Pearls
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Bronchiolitis accounts for 5% to 10% of total pediatric intensive care unit admissions in the United States.
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Treatment for critical bronchiolitis is predominantly supportive, particularly for hypoxia, hypercarbia, dyspnea, and dehydration.
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Use of medications and respiratory support modalities vary widely by region and between institutions without clear benefits on clinical outcomes.
Lower respiratory tract infection is a leading cause of global morbidity and mortality in young children; viral bronchiolitis comprises approximately one-quarter of these infections. , While overall mortality is low in high-resource areas, morbidity and associated healthcare costs are increasing. In 2009, the hospital charges related to bronchiolitis were approximately $1.7 billion in the United States alone. In the United States, bronchiolitis is the most common cause of hospitalization among infants. It accounts for approximately 5% to 10% of total pediatric intensive care unit (PICU) admissions in the United States, 8% of PICU admissions among children younger than 6 years in the United Kingdom, and 28% of nonelective PICU admissions in Australasia. As such, the pediatric intensivist should be familiar with the diagnosis and management of bronchiolitis, understand the high morbidity and cost associated with the disease, and appreciate the paucity of PICU-specific data and need for continued research. This chapter will review the microbiology, epidemiology, pathophysiology, clinical presentation, current therapeutics, and common complications associated with severe bronchiolitis requiring PICU admission, termed critical bronchiolitis .
Microbiology
The most common pathogen causing bronchiolitis is respiratory syncytial virus (RSV), accounting for approximately 50% to 80% of cases. The development of sensitive viral testing methods, including polymerase chain reaction, has increased the number of viruses implicated in lower respiratory tract infections. , Rhinovirus; parainfluenza virus types 1, 2, and 3; influenza types A, B, and H1N1; human metapneumovirus; coronaviruses; enterovirus; and adenovirus are all associated with bronchiolitis. Up to one-third of children with RSV and nearly three-quarters of children with rhinovirus are coinfected. There is some evidence to suggest that RSV causes more severe disease than other viruses and that coinfections predispose children to more hypoxia and prolonged hospital length of stay (LOS). , These findings are not consistent across all studies; thus, there are currently no recommendations to change medical treatments based on viral etiology. ,
Epidemiology and risk factors
The timing and duration of the bronchiolitis “season” varies annually and geographically. The Centers for Disease Control and Prevention monitor the temporal and circulation patterns of viruses, including RSV, through the National Respiratory and Enteric Virus Surveillance System. From 2014 to 2017, the median duration of the RSV season in the United States was 31 weeks, from mid-October to early May, with a peak in early February. This pattern is not repeated internationally, however. RSV global surveillance data from low- and middle-income countries show that onset, duration, and peak activity vary widely between countries and coincide with rainy seasons and low temperatures, suggesting that indoor crowding likely contributes to RSV transmission.
Most children admitted to the PICU with bronchiolitis are otherwise generally healthy, but several comorbidities have been consistently identified as risk factors for severe illness and PICU admission. , , , Prematurity is a well-established risk factor. In one single-center study, a history of preterm birth conferred an odds ratio of 24.5 (95% confidence interval, 3.2–186.9) for PICU admission. In addition to prematurity, hemodynamically significant congenital heart disease, chronic lung disease, neuromuscular disease, and being profoundly immunocompromised are well-known risk factors for severe disease. Accordingly, these children are candidates for palivizumab prophylaxis.
There is also evidence that some demographic and social factors may predispose children to more severe disease. These include younger age, male gender, cigarette smoke exposure, and low socioeconomic status. Young infants are more likely to require hospitalization, PICU admission, mechanical ventilation, and have longer LOS. In a meta-analysis including 60 studies, exposure to household smoking increased the risk of bronchiolitis by an odds ratio of 2.51 (95% CI, 1.96–3.21). A child’s socioeconomic status may have an impact on illness severity in bronchiolitis. Children living in disadvantaged communities have been shown to have higher risk of hospital admission, higher risk of PICU admission, and longer hospital LOS.
