Elsevier

Vaccine

Volume 26, Issue 33, 5 August 2008, Pages 4284-4289
Vaccine

Additive effect of pneumococcal vaccine and influenza vaccine on acute exacerbation in patients with chronic lung disease

https://doi.org/10.1016/j.vaccine.2008.05.037Get rights and content

Abstract

To determine the clinical efficacy of combined vaccination with 23-valent pneumococcal vaccine (PV) and influenza vaccine (IV) against pneumonia and acute exacerbation of chronic lung diseases (CLD), we conducted an open-label, randomized, controlled study among 167 adults with CLD over a 2-year period. Subjects were randomly assigned to a PV + IV group (n = 87) or an IV group (n = 80). The number of patients with CLD experiencing infectious acute exacerbation (P = 0.022), but not pneumonia (P = 0.284), was significantly lower in the PV + IV group compared with the IV group. When these subjects were divided into subgroups, an additive effect of PV with IV in preventing infectious acute exacerbation was significant only in patients with chronic obstructive pulmonary diseases (P = 0.037). In patients with CLD, the Kaplan–Meier survival curves demonstrated a significant difference for infectious acute exacerbation (P = 0.016) between the two groups. An additive effect of PV with IV on infectious acute exacerbation was found during the first year after vaccination (P = 0.019), but not during the second year (P = 0.342), and was associated with serotype-specific immune response in sera of these patients who used PV during the same period.

Introduction

Acute exacerbation frequently occurs among patients with chronic lung diseases (CLD), such as chronic obstructive pulmonary disease (COPD) and sequelae of pulmonary tuberculosis (SPTB) [1], [2]. Morbidity, mortality and health-care costs of these patients largely result from on acute exacerbations [3]. Acute exacerbations are primarily triggered by bacterial or viral pathogens in COPD and SPTB. While Streptococcus pneumoniae (S. pneumoniae) is the most commonly identified cause of community-acquired pneumonia (CAP) by accounting for 16.5–38.9% of CAP among adults [4], [5], this pathogen is also responsible for 8–25% of acute exacerbation in patients with CLD or COPD, which makes it a major bacterial pathogen [2], [6], [7]. Viral pathogens are also capable of inducing acute exacerbation of COPD, and the influenza virus was frequently detected in 5–29% of exacerbation of COPD [8], [9].

Since antibodies to pneumococcal capsular polysaccharide (PPS) and complement provide protection against S. pneumoniae with homologous or cross-reactive capsular serotypes [10], pnemococcal polysaccharide vaccine (PV) is effective for preventing invasive pneumococcal diseases in patients with chronic illness, such as CLD. PV is, therefore, recommended for these patients [11], [12], [13]. Although the previous studies reported that PV is not effective in preventing pneumonia or acute exacerbation in patients with COPD [14], [15], [16], a recent, prospective study demonstrated an effect of PV in preventing pneumonia in such patients with less than 65 years of age with severe airflow obstruction [17]. In addition, a retrospective study previously reported the additive effects of PV with influenza vaccine (IV) in the reduction of hospitalization stays and death among elderly persons with CLD [18], [19]. Although a large-scale prospective study demonstrated the additive effects of PV and IV in reducing hospital mortality due to pneumonia among elderly persons [20], no prospective study has been conducted to find the additive effects of PV combined IV for preventing pneumonia or acute exacerbation in patients with CLD. This open-label, randomized, controlled study was designed to determine whether PV and IV combined are superior to IV alone in preventing pneumonia or acute exacerbation among patients with CLD.

Section snippets

Study design

For this study, 191 patients with CLD in a stable condition were enrolled after providing written informed consent at the respiratory clinic of 13 hospitals in the district of Kyushu and Okinawa, Japan between November 2001 and April 2002. All potentially eligible subjects (at least twice as many as the enrolled cases) were contacted by the members of the Pneumococcal Vaccine Trialist Group, belonging to one of these hospitals. As the study investigators, these doctors had a role in selecting

Results

Ages (mean ± S.D. years) and male sex (%) were 69.0 ± 9.0 and 63.5 for total subjects, 67.8 ± 9.5 and 69.0 for the PV + IV group, and 70.1 ± 7.4 and 57.5 for the IV group. The numbers of patients with three subcategories of CLD (COPD, SPTB and other CLDs) in the PV + IV and the IV groups are shown in Table 1. Other CLDs were bronchiectasis (n = 20; 10 for the PV + IV group and 10 for the IV group), bronchial asthma (n = 13, 6 for the PV + IV group and 7 for the IV group), pneumoconiosis (n = 14, 7 for the PV + IV

Discussion

This study demonstrated an additive effect of PV with IV in preventing infectious acute exacerbation, but not pneumonia or non-infectious acute exacerbation, when compared to IV alone in patients with CLD. When theses subjects were divided into three subgroups according to their type of CLD, an additive effect of PV with IV in preventing infectious acute exacerbation was found only in COPD patients, but not in patients with SPTB or other pulmonary diseases. Since no attempt was made to blind

Acknowledgments

This study was supported by a Research Grant “Studies on preventable vaccines for varicella, mumps, and pneumococcal pneumonia and other diseases” for Science and Welfare, Ministry of Health, Labor and Welfare, Japan.

We are grateful to Naoko Kitajima, Miki Magome for technical assistance and the members of Pneumococcal Vaccine Trialist Group in the Kyushu and Okinawa districts: Yoshiaki Tao, National Fukuoka-Higashi Medical Center; Nobuhiro Kamikawaji, Fukuoka National Hospital; Yoshiya

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