Bronchiolitis: a virus of infancy.
While usually mild and self-limiting, bronchiolitis causes increased rates of illness and death in infants and can result in substantial cost to families, including loss of caregiver earnings. It has also been linked to an increased risk of chronic respiratory conditions such as asthma in later life.
Management of bronchiolitis is largely supportive but there is considerable debate about many common interventions. Nurses are key providers of support and advice to parents and caregivers of children about care in the home and when to seek help. In primary and acute care, monitoring an infant's respiratory status and response to treatment depends on a detailed understanding of physiological and pathophysiological events underlying infant respiratory function in health and in response to infection.
Up to three per cent of children in developed nations are admitted to hospital with bronchiolitis before one year of age, and up to 59 per cent of general practitioner consultations in this age group are for viral respiratory infections. (1,2) While the mortality rate for this disease is low in developed nations (less than one per cent on average), prematurity or the presence of lung or cardiac disease increases mortality to three to five per cent. (3)
Worldwide, 18 per cent of deaths for children under the age of five are due to respiratory infections (greater than diarrhoeal disease and malaria). (1) Lower respiratory tract infections (LRTI), including pneumonia and bronchiolitis, cause two millions deaths annually in Africa and South-East Asia. The causative pathogens are both viral and bacterial but it is unclear how many bacterial LRTIs are due to secondary infection following a virus. (4)
In New Zealand, the average number of admissions for bronchiolitis is around 80 per 1000 infants under one year of age, while the averaged mortality rate is one death per year. There is a much higher rate of admission for male infants, for Pacific (169 per 1000) and Maori (115 per 1000), and for young children from more deprived socio-economic circumstances. (5,6)
Bronchiolitis has been linked to the development of wheeze and asthma in later childhood but it is not definite whether the viral infection contributes to wheeze development or if it is an early marker of an asthma-prone child. (1,7) There is some evidence that viral LRTI may also have extrapulmonary effects: about two per cent of infants with bronchiolitis will display central nervous symptoms such as seizures, lethargy, central apnoea and even encephalopathy. There may also be cardiovascular and hepatic symptoms for a small number of infants, but whether this is a direct result of the virus or related to pulmonary events is unclear.,
The major causative organism of viral LRTI in infants has been identified as respiratory syncytial virus (RSV). This is a seasonal virus in temperate climates, with peak incidence in late winter. On average in New Zealand, admissions to hospital with bronchiolitis range from 100-200 in summer to more than 1000 in August (6) In the Northern Hemisphere, peak admissions occur in January and February, while in tropical regions, peak incidence coincides with the rainy season. It is believed nearly every child will get at least one RSV infection before age three. (3)
Other viruses have been identified as causes of LRTI in infants, including influenza viruses, adenovirus, parainfluenza virus, metapneumovirus, bocavirus and coronavirus. Coinfection with two or more viruses is relatively common in infant LRTI, but the impact of this on disease severity is variable. (1,8) Identification of the causative micro-organism in viral LRTI is generally not necessary, since management is the same. However, identifying the virus infecting infants admitted to hospital can help reduce cross-infection.
RESPIRATORY SYNCYTIAL VIRUS
RSV is an RNA virus associated with cold-like symptoms (upper respiratory tract infection) in older children and adults, and with otitis media in older children. (9) It causes increased morbidity and mortality in immunocompromised adults and institutionalised older adults. There are two subtypes of RSV--A and B--both present in the community, but with one type usually predominating in any given season. Type A may cause a more severe degree of illness--perhaps accounting for the "bad" years for bronchiolitis. (10)
Previous infection with RSV (as with the common cold) does not confer immunity, and there may even be second or more infections in the same season. RNA viruses are particularly susceptible to copying errors, which can alter the virus sufficiently that it evades immune surveillance on subseguent infection. In older children and adults, RSV infection presents as a more severe common cold, of seven to 10 days' duration and a mean absence from work of six days. (3)
RSV is transmitted when contaminated secretions come in contact with the respiratory or conjunctival mucosa, or via inhalation of droplets. The virus has a prolonged survival time in the environment--up to six hours on hard surfaces, 90 minutes on gloves and 20 minutes on the skin. (11) In infants, clinical signs and symptoms appear after incubation of two to eight days, starting with upper respiratory symptoms: coryza (runny nose and nasal congestion), fever, sneezing and decreased appetite. The virus can be shed from eight to 21 days following infection in healthy individuals but may be present for months where there is poor immune function. (11) Risk of becoming infected is increased by the following factors (see Figure 1, p23):
* Having siblings, especially if they attend day-care or school.
