Clinical Review - Bronchiolitis in children

By Dr Prasad Nagakumar, paediatric respiratory registrar, Royal Brompton Hospital and Professor Andrew Bush, paediatric respirology professor, Imperial College and Royal Brompton, London.

A premature baby with severe bronchiolitis may benefit from CPAP (photograph:spl)
A premature baby with severe bronchiolitis may benefit from CPAP (photograph:spl)

Section 1: Aetiology and classification
Acute bronchiolitis is a major cause of respiratory morbidity in young children.

The bronchiolitis 'season' in the UK is between November and March. The exact cause for this seasonal variation is not known.

It commonly presents in infants three to six months of age although the definition includes children up to two years of age.

Bronchiolitis is the commonest cause of hospital attendance in infancy. It results in 20,000 hospital admissions annually,1 resulting in significant morbidity and even mortality.

This puts enormous pressure on paediatric wards and intensive care units.

Characteristics
Acute bronchiolitis is a clinically diagnosed viral respiratory condition defined as 'a seasonal viral illness, characterised by fever, nasal discharge and dry, wheezy cough. On examination, there are fine inspiratory crackles and/or high-pitched expiratory wheeze'.2

Internationally, the definition is sometimes broadened to include a first episode of acute viral wheeze.

Terms like 'wheezy bronchitis' and 'acute bronchitis' are still in use and the term 'acute viral lower respiratory tract infection' may be more appropriate as an umbrella term for all these conditions.

However, it should be noted that true acute bronchiolitis is characterised by fine crackles, and not the polyphonic wheeze characteristic of episodic viral wheeze or viral exacerbations of asthma or multiple trigger wheeze.

Viral cause
Respiratory syncytial virus (RSV) accounts for up to 80 per cent of cases.

Metapneumovirus is said to be the second commonest cause for bronchiolitis. Other aetiological agents include adenovirus, influenza, parainfluenza, coronavirus, and enterovirus. Human bocavirus is the recent addition to this growing list.

By three years of age nearly all children have serological evidence of RSV infection. Viral infection of the lower respiratory tract results in epithelial necrosis and destruction of the cilia.

The resulting inflammation is neutrophilic, not at all like the eosinophilic inflammation in asthma, and leads to plugging of distal airways.3

These plugs cause obstruction of the bronchioles which ultimately results in hypoxaemia due to ventilation-perfusion mismatch.

In premature infants who have airway obstruction as a consequence of prematurity or its treatment, a lesser degree of airway inflammation can cause severe respiratory compromise.

Section 2: Making the diagnosis
Infants with bronchiolitis present typically with a prodrome of coryzal symptoms followed two to three days later by worsening cough, poor feeding, tachypnoea, chest recession and sometimes wheeze, and showers of characteristically fine crackles on chest auscultation.

In ex-preterm and very young infants apnoea may be the sole presenting feature. A focused history and full clinical examination with assessment of the severity of the disease is vital.

Conditions which mimic bronchiolitis should always be kept in mind (see box, right). It should be noted that in infants with congenital heart disease (especially left to right shunts), bronchiolitis can precipitate congestive cardiac failure. Pertussis can mimic bronchiolitis in young infants where typical 'whoop' is not seen.

Most, but not all, infants with bronchiolitis have a mild fever.

A temperature above 39 degrees and features of systemic toxicity (drowsy, lethargic, irritable, pale, mottled and tachycardia) should prompt a search for an alternative diagnosis.

Investigations
Bronchiolitis is a clinical diagnosis and no investigations are needed routinely. In particular, chest X-ray is not useful.

Pulse oximetry should be performed in infants where hypoxia is suspected. The infant's weight should be checked and plotted on the growth chart.

Rapid RSV diagnostic tests using immunofluorescence or PCR on nasopharyngeal secretions will confirm the diagnosis and help infection control in hospitalised infants.

Laboratories perform a panel of viral immunofluorescence on a nasopharyngeal aspirate sample including RSV, metapneumovirus, adenovirus, influenza and parainfluenza. This will reduce unnecessary interventions including antibiotic use.

In hospital, RSV positive infants should be nursed in single rooms or in cohorts when single rooms are not available.

Conditions which mimic acute bronchiolitis

  • Pertussis
  • Pneumonia
  • Inhaled foreign body
  • Sepsis
  • Cystic fibrosis
  • Congenital heart disease
  • Metabolic conditions

Section 3: Managing the condition
Most infants with acute bronchiolitis have mild disease and can be managed at home with primary care support.

Infants with mild respiratory distress, who tolerate feeds and are not hypoxic fall in to this category. Carers should be given information on how to recognise deterioration of the infant's condition and when to seek further medical help.

Indications for admission to hospital are given below.

Signs for hospital referral of acute bronchiolitis
  • Cyanosis or really severe respiratory distress (respiratory rate >70 breaths/min, nasal flaring and/or grunting, severe chest wall recession)
  • Marked lethargy
  • Poor feeding leading to inadequate fluid intake
  • Respiratory distress preventing feeding (<50 per cent of usual intake in past 24 hours)
  • Apnoeic episodes
  • Diagnostic uncertainty (toxic infant, temperature ≥ 39 oC)
  • Infants with high-risk factors (see box below)
  • Social factors

Management in secondary care
Children with bronchiolitis require hospital admission if they are hypoxic or are unable to maintain adequate hydration; those in high-risk groups may warrant admission at an earlier stage of illness than otherwise healthy children (see box, bottom right).

Three per cent of infants with bronchiolitis need hospitalisation. There is no specific treatment, and management is supportive. This includes gentle nasal suctioning; supplemental oxygen to keep saturations above 92 per cent and nasogastric feeds.

