No differences were observed between groups receiving active vaccine and placebo in the mean PEF in the morning, noon, or evening during the first seven days after vaccination (Fig 1). Symptom scores for dyspnea, cough, and production of sputum and also the need for medication were similar in the two groups. Age, sex, duration of the disease, hypersensitivity to aspirin, atopic status, history of attacks of asthma induced by viral infections, diurnal variation of baseline PEF of 20 percent or more, or continuous oral steroid medication did not predict exacerbations following vaccination (Table 2).
The antibody response to vaccination was good (Table 3), not only in subjects seropositive in the phase before vaccination, but also in seronegative subjects, a part of whom may have been unprimed. During the follow-up period, the incidence of influenza was very low in Finland. Serologic evidence of infection (more than fourfold increase in antibody titer in sample 3, as compared to sample 2) was demonstrated only once (an influenza B infection in the placebo group).
There was no difference between the groups in the severity of asthma as evaluated by daily measurements of PEF, symptom scores, changes in daily medication, courses of oral corticosteroids, or hospitalization because of asthma during the eight-month follow-up period between September 1981 and April 1982.
Discussion
Our results demonstrate that immunization with killed influenza virus vaccine does not impair the clinical status in adult patients with chronic asthma. Absence of adverse effects was documented by several independent indicators. Our study is in keeping with the results of Campbell and Edwards, who found no adverse effects of influenza immunization in 28 asthmatic subjects in a placebo-controlled study.
In contrast to our observations, several earlier reports have suggested that asthmatic patients may experience an exacerbation of bronchial symptoms following immunization with killed influenza vaccine. Bell et al found an increase in the need for medication during the first 48 hours after vaccination in children with severe chronic asthma. In the study by Dejongste et al, immunization with inactivated influenza vaccine caused a significant fall in the forced expiratory volume in one second but no change in bronchial responsiveness to histamine in six of nine asthmatic children. Other investigators’ have observed increased obstruction or impairment in clinical symptoms after immunization in adult patients with asthma or chronic bronchitis. In one study, immunization with inactivated vaccine increased sensitivity to meth-acholine but did not cause spontaneous obstruction in asthmatic adults. Banks et al found a correlation between the antibody response and bronchial reactivity to histamine following vaccination with killed influenza virus but no increase in symptoms after vaccination.
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The reasons for the discrepancy between these reports can be explained in several ways. First, it is possible that clinically significant impairment of bronchial symptoms is seen only in patients with particularly severe or labile asthma. No support for such an explanation was found in our study, but it should be borne in mind that medication was carefully adjusted in all of the patients during the run-in period. This factor, together with better compliance with treatment because of regular recording of PEF and clinical symptoms, may have improved bronchial stability and diminished the sensitivity of the patients to any adverse effects of vaccination. Secondly, it is possible that bronchial obstruction after immunization is restricted to some relatively small group of patients. Our analysis did not identify any group of patients with exceptional responsiveness to vaccination; however, it should be emphasized that in contrast to many previous studies, we used a rigidly placebo-controlled double-blind study. The greater frequency of symptoms after immunization seen in other studies may represent a placebo response to the procedure in the study.
No direct conclusions about the protective effect of the vaccination can be made, because during the season of 1981 to 1982, the epidemic of influenza did not occur as expected in Finland. The epidemic activity, mainly due to influenza B viruses, increased exceptionally late in spring (unpublished observations of the National Influenza Centre, National Public Health Institute, Helsinki), ie, after the end of the study. According to the seroepidemiologic follow-up survey, which was started in the winter of 1971 to 197219 and has been continued every epidemic season since then, the frequency of serologic infection in 1981 to 1982 for influenza A and B viruses was 3 percent (9/291). This was the lowest value recorded since the beginning of the survey. Thus, the efficacy of the vaccination could be estimated only by means of antibody response. A significant rise in the number of individuals with a protective antibody titer of 48 or more was seen for all three antigens which represented the viruses of the vaccine.
