Asthma Exacerbations & COVID-19: Risk Factor Analysis

Articles
Modifiable risk factors for asthma exacerbations during
the COVID-19 pandemic: a population-based repeated
cross-sectional study using the Research and Surveillance
Centre primary care database
Mome Mukherjee,a,b,c,d,∗ Cecilia Okusi,e Gavin Jamie,e Rachel Byford,e Filipa Ferreira,e Utkarsh Agarwal,e David Weatherill,a Monica Fletcher,a,c
Jennifer K. Quint,c,f Mohammad Romel Bhuia,g Simon de Lusignan,e,h and Sir Aziz Sheikha,b,c,i
a
Asthma UK Centre for Applied Research, Usher Institute, The University of Edinburgh, Edinburgh, UK
HDR UK Better Care, The University of Edinburgh, Edinburgh, UK
c
HDR UK BREATHE Data Hub, The University of Edinburgh, Edinburgh, UK
d
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
e
Clinical Informatics and Health Outcomes Research Group, Nuffield Department of Primary Care Health Sciences, University of Oxford,
Eagle House, Walton Well Rd, Oxford, OX2 6ED, UK
f
School of Public Health & National Heart and Lung Institute, Imperial College London, London, UK
g
Department of Statistics, Shahjalal University of Science and Technology (SUST), Sylhet, 3114, Bangladesh
h
Royal College of General Practitioners (RCGP), 30 Euston Square, London, NW1 2FB, UK
i
Nuffield Department of Primary Care Health Sciences, University of Oxford, Eagle House, Walton Well Rd, Oxford, OX2 6ED, UK
b
Summary
Background There were substantial reductions in asthma exacerbations during the COVID-19 pandemic for reasons
that remain poorly understood. We investigated changes in modifiable risk factors which might help explain the
reductions in asthma exacerbations.
Methods Multilevel generalised linear mixed models were fitted to examine changes in modifiable risk factors for
asthma exacerbations during 2020–2022, compared to pre-pandemic year (2019), using observational, routine data
from general practices in the Oxford-Royal College of General Practitioners Research and Surveillance Centre.
Asthma exacerbations were defined as any of GP recorded: asthma exacerbations, prescriptions of prednisolone,
accident and emergency department attendance or hospitalisation for asthma. Modifiable risk factors of interest
were ownership of asthma self-management plan, asthma annual review, inhaled-corticosteroid (ICS)
prescriptions, influenza vaccinations and respiratory-tract-infections (RTI).
The Lancet Regional
Health - Europe
2024;42: 100938
Published Online 24 May
2024
https://doi.org/10.
1016/j.lanepe.2024.
100938
Findings Compared with 2019 (n = 550,995), in 2020 (n = 565,956) and 2022 (n = 562,167) (p < 0.05): asthma
exacerbations declined from 67.1% to 51.9% and 61.1%, the proportion of people who had: asthma exacerbations
reduced from 20.4% to 15.1% and 18.5%, asthma self-management plans increased from 28.6% to 37.7% and 55.9%;
ICS prescriptions increased from 69.9% to 72.0% and 71.1%; influenza vaccinations increased from 14.2% to 25.4%
and 55.3%; current smoking declined from 15.0% to 14.5% and 14.7%; lower-RTI declined from 10.5% to 5.3% and
8.1%; upper-RTI reduced from 10.7% to 5.8% and 7.6%. There was cluster effect of GP practices on asthma
exacerbations (p = 0.001). People with asthma were more likely (p < 0.05) to have exacerbations if they had LRTI
(seven times(x)), had URTI and ILI (both twice), were current smokers (1.4x), PPV vaccinated (1.3x), seasonal flu
vaccinated (1.01x), took ICS (1.3x), had asthma reviews (1.09x). People with asthma were less likely to have
exacerbations if they had self-management plan (7%), and were partially (4%) than fully COVID-19 vaccinated.
Interpretation We have identified changes in modifiable risk factors for asthma exacerbation that need to be
maintained in the post-pandemic era.
Funding Asthma UK Centre for Applied Research and Health Data Research UK.
Copyright © 2024 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).
DOI of original article: https://doi.org/10.1016/j.lanepe.2024.100957
*Corresponding author. The University of Edinburgh, Edinburgh, UK.
E-mail address: [email protected] (M. Mukherjee).
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Articles
Keywords: Asthma; Risk factors; Exacerbations; COVID-19; Prevalence; Cluster analysis
Research in context
Evidence before this study
Several countries have reported substantial reductions in
asthma exacerbations during the COVD-19 pandemic, but the
reasons underpinning these reductions remain poorly
understood. We searched PubMed for observational studies,
with no language restrictions, using the terms “asthma”,
“attack”, “exacerbation”, “emergency”, “hospital admission”,
“death”, “modifiable factors”, “risk factors”, “SARS-CoV-2”,
“COVID-19”, published between January 1, 2020, and August
10, 2023. One of the 52 studies identified reported an
association between reduced rates of respiratory syncytial
virus infection and asthma exacerbation in children. Three
other studies reported rebounds of asthma exacerbations
during the latter stages of the pandemic, which were
attributed to viral resurgence associated with increased social
mixing and reductions in use of face masks.
Implications of all the available evidence
This national analysis has identified beneficial changes in
modifiable risk factors during the pandemic. There is a need
to find ways to maintain the beneficial changes in risk factor
exposure for asthma exacerbations and outcomes seen during
the pandemic.
