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The World Health Organization (WHO) has been tracking the global burden of infectious diseases for several decades. During that time, mortality resulting from acute respiratory infections has been increasing, surpassing diarrheal disease in the late 1990s to become the number one killer of children worldwide. Since 1990, the WHO has used the Burden of Disease Project to assess disease-related morbidity and mortality, including the summary measure of disability-adjusted life years (DALYs) lost, which takes into account the degree and duration of morbidity in addition to mortality. When data are assessed by the DALYs measure, lung infections are again remarkably prominent. The attributable morbidity and mortality of acute respiratory infections exceeds HIV/AIDS, cancer, and heart disease. Of particular note is that these data do not include morbidity and mortality resulting from tuberculosis or to AIDS-related pneumonias, thereby underestimating the true impact of respiratory infections (Fig. 504-1). When stratified by age, there is a large and disproportionate burden of morbidity and mortality attributable to lower respiratory tract infections (LRIs) in the 0-to-4 and 5-to-14 age groups. Across the decades, even for the youngest patients, the burden of disease from LRIs exceeds that from malaria or diarrheal disease (Fig. 504-2). Although there is a strong association of LRIs with poverty, LRIs account for remarkable morbidity and mortality in wealthy countries as well.1 In the wealthiest countries, LRIs cause a greater burden than any other infectious disease. Although effective vaccines are available for specific pathogens such as Hemophilus influenzab and some serotypes of Streptococcus pneumoniae, the number of organisms capable of causing lung infections is too numerous to feasibly vaccinate against each. An approach that bolsters lung immunity per se may have the greatest impact in reducing morbidity and mortality against LRIs. It is imperative to advance our understanding of both innate and adaptive immunity to pathogens in the lung.

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Figure 504-1.
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Global burden of disease as measured by the disability-adjusted life years (DALYs). Acute respiratory infections cause more morbidity than HIV/AIDS, cancer, diarrhoeal disease, malaria, or tuberculosis (TB).

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Figure 504-2.
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Disproportionate burden of disease in children ages 0 to 4 and 5 to 14. Acute respiratory infection causes the greatest combined morbidity and mortality in children.

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With the exceptions of neonatal pneumonias in which the lungs become seeded by hematogenous dissemination of group B streptococcus or Escherichia coli, most pneumonias result from aspiration of organisms colonizing the upper airways.2 If this inoculum is small or of lower virulence, innate immunity consisting of cough, mucociliary clearance, antimicrobial peptides, and/or resident airway or alveolar macrophages can eradicate the infection. However, if the inoculum is large (as can occur with oral anerobes in children with poor dentition) or if more virulent pathogens (such as encapsulated bacteria) are aspirated, then the ...

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