improving clinical assessment of asthma symptoms by...

Improving clinical assessment of asthma by studying the

relation between spirometry and assessment of EIB

‘Never judge a book by its cover’

Exercise-induced bronchoconstriction (EIB) in children

Maaike van Hoesel, 1726420

Dr. B. Thio, pediatrician

Department of Pediatrics, Medisch Spectrum Twente, Enschede

http://www.google.nl/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http://blog.fysiosupplies.nl/onderzoek-fysiotherapie/inspanningsastma-al-bij-jonge-kinderen-aantoonbaar/&ei=DCNKVZTEE6Wc7gaL4oHwDA&bvm=bv.92291466,d.ZGU&psig=AFQjCNFaKbmiKm1kHhy129KCRYTGdGLP0w&ust=1431008380211527

Improving clinical assessment of asthma by studying the relation between spirometry and assessment of EIB

M.H.T. van Hoesel

Summary

English Background Exercise induced bronchoconstriction (EIB) is a highly specific symptom of

asthma in childhood and a strong sign of uncontrolled asthma. The diagnosis of EIB from a

medical history is difficult; perception of EIB by children and recognition by others can be low.

EIB can be identified with an exercise challenge test (ECT), however these tests are time-

consuming and expensive. There is a need for objective tools to diagnose EIB in asthmatic

children. Video evaluation of asthma symptoms could be a potential low-end and objective

addition for diagnosis and monitoring of EIB, improving asthma treatment, reducing cost and

increasing efficiency.

Objective The aim of this study is to investigate whether paediatricians can predict the severity

of EIB as measured with an ECT from the medical history, physical examination and pre-

exercise video, and if the addition of pre-exercise lungfunction can improve this prediction.

The second aim of this study is to investigate the relation between asthma dyspnoea scores, as

assessed by pediatricians from videos, and the severity of airway obstruction as measured with

pulmonary function.

Methods 20 asthmatic children (age 4-17 years) performed an ECT. Pulmonary function testing

was measured before and after exercise. Children with a fall of ≥ 10% in FEV1 were considered

to have EIB. A fall of <10% but >25% was considered mild, >25% but <50% moderate and

>50% or >30% if treated with inhaled corticosteroids (ICS) was considered severe EIB. Before

and after exercise video recordings were made. Pediatricians predicted the severity of EIB,

based on a pre-exercise video, medical history and physical examination, and again predicted

the severity of EIB when they were informed about the pre-exercise pulmonary function.

Further they assessed dyspnoea from a post-exercise video and their assessment was compared

with the severity of EIB as categorised above.

Results 20 children (11 male, 9 female) with a mean age of 11.6 ± 3.4 had a median fall in

FEV1 of 15.1% (1.2-65.1) after exercise. 9 children showed no EIB, 4 children showed mild, 2

children showed moderate and 5 children showed severe EIB. Pediatrician’s prediction of the

severity of EIB from the medical history, physical examination and pre-exercise video was

poor. This poor prediction was not improved when pediatricians were informed about the pre-

exercise pulmonary function. Pediatrician’s assessments of dyspnoea on post-exercise videos

correlated fairly well with the severity of EIB.

Conclusion There still seems to be a substantial need of an ECT to identify EIB. Pediatricians

have a fair ability to assess EIB from post-exercise videos. This provides opportunities to

diagnose EIB from home made post-exercise videos.


M.H.T. van Hoesel

Summary

Nederlands Achtergrond Inspanningsastma is een specifiek symptoom van kinderen met astma en een

duidelijk teken van ongecontroleerd astma. Diagnosestelling van inspanningsastma op basis

van anamnese en lichamelijk onderzoek is moeilijk, omdat de perceptie en herkenning zeker

bij jonge kinderen lastig is. De diagnose inspanningsastma wordt vaak gesteld met behulp van

een inspanningstest, wat een tijdrovende en dure diagnostische test is. Er is derhalve behoefte

aan objectieve metingen om de ernst van inspanningsastma in kinderen vast te stellen. Video

evaluatie zou een objectieve en kosten-effectieve toevoeging zijn aan de hedendaagse astma-

diagnostiek en zou kunnen leiden tot een verbetering van de astma zorg door en sneller

diagnostisch proces en monitoring van dagelijkse astmaklachten.

Doel Het doel van deze studie is om te onderzoeken of kinderartsen de ernst van

inspanningsastma, gemeten met een inspanningstest, kunnen voorspellen op basis van

anamnese en lichamelijk onderzoek en videos voor inspanning, en of toevoeging van een

longfunctie gemeten voor inspanning deze voorspelling kan verbeteren.

Het tweede doel van deze studie is om de relatie te onderzoek tussen astma scores, voorspeld

door kinderartsen op basis van video’s, en de ernst van de benauwdheid gemeten met

longfunctie.

Methoden 20 kinderen (4-17 jaar oud) ondergingen een inspanningstest. Voor en na inspanning

werden er longfunctie metingen verricht. Kinderen met een FEV1-daling ≥ 10% werden

beschouwd als hebbende inspanningsastma. Een daling van >10% en <25% werd als milde,

>25% en <50% als matige en >50% als ernstige benauwdheid (of >30% wanneer ze behandeld

zijn met corticosteroïden). Voor en na inspanning zijn er video’s gemaakt. Kinderartsen

voorspelden de ernst van inspanningsastma na de inspanningstest, op basis van een video voor

de inspanning, anamnese en lichamelijk onderzoek. Ook voorspelden zij de ernst van de

benauwdheid wanneer aan deze informatie de longfunctie voor inspanning werd toegevoegd.

Kinderartsen beoordeelden ook de ernst van inspanningsastma aan de hand van een video na

inspanning, welke werden vergeleken met de ernst van inspanningsastma zoals hierboven

gecategoriseerd

Resultaten 20 kinderen (11 jongens, 9 meisjes) met een gemiddelde leeftijd van 11.6 ± 3.4

lieten een gemiddelde FEV1-daling zien van 15.1% (1.2-65.1) na inspanning. 9 kinderen hadden

geen EIB, 4 kinderen een milde, 2 kinderen een matige en 5 kinderen een ernstige EIB. De

resultaten van onze studie laten zien dat de voorspelling van inspanningsastma op basis van een

video voor inspanning, anamnese en lichamelijk onderzoek slecht is. Deze slechte voorspelling

verbeterde niet wanneer een electieve longfunctie meting werd toegevoegd. Wel konden

kinderartsen redelijk de ernst van inspanningsastma inschatten wanneer een video werd

toegevoegd.

Conclusie Dit onderzoek laat zien dat met het gebruik van videomateriaal in de praktijk

voorzichtig moet worden omgegaan. Ook lijkt het nog steeds nodig te zien om een

inspanningstest te laten doen als onderdeel van de diagnostiek. Kinderartsen kunnen

inspanningsastma redelijk voorspellen aan de hand van videos na inspanning. Dit geeft

mogelijkheden in het maken van video’s in de thuissituatie. Objectieve metingen, zoals

longfunciemetingen, zouden dit verder kunnen verbeteren en de behandeling optimaliseren.

Tevens moet er meer onderzoek worden gedaan naar validatie met longfunctiemetingen.