Introduction
Setting
A number of studies have reported substantial
reductions in asthma exacerbations during the early
pandemic years.1–16 There were initially concerns that
these reductions in presentation of asthma exacerbations to health systems may have reflected from changes
in health seeking behaviour during lockdowns.17,18 But
these concerns have been allayed by analyses showing
improvements in a range of outcomes relating to
asthma exacerbations, including use of oral steroids,
and reductions in emergency department attendance
and hospital admission for asthma,14,19,20 with no
corresponding increases in asthma deaths.2
The reasons behind these unprecedented declines in
asthma exacerbations remain poorly understood. The
limited body of empirical evidence available suggests that
the reduction in exposure to respiratory tract infections
(RTIs) may have been important,6,16,20,21 particularly respiratory syncytial virus exposure in children.8
In the context of reports suggesting that asthma
exacerbations are beginning to return to pre-pandemic
levels,21,22 we sought to investigate changes in (potentially) modifiable risk factors for asthma exacerbations
comparing the immediate pre-pandemic year (2019) to
the first three years of the pandemic (2020–2022) with a
view to identifying which if any of these risk factors
might help explain the reductions in asthma exacerbations rates seen.
We used pseudonymised data from the primary care
sentinel cohort of the Oxford-Royal College of General
Practitioners (RCGP) Research and Surveillance Centre
(RSC) in England, in the UK.23 Participating practices
were recruited to be nationally representative and were
involved in virological and serological surveillance.24
Accident and emergency (A&E) department attendance
and hospital admission for asthma were obtained from
GP records.
Methods
Study design
We undertook a repeated cross-sectional, observational
study using routine primary care data.
2
Added value of this study
To our knowledge, this is the first study that has investigated
changes in modifiable risk factors for asthma exacerbations
before and during the pandemic using primary care data. Our
large, population-based analysis identified beneficial changes
in several modifiable risk factors for asthma exacerbations,
which may be causally associated with the reductions in
exacerbations seen over the study period.
Study period
Four years were studied—the year prior to the pandemic
(i.e., January 1, to December 31, 2019) and the three
subsequent pandemic calendar years (i.e., January 1,
2020 to December 31, 2022).
Participants
Anyone who ever had a diagnosis of asthma by their GP
and was treated with any asthma medication in the
previous 12 months or had a hospital admission with
asthma as their primary reason for admission was
identified as having asthma. Records of people who had
codes indicating they opted out of record sharing were
not included in the analyses.25
Outcomes
The outcomes of interest were counts of people who had
GP-recorded:
i) Asthma exacerbations
ii) Prescriptions of prednisolone for asthma exacerbation
iii) A&E department attendance for asthma
iv) Hospital admission for asthma
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Articles
and also counts of events (i, iii, iv) and prescriptions of
prednisolone.
While other oral corticosteroids exist, such as dexamethasone and prednisone, these were not included as
these were very rarely used for the community-based
treatment of asthma in the UK.26,27 Since prednisolone
may also have been prescribed on repeat to manage
poorly controlled asthma, prescriptions recorded in
RSC as repeats were excluded. To ensure we did not
miss any hospital event for asthma due to sub-optimal
coding of hospital events in primary care, we
used additional hospital codes with ±7 days of the
asthma exacerbation recorded by GPs or prednisolone
prescriptions.
People with asthma exacerbations were defined as
people who had either GP-recorded asthma exacerbations, prescriptions of prednisolone for an asthma
exacerbation, A&E attendance or hospital admission for
asthma. The number of asthma exacerbations were
defined as events of GP-recorded asthma exacerbations,
prescriptions of prednisolone for an asthma exacerbation, A&E attendance, or hospital admission for asthma.
patient with the latest smoking status start date at the
end of the calendar year was included, with the corresponding status end date, smoking status, worst status
so far, and adjusted smoking status.
In the UK, the pneumococcal vaccination programme was introduced in 2003 with PPV, for people
80 years and above. Since 2005, this was extended so
that people 65 years and above also became eligible for
the vaccine.28 In contrast, pneumococcal conjugate vaccine (PCV13) was used in the childhood immunisation
programme for children two years and under and not
routinely administered after two years of age.28 PCVs are
centrally administered and the data not routinely
collected in primary care. We used UK SNOMED code
4837, which captured high level (parent) codes for
pneumococcal vaccination, including both PPV and
PCV vaccines. For this analysis, we restricted pneumococcal vaccination to 65 years and above, thus essentially
only capturing PPV administration.
Since the study period included the pandemic years,
we also examined if people with asthma were vaccinated
against COVID-19, and whether fully or partially.
Potentially modifiable risk factors
Data analyses
The inclusion criterion was any person with asthma,
irrespective of exacerbation or how long they were in the
database, in whom there was a record of any of the
variables of interest:
Only coded data were extracted, pseudonymising as
close to sources as possible.29
Our primary analyses were on number of people and
count of events or prescriptions. The definition we used
for asthma prevalence was proportion of the registered
people who consulted GP and were treated or were
hospitalised for asthma. This definition included people
with asthma who sought healthcare in either primary or
secondary care, as recorded in RSC. For estimates other
than prevalence, people with asthma was the denominator for analyses for respective years. Systematized
Nomenclature of Medicine–Clinical Terms (SNOMEDCT) were used to extract the data (Supplement).30 Since
asthma review, asthma self-management plan, influenza vaccination, PPV vaccination were reviewed and
administered once a year, aggregated annual data were
examined. A single ICS prescription may generally have
been for two inhalers. Thus, people who had an ICS
prescription had at least one ICS item.
Relative changes were measured in percentages for
the years 2020-22 compared with 2019, by finding the
difference in percentages and comparing to the
respective percentage in 2019.
In our data, patients were clustered by GP practices.
Thus, individual-level data of patients within each cluster (GP practice) were correlated. To account for this
nested structure of data, we fitted multilevel generalised
linear mixed model (GLMM) with GP practices as
random effect. We included all the variables mentioned
above, along with age, sex assigned at birth, urban/rural,
socio-economic status measured by quintiles of Index of
Multiple Deprivation (IMD) and ethnicity (White, Asian,
Black, mixed, other, unknown) as fixed effects. GP
i) An asthma self-management plan being given
ii) An asthma review in last 12 months
iii) Prescriptions of ICS
iv) Number of ICS prescriptions
v) Being a current smoker
vi) Influenza vaccination
vii) Pneumococcal polysaccharide vaccination (PPV)
in those aged ≥65 years
viii) Consultation for one or more of upper (URTI) or
lower respiratory tract infection (LRTI) or
influenza-like illness (ILI).
