Journal of Asthma

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ijas20

Factors associated with future hospitalization

among children with asthma: a systematic review

Simran Aggarwal, Tanita Cepalo, Sana Gill, Madhura Thipse, Kerry-Lee

Clifton, Andrea Higginson, James Vu, Vid Bijelić, Nick Barrowman, Sandra
Giangioppo & Dhenuka Radhakrishnan

To cite this article: Simran Aggarwal, Tanita Cepalo, Sana Gill, Madhura Thipse, Kerry-
Lee Clifton, Andrea Higginson, James Vu, Vid Bijelić, Nick Barrowman, Sandra Giangioppo
& Dhenuka Radhakrishnan (2023) Factors associated with future hospitalization among
children with asthma: a systematic review, Journal of Asthma, 60:3, 425-445, DOI:
10.1080/02770903.2022.2070762

To link to this article: https://doi.org/10.1080/02770903.2022.2070762

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Journal of Asthma
2023, VOL. 60, NO. 3, 425–445
https://doi.org/10.1080/02770903.2022.2070762

Review

Factors associated with future hospitalization among children with

asthma: a systematic review
Simran Aggarwal, MD Candidatea, Tanita Cepalo, BScb, Sana Gill, MDa, Madhura Thipse, MDc, Kerry-Lee
Clifton, MD Candidatec , Andrea Higginson, RN, MScN, CAEd, James Vu, MDa, Vid Bijelić, MScc, Nick
Barrowman, PhDc, Sandra Giangioppo, MDe,f and Dhenuka Radhakrishnan, MDd,g,h
a
Faculty of Medicine, University of Ottawa, Ottawa, Canada; bFaculty of Science, Carleton University, Ottawa, Canada; cChildren’s
Hospital of Eastern Ontario Research Institute, Ottawa, Canada; dChildren’s Hospital of Eastern Ontario, Ottawa, Canada; eUniversity of
Toronto, Toronto, Canada; fThe Hospital for Sick Children, Toronto, ON, Canada; gDepartment of Pediatrics, University of Ottawa,
Ottawa, Canada; hICES, Ottawa, ON, Canada

ABSTRACT ARTICLE HISTORY

Objective: Asthma is a leading cause of emergency department (ED) visits and hospitalizations Received 25 September 2021
in children, though many could be prevented. Our study objective was to identify factors Revised 15 April 2022
Accepted 22 April 2022
from the published literature that are associated with future hospitalization for asthma
beyond 30 days following an initial asthma ED visit. KEYWORDS
Data Sources: We searched CINAHL, CENTRAL, MEDLINE, and Embase for all studies examining Child; risk factors; readmission;
factors associated with asthma-related hospitalization in children from January 1, 1992 to future risk; predictors
February 7, 2022.
Selecting Studies: All citations were reviewed independently by two reviewers and studies
meeting inclusion criteria were assessed for risk of bias. Data on all reported variables were
extracted from full text and categorized according to identified themes. Where possible,
data were pooled for meta-analysis using random effects models.
Results: Of 2262 studies, 68 met inclusion criteria. We identified 28 risk factors and categorized
these into six themes. Factors independently associated with future hospitalization in
meta-analysis include: exposure to environmental tobacco smoke (OR = 1.94 95%CI 0.67–5.61),
pets exposure (OR = 1.67 95%CI 1.17–2.37), and previous asthma hospitalizations (OR = 3.47
95% CI 2.95–4.07). Additional related factors included previous acute care visits, comorbid
health conditions (including atopy), allergen exposure, severe-persistent asthma phenotype,
inhaled steroid use prior to ED visit, poor asthma control, higher severity symptoms at ED
presentation, warmer season at admission, longer length of stay or ICU admission, and
African-American race/ethnicity.
Conclusions: We identified multiple factors that are consistently associated with future
asthma hospitalization in children and could be used to identify those who would benefit
from targeted preventative interventions.

Abbreviations: BMI: Basal metabolic index; CTAS: Canadian triage and acuity scale; ETS:
Environmental Tobacco smoke; ED: Emergency department; Future hospitalization: Future
hospitalization for asthma; HR: Hazard ratio; ICU: Intensive care unit; OCS: Oral corticosteroids;
OR: Odds ratio; PRISMA: Preferred Reporting Items for Systematic Reviews and MetaAnalyses
Protocol; QUIPS: Quality In Prognosis Studies tool; RR: Risk ratio; SES: Socioeconomic status.

Introduction department (ED) visits and hospitalizations (4,5) with

Asthma is the most common chronic disease among
children worldwide, ranking among the top 20 con-
ditions for disability-adjusted life years in children
(1). Global estimates for childhood asthma prevalence
range from 1.72% to 15% (2,3) depending on the age
group and country studied. In addition to its high
prevalence, asthma can lead to significant morbidity
and continues to be a leading cause of emergency
repeat ED visits estimated to account for 22–24% of
all asthma ED visits in some countries (5,6) Repeat
ED visits and hospital admissions represent failed
opportunities for prevention during the first health-
care encounter as well as avoidable healthcare costs
and morbidity related to symptom burden, school
absence and loss of work productivity for care-
givers (7).

CONTACT Dhenuka Radhakrishnan dradhakrishnan@cheo.on.ca Children’s Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ONK1H 8L1, Canada.
Supplemental data for this article can be accessed online at https://doi.org/10.1080/02770903.2022.2070762.
© 2022 Taylor & Francis Group, LLC
426 S. AGGARWAL ET AL.
Previous studies and systematic reviews in children
have identified factors associated with any asthma
hospitalization or immediate re-admission to hospital
within 30 days including age, lower socioeconomic
status, ethnicity, sex, medical comorbidities, exposure
to tobacco smoke, family history of asthma and atopy,
allergen exposure, baseline lung function, previous
ED visits, and hospitalizations (4,6–14). However, rel-
atively fewer studies have specifically explored risk
factors for future hospitalization for asthma (hereafter
mentioned as future hospitalization) beyond 30 days
following an initial ED visit for asthma. These future
hospitalizations are less likely to reflect ED manage-
ment and may imply the need for more tailored pre-
ventative interventions. Understanding the specific
risk factors for future hospitalization in this more
vulnerable subgroup with asthma hospitalization
30 days following an initial asthma ED visit (which
may differ from factors that predict overall asthma
hospitalization risk) would allow for more efficient
screening to identify and target this captive population
while in the ED. In this study, we aimed to identify
risk factors associated with future hospitalization
among children beyond 30 days following a prior
emergency room visit for asthma through a rigorous
systematic literature review.
Methods
Design of this study was informed by the Preferred
Reporting Items for Systematic Reviews and
Meta-Analyses Protocol (PRISMA-P) checklist
(Appendix 1) (15,16). The protocol has been regis-
tered with the PROSPERO International Prospective
Register of Systematic Reviews (PROSPERO #
CRD42017060934).
Data sources and search strategy
We conducted a comprehensive literature search in
MEDLINE including Epub Ahead of Print, In-Process
& Other Non-Indexed Citations (January 1, 1992–
February 7, 2022), CINAHL, CENTRAL, and Embase
(1980–February 7, 2022). Reference lists of all included
primary studies and any identified narrative and sys-
tematic reviews were hand-searched for relevant
studies.
The search strategy was developed and conducted
by a librarian experienced in systematic reviews, using
a method designed to optimize term selection (17).
No language or study design limits were applied at
this step; however, searches were limited to the pedi-
atric age group.
Study selection
Studies reporting on the following criteria were as
follows: (a) children aged 2 to 16.99 years old and
with a previous ED visit for asthma (hereby referred
to as the index visit), (b) admission or readmission
to hospital for asthma between 1 and 12 months fol-
lowing the index visit as the outcome, (c) any and
all risk factors excluding those pertaining to specific
medication, management or education interventions.
We only included studies that reported on children
with a diagnosis of “asthma” and excluded those that
only reported on “wheeze” or “reactive airways dis-
ease”. Studies only examining children <2 years were
excluded due to difficulties in diagnosis of asthma in
this age group and potential overlap with bronchiolitis.
Studies that only commented on risk of life threat-
ening or intensive care unit readmission and not all
hospital readmissions were excluded.
We included any completed clinical studies of all
design types; however, case reports (i.e. sample sizes less
than five), reviews, and letters to the editor were
excluded. Studies were restricted to the English language
and publication date range of January 1, 1992–February
7, 2022 to capture the most recent 30 years of the liter-
ature which would be most relevant to current practice.
After removal of duplicates, citations were uploaded
to InsightScope (www.insightscope.ca) for title/abstract
and full text screening. Insight scope is a systematic
review platform that accelerates the review process
through the use of crowdsourcing (18,19). At both levels
of screening, citations were assessed independently in
duplicate by at least two members of a team of ten
reviewers that included registered nurses, physicians and
medical trainees. All reviewers were trained and com-
pleted a test set of up to 20 citations with an achieved
sensitivity of at least 80% prior to formal citation review.
Risk of bias assessment
Risk of bias for each included study was assessed
independently by two reviewers using the Quality In
Prognosis Studies (QUIPS) tool, recommended by the
Cochrane Prognosis Methods Group to assess risk of
bias in prognostic factor studies (20). The QUIPS tool
considers bias across six domains: participation, attri-
tion, prognostic factor measurement, confounding
measurement, outcome measurement, and analysis and
reporting (20).
Data extraction
Data was extracted by four separate reviewers using
REDCap, a secure online data collection application