M.H.T. van Hoesel

List of abbreviations ACQs Asthma Questionnaires

ASM Airway Smooth Muscles

BHR Bronchial Hyperreactivity

BPT Bronchial Provocation Test

(C)ACT (Childhood) Asthma Control Test a score ≤19 indicates uncontrolled

asthma CI Confidence Intervals

ECT Exercise Challenge Test

EIB Exercise Induced Bronchoconstriction

FEV1 Forced Expiratory Volume, the volume air that can be exhaled in the

first second during a forced exhalation maneuver started from the level

of the total lung capacity

FEV1% from Predicted value of forced expiratory volume in 1 s of the patient

predicted compared with the average predicted value of FEV1 in the population

for any person of similar age, sex and height

ICS Inhaled corticosteroids

LTRAs Leukotriene Receptor Antagonists

METC Medical Ethics Committee

SABAs Short-acting β2-agonist

SD Standard Deviation

QOL Quality of Life

WHO World Health Organization


M.H.T. van Hoesel

Table of contents 1. Introduction ........................................................................................................................7

1.1 Pathophysiology of EIB ................................................................................................7

1.2 Exercise induced bronchoconstriction ...........................................................................8

1.3 Diagnosis of asthma .................................................................................................... 10

1.3.1 Spirometry ............................................................................................................ 10

1.3.2 Bronchial provocation tests ................................................................................... 11

1.3.3 Questionnaires ...................................................................................................... 12

1.4 Classification of exercise induced bronchoconstriction ................................................ 12

1.5 Treatment .................................................................................................................... 12

1.5.1 Prophylactic treatment of EIB ............................................................................... 13

1.5.2 Premedication ....................................................................................................... 13

1.6 Video-analysis ............................................................................................................ 13

2.1 Research questions ...................................................................................................... 15

2.2 Hypothesis .................................................................................................................. 15

2.3 Primary outcome ......................................................................................................... 15

2.4 Secundary outcome ..................................................................................................... 15

3. Methods............................................................................................................................ 16

3.1 Study design and procedure ......................................................................................... 16

3.1.1 Design .................................................................................................................. 16

3.1.2 Procedure.............................................................................................................. 16

3.2 Study population ......................................................................................................... 16

3.2.1 Inclusion criteria ................................................................................................... 16

3.2.2 Exclusion criteria .................................................................................................. 17

3.2.3 Exclusion criteria for selection of videos ............................................................... 17

3.2.4 Exclusion criteria for subanalysis of asthma questionnaires................................... 17

3.2.5 Sample size calculation ......................................................................................... 17

3.3 Methods ...................................................................................................................... 17

3.3.1 Measurement instruments ..................................................................................... 17

3.3.2 Video material ...................................................................................................... 18

3.3.3 Questionnaires ...................................................................................................... 19

3.3.4 Randomization ...................................................................................................... 19

3.3.5 Statistical analysis ................................................................................................. 19


M.H.T. van Hoesel

4. Results .............................................................................................................................. 20

4.1 Baseline characteristics of included children ............................................................... 20

4.2 Baseline characteristics of pediatricians....................................................................... 21

4.3 Prediction of EIB by specialists ................................................................................... 21

4.4 Prediction of EIB by parents and children ................................................................... 22

4.4.1 Baseline characteristics of asthma questionnaires .................................................. 22

4.4.2. Validation of dyspnoea scores against pulmonary function .................................. 23

5. Discussion ........................................................................................................................ 27

5.1 Result analysis ............................................................................................................ 27

5.2 Strengths and limitations ............................................................................................. 27

5.3 Further research .......................................................................................................... 28

6. Conclusion ....................................................................................................................... 28

7. References ........................................................................................................................ 29

8. Appendix ....................................................................................................................... 34

8.1 CRF video study ......................................................................................................... 34

8.2 Crosstabs ..................................................................................................................... 36

8.3 Questionnaires ............................................................................................................ 39

8.4 Instruction assessment videos ...................................................................................... 42


M.H.T. van Hoesel

1. Introduction Asthma is the most common chronic disease worldwide and currently around 235 million

people are diagnosed with asthma.1 Asthma is a serious health issue that affects people from all

ages, but especially children are affected. In 2008, the prevalence of asthma in Dutch children

between 4-12 years old, was approximately 10%.2

Exercise induced bronchoconstriction (EIB) is the most common trigger for asthma. The

prevalence of EIB in the pediatric population is between 6 and 20% and it increases with the

severity of asthma.3,4,5 In children with moderate or severe asthma, prevalence is even greater.

However, research of Cabral et al. showed that the severity of EIB is not consistently related to

the severity of asthma.6 The prevalence of asthma is still increasing in most countries around

the world. When it remains uncontrolled, it can lead to severe limitations in daily life and it can

even be fatal.

Asthma is characterized by chronic airway inflammation and bronchial hyperreactivity

(BHR), which can cause reversible airway obstruction. This leads to recurrent attacks of

dyspnoea, cough and wheezing. These attacks vary in severity, time and frequency from person

to person. Frequency of symptoms can vary from a few times a week till daily. Besides physical

activity, other factors that can trigger asthma symptoms are a change in weather circumstances,

viral respiratory infections and allergen exposure.7 These stimuli can cause an increase of

responsiveness of airways, which can be partially or completely reversible.8

1.1 Pathophysiology of EIB

The pathophysiology of asthma is complex. Airway inflammation, hyperresponsiveness of

airways to different allergic and non-specific triggers and hypersecretion of mucus are the

components included in the pathophysiology.

EIB characterizes the transient narrowing of airways, which is provoked by vigorous exercise.

It is measured as the reduction of pulmonary function post-exercise. The mechanism of EIB is

still under debate, but there are two major hypothesis: the thermal hypothesis and the osmotic

hypothesis.9,10

The osmotic hypothesis proposes that EIB is the result of dehydration of the airways, caused

by evaporation of mucosal water. Dehydration causes a transient hyperosmolarity of the

tracheal surface, which could lead to release of degranulation of mast cells, airway narrowing

and constriction of airway smooth muscles (ASM).10 ASM surrounds the airway and reduces

the luminal diameter in the airways. This plays a major role in acute bronchoconstriction and

causes airflow obstruction. In asthma, ASM become more sensitive to these stimuli by repeated


M.H.T. van Hoesel

exposure, which can lead to airway hyperresponsiveness.11 A study of Smith et al. also showed

that the use of hypertonic saline stimulates airway narrowing in asthmatic subjects, which

reveals potential for EIB.12

Another hypothesis is the thermal hypothesis. The thermal hypothesis considers that airway

cooling during exercise and rapid rewarming after exercise, causes hyperemia of the bronchial

vasculature and edema of the airways after exercise, resulting in broncho-obstruction. The more

rapidly the airways rewarm, the more severe the EIB.13 A study by Stensrud et al. demonstrated

that airway cooling during exercise increases symptoms of EIB diminishing athletic

performance.14

The proposed mechanism of EIB could also be both osmotically an thermally driven. In adults

EIB can also occur without the syndrome of asthma, which is a consequence of repeated

exposure to osmotic and thermal stress. This causes injury and alterations of ASM contractile

properties by a inflammation cascade.15,16 A study of Hallstrand showed that during EIB mast

cell activation occurs and that the balance between bronchoconstricting CysLTs and histamine

and bronchodilating PGE2 is altered, which leads to injury of airway epithelium. This causes

development and progression of EIB.17 The severity of EIB depends on the severity of

inflammation, which showes that the presence of EIB indicates not well controlled asthma.

1.2 Exercise induced bronchoconstriction

Exercise induced dyspnoea is not always a sign of asthma. Symptoms can also be caused by a

lack of cardiovascular fitness, exercise-induced laryngeal obstruction, dysfunctional breathing

or other diseases. EIB is the most common cause of exercise-induced dyspnoea in children. EIB

describes acute, reversible narrowing of airways provoked by exercise and is characterized by

the same symptoms as normal asthma. 80% of asthmatic patients experience these symptoms.3

Children noted EIB as the most frustrating part of their asthma and if they could eliminate one

feature, it would be EIB.18


M.H.T. van Hoesel

Exercise comes with a lot of short and longterm benefits. It improves self-esteem, physical

conditioning, it reduces cardio-vascular diseases and obesity, it improves quality of life and it

can increase academic performance.19,20 It can also decrease the need for maintenance

medication for symptoms of asthma in asthmatic patients.21,22

But, because of EIB, children and young adults often avoid participation in sports. This can

have negative influences in psycho-motor development, cardio-vascular condition and quality

of life. Quality of life (QoL) is defined by the World Health Organization (WHO) as the

individual’s perecption of their position of life in the context of the culture and value systems

in which they live and in relation to their goals, expectations, standards and concerns.23 A study

of Merikallio et al. showed that the QoL was impaired in children with symptoms of asthma

compared to healthy children.24

Especially children and young adults are at risk of EIB, because they participate in a lot of

strenuous activities.25 Also, children are supposed to have a higher activity rate, compared to

adults, and they are also more active in environments with a higher level of pollution. Research

of Esposito et al. showed that especially children with pre-existing asthma who are exposed to

traffic-related polution have an increased risk of respiratory morbidity.26 Moreover lungs of

children are still developing and vulnerable to toxicants potentially changing pulmonary

function.