Smoking status was ascertained by looking at
consultation-level for any old records of smoking in
primary care records, and ‘current smoker’, ‘nonsmoker’ or ‘ex-smoker’ was flagged for each of those
dates. These were then ordered by the earliest to the
latest smoking status for each calendar year. The next
staging was a patient-level table which flagged the bestcase smoking status per patient per day. The algorithm
defined the smoking status end date column by checking the status start dates of historical smoking data and
assigned a status end date of ‘9999-01-01’ for the most
recent consultation date, and the day before the prior
consultation date. If a patient’s latest smoking status
was a non-smoker but their worst status so far was
either an ex-smoker or current smoker their adjusted
smoking status became an ex-smoker. Only one row per
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Articles
practices were treated as random effect. Asthma exacerbation as a binary variable (yes/no) was the outcome
variable of interest. We conducted a sensitivity analysis
with the general practices that were available over the
whole of the study period to account for the changes in
GP practices participation in RSC during the study
period. In the sensitivity analysis, we fitted the same
multilevel GLMM with only the common GP practices
which were there across all four years, to examine
whether the findings of our study are sensitive to the
changes in GP practices participation in RSC during the
study period.
Likelihood ratio test (Chi-square test) was performed
(in the form of analysis of variance (ANOVA) test), to
assess whether the mixed models were an improvement
in terms of goodness of fit. For sensitivity analysis, the
‘receiver operating characteristic’ (ROC) and ‘area under
the curve’ (AUC) were examined of the actual exacerbations to the predicted exacerbations from the respective two mixed models. Effect sizes of the included
variables in the models were reported as odds ratios
(OR) and 95% confidence intervals (CI).
Since COVID-19 vaccinations started in the UK in
December 2020, and these COVID-19 vaccinations data
were mainly available in 2021 and 2022, we examined
the association between COVID-19 vaccinations and
asthma exacerbations in 2021 and 2022, respectively.
SQL was used to process data using Microsoft SQL
Server Management Studio, version 15.0 and analyses
were done in R using R Studio Server, version
2022.02.3.
Ethics and permissions
As anonymised individual level data were interrogated,
the Health Research Authority (HRA) decision tool was
used,31 to confirm that NHS Research Ethics Committee
(REC) was not required. Edinburgh Medical School
Research Ethics Committee (EMREC) approval was obtained (ref: 21-EMREC-032).
Reporting
Strengthening the Reporting of Observational studies in
Epidemiology (STROBE) and REporting of studies
Conducted using Observational Routinely-collected Data
(RECORD) checklists were used to guide transparent
reporting (Supplement).32,33
Role of the funding source
The funder had no role in the study design, any aspect
of undertaking the study, interpretation of findings or
the decision to publish.
Results
In the years 2019–2022, the number of people who were
registered in RSC were 8,355,263, 8,566,545, 7,978,750
and 7,634,642 respectively. Asthma prevalence in the
respective years were 6.8% (95% CI 6.8–6.9), 6.9%
(6.8–6.9), 7.3% (7.3–7.3) and 7.6% (7.6–7.7) (Table 1).
Since these were the people with asthma who sought
health care, we found an increase of 11.8% in 2022 than
in 2019. Across all study years, in under-five-year-olds
and five-14-year-olds male preponderance was found,
which reversed to female preponderance in 15–44,
45–64 and 65-and-above year olds (Table 2).
The proportion of people who had asthma exacerbations in 2019 (20.4%, n = 116,481) reduced by 25.7%
in 2020 (15.1%, n = 88,908), by 24.9% in 2021 (15.5%
n = 89,161), and by 9.1% in 2022 (18.5%, n = 108,047)
(Fig. 1, Table 3). Whereas compared with 2019, the
proportion of asthma exacerbations declined by 22.7%
in 2020 from 67.1% to 51.9%, by 18.7% in 2021
(54.6%), and by 9.0% in 2022 (61.1%) (Fig. 1 and
Table 4).
Fig. 1 (and Table 3) show that compared with 2019,
there were increases in the proportion of the population
who had:
• Influenza vaccinations by 79.5% in 2020 (25.4% vs
14.2%), by 247.3% in 2021 (49.1%) and by 290.5% in
2022 (55.3%);
• Asthma self-management plans by 31.8% in 2020
(37.7% vs 28.6%), by 65.5% in 2021 (47.4%) and by
95.3% in 2022 (55.9%);
• ICS prescriptions by 2.9% in 2020 (72.0% vs 69.9%)
and by 1.7% in 2022 (71.1%). The average number of
ICS prescriptions, which might have had more
than one ICS item, were 3.5, 3.7, 3.6 and 3.7,
respectively;
• PPV vaccinations by 0.2% in 2020 (34.3%) compared
to 2019 (34.3%), by 0.7% in 2021 and by 0.6%
in 2022.
Patient and public involvement (PPI)
PPI members were consulted twice, once before the
study and with interim results before writing up. Based
on the first PPI consultation, we also included people
who had asthma as their primary reason for hospital
admission as it was noted that some people with asthma
may not see their GP and seek hospital care directly. PPI
members provided additional insights on interpretation
of findings, which have been incorporated into the discussion. One of the PPI members is a co-author.
4
People
registered
People with
asthma
Asthma prevalence
(95% CI)
2019
8,355,263
571,884
6.8 (6.8–6.9)
2020
8,566,545
587,302
6.8 (6.8–6.9)
2021
7,978,750
583,016
7.3 (7.3–7.3)
2022
7,634,642
583,519
7.6 (7.6–7.6)
Table 1: Numbers of people registered and with asthma, and
prevalence of asthma, in Research and Surveillance Centre (RSC)
primary care database.
