Linking COPD epidemiology with pediatric asthma care;
implications for the patient and the physician
Erik Melén1,2,3, Stefano Guerra4,5, Jenny Hallberg1,2,3, Deborah
Jarvis6, Sanja Stanojevic7
1Institute of Environmental Medicine, Karolinska Institutet,
Stockholm, Sweden
2Department of Clinical Science and Education, Södersjukhuset,
Karolinska Institutet, Stockholm, Sweden
3Sachs’ Children and Youth Hospital, Södersjukhuset, Stockholm,
Sweden
4Asthma and Airway Disease Research Center, University of
Arizona, Tucson, AZ, USA
5ISGlobal, Barcelona, Spain
6National Heart and Lung Institute, Imperial College, London,
United Kingdom
7Translational Medicine, Hospital for Sick Children, Toronto,
Canada
Corresponding author:
Erik Melén, MD, PhD
Karolinska Institutet, Institute of Environmental Medicine
Nobels väg 13 Box 210, SE- 171 77, Stockholm, Sweden
E-mail: [email protected]
Phone: +46-8-524 87508
Running title:
Childhood Asthma and future COPD risk
Key words:
Asthma, children, COPD, prevention, trajectories.
Introduction
A 10-year-old patient with asthma, diagnosed in early childhood,
with a pre-bronchodilator forced expiratory volume in 1 second
(FEV1) of 75% of predicted attends a routine follow-up visit. The
patient and family perceive his asthma as ‘well controlled’, but
should his physician be concerned about his reduced lung function?
What are the implications of a lower than expected FEV1 in
childhood on the respiratory health of this patient in adulthood?
Lung function is known to track with age1, and there is a high
likelihood that this patient will enter adulthood with a
sub-optimal lung function. A FEV1 measurement less than 80%
predicted would characterize this patient as a high-risk patient
for later chronic airflow limitation, or even chronic obstructive
pulmonary disease (COPD) according to recent studies.2 How does
this apply to a young child, and how can we use the information to
better understand whether early, targeted intervention is
warranted?
COPD is estimated by the WHO to become the 3rd leading cause of
death by 20303, which urges for preventive actions as early as
possible. By the age of 50-60 years, low lung function trajectories
that are associated with early life exposures and developmental
processes, may contribute up to 75% of COPD burden.4 Can we
translate findings from longitudinal epidemiologic studies to
individual risk predictions and preventive guidelines in our
pediatric care? Should we take action immediately to preserve lung
function in this patient or should we hope for lung function
catch-up with age? The evidence from longitudinal cohort studies
around the world is clear – the lower the lung function in
childhood and young adulthood, the higher the risk of COPD and the
higher the risk of premature death.2,5 But how do you communicate
long-term risks for chronic airflow limitation to a 10-year-old boy
and his parents (Figure 1)? In this review, we discuss the clinical
implementations of recent epidemiological respiratory studies and
the importance of preserved lung health across the life course.
Also, we evaluate available clinical tools, primarily lung function
measures, and profiles of risk factors, including biomarkers, that
may help identifying children at risk of chronic airway disease in
adulthood.
Preserved lung health across the life course
To date, epidemiological studies that have examined risk factors
for low lung function across the life course have usually reported
on lung function measures from forced expiratory spirometric
manoeuvres. Factors associated with lower forced vital capacity,
FVC, which can be related to low total lung capacity, are not
necessarily associated with airway obstruction (FEV1/FVC).
Sometimes reports describe relationships with FEV1 without mention
of its relationship with FVC, which means that the associations
with FEV1 may be telling us about either airway obstruction or
about ‘lung volume’. With this in mind, what information should we
take from the available studies to inform clinical advice and
management of patients with asthma and low lung function at the age
of 10 years?
