Acute Bronchiolitis

Inflammation of the distant bronchioles

The main causes of inflammation include:

• Viruses: Respiratory Syncytial Virus (RSV), Parainfluenza Virus Type 3 (PIV 3), human metapneumoviruses, adenoviruses (ADV) especially types 3, 7, and 21, rhinoviruses, influenza viruses, and enteroviruses (in a much lower proportion of cases)
• Bacteria: Mycoplasma pneumoniae and Chlamydia trachomatis

Age: Due to anatomical reasons related to the size of the distal respiratory tree (bronchioles), acute viral bronchiolitis is common among children under 2 years of age. The peak incidence occurs between the second and the 10th month of life.

Gender: There is a male preponderance of cases. Attack rates in males may be 1.5 times greater than in females.

Breastfeeding: Lack of exclusive breastfeeding in the first six months of life.

Opportunities for Exposure: Infants of working mothers are exposed early to settings such as day-care centers or creches, indoor crowding, and the presence of older siblings and adults with minor respiratory illnesses.

Seasonal Factors: In temperate regions, the peak period is during the winter to spring months. However, in the West African subregion, most cases are observed during the rainy season (May-October) or the cold-but-dry harmattan season (November-December) (Johnson et al, 1996).

Others: Racial factors are reportedly unimportant, but black infants were said to be more vulnerable to parainfluenza type III–associated wheezy illnesses (Welliver et al, 1986). Additionally, unlike in pneumonia, malnutrition is an uncommon associated feature of acute viral bronchiolitis (Johnson, 1993).

Viral infection of the infant’s upper respiratory passages usually occurs following inhalation of infected respiratory droplets, or inoculation of the nostrils or conjunctivae from contaminated hands.

The spread of the infection to the distal bronchi and bronchioles causes:

• Mucous hypersecretion
• Necrosis of the respiratory epithelium
• Submucosal inflammatory edema

There is preservation of submucosal collagen and elastic tissue.

Subsequently, intraluminal plugs of sloughed (epithelial) cellular debris and fibrin are formed.

Characteristically, there is peribronchiolar infiltration by mononuclear cells, and except those adjoining the inflamed bronchioles, the alveoli are relatively spared.

Several cytokines/chemokines (notably interleukin (IL)-8, macrophage inflammatory protein [MIP]1-α and regulated on activation normal T-cell expressed and secreted (RANTES)), interferon-ү and leukotrienes are released due to cellular injury.

The consequent cellular dysregulation initiate, orchestrate and sustain airway inflammation involving the epithelia of the distal bronchi and the bronchioles.

By virtue of their smaller dimensions, the peripheral airway of infants and toddlers has a greater propensity for obstruction (and the related increase in airway resistance) from the inflammatory edema and intraluminal mucus plugs and epithelial debris.

Flow of air past the sites of obstruction is aided by the generation of negative intra-thoracic pressure (by the active contraction of the diaphragm), but with the generation of positive pressure at expiration, there is dynamic airway compression with the consequent smaller luminal dimensions.

Air-trapping beyond the site of obstruction causes progressive hyperinflation (ball-valve obstruction). The consequent increase in the functional residual capacity accounts for the difficulty and prolongation of the expiratory phase of breathing.

Uneven distribution of resistance and a general decrease in lung compliance result in a significant increase in the work of breathing.

Progression of the inflammatory events causes complete (check-valve) obstruction in some bronchioles. The consequent absorption of the trapped air causes multiple but patchy atelectases, which may be difficult to distinguish from the patchy infiltrates of a complicating bronchopneumonia on the chest radiograph.

As the resistance to airflow increases, so does the work of breathing, volume of trapped (dead space) air and the respiratory rate. The tendency for developing fast shallow breathing on a high functional residual capacity leads to a decreasing amount of inhaled air getting to the alveolar exchange surfaces. Although the physiological consequence of this is hypercarpnia (elevation of arterial PCO2), hypoxemia (low arterial O2) appears earlier, due to the inevitable ventilation-perfusion (V/Q) mismatch associated with the disease. V/Q mismatch is a feature of most hospitalized cases of acute bronchiolitis, and results from relative hyperperfusion of poorly ventilated alveoli (occasioned by inflammatory obstruction of the peripheral airway). That the low arterial O2 frequently outlasts clinical improvement underscores the slow resolution of the initial inflammatory events.