Younger children have different breathing rates and patterns. As they breathe more to their

mouth compared to adults, air will not pass the nasal-filter and higher levels of pollutants will

deposit in the respiratory tract.27 A high level of physical activity combined with their mostly

immature lungs make them more prone to inhalational toxicants. These toxicants can worsen

EIB.28

EIB can be documented as a reduction in pulmonary function after exercise.29

Bronchoconstriction develops around 2-4 minutes and reaches its maximum within 5-10

minutes post-exercise. Normally recovery of pulmonary function appears spontaneous, after 3-

till 60 minutes, but in 30% of children with EIB, it can take 45 minutes up till 3 hours.3,30

However, several studies assessing EIB during exercise discovered that EIB can also occur

during exercise. This is called breakthrough EIB and is defined as a decrease in pulmonary

function (FEV1) of 15% during exercise and occurs between 2 and 10 minutes after starting

exercise.31,32 Breakthrough EIB is a strong sign of uncontrolled asthma. The time to maximal

post-exercise bronchoconstriction varies between children and adults, but it occurs faster in

younger childen.32,33

Approximately 9% of all individuals with EIB claim to have no medical history of asthma

symptoms or allergies. In a study of Kattal et al., around 50% of children with EIB who claimed

not to have a history of asthma were responding positively to exercise tests.34 Also, severe

airway obstruction can be present in patients without symptoms. Patients who are diagnosed

with EIB could have a normal pulmonary function while resting, but while exercising they can

have a severe airway obstruction and a totally different pulmonary function outcome.3


M.H.T. van Hoesel

1.3 Diagnosis of asthma

Diagnosis of asthma is often based on

clinical features, medical history and

physical examination, wich are not

specific measurements for diagnosing

asthma.35 Variability of symptoms

during different seasons and a positive

family history of atopy and asthma are

also helpful diagnostic tools.7

Although wheezing is a specific

feature of asthma, not every child with

asthma wheezes. Previous studies have

shown a poor association between

physical appearance of dyspnoeic

children and the severity of airway obstruction.36 As respiratory symptoms occur outside of the

hospital and are mostly absent during a visit to the doctor, diagnosing asthma based on clinical

judgement is challenging.7,37

Asthma can have its onset at every age, but the majority of all asthma patients start to having

symptoms in early childhood.38,39 A study of Bergmann et al. showed that the incidence of

wheezing in young children is very high.40 Although the prevalence and incidence of asthma

in young children is high, it is one of the most difficult diseases for physicians to diagnose,

mainly due to this age group and other non-specific wheezing disorders.

Approximately 35% of children worldwide had asthmatic symptoms in their first years of

their life, which is associated with viral respiratory illnessess, but not specifically with

asthma.41,42 A study of Yunginger et al. demonstrated that in the majority of cases

distinguishment between different wheezing disorders is difficult to make.38

There is evidence that over 70% of people with asthma and 63% of people newly diagnosed

with asthma at the age of 22 years, had recurrent episodes of wheezing during their early

childhood.43 Development of the immune response in children and exposure to allergens and

infectious substances during the first few years in childhood are important factors that could

change the risk of devopment of asthma in people who are genetically susceptible.7

A study of Porsbjerg et al. showed that absence of wheezing in young children, allergic

sensitization to house dust mite and a medical history of atopy decreases the risk of developing

of asthma in adulthood.44 For children who will reveal asthma, an early diagnosis of asthma is

important. Diagnosis in early childhood will lead to early anti-inflammatory treatment, which

can lead to prevention of long-term remodelling of the airway wall in children and improvement

of prognosis of asthma in childhood and adolescence.45

1.3.1 Spirometry

Spirometry is non-invasive and objective and acknowledged as the gold standard for assessment

of asthma.46 Pulmonary function tests are frequently used as a diagnostic tool and have a big

impact in asthma classification. Clinical evaluation with anamnesis and physical examination

alone is less sensitive for assessing airway obstruction than pulmonary function measurement.

A study by Kerem et al. showed that some patients could have severe airway obstruction, which

is not suggested by clinical evaluation. If these patients would be treated after clinical

evaluation alone, they would be given undertreatment.36 This shows that diagnosis with asthma

should be confirmed with pulmonary function tests.7,47,48

It can also help prevent misclassification of the severity of asthma among pediatric patients.

A study by Holt et al. showed that one third of the treatment plans were changed after


M.H.T. van Hoesel

spirometry results.49 Especially in pre-school children physical examination alone cannot

always predict the degree of airway obstruction and pulmonary function abnormalities, which

makes additional pulmonary function testing considerable to obtain more objective information

to diagnose asthma.50

Most children over 5 years of age are

capable of performing spirometry, which

can aid to confirm a diagnosis of asthma.

But, a normal pulmonary function does not

exclude a diagnosis of asthma.51 Spirometry

measures the ventilatory function of the

lung. Besides diagnosing asthma, it can help

in following the history of disease,

demonstrate the degree of airflow limitation

and its reversibility and assess the effects of

treatment.52 Spirometry uses the maximal

forced expiratory volume in one second

(FEV1) initiated at full inspiration as a

variable to identify limitations in expiratory

airflow. Many lung diseases result in

reduced FEV1, therefore FEV1/VC ratio is

used to assess airflow limitation. Normally,

the FEV1/VC ratio is between >75-80% for

adults and >90% for children. A lower ratio

implies airflow limitation.7

EIB is defined as the maximum

percentage fall in FEV1 post-exercise

compared to baseline. Children with a fall

of ≥ 10% in FEV1 are considered to have

EIB, but a fall of 15% is also used as diagnostic for EIB.53

Particularly the degree of reversibility contributes to a diagnosis of asthma. Testing for

reversibility has high specificity and low sensitivity. Reversibility refers to changes in

symptoms, or changes in airflow limitation spontaneously or after treatment with a short-acting

bronchodilator. Reversibility of ≥ 12% from the pre-bronchodilator FEV1 value, indicates

asthma.7,54

Without pulmonary function testing the degree of asthma can be either overrated or

underestimated, which could result in suboptimal therapy.55

1.3.2 Bronchial provocation tests

Stimuli, such as exercise, hyperventilation, inhalation of histamine or metacholine leads to

BHR, which is often used to diagnose and evaluate asthma by bronchoprovocation tests (BPT).

BPTs are often used to assess BHR and they are helpful in diagnosing asthma. BPTs are divided

in two categories: ‘direct’ challenges and ‘indirect’ challenges. Direct challenges are tests in

which bronchoconstriction is induced by inhalation of metacholine or histamine. Metacholine

acts on smooth muscle receptors. Indirect challenges, such as exercise, hypertonic saline and

mannitol, act on inflammatory cells, which release pro-inflammatory mediators and cause

airflow limitation.56

Exercise is widely used as an indirect BPT to assess and diagnose EIB in patients with a

history of wheezing or breathlessnes after exercise. Exercise is also used to determine the

effectiveness of medication prescribed for prevention of EIB. A study by Carlsen et al. showed


M.H.T. van Hoesel

that children with asthma demonstrate a greater reduction in pulmonary function after exercise

compared to children with other chronic lung diseases. Besides, cold air inhalation influences

the exercise tolerance much more in ashtmatic children, which results in a larger increase of

EIB compared to children with other chronic lung diseases. Although both direct- and indirect

challenge tests are sensitive for identifying asthma, indirect challenge tests showed a higher

sensitivity and maintained the specificity for asthma.57 There is evidence that direct challenges

are inferior for confirming asthma and indirect challenges would be preferred for diagnosing

and monitoring asthma.58

1.3.3 Questionnaires

Asthma questionnaires are often used for assessment and monitoring the severity of EIB. For

assessment of EIB it is important that children and their parents adequately report on asthma

symptoms. Their observations need to be accurate, because a pediatricians rely on their

observations to make decisions about modifying therapy. A study of Panditi et al. showed that

children and parents have poor perception and report of asthma symptoms is not adequately,

which can lead to under- or overestimation of asthma severity and over- or undertreatment.59

Bacharier et al. showed that pulmonary function tests relate well to asthma severity as

assessed by medication, or a combination of symptom reports and medication requirements, but

that there’s no relationship found for symptom reports alone. This suggests a disconnection

between perception and degree of airflow obstruction.47,60

Perception of dyspnoea does not only depend on the degree of narrowing in their airways,

symptoms and drug therapy. It depends on psychological influences, such as previous

experiences and in case of children, the opinion of their parents.61 Poor perception could also

be associated with a low level of fear and adaptation to asthma resulting of a long-standig

airway obstruction.62 Children with a long history of asthma are less likely to complain about

dyspnoea compared to children with acute symptoms of asthma. This may result presentations

with hypoxia during an exacerbation, which could lead to severe or life threatening asthma

attacks.63 Adequate reporting of asthma enables pediatricians to evaluate the severity of asthma

and asthma control and prevent these life threatening events.

