Discussion
The main finding of these prospective population-based cohort studies
was that the incidence of asthma among adults in Northern Sweden was
stable from 1996 to 2016, and at similar level as from 1986 to 1996
[12,15]. Thus, the reported increase in asthma prevalence during the
last decades is not explained by an increase in asthma incidence, but by
the stable and relatively high incidence, 2-3/1000/year. The incidence
was consistently higher among women than men. In analyzes adjusted for
covariates, allergic rhino-conjunctivitis was the main risk factor for
incident asthma both 1996 to 2006 and 2006 to 2016.
To the best of our knowledge we are the first to report about trends in
asthma incidence among adults over several decades. A review article
including incidence studies from 1950s to 1990s indicated an increase in
incidence rate by time, however, the methods varied substantially
between the included studies [28]. Three longitudinal
population-based studies performed in Sweden and neighboring countries
during the 1980´s and 1990´s with almost identical methods found
incidence rates of 2-3/1000/year [15,16,18]. Our results,
2.4/1000/year from 1996 to 2006 and 2.6/1000/year from 2006 to 2016, are
in line with these studies, including the previous study in our region
(Figure 1) [15], and indicate a continuing stable trend in incidence
rate in Sweden as a whole. However, an incidence rate of 2-3/1000/year
in combination with low remission of asthma in adulthood [6,7,18]
and similar mortality among adults with asthma as in the general
population, means about 1% unit increase in prevalence every ten years
and thus contribute to the slowly increasing prevalence of asthma among
adults.
Only a limited number of studies about the incidence rate of asthma in
adulthood are based on prospective longitudinal population-based studies
[12-21,23], while others are based on registers or retrospective
estimates [22,24]. These studies show considerable variation in
results, 0.7-6/1000/year due to variations in the study design including
the age of the population [11,13,14,25], and the definitions of the
outcome and the population at risk [12, 14-16,18]. Studies ending up
with high incidence rates have often not excluded individuals with
symptoms common in asthma from the population at risk. To enable valid
comparisons between different studies it is paramount to use identical
methods.
Symptoms of asthma may occur several years before a diagnosis of asthma
is made and these symptoms may reflect undiagnosed asthma in the
population, why the incidence rate measured prospectively may be
overestimated. To reduce this bias it is reasonable to also exclude
subjects reporting symptoms of asthma from the population at risk. When
comparing different populations at risk (model A vs B) we found that the
difference in incidence rate of physician-diagnosed asthma between the
two models was much smaller in the two current cohorts under study
compared with the study from the 1980s (Figure 1). When using model B
(not correcting for possible under-diagnosis), the incidence of
physician-diagnosed asthma was 4.4-4-8/1000/year in the current cohorts,
while it was 8/1000/year in the 1980s cohort [12]. This may reflect
a decrease in under-diagnosis of asthma since the 1980s, probably due to
changed diagnostic practice and higher awareness of asthma in healthcare
and society today [2,26]. However, at the follow-up of our two
current cohorts in 2006 and 2016, individuals with incident asthma
reported similar prevalence of symptoms of asthma and use of asthma
medication. This indicate a similar disease burden among individuals
with adult onset asthma today as ten years ago, which in part
contradicts the suggested diagnostic drift regarding asthma in
healthcare. On the other hand, the major change may have occurred before
the millennium shift as a consequence of a Swedish national program
focusing on asthma during 1995, and perhaps even related to the start of
the OLIN-research program in the study area in 1986, resulting in
increased awareness of asthma in the society. Still, the higher
incidence rate of use of asthma medication compared with asthma
diagnosis may indicate some under-diagnosis of asthma also today.
However, asthma medication is also used in other respiratory diseases,
such as bronchitis and COPD, which may contribute to the high incidence.
In line with previous studies, we found that women had a higher
incidence rate of asthma compared with men [12-24,29,30] (Figure 2).
This is in contrast to children, where the incidence is higher among
boys than girls [8,9,11,22]. The reason for the sex differences is
unclear but may be related to hormonal status [29]. The obese-asthma
phenotype, often found in adult onset asthma among women [5,29], may
be mediated by interactions between sex hormones and systemic
inflammation [31]. However, female sex has been reported to be a
predictor for persistent asthma from childhood to adulthood [32,33]
and it seems that the increasing prevalence of asthma among adults is
mainly driven by women, i.e. by lower remission rate of childhood asthma
and higher incidence rates of asthma in adult age in women than in men.
Allergic rhino-conjunctivitis is a well-known risk factor for asthma
[4,17,19,21] and is a reasonable proxy for allergic sensitization,
at least among younger and middle-aged [21]. In the current study it
was the strongest and most stable risk factor for asthma which further
strengthen the causality of the association. Several previous studies
have found smoking or ex-smoking associated with incidence of asthma
[4,10,12,15,19,23]. In the current study we found that, from 2006,
neither smoking nor ex-smoking remained as risk factors for incident
asthma among adults. This change is probably a result of the
considerable decrease in smoking that have occurred during the last two
decades in Sweden [2,26]. Not only the prevalence of smoking has
decreased but, also the number of cigarettes smoked per day has been
reduced [2]. Thus, the total level of tobacco exposure had decreased
significantly which is beneficial also for the general public health. In
contrast to previous studies which have reported several markers for low
socioeconomic status to be associated with incident asthma [34-36],
we did not find any consistent associations with socioeconomic status
based on occupation. However, though not significant, the risk ratio for
manual work was 1.75 in the 1996 cohort while the RR was close to 1 in
the most recent cohort. This may be due to improvement of the working
environment, but also due to lack of power in our study, not allowing
more detailed occupational classifications.
Several strengths support the validity of the results. First, we used
two large population-based cohorts within the same age-span and
geographical area and both cohorts were followed for ten years. Second,
the response rate was high in both cohorts, both at recruitment and
follow-up. Third, for high comparability with previous studies
[12,15,18] we used identical methods in the calculations of
incidence, and these were based on the same validated questionnaire
[27]. Furthermore, the prospective design is, compared with
retrospective studies, less associated with recall bias [11,25].
Although the internal validity can be regarded as high, the external
validity is unclear due to the lack of studies of trends in asthma
incidence. A limitation worth noting is that despite the large sample
sizes of the cohorts and the relatively long follow-up, the study lacks
power for subgroups analyses. The studies were based on questionnaire
data which may have introduced some bias, why we cannot exclude that
some of those diagnosed as having asthma in reality had COPD. However,
the incidence were similar across all age groups. Another weakness is
the limited information about risk factors, such as body mass index and
education level, factors that have been associated with adult-onset
asthma [4,5,29,34].