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Articles
<5
years
5–14
years
15–44
years
45–64
years
≥65
years
Total
In 2020, 0.02% people with asthma were fully and
2.3% were partially vaccinated against COVID-19
(Table 5). There were 78.4% people with asthma who
were fully vaccinated against COVID-19 in 2022,
compared to 74.8% in 2021. In 2022 there were 19.2%
people with asthma who were not COVID-19 vaccinated.
In the full mixed model analysis (Table 6) it was
found the cluster effect of GP practices were significant
at better than 0.001 level, and that people with asthma
who:
2019
Females
0.3
3.9
18.6
18.1
14.8
318,009
Males
0.4
5.8
15.3
13.4
9.5
253,875
2020
Females
0.2
3.7
18.9
18.5
14.6
327,923
Males
0.3
5.5
15.4
13.6
9.4
259,379
2021
Females
0.2
3.4
19
18.7
14.8
326,814
Males
0.3
5.2
15.3
13.7
9.5
256,202
Females
0.2
3.2
19
18.7
15.1
328,021
Males
0.3
4.9
15.2
13.6
9.7
255,498
i) had LRTI (OR: 6.59; 95% CI: 6.52–6.66) were
seven times more likely to have exacerbations
than people who did not have LRTI,
ii) had URTI (OR: 1.87; 95% CI: 1.85–1.90) and ILI
(OR: 1.71; 95% CI: 1.64–1.78) were 2 times more
likely to have exacerbations than people who
didn’t,
iii) were current smokers (OR: 1.39; 95% CI:
1.38–1.41) were 1.4 times more likely to have exacerbations than non-active smokers,
iv) were PPV vaccinated (OR: 1.29; 95% CI:
1.28–1.30) were 1.3 times more likely to have exacerbations than who were not vaccinated,
v) lived in urban areas (OR: 1.04; 95% CI: 1.03–1.06)
were 1.04 times more likely to have exacerbations
than who lived rurally,
vi) were seasonal flu vaccinated (OR: 1.011; 95% CI:
1.002–1.021) were 1.01 times more likely to have
exacerbations than who were not vaccinated,
2022
Table 2: Percentages of females and males by age-groups in the
calendar years in Research and Surveillance Centre (RSC) primary care
database.
Compared with 2019 (Fig. 1 and Table 3), the proportion of people who:
• Had URTI reduced by 46.2% in 2020 (5.8% vs
10.7%), 51.8% in 2021 and 28.8% in 2022;
• Had LRTI reduced by 49.8% (5.3% vs 10.5), 46.6% in
2021 and 22.5% in 2022;
• Had ILI increased by 10.6% (0.7% vs 0.6%) in 2020
then decreased by 47.5% in 2021 and 23.8% in 2022;
• Were current smokers reduced by 3.9% (14.5% vs
15.0% (), by 4.1% in 2021 and by 2.9% in 2022.
Outcomes
asthma exacerba ons (any of asthma exacerba ons recorded
by GPs or prednisolone prescrip ons or A&E or hospitalisa ons) asthma exacerba ons recorded by GPs
6
26
26
13
3
13
0
0
0
2019
2020
2021
2019
2022
2021
2022
2
hospitalisa ons
accident & emergency
1
1
0
0
2019
2020
LRTI
URTI
Infec ons
2020
prednisolone prescrip ons
2021
2019
2022
2020
2021
2019
2022
2020
2021
2022
ILI
1
10
10
Percentages
5
0
0
0
2019
2020
2021
2019
2022
2020
2021
2022
2021
2022
2019
2020
2021
2022
PPV vaccinations
Vaccina ons
flu vaccinations
40
50
20
25
0
2019
2020
2021
2022
0
2019
2020
ICS prescriptions
self-management plan
Other
60
30
0
2019
2020
2021
2022
annual reviews
current smokers
80
16
54
40
8
27
0
0
0
2019
2020
2021
2022
2019
2020
2021
2022
2019
2020
2021
2022
Fig 1: Percentages of people with asthma modifiable factors, respiratory tract infections and outcomes in Research and Surveillance
Centre (RSC) primary care database.
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People with
2019
2020
2021
2022
n
%
n
%
n
%
n
Active asthma–treated in last 12 months (denominator)
571,884
100
587,302
100
583,016
100
583,519
100
Asthma annual reviews
284,700
49.8
277,936
47.3
257,436
44.2
281,937
48.3
Asthma self-management plan
163,572
28.6
221,449
37.7
276,061
47.4
326,024
55.9
Influenza vaccinations
80,930
14.2
149,163
25.4
286,510
49.1
322,440
55.3
PPV vaccinations
195,944
34.3
201,530
34.3
201,099
34.5
201,209
34.5
Current smokers
85,854
15.0
85,018
14.5
84,313
14.5
85,523
14.7
ICS prescriptions
400,016
69.9
422,753
72.0
407,020
69.8
415,044
71.1
URTI
61,130
10.7
33,791
5.8
30,023
5.1
44,423
7.6
LRTI
59,903
10.5
30,868
5.3
32,594
5.6
47,365
8.1
ILI
3646
0.6
4143
0.7
1952
0.3
2833
0.5
116,481
20.4
88,908
15.1
89,161
15.3
108,047
18.5
3.9
Asthma exacerbations (any of asthma exacerbations
recorded by GPs or prednisolone prescriptions
or A&E or hospitalisations)
%
Asthma exacerbations recorded by GPs
31,107
5.4
17,908
3.0
19,413
3.3
22,671
Prednisolone prescriptions
111,286
19.5
85,202
14.5
84,876
14.6
103,703
17.8
A&E
7370
1.3
4961
0.8
5661
1.0
6456
1.1
Hospitalisations
3287
0.6
1974
0.3
2057
0.4
2333
0.4
Table 3: Number and percentages of people with asthma modifiable factors, respiratory tract infections and outcomes in Research and Surveillance
Centre (RSC) primary care database.
