Pediatrics, BronchiolitisArticle Last Updated: Nov 1, 2007

AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

Author: Mark Louden, MD, FACEP, Assistant Medical Director, Emergency Department, Duke Raleigh Hospital

Mark Louden is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians

Editors: Kirsten A Bechtel, MD, Associate Professor of Pediatrics, Department of Pediatrics, Yale University School of Medicine; Consulting Staff, Department of Pediatric Emergency Medicine, Yale-New Haven Children's Hospital; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Wayne Wolfram, MD, MPH, Clinical Associate Professor, Departments of Pediatrics, Children's Hospital and University of Cincinnati; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Richard G Bachur, MD, Assistant Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Attending Physician, Division of Emergency Medicine, Children's Hospital of Boston

Author and Editor Disclosure

Synonyms and related keywords: upper respiratory tract infection, URI, respiratory syncytial virus, RSV, rhinorrhea, tachypnea, bronchiolitis, asthma, lower respiratory tract infection, infection of the small airways, viral infection of the small airways, bronchioles, adenovirus, parainfluenza virus, Mycoplasma pneumoniae, M pneumoniae, rhinovirus, enterovirus, influenza virus, Chlamydia pneumoniae, C pneumoniae, infection of bronchiolar respiratory cells, infection of ciliated epithelial cells, peribronchiolar lymphocytic infiltrate

INTRODUCTION

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Background

Bronchiolitis is an acute infectious disease of the lower respiratory tract that occurs primarily in young infants, most often in those aged 2-24 months.

Pathophysiology

Bronchiolitis is usually due to a viral infection of the small airways (bronchioles). Infection of bronchiolar respiratory and ciliated epithelial cells produces increased mucus secretion, cell death, and sloughing, followed by a peribronchiolar lymphocytic infiltrate and submucosal edema. The combination of debris and edema produces critical narrowing and obstruction of small airways.

Decreased ventilation of portions of the lung causes ventilation/perfusion mismatching, resulting in hypoxia. During the expiratory phase of respiration, further dynamic narrowing

of the airways produces disproportionate airflow decrease and resultant air trapping. Work of breathing is increased due to increased end-expiratory lung volume and decreased lung compliance. Recovery of pulmonary epithelial cells occurs after 3-4 days, but cilia do not regenerate for about 2 weeks. The debris is cleared by macrophages.

Infection is spread by direct contact with respiratory secretions. In the United States, epidemics last 2-4 months beginning in November and peaking in January or February. While 93% of cases occur between November and early April, sporadic cases may occur throughout the year. Attack rates within families are as high as 45% and are higher in daycare centers. Rates of hospital-acquired infection range from 20-47%. Previous infection with the common etiologic viruses does not confer immunity. Reinfection is common.

Frequency

United States

Annual incidence is 11.4% in children younger than 1 year and 6% in those aged 1-2 years. The illness accounts for 4500 deaths and 90,000 hospital admissions per year. Prevalence may be higher in urban areas.

In children aged 2 years, approximately 95% have serologic evidence of past infection with the predominant causative agent, respiratory syncytial virus (RSV). Unfortunately, presence of antibodies to RSV does not confer immunity.

International

RSV is an important respiratory pathogen worldwide. The frequency of bronchiolitis in developed countries appears to be similar to that in the United States. Epidemiologic data for underdeveloped countries are incomplete. Peak incidence of bronchiolitis usually occurs during winter months in temperate climates and during the rainy season in tropical climates. In the United States, the peak occurs in February. Morbidity and mortality may be higher in less developed countries because of poor nutrition and lack of resources for supportive medical care.

Mortality/Morbidity

Significant morbidity is unusual.

Hospitalization is required in up to 2% of cases; most of those patients are younger than 6 months. These patients account for as many as 17% of all infant hospitalizations. Hospitalization is significantly more likely at altitudes above 2500 meters (8000 ft). Mechanical ventilation is required for 3-7% of admitted patients.

