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2007

2007 Role of pneumococcal polysaccharide vaccines in COPD patients: a literature review

Dr Lo Chi Wai, Department of Medicine, Yan Chai Hospital

According to World Health Organization estimates, chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide resulting in more than 2.7 million deaths in 2000. The prevalence rate of moderate to severe COPD in subjects 30 years and older was estimated to be 3.5% in HK. The mortality rate of COPD in 1998/99 was 31.1 per 100,000, which ranked fifth among the top ten causes of death in HK. The disease also accounted for 3.9% and 4.3% of all discharges or deaths and bed days respectively within the Hospital Authority.

Streptococcus pneumoniae is one of the most important pathogens in COPD patients. This high risk population is particularly susceptible to the potential complications of pneumococcal infection, especially when resistant strains are acquired. Despite appropriate antibiotic therapy and intensive care treatment, there is still considerable morbidity and mortality. A recent prospective HK study on the infectious etiology related to acute exacerbation of COPD (AECOPD) found that among sputum samples from the 530 episodes of AECOPD hospital admissions that were saved, 5.5% had positive growth of Streptococcus pneumoniae. A high prevalence of penicillin resistance, with 69.9% showing at least intermediate resistance to penicillin was also noted.

The availability of pneumococcal vaccines makes pneumococcal infections a potentially preventable disease in vulnerable subjects. Patients with COPD are included in several international pneumococcal vaccination recommendations. Despite the recommendations, pneumococcal vaccination rates have historically been low for high risk individuals. The utilization rate of the 23-valent pneumococcal polysaccharide vaccine (PPV) in Hong Kong is low (with estimated coverage of <10% for those >65 years). Part of the problem is the frequent disparity of results between various clinical trials including recent meta-analyses that included the 23-valent PPV.

Earlier randomized controlled trials on efficacy of pneumococcal vaccines were targeted on previously healthy young adults in Africa and showed significant protective effect of polyvalent pneumococcal vaccine against pneumococcal bacteraemia and pneumonia. These trials represented special situations with which the attack rates for pneumococcal disease were very high, and epidemics of one or two serotypes were common in overcrowded and poorly ventilated settings; the results cannot be generalized to all less developed countries or to populations in modern industrial countries, where the range of serotypes causing disease differs.

Controlled trials of the 23-valent pneumococcal polysaccharide vaccine have since been completed in elderly populations targeted for adult vaccination in the more developed countries. None of these has shown that the polysaccharide pneumococcal vaccine protects against pneumococcal pneumonia, pneumonia in general, or death. The first study was a double-blind randomized controlled trial in about 700 people aged 50–85 years who had been treated in hospital for community-acquired pneumonia. No effect against radiologically diagnosed pneumonia or sputum-positive pneumococcal pneumonia was detected. Another inconclusive trial was the Finnish trial of pneumococcal and influenza vaccine compared with influenza vaccine alone in 26 000 people aged at least 65 years. No effect was seen against radiologically diagnosed pneumonia, pneumococcal pneumonia identified by serological tests, or all-cause pneumonia.

Until recently, policy on the use of pneumococcal polysaccharide vaccine in elderly and those high risks groups including COPD patients is largely based on observational studies. Most published observational studies have found a vaccine efficacy of 60–80% against pneumococcal bacteraemia in elderly people in more developed countries. One study by Forrester and co-workers, however, suggested no protective effect of the polysaccharide vaccine.

Concerning COPD patients, there are only few randomized controlled trials performed to evaluate its efficacy. Two of them are conducted in year 1987 and both suggested that pneumococcal vaccine were not as protective as we would expect. However, immunological studies on the antibody response after pneumococcal vaccination in COPD patients supported the belief that these high risk elderly patients could mount an immune response to the pneumococcal polysaccharide vaccine. In fact, systemic steroid was shown not to affect the immune response toward PPV in COPD patients. A recent randomized controlled study suggested that PPV is effective in preventing community acquired pneumonia in patients with COPD aged less than 65 years and in those with severe airflow obstruction (FEV1<40% predicted). However, a meta-analysis showed that there is no evidence from randomized controlled trials that pneumococcal vaccination in persons with COPD has a significant impact on morbidity and mortality.

The issue of research on efficacy of 23-valent PPV has become more complex with the advent of pneumococcal conjugate vaccines. The ability of conjugate vaccine to eradicate colonization may be especially useful in patients with COPD, since colonization likely contributes to airway inflammation and exacerbations are mucosal infections. Therefore, future direction of vaccine study in COPD patients should include conjugate vaccines. Although this vaccine was designed for the common pneumococcal serotypes affecting children, an effect has been seen on adult disease since its introduction into the routine childhood immunization programme in 2000.

In conclusion, burdens of handling COPD patients in the era of pneumococcal antimicrobial resistance are of particular concern. The solution to the problem of pneumococcal morbidity and mortality lies not in the development of new antibiotics. It is high time for us to consider preventive measures.

The encouraging results on one hand could provide some insight for our future practice as mentioned in the latest GOLD guideline. On the other hand, in the absence of clinical data on the true burden of pneumococcal pneumonia and convincing efficacy of PPV in our local COPD patients, large scale recommendation in this high risk group cannot be justified at the moment. Clinical experience and recommendation of using the pneumococcal polysaccharide vaccine are all coming from the Western countries. In view of the potential differences in pneumococcal serotype distribution as well as immunological response to the pneumococcal vaccine, it would be essential for us to design our own locally targeted polyvalent pneumococcal vaccines.

Importantly, background knowledge on the epidemiology and disease burden of pneumococcal pneumonia in COPD patients should be obtained. In addition, more reliable and specific diagnostic tools in detection of pneumococcal pneumonia are required. Furthermore, continual surveillance of the patterns of antibiotic resistance and distribution of the common serotypes are essential to monitor the changes in serotypes both before and after the implementation of the pneumococcal vaccine. Last but not the least; randomized controlled trials of adequate sample size are needed to examine the possible protective effect in COPD patients, preferably with stratification of the disease severity.

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