2019
Asthma exacerbations (any of asthma exacerbations recorded
by GPs or prednisolone prescriptions or A&E or hospitalisations)
2020
2021
2022
n
%
n
%
n
%
n
%
383,927
67.1
304,605
51.9
318,203
54.6
356,400
61.1
5.2
Asthma exacerbations recorded by GPs
42,210
7.4
24,396
4.2
26,454
4.5
30,185
Prednisolone prescriptions
211,170
36.9
166,948
28.4
161,523
27.7
193,185
33.1
A&E
137,051
24.0
111,104
18.9
127,654
21.9
133,719
22.9
Hospitalisations
37 417
6.5
29,195
5.0
31,036
5.3
30,835
5.3
Table 4: Number and percentages of events of asthma exacerbations in Research and Surveillance Centre (RSC) primary care database.
Treated for active
asthma in last
12 months
Fully COVID-19
vaccinated
Partially COVID-19
vaccinated
Not COVID-19
vaccinated
n
%
n
%
n
%
n
%
2019
571,884
100
0
0
0
0
571,884
100
2020
587,302
100
121
0
13,275
2.3
573,906
97.7
2021
583,016
100
435,950
74.8
26,041
4.5
121,025
20.8
2022
583,519
100
457,241
78.4
14,375
2.5
111,903
19.2
Table 5: COVID-19 vaccination status in people with asthma, by years, in Research and Surveillance Centre (RSC) primary care database.
vii) took ICS (OR: 1.27; 95% CI: 1.25–1.28) were 1.3
times more likely to have exacerbations than who
did not,
viii) had asthma reviews (OR: 1.09; 95% CI: 1.08–1.10)
were 1.09 times likely to have exacerbations than
who did not,
ix) had asthma self-management plan (OR: 0.93; 95%
CI: 0.92–0.94) were 7% less likely to have exacerbations than who did not,
6
x) were partially (OR: 0.96; 95% CI: 0.94–0.99)
COVID-19 vaccinated were 4% less likely to have
exacerbations than who were fully COVID-19
vaccinated.
The odds of asthma exacerbation were lower during
the years 2020–2022 than in the year 2019. White, Black,
Mixed or people with unknown ethnicity had reduced
odds of asthma exacerbations as compared to Asian
www.thelancet.com Vol 42 July, 2024
Articles
Odds
ratio
95% CI
lower
limit
95% CI
upper
limit
Age
1.003
1.002
1.003
Sex Male
0.72
0.71
0.73
Year 2020
0.79
0.78
0.79
Year 2021
0.80
0.78
0.81
Year 2022
0.94
0.92
0.95
Ethnicity Black
0.86
0.83
0.89
Ethnicity Mixed
0.92
0.89
0.96
0.90
Ethnicity Unknown
0.88
0.86
Ethnicity White
0.95
0.94
0.97
IMD 2
0.94
0.93
0.95
IMD 3
0.90
0.89
0.91
IMD 4
0.86
0.84
0.87
IMD 5 least deprived
0.81
0.79
0.82
Urban-Rural Urban
1.04
1.03
1.06
Asthma Review Yes
1.09
1.08
1.10
Asthma Self-Management
Plan Yes
0.93
0.92
0.94
URLI Yes
1.87
1.85
1.90
LRTI Yes
6.59
6.52
6.66
ILI Yes
1.71
1.64
1.78
ICS Yes
1.27
1.25
1.28
Number of ICS prescription
1.07
1.07
1.07
PPV Yes
1.29
1.28
1.30
Seasonal flu vaccination Yes
1.011
1.002
1.021
Current Smoker Yes
1.39
1.38
1.41
COVID-19 vaccination Partially
0.96
0.94
0.99
GP practices (random effect): p < 0.0001. References: Sex female, Year 2019,
Ethnicity Asian, IMD 1 most deprived, Rural, Asthma Review No, Asthma SelfManagement Plan No, URLI No, LRTI No, ILI No, ICS No, PPV No, Seasonal flu
vaccination No, Current Smoker No, COVID-19 vaccination Fully.
Table 6: Odds Ratio of asthma exacerbations with lower and upper
limit of 95% CI of the multilevel model with GP practices as random
effect in Research and Surveillance Centre (RSC) primary care
database.
people. Compared to people with asthma in most
deprived areas, people in areas of lesser deprivation had
reduced exacerbations. The odds of asthma exacerbation
increased 1.003 times if age increased by one year.
Males with asthma were 28% less likely to have
exacerbations than females. All the fixed effects were
significant at better than 0.001 probability level, except
seasonal flu vaccinated (p = 0.02).
Sensitivity analysis
Over the years (2019–2022) there were 778, 773, 775 and
777 GP practices, respectively. In the sensitivity analysis
focused on 768 GP practices which were common in all
four years, it was found that the cluster effect of GP
practices and the fixed effects were significant at better
than 0.001 level, except seasonal flu vaccinated
(p = 0.01). The AUC from this model was 0.7341, while
of the model that included all the GP practices was
0.7342, which are almost same.
www.thelancet.com Vol 42 July, 2024
When the models were restricted to 2021 and 2022,
cluster effect of GP practices and the fixed effects were
significant at better than 0.001 level, except mixed
ethnicity (0.01), white ethnicity (p = 0.02), other ethnicity
(p = 0.04), and seasonal flu vaccinated (p = 0.06).
Discussion
In this national observational study, we observed
reductions in both the proportion of people who had
asthma exacerbations and the proportion of asthma
exacerbations, and corresponding changes in a number
of potentially modifiable risk factors for asthma exacerbations. We found people with asthma were less likely to
have exacerbations if they had asthma self-management
plan (7% less likely), and were partially (4% less likely)
than fully COVID-19 vaccinated. People with asthma
who were PPV and seasonal flu vaccinated, who took
ICS, had asthma reviews, were Asian, lived in urban
areas and in more deprived areas, were more likely to
have asthma exacerbations. Whilst causality cannot be
inferred from observational study designs, our study
demonstrated association of these observed changes in
risk factors with the reductions in asthma exacerbations
seen.
