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.
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
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.
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 end result ...