presented higher geometric mean antibody titers for strains H1N1 ( p = 0.07 ) and H3N2 ( p = 0.08 ) . Bacterial immunostimulants appear as possible adjuvants in the prevention of influenza episodes , and may prolong antibody response to influenza vaccine strains BACKGROUND Although influenza causes substantial morbidity and mortality in all age groups , current recommendations emphasize annual immunization for people at high risk for complications of influenza . We conducted a double-blind , placebo-controlled trial of vaccination against influenza in healthy , working adults . METHODS In the fall of 1994 , we recruited working adults from 18 to 64 years of age from in and around the Minneapolis-St . Paul area and r and omly assigned them to receive either influenza vaccine or placebo injections . The primary study outcomes included upper respiratory illnesses , absenteeism from work because of upper respiratory illnesses , and visits to physicians ' offices for upper respiratory illnesses . The economic benefits of vaccination were analyzed by estimating the direct and indirect costs associated with immunization and with upper respiratory illnesses . RESULTS We enrolled a total of 849 subjects . Baseline characteristics were similar in the two groups . During the follow-up period , consisting of the 1994 - 1995 influenza season ( December 1 , 1994 , through March 31 , 1995 ) , those who received the vaccine reported 25 percent fewer episodes of upper respiratory illness than those who received the placebo ( 105 vs. 140 episodes per 100 subjects , P < 0.001 ) , 43 percent fewer days of sick leave from work due to upper respiratory illness ( 70 vs. 122 days per 100 subjects , P = 0.001 ) , and 44 percent fewer visits to physicians ' offices for upper respiratory illnesses ( 31 vs. 55 visits per 100 subjects , P = 0.004 ) . The cost savings were estimated to be $ 46.85 per person vaccinated . CONCLUSIONS Vaccination against influenza has substantial health-related and economic benefits for healthy , working adults The safety and potency of two live attenuated influenza A virus vaccines , administered intranasally , were tested in out patients suffering from chronic obstructive lung disease , during two successive trials performed between 1972 and 1974 . The vaccine strains were representative of the prevalent influenza A virus types ; the Ann strain was derived from a classical H3N2 ( A/Hong-Kong/878/69 ) isolated and the Alice strain from a recent H3N2 drift ( A/Engl and /42/72 ) . The serum and nasal antibody responses were studied in a total of 40 vaccinees . When a sufficient virus dose was administered , the hemagglutination-inhibition ( HI ) seroconversion rate was , respectively , 86 and 73 % for each vaccine trial in patients with low ( less than or equal to 32 ) prevaccination antibody titers . A booster effect was also observed in some subjects with higher prevaccination titers . In the two trials , clear-cut rises in local antibody activity , as tested in nasal washings ' sample s were found in , respectively , 92 and 75 % of the patients devoid of initial titer before vaccination and in 40 and 37 % , respectively , of the subjects having low prevaccination titers . Clinical symptoms were observed in 29 % of the cases ; they were , however , mild and transient and their occurrence was not necessarily related to the vaccination . Two administrations of intranasal attenuated virus appear therefore to be safe and to lead to a satisfactory antibody response in this " high risk " group of patients The National Influenza Immunization Program included a Presidential directive to provide A/  New Jersey/76 vaccine for all citizens and to immunize as many persons as possible . Before a vaccine could be offered on such a scale , it was necessary to obtain clinical data on the immunogenicity and reactogenicity of this vaccine before final recommendations could be made regarding dosage and formulation . This task was assigned to the National Institute of Allergy and Infectious Diseases ( NIAID ) of the National Institutes of Health , Bethesda , Md. The OBJECTIVE To evaluate the efficacy of adding intranasal live attenuated cold-adapted influenza A vaccine to inactivated influenza vaccine to prevent influenza A in elderly residents of long-term-care institutions . DESIGN R and omized , double-blind , placebo-controlled study conducted over 3 years . SETTING Three large nursing homes . PARTICIPANTS A total of 523 residents of nursing homes ( mean age , 84.2 years ) . INTERVENTIONS All participants received trivalent inactivated influenza vaccine parenterally and were r and omly assigned to receive either live attenuated influenza A ( H3N2 ) virus vaccine or placebo intranasally . MEASUREMENTS Laboratory-documented influenza A was defined as a respiratory illness plus isolation of influenza A virus from nasal secretions , significant serologic response , or both . Participants were considered to have been exposed to influenza A if they resided in an institution in which cases of influenza A were documented . Outbreak-associated illnesses were defined as those occurring between the first and last isolation of influenza virus from within the institution , + /- 3 days . RESULTS Participants who