eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Bronchiolitis

Author: Lucian Kenneth DeNicola, MS, MD, FAAP, FCCM, Professor, Department of Pediatrics, University of Florida Health Science Center at Jacksonville
Coauthor(s): Nizar F Maraqa, MD,, Assistant Professor of Pediatrics, Pediatric Infectious Diseases, University of Florida College of Medicine at Jacksonville; Haidee T Custodio, MD, Fellow in Pediatric Infectious Diseases and Immunology, University of Florida College of Medicine
Contributor Information and Disclosures

Updated: Oct 28, 2009

Introduction

Background

Bronchiolitis is an acute, infectious, inflammatory disease of the upper and lower respiratory tract that may result in obstruction of the small airways. Although it may occur in all age groups, the larger airways of older children and adults better accommodate mucosal edema; severe respiratory symptoms are usually limited to young infants.

A chest radiography revealing lung hyperinflation...

A chest radiography revealing lung hyperinflation with a flattened diaphragm and bilateral atelectasis in the right apical and left basal regions in a 16-day-old infant with severe bronchiolitis.

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A chest radiography revealing lung hyperinflation...

A chest radiography revealing lung hyperinflation with a flattened diaphragm and bilateral atelectasis in the right apical and left basal regions in a 16-day-old infant with severe bronchiolitis.


Pathophysiology

Necrosis of the respiratory epithelium is one of the earliest lesions in bronchiolitis and occurs within 24 hours of the acquisition of infection.1 Proliferation of goblet cells results in excessive mucus production, whereas epithelial regeneration with nonciliated cells impairs elimination of secretions. Lymphocytic infiltration may result in submucosal edema. Cytokines and chemokines, released by infected respiratory epithelial cells, amplify the immune response by increasing cellular recruitment into infected airways. Interferon and interleukin (IL)-4, IL-8, and IL-9 are found in high concentrations in respiratory secretions of infected patients.2,3  

In 2007, Johnson et al analyzed autopsy findings of children who died due to respiratory syncytial virus (RSV) from 1925-1959, before modern intensive care, and autopsy findings of a child with RSV bronchiolitis who died in a motor vehicle accident.4 They found that small bronchiole epithelium was circumferentially infected, but basal cells were spared. Both type 1 and type 2 alveolar pneumocytes were also infected. Airway obstruction was due to epithelial and inflammatory cell debris mixed with fibrin, mucus, and edema fluid but not bronchial smooth muscle constriction.4 Neutrophile inflammation, but not eosinophile inflammation, is related to the severity of a first infection in infants.5

The pathology results in obstruction of bronchioles from inflammation, edema, and debris, leading to hyperinflation, increased airway resistance, atelectasis, and ventilation-perfusion mismatching. Bronchoconstriction has not been described.

Infants are affected most often because of their small airways, high closing volumes, and insufficient collateral ventilation. Recovery begins with regeneration of bronchiolar epithelium after 3-4 days, but cilia do not appear for as long as 2 weeks. Macrophages remove mucus plugs. Risk factors include the following:6,7,8,9

  • Low birth weight, particularly premature infants10
  • Gestational age (independently associated with hospital resource use and outcome among infants hospitalized for RSV){Ref182}
  • Lower socioeconomic group11
  • Crowded living conditions, daycare, or both
  • Parental smoking12
  • Chronic lung disease, particularly bronchopulmonary dysplasia
  • Severe congenital or acquired neurologic disease
  • Congenital heart disease (CHD) with pulmonary hypertension13 (Interestingly, French children with CHD did not show increased risk.14 )
  • Congenital or acquired immune deficiency diseases
  • Age less than 3 months
  • Airway anomalies

Virtually all children experience RSV infection within the first 3 years of life, but previous infection does not convey complete immunity. Reinfection is common, but significant antibody titers ameliorate severity of symptoms.15

Frequency

United States

Respiratory infection is observed in 25% of children younger than 12 months and 13% of children aged 1-2 years. Of these 25%, one-half have wheezing-associated respiratory disease. RSV can be cultured from one third of these outpatients and from 80% of hospitalized children younger than 6 months. Nearly 100% of children experience an RSV infection within 2 RSV seasons, and 1% are hospitalized. Among healthy full-term infants, 80% of hospitalizations occur in the first year, and 50% of hospitalizations occur in children aged 1-3 months.11

From 1980-1995, admissions associated with bronchiolitis totalled 1.65 million. The hospitalization rate for children younger than 1 year doubled from 12.9 to 31.2 per 1000 population, and the number of hospitalized children diagnosed with bronchiolitis tripled from 5.4% to 16.4%.11 From 2003-2004, the morbidity and mortality rates of bronchiolitis were unchanged. However, an estimated 51,000-82,000 patients were hospitalized annually for bronchiolitis. The increase in hospitalizations is not due to increased pediatrician risk aversion, but rather is attributable to physicians' desire to treat the condition with bronchodilators. The cost of hospitalization for bronchiolitis in children younger than 1 year is estimated to be more than $700 million per year.12,15

Fewer than 5% of hospitalizations occur in the first 30 days of life, presumably because of transplacental transfer of maternal antibody.

