Table 1.
Summary of the details of randomized controlled trials evaluated in the Cochrane review, measuring vaccine efficacy of the trivalent influenza vaccine amongst older patients and individuals with chronic lung disease [Poole et al. 2006].
| Study | Author | Study design | Setting | Details of patient recruitment | Primary outcome measurement | Results and conclusion |
|---|---|---|---|---|---|---|
| Clinical trials of bivalent influenza/A/New Jersey/76-A/Victoria/75vaccines in the elderly, | Cate et al. | Double-blind RCT | Texas Medical Centre, 1976 | A cohort of 413 older subjects were recruited, 5% of whom had chronic lung disease | Adverse reactions to vaccination were measured in the 1- and 2-day postvaccination period | A mild and moderate adverse systemic reaction to vaccination was seen in 7.8% and 4.9% of this cohort respectively. In contrast, control subjects who received a saline placebo did not experience any moderate or severe adverse reactions. 18.5% of patients experienced erythema at the injection site compared with none in the control group |
| Longer term effects of live influenza vaccine in patients with chronic pulmonary disease | Fell et al. | Double-blind RCT | Oxfordshire, 1975 | This cohort comprised 44 subjects with chronic bronchitis, 21 of whom were vaccinated and 23 were placebo treated | Self-assessment of the presence and severity of symptoms such as cough, dyspnoea, tightness, wheeze and sputum production following vaccination. A symptom score was assigned to every individual in the first 2 weeks after vaccination or placebo treatment to establish a baseline | At baseline, symptoms were more commonly reported in the vaccinated cohort compared with the placebo-treated group. This was not statistically significant, except for the occurrence of wheeze, which was significantly higher in vaccinated individuals than their placebo-treated counterparts Breathlessness was significantly lower in incidence amongst the vaccinated subjects who had a serological response to vaccination compared with the placebo group During the 18-week postvaccination surveillance period, symptoms of dyspnoea, chest tightness, wheeze and cough were significantly more common in vaccinated subjects compared with their placebo-treated counterparts, correlating with more common antibiotic usage in this group |
| Increased anti-influenza A viruscytotoxic T-cell activity following vaccination of older patients with chronic disease with live attenuated or inactivated influenza virus vaccine |
Gorse et al. | Single-blinded RCT | 1993–1994, St Louis VA Medical Centre and at St Louis Altenheim nursing home | A cohort of 50 older nursing home residents were given TIV, which was coadministered with either the bivalent live attenuated influenza A vaccine or a saline placebo |
Virus memory cytotoxic T cell response was measured in each subject. | The authors concluded that it could be advantageous to co-administer LAIV with TIV because a rise in anti-influenza A cytotoxic T lymphocyte activity was more commonly seen in subjects who were co-administered both formulations of the influenza vaccine compared to those administered TIV with a placebo. |
| Influenza virus vaccination of patients with chronic lung disease. | Gorse et al. | Single-blinded RCT |
Outpatient clinics of St Louis Department of Veterans Affairs Medical Centre, 1994–1995 | 29 volunteers, aged between 42 and 88 years old, with pre-existing COPD were recruited. Each volunteer received an intramuscular injection of TIV, in addition to either the bivalent LAIV or a saline solution placebo intranasally | Clinical status was assessed alongside pulmonary function, measured via spirometry. Levels of anti-HA immunoglobulin A antibodies were measured in nasal washings |
Vaccination status did not affect clinical status or pulmonary function. There was no significant difference in the incidence of exacerbations or in reports of respiratory tract symptoms between the two groups in the cohort Levels of anti-HA immunoglobulin A antibodies in nasal washings and levels of IL-2 and IL-4 increased significantly post vaccination in subjects with combined LAIV and TIV compared with pre vaccination, but did not significantly increase post vaccination in subjects administered TIV with a placebo. The authors concluded that there could be some benefit of administering TIV with LAIV |
| Adverse reactions to influenza vaccine in older people: randomized double-blind placebo controlled trial | Govaert et al. | Double-blind RCT | 15 general practises in the southern Netherlands, 1991–1992. | 1806 participants aged 60 or older were recruited on to the study. The cohort was divided into a group which received the influenza vaccine and a group that received a placebo | Adverse reactions reported on postal questionnaire completed 4 weeks after vaccination | Local side effects were significantly more common in the vaccinated group compared with the placebo group but there was no difference in systemic adverse reactions. All side effects were mild |
| The efficacy of influenza vaccination in older individuals. A randomized double-blind placebo-controlled trial | Govaert et al. | Double-blind RCT | 15 general practises in the southern Netherlands, 1991–1992 | 1836 participants aged 60 years or older were recruited on to the study. Individuals in the cohort were randomly assigned either the purified split-virion vaccine or an intramuscular saline placebo | Patients presenting with influenza-like illness up to 5 months after vaccination; self-reported influenza in postal questionnaires 10 weeks and 5 months after vaccination. The presence of serological influenza was also measured via antibody titres | The incidence of serological influenza and clinical influenza was lower in the vaccinated group than the placebo group. The authors concluded that vaccination against influenza was responsible for a 50% reduction in the incidence of serological and clinical influenza |
