Discussion
After a continuous rise in the prevalence of wheeze/asthma since 1978
and a phase of stabilization from 2003 to 2008, the sixth (2013) and
seventh (2018) follow-up surveys of Patras epidemiological study showed
a continuing decline in wheeze/asthma rates among 8- and 9-year-old
schoolchildren in Greece.
Interestingly, persistent and non-current wheeze/asthma followed this
overall trend, while the prevalence of recent-onset disease remained
essentially unchanged. In our surveys, both the persistent and the
non-current group included children in whom wheeze/asthma was diagnosed
more than two years prior to the survey, whereas the recent-onset group
consisted of children with symptoms that were manifested more recently
(i.e. solely within the last two years). It seems, therefore, that the
prevalence trends of childhood wheeze/asthma in Patras were primarily
determined by changes in the dissemination of wheeze/asthma diagnosis at
younger ages (i.e. to children younger than 6-7 years).
It is worth noting that the diagnosis of asthma was also particularly
applied to persistent and non-current wheezers (Figure 3), i.e., to
children in whom the onset of wheeze occurred at preschool age.
Conversely, asthma was reported at significantly lower rates in children
with recent-onset wheeze. These findings suggest that Greek
paediatricians tend to assign the diagnosis of asthma to preschoolers
with troublesome respiratory symptoms, thus resulting in transfer of
asthma diagnosis towards younger ages. Conversely, asthma may be
underdiagnosed and therefore undertreated in older children with
recent-onset symptoms. Our spirometric findings of lower
FEV1 and FEV1/FVC in recent-onset
wheezers/asthmatics (see below) reinforce the above assumption.
Many studies from Europe, North America and other parts of the world
have reported an increase in the prevalence of asthma through the late
1990s1-7,13,18. However, studies of the last 20 years
have shown that the ‘asthma epidemic’ has reached a peak and may even be
declining in high prevalence societies8-18. A series
of repeated surveys from 1964 to 2014 in the city of Aberdeen, Scotland,
indicate a continuing decline in asthma prevalence after 2004 among the
5-12-years-old schoolchildren14,15; after its peak in
2004 (29.5%), the prevalence of lifetime asthma (i.e. ever-had asthma)
declined to 22.7% in 2009 and to 18.6% in 2014, i.e. lower than the
1994 levels (19.5%)14,15. Data from the National
Health Interview Survey also indicate a decrease in the prevalence of
current childhood asthma in the USA, from 9.6% in 2009 to 8.4% in
201718,23.
The Patras epidemiological study is one of the longest worldwide (40
years; second only to the Aberdeen study) that has captured the
prevalence of childhood asthma at several time points by using identical
methodology. The two most recent surveys of 2013 and 2018, showed -for
the first time- a decline in wheeze/asthma prevalence: from 6.9% in
2008 to 5.2% in 2013 and 4.3% in 2018 for current wheeze/asthma, and
from 12.6% in 2008 to 9.6% in 2013 and 6.6% in 2018 for lifetime
wheeze/asthma. These rates are two- to almost four-fold lower than those
reported in the Aberdeen and other studies14,15,18,24,
which may be attributed to the more ‘restrictive’ phrasing of our
questionnaire (i.e. physician-diagnosed wheeze/asthma) and the prompting
of parents to respond with a negative answer if in doubt. Nevertheless,
the relative prevalence changes between Patras surveys (Figure 2) are
comparable to those of the Aberdeen19.
In contrast to the ‘asthma epidemic’ of the 1980s and 1990s, the
reversed trends in the prevalence of childhood asthma are difficult to
explain. Although the decline has been generally attributed to lifestyle
changes or/and to improved diagnostic and management
practices12,15,25, such causal relationships have not
been proven to date. Our study was not designed to evaluate the
influence of various risk factors on asthma prevalence. However, it is
highly unlikely that lifestyle and environmental parameters (allergen
exposure, viral epidemics, nutrition, overweight/obesity, physical
activity, atmospheric pollution, etc)26 have shifted
during the last decade in a manner that would favor a substantial
decline in asthma prevalence. The increase in disease awareness in
association with the broad dissemination of pediatric asthma guidelines
and the establishment of controller therapy, may have led to the
significant reduction of asthma admissions since the early 1990s in
Athens, Greece,27 i.e. in an urban environment similar
to ours. However, the decrease in admission rates occurred almost two
decades before the decline in asthma prevalence that we report herein
and was noted in a period during which childhood asthma rates were in
fact still increasing.