1.4 Classification of exercise induced bronchoconstriction

Classification of asthma is useful in determining treatment in patients, which divides between

mild, moderate en severe, based on airflow limitation and pulmonary function variability. The

severity of EIB is expressed as the maximum percentage reduction in FEV1 after exercise.64

Table 1. Classification of severity of EIB. Adapted from Anderson et al.63

Degree of severity of EIB Maximum fall in FEV1 after exercise (%)

No EIB <10%

Mild EIB >10% but <25%

Moderate EIB >25% but <50%

Severe EIB >50% for steroid-naïve patients

>30% for steroid-naïve patients

1.5 Treatment

EIB is a sign of uncontrolled asthma. The goal of treatment of EIB is to achieve control of

asthma, minimize exacerbations and most of all preventing children from avoiding exercise.

Optimal treatment of asthma is important for children to participate in sports and other physical


M.H.T. van Hoesel

activities.4 It is very important that symptoms of EIB are recognized, because EIB can be treated

very effectively and with maintenance medication even be prevented.21

Non-pharmalogical measures, such as physical activity, are important in achieving

rehabilitation.4 Many asthmatic atheletes have succeeded in sports, demonstrating that having

asthma does not limit participation in sports and physical training can improve cardiopulmonary

fitness. But medical supervision is neccesary for monitoring ashtma and adjustment of

treatment, when needed.21,65

Non-pharmalogical measures are a warm up and cooling down prior and after exercise and

reducing loss of water and heat for example by wearing a scarf before the nose.48,66

Besides non-pharmalogical measures, pharmacological interventions can be considered. For

pharmacological treatment there are two main paths: prophylactic treatment and premedication.

1.5.1 Prophylactic treatment of EIB

Presentation with EIB indicates inflammation of the airways. Anti-inflammatory treatment by

inhaled corticosteroids (ICS) is the most important and effective treatment in managing EIB.

Jonasson et al. found that daily treatment with ICS provided significant protection against EIB

and improvement in airway hyperresponsiveness. It also reduced other symptoms during the

treatment and improvement in severity of asthma symptoms.67,68 A study of Waalkens et al.

showed that EIB improved after 1 week of treatment with ICS, but 3-4 weeks of treatment were

necessary to improve pulmonary function. Long-term treatment with ICS reduced the

prevalence by 33% and the severity by 50%. Still, around 50% of patients who were treated

with ICS for 2 months and supposingly controlled asthma exhibit EIB while exercising.69

When ICS are not effective enough, there are 3 options for anti-inflammatory treatment:

leukotriene antagonists (LTRA), nasal corticosteroids (NCS) or increasing the use of ICS. The

step-up therapy that is mostly used, are LTRA’s.70 Leff et al. showed that LTRA provided a

significant protection against EIB compared with placebo treatment over a 12-week period.71

1.5.2 Premedication

The preferred group of pre-medication are short-acting β2-agonists (SABA), but this is not

feasible in kids as they usually have multiple exercise bouts on a daily base and this would lead

to over consumption of SABA’s.7,70 Ineffectiveeness of SABA’s suggests another cause of

exercise induced dyspnoea, such as dysfunctional breathing or reduced cardiovascular fitness.

1.6 Video-analysis

Diagnosis and monitoring of asthma in the clinical practice depends on adequate perception of

symptoms by children and parents, anamnesis and physical examination. Those measurements

are not specific nor sensitive in diagnosing asthma. Also elective pulmonary function testing is

not informative. As normal pulmonary function tests have low diagnostic sensitivity.70

Pulmonary function tests which make use of a bronchial provocative stimulus are an exemption.

In this type of test, a bronchial provocative stimulus induces bronchial obstruction, which gives

an objective measurement of bronchial hyper-reactivity. A specific stimulus for provocation of

asthma in children is exercise, however exercise challenge tests can only be executed according

to guidelines specialized facilities.

Frequency and content of monitoring of children with asthma is based on the presence of

symptoms, exacerbations, use of corticosteroids or antibiotics, school absence, compliance,

inhalation technique, asthma symptom scores and more. Suboptimal treatment leads to frequent

and costly emergency visits to the doctor.70

Moreover, research by Bekhof et al. showed that there is a poor inter-observer reliability of

clinical dyspnoea assessment in children and there are limits to its usefulness in clinical practice


M.H.T. van Hoesel

and research. Therefore, there is a need for low-cost and objective measurements to assess

severity of symptoms in asthmatic children. Not only to improve diagnostic process, but also

to enhance self-management.72

A study of Wolf et al. stated that education of parents and children with asthma (targeted at

improved self-management) may lead to better pulmonary functions, than usual care and that

there's a desirability of including self-management education consisting of prevention and

attack management into routine asthma care for children.73

Evaluation of asthma symptoms in a home setting could lead to better insight in presence of

symptoms, severity and control of asthma symptoms in children. Video evaluation of asthma

symptoms could be a potential low-end and objective addition to the clinical practice of asthma,

which could lead to improvement of the diagnostic process and monitoring of asthma in order

to optimalize treatment, reduce cost and increase efficiency.

In order to use videos in a home setting, it has to be investigated if and how well specialists

can assess dyspnoea on video material. By making video recordings of children before and

after ECTs, the relationship between assesment of dyspnoea by specialist based on videos and

pulmonary function can be explored in an experimental setting.

The aim of this study is to investigate whether paediatricians can predict the severity of EIB

as measured with an ECT from the medical history, physical examination and pre-exercise

video, and if the addition of pre-exercise lungfunction can improve this prediction.

The second aim of this study is to investigate the relation between asthma dyspnoea scores, as

assessed by pediatricians from videos, and the severity of airway obstruction as measured with

pulmonary function.


M.H.T. van Hoesel

2. Problem definition

2.1 Research questions

1. Can specialists predict the severity of EIB based on video recordings?

1.1 Can physicians recognise asthma symptoms based on post-exercise videos?

1.2 Can spirometry after an ECT improve the the prediction of EIB?

1.3 Can parents and children recognise asthma symptoms?

2.2 Hypothesis

We hypothesize that prediction of dyspnoea from videos are not related to asthma scores of

physicians. We also hypothesize results of spirometry will not improve prediction and

management of asthma.

2.3 Primary outcome

To study the reliability of assessment of airway obstruction by specialists;

To compare the relation between prediction of EIB by specialists, pulmonary function

results and pre- and post-exercise videos;

We consider comparison between the prediction of specialists, video-analysis and pulmonary

function tests as an objective addition to the clinical practice of asthma.

2.4 Secundary outcome

To study the relation between asthma symptoms, spirometry and the VAS dyspnea score

filled in by the subjects (children) and their parents before and after the ECT.

We encounter patient- and parent-recorded findings as a valuable secondary study-endpoint,

because how a patient or parent perceive the severity of asthma and the level of control, is of

great importance for the ability to self-manage the asthma.


M.H.T. van Hoesel

3. Methods 3.1 Study design and procedure

3.1.1 Design

We performed a cross-sectional study to investigate the relation between asthma dyspnoea

scores, as assessed by pediatricians from videos, and the severity of airway obstruction as

measured with pulmonary function.

3.1.2 Procedure

The child’s medical history, anamnesis, need or use of medication and physical examination

were performed in a standardised way (appendix 8.1). Exercise challenge test were completed

as a part of the routine evaluation of asthma, with the addition of recording the patients before

and after the ECT. Before and after exercise spirometry was performed. No short- or

longacting bronchodilators were used 24 hours before testing.

Pre- and post-exercise videos were made from the patient’s head and upperchest, recorded on

an ipad before and after ECT (2x20 seconds). The pre-and post-exercise videos included

recording of sound. These videos were edited in short fragments before and after exercise and

assessed by pediatricians.