* Attending day-care, creche or playgroup.
* Season of birth.
* Crowded housing.
On contact with the epithelial celts of the upper airway, RSV attaches and inserts its RNA into the infected cell. It then induces the formation of syncitia--giant multinucleated cells formed by the fusion of neighbouring epithelial cells infected with the virus. These structures help the virus evade the immune system and spread down the airways.
In the lower airways, RSV targets type 1 alveolar cells, immune cells and the epithelial cells lining the bronchi and bronchioles. This leads to cell death and sloughing into the airway, and impaired ciliary activity. Debris accumulates and obstructs the lower airways. Sloughing of the epithelium also exposes nociceptors, triggering coughing. (11)
There is much debate about whether the clinical effects of RSV bronchiolitis are due mainly to the actions of the virus itself or to the immune response. Neonates and young children exhibit different immune responses to the virus from older children and adults, and this may account for the severity of disease in the younger group. (12)
INFANT IMMUNE FUNCTION
Foetuses and young infants have an under-responsive immune system and a high level of type 2 helper T-cell activity (TH2). Reduced immune activity is due in part to the naivety of the infant immune system--having little previous exposure to pathogens, the immune system is not primed for defence. This is essential in the transition to life outside the womb, where the infant will encounter non-pathogenic antigens that should not evoke immune reactions, a process assisted by the predominant TH2 cells.
Developmentally infants have immature immune cells and low ability to synthesise antibodies. Cytokine production and signalling molecules and receptors are all lower than those in adults, reducing the function of both the innate and acquired immune systems. (1) This is why vaccination programmes targeting the very young have reduced efficacy.
Premature babies have even less immune function, since T-cells mature mainly in the third trimester of pregnancy. The premature infant also receives less passive protection due to reduced placental transfer of maternal antibodies. (11) Several genetic polymorphisms related to immune cell function have also been identified as increasing LRTI risk.
A predominantly TH2 response to infection suppresses many activities required for viral defence (such as activation of cytotoxic T-cells and viral clearance) and impairs the regulatory T-lymphocytes that limit inflammation. Infants show increased recruitment of inflammatory cells and increased production of inflammatory cytokines in response to RSV infection. The subsequent inflammation causes increased mucous production and oedema of the airways and is responsible for many of the clinical features of LRTI in infants.
Infection of the airways brings a higher risk of respiratory compromise in newborns and infants due to anatomical differences in their respiratory system, compared with older children and adults. The structure of the airways changes with age. Under six months, infants are obligate nasal breathers--they cannot breathe through their mouths. This, combined with proportionately narrower nasal passages, increases their risk of respiratory compromise with upper respiratory tract infections. Infants in respiratory distress exhibit nasal flaring, a mechanism to reduce airway resistance in the nose. Infants' proportionately larger tongue, softer trachea and shorter neck increase the risk of airway narrowing or obstruction with both extension and flexion, making appropriate positioning for infants with LRTI essential. (13)
The chest wall of infants and young children is highly compliant, as the ribs are not well ossified. During inspiration, when the diaphragm moves downward, the infant's rib cage moves inward, rather than outward as for adults. This means infants cannot easily expand their lung volume to take deeper breaths (tidal volume), so increased ventilation relies solely on the ability to increase respiratory rate.
High compliance also means the infant's chest wall collapses during exhalation. This must be opposed through active "braking" by the inspiratory muscles or by closure of the glottis. Loss of these mechanisms can lead to atelectasis (collapse of blocked alveoli and bronchioles), especially since the natural pressure at the end of expiration is the same pressure required to compress and close off smaller airways. (14) Grunting occurs where there is partial closure of the glottis at the end of expiration, which raises end expiratory pressure to keep the smaller airways open.