In conclusion, immunization with killed influenza vaccine does not induce clinical exacerbations in adult patients with chronic asthma. With the exception of subjects with possible or manifest allergy to egg protein, asthmatic adults can safely be immunized with killed influenza virus. Other studies have previously shown that vaccination against influenza is effective in the prevention of acute episodes of chronic bronchitis. Thus, it is likely that patients in whom respiratory infections provoke exacerbations of asthma will benefit from immunization against influenza.
You may read previous research concerning this topic in “Details of Clinical Exacerbations in Adults with Chronic Asthma after Immunization with Killed Influenza Virus“.
Figure 1. Effect of immunization with killed influenza virus on PEF in morning before medication in all subjects. Values are expressed as percentage of mean PEF in morning before medication during second week of run-in period. Dashed lines indicate active vaccine (n = 161); solid lines indicate placebo (n = 157). Vertical bars indicate mean ± SD. Differences between groups are not statistically significant.
Table 2—Values for PEF in Morning before Treatment in Some Patient Subgroups during the First 7 Days After Intramuscular Injections cf Influenza Vaccine or Placebo
| Croup | Treatment | No. of Subjects | Day* | ||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | |||
| Aspirin intolerance | Active | 24 | 106 ±20 | 103 ±17 | 99± 13 | 98 ±16 | 98 ±17 | 95± 16 | 93± 19 |
| Placebo | 28 | 104 ±20 | 93 ±17 | 98± 15 | 99± 12 | 98 ±13 | 90± 16 | 97 ±15 | |
| Atopic asthma | Active | 69 | 102 ±8 | 101 ±11 | 99± 14 | 100 ±13 | 101 ±13 | 99± 13 | 99± 12 |
| Placebo | 59 | 102 ±15 | 98± 16 | 99± 13 | 100 ±15 | 98± 15 | 97 ±18 | 99± 19 | |
| Intrinsic asthma | Active | 69 | 105 ±21 | 103 ±15 | 99± 17 | 98± 16 | 101 ±17 | 101 ±20 | 99 ±25 |
| Placebo | 79 | 101 ±14 | 99± 14 | 100 ±13 | 98± 16 | 99± 14 | 96± 17 | 97 ±13 | |
| Asthma during | Active | 113 | 105 ±17 | 102 ±15 | 99± 17 | 99± 16 | 102 ±17 | 101 ±18 | 99 ±21 |
| viral infections’!* | Placebo | 119 | 102 ±14 | 97 ±15 | 99± 12 | 99± 15 | 98 ±15 | 96 ± 17 | 98 ±16 |
| Oral steroid | Active | 27 | 106 ±14 | 103 ±16 | 94 ±20 | 96 ±21 | 100 ±21 | 100 ±19 | 97 ±17 |
| medication | Placebo | 33 | 103 ±20 | 92 ± 19 | 96± 15 | 92 ±18 | 97 ±22 | 92 ±22 | 93 ±21 |
Table 3—Effect cf Vaccination on Hemagglutination-Inhibiting Antibodies
| Group | A/Bangkok/ 1/79(H3N 2) | A/Brazil/11/78(H INI) | B/HongKong/5/72 | |||
| Vaccine | Placebo | Vaccine | Placebo | Vaccine | Placebo | |
| Seropositive subjectst | ||||||
| Serum before vaccination (sample 1) | 58 | 65 | 40 | 50 | 79 | 79 |
| Serum after vaccination (sample 2) | 95 | 67 | 95 | 50 | 100 | 79 |
| Subjects showing ^4-fold increase in titer in sample 2 as compared with sample 3 | ||||||
| Subjects seropositive in sample 1 | 74 | 0 | 61 | 0 | 54 | 0 |
| Subjects seronegative in sample 1 | 77 | 0 | 84 | 0 | 100 | 3 |
| Subjects showing protective titer of ^48 in sample 2 | 79 | 27 | 77 | 22 | 97 | 48 |