The (selected) children followed the procedure below:

Anamnesis with pediatrician/ investigator about medical history, symptoms and treatment;

Anthropometric measurements (height, weight);

Pulmonary auscultation;

An ECT, which either consisted of running on a treadmill or jumping on a jumping castle

for 6 minutes;

Pulmonary function measurements before (duplicated), during and after exercise at t=1, 3,

6, 9, 12 and 15 minutes;

Recording videos 20 seconds before and after ECT.

3.2 Study population

Approximately 39 children, aged 4 to 17 years, were consecutively recruited from the

outpatient clinic of the pediatric department of the Medisch Spectrum Twente in the period of

May 2015 to July 2015. These children must have a pediatrician diagnosed asthma and be

referred to a specialized centre for a bronchial challenge test, or, children must be suspected

of having asthma and referred to an exercise challenge test as part of the diagnostic workup.

These videos were assessed by pediatricians of 4 different hospitals (Medisch Spectrum

Twente, Isala Klinieken Zwolle, ZGT Almelo and ZGT Hengelo).

This study was approved the Medical Ethics Committee of Medisch Spectrum Twente (METC),

Enschede. All children and parents/guardians received written patient information, and signed

an informed consent form before acceptance in the study.

3.2.1 Inclusion criteria

- Clinical history of asthma or suspected of having asthma;

- Age between 4-17 years;

- Ability to perform reproducible pulmonary function tests, i.e. coefficient of the

predicted value variation in 3 of 5 consecutive measurements < 5%.


M.H.T. van Hoesel

3.2.2 Exclusion criteria

- Airflow limitiation in baseline spirometry (forced expiratory volume in the first

second (FEV1), <60% of predicted);74,75

- Spirometry induced bronchoconstriction;

- Use of short- or longacting bronchodilators <24 hours before testing.

3.2.3 Extra exclusion criteria for selection of videos

- Less than ½ of the chest visible on pre- or postexercise video

- Fully dressed children before and after ECT

- Speaking less than one sentence before or after ECT

3.2.4 Exclusion criteria for subanalysis of asthma questionnaires

- Missing pre-FEV1 or post-FEV1

- Non-independent assessment of dyspnoea by parent or child

3.2.5 Sample size calculation

In our study 39 children were consecutively enrolled. After inclusion of the participants, 20

participants were included in our study. Every case was assessed independently by five

different pediatricians. To assess every case five times, we calculated that we needed 20

pediatricians.

3.3 Methods

3.3.1 Measurement instruments

3.3.1.1 Excercise challenge test

All ECT’s were performed in a climate chamber at ZGT Hengelo, the Netherlands. Cold and

dry air was obtained during ECT with a temperature of 10.0-12.0°C. During the study ECT

was performed following standard protocol.53

Children aged 10-17 years performed the ECT on a treadmill (H/P-Cosmos Quasar 4.0) for 6

minutes with a submaximal exercise load and their nose clipped.48 The inclination of the

treadmill was 10%. The speed of the treadmill was accelerated until a steady-state heart rate

was achieved of at least 180 beats per minute. The heartrate was continuously measured by a

radiographic ECG-device (Custo cardio 100 BT).

Children aged 4-9 years old performed the ECT by jumping on a jumping castle for 6 minutes.

Van Leeuwen et al, showed that an age-adjusted ECT is preferable in younger children and

using a jumping castle is a feasible method to assess and diagnose EIB.32,76

3.3.1.3 Spirometry

Pulmonary function was measured by using standard pulmonary function tests before

(baseline), after exercise and after inhalation of salbutamol. We used a MicroLoop® MK 8

hand-held spirometer (ML3535). Baseline spirometry was performed in duplicate.48 After

exercise the expiratory flow volume curves were replicated twice. Maximal effort was

enhanced by visual incentives. The children were seated while performing spirometry.75 At

least three acceptable pulmonary function measurements were obtained, with less than 5%

variability between the three measurements.74,75

During spirometry FEV1 was measured. Spirometry was performed before exercise, after 1

minute, and 3, 6, 9, 12 and 15 minutes after cessation of exercise. After 15 minutes

bronchodilator therapy was administered and 5 minutes after inhalation, spirometry was

performed to measure reversibility. When patients experienced severe bronchoconstriction or a


M.H.T. van Hoesel

fall of ≥ 60% in FEV1 post-exercise before completing the protocol, bronchodilator therapy

with SABA was administered to reverse bronchoconstriction. Children with a fall of ≥ 10% in

FEV1 post-exercise were considered to have EIB.

Maximum fall in FEV1 after exercise challenge test was calculated by:

3.3.2 Video material

We used an iPad mini attached to a tripod in the consultation room, where the consultation and

pulmonary function measurements took place. The optimal settings for recording were

examined and the main goal was to have video-material of the children’s upper chest and head.

Video-recordings were made during consultation to for an overall view of the child. Pre- and

post-exercise a 20 second video was made in the same setting, but with the child’s face straight

into the camera. Below in figure 5 an overview of the camera position.

3.3.2.1 Assessment of video recordings

We used a panel of pediatricians in different hospitals for assessment of the videos. The

recorded video material of all cases of children with dyspnoea were randomised and assigned

to different pediatricians. Every case was assessed independently by five different pediatricians.

Before assessment they were given verbal and written instructions.

Each pediatrician scored the videos on different features of airway obstruction; wheezing,

prolonged expirium, nasal flaring, jugular retractions and supraclavicular retractions. These

features weren chosen based on previous literature and graded as a binary variable (present or

absent).77 The pediatricians were also asked to give an prediction of the severity of EIB based

on the classification of EIB (table 1) and on a Likert scale ranging from no EIB to very severe

EIB (0 to 10).


M.H.T. van Hoesel

The (selected) pediatricians followed the procedure

below (Figure 6.)

Predicting classification of EIB, features of

dyspnoea and likert scale based on medical history,

physical examination and a pre-exercise video;

Predicting classification of EIB and likert scale

based on the addition of baseline spirometry before

exercise;

Predicting classification of EIB, features of

dyspnoea and likert scale based on a post-exercise

video.

3.3.3 Questionnaires

Asthma control questionnaires, such as (Childhood)

Asthma Control Test (C-ACT)78,79, Asthma Control

Test (ACT) and the VAS-score, are widely used and

validated questionnaires to complement assessment of

asthma control.7 The C-ACT is designed for children

aged 4-11 years old, which consists of 7 question for

either child or parent. There were 4 questions for the

child, scoring 0-3, and 3 for the parent, scoring 1-5.

Scores of the questions were summed, ranging 3-27. A C-ACT-score of ≤19 indicates poor

asthma control.

The ACT is designed for children older than 12 years, which consists of 5 questions, scoring 1-

5. Scores of the questions were summed, ranging 5-25. An ACT-score of ≤19 indicates poor

asthma control. Children and parents filled out both questionnaires in Dutch and before the start

of the ECT. The VAS score was filled out before exercise, 2 minutes after exercise and 6

minutes after bronchodilator therapy.

3.3.4 Randomization

Every case was allocated five times to five different pediatricians. When a case was allocated

five time, it could not be selected anymore. The randomization list was designed with the aid

of a computerized randomization method using SPSS® version 22.0 analytical software.

3.3.5 Statistical analysis

Results were expressed as mean values ± standard deviations (SD) for normally distributed

data, as median (minimum;maximum) for non-normally distributed data, or as numbers with

correpsonding percentages if nominal or ordinal. For the measure of concordance between the

prediction of classification of EIB before ECT, baseline pulmonary function and after ECT, and

the validated classification of EIB by pulmonary function, we calculated a weighted Cohen’s

kappa. Cohen’s kappa values were classified as following: <0, poor; 0-0.2, slight; 0.2-0.4, fair;

0.4-0.6, moderate; 0.6-0.8, substantial; 0.8-1.0, almost perfect.80 To assess the difference of two

correlated proportions a McNemar test was used. For our subanalysis, correlations were

calculated with Pearson’s correlation coefficient for normally distributed continuous variables,

or with Spearman’s rho for non-normally distributed continuous variables. A two-sided p-value

of less than 0.01 was considered statistically significant. All data analyses were performed with

SPSS® Statistics, version 22.0.


