Continuing Education Activity

Globally, pneumonia is a leading cause of morbidity and mortality in children younger than the age of 5. Although the majority of deaths attributed to pneumonia in children are mostly in the developing world, the burden of the disease is substantial, and there are significant healthcare-associated costs related to pneumonia in the developed world. This activity reviews the cause, pathophysiology, and presentation of pediatric pneumonia and highlights the role of the interprofessional team in its management.

Objectives:

• Identify the etiology of pediatric pneumonia.

• Review the presentation of pediatric pneumonia.

• Outline the treatment and management options available for pediatric pneumonia.

• Describe interprofessional team strategies for improving care coordination and outcomes in pediatric patients with pneumonia.

Introduction

Globally, pneumonia is a leading cause of morbidity and mortality in children younger than 5.[1] Although the majority of deaths attributed to pneumonia in children are mostly in the developing world, the burden of the disease is substantial, and there are significant healthcare-associated costs related to pneumonia in the developed world.[2]

Etiology

The etiology of pneumonia in the pediatric population can be classified by age-specific versus pathogen-specific organisms.[3] Neonates are at risk for bacterial pathogens present in the birth canal, and this includes organisms such as group B streptococci, Klebsiella, Escherichia coli, and Listeria monocytogenes.[4][5][6] Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus can be identified in late-onset neonatal pneumonia.[4] Viruses are the main cause of pneumonia in older infants and toddlers between 30 days and 2 years old.[7] In children 2 to 5 years old, respiratory viruses are also the most common.[8][9] The rise of cases related to S pneumoniae and H influenzae type B is observed in this age group.[10][11] Mycoplasma pneumonia frequently occurs in children in the range of 5 to 13 years old[12][13]; however, S pneumoniae is still the most commonly identified organism.[8] Adolescents usually have the same infectious risks as adults. It is important to consider tuberculosis (TB) in immigrants from high-prevalence areas and children with known exposures. Children with chronic diseases are also at risk for specific pathogens. In cystic fibrosis, pneumonia secondary to S aureus and Pseudomonas aeruginosa is ubiquitous.[14] Patients with sickle cell disease are at risk of infection from encapsulated organisms.[15] Children who are immunocompromised should be evaluated for Pneumocystis jirovecii, cytomegalovirus, and fungal species if no other organism is identified.[16] Unvaccinated children are at risk for vaccine-preventable pathogens.

Epidemiology

There are an estimated 120 million cases of pneumonia annually worldwide, resulting in as many as 1.3 million deaths.[3] Younger children under the age of 2 in the developing world account for nearly 80% of pediatric deaths secondary to pneumonia.[17] The prognosis of pneumonia is better in the developed world, with fewer lives claimed, but the burden of disease is extreme, with roughly 2.5 million cases yearly. Approximately a third to half of these cases lead to hospitalizations.[18] The introduction of the pneumococcal vaccine has significantly lowered the risk of pneumonia in the United States.

Pathophysiology

Pneumonia is an invasion of the lower respiratory tract below the larynx by pathogens either by inhalation, aspiration, respiratory epithelium invasion, or hematogenous spread.[19] There are barriers to infection that include anatomical structures (nasal hairs, turbinates, epiglottis, cilia) and humoral and cellular immunity.[19] Once these barriers are breached, infection, either by fomite/droplet spread (mostly viruses) or nasopharyngeal colonization (mostly bacterial), results in inflammation and injury or death of surrounding epithelium and alveoli. This is ultimately accompanied by a migration of inflammatory cells to the site of infection, causing an exudative process, which in turn impairs oxygenation.[20] In the majority of cases, the microbe is not identified, and the most common cause is viral etiology.

There are 4 stages of lobar pneumonia: 

• The first stage occurs within 24 hours and is characterized by alveolar edema and vascular congestion. Both bacteria and neutrophils are present.
• Red hepatization is the second stage, and it has the consistency of the liver. The stage is characterized by neutrophils, red blood cells, and desquamated epithelial cells. Fibrin deposits in the alveoli are common.
• The third stage of gray hepatization stage occurs 2 to 3 days later, and the lung appears dark brown. There is an accumulation of hemosiderin and hemolysis of red cells.
• The fourth stage is the resolution stage, where the cellula infiltrates is resorbed, and the pulmonary architecture is restored. If the healing is not ideal, then it may lead to parapneumonic effusions and pleural adhesions.