That people with asthma who were either PPV or
seasonal flu vaccinated, or had asthma reviews were
likely to have more exacerbations could be due to each of
these being targeted to at-risk people in the UK,
including people with asthma and the elderly, who are
prone to exacerbations. Also, it could be due to individual’s perception of risk, particularly if they are
having exacerbations, to get themselves vaccinated and
attend asthma reviews. Equally COVID-19 vaccination
was targeted to similar group of people and we found
that compared to fully vaccinated COVID-19 people,
those who were not or partially vaccinated had lesser
exacerbations. People with asthma who had ICS prescriptions during our study period were more likely to
have asthma exacerbations perhaps because they had
persistence of symptoms or had severity. RSC database
does not have data on prescriptions dispensed. It seems
people with asthma who were proactive and had asthma
self-management plan could ward off exacerbations.
Thus, people’s behaviour might have played a role in
their own asthma outcome. Furthermore, cluster effect
of GP practices was found on asthma exacerbations.
Thus, besides people’s behaviour, it could be how GP
practices managed care of people with asthma which
affected their asthma outcome.
The directions of the estimates of model parameters
and their inferences were almost same in our final fitted
model and the model used in sensitivity analysis, along
with the AUC values. That implies that the findings of
our study are not sensitive to changes in GP practices
participation in RSC during the study period.
7
Articles
At the onset of the pandemic, respiratory services
were particularly impacted whereby there were cancellations of routine care by GPs and hospitals, and a
reduction in face-to-face consultations.34 But a large
study on over nine million consultations in primary care
in England found there were 15% more consultations in
2021-22 than in 2018-19, whereby remote consultations
were 155.3% higher and face-to-face consultations were
17.1% lower than in 2018-19.35 Although we did not
calculate the number of GP consultations for asthma,
the proportion of people who were treated for their
asthma in primary and secondary care, as recorded in
primary care, increased by 17.1% in 2022 when
compared to 2019. We found a decline in asthma annual
reviews by 4.9% in 2020 and 1.9% in 2022. This could
be a result of NHS England changing the GP contract,
which allowed GPs to curtail annual reviews during
the pandemic so as to increase capacity for frontline
services to respond to COVID-19.36 Despite the
reductions in asthma annual reviews, we found a
reduction in asthma exacerbations. Clinician-reporteddiagnosed-treated asthma prevalence in Quality and
Outcomes Framework (QoF), a GP incentivisation system, in England in 2019-20 for all ages and in 2020-21
for ages above-six-years was both 6.5%,37 which is close
to our prevalence estimates. The asthma profile
described here with a wide base of 0.6 million people, of
whom a relatively small proportion (0.4%) experienced
hospitalisation for their asthma is similar to a Scottish
study.38
Key strengths of this work include the large primary
care-based database interrogated with coded data on a
number of potentially important risk factors.
Limitations include using a routine primary care
database means there could be potential over- or underdiagnosis of asthma, and also bias in the collection of
some of the exposure variables of interest.39 Analyses
were limited to coded data that can also be subject to
recording bias. That said, given that these electronic
health record derived data represent the main clinical
record, we anticipate that these would have been unlikely to have a major impact on our overall findings.
Our estimates of exacerbations are likely to be underestimates for people who managed their exacerbations at home and did not report to GP. On the other
hand, we did not put any restriction on number of days
around an exacerbation and counted every event as an
exacerbation if they met our criteria above. We might
have under-estimated A&E and hospitalisation records
since these may not be fully captured in primary care.
Community surveillance indicators in the UK reported the impact of social and physical distancing
measures on COVID-19 activity within one week.40 Face
masks and other non-pharmaceutical interventions
(NPI) were in widespread use during the early stages of
the pandemic and these may have contributed to reductions in the incidence of respiratory tract infections,
8
which are important triggers for asthma exacerbations.
Definitely establishing the effectiveness of NPIs in
preventing asthma exacerbations would require a formal
randomised controlled trial, but there is considerable
uncertainty as to whether this could be successfully
delivered in the UK context.
Our analysis now needs to be built on with studies
investigating patient behaviours and how these may
have changed during these early pandemic years
through surveys and qualitative evaluations. There is
also a need to consider which aspects of behaviour
change may persist beyond the early pandemic years,
which could be achieved both through extending the
present analysis and in-depth work with patients to
understand their behavioural patterns.
In summary, this national observational study found
reductions in people who had asthma exacerbations.
Over the same period, we noted increases in asthma
self-management ownership, ICS prescriptions and
influenza vaccination, and reductions in smoking and
RTIs. There is a need to find ways of maintaining
and building on these improvements in behaviours, care
processes and exposures to achieve sustained improvements in asthma outcomes in the post-pandemic era.
Contributors
AS, MM, SdeL conceived the study and contributed to the study design.
SdeL was the director, guarantor for these data, assisted with clinical
knowledge, system design and problem solving, and commented on the
drafts. MM led the analysis plan, oversaw the analysis, analysed data, led
the writing of the paper and edited the manuscripts. CO produced the
base data tables and summary data. RB designed and developed much of
the database structure. GJ was responsible for curation of clinical variables. UA advised on COVID-19 vaccinations. DW provided patient and
public perspective. FF was responsible for project and contract management in RSC. MRB advised and oversaw the statistical analysis. MM,
CO, GJ and SdeL have verified the data. AS, MRB, DW, GJ, JQ, MF,
MM, CO, SdeL commented on the draft and revised the manuscript for
important intellectual content. All authors had final responsibility for
the decision to submit for publication.
Data sharing statement
Access to confidential Oxford-RCGP RSC data can be requested by
submitting a written protocol and data request form to Oxford-RCGP
RSC.