The ’double jeopardy’The clear signals emerging from studies
that have examined lung function in pediatric cohorts is that
children with low FEV1 and FEV1/FVC become young adults with low
maximally attained lung function in their mid 20’s.4,6,7 While the
childhood studies suggest that in young adulthood, those with
asthma already have lower lung function, the adults studies show
they go on to have more rapid decline.8 This ‘double jeopardy’ is
of concern and one of the major interventions open to physicians is
to ensure effective treatment of disease. There are no (and never
will be) real long-term randomised controlled trials to test
whether daily treatment with inhaled steroids (or other
medications) prevents the excess decline in FEV1, but current
observational evidence, some of which spans twenty years or more,
of follow-up in adults suggest this may be the case particularly if
there is evidence of underlying atopy.9
The benefits of healthy lifestyle across the life-course To
date, there are few factors that appear likely to alter the
persistent low lung function trajectory seen through the teenage
years. As with all patients, it is important that physicians
emphasise the role of healthy lifestyles on lung health in those
showing evidence of low lung function in childhood. One major study
has identified a group of children (8% of the population-based
sample studied) who followed a trajectory suggestive of ‘catch-up’
growth from a low FEV1 at age 7 to a normal maximal FEV1.4 These
children were more likely to be underweight at age 7 and to be
female. The likely importance of body composition on lung function
growth is supported by work showing that higher lean body mass
during childhood and adolescence was associated with higher levels
of growth in FEV1, FVC and FEF25-75% between 8 and 15 years while
higher fat mass was associated with lower growth in FEV1/FVC.10
Such observations could be explained by positive effects of
nutritional factors within a healthy diet and/or by levels of
physical activity. Adolescents, particularly girls, have better FVC
(not FEV1/FVC) if they are more physically active in the previous
years.11
Taken as a whole, these observations emphasise the potential
benefits of healthy lifestyles during adolescence to increase the
chance that maximally attained lung function is at its greatest by
adulthood. Such measures may impact on other physiological
processes and will also be beneficial for prevention of other
diseases. Poor diet, obesity and low physical activity may promote
early puberty12 and children with early puberty have lower lung
function as adults – but this association is largely seen with FVC
rather than airway obstruction.13 This observation is interpreted
as a failure to reach the expected maximal lung function and has
been investigated and confirmed using sophisticated Mendelian
Randomisation approaches.14
The impact of adult smoking on lung function decline remains the
major cause of fixed airway obstruction in later life, but smoking
during adolescence may equally impact on lung development through
the teenage years.15 There is conflicting evidence whether the
effect of smoking and asthma are additive or multiplicative risks
for poor lung growth and excess lung function decline, but there is
every reason to strongly advocate the complete avoidance of smoking
in any child or adult with asthma and/or low lung function. One
study from childhood to later adult life indicated the presence of
a group of children (4% of the population-based sample studied)
following a lung function trajectory characterised by failure to
achieve maximal FEV1 followed by a rapid decline in FEV1. Within
this group both smokers and those with childhood asthma were
over-represented and almost half had developed fixed airway
obstruction by their mid 50’s.4 In those who do smoke there is
evidence that diets rich in anti-oxidants16 and remaining
physically active17 may modify lung function decline - yet further
evidence of the importance of healthy lifestyles on maintenance of
lung function.
Patients and their families will be concerned over the potential
effect of traffic related air pollution on their lung health.
Traffic related pollution at the levels observed in most of Western
Europe has yet to be shown to have major deleterious effect on lung
function decline in adults.18 However, its impact on lung growth in
children has been reported in numerous studies, which suggest that
air pollution has an adverse effect on both FVC and FEV1.19,20
Relevance of occupational exposuresCross-sectional and
longitudinal studies suggest that up to 15% of COPD in adult life
could be related to exposures to vapours, gases, dust and fumes in
the work place.21,22 Substances that have been linked to COPD
include cadmium dust and fumes, mineral dusts, welding fumes, grain
and flour dusts, organic dusts and silica dusts. Such exposures may
add to risk of chronic air flow limitation and COPD in children
with asthma and low lung function, but to date there is little
evidence these children are particularly susceptible to such
exposures. It is an employer’s duty to provide a safe working
environment for all their workers through minimising harmful
airborne agents, provision of respiratory protection equipment and
appropriate health surveillance. However, anyone who as a child had
low lung function and asthma should remain alert to the potential
harms of their job. One of the occupational exposures that has
gained particular attention more recently is increased lung
function decline in those exposed to cleaning agents.23 The
mechanism of action is unknown but the observation has wider
implications for the use of cleaning products in the home where it
would appear wise to minimise their use and avoid cleaning sprays
where possible.