M.H.T. van Hoesel

4. Results 4.1 Baseline characteristics of included children

Thirty-nine children participated in this study. They performed an ECT in dry and cold air and

videos were taken before and after exercise. They also performed spirometry before and after

exercise. Three children were excluded because of spirometry-induced bronchoconstriction and

one child had taken salbutamol <24h before the ECT. With fifteen children we were not able to

make usefull videos. Twenty children (11 male) with a mean age of 11.6 ± 3.4 were included

in the analysis. The baseline characteristics of the included patients were shown in table 2. Table 2. Baseline characteristics of included children

Characteristics Value

Number of children 20 Age (years) 11.6 ± 3.4

Male 11 (55.0)

Treadmill 17 (85.0) Height (cm) 155.1 ± 19.2

Weight (kg) 49.1 ± 21.7

BMI (kg/m2) 19.4 ± 4.7

Allergy* 11 (55.0) Exercise induced symptoms 8 (40.0)

Medication use:

SABA 13 (65.0)

ICS 10 (50.0) LABA 2 (10.0)

LTRA 6 (30.0) NCS 5 (25.0)

Baseline FEV₁ (% predicted) 92.7 ± 13.9

Maximum decrease in FEV₁ (%) 15.1 (1.2;65.1)

Classification

No EIB (<10%) 9 (45.0)

Mild EIB (10-25%) 4 (20.0)

Moderate EIB (25-50%) 2 (10.0)

Severe EIB (>50%) or if ICS (> 30%) 5 (25.0)

Reversibility (%) 18.9 (-11.0;62.3)

Results expressed as medians (minimums;maximums), mean values ± SDs, or numbers (percentages). SABA,

short-acting β2-agonist; LABA, long-acting β2-agonist; ICS, inhaled corticosteroid; NCS, nasal corticosteroid;

LTRA, leukotriene receptor antagonist; EIB, exercise induced bronchoconstriction; FEV1, forced expiratory

volume in 1 second; *allergy screening in 11 of 38 children.

The included children showed a mean baseline FEV1 of 92.7% (±13.9) and a median fall in

FEV1 of 15.1% (1.2-65.1). Eleven children (6 male, 5 female) showed EIB (decrease in FEV1

of >10% from baseline). Four children showed mild, two children moderate and five children

showed severe EIB.


M.H.T. van Hoesel

4.2 Baseline characteristics of pediatricians

Twenty pediatricians were selected to assess pre- and postvideos of children with dyspnoea.

Two pediatricians were subspecialized in pediatrician-pulmonologist. Their years of experience

have a mean of 14.4 years (±9.8). There baseline characteristics were shown in table 3.

Results expressed as medians (minimums;maximums), mean values ± SDs, or numbers (percentages).

4.3 Prediction of EIB by specialists

We included and video-recorded 20 children. Each child had two videos, one before and one

after an ECT. Every child was randomly assigned five times to a different pediatrician. Every

pediatrician viewed videos of five children, resulting in 100 assessments. Characteristics of the

included children are listed in table 2. The included children showed a mean baseline FEV1 of

92.7% (±13.9) and a median fall in FEV1 of 15.1% (1.2-65.1) after exercise (table 3). Children

were categorised in a classification model (table 1) and showed no, mild, moderate or severe

EIB (table 2). Pediatricians predicted in which classification children were after a 6-minute

ECT.

Table 4 shows the agreement between the predicted classifications. Agreement between

predicted classification of pre-exercise videos and predicted classification of pre-pulmonary

function was substantial (Kappa = 0.70 (95% CI 0.58-0.81)). Agreement between predicted

classification of pre-pulmonary function and predicted classification of post-exercise videos

was fair (Kappa = 0.39 (95% CI 0.25-0.52)). Agreement between predicted classification of

pre-exercise videos and predicted classification of post-exercise videos was slight to fair (Kappa

= 0.20 (95% CI 0.06-0.34)). Agreement between predicted classification of pre-exercise videos

and the classification validated with pulmonary function was slight (Kappa = 0.05 (95% CI

0.00-0.17)). Agreement between predicted classification of pre-pulmonary function and the

classification validated with pulmonary function was slight (Kappa = 0.19 (95% CI 0.06-0.32)).

Agreement between predicted classification of post-exercise videos and the classification

validated with pulmonary function was fair (Kappa = 0.36 (95% CI 0.23-0.48)).

Table 3. Baseline characteristics of pediatricians


Number of specialists 20

Years of experience 14.4 (±9.8)

Pediatrician-pulmonologist 2 (10.0)

Table 4. Agreement between predicted classifications

Kappa* (95% CI) Approx. Sig.

Classification Pre * classification PreLf 0.70 (0.58-0.81) P < 0.001

Classification PreLf * classification Post 0.39 (0.25-0.52) P < 0.001

Classification Pre * classification Post 0.20 (0.06-0.34) P = 0.128

Classification Pre * classification validated 0.05 (0.00-0.17) P = 0.400

Classification PreLf * classification validated 0.19 (0.06-0.32) P = 0.005

Classification Post * classification validated 0.36 (0.23-0.48) P < 0.001

* Weighted Cohen’s kappa; CI, confidence interval.


M.H.T. van Hoesel

Pediatrician’s prediction of the severity of EIB from the medical history, physical examination

and pre-exercise video was poor. This poor prediction was not improved when pediatricians

were informed about the pre-exercise pulmonary function. Pediatrician’s assessments of

dyspnoea on post-exercise videos correlated fairly well with the severity of EIB.

4.4 Prediction of EIB by parents and children

4.4.1 Baseline characteristics of asthma questionnaires

For this sub-analysis forty-seven children were enrolled. Nine children were excluded because

of missing pre-FEV1 or post-FEV1. One child was excluded because of non-independent

completion of the questionnaires. Thirty-eight children were included for analysis. The baseline

characteristics of these patients were shown in table 2.

Table 7. Baseline characteristics of asthma questionnaires ((C)-ACT and VAS-scores)


Number of children 38

Age (years) 10.8 ± 3.3

Male 22 (57.9)

(C)-ACT score 19 (10;27)

PreVASscore Child 1.4 ± 1.8

PostVASscore Child 5.1 ± 3.1

PreVASscore Parent 1.1 ± 1.4

PostVASscore Parent 4.1 ± 2.6

Results expressed as medians (minimums;maximums), mean values ± SDs, or numbers (percentages). (C)ACT, (childhod) asthma control test; VAS, visual analogue scale.

Table 5. Agreement of concordance

McNemar-Bowker Asymp. Sig. (2-sided)

Classification Pre * classification PreLf 7.571 P = 0.181

Classification PreLf * classification Post 6.733 P = 0.241

Classification Pre * classification Post 4.333 P = 0.502

Classification Pre * classification validated 38.734 P < 0.001

Classification PreLf * classification validated 35.876 P < 0.001

Classification Post * classification validated 29.591 P < 0.001

Table 6. Prevalence of dyspnoea features

100 assessments Prevalence

Wheezing (pre-video) 2.0%

Wheezing (post-video) 15.0%

Prolonged expirium (pre-video) 9.0%

Prolonged expirium (post-video) 49.0%

Nasal flaring (pre-video) 2.0%

Nasal flaring (post-video) 22.0%

Jugular retractions (pre-video) 16.0%

Jugular retractions (post-video) 56.0%

Supraclavicular retractions (pre-video) 8.0%

Supraclavicular retractions (post-video) 47.0%


M.H.T. van Hoesel

The pre-VAS scores of the included children showed a mean score of 1.4 (±1.8). The post-VAS

scores showed a mean score of 5.1 (±3.1). The pre-VASscores of the parents showed a mean

score of 1.1 (±1.4). The post-VAS scores showed a mean score of 4.1 (±2.6).

4.4.2. Validation of dyspnoea scores against pulmonary function


M.H.T. van Hoesel


M.H.T. van Hoesel

When plotting the postVASscoreChild against the postVASscoreParent, a significant

correlation was found (Spearman’s rho 0,738; p = 0.000). When plotting the

postVASscoreChild against the post-FEV1, no correlation was found (Spearman’s rho -0,238;

p = 0.151). When plotting the postVASscoreParent against the post-FEV1, no correlation was

found (Spearman’s rho -0,276; p = 0.099).