Declaration of interests
AS was a member of the Scottish Government Chief Medical Officer’s
COVID-19 Advisory Group and Astra-Zeneca’s COVID-19 Thrombotic
Thrombocytopenic Advisory Group and is a member of the Scottish
Government’s Standing Committee on Pandemic Preparedness; all
roles are unremunerated. SdeL is the director of Royal College of GPs
Research and Surveillance Centre (RSC) the primary care sentinel
network, UK Health Security Agency funded. SdeL has had research
funded by AstraZeneca, Moderna, GSK, Sanofi and Seqirus, has spoken
at Seqirus and Roche funded events, was a member of advisory boards
for AstraZeneca, Sanofi and Seqirus and had AstraZeneca funded
attendance at a European conference, all fees for these events were paid
to the University of Oxford.
Acknowledgements
This work uses data provided by patients and collected by the NHS as
part of their care and support. Patients who consented to virology
specimens to be collected and for allowing their data to be used for
surveillance and research. Practices who have agreed to be part of the
www.thelancet.com Vol 42 July, 2024
Articles
RCGP RSC and allow us to extract and used health data for surveillance and research. The practice liaison team, John Williams (Senior
Clinical Research Fellow) and other members of the Clinical Informatics and Health Outcomes Research Group at Oxford University.
Wellbeing Medical Systems for data extraction and pseudonymisation. Collaboration with EMIS, TPP, and In-Practice CMR suppliers
for facilitating data extraction. Colleagues at UK Health Security
Agency.
Open access For the purpose of open access, the author has applied
a Creative Commons Attribution (CC BY) licence to any Author
Accepted Manuscript version arising from this submission.
Funding: This work is carried out with the support of BREATHE The Health Data Research Hub for Respiratory Health [MC_PC_19004]
in partnership with Oxford-RCGP Clinical Informatics Digital Hub
(ORCHID), a trusted research environment. BREATHE is funded
through the UK Research and Innovation Industrial Strategy Challenge
Fund and delivered through Health Data Research UK. Health Data
Research UK is funded by UK Research and Innovation, the Medical
Research Council, the British Heart Foundation, Cancer Research UK,
the National Institute for Health and Care Research, the Economic and
Social Research Council, the Engineering and Physical Sciences
Research Council, Health and Care Research Wales, Health and Social
Care Research and Development Division (Public Health Agency,
Northern Ireland), Chief Scientist Office of the Scottish Government
Health and Social Care Directorates. This work was also funded by The
Health Data Research UK, reference EDIN1 and Asthma + Lung UK,
reference AUK-AC-2018-01.
Appendix A. Supplementary data
Supplementary data related to this article can be found at https://doi.
org/10.1016/j.lanepe.2024.100938.
References
1 Kenyon CC, Hill DA, Henrickson SE, Bryant-Stephens TC, Zorc JJ.
Initial effects of the COVID-19 pandemic on pediatric asthma
emergency department utilization. J Allergy Clin Immunol Pract.
2020;8(8):2774–2776.e1.
2 Davies GA, Alsallakh MA, Sivakumaran S, et al. Impact of COVID19 lockdown on emergency asthma admissions and deaths: national interrupted time series analyses for Scotland and Wales.
Thorax. 2021;76:867–873.
3 Fan H-F, He C-H, Yin G-Q, et al. Frequency of asthma exacerbation
in children during the coronavirus disease pandemic with strict
mitigative countermeasures. Pediatr Pulmonol. 2021;56(6):
1455–1463.
4 Salciccioli JD, She L, Tulchinsky A, Rockhold F, Cardet JC, Israel E.
Effect of COVID-19 on asthma exacerbation. J Allergy Clin Immunol
Pract. 2021;9(7):2896–2899.e1.
5 Sykes DL, Faruqi S, Holdsworth L, Crooks MG. Impact of COVID19 on COPD and asthma admissions, and the pandemic from a
patient’s perspective. ERJ Open Res. 2021;7(1):822–2020.
6 Wee LE, Conceicao EP, Tan JY, Sim JXY, Venkatachalam I.
Reduction in asthma admissions during the COVID-19 pandemic:
consequence of public health measures in Singapore. Eur Respir J.
2021;57(4).
7 Yamaguchi H, Nozu K, Ishiko S, et al. Impact of the state of
emergency during the COVID-19 pandemic in 2020 on asthma
exacerbations among children in Kobe City, Japan. Int J Environ Res
Public Health. 2021;18(21):11407.
8 Sayed S, Diwadkar AR, Dudley JW, et al. COVID-19 pandemicrelated reductions in pediatric asthma exacerbations corresponded with an overall decrease in respiratory viral infections.
J Allergy Clin Immunol Pract. 2022;10(1):91–99.e12.
9 Shah SA, Quint JK, Nwaru BI, Sheikh A. Impact of COVID-19
national lockdown on asthma exacerbations: interrupted timeseries analysis of English primary care data. Thorax. 2021;76:860–
866.
10 Shah SA, Quint JK, Sheikh A. Impact of COVID-19 pandemic on
asthma exacerbations: retrospective cohort study of over 500,000
patients in a national English primary care database. Lancet Reg
Health Eur. 2022;19:100428.
www.thelancet.com Vol 42 July, 2024
11 Alsulaiman JW, Kheirallah KA, Ajlony MJ, Al-Tamimi TM,
Khasawneh RA, Al-Natour L. Paediatric asthma exacerbation admissions and stringency of non-pharmaceutical interventions:
results from a developing country. Int J Clin Pract. 2021;75(9):
e14423.
12 Pepper MP, Leva E, Trivedy P, Luckey J, Baker MD. Analysis of
pediatric emergency department patient volume trends during the
COVID-19 pandemic. Medicine (Baltim). 2021;100(27):e26583.
13 Bun S, Kishimoto K, Shin J-H, et al. Impact of the COVID-19
pandemic on asthma exacerbations in children: a multi-center
survey using an administrative database in Japan. Allergol Int.
2021;70(4):489–491.
