Near fatal asthma in children and young people

Abstract

INTRODUCTION: Asthma is a common respiratory condition affecting 1 in 11 children in the UK. There are approximately 1200 deaths from asthma every year in the UK across all ages. Within Europe, the UK has the highest rate of asthma mortality in children 0 – 19 years old. In the UK the diagnosis and management of asthma has been standardised, with specific management for acute asthma attacks depending on the severity of symptoms. Acute asthma attacks are categorised by national guidelines into severity: mild, moderate, severe and life threatening4. Life threatening asthma is a broad category that is not further subcategorised to differentiate near fatal asthma (NFA). The lack of a clearly defined category of near fatal asthma attack may have an impact on its clinical recognition and the possibility of intervention to prevent future fatal asthma attack. The definition of near fatal asthma has evolved over time but remains poorly defined beyond the most severe form of survivable acute asthma. Unlike severe asthma, near fatal asthma does not describe chronic symptoms. Factors associated with more acute severe progression of asthma attacks remain poorly elucidated. The terms severe asthma, life threatening asthma and near fatal asthma are often used interchangeably and without precision. Terminology such as ‘life threatening attack’ or ‘status asthmaticus’ had previously described severe asthma attacks but these terms also lack clear definition in terms of comparative severity. In contrast, near fatal asthma indicates a pre terminal attack which would most probably result in asthma death without intervention. Understanding these attacks could be key to reducing and ideally preventing asthma deaths. The management of children with near fatal asthma is neither standardised or well described. In part through the lack of a distinct category, the frequency of these attacks in children and young people in the UK is not known.

In this thesis, I will ascertain the frequency of NFA (as defined by an e-Delphi consensus) and characterise NFA attacks in detail through an observational surveillance project. Through a systematic review, the influence of environmental risk factors, specifically outdoor air pollution will be examined in the context of near fatal asthma attacks.

OBJECTIVES: 1.To conduct a systematic review on ambient outdoor air pollution and its association with severe asthma attacks in children. As a secondary outcome review the multiplicity of associated asthma risk factors that may contribute to near fatal asthma.

2.Through an observational surveillance study, measure the annual frequency of NFA attacks in children and young people in the UK and Republic of Ireland, and to describe key characteristics and potential risk factors.

3.Using the data set identified in the surveillance study, assess the effect of environmental and infective factors on NFA attacks in children and young people, to include air pollution, weather, pollen levels and prevalent respiratory viruses.

4.Assess if the method of surveillance was adequate to draw conclusions from the data and consider if the use of an alternative research methodology to identify near fatal attacks such as disease registries could strengthen analysis.

METHODS: To identify relevant literature observing any association between outdoor air pollution and near fatal and fatal asthma in children and young people, a systematic review was completed following Cochrane methodology.

To determine the frequency of near fatal asthma in children and young people in the UK, I conducted an observational surveillance study. Data were collected on near fatal asthma attacks in children aged 5 – 15 years over 18 months (1st October 2022 – 1st April 2024). Detailed questionnaires were sent to clinicians who are part of the British Paediatric Surveillance Unit and receive monthly e-reporting cards. An eDelphi consensus definition of near fatal asthma was included on the monthly reporting cards. Any clinicians who reported a case of near fatal asthma completed a questionnaire. Data were submitted to and analysed within a safe haven (Health Informatics Centre (HIC) Dundee). Data linkage was carried out within the safe haven. Cases were described in detail. Patient demographics and presentations were compared to current literature on near fatal asthma in children.

Within the safe haven, data on air pollution, respiratory viral infections in the UK, weather, social deprivation and seasonal pollen data were observed throughout the study period using publicly available data sources.

RESULTS: Only four studies met the inclusion criteria of the systematic review for near fatal and fatal asthma attacks in children associated with outdoor air pollution. The heterogeneity of these studies limited synthesis of the data. A key finding of the review was the lack of definition of asthma severity in studies attempting to associate outdoor air pollution with asthma attacks in children. A significant number of studies (n = 217) could not be included in the review as the severity of the asthma attack was not specified by the paper.

Observational surveillance study results: Fifty one near fatal cases were reported during the study period (1st October 2022 – 1st April 2024). Two cases had two attacks within the study period (n = 49 patients, 51 cases of NFA). Cases were more frequently observed in males (n=30) compared to females (n=19). The median age of a NFA case was 10.7 years. Of the 51 cases 19.7% (n = 10) of cases did not require invasive ventilation or experience cardiorespiratory arrest. The median duration of admission was 5.5 days (IQR 3 – 10 days). Eight cases (18.2%) were not known to have asthma prior to near fatal attack. Fewer than 5 cases did not make a full recovery from the attack and were discharged with neurological or other sequelae. 1 in 5 cases did not have a change in medication on discharge and 25% were known to be discharged home without an asthma action plan. Follow up varied from asthma nurse only (n= 1) to respiratory paediatrician (n= 28). One third of patients were from the lowest deprivation quintile in England.

Air pollution data based on postcode was available for 44 of the 49 patients. Annual mean modelled background Particulate Matter (PM) levels for PM10, PM2.5 and Nitrogen dioxide (NO2) were obtained for patient postcode from the Department of Environment, Food and Rural Affairs (DEFRA). The median PM10 concentration was 12.2µg/m3 (IQR 10.8 – 14.7) with 11 patients (11/44, 25%) exceeding the World Health Organization (WHO) recommended limit for annual PM10 exposure (15µg/m3). Forty two patients (42/44 cases, 95%) exceeded the WHO recommendation for PM2.5 annual exposure level (5µg/m3). Twenty seven patients (27/44, 61.4%) exceeded the WHO recommended annual exposure for NO2 (10µg/m3).

CONCLUSION: Near fatal asthma is rare in children and young people (51 cases in the UK and Ireland in 18 months). The results of this study present baseline characteristics for this population (age, gender, ethnicity) and reaffirm previous studies observing an increase in cases in patients from lower social deprivation quintiles. Follow up care is not standardised throughout the UK and Ireland and must be addressed to prevent further near fatal asthma attacks in this population. Outdoor air pollution exceeding WHO recommended guidelines was commonly observed particularly for PM2.5 and outdoor air pollution exposure should be considered in collateral history for near fatal asthma. Results from the systematic review support the need for further studies on clearly defined near fatal asthma and outdoor air pollution. Estimating the frequency of cases through clinician surveillance presented challenges such as clinician engagement, incomplete data and survey fatigue and future studies must consider if clinician surveillance is the most effective method to gain insight into near fatal asthma attacks. Identification of near fatal asthma, recognition of outdoor air pollution as a potential risk factor for attacks and clear management pathways are required to ensure standardised care of children with near fatal asthma in the UK and Ireland.