Table 8. Correlation between dyspnoea scores before exercise and baseline pulmonary function

PreVASscore

Child

PreVASscore

Parent

PreFEV1

(baseline)

Spearman's rho PreVASscore

Child

Correlation Coefficient 1,000 ,500** -,133

Sig. (2-tailed) . ,001 ,427

N 38 38 38

PreVASscore

Parent

Correlation Coefficient ,500** 1,000 -,299

Sig. (2-tailed) ,001 . ,068

N 38 38 38

PreFEV1 Correlation Coefficient -,133 -,299 1,000

Sig. (2-tailed) ,427 ,068 .

N 38 38 38

**. Correlation is significant at the 0.01 level (2-tailed).

When plotting the preVASscoreChild against the preVASscoreParent, a significant

correlation was found (Spearman’s rho 0,500; p = 0.001). When plotting the

preVASscoreChild against the baseline FEV1, no correlation was found (Spearman’s rho -

0,133; p = 0.427). When plotting the preVASscoreParent against the baseline FEV1, no

correlation was found (Spearman’s rho -0,299; p = 0.068).

Table 9. Correlation between dyspnoea scores after exercise and pulmonary function after exercise

PostVASscore

Child

PostVASscore

Parent

PostFEV1

Spearman's rho PostVASscore

Child

Correlation Coefficient 1,000 ,738** -,238

Sig. (2-tailed) . ,000 ,151

N 38 37 38

PostVASscore

Parent

Correlation Coefficient ,738** 1,000 -,276

Sig. (2-tailed) ,000 . ,099

N 37 37 37

PostFEV1 Correlation Coefficient -,238 -,276 1,000

Sig. (2-tailed) ,151 ,099 .

N 38 37 38

**. Correlation is significant at the 0.01 level (2-tailed).


M.H.T. van Hoesel

5. Discussion 5.1 Result analysis

The results of our study show that pediatrician’s prediction of the severity of EIB from the

medical history, physical examination and pre-exercise video was poor. This poor prediction

was not improved when pediatricians were informed about the pre-exercise pulmonary

function. Pediatrician’s assessments of dyspnoea on post-exercise videos correlated fairly well

with the severity of EIB. These results implicate that an ECT is a valuable tool to identify EIB

and that videos of children after exercise may be a future tool to diagnose and monitor EIB.

To our knowledge, this is the first study using videomaterial of asthmatic children

performing an ECT and relating pediatrician’s assessments of video’s with EIB as measured

with pulmonary function.

Our results implicate that exercise challenge tests are still needed to identify EIB and are

therefore a useful tool in diagnostics of asthma. The diagnosis of EIB from a medical history is

difficult; perception of EIB by children and recognition by others can be low.36,60 Moreover

Bekhof et al. showed that there’s a poor inter- and intraobserver variability in clinical dyspnoea

assessment and that use of more objective parameters should be taken into account in the

diagnostic process.72 Holt et al. also showed that one third of the treatment plans are changed

after pulmonary function tests.49 Pulmonary function tests could give a more reliable

assessment of dyspnoeic children.

Our study show that the addition of a pre-exercise pulmonary function did not improve the

ability of pediatricians to predict EIB compared to the prediction of EIB based on pre-exercise

videos, medical history and physical examination. This is consistent with previous literature

showing that elective pulmonary function testing is not sensitive and useful mostly during

symptoms.70 But a normal pulmonary function does not always exclude asthma, because

children who are diagnosed with asthma could have a normal pulmonary function before

exercise and a totally different pulmonary function after exercise.3

Our results show that there is no significant relation between assessment of EIB from VAS

scores of both children and parents compared to the severity of EIB as measured by pulmonary

function. This is in line with previous literature that showed that both children and parents have

a poor perception of the severity of dyspnoea.60,81 This disconnection could be the result of

adaptation to severe asthma and a longterm airway obstruction.62 Van Leeuwen et al. also found

that there was no difference in asthma scores between children with or without EIB, which

confirms our results and there is great caution needed with interpretation of these scores.32

5.2 Strengths and limitations

The major strengths of this study include the use of spirometry results. Pulmonary function

testing is acknowledged as the gold standard for assessment of asthma and it is non-invasive

and objective.46 Besides an objective measurement of the severity of asthma, it can assess the

effects of treatment. Recently, Bekhof et al. described that no dyspnoea scoring system has

been sufficiently validated against pulmonary function and that there’s a need for further

validation of scoring systems.77 Eventhough, there are studies which report validation of

scoring systems against pulmonary function82, there has never been assessment of dyspnoea

on videos with validation against pulmonary function, which makes this study unique.

Also, all ECTs were performed in a standardized ‘climate room’, which simulates the air

condition in the Netherlands in the winter, where most patients experience symptoms of EIB.

ECTs mimic real life circumstances in which periods of airway obstruction can be provoked.

The before- and after ECT video recordings provide pediatricians insight in symptoms, which

are mostly absent during elective doctor visits.


M.H.T. van Hoesel

Another strength is that child- and parent-assessed EIB both are validated against pulmonary

function. Current literature included a validated assessment of the child’s symptom scores, but

lacked validated parent-assesed dyspnoea scores.83

We acknowledge the following limitations in our study. First, the use of videomaterial has

its limitations. The length of the videos were relatively short (30 sec-1minute), which could

have lead to missed observations and less accurate detection of subtle signs of dyspnoea. For

our study purpose, to find a more low-cost measurements to use in a home setting, video

recordings were the only practical method.

Also, assessment of EIB was based on different scoring systems, which included different

characteristics of dyspnoea.77 During recording of the videos we did not expose the whole chest,

which also could have led to less accurate assessment and prediction of the severity of EIB. In

experimental setting you can create these perfect circumstances, but our purpose was to use

video recordings in a home setting, were these circumstances cannot always be realized.

Thirdly, the lack of chest auscultation after the ECT could also be recognized as a limitation.

A few specialists reported that they could not assess EIB without chest auscultation, because

chest auscultation in dyspnoeic children helps the pediatrician to detect lower airway

obstruction. Chest auscultation is mostly used in clinical practice. However, our study

investigates prediction of EIB in videos for the purpose of usefulness in a home setting, where

no chest auscultation is possible. But although chest auscultation is very subjective and requires

specific skills, it can be argued that the degree of EIB can only be assessed with chest

auscultation.

Classification of EIB based on decrease in FEV1 was used to validate prediction of EIB by

pediatricians. Pediatricians are not used to estimate the degree of EIB and the dyspnoea scoring

system was judged impractical to use for prediction, which could lead to a less reliable

prediction. Our results also suggest that the use of classification of EIB by pulmonary function

as validation instrument is not suitable for the use in clinical practice.

5.3 Further research

Pediatricians were fairly capable of identifying severity of EIB from videos of children with

EIB. This provides opportunities to diagnose EIB outside the hospital where symptoms of EIB

occur. Future research should investigate the feasibility and validity of home videos of children

with putative symptoms of EIB. This may reduce the need for expensive hospital based ECTs.

Furthermore measuring VAS scores of children and parents during ECTs can identify children

poor perception and parents with poor recognition of EIB. Videos of symptomatic children can

show these parents (subtle) signals of EIB of their child preventing patient related delay in

treatment. Future research could investigate this potential reduction in delayed treatment.

6. Conclusion In conclusion, as prediction of EIB from medical history, physical examination and lung

function is poor ECTs are still needed to identify EIB. Pediatricians have a fair ability to assess

EIB from post-exercise videos, providing opportunities to diagnose EIB from home made post-

exercise videos. Our results also show that average perception of children and parents of the

severity of EIB is poor. Individual assessment of perception could identify asthmatic children

at risk for patient related delay in therapy.


M.H.T. van Hoesel

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http://www.who.int/mediacentre/factsheets/fs307/en/index.html. Accessed May 11, 2015.

2. Centraal Bureau voor de Statistiek. Één op de vijf kinderen heeft chronische ziekte. 2008;

Available at: http://www.cbs.nl/nl-NL/menu/themas/gezondheid-

welzijn/publicaties/artikelen/archief/2008/2008-2606-wm.htm. Accessed May 18, 2015.

