Pneumonia is a lower respiratory tractinfection, causing inflammation and consolidation of the lung parenchyma and impairingits gas exchange function. Infection is primarily caused by bacterial or viralpathogens, and less commonly by fungal and parasitic organisms (1). Most cases of community acquiredpneumonia (CAP) are bacterial in nature (2), with Streptococcus pneumoniae (pneumococcus) being the most commoncausative agent, accounting for 20-60% of all CAP cases (3). A number of factors can increase thesusceptibility of bacterial lung infections, such as age (> 65 yearsold), smoking, and chronic obstructive pulmonary disorder (COPD) (4).
In this case, the patient presentswith the major risk factors associated with lung infection, which increases thelikelihood of respiratory disease. Spread andColonisation S. pneumoniae is a gram-positive, -hemolytic pathogen; it is anopportunistic invader and colonizer of the upper respiratory tract, and is mostcommonly found in the nasopharynx (5). It exists asymptomatically in ahealthy carrier, but becomes pathogenic when shown to be infiltrating the lowerrespiratory tract (6). Therefore, colonization is aprerequisite for pneumococcal disease (7), as it drives the virulence factors necessaryfor the development of pneumonia. S. pneumoniae is spread through person-to-personcontact via respiratory droplets, either from an asymptomatic carrier orsymptomatic individual. Local spread within the nasopharynx can extend intonormally sterile sites, including the sinuses and lungs.
Aspiration of bacteria from thenasopharynx into the lower respiratory tract is the most common route ofacquisition of the pathogen into the lungs, accounting for 90% of pneumonias (3). Immune Responseto S. pneumoniae and Pathogenesis In the nasopharynx, pneumococcus encounters mucus,which acts as the first-line defense and serves as a physical barrier againstinvading pathogens through mucociliary clearance.
Mucin also acts as a scaffoldfor antimicrobial proteins, thus the polysaccharide capsule encasingpneumococci have evolved to limit opsonisation by complement and antibody (8). Additionally, pneumococcal capsulesare negatively charged, which enforces repulsion of the bacterium from theanionic mucous barrier, facilitating the avoidance of destruction throughmucociliary clearance (8). Once colonizing bacteria has reached the epithelialsurface, lipopoteichoic acids of pneumococci are recognized by Toll-likereceptor 2 (TLR2). Neutrophils are initially recruited to the site of infection,but its response to pneumococcal acquisition is insufficient in the absence ofadaptive immunity. In the lower respiratory tract, the pulmonary capillary bedcontains a vast reservoir of intravascular neutrophils, which can be rapidlyactivated to the alveolar space during infection. Activation of patternrecognition receptors (PRRs) also promotes inflammatory response by cytokines, whichactivates and enhances macrophage clearance of the invading pathogen in thealveoli (9). Alveolar macrophage offers first-line protection inpulmonary host defense, by killing pathogens through generation of reactiveoxygen species (ROS) and serine proteases. However, they exhibit lessphagocytic activity and oxidative burst than other macrophages, and are lesslikely to activate T-cells (10).
Altogether, this leads to increased likelihoodof pathogen evasion from the immune system. In the presence of low numbers of S. penumoniae in the lungs, alveolarmacrophages are able to identify (through PRR), phagocytose and kill theinvading bacteria (10).
However, high levels of infection inthe lung can overwhelm the alveolar-mediated clearance. This initiates aninflammatory-response propagated by pro-inflammatory cytokines (such as TNF, IL6, and IL8), and recruitment ofadditional mechanisms of clearance (such as neutrophils) to the air spaces (11). Activation of the complement system byC-reactive protein also aids in leukocyte recruitment, amplifying immuneclearance within the alveolar spaces during acute-phase infection (12). In the resolution of inflammation, alveolarmacrophages remove apoptotic neutrophils, however, failure to clear these cellsmay lead to further tissue injury by the release of ROS and proteases, causingchronic inflammation (13). It is the massive inflammatory response in the lungparenchyma, caused by the invading pathogen (S. pneumoniae), thatconstitutes as pneumonia. It is marked by neutrophils and inflammatory exudatesfilling alveolar spaces, impairing lung function and resulting in the clinicalhallmarks of the disease, such as shortness of breath, consolidation in thelungs and chest pain.
Relation to thePatient In regard to the patient, his COPD and old age put him at greater risk of pneumonia. This can beattributed to impaired pulmonary function caused by emphysema and chronic bronchitisin COPD, and a general weakened immune system due to old age. Additionally, theuse of inhaled corticosteroids in the treatment of COPD may have increased therisk of pneumonia (14). Although the specific mechanisms ofthis is not clearly known, the anti-inflammatory properties and local immunesuppression of the airways may be contributing factors to this effect (2). Smoking produces structural changes in the respiratorytract, such as disruption of the ciliated respiratory epithelium, impairing itsability to clear invasive agents. Reduction in ciliary motility means thatremoval of pathogenic substances can invade the lower respiratory tract,resulting in overwhelming infection.
Furthermore, tobacco smoke may promote theproduction of pro-inflammatory mediators by epithelial cells, hence worseningthe pneumococcus infection (15). Smoking also increases the likelihoodof development of lung cancer, coronary heart disease, and stroke. Since thepatient is a current smoker, smoking cessation is recommended to preventfurther exacerbation of COPD, recurrence of pneumonia, and the development ofother diseases related to smoking.