(21). Disagreements or discrepancies at any stage of
the systematic review were resolved by discussion
between the reviewers and a clinical expert.
Data interpretation and analysis
All identified variables were categorized according to
themes and their association with future hospitalization
and summarized in tables. Variables that demonstrated
a consistent direction of association with future hos-
pitalization in the majority of studies, (i.e. more than
50% of studies demonstrating either a positive or neg-
ative association) whether pooled or unpooled, were
classified as having a “positive association” with this
outcome, and others classified as having an “inconsis-
tent association”. For this categorization, each study was
treated as having equal weighting to another, irrespec-
tive of sample size or duration of observation. All esti-
mates where 95% confidence intervals crossed 1 were
categorized as no association. In order to report on
the independent association of variables with the future
hospitalization outcome, where possible, we pooled
studies and performed a meta-analysis for those that
described similar study methodology, variables and
adjusted analyses. We used the DerSimonian and Laird
procedure to fit random effects models for meta-analysis.
Heterogeneity of studies was determined by calculation
of the I2 statistic; data was not pooled when I2 was
greater than 75% which would correspond to high
heterogeneity. In all cases where both unadjusted and
adjusted results were reported, only adjusted estimates
were included.
Results
Search results
The searches yielded 2262 records with 222 retained for
full-text review and 68 included in the final analysis (see
Figure 1 (PRISMA diagram) and Table 1 for details).
Study characteristics
We included a total of 63 cohort, 3 case-control, 1
cross-sectional, and 1 case-control cohort studies; the
majority of them (51) were retrospective. Study sample
size varied from 20 to 2.3 million participants and
originated from 18 countries: USA (40), Canada (7),
Australia (4), Sweden (1), New Zealand (2), China
(2), and 1 each from Thailand, Saudi Arabia, Brazil,
Norway, Colombia, France, Lebanon, Taiwan,
Netherlands, England, South Africa, and Japan.
Publication dates ranged from 1974 to 2022.
Journal of Asthma 427
Overview of results
Risk of Bias across studies varied (see Supplementary
Data 4, Figure S2). There was a range of at least 28
risk factors that were reported on in more than one
of the included studies, and these were broadly cat-
egorized into six themes with results summarized
below (details in Table 2, Figure 3 and Supplementary
Data 1, Table S1). Results of meta-analyses are
described below and in Figure 2.
Theme I—physical and health characteristics
Age (studies = 22 inconsistent association)
The effect of age on the future risk of ED or hospital
readmission was examined in 22 studies (Table 2),
with marked variation in the age group classification
and statistical methods used for the comparisons.
Although the age group classifications varied, out of
the 11 studies that reported any association (positive
or negative) between age and risk of future hospital-
ization, 8 demonstrated that younger age at index
admission led to increased risk of future ED visits or
hospitalizations. Mitchell et al. (25) found that the
adjusted relative risk of future hospitalizations
increased if children were <5 years old at index ED
visit (aRR =1.17, 95%CI 1.41–2.08), and Lasmar et al.
(36) found increased future hospitalizations in chil-
dren who were <2 years old at first hospitalization.
Sex (studies = 16; inconsistent association)
There was no clear consensus on whether future hos-
pitalizations were more frequent in males or females.
Four studies found an association between female sex
and future hospitalizations (39,54,61,81) and in three
studies, male sex was found to reduce the risk of
readmission (58,59,63)
A small number of studies demonstrated an inter-
action between age and sex, with an association seen
between future hospitalizations and older female chil-
dren but not older male children. One study (61)
reported increased odds of future hospitalizations in
older females aged 7 or above (aOR =1.3 95%CI
1.01–1.8) but a decreased odds of future hospitaliza-
tions in younger females aged 2–6 years old (aOR=
0.7 95% CI 0.5–0.8). Similarly, Kao et al. (59) demon-
strated increased re-admissions in females aged
5–14 years, as opposed to their male counterparts.
Race and ethnicity (studies = 16; positive
association)
Of fourteen (28,31,32,40,42,44,50,53,55,67,71,79,81,8
4,86,) studies specifically looking at African-American
428 S. AGGARWAL ET AL.
versus Caucasian race, nine studies showed a statis-
tically significant positive association with future
hospitalizations. Of these, four adjusted for various
factors related to socioeconomic status. In one study,
a higher degree of African ancestry, as evaluated by
genetic testing, was associated with a significant
increase in asthma readmission (OR= 1.11 for every
10% increase in African ancestry, 95% CI 1.05–1.18).
The authors also evaluated several socioeconomic
factors alongside ancestry and found that this positive
association was mediated by non-genetic factors,
Figure 1. PRISMA flow diagram of included and excluded studies.
broadly categorized as hardship and disease manage-
ment (84). In only one study was African-American
race associated with a lower hazard of future hospi-
talization. Bloomberg et al. (40) reported a negative
hazard of readmission in people of African-American
race (HR = 0.83, 95% CI 0.73–0.94, p = 0.0042); how-
ever, the analysis in this study also demonstrated a
significant interaction between race and insurance
type, with individuals of African-American race on
Medicaid or self-pay having the highest hazard of
future hospitalizations (HR = 1.28, 95%CI 1.03–1.58).
Table 1. Included studies.
Study design, e.g.
RCT, prospective
cohort, retrospective Sample selection and Sample
No. Study cohort etc. Location setting Age (years) size Years Predictors
1 Bettenhausen Retrospective cross USA Inpatient admission 5 to 17 518 10-2011 to 09 BMI at admission
2015 (22) sectional study for asthma 2012
2 Raymond Prospective cohort. Australia Inpatient admission 1 to 7 103 Severity of attack, past asthma pattern, intention to treat,
1998 (23) Survey for asthma perceived consequence of treatment
3 Visitsunthorn Retrospective Thailand Inpatient admission ≤ 14 20 1-01-2006 to Age, sex, SES, parental history of allergic disease, co-morbid
2013 (24) case-control study for asthma 31-12-2007 diseases, level of asthma control, skin prick test results,
influenza vaccine injection, asthma severity before admission
4 Mitchell Observational cohort New Zealand Inpatient admission 0 to 14 1034 1-03-1986 to Demographics, asthma severity, inpatient treatment at the
1994( study for asthma 28-02-1987 index episode, discharge
(25))
5 Alshehri Retrospective case Saudi Arabia Inpatient admission 0-4 years 28 1-08-1998 to Demographics, route of admission, previous medical history,
2005 (26) control study for asthma and > 4 years 31-12-2002 clinical assessment at admission, hospital treatment and
discharge
6 Brittan Retrospective cohort USA Inpatient admission 2 to 18 9288 1-01-2009 to Post discharge emergency department visits, oral corticosteroid
et al.2017 study for asthma 30-06-2011
(
(27))
7 Hasegawa Case control study USA Inpatient admission 2 to 17 & 18 369 1-01-2012 to Demographics-age, sex, ethnicity, insurance status, chronic
2015 (28) for asthma to 54 31-12-2013 asthma factors-ETS, past ED visits, intubation, asthma
management OCS, ICS.
8 Kenyon 2015 Retrospective cohort USA Inpatient admission 2 to 18 1986 1-01-2006 to Post hospitalization prescription fills for recommended asthma
(29) study for asthma 30-09-2007 discharge medication classes
9 Moncrief Prospective cohort USA Inpatient admission 1 to 16 774 11-08-2010 to Age, sex, race, income, parent’s marital status, number of nights
2014 (30) study for asthma 20-10-2011 spent away from home
10 Kenyon 2014 Retrospective cohort USA Inpatient admission >2 1-07-2008 to Age, sex, race, insurance status, home disposition, complex
(31) analysis for asthma 30-06-2010 chronic condition, past hospitalization and treatment
11 Liu 2009 (32) Retrospective cohort USA Inpatient admission 0 to 18 451 2001 to 2005 Age, sex, race, insurance status, season of index admission,
analysis for asthma length of stay at index admission, residence in the same zip
code as a hospital emergency room
12 Beck 2012 Secondary analysis of a USA Inpatient admission 1 to 16 1-April-2008 to Geographic social risk index
(33) prospective, for asthma 1-May-2009
observational cohort
13 Triasih 2011 Retrospective Cohort Australia Inpatient admission 2 to 18 410 1-01-1990 to Demographics, clinical data prior to the index admission,
(34) Study for asthma 31-12-2004 history of prematurity, atopy, family history of asthma, age
at diagnosis, length of hospital stay, length of ICU stay,
history of intubation, baseline asthma pattern
14 Chang 2008 Retrospective Cohort USA Inpatient admission 0 to 18 3983 1-01-2000- Neighborhood traffic burden, local traffic-related air pollution
(35) Study for asthma 31-12-2003 exposure levels
15 Lasmar 2006 Retrospective Cohort Brazil Inpatient admission 0 to 15 202 1-10-1994 to Sociodemographic variables, quality of health care, clinical
(36) Study for asthma 31-12-1995 variables – exacerbations in past 12 months
16 Kocevar 2005 Population-based Norway At risk cohort 0 to 14 795 1998 to 1999 Allergic rhinitis
(37) retrospective cohort
study
17 Wallace 2004 Retrospective Cohort USA Inpatient admission 1 to 14 4808 1994-2000 Demographics- race, sex, age
(38) Study for asthma
Journal of Asthma

