What's New in Pediatric Lower Respiratory Tract Infections?

June 26, 2012

Lower respiratory tract infections are among the most frequent causes for office visits and hospitalizations of otherwise healthy young US children. Here, an overview of current guidance on diagnosis and management.

Lower respiratory tract infections (LRTIs) remain one of the most frequent reasons for health care visits and hospitalizations in otherwise healthy, young children living in the United States. Familiarity with the causes of LRTIs and accurate clinical diagnosis remain the cornerstones of appropriate management. Currently available vaccines and annual immune-protectants such as palivizumab are important for reducing the burden of disease.

How can the cause of LRTI best be determined?

In most cases, the cause of LRTI can be determined on the basis of epidemiologic features, the child’s age and clinical presentation, and judicious use of ancillary laboratory testing and radiographs (eg, to confirm diagnostic suspicion or assess clinical severity). Making a clinical diagnosis first helps prevent the pitfall of overreliance on chest radiograph findings, which is known to increase unnecessary antibiotic use in children whose clinical syndrome is consistent with viral infection.
 
Once a child presents with symptoms of LRTI-fever, cough, reduced energy or oral intake, and some degree of respiratory distress and/or hypoxemia-the first step toward diagnosis is a history and physical examination to localize the infection and determine the clinical syndrome. Useful characteristics for distinguishing between tracheobronchitis, bronchiolitis, and community-acquired pneumonia (CAP) are described in the Table (see page 3). (Age and epidemiologic risk factors are fundamentally important to diagnosis and are the basis of empiric treatment decisions in CAP.)
 
Diagnosing common types of LRTIsAcute tracheobronchitis is often diagnosed when a patient presents with cough, gagging, and substernal chest pain accompanied by low-grade fever, rhinitis and, occasionally, conjunctivitis. The lung examination is typically clear. This, along with absence of tachypnea and hypoxemia, distinguishes tracheobronchitis from viral or atypical pneumonia. Nearly all cases of acute tracheobronchitis in children are related to viral nasopharyngitis. The infection resolves spontaneously.

Children and adults who present with persistent (>2 weeks) unabating cough may be infected with Bordetella pertussis. This organism causes epidemic pertussis and is an increasingly common cause of tracheobronchitis in some areas (most recently, California and Washington). In infants, B pertussis can cause apnea, recurrent choking, or an apparent life-threatening event. The pertussis cough alone, however, is indistinguishable from a viral cough.

Bronchiolitis, an inflammation of the airways down into the bronchioles, is characterized by significant nasal congestion and profuse rhinorrhea that occurs simultaneously with lower respiratory tract signs. This pattern is in contrast to that of pneumonia, which is characterized by an upper respiratory tract prodrome followed by sequential onset of lower respiratory tract involvement. Infants with bronchiolitis typically are fussy and have prominent nasal symptoms, nasal flaring, retractions, tachypnea, diffuse inspiratory crackles and expiratory wheezes, and hypoxemia.

Bacterial pneumonia causes infants to appear listless, drowsy, or anxious. They have high fever, tachypnea, and tachycardia, but a surprisingly quiet chest.

In both infants and children, careful examination may reveal focally decreased breath sounds or dullness to percussion over an area of consolidation. Older children typically have dry cough and may complain of vomiting, diarrhea, chest pain, or abdominal pain. In a cooperative child with a larger chest, the examiner may discover splinting, egophony, bronchial breath sounds, fine end-inspiratory rales, and a reduction in fremitus.

Viral and atypical pneumonia are more common than bacterial pneumonia. Both are typically characterized by diffuse or multifocal crackles or wheezes accompanied by fever, tachypnea, and hypoxemia. Wheezing alone, without fever or hypoxemia, is unlikely to be related to CAP (2% vs 20% with fever and oxygen saturation < 92%).3

Evidence indicates a significant rate of viral-viral and viral-bacterial coinfection in patients with CAP. One recent study found Streptococcus pneumoniae in 20% to 40% of patients who had severe CAP associated with positive Mycoplasma pneumoniae serology or a positive viral antigen (respiratory syncytial virus [RSV], influenza) test.4 This reminds us to be vigilant when following and reevaluating patients whose initial diagnosis is a viral syndrome.

When should ancillary testing be performed?