| Prophylactic use of influenza vaccine in patients with chronic bronchitis. A pilot trial | Howells et al. (1961) | Double-blind RCT | Winter 1960, NW Wolverhampton | 55 participants with chronic bronchitis were recruited on to the study, 26 of whom were randomly selected to be in the vaccinated group and 29 in the placebo group | The incidence of exacerbations was recorded by clinical examination and peak expiratory flow, with bacteriological and complement fixation to find the causative microorganism. Hospitalization rates and mortality were also recorded | This study demonstrated no significant difference in the incidence of early exacerbations between the vaccinated and placebo group. There was a significant reduction in the number of patients with late exacerbations in the vaccinated group compared with the placebo group. It was therefore concluded that vaccination significantly reduced the number of exacerbations during the follow-up period, per patient |
| Recognizing influenza in older patients with COPD who have received influenza vaccine | Neuzil et al. | Double-blind RCT | Various veterans affairs sites throughout the US and Puerto Rico during the 1998–1999 Influenza season | 2215 veterans with COPD were recruited on to this study. Each individual then received TIV, which was coadministered with either LAIV or an intranasal placebo | The presence of symptomatic, laboratory-documented influenza was recorded in this cohort | The authors state that it was difficult to clinically distinguish the symptoms associated with influenza-related illness from noninfluenza illness. Myalgia was reported in 80.9% of patients with laboratory-confirmed influenza but the presence of laboratory-confirmed influenza was low in the vaccinated population The authors concluded that receipt of LAIV as well as TIV, in comparison to TIV and a placebo, was associated with improvement in chronic lung disease severity index, which was used to assess functional status and wellbeing |
| A study of live influenza virus vaccine in patients with chronic bronchitis. Report to Medical Research Council’s Committee on Influenza and Other Respiratory Virus Vaccines. Advisory Group on pulmonary function tests in relation to live influenza virus vaccines | Medical Research Council | Double-blind RCT | No details | 86 participants with chronic bronchitis were initially recruited. Of these, 16 subjects had no baseline data and 15 had incomplete records. Thus only 55 were included in the final analysis. Each subject was randomly assigned to be administered the live attenuated RIT 4050 (H2N3) vaccine virus whilst others received a placebo preparation | 7-day post vaccination, subjects were assessed for respiratory and systemic symptoms. Spirometry was also conducted On day 21 in the postvaccination period, all of these measures were repeated and a HAI antibody test was also conducted |
The authors concluded that the influenza vaccine did not cause a clinical or physiological deterioration, but that there was a small and insignificant decrease in lung function tests 1 and 3 weeks following vaccination in the vaccinated group compared with the placebo group |
| Protective efficacy of combined live intranasal and inactivated influenza A virus vaccines in older people | Treanor et al. | Double-blind RCT | Three large nursing homes | A total of 523 nursing home residents were recruited on to the study. Subject were coadministered TIV with either the live attenuated influenza A vaccine or a placebo | Laboratory-documented influenza A was diagnosed in patients with respiratory illness in addition to isolation of influenza A in nasal secretions or serological response | It was concluded that intranasal immunization with LAIV provided additional protection as prophylaxis against influenza infection when coadministered with TIV, resulting in significantly reduced rates of laboratory-confirmed influenza A and outbreak-associated respiratory illness |
| Evaluation of cold-adapted, reassortant influenza B virus vaccines in older and chronically ill adults | Treanor et al. | Double-blind RCT | Outpatient clinics of Strong Memorial Hospital; Rochester, NY and a private practice | 81 older subjects were recruited from outpatient clinics, 34 of whom were given LAIV, 30 of whom were given parenteral TIV and 11 controls who were given a placebo | In the 3–4 day postvaccination period, pulse oximetry, spirometry, virus cultures and HAI tests were measured. It was also assessed whether the patient had any respiratory or systemic symptoms At 4 weeks post vaccination, serology was repeated. It was also recorded whether any subjects were hospitalized |
Symptoms of malaise and myalgia were reported in 12% of subjects vaccinated with LAIV, 10% of subjects vaccinated with TIV and in no placebo-treated subjects. Lower and upper respiratory tract symptoms were reported in 26% and 29% of subjects vaccinated with LAIV respectively, 13% and 37% of those vaccinated with TIV respectively, and 9% and 18% of the placebo group respectively. Febrile illness was experienced by 6% of those who received LAIV, 2.5% of those were vaccinated with TIV and by no one in the placebo group There was no significant difference in lung function between groups 8% of the treatment groups developed respiratory illness compared with 20% of the control group after a documented outbreak of influenza A occurred. Additionally, only 4% of the treatment group experienced influenza-like illness compared with 11% if the control group |
| Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study | Wongsurakiat et al. (2004) | Stratified randomized double-blind placebo-controlled trial | 1997–1998 at a single university hospital | 125 patients with COPD were recruited and then stratified based on disease severity. Individuals within each stratified group were randomized into a vaccinated group and a placebo group | Number and severity of episodes of acute respiratory illness, including influenza-like respiratory illness. Number and severity of episodes of acute respiratory illness (ARI) including influenza-like respiratory illness. This was measured via outpatient treatment, the incidence of hospitalization and requirement of mechanical ventilation | It was concluded that regardless of severity, vaccination against influenza is effective in prevention of influenza-related acute respiratory illness in patients with COPD. However, there was no significant difference in the incidence or severity of total acute respiratory illness between the vaccinated and placebo group, suggesting that TIV does not prevent other ARIs unrelated to influenza |
COPD, chronic obstructive pulmonary disease; HA, haemagglutinin; HAI, haemagglutinin inhibition; IL, interleukin; LAIV, live attenuated influenza vaccine; RCT, randomized controlled trial; TIV, trivalent influenza vaccine.