Having a very compliant chest wall causes marked indrawing of intercostal and accessory muscles when extra respiratory effort is exerted. Retraction of the intercostal, supra- and sub-sternal, and supraclavicular spaces is seen where there is airway obstruction or when the compliance (stiffness) of the lungs/alveoli is increased (eg, when there is reduced surfactant in the alveoli or inflammatory damage to the pneumocytes).
The bronchi and bronchioles of infants are more prone to obstruction, as they are narrower than those of adults. Halving the diameter of an airway increases its resistance to airflow by 16 times, having an enormous impact on the infant's work of breathing and entry of air to the alveoli. (13) A viral LRTI narrows airways, both through increased mucus secretion (with reduced clearance due to cilia damage) and inflammation of the airway walls.
Infants rely largely on their diaphragm for breathing. The type of muscle fibres in neonatal and infant diaphragms are much more prone to fatigue than those in older children and adults, increasing risk of respiratory failure. (13) Bulky abdominal contents (such as enlarged organs or a stomach filled with gas) act as a splint on the diaphragm, preventing full descent and reducing air entry to the lungs.
CLINICAL MANIFESTATIONS OF BRONCHIOLITIS
The appearance and severity of bronchiolitis in an infant depends on a variety of risk factors: (1)
* Younger age.
* Smaller body size (prematurity, malnutrition or birth weight).
* No breastfeeding or reduced IgG immunoglobulin in breast milk.
* Exposure to tobacco smoke or air pollution.
* Pre-existing comorbidities, eg congenital cardiovascular conditions, lung disease, neuromuscular disorders, immunodeficiency (see Figure 1).
Generally, upper respiratory tract symptoms (congestion, runny nose, sneezing) are followed, within a few days, by cough, tachypnoea, increased work of breathing and the use of accessory muscles, wheeze and/or crackles on auscultation (or reduced breath sounds due to air trapping and peripheral hyperinflation). Fever is present in about 30 per cent of infants but this is usually less than 39degC (a high fever may indicate pneumonia). (15)
Poor feeding is common in LRTI, and must be monitored to ensure the infant has adequate fluid and nutrient intake. A baby with an elevated respiratory rate loses body water faster than normal and uses significantly more energy.
A number of infants with bronchiolitis will develop apnoea, especially premature infants and those under one month of age, probably due to immaturity of ventilatory control mechanisms in the brainstem.
Duration of LRTI symptoms varies, but the median duration of cough is 12 days, wheeze and difficulty breathing six to seven days, and poor feeding seven days. Eighteen per cent of infants will still experience symptoms after 21 days, nine per cent after 28 days. (16)
Exposure to tobacco smoke
Passive exposure to tobacco smoke and to particulate air pollution is known to increase both the severity of LRTI and risk for hospitalisation. (17) Laboratory tests show the presence of aldehydes from tobacco smoke causes increased necrosis of virally infected epithelial cells, leading to increased inflammation. At the same time, viral replication is also increased, worsening the disease burden for an infant exposed to smoke and pollution. (9)
PROGRESSION OF THE DISEASE
Airway obstruction, caused by mucus, cell debris and inflammation, traps air in the distal portions of the lungs. This generates ventilation-perfusion mismatching--where portions of the lung are receiving blood flow but not air flow--that triggers a sequence of events leading, in severe cases, to marked respiratory compromise and respiratory failure.
Trapped air in the alveoli is absorbed by the blood, causing atelectasis. The rate of collapse depends on the proportion of oxygen to nitrogen in the trapped air: nitrogen is absorbed very slowly but a higher fraction of oxygen in the trapped air (from supplemental oxygen therapy and/or mechanical ventilation) will increase the rate of collapse.
Atelectasis has the following effects:
1) Reduced lung compliance: collapsed airways require greater pressure to reinflate and are more likely to collapse again following inflation.
2) Ventilation-perfusion mismatch is increased, causing hypoxaemia, as the blood from unventilated portions of the lungs returns to the systemic circulation without fresh oxygen.
3) Risk of pneumonia increases due to tissue damage in the alveoli.
