Financial support
Financial/nonfinancial disclosures : None declared.
Funding/support : The Precision Medicine for more Oxygen (P4O2)
consortium is co-funded by a PPP Allowance made available by
Health~Holland, Top Sector Life Sciences & Health
(LSHM20104; LSHM20068), to stimulate public-private partnerships and by
Novartis. Partners in the Precision Medicine for more Oxygen (P4O2)
consortium are the Amsterdam UMC, Leiden University Medical Center,
Maastricht UMC+, Maastricht University, UMC Groningen, UMC Utrecht,
Utrecht University, TNO, Aparito, Boehringer Ingelheim, Breathomix,
Clear, Danone Nutricia Research, Fluidda, MonitAir, Ncardia, Ortec
Logiqcare, Philips, Proefdiervrij, Quantib-U, RespiQ, Roche, Smartfish,
SODAQ, Thirona, TopMD, Lung Alliance Netherlands (LAN) and the Lung
Foundation Netherlands (Longfonds).
Key message : Influences of the COVID-19 pandemic on severe
acute asthma (SAA) requiring pediatric intensive care unit (PICU)
admission remains a poorly understood issue. While during the
Coronavirus Disease 2019 (COVID-19) lockdown the number of patients with
SAA decreased, after lifting of these restrictions, PICU admissions
drastically increased again. This increase was higher than in
pre-pandemic years and increased susceptibility to viral infections
other than SARS-CoV-2 is, most likely, the main cause. In the future,
more precaution should be taken for children with SAA in similar
situations. Additionally, it is important to be aware of the large
variety of (external) triggers SAA might have, and how they may impact
trends seen at the PICU.
To the Editor,
Severe acute asthma (SAA) is an
asthma exacerbation unresponsive to conventional oral and inhalation
therapy and requires a PICU admission for intravenous therapy. It may
even lead to the necessity for intubation and can cause serious
morbidity and mortality1. SAA is usually triggered by
a viral infection, but environmental factors such as allergens and air
pollution are also common1. The Coronavirus Disease
2019 (COVID-19) pandemic is also an external factor which might affect
the number of asthma exacerbations, as a result of changes to the
environment as well as medical practice and
management2. While the incidence of asthma
exacerbations in children during the COVID-19 pandemic has been
evaluated3, the incidence of SAA requiring PICU
admission during the pandemic is, to our knowledge, not known. This is
especially of interest as the unique event of the pandemic might teach
us about the effect of environmental factors on SAA. Therefore, we
evaluated PICU admission trends for SAA before and during the COVID-19
pandemic and its link to the COVID-19 restrictions and other relating
environmental triggers.
This study is a single-center, retrospective cohort study conducted at
the Amsterdam University Medical Center (UMC), a tertiary hospital in
the Netherlands. All patients with a diagnosis of SAA above two years of
age admitted to the PICU between 2018 and 2021 were included. Children
below the age of two were excluded as they will more likely present with
bronchiolitis, and differentiation between bronchiolitis and asthma is
difficult. The total number of PICU admissions of the Amsterdam UMC was
also extracted. The diagnosis of SAA was made by a pediatrician and
based on the definition: “Severe aggravation of bronchial obstruction
not improving after a few doses of bronchodilator inhalation”.
The exact dates and levels of governmental COVID-19 restrictions in the
Netherlands were obtained from the Oxford COVID response tracker, i.e.
school closure, a working from home order or both4.
Air pollution was represented by hourly concentrations of particulate
material with an aerodynamic diameter of less than 2.5 microns (PM2.5),
measured at the closest official measuring station to the Amsterdam UMC
(“Stadhouderskade” station at 11 km. distance) by the Dutch National
Institute for Public Health and the Environment
(RIVM)5. Pollen exposure was obtained by the pollen
index from the monitoring station of the Leiden University Medical
Center, located at 35 km. distance6.
Because of the retrospective design of the study, the Medical Ethics
Committee waived the need for informed consent. Statistical analysis was
conducted using IBM SPSS Statistics for Windows version 28.0.1.1 (SPSS,
Chicago IL, USA). Only descriptive analyses were executed because of the
small study population. Graphs were generated using R version 4.2.2.
In total, 168 children were admitted to the PICU of the Amsterdam UMC
for SAA between 2018 and 2021. The mean age of the participants was 7.4
years and a minority was female (Table 1). In the pre-pandemic years,
admissions tended to increase to the highest rate in April, while in
2021 a peak in admissions was observed in the months August to November
(Figure 1). This peak of SAA admissions in the fall of 2021 did not
correspond to an overall increased PICU admission rate. Moreover, the
annual relative percentage of PICU admissions due to SAA of the total
PICU admissions was highest in 2021 (8.0%), followed by 2019 (5.8%),
then 2020 (5.4%) and 2018 (4.7%) (Table 1). A relationship between
lockdown measures during the pandemic and PICU admissions was observed,
with decreased admissions during stricter lockdown measures and
increased admission rates after lockdown restrictions were lifted
(Figure 2).
