Methods
Study design and subjects – This study is a single-center,
retrospective cohort study conducted at the Amsterdam University Medical
Center (UMC), a tertiary medical center. The PICU has a 12–bed facility
providing intensive care treatment for the northwestern parts of the
Netherlands. The demographic, social, and clinical data were extracted
from the electronic hospital records of all children admitted to the
PICU of the Amsterdam UMC between 2018 and 2021 with a diagnosis of SAA.
The diagnosis of SAA was made by a pediatrician and based on the
following definition: “Severe aggravation of bronchial obstruction due
to asthma that does not improve after a few doses of a bronchodilator by
inhalation”. Wheezing children aged less than two years were excluded
as these children will more likely present with bronchiolitis, and
differentiation between bronchiolitis and asthma is extremely difficult.
Additionally, the total number of children admitted to the PICU of the
Amsterdam UMC was also extracted from the electronic patient file
database.
Institutional Review Board approval – The study design was
reviewed by the ethical committee of the Amsterdam UMC. Owing to the
retrospective and anonymous nature of the current study it was deemed
that informed consent was not necessary.
Data collection – The
exact dates and levels of governmental COVID-19 restrictions in the
Netherlands were obtained from the Oxford COVID response
tracker16. The key stringency criteria examined within
the current study were the complete closure of schools, a complete
working from home order, or both being in effect. Environmental
exposures were defined as the amount of ambient air pollution and pollen
exposure in the Netherlands. Ambient air pollution was represented by
particulate material with an aerodynamic diameter of less than 2.5
microns (PM2.5) which has previously been associated with respiratory
(and other) diseases17. Also, high concentrations of
PM2.5 have been associated with an increase in asthma exacerbations, and
children with asthma were at a higher risk of requiring an ED visit for
an exacerbation18. Hourly concentrations of ambient
PM2.5 were measured at the official monitoring stations of the Dutch
National Institute for Public Health and the Environment (RIVM) (in
concentrations of µg/m3)19. As the
residential information of the patients was not available, the
“Stadhouderskade” station, which was the closest measuring station to
the Amsterdam UMC (with a distance of 11 km) was considered the proxy
for exposures in the area. The daily amount of total pollen in the
Netherlands (pollen index) was obtained from the pollen monitoring
station of the Leiden University Medical Center20,
located approximately 35 km. from the Amsterdam UMC. Pollen grains were
collected at the roof-top level (approx. 20 m. above ground level) and
counted following the requirements of the European Aerobiology
Society21. The total daily values of all pollen types
(in pollen/m3) were summed to give the pollen index
used in this study, and then collapsed to monthly and annual averages.
Analysis – Statistical analysis was conducted using IBM SPSS
Statistics for Windows version 28.0.1.1 (SPSS, Chicago IL, USA). Because
of the small study population, only descriptive analyses were executed.
Subgroups, based on period of time/years, were described by the means
with standard deviation (for variables with a normal distribution) or
median with 25th-75th percentiles (for variables not normally
distributed) or by frequency with percentages for quantitative
variables. Spearman correlations were calculated to evaluate the
relationship between admission numbers and PM2.5 as well as pollen
concentrations. Graphical representations of the collected data were
generated using R version 4.2.222.