Trapped air also causes hyperinflation of the infant lung. This flattens the diaphragm, impeding its activity and reducing tidal volume during breathing. The infant must then breathe more rapidly to compensate, accelerating exhaustion. Hyperinflation also leads to lower excretion of carbon dioxide via the lungs. As a consequence, the infant will experience hypercapnia--an increase in arterial carbon dioxide concentration. This may be aggravated by increased metabolic activity and low arterial oxygen, if the infant's respiratory condition continues to deteriorate. (18) Deteriorating respiratory function is the main reason for admission to intensive care for infants with LRTI. The use of noninvasive respiratory support, such as nasal continuous positive airway pressure (CPAP) and mechanical ventilation, help reverse the effects of airway obstruction and reinflate collapsed portions of the lungs. (18)
ASSESSMENT OF SEVERITY
Establishing the severity of bronchiolitis in infants is essential in determining how to manage it. There are a number of clinical scoring systems, varying in complexity and ease of use, but few have been validated or tested for more than inter-rater reliability. (16,19) The National Institute of Health and Care Excellence (NICE) 2015 guidelines (15) do not recommend specific scoring tools and also consider generalised paediatric early warning scores (PEWS) as not sufficiently well studied in predicting deterioration for infants with bronchiolitis.
In Australia, a study looked at reliability of a scoring system that can be used by trained nurses, and is especially useful for those working in remote communities. The modified Tal scoring system replaces assessment of cyanosis with oxygen saturation readings to determine severity of bronchiolitis. The other parameters assessed are: respiratory rate, wheeze, and use of accessory muscles. (19) The study found good interrater reliability, and internal consistency with ease of use but was not able to predict need for oxygen or admission to hospital.
New Zealand and Australian algorithms are available to provide a guide to severity. (2,20) However, these algorithms do not take account of risk factors related to medical history (such as prematurity or presence of heart or lung conditions) and the infant's age, and should not be used as the sole criteria for determining referral, admission or management.
Bronchiolitis is considered to be moderate when there is increased respiratory rate (> 60 breaths per minute [bpm] for infants under two months and > 50bpm for two-12 month olds) with minor use of accessory muscles. Tachycardia, difficulty breastfeeding (or less than 50-75 per cent of usual volume of bottle feed) and mild dehydration will also be present. Oxygen saturations are sustained between 92-95 per cent.
Evidence of severe or life-threatening LRTI includes any of the following:
* Sustained oxygen saturations of less than 90-92 per cent.
* Respiratory rate greater than 70bpm.
* Maximal use of accessory muscles or evident exhaustion with poor respiratory effort.
* Nasal flaring and grunting.
* Marked tachycardia.
* Unable to feed or not interested. Choking, frequent pauses or desaturations during feeding.
* Marked dehydration.
* Child may appear pale, sweaty, lethargic or cyanotic.
The use of pulse oximetry to assess respiratory function in LRTI and determine referral and management, is controversial. There is no agreed cut-off point for oxygen saturations in determining disease severity, and little research to support cut-offs in published guidelines. The 2014 guidelines from the American Academy of Pediatrics state that oxygen need not be given to infants with saturations of 90 per cent or higher (although the evidence for this is acknowledged to be weak) (17) but this has been criticised by other clinicians. (21) The 2015 NICE guidelines recommend oxygen therapy for infants with saturations persistently less than 92 per cent. (15)
An interesting 2014 study has raised concerns that decisions to manage bronchiolitis (including admission and use of oxygen therapy) are increasingly being based on oxygen saturation readings alone, with less consideration of other clinical signs and symptoms such as respiratory rate. This may account, in part, for the increasing rate of hospitalisation for bronchiolitis in the last 20 years. It also raises concerns that infants with adequate saturation readings may have other signs of clinical deterioration overlooked. (22)
Diagnosis of bronchiolitis is based on history and clinical examination. There is no role for radiographic imaging or laboratory testing unless there is a suspicion of other causes of the clinical presentation. (15,17)
MANAGEMENT OF BRONCHIOLITIS
The impact of infection on an infant is determined by two factors: the damage caused by the virus directly, and the damage caused by the body's immune response to infection. While it is difficult to separate these two in terms of pathology, they can be used to guide management --treating the virus (with vaccines, passive immunisation and antiviral drugs) or treating the inflammation (with corticosteroids or specific anti-inflammatory mediator-targeted drugs).
Evidence for many common interventions in bronchiolitis is poor, so current guidelines recommend few, other than supportive care.
