treatment of childhood bronchiolitis · infants with mild bronchiolitis will require ......

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Vol 2 July/August 2010 Clinical Pharmacist 257

By Doreen Cochrane, PhD, MRPharmS

Bronchiolitis is an acute seasonal viralillness characterised by fever, nasaldischarge and dry wheezy cough. On

examination, fine inspiratory crackles orhigh-pitched expiratory wheeze may beheard. Around one third of childrendevelop bronchiolitis in the first year of life.

The symptoms of mild disease aresimilar to those of a cold. About one in 10infants with mild bronchiolitis will requireadmission to hospital because ofprogression to severe bronchiolitis orpneumonia. Respiratory syncytial virus(RSV) is the most common cause ofbronchiolitis. However, the condition canalso be caused by the parainfluenza viruses,influenza virus and humanmetapneumovirus.1

RSV-associated bronchiolitis may beassociated with short-term and long-termcomplications, including wheeze andasthma.1,2 Characteristics that increase therisk of severe RSV-associated bronchiolitisin infants and children include pretermbirth, cyanotic or complicated coronaryheart disease, pulmonary hypertension,chronic lung disease and congenital oracquired immunodeficiency. Lowersocioeconomic status is also a risk factor forsevere RSV-associated disease.

As people get older the likelihood of aviral infection progressing to bronchiolitisis reduced (because airway size increases,the immune system is more mature andthere is less transmission since olderchildren have fewer close contacts withinfected infants).

Nevertheless, RSV can cause repeatedinfections throughout life and cause severebronchiolitis in older children and adults,especially immunocompromised patients,elderly patients and patients with heartdisease. This article will focus on theprevention and treatment of severebronchiolitis in childhood.

TreatmentThe surface glycoproteins of RSV lackneuraminidase activity leaving theneuraminidase inhibitors oseltamivir andzanamivir ineffective against RSV. Inhaledribavirin is licensed for the treatment of

moderate-to-severe bronchiolitis. Moststudies that have investigated the use of oralcorticosteroids failed to demonstratesignificant reduction in length of hospitalstay or clinical symptom score for infantsand young children.3 The results of recentstudies indicate that for infants agedbetween six weeks and 12 months withmoderate-to-severe bronchiolitis, treated inthe emergency department, combinedtherapy with a corticosteroid (oraldexamethasone) and a bronchodilator(nebulised adrenaline) reduced the numberof hospital admissions (P=0.02).4 Althoughrecent research does not support the routineuse of bronchodilators or corticosteroids,further investigation is needed to explorethe combination of these treatments.

Another recent and promisingdevelopment is the use of nebulisedhypertonic saline; treatment with 3% salineresulted in a 26% reduction in duration ofhospital stay for infants with viralbronchiolitis.5,6 Further studies arenecessary to investigate more fully theeffectiveness of nebulised hypertonic salineand its place in therapy.

Supportive measures includesupplementation of oxygen (increasing tonasal bi-level positive-airway pressure orintubation and mechanical ventilation ifrequired), enteral feeding and intravenousfluids.

Bronchiolitis is a condition of the lower respiratory tract that is common in infants and youngchildren. This article outlines the treatment and prophylaxis of severe bronchiolitis in these patients

Treatment of childhood bronchiolitis

severe RSV bronchiolitis; at least one studyhas reported a reduction in post-bronchiolitic asthma and recurrent wheezein six-year-old children treated withnebulised ribavirin during RSVbronchiolitis.2

Ribavirin is teratogenic and thereforecannot be administered as an aerosol to, orin the presence of, women who arepregnant or may become pregnant. Infantsand young children with viral bronchiolitisdo not benefit from treatment withantibiotics.2

A recent Cochrane review concludedthat inhaled bronchodilators (beta2-agonists and antimuscarinics) can reduceclinical symptom scores in the short termbut do not reduce the rate of hospitaladmissions for infants and children with

OBJECTIVESStudying this article will help you gain a better understanding of:

� The clinical features of bronchiolitisand the risk factors for developingmoderate-to-severe disease

� The treatment of moderate-to-severebronchiolitis in infants and children

� The prophylaxis of bronchiolitiscaused by RSV

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258 Clinical Pharmacist July/August 2010 Vol 2

ProphylaxisPalivizumab is a humanised murinemonoclonal anti-F glycoprotein withneutralising and fusion inhibitory activityagainst RSV. It is administeredintramuscularly at a dose of 15mg/kg onceevery 30 days during the peak infectionperiod to those at high risk of infection.The efficacy of palivizumab was

established in two randomised, placebo-controlled trials. The Impact-RSV study evaluated the

effectiveness of palivizumab for infants withchronic lung disease and also for infantswho were premature at birth and below sixmonths of age during the RSV season (fromOctober through to March in the UK). Inthis study, prophylaxis reduced the numberof RSV cases requiring hospital admissionby 55% (P<0.001).7 The second studyinvolved administration of palivizumab toinfants with coronary heart disease; RSV-related hospital admissions were reduced by45% (P=0.003).8 Based on the results ofthese two studies, it is believed that infantsborn prematurely will benefit the mostfrom prophylaxis with palivizumab.7

No clinical trials of palivizumab havereported a reduction in deaths caused byRSV-associated bronchiolitis. Motavizumab, an anti-RSV antibody, has

been evaluated in phase III clinical trials forthe prophylaxis of RSV-associatedbronchiolitis and observational prospectivestudies are currently under way. Measures to prevent viral transmission

are also important (eg, reducing contact

between infants, reducing exposure of at-risk infants to infected individuals and useof hospital infection-control policies).Infants should not be exposed to tobaccosmoke — especially those known to be athigh risk of developing bronchiolitis. It isunclear whether or not breastfeeding canprevent RSV infection.

