Efficacy of pneumococcal vaccine in severe chronic obstructive pulmonary disease. Clinical efficacy of anti-pneumococcal vaccination in patients with COPD. Clinical efficacy of pneumococcal vaccine in the elderly: a randomized, single-blind population-based trial. Effect of a conjugate pneumococcal vaccine on the occurrence of respiratory infections and antibiotic use in day-care center attendees. Response to pneumococcal vaccine in chronic obstructive lung disease--the effect of ongoing, systemic steroid treatment. Pneumococcal infection and immunologic response to pneumococcal vaccine in chronic obstructive pulmonary disease. A pilot study. Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study. Randomised trial of 23-valent pneumococcal capsular polysaccharide vaccine in prevention of pneumonia in middle-aged and elderly people. Swedish Pneumococcal Vaccination Study Group. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial.
Although pneumococcal vaccine has been recommended for patients with chronic obstructive pulmonary disease (COPD), its efficacy in this population has not been shown. A double-blind randomized controlled trial of 14-valent pneumococcal vaccine was carried out in 189 men and women aged 40 to 89 years with a clinical diagnosis of COPD and a forced expiratory volume in 1 second of less than 1.5 L. Of the 189, 92 received the vaccine and 97 received saline placebo. In a randomly chosen subsample of those who received the vaccine the mean titres of specific IgG antibody to selected pneumococcal polysaccharide serotypes increased two- to threefold by 4 weeks after vaccination. Over a 2-year period the rates of death, hospital admissions and emergency visits and the mean length of hospital stay were not significantly different in the two groups. Although a protective effect of 14-valent pneumococcal vaccine could not be shown, the small size of the sample and the relatively low follow-up rates preclude firm conclusions about efficacy from these data alone. The elevated antibody levels before vaccination in some of the patients, suggesting prior infection with Diplococcus pneumoniae, may partly explain the findings. A study was undertaken to evaluate the clinical efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV) in immunocompetent patients with chronic obstructive pulmonary disease (COPD).
                A randomised controlled trial was carried out in 596 patients with COPD of mean (SD) age 65.8 (9.7) years, 298 of whom received PPV. The main outcome was radiographically proven community acquired pneumonia (CAP) of pneumococcal or unknown aetiology after a mean period of 979 days (range 20-1454).
                There were 58 first episodes of CAP caused by pneumococcus or of unknown aetiology, 25 in the intervention group and 33 in the non-intervention group. Kaplan-Meier survival curves for CAP did not show significant differences between the intervention and non-intervention arms (log rank test = 1.15, p = 0.28) in the whole group of patients. The efficacy of PPV in all patients was 24% (95% CI -24 to 54; p = 0.333). In the subgroup aged <65 years the efficacy of PPV was 76% (95% CI 20 to 93; p = 0.013), while in those with severe functional obstruction (forced expiratory volume in 1 second <40%) it was 48% (95% CI -7 to 80; p = 0.076). In younger patients with severe airflow obstruction the efficacy was 91% (95% CI 35 to 99; p = 0.002). There were only five cases of non-bacteraemic pneumococcal CAP, all in the non-intervention group (log rank test = 5.03; p = 0.025). Multivariate analysis gave a hazard ratio for unknown and pneumococcal CAP in the vaccinated group, adjusted for age, of 0.20 (95% CI 0.06 to 0.68; p = 0.01).
                PPV is effective in preventing CAP in patients with COPD aged less than 65 years and in those with severe airflow obstruction. No differences were found among the other groups of patients with COPD. To study the efficacy of pneumococcal capsular polysaccharide vaccine among the elderly by use of a population-based intervention in one township, Varkaus, Eastern Finland.
                A randomized, controlled trial in which elderly inhabitants (aged 60 years or older) of the catchment area were randomized to receive either pneumococcal and influenza vaccines (PI group = vaccinated) or influenza vaccine alone (I group = controls) and offered participation. The response rate was 67.4%. The PI group consisted of 1,364 persons and the I group of 1,473 persons. The vaccinations were performed in the municipal health center in the fall of 1982, and all elderly inhabitants were followed for 3 years for the development of radiologically confirmed pneumonia. Pneumococcal etiology was identified by serological methods.
                The incidence of pneumonia was 18.8 per 1,000 person-years in the PI group (73 pneumonia episodes) and 16.6 per 1,000 person-years in the I group (69 episodes). Pneumococcal etiology was found in 27 episodes in the PI group (incidence 7.0 per 1,000 person-years) and in 36 episodes in the I group (incidence 8.6 per 1,000 person-years). In controls (I group) the incidence of pneumococcal pneumonia was significantly higher among persons with increased risk for contracting pneumonia (19 per 1,000 person-years) than among controls with low risk status (4 per 1,000 person-years). No significant protection from pneumococcal pneumonia was found in the study group as a whole (vaccine efficacy 15%, 95% CI -43% to 50%). However, in persons with medical risk factors for contracting pneumonia, there was a statistically significant protective efficacy of 59% (95% CI, 6% to 82%).