The typical clinical scenario is that of an infant or toddler below 2 years, presenting with an initial coryzal illness during the vulnerable wet season (rainy season or winter), frequently in close temporal association with (a preceding exposure to) an older contact with an undifferentiated upper respiratory illness.

This initial prodrome of clear rhinorrhoea, nasal congestion, excessive sneezing and cough is associated with a mild fever lasting for 1 – 7 days.

The definitive disease is heralded by a sudden onset of wheezy breathlessness, episodic or paroxysmal cough, irritability, poor feeding, and (especially in tropical environments where malaria may coexist) an exacerbation of the initial pyrexia.

Cough and wheezing may be minimal in the neonates/younger infants in whom apnoea is a more frequent presenting feature.

Those requiring admission will usually present with severe symptoms within the first 3-4 days of the definitive stage.

Examination-

• Fast breathing for the age, chest retraction, and tachycardia are near-constant findings;
• An occasional child may present with grunting and/or cyanosis.
• Auscultatory rhonchi (typically expiratory and polyphonic) and fine inspiratory crepitations may be associated with (non-auscultatory) wheezing, which is usually suggested by the prolonged expiration (“visible wheeze”).
• The temperature may range from 38.0 – 40°C.
• Irritability (or sometimes lethargy), cyanosis, features of “increased work of breathing”
• A palpable liver is consequent on the hyperinflation, as is splenomegaly.
• Other findings include those of co-morbid conditions like otitis media (seen in ~20% of cases), or complications like a bacterial pneumonia (usually associated with unusual bacterial agents), dehydration or metabolic acidosis.

The natural course

• An initial 48-72 hours of a frightening severity of the respiratory distress with the attendant highest risk of precipitous respiratory/metabolic decompensation causing a fatal outcome in a few (< 1%).
• In the majority of affected children, there is a gradual resolution of the respiratory distress, an improvement in the paroxysms of cough, fever, appetite and other features over the subsequent 1-2 weeks.

• Underlying congenital heart disease (especially the cyanotic types),
• Underlying congenital or acquired chronic respiratory illness (e.g. laryngo- or tracheomalacia, bronchopulmonary dysplasia),
• A neonatal age.
• Adenovirus aetiology may result in obliterative bronchiolitis (a chronic lung disease) and rarely unilateral hyperluscent lung syndrome (Swyer-James syndrome).
• Prematurity

Clinical Premise

Radiological Investigations: The chest radiograph provides useful anatomic clues of the disease extent and complications.

• A postero-anterior chest X-ray shows:
• Peribronchial thickening
• Features of hyperinflation
• Horizontal splaying of the ribs
• Flattened diaphragmatic domes
• "Relative microcardia" (due to hyperinflation)
• Increased bronchovascular markings
• Interstitial streaks radiating from the hilar area are frequent findings.
• The lateral radiograph:
• Likely corroborates hyperinflation
• Shows increased anteroposterior diameter of the chest
• Patchy or segmental shadows may suggest:
• Atelectasis
• Superimposed bacterial consolidation

Microbiological Investigations:

• Nasopharyngeal aspirate or nasopharyngeal swab
• Immunofluorescence (IF) studies or polymerase chain reaction analysis
• Viral cultures
• Serological diagnosis (using paired sera obtained 10-14 days apart) serves little therapeutic purpose for the individual case, but may be useful in confirming epidemics.
• A superimposed bacterial pneumonia (usually Staphylococcus aureus or S. epidermidis in severe cases requiring hospitalization) may be occasionally confirmed with a blood culture

Other Investigations:

• Blood gas/acid-base aberrations include metabolic acidosis, and less commonly respiratory alkalosis, initial (arterial) hypoxemia, and with the subsequent CO2 retention, acute respiratory acidosis.
• Pulse oximetry
• The hematological findings are non-specific and may be normal without the typical viral leukopenia with relative lymphocytosis. Furthermore, the presence of leukocytosis, with or without polymorphonuclear predominance, is not enough to suggest the advent of a superimposed bacterial pneumonia.