The mortality rate is 1-2% of all hospitalized patients and 3-4% for patients with underlying cardiac or pulmonary disease.

Most deaths occur in infants younger than 6 months.

Race

Race and socioeconomic status may affect the frequency of contracting bronchiolitis.

Lower socioeconomic status may increase the likelihood of hospitalization. Hospitalization rates are higher in Native American, Alaskan, and Hispanic populations, but it is not clear if this is due to more severe infection or a lower threshold for admission.

Sex

Bronchiolitis occurs as many as 1.25 times more frequently in males than in females.

Age

Although infection with etiologic agents may occur at any age, the clinical entity of bronchiolitis includes only infants and young children. Seventy-five percent of cases of bronchiolitis occur in children younger than 1 year, and 95% in children younger than 2 years. Incidence peaks in those aged 2-8 months.

CLINICAL

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History

History and physical examination form the primary basis for the diagnosis of bronchiolitis.

Early symptoms are those of a viral upper respiratory tract infection (URI), including mild rhinorrhea, cough, and sometimes low-grade fever.

Adults, older children, and many infants do not progress beyond this stage of URI. For the 40% of infants and young children who progress to lower respiratory tract

involvement, paroxysmal cough and dyspnea develop within 1-2 days. Other common symptoms include the following:

o Fever o Increased work of breathing o Wheezing o Cyanosis o Grunting o Noisy breathing o Vomiting, especially post-tussive o Irritability o Poor feeding or anorexia

Physical

Most patients with bronchiolitis have the following signs:

Tachypnea, often at rates over 50-60 breaths per minute (most common physical sign)

Tachycardia Fever, usually in the range of 38.5-39°C Mild conjunctivitis or pharyngitis Diffuse expiratory wheezing Nasal flaring Intercostal retractions Cyanosis Inspiratory crackles Otitis media Apnea, especially in infants younger than 6 weeks Palpable liver and spleen from hyperinflation of the lungs and consequent

depression of the diaphragm

Causes

RSV is the most common pathogen (85%), but other organisms occasionally produce a similar clinical picture.

Adenovirus (11%) occasionally causes a similar syndrome with a more virulent course.

Epidemics of bronchiolitis due to parainfluenza virus usually begin earlier in the year and tend to occur every other year.

Other less common etiologic agents include the following: o Mycoplasma pneumoniae o Enterovirus o Influenza virus o Rhinovirus o Chlamydia pneumoniae

Ear, nose, or mouth inoculation o Exposure to an adult with a URI o Daycare exposure (significant) o Idiopathic

DIFFERENTIALS

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AsthmaBronchitisCongestive Heart Failure and Pulmonary EdemaPediatrics, ApneaPediatrics, Foreign Body IngestionPediatrics, PneumoniaPneumonia, AspirationPneumonia, BacterialPneumonia, MycoplasmaPneumonia, Viral

Other Problems to be Considered

Cystic fibrosis Vascular ring Lobar emphysema Foreign body Cardiac disease Reflux Aspiration

WORKUP

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Lab Studies

Routine laboratory testing is not warranted for diagnosis of bronchiolitis. A complete blood count (CBC) is seldom useful since the white blood cell (WBC)

count is usually within normal limits. Urine specific gravity may provide useful information regarding fluid balance and

possible dehydration. Serum chemistries are not affected directly by the infection but may aid in gauging

severity of dehydration. Arterial blood gases (ABG) may be needed in the severely ill patients, especially

those requiring mechanical ventilation.

Imaging Studies

Chest radiographs are not routinely necessary.1 If clinically indicated, chest radiographs should include anterior-posterior (AP) and

lateral views. o Hyperinflation and patchy infiltrates may be seen; these findings are

nonspecific and may be observed in asthma, viral or atypical pneumonia, and aspiration.

o Focal atelectasis o Air trapping o Flattened diaphragm o Increased anteroposterior diameter o Peribronchial cuffing o Chest radiographs may also reveal evidence of alternative diagnoses, such

as lobar pneumonia, congestive heart failure, or foreign body aspiration.