                Pneumococcal vaccination significantly reduced the incidence of pneumococcal pneumonia in elderly persons at increased risk for contracting pneumonia. This increased/high-risk category comprised 34% of the population aged 60 years or older. Because targeted vaccination of this large group may be difficult to organize in an efficient manner, vaccinating all elderly persons may be the best strategy to prevent this rather common and often fatal disease. Incidence and severity of respiratory infections are increased in day-care center attendees. Streptococcus pneumoniae is an important contributor to these infections.
                To examine whether the use of a pneumococcal conjugate vaccine could reduce the occurrence of respiratory infections and the ensuing antibiotic drug use in the day care.
                In this double blind, randomized, controlled study performed in 8 day-care centers located in Beer-Sheva, Israel, 264 toddlers ages 12 to 35 months at enrollment were randomized to receive either a 9-valent conjugate pneumococcal vaccine (conjugated to CRM197) or a control vaccine [conjugate meningococcus C vaccine (conjugated to CRM197)] and were followed for an average of 22 months. The main outcome measures were respiratory morbidity and antibiotic use.
                An overall reduction of 7% in child months with > or = 1 reported illness episodes was observed among vaccinees (P = 0.008), and 85% of all episodes were related to the respiratory tract. Reductions of 15, 16 and 17% were observed in upper respiratory infections, lower respiratory problems and otitis media, respectively. An overall reduction of 17% in antibiotic days was observed [10% for upper respiratory infections, 20% for otitis and 47% for lower respiratory problems (P < or = 0.005 for each entity)]. The reduction in episodes and antibiotic use was greater for those <36 months of age than for the older children.
                The reduction of respiratory problems, including those not traditionally considered of pneumococcal origin and the ensuing lowered antibiotic use in day-care center attendees by pneumococcal conjugate vaccination suggest a broader benefit from the vaccine than preventing invasive disease only. Forty-nine patients with chronic obstructive lung disease (COPD) were block-randomized in four groups to investigate, if different degrees of steroid-load influenced the effect of pneumococcal-vaccination on antibody level and clinical variables during 6 months of follow-up. The groups included 13 patients without systemic steroids for the previous 3 months, all vaccinated at entrance in the study and treated with steroids for 4 weeks. Nine patients had chronic steroid treatment both before and during the investigation; they were vaccinated at the entrance in the study. Fifteen patients without systemic steroids for the previous 3 months were vaccinated after the end of a 4-week steroid treatment. Twelve patients served as controls, and were not vaccinated. Totally, 60%-78% of vaccinated patients in the three groups had a rise in antibody level, and a later decrease compared to two of the 12 control patients (p<0.01). This difference was also significant (p<0.05) for the patients vaccinated at entrance in the hospital. No differences were observed among the clinical variables: pneumonia, exacerbations, admittance to hospital, increase in the use of steroids or beta-agonists, and the use of antibiotics. We conclude that a rise in antibody level after pneumococcal vaccination can be expected in patients with COPD despite of the use of systemic steroids. The clinical effect of vaccination is debatable. We assessed the importance of Streptococcus pneumoniae and immunologic response to 14-valent pneumococcal vaccine in a randomized (saline placebo or vaccine) double-blind pilot study involving 103 patients with chronic obstructive pulmonary disease (COPD). Antibody titers, the flora of the sputum, respiratory infections or pneumonias, and deaths were monitored. The patients' antibody titers before immunization were higher than healthy control subjects. Titers rose normally in those vaccinated but declined more rapidly. Differences between the group receiving placebo and vaccine were not significant at 12 and 24 months. The incidence of pneumonia was high before and after vaccine (47/1,000 vs 41/1,000 patient-years). Nonpneumococcal causes predominated (73 percent of pneumonias; 83.4 percent of lethal pneumonias). Isolates from sputum were predominantly nonvaccine types (50 to 62.5 percent). Twenty-seven patients died; pneumonia occurred in six (one pneumococcal in a vaccinated patient) as a terminal complication of other diseases. Thus, although pneumonia occurred frequently in these patients with COPD and contributed to mortality in 22 percent (six) of the 27 deaths, the predominance of nonpneumococcal causes and the data on antibodies and sputum suggest that pneumococcal vaccine may not be as beneficial for patients with COPD as was hoped. More observations are needed. To determine the effectiveness of influenza vaccination on influenza-related acute respiratory illness (ARI) and overall ARI in patients with COPD, and its relationship to the degree of airflow obstruction.
                Stratified, randomized, double-blind, placebo-controlled trial.
                From June 1997 to November 1998 at a single university hospital. Patients and interventions: One hundred twenty-five patients with COPD were stratified based on their FEV(1) as having mild, moderate, and severe COPD. Within each group, they were randomized to the vaccine group (62 patients who received purified, trivalent, split-virus vaccine) or the placebo group (63 patients).