The majority of patients (70.2%) showed signs of a viral infection as a
trigger; however, not all of these clinical diagnoses were confirmed by
a nasal or throat swab, as in only 60.1% a viral test was taken with
the highest load of testing in 2020 and 2021. The pandemic led to an
increased rate of viral testing at the PICU, as the updated infection
control measures required an active SARS-CoV-2 infection to be confirmed
or ruled out by a rapid test before admission. Nevertheless, more
extensive viral testing for respiratory viruses was limited because of
decreased laboratory capacity during the pandemic so the causative viral
agent was usually still unknown in our study group. Regarding other
environmental triggers, no
correlations were observed between the monthly PICU admission numbers
and pollen or PM2.5 concentrations (rs=-0.04 for pollen
and rs=0.23 for PM2.5).
An explanation for the peak in the fall of 2021 could be the
COVID-19-related regulations of increased hygienic measures, wearing
face masks and social distancing, as these reduced the spread SARS-CoV-2
but also the spread of other viruses2. Additionally,
the “Hygiene Theory”, introduced by Strachan in 1989, further supports
this hypothesis, as it states that the trend of allergic diseases may be
associated with infectious diseases and unhygienic contact in early
childhood could prevent allergic disorders7. As during
this peak period of 2021, respiratory viruses were the most frequent
trigger for SAA, we hypothesize that when restrictions were lifted,
children were exposed to these viruses again and admissions peaked.
Furthermore, these COVID-19-related regulations may have contributed to
an ‘immunity debt’, which implies the lack of protective immunity caused
by prolonged low exposure to a specific pathogen, making children
susceptible to viral diseases, especially those whose transient immunity
is acquired through physical contact8.
According to previous studies, declines in the rate of general asthma
exacerbations during the pandemic have been attributed to better air
quality because of reduced travel and decreased exposure to other asthma
triggers3,9. Additionally, an increased risk for
asthma exacerbations in association with tree pollen has been
observed10. However, no clear association between
pollen, PM2.5 concentration and SAA were found in this study.
Our study was conducted in a single center, making it subject to
selection bias. Moreover, given the retrospective nature of this study,
we had limited information regarding details of some of the variables.
Also, as we did not have information on the residential addresses of the
participants, we used data from one air quality monitoring station as a
proxy for personal exposure to PM2.5. Finally, viral testing was not
available for all participants.
In conclusion, this study demonstrates that the incidence of SAA at the
PICU was lower in the first year of the COVID-19 pandemic with a
high-peak incidence in the fall of 2021 after all governmental
restrictions had been lifted. This could be due to an increase in
exposure to viruses other than SARS-CoV-2. No association between air
pollution and pollen index was observed, which could be because of the
more prominent role of a viral infection as a trigger for SAA.
Keywords: asthma exacerbation, severe acute asthma, pediatric
intensive care unit, children, COVID-19 pandemic, environmental,
lockdown
Somayeh Bazdar1, 2, 3*, Sarah van den
Berg4, 5*, Niels W. Rutjes4, Lizan
D. Bloemsma1, 2, 3, George S.
Downward6, 7, Letty A. De Weger8,
Suzanne W.J. Terheggen-Lagro3, Yolanda de Wit-van
Wijck1, 2, 3, Anke H. Maitland van der
Zee1, 2, 3,4, Berber Kapitein5
- Department of Pulmonary Medicine, Amsterdam UMC, Amsterdam, The
Netherlands
- Amsterdam Institute for Infection and Immunity, Amsterdam, The
Netherlands
- Amsterdam Public Health, Amsterdam, The Netherlands
- Department of Pediatric Pulmonology, Emma Children’s Hospital,
Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Pediatric Intensive Care Unit, Emma Children’s Hospital, Amsterdam
UMC, University of Amsterdam, Amsterdam, The Netherlands
- Department of Environmental Epidemiology, Institute for Risk
Assessment Sciences (IRAS), Utrecht University, Utrecht, The
Netherlands
- Julius Center for Health Sciences and Primary Care, University Medical
Center Utrecht, Utrecht, The Netherlands
- Leiden University Medical Center, Department of Pulmonology and
Department of Public Health and Primary Care, Postbus 9600, 2300 RC
Leiden, The Netherlands
* Both Somayeh Bazdar and Sarah van den Berg are first authors
and contributed equally.