Other Tests

Antigen tests of nasal washings provide rapid (usually within 30 min) and accurate (sensitivity 87-91%, specificity 96-100%) detection of RSV.

o A positive culture or direct fluorescent antibody test result can confirm the

diagnosis of RSV infection. o Nasal washings should be obtained from children requiring hospitalization

and children at risk for severe disease. o Cultures of RSV are considerably less sensitive (60%) but are 100%

specific. o Respiratory viral panels, cultures for RSV or other viruses, or detection by

direct fluorescent antibody (DFA) or polymerase chain reaction (PCR) may be useful for the following reasons:

As another means of confirmation To search for other possible infectious agents For epidemiologic purposes

TREATMENT

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Prehospital Care

Prehospital care consists of cardiorespiratory monitoring, positioning to facilitate respiratory efforts (ie, upright posture), administration of oxygen, and possibly a trial of bronchodilators.

Emergency Department Care

General supportive measures are the mainstay of treatment for patients with bronchiolitis.

Patients should be made as comfortable as possible (held in a parent's arms or sitting in the position of comfort).

Cardiorespiratory monitoring is essential. Pulse oximetry is a helpful tool, as hypoxia is common. Humidified oxygen should be administered if the oxygen saturation is less than 94%

on room air. The ability to maintain adequate hydration should be assessed by observing patient

oral intake. Many dyspneic infants have difficulty taking a bottle. Fever and tachypnea increase insensible fluid losses.

Early effort should be made to isolate or cohort patients confirmed or likely to have RSV infection, especially from other patients at risk for severe disease.

Antibiotics are not indicated unless bacterial infection is suggested (eg, toxic appearance, hyperpyrexia, consolidation or focal lobar infiltrates on chest radiograph, leukocytosis, positive bacterial cultures).

Concomitant otitis media is common and may be treated with oral antibiotics.

Consultations

Early consultation with a pediatrician is advisable when the need for admission is anticipated. Intensive care consultation should be sought for patients who are severely ill.

MEDICATION

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Drug Category: Adrenergic agents

The use of bronchodilators is controversial. These agents relieve reversible bronchospasm by relaxing smooth muscles of the bronchi. Meta-analyses of clinical studies show little or no benefit from treatment with inhaled beta-adrenergic agents (with or without ipratropium bromide). These are plagued by the heterogeneous methods of the studies included. Empiric treatment with beta-agonists seems to be the standard of care. Such treatment is most reasonable in the child with documented improvement after initial treatment with bronchodilators. Drugs and dosages are the same as those for asthma. Nebulized epinephrine may occasionally be useful.

Drug Name Albuterol (Proventil, Ventolin, Salbutamol)

Description

Beta-agonist for bronchospasm refractory to epinephrine. Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on cardiac muscle contractility. May inhibit airway microvascular leakage. Administered by nebulizer or metered dose inhaler (MDI).

Adult Dose

Nebulizer: 5 mg/mL; 5 mg q15-20min for 3 doses, or continuous nebulizationMDI: 90 mcg/actuation; 4-8 inhalations q20min up to 4 h, then 2-4 inhalations q1-4h; use with a spacer device

Pediatric Dose

Nebulizer: (5 mg/mL) 0.15 mg/kg (2.5-5 mg) q15-20min for 3 doses, then 0.15-0.3 mg/kg q1-4h prn or 0.5 mg/kg/h continuous nebulizationMDI: 90 mcg/actuation; 4-8 inhalations q20min up to 4 h, then q1-4h prn; use with a spacer device

Contraindications Documented hypersensitivity

Interactions

Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents

PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

PrecautionsCaution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders; decreased serum potassium may occur

Drug Name Epinephrine (Adrenalin) or racemic epinephrine (microNefrin)

Description No proven advantage over inhaled beta2-agonists exists.

