Characteristics of children admitted to intensive care with acute bronchiolitis

Acute bronchiolitis is a leading cause of hospitalization in young children. Although children with bronchiolitis do not usually require hospitalization, approximately 3% of affected children are admitted to hospital [7, 30].In the developed world, infants aged < 1 year with bronchiolitis account for 18% of all paediatric hospital admissions [13]. In December 2011 in England, there were 30,451 hospital admissions for bronchiolitis [6]. Bronchiolitis admission rates in infants under 1 year have previously been estimated to be 24.2 to 31.2 per 1000 in the UK and USA, respectively [4, 12, 21].

Most children hospitalized due to acute bronchiolitis have an uneventful course [3, 15]; however, approximately 2–6% requires admission to a paediatric intensive care unit (PICU), with 2–3% of hospitalizations requiring invasive mechanical ventilation [13]. Acute bronchiolitis accounts for around 13% of PICU admissions in the UK [9], thus being a significant burden on PICU beds, with a “winter surge” in activity occurring predictably each November to February [7, 11, 12, 29].

Prior studies have identified risk factors associated with hospitalization for bronchiolitis, including prematurity, younger age, environmental factors (e.g. passive smoking, crowded household) and presence of co-morbidities (e.g. chronic pulmonary disease, congenital heart disease, immunodeficiency, neurologic disease) [4, 18, 28, 31]. However, few studies have yet described factors associated with PICU admission and outcome.

Despite the high hospitalization rate associated with bronchiolitis, it is however uncommon for bronchiolitis to cause death. Data from children with bronchiolitis due to the most commonly associated cause—respiratory syncytial virus (RSV)—notes that deaths are rare in the developed world and range from 2.9 (UK) to 5.3 (USA) per 100,000 children below 12 months [7, 30]. In October 2009 in England, there were 72 recorded deaths of children within 90 days of hospital admission for acute bronchiolitis [6].

We aimed to investigate factors associated with outcome in children with a diagnosis of bronchiolitis admitted to a single PICU over a 6-year period, between January 2011 and December 2016.

We identified 274 children who fulfilled the inclusion criteria. The total number of PICU admissions in this period was 1967 patients; therefore, children with bronchiolitis constituted 13.5% of all PICU admissions.

The majority of patients (173, 63%) were males and 100 (36%) were Caucasian (Table 1). The median age of children admitted to PICU with bronchiolitis was 60 days (IQR 28–150 days). Across all years of the study, children in the first 42 days of life were the most common age group admitted. Overall, children < 1 year of age accounted for 97% of admissions with bronchiolitis.

Our study presents a comprehensive review of the characteristics and clinical outcomes of children admitted to a single PICU in London, UK, with a clinical diagnosis of acute bronchiolitis. While only examining a single unit’s admissions, we feel this is a representative sample of admissions to PICUs in the UK. Our unit is primarily a medical PICU, taking predominantly unplanned acute admissions. The proportion of children admitted to this PICU is reflective of the data observed by Green et al., who found that infants aged < 1 year accounted for 93% of all PICU bronchiolitis admissions in England and 11.8% (95% CI 10.5 to 13.1%) of PICU admissions in England each year. They estimated the PICU admission rate for bronchiolitis to be between 1.3 and 1.6 per 1000 infants aged < 1 year [9].

In our study, infants aged < 1 year accounted for 97% of all admissions to our PICU with bronchiolitis. The majority of our cases were infants aged ≤ 2 months (n = 150), and 70% of these were RSV positive, suggesting that younger infants are more vulnerable to severe RSV disease, which is consistent with the findings from previous studies [12, 18, 28].The association of younger age and prematurity with an increased risk of PICU admission was not unexpected and has been well described previously.

RSV was the most common virus identified in our study (60%). In most studies, it accounts for 60–80% of bronchiolitis cases in children below 12 months of age [14, 22, 23, 26]. Rhinovirus was the second most common virus detected (26%), followed by human metapneumovirus (7%), parainfluenza, adeno- and influenza viruses (1–8%). Dual infections were found in 46% of children in our study, while it has been reported in 20–40% of patients in previous studies [14, 20, 22, 23, 26]. Some studies suggest that co-infection is associated with more severe disease [5]. However, it is sometimes hard to determine the pathogenicity of co-infecting viruses, particularly rhinovirus. Co-infection was also a significant determining factor for length of PICU stay in our study. Richard et al. [25], also reported an increased risk of admission to the ICU when a dual viral infection was found, but the population in their study included many premature infants and children with underlying chronic illnesses. In contrast, Marguet et al. [17] did not find any difference in bronchiolitis severity in patients solely infected with RSV compared to those with RSV—rhinovirus co-infection. As the numbers of children with co-infection in our cohort and in other reports are significant, efforts to determine the contribution of more than one infecting virus would be an important element in any efforts to promote antiviral or preventative therapy for bronchiolitis.