Pathophysiology
The pathology of viral lower respiratory tract infection is best described in RSV infection. Not all infected children will develop the clinical symptoms of lower respiratory tract illness, and host anatomic and immunologic properties likely play an important role in the severity of disease. In acutely ill children, the innate immune system is activated as the infected airway cells secrete cytokine and chemokine inflammatory mediators. Infectious bronchiolitis is characterized by intense neutrophilic and mononuclear peribronchial infiltration leading to tissue edema. , In severe RSV infection, the peak viral load corresponds to peak disease severity. As the viral load decreases, an influx of plasma neutrophil precursors occurs, followed by activation of CD8 + T cells. The neutrophil-mediated inflammation of the lower respiratory tract is an important mechanism of pathophysiology in a variety of viral lower respiratory tract illnesses, including RSV, influenza A, human metapneumovirus, adenovirus, rhinovirus, and coronavirus.
In an autopsy study, children who died from RSV infection were found to have extensive RSV antigen in lung epithelium, sloughed epithelial cells blocking the small airways, significant apoptosis, low quantities of lymphocyte cytokines, and a near absence of CD8 + lymphocytes and natural killer cells. These findings suggest that the pathogenesis of fatal RSV infection may be secondary to the failure of the child to develop an appropriate adaptive cytotoxic T cell response to infection. A larger autopsy study included 250 children who died from a variety of acute respiratory infections, including RSV, adenovirus, influenza, and parainfluenza. This study described RSV as causing the most profound damage and inflammation to the bronchiolar epithelial cells. More recent studies have described a pattern of necrotic RSV-infected epithelial cells contributing to small airway inflammation. , , Furthermore, RSV likely destroys ciliated cells, contributing to impaired mechanical clearance of the distal airways.
Young children and infants are disproportionately burdened by viral lower respiratory tract disease. In addition to functionally immature immune systems, infant respiratory anatomy and mechanics predispose to severe disease. The viral-induced inflammatory response occurring in proportionally smaller bronchioles leads to alveolar obstruction and collapse with edema, mucus, and cellular debris. The increased resistance affects both inspiration and expiration in the small airways, ultimately leading to a “ball-valve” mechanism of air-trapping, hyperinflation, and resorption atelectasis. The subsequent pulmonary ventilation and perfusion mismatch may lead to hypoxemia.
Clinical features and diagnosis
Bronchiolitis is a clinical diagnosis, often defined by an age of less than 2 years with low-grade fever, tachypnea, dyspnea, upper respiratory tract symptoms (e.g., rhinorrhea), and lower respiratory tract symptoms (e.g., cough, wheezing, and rales). Tachypnea may progress to respiratory embarrassment manifested by retractions, nasal flaring, head bobbing, and grunting, ultimately leading to respiratory failure necessitating ventilatory support. Mechanical ventilation may also be needed to support infants with apnea. Apnea occurs in approximately 5% of hospitalized children and is more likely in younger infants presenting with more severe respiratory distress. In one single-center study, the relative risk for mechanical ventilation was 6.5 (95% CI, 3.3–12.9) for infants with recurrent apnea.
While only 2% to 3% of children with severe bronchiolitis require mechanical ventilation, this percentage may be as high as 35% in high-risk children with chronic comorbidities. , , Predicting the subset of children who will go on to require intensive care management is challenging for clinicians. Clinical scoring systems may be helpful; however, none has been proved universally beneficial to date. Originally developed for use in controlled trials of therapeutics, the respiratory distress assessment instrument (RDAI) and the respiratory assessment change score (RACS) may be predictive of illness severity. In a recent multicenter, international retrospective study, investigators developed a severity prediction score for children presenting to the emergency department. Predictive variables included patient age, poor feeding, oxygen desaturation, apnea, flaring or grunting, retractions, and dehydration. In a large population, the score was able to quantify risk for escalated care—defined as PICU care, or need for noninvasive or invasive ventilatory support—with good discrimination and stability.