• Bronchial Asthma: Differentiating bronchiolitis from asthma is important due to differences in treatment and management.
• Pertussis: Whooping cough can present with similar symptoms, such as paroxysmal coughing.
• Foreign Body or Food Aspiration: Inhalation of foreign objects or food into the airways can cause respiratory distress.
• Gastroesophageal Reflux: Reflux of stomach contents can lead to cough and respiratory symptoms.
• Upper Airway Obstructive Lesions: Conditions like adenoidal hypertrophy and croup can cause airway obstruction and similar symptoms.
• Congestive Cardiac Failure: Heart failure can lead to respiratory symptoms and difficulty breathing.

Microscopy of nasopharyngeal secretions for alveolar macrophages and/or pH studies can help differentiate these conditions.

The management is essentially supportive care. In hospitalized cases, the goals comprise:

1. Supporting the child to mitigate the consequences of airway obstruction and the related mismatch of ventilation and lung perfusion.
2. Ascertaining the presence of (and initiating appropriate measures for) complications.
3. Protecting other children at risk.

The important elements of supportive care in acute bronchiolitis, categorized under these three goals, include:

• Oxygen Therapy: Humidified oxygen at a concentration of 30-40% will suffice.
• Amelioration of Fever and Control of Environmental Temperature: Use of antipyretics (especially paracetamol) and providing a thermoneutral environment like an incubator or a radiant warmer for the affected infant.
• Provision of Additional Fluid and Feeds: Besides judicious fluid supplementation, there is a need to provide additional calories via frequent small-volume, calorie-dense nutrients. Breast-fed infants will need to be offered more frequently than before the illness.
• Antimicrobial/Antibiotic Therapy: Specific antimicrobial agents are rarely required in the majority of cases of this predominantly viral disease. Ribavirin for RSV bronchiolitis is reportedly associated with more rapid viral shedding and overall clinical improvement.

Ribavirin is administered as small particle aerosol via an oxygen hood or ventilator as a 3-5 day course, comprising 12-20 hours of treatment per day. It is recommended for mortality-prone infants with bronchiolitis.

The use of antibiotics or antibacterial chemotherapy should be individualized for those with superimposed bacterial pneumonia, based on a combination of clinical and radiographic parameters. The choice of an antibacterial agent must take cognizance of Staphylococcus species in addition to the usual agents associated with community-acquired pneumonia.

Others:

• Trial of Bronchodilators: Consideration of bronchodilators for management.
• Nasal Decongestion: The potential benefit of nasal decongestion in infants with bronchiolitis lies in the fact that most infants are obligate nasal breathers. Nasal decongestion will not only ameliorate the respiratory distress but enhance oral intake of fluids and calories. Intermittent gentle suctioning of the nostrils and the nasopharynx (with or without saline nasal drops) using a suctioning machine in hospitalized infants and parent-assisted mouth to nose clearing of secretions in ambulatory cases are useful adjunctive treatment measures.

Immunisation:

• Periodic passive immunoprophylaxis with palivizumab before or during the peak season has proved to be an effective preventative tool in children with high-risk disease.
• Intravenous polyclonal RSV-hyperimmune immunoglobulin (RespiGAM) may serve a similar purpose, though it should be avoided in infants with underlying congenital cyanotic heart disease.

Protecting Other Children / Preventing Child-to-Child Transmission:

• Inter-contact hand-washing is required to minimize the risk of child-to-child spread of the virus, especially in nurseries and emergency rooms.
• Excusing children and staff with acute respiratory illness from attendance, at least during the active phase.