18 Chen 2003 Retrospective Cohort Canada Inpatient admission 0 to <20 86863 1-04-1994 to Age and sex
(39) Study for asthma 31-03-1997
(Continued)
429
 430

Table 1. Continued.
Study design, e.g.
RCT, prospective
cohort, retrospective Sample selection and Sample
No. Study cohort etc. Location setting Age (years) size Years Predictors
19 Bloomberg Retrospective Cohort USA Inpatient admission 0 to 20 2619 1990-1999 Race/Ethnicity, insurance type
2003 (40) Study for asthma
20 Chen 2003 Retrospective Cohort USA Inpatient admission 4 to 18 260 1-06-1999 to Psychosocial Factors, SES, family environmental scale-conflict,
(41) Study for asthma 31-12-1999 cohesion, expressiveness.
S. AGGARWAL ET AL.

21 Chabra 1998 Retrospective Cohort USA Inpatient admission 1 to 12 4947 1-01-1994 to Age, sex, race, index admission-source, season, length of stay
(42) Study for asthma 31-12-1994
22 Beck 2016 Retrospective Cohort USA Inpatient admission 2 to 17 4638 1-01-2011 to census tract rate of violent crime as recorded by the police, all
(43) Study for asthma or 31-12-2013 crime (violent plus non-violent) rate
emergency
department visit
for asthma
23 Beck 2014 Retrospective Cohort USA Inpatient admission 1 to 16 4355 1-01-2009 to Density of housing code violations in census tracts, in-tract
(44) Study for asthma or 31-12-2012 asthma-relevant violations (such as the presence of mold or
emergency cockroaches
department visit
for asthma
24 Vicendese Other non-included Australia Inpatient admission 2 to 17 251 1-09-2009 to indoor environmental factors, lifestyle
2015 (45) study design for asthma 31-12-2011 characteristics-overcrowding, living in disadvantaged area
25 Moncrief Population-based USA Inpatient admission 1 to 16 774 08 2010 to 10 Caregiver marital status, shift work, child’s race, income,
2014 (46) prospective for asthma 2011 psychological distress,
observational cohort
26 Rodriguez- Prospective cohort Colombia Inpatient admission 1 to 18 109 2013 to 2019 Age, pets, parental knowledge about asthma, maternal
Martinez for asthma depression level, allergic rhinitis, maternal education,
2014 (47) maternal smoking
27 Wu 2016 Retrospective USA Emergency 1 to 17 108 2011 to 2012 Changes in asthma status over the prior 12 months, disease
(48) population-based department visit burden, reports of ED visits, hospitalizations, and oral steroid
cohort for an acute use over the prior 12 months, adherence, asthma control
asthma
exacerbation.
28 Giarola 2014 Population based New Zealand Inpatient admission 0 to 15 200 2005 to 2006 & Indigenous status
(49) retrospective cohort for asthma 2010 to 2011
29 Beck 2014 Prospective cohort USA Inpatient admission 1 to 16 774 11-08-2010 to Child race, SES, hardship, marital status
(50) for asthma 20-10-2011
30 Newman Population based USA Inpatient admission 1 to 16 774 2-08-2010 to Race, viral infections, allergen exposure (in atopic individuals),
2014 (51) prospective for asthma 2-10-2011 medication adherence, and traffic-related air pollution (TRAP)
observational cohort exposure.
31 Howrylak Population based USA Inpatient admission 1 to 18 4774 1-01-2004 to Age, gender, race, tobacco exposure at home, in a secondary
2014 (52) retrospective cohort for asthma 31-12-2008 residence, or in the car.
32 Auger 2013 Prospective cohort USA Inpatient admission 1 to 16 601 1-04-2008 to Child age, race, insurance, household income, maternal
(53) for asthma 31-05-2009 education, and past history of inhaled corticosteroids, access
to medical home
33 Li 2012 (4) Population based Canada Emergency 2 to 17 801 14-04-2006 to Sex, age, SES, follow-Up Care after an ED visit
retrospective cohort department visit 28-02-2009
for asthma.
34 Delmas 2011 Retrospective cohort France Inpatient admission 2 to 44 16628 2002 to 2005 Age, sex, length of stay at index admission
(54) for asthma
(Continued)
Table 1. Continued.
Study design, e.g.
RCT, prospective
cohort, retrospective Sample selection and Sample
No. Study cohort etc. Location setting Age (years) size Years Predictors
35 Carroll 2010 Retrospective cohort USA Inpatient admission 2 to 18 306 1-04-1997 to ICU admission, asthma classification, admission illness severity,
(55) for asthma 31-12-2007 durations of therapy or LOS
36 Tolomeo (56) Retrospective cohort USA Inpatient admission 2 to 15 298 1-01-2006 to Age, sex, race, insurance status, previous ED visit, previous
for asthma 31-12-2006 hospitalization, median household income
37 Delfino 2009 Retrospective cohort USA Inpatient admission 0 to 18 2768 1-01-2000 to Local traffic generated air pollution
(57) for asthma or 31-12-2003
emergency visit
for asthma
38 Kalaajieh Retrospective cohort Lebanon Emergency 6 to 15 288 31-12-1993 to Age, sex, previous admissions for asthma , maternal smoking,
2002 (58) study department visit 1-01-2000 previous URTI, history of allergy
for acute asthma
exacerbation
39 Kao 2001 Retrospective cohort Taiwan Inpatient admission 2 to 14 2283 1990 to 1998 Age, sex, seasonality
(59) study for asthma
40 Wever-Hess Prospective cohort Netherlands 0 to 4 257 Age, sex, history and laboratory tests for atopic status at initial
2000 (60) Study presentation, clinical data on admission
41 Taylor 1999 Retrospective Cohort Canada N/A 16994 Previous ED visit, hospitalization for asthma
(9) Study
42 Hjern 1999 Retrospective Cohort Sweden Inpatient admission 2 to 18 2319176 1-01-1990 to Age, sex, SES, maternal smoking during pregnancy, maternal
(61) for asthma 31-12-1994 education level, number of siblings
43 Minkovitz Nested case control USA Inpatient admission 0 to 14 119 1-07-1994 to Medical history, ambulatory care before and after discharge
1999 (62) study for asthma 31-06-1995
44 Schaubel Prospective Cohort Canada Inpatient admission 0 to 4 1543 1-01-1984 to Age, sex
1996 (63) for asthma 31-03-1985
45 Henry 1995 Prospective Cohort Australia Inpatient admission 1 to 15 263 1-11-1990 to Parental asthma knowledge, age, exposure to smoke, number
(64) for asthma 1-11-1991 of attacks in the past 12 months, father’s occupation
46 Sporik 1993 Prospective Cohort England Inpatient admission 1.1 to 15 73 1-09-1988 to Allergen exposure, exposure/sensitization to dust mite, cat
(65) for asthma 30-04-1989 allergen
47 Roux 1993 Retrospective South Africa Inpatient admission 2 to 15 40 1-01-1974 to Sex, socio-economic status, family history of allergy, pet
(66) longitudinal for asthma 31-12-1987 ownership, passive smoking, age of symptom onset, date of
case-controlled first hospital visit, maintenance therapy, date of first ICU
cohort admission, skin sensitivity and radio-allergosorbent test
(RAST)
48 Beck 2016 Prospective cohort USA Inpatient admission 1 to 16 774 1-08-2010 to Racial difference as regards biologic, environmental, disease
(67) Study for asthma 31-10-2011 management, access, and socioeconomic hardship variables
49 Beck 2017 Retrospective Cohort USA Inpatient admission 1 to 16 1845 01 2011 and 12 Educational, health/environmental, and social/economic
(68) for asthma or 2013. opportunity across census tracts
emergency
department visit
for asthma
50 Giangioppo Retrospective Cohort Canada Emergency visit for 2 to 17 2669 1-09-2012 to Age, sex, frequency of ED visits, Canadian triage and acuity
2019 (69) asthma. 31-08-2015 scale (CTAS) score at ED presentation
51 Lam 2019 Retrospective Cohort China Inpatient admission 0 to 5 6331 1-01-2002 to Meteorological parameters mean temperature, mean relative
Journal of Asthma

