Adverse effects associated with influenza vaccination in patients with COPD: a randomized controlled study. The safety of inactivated influenza vaccine in adults and children with asthma. Randomised placebo-controlled crossover trial on effect of inactivated influenza vaccine on pulmonary function in asthma. Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study. Influenza vaccination in adults with asthma: safety of an inactivated trivalent influenza vaccine. Influenza vaccination in children with asthma: randomized double-blind placebo-controlled trial. Effects of inactivated influenza virus vaccination on bronchial reactivity symptom scores and peak expiratory flow variability in patients with asthma. Efficacy of pneumococcal vaccine in severe chronic obstructive pulmonary disease. Randomized, placebo-controlled double blind study on the efficacy of influenza immunization on absenteeism of health care workers.
The aim of this study was to assess the frequency and type of adverse reactions following influenza vaccination and its effects on lung function, dyspnoeic symptoms, exercise capacity, and clinical acute respiratory illness (ARI) in patients with COPD, and the relationship of these adverse effects to the degree of airflow obstruction.
                A stratified, randomized, double-blind placebo-controlled study was conducted over an 18-month period at a single university hospital. In total, 125 patients with COPD were randomized to the vaccine group (62 patients who received purified trivalent split-virus vaccine injections) or the placebo group (63 patients). Local and systemic symptoms during the week following the injections were evaluated. Clinical ARI, lung function tests, dyspnoeic symptoms (assessed using a visual analogue scale), and a 6-min walking test were evaluated before and at 1 week and 4 weeks following vaccination.
                The frequency of local adverse reactions was 27% in the vaccine group and 6% in the placebo group (P = 0.002). There was no significant difference in systemic adverse reactions between the vaccine and placebo groups (76% vs. 81%; P= 0.5). No difference was observed in the incidence of ARI between the vaccine and placebo groups during the first week (6.4% vs. 6.3%; P= 1) and the first 4 weeks (24.2% vs. 31.7%; P= 0.5) following vaccination. There was no significant change in lung function, dyspnoeic symptoms, and exercise capacity of the patients in both groups, at 1 week and 4 weeks following vaccination, regardless of the severity of COPD.
                Influenza vaccination is associated with minimal local adverse reactions in patients with COPD. Vaccination does not cause systemic adverse reactions, induce clinical exacerbations or adversely affect lung function, dyspnoeic symptoms and exercise capacity in patients with COPD, regardless of the severity of airflow obstruction. Influenza causes substantial morbidity in adults and children with asthma, and vaccination can prevent influenza and its complications. However, there is concern that vaccination may cause exacerbations of asthma.
                To investigate the safety of the inactivated trivalent split-virus influenza vaccine in adults and children with asthma, we conducted a multicenter, randomized, double-blind, placebo-controlled, cross-over trial in 2032 patients with asthma (age range, 3 to 64 years). The order of injection of vaccine and placebo was assigned randomly, with a mean of 22 days between the injections. Each day during the two weeks after each injection, the patients recorded peak expiratory flow rates, symptoms thought to be related to the injection, use of asthma medications, unscheduled health care visits for asthma, and asthma-related absences from school or work. The primary outcome measure was an exacerbation of asthma in the two weeks after the injections.
                The frequency of exacerbations of asthma was similar in the two weeks after the influenza vaccination and after placebo injection (28.8 percent and 27.7 percent, respectively; absolute difference, 1.1 percent; 95 percent confidence interval, -1.4 percent to 3.6 percent). The exacerbation rates were similar in subgroups defined according to age, severity of asthma, and other factors. Among symptoms thought to be associated with the injection, only body aches were more frequent after the vaccine injection than after placebo injection (25.1 percent vs. 20.8 percent, P<0.001).
                The inactivated influenza vaccine is safe to administer to adults and children with asthma, including those with severe asthma. Given the morbidity of influenza, all those with asthma should receive the vaccine annually. Despite current recommendations, many people with asthma do not receive annual vaccination against influenza, partly because of concern that vaccine may trigger exacerbations. Colds can trigger exacerbations, which may be mistaken for vaccine-related adverse events. We undertook a double-blind placebo-controlled multicentre crossover study to assess the safety of influenza vaccine in patients with asthma, with allowance for the occurrence of colds.
                We studied 262 patients, aged 18-75 years, who recorded daily peak expiratory flow (PEF), respiratory symptoms, medication, medical consultations, and hospital admissions for 2 weeks before the first injection and until 2 weeks after the second injection. Order of injection (vaccine and placebo) was assigned randomly. There was an interval of 2 weeks between injections. The main outcome measure was an exacerbation of asthma within 72 h of injection (defined as a fall in PEF of >20%).
                Among 255 participants with paired data, 11 recorded a fall in PEF of more than 20% after vaccine compared with three after placebo (McNemar's test p=0.06); a fall of more than 30% was recorded by eight after vaccine compared with none after placebo (binomial test p=0.008). However, when participants with colds were excluded, there was no significant difference in the numbers with falls of more than 20% between vaccine and placebo (six vs three; binomial test p=0.51), although the difference for PEF decreases of more than 30% approached significance (five vs none; binomial test, p=0.06). This association was confined to first-time vaccinees.