In bronchopneumonia, there is often patch consolidation of one or more lobes. The neutrophilic infiltrate is chiefly around the center of the bronchi.

History and Physical

In many cases, complaints associated with pneumonia are nonspecific, including cough, fever, tachypnea, and difficulty breathing.[21] Young children may present with abdominal pain. Important history to obtain includes the duration of symptoms, exposures, travel, sick contacts, baseline health of the child, chronic diseases, recurrent symptoms, choking, immunization history, maternal health, or birth complications in neonates.[22] Physical exam should include observation for signs of respiratory distress, including tachypnea, nasal flaring, lower chest in-drawing, or hypoxia on room air.[21] 

Note that infants may present with a reported inability to tolerate feeds, with grunting or apnea. Auscultation for rales or rhonchi in all lung fields with the appropriately sized stethoscope can also aid in diagnosis. In the developed world, other adjuncts like laboratory testing and imaging can be a helpful part of the physical exam. No isolated physical exam finding can accurately diagnose pneumonia.[23] However, the combination of symptoms, including fever, tachypnea, focal crackles, and decreased breath sounds together, raises the sensitivity for finding pneumonia on x-ray.[23] Pneumonia is a clinical diagnosis that should take into consideration the history of present illness, physical exam findings, adjunct testing, and imaging modalities.

Evaluation

Laboratory evaluation in children suspected of having pneumonia should ideally start with non-invasive, rapid bedside testing, including nasopharyngeal swab assays for influenza, respiratory syncytial virus, and human metapneumovirus when available and appropriate. This can help minimize unnecessary imaging and antibiotic treatment in children with influenza or bronchiolitis. Children who present with severe disease and appear toxic should have complete blood count (CBC), electrolytes, renal/hepatic function testing, and blood cultures performed.[24] These tests are generally not required in children who present with mild disease. Inflammatory markers do not help distinguish between viral and bacterial pneumonia in the pediatric population.[24][25] However, these tests may be obtained to trend disease progression and serve as prognostic indicators. Children who have been in areas endemic to tubercluosis, or have an exposure history, and present with signs and symptoms suspicious of pneumonia should have sputum samples or gastric aspirates collected for culture.

Sputum Gram stain and culture are not productive as the samples are often contaminated by oral flora. Blood cultures can be done but are often negative. Today, serology is being used to determine the presence of mycoplasma, legionella, and chlamydia species. Polymerase chain reaction is becoming available in most hospitals, but still, the results take 24 to 48 hours. There are no clear guidelines for the routine use of chest x-ray in the pediatric population.[24] Although the chest x-ray can be helpful in the diagnosis and confirmation of pneumonia,[26] it carries with it risks, including radiation exposure, healthcare-associated costs, and false-negative results, increasing the use of unwarranted antibiotics. Imaging should be restricted to children who appear toxic, those with a recurrent or prolonged course of illness despite treatment, and infants ages 0 to 3 months with a fever, suspected foreign body aspiration, or congenital lung malformation. Imaging can also be considered in children younger than 5 years old who present with fever, leukocytosis, and no identifiable source of infection.[26] Imaging may also be useful in those with acute worsening of upper respiratory infections or to rule out underlying mass in children who have "round pneumonia."[27][28]

Treatment / Management

Treatment should be targeted to a specific pathogen that is suspected based on information obtained from history and physical exam. Supportive and symptomatic management is key and includes supplemental oxygen for hypoxia, antipyretics for fever, and fluids for dehydration. This is especially important for non-infectious pneumonitis and viral pneumonia for which antibiotics are not indicated.[21][29] Cough suppressants are not recommended.