In the temperate climates of the northern hemisphere, RSV epidemics generally occur annually in winter and late spring, whereas Parainfluenzae outbreaks usually occur in the fall. Conversely, in the southern hemisphere, wintertime epidemics occur from May to September. Evidence indicates that RSV is endemic throughout the year in the subtropical areas of the southeastern United States, with peaks from October to February and subsidence only from March through July.16

Secondary infections occur in 46% of family members, 98% of other children in daycare, 42% of hospital staff, and 45% of previously uninfected hospitalized infants. Infection is spread through self-inoculation of fomites via direct contact and environmental surfaces to nasopharyngeal or ocular mucous membranes. RSV can survive for several hours on hands and surfaces; therefore, handwashing and using disposable gloves and gowns may reduce nosocomial spread.17,18,10,1

International

Bronchiolitis is a significant cause of respiratory disease worldwide. Its incidence in developed countries appears similar to that in the United States. Epidemiologic data from underdeveloped countries are incomplete. Worldwide, RSV is responsible for 3-5 million deaths annually.

Mortality/Morbidity

RSV bronchiolitis accounts for more than 90,000 pediatric hospitalizations and as many as 4,500 deaths annually. Overall, the mortality rate in children hospitalized for bronchiolitis in different series is 0.2-7%. This large variability is based on investigations of different cohorts with different risk factors and different points in time relative to modern intensive care. Recent studies in pediatric ICUs (PICUs) of children with RSV bronchiolitis without comorbidities show a 2-3% death rate, regardless of whether the children had CHD with pulmonary hypertension.8

Sex

Boys are affected 1.7 times more often than girls; the male-to-female ratio of hospitalization among these children is 1.5:1. Death is 1.5 times more likely in males.

Age

Although RSV bronchiolitis is clearly a significant disease of the young child, no lifelong immunity occurs; mildly symptomatic or asymptomatic adults can be infected and act as carriers. With the increasing use of treatment modalities that compromise cellular immunity, RSV infection may be life threatening to older children and adults undergoing organ and bone marrow transplantation.

Clinical

History

Because bronchiolitis primarily affects young infants, clinical manifestations are initially subtle. Infants may become increasingly fussy and have difficulty feeding during the 2-day to 5-day incubation period. A low-grade fever, usually less than 101.5°F, and increasing coryza and congestion usually follow the incubation period. Sixty percent of primary respiratory syncytial virus (RSV) infections are confined to the upper airway. During a period of 2-5 days, this may progress to lower respiratory tract involvement with the development of cough, dyspnea, wheezing, and feeding difficulties. When the patient is brought to medical attention, the fever has usually resolved. Infants younger than 1 month may present as hypothermic. Severe cases progress to respiratory distress with tachypnea, nasal flaring, retractions and irritability, and, possibly, cyanosis.

Physical

  • Examination often reveals the following:
    • Otitis media
    • Tachypnea
    • Tachycardia
    • Fever (38-39 º C)
    • Retractions
    • Fine rales (47%)
    • Diffuse, fine wheezing
  • Diagnosis is made based on age and seasonal occurrence, tachypnea, and the presence of profuse coryza and fine rales, wheezes, or both upon auscultation of the lungs.
    • Hypoxia is the best predictor of severe illness and correlates best with the degree of tachypnea (>50 breaths per min). The degree of wheezing or retractions correlates poorly with hypoxia.
    • First-time infections are usually most severe. Subsequent attacks are generally milder, particularly in older children.
    • Nonrespiratory manifestations of RSV infections include otitis media, myocarditis, supraventricular and ventricular dysrhythmias, and inappropriate secretion of antidiuretic hormone.
  • In one study, apnea developed in 18-20% of young infants hospitalized with RSV bronchiolitis. Other studies have noted far lower rates of apnea. Frequency of apnea increases among premature infants whose gestation was less than 32 weeks, infants who have not yet reached age 44 weeks from conception, and especially among those who have neonatal apnea. Using the criteria of (1) full-term age less than 1 month, (2) preterm age less than 48 weeks, and (3) observed apnea Willwerth et al found the incidence of in-hospital apnea was only 2.7%.19
    • Apnea occurs early in the course of the disease and may be the presenting symptom.
    • Nonobstructive central apnea occurs during quiet sleep and is associated with increases in the apnea index (percentage of time the baby spends apneic), apnea attack rate (the number of episodes of apnea per unit time), and apnea percentage (the distribution of episodes of apnea while in a given sleep state).
    • Apnea rarely lasts longer than a few days; however, approximately 10% of these patients require intubation and mechanical ventilation. Because very few cases of sudden infant death syndrome are attributable to bronchiolitis, most infants with apnea apparently self stimulate and recover spontaneously. Mild RSV disease in young infants is not an indication for hospitalization to observe for apnea.