                The number of episodes and severity of total ARI, classified as outpatient treatment, hospitalization, and requirement of mechanical ventilation; and the number of episodes and severity of influenza-related ARI.
                The incidence of influenza-related ARI was 28.1 per 100 person-years and 6.8 per 100 person-years in the placebo group and vaccine group, respectively (relative risk [RR], 0.24 [p = 0.005]; vaccine effectiveness, 76%). The incidences were 28.2, 23.8, and 31.2 per 100 person-years in the patients with mild, moderate, and severe COPD, respectively, in the placebo group, and 4.5, 13.2, and 4.6 per 100 person-years in the patients with mild, moderate, and severe COPD, respectively, in the vaccine group (RR, 0.16 [p = 0.06]; vaccine effectiveness, 84%; RR, 0.55 [p = 0.5]; vaccine effectiveness, 45%; and RR, 0.15 [p = 0.04]; vaccine effectiveness, 85%, in the patients with mild, moderate, and severe COPD, respectively). Bivariate analysis revealed that the effectiveness of influenza vaccination was not modified by the severity of COPD, comorbid diseases, age, gender, or current smoking status. There was no difference in the incidence or severity of total ARI between the placebo group and the vaccine group.
                Influenza vaccination is highly effective in the prevention of influenza-related ARI regardless of the severity of COPD. Influenza vaccination does not prevent other ARIs unrelated to influenza. The effectiveness of influenza vaccination in the prevention of overall ARI in patients with COPD will depend on how much the proportion of influenza-related ARI contributes to the incidence of total ARI. Influenza vaccination should be recommended to all patients with COPD. We assessed the effectiveness of a 23-valent pneumococcal vaccine in the prevention of pneumococcal pneumonia and of pneumonia overall in non-immunocompromised middle-aged and elderly people.
                The prospective, multicentre, double-blind, randomised, placebo-controlled trial was carried out across departments of infectious diseases at six tertiary-care or university hospitals in Sweden. 691 non-immunocompromised patients aged 50-85 years who had been treated as inpatients for community-acquired pneumonia (CAP) were randomly assigned either 23-valent pneumococcal capsular polysaccharide vaccine or placebo (sodium chloride). We used Cox regression models to estimate the relative risks of pneumonia overall and pneumococcal pneumonia for the placebo group compared with the vaccine group.
                63 (19%) of 339 patients in the vaccine group and 57 (16%) of 352 patients in the placebo group developed a new pneumonia, corresponding to a relative risk over time for the placebo group compared with the vaccine group of 0.83 (95% CI 0.58-1.12, p=0.31). Pneumococcal pneumonia was diagnosed in 16 (4.5%) patients in the placebo group and in 19 (5.6%) in the vaccine group, corresponding to a relative risk for the placebo group of 0.78 (95% CI 0.40-1.51, p=0.45). We found no difference in the death rate between the two study groups.
                The 23-valent pneumococcal polysaccharide vaccine did not prevent pneumonia overall or pneumococcal pneumonia in middle-aged and elderly individuals. Pneumonia is estimated to cause 2 million deaths every year in children. Streptococcus pneumoniae is the most important cause of severe pneumonia. We aimed to assess the efficacy of a nine-valent pneumococcal conjugate vaccine in children.
                We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause admissions. Analyses were per protocol and intention to treat.
                529 children assigned vaccine and 568 allocated placebo were not included in the per-protocol analysis. Results of per-protocol and intention-to-treat analyses were similar. By per-protocol analysis, 333 of 8189 children given vaccine had an episode of radiological pneumonia compared with 513 of 8151 who received placebo. Pneumococcal vaccine efficacy was 37% (95% CI 27-45) against first episode of radiological pneumonia. First episodes of clinical pneumonia were reduced overall by 7% (95% CI 1-12). Efficacy of the conjugate vaccine was 77% (51-90) against invasive pneumococcal disease caused by vaccine serotypes, 50% (21-69) against disease caused by all serotypes, and 15% (7-21) against all-cause admissions. We also found an efficacy of 16% (3-28) against mortality. 110 serious adverse events arose in children given the pneumococcal vaccine compared with 131 in those who received placebo.
                In this rural African setting, pneumococcal conjugate vaccine has high efficacy against radiological pneumonia and invasive pneumococcal disease, and can substantially reduce admissions and improve child survival. Pneumococcal conjugate vaccines should be made available to African infants.
The limited evidence from randomised controlled trials (RCTs) included in this review suggests that, while it is possible that injectable polyvalent pneumococcal vaccines may provide some protection against morbidity in persons with COPD, no significant effect on any of the outcomes was shown. Further large RCTs in this population would be needed to confirm effectiveness of the vaccine suggested by results from longitudinal studies.