Diagnostic testing is not recommended in current clinical practice guidelines for children with bronchiolitis in the non-ICU setting. In children with mild disease, multiple studies have suggested that chest radiographs are not needed and may lead to longer hospital LOS. Routine laboratory tests have not been shown to improve clinical outcomes of mild disease, including little utility of either abnormally low (<5000) or high (>15,000) white blood cell count in identifying children with a concurrent serious bacterial infection. However, the utility of radiographs and laboratory testing in children with critical bronchiolitis has been less studied; thus, fewer specific recommendations regarding diagnostic studies for children with critical bronchiolitis are available. The American Academy of Pediatrics (AAP) suggests that radiography “should be reserved for cases in which respiratory effort is severe enough to warrant ICU admission” or when the diagnosis is unclear. The differential diagnosis of respiratory distress and wheeze in infants is broad and includes potentially life-threatening illness, such as congestive heart failure, anatomic abnormalities, mediastinal mass, foreign body, and bacterial pneumonia. These alternate or coexisting diagnoses may be more likely in children presenting with an atypical course of bronchiolitis, including disease severe enough to warrant PICU admission. Additionally, clinicians should consider monitoring electrolytes, as children with severe bronchiolitis may be at risk for syndrome of inappropriate diuretic hormone release, and hyponatremia has been shown in multiple studies to be associated with greater illness severity. It is our practice to routinely obtain chest radiographs, complete blood cell count, and serum electrolytes in children with critical bronchiolitis. Studies of the utility of these tests in the PICU setting are needed.
Prevention
Viruses that cause bronchiolitis, such as RSV and rhinovirus, are spread via multiple mechanisms, including aerosols, direct contact with virus-containing secretions, and indirect contact (e.g., fomites). , RSV can survive on surfaces for several hours. Many patients in the PICU without bronchiolitis have risk factors for severe disease; thus, preventing spread to these susceptible children may help to improve their outcomes. Hand disinfection, with either alcohol-based rubs or soap and water (if hands are visibly soiled), is recommended by the AAP before and after direct contact with patients, after contact with nearby inanimate objects, and after removing gloves. Use of gowns, gloves, and face protection also reduce transmission. , Children at high risk for severe and life-threatening disease from RSV may be candidates for prophylactic passive immunization. Palivizumab, a monoclonal antibody against the RSV F glycoprotein, reduces the rates of hospitalization and ICU admission by 50% in high-risk children. Local guidelines vary by region, but prophylaxis may be warranted in children born extremely premature and those with chronic lung disease, hemodynamically significant congenital heart disease, immunodeficiency, and other comorbidities. Palivizumab does not improve clinical outcomes when given during acute illness to lower risk children. Vaccines against RSV are under development.
Treatment
Multiple national organizations have published guidelines for the treatment of children with bronchiolitis; however, these are generally intended for non-ICU clinicians. , Treatment for critical bronchiolitis is predominantly supportive, particularly for hypoxia, hypercarbia, dyspnea, and dehydration. , Use of medications and respiratory support modalities vary widely by region and among institutions without clear benefits on clinical outcomes. ,
Hypertonic saline
Hypertonic saline (HTS) may improve respiratory mechanics by increasing mucociliary clearance and reducing airway edema. HTS was prescribed to 13% of critical bronchiolitis subjects in one recent multicenter report and one-third of surveyed intensivists report prescribing HTS. , In general, treatment guidelines do not encourage its routine use in children hospitalized with bronchiolitis, though the AAP and Canadian Pediatric Society (CPS) suggest it may have some utility in inpatients. , , Two recent meta-analyses show that HTS may reduce hospital LOS, but results are nonsignificant if only studies with a very low risk of bias are included. , One included randomized controlled trial had 10 PICU patients (out of 408 total), but critically ill children were excluded from the vast majority of trials to date. A single retrospective study of PICU patients showed no differences in PICU LOS or duration of respiratory support between 45 children who received HTS and 59 who did not. Thus, there are insufficient data to support or refute the use of HTS for critical bronchiolitis, and it is not a common part of our practice.