received intranasal vaccine and were subsequently exposed to influenza A had significantly lower rates of laboratory-documented influenza A ( 9 of 162 vaccine recipients compared with 24 of 169 placebo recipients ; vaccine protective efficacy , 60.6 % ; 95 % CI , 18 % to 82 % ) , outbreak-associated respiratory illnesses ( 13 of 162 vaccine recipients compared with 34 of 169 placebo recipients ; vaccine protective efficacy , 56.8 % ; CI 23 % to 76 % ) , and outbreak-associated influenza-like illnesses ( 6 of 162 vaccine recipients compared with 18 of 169 placebo recipients ; vaccine protective efficacy , 65.0 % ; CI 17 % to 86 % ) . CONCLUSIONS Intranasal immunization with live attenuated influenza A virus vaccine provided additional protection against influenza A when added to parenteral trivalent inactivated influenza vaccine among elderly nursing home residents STUDY OBJECTIVES To evaluate the safety of , and mucosal and systemic immune responses induced by two influenza virus vaccine regimens in subjects with COPD . DESIGN Single-center , blinded , r and omized , prospect i ve clinical trial evaluating two vaccine regimens . SETTING Outpatient clinics of St. Louis Department of Veterans Affairs Medical Center . PARTICIPANTS Volunteers ( age range , 42 to 88 years ) had preexisting COPD with severe obstruction to airflow on average , were male , and were not receiving immunosuppressive medication . INTERVENTIONS Twenty-nine volunteers were r and omly assigned to receive either bivalent live attenuated influenza A virus vaccine ( CAV ) or saline solution placebo intranasally . All subjects also received an i.m . injection of trivalent inactivated influenza virus vaccine ( TVV ) simultaneously . MEASUREMENTS AND RESULTS Clinical status and pulmonary function measured by spirometry did not change significantly after vaccination . Using hemagglutinins ( H1 and H3 HA ) which more closely resembled those in CAV , mean levels of anti-HA immunoglobulin A ( IgA ) antibodies in nasal washings increased significantly after vaccination with CAV and TVV compared to prevaccination , but they did not increase significantly after TVV and intranasal placebo .  Mean levels of influenza A virus-stimulated interleukin-2 and -4 produced by peripheral blood mononuclear cells in vitro increased significantly after administration of the combination vaccine regimen and to a lesser extent after TVV and intranasal placebo compared to respective prevaccination levels . The timing of the cytokine response appeared different following CAV and TVV compared to TVV and intranasal placebo . CONCLUSIONS Intranasally administered CAV was safe when given with i.m . administered TVV and there may be an immunologic advantage to administration of the combination vaccine regimen compared to TVV with intranasal placebo WRL 105 strain live influenza vaccine or placebo was given to patients with chronic bronchitis in a double-blind study . The twenty-one vaccinated and twenty-three placebo-treated patients made daily self- assessment s of the severity of symptoms of cough , breathlessness , tightness , wheeze , and sputum production in the following 20 weeks . Symptom scores in the first 2 weeks after vaccination or treatment with placebo were used to calculate a baseline range for each patient . Comparison of symptoms in the two groups in the baseline period showed that symptoms were more often reported by vaccinated than by placebo-treated patients but the differences were not statistically significant . One patient who responded serologically to vaccination had a moderately severe influenzal illness starting on the day after vaccination . Comparison of symptom scores during the 18-week surveillance period with baseline values showed that symptoms of breathlessness , tightness , wheeze and cough were significantly more common in vaccinated than in placebo-treated patients and that antibiotic usage was more common in the vaccinated group This placebo-controlled evaluation in elderly persons of inactivated influenza virus vaccines containing 200 or 400 chicke cell-agglutinating units of both A/New Jersey/76 and A/Victoria/75 antigens  revealed mild systemic reactions in 7.8 % and moderate reactions in 4.9 % of vaccinees . These reactions were more common after administration of whole-virus than subvirion vaccines , more frequent in females than males , and more frequent in persons with low initial titers of antibody to A/New Jersey antigen . Local inflammation occurred in 18.7 % of vaccinees ( predominantly females ) and frequently was seen with systemic reactions , but did not correlate with antibody response . Titers of antibody to A/New Jersey antigen were initially high and 99 % of vaccinees had titers of greater than 1:20 after vaccination . Titers of antibody to A/Victoria antigen were initially low , and 56 % of vaccinees had titers of greater than 1:20 after vaccination . Fourfold or greater increases in titer occurred in about 50 % of vaccinees for each virus , most often concomitantly . Antibody responses to subvirion and whole-virus vaccines were similar , and increased responses with higher doses coincided with increased reactogenicity . Later revaccinations because of low titers of A/Victoria antibody produced negligible