Discussion
There were three primary findings of this prospective cohort study on
predictive factors for asthma in young adults after hospitalization for
viral wheezing episodes aged younger than 24 months. First, early life
wheezing, an asthma diagnosis one year after the index hospital
admission and physician-diagnosed asthma at median ages of 4.0, 7.2 and
12.3 years were consistently associated with asthma at a mean age of
18.8 years (n = 49). Second, asthma in parents and atopic
dermatitis in infancy were associated with asthma in early adulthood.
Third, elevated blood eosinophils on the index hospital admission for
viral wheezing episodes aged < 24 months were associated with
asthma in early adulthood. No such associations were found for other
markers of eosinophilic activity or laboratory markers of atopy. As
expected, asthma in early adulthood was associated with current allergy
and atopic sensitization. When the analyses were repeated and adjusted
for sex, age on admission, contact with household pets in infancy,
early-life exposure to tobacco smoke and current daily smoking, asthma
in parents marginally lost its significance. As we reported
previously,17 RSV and especially rhinovirus
infections, linked to the index wheezing episode requiring
hospitalization, were associated with asthma in early adulthood compared
to population controls.
In the present study, an asthma diagnosis at any of the four follow-up
visits until a mean age of 12.3 years was associated with an increased
risk of asthma at a mean age of 18.8 years. In a Swedish
post-bronchiolitis cohort, the risk of asthma in later life (i.e. 27
years) was 10-fold higher than in population-based
controls.7 In the same study, although an asthma
diagnosis at the age of 5 or 10 years did not predict asthma in
adulthood, an asthma diagnosis at the age of 18 years increased the risk
of asthma at the age of 27 years significantly to
6.5-fold.7 In the present cohort study, the risk of
asthma aged 18.8 years was increased most (22-fold) among those with
asthma aged 12.3 years. This finding is in line with the current
consensus on asthma evolution and age,23 whereby
wheezing in infants and asthma in toddlers seem to improve at school
age.6,7 The latter does not imply total recovery but
rather symptom remission, and relapses are common after puberty and in
early adulthood.6,7 Such relapses may remain
undiagnosed because adolescents and young adults are reluctant to
consult a doctor for asthma-related symptoms due to denying their
symptoms and negative perceptions of the disease among their peers4
In previous birth cohort and post-bronchiolitis studies, asthma in
family members, especially mothers, was the most common risk factor for
asthma in later life,1,4,7 as found in the present
cohort. In a meta-analysis, which included 18 studies from good-quality
systematic reviews, maternal asthma was associated with a 3.2-fold risk
and paternal asthma with a 2.6 fold risk of physician-diagnosed asthma
aged 5–18 years.11 Prenatal environmental tobacco
smoke exposure and premature births, particularly very preterm births,
were other significant early-life risk factors for later
asthma.11 Although some studies found that atopic
dermatitis in infancy was associated with asthma in later life, this
association was not constant.4,7
Tobacco smoke exposure during prenatal and early childhood periods are
well-known risk factors for bronchiolitis or viral wheezing in early
life and asthma and lung function deficiency even in
adulthood.23 However, neither maternal smoking nor
passive smoke exposure in early childhood was associated with asthma in
young adulthood in the present study. This finding may be explained by
early exposure to tobacco smoke increasing the likelihood of
hospitalization for viral wheezing episodes at young age and decreasing
the statistical power for asthma prediction in later years in the
within-cohort analyses. Slightly more than half (51.0%) of the study
group had exposure to tobacco smoke during infancy, and 48% of these
individuals were current smokers at the time of last follow-up visit.
The prevalence of smoking in our study group far exceeded that of the
current prevalence of smoking (mean: 11%) among young Finnish
adults.24
In algorithms aimed at predicting the risk of asthma in school-aged
children, a high eosinophil count (i.e. an absolute count of ≥0.45 ×
109/L) at preschool age has been linked to an elevated
risk of asthma at later life.25 It should be noted
that eosinophil sampling during an infection, as in the present study,
is not optimal, as infections often trigger a decrease in
eosinophils.26 Thus, the finding of a normal
eosinophil count in such cases would actually be abnormal
finding.26
The association of asthma with respiratory allergies is well known and
is termed united airway disease.27 Previous Swedish
and Finnish cohort studies investigated risk factors for asthma in 46
patients with a diagnosis of RSV-related bronchiolitis in childhood who
were followed up at a mean age of 18 years8 and 82
patients with a diagnosis of bronchiolitis in childhood who were
followed up at a mean age of 27 years, resepectively.9Both studies reported that current allergy, especially allergic
rhinoconjunctivitis, was a significant risk factor for asthma in
adulthood.8,9 In the present cohort, more than 75% of
those with current asthma reported allergic rhinitis and/or were
sensitized to airborne allergens.
RSV and especially rhinovirus infections, when associated with wheezing
in early childhood, is known to be associated with an increased risk of
asthma in later life.3,11,28 On the other hand, a
Danish cohort study on 313 children found that the number of respiratory
infections in the first years of life, independently from the causative
viral agents, was associated with asthma at the age of 7
years.29 As described earlier, hospitalization in
early childhood because of viral wheezing episodes increased the risk of
asthma in adulthood compared to controls in this cohort, and rhinovirus
increased the risk more than other viruses.17
The prevalence of asthma in our cohort was much higher (53%) than that
found in other prospective post-bronchiolitis follow-ups until adulthood
conducted in Finland and Sweden, which reported asthma in 18% and 39%,
respectively, of cohort subjects aged 18–29 years.7-9There are no other, similar published prospective, longitudinal studies
on patients hospitalized for viral wheezing episodes and followed up
until adulthood. An increasing trend of asthma prevalence by time was
clearly seen in these Finnish and Swedish studies; new studies reported
a higher asthma prevalence than old studies. Thus, the prevalence of
asthma in our study (53%) is in line with the current trend, although
higher than expected since the allergy and asthma epidemics have
decreased also in Nordic countries.30 In non-selected
birth cohorts, the prevalence of asthma varied from 12% to 15% in
longitudinal studies on adolescents and young adults aged 11–24
years.31 The prevalence of asthma among Finnish adults
was 10.9% in a population-based survey based on data collected using
postal questionnaires.30 The higher prevalence of
asthma among this cohort population might be due to participation bias -
individuals with asthma-related symptoms more likely to volunteer for
follow-up visits than those without symptoms.
Our cohort study had some limitations. The most important limitation was
the small number of participants, which resulted in underpowered
analyses and a risk of type-2 errors. On the other hand, all the
factors, such as previous asthma diagnoses at different ages through
childhood, that showed statistically significant associations in the
multivariate analyses in this small material, confirmed a real
association with high asthma risk after early life viral wheezing
episodes. Moreover, this cohort has been followed for more than 18
years, and therefore, dropouts are understandable. In terms of the
strengths of the study, the cohort offers unique longitudinal data on
the associations of viral wheezing episodes requiring hospitalization,
early childhood wheezing and asthma at preschool age with asthma
outcomes in adulthood.
In conclusion, this cohort study confirmed the results of previous
studies that an asthma diagnosis at any age during childhood and an
increased blood eosinophil count in early childhood are independent
predictive factors for asthma in early adulthood.