The immunogenicity of the intradermal injection of seasonal trivalent influenza vaccine containing influenza A(H1N1)pdm09 in COPD patients soon after a pandemic.

The antibody responses of a reduced-dose intradermal seasonal influenza vaccination have never been studied in COPD patients soon after a pandemic. A total of 149 COPD patients (60 y of age or older) were randomized to receive trivalent influenza vaccine (Sanofi-Pasteur, France) either 9 µg of hemagglutinin (HA) per strain split into 2-site intradermal (ID) injections via the Mantoux technique or one intramuscular (IM) injection of 15 µg of HA per strain. The geometric mean titers, seroconversion factors, seroconversion rates and seroprotection rates for influenza A(H3N2) and B administered through the ID injection (n = 75) were similar to those obtained with the IM injection (n = 74) 4 weeks post-vaccination. The antibody responses for influenza A(H1N1)pdm09 administered through the ID injection were lower than those obtained with the IM injection, but all of these responses met the 3 criteria proposed by the Committee for Proprietary Medicinal Products (CPMP) for annual re-licensure. The seroprotection rates 4 weeks post-vaccination for influenza A(H1N1)pdm09 were 64.0% (95%CI 52.7-74.0%) in the ID group vs. 78.4% (95% CI 67.6-86.3%) in the IM group (p = 0.053). Influenza-related acute respiratory illness (ARI), diagnosed as a 4-fold rise in HI titers with a convalescent titer > 1:40, and/or the RT-PCR between the ID group (5.3%) and the IM group (8.1%) were not significantly different. The reduced-dose intradermal influenza vaccine may expand vaccine coverage in cases of vaccine shortage.

The immunogenicity of intradermal influenza vaccination in COPD patients.

We evaluated the immunogenicity of a reduced-dose intradermal trivalent, inactivated, split-virion seasonal influenza vaccine compared to that of a conventional intramuscular vaccination in chronic obstructive pulmonary disease (COPD) patients. One hundred and fifty-six COPD patients randomly received either 0.2 ml (6 microg hemagglutinin (HA) per strain) split into two-site intradermal (ID) injections or a single 0.5 ml (15 microg HA per strain) intramuscular (IM) injection. Geometric mean titers, seroconversion factors, seroconversion rates and seroprotection rates at 4 weeks post-vaccination in the ID group were less than those in the IM group. Only the seroconversion factor to influenza B in the ID group was statistically less than in the IM group (18.8 in the ID group, n=81 versus 37.3 in the IM group, n=75, p=0.045). Nevertheless, each strain of the ID vaccination met all the Committee for Proprietary Medicinal Products (CPMP) criteria. Seroprotection rates were above 60% throughout the year in influenza A (H3N2), for at least 6 months in influenza A (H1N1) and at least 4 weeks in influenza B in both ID and IM groups. The reduced-dose intradermal vaccination may be considered for use in COPD patients in a vaccine shortage situation.

Adverse effects associated with influenza vaccination in patients with COPD: a randomized controlled study.

OBJECTIVE: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSION: 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.

Prevalence and incidence of Chlamydia pneumoniae antibodies among the healthy elderly and patients with chronic obstructive pulmonary diseases.

Chlamydia pneumoniae is an obligatory intracellular bacteria which can cause both acute and chronic respiratory tract infection. The significance of chronic and recurrent respiratory infection may be of prime importance in chronic obstructive pulmonary diseases (COPD). The purpose of this study was to determine the prevalence and incidence of C. pneumoniae antibodies in elderly COPD patients compared to a healthy elderly control group. C. pneumoniae antibodies were detected by an enzyme-linked immunosorbent assay in serum samples obtained from 127 elderly COPD patients and a 131 healthy elderly control group. The results showed that the seroprevalence of C. pneumoniae infection as determined by the existence of specific IgG or IgA or IgM antibodies was 96.1% in the COPD patients and 75.6% in the control group (p < 0.01). The prevalence of individual C. pneumoniae IgG, IgA and IgM in elderly COPD vs healthy control was 85.8% vs 66.4%, 85.0% vs 51.1% and 3.9% vs 0%, respectively. The incidence or seroconversion rate of C. pneumoniae antibodies after one year follow-up was found to be 33% in the COPD patients and 67.9% in the control group. High prevalence and incidence of C. pneumoniae antibodies indicates that both acute and chronic C. pneumoniae infection play a role in elderly COPD patients. Therefore, antibiotics of choice for C. pneumoniae infection should probably be considered.

Acute respiratory illness in patients with COPD and the effectiveness of influenza vaccination: a randomized controlled study.

STUDY OBJECTIVES: 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. DESIGN: Stratified, randomized, double-blind, placebo-controlled trial. SETTING: 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). MEASUREMENTS: 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. RESULTS: 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. CONCLUSIONS: 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.

Economic evaluation of influenza vaccination in Thai chronic obstructive pulmonary disease patients.