Inhaled bronchodilators
Inhaled racemic epinephrine may improve respiratory distress via activation of α-receptors (airway vasoconstriction and fluid resorption) and β-receptors (bronchodilation), though wheezing in bronchiolitis may be predominantly due to obstruction with debris and not bronchoconstriction. Meta-analysis of trials in children with bronchiolitis shows that inhaled epinephrine does not improve LOS among inpatients, and scheduled administration may actually prolong hospitalization. Small studies of mechanically ventilated children show that inhaled epinephrine modestly improves resistance of the respiratory system and peak inspiratory pressures. , Albuterol, a β-agonist bronchodilator, was also tested in one of those studies and had similar effects. More recent studies show that albuterol improves respiratory resistance by more than 20% in approximately 40% of subjects, though clinicians’ ability to identify “responders” based on subjective clinical examinations was generally no better than a coin flip. Meta-analyzed data support that albuterol does not shorten hospital LOS. The AAP, Australasian guidelines, and United Kingdom’s National Institute for Health and Care Excellence (NICE) guidelines , , state that neither epinephrine nor albuterol should be used in inpatients, though the AAP points out that critically ill children are generally excluded from the trials supporting that recommendation. Both the AAP and CPS suggest considering epinephrine specifically in select circumstances (e.g., “as a rescue agent in severe disease”). , In three recent multicenter studies, each from a different continent, approximately 50% to 75% of PICU patients received inhaled bronchodilators, and most of the surveyed intensivists report prescribing them. , , , While there is likely a role for bronchodilators, particularly epinephrine, in some children with critical bronchiolitis, objective ways to identify “responders” are needed to restrict use to only those children who actually benefit from them. Until those are available, we suggest considering bronchodilators (preferentially epinephrine) in children with worsening respiratory failure, with continued use ideally based on objective improvement in respiratory mechanics.
Corticosteroids
Inhaled and systemic corticosteroids reduce airway inflammation but have generally been shown to be ineffective in inpatients and outpatients with bronchiolitis. Thus, they are not recommended by national guidelines. , Data suggest that corticosteroids are also ineffective in children with bronchiolitis who later develop asthma; their use is not recommended even in bronchodilator responders. , Unlike many other therapies discussed in this chapter, corticosteroids have been prospectively studied versus placebo in critically ill children. In a randomized controlled trial of prednisolone versus placebo, there was no statistically significant difference in duration of mechanical ventilation (4.7 ± 1.1 vs. 6.3 ± 1.6 days, P = .56) in the subgroup of mechanically ventilated children ( n = 7 in each arm), but hospital LOS was significantly shorter (11.0 ± 0.7 vs. 17.0 ± 2.0 days, P < .01). The same research group completed two subsequent multicenter studies that randomized a total of 171 mechanically ventilated children with RSV lower respiratory tract infections to either dexamethasone or placebo and found no significant difference in duration of mechanical ventilation. , Results of another trial of dexamethasone similarly found no improvements in clinical outcomes. Recent data show that approximately 25% of contemporary PICU patients with bronchiolitis receive corticosteroids despite the absence of efficacy data. , , Unless supportive evidence becomes available, corticosteroids should not be used for children with critical bronchiolitis unless another indication exists concurrently.
Hydration and nutritional support
Children with bronchiolitis may be dehydrated secondary to increased fluid losses from the respiratory tract and/or decreased fluid intake. Furthermore, hospitalized patients may not be allowed oral intake due to concerns about the increased risk of aspiration , or progression to endotracheal intubation. Targeting euvolemia is likely appropriate given the risks of both hypovolemia and fluid overload. The AAP, CPS, and Australasian guidelines recommend either nasogastric feeding or intravenous fluids to maintain hydration, while the NICE guidelines preferentially support nasogastric feeding. , Both routes lead to similar outcomes, though there was more placement failure with peripheral intravenous lines than nasogastric tubes in one large randomized trial. For children with impending respiratory failure or those with significant hypovolemia, intravenous fluids are more appropriate. Isotonic fluids are recommended by the AAP and CPS and may help reduce the risk of iatrogenic hyponatremia and unfavorable clinical outcomes. Enteral nutrition should be started as soon as the risk of intubation is sufficiently low or once clinically stable following intubation. Children with bronchiolitis supported by high-flow nasal cannula (HFNC) and noninvasive positive pressure ventilation (NIPPV) can receive enteral nutrition, but there are insufficient data to state at what point in the disease course it is ideal to initiate feeds. Our general practice is to initiate oral nutrition after the first successful wean of HFNC flow rate. In sicker patients, we commence nasogastric feeds once the child is stabilized after endotracheal intubation.