Nebulised salbutamol: Salbutamol is a bronchodilator that relaxes the smooth muscle lining the bronchi. Narrowing of the airways in bronchiolitis is mainly due to inflammation--not reactive bronchoconstriction as with asthma--so there is minimal benefit from administering salbutamol or other bronchodilators. Research has shown some improvement in clinical severity scores, but no impact on disease duration, need for hospital admission or length of stay. (17) Benefits of administering bronchodilators are outweighed by potential adverse effects, which include tremors, and tachycardia and dysrhythmias (adding further stress to the infant's cardiovascular system).
Nebulised adrenaline: Adrenaline acts on both alpha- and beta- adrenergic receptors, with a stronger effect than salbutamol on the smooth muscle of the airways, but also on cardiovascular function. There is no evidence to support its use for mild to moderate bronchiolitis. (11,15)
Nebulised hypertonic (3%) saline: Saline solution is believed to help clear mucus from the airways. Theoretically, the saline attracts more water into the airway, causing hydration of mucus plugs and stimulating the cilia. There is no demonstrated benefit in terms of hospitalisation when used in emergency departments. It may reduce length of stay for infants hospitalised for longer than three days, but has not shown efficacy in primary care where single or short-term use is usual. (11,17)
Corticosteroids: Corticosteroids suppress the inflammatory response and seem a viable option for treating bronchiolitis, especially given their success in managing asthma and croup. However, they do not reduce admission or length of stay in bronchiolitis. There is insufficient understanding of the adverse effects in young infants, so risks cannot be realistically determined. It is known that corticosteroid use prolongs the time of viral shedding after recovery from bronchiolitis. (11)
Antibiotics: Bacterial co-infection, particularly during later stages of bronchiolitis, may be due to suppression of immune responses and damage to physical respiratory defences (thinning of the mucus layer, pooling of secretions, disrupted epithelial layers) caused by the virus itself. Bronchiolitis is a viral infection and unless there is clear evidence of bacterial secondary infection, antibiotics should not be used.
Antivirals: Ribavirin has been used in nebulised form to treat bronchiolitis but with no significant benefit to infants. (16) As a known teratogen, Ribavirin poses significant risks to health workers; it is also very expensive. (2) Use of nebulised ribavirin is not recommended. As yet there are no other antivirals used to treat bronchiolitis.
Monoclonal antibodies: Palivizumab is an engineered antibody against RSV. It cannot treat bronchiolitis once symptoms have appeared but may be used to prevent disease in certain groups of infants. Prevention of RSV is beneficial to infants at high risk of adverse outcomes and may be given monthly during peak RSV season during the first year of life. (8,17)
Oxygen: Supplemental oxygen should be given to infants with oxygen saturations persistently lower than 92 per cent. (15) Oxygen is usually administered via nasal cannula, but, most recently, high-flow humidified oxygen delivery devices have entered practice. These are believed to benefit infants with bronchiolitis because the humidification reduces insensible water loss from the airways (decreasing dehydration risk) and helps clear mucus. High flow rates generate continuous positive pressure in the airways that could help reduce the work of breathing in bronchiolitis and decrease the need for more invasive respiratory support. (17) Research is needed to support these proposed benefits for use of high-flow humidified oxygen. (15)
Nutrition and hydration: At high respiratory rates, coordination between breathing and swallowing may be impaired. Copious nasal secretions, especially early in the course of bronchiolitis, also impair feeding. There is increased risk of aspiration, dehydration and undernutrition. One-third of infants hospitalised with bronchiolitis need fluid replacement. (17)
Infants who cannot feed adequately need either nasogastric administration of breast milk or formula, or intravenous isotonic fluid. There is no significant difference in length of hospital stay, rates of admission to intensive care, need for ventilator support, or adverse events between these two feeding methods. Success with insertion is greater with nasogastric tubes than intravenous cannulae. (17,23)
Other interventions: Chest physiotherapy is not shown to benefit otherwise healthy infants with bronchiolitis. Routine upper airway suctioning is not recommended, but may be helpful where there is respiratory distress or feeding difficulties due to upper airway congestion, or if there is apnoea. (15) Positioning of the infant should be determined by what brings most comfort and least distress.