Ancillary testing is most useful to:

• Establish the onset of a seasonal epidemic (as with influenza and RSV rapid antigen testing)

• Confirm the diagnosis of an infection that may require specific treatment (eg, influenza, B pertussis, Mpneumoniae)

• Distinguish between viral and bacterial pneumonia, and

• Assess illness severity and check for complications in infants or children hospitalized with CAP.

Infants and children with clinically diagnosed viral bronchiolitis require no further diagnostic testing. The exception is if they do not improve as expected after symptoms peak at 3 to 4 days of illness.5

Continued on next page...

Types of ancillary testsNasopharyngeal culture and polymerase chain reaction (PCR). Infants and children in whom tracheobronchitis related to B pertussis is suspected should be evaluated by nasopharyngeal culture and PCR within 2 and 4 weeks, respectively, of starting to cough.

Complete blood cell (CBC) count, blood culture, chest radiographs. In infants in whom pertussis is diagnosed, a high or rapidly rising total white blood cell (WBC) count is a marker for disease severity and the test should be ordered on diagnosis.6

For infants and children with CAP who will be managed as outpatients, a CBC count, blood culture, and chest radiographs are not recommended: the WBC count has low specificity for bacterial pneumonia, mild to moderate pneumococcal disease produces low rates of bacteremia, and chest films do not direct beneficial changes in management. Studies show that while experienced radiologists have a high rate of inter-rater reliability when diagnosing alveolar pneumonia (believed to be the pattern most suggestive of bacterial disease), non-radiologists-including experienced pediatricians-tend to over-read interstitial infiltrates at a rate of 5 to 1.7

In children who are not sick enough to require hospitalization, it can be remarkably difficult to distinguish between viral and mild to moderate bacterial pneumonia. Although no single finding (from history and physical examination), inflammatory marker, or radiographic appearance is perfectly sensitive for supporting the diagnosis of bacterial pneumonia, there is value in interpreting these findings additively. For instance, a 3-year-old with fever and focal rales in the ED may have a 20% pre-test probability of having bacterial pneumonia; add to this a C-reactive protein (CRP) value of <2 (negative likelihood ratio for serious bacterial infection 0.33), and the post-test probability drops to 8%.8  Conversely, in a child hospitalized for suspicion of bacterial pneumonia with fever, focal rales, and oxygen saturation 94%, a CRP value >8 (positive likelihood ratio for serious bacterial infection 5 to 14) significantly shifts the post-test probability in favor of bacterial disease.

When an infant or child is sick enough to require hospitalization, a CBC count, blood culture, and chest radiograph are recommended: the CBC count may demonstrate clinically significant anemia or thrombocytopenia; bacteremia rates exceed false-positive rates (1.4% to 11.4%), and chest radiographs may delineate complications requiring additional therapy.3Rapid viral antigen testing is available for RSV, parainfluenza viruses 1 through 3, influenza A and B viruses, and adenovirus, and is useful for evaluating a patient with CAP. Viral detection facilitates early initiation of antiviral therapy for influenza. It also decreases ancillary testing and unnecessary antibiotic exposure when respiratory failure and signs of bacterial disease are otherwise absent.

Serologic testing for mycoplasma, when available, is most helpful for children (≥5 years) in whom prevalence is high and signs or symptoms are suggestive of, but not definitive for, atypical pneumonia. Laboratory-performed cold agglutinins in titers that exceed 1:64 have reasonable positive predictive value, but this testing has not been well studied in children, and the specificity of lower titers is unknown.

Which LRTIs require specific treatment, and what are the current treatment recommendations?

Acute viral respiratory conditions in children are responsible for 10 million unnecessary antibiotic prescriptions in the United States each year.9  

Tracheobronchitis and bronchiolitis. These conditions should be managed supportively. Hydration, humidified air, skin rubs containing menthol,10 and honey (in children >12 months)11 are beneficial and safe for managing cough. Avoid products containing codeine and dextromethorphan in children and young (<6 years) children, respectively; these products have a poor safety profile in this age group.