                Our findings indicate that pulmonary-function abnormalities may occur as a complication of influenza vaccination. However, the risk of pulmonary complications is very small and outweighed by the benefits of vaccination. 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. Despite recommendations in most countries for giving inactivated influenza vaccine to people with asthma, only a minority currently receive it. One reason for low vaccine coverage has been concern that vaccination may induce exacerbations of asthma. In this randomized trial, 291 patients between 18 and 65 years of age received either an inactivated influenza vaccine followed 14 days later by a saline placebo or placebo followed by the vaccine. Each patient received 1 dose of vaccine and 1 dose of placebo. The percentage of patients reporting at least one asthma exacerbation within 14 days after injection was similar following vaccine or placebo (28.3% and 25.5%, respectively). The combined exacerbation rate during the first 14-day interval was higher (31.5%) than that during the second 14-day interval (22.4%, P = 0.0135), indicating that the occurrence of exacerbations was not likely to be related to the sequence of injections. The percentages of individuals with solicited systemic symptoms were 56.6% and 44.8% after vaccine or placebo injection, respectively. We conclude that influenza vaccination did not increase the incidence of asthma exacerbations compared to placebo in this study and the vaccine was well tolerated. The results thus support annual influenza vaccination in patients with asthma. There is little evidence that influenza vaccination reduces asthma exacerbations. We determined whether influenza vaccination is more effective than placebo in 6-18-year-old children with asthma. We performed a randomized, double-blind, placebo-controlled trial. Parenteral vaccination with inactivated influenza vaccine or placebo took place approximately November 1, and children were followed until April 1 of the next year. Airway symptoms were reported in a diary. When symptom scores reached a predefined level, a pharyngeal swab was taken. Primary outcome was the number of asthma exacerbations associated with virologically proven influenza infection. Three hundred forty-nine children were assigned placebo, and 347 were assigned vaccine. Pharyngeal swabs positive for influenza were related to 42 asthma exacerbations, 24 in the vaccine group and 18 in the placebo group, a difference of 33% favoring placebo (31% after adjustment for confounders; 95% confidence interval, -34% to 161%). Influenza-related asthma exacerbations were of similar severity in both groups; they lasted 3.1 days shorter in the vaccine group (95% confidence interval, -6.2 to 0.002 days, p = 0.06). We conclude that influenza vaccination did not result in a significant reduction of the number, severity, or duration of asthma exacerbations caused by influenza. Additional studies are warranted to justify routine influenza vaccination of children with asthma. Even though annual influenza vaccinations are recommended by many authorities, some doctors may be reluctant to vaccinate asthmatic patients because of the risk of inducing bronchial reactivity and exacerbating the asthma. In this study we investigated the effect of inactivated trivalent influenza vaccine on airway reactivity symptom scores and peak expiratory flow (PEF) variability in 24 patients with mild stable asthma. Baseline spirometry and methacholine challenge tests were performed on all patients. Patients were then asked to record their peak expiratory flow every morning and evening, complete daily symptom score charts (morning tightness, daytime asthma, cough, and night asthma), and note bronchodilator usage for 1 week. After baseline measurements, the patients were allocated to inactivated vaccine and placebo in a random and single-blind manner. The lung function measurements and methacholine challenge tests were repeated 1 week after vaccination and placebo administration at the same time of day. PD20 (mg/mL) methacholine doses were 3.06+/-3.0 mg/mL before vaccination, 2.96+/-3.2 mg/mL after vaccination, and 2.76+/-2.91 mg/mL after placebo administration. There were no significant changes in PD20 methacholine after influenza vaccination (p>0.05). There were also no significant changes in symptom scores, bronchodilator usage, and PEFR after vaccination (p>0.05). None of the patients experienced significant local or systemic side effects after vaccination. Immunization with inactivated influenza vaccine does not induce clinical exacerbations of asthma or airway hyperreactivity in patients with mild asthma. 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. In healthy adults influenza immunization reduces absenteeism caused by respiratory infections, but data on its efficacy among health care workers are scarce.
                To determine the effect of the conventional inactivated influenza A vaccine on reducing absenteeism related to respiratory infections among pediatric health care providers.
                A randomized, placebo-controlled, double blind study on vaccine efficacy was conducted in two pediatric hospitals during the winter season 1996 to 1997. The primary endpoint was days of work lost from the hospital because of respiratory infections. The documentation of absenteeism was based on personal sickness logs.
                Of the 547 randomized vaccinees 427 (78%) persons completed the 4-month follow-up and returned the sickness logs. Immunization failed to reduce episodes of respiratory infections (1.8 episodes/study period among vaccinees vs. 2.0 among controls). Similarly the vaccine failed to affect the total number of days the vaccinees suffered from respiratory infections (13.5 days vs. 14.6 days, respectively). However, days of work lost because of respiratory infections (1.0 days vs. 1.4 days, respectively, P = 0.02) and especially total numbers of days the study persons felt themselves unable to work when either on or off duty (2.5 days vs. 3.5 days, P 0.02) were significantly decreased.
                Influenza vaccination reduced absenteeism related to respiratory infections by 28%. We therefore believe that routine annual influenza immunizations should be recommended to health care providers working in pediatric settings.
It appears, from the limited number of studies performed, that inactivated vaccine reduces exacerbations in COPD patients. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There is a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations.