Association between attention deficit hyperactivity disorder

and asthma: a systematic review and meta-analysis and a

Swedish population-based study.

Samuele Cortese, Shihua Sun, Junhua Zhang, Esha Sharma, Zheng Chang, Ralf Kuja-Halkola,
Catarina Almqvist, Henrik Larsson, Stephen V Faraone

The Lancet Psychiatry volume 5, issue 9, p717-726, September 01, 2018

• Asthma is the most prevalent chronic respiratory disease, estimated
to affect around 358 million people worldwide.

• Its prevalence ranges from 3–5% in low-income countries to more

than 20% in high-income countries
• Attention deficit hyperactivity disorder (ADHD), which is characterised
by age-inappropriate and impairing levels of inattention, hyperactivity,
and impulsivity, affects around 5% of school-age children and 2·5% of
adults worldwide
• A potential association between ADHD and asthma is of particular interest
because of its important clinical, public health, and research implications.

• From a clinical and public health perspective, awareness of a significant

association between these two conditions would prompt ADHD specialists to
refer patients with early forms of asthma, and asthma specialists to refer
patients with problems of inattention, hyperactivity, and impulsivity, for
appropriate assessment, thus helping to reduce the diagnostic delay that is of
concern for both.

• From a research standpoint, a significant link between asthma and ADHD

would yield insight into the pathophysiology of ADHD, including the possible
role of allergic mechanisms.
• Assuming that asthma predicts ADHD, inflammatory mechanisms
might mediate this link.

• An increase in inflammatory cytokines following the allergic

inflammation that characterises asthma might affect certain regions in
the prefrontal cortex and neurotransmitter systems that have been
implicated in ADHD.
Methods
• Database searched –
• PubMed
• PsycINFO
• Embase
• Embase Classic
• Ovid MEDLINE
• Web of Knowledge databases up to Oct 31, 2017, without any restrictions on
language, date, or article type.
• References of the included studies were also searched for any potential
pertinent study not detected in the search of databases.
INCLUSION & EXCLUSION CRITERIA
• Observational studies that allowed estimation of the association
between asthma and ADHD were included.
• Excluded studies were studies with fewer than ten participants per
group because of their low statistical power.
• For longitudinal studies, they extracted data at baseline or at the
earliest timepoint data were available.
• When several reports were available from the same cohort, to avoid
duplication of data, they included the publication reporting the largest
number of participants.
• The primary analysis indicated a significant association between asthma
and ADHD (pooled OR 1·66, 95% CI 1·22–2·26), although heterogeneity
was high (I2=99·47), and Egger’s test indicated the possibility of
publication bias (p=0·049).

• The pooled prevalence of asthma was 16·9% (95% CI 12·0–23·0) in

individuals with ADHD and 11·5% (9·8–13·4) in those without.

• The pooled prevalence of ADHD was 8·8% (6·2–12·2) in individuals with

asthma and 5·6% (4·5–7·0) in those without.
• To further investigate the association between asthma and ADHD, and rigorously
address the role of confounding for this association, they did a population-based
cohort study using data from Swedish national registers.
• A cohort of individuals born between Jan 1, 1992, and Dec 31, 2006, was extracted
from the Swedish Medical Birth Register.
• Linkage with other registers was done via unique personal identification numbers for
all cohort members.
• ADHD was defined as any clinical diagnosis (ICD-9 diagnosis code 314 or ICD-10
diagnosis code F90) recorded in the National Patient Register before Dec 31, 2013.
• In line with previous research, they identified individuals with asthma using a
validated algorithm that recognised either a clinical diagnosis (ICD-9 diagnosis code
493 or ICD-10 diagnosis code J45–J46) in the National Patient Register or filling of two
prescriptions for asthma medication (Anatomic Therapeutic Codes R03AC, A03AK,
R03BA, and R03DC) in the Prescribed Drug Register.
• ORs with 95% CIs were estimated by logistic regression to investigate the association
between asthma and ADHD at the population level.
• Of the 1575377 individuals in the Swedish population-based cohort
study, 259 253 (16·5%) had asthma and 57957 (3·7%) had ADHD.

• The prevalence of asthma was significantly higher in individuals with

ADHD than in those without (24·8% [95% CI 24·4–25·1] vs 16·1% [16·1–
16·2]; p<0·0001).
• Additionally, the prevalence of ADHD was significantly higher in
individuals with asthma than in those without (5·5% [5·5–5·6;
14347/259253] vs 3·3%[3·3–3·3;43610/1316124];p<0·0001).
LIMITATIONS
• This study did not aim to assess the longitudinal association between
asthma and ADHD, which would provide insight into the causal
association between the two disorders.
• They could not assess to what extent medications used to treat
asthma contributed to ADHD symptoms.
MERIT
• Regardless of whether there is a causal link, the cross- sectional association
between ADHD and asthma, even after controlling for a large number of
possible confounders, has important clinical and scientific implications.
• Existing guidelines for asthma management do not mention ADHD, and
available guidance on ADHD does not mention asthma.
• Awareness of this association might lead to prompt referral of patients with
ADHD with early signs or symptoms of respiratory problems to an asthma
specialist, and those with asthma and symptoms of hyperactivity,
impulsivity, or inattention to an ADHD specialist, instead of these symptoms
being attributed to an adjustment reaction to a chronic disorder or to the
effect of the pharmacological treatment for asthma.
• Awareness of the association between these two disorders might help to
reduce diagnostic delay, which is a clinical and public health issue
associated with both disorders in many countries, resulting in individual
and family strain and substantial additional health-care costs.
• Furthermore, effective management of disruptive behaviours associated
with ADHD symptoms might improve adherence to the treatment of
asthma, as reported for other somatic conditions, such as obesity.
• From a scientific perspective, the link between asthma and ADHD lends
support to the possible involvement of inflammatory mechanisms in the
pathophysiology of ADHD.
THANKS