Lung function measures to identify children at risk
Spirometry: Population vs individual measures
One of the primary reasons that spirometry (and FEV1) is used to
diagnose and monitor lung disease is that it tracks well with time
in both healthy populations and those with respiratory disease, and
most of the evidence linking early determinants of lung disease
across the life course is based on spirometry findings. However,
translation of epidemiological evidence to the individual patient
is not straight forward. A single low measure of lung function may
not represent an accurate estimate of an individual’s risk of later
obstructive disease, whereas repeated measurements may indicate
persistent reduction or rapid decline in lung function over time,
which are more likely to be associated with an increased risk of
COPD in early adulthood.24 In the case of the 10-year-old boy with
asthma, the interpretation of his reduced lung function must
consider the uncertainty of the measurement and prognosis, as well
as the age-related changes observed in the healthy population. The
spirometry result must be put in context of the clinical and family
history of the patient, as well as the current symptoms, and the
mental health implications of an early diagnosis for which
treatment options carry their own burden and risk factors.
Standardization of spirometry equipment, protocols and quality
control has meant that we can now obtain high quality objective
measures of lung function across the life span.25,26 In many
specialised research centres it is feasible to conduct high quality
spirometry in children as young as 3 years.27,28 Translation of
spirometry from a specialised test conducted in pulmonary function
laboratories to the primary care setting has had mixed
results29,30, especially for children for whom extra patience and a
friendly environment are necessary to obtain reliable measurements.
Early deficits in lung function may already be present by the time
objective measurements of lung function are feasible to obtain,
which represents yet another challenge.31 The critical window for
intervention may also depend on the specific exposures and risk
factors in an individual, in which case monitoring of lung function
should begin shortly after birth for some children. At present,
measurement of lung function during infancy is limited to a few
specialised centres32 and interpretation of results remains
challenging.
Another issue is the interpretation of spirometry results,
particularly in children. The range of lung function values
observed in healthy children is wide33, and an individual within
the persistently low lung function trajectory of an epidemiological
study can be well within the normal range. Indeed, children with
well controlled asthma often have lung function values within the
normal range. In addition, most populations used to define ‘normal’
lung function are based on cross-sectional samples of the
population that are free of a history of respiratory disease at the
time spirometry is measured, and may very well go on to have
respiratory disease at some time in the future. Therefore, the
normal range may be artificially wide and may miss early signs of
lung disease. Spirometry is also more variable in young children,
and it may be difficult to identify specific patients at risk of
disease with a high degree of confidence.
Further, the most commonly used measure of spirometry defined
COPD is an FEV1/FVC ratio of less than 70%; however, the definition
varies by study and population with some studies including a
post-bronchodilator reduction in FEV1/FVC, others using a
combination of deficits in FEV1 and the FEV1/FVC ratio, while other
studies use an age-specific lower limit of normal. Remarkably,
while the prevalence of COPD differs based on the criteria, the
risk factors for disease are similar regardless of the definition
used (for a given disease phenotype). In young children, FEV1 and
FVC are nearly equivalent, which further complicates interpretation
of the ratio. Applying these adult based cut-points in children and
young adults (like FEV1/FVC<70%) to identify a high risk group
is problematic, and would inevitably miss a large proportion of
patients at risk for COPD later in life. If low lung function in
childhood persists, then the 10-year old boy may be at risk of COPD
later in life. What remains challenging is how we determine who is
at high risk based on childhood measures, and what if any
intervention is appropriate to reduce the risk of later
disease.
At present, children with lung function values outside the range
observed in health, or in the lower range of healthy, may benefit
from more comprehensive lung function tests to determine the
underlying pathophysiology and best treatment options. For example,
bronchodilator or bronchoprovocation testing can help distinguish
fixed and reversible deficits and may help guide treatment
decisions. Although fixed airflow limitation is rare in childhood,
in children with asthma, poor bronchodilator response and increased
airway hyper responsiveness are risk factors for irreversible
airway obstruction in adulthood.24
Beyond spirometryThere are several sensitive physiological lung
function tests that may indicate disease in the smaller airways,
and therefore may be a more accurate way to identify early lung
disease or potentially, to provide a predictive risk indicator for
individuals likely to have poor lung function in the future. For
example, lung function tests such the forced oscillation technique
or the multiple breath washout (MBW) may provide complementary
evidence to the spirometry outcomes.
There is evidence that ventilation inhomogeneity (measured by
MBW), a marker of poor gas mixing efficiency, is worse in patients
with COPD compared with healthy controls.34 In addition, MBW
indices (lung clearing index, LCI) increased across the GOLD
grading criteria for spirometry suggesting that it may provide
complementary information to spirometry.34 Furthermore, lower
values of LCI measured in men at age 55 were associated with future
development of pulmonary obstruction and increased incidence of
COPD hospitalization later in life.35 There is currently no
evidence from longitudinal studies of ventilation inhomogeneity
measurements in childhood with outcomes in early adulthood.