(70) for asthma 1-01-2011 humidity and air-pollutants

(Continued)
431
 432

Table 1. Continued.
Study design, e.g.
RCT, prospective
S. AGGARWAL ET AL.

cohort, retrospective Sample selection and Sample

No. Study cohort etc. Location setting Age (years) size Years Predictors
52 Molina 2019 Retrospective Cohort USA Inpatient admission 2 to 18 480 1-06 2014 to Medicaid claims data to evaluate prescription fills,
(71) for asthma 31-12 2015 demographics, chronic asthma severity, admission Severity,
viral infection
53 Okubo 2017 Retrospective Cohort Japan Inpatient admission 6 to 18 38679 1-07-2010 to Obesity
(72) for asthma 31-03-2015
54 Sun 2019 Retrospective Cohort China Inpatient admission 0 to 18 205 1-01-2007 to Demographics, previous ED visits, hospitalization, history of
(73) for asthma 31-12-2015 allergy,
55 Tse 2017 Retrospective Cohort Canada Inpatient admission 2 to 17 26168 1-04-2008 to Previous ICU hospitalization
(74) for asthma 31-03-2014
56 Baek 2020 Retrospective Cohort USA Inpatient admission 5 to 18 902 1-01-2010 to Age, sex, ethnicity, insurance status, use of medication, LOS at
(75) for asthma 31-12-2016 index visit, seasonality, SES, Pollutants
57 Pinto 2020 Retrospective Cohort USA Inpatient admission 0.6 to 18 646 1-10-2012 to Insurance status, prior ED visits
(76) for asthma 30-09-2015
58 Baek 2020 Retrospective Cohort USA Inpatient admission 5 to 11 111 1-01-2010 to Environmental tobacco smoke
(77) for asthma 31-12-2014
59 Philips 2020 Retrospective Cohort USA Inpatient admission 2 to 18 613 1-06-2014 to Post discharge follow-up, past ED visit, Pets and allergens
(78) for asthma 31-05-2016
60 Abir 2020 Retrospective Cohort USA Inpatient admission 0 to 17 3170 1-01-2010 to Ethnicity, age, sex, comorbidities
(79) for asthma 31-12-2014
61 Molina 2020 Retrospective Cohort USA Inpatient admission 2 to 12+ 664 1-06-2014 to Area deprivation index, residential instability
(80) for asthma 31-12-2015
62 Jroundi 2020 Retrospective Cohort Canada Inpatient admission 2 to 17 66835 1-01-2005 to Socioeconomic status (SES)
(81) for asthma 31-12-2014
63 Hogan 2021 Retrospective Cohort USA Inpatient admission 5 to 18 1044 01-01-2013 to Insurance type, Socioeconomic status (SES), index
(82) for asthma 12-31-2013 hospitalization, season of discharge
64 Faison 2021 Retrospective Cohort USA Inpatient admission 2 to 17 85 01-01-2016 to Change in address, insurance type, previous healthcare
(83) for asthma 12-31-2018 encounters
65 Mersha 2021 Retrospective Cohort USA Inpatient admission 1 to 16 106 08-01-2010 to Race, global ancestry, insurance, socioeconomic status (SES),
(84) for asthma 10-31-2011 caregiver characteristics
66 Sakai-Bizmark Retrospective Cohort USA Inpatient admission 0 to 18 11202 01-01-2009 to ED, ICU, length of stay
2019 (85) for asthma 12-31-2014
67 Fisher-Owens Retrospective Cohort USA Inpatient admission 2 to 22 15740 07-01-2002 to Race
2006 (86) for asthma 06-30-2003
CTAS: Canadian Triage & Acuity Scale; ED: Emergency department; ICS: Inhaled corticosteroids; OCS: Oral corticosteroids; NHLBI: National Heart, Lung and Blood Institute; ICU: Intensive care unit.
 Journal of Asthma 433