Other inhaled therapies
Mechanically ventilated children with RSV have reduced levels of surfactant. Three trials totaling 39 children performed before 2002 showed no statistically significant improvement in the duration of mechanical ventilation (MV) when meta-analyzed. , However, two of those trials , were “positive,” and meta-analyzed data did show that surfactant shortened PICU LOS. A more recent trial of 165 children aged 2 years or younger—72 of whom had bronchiolitis—showed improved oxygenation with surfactant but no change in the duration of MV. Despite the lack of proven efficacy, some providers continue to use surfactant in severe bronchiolitis. Ribavirin is an antiviral agent. A meta-analysis of three older trials (1991–1999) showed that ribavirin decreases the duration of mechanical ventilation, but this may reflect the use of sterile water as the placebo in one of the three studies. Coupled with administration-related issues, ribavirin is rarely used in the current era and is not recommended by the AAP or CPS. , Trials of ipratropium have also been negative; thus, its use is not recommended by the NICE guidelines. ,
Other systemic therapies
Bronchiolitis is caused by viruses, and rates of serious bacterial infections are low among non-ICU patients. Therefore, national guidelines do not recommend routine use of antibiotics, though use “may be justified in some children with bronchiolitis who require intubation” per the AAP. , Limited data suggest that rates of bacteremia and urinary tract infections are low among PICU patients with bronchiolitis, but that 20% to 40% of children with bronchiolitis requiring MV may have bacterial pneumonia. , Provision of antibiotics for critical bronchiolitis patients requiring MV is a common practice among intensivists , , , , and may improve outcomes, but its efficacy has not been proven. Some clinicians prescribe caffeine for bronchiolitis-associated apnea, though a recent placebo-controlled trial of 90 patients showed that a single dose of caffeine did not impact the resolution of apnea nor the need for respiratory support.
Respiratory support
Most patients with critical bronchiolitis receive respiratory support modalities such as HFNC, continuous positive airway pressure (CPAP), or invasive MV. ,
High-flow nasal cannula
HFNC systems condition (i.e., heat and humidify) the inspiratory gas so that higher gas flows can be used compared to traditional “off-the-wall” nasal cannula systems without causing desiccation or discomfort. HFNC improves a patient’s respiratory status via several mechanisms, including reduced metabolic work of the nasopharyngeal tissues, improved mucociliary function, and reduced inspiratory resistance. Substantial effects of the use of HFNC are due to washout of the nasopharyngeal anatomic dead space, replacing the CO 2 -rich and O 2 -poor air that remains in the nasopharynx at the end of exhalation with CO 2 -free and O 2 -rich gas, thereby improving CO 2 removal and oxygenation. This may be particularly beneficial in young children, such as those with bronchiolitis, given the higher ratio of anatomic dead space to tidal volume in infants. HFNC is intended to be an open system, with the nares more than 50% unobstructed by the cannula to enable washout, thereby limiting the amount of positive airway pressure generated. Nasopharyngeal pressures may reach 4 to 8 cm H 2 O, with flows up to 2.5 L/kg per minute; however, pressures depend heavily on flow rate and whether the child’s mouth is open or closed and vary widely between patients even if those factors are equivalent. , How much of this pressure is transmitted to the alveoli is unclear. In one study, esophageal pressures on HFNC at 8 L/min were, on average, only 1 cm H 2 O higher than pressures on a standard nasal cannula at 2 L/min, though a recent bench study using a three-dimensionally printed airway model reported simulated alveolar pressures up to 10 cm H 2 O in the term neonate and toddler models with flows of ∼2 L/kg per minute. Regardless of the mechanisms, HFNC reduces the work of breathing in children with bronchiolitis, , with maximal effects seen at 1.5 to 2.0 L/kg per minute, and its introduction into clinical practice has been associated with reduced rates of intubation for bronchiolitis. , Still, approximately 10% of PICU patients with bronchiolitis who are initially supported with HFNC will require intubation, and the impending failure of HFNC may be identified by a lack of improvement in tachycardia/tachypnea within 60 minutes of HFNC initiation. ,