Based on our analysis, we maintain that the course of childhood asthma
prevalence over the past decades largely reflects the changing
perceptions regarding the disease among the physicians and/or
parents28, especially in the case of younger children
with troublesome respiratory symptoms. The diagnostic transfer at
younger ages most likely reflects the ‘asthma fashion’ of the last two
decades of the 20th century29, when
broad dissemination of asthma guidelines among physicians
occurred30. To the best of our knowledge, the present
study is the only one to evaluate physician-diagnosed wheeze and asthma,
both separately and in relation to their onset and duration (i.e.,
recent-onset, non-current, and persistent) over a period of three
decades. Furthermore, in the 2018 study, all children with at least one
positive answer to wheeze/asthma questions (recent-onset, persistent,
and non-current wheezers/asthmatics) and a random sample of those with
negative responses (healthy controls) were invited to perform
spirometry. Participants with recent-onset wheeze/asthma had
significantly lower FEV1 and FEV1/FVC
(i.e. an obstructive spirometric pattern) as compared to all other
groups; their FEF25-75 values were also lower than those
of healthy controls. These results, together with the fact that the
diagnosis of asthma was less frequently assigned to recent-onset
wheezers, suggest that asthma which occurs at late preschool age may
have been underdiagnosed and thus remained under suboptimal treatment in
our population. On the other hand, children with persistent
wheeze/asthma also had lower FEV1/FVC compared to
healthy controls, although the FEV1 did not differ
between the two groups. However, the distribution of
FEV1 values in the persistent wheeze/asthma group was
wide, thus including many cases with low FEV1 (Figure
4). Indeed, when only children with relatively low FEV1(i.e. less than -1 z-score) were considered, we found that both
persistent and recent-onset wheezers/asthmatics were overrepresented.
The latter finding is important, because it suggests that a considerable
percentage of preschool wheezers in whom the symptoms persist at school
age may exhibit decreased lung function. The cross-sectional design of
our study does not permit to draw further conclusions on the
trajectories of lung function in relation to the natural history of
wheeze/asthma in this group.
The limitations of studies based on written asthma questionnaires have
been addressed repeatedly; still, such studies remain the single most
useful tool to obtain information from large numbers of
participants13,19,24,31,32, It has also been
established that the understanding of the term ‘wheeze’ differs greatly
between parents and physicians33,34. In our surveys,
however, parents were asked to report not on the symptom as perceived by
themselves but on wheeze diagnosed by a physician. The reporting of
physician-diagnosed asthma was almost always accompanied by reporting of
physician-diagnosed wheeze; equivocal answers were resolved by telephone
contact and, if still doubtful, they were excluded from analysis. Cough
was not included in our questionnaire; it is our conviction that in
order to maintain the results between surveys comparable the phrasing of
the previous set of questions (1991, 1998, 2003, 2008) should not be
altered. Moreover, the inclusion of persistent or recurrent cough
without wheeze in the diagnosis of childhood asthma has been
challenged35,36.
In conclusion, the results of seven identical surveys over a 40-year
period show that the prevalence of childhood wheeze/asthma in Greece
declines continuously since its peak during the 2003-2008 period. This
reversing trend is most likely the result of changing asthma perceptions
among physicians and/or parents, especially in the case of preschool
children with troublesome respiratory symptoms. Concurrently, however,
true asthma may be underdiagnosed and thus remain under suboptimal
treatment. The lower lung function of children with recent-onset
wheeze/asthma and of a considerable fraction of those with persistent
disease, further strengthens the above hypothesis.