Numerous studies show no consistent benefit for corticosteroids, nasal decongestants, β-agonists, ribavirin, heliox, or antibiotics in infants and children with bronchiolitis. Currently, the American Academy of Pediatrics (AAP) does not recommend routine β-agonist therapy but acknowledges that a trial of albuterol or epinephrine is reasonable in the atopic patient. Small studies show that hypertonic saline decreases symptom scores in outpatients and length of stay in hospitalized patients, but does not affect hospitalization rates or inpatient symptom scores.12,13 Larger studies are needed to determine whether this therapy should be more widely adopted.

CAP. The Pediatric Infectious Diseases Society and the Infectious Diseases Society of America jointly sponsored guidelines for the management of pediatric CAP in August 2011.3 Antimicrobial therapy is not routinely recommended for preschool-aged children with CAP because of the preponderance of viral disease in this age group. Other recommendations are as follows:

- Fully immunized infants, children, and adolescents being treated for suspected bacterial pneumonia in the outpatient setting. Amoxicillin is recommended as first-line therapy, since S pneumoniae remains the most important cause of bacterial pneumonia across all age groups.

- School-aged and adolescent children who have signs and symptoms consistent with atypical CAP. Macrolide therapy is recommended. Influenza antiviral therapy is recommended for managing progressive influenza and influenza-like illness during seasonal epidemics. Younger children with documented M pneumoniae infection have high rates of spontaneous resolution.

- High-risk groups. The CDC provides detailed guidance regarding early treatment for groups at high risk for influenza-related complications, including children younger than 5 years, children with chronic conditions, and children with influenza requiring hospitalization.
 

How can LRTIs be prevented?

Many currently important LRTIs are vaccine-preventable, including those related to B pertussis, influenza A and B viruses, and many S pneumoniae serotypes.

Institution of the heptavalent pneumococcal conjugate vaccine (PCV7) in 2000 reduced the incidence of clinically diagnosed pneumonia and clinical pneumonia with a positive chest radiograph by 6% and almost 18%, respectively, in children younger than 24 months.14 The PCV7 has also reduced the incidence of human metapneumovirus (hMPV)-associated CAP, providing more evidence of a direct link between viral and pneumococcal disease.4

The 13-valent pneumococcal conjugate vaccine (PCV13), licensed in 2010, offers further protection against serotypes (primarily 1 and 19A) that have emerged as common causes of pneumococcal pneumonia since PCV7 was introduced. A single dose of PCV13 is recommended for further protection of children younger than 5 years who completed their vaccine series with PCV7.

Pediatricians, family physicians, and obstetricians have been asked to take a greater role in providing Tdap booster vaccination to caregivers of infants younger than 12 months in order to “cocoon” them against pertussis. A recent study showed this was not only feasible but important, since a significant proportion of those vaccinated had no routine medical care.15

No vaccine yet exists for preventing bronchiolitis or pneumonia related to RSV, the single largest cause of LRTI and hospitalization among infants and very young children. Appropriate use of palivizumab reduces hospitalization rates and disease severity for premature infants as well as those whose comorbid medical conditions put them at highest risk for negative outcomes from RSV infection. For these young children and for otherwise healthy infants, counseling parents to avoid smoke exposure can have a meaningful impact, because passive smoke exposure is associated with a 2.51 odds ratio (OR) of bronchiolitis and a 1.58 OR of LRTI overall.16 Breast-feeding and hand-washing with soap are additional strategies to help protect this vulnerable population.

Table and References on next page...

Localization of infectionClinical syndromeAgeImportant causesEpidemiologic features
Tracheobronchial treeTracheobronchitisAnyRespiratory viruses:   Parainfluenza       virus   Adenovirus   Influenza virus   Rhinovirus   RSV• Sick contacts
  AnyBordetella pertussis• Incomplete immunization against pertussis • Exposure to contact with > 2 wk cough and lack of Tdap booster
BronchioleBronchiolitis3 wk to 2 y (80% are < 1 y

Respiratory viruses:
  RSV (most 
    prevalent)
  Metapneumo-
    virus
 Rhinovirus