If bacterial pneumonia is suspected, treat empirically with antibiotics, keeping in mind significant history and bacterial pathogens that are common to specific age groups. Neonates should receive ampicillin plus an aminoglycoside or third-generation cephalosporin;[21][30] however, not ceftriaxone, as it can displace bound bilirubin and lead to kernicterus. Atypical pneumonia is common in infants 1 to 3 months old, and this group should have additional antibiotic coverage with erythromycin or clarithromycin.[21][30] For infants and children over 3 months old, S pneumoniae is the most common, for which the drug of choice is high-dose oral amoxicillin or another beta-lactam antibiotic.[21][30] In children older than 5, atypical agents have a more important role, and macrolide antibiotics are usually first-line therapy.[21]

Special attention should be given to children with chronic illnesses, as these might alter choices for antibiotics[21]. Children with sickle cell anemia will need cefotaxime, macrolide, and vancomycin if severely ill. Children with cystic fibrosis will require piperacillin or ceftazidime plus tobramycin. Treat fulminant viral pneumonia as indicated, depending on the virus identified. For Varicella, use acyclovir, and for the respiratory syncytial virus (RSV), use ribavirin for high-risk patients. Patients with human immunodeficiency virus should be treated with sulfamethoxazole/trimethoprim and prednisone, and for cytomegalovirus, ganciclovir, and gamma globulin are the preferred agents. If methicillin-resistant S aureus (MRSA) is suspected, clindamycin or vancomycin may be given.

It is important to have a high index of suspicion for complications, especially in patients returning for repeat evaluation. For patients sent home with symptomatic or supportive management for suspected viral pneumonia, consider a secondary bacterial infection or other diagnoses upon re-evaluation.[31] Children with uncomplicated bacterial infections who fail to respond to treatment within 72 hours should be assessed for complications, including pneumothorax, empyema, or pleural effusion.[32] Other systemic complications of pneumonia include sepsis, dehydration, arthritis, meningitis, and hemolytic uremic syndrome.

Neonates and infants younger than 90 days old should be hospitalized for treatment, in addition to children who are immunocompromised or have other underlying chronic diseases like sickle cell anemia or cystic fibrosis.[21] Children with social factors that preclude access to care have failed outpatient therapy, or present with presumed tuberculosis should also be hospitalized.[33] Admission is often required for patients with respiratory distress and low oxygenation. In most cases, the presence of a parapneumonic effusion requires admission. Children with severe respiratory distress may require chest therapy or even mechanical ventilation. A large pleural effusion requires drainage for diagnostic and therapeutic purposes. In patients with empyema, early video-assisted thoracic surgery (VATS) correlates with decreased mortality, hospital stay, and ionizing radiation from CT scans. It is essential to ensure that clear discharge instructions and return precautions are given to parents or caregivers of children being discharged home in addition to close pediatrician follow-up.

Differential Diagnosis

The differential diagnosis for pediatric pneumonia includes:

• Alveolar proteinosis
• Aortic stenosis
• Aseptic meningitis 
• Asphyxiating thoracic dystrophy 
• Aspiration syndromes 
• Asthma 
• Atelectasis
• AV septal defect, complete 
• AV septal defect, unbalanced 
• Bacteremia
• Birth trauma

Prognosis

For most children, the prognosis is good. Viral pneumonia tends to resolve without treatment. Long-term sequelae are rare. However, both staphylococcal and varicella pneumonia have guarded outcomes in children. Children with tuberculosis are at high risk for disease progression if the condition is not treated. Immunocompromized children have the worst prognosis. Each year, roughly 3 million children die from pneumonia, and the majority of these children also have other comorbidities like congenital heart disease, immunosuppression, or chronic lung disease of prematurity.

Complications

Complications of pediatric pneumonia include the following:

• Empyema
• Pleural effusion
• Lung abscess
• Necrotizing pneumonia
• Sepsis

Enhancing Healthcare Team Outcomes

Pediatric pneumonia is often undertreated or missed, leading to high morbidity and mortality. The condition is best managed by an interprofessional team to improve outcomes. The majority of patients are managed by the pediatrician, nurse practitioner, or primary care provider.  Patient and caregiver education is vital. Parents need to be told to avoid smoking, and the importance of handwashing cannot be overstated. In addition, all clinicians looking after children should emphasize vaccination against pneumococcus and influenza.

Healthcare professionals, including physicians, nurses, physician assistants, nurse practitioners, and pharmacists, ideally work together in close environments for optimum patient care. When caring for children with pneumonia, pharmacists can be of significant help with geographic resistance patterns for better treatment outcomes with selected antibiotic choices. Caregivers should be educated about signs of respiratory difficulty and when to seek medical assistance. Only through a team approach can pneumonia in children be treated promptly with minimal morbidity.