Causes

RSV is the most commonly isolated agent in 75% of children younger than 2 years who are hospitalized for bronchiolitis. RSV is an enveloped RNA virus that belongs to the Paramyxoviridae family within the Pneumovirus genus.

  • Agents that cause wheezing-associated respiratory infections include the following:
    • RSV causes 20-40% of all cases and 44% of cases that involve children younger than 2 years.
      • Two RSV subtypes, A and B, have been identified based on the structural variations in the G protein. Subtype A causes the most severe infections. One subtype usually predominates during a given season; thus, RSV disease has "good" and "bad" years.
      • The disease is highly contagious. Viral shedding in nasal secretions continues for 6-21 days after symptoms develop. The incubation period is 2-5 days.20
    • Parainfluenza virus causes 10-30% of all bronchiolitis cases.
    • Adenovirus accounts for 5-10% of bronchiolitis cases.
    • Influenza virus accounts for 10-20% of bronchiolitis cases.
    • Mycoplasma pneumoniae infection accounts for 5-15% of bronchiolitis cases, particularly among older children and adults.
    • A newly discovered virus, human metapneumovirus (hMPV), has been increasingly implicated as an etiologic agent in bronchiolitis. First identified in Holland in 2001, it is a paramyxovirus.
      • Serologic studies indicated that, by age 5 years, all Dutch children had seroconverted and that the virus had been prevalent in the population for at least 50 years.
      • In a retrospective examination of nasal washings obtained between 1976 and 2001 from 2009 children with acute respiratory tract illness, 248 had identifiable viruses. Of these, 20% were identified as hMPV, accounting for 12% of all viral lower respiratory illness in children younger than 2 years.
      • The mean age in the hMPV group was 11.6 months, with a male-to-female ratio of 1.8:1. They most often had illnesses between December and April, and 2% were hospitalized. The virus was associated with bronchiolitis in 59% of patients.
      • Subsequent studies have shown that hMPV accounts for 5-50% of bronchiolitis cases, seems to occur later in the bronchiolitis season, occurs with higher fevers, affects somewhat older children, and causes more wheezing but less oxygen requirement (possibly because the children are older and have less atelectasis).
      • Recent observations note that dual infections with both hMPV and RSV are strongly associated with severe bronchiolitis, with a 10-fold increase in PICU admission.
    • Human bocavirus (HBoV) was discovered in 2005 and causes both upper and lower respiratory infections. It has been implicated in both pertussis and bronchiolitislike syndromes. Arnold demonstrated that 5.6% of 1474 nasal scrapings collected over a 20-month period at San Diego Children's Hospital tested positive for HBoV, mostly in the months of March through May.21
  • Abundant evidence reveals that complex immunologic mechanisms play a role in the pathogenesis of RSV bronchiolitis. Type I allergic reactions mediated by the immunoglobulin E (IgE) antibody may account for clinically significant bronchiolitis. Breastfed babies, who receive colostrum rich in immunoglobulin A (IgA), appear relatively protected from bronchiolitis.

More on Bronchiolitis

Overview: Bronchiolitis
Differential Diagnoses & Workup: Bronchiolitis
Treatment & Medication: Bronchiolitis
Follow-up: Bronchiolitis
Multimedia: Bronchiolitis
References
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Further Reading

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Keywords

bronchiolitis, wheezy bronchitis, respiratory syncytial virus, RSV, lower respiratory tract infection, respiratory syncytial virus, wheeze, wheezing, parainfluenza virus, adenovirus, influenza, Mycoplasma pneumoniae, M pneumoniae

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Contributor Information and Disclosures

Author

Lucian Kenneth DeNicola, MS, MD, FAAP, FCCM, Professor, Department of Pediatrics, University of Florida Health Science Center at Jacksonville
Lucian Kenneth DeNicola, MS, MD, FAAP, FCCM is a member of the following medical societies: American Academy of Pediatrics, American College of Critical Care Medicine, Florida Medical Association, Florida Pediatric Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Nizar F Maraqa, MD,, Assistant Professor of Pediatrics, Pediatric Infectious Diseases, University of Florida College of Medicine at Jacksonville
Nizar F Maraqa, MD, is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Haidee T Custodio, MD, Fellow in Pediatric Infectious Diseases and Immunology, University of Florida College of Medicine
Disclosure: Nothing to disclose.

Medical Editor

David Jaimovich, MD, Chief Medical Officer, Joint Commission International and Joint Commission Resources
David Jaimovich, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Mark R Schleiss, MD, American Legion Chair of Pediatrics, Professor of Pediatrics, Division Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota Medical School
Mark R Schleiss, MD is a member of the following medical societies: American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Robert W Tolan Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society for Microbiology, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, Phi Beta Kappa, and Physicians for Social Responsibility
Disclosure: GlaxoSmithKline Honoraria Speaking and teaching; MedImmune Honoraria Speaking and teaching; Merck Honoraria Speaking and teaching; sanofi pasteur Honoraria Speaking and teaching; Baxter Healthcare Honoraria Speaking and teaching

Chief Editor

Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association
Disclosure: None None None

 
 
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