BRONCHIOLITIS & RSV


I. General info

  1. RSV is the most common cause; peak incidence is November-April (in WA, starts in early December)
  2. Other causes include human metapneumovirus, influenza, adenovirus, and parainfluenza
  3. "High risk" infants & children include those who were born premature and those with chronic lung disease, congenital heart disease, or immudeficient states
  4. Characterized by acute inflammation, edema, and necrosis of epithelial cells in the small airways; increased mucus production, and  bronchospasm.
  5. Clinical signs: rhinorrhea, tachypnea, wheezing, cough, crackles, use of accessory respiratory muscles, and/o nasal flaring
  6. Risk factors for severe disease: Age < 12wks, h/o prematurity, underlying cardiopulmonary disease, immunodeficiency
  7. Associated with increased risk of respiratory illness as older children, especially recurrent wheezing
  8. In a prospectie study of 103 infants < 12mo with ED visits for bronchiolitis but no current pneumonia or croup, prior h/o reactive airways disease or known immunosuppression, median time to resolution of illness (defined as no cough x 24h) was 15d; 25% of pts were symptomatic after 21d.  Testing positive for RSV at initial presentation did not significantly correlate with illness duration.  (Pediatrics 126:285, 2010-JW)

II. Assessment of a child with bronchiolitis:

  1. Assessment of severity of respiratory compromise iteself (keep in mind the variability of severity over the short term; serial observations over time to assess the child's status may be helpful).

