Acute Pneumonia and Its Complications

Epidemiology

In the US, lower respiratory infections (LRIs) occur throughout the year but excessively during the fall and winter when children are confined indoors, resulting in more efficient spread of the infections by contact or droplet transmission. Myriad factors predispose to acquisition of LRI: childcare and school attendance, indoor crowding, passive exposure to smoke, underimmunization, alcohol abuse in adolescents causing aspiration pneumonia, and underlying medical conditions such as low birth weight, bronchopulmonary dysplasia, asthma, heart disease, seizures, neuromuscular illness, gastroesophageal reflux disease, malnutrition, immunocompromised state, sickle cell disease, and cystic fibrosis. ^, Additional risk factors associated with pneumonia in children <5 years of age include frequent upper respiratory tract infections (URIs) ( >3 episodes in 12 months), wheezing at any age, and history of otitis media requiring tympanostomy tube placement before 2 years of age. Risk factors for pneumonia in children >5 years of age include wheezing at any age and ≥3 episodes of URI within 12 months.

Etiologic Agents

Viruses and bacteria cause most LRIs in infants and children. The true prevalence of the pathogens causing LRI is uncertain because microbial etiology is ascertained infrequently, owing to difficulty in differentiating infection from colonization and lack of dependable diagnostic laboratory tests. In two studies of immunocompetent children with pneumonia, specific etiologic agents were confirmed in only 43%–66%. ^, Some cases have more than one pathogen identified, making assigning etiology difficult. In a large multicenter study of children hospitalized for pneumonia who had specimens available for evaluation, a likely etiologic agent was detected in 81%, with >1 viruses in 66%, bacteria in 8%, and both bacterial and viral pathogens in 7% of cases. Confirmation of causative bacteria can be aided by blood cultures, but these are positive in only 1%–10% of hospitalized children with presumed bacterial pneumonia. ^{, ,} Etiologic agents causing pneumonia vary by age, underlying illness, maturity, and condition of the immune system. In most cases of acute pneumonia, extensive invasive testing is not warranted. Epidemiologic information frequently is useful in guiding differential diagnosis and management (see Chapter 21 ). Certain pathogens, particularly respiratory syncytial virus (RSV), rhinoviruses, influenza viruses, and Mycoplasma, are seasonal. In other instances, the pattern of family illness provides a clue to causative nonbacterial agents.

For purposes of management, the relative importance of etiologic agents in a series of patients who have been extensively evaluated is extrapolated to patients with similar clinical syndromes, physical findings, and laboratory results. Table 34.1 lists the common etiologic agents of acute pneumonia in children.

Pathogenesis and Pathology

Pneumonia occurs when a host susceptible to a pathogen is exposed to a high-density aerosol inoculum, has a compromised systemic or secretory immunity, or has an impaired clearance mechanism. ^, Most patients with pneumonia have initial colonization or infection of the upper respiratory tract. Invasion of the lower respiratory tract usually occurs when normal defense mechanisms are impaired, such as associated with a viral infection, chronic malnutrition, chronic aspiration, impaired cough reflex (e.g., after sedation, neurologic damage, intubation), or after exposure to environmental pollutants. Bacterial pneumonia occasionally occurs by the hematogenous route. In the early stages of lobar or bacterial pneumonia, protein-rich edema fluid containing numerous organisms fill the alveoli, leading to marked capillary congestion and causing neutrophil exudation and intra-alveolar hemorrhage. There is decrease in lung compliance, increase in pulmonary resistance, small airway obstruction, air trapping, and change in ventilation-perfusion ratio, all leading to the clinical signs of respiratory distress.