Table 2. Summarized quantitative findings of selected variables in relation to future asthma hospitalizations.
Suggestive of
Assessed No. of negative association Suggestive of no association OR/ Suggestive of positive
categories studies Predictors OR/HR/RR < 1 HR/RR =1 association OR/HR/RR > 1
Theme 1 Physical and health characteristics
Age 15 Younger vs. older Chabra; 1998 (42) Henry 1995 (64)
Abir 2020 (79) Wever-Hess 2000 (60)
Carroll 2010 (55) Jroundi 2020 (81)
Delmas 2011 (54) Kalaajieh 2002 (58)
Giangioppo 2019 (69) Kao 2001 (59)
Jroundi 2020 (81) Tolomeo 2006 (56)
Rodriguez-Martinez 2014 (47) Tse 2017 (74)
Sun 2019 (73) Hasegawa 2015 (28)
Tse 2017 (74)
Delmas 2011 (54)
7 Older vs. younger Baek 2020 October Beck 2014. November (44) Hasegawa; 2015 (28)
(75) Delmas 2011 (54)
Li 2012 (4) Hasegawa 2015 (28)
Liu S Y 2009 (32) Kenyon 2014 (31)
Sex 11 Male Li 2012 (4) Kalaajieh; 2002 (58)
Lasmar L M; 2006 (36) Kao 2001 (59)
Chabra 1998 (42) Schaubel 1996 (63)
Beck AF; 2014 (44)
Carroll CL; 2010 (55)
Giangioppo; 2019 (69)
Molina 2019 (71)
Abir 2020 (79)
5 Female Delmas 2011 (54) Delmas 2011 (54) Jroundi; 2020
(81)
Mitchell 1994 (25)
Kao; 2001 (59)
Hjern 1999 (61)
Race and 15 African-American or Bloomberg; 2003 (40) Carroll 2010 (55) Beck 2014 (50)
ethnicity Black Hasegawa 2015 (28) Auger 2013 (53) Kenyon 2014
Liu 2009 (32) (31)
Abir 2020 (79) Molina 2019 (71)
Beck 2014 November (44) Chabra 1998 (42)
Beck 2016 (67) Jroundi 2020
(81) Mersha 2021 (84)
Fisher-Owens 2006 (86)
7 Hispanic Carroll 2010 (55) A. Chabra 1998 (42)
Hasegawa 2015 (28)
Kenyon 2014 (31)
Jroundi 2020 (81)
Baek 2020 October (75)
Abir 2020 (79)
2 Caucasian Carroll CL 2010 (55) Abir 2020 (79)
7 Other + Asian Hasegawa 2015 (28) Chabra 1998(42)
Chabra 1998 (42)
Beck 2014 (44)
Jroundi 2020 (81)
Giarola 2014 (49)
Auger 2013 (53)
Kenyon C:2014 (31)
Comorbidities 12 All comorbidities Visitsunthorn; 2013 (24) Alshehri M A 2005 (26)
including Sun 2019 (73) Kenyon 2014 (31) Kalaajieh 2002
Atopy (allergic Philips 2020 (78) (58)
rhinitis, eczema, Bettenhausen 2015 (22) Minkovitz 1999 (62)
food allergy) Tse 2017 (74) Carroll 2010 (55)
Okubo 2017 (72)
Kocevar 2005 (37)
Kalaajieh 2002 (58)
Sun 2019 (73)
Theme II Family and social characteristics
Income 9 Roux 1993 (66) Beck 2014 (50) Moncrief 2014 (46)
Li 2012 (4) Jroundi; 2020 (81) (Income
Lasmar 2006 (36) within 1st & 2nd quartile)
Hasegawa 2015 (28) Li 2012 (4)
Chen 2003 (39)
Jroundi 2020 (81) (income above
3rd Quartile)
Auger 2013 (53)
(Continued)
434 S. AGGARWAL ET AL.

Table 2. Continued.
Suggestive of
Assessed No. of negative association Suggestive of no association OR/ Suggestive of positive
categories studies Predictors OR/HR/RR < 1 HR/RR =1 association OR/HR/RR > 1
Neighborhood/ 15 Hogan 2021 (82) Liu 2009 (32) Beck, 2014 (50)
Housing Micropolitan Beck 2012 (33) (Percentage of Beck 2012 (33)
households with > 1 person/ Kalaajieh; 2002 (58)
room); Beck 2014 (44) (vacancy rate:
Sun 2019 (73) medium–high & housing
Vicendese 2015 (45) density: medium-high)
Beck 2014 (44) Sakai-Bizmark; 2019 (85)
(Vacancy rate low-medium Molina A; 2020 (80)
and housing density:
low-medium)
Faison 2021 (83)
Change in address in past
12 months
Moncrief 2014 (30)
Abir M 2020 (79)
Chen Y 2003 (39)
Beck 2016 June (43)
Molina 2020 (80)
Insurance status 13 Public/Medicaid Pinto J; 2020 (76) Auger 2013 (53) Carroll 2010 (55)
& primary insurance Hogan; 2021 (82) Hasegawa 2015 (28). Liu 2009 (32)
care access Beck 2014 (44). Brittan 2017 (27)
Bloomberg 2003 Bloomberg 2003 (40)
Jroundi 2020 (81) Faison 2021 (83)
Baek 2020 (75) Hogan 2021 (82)
Kenyon 2014 (31)
Caregiver 7 Henry R L; 1995(64) Rodriguez-Martinez 2014 (47) Lasmar 2006 (36)
education & Beck 2014 (50) (Low education level of mother
occupation Beck 2012 (33) 0–3 years)
Henry 1995 (64) (unemployed/
manual work)
Roux 1993 (66)
Hjern 1999(61)
Caregiver 7 Rodriguez-Martinez 2014(47) Chen 2003 (39)
coping: Mitchell 1994 (25) Alshehri
asthma 2005(26)
knowledge, Henry 1995 (64)
beliefs, and Wu 2016 (48)
perceptions Raymond 1998 (87)
Chen 2003(39)
Family history 5 Visitsunthorn; 2013 (24). Rodriguez-Martinez 2014 (47)
Kalaajieh 2002 (58) Roux 1993 (66)
Triasih 2011 (34) Moncrief 2014 (30)
Other social 7 Beck 2017 (68) (COI-moderate & Beck 2014 (50)
factors low). Beck 2012 (33)
Chen 2003 (41)
Beck 2014 (50)
Beck 2014. November (44)
Hjern 1999 (61)
Baek 2020 October (75)
Theme III Environmental exposures
Air pollution 5 Residence distance Newman 2014 (51) Newman 2014 (51)
to nearest arterial Delfino 2009 (57) Delfino 2009 (57)
road or freeway, Chang 2008 (35) Chang 2008 (35)
PM2.5 & Ozone Baek 2020 October (75) Baek 2020 July (77)
levels Baek 2020 July (77)
Environmental 6 Household smoking Visitsunthorn 2013 (24). Kalaajieh 2002 (58)
Tobacco Hasegawa 2015 (28) Minkovitz 1999 (62)
Smoke (ETS) Henry 1995 (64) Howrylak 2014 (52)
3 Maternal smoking Rodriguez-Martinez 2014 (47)
Kalaajieh 2002 (58) Hjern
1999 (61)
Pets 5 Includes all pets Rodriguez-Martinez 2014 (47)
Visitsunthorn; 2013 (24), Roux P
1993 (66)
Minkovitz 1999 (62)
Vicendese 2015 (45)
Allergens 7 All possible allergens Roux 1993 (66) Vicendese 2015 (45) Sporik R 1993 (65) Sun 2019
(73) Vicendese 2015 (45)
Wever-Hess 2000 (60)
Philips; 2020 (78)
Kalaajieh; 2002 (58)
(Continued)
 Journal of Asthma 435