antibody responses The possible enhancement of anti-influenza A virus memory cytotoxic T cell ( CTL ) responses to inactivated influenza virus vaccine by coadministration of intranasal live attenuated influenza A virus vaccine was investigated . Fifty elderly nursing home residents received inactivated trivalent influenza virus vaccine intramuscularly and simultaneously were r and omly assigned to receive either bivalent live attenuated influenza A virus vaccine or saline placebo intranasally in a blinded fashion . A larger proportion of volunteers who received live attenuated virus vaccine than of those who received placebo experienced a postvaccination rise in anti-influenza A virus CTL activity ( 15 of 23 vs. 8 of 24 ; P < .05 ) . Anti-influenza A virus cytotoxicity was primarily mediated by CD8 + T cells and was influenza A virus-specific and HLA-restricted . There was a possible advantage of administering live attenuated with inactivated virus vaccine because of enhanced memory anti-influenza A virus CTL activity OBJECTIVE To determine the efficacy of influenza vaccination  in elderly people . DESIGN R and omized double-blind placebo-controlled trial . SETTING Fifteen family practice s in the Netherl and s during influenza season 1991 - 1992 . PARTICIPANTS A total of 1838 subjects aged 60 years or older , not known as belonging to those high-risk groups in which vaccination was previously given . INTERVENTION Purified split-virion vaccine containing A/Singapore/6/86(H1N1 ) , A/Beijing/353/89(H3N2 ) , B/Beijing/1/87 , and B/Panama/45/90 ( n = 927 ) or intramuscular placebo containing physiological saline solution ( n = 911 ) . MAIN OUTCOME MEASURES Patients presenting with influenzalike illness  up to 5 months after vaccination ; self-reported influenza in postal question naires 10 weeks and 5 months after vaccination ; serological influenza ( fourfold increase of antibody titer between 3 weeks and 5 months after vaccination ) . RESULTS The incidence of serological influenza was 4 % in the vaccine group and 9 % in the placebo group ( relative risk [ RR ] , 0.50 ; 95 % confidence interval [ CI ] , 0.35 to 0.61 ) . The incidences of clinical influenza were 2 % and 3 % , respectively ( RR , 0.53 ; 95 % CI , 0.39 to 0.73 ) . The effect was strongest for the combination of serological and clinical influenza ( RR , 0.42 ; 95 % CI , 0.23 to 0.74 ) . The effect was less pronounced for self-reported influenza . CONCLUSION In the elderly , influenza vaccination may halve the incidence of serological and clinical influenza ( in periods of antigenic drift ) A prospect i ve survey of acute respiratory illness ( RI ) was made among 329 vaccinated and unvaccinated ambulatory patients with high-risk factors for influenza . Surveillance for virus during the influenza season revealed the predominance of influenza A and B in sequential periods . During the influenza A period , febrile RI was greatest among patients with chronic pulmonary disease ; among 66 patients , vaccination significantly reduced RI .  Age greater than 65 y ( 199 patients ) and heart ( 90 patients ) and metabolic diseases ( 151 patients ) did not increase the relative frequency of febrile RI , and vaccine administration caused no apparent reduction in frequency of RI . During the influenza B period , no differences in RI were observed between the groups , and the frequency of RI was unrelated to vaccination . Variability in virus and vaccine specificities may have been important . Except for one subset of specific virus and host conditions , no overall reduction in influenza-like or total RI was observed from vaccinating ambulatory , high-risk patients OBJECTIVE --To assess the frequency and type of side effects after  influenza vaccination in elderly people . DESIGN --R and omised double blind placebo controlled study . SETTING --15 general practice s in the southern Netherl and s. SUBJECTS--1806 patients aged 60 or older , of whom 904 received influenza vaccine and 902 placebo .  MAIN OUTCOME MEASURES --Adverse reactions reported on postal question naire completed four weeks after vaccination . RESULTS --210 ( 23 % ) patients given vaccine reported one or more adverse reactions compared with 127 ( 14 % ) given placebo . The frequency of local adverse reactions were 17.5 % in the vaccine group and 7.3 % in the placebo group ( p < 0.001 ) . There was no difference in systemic adverse reactions ( 11 % v 9.4 % ; p = 0.34 ) . In general , men reported fewer side effects than women . CONCLUSION --Only local side effects were more common in vaccinated patients and all side effects were mild
BACKGROUND Influenza vaccinations are currently recommended in the care of people with COPD , but these recommendations are based largely on evidence from observational studies with very few r and omised controlled trials ( RCTs ) reported .
Influenza infection causes excess morbidity and mortality in COPD patients but there is also the potential for influenza vaccination to cause adverse effects or not to be cost effective .
OBJECTIVES To evaluate the evidence from RCTs for a treatment effect of  influenza vaccination in COPD subjects .
Outcomes of interest were exacerbation rates , hospitalisations , mortality , lung function and adverse effects .