14 Hurst JH, Zhao C, Fitzpatrick NS, Goldstein BA, Lang JE. Reduced
pediatric urgent asthma utilization and exacerbations during the
COVID-19 pandemic. Pediatr Pulmonol. 2021;56(10):3166–3173.
15 de Boer G, Braunstahl GJ, Hendriks R, Tramper-Stranders G.
Asthma exacerbation prevalence during the COVID-19 lockdown in
a moderate-severe asthma cohort. BMJ Open Respir Res. 2021;8(1):
e000758.
16 Hazan G, Fox C, Eiden E, Anderson N, Friger M, Haspel J. Effect of
the COVID-19 lockdown on asthma biological rhythms. J Biol
Rhythms. 2022;37(2):152–163.
17 Gupta A, Bush A, Nagakumar P. Asthma in children during the
COVID-19 pandemic: lessons from lockdown and future directions
for management. Lancet Respir Med. 2020;8(11):1070–1071.
18 Mansfield KE, Mathur R, Tazare J, et al. Indirect acute effects of the
COVID-19 pandemic on physical and mental health in the UK: a
population-based study. Lancet Digit Health. 2021;3(4):e217–e230.
19 Yang Z, Wang X, Wan XG, et al. Pediatric asthma control during
the COVID-19 pandemic: a systematic review and meta-analysis.
Pediatr Pulmonol. 2022;57(1):20–25.
20 Ho T, Shahzad A, Jones A, Raghavan N, Loeb M, Johnston N.
Examining the effect of the COVID-19 pandemic on community
virus prevalence and healthcare utilisation reveals that peaks in
asthma, COPD and respiratory tract infection occur with the
re-emergence of rhino/enterovirus. Thorax. 2023;78(12):1248–
1253.
21 Hazan G, Fox C, Mok H, Haspel J. Age-dependent rebound in
asthma exacerbations after COVID-19 lockdown. J Allergy Clin
Immunol Glob. 2022;1(4):314–318.
22 Tydeman F, Pfeffer PE, Vivaldi G, et al. Rebound in asthma exacerbations following relaxation of COVID-19 restrictions: a longitudinal population-based study (COVIDENCE UK). Thorax.
2022;78(8):752–759.
23 de Lusignan S, Correa A, Smith GE, et al. RCGP Research
and Surveillance Centre: 50 years’ surveillance of influenza, infections, and respiratory conditions. Br J Gen Pract. 2017;67(663):
440–441.
24 Leston M, Elson WH, Watson C, et al. Representativeness, vaccination uptake, and COVID-19 clinical outcomes 2020-2021 in the
UK Oxford-Royal College of general Practitioners research and
surveillance network: cohort profile summary. JMIR Public Health
Surveill. 2022;8.
25 de Lusignan S. Effective pseudonymisation and explicit statements
of public interest to ensure the benefits of sharing health data for
research, quality improvement and health service management
outweigh the risks. Inf Prim Care. 2014;21(2):61–63.
26 BTS/SIGN British guideline on the management of asthma; 2019.
Available from: https://www.brit-thoracic.org.uk/quality-improvement/
guidelines/asthma/.
27 Asthma, acute. British national formulary; 2024. Available from:
https://bnf.nice.org.uk/treatment-summaries/asthma-acute/.
28 Agency UHS. Green book, chapter 25, pneumococcal; 2023. Available
from: https://assets.publishing.service.gov.uk/media/64d68d6edd15ff
000d278019/Green_Book_Chapter_25_Pneumococcal_27_7_23.pdf.
29 de Lusignan S, van Weel C. The use of routinely collected computer
data for research in primary care: opportunities and challenges.
Fam Pract. 2006;23(2):253–263.
30 PRIMIS–The University of Nottingham. SNOMED CT codes for
asthma: PRIMIS covid vaccination uptake reporting; 2021. Available
from: https://www.opencodelists.org/codelist/primis-covid19-vaccuptake/ast/v1/#full-list.
31 UK Research and Innovation (UKRI) Medical Research Council
(MRC) NHS Health Research Authority (HRA). Is my study
research–decision tool NHS HRA; 2020. Available from: http://www.
hra-decisiontools.org.uk/research/.
9
Articles
32 Benchimol EI, Smeeth L, Guttmann A, et al. The REporting of
studies Conducted using Observational Routinely-collected health
Data (RECORD) statement. PLoS Med. 2015;12(10):e1001885.
33 Elm EV, Altman DG, Egger M, Pocock SJ, Gøtzsche PC,
Vandenbroucke JP. Strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines
for reporting observational studies. BMJ. 2007;335(7624):806–
808.
34 Asthma + Lung UK. Asthma care in a crisis. Annual Asthma Survey
2020; 2020.
35 Vestesson EM, De Corte KLA, Crellin E, Ledger J, Bakhai M,
Clarke GM. Consultation rate and mode by deprivation in English
general practice from 2018 to 2022: population-based study. JMIR
Public Health Surveill. 2023;9:e44944.
10
36 UK All Party Parliamentary Group for Respiratory Health.
Improving asthma outcomes in the UK. One Year On 2022.
Available from: https://www.appg-respiratory.co.uk/.
37 Public health profiles: office for health improvement & disparities. Available from: https://fingertips.phe.org.uk/search/
asthma%20prevalence.
38 Mukherjee M, Nwaru BI, Soyiri I, Grant I, Sheikh A. High health
gain patients with asthma: a cross-sectional study analysing national Scottish data sets. NPJ Prim Care Respir Med. 2018;28(1):27.
39 Kavanagh J, Jackson DJ, Kent BD. Over- and under-diagnosis in
asthma. Breathe. 2019;15(1):e20–e27.
40 Bernal JL, Sinnathamby MA, Elgohari S, et al. The impact of social and
physical distancing measures on COVID-19 activity in England: findings
from a multi-tiered surveillance system. Euro Surveill. 2021;26(11).
www.thelancet.com Vol 42 July, 2024