Table 2. Continued.
Suggestive of
Assessed No. of negative association Suggestive of no association OR/ Suggestive of positive
categories studies Predictors OR/HR/RR < 1 HR/RR =1 association OR/HR/RR > 1
Theme IV – Asthma symptom severity and treatments before the index asthma ED visit
Baseline medical 3 OCS therapy Rodriguez-Martinez 2014 (47) Brittan 2017 (66)
therapy Minkovitz 1999 (62)
5 ICS therapy-current Sun 2019 (73) Visitsunthorn 2013 (24)
or past Minkovitz 1999 (62)
Hasegawa 2015 (28);
Auger 2013 (53)
Previous acute 9 ED visits Brittan 2017 (66)
care visits Li 2012 (4) Hasegawa 2015 (28)
Taylor 1999 (9)
Giangioppo; 2019 (69)
Lasmar LM 2006 (36)
Wu 2016 (48)
Tolomeo; 2006 (56)
Philips 2020 (78)
10 Hospital Admission Rodriguez-Martinez 2014 (47) Philips 2020 (78)
Alshehri 2005 (26)
Mitchell 1994 (25)
Wu 2016 (48); Kenyon 2014 (31)
Brittan 2017 (66);
Li 2012 (4)
Triasih; 2011 (34)
Taylor 1999 (9)
6 ICU admission/ Triasih 2011 (34) Visitsunthorn 2013 (24)
mechanical Hasegawa 2015 (28) Philips 2020 (78)
ventilation Minkovitz 1999 (62) Alshehri 2005 (26)
Asthma severity/ 4 NHLBI classification: Beck 2014 (50) Beck 2014 (50)
phenotype Persistent vs. Philips 2020 (78)
intermittent Lasmar 2006 (36)
Molina 2019 (71)
Asthma control 3 Poor or partial Henry 1995 (64) Lasmar 2006 (36) Visitsunthorn
control vs good 2013 (24)
control
Theme V – Index visit characteristics
Characteristics 10 Length of Stay Liu 2009 (32) Chabra; 1998 (42)
related to Sun 2019 (73) Delmas 2011 (54)
index visit Liu 2009 (32)
Tse 2017 (74)
Baek 2020 (75)
Hogan 2021 (82)
Kenyon 2014 (31)
Jroundi 2020 (81)
Hogan 2021 (82)
3 Severe (CTAS 1,2) vs Li 2012 (4)
less severe (CTAS Giangioppo 2019 (69)
4,5) Alshehri 2005 (26)
7 ICU admission/ Tse 2017 (74) Kenyon C; 2014 (31); Sun; 2019 Alshehri 2005 (26);
mechanical (73) Philips 2020 (78); Jroundi 2020
ventilation at (81)
index Triasih 2011 (34)
3 Intravenous steroids Mitchell 1994 (25) Visitsunthorn; 2013 (24) Visitsunthorn2013 (24)
Mitchell 1994 (25)
Alshehri 2005 (26)
5 Index admission Lam 2019 (70) Liu 2009 (32) Liu 2009 (32)
seasonality: warm Brittan 2017 (27) Sun; 2019 (73) Lam 2019 (70)
vs. cold Baek 2020 October (75)
Theme VI – Asthma symptom severity and treatments captured after the index asthma ED
Discharge 6 Discharged with Kenyon C; 2015 (29) Alshehri M A; 2005 (26) Brittan M; 2017(27)
medications/ Minkovitz; 1999 (62) Philips; 2020(78)
medication fills Molina 2019 (71)
post-discharge
7 Post-discharge Philips; 2020 (78) Li 2012 (4) Minkovitz; 1999 (62)
follow-up Visitsunthorn; 2013 (24) Brittan 2017 (27)
Alshehri 2005 (26) Hogan A; 2021 (82)
Brittan 2017 (27)
Minkovitz 1999 (62)
CTAS: Canadian Triage & Acuity Scale; ED: Emergency department; ICS: Inhaled corticosteroids; OCS: Oral corticosteroids; NHLBI: National Heart, Lung
and Blood Institute; ICU: Intensive care unit; OR: Odds ratio; RR: Risk ratio; HR: Hazard ratio.
436 S. AGGARWAL ET AL.

Figure 2. Forest plot for meta-analyses: factors associated with future asthma hospital admission. TE: treatment effect; seTE:
standard error of the treatment effect; OR: odds ratio.

Figure 3. Summary of the number of studies showing an association between selected variables and future asthma
hospitalizations.

A similar effect was seen in one study which showed
higher odds of ED revisit within a year for nonwhite
children with public insurance compared to white
children with public insurance (aOR = 0.71, 95% CI
0.57–0.88, p < 0.01) (76).
Data on other races were limited. Of the seven
studies (28,31,42,55,75,79,81) comparing Hispanic/
Latino race to non-Hispanic/White race, only one
showed a positive association with future hospitaliza-
tion (OR = 1.34, 95% CI 1.04–1.72) (42). There was

only one reported comparison between Asian and
Caucasian race, which did not convincingly demon-
strate increased odds of future asthma hospitalization
(OR = 1.46, 95% CI 1.0–1.4) (42).
Comorbidities (studies = 12; positive association)
Of the variety of comorbidities studied, the strongest
associations were seen with allergy or atopy, and
increased body mass index. A personal history of
allergic rhinitis was significantly associated with
future hospitalizations in two studies (37,58).
Similarly, atopic dermatitis (OR = 11.93, 95%CI
5.81–24.53, p < 0.001) (58) and eczema (OR= 3.122,
95%CI 1.473–6.616, p = 0.003) (73) were also asso-
ciated with future hospitalizations. Total serum IgE
> 300 (KUI/l) and > 6% eosinophils in peripheral
blood were also associated with increased odds of
future hospitalization (50,58).
With regard to obesity, both Carroll and Okubo
(55,72) demonstrated increased odds of future hospi-
talization. Other studied comorbidities including pre-
mature birth, low birth weight <2500 g, and presence
of airway structural abnormalities did not demonstrate
any association with future hospitalizations.
Theme II—family and social characteristics
Income (studies = 9; inconsistent association)
Measures of factors relating to income varied consid-
erably, with some studies examining direct household
income, and others looking at overall neighborhood
income centile as a proxy for patient income.
According to three studies (4,46,81), low household
income and belonging to neighborhoods from low
income quintiles increased future hospitalization.
Neighborhood and housing (studies = 15;
inconsistent association)
Forty-five geographic areas and housing based
socio-economic factors were analyzed with several
positive associations identified. Residential instability,
as defined by increased frequency in change in pri-
mary residence, and homelessness increased the haz-
ard of future hospitalizations in two out of three
studies (53,80,83,85) (aHR = 1.09; 95% CI 1.03 − 1.14
p < 0.002) (80). Similarly, multiple studies by Beck
et al. found various geographic and housing-related
factors which increased the hazard of future hospi-
talizations including: not owning a home, housing
units with high vacancy rates, crowded housing, and
neighborhoods with extreme poverty (33,44,50,68).
Residing in a rural versus urban community was
Journal of Asthma 437
shown to have a protective effect on future hospital-
ization in two studies (58,82) (aHR 0.69; 95% CI
0.51–0.94, p < 0.05).
Insurance status and primary care access (studies
= 13; inconsistent association)
Four studies found a positive association between pub-
lic (32,55,82) or Medicaid (27) insurance plans versus
private insurance and future hospitalizations. As stated
above, when health insurance status was examined in
combination with race, African-American children had
increased hazard of future hospitalizations if they were
on Medicaid or self-pay insurance (HR = 1.28; 95%
CI 1.01 − 1.63 p = 0.042) (40). The same effect was seen
when race was categorized broadly as white or non-
white, with nonwhite children on public insurance
having higher odds of ED revisit as compared to their
white counterparts (aOR = 0.71, 95% CI 0.57–0.88,
p < 0.01) (76). In one study, Caucasian children had
decreased risk of future hospitalizations with both
private and public insurance (76).
Caregiver education/occupation/(studies = 7;
inconsistent association)
Five studies examined the relationship between low
caregiver education level and future asthma hospital-
ization and did not find any associations. Having an
unemployed caregiver or living in census tracts with
a higher percentage of persons without a high school
diploma was associated with higher hazards of future
asthma hospitalization (33,50).
Caregiver coping/beliefs/(studies = 7; inconsistent
association)
In seven studies, neither caregiver knowledge of
asthma, nor their perceptions or beliefs about their
child’s asthma or treatment had any significant
impact on future hospitalizations. However, caregiv-
ers who reported being less bothered emotionally by
their child’s asthma were more likely to have a child
who was re-hospitalized (OR 1.64; 95% CI 1.99–
2.70) (41)
Family history (studies = 5; inconsistent
association)
Two of three studies examining parental history of
allergic disease showed an increased odds of future
asthma hospitalization (OR1.3–3.17; 95% CI 1.10–
9.10) (24,88). Maternal-specific factors including death
from asthma, and caregiver mental health distress or
depression were not associated (30,47,66)
438 S. AGGARWAL ET AL.
Theme III—environmental exposures
Air pollution (studies = 5; inconsistent association)
With respect to air pollution, studies broadly exam-
ined the effects of living near high traffic areas and
exposure to various particulate matter and noxious
gases with no significant association with future
asthma hospitalization found.
Environmental tobacco smoke (ETS) (studies = 8;
positive association)
Seven studies examined household smoke exposure
and four demonstrated a positive association with
future hospitalizations. In the pooled, meta-analysis
that included three studies indoor smoke exposure was
significantly associated (OR = 1.94 95%CI 0.67–5.61,
I2:71%, total N = 88). Maternal smoking was also spe-
cifically associated with future hospitalization in three
studies (47,58,61) and Howrylak et al. (52) (N = 619)
found that the presence of serum or salivary cotinine
in children was positively associated with future hos-
pitalization (OR = 1.59–2.35, 95% CI 1.02–4.55) (52).
Pets (studies = 5; inconsistent association)
Although when examined individually, no studies
showed a significant association between pets expo-
sure and future hospitalization, in pooled meta-analysis
that included four studies (24,66,78), there was a clear
positive association between pets in the home and
future hospitalization (random effects OR = 1.59, 95%
CI 1.13 − 2.23, I2:0%, total N = 759)
Allergens (studies = 8; positive association)
Indoor allergen exposure was measured using a variety
of methodologies and a number of studies showed a
positive association with future hospitalization. For
example,
Vicendese et al. (45) (N = 44) found that less fre-
quent vacuuming (a few times a week versus daily)
significantly increased the odds of future hospitaliza-
tions (OR = 15.69 95% CI 2.82 − 87.18 p = 0.002).
Furthermore, having a carpet in the child’s room (OR
= 4.07 95% CI 1.03 − 16.06 p = 0.04) or having a syn-
thetic doona (quilt) both significantly increased the
odds of future hospitalizations (45).
Theme IV—asthma symptom severity and
treatments before index visit
Baseline inhaled corticosteroids (studies = 5;
positive association)
While Sun et al. (N = 205) reported no association
between ICS use at baseline and future hospitalizations
using chi-square analysis, four studies found baseline
inhaled corticosteroid (ICS) therapy increased future
hospitalizations (total N = 1109) (24,28,53,62).
Baseline oral corticosteroid therapy (studies = 3;
inconsistent association)
Out of three studies specifically examining oral cor-
ticosteroid (OCS) therapy, only Brittan et al. (27)
found increased odds of future hospitalizations when
an OCS prescription had been filled in the prior
6 months (OR = 2; 95% CI 1.5 − 2.7) (27). All three
studies used different definitions when evaluating the
impact of OCS use on future hospitalization and dif-
ferent populations and health care settings. For exam-
ple, Minkovitz et al. (62) and Brittan et al. (27)
examined populations in the United States vs.
Rodriguez-Martinez et al. (47) evaluated population
in Columbia.
Previous acute care visits (ED, hospital or intensive
care unit (ICU)) (studies = 17; positive association)
A previous history of ED visits was linked to future
hospitalizations in nine studies (9,27,28,36,48,56,69,78).
Similarly, the higher the number of past hospital
admissions, the stronger the relationship to future
hospitalizations (4,9,25–27,31,34,48,78). In pooled
meta-analysis including two studies (27,31), the odds
of future hospitalizations was significantly higher
among children with a previous hospital admission
(Random effects: OR = 3.47, 95% CI 2.95 − 4.07;
I 2:31%, total N = 16891) Previous history of ICU
admission was also linked to increased odds of future
hospitalizations in three out of four studies (24,26,78).
Asthma severity and phenotype (studies = 4;
positive association)
In classification of asthma severity according to
National Heart, Lung and Blood Institute (NHLBI)
guidelines, persistent moderate or severe asthma
increased the hazard of future hospitalizations when
compared to mild intermittent asthma in three of four
studies (36,50,78). In a different comparison, Molina
et al. (71) (N = 480) found that children with persistent
asthma, whether moderate or severe, had higher odds
of future hospitalizations when compared to intermit-
tent asthma (intermittent versus moderate persistent
OR 0.43, 95% CI 0.24–0.78).
Asthma control (studies = 3; positive association)
When asthma control was classified according to
GINA 2011 (89), increased risk of readmission was
found in partly controlled asthma (OR = 4.83; 95%