  2. Response to therapy, e.g. inhaled bronchodilators

  3. Impact on feeding and hydration

III. Treatment of bronchiolitis

  1. Consider nasal suctioning, as upper airway obstruction may increase the work of breathing
  2. O2-Per AAP 2006 (see reference below), use supplemental O2 (to maintain SaO2 at or above 90%) if SaO2 falls persistently < 90% in previously healthy infants
  3. Inhaled bronchodilators (albuterol and racemic epinephrine are most commonly used)
    1. Advice per AAP 2006 (see reference below):
      1. Do NOT routinely use bronchodilators though "a carefully monitored trial of [alpha-agonists or beta-agonists] is an option...should be continued only if there is a positive clinical response using objective means of evaluation," because the best evidence suggests that such meds produce at best modest improvements in oxygenation or clinical manifestations of bronchiolitis. 
      2. "Racemic epinephrine has demonstrated slightly better clinical effect than albuterol," but because of short duration of action and potential for adverse effects, it is not used in home settings, therefore "it would be more appropriate that a bronchodilator trial in the office use albuterol rather than racemic epinephrine."
    2. Albuterol vs. placebo
      1. 52 infants, mean age 5.6mos, hospitalized w/bronchiolitis, randomized to albuterol nebs Q2h x 24 then Q4h x 48h vs. placebo. No sig. difference in O2 sats, clinical features (wheeze, accessory mm. use, or meeting discharge criteria). (Pediatrics 101:361, 1998--JW)
      2. 129 infants presenting to an ER with mild-to-moderate bronchiolitis randomized to albuterol 0.1mg/kg TID PO vs. placebo x 7d; no sig. diff. in time to resolution of sx, return to normal feeding & sleeping, incidence of hospital admission, or repeat ER visits over 14d f/u (J. Peds. 142:509, 2003--JW)
    3. Epinephrine vs. placebo
      1. 194 pts < 12mo hospitalized for bronchiolitis randomized to epinephrine nebs vs. placebo; no diff. in length of hospital stay, duration of supplemental O2 use, ICU admission, or need for mechanical ventilation (NEJM 349:27, 2003--AFP)
      2. In a study in 800 full-term infants 6wks-12mos with moderately severe bronchiolitis randomized to inhaled epinephrine (3ml in 1:1000 x 2) vs. placebo in a trial that also involved oral dexamethasone vs. placebo in a 2 x 2 design, after adjustment for potential confounders, there was no sig. diff. in 7d incidence of hospital admission (NEJM 360:2079, 2009-JW)
    4. Albuterol vs. epinephrine
      1. 149 pts < 12mo hospitalized with bronchiolitis but no prior h/o wheezing randomized to inhaled epinephrine, albuterol, or placebo Q1-6h PRN; no sig. diff. among groups in mean hospital stay, time to normal O2 level, cessation of resp. distress, or adequate PO fluid intake (J. Peds. 141:818, 2002--JW)
      2. 149 previously-well children < 12mo hospitalized with bronchiolitis randomized to nebs Q1-6h with albuterol, epinephrine, or placebo, there were no sig. differences in mean length of stay, time to normal oxygenation, or time to resolution of respiratory distresss (J. Peds. 141:818, 2002--JW)
      3. 66 pts < 12mo with first episode of bronchiolitis randomized to nebulized epinephrine vs. albuterol.  No sig. diffs. were seen in improvements in clinical scores or degree of respiratory distress (Arch. Ped. Adol. Med. 158:113, 2004--JW)
      4. In a meta-analysis of 14 randomized trials of epinephrine vs. albuterol or placebo in kids 2y or less with bronchiolitis, only 1 of 10 outcomes was sig. better with epinephrine vs. placebo in inpts; similar results with epinephrine vs. albuterol in inpts; for outpts, 4 of 16 outcome measures favored epinephrine vs. albuterol (Arch. Pediat. Adol. Med. 157:957, 2003--JW)
  1. Cromolyn:
    1. In 100 infants under 2yo with bronchiolitis, adding nebulized cromolyn (20mg QID x 8wks then BID x 8 wks) or nebulized budesonide (500ug BID x 8wks then 250ug BID x 8wks) vs. placebo had less incidence of wheezing over the 16wk trial period and sig. less re-admission (Arch Pediatr Adolesc. Med 150:512, 1996-JW)
  2. Corticosteroids
    1. Per AAP 2006 (see reference below), do NOT routinely use corticosteroids (preponderance of evidence is that there is no improvement with corticosteroids in length of stay or clinical scores with either systemic or inhaled corticosteroids).
    2. A meta-analysis of 6 randomized trials of systemic steroids (none of which alone showed sig. diff's in outcome) showed a sig. reduction in length of hospital stay (0.43d) and sig. more rapid resolution of sx (Peds 105:44, 2000--JW)
    3. Dexamethasone 1mg/kg c/w placebo ass'd with sig. better improvements in resp. distress over 4h and sig. lower hosp. rates (19% vs. 44%) in a randomized trial in 70 kids < 2yo presenting to an ED with mod-to-severe bronchiolitis (J. Peds. 140:27, 2002--JW)
    4. In a randomized study in children 6-35mos old presenting with respiratory sx suggestive of viral etiology with whezing but no known prior h/o asthma, prednisolone 1mg/kg BID x 3d vs. placebo was ass'd with sig. faster resolution of sx (J. Peds. 143:700, 2003--AFP)
    5. In a study in 600 infants 2-12mos old presenting to an ED with mod-severe bronchiolitis but no prior h/o wheezing, randomized to receive dexamethasone 1mg/kg PO vs. placebo x 1, there was no sig. diff. in admission rate, mean length of stay for those admitted, or admissions within 7d after intervention (including in various subgroup analyses)  (NEJM 357:331, 2007-JW)
    6. In a study in 800 full-term infants 6wks-12mos with moderately severe bronchiolitis randomized to oral dexamethasone (1mg/kg to max 10mg initial dose then 0.6mg/kd QD x 5d) vs. placebo in a trial that also involved nebulized epinephrine vs. placebo in a 2 x 2 design, after adjustment for potential confounders, there was no sig. diff. in 7d incidence of hospital admission (NEJM 360:2079, 2009-JW)
  3. Heliox (a helium-oxygen mixture, us. 70-30% respectively)
    1. Heliox ass'd with sig. greater improvement in clinical status at 4h and sig. shorter ICU stays than placebo in a randomized trial in 38 pts 1mo-2yo with mod-severe RSV bronchiolitis (Peds. 109:68, 2002--JW)
    2. In a study in 19 infants < 3mos old admitted to an ICU for moderate-to-severe bronchiolitis from RSV randomized to heliox vs. regular oxygen, improvement in respiratory distress scores at 60min was sig. greater in the heliox group (Chest 129:676, 2006--JW)
  4. Inhaled nebulized hypertonic saline
    1. Theorized to reduce airways edema and improve mucus clearance
    2. Terbutaline 0.5mL (5mg) in 2mL of 3% saline TID x 5d, compared with same dose in 2mL of 0.9% saline, was ass'd with sig. better severity scores measured daily x 5d, but no diff. in indicendce of hospitalization, in a randomized trial of pts < 2yo with mild-moderate bronchiolitis (Chest 122:2018, 2002--AFP)
    3. In a meta-analysis of four randomized studies involving 189 inpatients and 65 outpatients with bronchiolitis < 24mos randomized to inhaled nebulized 3% saline vs. a 0.9% normal saline placebo, the mean length of stay was sig. shorter (by 1 day) (Cochrane review).
    4. In a study in 46 infants with bronchiolitis, all receiving nebulized racemic epinephrine randomized to administration with either 3% hypertonic saline or normal saline, there was no sig. diff. in O2 sat or respiratory distress measures at 2h, or in incidence of hospitalization (Arch. Ped. Adol. Med. 163:1007, 2009-JW)
    5. In a study in 171 infants 18mos or younger with moderate-to-severe bronchiolitis admitted to short-stay unit, all of whom received epinephrine 1.5mL nebulized mixed with (on a randomized basis) to 3%, 5%, or 0.9% saline Q4h, at 48h the 5% saline group had sig. lower mean severity score but there was no sig. diff. in mean length of stay (J. Pediat. 157:630, 2010-JW)
  5. Antibiotics
    1. Per 2006 AAP guidelines (see reference below), antibiotics should only be used if there is evidence of a coexisting bacterial infection.   "Approximately 25% of hospitalized infants with bronchiolitis will have radiographic evidence of atelectasis or infiltrates, often misinterpreted as possible bacterial infection"
  6. Ribavirin inhaled (for RSV bronchiolitis)
    1. 12-18h/d via nebulizer x 3-7d for severe RSV disease
    2. Use of Ribavirin in pts with confirmed RSV bronchiolitis have had inconsistent results
    3. Per 2006 AAP guidelines (see reference below), "Ribavirin may be considered for use in highly selected situations involving documented RSV bronchiolitis with severe disease or in those who are at risk for severe disease."