Lung parenchymaCAPNeonateGroup B     streptococcus Enteric organisms Cytomegalovirus• Perinatally or nosocomially acquired infection
  3 wk to 3 moRSV• Sick contacts • Prevalence 4% to 40% across all age groups
   C trachomatis B pertussis• Maternal history of STI • Exposure to contact with > 2 wk cough and lack of Tdap booster
  4 mo to 4 yRespiratory viruses:    RSV    Adenovirus   Metapneumo-     virus   Bocavirus   Influenza virus   Parainfluenza     virus• Viruses cause up to 80% of CAP at age 2 to 3 y (prevalence decreases thereafter)
   S pneumoniae• Prevalence 4% to 40% across all age groups
   S aureus• Maternal breast abscess, close contact with SSTI
   M pneumoniae• Up to 18% of CAP in this age group
  5 to 15 yM pneumoniae• 50% of CAP in children aged ≥ 5 y; prevalence increases with age
   S pneumoniae• Less frequent than
   C pneumoniae• 13% of CAP in children aged 5 to 10 y; 35% of CAP in those ≥ 10 y old

RSV, respiratory syncytial virus; CAP, community-acquired pneumonia; STI, sexually transmitted infections; SSTI, skin and soft tissue infection.

References
1. Korppi M. How to diagnose Mycoplasmapneumoniae etiology in a child with pneumonia? Eur J Pediatr. 2011;170:1619.
2. Korppi M, Heiskanen-Kosma T, Kleemola M. Incidence of community-acquired pneumonia in children caused by Mycoplasmapneumoniae: serological results of a prospective, population-based study in primary health care. Respirology. 2004;9:109-114.
3. Bradley JS, Byington CL, Shah SS, et al. The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America. Clin Infect Dis. 2011;53(7):e25-e76.
4. Esposito S, Cohen R, Domingo JD, et al. Antibiotic therapy for pediatric community-acquired pneumonia: do we know when, what, and for how long to treat? Pediatr Infect Dis J. 2012;31:e78-e85.
5. Wagner T. Bronchiolitis. Pediatr Rev. 2009;30:386-395.
6. Cherry JD. Characteristics of severe pertussis infections among infants ≤90 days of age admitted to pediatric intensive care units, Southern California, September 2009-June 2011. Presented at: International Conference on Emerging Infectious Diseases; March 12, 2012; Atlanta. Available at: www.iceid.org. Accessed June 13, 2012.  
7. Ben Shimol S, Dagan R, Givon-Lavi N, et al. Evaluation of the World Health Organization criteria for chest radiographs for pneumonia diagnosis in children. Eur J Pediatr. 2012;171:369-374.
8. Van den Bruel A, Thompson MJ, Haj-Hassan T, et al. Diagnostic value of laboratory tests in identifying serious infectious in febrile children: systematic review. BMJ. 2011;342:d3082.
9. Hersh AL, Shapiro DJ, Pavia AT, Shah SS. Antibiotic prescribing in ambulatory pediatrics in the United States. Pediatrics. 2011;128:1053-1061.
10. Paul IM, et al. “Vapor rub, petrolatum, and no treatment for children with nocturnal cough and cold symptoms. Pediatrics. 2010;126:1092-1099.
11. Coughs and colds: medicines or home remedies? American Academy of Pediatrics, HealthyChildren.Org. Available at: http://www.healthychildren.org/English/health-issues/conditions/ear-nose-throat/Pages/Coughs-and-Colds-Medicines-or-Home-Remedies.aspx. Accessed June 13, 2012.
12. Zhang L, Mendoza-Sassi RA, Wainwright C, Klassen TP. Nebulized hypertonic saline solution for acute bronchiolitis in infants. Cochrane Database Syst Rev. 2008;(4):CD006458. doi:10.1002/14651858.CD006458.pub2.
13. Wacogne I. Nebulised hypertonic saline reduced the severity of illness in infants with bronchiolitis. Arch Dis Child Educ Pract Ed. 2010;95:168. doi:10.1136/adc.2010.193557.
14. Black SB, Shinefield HR, Ling S, et al. Effectiveness of heptavalent pneumococcal conjugate vaccine in children younger than five years of age for prevention of pneumonia. Pediatr Infect Dis J. 2002;21:810-815.
15. Camenga DR, Kyanko K, Stepczynski J, et al. Increasing adult Tdap vaccination rates by vaccinating infant caregivers in the pediatric office. Acad Pediatr. 2012;12:20-25.
16. Jones LL, Hashim A, McKeever T, et al. Parental and household smoking and the increased risk of bronchitis, bronchiolitis and other lower respiratory infections in infancy: systematic review and meta-analysis. Respir Res. 2011;12:5.