Clinical and cost considerationsThe Joint Committee on Vaccination andImmunisation (2005)9 advised prophylaxisusing palivizumab for:

� Children under two years of age withchronic lung disease

� Infants less than six months of agewho have left-to-right cardiac shunt,haemodynamically significant congenital heart disease or pulmonary hypertension

� Children under two years of age withsevere congenital immunodeficiency

The American Academy of Paediatricsrecommends the use of palivizumab forRSV prophylaxis in premature infants (upto age 90 days or for up to three doses,whichever comes first) if they attendchildcare or if at least one other child agedunder five years lives permanently in thehousehold.10

In the new NHS climate of productivityand efficiency clinical pharmacists canassist in assessing the effectiveness of high-cost treatments (such as palivizumab) andcan advise multidisciplinary committees onhow to make best use of pharmaceuticalresources. Clinical pharmacists can helpdevelop guidelines for the prophylaxis andtreatment of RSV infection. Guidelinesneed to address the dose and reconstitutionprocedures, treatment of adverse reactions,duration of treatment and administration ofdoses in special situations (eg, for infantswho undergo coronary bypass surgery, sinceserum levels of palivizumab are reduced inthe postoperative period). Pharmacists canalso have input into hospital infection-control policies aimed at containingoutbreaks of RSV infection.

References1 Scottish Intercollegiate Guidelines Network.

Bronchiolitis in children. 2006. www.sign.ac.uk/pdf/sign91.pdf (accessed 4 April 2010).

2 Tregoning JS, Schwarz J. Respiratory viral infections ininfants: causes, clinical symptoms, virology andimmunology. Clinical Microbiology Reviews2010;23:74–98.

3 Gadomski AM, Bhasale AL. Bronchodilators forbronchiolitis. Cochrane Database of SystematicReviews 2006; issue 3.

4 Plint AC, Johnson DW, Patel H, et al. Epinephrine anddexamethasone in children with bronchiolitis. NewEngland Journal of Medicine 2009;360:2078–89.

5 Kuzik BA, Al-Qadhi SA, Kent S, et al. Nebulizedhypertonic saline in the treatment of viral bronchiolitisin infants. Journal of Pediatrics 2007;151:266–70.

6 Zhang LR, Mendoza-Sassi A, Wainwright C, et al.Nebulized hypertonic saline solution for acutebronchiolitis in infants. Cochrane Database ofSystematic Reviews 2008; issue 4.

7 IMpact-RSV Study Group. Palivizumab, a humanizedsyncytial virus monoclonal antibody, reduceshospitalization from respiratory syncytial virus infectionin high-risk infants. Pediatrics 1998;102:531–7.

8 Feltes TF, Cabalka AK, Meissner HC, et al. CardiacSynagis Study Group. Palivizumab prophylaxis reduceshospitalisation due to RSV in young children withhaemodynamically significant coronary heart disease.Journal of Pediatrics 2003;143:532–40.

9 Joint Committee on Vaccination and Immunisation.Minutes of meeting held on 22 June 2005.www.advisorybodies.doh.gov.uk/JCVI/mins220605.htm(accessed 4 April 2010).

10 American Academy of Paediatrics. ModifiedRecommendations for Use of Palivizumab forPrevention of Respiratory Syncytial Virus. Paediatrics2009;124:1694–1701.

Doreen Cochrane is a clinicalpharmacist and independent prescriberfor respiratory medicines who works inprimary care in London. E: d.cochrane@nhs.net

Answers

1e; 2c; 3a; 4e; 5d

TEST YOURSELF1 Which virus is not commonly associatedwith bronchiolitis?

a) Parainfluenza virus b) Human metapneumovirus c) Respiratory syncytial virus d) Influenza virus e) Epstein Barr virus

2 Which treatment for infants withmoderate-to-severe bronchiolitis isassociated with reduced hospitaladmissions?

a) Corticosteroids b) Beta2-agonist bronchodilator c) Adrenaline plus dexamethasone d) Antimuscarinics e) Hypotonic saline

3 Which statement about palivizumabprophylaxis is incorrect?

a) It reduces the risk of death caused by RSV among infants at risk of bronchiolitis

b) It is administered by intramuscular injection

c) The dose is 15mg/kg d) There are data supporting its use forinfants with coronary heart disease

e) There are data supporting its use forinfants with chronic lung disease

4 Which of the following is licensed forprophylaxis of respiratory diseasecaused by RSV?

a) Motavizumabb) Ribavirinc) Corticosteroidsd) Hypertonic salinee) Palivizumab

5 Which of the following would not beincluded in guidelines for RSVprophylaxis?

a) Specific indicationsb) Dosec) Reconstitution procedures d) Choice of antibacterialse) Duration of treatment

DISCUSSION POINTS� How do local guidelines forthe treatment andprophylaxis of bronchiolitis atyour institution differ from evidence-based recommendations?

� What precautions, if any, would yourecommend for nursing staff whoadminister medicines such asribavirin and palivizumab?

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