CI 1.24–18.88) and uncontrolled asthma (OR = 29;
95% CI 2.25 − 373.77) (24). Having a history of four
or more asthma attacks per month was associated
with increased odds of future hospitalizations but
not if the attacks were spread over 12 months
(36,64).
Theme V index visit characteristics
ICU/mechanical ventilation (studies = 7; positive
association)
Receiving mechanical ventilation during the index
admission was associated with higher odds of future
hospitalizations in two studies (26,34) and a lower
hazard in a study by Tse et al. (aHR = 0.51; 95% CI
0.28–0.94) (74), while ICU admission during the index
admission was associated with future asthma hospi-
talization in three studies.
Asthma severity (studies = 3; positive association)
Patients characterized with a moderate or severe clin-
ical assessment of asthma in the ED based on the
Canadian Triage Acuity Scale (CTAS) (90), or physi-
cian assessment, had increased odds (aOR = 1.12
95%CI 1.01 to 2.94 p < 0.05) (26) or hazard of future
hospitalizations in three studies (4,69).
Length of stay (studies = 10; positive association)
The length of hospital stay (LOS) at index admission
was positively related to increased future hospitaliza-
tions in eight studies (31,32,42,54,74,75,81,82) and
both Jroundi et al. (81) and Hogan et al. (82) further
reported significantly increased risk of future hospi-
talization with increasing length of stay in ICU (aHR
= 1.04; 95% CI 1.03 − 1.06, p < 0.001[26]; aHR = 1.35
vs. 1.63 for LOS between 2–3 days vs. LOS > 4 days,
p < 0.05).
Asthma medications—intravenous steroids (studies
= 3; positive association)
Three studies examined the relationship between use
of intravenous systemic steroids during the index
admission and future asthma hospitalization and
found a positive association, though other medications
used such as theophylline and antibiotics were not
associated (24–26).
Asthma season (studies = 5; positive association)
Being admitted to hospital during a warmer season
(i.e. spring, summer or fall) compared to winter was
generally associated with future hospitalization in five
studies) (27,32,70,75,82).
Journal of Asthma 439
Theme VI—Asthma symptom severity and
treatments after index visit
Discharge treatments (studies = 6; inconsistent
association)
Filling a prescription for OCS within 6 days post hos-
pital discharge was associated with increased odds of
future hospitalizations (OR = 3.2 95%CI 2.4 − 4.6)
(27). In contrast, patients who filled discharge pre-
scriptions for ICS within 3 days of discharge had
decreased hazards of future hospitalizations (HR =
0.87 95%CI 0.77 − 0.98) (29).
Post-discharge follow-up (studies = 7, inconsistent
association)
From the six studies, only Philips (78) showed that
attending a post-discharge visit (within 14 days of dis-
charge) decreased the odds of future hospitalizations
(OR= 50.65; 95% CI 50.43–0.97); however, this effect
was negated when patients attended a post-discharge
routine visit (within 3 months of discharge).
Discussion
This systematic review aimed at finding factors asso-
ciated with increased risk of future hospitalization
among children with a prior asthma ED visit. We
grouped these factors broadly into six different themes
reflecting a child’s inherent risk for asthma morbidity
due to: physical and health characteristics, their family
and social characteristics, environmental exposures,
and details of their symptoms and severity prior to,
during or following their index asthma visit. We were
able to pool and meta-analyze results for three vari-
ables where study methodology, population and
adjusted covariates were similar, and found that indoor
tobacco smoke exposure, presence of pets in the home,
and history of previous asthma hospitalization were
independently associated with future hospitalization.
Descriptive analysis of other variables that were too
diverse for pooling showed that comorbid health con-
ditions (particularly atopy), previous ED visits and
ICU admissions and severe-persistent asthma pheno-
type, allergen exposure, prior use of inhaled steroids
or poor asthma control as well as higher severity
symptoms at presentation, longer length of stay, use
of systemic steroids, and ICU/mechanical ventilation
during the index visit, a warmer season at admission,
and African American race were also associated with
future hospitalization.
The majority of studies examining ETS exposure,
demonstrated a positive correlation between household
smoking, maternal smoking and cotinine (as a marker
of ETS exposure) and future hospitalization. We were
440 S. AGGARWAL ET AL.
able to demonstrate this association in both pooled
meta-analysis and overall descriptive analysis, despite
varying definitions of ETS exposure in most included
studies. This review highlights the lack of uniformity
in defining ETS exposure or lack of rigor in the
description of how ETS exposure is assigned in many
observational studies. While the quantification of
first-hand smoke exposure in units of “pack-years”
has aided our understanding of the harmful effects
of smoking on various health conditions through epi-
demiologic studies, this is more challenging to do for
secondhand smoke. Nonetheless, this will become an
increasingly important exposure to delineate as new
devices for inhaling and vaping nicotine, such as elec-
tronic cigarettes become more prevalent. Based on
this review, we recommend that global and national
respiratory organizations develop a uniform method
to assign secondhand smoke exposure in children.
We identified a positive association between pets
in the home and future asthma hospitalization, but
this relationship is more likely a marker of atopy as
an important driver of asthma morbidity. In fact, the
most important comorbidity associated with future
hospitalization in this study was atopy. Reviewed stud-
ies included multiple measures of atopy, including
allergic rhinitis, atopic dermatitis, elevated serum
markers of atopy, and even family history of allergic
disease which were all associated with future hospi-
talization. Pets in the home increased the odds of
future hospitalization, but so did markers of other
allergen exposures, including dust mite burden in the
setting of less frequent vacuuming, and the use of
synthetic bedding. Taken together, the reviewed liter-
ature suggests that pets and other types of indoor
perennial allergens may be important triggers for
future hospitalization.
In our pooled meta-analysis, we found a clear
association between prior asthma hospitalizations and
future asthma hospitalization. However, our descrip-
tive analysis more broadly demonstrated a relation-
ship between measures of increased asthma severity
both prior to and during the index visit and future
hospitalization. For example, a moderate to severe
persistent asthma phenotype, poor asthma control,
and frequent attacks prior to the index asthma ED
visit were linked to future hospitalization. Similarly,
previous acute health care visits for asthma, including
previous asthma ED visits, hospitalizations and ICU
admissions demonstrated a positive association with
future hospitalization with a dose-response relation-
ship observed in some studies. Higher severity symp-
toms at index presentation, and both intravenous
steroid use and increased length of stay, which are
both markers of a more severe exacerbation, along
with ICU admission or mechanical ventilation were
all also associated with future hospitalization. There
was one contrasting Canadian study by Tse et al. that
reported lower rates of future hospitalization follow-
ing an ICU admission or where ventilation was used;
this may be due to the standard practice at most
Canadian centers where children admitted to the ICU
are preferentially referred to asthma specialist care,
which may lead to improved outcomes, in contrast
to other countries (91). Our review would suggest
that previous ED visits or hospitalizations should
likewise be considered as key variables in triggering
referral to asthma specialist care. One unexpected
finding in this review is that ICS use prior to the
index ED visit was associated with future asthma
hospitalization. This may be reflective of either poor
adherence to daily ICS use (which was not measured
in these studies), or a more severe asthma phenotype
that was sub-optimally controlled despite ICS use and
warrants a step-up in treatment or improved man-
agement to avoid future acute health care visits.
In this review we found a positive association
between African-American race and future asthma
hospitalization which is consistent with multiple pre-
vious studies that show higher asthma symptom sever-
ity and morbidity in this group (92). However, a few
studies included in this review raise the question of
whether this association with future asthma hospital-
ization is related to genetics and absolute differences
in airway inflammation, or if race is acting as a sur-
rogate marker of other social factors which are more
deterministic of future hospitalization risk. For exam-
ple, in the study by Bloomberg et al. (40) factoring
in insurance coverage, and access to private medical
insurance negated the effect of African American race
on future hospitalization. To further differentiate bio-
logic versus sociologic effects of African American
race on asthma outcomes, Mersha et al. (84) examined
participants’ degree of African ancestry as determined
by single nucleotide polymorphisms on a continuous
scale and found a higher rate of readmission in chil-
dren with >20% African ancestry, where >50% of the
increased risk could be attributed directly to social
factors related to hardship and disease management.
Upon adjusting for these factors, African ancestry was
no longer significantly associated with readmission.
Together, these two studies suggest that race-related
disparities in asthma outcomes for children are driven
by social factors and cannot be simply attributed to
biologic differences.
With respect to family and social factors, we iden-
tified a number of studies that demonstrated patients