Adult Dose Epinephrine: 0.3-0.5 mg/kg (ie, 0.3-0.5 mL of 1:1000 [1 mg/mL])

solution SC q20min up to 3 doses

Pediatric Dose

Epinephrine: 0.01 mL (ie, 0.01 mL/kg of 1:1000 solution [1 mg/mL]) SC q15-20min, not to exceed 0.3 mL/doseRacemic epinephrine:<2 years: 0.25 mL of 2.25% solution via nebulizer diluted in 3 mL NS>2 years: 0.5 mL of 2.25% solution via nebulizer diluted in 3 mL NS

Contraindications

Documented hypersensitivity; cardiac arrhythmias or angle-closure glaucoma; local anesthesia in areas such as fingers or toes because vasoconstriction may produce sloughing of tissue; not to use during labor (may delay second stage of labor)

InteractionsIncreases toxicity of beta-blocking and alpha-blocking agents and that of halogenated inhalational anesthetics

PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in elderly patients, prostatic hypertrophy, hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias

Drug Category: Corticosteroids

Clinical trials demonstrate that corticosteroids have no benefit in the treatment of bronchiolitis, and thus they should not be used routinely. However, one study (with a treatment group of 8 patients) showed some clinical improvement with the combination of dexamethasone and salbutamol. A larger and more recent double-blind, placebo-controlled trial of the same agents revealed no difference from placebo.

Nebulized steroid treatment has not been proven efficacious.

A subsequent study of prednisolone treatment of inpatients appeared to show a small benefit in a subgroup of 14 intubated patients. Corticosteroids may be useful in patients with history of reactive airway disease.

Steroid treatment has not been shown to decrease the long-term incidence of wheezing or asthma after RSV infection.

Drug Name Prednisone (Deltasone)

DescriptionBlocks release of inflammatory mediators by inhibition of phospholipase A2. May be useful in patients with asthma or in bronchiolitis with asthmatic qualities.

Adult Dose60 mg PO initial, then 40-60 mg qd for 5-10 d; taper for longer period

Pediatric Dose2 mg/kg PO initially, then 1 mg/kg/d qd or divided bid; not to exceed 60 mg/d for 3-10 d; taper for longer periods

ContraindicationsDocumented hypersensitivity; fungal, viral, connective tissue, or tubercular skin infections; peptic ulcer disease; hepatic dysfunction; GI disease

Interactions Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for

hypokalemia with coadministration of diuretics

PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Drug Name Methylprednisolone (Medrol, Solu-Medrol)

DescriptionBlocks release of inflammatory mediators by inhibition of phospholipase A2. May be useful in patients with asthma or in bronchiolitis with asthmatic qualities.

Adult Dose 60-80 mg IV

Pediatric Dose2 mg/kg PO initial, then 1 mg/kg/d qd/bid; not to exceed 60 mg/d for 3-10 d; taper for longer periods; 0.5-2 mg/kg IV q6h

ContraindicationsDocumented hypersensitivity; viral, fungal, or tubercular skin infections

Interactions

Coadministration with digoxin, may increase digitalis toxicity secondary to hypokalemia; estrogens may increase levels; phenobarbital, phenytoin, and rifampin may decrease levels of methylprednisolone (adjust dose); monitor patients for hypokalemia when taking medication concurrently with diuretics

PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, myopathy, and infections are possible complications of glucocorticoid use

Drug Category: Nucleoside analog

These agents inhibit viral replication by inhibiting DNA and RNA synthesis.

Drug Name Ribavirin (Virazole)

Description

May be used for inpatients who have, or who are at high risk for, severe RSV infection. In early trials, 3-7 d of ribavirin therapy produced significant reduction in mortality, length of hospitalization, and duration of mechanical ventilation. However, recent studies demonstrate no clinical benefit. Furthermore, this therapy is very expensive. Use of aerosolized ribavirin in mechanically ventilated patients requires administration by physicians and support staff familiar with this mode of administration and the specific ventilator.