In three interventional trials ( n = 1734) of children with bronchiolitis, an HFNC at 1 to 2 L/kg per minute has been shown to reduce the risk of treatment failure (generally defined as tachycardia, tachypnea, hypoxemia, and/or a clinical decision to escalate care) versus simple nasal cannula or facemask oxygen. In the two larger trials ( n = 1674), , HFNC did not shorten the duration of oxygen therapy or hospital LOS. More recent trials found equivalent outcomes when comparing 1 versus 2 L/kg per minute and 2 versus 3 L/kg per minute. Supported by its salutary effects on the work of breathing, modest side-effect profile, ease of setup, and tolerance by patients, HFNC use has increased for critical bronchiolitis to more than 60% to 70% of children in North America and Australasia. ,
Continuous positive airway pressure
CPAP is also commonly used for bronchiolitis, helping to maintain airway patency, increase functional residual capacity, and provide oxygen without entraining ambient air. Interventional trials show that CPAP can improve respiratory mechanics, the work of breathing, and ventilation, though some patients require sedation to tolerate the interface. Though none of those interventional trials found that CPAP improves clinical outcomes or reduces the need for invasive MV, introduction of NIPPV has been associated with reduced MV rates versus historical controls. , Approximately 20% of bronchiolitis patients on CPAP or bilevel positive airway pressure (BiPAP) will require MV, , even if first treated with HFNC.
Two randomized trials have compared HFNC to CPAP in children with bronchiolitis. The larger study ( n = 142) compared 2 L/kg per minute of HFNC to 7 cm H 2 O of CPAP and found more “failure” with HFNC, predominantly due to increases in either respiratory rate or work of breathing, though HFNC was better tolerated by the children. Interestingly, the rate of failure with CPAP in that study (31%) was similar to the failure rate with HFNC reported by the same research group in a subsequent study (39%), suggesting that the high failure rate with HFNC in the earlier study (51%) may have been related to clinician inexperience with HFNC. A smaller CPAP versus HFNC trial ( n = 31) found no differences in respiratory outcomes and reported that HFNC was better tolerated. A third, larger trial ( n = 225) found equivalent outcomes between HFNC and CPAP but also included older children (up to 4 years old) and those with bacterial pneumonia. Intubation rates were approximately 6% to 10% in all three trials and did not differ significantly between HFNC and CPAP, though none of the trials were sufficiently powered for this outcome. In a large database study ( n = 6496), intubation rates were higher following initial support with NIPPV versus HFNC (20% vs. 11%, P < .001). Though this relationship was statistically significant even after adjusting for available confounders, the risk of treatment bias in this study limits application at the bedside. In total, the available studies support that HFNC is more comfortable than CPAP, but there are insufficient data to state that HFNC or CPAP is superior as a first-line therapy for critical bronchiolitis. Recent multicenter studies suggest that some PICUs are “CPAP units,” while others predominantly use HFNC. , While our experience is that the vast majority of patients with critical bronchiolitis can be supported with HFNC alone, with rare need for either CPAP or invasive MV, clinicians should select the respiratory support modality based on local practice and patient-specific factors until a comparative trial powered to reduce need for MV and improve clinical outcomes becomes available.
