Background
Exercise-induced symptoms (EIS) are common in childhood and can lead to
physical activity avoidance, reduced quality of life, and overtreatment with inhaled
corticosteroids if mistakenly diagnosed as asthma. Diagnosis of EIS can be difficult because
different aetiologies share similar clinical presentations. Reported symptoms can be helpful
to identify the correct diagnosis, as certain symptoms are typically associated with specific
diagnoses (e.g. expiratory wheeze for exercise-induced bronchoconstriction, and throat
tightness for inducible laryngeal obstruction (ILO)). Only few studies have investigated
diagnosis, diagnostic evaluations, and reported symptoms in children with EIS.
Aims: The overall aim of this PhD thesis were to gain epidemiological knowledge about
diagnosis, diagnostic investigations, and reported symptoms in children with EIS. Specifically,
I aimed to 1) set up a prospective study including children referred to paediatric respiratory
outpatient clinics with respiratory symptoms 2) study diagnosis, diagnostic investigations
and management in children referred for EIS 3) study if parent reported EIS are helpful to
distinguish different diagnoses and 4) study EIS reported by physicians in the clinical history
and assess agreement with parent-reported symptoms. 5) Additionally, I aimed to validate a
model to predict asthma in preschool children.
Methods
To address the aims of this PhD thesis, I used data from the Swiss Paediatric
Airway Cohort (SPAC), a longitudinal observational clinical study of children referred with
respiratory symptoms to paediatric respiratory outpatient clinics in Switzerland. I used data
from medical records to get information on referral diagnosis, final diagnosis, diagnostic
investigations and proposed management from the outpatient clinics. I used data from
parental questionnaires to get information about symptoms. For publication 5, I used data
from the Leicestershire Respiratory Cohort (LRC) and the Avon Longitudinal Study of Parents
and Children (ALSPAC).
Results
The main body of this thesis consists of 5 articles (2 published, 1 in review, and 2 to
be submitted). These are the main findings in summary:
Publication 1: The SPAC study is a novel longitudinal observational cohort study of children
with respiratory symptoms. By January 7, 2020, the SPAC study includes 1893 children
5
recruited from 10 pulmonology clinics. The SPAC study will provide real-life data from
paediatric pulmonology clinics in Switzerland and will serve as a platform for nested studies.
Publication 2: Diagnosis given at the paediatric respiratory outpatient clinic differed from
suspected referral diagnosis in half of the children referred primarily for EIS. Dysfunctional
breathing was a common diagnosis at the outpatient clinic but rarely suspected at time of
referral. Diagnostic evaluation, management, and follow-up were inconsistent between
clinics and diagnostic groups.
Publication 3: Parent reported EIS (including information on type of symptoms, activities
triggering EIS, and characteristics of symptoms) can help to distinguish different diagnoses in
children seen with EIS.
Publication 4: Physicians reported EIS in the medical records in almost all children referred
for EIS. Activities triggering EIS and characteristics of EIS (e.g. localisation of symptoms,
respiratory phase, and onset and duration of symptoms) were reported only in around half
of the children. Agreement with parent questionnaire reported EIS ranged from poor to
moderate.
Publication 5: PARC predicted asthma at school age equally well in the validation cohort,
ALSPAC (AUC 0.77), compared with the development cohort, LRC (AUC 0.78). Apart from
severity of wheeze and cough, family history of symptoms, age, and sex, also exercise as
trigger for respiratory symptoms predicted asthma at school age in the development and
validation cohort. The discriminative ability of the PARC appeared to be robust to changes in
inclusion criteria, scoring variables, and outcome definitions. PARC may need recalibration
when applied in other populations.
Additionally, I contributed to further publications, which are included in this PhD thesis as
related publications.
Conclusion
In summary, diagnosis, diagnostic investigations, and management in children with EIS
differed between outpatient clinics and diagnosis groups, indicating a need for diagnostic
guidelines. Parental reported symptoms can help to distinguish diagnoses in children with
EIS. Future studies should focus on developing an algorithm for diagnosing children seen
with EIS including both reported symptoms and objective diagnostic tests.