Pediatric Dose20 mg/mL initial solution, with continuous aerosol administration of 12-18 h/d for 3-7 d

Contraindications Documented hypersensitivity

InteractionsZidovudine effects are decreased when administered concurrently with ribavirin

Pregnancy X - Contraindicated; benefit does not outweigh risk

Precautions Monitor closely patients with COPD and asthma for

deterioration of respiratory function; sudden deterioration of respiratory function associated with aerosolized ribavirin in infants

FOLLOW-UP

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Further Inpatient Care

Patients at high risk and patients with moderate respiratory distress or persistent hypoxemia should be admitted for the following:

o Supplemental oxygen o Apnea monitoring if indicated by age or history (RSV is associated with

central apnea for unknown reasons. Term infants younger than age 1 month and premature infants younger than 48 weeks postconception are at highest risk.)

o Restoration and/or maintenance of fluid balance Children with severe respiratory distress or impending respiratory failure should be

admitted to a pediatric ICU. Otherwise healthy children with bronchiolitis have a low risk for bacterial

superinfection or coexisting bacterial infection. The febrile infant with findings consistent with bronchiolitis but no other apparent source of infection may require some evaluation for alterative bacterial sources especially if very young (<3 mo) or if he or she appears ill.

Children with underlying cardiopulmonary disease, infants with a history of gestational age less than 34 weeks, infants younger than 6 weeks, and infants with congenital or acquired immunodeficiency are at high risk for severe RSV infection and require heightened vigilance. These patients should be referred to a facility where pediatric intensive care and pediatric subspecialty consultation are available.

Suggested guidelines for admission are as follows: o Oxygen saturation less than 94% after therapy o Respiratory distress (eg, respiratory rate >60/min or retractions at rest) o Apnea or risk of apnea o Age younger than 2 months or history of prematurity o Underlying cardiopulmonary disease or immunosuppression

Further Outpatient Care

Patients with mild disease with reliable caregivers may be discharged. Follow-up evaluation with a primary care provider within 24 hours is desirable.

Criteria for discharge o No respiratory distress (eg, respiratory rate <60/minute) at rest or with

feeding o Minimal retractions at rest (not crying) o Adequate hydration o SaO2 > 93% o Age older than 2 months without a history of prematurity o Reliable caregivers with transportation available o No underlying cardiopulmonary disease o Able to take liquids by mouth without difficulty

In/Out Patient Meds

Beta-agonists, administered by inhaler or nebulizer, may be continued as an outpatient if the child responds to them while in the ED.

If inhalers are prescribed, a mask and spacer should be provided and the patient's caregiver instructed in their use prior to discharge.

Transfer

Severely ill children should be admitted to a pediatric or neonatal intensive care unit. If this requires transfer to another hospital, transport personnel and vehicles specifically intended for pediatric transport are desirable.

Prognosis

Most children with bronchiolitis, regardless of severity, recover without sequelae. The course of disease is usually 7-10 days, but a few remain ill for weeks.

Bronchiolitis has been identified as a risk factor for asthma, but this does not necessarily imply causation. Children already predisposed to asthma may be more likely to wheeze when they have RSV or other respiratory infectious or allergic stimuli. On the other hand, it is postulated that RSV infection may predispose an individual to later bronchospasm by selective promotion of specific subsets of helper T cells.

Patient Education

Instructions at discharge include positioning, maintenance of oral hydration, temperature control, use of prescribed medications, avoidance of exposure to tobacco smoke or other irritants, methods to limit transmission (eg, hand washing, avoiding day care while ill), and criteria for return to the ED.

MISCELLANEOUS

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Special Concerns

Children with underlying cardiopulmonary disease, including congenital heart disease, bronchopulmonary dysplasia, premature infants, infants younger than 6 weeks and infants with congenital or acquired immunodeficiency (including transplant recipients) are at high risk for severe RSV infection.

In addition to heightened vigilance, these patients may require specialized and intensive care.

REFERENCES

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Pediatrics, Bronchiolitis excerpt

Article Last Updated: Nov 1, 2007