UNLABELLED: To determine the cost-effectiveness and cost-benefit of influenza vaccination in chronic obstructive pulmonary disease (COPD) patients the authors conducted a stratified randomized, double-blind, placebo-controlled trial from June 1997 to November 1998 at a university hospital in Thailand. A total of 125 COPD patients were stratified based on their FEV1 as mild COPD (FEV1 > or = 70% predicted), moderate COPD (FEV1 50-69% predicted) and severe COPD (FEV1 < 50% predicted) and in each severity stratum they were randomized to the vaccine group (received intramuscular injection with purified trivalent split-virus vaccine containing A/Texas/36/91 (H1N1), A/Nanchang 1933/95 (H3N2) and B/Harbin 107/94) or the placebo group (received intramuscular injection with vit B1). Number of episodes of acute respiratory illness (ARI) related to influenza (clinical ARI + a serum hemagglutination inhibition antibody titre of 38 or greater and a four fold titre increase in convalescent serum compared to acute serum) as well as severity of each ARI (outpatient treatment, hospitalization or required mechanical ventilation) and costs of treatment (direct medical costs comprised real drug costs from the hospital dispensary in outpatient cases and real charges in hospitalization cases) were collected and analyzed for the cost-effectiveness and cost-benefit of influenza vaccination. The incidence of influenza-related ARI in the study year was 27 per cent in the placebo group and 6.4 per cent in the vaccine group (relative risk [RR] 0.24, vaccine effectiveness 76%). The incidence was 27.3 per cent, 23.5 per cent and 29.2 per cent in mild, moderate and severe COPD respectively in the placebo group and 4.3 per cent, 12.5 per cent, and 4.3 per cent in the mild, moderate and severe COPD respectively in the vaccine group (RR 0.16, 0.53 and 0.15; vaccine effectiveness 84%, 47%, and 85% respectively). The incremental cost-effectiveness ratios demonstrated that for every 100 patients with mild COPD whom the authors decided to vaccinate, the cost would be 24,840 baht more and would prevent 18.2 outpatients, 4.8 hospitalizations and 0 patient from mechanical ventilation due to ARI related to influenza. Likewise, the authors would have prevented 5.1 outpatients, 5.9 hospitalizations, 5.9 mechanical ventilation and 20.8 outpatients, 3.9 hospitalizations, 8.3 mechanical ventilation for every 100 moderate COPD and every 100 severe COPD patients vaccinated respectively. More than 90 per cent of the costs of treatment of influenza-related ARI were costs of hospitalization and for patients with moderate and severe airflow obstruction, more than 90 per cent of these costs were attributed to the costs of treating the patients who required mechanical ventilation. Predicted cost savings for every 100 mild COPD, 100 moderate COPD and 100 severe COPD patients vaccinated were 125,629 baht, 538,184.3 baht, and 680,647.1 baht respectively. IN CONCLUSION: Influenza vaccination is highly effective in the prevention of acute respiratory illness related to influenza virus infection in COPD, regardless of severity of airflow obstruction. Vaccination is more cost-effective in preventing mechanical ventilation episodes and more cost-benefit in patients with more severe airflow obstruction. Influenza vaccination should be recommended to all patients with COPD with the higher priority provided to patients with more severe airflow obstruction.

Comparison between specified percentage and fifth percentile criteria for spirometry interpretation in Thai patients.

OBJECTIVES: The present study was conducted to determine the degree of agreement between the interpretation of spirometry using a specified percentage of predicted value (SPC) and the fifth percentile (FPC) as the cut off between normal and abnormal. METHODOLOGY: Spirometric values were collected for 1754 subjects attending the respiratory service at Siriraj Hospital between February 2000 and April 2001. These values included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, maximal mid-expiratory flow (FEF25-75%) and peak expiratory flow (PEF). A comparison of results between SPC and FPC was performed. The SPC cut-off values for FVC, FEV1, FEV1/FVC, FEF25-75% and PEF were 80% predicted, 80% predicted, 70%, 65% predicted and 80% predicted, respectively. The FPC cut-off values were calculated from reference equations for the Thai population. Inter-rater agreement was calculated as the kappa score. RESULTS: High kappa scores were obtained for FVC (0.84), FEV1 (0.88) and FEF25-75% (0.80). However, poor agreement was found for FEV1/FVC (0.72) and PEF (0.61). When the cut-off values for SPC were modified to 90% of predicted values for FEV1/FVC and to 65% of predicted values for PEF, agreement was substantially improved to 0.92 and 0.89, respectively. CONCLUSIONS: Interpretation by SPC using cut-off values of 80% predicted for FVC and FEV1 and 65% predicted for FEF25-75% resulted in good agreement with FPC. However, the SPC cut-off values for FEV1/FVC and PEF should be modified to 90% predicted and 65% predicted, respectively.

The prevalence and incidence of COPD among urban older persons of Bangkok Metropolis.

COPD substantially affects the national healthcare resource and healthcare cost especially among the older persons. Identifying the accurate prevalence and incidence reflects the scale of problem posed by COPD. This epidemiological study using the criteria for diagnosing COPD based on ratio of FEV1.0/FVC less than 70 per cent and the reversibility of less than 15 per cent increase of post bronchodilator FEV1.0 in the absence of parenchymal lesions and cardiomegaly in CXR (PA and lateral view) revealed the prevalence (1998) of COPD among the 3094 older persons aged 60 years and over in the communities of Bangkok Metropolis 10 km around Siriraj Hospital was 7.11 per cent (95% CI: 6.21-8.01), whereas the incidence (1999) of COPD was 3.63 per cent (95% CI: 2.83-4.43). Both the prevalence and the incidence were increased with increasing age. The disease occurred predominantly among male smokers. The distribution of mild : moderate : severe COPD in the prevalence study was 5.6:2.2:1. The current findings also suggest that tobacco smoking is the prime important cause of COPD and the indoor pollution especially cooking smoke is not significant. In particular, the unexpectedly high incidence compared with prevalence in this population probably represents the warning message to the national policy maker for prompt and effective health promotion and disease prevention to prevent further social and economic loss.