Defense mechanisms against LRI consist of (1) anatomic and physiologic barriers; (2) humoral and cell-mediated protection; and (3) phagocytic activity. The presence of hairs in the anterior nares (that trap particles >10 μm in size), configuration of the nasal turbinates, and acute branching of airways form protective anatomic barriers. Filtration and humidification capacities of the upper airways, mucus production, and middle airway protection by the epiglottis and cough reflex (eliminating particles 2–10 μm) form physiologic barriers. The mucociliary blanket transports microscopic amounts of normally aspirated oropharyngeal flora and particulate matter up the tracheobronchial tree, minimizing the presence of bacteria below the carina. Particles <1 μm can escape into the lower airways. Immunoglobulin A (IgA) antibody is secreted into the upper airways, and IgG and IgM leach from the local capillaries into the lower airways. Alveolar fluid surfactant, fibronectin, complement, lysozyme, and iron-binding proteins also have antimicrobial activity. The lower respiratory tract has three distinct populations of macrophages: alveolar, interstitial, and intravascular macrophages. Alveolar macrophages are the preeminent phagocytic cells that ingest and kill bacteria. In addition to phagocytic function, interstitial macrophages are antigen-processing cells, whereas the intravascular macrophages clear inflammatory debris through the bloodstream. Viral infection (especially due to influenza virus), high oxygen concentration, uremia, and use of alcohol or drugs can impair function of alveolar macrophages, predisposing to pneumonia. Cell-mediated immunologic mechanisms play an important role in pulmonary infections caused by viruses, and intracellular organisms such as Mycobacterium tuberculosis and Legionella that survive within pulmonary macrophages.

Clinical Manifestations

The symptoms of pneumonia are varied and nonspecific and may be subtle depending on several factors, including the etiologic agents, age of the host, inoculum size, and individual’s immune response (see Chapter 21 ). Acute onset of fever, cough, and tachypnea are classic. Fever can be absent in very young infants with C. trachomatis , B. pertussis , or Ureaplasma infection . Infants can manifest only poor feeding and fussiness. Children <5 years of age often have a prodrome of low-grade fever and rhinorrhea due to a viral URI before developing lower respiratory tract symptoms. Fever and rapid breathing can precede onset of cough in some children. Older children can complain of pleuritic chest pain or nuchal rigidity (each referable to the lobe involved). Signs of respiratory distress include tachypnea, hypoxemia (oxygen saturation <92%), apnea, increased work of breathing (subcostal, intercostal or suprasternal retractions; nasal flaring; or grunting) or altered mental status. Guidelines developed by the World Health Organization (WHO) for the clinical diagnosis of pneumonia in resource-limited countries highlight tachypnea and retractions as the two best indicators of LRI. Tachypnea is defined as >50 breaths/min in infants <12 months, >40 for those 1–5 years, and >30 for children >5 years of age. Among children <5 years of age, tachypnea (as defined by WHO) had the highest sensitivity (74%) and specificity (67%) for radiologically confirmed pneumonia but was less sensitive and specific early in the course of illness. ^, Tachypnea can occur with other conditions, such as fever, asthma, cardiac disease, and metabolic acidosis. The predictive values of clinical findings for pneumonia have been studied repeatedly. In one study, the combination of a respiratory rate >50 breaths/min, oxygen saturation <96%, and the presence of nasal flaring in children <12 months of age was highly associated with radiographically confirmed pneumonia. Oxygen saturation frequently is decreased with moderate to severe pneumonia and is an indication for hospital admission. ^, An hypoxemic infant or child may not appear cyanotic. Although hypoxemia, use of accessory muscles of respiration, head bobbing, nasal flaring, and grunting are predictive of pneumonia, their absence does not exclude pneumonia. ^, Decreased and bronchial breath sounds, egophony (“E” to “A” change), bronchophony, tactile fremitus, and dullness to percussion are specific signs of lung consolidation. Crackles heard upon auscultation are the hallmark of pneumonia but can be present due to noninfectious fluid and can be absent in a dehydrated patient. Isolated wheezing or prolonged expiration is associated with bronchiolitis and is uncommon in bacterial pneumonia. Almost three-fourths of children with radiographically confirmed pneumonia appear ill. Severity of illness correlates with the likelihood of a bacterial cause. Additionally, approximately 6%–25% of children <5 years of age with body temperature >39°C and a white blood cell (WBC) count >20,000/μL without an alternative source of major infection and with no symptoms or signs of lower respiratory tract disease have radiographically confirmed pneumonia.

In one study determining the interobserver agreement of signs of pneumonia, there was more observer agreement with clinical signs (respiratory rate and cyanosis) compared with retractions or auscultatory signs (crackles and wheezing) of pneumonia. Unfortunately, neither respiratory rate nor cyanosis is a sensitive or specific indicator of hypoxia. Oxygen saturation should be measured in any child with respiratory distress.