3. Milgrom H H, Milgrom H, Taussig LM. Keeping children with exercise-induced asthma

active. Pediatrics 1999-9;104(3).

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M.H.T. van Hoesel

8. Appendix 8.1 CRF video study


M.H.T. van Hoesel


M.H.T. van Hoesel

8.2 Crosstabs

Table 10. Crosstabs Classification Pre compared with Classification_PreLf

Classification_PreLf

Total 1 2 3 4

Classification_Pre 1 Count 18 2 1 0 21

% within Classification_Pre 85,7% 9,5% 4,8% 0,0% 100,0%

% within Classification_PreLf 90,0% 4,7% 3,3% 0,0% 21,0%

2 Count 2 37 10 2 51



3 Count 0 4 19 2 25



4 Count 0 0 0 3 3



Total Count 20 43 30 7 100



Table 11. Corsstabs Classification_PreLf compared to Classification_Post

Classification_Post

Total 1 2 3 4

Classification_PreLf 1 Count 13 6 1 0 20


% within Classification_Post 43,3% 14,3% 4,5% 0,0% 20,0%

2 Count 14 21 7 1 43



3 Count 3 14 11 2 30



4 Count 0 1 3 3 7



Total Count 30 42 22 6 100




M.H.T. van Hoesel

Table 12. Crosstabs Classification_Pre compared with Classification_Post

Classification_Post

Total 1 2 3 4




2 Count 14 21 13 3 51



3 Count 4 13 6 2 25



4 Count 0 1 1 1 3



Total Count 30 42 22 6 100



Table 13. Crosstabs Classification_Pre compared to Classification_validated

Classification_validated

Total 1 2 3 4



% within Classification_ validated 24,4% 25,0% 10,0% 16,0% 21,0%

2 Count 22 10 5 14 51



3 Count 10 5 4 6 25



4 Count 2 0 0 1 3



Total Count 45 20 10 25 100




M.H.T. van Hoesel

Table 14. Crosstabs Classification_PreLf compared to Classification_ validated

Classification_ validated

Total 1 2 3 4

Classification_PreLf 1 Count 11 5 1 3 20



2 Count 21 11 2 9 43



3 Count 10 4 7 9 30



4 Count 3 0 0 4 7



Total Count 45 20 10 25 100



Table 15. Crosstabs Classification_Post compared to Classification_ validated

Classification_ validated

Total 1 2 3 4

Classification_Post 1 Count 18 8 0 4 30



2 Count 23 11 3 5 42



3 Count 4 1 6 11 22



4 Count 0 0 1 5 6



Total Count 45 20 10 25 100




M.H.T. van Hoesel

8.3 Questionnaires

8.3.1 Dyspnoea scores – filled out by children and parents


M.H.T. van Hoesel

8.3.2 Childhood Asthma Control Test (age <12 years)


M.H.T. van Hoesel

8.3.3 Asthma Control Test (age >12 years)

1: Hoe vaak heb je door je astma op school of thuis minder kunnen doen dan normaal in

de afgelopen 4 weken?

Ο nooit

Ο zelden

Ο soms

Ο meestal

Ο altijd

2: Hoe vaak ben je kortademig geweest in de afgelopen 4 weken?

Ο helemaal niet

Ο 1 of 2 keer per week

Ο 3 tot 6 keer per week

Ο 1 keer per dag

Ο vaker dan 1 keer per dag

3: Hoe vaak ben je ’s nachts of ’s morgens vroeger dan normaal wakker geworden door

astmaklachten (piepen, hoesten, kortademigheid, een drukkend gevoel of pijn op de

borst) in de afgelopen 4 weken?

Ο helemaal niet

Ο 1 of 2 keer

Ο 1 keer per week

Ο 2 tot 3 nachten per week

Ο 4 of meer nachten per week

4: Hoe vaak heb je je blauwe pufje gebruikt om een astma aanval te stoppen in de

afgelopen 4 weken?

Ο helemaal niet

Ο 1 keer per week of minder

Ο een paar keer per week

Ο 1 of 2 keer per dag

Ο 3 keer of vaker per dag

5: Hoe vindt je dat je astma onder controle is de afgelopen 4 weken?

Ο volledig onder controle

Ο goed onder controle

Ο een beetje onder controle

Ο slecht onder controle

Ο helemaal niet onder controle


M.H.T. van Hoesel

8.4 Instruction assessment videos

Doel:

Deze studie is opgezet om de relatie te bestuderen tussen dyspnoe scores van kinderen met

astma gefilmd voor- en na inspanning, door kinderartsen, met simultaan vergeleken longfunctie

metingen.

Op deze manier hopen we inzicht te krijgen in de betrouwbaardheid van de klinische

beoordeling van dyspnoe op basis van videomateriaal.

Videomateriaal:

Er werden 20 kinderen geselecteerd tussen de 4 en 17 jaar aan de hand van inclusie- en exclusie

criteria. Alle kinderen hebben daarbij >24u geleden hun laatste medicatie gehad.

U ziet een video-fragment van voor- en na inspanning van een kind met astma. Deze bestaat uit

een deel wanneer het kind praat en tevens een deel waarin het kind recht in de camera kijkt.

Scoringssysteem:

De pre- en post-inspannings video’s zullen gescored worden op verschillende tekenen van

benauwdheid. Elke observeerder noteert de aanwezigheid en ernst van de volgende klinische

verschijnselen op een gestructureerde wijze; piepen, verlengd expirium, neusvleugelen,

jugulaire- en supraclaviculaire intrekkingen. Deze zullen als een binaire variabele worden

genoteerd (aan- of afwezig). Ook zal er een algehele score worden gegeven aan de hand van de

Likert schaal, variërend van 0 (geen benauwdheid) tot 10 (zeer ernstige benauwdheid). Tevens

zal er een indeling worden gemaakt over de mate van benauwdheid; geen, mild, matig of

ernstige benauwdheid, aan de hand van onderstaande indeling.

Tabel 16. Classificatie van de ernst van inspanningsastma

Ernst van inspanningsastma Maximal daling FEV1 na inspanning (%)

Geen inspanningsastma <10%

Milde inspanningsastma >10% - <25%

Gematigde inspanningsastma >25% - <50% Ernstige inspanningsastma >50% zonder ICS-gebruik

>30% met ICS-gebruik

Opbouw scoringssysteem

De observeerder beoordeelt het kind voorafgaand aan de

inspanning aan de hand van de pre-inspanningsvideo, waarbij er

een inschatting wordt gemaakt of het kind benauwd zal gaan

worden na de inspanning. Vervolgens krijgen de observeerders

de longfunctie voorafgaand aan de inspanning te zien en in de

volgende stap de post-inspanningsvideo. Hierna maken ze

nogmaals een inschatting van de dyspnoe.

Aan de hand van deze scores zal er worden gekeken of het

toevoegen van de longfunctie aan de casus en de pre-

inspanningsvideo (de ‘spreekkamer’ setting) zal zorgen voor een

verbetering van de voorspelling van artsen. Tevens zal gekeken

worden of het toevoegen van een post-inspanningsvideo en

daarmee het door de observeerders zien van de klachten die

optreden tijdens het benauwdheid, het mogelijk maakt de ernst

van EIB in te schatten. Figuur. 13 Beoordelingsmodel


M.H.T. van Hoesel

Casus + pre-inspanningsvideo:

Classification van benauwdheid

Geen (<10%) Mild (≥10 - <25%) Gematigd (≥25 - <50%) Ernstig (≥50%)

Benauwdheidskenmerken

Piepen Aanwezig Afwezig

Verlengd expirium Aanwezig Afwezig

Neusvleugelen Aanwezig Afwezig

Jugulaire intrekkingen Aanwezig Afwezig

Supraclaviculaire intrekkingen Aanwezig Afwezig

Likert scale

Casus + pre-inspanningsvideo + longfunctie



Likert scale


M.H.T. van Hoesel

Post-inspanningsvideo



Benauwdheidskenmerken

Piepen Aanwezig Afwezig

Verlengd expirium Aanwezig Afwezig

Neusvleugelen Aanwezig Afwezig

Jugulaire intrekkingen Aanwezig Afwezig

Supraclaviculaire intrekkingen Aanwezig Afwezig

Likert scale

improving clinical assessment of asthma symptoms by...

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