In children, there is less convincing evidence that MBW
distinguishes between patients with asthma and healthy controls,
with some smaller studies demonstrating small differences on the
population level,36-39 with others showing no differences. In a
large Cohort study of 646 children, MBW was not able to distinguish
children with persistent asthma symptoms from controls.40,41
However, in all of these studies, there were individual children
with ventilation inhomogeneity values well outside the normal
range. Many MBW studies also used the Scond index, a measure of gas
mixing efficiency in the larger airways where convection is the
primary mode of gas transport (as opposed to the small
airways/diffusion) to distinguish between health and
asthma.39,42-44 To date, the Scond outcome has yet to be fully
integrated into all commercial devices, and is also not straight
forward to explain to patients. To better understand the utility of
MBW tests in children, longitudinal data are needed to define how
these tests can be used to identify high risk individuals.
Impulse oscillometry (IOS) is a non‐invasive forced oscillation
method that provides information on airway resistance and
reactance. IOS has been evaluated both as an additional and
alternative option to spirometry. Given its simplicity, the method
is feasible in children as young as 2-3 years. IOS measures
during preschool years has been associated with spirometric lung
function in adolescence, albeit with a wide spread of data and
uncertainty around the estimates.45 In cross-sectional studies, the
IOS method was more sensitive than spirometry in differencing very
young asthmatic from healthy children46-48, and has also been shown
to correlate to disease severity and risk of exacerbation of both
children and adults with asthma.49,50 Further, peripheral airway
obstruction measured by IOS is suggested as a feature related to
the eosinophilic inflammation in allergic asthma.51 In patients
with COPD, IOS indices have been related to disease grading52,
symptoms53 and health status54, indicating that the method may
provide additional information to spirometry also on the
physiopathology of fixed airway obstruction. However, the potential
value of the method for finding individuals at risk for future
airflow obstruction remains to be studied.
In summary, both MBW and IOS have been applied in numerous
research studies, but have yet not been widely implemented in
clinical practice. The utility of MBW and FOT at the individual
level has yet to be defined, and both tests require expensive
equipment, trained personnel and time to perform the test compared
with spirometry.
Risk profiles
Lessons from birth cohorts and longitudinal studies
Given the established evidence of long term implications, it
becomes critical to establish risk factors that can be used to
identify children with asthma who, as adults, will go on to develop
COPD-like phenotypes (first and foremost irreversible airflow
limitation). Once this group of at-risk patients is identified, we
can determine whether the trajectory towards early COPD can be
modified.
Epidemiological evidence has consistently shown that the
frequency and severity of asthma-like symptoms is one of the
strongest predictors of the likelihood of developing lung function
deficits in adult life. In the Dunedin Multidisciplinary Health and
Development Study, participants with persistent wheezing had the
lowest levels of the FEV1/FVC ratio from age 9 years well into
their adult life55. Similarly, in the Melbourne study – a
longitudinal cohort study enriched for cases of severe asthma – the
group of participants who had severe asthma at age 10 was
characterized by lower levels of FEV1 and FEV1/FVC and by a greater
than 30-fold increased risk for COPD (defined as FEV1/FVC < 70%
after bronchodilator) by age 507,56. Indeed, as shown repeatedly by
birth cohort studies57-59, the link between recurrent asthma-like
symptoms (mainly persistent wheezing) and lung function deficits
begins at or even before school-age and tracks over time as
patients transition from childhood into adult life. Consequently,
among patients with asthma, low lung function in childhood strongly
predicts not only the risk of developing chronic airflow limitation
by adult life24 but also that of having persistent disease60,61,
suggesting a profound and possibly bi-directional link between
these two phenotypes.
If persistent childhood asthma is a strong risk factor for the
development of chronic lung function deficits into adult life, then
factors that increase the risk for the persistence of asthma may,
in turn, help identifying patients at risk for its long-term
sequela of COPD development. Atopy – as defined by specific IgE in
circulation or skin test sensitization – has emerged as a
consistent risk factor for forms of childhood asthma that persist
into adulthood. This is particularly true for atopic sensitization
that is already present early in life and directed towards multiple
allergens57,62. Consistent with this scenario, by using latent
class analysis on multiple dimensions of atopy, a recent study
identified a class of children with “severe atopy” that was
strongly associated with asthma and lung function deficits and
found the intensity of specific IgE production early in life to be
its main feature affecting asthma risk63. Children with asthma who
present simultaneously with rhinitis and/or eczema have been also
shown to be at increased risk of persistent disease. Among
participants with childhood asthma in the Tasmanian Longitudinal
Health Study, the co-existence of eczema and rhinitis increased
their risk of having persistent asthma in adult life by nearly 12
times64. Bronchial hyper-responsiveness is another characteristic
of children with asthma that is predictive of persistent disease.
