**1. Introduction**

422 Chronic Obstructive Pulmonary Disease – Current Concepts and Practice

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*Streptococcus Pneumoniae*, the most common cause of community-acquired pneumonia (CAP), remains a major cause of morbidity and mortality worldwide. Despite appropriate antibiotic therapy and intensive care treatment, mortality rates due to pneumococcal infections remain considerable, especially in elderly and high-risk individuals such as patients with chronic heart or pulmonary disease (Kyaw 2005).

The main reservoir of pneumococci is the nasopharynx, and the possible outcomes after colonisation are clearance by the organism, asymptomatic persistence of infection (carrier state), or progression to disease. Disease presentation depends on whether the bacteria spreads to adjacent mucosal tissues causing mucosal infections (otitis, sinusitis, bronchitis and nonbacteraemic pneumonias) or whether it invades the bloodstream, or other sterile sites, resulting in invasive pneumococcal disease (IPD), principally bacteraemic pneumonia, meningitis and sepsis. The outcome is a complex process that depends on interactions between factors related to the host, therapy and microorganism (Feikin 2000, Baddour 2004). Figure 1 illustrates the overlap between overall community-acquired pneumonia, pneumococcal pneumonia and IPD.

The reported incidences of IPD have widely varied in different studies. These differences probably reflect different rates of obtaining blood cultures from patients with pneumonia. The incidence of bacteremic pneumococcal pneumonia ranged from 9 to 18 cases per 100.000 adults-year in a multicentre study carried out in five countries (Kalin 2000). The true incidence of nonbacteremic pneumococcal pneumonia is unknown, but it is probably 3-4 fold higher considering that it has been estimated that 80% of all pneumococcal pneumonias happen without bacteremia (Orqvist 2005).

Chronic obstructive pulmonary disease (COPD) is a major risk factor for communityacquired pneumonia, and smoking (the most common cause of COPD) has been reported as an important risk factor for IPD (Torres 1996, Nuorti 2000).

Nowadays, COPD is a leading cause of morbidity and mortality worldwide. The prevalence of COPD increases with increasing age (approximately 1-3% in middle aged adults *vs* 6-10% in elderly people) and it is approximately three-fold higher in men than in women (Murtagh 2005). Likely, the prevalence of COPD is underestimated given the absence of systematic

Antipneumococcal Vaccination in COPD Patients 425

addition, those patients with COPD who develop pneumonia have more severe pneumonia and therefore are admitted to the intensive care unit more frequently and have significantly

Acute exacerbations (although they represent a less serious illness than CAP) are also an important cause of morbidity and mortality in COPD patients (NICE 2004, Papi 2006, GOLD 2008). Approximately 50% of acute exacerbations in chronic bronchitis are triggered by bacterial infection (Sethi 2000) being pneumococcus responsible for almost a third of bacterial acute exacerbations (Saint 2001). There is an increased risk of exacerbations in COPD patients with persisting bacterial colonisation in the respiratory tract, especially in COPD patients with pneumococcal colonisation. It has been reported that pneumococcus was recovered from sputum in 33% of patients with COPD exacerbation (Bogaert 2004).

Immunizations with influenza and pneumococcal vaccines (together with smoking cessation, inhaled long-acting bronchodilators or inhaled corticosteroids) are a variety of strategies that may be effective in order to reduce incidence of pneumonia and acute

The pneumococcus is surrounded by a polysaccharide capsule, and differences in this capsule permit serological differentiation into distinct serotypes (Hausdorff 2005). However, the existence of more than 90 distinct serotypes (differing in their chemical composition, potential immunogenicity and epidemiological impact on different population groups) has

At the moment, there are 3 established approaches to anti-pneumococcal vaccination: capsular polysaccharide pneumococcal vaccines (PPV), protein-polysaccharide conjugate pneumococcal vaccines (PCV) and protein-based pneumococcal vaccines (PBPV) (Fedson 2003, Abraham Van-Parijs 2004, Tai 2006). At present, only the "old" PPV-23 for use in adults and two "new" PCVs (PCV-10 and PCV-13), both licensed in 2010 for use in children,

The currently available PPV-23 was licensed in 1983 and is usually recommended for all elderly people and some at-risk groups including those with chronic respiratory diseases. The vaccine contains capsular polysaccharide antigens from the 23 most dominant serotypes among clinical isolates of *S. pneumoniae*, accounting for approximately 80-90% of overall invasive infections in the adult population. These antigens induce type-specific antibodies (by a T cell-independent mechanism) that enhance opsonization, phagocytosis and killing of

Antibody response is generally satisfactory after vaccination, but children aged <2 years and immunodeficient persons do not consistently develop immunity, and certain high-risk individuals (including some people with medical co-morbidities and elderly individuals) may respond poorly (Sankilampi 1996, CDC 1997, Fedson 2003). Following vaccination there is a slow but steady decline in serotype-specific antibody titres, and pre-vaccination levels are generally reached within 5-10 years. An anamnestic response does not occur at

exacerbations in COPD patients (CDC 1997, Black 2004, Poole 2009, Varkey 2009).

greatly complicated the development and evaluation of anti-pneumococcal vaccines.

**2. Types of antipneumococal vaccines** 

are available in clinical practice.

**2.1 Pneumococcal polysaccharide vaccine** 

pneumococci by phagocytic cells (Fedson 2003).

higher 30-day mortality than non-COPD patients (Restrepo 2008, Molinos 2009).