PREVENTION OF BRONCHIOLITIS
RSV is a highly infectious virus. Spread of infection in the community and in hospital is common and, in some settings, seemingly inevitable. The virus can survive for prolonged periods in the environment, so hand hygiene is an essential part of prevention.
RSV is most susceptible to alcohol hand rubs (more than hand-washing with soap and water). Alcohol hand rubs are more effective at removing organisms, less time-consuming and less irritating. They should be used before and after direct contact with every sick infant, after contact with any objects in the direct vicinity of the infant, before putting on gloves and after removing gloves. (17) This advice should also be given to family members caring for sick infants at home.
A vaccine against RSV was released in the United States in 1966. It used RSV that had been killed by formalin. The vaccine proved ineffective --vaccinated children still caught the disease, had worse symptoms and were hospitalised more often, and two infants died. It was thought that the formalin caused an alteration in the viral structure, which meant antibodies triggered by the vaccine were not able to adequately fight off the RSV on subsequent infection. More recently, the evidence suggests the vaccine was not sufficiently strong to cause "affinity maturation"--the process whereby antibodies become highly targeted to their specific antigen as the immune response to the vaccine progresses. (24) This requires either that the virus replicate within the body (and the formalin vaccine was unable to do this) or that the vaccine be administered with an adjuvant that stimulates maturation affinity without viral replication. The spectre of the 1966 vaccine disaster has had an impact on development of a RSV vaccine to this day. Many vaccines are under development but none have reached the market.
A further issue with vaccination programmes is immaturity of the infant immune system, especially in the very young. It is thought that, once a viable vaccine is developed, targeting older (school age) children may help reduce household transmission. Maternal vaccination may also help, through placental transmission of antibodies in the third trimester and via breast milk. Passive protection from RSV is increased where there is exclusive breastfeeding up to six months of age. (17,25)
Viral shedding occurs for at least one to two weeks following RSV infection and 30-70 per cent of family members may fall ill following exposure. The method of transmission and prolonged survival of RSV in the environment indicates the need for education on handwashing, contact precautions and reducing aerosol spread from coughing and sneezing.
Exposure to second-hand tobacco smoke is not just via direct exposure to exhaled smoke. Chemicals linger on clothing and furnishings for prolonged periods. Recent studies suggest fewer than half of children and infants exposed to smoking are identified in hospital outpatients, inpatients or emergency departments. (17) This information is important, both to identify increased risk of severe disease and to educate families on smoking cessation and limiting infants' smoke exposure.
Family education should emphasise the long duration of symptoms with bronchiolitis. Parents often visit primary care and emergency departments repeatedly over the two to three weeks of an infant's illness; reassurance that two to three weeks is a normal course for the illness may help to alleviate anxiety and reduce expenses and disruption. (17)
Limiting visitors during the peak bronchiolitis season can help prevent exposure of young infants to RSV. Education should emphasise the need for people who are symptomatic or recovering from "colds" to stay away from young families.
Infants assessed in the early stages of illness may deteriorate within 72 hours of becoming ill. Parents should be provided with specific and detailed information about warning signs of deterioration, and given clear direction about when and how to seek further help. New Zealand guidelines say infants assessed as having moderately severe disease should be seen again within 24 hours. Those with mild or moderate disease who have been ill for more than 72 hours should be provided with reassurance but not seen again unless concerned. (20) Decisions to refer and admit should consider the socioeconomic circumstances and coping ability of caregivers, including how far they need to travel for health care if the baby deteriorates, their ability to monitor for and recognise deterioration and their confidence in providing supportive care. (15)
After reading this article, and completing the accompanying online learning activities, you should be able to:
* Outline features of infant anatomy and physiology that increase vulnerability to viral respiratory tract infections.
* Discuss common causative organisms of bronchiolitis and their pathophysiological impact.
* Assess evidence for the effectiveness of commonly used therapies for managing bronchiolitis.
* Describe measures used to prevent bronchiolitis and the development of a vaccine.
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Georgina Casey, RN, BSc, PGDipSci, MPhil (nursing), is the director of CPD4nurses.co.nz. She has an extensive background in nursing education and clinical experience in a wide variety of practice settings.
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|Title Annotation:||CPD + nurses|
|Publication:||Kai Tiaki: Nursing New Zealand|
|Date:||Aug 1, 2015|
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