IV. Prevention of RSV bronchiolitis--Two tx's available as of 2000; both (RSV IVIG and Palivizumab) provide passive immunity by providing RSV-neutralizing Ab to the recipient

  1. RSV IVIG ("RespiGam") 750mg/kg IV over 3-4h, monitoring SaO2 & vital signs, Q1mo through RSV season
  1. In 510 kids < 2yo with h/o BDP or prematurity, RespiGam 750mg/kg Q30d through RSV season (Nov-April) ass'd with sig. reduction in risk of hosp. for RSV disease (8% vs. 13.5% with placebo); 1-3% had sig. adverse effects. (Peds 99:93, 1997-JW)
  2. Don't give MMR or Varicella vaccine < 9mo after last dose of RSV IVIG /c the latter may decrease efficacy
  3. Contraindicated in pts with cyanotic congenital heart disease (nonrandomized study showed increased surgical mortality in kids who had received it vs. those who hadn't)
  4. Advantages over Palivizumab: Reduces risk of infection w/viruses other than just RSV
  5. Adverse effects: Fever (5%), respiratory distress (2%), the latter presumably due to fluid overload
  1. Palivizumab (Synagis)--15mg/kg IM Q1mo through RSV season
  1. A monoclonal Ab against RSV
  2. 1,502 children at risk for RSV lower-airways infection randomized to palivizumab per dose above vs. placebo ("IMpact-RSV" Trial; Peds. 102:531, 1998--Med. Letter)
    1. Inclusion criteria: (< 6mo and born at < 36wks) or (< 2yo and chronic lung disease requiring "continuing medical therapy," i.e. daily O2, bronchodilator, diuretics, or corticosteroids)
    2. Palivizumab group was sig. less likely to be hosp'd for RSV (4.8% vs. 10.6%)
    3. Sig. differences in both subgroups, too
  3. Palivizumab 15mg/kg IM Qmo x 5 vs. placebo, over 150d f/u, was ass'd with RR 0.55 (sig.) for antigen-confirmed RSV-related hospitalization and a 56% reduction in total days of RSV-related hospitalization per child in a randomized trial in 1287 children with hemodynamically significant congenital heart disease (J. Peds. 143:532, 2003--abst)
  4. Advantages over RSV IVIG:
    1. Easier administration
    2. Not made from donated blood products (safety/availability)
    3. No interference w/live vaccines
  5. Adverse effects: Mainly local; reports exist of increases in serum AST levels
  1. Guidelines from American Academy of Pediatrics (Peds 102:1211, 1998)--"Consider" prophylaxis with RSV IVIG or Palivizumab (the latter generally preferred) IF:
    1. < 2yo with chronic lung disease requiring medical therapy within 6mos of onset of RSV season
      1. "Patients with more severe CLD may benefit from prophylaxis for two RSV seasons, esp. those who require medical therapy"
    2. Born at < 32wks gestational age, regardless of whether have CLD
      1. If < 28wks gestation at birth, consider prophylaxis until 12mo
      2. If 29-32wks gestation at birth, consider prophylaxis until 6mo
    3. Born at 32-35 wks--"Given the large number ofg patient born between 32 and 35wks and cost of the drug, use of Palivizumab in this population should be reserved for those infants with additional risk factors" (e.g. neurologic disease in very LBW infants, number of young siblings, day care attendance, tobacco smoke exposure)
    4. Immunodeficient kids--"Although...prophylaxis has not been evaluated in randomized trials in immunocompromised children...children with severe immunodeficiencies...may benefit from immunoprophylaxis."
  1. "Consensus of Pulmonary and Neonatal Groups in Washington" updted 11/99 (http://neonatal.peds.washington.edu/NICU-WEB/RSV_Prevention.asp)--Pts "most likely to benefit" from prophylaxis include:
    1. < 2yo at start of RSV season with "conditions that adversely affect respiratory function" and who have required daily tx within last 6mos (e.g. O2, diuretics, steroids, bronchodilators, and/or mechanical ventilation)
    2. < 6mo at start of RSV season and < 32wks gestational age at birth
    3. < 6mo at start of RSV season, 32-35wks gestational age at birth, and at least one environmental risk factor (tobacco smoke exposure, day care, siblings, or "persistent hospitalization"
    4. "May benefit but...currently no data to demonstrate efficacy" for pts < 2yo at onset of RSV season and congenital heart disease and either symptomatic or requiring daily meds (consult cardiologist before giving)
  1. RNA intererference
    1. RNA interference is the inhibition of expression of a gene by small segments of double-stranded RNA, which impede expression of a particular gene
    2. An "interfering RNA", RNA ALN-RSV01 was shown to reduce incidence of RSV infection after a standardized challenge in a randomized trial in healthy adults (Proc. Nat. Acad. Sci. USA 107:8800, 2010-JW)

(AAP guidelines: Peds 118:1774, 2006)