In the Tucson Children’s Respiratory Study (TCRS), bronchial
hyper-responsiveness to cold dry air at age 6 years increased the
risk for chronic asthma (i.e., asthma that was active both in
childhood and adulthood) by 4.5-fold, whereas this effect was much
weaker and non-significant for inactive asthma (i.e., asthma that
remitted in adult life)65. In the same birth cohort, among
participants with childhood asthma, being overweight or obese at
age 11 was also associated with a nearly 9-fold increased risk of
having persistent disease after the onset of puberty66. In addition
to these factors, when predicting persistence of asthma, attention
should be given to possible influences by sex (increased risk in
females has been described in multiple but not all population-based
studies55,56,67), race/ethnicity68, and socio-economic status
(particularly low parental education69), as well as to events that
may have occurred in early life. Among the latter, of particular
interest are early lower respiratory illnesses70 (LRIs). In TCRS,
participants who had radiologically ascertained pneumonia by age 3
had increased risk for active asthma and deficits in FEV1,
FEV1/FVC, and FEF25-25% that tracked from age 11 to 26 years71.
Other types of early LRIs were associated with similar, though
milder, trajectories of lung function deficits.
Molecular biomarkersDespite the tremendous progress made in
determining these and other early risk factors for lung function
deficits1, to what extent these characteristics can be used in an
effective and reproducible way to identify ahead of time children
with asthma who will go on to develop COPD-like phenotypes remains
elusive. While multiple prediction models (reviewed by Smit et
al72) have been developed to identify pre-school children with
wheezing who will have asthma in childhood, there is a paucity of
population-based studies that have systematically attempted a
similar approach to predict persistence and long-term sequelae of
childhood asthma into adult life. One of the reasons is that this
type of studies require large numbers of participants followed for
many years with repeated assessments of lung outcomes from
childhood well into their adult life. As of today, only a small
number of epidemiological studies have this type of data
available.
In this context, there has been growing interest by the
scientific community in exploring the contribution that molecular
biomarkers73 may provide not only to improve the performance of the
above risk factors in predicting children with asthma who will
progress into COPD, but also to identify possible endotypes and, in
turn, possible therapeutic targets for such progression. Apart from
IgE and skin test sensitization as discussed above, eosinophils in
circulation have been one of the biomarkers most extensively
studied in the context of the natural history of asthma and
multiple studies have found them positively associated with
persistent disease. In the TESAOD cohort, blood eosinophilia was
the strongest risk factor for developing persistent airflow
limitation among asthmatics with disease onset before age 2574 and
in the CAMP study eosinophil count in childhood was inversely
associated with remission of asthma in adult life60. In the latter
study, by combining information on better lung function, decreased
airway responsiveness, and lower eosinophil count in childhood, the
authors identified a group of patients with asthma who had a
greater than 80% probability of disease remission in adult life.
Related to these observations, the fraction of exhaled nitric oxide
(FeNO, a possible marker of eosinophilic airway inflammation), when
assessed among symptomatic pre-school children, was also found to
improve the prediction of subsequent active asthma at school
age75,76.
Additional potential biomarkers are emerging from omics-based
discovery studies. Although in asthma (as for most other complex
diseases) genetic variants that have been identified by GWAS
studies carry relatively small increases in disease risk77, the
strategy to combine information from multiple variants into genetic
scores has shown promising results. Interestingly, in the Dunedin
cohort a genetic risk score generated from 15 asthma-related single
nucleotide polymorphisms (SNPs) predicted life-course persistent
asthma and development of irreversible airflow limitation by adult
age among participants with childhood asthma, suggesting that this
polygenic approach may provide helpful information to predict the
natural history of the disease78. In the same cohort, life-course
persistent asthma was also associated with shorter leukocyte
telomere length in mid-adult life79, although it is unknown whether
this association would hold true earlier in life. Genetic scores
based on SNPs linked to adult lung function have been also
associated with lung function levels in childhood80 and lung
function trajectories from childhood into adult life6, but the
extent to which they may be involved in the development of chronic
lung function deficits among patients with asthma remains to be
determined. Contributions from other omics fields (from
epigenomics, transcriptomics down to proteomics and metabolomics)
are growing exponentially81, but these biomarkers have been rarely
evaluated in the context of prediction for asthma progression and
at the present time there are no validated molecular tools for
early risk stratification of development of chronic airflow
limitation and long-term sequelae of childhood asthma. In this
context, molecules that have been associated with both asthma
persistence and lung function deficits from childhood into adult
life, such as low levels of the pneumoprotein Club cell secretory
protein 16 (CC16)82,83, represent select candidates for further
investigation.