Eight percent of children in our study had rhinovirus as the only identified pathogen and 10% of children had no pathogen identified at all. This suggests that our current routine diagnostic methods are sub-optimal, and in these critical cases, it may be appropriate to carry out extended methods for pathogen detection. However, with no effective antiviral therapies yet available, the necessity to do this for diagnostic purposes, rather than for infection control or public health measures, remains unclear.

Consistent with previous studies [8, 9], the median length of PICU stay among bronchiolitis admissions was ~ 6 days. This was significantly longer in those children with RSV infection compared to the non-RSV group. As seen in these previous studies, RSV infection also appeared to be associated with relatively more severe disease, as determined by higher numbers of children requiring post-extubation respiratory support and supplemental oxygen.

Length of stay in the PICU may not be a very objective endpoint to evaluate disease severity as it is confounded by other factors such as co-morbidity. For example, patients may be observed for longer on PICU or clinicians may have a lower threshold for initiating CPAP after a period of mechanical ventilation. Therefore, duration of invasive mechanical ventilation may be a better endpoint from this point of view. Our regression analysis confirmed this, and only age on admission was found to be a statistically significant factor when allowing for pre-existing co-morbidity.

Prematurity was common in our cohort of patients, accounting for nearly half (46%) of all patients, with extremely preterm infants (≤ 28 weeks gestation) accounting for 11% of cases admitted to PICU, compared to only 3% of hospitalized children in previous studies [9, 21], although no other studies have focused purely on PICU admission with bronchiolitis. One study from Taiwan which examined risk factors associated with death in patients with severe RSV found that almost 50% of their patients admitted to their PICU were premature, and 25% had a nosocomial RSV infection [16]. None of our patients was found to have a nosocomial cause for their acute bronchiolitis illness. Moreover, we found prematurity particularly associated with admission for apnea, being found in 66% of all admissions to PICU for apnea in the context of bronchiolitis [27].

In our study, 38% of the admissions to PICU with bronchiolitis had documented co-morbidities prior to admission or discovered during their admission for bronchiolitis. This differs from previous studies which identified co-morbidity in only 24–27% of hospital admissions with bronchiolitis [8, 12] but is fewer than the study from Taiwan quoted above, where 72% of patients admitted to PICU with RSV had a co-morbidity [16]. However, this is an important message—in children admitted to PICU with bronchiolitis, a careful search for underlying cardiac, pulmonary, or neurological disease should be undertaken in what are thought to be previously healthy children. This may unmask a condition that may predispose the infant to more frequent or more severe respiratory infection.

There is evidence that children with underlying co-morbidities who should have received RSV-prophylaxis do not always receive it [1]. Our study and other studies have demonstrated that current guidelines for RSV-prophylaxis may exclude many patients who are at high risk but who do not fulfil the current guidelines for prophylaxis and suggests that further analysis to determine those patients who may benefit most from RSV-prophylaxis is required. Use of agents such as palivizumab has been shown to reduce the burden of hospitalization and mortality in bronchiolitis in a cost-effective manner [2, 19, 24]. However, if our data is representative of PICU admissions for bronchiolitis across the developed world, other factors may need to be taken into account when deciding on eligibility for palivizumab or other similar agents. Additionally, developments in RSV vaccines suggest that many admissions to PICU could be prevented by effective maternal immunization [10].

Our study was of children in one representative PICU and retrospectively examined data from an existing database, medical charts and diagnostic testing results. Therefore, there was some missing data and we were reliant on the accuracy of existing coding. However, we feel that our study is representative of the current situation of admissions to general PICUs with bronchiolitis in the UK.

Bronchiolitis is a significant cause of PICU admission in the developed world. Most children with bronchiolitis-related PICU admission required prolonged PICU stay and invasive ventilation.

A significant proportion of children admitted to PICU with bronchiolitis had no recognized risk factors. A careful search for co-morbidity should be made in children being admitted to PICU for bronchiolitis.

Many children admitted to PICU with RSV bronchiolitis did not fall into the recognized indications for RSV-prophylaxis, suggesting that these indications should be re-evaluated.

The increasing recognition of co-infections in acute bronchiolitis may impact the design and sample size of future studies in this field.