experiencing poverty without private insurance or with
poorer access to medical/primary care were more likely
to have future hospitalization. However, we equally
included a number of studies that did not show an
association between these social factors and future
hospitalization. Similarly, housing-related factors in
keeping with lower income and socioeconomic status
(SES) were also positively associated with future hos-
pitalization in some studies, but not all. These incon-
sistent relationships with future hospitalization risk
speak to the challenges in characterizing various mark-
ers of socioeconomic status and family factors in a
standard fashion so as to compare across studies.
Prior systematic reviews (92,93) have demonstrated
that younger patient age is associated with an overall
higher risk of asthma ED visits and hospitalizations
(69,93). However, in the current study, the relation
of age with future asthma hospitalization was incon-
sistent. This discrepancy is likely explained by the
interaction of sex and age with asthma hospitalization
risk. The study by Giangioppo et al. (69) characterizes
this interaction and clearly demonstrates the variable
effect of age on risk of asthma morbidity depending
on sex. That is, in younger age groups, future asthma
hospitalization is increased among males, but in ado-
lescents, is higher in females (69). The mechanisms
for this sex-related difference in morbidity with age
have not yet been elucidated.
Despite our systematic and rigorous process to
identify factors associated with future asthma hospi-
talization in this review, there were limitations to our
study. Due to the large variance in methodological,
statistical and reporting methods used, meta-analysis
was not possible in most cases. This highlights the
need for more rigorous and standardized methods to
define exposures even in observational studies, par-
ticularly for the assignment of secondhand smoke
exposure, and various social factors. Though many
studies reported on the association of race/ethnicity
with future hospitalization, the methods used to assign
and classify race/ethnicity were often not well
described. Suboptimal collection and classification of
this important variable may have led to bias in the
various studies’ results and in this review. Inclusion
of such as broad timeframe in this review prevented
missing exposures of interest, but may have diluted
some study findings as asthma management practices
may have changed over time. Finally, despite searching
a number of databases, we may have missed some
relevant articles, particularly those that were not pub-
lished in English, that could have added to our
findings.
Journal of Asthma 441
Regardless of these limitations, our study identifies
several factors, particularly related to environmental
tobacco smoke exposure, pet and allergen exposure
and atopy, more severe baseline asthma phenotype,
severity of the index visit, poor asthma control, pre-
vious asthma acute care visits and African-American
ethnicity/race, which may be a surrogate for other
social factors, that are consistently linked in multiple
studies with future hospitalization in children with
asthma. We propose that the information from this
review could be used to guide the development of
clinical prediction rules that could be used by ED
clinicians at the point of care to tailor preventative
interventions to children at higher risk for future
asthma hospitalization. Future asthma guidelines could
also use this information to develop more detailed
recommendations to lessen these specific exposures
where possible, and trigger referral to asthma specialty
care for vulnerable children in need of improved
asthma management.
Acknowledgements
We thank Dr. Dayre McNally, Katie O’Hearn, Henrietta
Blinder, Revathi Surapaneni, Daniel Chung, Julia Shen for their
assistance towards this project and Margaret Sampson, MLIS,
PhD, AHIP for developing and updating the searches used.
Disclosure statement
The authors have no conflicts of interest relevant to this
article to disclose.
Systematic review registration
PROSPERO #CRD42017060934
Prior presentation
The findings of this study were presented as a poster at
the Canadian Respiratory Conference on 8–10 April, 2021
Funding
The author(s) reported there is no funding associated with
the work featured in this article.
ORCID
Kerry-Lee Clifton http://orcid.org/0000-0001-9028-
7727
Dhenuka Radhakrishnan http://orcid.org/0000-0002-
8637-1480
442 S. AGGARWAL ET AL.
Data availability statement
The data supporting the findings of this study are available
within the article and its supplementary material.
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