Invasive mechanical ventilation
Indications for intubation for children with bronchiolitis are similar to those for children with other causes of respiratory failure. They include refractory hypoxemia/hypercarbia or intolerable dyspnea, though apnea is a somewhat unique indication in some children with bronchiolitis. Physiologic studies have shown patterns of both obstructive disease and restrictive disease during MV; thus, ventilator settings must be selected and adjusted based on each patient’s respiratory mechanics. , Use of MV has decreased in recent years as more children are supported noninvasively. Approximately 10% to 25% of PICU patients with bronchiolitis receive MV, , , , though rates vary between centers and are influenced by each institution’s criteria for admission to the PICU versus general ward. The median duration of MV is approximately 7 days. ,
Other respiratory support
Several other respiratory support modalities are used by some intensivists for critical bronchiolitis. These include negative pressure ventilation, nasal intermittent mandatory ventilation, and neutrally adjusted ventilation (invasively and noninvasively). , Inhaled nitric oxide and extracorporeal membrane oxygenation are used rarely. The prone position has been suggested as beneficial for children with bronchiolitis. Further data describing these practices in critical bronchiolitis are needed. Chest physiotherapy, while generally a low-risk therapy, has been shown to be unhelpful. Nasal suctioning may relieve obstruction, but “deep” nasopharyngeal suctioning has been associated with unfavorable outcomes. Some data suggest that heliox may improve respiratory distress but not necessarily clinical outcomes. ,
Complications
Most children with bronchiolitis recover fully, without any short-term or long-term complications. Mortality in the United States is less than 1%, but children from resource-limited countries die disproportionately. In high-resource countries, risk factors—including low birth weight, younger age, and comorbid conditions—are associated with mortality in bronchiolitis. , Though mortality is rare, the associated morbidity remains high. As one of the most common causes of hospitalization in pediatric patients, it remains a significant public health burden, with hospital charges exceeding $1.7 billion annually in the United States. Expenditures for outpatient-related care may be as high as one-third of direct healthcare costs. While most children hospitalized for bronchiolitis recover fully, hospital-associated complications are not uncommon. Retrospective data from a multicenter study including over 600 infants showed that most (79%) had at least one complication and 24% had a severe complication, defined as respiratory failure, apnea, pneumothorax, sepsis, shock, cardiopulmonary resuscitation, or seizures.
Like all PICU patients, children with critical bronchiolitis are at risk for neurofunctional morbidity that persists after PICU discharge (post–intensive care syndrome). In one single-center study, approximately 10% of 236 children with critical bronchiolitis had neurologic morbidity at the time of transfer to the general ward, including lethargy, abnormal tone, and feeding difficulty. In a long-term follow-up study from a different center, more than 25% of patients with bronchiolitis had a “fair” or worse quality of life months after PICU discharge, though it was unclear how directly attributable that was to the episode of critical bronchiolitis. More recently, a database study of 13,267 children without identifiable preexisting comorbidities reported a 13% incidence of post-ICU morbidity, such as the need for physical therapy or a feeding tube. Prospective studies that include assessment of preillness function are needed to better determine the rate of neurofunctional morbidity after critical bronchiolitis.
Observational studies show that children hospitalized with bronchiolitis have an approximately fourfold higher risk of having asthma and/or wheezing later in life, though this association becomes less pronounced after the first few years of life. Whether severe bronchiolitis causes subsequent respiratory morbidity, or if children who are already predisposed to asthma are also predisposed to more severe bronchiolitis as infants is not fully known. One interventional trial that randomized otherwise healthy preterm infants to palivizumab versus placebo may help to answer this question. Palivizumab effectively decreased wheezing during the first year of life, suggesting that RSV may be causative. However, at the age of 6 years, palivizumab improved parent-reported wheezing but not lung function (forced expiratory volume) or clinician-diagnosed asthma. This suggests that RSV is not causative but rather that severe bronchiolitis may be a marker for children already predisposed to pulmonary morbidity. As is the case for most elements of critical bronchiolitis, further research is needed to better answer this question.
Key references
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