Fig. 1. Overlap between overall community-acquired pneumonia (CAP), pneumococcal pneumonia (PP) and Invasive Pneumococcal Disease (IPD).

investigations in clinical practice for those patients with apparently non-severe or trivial symptoms. It has been estimated that approximately 15-25% people over 45 years-old have a moderate obstructive ventilatory disorder (GOLD 2008). If we consider mortality, a according to World Health Organization estimates, COPD is the fourth leading cause of death worldwide, with more than 2.7 million deaths in 2000 (NHLBI 2001).

Incidence data of pneumococcal infections focused on COPD patients is scarce but, given these persons are considered to be at risk of pneumococcal infections, incidence is believed to be very large. Among patients with pneumonia, COPD is the most commonly reported comorbidity. Among COPD patients with pneumonia, hospital admission increases with the intensity of airflow obstruction. The incidence of all-cause pneumonia among people with COPD is around 40-50 cases per 1000 patients-year (approximately 3-4 fold greater than in the general population). In the United States, the reported annual incidence of hospitalisation for CAP was 11 cases per 1000 among the general population over 65 yearsold and 41 cases per 1000 among those patients with chronic lung diseases (Jackson 2003). In Europe, incidences of 14 and 46 episodes per 1000 person-year have been reported among the general population and COPD patients, respectively (Vila-Corcoles 2006, Ochoa-Gondar 2008). Pneumococcus remains the most common microorganism identified among patients with chronic respiratory diseases with CAP (Liebermen 2002, Mandell 2007) although Gram-negative bacilli are increasing in patients with severe obstruction (Restrepo 2008, Ko 2008). Incidences of laboratory-confirmed pneumococcal CAP ranged from 0.5 to 2.1 per 1000 in the general population and 0.7 to 5.9 per 1000 among patients with chronic pulmonary disease (Jackson 2003, Vila-Corcoles 2006, Alfegeme 2006, Ochoa-Gondar 2008) of which approximately 25% were bacteremic and 75% non-bacteremic cases. These figures are likely to be an underestimation of the true incidence of pneumococcal bacteremia because they do not take into account persons from whom blood cultures were never obtained or those where the culture was performed after the start of antibiotic therapy. In

Fig. 1. Overlap between overall community-acquired pneumonia (CAP), pneumococcal

death worldwide, with more than 2.7 million deaths in 2000 (NHLBI 2001).

investigations in clinical practice for those patients with apparently non-severe or trivial symptoms. It has been estimated that approximately 15-25% people over 45 years-old have a moderate obstructive ventilatory disorder (GOLD 2008). If we consider mortality, a according to World Health Organization estimates, COPD is the fourth leading cause of

Meningitis, arthritis, peritonitis, etc.

Incidence data of pneumococcal infections focused on COPD patients is scarce but, given these persons are considered to be at risk of pneumococcal infections, incidence is believed to be very large. Among patients with pneumonia, COPD is the most commonly reported comorbidity. Among COPD patients with pneumonia, hospital admission increases with the intensity of airflow obstruction. The incidence of all-cause pneumonia among people with COPD is around 40-50 cases per 1000 patients-year (approximately 3-4 fold greater than in the general population). In the United States, the reported annual incidence of hospitalisation for CAP was 11 cases per 1000 among the general population over 65 yearsold and 41 cases per 1000 among those patients with chronic lung diseases (Jackson 2003). In Europe, incidences of 14 and 46 episodes per 1000 person-year have been reported among the general population and COPD patients, respectively (Vila-Corcoles 2006, Ochoa-Gondar 2008). Pneumococcus remains the most common microorganism identified among patients with chronic respiratory diseases with CAP (Liebermen 2002, Mandell 2007) although Gram-negative bacilli are increasing in patients with severe obstruction (Restrepo 2008, Ko 2008). Incidences of laboratory-confirmed pneumococcal CAP ranged from 0.5 to 2.1 per 1000 in the general population and 0.7 to 5.9 per 1000 among patients with chronic pulmonary disease (Jackson 2003, Vila-Corcoles 2006, Alfegeme 2006, Ochoa-Gondar 2008) of which approximately 25% were bacteremic and 75% non-bacteremic cases. These figures are likely to be an underestimation of the true incidence of pneumococcal bacteremia because they do not take into account persons from whom blood cultures were never obtained or those where the culture was performed after the start of antibiotic therapy. In

pneumonia (PP) and Invasive Pneumococcal Disease (IPD).

**CAP PP IPD** 

addition, those patients with COPD who develop pneumonia have more severe pneumonia and therefore are admitted to the intensive care unit more frequently and have significantly higher 30-day mortality than non-COPD patients (Restrepo 2008, Molinos 2009).

Acute exacerbations (although they represent a less serious illness than CAP) are also an important cause of morbidity and mortality in COPD patients (NICE 2004, Papi 2006, GOLD 2008). Approximately 50% of acute exacerbations in chronic bronchitis are triggered by bacterial infection (Sethi 2000) being pneumococcus responsible for almost a third of bacterial acute exacerbations (Saint 2001). There is an increased risk of exacerbations in COPD patients with persisting bacterial colonisation in the respiratory tract, especially in COPD patients with pneumococcal colonisation. It has been reported that pneumococcus was recovered from sputum in 33% of patients with COPD exacerbation (Bogaert 2004).

Immunizations with influenza and pneumococcal vaccines (together with smoking cessation, inhaled long-acting bronchodilators or inhaled corticosteroids) are a variety of strategies that may be effective in order to reduce incidence of pneumonia and acute exacerbations in COPD patients (CDC 1997, Black 2004, Poole 2009, Varkey 2009).