Conclusions
In this report, we have discussed the clinical implications of
recent longitudinal cohort studies on lung function and respiratory
health, also captured in the early origins of chronic airway
disease concept.84 The importance of preserved lung health across
the life course is reinforced, but translating population level
results to the individual patient in the pediatric care setting is
not straight forward (see Facts box). Any clinician would agree
that a single low lung function value in childhood may not be
sufficient to warrant pharmacotherapy, but a series of pulmonary
function tests that indicate airway obstruction would provide a
constellation of evidence to support early intervention. Treatment
plans that go beyond medication, including investigation of risk
factors in the household and environment, as well as encouragement
of a healthy lifestyle in general, will likely have a more profound
impact on the overall risk of lung disease in adulthood. Yet, we
acknowledge the difficulties to make correct diagnosis of chronic
airway disease in children and adolescents beyond asthma.
We conclude that there is a need for studies specifically
designed to evaluate performance of prediction of risk profiles
taking lung function indices, clinical data and molecular markers
into account for long-term sequelae of childhood asthma. MBW and
FOT techniques are promising as a supplement to spirometry in order
to capture disease in more detail. However, the prognostic value of
these methods needs to be assessed in longitudinal studies.
Emerging data suggest very early epigenetic changes in relation to
asthma85, some of which may be detected already at birth86,87, but
the long-term disease risk and outcomes remain to be elucidated.
Ideally, biomarkers should be analytically robust, easy to measure,
and non-invasive, the latter particularly important in pediatric
care settings. Promising early biomarkers for chronic airway
disease are now under study (e.g. CC1682,83), but we encourage
large-scale efforts in this research field in order to find the
most informative and clinically useful candidates.
Acknowledgements
This article was initiated during the three-day workshop
“Respiratory and allergic diseases from childhood to adulthood”
held in Stockholm, Sweden, August 23-25 2019. The workshop was
funded by the Swedish Heart-Lung Foundation, the Swedish Asthma and
Allergy Foundation, the Aii (allergy, immunology and inflammation)
doctoral programme at Karolinska Institutet and the BAMSE Study
(https://ki.se/en/imm/bamse-project). EM is supported by a grant
from the European Research Council (n° 757919). This article also
incorporates results and emerging evidence from the Ageing Lungs in
European Cohorts study (www.alecstudy.org) funded through the
European Union’s Horizon 2020 research and innovation programme
(Grant agreement No 633212).
Author Contributions
EM conceived and designed the study. SG, JH, DJ and SS
contributed expertise knowledge in the field. All co-authors
contributed equally in writing and finalizing the manuscript.
Conflict of interest
The authors have no conflict of interest in relation to this
work.
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From childhood to adulthood; clinical implications [in a Facts
box]
· Impaired lung function in childhood is associated with chronic
airway obstruction in adulthood. This risk is particularly strong
in persistent and severe forms of childhood asthma.
· In numbers, one to two in ten children with low lung function
will develop chronic airway obstruction in adulthood.
· Complete avoidance of smoking in any child or adult with
asthma and/or low lung function is recommended. Benefits of healthy
lifestyles are underscored.
· Translating population level results to the individual patient
in the pediatric care setting is, however, not straight
forward.
· Asthma control remains a clinical priority, despite its
effects to prevent long-term lung function deficits need to be
better understood.
· Repeated spirometry measures supplemented with assessment of
small airway involvement give insights about underlying
pathophysiology.
· Risk prediction models for long-term sequelae of childhood
asthma taking lung function indices, clinical data and molecular
markers into account are warranted.
Legend to Figure 1 [final figure in preparation; draft as
uploaded]:
Although we know that impaired lung function in childhood is
associated with chronic airway obstruction in adulthood,
translating population level results to the individual patient in
the pediatric care setting is not straight forward. Risk prediction
models for long-term sequelae of childhood asthma taking lung
function indices, clinical data and molecular markers into account
are warranted.