Bacteriological investigations are reserved for infants presenting with high fever or 'toxic' features and are not necessary in infants with typical bronchiolitis.

Serum electrolytes should be measured in infants on IV fluids. Blood gas analysis should only be performed in infants in imminent need of respiratory support.

Infants with severe symptoms may need mechanical ventilation. Continuous positive airway pressure (CPAP) may be beneficial in infants with moderate to severe disease and may stabilise their condition and avoid intubation.4

Pharmacological treatment
Trials of various different pharmacological treatments have all been disappointing.

Bronchodilators may help in short-term improvement of clinical scores but are not proven to shorten hospital stay, or reduce the risk of ventilation.

Beta-2 agonists, nebulised adrenaline and anticholinergics are not recommended.

Inhaled or oral corticosteroids, methylxanthines, antibiotics, antivirals and chest physiotherapy are not useful in the management of acute bronchiolitis.

Although a recent study showed a reduced risk of hospitalisation in infants with bronchiolitis treated in the emergency department with inhaled epinephrine and five days of high-dose oral dexamethasone,5 the side-effects of this approach compared with the trivial benefits mean this regime cannot be recommended.

Nebulised 3% saline has been shown to shorten hospital stay, but the use of hypertonic saline in infants is not benign and although a Cochrane review noted no adverse effects when used in conjunction with a bronchodilator, the total numbers of patients were small and no meaningful data about side- effects is available.

Preventive measures include encouraging hand washing in nursery and day care facilities. Washing shared toys may help in preventing spread of a virus. Breast feeding is protective and smoking should be certainly discouraged.

More specific measures include hyperimmune RSV immunoglobulin and the monoclonal antibody palivizumab.

Hyperimmune RSV immunoglobulin is not licensed for treatment in the UK.

The monoclonal RSV immunoglobulin palivizumab may be given as prophylaxis to high-risk infants. It requires a monthly intramuscular injection. It offers partial protection and is expensive.

It may be considered in infants aged less than 12 months who are survivors of extreme prematurity; have a cyanotic congenital heart disease (palivizumab was not effective in cyanotic congenital heart disease); are oxygen or technology dependent; or have a significant congenital or acquired immunodeficiency.

A systematic review concluded that the costs of the widespread use of palivizumab outweighed benefits.6

Since most admissions are among full-term, low-risk babies (because there are so many more of them than high-risk babies), palivizumab is unlikely ever to substantially affect the prevalence of bronchiolitis in the community.

High-risk factors for severe bronchiolitis

  • Prematurity
  • Chronic lung disease of prematurity, cystic fibrosis
  • Immunodeficiency
  • Congenital heart disease
  • Neuromuscular disorders
  • Chromosomal anomalies, especially Down's syndrome
  • Congenital defects in airway anatomy

Section 4: Prognosis
In most infants bronchiolitis is a self-limiting condition with symptoms lasting for four to seven days.

In the first 72 hours of illness, infants with bronchiolitis may deteriorate clinically before improvement.

Mortality is low (<1 per cent) in infants needing intensive care in the absence of underlying respiratory or cardiac disease and immunodeficiency.

About 20 per cent of infants have cough and wheeze for a rather prolonged period after a bout of bronchiolitis (post-bronchiolitic syndrome).

Most recover completely, but intermittent symptoms may continue for several years, particularly with subsequent viral infections. Treatment can be difficult. Neither inhaled steroids nor the leukotriene receptor antagonist montelukast are useful. RSV infection does not cause asthma.

Infants with acute severe adenovirus bronchiolitis in particular may go on to an obliterative bronchiolitis, in which there is widespread disease of the small and large airways, including bronchiectasis, leading to severe airflow obstruction.

Severe sequelae have rarely, if ever, been recorded after RSV bronchiolitis.

Summary

  • RSV bronchiolitis is an important cause of respiratory morbidity in young infants.
  • Avoid unnecessary investigations and treatments.
  • Infants with severe disease and comorbidity should be recognised and referred to secondary care.
  • Post-bronchiolitic symptoms should not be confused with asthma, nor treated with asthma medications.

References

1. Handforth J, Friedland JS, Sharland M. Basic epidemiology and immunopathy of RSV in children. Paediatr Respir Rev 2000; 1: 210-1.

2. Lakhanpaul M, Armon K, Bordley C, et al. An evidence based guideline for the management of children presenting with acute breathing difficulty. Nottingham: University of Nottingham, 2002. www.nottingham.ac.uk/paediatric-guideline/breathingguideline.pdf

3. McNamara PS, Ritson P, Selby A, Hart CA, Smyth RL. Bronchoalveolar lavage cellularity in infants with severe respiratory syncytial virus bronchiolitis. Arch Dis Child 2003; 88: 922-6.

4. Yanney M,Vyas H. The treatment of bronchiolitis. Arch Dis Child 2008; 93: 793-8.

5. Frohna JG, Frey U. Combination of epinephrine and dexamethasone may reduce hospitalisation in children with bronchiolitis. J Pediatr. 2009; 155(5): 761-2.

6. Embleton ND, Harkensee C, McKean MC. Palivizumab for preterm infants. Is it worth it? Arch Dis Child Fetal Neonat Ed 2005; 90: F286-9

Resources

Scottish Intercollegiate Guidelines Network

Bronchiolitis in children, 2006 www.sign.ac.uk

Parent information leaflets

1. Patient UK www.patient.co.uk

2. British Lung Foundation www.lunguk.org

This topic falls under section 15.8 of the RCGP curriculum 'Respiritory problems'

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